ZA200409420B

ZA200409420B - Methods and compositions for diagnosing and monitoring transplant rejection

Info

Publication number: ZA200409420B
Application number: ZA200409420A
Authority: ZA
Inventors: Wohlgemuth Jay; Fry Kirk; Woodward Robert; Ly Ngoc; Prentice James; Morris Macdonald; Rosenberg Steven
Original assignee: Expression Diagnostics Inc Dba
Priority date: 2002-04-24
Filing date: 2003-04-24
Publication date: 2007-05-30

Description

METHODS AND COMPOSITIONS FOR DIAGNOSING

AND MONITORING TRANSPLANT REJECTION

Related Applications

This application claims priority to U.S. Application No. 10/131,831, filed April 24, 2002, and

U.S. Application No. 10/325,899, filed December 20, 2002.

Field of the Invention

This invention is in the field of expression profiling following organ transplantation.

Background of the Invention

Many of the current shortcomings in diagnosis, prognosis, risk stratification and treatment of disease can be approached through the identification of the molecular mechanisms underlying a disease and through the discovery of nucleotide sequences (or sets of nucleotide sequences) whose expression pattems predict the occurrence or progression of disease states, or predict a patient’s response to a particular therapeutic intervention. In particular, identification of nucleotide sequences and sets of nucleotide sequences with such predictive value from cells and tissues that are readily accessible would be extremely valuable. For example, peripheral blood is attainable from all patients and can easily be obtained at multiple time points at low cost. This is a desirable contrast to most other cell and tissue types, which are less readily accessible, or accessible only through invasive and aversive procedures.

In addition, the various cell types present in circulating blood are ideal for expression profiling experiments as the many cell types in the blood specimen can be easily separated if desired prior to analysis of gene expression. While blood provides a very attractive substrate for the study of diseases using expression profiling techniques, and for the development of diagnostic technologies and the identification of therapeutic targets, the value of expression profiling in blood samples rests on the degree to which changes in gene expression in these cell types are associated with a predisposition to, and pathogenesis and progression of a disease.

Hematopoiesis is the development and maturation of all cell types of the blood. These include erythrocytes, platelets and leukocytes. Leukocytes are further subdivided into granulocytes (neutrophils, eosinophils, basophils) and mononuclear cells (monocytes, lymphocytes). These cells develop and mature from precursor cells to replenish the circulating pool and to respond to insults and challenges to the system. This occurs in the bone marrow, spleen, thymus, liver, lymph nodes, mucosal associated lymphoid tissue (MALT) and peripheral blood.

Precursor cells differentiate into immature forms of each lineage and these immature cells develop further into mature cells. This process occurs under the influence and direction of hematopoietic growth factors. When hematopoiesis is stimulated, there is an increase in the number of immature cells in the peripheral blood and in some cases, precursor cells are found at increased frequency. For example, CD34+ cells (hematopoietic stem cells) may increase in frequency in the peripheral blood with an insult to the immune system. For neutrophils, “band” forms are increased, for erythrocytes, reticulocytes or nucleated red cells are seen. Lymphocytes are preceeded by lymphoblasts (immature lymphocytes).

It may be an important clinical goal to measure the rate of production of blood cells of a variety of lineages. Hematological disorders involving over or under production of various blood cells may be treated pharmacologically. For example, anemia (low red blood cells) may be treated with erythropoietin (a hematopoietic growth factor) and response to this therapy can be assessed by measuring RBC production rates. Low neutrophils counts can be treated by administration of G-CSF and this therapy may be monitored by measuring neutrophil production rates. Alternatively, the diagnosis of blood cell disorders is greatly facilitated by determination of lineage specific production rates. For example, anemia (low RBCs) may be caused by decreased cellular production or increased destruction of cells. In the latter case, the rate of cellular production will be increased rather than decreased and the therapeutic implications are very different. Further discussion of the clinical uses of measures of blood cell production rates is given in below.

Assessment of blood cell production rates may be useful for diagnosis and management of non-hematological disorders. In particular, acute allograft rejection diagnosis and monitoring may benefit from such an approach. Current diagnosis and monitoring of acute allograft rejection is achieved through invasive allograft biopsy and assessment of the biopsy histology. This approach is sub-optimal because of expense of the procedure, cost, pain and discomfort of the patient, the need for trained physician operators, the risk of complications of the procedure, the lack of insight into the functioning of the immune system and variability of pathological assessment. In addition, biopsy can diagnose acute allograft rejection only after significant cellular infiltration into the allograft has occurred. At this point, the process has already caused damage to the allograft. For all these reasons, a simple blood test that can diagnose and monitor acute rejection at an earlier stage in the process is needed. Allograft rejection depends on the presence of functioning cells of the immune system. In addition, the process of rejection may cause activation of hematopoiesis. Finally, effective immunosuppressive therapy to treat or prevent acute rejection may suppress hematopoiesis. For these reasons, assessment of hematopoietic cellular production rates may be useful in the diagnosis and . monitoring of acute rejection.

Current techniques for measuring cellular development and production rates are inadequate.

The most common approach is to measure the number of mature cells of 2 lineage of interest over time.

For example, if a patient is being treated for anemia (low red blood cell counts), then the physician will order a blood cell count to assess the number of red blood cells (RBCs) in circulation. For this to be effective, the physician must measure the cell count over time and may have to wait 2-4 weeks before being able to assess response to therapy. The same limitation is true for assessment of any cell lineage in the blood.

An alternative approach is to count the number of immature cells in the peripheral blood by counting them under the microscope. This may allow a more rapid assessment of cellular production rates, but is limited by the need for assessment by a skilled hematologist, observer variability and the inability to distinguish all precursor cells on the basis of morphology alone.

Bone marrow biopsy is the gold standard for assessment of cellular production rates. In addition to the limitations of the need for skilled physicians, reader variability and the lack of sensitivity of morphology alone, the technique is also limited by the expense, discomfort to the patient and need for a prolonged visit to a medical center. Thus there is a need for a reliable, rapid means for measuring the rate of hematopoeisis in a patient.

In addition to the relationship between hematopoiesis and variety of disease processes, there is an extensive literature supporting the role of leukocytes, e.g., T-and B-lymphocytes, monocytes and granulocytes, including neutrophils, in a wide range of disease processes, including such broad classes as cardiovascular diseases, inflammatory, autoimmune and rheumatic diseases, infectious diseases, transplant rejection, cancer and malignancy, and endocrine diseases. For example, among cardiovascular diseases, such commonly occurring diseases as atherosclerosis, restenosis, transplant vasculopathy and acute coronary syndromes all demonstrate significant T cell involvement (Smith-

Norowitz et al. (1999) Clin Immunol 93:168-175; Jude et al. (1994) Circulation 90:1662-8; Belch et al. (1997) Circulation 95:2027-31). These diseases are now recognized as manifestations of chronic inflammatory disorders resulting from an ongoing response to an injury process in the arterial tree (Ross et al. (1999) Ann Thorac Surg 67:1428-33). Differential expression of lymphocyte, monocyte and neutrophil genes and their products has been demonstrated cleatly in the literature. Particularly interesting are examples of differential expression in circulating cells of the immune system that demonstrate specificity for a particular disease, such as arteriosclerosis, as opposed to a generalized association with other inflammatory diseases, or for example, with unstable angina rather than quiescent coronary disease.

A number of individual genes, e.g., CD11b/CD18 (Kassirer et al. (1999) Am Heart J 138:555- 9); leukocyte elastase (Amaro et al. (1995) Eur Heart J 16:615-22; and CDA0L (Aukrust et al. (1999)

Circulation 100:614-20) demonstrate some degree of sensitivity and specificity as markers of various vascular diseases. In addition, the identification of differentially expressed target and fingerprint genes isolated from purified populations of monocytes manipulated in various in vitro paradigms has been proposed for {he diagnosis and monitoring of 2 range of cardiovascular diseases, see, e.g, US Patents

Numbers 6,048,709; 6,087,477; 6,099,823; and 6,124,433 “COMPOSITIONS AND METHODS FOR

THE TREATMENT AND DIAGNOSIS OF CARDIOVASCULAR DISEASE” to Falb (see also, WO 97/30065). Lockhart, in US Patent Number 6,033,860 “EXPRESSION PROFILES IN ADULT AND

FETAL ORGANS” proposes the use of expression profiles for a subset of identified genes in the identification of tissue samples, and the monitoring of drug effects.

The accuracy of technologies based on expression profiling for the diagnosis, prognosis, and monitoring of disease would be dramatically increased if numerous differentially expressed nucleotide sequences, each with a measure of specificity for a disease in question, could be identified and assayed in a concerted manner. PCT application WO 02/057414 “LEUKOCYTE EXPRESSION PROFILING" to Wohlgemuth identifies one such set of differentially expressed nucleotides.

In order to achieve this improved accuracy, the sets of nucleotide sequences once identified nced to be validated to identify those differentially expressed nucleotides within a given set that are most useful for diagnosis, prognosis, and monitoring of disease. The present invention addresses these and other needs, and applies to transplant rejection and detection of the rate of hematopoeisis for which differential regulation of genes, or other nucleotide sequences, of peripheral blood can be demonstrated.

Summary of the Invention

In order to meet these needs, the present invention is thus directed to a system for detecting differential gene expression. In one format, method are provided for assessing the immune status of an individual by detecting the expression level of one or more genes expressed at different levels depending upon the rate of hematopoiesis or the distribution of hematopoietic cells along their maturation pathway in the individual. The one or more genes may include a nucleotide selected from a nucleotide sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ

ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID

NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID

NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID

NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID

NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID

NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID

NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID

NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID

NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID

NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID

NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID

NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID

NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID

NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID

NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID

NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID

NO:102, SEQ ID NO:103, SEQ ID NO: 104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ

ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113,

SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID

NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ

ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130,

SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID

NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO: 139, SEQ ID NO:140, SEQ ID NO:141, SEQ

ID NO:142, SEQ ID NO:143, SEQ ID NO: 144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147,

SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID

NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ

ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164,

SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID

NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ .

ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181,

SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID

NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ

ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198,

SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID

NO:204, SEQ ID NO:205, SEQ ID N0:206, SEQ ID N0:207, SEQ ID NO:208, SEQ ID NO:209, SEQ

ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215,

SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID N0:220, SEQ ID

NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ

ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232,

SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID N0:237, SEQ ID

NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ

ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249,

SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID

NO:255, SEQ ID NO:256, SEQ ID N0:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ

ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266,

SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID

NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ

ID NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283,

SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID

NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ

ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID N0O:298, SEQ ID N0O:299, SEQ ID NO:300,

SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID

NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ

ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317,

SEQ ID NO:218, SEQ ID NO:319, SEQ ID NO:320, SEQ ID NG:32i, SEQ ID NO:322, SEQ iD

NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID N0:326, SEQ ID NO:327, SEQ ID NO:328, SEQ

ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID

NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID N0O:2717, SEQ ID NO:2646, SEQ ID

NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID

NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID

NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID N0:2719, SEQ ID NO:2684, SEQ ID

NO:2677, SEQ ID N0:2748, SEQ ID N0:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID

NO:2657, SEQ ID NO:2683, SEQ 1D NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID

NO:2664, SEQ ID N0:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID

NO:2713, SEQ ID N0O:2736, SEQ ID NO:2708, SEQ ID N0:2670, SEQ ID NO:2661, SEQ ID

NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID

NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID

NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID

NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID

NO:2691, SEQ ID N0O:2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID

NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID

NO:2730, SEQ ID N0:2710, SEQ ID NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID

NO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID N0:2675, SEQ ID NO:2700, SEQ ID

NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID

NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID

NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID NO:2673, SEQ ID NO:2733, SEQ ID

NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ ID

NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID

NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID

NO:2699, SEQ ID N0O:2633, SEQ ID NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID

NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID

NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID

NO:2709, SEQ ID NO:2653, SEQ ID NO:2729. The expression level may be detected by measuring the RNA level expressed by the one or more genes. In one variation, the RNA level is detected by

PCR. In another variation, the RNA level is detected by hybridization. The expression level may also be detected by measuring one or more proteins expressed by the one or more genes.

The present invention is further directed to methods of diagnosing or monitoring transplant rejection in an individual by detecting a rate of hematopoiesis. The detection may be applied directly to the individual, or to a sample isolated from the individual. Detection may be accomplished by RNA profiling assay, immunoassay, fluorescent activated cell sorting, protein assay, peripheral blood cytology assay, MRI imaging, bone marrow aspiration, and/or nuclear imaging. In one variation, the

RNA profile assay is a PCR based assay. In another variation, the RNA profile assay is a hybridization based assay. The RNA profile assay may further include detecting the expression level of one or more genes in the individual where the one or more genes include a nucleotide sequence selected from SEQ

ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8,

SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NQO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ

ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID

NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID

NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID

NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID

NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID

NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID

NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID

NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID

NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID

NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID

NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID

NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID

NO:87, SEQ ID NO:88, SEQ ID NO0:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID

NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID

NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ

ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110,

SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID

NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO: 121, SEQ

ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127,

SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID

NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO: 138, SEQ

ID NO:139, SEQ 1D NO: 140, SEQ ID NO: 141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO: 144,

SEQ ID NO: 145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID

NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO: 154, SEQ ID NO:155, SEQ

ID NO:156, SEQ ID NO:157, SEQ ID NO: 158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161,

SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO: 166, SEQ ID

NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ

ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178,

SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID NO: 183, SEQ ID

NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO: 188, SEQ ID NO:189, SEQ

ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195,

SEQ ID NO: 196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID

NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ

ID NO:207, SEQ ID NO:208, SEQ ID N0:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212,

SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID

NO:218, SEQ ID N0:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ

ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID N0O:227, SEQ ID NO:228, SEQ ID NO:229,

SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID

NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID N0:239, SEQ ID NO:240, SEQ

ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246,

SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID

NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ

ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:263,

SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID

NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ

ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280,

SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID

NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ

ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297,

SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID

NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ

ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314,

SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID NO:319, SEQ ID

NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ

ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331,

SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID

NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID

NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID

NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID

NO:2719, SEQ ID NO:2684, SEQ ID N0:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID

NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID

NO:2687, SEQ ID NO:2644, SEQ 1D NO:2664, SEQ 1D NO:2747, SEQ ID NO:2744, SEQ ID

NO:2678, SEQ ID NO:2731, SEQ ID NO0:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID

NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID

NO:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID

NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID

NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID

NO:2695, SEQ ID NO:2741, SEQ ID N0:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID

NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID

NO:2676, SEQ ID NO:2701, SEQ ID N0:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID

NO:2724, SEQ ID NO:2698, SEQ ID N0:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID

NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID

NO:2688, SEQ ID NO:2735, SEQ ID N0:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID

NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID

NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID

NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID

NO:2692, SEQ ID N0:2693, SEQ ID NO:2648, SEQ ID NO:2650, SEQ ID N0O:2720, SEQ ID

NO:2660, SEQ ID NO:2666, SEQ ID N0:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID

NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID N0:2630, SEQ ID NO:2745, SEQID

NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID

NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID NO:2653, SEQ ID NO:2729. Transplant rejection may include one or more of heart transplant rejection, kidney transplant rejection, liver transplant rejection, pancreas transplant rejection, pancreatic islet transplant rejection, lung transplant rejection, bone marrow transplant rejection, stem cell transplant rejection, xenotransplant rejection, and mechanical organ replacement rejection.

In another aspect, the invention is directed to a method of diagnosing or monitoring transplant rejection in a patient by detecting the expression level of one or more genes in the patient to diagnose or monitor transplant rejection in the patient, wherein the one or more genes include a nucleotide sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6,

SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ

ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID

NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID

NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID

NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID

NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQID

NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQID

NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQID

NO:56, SEQ 1D NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID

NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID N0:66, SEQ ID NO:67, SEQ ID

NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID

NO:74, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID

NO:87, SEQ 1D NO:88, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID

NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID

NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ

ID NO:109, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO: 118,

SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID

NO:124, SEQ ID NO:125, SEQ ID NO: 126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ

ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO: 135,

SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:152, SEQ ID

NO:153, SEQ ID NO: 154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ

ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO: 164,

NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ

NO:187, SEQ ID NO: 188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ

ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, :

NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NC:209, SEQ

SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID N0O:219, SEQ ID NO:220, SEQ ID

SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID

NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ

NO:289, SEQ 1D N0:290, SEQ ID NO:291, SEQ ID N0:292, SEQ ID NO:293, SEQ ID NO:294, SEQ

ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300,

SEQ ID NO:318, SEQ ID NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID

NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ

ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID

NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID N0:2717, SEQ ID NO:2646, SEQ ID

NO:2667, SEQ ID NO:2706, SEQ ID N0:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ 1D

NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID

NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID

NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID

NO0:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID

NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID

NO:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID N0:2670, SEQ ID NO:2661, SEQ ID

NO0:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID

NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID

NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID

NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID : NO:2691, SEQ ID N0:2726, SEQ ID N0:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID

NO0:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID

NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ 1D NO:2724, SEQ ID N0O:2698, SEQ ID

NO0:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID NO:2675, SEQ ID NO:2700, SEQ ID

NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID

NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID

N0:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID NO:2673, SEQ ID NO:2733, SEQ ID

NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ ID

NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID

NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID N0:2660, SEQ ID NO:2666, SEQ ID

NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID

NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:26594, SEQ ID

NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID

NO:2709, SEQ ID NO:2653, SEQ ID NO:2729. In one variation, the invention is further directed to detecting the expression level of one or more additional genes in the patient to diagnose or monitor transplant rejection in the patient, wherein the one or more additional genes include a nucleotide sequence selected from SEQ ID NO:8, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID

NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:89, SEQ ID NO:97, SEQ ID

NO:99, SEQ ID NO:100, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ

ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145,

SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO: 148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID

NO:15.

In a further variation, the invention is directed to a method of diagnosing or monitoring cardiac transplant rejection in a patient by detecting the expression level of one or more genes in the patient to diagnose or monitor cardiac transplant rejection in the patient wherein the one or more genes include a nucleotide sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO4, SEQ ID

NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO:11, SEQ ID NO:12,

SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO: 16, SEQID NO:17, SEQ ID NO: 18,

SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24,

SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30,

SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36,

SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,

SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48,

SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54,

SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60,

SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66,

SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72,

SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82,

SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88,

SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94,

SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101,

SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID

NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ

ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118,

NO:124, SEQ iD NO: 125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128 SEQ ID NO0:129, SEQ

ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135,

NO:153, SEQ ID NO:154, SEQ ID NO:15S, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ

SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO: 167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID

NO:170, SEQ ID NO:171, SEQ 1D NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ

SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO: 184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID

ID NO:193, SEQ ID NO:194, SEQ ID NO: 195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198,

NO:204, SEQ ID NO:205, SEQ ID N0:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ

SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID

NO:221, SEQ ID NO:222, SEQ ID N0:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NQ:226, SEQ

ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID N0O:232,

NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ oo

SEQ ID N0O:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID

ID NO:261, SEQ ID NO:262, SEQ ID N0:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266,

SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ 1D N0:270, SEQ ID NO:271, SEQ ID

ID NO:295, SEQ ID NO:296, SEQ ID N0:297, SEQ ID NO:298, SEQ ID N0:299, SEQ ID NO:300,

SEQ ID NO:318, SEQ ID NO:319, SEQ ID NO:320, SEQ 1D NO:321, SEQ ID NO:322, SEQ ID

NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ 1D NO:328, SEQ

ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332. In one variation, the method includes detecting the expression level of one or more additional genes in the patient to diagnose or monitor cardiac transplant rejection in the patient, wherein the one or more additional genes include a nucleotide sequence selected from SEQ ID NO:8, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78,

SEQ ID NO:79, SEQ ID NO:97, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID

NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ

ID NO:149, SEQ ID NO:150, SEQ ID NO:151. :

The invention is also directed to a method of diagnosing or monitoring kidney transplant rejection in a patient by detecting the expression level of one or more genes in the patient to diagnose or monitor kidney transplant rejection in the patient wherein the one or more genes include a nucleotide sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6,

SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ

ID NO:13, SEQ ID NO: 14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID

NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID

NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID

NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID

NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID

NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID

NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID

NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NQ:59, SEQ ID NO:60, SEQ ID

NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID

NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID

NO:73, SEQ ID NO:74, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID

NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:91, SEQ ID

NO:92, SEQ ID NO:93, SEQ 1D NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID

NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ 1D NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ iD NO:109, SEQ ID NO:114, SEQ ID NO:115,

SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO: 118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID

NO:121, SEQ ID NO:122, SEQ 1D NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO: 126, SEQ

ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132,

SEQ ID NO:133, SEQ ID NO: 134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID

NO:138, SEQ ID NO:139, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ

ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161,

SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID

SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID NO:183, SEQ ID

NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ

SEQ ID NO:196, SEQ ID NO: 197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID

NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ

ID NO:224, SEQ ID NO:225, SEQ ID N0:226, SEQ ID N0:227, SEQ ID NO:228, SEQ ID NO:229,

SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID N0:234, SEQ ID

NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ

SEQ ID NO:247, SEQ ID NO:248, SEQ ID N0:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID

ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID N0:278, SEQ ID N0:279, SEQ ID NO:280,

ID NO:292, SEQ ID NO:293, SEQ ID NO0:294, SEQ ID NO:295, SEQ ID N0:296, SEQ ID NO:297,

NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ 1D NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331,

SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID N0:2707, SEQ ID NO:2679, SEQ ID

NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID

NO:2669, SEQ ID NO:2674, SEQ ID N0O:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID

NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID

NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID

NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID

NO:2687, SEQ 1D NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID

NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID

NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID

NO:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID

NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID

NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID

NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID

NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID

NO:2676, SEQ ID NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID

NO:2724, SEQ ID NO:2698, SEQ ID NO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID

NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID

NO:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID

NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID

NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID

NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID

NO:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID

NO:2660, SEQ ID NO:2666, SEQ ID N0:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID

NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID

NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID

NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID NO:2653, SEQ ID NO:2729. In one variation, the method further includes detecting the expression level of one or more additional genes in : the patient to diagnose or monitor kidney transplant rejection in a patient, wherein the one or more additional genes includes a nucleotide sequence selected from SEQ ID NO: 75, SEQ ID NO:76, SEQ

ID NO:77, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:89, SEQ ID NO:99, SEQ ID

NO:100, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:140, SEQ

ID NO:141, SEQ ID NO:142, SEQ ID NQ:143, SEQ ID NO: 144, SEQ ID NO:145, SEQ ID NO:146,

SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151.

In another aspect, the methods of diagnosing or monitoring transplant rejection include detecting the expression level of at least two of the genes. In another variation, methods of diagnosing or monitoring transplant rejection include detecting the expression level of at least ten of the genes. In a further variation, the methods of diagnosing or monitoring transplant rejection include detecting the expression level of at least one hundred of the genes. In still a further variation, the methods of diagnosing or monitoring transplant rejection include detecting the expression level of all the listed genes.

In another variation, transplant rejection may be selected from heart transplant rejection, kidney transplant rejection, liver transplant rejection, pancreas transplant rejection, pancreatic islet transplant rejection, lung transplant rejection, bone marrow transplant rejection, stem cell transplant rejection, xenotransplant rejection, and mechanical organ replacement rejection.

In another aspect, the methods of detecting transplant rejection include detecting the expression level by measuring the RNA level expressed by one or more genes. The method may further including isolating RNA from the patient prior to detecting the RNA level expressed by the one or more genes.

In one variation, the RNA level is detected by PCR. In a still further variation, the PCR uses primers consisting of nucleotide sequences selected from the group consisting of SEQ ID NO:665,

SEQ ID NO:666, SEQ ID NO:667, SEQ ID NO:668, SEQ ID NO:669, SEQ ID NO:670, SEQ ID

NO:671, SEQ ID NO:672, SEQ ID NO:673, SEQ ID NO:674, SEQ ID NO:675, SEQ ID NO:676, SEQ

ID NO:677, SEQ ID NO:678, SEQ ID NO:679, SEQ ID N0:680, SEQ ID NO:681, SEQ ID NO:682,

SEQ ID NO:683, SEQ ID NO:684, SEQ ID NO:685, SEQ ID NO:686, SEQ ID NO:687, SEQ ID

NO:688, SEQ ID NO:689, SEQ ID NO:690, SEQ ID NO:691, SEQ ID NO:692, SEQ ID NO:693, SEQ

ID NO:694, SEQ ID NO:695, SEQ ID N0:696, SEQ ID NO:697, SEQ ID NO:698, SEQ ID NO:699,

SEQ ID NO:700, SEQ ID NO:701, SEQ ID NO:702, SEQ ID NO:703, SEQ ID NO:704, SEQ ID

NO:705, SEQ ID NO:706, SEQ ID NO:707, SEQ ID NO:708, SEQ ID NO:709, SEQ ID NO:710, SEQ

ID NO:711, SEQ ID NO:712, SEQ ID NO:713, SEQ ID NO:714, SEQ ID NO:715, SEQ ID NO:716,

SEQ ID NO:717, SEQ ID NO:718, SEQ ID NO:719, SEQ 1D NO:720, SEQ ID NO:721, SEQ ID

NO:722, SEQ ID NO:723, SEQ ID NO:724, SEQ ID NO:725, SEQ ID NO:726, SEQ ID NO:727, SEQ

ID NO:728, SEQ ID NO:729, SEQ ID NO:730, SEQ ID NO:731, SEQ ID NO:732, SEQ ID NO:733,

SEQ ID NO:734, SEQ ID NO:735, SEQ ID NO:736, SEQ ID NO:737, SEQ ID NO:738, SEQ ID

NO:739, SEQ 1D NO:740, SEQ ID NO:741, SEQ ID NO:742, SEQ ID NO:743, SEQ ID NO:744, SEQ

ID NO:745, SEQ ID NO:746, SEQ ID NO:747, SEQ ID NO:748, SEQ ID NO:749, SEQ ID NO:750,

SEQ ID NO:751, SEQ ID NO:752, SEQ ID NO:753, SEQ ID NO:754, SEQ ID NO:755, SEQ ID

NO:756, SEQ ID NO:757, SEQ ID NO:758, SEQ ID NO:759, SEQ ID NO:760, SEQ ID NO:761, SEQ

ID NO:762, SEQ ID NO:763, SEQ ID NO:764, SEQ ID NO:765, SEQ ID NO:766, SEQ ID NO:767,

SEQ ID NO:768, SEQ ID NO:769, SEQ ID NO:770, SEQ ID NO:771, SEQ ID NO:772, SEQID

NO:773, SEQ ID NO:774, SEQ ID NO:775, SEQ ID NO:776, SEQ ID NO:777, SEQ ID NO:778, SEQ

ID NO:779, SEQ ID NO:780, SEQ ID NO:781, SEQ ID NO:782, SEQ ID NO:783, SEQ ID NO:784,

SEQ ID NO:785, SEQ ID NO:786, SEQ ID NO:787, SEQ ID NO:788, SEQ ID NO:789, SEQ ID

NO:790, SEQ ID NO:791, SEQ ID NO:792, SEQ ID NO:793, SEQ ID NO:794, SEQ ID NO:795, SEQ

ID NO:796, SEQ ID NO:797, SEQ ID NO:798, SEQ ID N0:799, SEQ ID NO:800, SEQ ID NO:801,

SEQ ID NO:802, SEQ ID NO:803, SEQ ID NO:804, SEQ ID NO:805, SEQ ID NO:806, SEQ ID

NO:807, SEQ ID NO:808, SEQ ID NO:809, SEQ ID NO:810, SEQ ID NO:811, SEQ ID NO:812, SEQ

ID NO:813, SEQ ID NO:814, SEQ ID NO:815, SEQ ID NO:816, SEQ ID NO:817, SEQ ID NO:818,

SEQ ID NO:819, SEQ ID NO:820, SEQ ID NO:821, SEQ ID NO:822, SEQ ID NO:823, SEQ ID

NO:824, SEQ ID NO:825, SEQ ID NO:826, SEQ ID NO:827, SEQ ID NO:828, SEQ ID NO:829, SEQ

ID NO:830, SEQ ID NO:831, SEQ ID NO:832, SEQ ID NO:833, SEQ ID NO:834, SEQ ID NO:835,

SEQ ID NO:836, SEQ ID NO:837, SEQ ID NO:838, SEQ ID NO:839, SEQ ID NO:840, SEQID

NO:841, SEQ ID NO:842, SEQ ID NO:843, SEQ ID NO:844, SEQ ID NO:845, SEQ ID NO:846, SEQ

1D NO:847, SEQ ID NO:848, SEQ ID NO:849, SEQ ID NO:850, SEQ ID NO:851, SEQ ID NO:852,

SEQ ID NO:853, SEQ ID NO:854, SEQ ID NO:855, SEQ ID NO:856, SEQ ID NO:857, SEQ ID

NO:858, SEQ ID NO:859, SEQ ID NO:860, SEQ ID NO:861, SEQ ID NO:862, SEQ ID NO:863, SEQ

ID NO:864, SEQ ID NO:865, SEQ ID NO:866, SEQ ID NO:867, SEQ ID NO:868, SEQ ID NO:869,

SEQ ID NO:870, SEQ ID NO:871, SEQ ID NO:872, SEQ ID NO:873, SEQ ID NO:874, SEQ ID

NO:875, SEQ ID NO:876, SEQ ID NO:877, SEQ ID NO:878, SEQ ID NO:879, SEQ ID NO:880, SEQ

ID NO:881, SEQ ID NO:882, SEQ ID NO:883, SEQ ID NO:884, SEQ ID NO:885, SEQ ID NO:886,

SEQ ID NO:887, SEQ ID NO:888, SEQ ID NO:889, SEQ ID NO:890, SEQ ID NO:891, SEQ ID

NO:892, SEQ ID NO:893, SEQ ID NO:894, SEQ ID NO:895, SEQ ID NO:896, SEQ ID NO:897, SEQ

ID NO:898, SEQ ID NO:899, SEQ ID N0:900, SEQ ID NO:901, SEQ ID NO:902, SEQ ID NO:903,

SEQ ID NO:904, SEQ ID NO:905, SEQ ID NO:906, SEQ ID N0:907, SEQ ID NO:908, SEQ ID

NO:909, SEQ ID NO:910, SEQ ID NO:911, SEQ ID NO:912, SEQ ID NO:913, SEQ ID NO:914, SEQ

ID NO:915, SEQ ID NO:916, SEQ ID NO:917, SEQ ID NO:918, SEQ ID NO:919, SEQ ID NO:920,

SEQ ID NO:921, SEQ ID N0:922, SEQ ID NO:923, SEQ ID N0:924, SEQ ID NO:925, SEQ ID

NO:926, SEQ ID NO:927, SEQ ID NO:928, SEQ ID N0:929, SEQ ID NO:930, SEQ ID NO:931, SEQ

ID NO:932, SEQ ID NO:933, SEQ ID NO:934, SEQ ID NO:935, SEQ ID N0O:936, SEQ ID NO:937,

SEQ ID NO:938, SEQ ID N0:939, SEQ ID NO:940, SEQ ID NO:941, SEQ ID NO:942, SEQ ID

NO:943, SEQ ID NO:944, SEQ ID NO:945, SEQ ID N0:946, SEQ ID NO:947, SEQ ID NO:948, SEQ

ID NO:949, SEQ ID NO:950, SEQ ID NO:951, SEQ ID NO:952, SEQ ID N0O:953, SEQ ID NO:954, : SEQ ID NO:955, SEQ ID NO:956, SEQ ID NO:957, SEQ ID NO:958, SEQ ID NO:959, SEQ ID

NO0:960, SEQ ID NO:961, SEQ ID NO:962, SEQ ID NO:963, SEQ ID NO:964, SEQ ID NO:965, SEQ

ID NO:966, SEQ ID NO:967, SEQ ID NO:968, SEQ ID N0:969, SEQ ID NO:970, SEQ ID NO:971,

SEQ ID NO:972, SEQ ID NO:973, SEQ ID NO:974, SEQ ID NO:975, SEQ ID N0O:976, SEQ ID

NO:977, SEQ ID NO:978, SEQ ID NO:979, SEQ ID NO:980, SEQ ID NO:981, SEQ ID NO:982, SEQ

ID NO:983, SEQ ID NO:984, SEQ ID NO:985, SEQ ID NO:986, SEQ ID NO:987, SEQ ID NO:988,

SEQ ID NO:989, SEQ ID NO:990, SEQ ID NO:991, SEQ ID N0:992, SEQ ID NO:993, SEQ ID

NO:994, SEQ ID NO:995, SEQ ID N0:996, SEQ ID N0:997, SEQ ID NO:998, SEQ ID NO:999, SEQ

ID NO:1000, SEQ ID NO:1001, SEQ ID NO:1002, SEQ ID NO:1003, SEQ ID NO:1004, SEQ ID

NO:1005, SEQ ID NO:1006, SEQ ID NO:1007, SEQ ID NO:1008, SEQ ID NO:1009, SEQ ID

NO:1010, SEQ ID NO:1011, SEQ ID NO:1012, SEQ ID NO:1013, SEQ ID NO:1014, SEQ ID

NO:1015, SEQ ID NO:1016, SEQ ID NO:1017, SEQ ID NO:1018, SEQ ID NO:1019, SEQ ID

NO:1020, SEQ ID NO:1021, SEQ ID NO:1022, SEQ ID NO:1023, SEQ ID NO:1024, SEQ ID

NO:1025, SEQ ID NO:1026, SEQ ID NO:1027, SEQ ID NO:1028, SEQ ID N0:1029, SEQ ID

NO0:1030, SEQ ID NO:1031, SEQ ID NO:1032, SEQ ID NO:1033, SEQ ID NO:1034, SEQ ID

NO:1035, SEQ ID NO:1036, SEQ ID N0O:1037, SEQ ID NO:1038, SEQ ID N0:1039, SEQ ID

NO:1040, SEQ ID NO:1041, SEQ ID NO:1042, SEQ 1D NO:1043, SEQ ID NO:1044, SEQ ID

NO:1045, SEQ ID NO:1046, SEQ ID NO:1047, SEQ ID NO:1048, SEQ ID NO:1049, SEQ ID

NO:1050, SEQ ID NO:1051, SEQ ID NO:1052, SEQ 1D NO:1053, SEQ ID NO:1054, SEQ ID

NO:1055, SEQ ID NO:1056, SEQ ID NO:1057, SEQ ID NO:1058, SEQ ID NO:1059, SEQ ID

NO:1060, SEQ ID NO:1061, SEQ ID NO:1062, SEQ ID NO:1063, SEQ ID NO:1064, SEQ ID

NO:1065, SEQ ID NO:1066, SEQ ID NO:1067, SEQ ID NO:1068, SEQ ID NO:1069, SEQID

NO:1070, SEQ ID NO:1071, SEQ ID NO:1072, SEQ ID NO:1073, SEQ ID NO:1074, SEQ ID

NO:1075, SEQ ID NO:1076, SEQ ID NO:1077, SEQ ID NO:1078, SEQ ID NO:1079, SEQ ID

NO:1080, SEQ ID NO:1081, SEQ ID NO:1082, SEQ ID NO:1083, SEQ ID NO:1084, SEQ ID

NO:1085, SEQ ID NO:1086, SEQ ID NO:1087, SEQ ID NO:1088, SEQ ID NO:1089, SEQ ID,

NO: 1090, SEQ ID NO:1091, SEQ ID NO:1092, SEQ ID NO:1093, SEQ ID NO:1094, SEQ ID

NO:1095, SEQ ID NO:1096, SEQ ID NO:1097, SEQ ID NO:1098, SEQ ID NO:1099, SEQ ID

NO:1100, SEQ ID NO:1101, SEQ ID NO:1102, SEQ ID NO:1103, SEQ ID NO:1104, SEQ ID

NO:1105, SEQ ID NO:1106, SEQ ID NO:1107, SEQ ID NO:1108, SEQ ID NO:1109, SEQ ID

NO:1110, SEQ ID NO:1111, SEQ ID NO:1112, SEQ ID NO:1113, SEQ ID NO:1114, SEQ ID

NO:1115, SEQ ID NO:1116, SEQ ID NO:1117, SEQ ID NO:1118, SEQ ID NO:1119, SEQ ID

NO:1120, SEQ ID NO:1121, SEQ ID NO:1122, SEQ ID NO:1123, SEQ ID NO:1124, SEQ ID

NO:1125, SEQ ID NO:1126, SEQ ID NO:1127, SEQ ID NO:1128, SEQ ID NO:1129, SEQ ID

NO:1130, SEQ ID NO:1131, SEQ ID NO:1132, SEQ ID NO:1133, SEQ ID NO:1134, SEQ ID

NO:1135, SEQ ID NO:1136, SEQ ID NO:1137, SEQ ID NO:1138, SEQ ID NO:1139, SEQ ID

NO:1140, SEQ ID NO:1141, SEQ ID NO:1142, SEQ ID NO:1143, SEQ ID NO:1144, SEQ ID

NO:1145, SEQ ID NO:1146, SEQ ID NO:1147, SEQ ID NO:1148, SEQ ID NO:1149, SEQ ID " NO:1150, SEQ ID NO:1151, SEQ ID NO:1152, SEQ ID NQO:1153, SEQ ID NO:1154, SEQ ID

NO:1155, SEQ ID NO:1156, SEQ ID NO:1157, SEQ ID NO:1158, SEQ ID NO:1159, SEQ ID

NO:1160, SEQ ID NO:1161, SEQ ID NO:1162, SEQ ID NO:1163, SEQ ID NO:1164, SEQ ID

NO:1165, SEQ ID NO:1166, SEQ ID NO:1167, SEQ ID NO:1168, SEQ ID NO:1169, SEQ ID

NO:1170, SEQ ID NO:1171, SEQ ID NO:1172, SEQ ID NO:1173, SEQ ID NO:1174, SEQID

NO:1175, SEQ ID NO:1176, SEQ ID NO:1177, SEQ ID NO:1178, SEQ ID NO:1179, SEQID

NO:1180, SEQ ID NO:1181, SEQ ID NO:1182, SEQ ID NO:1183, SEQ ID NO:1184, SEQ ID

NO:1185, SEQ ID NO:1186, SEQ ID NO:1187, SEQ ID NO:1188, SEQ ID NO:1 189, SEQ ID

NO:1190, SEQ ID NO:1191, SEQ ID NO:1192, SEQ ID NO:1193, SEQ ID NO:1194, SEQID

NO:1195, SEQ ID NO:1196, SEQ ID NO:1197, SEQ ID NO:1198, SEQ ID NO:1199, SEQID

NO:1200, SEQ ID NO:1201, SEQ ID NO:1202, SEQ ID NO:1203, SEQ ID NO:1204, SEQ ID .

NO:1205, SEQ ID NO:1206, SEQ ID NO:1207, SEQ ID NO:1208, SEQ ID NO:1209, SEQID .

NO:1210, SEQ ID NO:1211, SEQ ID NO:1212, SEQ ID NO:1213, SEQ ID NO:1214, SEQ ID

NO:1215, SEQ ID NO:1216, SEQ ID NO:1217, SEQ ID NO:1218, SEQ ID NO:1219, SEQID

NO:1220, SEQ ID NO:1221, SEQ ID NO:1222, SEQ ID NO:1223, SEQ ID NO:1224, SEQ ID

NO:1225, SEQ ID NO:1226, SEQ ID NO:1227, SEQ ID NO:1228, SEQ ID NO:1229, SEQ ID

NO:1230, SEQ ID NO:1231, SEQ ID NO:1232, SEQ ID N0:1233, SEQ ID NO:1234, SEQ ID

NO:1235, SEQ ID NO:1236, SEQ ID NO:1237, SEQ ID NO:1238, SEQ ID NO: 1239, SEQ ID

NO:1240, SEQ ID NO:1241, SEQ ID NO:1242, SEQ ID NO:1243, SEQ ID NO:1244, SEQ ID

NO:1245, SEQ ID NO:1246, SEQ ID NO:1247, SEQ ID NQ:1248, SEQ ID NO:1249, SEQ ID

NO:1250, SEQ ID NO:1251, SEQ ID NO:1252, SEQ ID NO:1253, SEQ ID NO:1254, SEQ ID ‘NO:1255, SEQ ID NO:1256, SEQ ID NO:1257, SEQ ID NG:1258, SEQ ID NO:1259, SEQ ID

NO:1260, SEQ ID NO:1261, SEQ ID NO:1262, SEQ ID NO:1263, SEQ ID NO:1264, SEQ ID

NO:1265, SEQ ID NO:1266, SEQ ID NO:1267, SEQ ID NO:1268, SEQ ID NO:1269, SEQ ID

NO:1270, SEQ ID NO:1271, SEQ ID NO:1272, SEQ ID NO:1273, SEQ ID NO:1274, SEQ ID

NO:1275, SEQ ID NO:1276, SEQ ID NO:1277, SEQ ID NO:1278, SEQ ID NO:1279, SEQ ID

NO:12380, SEQ ID NO:1281, SEQ ID NO:1282, SEQ ID NO:1283, SEQ ID NO:1284, SEQ ID

NO:1285, SEQ ID NO:1286, SEQ ID NO:1287, SEQ ID NO:1288, SEQ ID NO:1289, SEQ ID

NO:1290, SEQ ID NO:1291, SEQ ID NO:1292, SEQ ID NO:1293, SEQ ID NO:1294, SEQID

NO:1295, SEQ ID NO:1296, SEQ ID NO:1297, SEQ ID NO:1298, SEQ ID NO:1299, SEQ ID

NO:1300, SEQ ID NO:1301, SEQ ID NO:1302, SEQ ID NO:1303, SEQ ID NO:1304, SEQID

NO:1305, SEQ ID NO:1306, SEQ ID NO:1307, SEQ ID NO:1308, SEQ ID NO:1309, SEQID

NO:1310, SEQ ID NO:1311, SEQ ID NO:1312, SEQ ID NO:1313, SEQ ID NO:1314, SEQID

NO:1315, SEQ ID NO:1316, SEQ ID NO:1317, SEQ ID NO:1318, SEQ ID NO:1319, SEQID

NO:1320, SEQ ID NO:1321, SEQ ID NO:1322, SEQ ID NO:1323, SEQ ID NO:1324, SEQID ’

NO:1325, SEQ ID NO:1326, SEQ ID NO:1656, SEQ ID NO:1657, SEQ ID NO:1658, SEQ ID

NO:1659, SEQ ID NO:1660, SEQ ID NO:1661, SEQ ID NO:1662, SEQ ID NO:1663, SEQID

NO:1664, SEQ ID NO:1665, SEQ ID NO:1666, SEQ ID NO:1667, SEQ ID NO:1668, SEQ ID :

NO:1669, SEQ ID NO:1670, SEQ ID NO:1671, SEQ ID NO:1672, SEQ ID NO:1673, SEQ ID

NO:1674, SEQ ID NO:1675, SEQ ID NO:1676, SEQ ID NO:1677, SEQ ID NO:1678, SEQ ID

NO:1679, SEQ ID NO:1680, SEQ ID NO:1681, SEQ ID NO:1682, SEQ ID NO:1683, SEQ ID

NO:1684, SEQ ID NO:1685, SEQ ID NO:1686, SEQ ID NO:1687, SEQ ID NO:1688, SEQID

NO:1689, SEQ ID NO:1690, SEQ ID NO:1691, SEQ ID NO:1692, SEQ ID NO:1693, SEQ ID

NO:1694, SEQ ID NO:1695, SEQ ID NO:1696, SEQ ID NO:1697, SEQ ID NO: 1698, SEQ ID

NO:1699, SEQ ID NO:1700, SEQ ID NO:1701, SEQ ID NO:1702, SEQ ID NO:1703, SEQID

NO:1704, SEQ ID NO:1705, SEQ ID NO:1706, SEQ ID NO:1707, SEQ ID NO:1708, SEQ ID

NO:1709, SEQ ID NO:1710, SEQ ID NO:1711, SEQ ID NO:1712, SEQ ID NO:1713, SEQ ID

NO:1714, SEQ ID NO:1715, SEQ ID NO:1716, SEQ ID NO:1717, SEQ ID NO:1718, SEQ ID

NO:1719, SEQ ID NO:1720, SEQ ID NO:1721, SEQ ID NO:1722, SEQ ID NO:1723, SEQID

NO:1724, SEQ ID NO:1725, SEQ ID NO:1726, SEQ ID NO:1727, SEQ ID NO:1728, SEQ ID

NO:1729, SEQ ID NO:1730, SEQ ID NO:1731, SEQ ID NO:1732, SEQ ID NO:1733, SEQID :

NO:1734, SEQ ID NO:1735, SEQ ID NO:1736, SEQ ID NO:1737, SEQ ID NO:1738, SEQ ID

NO:1739, SEQ ID NO:1740, SEQ ID NO:1741, SEQ ID NO:1742, SEQ ID NO:1743, SEQ ID

NO:1744, SEQ ID NO:1745, SEQ ID NO:1746, SEQ ID NO:1747, SEQ ID NO:1748, SEQID :

NO:1749, SEQ ID NO:1750, SEQ ID NO:1751, SEQ ID NO:1752, SEQ ID NO:1753, SEQ ID .

NO:1754, SEQ ID NO:1755, SEQ ID NO:1756, SEQ ID NO:1757, SEQ ID NO:1758, SEQ ID

NO:1759, SEQ ID NO:1760, SEQ ID NO:1761, SEQ ID NO:1762, SEQ ID NO:1763, SEQ ID

NO:1764, SEQ ID NO:1765, SEQ ID NO:1766, SEQ ID NO:1767, SEQ ID NO:1768, SEQ ID

NO:1769, SEQ ID NO:1770, SEQ ID NO:1771, SEQ ID NO:1772, SEQ ID NO:1773, SEQ ID

NO:1774, SEQ ID NO:1775, SEQ ID NO:1776, SEQ ID NO:1777, SEQ ID NO:1778, SEQ ID

NO:1779, SEQ ID NO:1780, SEQ ID NO:1781, SEQ ID NO: 1782, SEQ ID NO:1783, SEQ ID

NO:1784, SEQ ID NO:1785, SEQ ID NO:1786, SEQ ID NO:1787, SEQ ID NO:1788, SEQ ID

NO:1789, SEQ ID NO: 1790, SEQ ID NO:1791, SEQ ID N0O:1792, SEQ ID NO:1793, SEQ ID

-_—

NO:1794, SEQ ID NO:1795, SEQ ID NO:1796, SEQ ID NO:1797, SEQ ID NO:1798, SEQ ID

NO:1799, SEQ 1D NO:1800, SEQ ID NO:1801, SEQ ID NO:1802, SEQ ID NO:1803, SEQ ID

NO:1804, SEQ ID NO:1805, SEQ ID NO: 1806, SEQ ID NO:1807, SEQ ID NO:1808, SEQ ID

NO:1809, SEQ ID NO:1810, SEQ ID NO:1811, SEQ ID NO:1812, SEQ ID NO:1813, SEQ ID

NO:1814, SEQ ID NO:1815, SEQ ID NO: 1816, SEQ ID NO:1817, SEQ ID NO:1818, SEQ ID

NO:1819, SEQ ID NO:1820, SEQ ID NO:1821, SEQ ID NO:1822, SEQ ID NO:1823, SEQ ID

NO:1824, SEQ ID NO:1825, SEQ ID NO:1826, SEQ ID NO:1827, SEQ ID NO:1828, SEQ ID

NO:1829, SEQ ID NO:1830, SEQ ID NO:1831, SEQ ID NO:1832, SEQ ID NO:1833, SEQ ID

NO:1834, SEQ ID NO:1835, SEQ ID NO:1836, SEQ ID NO:1837, SEQ ID NO:1838, SEQ ID

NO:1839, SEQ ID NO:1840, SEQ ID NO:1841, SEQ ID NO:1842, SEQ ID NO:1843, SEQ ID

NO:1844, SEQ ID NO:1845, SEQ ID NO:1846, SEQ ID NO:1847, SEQ ID NO:1848, SEQ ID

NO:1849, SEQ ID NO:1850, SEQ ID NO:1851, SEQ ID NO:1852, SEQ ID NO:1853, SEQ ID

NO:1854, SEQ ID NO:1855, SEQ ID NO:1856, SEQ ID NO:1857, SEQ ID NO: 1858, SEQ ID

NO:1859, SEQ ID NO:1860, SEQ ID NO:1861, SEQ ID NO:1862, SEQ ID NO:1863, SEQ ID

NO:1864, SEQ ID NO:1865, SEQ ID NO:1866, SEQ ID NO:1867, SEQ ID NO:1868, SEQ ID

NO:1869, SEQ ID NO:1870, SEQ ID NO: 1871, SEQ ID NO:1872, SEQ ID NO:1873, SEQ ID

NO:1874, SEQ ID NO:1875, SEQ ID NO:1876, SEQ ID NO:1877, SEQ ID NO:1878, SEQ ID

NO:1879, SEQ ID NO:1880, SEQ ID NO:1881, SEQ ID NO:1882, SEQ ID NO:1883, SEQ ID

NO:1884, SEQ ID NO:1885, SEQ ID NO:1886, SEQ ID NO:1887, SEQ ID NO:1888, SEQ ID

NO:1889, SEQ ID NO:1890, SEQ ID NO:1891, SEQ ID NO:1892, SEQ ID NO:1893, SEQ ID

NO:1894, SEQ ID NO:1895, SEQ ID NO:1896, SEQ ID NO:1897, SEQ ID NO: 1898, SEQ ID

NO:1899, SEQ ID NO:1900, SEQ ID NO:1901, SEQ ID N0:1902, SEQ ID NO:1903, SEQ ID

NO:1904, SEQ ID NO:1905, SEQ ID NO:1906, SEQ ID NO:1907, SEQ ID NO:1908, SEQ ID

NO:1909, SEQ ID NO:1910, SEQ ID NO:1911, SEQ ID NO:1912, SEQ ID NO:1913, SEQ ID

NO:1914, SEQ ID NO:1915, SEQ ID NO:1916, SEQ ID NO:1917, SEQ ID NO:1918, SEQ ID

NO:1919, SEQ ID NO:1920, SEQ ID NO:1921, SEQ ID NO:1922, SEQ ID NO:1923, SEQ ID

NO:1924, SEQ ID NO:1925, SEQ ID NO:1926, SEQ ID N0:1927, SEQ ID NO:1928, SEQ ID

NO:1929, SEQ ID NO:1930, SEQ ID NO:1931, SEQ ID NO:1932, SEQ ID NO:1933, SEQ ID

NO:1934, SEQ ID NO:1935, SEQ ID NO:1936, SEQ ID NO:1937, SEQ ID NO:1938, SEQ ID :

NO:1939, SEQ ID NO:1940, SEQ ID NO:1941, SEQ ID NO:1942, SEQ ID NO:1943, SEQ ID

NO:1944, SEQ ID NO:1945, SEQ ID NO:1946, SEQ ID NO:1947, SEQ ID NO:1948, SEQ ID

NO:1949, SEQ ID NO:1950, SEQ ID NO:1951, SEQ ID NO:1952, SEQ ID NO:1953, SEQ ID

NO:1954, SEQ ID NO:1955, SEQ ID NO:1956, SEQ ID N0:1957, SEQ ID NO:1958, SEQ ID

NO:1959, SEQ ID NO:1960, SEQ ID NO:1961, SEQ ID NO:1962, SEQ ID NO:1963, SEQ ID

NO:1964, SEQ ID NO:1965, SEQ ID NO:1966, SEQ ID N0:1967, SEQ ID NO:1968, SEQ ID

NO:1969, SEQ ID NO:1970, SEQ ID NO:1971, SEQ ID N0:1972, SEQ ID NO:1973, SEQ ID

NO:1974, SEQ ID NO:1975, SEQ ID NO:1976, SEQ ID N0:1977, SEQ ID NO:1978, SEQ ID

NO:1979, SEQ ID NO:1980, SEQ ID NO:1981, SEQ ID N0:1982, SEQ ID NO:1983, SEQ ID

NO:1984, SEQ ID NO:1985, SEQ ID NO:1986, SEQ ID NO:1987, SEQ ID NO:1988, SEQ ID

NO:1989, SEQ ID N0:1990, SEQ ID NO:1991, SEQ ID N0:1992, SEQ ID NO:1993, SEQ ID

NO:1994, SEQ ID NO:1995, SEQ ID NO:1996, SEQ ID NO:1997, SEQ ID NO:1998, SEQ ID

NO:1999, SEQ ID NO:2000, SEQ ID NO:2001, SEQ ID NO:2002, SEQ ID NO:2003, SEQ ID

NO:2004, SEQ ID NO:2005, SEQ ID NO:2006, SEQ ID NO:2007, SEQ ID NO:2008, SEQ ID

NO:2009, SEQ ID NO:2010, SEQ ID NO:2011, SEQ ID NO:2012, SEQ ID NO:2013, SEQ ID

NO:2014, SEQ ID N0:2015, SEQ ID NO:2016, SEQ 1D NO:2017, SEQ ID NO:2018, SEO ID

NO:2019, SEQ ID NO:2020, SEQ ID NO:2021, SEQ ID NO:2022, SEQ ID NO:2023, SEQ ID

NO:2024, SEQ ID NO:2025, SEQ ID N0:2026, SEQ ID NO:2027, SEQ ID NO:2028, SEQ ID

NO0:2029, SEQ ID NO:2030, SEQ ID NO:2031, SEQ ID NO:2032, SEQ ID NO:2033, SEQ ID

NO:2034, SEQ ID NO:2035, SEQ ID NO:2036, SEQ ID NO:2037, SEQ ID NO:2038, SEQ ID

NO:2039, SEQ ID NO:2040, SEQ ID NO:2041, SEQ ID NO:2042, SEQ ID NO:2043, SEQ ID

NO:2044, SEQ ID NO:2045, SEQ ID NO:2046, SEQ ID NO:2047, SEQ ID NO:2048, SEQ ID

NO:2049, SEQ ID N0:2050, SEQ ID NO:2051, SEQ ID NO:2052, SEQ ID NO:2053, SEQ ID

NO:2054, SEQ ID NO:2055, SEQ ID NO:2056, SEQ ID NO:2057, SEQ ID NO:2058, SEQ ID

NO:2059, SEQ ID NO:2060, SEQ ID NO:2061, SEQ ID NO:2062, SEQ ID NO:2063, SEQ ID

NO:2064, SEQ ID N0:2065, SEQ ID NO:2066, SEQ ID NO:2067, SEQ ID NO:2068, SEQ ID

NO:2069, SEQ ID NO:2070, SEQ ID NO:2071, SEQ ID NO:2072, SEQ ID NO:2073, SEQ ID

NO:2074, SEQ ID N0:2075, SEQ ID N0:2076, SEQ ID N0O:2077, SEQ ID NO:2078, SEQ ID

NO:2079, SEQ ID NO:2080, SEQ ID NO:2081, SEQ ID N0:2082, SEQ ID NO:2083, SEQ ID

NO:2084, SEQ ID NO:2085, SEQ ID NO:2086, SEQ ID NO:2087, SEQ ID NO:2088, SEQ ID :

NO:2089, SEQ ID N0:2090, SEQ ID NO:2091, SEQ ID N0:2092, SEQ ID NO:2093, SEQ ID

NO:2094, SEQ ID NO:2095, SEQ ID NO:2096, SEQ ID NO:2097, SEQ ID NO:2098, SEQ ID

NO:2099, SEQ ID NO:2100, SEQ ID NO:2101, SEQ ID NO:2102, SEQ ID NO:2103, SEQ ID

NO:2104, SEQ ID N0:2105, SEQ ID NO:2106, SEQ ID NO:2107, SEQ ID NO:2108, SEQ ID

NO:2109, SEQ ID NO:2110, SEQ ID NO:2111, SEQ ID NO:2112, SEQ ID NO:2113, SEQID

NO:2114, SEQ ID NO:2115, SEQ ID NO:2116, SEQ ID NO:2117, SEQ ID NO:2118, SEQ ID

NO:2119, SEQ ID N0:2120, SEQ ID NO:2121, SEQ ID NO:2122, SEQ ID NO:2123, SEQ ID

NO:2124, SEQ ID NO:2125, SEQ ID N0O:2126, SEQ ID NO:2127, SEQ ID NO:2128, SEQ ID

NO:2129, SEQ ID N0:2130, SEQ ID NO:2131, SEQ ID NO:2132, SEQ ID NO:2133, SEQ ID

NO:2134, SEQ ID NO:2135, SEQ ID NO:2136, SEQ ID NO:2137, SEQ ID NO:2138, SEQ ID

NO:2139, SEQ ID NO:2140, SEQ ID NO:2141, SEQ ID NO:2142, SEQ ID NO:2143, SEQ ID

NO:2144, SEQ ID NO:2145, SEQ ID NO:2146, SEQ ID NO:2147, SEQ ID NO:2148, SEQ ID

NO:2149, SEQ ID NO:2150, SEQ ID NO:2151. Alternatively, the PCR uses corresponding probes consisting of nucleotide sequences selected from the group consisting of SEQ ID NO:1327, SEQ ID

NO:1328, SEQ ID NO:1329, SEQ ID NO:1330, SEQ ID NO:1331, SEQ ID NO:1332, SEQ ID

NO:1333, SEQ ID NO:1334, SEQ ID NO:1335, SEQ ID NO:1336, SEQ ID NO:1337, SEQ ID

NO:1338, SEQ ID NO:1339, SEQ ID NO:1340, SEQ ID NO:1341, SEQ ID NO:1342, SEQ ID

NO:1343, SEQ ID NO:1344, SEQ ID NO:1345, SEQ ID NO:1346, SEQ ID NO:1347, SEQ ID © NO:1348, SEQ ID NO:1349, SEQ ID NO:1350, SEQ ID NO:1351, SEQ ID NO:1352, SEQ ID

NO:1353, SEQ ID NO:1354, SEQ ID NO:1355, SEQ ID NO:1356, SEQ ID NO:1357, SEQ ID

NO:1358, SEQ ID NO:1359, SEQ ID NO:1360, SEQ ID NO:1361, SEQ ID NO:1362, SEQ ID

NO:1363, SEQ ID NO:1364, SEQ ID NO:1365, SEQ ID NO:1366, SEQ ID NO: 1367, SEQ ID

NO:1368, SEQ 1D NO:1369, SEQ ID NO:1370, SEQ ID NO:1371, SEQ ID NO:1372, SEQ ID

NO:1373, SEQ ID NO:1374, SEQ ID NO:1375, SEQ ID NO:1376, SEQ ID NO: 1377, SEQ ID

NO:1378, SEQ ID NO:1379, SEQ ID NO:1380, SEQ ID NO'1381, SEQ ID NO:1382, SEQ ID _ NO:1383, SEQ ID NO:1384, SEQ ID NO:1385, SEQ ID NO:1386, SEQ ID NO: 1387, SEQ ID _ © NO:1388, SEQ ID NO:1389, SEQ ID NO:1390, SEQ ID NO:1391, SEQ ID NO:1392, SEQ ID Co

NO:1393, SEQ ID NO:1394, SEQ ID NO:1395, SEQ ID NO:1396, SEQ ID NO:1397, SEQ ID

NO: 1398, SEQ ID NO:1399, SEQ ID NO: 1400, SEQ ID NO:1401, SEQ ID NO:1402, SEQ ID

NO:1403, SEQ ID NO:1404, SEQ ID NO: 1405, SEQ ID NO:1406, SEQ ID NO: 1407, SEQ ID

NO:1408, SEQ ID NO:1409, SEQ ID NO:1410, SEQ ID NO:1411, SEQ ID NO:1412, SEQ ID

NO:1413, SEQ ID NO:1414, SEQ ID NO: 1415, SEQ ID NO:1416, SEQ ID NO:1417, SEQ ID

NO:1418, SEQ ID NO:1419, SEQ ID NO:1420, SEQ ID NO:1421, SEQ ID NO:1422, SEQ ID

NO:1423, SEQ ID NO:1424, SEQ ID NO:1425, SEQ ID NO:1426, SEQ ID NO:1427, SEQ ID

NO:1428, SEQ ID NO:1429, SEQ ID NO:1430, SEQ ID NO:1431, SEQ ID NO:1432, SEQ ID

NO:1433, SEQ ID NO: 1434, SEQ ID NO:1435, SEQ ID NO:1436, SEQ ID NO:1437, SEQ ID

NO:1438, SEQ ID NO:1439, SEQ ID NO:1440, SEQ ID NO:1441, SEQ ID NO:1442, SEQ ID

NO:1443, SEQ ID NO:1444, SEQ ID NO: 1445, SEQ ID NO:1446, SEQ ID NO:1447, SEQ ID

NO:1448, SEQ ID NO:1449, SEQ ID NO: 1450, SEQ ID NO:1451, SEQ ID NO: 1452, SEQ ID

NO:1454, SEQ ID NO:1455, SEQ ID NO: 1456, SEQ ID NO:1457, SEQ ID NO:1458, SEQ ID

NO:1459, SEQ ID NO:1460, SEQ ID NO: 1461, SEQ ID NO:1462, SEQ ID NO:1463, SEQ ID

NO:1464, SEQ ID NO: 1465, SEQ ID NO: 1466, SEQ ID NO:1467, SEQ ID NO:1468, SEQ ID

NO:1469, SEQ ID NO:1470, SEQ ID NO:1471, SEQ ID NO:1472, SEQ ID NO:1473, SEQ ID

NO:1474, SEQ ID NO:1475, SEQ ID NO:1476, SEQ ID NO:1477, SEQ ID NO:1478, SEQ ID

NO:1479, SEQ ID NO:1480, SEQ ID NO: 1481, SEQ ID NO:1482, SEQ ID NO:1483, SEQID

NO:1484, SEQ ID NO: 1485, SEQ ID NO:1486, SEQ ID NO:1487, SEQ ID NO:1488, SEQ ID

NO:1489, SEQ ID NO:1490, SEQ ID NO: 1491, SEQ ID NO:1492, SEQ ID NO:1493, SEQ ID

NO:1494, SEQ ID NO: 1495, SEQ ID NO:1496, SEQ ID NO:1497, SEQ ID NO:1498, SEQ ID

NO:1499, SEQ ID NO:1500, SEQ ID NO: 1501, SEQ ID NO:1502, SEQ ID NO:1503, SEQ ID

NO:1504, SEQ ID NO:1505, SEQ ID NO:1506, SEQ ID NO:1507, SEQ ID NO: 1508, SEQ ID

NO:1509, SEQ ID NO:1510, SEQ ID NO:1511, SEQ ID NO:1512, SEQ ID NO:1513, SEQ ID

NO:1514, SEQ ID NO:1515, SEQ ID NO:1516, SEQ ID NO:1517, SEQ ID NO:1518, SEQ ID

NO:1519, SEQ ID NO:1520, SEQ ID NO:1521, SEQ ID NO:1522, SEQ ID NO: 1523, SEQ ID

NO:1524, SEQ ID NO:1525, SEQ ID NO: 1526, SEQ ID NO:1527, SEQ ID NO:1528, SEQ ID

NO:1529, SEQ ID NO:1530, SEQ ID NO:1531, SEQ ID NO:1532, SEQ ID NO:1533, SEQ ID

NO:1534, SEQ ID NO:1535, SEQ ID NO: 1536, SEQ ID NO:1537, SEQ ID NO: 1538, SEQ ID

NO:1539, SEQ ID NO:1540, SEQ ID NO:1541, SEQ ID NO:1542, SEQ ID NO:1543, SEQ ID © NO:1544, SEQ ID NO:1545, SEQ ID NO:1546, SEQ ID NO:1547, SEQ ID NO:1548, SEQ ID

NO:1549, SEQ ID NO:1550, SEQ ID NO:1551, SEQ ID NO:1552, SEQ ID NO:1553, SEQ ID

NO:1554, SEQ ID NO:1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO:1558, SEQ ID

NO:1559, SEQ ID NO:1560; SEQ ID NO:1561, SEQ ID NO:1562, SEQ ID NO:1563, SEQ ID

N

NO:1564, SEQ ID NO:1565, SEQ ID NO: 1566, SEQ ID NO:1567, SEQ ID NO: 1568, SEQ ID

NO:1569, SEQ ID NO:1570, SEQ ID NO: 1571, SEQ ID NO:1572, SEQ ID NO: 1573, SEQ ID

NO:1574, SEQ ID NO:1575, SEQ ID NO: 1576, SEQ ID NO:1577, SEQ ID NO: 1578, SEQ ID

NO:1579, SEQ ID NO:1580, SEQ ID NO:1581, SEQ ID NO:1582, SEQ ID NO: 1583, SEQ ID

NO:1584, SEQ ID NO: 1585, SEQ ID NO:1586, SEQ ID NO:1587, SEQ ID NO:1588, SEQ ID

NO:1589, SEQ ID NO: 1590, SEQ ID NO:1591, SEQ ID NO:1592, SEQ ID NO: 1593, SEQ ID

NO:1594, SEQ ID NO:, SEQ ID NO:1595, SEQ ID NO:1596, SEQ ID NO:1597, SEQ ID NO:1598,

SEQ ID NO:1599, SEQ ID NO: 1600, SEQ ID NO:1601, SEQ ID NO:1602, SEQ ID NO:1603, SEQ ID

NO:1604, SEQ ID NO:1605, SEQ ID NO:1606, SEQ ID NO:1607, SEQ ID NO:1608, SEQ ID

NO:1609, SEQ ID NO:1610, SEQ ID NO:1611, SEQ ID NO:1612, SEQ ID NO:1613, SEQ ID

NO:1614, SEQ ID NO:1615, SEQ ID NO: 1616, SEQ ID NO:1617, SEQ ID NO:1618, SEQ ID

NO:1619, SEQ ID NO:1620, SEQ ID NO:1621, SEQ ID NO:1622, SEQ ID NO:1623, SEQ ID

NO:1624, SEQ ID NO:1625, SEQ ID NO: 1626, SEQ ID NO:1627, SEQ ID NO:1628, SEQ ID

NO:1629, SEQ ID NO:1630, SEQ ID NO:1631, SEQ ID NO:1632, SEQ ID NO:1633, SEQ ID

NO:1634, SEQ ID NO: 1635, SEQ ID NO: 1636, SEQ ID NO:1637, SEQ ID NO:1638, SEQ ID

NO:1639, SEQ ID NO: 1640, SEQ ID NO:1641, SEQ ID NO: 1642, SEQ ID NO:1643, SEQ ID

NO:1644, SEQ ID NO: 1645, SEQ ID NO: 1646, SEQ ID NO:1647, SEQ ID NO:1648, SEQ ID

NO:1649, SEQ ID NO: 1650, SEQ ID NO:1651, SEQ ID NO:1652, SEQ ID NO:1653, SEQ ID

NO:1654, SEQ ID NO:1655, SEQ ID NO:1656, SEQ ID NO:1657, SEQ ID NO:2152, SEQ ID NO,

SEQ ID NO:2153, SEQ ID NO:, SEQ ID NO:2154, SEQ ID NO:, SEQ ID NO:, SEQ ID NO:, SEQ ID

NO:2145, SEQ ID NO:, SEQ ID NO:2156, SEQ ID NO:2157, SEQ ID NO:2158, SEQ ID NO:2159,

SEQ ID NO, SEQ ID NO:2160, SEQ ID NO:2161, SEQ ID NO:2162, SEQ ID NO:2163, SEQ ID

NO:2164, SEQ ID NO:, SEQ ID NO:2165, SEQ ID NO:, SEQ ID NO:2166, SEQ ID NO:2167, SEQ

ID NO:2168, SEQ ID NO:2169, SEQ ID NO:2170, SEQ ID NO:2171, SEQ ID NO:2172, SEQ ID

NO:2173, SEQ ID NO:2174, SEQ ID NO:2175, SEQ ID NO:2176, SEQ ID NO:2177, SEQ ID

NO:2178, SEQ ID NO:2179, SEQ ID NO:2180, SEQ ID NO:2181, SEQ ID NO:2182, SEQ ID

NO:2183, SEQ ID NO:2184, SEQ ID NO:2185, SEQ ID NO:2186, SEQ ID NO:2187, SEQ ID

NO:2188, SEQ ID NO:2189, SEQ ID NO:2190, SEQ ID NO:2191, SEQ ID NO:2192, SEQ ID

NO:2193, SEQ ID NO:2194, SEQ ID NO:2195, SEQ ID NO:2196, SEQ ID NO:2197, SEQ ID

NO:2198, SEQ ID NO:2199, SEQ ID NO:2200, SEQ ID NO:2201, SEQ ID N0:2202, SEQ ID

NO:2203, SEQ ID NO:2204, SEQ ID NO:2205, SEQ ID NO:2206, SEQ ID N0:2207, SEQ ID

NO:2208, SEQ ID NO:2209, SEQ ID NO:2210, SEQ ID NO:2211, SEQ ID NO:2212, SEQ ID

NO:2213, SEQ ID NO:2214, SEQ ID NO:2215, SEQ ID NO:2216, SEQ ID NO:2217, SEQ ID

NO:2218, SEQ ID NO:2219, SEQ ID NO:2220, SEQ ID NO:2221, SEQ ID N0:2222, SEQ ID

NO:2223, SEQ ID NO:2224, SEQ ID N0:2225, SEQ ID NO:2226, SEQ ID N0:2227, SEQ ID

NO:2228, SEQ ID NO:2229, SEQ ID NO:2230, SEQ ID NO:2231, SEQ ID N0:2232, SEQ ID

NO:2233, SEQ ID NO:2234, SEQ ID NO:2235, SEQ ID NO:2236, SEQ ID N0:2237, SEQ ID

NO:2238, SEQ ID NO:2239, SEQ ID NO:2240, SEQ ID NO:2241, SEQ ID N0:2242, SEQ ID

NO:2243, SEQ ID NO:2244, SEQ ID NO:2245, SEQ ID NO:2246, SEQ ID NO:2247, SEQ ID

NO:2248, SEQ ID NO:2249, SEQ ID NO:2250, SEQ ID NO:2251, SEQ ID N0:2252, SEQ ID

NO:2253, SEQ ID NO:2254, SEQ ID NO:2255, SEQ ID NO:2256, SEQ ID NO:2257, SEQ ID

NO:2258, SEQ ID NO:2259, SEQ 1D NO:2260, SEQ ID NO:2261, SEQ ID NO:2262, SEQ ID

NO:2263, SEQ ID NO:2264, SEQ ID NO:2265, SEQ ID NO:2266, SEQ ID NO:2267, SEQ ID

NO:2268, SEQ ID NO:2269, SEQ ID NO:2270, SEQ ID NO:2271, SEQ ID NO:2272, SEQ ID

NO:2273, SEQ ID N0:2274, SEQ ID NO:2275, SEQ ID NO:2276, SEQ ID NO:2277, SEQ ID

NO:2278, SEQ ID NO:2279, SEQ ID NO:2280, SEQ ID NO:2281, SEQ ID NO:2282, SEQ ID

NO:2283, SEQ ID NO:2284, SEQ ID NO:2285, SEQ ID N0O:2286, SEQ ID NO:2287, SEQ ID

NO:2288, SEQ ID NO:2289, SEQ ID NO:2290, SEQ ID NO:2291, SEQ ID N0O:2292, SEQ ID

NO:2293, SEQ 1D NO:2294, SEQ ID NO:2295, SEQ ID NO:2296, SEQ ID NO:2297, SEQ ID

NO:2298, SEQ ID NO:2299, SEQ ID NO:2300, SEQ ID NO:2301, SEQ ID NO:2302, SEQ ID

NO:2303, SEQ ID NO:2304, SEQ ID NO:2305, SEQ ID NO:2306, SEQ ID NO:2307, SEQ ID

NO:2308, SEQ ID NO:2309, SEQ ID N0:2310, SEQ ID NO:2311, SEQ ID NO:2312, SEQ ID

NO:2313, SEQ ID NO:2314, SEQ ID NO:2315, SEQ ID N0:2316, SEQ ID NO:2317, SEQ ID

NO:2318, SEQ ID NO:2319, SEQ ID NO:2320, SEQ ID NO:2321, SEQ ID NO:2322, SEQ ID

NO0:2323, SEQ ID NO:2324, SEQ ID NO:2325, SEQ ID N0:2326, SEQ ID NO:2327, SEQ ID

NO:2328, SEQ ID N0:2329, SEQ ID NO:2330, SEQ ID N0:2331, SEQ ID NO:2332, SEQ ID

NO:2333, SEQ ID NO:2334, SEQ ID NO:2335, SEQ ID N0:2336, SEQ ID N0O:2337, SEQ ID

NO:2338, SEQ ID N0:2339, SEQ ID NO:2340, SEQ ID NO:2341, SEQ ID NO:2342, SEQ ID

NO:2343, SEQ ID NO:2344, SEQ ID NO:2345, SEQ ID NO:2346, SEQ ID NO:2347, SEQ ID

NO:2348, SEQ ID NO:2349, SEQ ID NO:2350, SEQ ID NO:2351, SEQ ID N0O:2352, SEQ ID

NO:2353, SEQ ID NO:2354, SEQ ID NO:2355, SEQ ID NO:2356, SEQ ID NO:2357, SEQ ID

NO:2358, SEQ ID NO:2359, SEQ ID NO:2360, SEQ ID NO:2361, SEQ ID N0O:2362, SEQ ID

NO:2363, SEQ ID NO:2364, SEQ ID NO0:2365, SEQ ID N0:2366, SEQ ID NO:2367, SEQ ID

NO:2368, SEQ ID N0:2369, SEQ ID NO:2370, SEQ ID N0:2371, SEQ ID N0:2372, SEQ ID

NO:2373, SEQ ID N0O:2374, SEQ ID NO:2375, SEQ ID N0O:2376, SEQ ID NO:2377, SEQ ID

NO:2378, SEQ ID N0:2379, SEQ ID NO0:2380, SEQ ID N0:2381, SEQ ID N0:2382, SEQ ID :

NO:2383, SEQ ID NO:2384, SEQ ID NO:2385, SEQ ID NO:2386, SEQ ID NO:2387, SEQ ID :

NO:2388, SEQ ID NO:2389, SEQ ID N0:2390, SEQ ID N0:2391, SEQ ID NO:2392, SEQ ID

NO0:2393, SEQ ID NO:2394, SEQ ID N0:2395, SEQ ID N0:2396, SEQ ID NO:2397, SEQ ID

NO:2398, SEQ ID NO:2399. The RNA level may be detected by hybridization to the probes. Ina further variation, the RNA level is detected by hybridization to an oligonucleotide. Examples of oligonucleotide include oligonucleotides having a nucleotide sequence selected from SEQ ID NO:2,

SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID

NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID

NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID © NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID

NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID © NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID . ’y

NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ 1D NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID oo © NOI, SEQID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID

NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID

SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO: 113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID

NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO: 119, SEQ ID NO:120, SEQ ID NO:121, SEQ

NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO: 136, SEQ ID NO:137, SEQ ID NO:138, SEQ

ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO: 144,

SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID

NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO: 153, SEQ ID NO:154, SEQ ID NO:155, SEQ

ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO: 161,

SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO: 164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID

NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO: 170, SEQ ID NO:171, SEQ ID NO:172, SEQ

NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO: 187, SEQ ID NO:188, SEQ ID NO:189, SEQ

ID NO:190, SEQ ID NO: 191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195,

SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID

NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ 1D NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212,

ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229,

ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID N0:262, SEQ ID NO:263,

SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ iD NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ

ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280, y Sa

ID NO:292, SEQ ID NO:293, SEQ ID N0:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297,

SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID ~_ NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ 1D NO:307, SEQ ID NO:308, SEQ

SEQ ID N0:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID

NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID

NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID

NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID NO:2752, SEQ ID NO0:2737, SEQ ID

NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID

NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID

NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID .

NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID NO:2736, SEQ ID NQ:2708, SEQ ID : .

NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID

NO:2742, SEQ ID N0:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID

NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID N0:2628, SEQ ID NO:2638, SEQ ID

NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID

NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID NO:2726, SEQ ID N0:2722, SEQ ID

NO:2689, SEQ ID NO:2734, SEQ ID N0O:2631, SEQ ID N0:2656, SEQ ID NO:2696, SEQ ID

NO:2676, SEQ ID NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID

NO:2724, SEQ ID NO:2698, SEQ ID N0:2662, SEQ ID N0:2753, SEQ ID NO:2704, SEQ ID :

NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID N0:2723, SEQ ID N0O:2658, SEQ ID

NO:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID

NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ 1D NO:2651, SEQ ID NO:2718, SEQ ID

NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID N0:2659, SEQ ID NO:2654, SEQID

NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID N0O:2705, SEQ ID NO:2685, SEQ ID

NO:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID N0:2650, SEQ ID N0:2720, SEQID

NO:2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID N0:2633, SEQ ID NO:2672, SEQ ID

NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID N0:2630, SEQ ID NO:2745, SEQ ID

NO:2643, SEQ ID NO:2694, SEQ ID N0:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQID

NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID N0:2653, SEQ ID NO:2729. Ina further variation, the oligonucleotide has the nucleotide sequence SEQ ID NO: 36. Instill a further variation, the oligonucleotide has the nucleotide sequence SEQ ID NO: 87. In yet a further variation, the oo oligonucleotide has the nucleotide sequence SEQ ID NO: 94. In an additional variation, the

Co oligonucleotide has a nucleotide sequence consisting of SEQ ID NO: 91. In another variation, the oligonucleotide has a nucleotide sequence consisting of SEQ ID NO: 107. The oligonucleotide may be DNA, RNA, cDNA, PNA, genomic DNA, or synthetic oligonucleotides.

In another aspect, the methods of detecting transplant rejection include detecting the expression level by measuring one or more proteins expressed by the one or more genes. In one _ variation, the one or more proteins include an amino acid sequence selected from SEQ 1D NO:2400,

SEQ ID NO:2401, SEQ ID NO:2402, SEQ 1D NO:2403, SEQ ID NO:2404, SEQ ID NO:2405, SEQ ID

NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID NO:2410, SEQ ID NO:2411, SEQ ID

NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO:2415, SEQ ID NO:2416, SEQ ID

NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ 1D NO:2421, SEQ ID

NO:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID NO:2426, SEQ ID

NO:2427, SEQ ID NO:2428, SEQ ID NO:2429, SEQ ID NO:2430, SEQ ID NO:2432, SEQ ID

NO:2433, SEQ ID NO:2434, SEQ ID NO:2435, SEQ ID NO:2436, SEQ ID NO:2437, SEQ ID

NO:2438, SEQ ID NO:2439, SEQ ID NO:2440, SEQ ID NO:2441, SEQ ID NO:2442, SEQ ID

NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID NO:2447, SEQ ID

NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID NO:2451, SEQ ID NO:2452, SEQ ID

NO:2453, SEQ ID NO:2454, SEQ ID NO:2455, SEQ ID NO:2456, SEQ ID NO:2457, SEQ ID

NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID NO:2462, SEQ ID

NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ 1D NO:2467, SEQ ID

NO:2468, SEQ ID NO:2469, SEQ ID NO:2470, SEQ ID N0O:2478, SEQ ID NO:2479, SEQ ID

NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2485, SEQ ID

NO:2486, SEQ ID NO:2488, SEQ ID NO:2491, SEQ ID NO:2492, SEQ ID NO:2493, SEQ ID

NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID NO:2497, SEQ ID NO:2502, SEQ ID

NO:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID NO:2507, SEQ ID

NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID NO:2512, SEQ ID

NO:2513, SEQ ID NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQ ID NO:2517, SEQ ID

NO:2518, SEQ ID NO:2519, SEQ ID N0:2520, SEQ ID NO:2521, SEQ ID NO:2528, SEQ ID

NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID NO:2533, SEQ ID

NO:2534, SEQ ID NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID NO:2538, SEQ ID

NO:2539, SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID NO:2543, SEQ ID

NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID NO:2548, SEQ ID

NO:2549, SEQ ID NO:2550, SEQ ID N0:2551, SEQ ID NO:2552, SEQ ID NO:2553, SEQ ID

NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID NO:2558, SEQ ID

NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID NO:2563, SEQ ID

NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID NO:2568, SEQ ID _ NO:2569, SEQ ID N0:2570, SEQ 1D NO:2571, SEQ ID NO:2572, SEQ ID NO:2573, SEQ ID

NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ 1D NO:2578, SEQ ID

NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID NO:2583, SEQ ID

NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID NO:2588, SEQ ID

NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID NO:2593, SEQ ID ’ NO:2594, SEQ ID NO:2595, SEQ ID N0:2596, SEQ ID NO:2597, SEQ ID NO:2598, SEQ ID

NO0:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID NO:2603, SEQ ID

NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID NO:2608, SEQ ID

NO0:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NQ:2612, SEQ ID NO:2613, SEQ ID

NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID NO:2618, SEQ ID

NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID NO:2623, SEQ ID

NO:2624, SEQ ID NO:2625, SEQ ID NO:2626, SEQ ID NO:2925, SEQ ID NO:2926, SEQ ID

NO:2927, SEQ ID NO:2928, SEQ ID N0:2929, SEQ ID NO:2930, SEQ ID NO:2932, SEQ 1D

NO0:2933, SEQ ID NO:2935, SEQ ID NO:2936, SEQ ID NO:2937, SEQ ID NO:2938, SEQ ID

N0:2939, SEQ ID NO:2941, SEQ ID NO:2942, SEQ ID NO:2943, SEQ ID NO:2945, SEQ ID

NO:2946, SEQ ID NO:2947, SEQ ID NO:2948, SEQ ID NO:2949, SEQ ID NO:2950, SEQ ID

NO:2951, SEQ ID N0:2952, SEQ ID NO:2953, SEQ ID NO:2954, SEQ ID NO:2955, SEQ ID

NO0:2956, SEQ ID N0:2957, SEQ ID NO:2959, SEQ ID NO:2960, SEQ ID NO:2961, SEQ ID

NO:2962, SEQ ID N0:2963, SEQ ID NO:2964, SEQ ID NO:2965, SEQ ID NO:2966, SEQ ID

NO:2967, SEQ ID NO:2968, SEQ ID NO:2969, SEQ ID NO:2970, SEQ ID NO:2971, SEQ ID

NO0:2972, SEQ ID NO:2973, SEQ ID NO:2974, SEQ ID NO:2975, SEQ ID NO:2976, SEQ ID

NO0:2977, SEQ ID NO:2978, SEQ ID NO:2979, SEQ ID NO:2980, SEQ ID NO:2981, SEQ ID

NO:2982, SEQ ID NO:2983, SEQ ID NO:2984, SEQ ID NO:2985, SEQ ID NO:2986, SEQ ID

NO0:2987, SEQ ID NO:2988, SEQ ID N0:2989, SEQ ID NO:2990, SEQ ID NO:2991, SEQ ID

NO0:2992, SEQ ID N0:2993, SEQ ID NO:2994, SEQ ID NO:2995, SEQ ID NO:2996, SEQ ID

NO0:2997, SEQ ID NO:2998, SEQ ID N0:2999, SEQ ID NO:3000, SEQ ID NO:3001, SEQ ID

NO:3002, SEQ ID NO:3003, SEQ ID NO:3004, SEQ ID NO:3005, SEQ ID NO:3006, SEQ ID

NO0:3007, SEQ ID NO:3008, SEQ ID NO:3009, SEQ ID NO:3010, SEQ ID NO:3011, SEQ ID

NO:3012, SEQ ID NO:3013, SEQ ID NO:3014, SEQ ID NO:3015. In a further variation, the the method includes detecting one or more additional proteins expressed by SEQ ID NO:2406, SEQ ID

NO:2431, SEQ ID NO:2471, SEQ ID NO:2472, SEQ ID NO:2473, SEQ ID NO:2474, SEQ ID -

NO0:2475, SEQ ID NO:2476, SEQ ID N0:2477, SEQ ID NO:2484, SEQ ID NO:2487, SEQ ID

NO:2489, SEQ ID NO:2490, SEQ ID N0:2498, SEQ ID N0:2499, SEQ ID NO:2500, SEQ ID

NO:2501, SEQ ID NO:2522, SEQ ID N0:2523, SEQ ID N0:2524, SEQ ID NO:2525, SEQ ID

NO0:2526, SEQ ID NO:2527. In still another variation, one or more proteins may be selected from

SEQ ID NO:2400, SEQ ID NO:2401, SEQ ID N0:2402, SEQ ID NO:2403, SEQ ID NO:2404, SEQ ID

NO:2405, SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID NO:2410, SEQ ID

NO:2411, SEQ ID NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO:2415, SEQ ID

NO:2416, SEQ ID NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ ID

NO:2421, SEQ ID N0:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID

NO:2426, SEQ ID NO:2427, SEQ ID NO:2428, SEQ ID N0:2429, SEQ ID NO:2430, SEQ ID

NO:2432, SEQ ID NO:2433, SEQ ID NO:2434, SEQ ID N0:2435, SEQ ID NO:2436, SEQ ID ~ NO:2437, SEQ ID NO:2438, SEQ ID NO:2439, SEQ ID N0:2440, SEQ ID NO:2441, SEQ ID

NO:2442, SEQ ID NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID

NO:2447, SEQ ID NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID NO:2451, SEQ ID

NO0:2452, SEQ ID NO:2453, SEQ ID NO:2454, SEQ ID NO0:2455, SEQ ID NO:2456, SEQ ID

C27

NO:2457, SEQ ID NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID

NO:2462, SEQ ID NO:2463, SEQ 1D NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ ID

NO:2467, SEQ ID NO:2468, SEQ 1D NO:2469, SEQ ID NO:2470, SEQ ID NO:2478, SEQ ID

NO:2479, SEQ ID NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID

NO:2485, SEQ 1D NO:2486, SEQ ID NO:2488, SEQ ID NO:2491, SEQ ID NO:2492, SEQ ID © NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID NO:2497, SEQ ID

NO:2502, SEQ ID NO:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID

NO:2507, SEQ ID NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID

NO:2512, SEQ ID NO:2513, SEQ ID NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQ ID

NO:2517, SEQ ID NO:2518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID

NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID :

NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID

NO:2538, SEQ ID NO:2539, SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID

NO:2543, SEQ ID NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID

NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID

NO:2553, SEQ ID NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID

NO:2558, SEQ ID NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID

NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID

NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID

NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID

NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NQ:2582, SEQ ID

NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID

NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID

NO:2593, SEQ ID NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID

NO:2598, SEQ ID NO:25%99, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID

NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID

NO:2608, SEQ ID NO:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID

NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID

NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID :

NO:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID NO:2626, SEQ ID N0:2925, SEQ ID

NO:2926, SEQ ID NO:2927, SEQ ID NO:2928, SEQ ID N0:2929, SEQ ID NO:2930, SEQ ID

NO:2932, SEQ ID N0O:2933, SEQ ID NO:2935, SEQ ID NO:2936, SEQ ID NO:2937, SEQ ID

NO:2938, SEQ ID N0O:2939, SEQ ID NO:2941, SEQ ID NO:2942, SEQ ID NO:2943, SEQ ID

NO:2945, SEQ ID NO:2946, SEQ ID NO:2947, SEQ ID NO:2948, SEQ ID N0:2949, SEQ ID

NO:2950, SEQ ID NO:2951, SEQ ID NO:2952, SEQ ID NO:2953, SEQ ID NO:2954, SEQ ID

NO:2955, SEQ ID NO:2956, SEQ ID NO:2957, SEQ ID N0O:2959, SEQ ID NO:2960, SEQ ID

NO:2961, SEQ ID NO:2962, SEQ ID NO:2963, SEQ ID N0:2964, SEQ ID NO:2965, SEQ ID " 'NO:2966, SEQ ID NO:2967, SEQ ID NO:2968, SEQ ID NO:2969, SEQ ID NO:2970, SEQ ID

NO:2971, SEQ ID NO:2972, SEQ ID NO:2973, SEQ ID NO:2974, SEQ ID NO:2975, SEQ ID

N0:2976, SEQ 1D NO:2977, SEQ ID NO:2978, SEQ ID NO:2979, SEQ ID NO:2980, SEQ ID

Co 2g

NO:2981, SEQ ID NO:2982, SEQ ID NO:2983, SEQ ID NO:2984, SEQ ID NO:2985, SEQ ID

NO:2986, SEQ ID NO:2987, SEQ ID NO:2988, SEQ ID NO:2989, SEQ ID NO:2990, SEQ ID }

NO:2991, SEQ ID NO:2992, SEQ ID NO:2993, SEQ ID NO:2994, SEQ ID NO:2995, SEQ ID

NO:2996, SEQ ID NO:2997, SEQ ID NO:2998, SEQ ID NO:2999, SEQ ID NO:3000, SEQ ID . NO:3001, SEQ ID NO:3002, SEQ 1D NO:3003, SEQ ID NO:3004, SEQ ID NO:3005, SEQ ID

NO:3006, SEQ 1D NO:3007, SEQ ID NO:3008, SEQ ID NO:3009, SEQ ID NO:3010, SEQ ID

NO:3011, SEQ ID NO:3012, SEQ ID NO:3013, SEQ ID NO:3014, SEQ ID NO:3015, and one or more proteins may be selected from SEQ ID NO:2406, SEQ ID NO:2431, SEQ ID NQ:2471, SEQ ID

NO:2472, SEQ ID NO:2473, SEQ ID NO:2474, SEQ ID NO:2475, SEQ ID N0O:2476, SEQ ID

NO:2477, SEQ ID NO:2484, SEQ ID NO:2487, SEQ ID NO:2489, SEQ ID NO:2490, SEQ ID

NO:2498, SEQ ID NO:2499, SEQ ID NO:2500, SEQ ID NO:2501, SEQ ID NO:2522, SEQ ID

NO:2523, SEQ ID NO:2524, SEQ ID NO:2525, SEQ ID NO:2526, SEQ ID NO:2527.

In another aspect, the method of diagnosing or monitoring cardiac transplant rejection in a patient includes detecting the expression level of one or more genes in the patient to diagnose or monitor cardiac transplant rejection in the patient by measuring one or more proteins expressed by the one or more genes. The one or more proteins may include an amino acid sequence selected from SEQ

ID NO:2400, SEQ ID NO:2401, SEQ ID NO:2402, SEQ ID NO:2403, SEQ ID NO:2404, SEQ ID :

NO:2405, SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID N0:2409, SEQ ID N0:2410, SEQ ID

NO:2411, SEQ ID NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO:2415, SEQ ID

NO:2416, SEQ ID NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ ID

NO:2421, SEQ ID NO:2422, SEQ ID NO0:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID

NO:2426, SEQ ID NO:2427, SEQ ID NO:2428, SEQ ID N0:2429, SEQ ID N0:2430, SEQ ID

NO:2432, SEQ ID NO:2433, SEQ ID NO:2434, SEQ ID NO:2435, SEQ ID NO:2436, SEQ ID

NO:2437, SEQ ID NO:2438, SEQ ID NO0:2439, SEQ ID NO0:2440, SEQ ID NO:2441, SEQ ID

NO:2442, SEQ ID NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID .

NO:2447, SEQ ID NO:2448, SEQ ID NO:2449, SEQ ID N0:2450, SEQ ID NO:2451, SEQ ID

NO:2452, SEQ ID NO:2453, SEQ ID NO:2454, SEQ ID N0:2455, SEQ ID N0:2456, SEQ ID

NO:2457, SEQ ID NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID

NO:2462, SEQ ID NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ ID

NO:2467, SEQ ID NO:2468, SEQ ID N0:2469, SEQ ID N0:2470, SEQ ID NO:2471, SEQ ID

NO:2476, SEQ ID NO:2477, SEQ ID NO:2478, SEQ ID NO:2479, SEQ ID NO:2480, SEQ ID

NO:2481, SEQ ID NO:2482, SEQ ID N0:2483, SEQ ID NO:2484, SEQ ID NO:2485, SEQ ID

NO:2486, SEQ ID NO:2488, SEQ ID NO:2489, SEQ ID NO:2490, SEQ ID NO:2491, SEQ ID

NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID

NO:2497, SEQ ID NO:2498, SEQ ID NO:2499, SEQ ID NO:2500, SEQ ID NO:2501, SEQ ID

NO:2502, SEQ ID NO:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID . NO:2507, SEQ ID NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID

NO:2512, SEQ ID NO:2513, SEQ ID NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQID

NO:2517, SEQ ID NO:2518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID

NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID 29 a

NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID

NO:2538, SEQ ID NO:2539, SEQ ID NO:2540, SEQ 1D NO:2541, SEQ ID NO:2542, SEQ ID

NO:2543, SEQ 1D NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID

NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID } NO:2553, SEQ ID NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID )

NO:2558, SEQ ID NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID

NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID

NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID

NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID

NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID

NO:2583, SEQ ID NO:2584, SEQ ID NO:258S, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID

NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID

NO:2593, SEQ ID NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID

NO:2598, SEQ ID NO:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID

NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID

NO:2608, SEQ ID NO:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID

NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID

NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID

NO:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID NO:2626. Alternatively, the expression level of the one or more genes may be detected by measuring one or more proteins expressed by one or more genes, and one or more proteins expressed by one or more additional genes. In one variation, the one or more proteins expressed by the one or more genes include an amino acid sequence selected from

NO:2405, SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID N0O:2409, SEQ ID NO:2410, SEQ ID

NO:2411, SEQ ID NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO:2415, SEQ ID

NO:2416, SEQ ID NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ ID

NO:2421, SEQ ID NO:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID

NO:2426, SEQ ID NO:2427, SEQ ID NO:2428, SEQ ID NO:2429, SEQ ID NO:2430, SEQ ID

NO0:2432, SEQ ID NO:2433, SEQ ID NO:2434, SEQ ID NO:2435, SEQ ID NO:2436, SEQ ID

NO:2437, SEQ ID NO:2438, SEQ ID NO:2439, SEQ ID NO:2440, SEQ ID NO:2441, SEQ ID

NO:2442, SEQ ID NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID

NO:2447, SEQ ID NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID NO:2451, SEQ ID

NQO:2452, SEQ ID NO:2453, SEQ ID NO:2454, SEQ ID NO:2455, SEQ ID NO:2456, SEQ ID

NO:2457, SEQ ID NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID

NO:2462, SEQ ID NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ ID

NO:2467, SEQ ID NO:2468, SEQ ID NO:2469, SEQ ID NO:2470, SEQ ID NO:2471, SEQ ID } ~ NO:2476, SEQ ID NO:2477, SEQ ID NO:2478, SEQ ID NO:2479, SEQ ID NO:2480, SEQID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2484, SEQ ID NO:2485, SEQ ID

NO:2486, SEQ ID NO:2488, SEQ ID NO:2489, SEQ ID NO:2490, SEQ ID NO:2491, SEQ ID

NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID

NO:2497, SEQ ID NO:2498, SEQ ID NO:2499, SEQ ID NO:2500, SEQ ID NO:2501, SEQ ID

NO:2502, SEQ ID N0:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID

NO:2507, SEQ ID NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID

NO:2512, SEQ ID NO:2513, SEQ ID NO:2514, SEQ 1D NO:2515, SEQ ID NO:2516, SEQ 1D

NO:2517, SEQ ID NO;2518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID

NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID

NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID N0:2536, SEQ ID NO:2537, SEQ ID

NO:2538, SEQ ID N0:2539, SEQ ID N0:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID

NO:2543, SEQ ID NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID

NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID

NO0:2553, SEQ ID NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID

NO0:2558, SEQ ID N0:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID

NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID

NO:2568, SEQ ID N0:2569, SEQ ID NO:2570, SEQ ID N0:2571, SEQ ID NO:2572, SEQ ID

NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID

NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID

NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID

NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID

NO:2593, SEQ ID NO:2594, SEQ ID N0:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID

NO:2598, SEQ ID NO:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID

NO:2603, SEQ ID NO:2604, SEQ ID N0:2605, SEQ ID N0:2606, SEQ ID NO:2607, SEQ ID

NO:2608, SEQ ID NO:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID

NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID N0O:2616, SEQ ID NO:2617, SEQ ID

NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID N0:2621, SEQ ID NO:2622, SEQ ID

NO0:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID N0:2626, and the one or more protein expressed by the one or more additional genes include an amino acid sequence selected from the group consisting of SEQ ID NO:2406, SEQ 1D N0O:2431, SEQ ID NO:2472, SEQ ID NO:2473, SEQ ID

NO:2474, SEQ ID NO:2475, SEQ ID N0:2487, SEQ ID N0:2522, SEQ ID N0O:2523, SEQ ID

NO:2524, SEQ ID NO:2525, SEQ ID NO:2526, SEQ ID NO:2527.

In another aspect, the method of diagnosing or monitoring kidney transplant rejection ina patient includes detecting the expression level of one or more genes in the patient to diagnose or monitor kidney transplant rejection in the patient by measuring one or more proteins encoded by the one or more genes. In one variation, the one or more proteins include an amino acid sequence selected from SEQ ID NO:2400, SEQ ID NO:2401, SEQ ID NO:2402, SEQ ID NO:2403, SEQ ID NO:2404,

SEQ ID NO:2405, SEQ ID NO:2406, SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID

NO:2410, SEQ ID NO:2411, SEQ ID N0:2412, SEQ ID NO0:2413, SEQ ID NO:2414, SEQ ID

NO:2415, SEQ ID NO:2416, SEQ ID NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID .

NO:2420, SEQ ID NO:2421, SEQ ID NO:2422, SEQ ID N0:2423, SEQ ID NO:2424, SEQ ID

NO:2425, SEQ ID NO:2426, SEQ ID NO:2427, SEQ ID NO:2428, SEQ 1D NO:2429, SEQ ID

NO:2430, SEQ ID NO:2432, SEQ ID NO:2433, SEQ ID N0:2434, SEQ ID NO:2435, SEQ ID

NO:2436, SEQ LD NO:2437, SEQ ID NO:2438, SEQ 1D NO:2439, SEQ ID NO:2440, SEQ ID

NO:2441, SEQ ID NO:2442, SEQ ID NO:2443, SEQ 1D NO:2444, SEQ ID NO:2445, SEQ ID

NO:2446, SEQ ID NO:2447, SEQ 1D NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID

NO:2451, SEQ ID NO:2452, SEQ ID NO:2453, SEQ 1D NO:2454, SEQ ID NO:2455, SEQ ID

NO:2456, SEQ ID NO:2457, SEQ ID NO:2458, SEQ ID NO;2459, SEQ ID NO:2460, SEQ ID

NO:2461, SEQ ID NO:2462, SEQ ID NO:2463, SEQ 1D NO:2464, SEQ ID NO:2465, SEQ ID

N0:2466, SEQ ID NO:2467, SEQ ID NO:2468, SEQ ID NO:2469, SEQ ID NO:2470, SEQ ID

NO:2474, SEQ ID NO:2478, SEQ ID NO:2479, SEQ 1D NO:2480, SEQ ID NO:2481, SEQ ID

NO:2482, SEQ ID NO:2483, SEQ ID NO:2485, SEQ ID NO:2486, SEQ ID NO:2487, SEQ ID

NO:2488, SEQ ID NO:2491, SEQ ID NO:2492, SEQ 1D NO:2493, SEQ ID NO:2494, SEQ ID

NO:2495, SEQ ID NO:2496, SEQ ID NO:2497, SEQ ID N0:2502, SEQ ID NO:2503, SEQID ~~

NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID N0:2507, SEQ ID NO:2508, SEQ ID

NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID NO:2512, SEQ ID NO:2513, SEQ ID

NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQ ID NO:2517, SEQ ID NO:2518, SEQ ID

NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID NO:2528, SEQ ID NO:2529, SEQ ID

NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID NO:2533, SEQ ID NO:2534, SEQ ID

NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID NO:2538, SEQ ID NO:2539, SEQ ID

NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID NO:2543, SEQ ID NO:2544, SEQ ID

NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID NO:2548, SEQ ID NO:2549, SEQ ID

NO0:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID NO:2553, SEQ ID NO:2554, SEQ ID

NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ 1D NO:2558, SEQ ID NO:2559, SEQ ID

NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID NO:2563, SEQ ID NO:2564, SEQ ID

NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID NO:2568, SEQ ID NO:2569, SEQ ID

NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID N0:2573, SEQ ID NO:2574, SEQ ID

NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID NO:2578, SEQ ID NO:2579, SEQ ID

NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID NO:2583, SEQ ID NO:2584, SEQ ID

NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID NO:2588, SEQ ID NO:2589, SEQ ID

NO:2590, SEQ ID NO:2591, SEQ ID N0:2592, SEQ ID NO:2593, SEQ ID NO:2594, SEQ ID

NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID NO:2598, SEQ ID NO:2599, SEQ ID :

NO:2600, SEQ 1D NO:2601, SEQ ID NO:2602, SEQ ID NO:2603, SEQ ID N0O:2604, SEQ ID

NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID NO:2608, SEQ ID NO:2609, SEQ ID

NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID NO:2613, SEQ ID NO:2614, SEQ ID

NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID NO:2618, SEQ ID NO:2619, SEQ ID

NO:2620, SEQ ID N0O:2621, SEQ ID NO:2622, SEQ ID NO:2623, SEQ ID N0:2624, SEQ ID

NO:2625, SEQ ID NO:2626, SEQ ID NO:2925, SEQ ID NO:2926, SEQ ID N0:2927, SEQ ID

NO:2928, SEQ ID N0O:2929, SEQ ID N0:2930, SEQ ID N0:2932, SEQ ID NO0:2933, SEQ ID

NO:2935, SEQ ID NO:2936, SEQ ID NO:2937, SEQ ID NO:2938, SEQ ID N0:2939, SEQ ID " NO:2941, SEQ ID NO:2942, SEQ ID NO:2943, SEQ ID NO:2945, SEQ ID NO:2946, SEQ ID ' ND:2947, SEQ ID NO:2948, SEQ ID NO:2949, SEQ ID NO:2950, SEQ ID N0:2951, SEQ ID

N0:2952, SEQ ID NO:2953, SEQ ID NO:2954, SEQ ID NO:2955, SEQ ID N0:2956, SEQ ID

C32 )

NO:2957, SEQ ID N0:2959, SEQ ID NO:2960, SEQ ID NO:2961, SEQ ID NO:2962, SEQ ID

NO:2963, SEQ ID NO:2964, SEQ ID NO:2965, SEQ ID NO:2966, SEQ ID NO:2967, SEQ ID

NO:2968, SEQ ID NO:2969, SEQ 1D NO:2970, SEQ ID N0:2971, SEQ ID NO:2972, SEQ ID

NO:2973, SEQ ID NO:2974, SEQ ID NO:2975, SEQ ID NO:2976, SEQ ID NO:2977, SEQ ID

NO:2978, SEQ ID NO:2979, SEQ ID N0O:2980, SEQ ID N0:2981, SEQ ID NO:2982, SEQ ID

NO:2983, SEQ ID NO:2984, SEQ ID NO:2985, SEQ ID N0:2986, SEQ ID NO:2987, SEQ ID

NO:2988, SEQ ID NO:2989, SEQ ID NO:2990, SEQ ID NO:2991, SEQ ID NO:2992, SEQ ID

NO:2993, SEQ ID NO:2994, SEQ ID NO:2995, SEQ ID N0:2996, SEQ ID NO:2997, SEQ ID

NO:2998, SEQ ID NO:2999, SEQ ID NO:3000, SEQ ID NO:3001, SEQ ID NO:3002, SEQ ID

NO:3003, SEQ ID NO:3004, SEQ ID NO:3005, SEQ ID N0:3006, SEQ ID NO:3007, SEQ ID

NO:3008, SEQ ID NO:3009, SEQ ID NO:3010, SEQ ID NO:3011, SEQ ID NO:3012, SEQ ID

NO:3013, SEQ ID NO:3014, SEQ ID NO:3015. In another variation, the method includes detectin g the expression level of one or more additional genes by measuring one or more proteins expressed by the one or more additional genes. The one or more proteins expressed by the one or more genes comprises an amino acid sequence selected from SEQ 1D NO:2400, SEQ ID NO:2401, SEQ ID

NO:2402, SEQ ID NO:2403, SEQ ID NO:2404, SEQ ID NQ:2405, SEQ ID NO:2406, SEQ ID

NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID N0:2410, SEQ ID NO:2411, SEQ ID

NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO0:2415, SEQ ID N0O:2416, SEQ ID

NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID N0:2420, SEQ ID NO:2421, SEQ ID

NO:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID N0:2425, SEQ ID NO:2426, SEQ ID

NO:2427, SEQ ID NO:2428, SEQ ID NO:2429, SEQ ID N0:2430, SEQ ID NO:2432, SEQ ID

NO:2433, SEQ ID NO:2434, SEQ ID N0:2435, SEQ ID N0:2436, SEQ ID N0:2437, SEQ ID

NO:2438, SEQ ID NO:2439, SEQ ID NO:2440, SEQ ID N0:2441, SEQ ID NO:2442, SEQ ID

NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID NO:2447, SEQ ID

NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID N0:2451, SEQ ID NO:2452, SEQID

NO:2453, SEQ ID NO:2454, SEQ ID NO:2455, SEQ ID NO:2456, SEQ ID NO:2457, SEQ ID

NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID N0:2461, SEQ ID NO:2462, SEQ ID So

NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID N0:2466, SEQ ID NO:2467, SEQ ID

NO:2468, SEQ 1D NO:2469, SEQ ID N0:2470, SEQ ID N0:2474, SEQ ID NO:2478, SEQ ID

NO:2479, SEQ ID NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQID

NO:2485, SEQ ID NO:2486, SEQ ID NO:2487, SEQ ID N0:2488, SEQ ID NO:2491, SEQID

NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO0:2495, SEQ ID NO:2496, SEQID

NO:2497, SEQ ID NO:2502, SEQ ID NO:2503, SEQ ID N0:2504, SEQ ID NO:2505, SEQID

NO:2506, SEQ ID NO:2507, SEQ ID N0O:2508, SEQ ID N0:2509, SEQ ID NO:2510, SEQID

NO:2511, SEQ ID NO:2512, SEQ ID NO:2513, SEQ ID N0:2514, SEQ ID NQO:2515, SEQ ID

NO:2516, SEQ ID NO:2517, SEQ ID NO:2518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID oo NO:2521, SEQ ID NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID

NO:2532, SEQ ID NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NQO:2536, SEQ ID

NO:2537, SEQ ID NO:2538, SEQ ID NO:2539, SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID

NO:2542, SEQ ID NO:2543, SEQ ID NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID

NO:2547, SEQ ID NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID

NO:2552, SEQ ID NO:2553, SEQ ID NO:2554, SEQ 1D NO:2555, SEQ ID N0:2556, SEQ ID

NO:2557, SEQ ID NO:2558, SEQ ID N0:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID

NO:2562, SEQ ID N0:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID

NO:2567, SEQ ID NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NQ:2571, SEQ ID © NO:2572, SEQ ID NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID

NO:2577, SEQ ID NO:2578, SEQ ID NO:2579, SEQ 1D NO:2580, SEQ ID NO:2581, SEQ ID

NO:2582, SEQ ID NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID

NO:2587, SEQ ID NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID

N0:2592, SEQ ID NO:2593, SEQ 1D NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID

N0:2597, SEQ ID NO:2598, SEQ ID N0:2599, SEQ ID NO:2600, SEQ ID N0:2601, SEQ ID

NO:2602, SEQ ID NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID

NO:2607, SEQ ID NO:2608, SEQ ID N0O:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID

NO:2612, SEQ ID NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID :

NO:2617, SEQ ID NO:2618, SEQ ID N0:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID

NO:2622, SEQ ID NO:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID N0:2626, SEQ ID

NO:2925, SEQ ID N0:2926, SEQ ID N0O:2927, SEQ ID NO:2928, SEQ ID N0:2929, SEQ ID

NO:2930, SEQ ID NO:2932, SEQ ID N0O:2933, SEQ ID NO:2935, SEQ ID N0:2936, SEQ ID

NO:2937, SEQ ID NO:2938, SEQ ID N0:2939, SEQ ID NO:2941, SEQ ID N0:2942, SEQ ID

NO:2943, SEQ ID NO:2945, SEQ ID NO:2946, SEQ ID NO:2947, SEQ ID NO:2948, SEQ ID

NO:2949, SEQ ID NO:2950, SEQ ID NO:2951, SEQ ID NO:2952, SEQ ID N0O:2953, SEQ ID

NO:2954, SEQ ID NO:2955, SEQ ID NO:2956, SEQ ID NO:2957, SEQ ID N0:2959, SEQ ID

NO:2960, SEQ ID NO:2961, SEQ ID N0O:2962, SEQ ID NO:2963, SEQ ID NO:2964, SEQ ID

NO:2965, SEQ ID NQ:2966, SEQ ID NO:2967, SEQ ID NO:2968, SEQ ID NO:2969, SEQ ID

N0:2970, SEQ ID NO:2971, SEQ ID N0:2972, SEQ ID NO:2973, SEQ ID NO:2974, SEQ ID

N0:2975, SEQ ID N0:2976, SEQ ID NO:2977, SEQ ID NO:2978, SEQ ID N0O:2979, SEQ ID

NO:2980, SEQ ID NO:2981, SEQ ID NO:2982, SEQ ID NO:2983, SEQ ID NO:2984, SEQ ID :

NO:2985, SEQ ID NO:2986, SEQ ID NO:2987, SEQ ID NO:2988, SEQ ID NO:2989, SEQ ID

N0:2990, SEQ ID NO:2991, SEQ ID N0O:2992, SEQ ID N0O:2993, SEQ ID NO:2994, SEQ ID

NO:2995, SEQ ID N0O:2996, SEQ ID NO:2997, SEQ ID NO:2998, SEQ ID NO:2999, SEQ ID

NO:3000, SEQ ID NO:3001, SEQ ID NO:3002, SEQ ID NO:3003, SEQ ID NO:3004, SEQ ID

NO:3005, SEQ ID NO:3006, SEQ ID NO:3007, SEQ ID NO:3008, SEQ ID NO:3009, SEQ ID

NO:3010, SEQ ID NO:3011, SEQ ID NO:3012, SEQ ID NO:3013, SEQ ID NO:3014, SEQ ID

NO:3015, and the one or more proteins expressed by the one or more additional genes may include an amino acid sequence selected from SEQ 1D NO:2431, SEQ ID NO:2471, SEQ ID NO:2472, SEQ ID

NO:2473, SEQ ID NO:2475, SEQ ID NO:2476, SEQ ID NO:2477, SEQ ID NO:2484, SEQ ID © NO:2489, SEQ ID NO:2490, SEQ ID NO:2498, SEQ ID NO:2499, SEQ ID NO:2500, SEQ ID © NO:2501, SEQ ID NO:2522, SEQ ID NO:2523, SEQ ID NO:2524, SEQ ID NO:2525, SEQ ID _ NO:2526, SEQ ID NO:2527. oo

Protein detection may be accomplished by measuring serum. In another variation, the protein is a cell surface protein. In a further vanation, the measuring includes using a fluorescent activated cell sorter.

In another aspect, the invention is directed to a substantially purified oligonucleotide having the nucieotide sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5,

SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO:11, SEQ ID

NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ 1D NO: 15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID

NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID ) NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID

NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQID

NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQID

NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID :

NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQID

NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQID

NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ

NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ °

ID NO: 142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147,

NO: 187, SEQ ID NO: 188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ

ID NO:193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO:197, SEQ ID NO: 198, © SEQID NO:199, SEQ ID NO:200, SEQ ID N0:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID

NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ

NO:221, SEQ ID NO:222, SEQ ID N0:223, SEQ ID NO:224, SEQ ID N0:225, SEQ ID NO:226, SEQ

ID NO:227, SEQ ID NO:228, SEQ ID N0:229, SEQ ID N0O:230, SEQ ID NO:231, SEQ ID NO:232,

SEQ ID N0:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID

NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ 1D NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ 1D N0:248, SEQ ID NO:249,

SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID N0:270, SEQ ID NO:271, SEQ ID

NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID N0:276, SEQ ID NO:277, SEQ

SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID - NO:289, SEQ ID N0:290, SEQ ID NO:291, SEQ ID N0:292, SEQ ID N0O:293, SEQ ID NO:294, SEQ

ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID N0:298, SEQ ID NO:299, SEQ ID NO:300,

ID NO:329, SEQ ID NO:330, SEQ ID NO:33t, SEQ ID NO:332, SEQ ID N0:2697, SEQ ID

NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID

NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID

NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID

NO:2671, SEQ ID NO:2752, SEQ ID NQ:2737, SEQ ID NQ:2719, SEQ ID NO:2684, SEQ 1D

NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID

NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID

NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID

NO:2713, SEQ ID NO:2736, SEQ ID N0:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID

NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID

NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID

NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID

NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID NO:269S, SEQ ID NO:2741, SEQ ID

NO:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID

NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID

NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID

NO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID NO:2675, SEQ ID NO:2700, SEQ ID = NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID . NO0:2702, SEQ ID NO:2681, SEQ ID-NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID

NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID NO:2673, SEQ ID NO:2733, SEQ ID

NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQID

NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID

NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID

NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID

NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID .NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID NO:2637. SEQ ID NO:2634, SEQ ID

NO:2709, SEQ ID NO:2653, SEQ ID NO:2729, a substantially purified oligonucleotide having the nucleotide sequence selected from SEQ ID NO:333-664, and substantially purified oligonulkcleotides having at least 90% sequence identity to an oligonucleotide having the nucleotide sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ

ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:1 1, SEQ ID NO:12, SEQ ID NO: 13, SEQ ID

NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO: 19, SEQ ID

NO:38, SEQ ID NO:39, SEQ ID N0:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID

NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID

NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID

NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID

NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID

NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID

NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID

NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID

NO:92, SEQ ID N0O:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQID

NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ

ID NO:104, SEQ ID NO:105, SEQ ID NO: 106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109,

SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:1 12, SEQ ID NO:113, SEQ ID NO:114, SEQ ID

NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO: 119, SEQ ID NO:120, SEQ

ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO: 126,

SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID

NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ

ID NO:138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO: 143,

SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO- 146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID

NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ

ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, oo SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:1 63, SEQ ID NO:164, SEQ ID NO:165, SEQ ID

NO:166, SEQ ID NO:167, SEQ ID NO: 168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ - IDNO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, : EE 37"

SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ 1D NO:182, SEQ ID

NO:183, SEQ ID NO: 184, SEQ ID NO:185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO:188, SEQ

ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194,

SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQIDNO:199,SEQID

NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ

ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, , SEQID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID LL

NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ

ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO0:226, SEQ ID N0O:227, SEQ ID NO:228,

SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID N0O:233, SEQ ID

NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ

ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245,

SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID N0:250, SEQ ID

NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ- ) ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262,

SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID

NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ

ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279,

SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID

NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ

ID NO:291, SEQ ID N0:292, SEQ ID N0O:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296,

SEQ ID NO:297, SEQ ID NO:298, SEQID N0:299, SEQ ID NO:300, SEQ ID N0:301, SEQ ID

NO:302, SEQ ID NO:303, SEQ 1D NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ

ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313,

SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID . NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ

ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330,

SEQ ID NO:331, SEQ ID NO:332, SEQ ID N0:2697, SEQ ID N0:2645, SEQ ID N0O:2707, SEQ ID

N0:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID N0:2706, SEQ ID

NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID N0:2716, SEQ ID

NO:2727, SEQ ID NO:2721, SEQ ID N0:2641, SEQ ID NO:2671, SEQ ID N0:2752, SEQ ID

NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID NO:2748, SEQ ID

NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID

NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID N0:2747, SEQ ID

NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID NO:2736, SEQ ID

NO:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NO:2754, SEQ ID

NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID

NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628,SEQID 'NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID

NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID N0:2726, SEQ ID . oe

NO:2722, SEQ ID NO:268%, SEQ ID N0:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID

NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID

NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID NO:2662, SEQ ID NO:2753, SEQ ID

NO:2704, SEQ ID N0:2675, SEQ ID NO:2700, SEQ 1D NO:2640, SEQ ID NO:2723, SEQ ID

NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID NO:2681, SEQ ID 'N0:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID 'NO:2718, SEQ ID N0:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID _

NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:2705, SEQ ID

NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID NO:2650, SEQ ID

NO:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID NO:2633, SEQ ID

NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID NO:2630, SEQ ID

NQO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID

NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID NO:2653, SEQ ID

NO:2729 and/or SEQ ID NO:333-664. Ina further aspect, the invention is directed to a substantially purified oligonucleotide that hybridizes at high stringency to an oligonucleotide having the nucleotide sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:3, SEQ ID NO:6,

SEQ ID NO:7, SEQ ID NO:8, SEQ ID NQ:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ

ID NO:13, SEQ ID NO:14, SEQ ID NO: 15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID

NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID N0:36, SEQ ID

NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID :

NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID

NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID. : NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID

NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID

NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID

NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:50, SEQ ID

NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID

NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID

ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114,

SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID

NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ

ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131,

SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO: 134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID

NO:137, SEQ 1D NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ } ID NO:143, SEQ ID NO: 144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148,

SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID

NO:154, SEQ ID NO:155, SEQ ID NO: 156, SEQ ID NO:157, SEQ 1D NO:158, SEQ ID NO:159, SEQ

ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO: 165,

SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO: 168, SEQ 1D NO:169, SEQ ID NO:170, SEQ ID

NO:171, SEQ ID NO: 172, SEQ 1D NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ

ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ 1D NO:181, SEQ ID NO:182,

SEQ ID NO:183, SEQ ID NO;184, SEQ ID NO: 185, SEQ ID NO:186, SEQ ID NO:187, SEQID

NO:188, SEQ ID NO:189, SEQ ID NO: 190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ

ID NO:194, SEQ ID NO: 195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199,

SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID

NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ 1D NO:210, SEQ

ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216,

SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID

NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ

ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233,

SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID

NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ 1D NO:244, SEQ

ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250,

SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID

NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ

ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267,

SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID

NO:273, SEQ ID NO:274, SEQ ID N0:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ

ID NO:279, SEQ ID NO-280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284,

SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID

NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ

ID NO:296, SEQ ID N0:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301,

SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID

NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ

ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQID NO:318,

SEQ ID NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID

NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ

ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID

NO:2707, SEQ ID NO:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID

NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID

NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID

NO:2752, SEQ ID NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID © NO:2748, SEQ ID NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ TD

NO:2683, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID

NO:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID . Ca

NO:2736, SEQ ID NO:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID

NO:2754, SEQ ID N0O:2728, SEQ ID N0:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID

NO:2746, SEQ ID NO:2738, SEQ ID N0:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID

NO:2628, SEQ ID NO:2638, SEQ ID N0:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID

NO:2751. SEQ ID NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID Co

NO.2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID

NO:2656, SEQ ID NO:2696, SEQ ID NQ:2676, SEQ ID NQ:2701, SEQ ID NO:2730, SEQ ID

NO:2710, SEQ ID NO:2632, SEQ ID NO:2724, SEQ ID NO0:2698, SEQ ID NO:2662, SEQ ID

NO:2753, SEQ ID NO:2704, SEQ ID NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID

NO0:2723, SEQ ID NO:2658, SEQ ID N0O:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID

NO:2681, SEQ ID NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID

NO:2651, SEQ ID NO:2718, SEQ ID NO:2673, SEQ ID N0:2733, SEQ ID NO:2712, SEQ ID :

N0:2659, SEQ ID NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ 1D N0:2690, SEQ ID

NO:2705, SEQ ID NO:2685, SEQ ID N0:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID

NO:2650, SEQ ID NO:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID

NO:2633, SEQ ID NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID

NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ 1D

NO:2665, SEQ ID NO:2649, SEQ ID NO:2637, SEQ ID N0:2634, SEQ ID NO:2709, SEQ ID

NO:2653, SEQ ID NO:2729 or SEQ ID NOS:333-664. The sequences may be used as diagnostic oligonucleotides for transplant rejection and/or cardiac transplant rejection. The oligonucleotide may have nucleotide sequence including DNA, cDNA, PNA, genomic DNA, or synthetic oligonucleotides.

In another aspect, the invention is directed to a method of diagnosing or monitoring transplant rejection in a patient wherein the expression level of one or more genes in a patient’s bodily fluid is detected. In a further variation, the bodily fluid is peripheral blood.

In another aspect, the invention is directed to a method of diagnosing or monitoring transplant rejection in a patient, comprising detecting the expression level of four or more genes in the patient to diagnose or monitor transplant rejection in the patient wherein the four or more genes include a nucleotide sequence selected from SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:S5, SEQ

ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID

NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQID

NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQID

NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQID

NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35,SEQID

NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQID ) ". NO:54, SEQID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID "'NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID

NO:66, SEQ ID NO67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID

NO:72, SEQID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID i .

NO:90, SEQ ID NO:91, SEQ ID N0:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID i NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID

NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO: 105, SEQ ID NO:106, SEQ ID NO:107, SEQ

ID NO: 108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO: 112, SEQ ID NO:113,

NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ

ID NO:142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147,

NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO: 173, SEQ ID NO:174, SEQ ID NO:175, SEQ

SEQ ID NO: 182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID

NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID N0:207, SEQ ID NO:208, SEQ ID NO:209, SEQ

SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID N0:219, SEQ 1D NO:220, SEQ ID

NO:221, SEQ ID NO:222, SEQ ID N0:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ

ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, :

ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID N0:265, SEQ ID NO:266,

NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ © ID.NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283,

SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID © NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ iD N0:292, SEQ ID NO:293, SEQ ID NO:294, SEQ

ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298; SEQ ID NO:299, SEQ ID NO:300,

ID NO:329, SEQ ID NO:330, SEQ ID N0:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID

NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID ~. NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQID : NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID

NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID

NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID

NO:2657, SEQ ID NO:2683, SEQ 1D NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID

NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID N0:2678, SEQ ID NO:2731, SEQ ID

NO:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID

NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID

NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID :

NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID

NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID

NO:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID

NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ ID N0:2701, SEQ ID

NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID N0O:2724, SEQ ID NO:2698, SEQ ID

NO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID NO:2675, SEQ ID NQ:2700, SEQ ID

NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID N0:2688, SEQ ID NO:2735, SEQ ID

NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID N0:2715, SEQ ID NO:2732, SEQ ID

NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID N0:2673, SEQ ID NO:2733, SEQ ID

NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID NO0:2636, SEQ ID NO:2639, SEQ ID

NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID N0O:2692, SEQ ID NO:2693, SEQ ID

NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID N0:2660, SEQ ID NO:2666, SEQ ID

NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID N0O:2642, SEQ ID NO:2682, SEQ ID

NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID :

NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID

NO:2709, SEQ ID NO:2653, SEQ ID NO:2729.

In another aspect, the invention is directed to a method of diagnosing or monitoring kidney transplant rejection in a patient by detecting one or more proteins in a bodily fluid of the patient to diagnose or monitor transplant rejection in the patient wherein the one or more proteins have a protein sequence selected from SEQ ID NO:76, SEQ ID NO:2663, SEQ ID NO.98, SEQ ID NO0:2696, SEQ ID

NO:2736, SEQ ID NO:2751, SEQ ID NO:2631, SEQ ID NO:2675, SEQ ID N0:2700, and SEQ ID

NO:2693. oo

Ina further aspect, the invention is also directed to a system for detecting gene expression in body fluid including at least two isolated polynucleotides wherein the isolated polynucleotides detect expression of a gene wherein the gene includes a nucleotide sequence selected from SEQ ID NO:2,

RR SE

SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID

NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID

NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID

NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID

NO:28, SEQ ID NO:29, SEQ ID NG'30, SEQ ID NO'31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID

NO134, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID oo NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQID

NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID

NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID

NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID

NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID N0:69, SEQ ID

NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:82, SEQ ID

NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID

NO:96, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ

ID NO: 105, SEQ ID NO:106, SEQ ID N0:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:114,

ID NO: 126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131,

SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID

NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ

ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ 1D NO:158, SEQ ID NO:159, SEQ ID NO:160,

SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID

NO:166, SEQ ID NO: 167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ

ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177,

SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID

NO:183, SEQ ID NO: 184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ -

SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID

ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211,

SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID

NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID N0:220, SEQ ID NO:221, SEQ ID N0:222, SEQ

ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228,

SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID

NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID N0:239, SEQ

SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248; SEQ ID NO:249, SEQ ID NO:250, SEQ ID SE

NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ

ID NO:257, SEQ ID NO:258, SEQ ID N0:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, : a4

NO:268, SEQ 1D NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ

ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ 1D NO:279,

ID NO:291, SEQ 1D NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296,

SEQ ID N0:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID " NO:302, SEQ ID N0:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ

SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID

NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ

SEQ ID NO:331, SEQ ID NO:332, SEQ 1D NO:2697, SEQ ID NO:2645, SEQ ID NO:2707, SEQ ID

NO:2679, SEQ ID N0:2717, SEQ ID NO:2646, SEQ ID NQO:2667, SEQ ID NO:2706, SEQ ID

NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID NQ:2743, SEQ ID NO:2716, SEQ ID

NO:2727, SEQ ID N0O:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ 1D NO:2752, SEQ ID

NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID N0:2677, SEQ ID NO:2748, SEQ ID :

NO0:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID NO0:2657, SEQ ID NO:2683, SEQ ID

NO:2686, SEQ ID N0O:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID

NO:2744, SEQ 1D NO:2678, SEQ ID NO:2731, SEQ ID N0:2713, SEQ ID NO:2736, SEQ ID

NO:2708, SEQ ID N0:2670, SEQ ID NO:2661, SEQ ID NO0:2680, SEQ 1D NO:2754, SEQ ID :

NO0:2728, SEQ ID N0:2742, SEQ ID NO:2668, SEQ ID NO0:2750, SEQ ID NO:2746, SEQ ID

NO:2738, SEQ ID N0:2627, SEQ ID NO:2739, SEQ ID NO0:2647, SEQ ID N0:2628, SEQ ID

NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID N0:2635, SEQ ID NO:2751, SEQ ID

NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID NO:2726, SEQ ID

NO0:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID NO0:2631, SEQ ID NO:2656, SEQ ID

NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID

NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID NO:2662, SEQ ID NO:2753, SEQ ID

NO:2704, SEQ ID N0:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID NO:2723, SEQ ID

NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID NO:2681, SEQ ID

NO:2755, SEQ ID NO:2715, SEQ ID N0O:2732, SEQ ID NO0:2652, SEQ ID NO:2651, SEQ ID

NO:2718, SEQ ID NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID

NO:2654, SEQ ID N0:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:2705, SEQ ID

NO:2685, SEQ ID N0O:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID NO:2650, SEQ ID

NO0:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID NO:2633, SEQ ID

NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID NO:2630, SEQ ID

NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID © NO2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID N0:2709, SEQ ID NO:2653, SEQ ID

NO:2729 and the gene is differentially expressed in body fluid in an individual rejecting a transplanted organ compared to the expression of the gene in leukocytes in an individual not rejecting a transplanted organ. Co

In another aspect, the invention is directed to a system for detecting gene expression in body fluid including at least two isolated polynucleotides wherein the isolated polynucleotides detect expression of a gene wherein the gene includes a nucleotide sequence selected from SEQ ID NO:22,

NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID

NO:27, SEQ ID NO:28, SEQ ID N0:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID

NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ 1D NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQID

NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ

SEQ ID NO:128, SEQ ID NO0:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQID

NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ

ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NQ:144,

NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ

ID NO:190, SEQ ID NO:191, SEQ TD NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO: 195,

SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO: 198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID

ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212,

SEQ ID NO:213, SEQ 1D NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID

ID NO:224, SEQ ID NO:225, SEQ ID N0O:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229,

ID NO:241, SEQ ID NO:242, SEQ ID N0:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246,

NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ -

ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID N0O:296, SEQ ID NO:297,

SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID :

SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID NO:2707, SEQ ID N0:2679, SEQ ID

NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID

NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID N0:2716, SEQ ID N0O:2727, SEQ ID

NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID

NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID N0:2748, SEQ ID NO:2703, SEQ ID

NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID

NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID

NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID N0:2736, SEQ ID NO:2708, SEQ ID

NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID N0:2754, SEQ ID NO:2728, SEQ ID

NO:2742, SEQ ID NO:2668, SEQ ID N0:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID

NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID

NO:2725, SEQ ID NO:2714, SEQ ID N0:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID

NO:2695, SEQ 1D NO:2741, SEQ ID NO:2691, SEQ ID N0:2726, SEQ ID NO:2722, SEQ ID

NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID

N NO:2676, SEQ ID NO:2701, SEQ ID N0:2730, SEQ ID NO:2710, SEQ ID N0:2632, SEQ ID Co

NO:2724, SEQ ID NO:2698, SEQ ID NO:2662, SEQ ID N0:3753, SEQ iD NO:2704, SEQ ID NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID.NO:2723, SEQ ID NO:2658, SEQ ID

NO:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID N0:2681, SEQ ID NO:2755, SEQ ID

NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID

NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID

NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID

NO:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID N0:2650, SEQ ID NO:2720, SEQ ID " NO2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQID =

NO:2642, SEQ ID NO:2682, SEQ ID N0O:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID

NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID

NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID NO:2653, SEQ ID NO:2729 and the gene expression is related to the rate of hematopoiesis or the distribution of hematopoeitic cells along their maturation pathway.

The invention is also directed to methods of diagnosing or monitoring transplant rejection in a patient by detecting the expression level of one or more genes including a nucleotide sequence selected from SEQ ID NOS: 3016-3117. SEQ ID NOS:3108-3117 are useful in detecting CMV infection.

Brief Description of the Sequence Listing

SEQ ID’s 1-332 are 50mer oligonucleotides corresponding to gene expression markers for diagnosis and monitoring of allograft rejection and other disorders.

SEQ ID’s 333-664 are Reference mRNA sequences for genes identified by probes 1-332.

SEQ ID’s 665-995 are a first set of Left PCR primers for genes 1-332.

SEQ ID’s 996-1326 are a first set of Right PCR primers for genes 1-332.

SEQ ID’s 1327-1657 are Tagman probes for the first set PCR primers for genes 1-332.

SEQ ID’s 1658-1903 are a second alternative set of left PCR primers for selected genes 1-332

SEQ ID’s 1904-2151 are a second alternative set of right PCR primers for selected genes 1-332

SEQ ID’s 2152-2399 are Taqman probes for the second alternative set of PCR primers for selected genes 1-332.

SEQ ID’s 2400-2626 are Proteins encoded by mRNAs from genes identified in 1-332.

SEQ ID’s 2627-2795 are S50mer oligonucleotide array probes used to identify genes in Figure 7 and

Tables 6 and 8.

SEQ ID’s 2796-2924 are reference mRNA sequences for genes in Table 8 which show altered expression in renal transplantation and rejection.

SEQ ID’s 2925-3015 are proteins coded by genes which show altered expression in Table 8.

SEQ ID's 3016-3081 are S0mer oligonucleotide array probes and used to identify genes in the

Examples.

SEQ ID’s 3082-3107 are genes and primers discussed in the Examples.

SEQ ID’s 3108-3117 are mRNAs from human genes in which regulation is altered upon CMV infection.

F igure 1: Figure 1 is a schematic flow chart illustrating a schematic instruction set for characterization of the nucleotide sequence and/or the predicted ‘protein sequence of novel nucleotide sequences.

Figure 2: Figure 2 depicts the components of an automated RNA preparation machine.

Figure 3 shows the results of six hybridizations on a mini array graphed (n=6 for each column). The error bars are the SEM. This experiment shows that the average signal from AP prepared RNA is 47% of the average signal from GS prepared RNA for both Cy3 and Cy5.

Figure 4 shows the average background subtracted signal for each of nine leukocyte-specific genes on a mini aay. This average is for 3.6 of the above-described hybridizations for each gene. The error bars are the SEM.

Figure 5 shows the ratio of Cy3 to Cy5 signal for a number of genes. After normalization, this ratio corrects for variability among hybridizations and allows comparison between experiments done at different times. The ratio is calculated as the Cy3 background subtracted signal divided by the CyS background subtracted signal. Each bar is the average for 3-6 hybridizations. The error bars are SEM.

Figure 6 shows data median Cy3 background subtracted signals for control RNAs using mini arrays.

Figure 7: Cardiac Allograft rejection diagnostic genes.

A. Example of rejection and no-rejection samples expression data for S marker genes. For each sample, the associated rejection grades are shown as are the expression ratios for 5 differentially expressed genes. The genes are identified by the SEQ ID number for the oligonucleotide. The average fold difference between grade 0 and grade 3A samples is calculated at the bottom.

B. CART classification model. Decision tree for a 3 gene classification model for diagnosis of cardiac rejection. In the first step, expression of gene 223 is used to divide the patients to 2 branches.

The remaining samples in each branch are then further divided by one remaining gene. The samples are classified as either rejection or no rejection. 1 no rejection sample is misclassified as a rejection sample.

C. Surrogates for the CART classification model. For each of the 3 splitter genes in the CART rejection model described in the example, 5 top surrogate genes are listed that were identified by the

CART algorithm.

Figure 8: Validation of differential expression of a gene discovered using microarrays using real-time

PCR

Figure 8A. The Ct for each patient sample on multiple assays is shown along with the Ct in the R50 control RNA. Triangles represent —RT (reverse transcriptase) controls.

Figure 8B. The fold difference between the expression of Granzyme B and an Actin reference is shown for 3 samples from patients with and without CMV disease.

Figure 9: Endpoint testing of PCR primers

Electrophoresis and microfluidics are used to assess the product of gene specific PCR primers.

B-GUS gel image. Lane 3 is the image for primers F178 and R242. Lanes 2 and 1 correspond to the no-template control and -RT control, respectively.

The electropherogram of $-GUS primers F178 and R242, a graphical representation of Lane 3 from the gel image. : } .

B-Actin gel image. Lane 3 is the image for primers F75 and R178. Lanes 2 and 1 correspond to the ‘no-template control and RT control, respectively. h : N : The electropherogram of B-Actin primers F75 and R178, 2 graphical representation of Lave 3 from the gel image. :

Figure 10: PCR Primer efficiency testing. A standard curve of Ct versus log of the starting RNA amount is shown for 2 genes.

Figure 11: Real-time PCR control gene analysis 11 candidate control genes were tested using real-time PCR on 6 whole blood samples (PAX) paired with 6 mononuclear samples (CPT) from the same patient. Each sample was tested twice. For each gene, the variability of the gene across the samples is shown on the vertical axis (top graph). The average Ct value for each gene is also shown (bottom graph). 2ug RNA was used for PAX samples and 0.5 ug total RNA was used for the mononuclear samples (CPT).

Figure 12: Rejection marker discovery by co-expression with established marker

Microarrays were used to measure expression of genes SEQ ID 85 and 302 in samples derived from 240 transplant recipients. For each sample, the expression measurement for 85 is plotted against 302.

Figure 13: ROC (receiver operator characteristics) curve for a 3-gene PCR assay for diagnosis of rejection (see example 17). The Sensitivity and False Positive Rate for each test cutoff is shown.

Brief Description of the Tables

Table 1: Table 1 lists diseases or conditions amenable to study by leukocyte profiling.

Table 2: Transplant Markers

A. Transplant Genes: Genes useful for monitoring of allograft rejection are listed in this here. The gene symbol and name are given. SEQ ID 50mer is the sequence ID of a 50mer oligonucleotide that is specific for the gene. The NCBI Unigene number (HS) from (Build 160, 16 Feb 2003) is given as is an accession number (ACC) from (Genbank Release 135, 15 April 2003) for an RNA or cDNA is

Genbank that corresponds to the gene. The sequence identified by the ACC number is in the sequence listing (SEQ ID RNA/cDNA).

B. Microarray Data: SEQ ID 50mer, Gene, Gene Name, ACC and SEQ ID RNA/cDNA are given for each gene as in A (above). Each identified gene has a Non-Parametric Score and Median Rank in NR given from the non-parametric analysis of the data. The genes are ranked from highest to lowest scoring. Down Regulated genes are noted with a 1 in this column.

C. PCR Primers: Primers and probes for real-time PCR assays for each gene are given along with their

SEQ ID #s. Each gene has 1 or 2 sets of a forward and reverse PCR primer and a hybridization probe for detection in TaqMan or similar assays.

D. PCR Data: Real-time PCR data was generated on a set of transplant samples using sybr green technology as described in the text. For each gene the number of samples (n) used in the analysis is given. An odds ratio and the p-values for a Fisher test and t-test are given for the comparison of acute rejection samples is given (see text).

E. Transplant proteins: For each gene, the corresponding protein in the RefSeq data base (Genbank

Release 135, 18 April 2003) is given (RefSeq Peptide Accession #) along the the SEQ ID for that protein for the sequence listing.

Table 3: Viral gene for arrays. Viral genomes were used to design oligonucleotides for the microarrays. The accession numbers for the viral genomes used are given, along with the gene name and location of the region used for oligonucleotide design.

Table 4. Dependent variables for discovery of gene expression markers of cardiac allograft rejection.

A stable Grade 0 is a Grade 0 biopsy in a patient who does not experience rejection with the subsequent biopsy. HG or highest grade means that the higher of the biopsy grades from the centralized and local pathologists was used for a definition of the dependent variable.

Table 5: Real-time PCR assay reporter and quencher dyes. Various combinations of reporter and quencher dyes are useful for real-time PCR assays. Reporter and quencher dyes work optimally in . specific combinations defined by their spectra. For each reporter, appropriate choices for quencher dyes are given.

Table 6: Rejection marker PCR assay results

Results of real-time PCR assays are listed for the comparison of rejection samples to no rejection samples. The fold change is given for expression of each gene in rejection/no rejection samples. The p-value for the t-test comparing the rejection and no rejection classes is given.

Table 7: Summary results of array rejection significance analysis. Summary results are given for correlation analysis of leukocyte gene expression to acute rejection using significance analysis for microarrays (SAM). Five analyses are described. The ISHLT grades used to define the rejection and no rejection classes are given. In each case the highest grade from three pathology reading was taken for analysis. All samples are used for two analyses. The other analyses reduce redundancy of patients used in the analysis by using only one sample per patient (“Non-redundant”) or using only one sample per patient within a given class (“Non-redundant within class”). The number of samples used in the analysis is given and the lowest false detection rate (FDR) achieved is noted.

Table 8: Renal tissue rejection array significance analysis. Genes are listed that were identified as upregulated using microarrays on renal tissue with acute rejection versus controls. Significance analysis for microarrays (SAM) was used to determine the false detection rate for each gene (FDR).

Genes with known expression in leukocytes are noted in the table.

Table 9: Rejection marker sequence analysis. For 63 of the allograft rejection markers listed in Table - 2, an analysis of the gene sequence was done. The genes and proteins are identified by accession numbers. The cellular localization of each gene is described as either secreted, nuclear, mitochondrial, cytoplasmic or cellular membrane. The function of the gene is also described.

Table 10: Gene expression markers for immature cells of a variety of lineages are given in Table 10 by way of example

Table 11: Changes in the rate of hematopoiesis have been correlated to a number of disease states and other pathologies. Examples of such conditions are listed in Table 11.

Table 12: This table lists the oligonucleotides and associated genes identified as having value for the diagnosis and monitoring of CMV infection. The first colurmn gives the SEQ ID that corresponds to the oligonuclotide in the sequence listing. The unigene number, genebank accession and GI number are also given for each sequence when known. The name of the gene associated with the accession number "is noted. The strand is noted as —1 or I, meaning that the probe was designed from the complement of a the sequence -1 or directly from the sequence (1). Next, the nucleotide sequence of each probe is also "given. For each gene, the false detection rate (FDR) from the significance analsysis described in example 7 is given if applicable. WBC is the white blood cell count. WPT is the number of weeks past transplant.

Detailed Description of the Invention Definitions

Unless defined otherwise, all scientific and techmcal terms are understood to have the same meaning as commonly used in the art to which they pertain. For the purpose of the present invention, the following terms are defined below. ~

In the context of the invention, the term "genc expression system" refers to any system, device or means to detect gene expression and includes diagnostic agents, candidate libraries, oligonucleotide sets or probe sets.

The term “monitoring” is used herein to describe the use of gene sets to provide useful * information about an individual or an individual’s health or disease status. “Monitoring” can include, determination of prognosis, risk-stratification, selection of drug therapy, assessment of ongoing drug, therapy, prediction of outcomes, determining response to therapy, diagnosis of a disease or disease complication, following progression of a disease or providing any information relating to a patients’ health status over time, selecting patients most likely to benefit from experimental therapies with known molecular mechanisms of action, selecting patients most likely to benefit from approved drugs with known molecular mechanisms where that mechanism may be important in a small subset of a disease for which the medication may not have a label, screening a patient population to help decide on a more invasive/expensive test, for example a cascade of tests from a non-invasive blood test to a more invasive option such as biopsy, or testing to assess side effects of drugs used to treat another indication.

The term “diagnostic oligonucleotide set” generally refers to a set of two or more oligonucleotides that, when evaluated for differential expression of their products, collectively yields predictive data. Such predictive data typically relates to diagnosis, prognosis, monitoring of therapeutic outcomes, and the like. In general, the components of a diagnostic oligonucleotide set are distinguished from nucleotide sequences that are evaluated by analysis of the DNA to directly determine the genotype of an individual as it correlates with a specified trait or phenotype, such as a disease, in that it is the pattern of expression of the components of the diagnostic nucleotide set, rather than mutation or polymorphism of the DNA sequence that provides predictive value. It will be understood that a particular component (or member) of a diagnostic nucleotide set can, in some cases, also present one or more mutations, or polymorphisms that are amenable to direct genotyping by any of a variety of well known analysis methods, e.g., Southern blotting, RFLP, AFLP, SSCP, SNP, and the like.

A “disease specific target oligonucleotide sequence” is a gene or other oligonucleotide that . encodes a polypeptide, most typically a protein, or a subunit of a multi-subunit protein, that is a " therapeutic target for a disease, or group of diseases.

A “candidate library” or a “candidate oligonucleotide library” refers to a collection of oligonucleotide sequences (or gene sequences) that by one or more criteria have an increased probability of being associated with a particular disease or group of diseases. The criteria can be, for example, a differential expression pattern in a disease state or in activated or resting leukocytes in vitro as reported in the scientific or technical literature, tissue specific expression as reported in a sequence database, differential expression in a tissue or cell type of interest, or the like. Typically, a candidate library has at least 2 members or components; more typically, the library has in excess of about 10, or about 100, or about 1000, or even more, members or components.

The term “disease criterion” is used herein to designate an indicator of a disease, suchas a oo diagnostic factor, a prognostic factor, a factor indicated by a medical or family history, a genetic factor, or a symptom, as well as an overt or confirmed diagnosis of a disease associated with several indicators such as those selected from the above list. A disease critenan includes data describing a patient’s health status, including retrospective or prospective health data, e.g. in the form of the patient’s medical history, laboratory test results, diagnostic test result, clinical events, medications, lists, response(s) to treatment and risk factors, etc.

The terms “molecular signature” or “expression profile” refers to the collection of expression values for a plurality (e.g., at least 2, but frequently about 10, about 100, about 1000, or more) of members of a candidate library. In many cases, the molecular signature represents the expression pattern for all of the nucleotide sequences in a library or array of candidate or diagnostic nucleotide sequences or genes. Alternatively, the molecular signature represents the expression pattern for one or more subsets of the candidate library. The term “oligonucleotide” refers to two or more nucleotides.

Nucleotides may be DNA or RNA, naturally occurring or synthetic.

The term “healthy individual,” as used herein, is relative to a specified disease or disease criterion. That is, the individual does not exhibit the specified disease criterion or is not diagnosed with the specified disease. It will be understood, that the individual in question, can, of course, exhibit symptoms, or possess various indicator factors for another disease.

Similarly, an “individual diagnosed with a disease” refers to an individual diagnosed with a specified disease (or disease criterion). Such an individual may, or may not, also exhibit a disease . criterion associated with, or be diagnosed with another (related or unrelated) disease.

An “array” is a spatially or logically organized collection, e.g., of oligonucleotide sequences or nucleotide sequence products such as RNA or proteins encoded by an oligonucleotide sequence. In some embodiments, an array includes antibodies or other binding reagents specific for products of a candidate library.

When referring to a pattern of expression, a “qualitative” difference in gene expression refers to a difference that is not assigned a relative value. That is, such a difference is designated by an “all or nothing” valuation. Such an all or nothing variation can be, for example, expression above or below a threshold of detection (an on/off pattern of expression). Alternatively, a qualitative difference can refer to expression of different types of expression products, e.g., different alleles (e.g., a mutant or polymorphic allele), variants (including sequence variants as well as post-translationally modified i variants), etc. oo R oo

In contrast, a “quantitative” difference, when referring to a pattern of gene expression, refers nL © to a difference in expression that can be assigned a value on a graduated scale, (e.g., a 0-5 or 1-10 scale, a + - +++ scale, a grade 1- grade S scale, or the like; it will be understood that the numbers selected for illustration are entirely arbitrary and in no-way are meant to be interpreted to limit the invention).

Gene Expression Systems of the Invention

The invention is directed to a gene expression system having one or more DNA molecules wherein the one or more DNA molecules has a nucleotide sequence which detects expression of a gene cotresponding to the oligonucleotides depicted in the | Sequence Listing. In one format, the oligonucleotide detects expression of a gene that is differentially expressed in leukocytes. The gene expression system may be a candidate library, a diagnostic agent, a diagnostic oligonucleotide set or a diagnostic probe set. The DNA molecules may be genomic DNA, protein nucleic acid (PNA), ¢DNA or synthetic oligonucleotides. Following the procedures taught herein, one can identity sequences of interest for analyzing gene expression in leukocytes. Such sequences may be predictive of a disease state.

Diagnostic oligonucleotides of the invention

The invention relates to diagnostic nucleotide set(s) comprising members of the leukocyte candidate library listed in Table 2, Table 8, and in the Sequence Listing, for which a correlation exists ) between the health status of an individual, the individual’s expression of RNA or protein products corresponding to the nucleotide sequence, and the diagnosis and prognosis of transplant rejection. In some instances, only one oligonucleotide is necessary for such detection. Members of a diagnostic oligonucleotide set may be identified by any means capable of detecting expression of RNA or protein products, including but not limited to differential expression screening, PCR, RT-PCR, SAGE analysis, high-throughput sequencing, microarrays, liquid or other arrays, protein-based methods (e.g., westem blotting, proteomics, and other methods described herein), and data mining methods, as further descnbed herein.

In one embodiment, a diagnostic oligonucleotide set comprises at least two oligonucleotide sequences listed in Table 2, Table 8, or the Sequence Listing which are differentially expressed in leukocytes in an individual with at least one disease criterion for at least one leukocyte-implicated disease relative to the expression in individual without the at least one disease criterion, wherein expression of the two or more nucleotide sequences is correlated with at least one disease criterion, as described below.

In another embodiment, a diagnostic nucleotide set comprises at least one oligonucleotide having an oligonucleotide sequence listed in Table 2, Table 8, or the Sequence Listing which is differentially expressed, and further wherein the differential expression/correlation has not previously been described. In some embodiments, the diagnostic nucleotide set is immobilized on an array.

In another embodiment, diagnostic nucleotides (or nucleotide sets) are related to the members of the leukocyte candidate library listed in Table 2, Table 8, or in the Sequence Listing, for which a } "correlation exists between the health status, diagnosis and prognosis of transplant rejection (or disease criterion) of an individual. The diagnostic nucleotides are partially or totally contained in (or derived from) full-length gene sequences (or predicted full-length gene sequences) for the members of the . candidate library listed in Table 2, Table 8, and the sequence listing. In some cases, oligonucleotide sequences are designed from EST or Chromosomal sequences from a public database. In these cases the full-length gene sequences may not be known. Full-length sequences in these cases can be predicted using gene prediction algorithms. Alternatively the full-length can be determined by cloning and sequencing the full-length gene or genes that contain the sequence of interest using standard molecular biology approaches described here. The same is true for olignonucleotides designed from our sequencing of cDNA libraries where the cDNA does not match any sequence in the public databases.

The diagnostic nucleotides may also be derived from other genes that are coexpressed with the correlated sequence or full-length gene. Genes may share expression patterns because they are regulated in the same molecular pathway. Because of the similarity of expression behavior genes are identified as surrogates in that they can substitute for a diagnostic gene in a diagnostic gene set.

Example 4 demonstrates the discovery of surrogates from the data and the sequence listing identifies and gives the sequence for surrogates for cardiac diagnostic genes.

As used herein the term “gene cluster” or “cluster” refers to a group of genes related by expression pattern. In other words, a cluster of genes is a group of genes with similar regulation across different conditions, such as graft non-rejection verus graft rejection. The expression profile for each gene in a cluster should be correlated with the expression profile of at least one other gene in that cluster. Correlation may be evaluated using a variety of statistical methods. As used herein the term : “surrogate” refers to a gene with an expression profile such that it can substitute for a diagnostic gene in a diagnostic assay. Such genes are often members of the same gene cluster as the diagnostic gene.

For each member of a diagnostic gene set, a set of potential surrogates can be identified through identification of genes with similar expression patterns as described below. .

Many statistical analyses produce a correlation coefficient to describe the relatedness between two gene expression patterns. Patterns may be considered correlated if the correlation coefficient is greater than or equal to 0.8. In preferred embodiments, the correlation coefficient should be greater than 0.85, 0.9 or 0.95. Other statistical methods produce a measure of mutual information to describe the relatedness between two gene expression patterns. Patterns may be considered correlated if the normalized mutual information value is greater than or equal to 0.7. In preferred embodiments, the normalized mutual information value should be greater than 0.8, 0.9 or 0.95. Patterns may also be considered similar if they cluster closely upon hierarchical clustering of gene expression data (Eisen et al. 1998). Similar patterns may be those genes that are among the 1, 2, 5, 10, 20, 50 or 100 nearest neighbors in a hierarchical clustering or have a similarity score (Eisen et al. 1998) of > 0.5, 0.7, 0.8, 0.9, 0.95 or 0.99. Similar patterns may also be identified as those genes found to be surrogates in a classification tree by CART (Breiman et al. 1994). Often, but not always, members of a gene cluster have similar biological functions in addition to similar gene expression patterns.

Correlated genes, clusters and surrogates are identified for the diagnostic genes of the

Co invention. These surrogates may be used as diagnostic. genes in an assay instead of, or in addition to, the diagnostic genes for which they are surrogates. Co

The invention also provides diagnostic probe sets. It is understood that a probe includes any reagent capable of specifically identifying a nucleotide sequence of the diagnostic nucleotide set, including but not limited to amplified DNA, amplified RNA, cDNA, synthetic oligonucleotide, partial

Css or full-length nucleic acid sequences. In addition, the probe may identify the protein product of a diagnostic nucleotide sequence, including, for example, antibodies and other affinity reagents.

It is also understood that each probe can correspond to one gene, or multiple probes can correspond to one gene, or both, or one probe can correspond to more than one gene.

Homologs and variants of the disclosed nucleic acid molecules may be used in the present invention. Homologs and variants of these nucleic acid molecules will possess a relatively high degree of sequence identity when aligned using standard methods. The sequences encompassed by the invention have at least 40-50, 50-60, 70-80, 80-85, 85-90, 90-95 or 95-100% sequence identity to the sequences disclosed herein.

It is understood that for expression profiling, variations in the disclosed sequences will still permit detection of gene expression. The degree of sequence identity required to detect gene expression varies depending on the length of the oligomer. For a 60 mer, 6-8 random mutations or 6-8 random deletions in a 60 mer do not affect gene expression detection. Hughes, TR, et al. "Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer. Nature Biotechnology, 19:343-347(2001). As the length of the DNA sequence is increased, the number of mutations or deletions permitted while still allowing gene expression detection is increased.

As will be appreciated by those skilled in the art, the sequences of the present invention may contain sequencing errors. That is, there may be incorrect nucleotides, frameshifts, unknown nucleotides, or other types of sequencing errors in any of the sequences; however, the correct sequences will fall within the homology and stringency definitions herein. .

The minimum length of an oligonucleotide probe necessary for specific hybridization in the human genome can be estimated using two approaches. The first method uses a statistical argument that the probe will be unique in the human genome by chance. Briefly, the number of independent perfect matches (Po) expected for an oligonucleotide of length L in a genome of complexity C can be - calculated from the equation (Laird CD, Chromosoma 32:378 (1971):

Po=(1/4)* *2C

In the case of mammalian genomes, 2C = ~3.6 X 10”, and an oligonucleotide of 14-15 nucleotides is expected to be represented only once in the genome. However, the distribution of nucleotides in the coding sequence of mammalian genomes is nonrandom (Lathe, R. J. Mol. Biol. 183:1 (1985) and longer oligonucleotides may be preferred in order to in increase the specificity of hybridization. In practical terms, this works out to probes that are 19-40 nucleotides long (Sambrook J et al., infra). The second method for estimating the length of a specific probe is to use a probe long enough to hybridize under the chosen conditions and use a computer to search for that sequence or close matches to the sequence in the human genome and choose a unique match. Probe sequences are chosen based on the desired hybridization properties as described in Chapter 11 of Sambrook et al, infra. The PRIMERS3 program is useful for designing these probes (S. Rozen and H. Skaletsky a oo 1996,1997; Primer3 code available at the web site located at . genome. wi.mit.edw/genome_software/other/primer3. html). The sequences of these probes are then compared pair wise against a database of the human genome sequences using a program such as ‘BLAST or MEGABLAST (Madden, T.L et al.(1996) Meth. Enzymol. 266:131-141). Since most of the human genome is now contained in the database, the number of matches will be determined. Probe sequences are chosen that are unique to the desired target sequence. .

In some embodiments, a diagnostic probe set is immobilized on an array. The array is optionally comprises one or more of: a chip array, a plate array, a bead array, a pin array, a membrane array, a solid surface array, a liquid array, an oligonucleotide array, a polynucleotide array or a cDNA array, a microtiter plate, a pin aay, a bead array, a membrane or a chip.

In some embodiments, the leukocyte-implicated disease is selected from the diseases listed in

Table 1. In other embodiments, In some embodiments, the disease is atherosclerosis or cardiac allograft rejection. In other embodiments, the disease is congestive heart failure, angina, and myocardial infarction.

In some embodiments, diagnostic nucleotides of the invention are used as a diagnostic gene set in combination with genes that are know to be associated with a disease state (“known markers”).

The use of the diagnostic nucleotides in combination with the known markers can provide information that is not obtainable through the known markers alone. The known markers include those identified by the prior art listing provided.

Hematopoeisis

The present invention is also directed to methods of measurement of the rate of hematopoiesis using the diagnostic oligonucleotides of the invention and measurement of the rates of hematopoesis by any technique as a method for the monitoring and diagnosis of transplant rejection. Precursor and immature cells often have cell specific phenotypic markers. These are genes and/or proteins that expressed in a restricted manner in immature or precursor cells. This expression decreases with maturation. Gene expression markers for immature cells of a variety of lineages are given in Table 10 below by way of example.

Table 10: [Gene [cen type

CD10 B-lymphoblasts

Blymphoblasts

Bdymphoblasts

NF-E2 Piatelets/Megakaryocyte/Erythroid

GATA-1 Platelets/Megakaryocyte

GP lib Platelets pl [Platelets

EPO-R Erythroblast

Band 4.1 Erythrocyte

ALAS2 Erythroid specific heme biosynthesis hemoglobin chains |Erythocyte 2,3-BPG mutase {Erythrocyte

CD16b Neutrophil

LAP [Neutrophil RENE

CD16 NK cells

CD159a - [NK cells RE ce ‘

By measuring the levels of these and other genes in peripheral blood samples, an assessment : of the number and proportion of immature or precursor cells can be made. Of particular use is RNA quantification in erythrocytes and platelets. These cells are anucleated in their mature forms. During development, platelets pinch off of a megakaryocyte and take a compliment of RNA without a nucleus.

This RNA is quickly consumed by the platelet. Erythrocytes start as nucleated cells, but the nucleus extrudes toward the end of the maturation process. These cells have RNA which is rapidly consumed within the first 2 days of the cells 120 day life span.

For these anucleated cell types, gene expression markers must be specific only to the cell line (and not the immature form) to be useful as measures of cellular production rates. Genes specific to the lineage vs. other blood cell types will serve as markers of cellular production rates when measured on the RNA level. This is because RNA is specific to immature forms in these cases. For example, hemoglobin is specific to erythrocytes, but hemoglobin RNA is specific to newly produced erythrocytes. Therefore, if the rate of production of erythrocytes increases, so will the level of a lineage specific RNA (e.g., hemoglobin).

Hematopoietic growth factors and cytokines have incomplete lineage specificity. G-CSF is administered to patient with low granulocyte counts and the effect is a stimulation of all lineages (granulocytes, erythrocytes, platelets, etc...). Hemolytic anemia leads to increased production of multiple cell lineages although the only lineage in increased demand is the erythrocyte. Because of this lack of specificity of hematopoietic responses, erythrocyte and platelet production rates may serve as surrogates of increased production of lymphocyte lineages. Using RBCs and platelets production rates as surrogates for lymphocyte lineages may be useful because of the lack of a nucleus in these cells and the ease of measuring cellular production rates by simply measuring lineage specific RNA levels.

Hematopoieis rates can be measured using gene expression profiling of peripheral blood.

RBC and platelet specific genes provide unique opportunity for this because of their lack of a nucleus and kinetics. New cells = new / much more RNA from these cell types in peripheral blood. Immature lymphocytes may be even more specific for immune activation and rejection. Cell specific markers of ’ lymphocyte precursors were identified (aka lymphoblasts) see below. Granulocyte precursors and markers of megakaryocytes or premature forms of any blood cells may be useful in this regard.

Applications for measuring the rate of hematopoiesis

Changes in the rate of hematopoiesis have been correlated to a number of disease states and other pathologies. Examples of such conditions are listed in Table 11. One of skill in the art would be aware of other such conditions. In addition, one aspect of the present invention is the identification of the linkage between changes in the rate of hematopoiesis. The methods of the present invention directed to measuring the rates of hematopoiesis can therefore be applied to the diagnosis and monitoring of a number of disease states and other pathologies. In addition, these methods can be beneficial in determining appropriate therapies for patients.

Table: 11 al |: PPO J } production .

Deficienc deficienc

Anemia — hemolytic Erythrocyte Increased Immunosuppression,

Splenectom : Anemia — Renal failure | Erythrocyte | Decreased | Erythropoietin

Anemia — Chronic Erythrocyte Decreased Treat underlying cause disease ’ ’

Polycythemia rubra .. | Erythrocyte Increased vera .

Idiophic Platelet "| Increased Immunosuppression,

Thrrombocytopenic Splenectomy . purpura .

Thrombotic Platelet Increased or Immunosuppression,

Thrombocytopenic decreased plasmapheresis purpura

Essential Platelet Increased thrombocytosis

Leukemia All lineages, Increase, Chemotherapy, BMT variable decreased or abnomal

Cytopenias due to All lineages, Epo, neupogen immunosupression variable Decreased

Cytopenias due to All lineages, Decreased Epo, GCSF, GMCSF

Chemotherap variable

GVHD All lineages, Decreased Immunosuppression variable

Myelodysplasia All lineages, Decreased, Chemo? variable increased or abnormal

Allograft rejection Lymphocytes, Increased Immunosuppression

All lineages

Autoimmune diseases Lymphocytes, Increased Immunosuppression man All lineages

The methods of the present invention are also useful for monitoring treatinent regimens of diseases or other pathologies which are correlated with changes in the rate of hematopoiesis.

Furthermore, the methods may be used to monitor treatment with agents that affect the rate of hematopoiesis. One of skill in the art is aware of many such agents. The following agents are examples of such.

Erythropoietin is a growth factor that is used to treat a variety of anemias that are due to decreased red cell production. Monitoring of red cell production by gene expression or other means may improve dosing and provide a means for earlier assessment of response to therapy for this : expensive drug.

Neupogen (G-CSF) is used for the treatment of low neutrophil counts (neutropenia) usually related to immunosuppression or chemotherapy. Monitoring neutrophil production by gene expression testing or another means may improve dosing, patient selection, and shorten duration of therapy.

Prednisone / Immunosuppression — One of most common side effects of immunosuppression . is suppression of hematopoiesis. This may occur in any cell lineage. Gene expression monitoring or other measures of hematopoietic rates could be used to monitor regularly for cytopenias in a particular cell line and the information could be used to modify dosing, modify therapy or add a specific ‘hematologic growth factor. Following cell counts themselves is less sensitive and results in the need for prolonged trials of therapies at a given dose before efficacy and toxicity can be assessed. :

Monitoring of chemotherapeutic agents ~Most chemotherapy agents suppress the bone marrow for some or all lineages. Gene expression testing or other means of assessing hematopoietic rates could be used to monitor regularly for cytopenias in a particular cell line and use information to modify dosing, modify therapy or add a specific hematologic growth factor.

General Molecular Biology References ’ In the context of the invention, nucleic acids and/or proteins are manipulated according to well known molecular biology techniques. Detailed protocols for numerous such procedures are described in, e.g., in Ausubel et al. Current Protocols in Molecular Biology (supplemented through 2000) John

Wiley & Sons, New York (“Ausubel”); Sambrook et al. Molecular Cloning - A Laboratory Manual (2nd Ed.), Vol. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1989 (Sambrook), and Berger and Kimmel Guide to Molecular Cloning Techniques, Methods in

Enzymology volume 152 Academic Press, Inc., San Diego, CA (“Berger”).

In addition to the above references, protocols for in vitro amplification techniques, such as the polymerase chain reaction (PCR), the ligase chain reaction (LCR), Q-replicase amplification, and other

RNA polymerase mediated techniques (e.g., NASBA), useful e.g., for amplifying cDNA probes of the invention, are found in Mullis et al. (1987) U.S. Patent No. 4,683,202; PCR Protocols A Guide to

Methods and Applications (Innis et al. eds) Academic Press Inc. San Diego, CA (1990) (“Innis”);

Arnheim and Levinson (1990) C&EN 36; The Journal Of NIH Research (1991) 3:81; Kwoh et al. (1989) Proc Natl Acad Sci USA 86, 1173; Guatelli et al. (1990) Proc Natl Acad Sci USA 87:1874;

Lomell et al. (1989) J Clin Chem 35:1826; Landegren et al. (1988) Science 241:1077; Van Brunt (1990) Biotechnology 8:291; Wu and Wallace (1989) Gene 4: 560; Barringer et al. (1990) Gene 89:117, and Sooknanan and Malek (1995) Biotechnology 13:563. Additional methods, useful for cloning nucleic acids in the context of the present invention, include Wallace et al. U.S. Pat. No. ) 5,426,039. Improved methods of amplifying large nucleic acids by PCR are summarized in Cheng et al. (1994) Nature 369:684 and the references therein.

Certain polynucleotides of the invention, e.g., oligonucleotides can be synthesized utilizing various solid-phase strategies involving mononucleotide- and/or trinucleotide-based phosphoramidite coupling chemistry. For example, nucleic acid sequences can be synthesized by the sequential addition of activated monomers and/or trimers to an elongating polynucleotide chain. See e.g., Caruthers, M.H. et al. (1992) Meth Enzymol 211:3.

In lieu of synthesizing the desired sequences, essentially any nucleic acid can be custom ordered from any of a variety of commercial sources, such as The Midland Certified Reagent

Company, The Great American Gene Company ExpressGen, Inc., Operon Technologies, Inc. and many others.

Similarly, commercial sources for nucleic acid and protein microarrays are available, and include, eg. Agilent Technologies, Palo Alto, CA Affymetrix, Santa Clara,CA ; and others. " One area of relevance to the present invention is hybridization of oligonucleotides. Those of skill in the art differentiate hybridization conditions based upon the stringency of hybridization. For example, highly stringent conditions could include hybridization to filter-bound DNA in 0.5 M

NaHPO,, 7% sodium dodecyl sulfate (SDS), | mM EDTA at 65° C, and washing in 0.1XSSC/0.1%

SDS at 68° C. (Ausubel F. M. et al, eds., 1989, Current Protocols in Molecular Biology, Vol. 1, Green

Publishing Associates, Inc., and John Wiley & sons, Inc., New York, at p- 2.10.3). Moderate stringency conditions could include, e.g., washing in 0.2XSSC/0.1% SDS at 42°C. (Ausubel et al., 1989, supra).

The invention also includes nucleic acid molecules, preferably DNA molecules, that hybridize to, and are therefore the complements of, the DNA sequences of the present invention. Such hybridization conditions may be highly stringent or less highly stringent, as described above. In instances wherein the nucleic acid molecules are deoxyoligonucleotides ("oligos"), highly stringent conditions may refer, €.g., to washing in 6xSSC/0.05% sodium pyrophosphate at 37°C. (for 14-base oligos), 48°C. (for 17- base oligos), 55°C. (for 20-base oligos), and 60°C. (for 23-base oligos). These nucleic acid molecules may act as target nucleotide sequence antisense molecules, useful, for example, in target nucleotide sequence regulation and/or as antisense primers in amplification reactions of target nucleotide sequence nucleic acid sequences. Further, such sequences may be used as part of ribozyme and/or triple helix sequences, also useful for target nucleotide sequence regulation. Still further, such molecules may be used as components of diagnostic methods whereby the presence of a disease-causing allele, may be detected.

Hdentification of diagnostic nucleotide sets

Candidate library

Libraries of candidates that are differentially expressed in leukocytes are substrates for the identification and evaluation of diagnostic oligonucleotide sets and disease specific target nucleotide sequences.

The term leukocyte is used generically to refer to any nucleated blood cell that is not a nucleated erythrocyte. More specifically, leukocytes can be subdivided into two broad classes. The first class includes granulocytes, including, most prevalently, neutrophils, as well as eosinophils and basophils at low frequency. The second class, the non-granular or mononuclear leukocytes, includes monocytes and lymphocytes (e.g., T cells and B cells). There is an extensive literature in the art implicating leukocytes, e.g., neutrophils, monocytes and lymphocytes in a wide variety of disease processes, including inflammatory and rheumatic diseases, neurodegenerative diseases (such as

Alzheimer’s dementia), cardiovascular disease, endocrine diseases, transplant rejection, malignancy and infectious diseases, and other diseases listed in Table 1. Mononuclear cells are involved in the chronic immune response, while granulocytes, which make up approximately 60% of the leukocytes, have a non-specific and stereotyped response to acute inflammatory stimuli and often have a life span of only 24 hours.

In addition to their widespread involvement and/or implication in numerous disease related processes, leukocytes are particularly attractive substrates for clinical and experimental evaluation for a variety of reasons. Most importantly, they are readily accessible at low cost from essentially every potential subject. Collection is minimally invasive and associated with little pain, disability or recovery time. Collection can be performed by minimally trained personne! (e.g., phlebotomists, medical technicians, etc.) in a variety of clinical and non-clinical settings without significant a.

technological expenditure. Additionally, leukocytes are renewable, and thus available at multiple time points for a single subject.

Assembly of an initial candidate library

The initial candidate library was assembled from a combination of “mining” publication and sequence databases and construction of a differential expression library. Candidate oligonucleotide sequences in the library may be represented bya full-length or partial nucleic acid sequence, deoxyribonucleic acid (DNA) sequence, cDNA sequence, RNA sequence, synthetic oligonucleotides, etc. The nucleic acid sequence can be at least 19 nucleotides in length, at least 25 nucleotides, at least 40 nucleotides, at least 100 nucleotides, or larger. Alternatively, the protein product of a candidate nucleotide sequence may be represented in a candidate library using standard methods, as further described below. In selecting and validatating diagnostic oligonucleotides, an initial library of 8,031 candidate oligonucleotide sequences using nucleic acid sequences of 50 nucleotides in length was constructed as described below.

Candidate nucleotide library of the invention :

We identified members of an initial candidate nucleotide library that are differentially expressed in activated leukocytes and resting leukocytes. From that initial candidate nucleotide library, a pool of candidates was selected as listed in Table 2, Table 8, and the seugnce listing. Accordingly, the invention provides the candidate leukocyte nucleotide library comprising the nucleotide sequences listed in Table 2, Table 8, and in the sequence listing. In another embodiment, the invention provides an candidate library comprising at least one nucleotide sequence listed in Tables 2 and 8 and the sequence listing. In another embodiment, the invention provides an candidate library comprising at least two nucleotide sequences listed in Tables 2 and 8 and the sequence listing. In another embodiment, the at least two nucleotide sequence are at least 19 nucleotides in length, at least 35 nucleotides, at least 40 nucleotides or at least 100 nucleotides. In some embodiments, the nucleotide : sequences comprises deoxyribonucleic acid (DNA) sequence, ribonucleic acid (RNA) sequence, synthetic oligonucleotide sequence, or genomic DNA sequence. It is understood that the nucleotide sequences may each correspond to one gene, or that several nucleotide sequences may correspond to one gene, or both.

The invention also provides probes to the candidate nucleotide library. In one embodiment of the invention, the probes comprise at least two nucleotide sequences listed in Table 2, Table 8, or the sequence listing which are differentially expressed in leukocytes in an individual with a least one disease criterion for at least one leukocyte-related disease and in leukocytes in an individual without the at least one disease criterion, wherein expression of the two or more nucleotide sequences is correlated with at least one disease criterion. It is understood that a probe may detect either the RNA expression or protein product expression of the candidate nucleotide library. Alternatively, or in addition, a probe can detect a genotype associated with a candidate nucleotide sequence, as further described below. In another embodiment, the probes for the candidaten ucleotide library are immobilized on an array. : - a

The candidate nucleotide library of the invention is useful in identifying diagnostic nucleotide . sets of the invention and is itself a diagnostic nucleotide set of the invention, as described below. The candidate nucleotide sequences may be further characterized, and may be identified as a disease target © wo nucleotide sequence and/or a novel nucleotide sequence, as described below. The candidate nucleotide sequences may also be suitable for use as imaging reagents, as described below.

Detection of non-lenkocyte expressed genes

When measuring gene expression levels in a blood sample, RNAs may be measured that are not derived from leukocytes. Examples are viral genes, free RNAs that have been released from damaged non-lfeukocyte cell types or RNA from circulating non-leukocyte cell types. For example, in the process of acute allograft rejection, tissue damage may result in release of allograft cells or RNAs derived from allograft cells into the circulation. In the case of cardiac allografts, such transcripts may be specific to muscle (myoglobin) or to cardiac muscle (Troponin I, Toponin T, CK-MB). Presence of cardiac specific mRNAs in peripheral blood may indicate ongoing or recent cardiac cellular damage (resulting from acute rejection). Therefore, such genes may be excellent diagnostic markers for allograft rejection.

Generation of Expression Patterns

RNA, DNA or protein sample procurement

Following identification or assembly of a library of differentially expressed candidate nucleotide sequences, leukocyte expression profiles corresponding to multiple members of the candidate library are obtained. Leukocyte samples from one or more subjects are obtained by standard methods. Most typically, these methods involve trans-cutaneous venous sampling of peripheral blood.

While sampling of circulating leukocytes from whole blood from the peripheral vasculature is generally the simplest, least invasive, and lowest cost alternative, it will be appreciated that numerous alternative sampling procedures exist, and are favorably employed in some circumstances. No pertinent distinction exists, in fact, between leukocytes sampled from the peripheral vasculature, and those obtained, e.g., from a central line, from a central artery, or indeed from a cardiac catheter, or during a surgical procedure which accesses the central vasculature. In addition, other body fluids and tissues that are, at least in part, composed of leukocytes are also desirable leukocyte samples. For example, fluid samples obtained from the lung during bronchoscopy may be rich in leukocytes, and amenable to expression profiling in the context of the invention, e.g., for the diagnosis, prognosis, or monitoring of lung transplant rejection, inflammatory lung diseases or infectious lung disease. Fluid samples from other tissues, e.g., obtained by endoscopy of the colon, sinuses, esophagus, stomach, small bowel, pancreatic duct, biliary tree, bladder, ureter, vagina, cervix or uterus, etc., are also suitable. Samples may also be obtained other sources containing leukocytes, e.g., from urine, bile, cerebrospinal fluid, feces, gastric or intestinal secretions, semen, or solid organ or joint biopsies. :

Most frequently, mixed populations of leukocytes, such as are found in whole blood are utilized in the methods of the present invention. A crude separation, e.g., of mixed leukocytes from red _ blood cells, and/or concentration, e.g., over a sucrose, percoll or ficoll gradient, or by other methods ~~. known in the art, can be employed to facilitate the recovery of RNA or protein expression products at sufficient concentrations, and to reduce non-specific background. In some instances, it can be desirable to purify sub-populations of leukocytes, and methods for doing so, such as density or affinity gradients, flow cytometry, fluorescence Activated Cell Sorting (FACS), immuno-magnetic separation, “panning,” and the like, are described in the available literature and below. cr 3 : RE :

Obtaining DNA, RNA and protein samples for expression profiling

Expression patterns can be evaluated at the level of DNA, or RNA or protein products. For example, a variety of techniques are available for the isolation of RNA from whole blood. Any technique that allows isolation of mRNA from cells (in the presence or absence of rRNA and tRNA) can be utilized. In brief, one method that allows reliable isolation of total RNA suitable for subsequent gene expression analysis, is described as follows. Peripheral blood (either venous or arterial) is drawn

Lo from a subject, into one or more sterile, endotoxin free, tubes containing an anticoagulant (e.g., EDTA, citrate, heparin, etc.). Typically, the sample is divided into at least two portions. One portion, e.g., of 5-8 ml of whole blood is frozen and stored for future analysis, e.g., of DNA or protein. A second portion, e.g., of approximately 8 ml whole blood is processed for isolation of total RNA by any of a variety of techniques as described in, e.g, Sambook, Ausubel, below, as well as U.S. Patent Numbers: 5,728,822 and 4,843,155.

Typically, a subject sample of mononuclear leukocytes obtained from about 8 ml of whole blood, a quantity readily available from an adult human subject under most circumstances, yields 5-20 ug of total RNA. This amount is ample, ¢.g., for labeling and hybridization to at least two probe arrays. Labeled probes for analysis of expression patterns of nucleotides of the candidate libraries are prepared from the subject’s sample of RNA using standard methods. In many cases, cDNA is synthesized from total RNA using a polyT primer and labeled, e.g., radioactive or fluorescent, nucleotides. The resulting labeled cDNA is then hybridized to probes corresponding to members of the candidate nucleotide library, and expression data is obtained for each nucleotide sequence in the library. RNA isolated from subject samples (e.g., peripheral blood leukocytes, or leukocytes obtained from other biological fluids and samples) is next used for analysis of expression patterns of nucleotides of the candidate libraries.

In some cases, however, the amount of RNA that is extracted from the leukocyte sample is limiting, and amplification of the RNA is desirable. Amplification may be accomplished by increasing the efficiency of probe labeling, or by amplifying the RNA sample prior to labeling. It is appreciated that care must be taken to select an amplification procedure that does not introduce any bias (with respect to gene expression levels) during the amplification process.

Several methods are available that increase the signal from limiting amounts of RNA, e.g. use of the Clontech (Glass Fluorescent Labeling Kit) or Stratagene (Fairplay Microarray Labeling Kit), or the Micromax kit (New England Nuclear, Inc.). Alternatively, cDNA is synthesized from RNA using a

T7- polyT primer, in the absence of label, and DNA dendrimers from Genisphere (3DNA Submicro) are hybridized to the poly T sequence on the primer, or to a different “capture sequence” which is complementary to a fluorescently labeled sequence. Each 3DNA molecule has 250 fluorescent molecules and therefore can strongly label each cDNA. oo Alternatively, the RNA sample is amplified prior to labeling. For example, linear amplification may be performed, as described in U.S. Patent No. 6,132,997. A T7-polyT primer is used to generate the cDNA copy of the RNA. A second DNA strand is then made to complete the . substrate for amplification. The T7 promoter incorporated into the primer is used by a T7 polymerase to produce numerous antisense copies of the original RNA. Fluorescent dye labeled nucleotides are :

directly incorporated into the RNA. Alternatively, amino allyl labeled nucleotides are incorporated into the RNA, and then fluorescent dyes are chemically coupled to the amino allyl groups, as described - in Hughes. Other exemplary methods for amplification are described below.

Itis appreciated that the RNA isolated must contain RNA derived from leukocytes, but may also contain RNA from other cell types to a variable degree. Additionally, the isolated RNA may come from subsets of leukocytes, e.g. monocytes and/or T-lymphocytes, as described above. Such consideration of cell type used for the derivation of RNA depend on the method of expression profiling used. Subsets of leukocytes can be obtained by fluorescence activated cell sorting (FACS), microfluidics cell seperation systems or a variety of other methods. Cell sorting may be necessary for the discovery of diagnostic gene sets, for the implementation of gene sets as products or both. Cell sorting can be achieved with a variety of technologies (See Galbraith et al. 1999, Cantor et al. 1975, see also the technology of Guava Technologies, Hayward, CA).

DNA samples may be obtained for analysis of the presence of DNA mutations, single nucleotide polymorphisms (SNPs), or other polymorphisms. DNA is isolated using standard techniques, e.g. Maniatus, supra.

Expression of products of candidate nucleotides may also be assessed using proteomics.

Protein(s) are detected in samples of patient serum or from leukocyte cellular protein. Serum is prepared by centrifugation of whole blood, using standard methods. Proteins present in the serum may ~ have been produced from any of a variety of leukocytes and non-leukocyte cells, and include secreted proteins from leukocytes. Alternatively, leukocytes or a desired sub-population of leukocytes are prepared as described above. Cellular protein is prepared from leukocyte samples using methods well known in the art, e.g., Trizol (Invitrogen Life Technologies, cat # 15596108; Chomczynski, P. and

Sacchi, N. (1987) Anal. Biochem. 162, 156; Simms, D., Cizdziel, P.E., and Chomczynski, P. (1993)

Focus® 15, 99; Chomczynski, P., Bowers-Finn, R., and Sabatini, L. (1987) J. of NIH Res. 6, 83;

Chomczynski, P. (1993) Bio/Techniques 15, 532; Bracete, A.M, Fox, D.K,, and Simms, D. (1998)

Focus 20, 82; Sewall, A. and McRae, S. (1998) Focus 20, 36; Anal Biochem 1984 Apr;138(1):141-3, A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids; Wessel D, Flugge UI. (1984) Anal Biochem. 1984 Apr;138(1):141-143.

The assay itself may be a cell sorting assay in which cells are sorted and/or counted based on cell surface expression of a protein marker. (See Cantor et al. 1975, Galbraith et al. 1999)

Obtaining expression patterns

Expression patterns, or profiles, of a plurality of nucleotides corresponding to members of the candidate library are then evaluated in one or more samples of leukocytes. Typically, the leukocytes are derived from patient peripheral blood samples, although, as indicated above, many other sample sources are also suitable. These expression patterns constitute a set of relative or absolute expression . values for a some number of RNAs or protein products corresponding to the plurality of nucleotide sequences evaluated, which is referred to herein as the subject’s “expression profile” for those nucleotide sequences. While expression patterns for as few as one independent member of the . _ candidate library can be obtained, it is generally preferable to obtain expression patterns corresponding to a larger number of nucleotide sequences, e.g., about 2, about 5, about 10, about 20, about 50, about

100, about 200, about 500, or about 1000, or more. The expression pattern for cach differentially expressed component member of the library provides a finite specificity and sensitivity with respect to predictive value, e.g., for diagnosis, prognosis, monitoring, and the like.

Clinical Studies, Data and Patient Groups

For the purpose of discussion, the term subject, or subject sample of leukocytes, refers to an individual regardless of health and/or disease status. A subject can be a patient, a study participant, a . control subject, a screening subject, or any other class of individual from whom a leukocyte sample is obtained and assessed in the context of the invention. Accordingly, a subject can be diagnosed with a disease, can present with one or more symptom of a disease, or a predisposing factor, such as a family (genetic) or medical history (medical) factor, for a disease, or the like. Alternatively, a subject can be healthy with respect 10 any of the aforementioned factors or criteria. It will be appreciated that the term “healthy” as used herein, is relative to a specified disease, or disease factor, or disease criterion, as the term “healthy” cannot be defined to correspond to any absolute evaluation or status. Thus, an individual defined as healthy with reference to any specified disease or disease criterion, can in fact be diagnosed with any other one or more disease, or exhibit any other one or more disease criterion.

Furthermore, while the discussion of the invention focuses, and is exemplified using human sequences and samples, the invention is equally applicable, through construction or selection of appropriate candidate libraries, to non-human animals, such as laboratory animals, e.g., mice, rats, } guinea pigs, rabbits; domesticated livestock, e.g., cows, horses, goats, sheep, chicken, etc.; and companion animals, e.g., dogs, cats, etc.

Methods for obtaining expression data

Numerous methods for obtaining expression data are known, and any one or more of these techniques, singly or in combination, are suitable for determining expression profiles in the context of the present invention. For example, expression patterns can be evaluated by northern analysis, PCR,

RT-PCR, Taq Man analysis, FRET detection, monitoring one or more molecular beacon, hybridization to an oligonucleotide array, hybridization to a cDNA array, hybridization to a polynucleotide array, hybridization to a liquid microarray, hybridization to a microelectric array, molecular beacons, cDNA sequencing, clone hybridization, cDNA fragment fingerprinting, serial analysis of gene expression (SAGE), subtractive hybridization, differential display and/or differential screening (see, e.g., Lockhart and Winzeler (2000) Nature 405:827-836, and references cited therein).

For example, specific PCR primers are designed to a member(s) of an candidate nucleotide library. ¢cDNA is prepared from subject sample RNA by reverse transcription from a poly-dT oligonucleotide primer, and subjected to PCR. Double stranded cDNA may be prepared using primers suitable for reverse transcription of the PCR product, followed by amplification of the cDNA using in vitro transcription. The product of in vitro transcription is a sense-RNA corresponding to the original oo member(s) of the candidate library. PCR product may be also be evaluated in a number of ways known in the art, including real-time assessment using detection of labeled primers, eg. TaqMan or molecular beacon probes. Technology platforms suitable for analysis of PCR products include the ABI 7700, 5700, or 7000 Sequence Detection Systems (Applied Biosystems, Foster City, CA), the MJ Research

Opticon (MJ Research, Waltham, MA), the Roche Light Cycler (Roche Diagnositics, Indianapolis, IN),

the Stratagene MX4000 (Stratagene, La Jolla, CA), and the Bio-Rad iCycler (Bio-Rad Laboratories,

Hercules, CA). Alternatively, molecular beacons are used to detect presence of a nucleic acid sequence in an unamplified RNA or cDNA sample, or following amplification of the sequence using any method, e.g. IVT (In Vitro transcription) or NASBA (nucleic acid sequence based amplification).

Molecular beacons are designed with sequences complementary to member(s) of an candidate nucleotide library, and are linked to fluorescent labels. Each probe has a different fluorescent label with non-overlapping emission wavelengths. For example, expression of ten genes may be assessed using ten different sequence-specific molecular beacons.

Alternatively, or in addition, molecular beacons are used to assess expression of multiple nucleotide sequences at once. Molecular beacons with sequence complimentary to the members of a diagnostic nucleotide set are designed and linked to fluorescent labels. Each fluorescent label used must have a non-overlapping emission wavelength. For example, 10 nucleotide sequences can be assessed by hybridizing 10 sequence specific molecular beacons (each labeled with a different fluorescent molecule) to an amplified or un-amplified RNA or cDNA sample. Such an assay bypasses the need for sample labeling procedures.

Alternatively, or in addition bead arrays can be used to assess expression of multiple sequences at once. See, e.g, LabMAP 100, Luminex Corp, Austin, Texas). Alternatively, or in addition electric arrays are used to assess expression of multiple sequences, as exemplified by the e-

Sensor technology of Motorola (Chicago, 111.) or Nanochip technology of Nanogen (San Diego, CA.)

Of course, the particular method elected will be dependent on such factors as quantity of RNA recovered, practitioner preference, available reagents and equipment, detectors, and the like. Typically, however, the elected method(s) will be appropriate for processing the number of samples and probes of interest. Methods for high-throughput expression analysis are discussed below.

Alternatively, expression at the level of protein products of gene expression is performed. For example, protein expression, in a sample of leukocytes, can be evaluated by one or more method selected from among: western analysis, two-dimensional gel analysis, chromatographic separation, mass spectrometric detection, protein-fusion reporter constructs, colorimetric assays, binding to a protein array and characterization of polysomal mRNA. One particularly favorable approach involves binding of labeled protein expression products to an array of antibodies specific for members of the candidate library. Methods for producing and evaluating antibodies are widespread in the art, see, €.g.,

Coligan, supra; and Harlow and Lane (1989) Antibodies: A Laboratory Manual, Cold Spring Harbor

Press, NY (“Harlow and Lane™). Additional details regarding a variety of immunological and immunoassay procedures adaptable to the present invention by selection of antibody reagents specific . for the products of candidate nucleotide sequences can be found in, e.g., Stites and Terr (eds.)(1991)

Basic and Clinical Immunology, 7™ ed., and Paul, supra. Another approach uses systems for performing desorption spectrometry. Commercially available systems, e.g., from Ciphergen

Biosystems, Inc. (Fremont, CA) are particularly well suited to quantitative analysis of protein expression. Indeed, Protein Chip® arrays (see, e.g., the web site ciphergen.com) used in desorption ] spectrometry approaches provide arrays for detection of protein expression. Alternatively, affinity . reagents, e.g., antibodies, small molecules, etc.) are developed that recognize epitopes of the protein product. Affinity assays are used in protein array assays, €.g. to detect the presence or absence of particular proteins. Alternatively, affinity reagents are used to detect expression using the methods described above. In the case of a protein that is expressed on the cell surface of leukocytes, labeled affinity reagents are bound to populations of leukocytes, and leukocytes expressing the protein are identified and counted using fluorescent activated cell sorting (FACS),

It is appreciated that the methods of expression evaluation discussed herein, although discussed in the context of discovery of diagnostic nucleotide sets, are equally applicable for oo expression evaluation when using diagnostic nucleotide sets for, e.g. diagnosis of diseases, as further discussed below.

High Throughput Expression Assays

A number of suitable high throughput formats exist for evaluating gene expression. Typically, the term high throughput refers to a format that performs at least about 100 assays, or at least about 500 assays, or at least about 1000 assays, or at least about 5000 assays, or at least about 10,000 assays, or more per day. When enumerating assays, either the number of samples or the number of candidate . nucleotide sequences evaluated can be considered. For example, a northern analysis of, e.g., about 100 samples performed in a gridded array, e.g., a dot blot, using a single probe corresponding to an candidate nucleotide sequence can be considered a high throughput assay. More typically, however, such an assay is performed as a series of duplicate blots, each evaluated with a distinct probe : corresponding to a different member of the candidate library. Alternatively, methods that simultaneously evaluate expression of about 100 or more candidate nucleotide sequences in one or more samples, or in multiple samples, are considered high throughput.

Numerous technological platforms for performing high throughput expression analysis are known. Generally, such methods involve a logical or physical array of either the subject samples, or the candidate library, or both. Common array formats include both liquid and solid phase arrays. For example, assays employing liquid phase arrays, e.g., for hybridization of nucleic acids, binding of antibodies or other receptors to ligand, etc., can be performed in multiwell, or microtiter, plates.

Microtiter plates with 96, 384 or 1536 wells are widely available, and even higher numbers of wells, e.g, 3456 and 9600 can be used. In general, the choice of microtiter plates is determined by the methods and equipment, e.g., robotic handling and loading systems, used for sample preparation and analysis. Exemplary systems include, e.g., the ORCA™ system from Beckman-Coulter, Inc. (Fullerton, CA) and the Zymate systems from Zymark Corporation (Hopkinton, MA).

Alternatively, a variety of solid phase arrays can favorably be employed in to determine expression patterns in the context of the invention. Exemplary formats include membrane or filter arrays (e.g, nitrocellulose, nylon), pin arrays, and bead arrays (e.g., in a liquid “slurry™). Typically, probes corresponding to nucleic acid or protein reagents that specifically interact with (e.g., hybridize . . to or bind to) an expression product corresponding to a member of the candidate library are } "immobilized, for example by direct or. indirect cross-linking, to the solid support. Essentially any solid support capable of withstanding the reagents and conditions necessary for performing the particular expression assay can be utilized. For example, functionalized glass, silicon, silicon dioxide, modified . silicon, any of a variety of polymers, such as (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, : | Co | 68 polystyrene, polycarbonate, or combinations thereof can all serve as the substrate for a solid phase - array. a

In a preferred embodiment, the array is a “chip” composed, e.g., of onc of the above specified materials. Polynucleotide probes, e.g., RNA or DNA, such as cDNA, synthetic oligonucleotides, and the like, or binding proteins such as antibodies, that specifically interact with expression products of individual components of the candidate library are affixed to the chip in a logically ordered manner, } Le., in an array. In addition, any molecule with a specific affinity for either the sense or anti-sense sequence of the marker nucleotide sequence (depending on the design of the sample labeling), can be fixed to the array surface without loss of specific affinity for the marker and can be obtained and : produced for array production, for example, proteins that specifically recognize the specific nucleic acid sequence of the marker, ribozymes, peptide nucleic acids (PNA), or other chemicals or molecules with specific affinity.

Detailed discussion of methods for linking nucleic acids and proteins to a chip substrate, are found in, e.g., US Patent No. 5,143,854 “LARGE SCALE PHOTOLITHOGRAPHIC SOLID PHASE

SYNTHESIS OF POLYPEPTIDES AND RECEPTOR BINDING SCREENING THEREOF” to

Pirrung et al, issued, September 1, 1992; US Patent No. 5,837,832 “ARRAYS OF NUCLEIC ACID

PROBES ON BIOLOGICAL CHIPS” to Chee et al., issued November 17, 1998; US Patent No. 6,087,112 “ARRAYS WITH MODIFIED OLIGONUCLEOTIDE AND POLYNUCLEOTIDE

COMPOSITIONS?” to Dale, issued July 11, 2000; US Patent No. 5,215,882 “METHOD OF

IMMOBILIZING NUCLEIC ACID ON A SOLID SUBSTRATE FOR USE IN NUCLEIC ACID

HYBRIDIZATION ASSAYS” to Bahl et al, issued June 1, 1993; US Patent No. 5,707,807 “MOLECULAR INDEXING FOR EXPRESSED GENE ANALYSIS” to Kato, issued J anuary 13, 1998; US Patent No. 5,807,522 “METHODS FOR FABRICATING MICROARRAYS OF

BIOLOGICAL SAMPLES” to Brown et al., issued September 15, 1998; US Patent No. 5,958,342 “JET DROPLET DEVICE” to Gamble et al., issued Sept. 28, 1999; US Patent 5,994,076 “METHODS

OF ASSAYING DIFFERENTIAL EXPRESSION” to Chenchik et al., issued Nov. 30, 1999; US Patent

No. 6,004,755 “QUANTITATIVE MICROARRAY HYBRIDIZATION ASSAYS” to Wang, issued

Dec. 21, 1999; US Patent No. 6,048,695 “CHEMICALLY MODIFIED NUCLEIC ACIDS AND

METHOD FOR COUPLING NUCLEIC ACIDS TO SOLID SUPPORT” to Bradley et al., issued April 11, 2000; US Patent No. 6,060,240 “METHODS FOR MEASURING RELATIVE AMOUNTS OF

NUCLEIC ACIDS IN A COMPLEX MIXTURE AND RETRIEVAL OF SPECIFIC SEQUENCES

THEREFROM” to Kamb et al., issued May 9, 2000; US Patent No. 6,090,556 “METHOD FOR

QUANTITATIVELY DETERMINING THE EXPRESSION OF A GENE” to Kato, issued July 18, 2000; and US Patent 6,040,138 “EXPRESSION MONITORING BY HYBRIDIZATION TO HIGH

DENSITY OLIGONUCLEQTIDE ARRAYS” to Lockhart et al, issued March 21, 2000 each of which are hereby incorporated by reference in their entirety, » ’ } "For example, cDNA inserts corresponding to candidate nucleotide sequences, in a standard }

TA cloning vector are amplified by a polymerase chain reaction for approximately 30-40 cycles. The amplified PCR products are then arrayed onto a glass suppor by any of a variety of well known techniques, e.g, the VSLIPS™ technology described in US Patent No. 5,143,854. RNA, or cDNA

EE | 69 corresponding to RNA, isolated from a subject sample of leukocytes is labeled, e.g., with a fluorescent tag, and a solution containing the RNA (or cDNA) is incubated under conditions favorable for hybridization, with the “probe” chip. Following incubation, and washing to eliminate non-specific hybridization, the labeled nucleic acid bound to the chip is detected qualitatively or quantitatively, and oo the resulting expression profile for the corresponding candidate nucleotide sequences is recorded. It is appreciated that the probe used for diagnostic purposes may be identical to the probe used during diagnostic nucleotide sequence discovery and validation. Alternatively, the probe sequence may be different than the sequence used in diagnostic nucleotide sequence discovery and validation. Multiple cDNAs from a nucleotide sequence that are non-overlapping or partially overlapping may also be used.

In another approach, oligonucleotides corresponding to members of an candidate nucleotide library are synthesized and spotted onto an array. Alternatively, oligonucleotides are synthesized onto the array using methods known in the art, e.g. Hughes, et al. supra. The oligonucleotide is designed to be complementary to any portion of the candidate nucleotide sequence. In addition, in the context of expression analysis for, e.g. diagnostic use of diagnostic nucleotide sets, an oligonucleotide can be designed to exhibit particular hybridization characteristics, or to exhibit a particular specificity and/or sensitivity, as further described below.

Hybridization signal may be amplified using methods known in the art, and as described herein, for example use of the Clontech kit (Glass Fluorescent Labeling Kit), Stratagene kit (Fairplay

Microarray Labeling Kit), the Micromax kit (New England Nuclear, Inc.), the Genisphere kit (3DNA

Submicro), linear amplification, e.g. as described in U.S. Patent No. 6,132,997 or described in Hughes,

TR, et al, Nature Biotechnology, 19:343-347 (2001) and/or Westin et al. Nat Biotech. 18:199-204.

Alternatively, fluorescently labeled cDNA are hybridized directly to the microarray using methods known in the art. For example, labeled cDNA are generated by reverse transcription using

Cy3- and Cy5-conjugated deoxynucleotide, and the reaction products purified using standard methods.

It 1s appreciated that the methods for signal amplification of expression data useful for identifying diagnostic nucleotide sets are also useful for amplification of expression data for diagnostic purposes.

Microarray expression may be detected by scanning the microarray with a variety of laser or

CCD-based scanners, and extracting features with numerous software packages, for example, Imagene (Biodiscovery), Feature Extraction (Agilent), Scanalyze (Eisen, M. 1999. SCANALYZE User Manual;

Stanford Univ., Stanford, CA. Ver 2.32.), GenePix (Axon Instruments).

In another approach, hybridization to microelectric arrays is performed, e.g. as described in

Umek et al (2001) J Mol Diagn. 3:74-84. An affinity probe, e.g. DNA, is deposited on a metal surface.

The metal surface underlying each probe is connected to a metal wire and electrical signal detection system. Unlabelled RNA or cDNA is hybridized to the array, or alternatively, RNA or cDNA sample is amplified before hybridization, e.g. by PCR. Specific hybridization of sample RNA or cDNA results i oo } in generation of an electrical signal, which is transmitted to a detector, See Westin (2000) Nat Biotech, - | 1 8:199-204 (describing anchored multiplex amplification of a microelectronic chip array); Edman : (1997) NAR 25:4907-14; Vignali (2000) J Immunol Methods 243:243-55.

In another approach, a microfluidics chip is used for RNA sample preparation and analysis.

This approach increases efficiency because sample preparation and analysis are streamlined. Briefly,

microfluidics may be used to sort specific leukocyte sub-populations prior to RNA preparation and analysis. Microfluidics chips are also useful for, e.g., RNA preparation, and reactions involving RNA (reverse transcription, RT-PCR). Briefly, a small volume of whole, anti-coagulated blood is loaded onto a microfluidics chip, for example chips available from Caliper (Mountain View, CA) or Nanogen (San Diego, CA) A microfluidics chip may contain channels and reservoirs in which cells are moved "and reactions are performed. Mechanical, electrical, magnetic, gravitational, centrifugal or other forces are used to move the cells and to expose them to reagents. For example, cells of whole blood are moved into a chamber containing hypotonic saline, which results in selective lysis of red blood cells after a 20-minute incubation. Next, the remaining cells (leukocytes) are moved into a wash chamber and finally, moved into a chamber containing a lysis buffer such as guanidine isothyocyanate. The leukocyte cell lysate is further processed for RNA isolation in the chip, or is then removed for further processing, for example, RNA extraction by standard methods. Alternatively, the microfluidics chip is a circular disk containing ficoll or another density reagent. The blood sample is injected into the center of the disc, the disc is rotated at a speed that generates a centrifugal force appropriate for density gradient separation of mononuclear cells, and the separated mononuclear cells are then harvested for further analysis or processing. 1t is understood that the methods of expression evaluation, above, although discussed in the context of discovery of diagnostic nucleotide sets, are also applicable for expression evaluation when using diagnostic nucleotide sets for, e.g. diagnosis of diseases, as further discussed below.

Evaluation of expression patterns

Expression patterns can be evaluated by qualitative and/or quantitative measures. Certain of the above described techniques for evaluating gene expression (as RNA or protein products) yield data that are predominantly qualitative in nature. That is, the methods detect differences in expression that classify expression into distinct modes without providing significant information regarding quantitative aspects of expression. For example, a technique can be described as a qualitative technique if it detects the presence or absence of expression of an candidate nucleotide sequence, i.e., an on/off pattern of expression. Alternatively, a qualitative technique measures the presence (and/or absence) of different alleles, or variants, of a gene product.

In contrast, some methods provide data that characterizes expression in a quantitative manner.

That is, the methods relate expression on a numerical scale, e.g., a scale of 0-5, a scale of 1-10, a scale of + - +++, from grade 1 to grade 5, a grade from a to z, or the like. It will be understood that the numerical, and symbolic examples provided are arbitrary, and that any graduated scale (or any symbolic representation of a graduated scale) can be employed in the context of the present invention to describe quantitative differences in nucleotide sequence expression. Typically, such methods yield information corresponding to a relative increase or decrease in expression.

Any method that yields either quantitative or qualitative expression data is suitable for evaluating expression of candidate nucleotide sequence ia subject sample of leukocytes. In some cases, eg. when multiple methods are employed to determine expression patterns for a plurality of candidate nucleotide sequences, the recovered data, e.g., the expression profile, for the nucleotide sequences is a combination of quantitative and qualitative data. : mn

In some applications, expression of the plurality of candidate nucleotide sequences is evaluated sequentially. This is typically the case for methods that can be characterized as Jow- to moderate-throughput. In contrast, as the throughput of the elected assay increases, expression for the plurality of candidate nucleotide sequences in a sample or multiple samples of leukocytes, is assayed . . . simultaneously. Again, the methods (and throughput) are largely determined by the individual ] practitioner, although, typically, it is preferable to employ methods that permit rapid, e.g. automated or partially automated, preparation and detection, on a scale that is time-efficient and cost-effective.

It is understood that the preceding discussion, while directed at the assessment of expression of the members of candidate libraries, is also applies to the assessment of the expression of members of diagnostic nucleotide sets, as further discussed below.

Genotyping

In addition to, or in conjunction with the correlation of expression profiles and clinical data, it is often desirable to correlate expression patterns with the subject’s genotype at one or more genetic loci. The selected loci can be, for example, chromosomal loci corresponding to one or more member of the candidate library, polymorphic alleles for marker loci, or alternative disease related loci (not contributing to the candidate library) known to be, or putatively associated with, a disease (or disease criterion). Indeed, it will be appreciated, that where a (polymorphic) allele at a locus is linked to a disease (or to a predisposition to a disease), the presence of the allele can itself be a disease criterion.

Numerous well known methods exist for evaluating the genotype of an individual, including southern analysis, restriction fragment length polymorphism (RFLP) analysis, polymerase chain reaction (PCR), amplification length polymorphism (AFLP) analysis, single stranded conformation polymorphism (SSCP) analysis, single nucleotide polymorphism (SNP) analysis (e.g., via PCR,

Tagman or molecular beacons), among many other useful methods. Many such procedures are readily adaptable to high throughput and/or automated (or semi-automated) sample preparation and analysis methods. Most, can be performed on nucleic acid samples recovered via simple procedures from the same sample of leukocytes as yielded the material for expression profiling. Exemplary techniques are described in, e.g., Sambrook, and Ausubel, supra.

Identification of the diagnostic nucleotide sets of the invention

Identification of diagnostic nucleotide sets and disease specific target nucleotide sequence proceeds by correlating the leukocyte expression profiles with data regarding the subject’s health status to produce a data set designated a “molecular signature.” Examples of data regarding a patient’s health status, also termed “disease criteria(ion)”, is described below and in the Section titled “selected diseases,” below. Methods useful for correlation analysis are further described elsewhere in the specification. ‘Generally, relevant data regarding the subject’s health status includes retrospective or ) prospective health data, eg, in the form of the subject’s medical history, as provided by the subject, physician or third party, such as, medical diagnoses, laboratory test results, diagnostic test results, clinical events, or medication lists, as further described below. Such data may include information : regarding a patient’s response to treatment and/or a particular medication and data regarding the presence of previously characterized “risk factors.” For example, cigarette smoking and obesity are

Ea oo previously identified risk factors for heart disease. Further examples of health status information, including diseases and disease criteria, 1s described in the section titled Selected diseases, below.

Typically, the data describes prior events and evaluations (i.e., retrospective data). However, it is envisioned that data collected subsequent to the sampling (i.e., prospective data) can also be correlated with the expression profile. The tissue sampled, e.g., peripheral blood, bronchial lavage, etc., can be obtained at one or more multiple time points and subject data is considered retrospective or prospective with respect to the time of sample procurement.

Data collected at multiple time points, called “longitudinal data”, is often useful, and thus, the invention encompasses the analysis of patient data collected from the same patient at different time points. Analysis of paired samples, such as samples from a patient at different time, allows identification of differences that are specifically related to the disease state since the genetic variability specific to the patient is controlled for by the comparison. Additionally, other variables that exist between patients may be controlled for in this way, for example, the presence or absence of inflammatory diseases (e.g., rheumatoid arthritis) the use of medications that may effect leukocyte gene expression, the presence or absence of co-morbid conditions, etc. Methods for analysis of paired samples are further described below. Moreover, the analysis of a pattern of expression profiles (generated by collecting multiple expression profiles) provides information relating to changes in expression level over time, and may permit the determination of a rate of change, a trajectory, or an expression curve. Two longitudinal samples may provide information on the change in expression of a gene over time, while three longitudinal samples may be necessary to determine the “trajectory” of expression of a gene. Such information may be relevant to the diagnosis of a disease. For example, the expression of a gene may vary from individual to individual, but a clinical event, for example , a heart attack, may cause the level of expression to double in each patient. In this example, clinically interesting information is gleaned from the change in expression level, as opposed to the absolute level of expression in each individual.

When a single patient sample is obtained, it may still be desirable to compare the expression profile of that sample to some reference expression profile. In this case, one can determine the change of expression between the patient’s sample and a reference expression profile that is appropriate for that patient and the medical condition in question. For example, a reference expression profile can be determined for all patients without the disease criterion in question who have similar characteristics, such as age, sex, race, diagnoses etc.

Generally, small sample sizes of 20-100 samples are used to identify a diagnostic nucleotide set. Larger sample sizes are generally necessary to validate the diagnostic nucleotide set for use in large and varied patient populations, as further described below. For example, extension of gene expression correlations to varied ethnic groups, demographic groups, nations, peoples or races may

Co require expression correlation experiments on the population of interest. “Expression Reference Standards a.

Expression profiles derived from a patient (i.e., subjects diagnosed with, or exhibiting symptoms of, or exhibiting a disease criterion, or under a doctor's care for a disease) sample are compared 10 a control or standard expression RNA to facilitate comparison of expression profiles (e.g.

of a set of candidate nucleotide sequences) from a group of patients relative to each other (i.e., from one patient in the group to other patients in the group, of to patients in another group).

The reference RNA used should have desirable features of low cost and simplicity of production on a large scale. Additionally, the reference RNA should contain measurable amounts of as many of the genes of the candidate library as possible. Cl

For example, in one approach to identifying diagnostic nucleotide sets, expression profiles derived from patient samples are compared to a expression reference “standard.” Standard expression reference can be, for example, RNA derived from resting cultured leukocytes or commercially available reference RNA, such as Universal reference RNA from Stratagene. See Nature, V406, 8-17- 00, p. 747-752. Use of an expression reference standard is particularly useful when the expression of large numbers of nucleotide sequences is assayed, e.g. in an array, and in certain other applications, e.g. qualitative PCR, RT-PCR, etc., where it is desirable to compare a sample profile to a standard profile, and/or when large numbers of expression profiles, e.g. a patient population, are to be compared.

Generally, an expression reference standard should be available in large quantities, should be a good substrate for amplification and labeling reactions, and should be capable of detecting a large percentage of candidate nucleic acids using suitable expression profiling technology.

Alternatively, or in addition, the expression profile derived from a patient sample is compared with the expression of an internal reference control gene, for example, B-actin or CD4. The relative expression of the profiled genes and the internal reference control gene (from the same individual) is obtained. An internal reference control may also be used with a reference RNA. For example, an expression profile for “gene 1” and the gene encoding CD4 can be determined in a patient sample and in a reference RNA. The expression of each gene can be expressed as the “relative” ratio of expression the gene in the patient sample compared with expression of the gene in the reference RNA.

The expression ratio (sample/reference) for gene 1 may be divided by the expression ration for CD4 (sample/reference) and thus the relative expression of gene 1 to CD4 is obtained.

The invention also provides a buffy coat control RNA useful for expression profiling, and a method of using control RNA produced from a population of buffy coat cells, the white blood cell layer derived from the centrifugation of whole blood. Buffy coat contains all white blood cells, including granulocytes, mononuclear cells and platelets. The invention also provides a method of preparing control RNA from buffy coat cells for use in expression profile analysis of leukocytes. Buffy coat fractions are obtained, e.g. from a blood bank or directly from individuals, preferably from a large number of individuals such that bias from individual samples is avoided and so that the RNA sample represents an average expression of a healthy population. Buffy coat fractions from about 50 or about 100, or more individuals are preferred. 10 ml buffy coat from each individual is used. Buffy coat samples are treated with an erthythrocyte lysis buffer, so that erthythrocytes are selectively removed.

B The leukocytes of the buffy coat layer are collected by centrifugation, Alternatively, the buffy cell oo sample can be further enriched for a particular leukocyte sub-populations, e.g. mononuclear cells, T- lymphocytes, etc. To enrich for mononuclear cells, the buffy cell pellet, above, is diluted in PBS (phosphate buffered saline) and loaded onto a non-polystyrene tube containing a polysucrose and sodium diatrizoate solution adjusted to a density of 1.077+/-0.001 g/ml. To enrich for T-lymphocytes,

45 ml of whole blood is treated with RosetieSep (Stem Cell Technologies), and incubated at room temperature for 20 minutes. The mixture is diluted with an equal volume of PBS plus 2% FBS and mixed by inversion. 30 ml of diluted mixture is layered on top of 15 ml DML medium (Stem Celt

Technologies). The tube is centrifuged at 1200 x g, and the enriched cell layer at the plasma : medium interface is removed, washed with PBS + 2% FBS, and cells collected by centrifugation at 1200 x g.

The cell pellet is treated with S ml of erythrocyte lysis buffer (EL buffer, Qiagen) for 10 minutes on ice, and enriched T-lymphoctes are collected by centrifugation. } }

In addition or alternatively, the buffy cells (whole buffy coat or sub-population, e.g. mononuclear fraction) can be cultured in vitro and subjected to stimulation with cytokines or activating chemicals such as phorbol esters or ionomycin. Such stimuli may increase expression of nucleotide sequences that are expressed in activated immune cells and might be of interest for leukocyte expression profiling experiments.

Following sub-population selection and/or further treatment, e.g. stimulation as described above, RNA is prepared using standard methods. For example, cells are pelleted and lysed with a phenol/guanidinium thiocyanate and RNA is prepared. RNA can also be isolated using a silica gel- based purification column or the column method can be used on RNA isolated by the phenol/guanidinium thiocyanate method. RNA from individual buffy coat samples can be pooled during this process, so that the resulting reference RNA represents the RNA of many individuals and individual bias is minimized or eliminated. In addition, a new batch of buffy coat reference RNA can be directly compared to the last batch to ensure similar expression pattern from one batch to another, using methods of collecting and comparing expression profiles described above/below. One or more expression reference controls are used in an experiment. For example, RNA derived from one or more of the following sources can be used as controls for an experiment: stimulated or unstimulated whole buffy coat, stimulated or unstimulated peripheral mononuclear cells, or stimulated or unstimulated T- lymphocytes.

Alternatively, the expression reference standard can be derived from any subject or class of subjects including healthy subjects or subjects diagnosed with the same or a different disease or disease - criterion. Expression profiles from subjects in two distinct classes are compared to determine which subset of nucleotide sequences in the candidate library best distinguish between the two subject classes, as further discussed below. It will be appreciated that in the present context, the term “distinct classes” is relevant to at least one distinguishable criterion relevant to a disease of interest, a “disease criterion.”

The classes can, of course, demonstrate significant overlap (or identity) with respect to other disease criteria, or with respect to disease diagnoses, prognoses, or the like. The mode of discovery involves, ¢.g., comparing the molecular signature of different subject classes to each other (such as patient to control, patients with a first diagnosis to patients with a second diagnosis, etc.) or by comparing the molecular signatures of a single individual taken at different time points. The invention can be applied to a broad range of diseases, disease criteria, conditions and other clinical and/or epidemiological questions, as further discussed above/below. 1t is appreciated that while the present discussion pertains to the use of expression reference controls while identifying diagnostic nucleotide sets, expression reference controls are also useful during use of diagnostic nucleotide sets, e.g. use of a diagnostic nucleotide set for diagnosis of a disease, as further described below. ol

Analvsis of expression profiles

In order to facilitate ready access, e. g., for comparison, review, recovery, and/or modification, the molecular signatures/expression profiles are typically recorded in a database. Most typically, the database is a relational database accessible by a computational device, although other formats, e.g., i _. . manually accessible indexed files of expression profiles as photographs, analogue or digital imaging readouts, spreadsheets, etc. can be used. Further details regarding preferred embodiments are provided below. Regardless of whether the expression patterns initially recorded are analog or digital in nature and/or whether they represent quantitative or qualitative differences in expression, the expression patterns, expression profiles (collective expression patterns), and molecular signatures (correlated expression patterns) are stored digitally and accessed via a database. Typically, the database is compiled and maintained at a central facility, with access being available locally and/or remotely.

As additional samples are obtained, and their expression profiles determined and correlated with relevant subject data, the ensuing molecular signatures are likewise recorded in the database.

However, rather than each subsequent addition being added in an essentially passive manner in which the data from one sample has little relation to data from a second (prior or subsequent) sample, the algorithms optionally additionally query additional samples against the existing database to further refine the association between a molecular signature and disease criterion. Furthermore, the data set comprising the one (or more) molecular signatures is optionally queried against an expanding set of additional or other disease criteria. The use of the database in integrated systems and web embodiments is further described below.

Analysis of expression profile data from arrays

Expression data is analyzed using methods well known in the art, including the software packages Imagene (Biodiscovery, Marina del Rey, CA), Feature Extraction Software (Agilent, Palo

Alto, CA), and Scanalyze (Stanford University). In the discussion that follows, a “feature” refers to an individual spot of DNA on an array. Each gene may be represented by more than one feature. For example, hybridized microarrays are scanned and analyzed on an Axon Instruments scanner using

GenePix 3.0 software (Axon Instruments, Union City, CA). The data extracted by GenePix is used for all downstream quality control and expression evaluation. The data is derived as follows. The data for all features flagged as “not found” by the software is removed from the dataset for individual hybridizations. The “not found” flag by GenePix indicates that the software was unable to discriminate the feature from the background. Each feature is examined to determine the value of its signal. The median pixel intensity of the background (B,) is subtracted from the median pixel intensity of the feature (F,) to produce the background-subtracted signal (hereinafter, “BGSS™). The BGSS is divided } by the standard deviation of the background pixels to provide the signal-to-noise ratio (hereinafter, a. “S/N. Features with 2 S/N of three or greater in both the Cy3 channel (corresponding to the sample

RNA) and CyS5 channel (corresponding to the reference RNA) are used for further analysis (hereinafter denoted “useable features”). Alternatively, different S/N are used for selecting expression data for an analysis. For example, only expression data with signal to noise ratios > 3 might be used in an analysis. Alternatively, features with S/N values < 3 may be flagged as such and included in the analysis. Such flagged data sets include more values and may allow one to discover expression markers that would be missed otherwise. However, such data sets may have a higher variablilty than filtered data, which may decrease significance of findings or performance of correlation statistics.

For each usable feature (i), the expression level (e) is expressed as the logarithm of the ratio ’ (R) of the Background Subtracted Signal (hereinafter “BGSS™) for the Cy3 (sample RNA) channel divided by the BGSS for the Cy5 channel (reference RNA). ‘This “log ratio” value is used for comparison to other experiments. 2 = BOSSum on " BGSS, rence e, =logr, 0.2)

Variation in signal across hybridizations may be caused by a number of factors affecting hybridization, DNA spotting, wash conditions, and labeling efficiency.

A single reference RNA may be used with all of the experimental RNAs, permitting multiple comparisons in addition to individual comparisons. By comparing sample RNAs to the same reference, the gene expression levels from each sample are compared across arrays, permitting the use of a consistent denominator for our experimental ratios.

Alternative methods of analyzing the data may involve 1) using the sample channel without normalization by the reference channel, 2) using an intensity-dependent normalization based on the reference which provides a greater correction when the signal in the reference channel is large, 3) using the data without background subtraction or subtracting an empirically derived function of the background intensity rather than the background itself.

Scaling

The data may be scaled (normalized) to control for labeling and hybridization variability within the experiment, using methods known in the art. Scaling is desirable because it facilitates the comparison of data between different experiments, patients, etc. Generally the BGSS are scaled to a factor such as the median, the mean, the trimmed mean, and percentile. Additional methods of scaling include: to scale between 0 and 1, to subtract the mean, or to subtract the median.

Scaling is also performed by comparison to expression patterns obtained using a common reference RNA, as described in greater detail above. As with other scaling methods, the reference

RNA facilitates multiple comparisons of the expression data, e.g., between patients, between samples, etc. Use of a reference RNA provides a consistent denominator for experimental ratios.

SA In addition to the use of a reference RNA, individual expression levels may be adjusted to correct for differences in labeling efficiency between different hybridization experiments, allowing direct comparison between experiments with different overall signal intensities, for example. A scaling - factor (a) may be used to adjust individual expression levels as follows. The median of the scaling factor (a), for example, BGSS, is determined for the set of all features with a S/N greater than three.

Next, the BGSS; (the BGSS for each feature "i") is divided by the median for all features (a), generating a scaled ratio. The scaled ration is used to determine the expression value for the feature (e)), or the log ratio.

BGSS,

S, = ———— (0.3) ’ a

Cy3S,; e; =lo =r, (0.4)

CySS,

In addition, or alternatively, control features are used to normalize the data for labeling and hybridization variability within the experiment. Control feature may be cDNA for genes from the plant, Arabidopsis thaliana, that are included when spotting the mini-array. Equal amounts of RNA . complementary to control cDNAs are added to each of the samples before they were labeled. - Using the signal from these control genes, a normalization constant (L) is determined according to the following formula:

N

3 BGSS,, i=] _ N

L; ~~ . > BGSS,, i=l j=! N

K where BGSS; is the signal for a specific feature, N is the number of A. thaliana control features, K is the number of hybridizations, and L; is the normalization constant for each individual hybridization.

Using the formula above, the mean for all control features of a particular hybridization and dye (e.g., Cy3) is calculated. The control feature means for all Cy3 hybridizations are averaged, and the control feature mean in one hybridization divided by the average of all hybridizations to generate a normalization constant for that particular Cy3 hybridization (L;), which is used as a in equation (0.3).

The same normalization steps may be performed for Cy3 and Cy5 values.

An alternative scaling method can also be used. The log of the ratio of Green/Red is determined for all features. The median log ratio value for all features is determined. The feature values are then scaled using the following formula: Log Scaled Feature Ratio = Log_Feature_Ratio —- - Median_Log_Ratio. : E :

Many additional methods for normalization exist and can be applied to the data. In one method, the average ratio of Cy3 BGSS / Cy5 BGSS is determined for all features on an array. This ratio is then scaled to some arbitrary number, such as 1 or some other number. The ratio for each probe : is then multiplied by the scaling factor required to bring the average ratio to the chosen level. This is /.

performed for each array in an analysis. Alternatively, the ratios are normalized to the average ratio across all arrays in an analysis. Other methods of normalization include forcing the distribution of signal strengths of the various arrays into greater agreement by transforming them to match certain points (quartiles, or deciles, etc.) in a standard distribution, or in the most extreme case using the rank of the signal of each oligonucleotide relative to the other oligonucleotides on the array.

If multiple features are used per gene sequence or oligonucleotide, these repeats can be used to derive an average expression value for each gene. 1f some of the replicate features are of poor qualitay and don’t meet requirements for analysis, the remaining features can be used to represent the gene or gene sequence.

Correlation analysis :

Correlation analysis is performed to determine which array probes have expression behavior that best distinguishes or serves as markers for relevant groups of samples representing a particular clinical condition. Correlation analysis, or comparison among samples representing different disease criteria (e.g., clinical conditions), is performed using standard statistical methods. Numerous algorithms are useful for correlation analysis of expression data, and the selection of algorithms depends in part on the data analysis to be performed. For example, algorithms can be used to identify the single most informative gene with expression behavior that reliably classifies samples, or to identify all the genes useful to classify samples. Alternatively, algorithms can be applied that determine which set of 2 or more genes have collective expression behavior that accurately classifies samples. The use of multiple expression markers for diagnostics may overcome the variability in expression of a gene between individuals, or overcome the variability intrinsic to the assay. Multiple expression markers may include redundant markers (surrogates), in that two or more genes or probes may provide the same information with respect to diagnosis. This may occur, for example, when two or more genes or gene probes are coordinately expressed. For diagnostic application, it may be appropriate to utilize a gene and one or more of its surrogates in the assay. This redundancy may overcome failures (technical or biological) of a single marker to distinguish samples. Alternatively, one or more surrogates may have properties that make them more suitable for assay development, such as a higher baseline level of expression, better cell specificity, a higher fold change between sample groups or more specific sequence for the design of PCR primers or complimentary probes. It will be appreciated that while the discussion above pertains to the analysis of RNA expression profiles the discussion is equally applicable to the analysis of profiles of proteins or other molecular markers.

Prior to analysis, expression profile data may be formatted or prepared for analysis using methods known in the art. For example, often the log ratio of scaled expression data for every array probe is calculated using the following formula: log (Cy 3 BGSS/ Cy5 BGSS), where Cy 3 signal corresponds to the expression of the gene in } the clinical sample, and Cys signal corresponds to expression of ihe gene in the reference RNA.

Data may be further filtered depending on the specific analysis to be done as noted below. For example, filtering may be aimed at selecting only samples with expression above a certain level, or . probes with variability above a certain level between sample sets. 79 hn

The following non-limiting discussion consider several statistical methods known in the art.

Briefly, the t-test and ANOVA are used to identify single genes with expression differences between or among populations, respectively. Multivariate methods are used to identify a set of two or more genes ~ for which expression discriminates between two disease states more specifically than expression of any single gene. t-test i . The simplest measure of a difference between two groups is the Student's t test. See, e.g,

Welsh et al. (2001) Proc Natl Acad Sci USA 98:1176-81 (demonstrating the use of an unpaired

Student’s t-test for the discovery of differential gene expression in ovarian cancer samples and control tissue samples). The t- test assumes equal variance and normally distributed data. This test identifies the probability that there is a difference in expression of a single gene between two groups of samples.

The number of samples within each group that is required to achieve statistical significance is dependent upon the variation among the samples within each group. The standard formula for a t-test is: te) = Jk J (0.5)

Jis2 fn) + (sE [n,) where ¢; is the difference between the mean expression level of gene i in groups c and t, 5; , is the variance of gene x in group c and s;, is the variance of gene x in group t. n, and n, are the numbers of samples in groups c and t.

The combination of the t statistic and the degrees of freedom [min(n, n.)-1] provides a p value, the probability of rejecting the null hypothesis. A p-value of £0.01, signifying a 99 percent probability the mean expression levels are different between the two groups (a 1% chance that the mean expression levels are in fact not different and that the observed difference occurred by statistical chance), is often considered acceptable.

When performing tests on a large scale, for example, on a large dataset of about 8000 genes, a correction factor must be included to adjust for the number of individual tests being performed. The most common and simplest correction is the Bonferroni correction for multiple tests, which divides the p-value by the number of tests run. Using this test on an 8000 member dataset indicates that a p value of <0.00000125 is required to identify genes that are likely to be truly different between the two test conditions.

Significance analysis for microarrays (SAM) ‘Significance analysis for microarrays (SAM) (Tusher 2001) is a method through which genes with a correlation between their expression values and the response vector are statistically discovered and assigned a statistical significance. The ratio of false significant to significant genes is the False

Discovery Rate (FDR). This means that for each threshold there are a set of genes which are called significant, and the FDR gives a confidence level for this claim. If a gene is called differentially expressed between 2 classes by SAM, with a FDR of 5%, there is a 95% chance that the gene is actually differentially expressed between the classes. SAM takes intoaccount the variability and large number of variables of microarrays. SAM will identiy genes that are most globally differentially expressed between the classes. Thus, important genes for identifying and classifying outlier samples or patients may not be identified by SAM. ’

Wilcoxon's signed ranks method is one example of a non-parametric test and is utilized for paired comparisons. See e.g., Sokal and Rohlf (1987) Introduction to Biostatistics 2™ edition, WH

Freeman, New York. At least 6 pairs are necessary to apply this statistic. This test is useful for analysis of paired expression data (for example, a set of patients who have cardiac transplant biopsy on 2 occasions and have a grade 0 on one occasion and a grade 3A on another). The Fisher Exact Test with a threshold and the Mann-Whitney Test are other non-parametric tests that may be used.

ANOVA

Differences in gene expression across multiple related groups may be assessed using an

Analysis of Variance (ANOVA), a method well known in the art (Michelson and Schofield, 1996).

Multivariate analysis

Many algorithms suitable for multivariate analysis are known in the art. Generally, a set of two or more genes for which expression discriminates between two disease states more specifically than expression of any single gene is identified by searching through the possible combinations of genes using a criterion for discrimination, for example the expression of gene X must increase from normal 300 percent, while the expression of genes Y and Z must decrease from normal by 75 percent.

Ordinarily, the search starts with a single gene, then adds the next best fit at each step of the search.

Alternatively, the search starts with all of the genes and genes that do not aid in the discrimination are eliminated step-wise.

Paired samples

Paired samples, or samples collected at different time-points from the same patient, are often useful, as described above. For example, use of paired samples permits the reduction of variation due to genetic variation among individuals. In addition, the use of paired samples has a statistical significance, in that data derived from paired samples can be calculated in a different manner that recognizes the reduced variability. For example, the formula for a t-test for paired samples is: te) = EI FE (0.5)

Yb? (3.0) Jb b-1 "where D is the difference between each set of ‘paired samples and b is the number of sample pairs, i. D is the mean of the differences between the members of the pairs. In this test, only the differences between the paired samples are considered, then grouped together (as opposed to taking all possible differences between groups, as would be the case with an ordinary t-test). Additional statistical tests useful with paired data, e.g., ANOVA and Wilcoxon's signed rank test, are discussed above. oo 81

Diagnostic classification : Once a discriminating set of genes is identified, the diagnostic classifier (a mathematical function that assigns samples to diagnostic categories based on expression data) is applied to unknown "sample expression levels.

Methods that can be used for this analysis include the following non-limiting list: . CLEAVER is an algorithm used for classification of useful expression profile data. See _ Raychaudhuri et al. (2001) Trends Biotechnol 19:189-193. CLEAVER uses positive training samples (e.g., expression profiles from samples known to be derived from a particular patient or sample diagnostic category, disease or disease criteria), negative training samples (e.g., expression profiles from samples known not to be derived from a particular patient or sample diagnostic category, disease or disease criteria) and test samples (e.g., expression profiles obtained from a patient), and determines whether the test sample correlates with the particular disease or disease criteria, or does not correlate with a particular disease or disease criteria. CLEAVER also generates a list of the 20 most predictive genes for classification.

Artificial neural networks (hereinafter, “ANN") can be used to recognize patterns in complex data sets and can discover expression criteria that classify samples into more than 2 groups. The use of artificial neural networks for discovery of gene expression diagnostics for cancers using expression data generated by oligonucleotide expression microarrays is demonstrated by Khan et al. (2001) Nature

Med. 7:673-9. Khan found that 96 genes provided 0% error rate in classification of the tumors. The most important of these genes for classification was then determined by measuring the sensitivity of the classification to a change in expression of each gene. Hierarchical clustering using the 96 genes results in correct grouping of the cancers into diagnostic categories.

Golub uses cDNA microarrays and a distinction calculation to identify genes with expression behavior that distinguishes myeloid and lymphoid leukemias. See Golub et al. (1999) Science 286:531-7. Self organizing maps were used for new class discovery. Cross validation was done with a “leave one out” analysis. 50 genes were identified as useful markers. This was reduced to as few as 10 genes with equivalent diagnostic accuracy.

Hierarchical and non-hierarchical clustering methods are also useful for identifying groups of genes that correlate with a subset of clinical samples such as with transplant rejection grade. Alizadeh used hierarchical clustering as the primary tool to distinguish different types of diffuse B-cell lymphomas based on gene expression profile data. See Alizadeh et al. (2000) Nature 403:503-11.

Alizadeh used hierarchical clustering as the primary tool to distinguish different types of diffuse B-cell lymphomas based on gene expression profile data. A cDNA array carrying 17856 probes was used for these experiments, 96 samples were assessed on 128 arrays, and a set of 380 genes was identified as being useful for sample classification. 3

Co Perou demonstrates the use of hierarchical clustering for the molecular classification of breast tumor samples based on expression profile data. See Perou el al. (2000) Nature 406:747-52. In this work, a cDNA array carrying 8102 gene probes was used. 1753 of these genes were found to have high variation between breast tumors and were used for the analysis.

Hastie describes the use of gene shaving for discovery of expression markers. Hastie et al. (2000) Genome Biol. 1(2):RESEARCH 0003.1-0003.21. The gene shaving algorithm identifies sets of genes with similar or coherent expression patterns, but large variation across conditions (RNA samples, "sample classes, patient classes). In this manner, genes with a tight expression pattern within a transplant rejection grade, but also with high variability across rejection grades are grouped together.

The algorithm takes advantage of both characteristics in one grouping step. For example, gene shaving can identify useful marker genes with co-regulated expression. Sets of useful marker genes can be reduced to a smaller set, with each gene providing some non-redundant value in classification. This algorithm was used on the data set described in Alizadeh et al. supra, and the set of 380 informative gene markers was reduced to 234.

Supervised harvesting of expression trees (Hastie 2001) identifies genes or clusters that best distinguish one class from all the others on the data set. The method is used to identify the genes/clusters that can best separate one class versus all the others for datasets that include two or more classes or all classes from each other. This algorithm can be used for discovery or testing of a diagnostic gene set.

CART is a decision tree classification algorithm (Breiman 1984). From gene expression and or other data, CART can develop a decision tree for the classification of samples. Each node on the decision tree involves a query about the expression level of one or more genes or variables. Samples that are above the threshold go down one branch of the decision tree and samples that are not go down the other branch. See example 4 for further description of its use in classification analysis and examples of its usefulness in discovering and implementing a diagnostic gene set. CART identifies surrogates for each splitter (genes that are the next best substitute for a useful gene in classification.

Multiple Additive Regression Trees (Friedman, JH 1999, MART) is similar to CART in that it is a classification algorithm that builds decision trees to distinguish groups. MART builds numerous trees for any classification problem and the resulting model involves a combination of the multiple trees. MART can select variables as it build models and thus can be used on large data sets, such as those derived from an 8000 gene microarray. Because MART uses a combination of many trees and does not take too much information from any one tree, it resists over training. MART identifies a set of genes and an algorithm for their use as a classifier.

A Nearest Shrunken Centroids Classifier can be applied to microarray or other data sets by the methods described by Tibshirani et al. 2002. This algorithms also identified gene sets for classification and determines their 10 fold cross validation error rates for each class of samples. The algorithm determines the error rates for models of any size, from one gene to all genes in the set. The error rates for either or both sample classes can are minimized when a particular number of genes are used. When this gene number is determined, the algorithm associated with the selected genes can be identified and employed as a classifier on prospective sample. } .

Once a set of genes and expression criteria for those genes have been established for classification, cross validation is done. There are many approaches, including a 10 fold cross validation analysis in which 10%, of the training samples are left out of the analysis and the : classification algorithm is built with the remaining 90%. The 10% are then used as a test set for the 83 y algorithm. The process is repeated 10 times with 10% of the samples being left out as a test set each time. Through this analysis, one can derive a cross validation error which helps estimate the robustness of the algorithm for use on prospective (test) samples.

Clinical data are gathered for every patient sample used for expression analysis. Clinical variables can be quantitative or non-quantitative. A clinical variable that is quantitiative can be used as a variable for significance or classification analysis. Non-quantitative clinical variables, such as the sex of the patient, can also be used in a significance analysis or classification analysis with some statistical } tool. It is appreciated that the most useful diagnostic gene set for a condition may be optimal when considered along with one or more predictive clinical variables. Clinical data can also be used as supervising vectors for a correlation analysis. That is to say that the clinical data associated with each sample can be used to divide the samples into meaningful diagnostic categories for analysis. For example, samples can be divided into 2 or more groups based on the presence or absence of some diagnostic criterion (a). In addition, clinical data can be utilized to select patients for a correlation analysis or to exclude them based on some undesirable charactenstic, such as an ongoing infection, a medicine or some other issue. Clincial data can also be used to assess the pre-test probability of an outcome. For example, patients who are female are much more likely to be diagnosed as having systemic lupus erythematosis than patients who are male.

Once a set of genes are identified that classify samples with acceptable accuracy. These genes are validated as a set using new samples that were not used to discover the gene set. These samples can be taken from frozen archieves from the discovery clinical study or can be taken from new patients prospectively. Validation using a “test set” of samples can be done using expression profiling of the gene set with microarrays or using real-time PCR for each gene on the test set samples. Alternatively, a different expression profiling technology can be used.

Immune Monitoring

Leukocyte gene expression can be used to monitor the immune system. Immune monitoring examines both the level of gene expression for a set of genes in a given cell type and for genes which are expressed in a cell type selective manner gene expression monitoring will also detect the presence or absence of new cell types, progenitor cells, differentiation of cells and the like. Gene expression patterns may be associated with activation or the resting state of cells of the immune system that are responsible for or responsive to a disease state. For example, in the process of transplant rejection, cells of the immune system are activated by the presence of the foreign tissue. Genes and gene sets that monitor and diagnose this process are providing a measure of the level and type of activation of the immune system. Genes and gene sets that are useful in monitoring the immune system may be useful for diagnosis and monitoring of all diseases that involve the immune system. Some examples are transplant rejection, rheumatoid arthritis, lupus, inflammatory bowel diseases, multiple sclerosis,

HIV/AIDS, and viral, bacterial and fungal infection. All disorders and diseases disclosed herein are contemplated. Genes and gene sets that monitor immune activation are useful for monitoring response to immunosuppressive drug therapy, which is used to decrease immune activation. Genes are found to correlate with immune activation by correlation of expression patterns to the known presence of immune activation or quiescence in a sample as determined by some other test.

Selected Diseases

In principle, diagnostic nucleotide sets of the invention may be developed and applied to essentially any disease, or disease criterion, as long as at least one subset of nucleotide sequences is differentially expressed in samples derived from one or more individuals with a disease criteria or disease and one or more individuals without the disease criteria or disease, wherein the individual may be the same individual sampled at different points in time, or the individuals may be different __ individuals (or populations of individuals). For example, the subset of nucleotide sequences may be } differentially expressed in the sampled tissues of subjects with the disease or disease criterion (e.g, a patient with a disease or disease criteria) as compared to subjects without the disease or disease criterion (e.g., patients without a disease (control patients)). Alternatively, or in addition, the subset of nucleotide sequence(s) may be differentially expressed in different samples taken from the same patient, e.g at different points in time, at different disease stages, before and after a treatment, in the presence or absence of a risk factor, etc.

Expression profiles corresponding to sets of nucleotide sequences that correlate not with a diagnosis, but rather with a particular aspect of a disease can also be used to identify the diagnostic nucleotide sets and disease specific target nucleotide sequences of the invention. For example, such an aspect, or disease criterion, can relate to a subject’s medical or family history, e.g., childhood illness, cause of death of a parent or other relative, prior surgery or other intervention, medications, symptoms (including onset and/or duration of symptoms), etc. Alternatively, the disease criterion can relate to a diagnosis, e.g., hypertension, diabetes, atherosclerosis, or prognosis (e.g., prediction of future diagnoses, events or complications), e.g., acute myocardial infarction, restenosis following angioplasty, reperfusion injury, allograft rejection, rheumatoid arthritis or systemic lupus erythematosis disease activity or the like. In other cases, the disease criterion corresponds to a therapeutic outcome, e.g., transplant rejection, bypass surgery or response to a medication, restenosis after stent implantation, collateral vessel growth due to therapeutic angiogenesis therapy, decreased angina due to revascularization, resolution of symptoms associated with a myriad of therapies, and the like.

Alternatively, the disease criteria corresponds with previously identified or classic risk factors and may correspond to prognosis or future disease diagnosis. As indicated above, a disease criterion can also : correspond to genotype for one or more loci. Disease criteria (including patient data) may be collected (and compared) from the same patient at different points in time, from different patients, between patients with a disease (criterion) and patients respresenting a control population, etc. Longitudinal data, i.e., data collected at different time points from an individual (or group of individuals) may be used for comparisons of samples obtained from an individual (group of individuals) at different points in time, to permit identification of differences specifically related to the disease state, and to obtain information relating to the change in expression over time, including a rate of change or trajectory of expression over time. The usefulness of longitudinal data is further discussed in the section titled “Identification of diagnostic nucleotide sets of the invention”.

It is further understood that diagnostic nucleotide sets may be developed for use in diagnosing conditions for which there 1s no present means of diagnosis. For example, in rheumatoid arthritis, joint destruction is often well under way before a patient experience symptoms of the condition. A diagnostic nucleotide set may be developed that diagnoses rheumatic joint destruction at an earlier stage than would be possible using present means of diagnosis, which rely in part on the presentation of symptoms by a patient. Diagnostic nucleotide sets may also be developed to replace or augment current diagnostic procedures. For example, the use of a diagnostic nucleotide set to diagnose cardiac : allograft rejection may replace the current diagnostic test, a graft biopsy.

It is understood that the following discussion of diseases is exemplary and non-limiting, and further that the general criteria discussed above, e.g. use of family medical history, are generally applicable to the specific diseases discussed below.

In addition to leukocytes, as described throughout, the general method is applicable to nucleotide sequences that are differentially expressed in any subject tissue or cell type, by the collection and assessment of samples of that tissue or cell type. However, in many cases, collection of such samples presents significant technical or medical problems given the current state of the art.

Organ transplant rejection and success

A frequent complication of organ transplantation is recognition of the transplanted organ as : foreign by the immune system resulting in rejection. Diagnostic nucleotide sets can be identified and validated for monitoring organ transplant success, rejection and treatment. Medications currently exist that suppress the immune system, and thereby decrease the rate of and severity of rejection. However, these drugs also suppress the physiologic immune responses, leaving the patient susceptible to a wide variety of opportunistic infections and cancers. At present there is no easy, reliable way to diagnose transplant rejection. Organ biopsy is the preferred method, but this is expensive, painful and associated with significant risk and has inadequate sensitivity for focal rejection.

Diagnostic nucleotide sets of the present invention can be developed and validated for use as diagnostic tests for transplant rejection and success. It is appreciated that the methods of identifying diagnostic nucleotide sets are applicable to any organ transplant population. For example, diagnostic nucleotide sets are developed for cardiac allograft rejection and success.

In some cases, disease criteria correspond to acute stage rejection diagnosis based on organ biopsy and graded using the International Society for Heart and Lung Transplantation (“ISHLT") criteria. This grading system classifies endomyocardial biopsies on the histological level as Grade 0, 1A, 1B, 2, 3A, 3B, or 4. Grade 0 biopies have no evidence of rejection, while each successive grade has increased severity of leukocyte infiltration and/or damage to the graft myocardial cells. It is appreciated that there is variability in the Grading systems between medical centers and pathologists and between repeated readings of the same pathologist at different times. When using the biopsy grade as a disease criterion for leukocyte gene expression correlation analysis, it may be desirable to have a single pathologist read all biopsy slides or have multiple pathologists read all slides to determine the variablility in this disease criterion. It is also appreciated that cardiac biopsy, in part due to variability, oo is not 100% sensitive or 100% specific for diagnosing acute rejection. When using the cardiac biopsy grade as a disease criterion for the discovery of diagnostic gene sets, it may be desirable to divide oo patient samples into diagnostic categories based on the grades. Examples of such classes are those : ‘patients with: Grade 0 vs. Grades 1A-4, Grade 0 vs. Grades 1B-4, Grade 0 vs. Grades 2-4, Grade 0-1 vs. Grade 2-4, Grade 0-1 vs. Grade 3A-4, or Grade 0 vs. Grade 3A-4.

Other disease criteria correspond to the cardiac biopsy results and other criteria, such as the results of cardiac function testing by echocardiography, hemodynamics assessment by cardiac catheterization, CMV infection, weeks post transplant, medication regimen, demographics and/or results of other diagnostic tests. _ Other disease criteria correspond to information from the patient’s medical history and information regarding the organ donor. Alternatively, disease criteria include the presence or absence of cytomegalovirus (CMV) infection, Epstein-Barr virus (EBV) infection, allograft dysfunction } measured by physiological tests of cardiac function (e.g., hemodynamic measurements from catheterization or echocardiograph data), and symptoms of other infections. Alternatively, disease criteria correspond to therapeutic outcome, e.g. graft failure, re-transplantation, death, hospitalization, need for intravenous immunosuppression, transplant vasculopathy, response to immunosuppressive medications, etc. Disease criteria may further correspond to a rejection episode of at least moderate histologic grade, which results in treatment of the patient with additional corticosteroids, anti-T cell antibodies, or total lymphoid irradiation; a rejection with histologic grade 2 or higher; a rejection with histologic grade <2; the absence of histologic rejection and normal or unchanged allograft function (based on hemodynamic measurements from catheterization or on echocardiographic data); the presence of severe allograft dysfunction or worsening allograft dysfunction during the study period (based on hemodynamic measurements from catheterization or on echocardiographic data).; documented CMV infection by culture, histology, or PCR, and at lcast one clinical sign or symptom of infection; specific graft biopsy rejection grades; rejection of mild to moderate histologic severity prompting augmentation of the patient’s chronic immunosuppressive regimen; rejection of mild to moderate severity with allograft dysfunction prompting plasmaphoresis or a diagnosis of “humoral” rejection; infections other than CMV, especially infection with Epstein Barr virus (EBV); lymphoproliferative disorder (also called post-transplant lymphoma); transplant vasculopathy diagnosed by increased intimal thickness on intravascular ultrasound (IVUS), angiography, or acute myocardial infarction; graft failure or retransplantation; and all cause mortality. Further specific examples of clinical data useful as disease criteria are provided in Example 3.

In another example, diagnostic nucleotide sets are developed and validated for use in diagnosis and monitoring of kidney allograft recipients. Disease criteria correspond to, e.g., results of biopsy analysis for kidney allograft rejection, serum creatine level, creatinine clearance, radiological imaging results for the kidney and urinalysis results. Another disease criterion corresponds to the need for hemodialysis, retransplantation, death or other renal replacement therapy. Diagnostic nucleotide sets are developed and validated for use in diagnosis and treatment of bone marrow transplant and liver transplantation pateints, respectively. Disease criteria for bone marrow transplant correspond to the diagnosis and monitoring of graft rejection and/or graft versus host disease, the recurrence of cancer, complications due to immunosuppression, hematologic abnormalities, infection, hospitalization and/or death. Disease criteria for liver transplant rejection include levels of serum markers for liver damage and liver function such as AST (aspartate aminotransferase), ALT (alanine aminotransferase), Alkaline phosphatase, GGT, (gamma-glutamyl transpeptidase) Bilirubin, Albumin and Prothrombin time.

Further disease criteria correspond to hepatic encephalopathy, medication usage, ascites, graft failure,

retransplantation, hospitalization, complications of immunosuppression, results of diagnostic tests, results of radiological testing, death and histological rejection on graft biopsy. In addition, urine can be utilized for at the target tissue for profiling in renal transplant, while biliary and intestinal secretions and feces may be used favorably for hepatic or intestinal organ allograft rejection. Diagnostic nuclotide sets can also be discovered and developed for the diagnosis and monitoring of chronic renal allograft rejection .

In the case of renal allografts, gene expression markers may be identified that are secreted proteins. These proteins may be detected in the urine of allograft recipients using standard immunoassays. Proteins are more likely to be present in the urine if they are of low molecular weight.

Lower molecular weight proteins are more likely to pass through the glomerular membrane and into the urine.

In another example, diagnostic nucleotide sets are developed and validated for use in diagnosis and treatment of xenograft recipients. This can include the transplantation of any organ from a non-human animal to a human or between non-human animals. Considerations for discovery and application of diagnostics and therapeutics and for disease criterion are substantially similar to those for allograft transplantation between humans.

In another example, diagnostic nucleotide sets are developed and validated for use in diagnosis and treatment of artificial organ recipients. This includes, but is not limited to mechanical circulatory support, artificial hearts, left ventricular assist devices, renal replacement therapies, organ prostheses and the like. Disease criteria are thrombosis (blood clots), infection, death, hospitalization, and worsening measures of organ function (e.g., hemodynamics, creatinine, liver function testing, renal function testing, functional capacity).

In another example, diagnostic nucleotide sets are developed and validated for use in matching donor organs to appropriate recipients. Diagnostic gene set can be discovered that correlate with successful matching of donor organ to recipient. Disease criteria include graft failure, acute and chronic rejection, death, hospitalization, immunosuppressive drug use, and complications of immunosuppression. Gene sets may be assayed from the donor or recipient’s peripheral blood, organ tissue or some other tissue.

In another example, diagnostic nucleotide sets are developed and validated for use in diagnosis and induction of patient immune tolerance (decrease rejection of an allograft by the host immune system). Disease criteria include rejection, assays of immune activation, necd for immunosupression and all disease criteria noted above for transplantation of each organ.

Viral diseases

Diagnostic leukocyte nucleotide sets may be developed and validated for use in diagnosing viral disease, as well as diagnosing and monitoring transplant rejection. In another aspect, viral

Co nucleotide sequences may be added toa leukocyte nucleotide set for use in diagnosis of viral diseases, as well as diagnosing and monitoring transplant rejection. Alternatively, viral nucleotide sets and leukocyte nucleotides sets may be used sequentially.

Epstein-Barr virus (EBV)

EBV causes a variety of diseases such as mononucleosis, B-cell lymphoma, and pharyngeal carcinoma. It infects mononuclear cells and circulating atypical lymphocytes are a common manifestation of infection. Peripheral leukocyte gene expression is altered by infection. Transplant recipients and patients who are immunosuppressed are at increased risk for EBV-associated lymphoma. -

Diagnostic nucleotide sets may be developed and validated for usc in diagnosis and monitoring of EBV, as well as diagnosing and monitoring transplant rejection. In one aspect, the diagnostic nucleotide set is a leukocyte nucleotide set. Alternatively, EBV nucleotide sequences are added to a leukocyte nucleotide set, for use in diagnosing EBV. Disease criteria correspond with diagnosis of EBV, and, in patients who are EBV-sero-positive, presence (or prospective occurrence ) of

EBV-related illnesses such as mononucleosis, and EBV-associated lymphoma. Diagnostic nucleotide sets are useful for diagnosis of EBV, and prediction of occurrence of EBV-related illnesses.

Cytomegalovirus (CMV)

Cytomegalovirus cause inflammation and disease in almost any tissue, particularly the colon, lung, bone marrow and retina, and is a very important cause of disease in immunosuppressed patients, e.g. transplant, cancer, AIDS. Many patients are infected with or have been exposed to CMV, but not all patients develop clinical disease from the virus. Also, CMV negative recipients of allografts that come from CMV positive donors are at high risk for CMV infection. As immunosuppressive drugs are developed and used, it is increasingly important to identify patients with current or impending clinical

CMV disease, because the potential benefit of immunosuppressive therapy must be balanced with the increased rate of clinical CMV infection and disease that may result from the use of immunosuppression therapy. CMV may also play a role in the occurrence of atherosclerosis or restenosis after angioplasty. CMV expression also correlates to transplant rejection, and is useful in diagnosing and monitoring transplant rejection.

Diagnostic nucleotide sets are developed for use in diagnosis and monitoring of CMV infection or re-activation of CMV infection. In one aspect, the diagnostic nucleotide set is a leukocyte nucleotide set. In another aspect, CMV nucleotide sequences are added to a leukocyte nucleotide set, for use in diagnosing CMV. Disease criteria correspond to diagnosis of CMV (e.g., sero-positive state) and presence of clinically active CMV. Disease criteria may also correspond to prospective data, e.g. the likelihood that CMV will become clinically active or impending clinical CMV infection. Antiviral medications are available and diagnostic nucleotide sets can be used to select patients for early treatment, chronic suppression or prophylaxis of CMV activity.

Hepatitis B and C

These chronic viral infections affect about 1.25 and 2.7 million patients in the US, respectively. Many patients are infected, but suffer no clinical manifestations. Some patients with infection go on to suffer from chronic liver failure, Cirrhosis and hepatic carcinoma.

Diagnostic nucleotide sets are developed for use in diagnosis and monitoring of HBV or HCV infection. In one aspect, the diagnostic nucleotide set is a leukocyte nucleotide set. In another aspect, viral nucleotide sequences are added to a leukocyte nucleotide set, for use in diagnosing the virus and monitoring progression of liver disease. Disease criteria correspond to diagnosis of the virus (e.g.,

sero-positive state or other disease symptoms). Alternatively, disease criteria correspond to liver damage, e.g., elevated alkaline phosphatase, ALT, AST or evidence of ongoing hepatic damage on liver biopsy. Alternatively, disease criteria correspond to serum liver tests (AST, ALT, Alkaline

Phosphatase, GGT, PT, bilirubin), liver biopsy, liver ultrasound, viral load by serum PCR, cirrhosis, hepatic cancer, need for hospitalization or listing for liver transplant. Diagnostic nucleotide sets are used to diagnose HBV and HCV, and to predict likelihood of disease progression. Antiviral therapeutic usage, such as Interferon gamma and Ribavirin, can also be disease criteria.

Hv oo

HIV infects T cells and certainly causes alterations in leukocyte expression. Diagnostic nucleotide sets are developed for diagnosis and monitoring of HIV. In one aspect, the diagnostic nucleotide set is a leukocyte nucleotide set. In another aspect, viral nucleotide sequences are added to a leukocyte nucleotide set, for use in diagnosing the virus. Disease criteria correspond to diagnosis of the virus (e.g., sero-positive state). In addition, disease criteria correspond to viral load, CD4 T cell counts, opportunistic infection, response to antiretroviral therapy, progression to AIDS, rate of progression and the occurrence of other HIV related outcomes (e.g., malignancy, CNS disturbance). Response to antiretrovirals may also be disease criteria.

Pharmacogenomics

Pharmocogenomics is the study of the individual propensity to respond to a particular drug therapy (combination of therapies). In this context, response can mean whether a particular drug will work on a particular patient, e.g. some patients respond to one drug but not to another drug. Response can also refer to the likelihood of successful treatment or the assessment of progress in treatment.

Titration of drug therapy to a particular patient is also included in this description, e.g. different patients can respond to different doses of a given medication. This aspect may be important when drugs with side-effects or interactions with other drug therapies are contemplated.

Diagnostic nucleotide sets are developed and validated for use in assessing whether a patient will respond to a particular therapy and/or monitoring response of a patient to drug therapy(therapies).

Disease criteria correspond to presence or absence of clinical symptoms or clinical endpoints, presence of side-effects or interaction with other drug(s). The diagnostic nucleotide set may further comprise nucleotide sequences that are targets of drug treatment or markers of active disease.

Validation and accuracy of diagnostic nucleotide sets

Prior to widespread application of the diagnostic probe sets of the invention the predictive value of the probe set is validated. When the diagnostic probe set is discovered by microarray based expression analysis, the differential expression of the member genes may be validated by a less variable and more quantitive and accurate technology such as real time PCR. In this type of experiment the amplification product is measured during the PCR reaction. This enables the researcher to observe the ) : amplification before any reagent becomes rate limiting for amplification. In kinetic PCR the measurement is of Ct (threshold cycle) or Cp (crossing point). This measurement (C1=Cp) is the point at which an amplification curve crosses a threshold fluorescence value. The threshold is set to a point } within the area where all of the reactions werc in their linear phase of amplification. When measuring

Cy, a lower Cy value is indicative of a higher amount of starting material since an earlier cycle number means the threshold was crossed more quickly.

Several fluorescence methodologies are available to measure amplification product in real- time PCR. Taqman (Applied BioSystems, Foster City, CA) uses fluorescence resonance energy transfer (FRET) to inhibit signal from a probe until the probe is degraded by the sequence specific binding and Taq 3’ exonuclease activity. Molecular Beacons (Stratagene, La Jolla, CA) also use FRET technology, whereby the fluorescence is measured when a hairpin structure is relaxed by the specific probe binding to the amplified DNA. The third commonly used chemistry is Sybr Green, a DNA- binding dye (Molecular Probes, Eugene, OR). The more amplified product that is produced, the higher the signal. The Sybr Green method is sensitive to non-specific amplification products, increasing the importance of primer design and selection. Other detection chemistries can also been used, such as ethedium bromide or other DNA-binding dyes and many modifications of the fluorescent dye/quencher dye Taqman chemistry, for example scorpions.

Real-time PCR validation can be done as described in Example 12.

Typically, the oligonucleotide sequence of each probe is confirmed, e.g. by DNA sequencing using an oligonucleotide-specific primer. Partial sequence obtained is generally sufficient to confirm the identity of the oligonucleotide probe. Alternatively, a complementary polynucleotide is fluorescently labeled and hybridized to the array, or to a different array containing a resynthesized version of the oligo nucleotide probe, and detection of the correct probe is confirmed.

Typically, validation is performed by statistically evaluating the accuracy of the correspondence between the molecular signature for a diagnostic probe set and a selected indicator.

For example, the expression differential for a nucleotide sequence between two subject classes can be expressed as a simple ratio of relative expression. The expression of the nucleotide sequence in subjects with selected indicator can be compared to the expression of that nucleotide sequence in subjects without the indicator, as described in the following equations. 2Eai/N =E,A the average expression of nucleotide sequence x in the members of group A; 2EDbi/M =E,B the average expression of nucleotide sequence x in the members of group B; :

E,A/ ExB =AE,AB the average differential expression of nucleotide sequence x between groups

A and B: where 3 indicates a sum; Ex is the expression of nucleotide sequence x relative to a standard; ai are the individual members of group A, group A has N members; bi are the individual members of group B, group B has M members.

The expression of at least two nucleotide sequences, e.g., nucleotide sequence X and nucleotide sequence Y are measured relative to a standard in at least one subject of group A (e.g., with a disease) and group B (e.g., without the disease). Ideally, for purposes of validation the indicator is independent from (i.e., not assigned based upon) the expression pattern. Alternatively, a minimum : threshold of gene expression for nucleotide sequences X and, relative to the standard, are designated for assignment to group A. For nucleotide sequence x, this threshold is designated AEx, and for nucleotide sequence y, the threshold is designated AEy.

The following formulas are used in the calculations below: . 0 _

Sensitivity = (true positives/true positives + false negatives)

Specificity = (true negatives/true negatives + false positives)

If, for example, expression of nucleotide sequence x above a threshold: x > AEX, is observed for 80/100 subjects in group A and for 10/100 subjects in group B, the sensitivity of nucleotide sequence x for the assignment to group A, at the given expression threshold AEX, is 80%, and the a specificity is 90%.

If the expression of nucleotide sequence y is > AEy in 80/100 subjects in group A, and in 10/100 subjects in group B, then, similarly the sensitivity of nucleotide sequence y for the assignment to group A at the given threshold AEy is 80% and the specificity is 90%. If in addition, 60 of the 80 subjects in group A that meet the expression threshold for nucleotide sequence y also meet the expression threshold AEx and that 5 of the 10 subjects in group B that meet the expression threshold for nucleotide sequence y also meet the expression threshold AEx, the sensitivity of the test (x>AEx and y>AEy)for assignment of subjects to group A is 60% and the specificity is 95%.

Alternatively, if the criteria for assignment to group A are change to: Expression of x > AEx or expression of y > AEy, the sensitivity approaches 100% and the specificity is 85%.

Clearly, the predictive accuracy of any diagnostic probe set is dependent on the minimum expression threshold selected. The expression of nucleotide sequence X (relative to a standard) 1s measured in subjects of groups A (with disease) and B (without disease). The minimum threshold of nucleotide sequence expression for x, required for assignment to group A is designated AEx 1. 1£ 90/100 patients in group A have expression of nucleotide sequence x > AEx 1 and 20/100 patients in group B have expression of nucleotide sequence x > AEx 1, then the sensitivity of the expression of nucleotide sequence x (using AEx 1 as a minimum expression threshold) for assignment of patients to group A will be 90% and the specificity will be 80%.

Altering the minimum expression threshold results in an alteration in the specificity and sensitivity of the nucleotide sequences in question. For example, if the minimum expression threshold of nucleotide sequence x for assignment of subjects to group A is lowered to AEx 2, such that 100/100 subjects in group A and 40/100 subjects in group B meet the threshold, then the sensitivity of the test for assignment of subjects to group A will be 100% and the specificity will be 60%. .

Thus, for 2 nucleotide sequences X and Y: the expression of nucleotide sequence x and nucleotide sequence y (relative to a standard) are measured in subjects belonging to groups A (with disease) and B (without disease). Minimum thresholds of nucleotide sequence expression for nucleotide sequences X and Y (relative to common standards) are designated for assignment to group

A. For nucleotide sequence x, this threshold is designated AEx1 and for nucleotide sequence y, this threshold is designated AEy1.

If in group A, 90/100 patients meet the minimum requirements of expression AEx1 and AEy1, and in group B, 10/100 subjects meet the minimum requirements of expression AEx]1 and AEy1, then the sensitivity of the test for assignment of subjects to group A is 90% and the specificity is 90%.

Increasing the minimum expression thresholds for X and Y to AEx2 and AEy2, such that in group A, 70/100 subjects meet the minimum requirements of expression AEx2 and AEy2, and in group

B, 3/100 subjects meet the minimum requirements of expression AEx2 and AEy2. Now the sensitivity of the test for assignment of subjects to group A is 70% and the specificity is 97%.

If the criteria for assignment to group A is that the subject in question meets either threshold,

AEX2 or AEy2, and it is found that 100/100 subjects in group A meet the criteria and 20/100 subjects in group B meet the criteria, then the sensitivity of the test for assignment to group A is 100% and the } specificity is 80%.

Individual components of a diagnostic probe set each have a defined sensitivity and specificity for distinguishing between subject groups. Such individual nucleotide sequences can be employed in concert as a diagnostic probe set to increase the sensitivity and specificity of the evaluation. The database of molecular signatures is queried by algorithms to identify the set of nucleotide sequences (i.e., corresponding to members of the probe set) with the highest average differential expression between subject groups. Typically, as the number of nucleotide sequences in the diagnostic probe set increases, so does the predictive value, that is, the sensitivity and specificity of the probe set. When the probe sets are defined they may be used for diagnosis and patient monitoring as discussed below. The diagnostic sensitivity and specificity of the probe sets for the defined use can be determined for a given probe set with specified expression levels as demonstrated above. By altering the expression threshold required for the use of each nucleotide sequence as a diagnostic, the sensitivity and specificity of the probe set can be altered by the practitioner. For example, by lowering the magnitude of the expression differential threshold for each nucleotide sequence in the set, the sensitivity of the test will increase, but the specificity will decrease. As is apparent from the foregoing discussion, sensitivity and specificity are inversely related and the predictive accuracy of the probe set is continuous and dependent on the expression threshold set for each nucleotide sequence. Although sensitivity and specificity tend to have an inverse relationship when expression thresholds are altered, both parameters can be increased as nucleotide sequences with predictive value are added to the diagnostic nucleotide set. In addition a single or a few markers may not be reliable expression markers across a population of patients. This is because of the variability in expression and measurement of expression that exists between measurements, individuals and individuals over time. Inclusion of a large number of candidate nucleotide sequences or large numbers of nucleotide sequences in a diagnostic nucleotide set allows for this variability as not all nucleotide sequences need to meet a threshold for diagnosis. Generally, more markers are better than a single marker. If many markers are used to make a diagnosis, the likelihood that all expression markers will not meet some thresholds based upon random variability is low and thus the test will give fewer false negatives. :

It is appreciated that the desired diagnostic sensitivity and specificity of the diagnostic nucleotide set may vary depending on the intended use of the set. For example, in certain uses, high specificity and high sensitivity are desired. For example, a diagnostic nucleotide set for predicting which patient population may experience side effects may require high sensitivity so as to avoid treating such patients. In other settings, high sensitivity is desired, while reduced specificity may be tolerated. For example, in the case of a beneficial treatment with few side effects, it may be important to identify as many patients as possible (high sensitivity) who will respond to the drug, and treatment of some patients who will not respond is tolerated. In other settings, high specificity is desired and 93 } _

reduced sensitivity may be tolerated. For example, when identifying patients for an early-phase clinical trial, it is important to identify patients who may respond to the particular treatment. Lower sensitivity is tolerated in this setting as it merely results in reduced patients who enroll in the study or requires that more patients are screened for enrollment. ’ Methods of using diagnostic nucleotide sets.

The invention also provide methods of using the diagnostic nucleotide sets to: diagnose disease; assess severity of disease; predict future occurrence of disease; predict future complications of disease; determine disease prognosis; evaluate the patient's risk, or “stratify” a group of patients; assess response to current drug therapy; assess response to current non-pharmacological therapy; determine the most appropriate medication or treatment for the patient; predict whether a patient is likely to respond to a particular drug; and determine most appropriate additional diagnostic testing for the patient, among other clinically and epidemiologically relevant applications.

The nucleotide sets of the invention can be utilized for a variety of purposes by physicians, healthcare workers, hospitals, laboratories, patients, companies and other institutions. As indicated previously, essentially any disease, condition, or status for which at least one nucleotide sequence is differentially expressed in leukocyte populations (or sub-populations) can be evaluated, e.g., diagnosed, monitored, etc. using the diagnostic nucleotide sets and methods of the invention. In addition to assessing health status at an individual level, the diagnostic nucleotide sets of the present invention are suitable for evaluating subjects at a “population level,” e.g., for epidemiological studies, or for population screening for a condition or disease.

Collection and preparation of sample

RNA, protein and/or DNA is prepared using methods well-known in the art, as further described herein. It is appreciated that subject samples collected for use in the methods of the invention are generally collected in a clinical setting, where delays may be introduced before RNA samples are prepared from the subject samples of whole blood, e.g. the blood sample may not be promptly delivered to the clinical lab for further processing. Further delay may be introduced in the clinical lab setting where multiple samples are generally being processed at any given time. For this reason, methods which feature lengthy incubations of intact leukocytes at room temperature are not preferred, because the expression profile of the leukocytes may change during this extended time period. For example, RNA can be isolated from whole blood using a phenol/guanidine isothiocyanate reagent or another direct whole-blood lysis method, as described in, e.g., U.S. Patent Nos. 5,346,994 and 4,843,155. This method may be less preferred under certain circumstances because the large majority of the RNA recovered from whole blood RNA extraction comes from erythrocytes since these cells outnumber leukocytes 1000:1. Care must be taken to ensure that the presence of erythrocyte RNA and protein does not introduce bias in the RNA expression profile data or lead to inadequate sensitivity or specificity of probes. oo

Alternatively, intact leukocytes may be collected from whole blood using a lysis buffer that selectively lyses erythrocytes, but not leukocytes, as described, e.g., in (U.S. Patent Nos. 5,973,137, and 6,020,186). Intact leukocytes are then collected by centrifugation, and leukocyte RNA is isolated using standard protocols, as described herein. However, this method does not allow isolation of sub-

populations of leukocytes, €-8. mononuclear cells, which may be desired. In addition, the expression profile may change during the lengthy incubation in lysis buffer, especially in a busy clinical lab where large numbers of samples are being prepared at any given time. © Alternatively, specific leukocyte cell types can be separated using density gradient reagents (Boyum, A, 1968.). For example, mononuclear cells may be separated from whole blood using density gradient centrifugation, as described, e.g., in U.S. Patents Nos. 4190535, 4350593, 4751001, 4818418, and 5053134. Blood is drawn directly into a tube containing an anticoagulant and a density reagent (such as Ficoll or Percoll). Centrifugation of this tube results in separation of blood into an erythrocyte and granulocyte layer, a mononuclear cell suspension, and a plasma layer. The mononuclear cell layer is easily removed and the cells can be collected by centrifugation, lysed, and frozen. Frozen samples are stable until RNA can be isolated. Density centrifugation, however, must be conducted at room temperature, and if processing is unduly lengthy, such as in a busy clinical lab, the expression profile : may change.

Alternatively, cells can be separated using fluorescence activated cell sorting (FACS) or some other technique, which divides cells into subsets based on gene of protein expression. This may be desirable to enrich the sample for cells of interest, but it may also introduce cell manipulations and time delays, which result in alteration of gene expression profiles (Cantor et al. 1975; Galbraith et al. 1999).

The quality and quantity of each clinical RNA sample is desirably checked before amplification and labeling for array hybridization, using methods known in the art. For example, one microliter of each sample may be analyzed on a Bioanalyzer (Agilent 2100 Palo Alto, CA. USA) using an RNA 6000 nano LabChip (Caliper, Mountain View, CA. USA). Degraded RNA is identified by the reduction of the 28S to 18S ribosomal RNA ratio and/or the presence of large quantities of RNA in the 25-100 nucleotide range.

It is appreciated that the RNA sample for use with a diagnostic nucleotide set may be produced from the same or a different cell population, sub-population and/or cell type as used to identify the diagnostic nucleotide set. For example, a diagnostic nucleotide set identified using RNA extracted from mononuclear cells may be suitable for analysis of RNA extracted from whole blood or mononuclear cells, depending on the particular characteristics of the members of the diagnostic nucleotide set. Generally, diagnostic nucleotide sets must be tested and validated when used with RNA derived from a different cell population, sub-population or cell type than that used when obtaining the diagnostic gene set. Factors such as the cell-specific gene expression of diagnostic nucleotide set members, redundancy of the information provided by members of the diagnostic nucleotide set, expression level of the member of the diagnostic nucleotide set, and cell-specific alteration of expression of a member of the diagnostic nucleotide set will contribute to the usefulness of using a different RNA source than that used when identifying the members of the diagnostic nucleotide set. It is appreciated that it may be desirable to assay RNA derived from whole blood, obviating the need to isolate particular cell types from the blood. 95

Rapid method of RNA extraction suitable for production in a clinical setting of high quality

RNA for expression profiling

In a clinical setting, obtaining high quality RNA preparations suitable for expression profiling, from a desired population of leukocytes poses certain technical challenges, including: the lack of capacity for rapid, high-throughput sample processing in the clinical setting, and the possibility that delay in processing (in a busy lab or in the clinical setting) may adversely affect RNA quality, e.g. by a permitting the expression profile of certain nucleotide sequences to shift. Also, use of toxic and expensive reagents, such as phenol, may be disfavored in the clinical setting due to the added expense associated with shipping and handling such reagents.

A useful method for RNA isolation for leukocyte expression profiling would allow the isolation of monocyte and lymphocyte RNA in a timely manner, while preserving the expression profiles of the cells, and allowing inexpensive production of reproducible high-quality RNA samples.

Accordingly, the invention provides a method of adding inhibitor(s) of RNA transcription and/or inhibitor(s) of protein synthesis, such that the expression profile is “frozen” and RNA degradation is reduced. A desired leukocyte population or sub-population is then isolated, and the sample may be frozen or lysed before further processing to extract the RNA. Blood is drawn from subject population and exposed to ActinomycinD (to a final concentration of 10 ug/ml) to inhibit transcription, and cycloheximide (to a final concentration of 10 ug/ml) to inhibit protein synthesis. The inhibitor(s) can be injected into the blood collection tube in liquid form as soon as the blood is drawn, or the tube can be manufactured to contain either lyophilized inhibitors or inhibitors that are in solution with the anticoagulant. At this point, the blood sample can be stored at room temperature until the desired leukocyte population or sub-population is isolated, as described elsewhere. RNA is isolated using standard methods, e.g., as described above, or a ccll pellet or extract can be frozen until further processing of RNA is convenient.

The invention also provides a method of using a low-temperature density gradient for separation of a desired leukocyte sample. In another embodiment, the invention provides the combination of use of a low-temperature density gradient and the use of transcriptional and/or protein synthesis inhibitor(s). A desired leukocyte population is separated using a density gradient solution for cell separation that maintains the required density and viscosity for cell separation at 0-4°C. Blood is drawn into a tube containing this solution and may be refrigerated before and during processing as the low temperatures slow cellular processes and minimize expression profile changes. Leukocytes are separated, and RNA is isolated using standard methods. Alternately, a cell pellet or extract is frozen until further processing of RNA is convenient. Care must be taken to avoid rewarming the sample during further processing steps.

Alternatively, the invention provides a method of using low-temperature density gradient separation, combined with the use of actinomycin A and cyclohexamide, as described above.

Assessing expression for diagnostics

Expression profiles for the set of diagnostic nucleotide sequences in a subject sample can be evaluated by any technique that determines the expression of each component nucleotide sequence.

Methods suitable for expression analysis are known in the art, and numerous examples are discussed in the Sections titled “Methods of obtaining expression data” and “high throughput expression Assays”, above.

In many cases, evaluation of expression profiles is most efficiently, and cost effectively, performed by analyzing RNA expression. Alternatively, the proteins encoded by each component of the diagnostic nucleotide set are detected for diagnostic purposes by any technique capable of determining protein expression, €.g., as described above. Expression profiles can be assessed in subject leukocyte sample using the same or different techniques as those used to identify and validate the diagnostic nucleotide set. For example, a diagnostic nucleotide set identified as a subset of sequences on a cDNA microarray can be utilized for diagnostic (or prognostic, or monitoring, etc.) purposes on the same array from which they were identified. Alternatively, the diagnostic nucleotide sets for a given disease or condition can be organized onto a dedicated sub-array for the indicated purpose. It is important to note that if diagnostic nucleotide sets are discovered using one technology, e.g. RNA expression profiling, but applied as a diagnostic using another technology, e.g. protein expression profiling, the nucleotide sets must generally be validated for diagnostic purposes with the new technology. In addition, it is appreciated that diagnostic nucleotide sets that are developed for one use, e.g. to diagnose a particular disease, may later be found to be useful for a different application, e.g. to predict the likelihood that the particular disease will occur. Generally, the diagnostic nucleotide set will need to be validated for use in the second circumstance. As discussed herein, the sequence of diagnostic nucleotide set members may be amplified from RNA or cDNA using methods known in the art providing specific amplification of the nucleotide sequences.

General Protein Methods

Protein products of the nucleotide sequences of the invention may include proteins that represent functionally equivalent gene products. Such an equivalent gene product may contain deletions, additions or substitutions of amino acid residues within the amino acid sequence encoded by the nucleotide sequences described, above, but which result in a silent change, thus producinga functionally equivalent nucleotide sequence product. Amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved.

For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. "Functionally equivalent”, as utilized herein, refers to a protein capable of exhibiting a substantially similar in vivo activity as the endogenous gene products encoded by the nucleotide described, above.

The gene products (protein products of the nucleotide sequences) may be produced by recombinant DNA technology using techniques well known in the art. Thus, methods for preparing the gene polypeptides and peptides of the invention by expressing nucleic acid encoding nucleotide sequences are described herein. Methods which are well known to those skilled in the art can be used to construct expression vectors containing nucleotide sequence protein coding sequences and appropriate transcriptional/transiational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques and in vivo recombination/genetic recombination.

See, for example, the techniques described in Sambrook et al., 1989, supra, and Ausubel et al., 1989, supra. Alternatively, RNA capable of encoding nucleotide sequence protein sequences may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in "Oligonucleotide Synthesis”, 1984, Gait, M. J. ed., IRL Press, Oxford, which is incorporated by reference herein in its entirety

A variety of host-expression vector systems may be utilized to express the nucleotide sequence coding sequences of the invention. Such host-expression systems represent vehicles by which the coding sequences of interest may be produced and subsequently purified, but also represent cells which may, when transformed or transfected with the appropriate nucleotide coding sequences, exhibit the protein encoded by the nucleotide sequence of the invention in situ. These include but are not limited to microorganisms such as bacteria (e.g., E. coli, B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing nucleotide sequence protein coding sequences; yeast (e.g. Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing the nucleotide sequence protein coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing the nucleotide sequence protein coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing nucleotide sequence protein coding sequences; or mammalian cell systems (e.g. COS, CHO, BHK, 293, 3T3) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5 K promoter).

In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the nucleotide sequence protein being expressed. For example, when a large quantity of such a protein is to be produced, for the generation of antibodies or to screen peptide libraries, for example, vectors which direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited, to the E. coli expression vector pUR278 (Ruther et al., 1983, EMBO J. 2:1791), in which the nucleotide sequence protein coding sequence may be ligated individually into the vector in frame with the lac Z coding region so that a fusion protein is produced; pIN vectors (Inouye & Inouye, 1985, Nucleic Acids

Res. 13:3101-3109; Van Heeke & Schuster, 1989, 1. Biol. Chem. 264:5503-5509); and the likes of pGEX vectors may also be used to express foreign polypeptides as fusion proteins with glutathione S- transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads followed by elution in the presence of free glutathione.

The pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target nucleotide sequence protein can be released from the GST moiety. Other systems useful in the invention include use of the FLAG epitope or the 6-HIS systems.

In an insect system, Autographa californica nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign nucleotide sequences. The virus grows in Spodoptera frugiperda cells. The nucleotide sequence coding sequence may be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter). Successful insertion of nucleotide sequence coding sequence will result in inactivation of the polyhedrin gene and production of non-occluded recombinant virus (i.e., virus lacking the proteinaceous coat coded for by the polyhedrin gene). These recombinant viruses are then used to infect Spodoptera frugiperda cells in which the inserted nucleotide sequence is expressed. (E.g., see Smith etal, 1983, J. Virol. 46: 584; Smith, U.S. Pat. No. 4,215,051).

In mammalian host cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, the nucleotide sequence coding sequence of interest may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric nucleotide sequence may then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g, region E1 or E3) will result in a recombinant virus that is viable and capable of expressing nucleotide sequence encoded protein in infected hosts. (E.g., See Logan & Shenk, 1984,

Proc. Natl. Acad. Sci. USA 81:3655-3659). Specific initiation signals may also be required for efficient translation of inserted nucleotide sequence coding sequences. These signals include the ATG initiation codon and adjacent sequences. In cases where an entire nucleotide sequence, including its own initiation codon and adjacent sequences, is inserted into the appropriate expression vector, no additional translational control signals may be needed. However, in cases where only a portion of the : nucleotide sequence coding sequence is inserted, exogenous translational control signals, including, perhaps, the ATG initiation codon, must be provided. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert.

These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see Bittner et al., 1987, Methods in

Enzymol. 153:516-544).

In addition, a host cell strain may be chosen which modulates the expression of the inserted sequences, or modifies and processes the product of the nucleotide sequence in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. Such mammalian host cells include but are not limited to CHO, VERO, BHK, Hela, COS, ‘ MDCK, 293, 3T3, WI38, etc.

For long-term, high-yield production of recombinant proteins, stable expression is preferred. ‘For example, cell lines which stably express the nucleotide sequence encoded protein may be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. "Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days "in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines.

This method may advantageously be used to engineer cell lines which express nucleotide sequence encoded protein. Such engineered cell lines may be particularly useful in screening and evaluation of compounds that affect the endogenous activity of the nucleotide sequence encoded protein.

A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler, et al., 1977, Cell 11:223), hypoxanthine-guanine phasphoribosyltransferase (Szybalska & Szybalski, 1962, Proc. Natl. Acad. Sci. USA 48:2026), and adenine phosphoribosyltransferase (Lowy, et al., 1980, Cell 22:817) genes can be employed in tk-, hgprt- or aprt- cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for dhfr, which confers resistance to methotrexate (Wigler, et al, 1980, Natl. Acad. Sci. USA 77:3567,

O'Hare, et al, 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin, et al., 1981, J. Mol. Biol. 150:1); and hygro, which confers resistance to hygromycin (Santerre, et al., 1984, Gene 30:147) genes.

An alternative fusion protein system allows for the ready purification of non-denatured fusion proteins expressed in human cell lines (Janknecht, et al., 1991, Proc. Natl. Acad. Sci. USA 88: 8972- 8976). In this system, the nucleotide sequence of interest is subcloned into a vaccinia recombination plasmid such that the nucleotide sequence’s open reading frame is translationally fused to an amino- terminal tag consisting of six histidine residues. Extracts from cells infected with recombinant vaccinia virus are loaded onto Ni.sup.2 +-nitriloacetic acid-agarose columns and histidine-tagged proteins are selectively eluted with imidazole-containing buffers.

Where recombinant DNA technology is used to produce the protein encoded by the nucleotide sequence for such assay systems, it may be advantageous to engineer fusion proteins that can facilitate labeling, immobilization and/or detection.

Antibodies

Indirect labeling involves the use of a protein, such as a labeled antibody, which specifically binds to the protein encoded by the nucleotide sequence. Such antibodies include but are not limited to polyclonal, monoclonal, chimeric, single chain, Fab fragments and fragments produced by an Fab expression library.

The invention also provides for antibodies to the protein encoded by the nucleotide sequences.

Described herein are methods for the production of antibodies capable of specifically recognizing one or more nucleotide sequence epitopes. Such antibodies may include, but are not limited to polyclonal antibodies, monoclonal antibodies (mAbs), humanized or chimeric antibodies, single chain antibodies,

Fab fragments, F(ab')2 fragments, fragments produced by a Fab expression library, anti-idiotypic (anti-

1d) antibodies, and epitope-binding fragments of any of the above. Such antibodies may be used, for example, in the detection of a nucleotide sequence in a biological sample, or, alternatively, as a method for the inhibition of abnormal gene activity, for example, the inhibition of a disease target nucleotide ’ sequence, as further described below. Thus, such antibodies may be utilized as part of cardiovascular or other disease treatment method, and/or may be used as part of diagnostic techniques whereby patients may be tested for abnormal levels of nucleotide sequence encoded proteins, or for the presence of abnormal forms of the such proteins.

For the production of antibodies to a nucleotide sequence, various host animals may be immunized by injection with a protein encoded by the nucleotide sequence, or a portion thereof. Such host animals may include but are not limited to rabbits, mice, and rats, to name but a few. Various adjuvants may be used to increase the immunological response, depending on the host species, including but not limited to Freund's (complete and incomplete), mineral gels such as aluminum hydroxide, surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, keyhole limpet hemocyanin, dinitrophenol, and potentially useful human adjuvants such as

BCG (bacille Calmette-Guerin) and Corynebacterium parvum.

Polyclonal antibodies are heterogeneous populations of antibody molecules derived from the sera of animals immunized with an antigen, such as gene product, or an antigenic functional derivative thereof. For the production of polyclonal antibodies, host animals such as those described above, may be immunized by injection with gene product supplemented with adjuvants as also described above.

Monoclonal antibodies, which are homogeneous populations of antibodies to a particular antigen, may be obtained by any technique which provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to the hybridoma technique of Kohler and Milstein, (1975, Nature 256:495-497; and U.S. Pat. No. 4.376,110), the human B-cell hybridoma technique (Kosbor et al., 1983, Immunology Today 4:72; Cole et al., 1983, Proc. Natl. Acad. Sci. USA 80:2026-2030), and the EBV-hybridoma technique (Cole et al., 1985, Monoclonal Antibodies And

Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Such antibodies may be of any immunoglobulin class including IgG, 1gM, IgE, IgA, IgD and any subclass thereof. The hybridoma producing the mAb of this invention may be cultivated in vitro or in vivo.

In addition, techniques developed for the production of "chimeric antibodies" (Morrison et al, : 1984, Proc. Natl. Acad. Sci., 81:6851-6855; Neuberger et al., 1984, Nature, 312:604-608; Takeda et al., 1985, Nature, 314:452-454) by splicing the genes from a mouse antibody molecule of appropnate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived froma murine mAb and a human immunoglobulin constant region. "Alternatively, techniques described for the production of single chain antibodies (U.S. Pat.

No. 4,946,778; Bird, 1988, Science 242:423-426; Huston etal, 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; and Ward et al., 1989, Nature 334:544-546) can be adapted to produce nucleotide sequence-single chain antibodies. Single chain antibodies are formed by linking the heavy and light chain fragments of the Fv region via an amino acid bridge, resulting in a single chain polypeptide.

Antibody fragments which recognize specific epitopes may be generated by known techniques

For example, such fragments include but are not limited to: the F(ab')2 fragments which can be produced by pepsin digestion of the antibody molecule and the Fab fragments which can be generated by reducing the disulfide bridges of the F(ab')2 fragments. Alternatively, Fab expression libraries may be constructed (Huse et al., 1989, Science, 246:1275-1281) to allow rapid and easy identification of ‘monoclonal Fab fragments with the desired specificity.

Disease specific target nucleotide sequences

The invention also provides disease specific target nucleotide sequences, and sets of discase specific target nucleotide sequences. The diagnostic nucleotide sets, subsets thereof, novel nucleotide sequences, and individual members of the diagnostic nucleotide sets identified as described above are also disease specific target nucleotide sequences. In particular, individual nucleotide sequences that are differentially regulated or have predictive value that is strongly correlated with a disease or disease criterion are especially favorable as disease specific target nucleotide sequences. Sets of genes that are co-regulated may also be identified as disease specific target nucleotide sets. Such nucleotide sequences and/or nucleotide sequence products are targets for modulation by a variety of agents and techniques. For example, disease specific target nucleotide sequences (or the products of such nucleotide sequences, or sets of disease specific target nucleotide sequences) can be inhibited or activated by, e.g., target specific monoclonal antibodies or small molecule inhibitors, or delivery of the nucleotide sequence or gene product of the nucleotide sequence to patients. Also, sets of genes can be inhibited or activated by a variety of agents and techniques. The specific usefulness of the target nucleotide sequence(s) depends on the subject groups from which they were discovered, and the disease or disease criterion with which they correlate.

Imaging

The invention also provides for imaging reagents. The differentially expressed leukocyte nucleotide sequences, diagnostic nucleotide sets, or portions thereof, and novel nucleotide sequences of the invention are nucleotide sequences expressed in cells with or without disease. Leukocytes expressing a nucleotide sequence(s) that is differentially expressed in a disease condition may localize within the body to sites that are of interest for imaging purposes. For example, a leukocyte expressing a nucleotide sequence(s) that are differentially expressed in an individual having atherosclerosis may localize or accumulate at the site of an atherosclerotic placque. Such leukocytes, when labeled, may provide a detection reagent for use in imaging regions of the body where labeled leukocyte accumulate or localize, for example, at the atherosclerotic plaque in the case of atherosclerosis. For example, leukocytes are collected from a subject, labeled in vitro, and reintroduced into a subject. Alternatively, the labeled reagent is introduced into the subject individual, and leukocyte labeling occurs within the patient. i _ Imaging agents that detect the imaging targets of the invention are produced by well-known

B molecular and immunological methods (for exemplary protocols, see, e.g. Ausubel, Berger, and

Sambrook, as well as Harlow and Lane, supra). oo For example, a full-length nucleic acid sequence, or alternatively, a gene fragment encoding an immunogenic peptide or polypeptide fragments, is cloned into a convenient expression vector, for example, a vector including an in-frame epitope or substrate binding tag to facilitate subsequent purification. Protein is then expressed from the cloned cDNA sequence and used to generate antibodies, or other specific binding molecules, to one or more antigens of the imaging target protein.

Alternatively, a natural or synthetic polypeptide (or peptide) or small molecule that specifically binds ( or is specifically bound to) the expressed imaging target can be identified through well established ) "techniques (see, e.g., Mendel et al. (2000) Anticancer Drug Des 15:29-41; Wilson (2000) Curr Med

Chem 7:73-98; Hamby and Showwalter (1999) Pharmacol Ther 82:169-93; and Shimazawa et al. (1998) Curr Opin Struct Biol 8:451-8). The binding molecule, e.g., antibody, small molecule ligand, etc., is labeled with a contrast agent or other detectable label, e.g., gadolinium, iodine, or a gamma- emitting source. For in-vivo imaging of a disease process that involved leukocytes, the labeled antibody is infused into a subject, e.g., a human patient or animal subject, and a sufficient period of time is passed to permit binding of the antibody to target cells. The subject is then imaged with appropriate technology such as MRI (when the label is gadolinium) or with a gamma counter (when the label is a gamma emitter).

Identification of nucleotide sequence involved in leukocyte adhesion

The invention also encompasses a method of identifying nucleotide sequences involved in leukocyte adhesion. The interaction between the endothelial cell and leukocyte is a fundamental mechanism of all inflammatory disorders, including the diagnosis and prognosis of allograft rejection the diseases listed in Table 1. For example, the first visible abnormality in atherosclerosis is the adhesion to the endothelium and diapedesis of mononuclear cells (e.g., T-cell and monocyte). Insults to the endothelium (for example, cytokines, tobacco, diabetes, hypertension and many more) lead to endothelial cell activation. The endothelium then expresses adhesion molecules, which have counter receptors on mononuclear cells. Once the leukocyte receptors have bound the endothelial adhesion molecules, they stick to the endothelium, roll a short distance, stop and transmigrate across the endothelium. A similar set of events occurs in both acute and chronic inflammation. When the leukocyte binds the endothelial adhesion molecule, or to soluble cytokines secreted by endothelial or other cells, a program of gene expression is activated in the leukocyte. This program of expression leads to leukocyte rolling, firm adhesion and transmigration into the vessel wall or tissue parenchyma.

Inhibition of this process is highly desirable goal in anti-inflammatory drug development. In addition, leukocyte nucleotide sequences and epithelial cell nucleotide sequences, that are differentially expressed during this process may be disease-specific target nucleotide sequences.

Human endothelial cells, e.g. derived from human coronary arteries, human aorta, human pulmonary artery, human umbilical vein or microvascular endothelial cells, are cultured as a confluent monolayer, using standard methods. Some of the endothelial cells are then exposed to cytokines or another activating stimuli such as oxidized LDL, hyperglycemia, shear stress, or hypoxia (Moser et al. ©1992). Some endothelial cells are not exposed to such stimuli and serve as controls. For example, the endothelial cell monolayer is incubated with culture medium containing 5 U/ml of human recombinant

IL-1alpha or 10 ng/ml TNF (tumor necrosis factor), for a period of minutes to overnight. The culture medium composition is changed or the flask is sealed to induce hypoxia. In addition, tissue culture plate is rotated to induce sheer stress.

Human T-cells and/or monocytes are cultured in tissue culture flasks or plates, with LGM-3 media from Clonetics. Cells are incubated at 37 degree C, 5% CO2 and 95% humidity. These leukocytes are exposed to the activated or control endothelial layer by adding a suspension of leukocytes on to the endothelial cell monolayer. The endothelial cell monolayer is cultured on a tissue culture treated plate/ flask or on a microporous membrane. After a variable duration of exposures, the endothelial cells and leukocytes are harvested separately by treating all cells with trypsin and then ; sorting the endothelial cells from the leukocytes by magnetic affinity reagents to an endothelial cell specific marker such as PECAM-1 (Stem Cell Technologies). RNA is extracted from the isolated cells by standard techniques. Leukocyte RNA is labeled as described above, and hybridized to leukocyte candidate nucleotide library. Epithelial cell RNA is also labeled and hybridized to the leukocyte candidate nucleotide library. Alternatively, the epithelial cell RNA is hybridized to a epithelial cell candidate nucleotide library, prepared according to the methods described for leukocyte candidate libraries, above.

Hybridization to candidate nucleotide libraries will reveal nucleotide sequences that are up- regulated or down-regulated in leukocyte and/or epithelial cells undergoing adhesion. The differentially regulated nucleotide sequences are further characterized, e.g. by isolating and sequencing } the full-length sequence, analysis of the DNA and predicted protein sequence, and functional characterization of the protein product of the nucleotide sequence, as described above. Further characterization may result in the identification of leukocyte adhesion specific target nucleotide sequences, which may be candidate targets for regulation of the inflammatory process. Small molecule or antibody inhibitors can be developed to inhibit the target nucleotide sequence function. Such inhibitors are tested for their ability to inhibit leukocyte adhesion in the in vitro test described above.

Integrated systems

Integrated systems for the collection and analysis of expression profiles, and molecular signatures, as well as for the compilation, storage and access of the databases of the invention, typically include a digital computer with software including an instruction set for sequence searching and analysis, and, optionally, high-throughput liquid control software, image analysis software, data interpretation software, a robotic control armature for transferring solutions from a source to a . destination (such as a detection device) operably linked to the digital computer, an input device (e.g., a computer keyboard) for entering subject data to the digital computer, or to control analysis operations or high throughput sample transfer by the robotic control armature. Optionally, the integrated system further comprises an image scanner for digitizing label signals from labeled assay components, e.g., labeled nucleic acid hybridized to a candidate library microarray. The image scanner can interface with image analysis software to provide a measurement of the presence or intensity of the hybridized label, i.e., indicative of an on/off expression pattern or an increase or decrease in expression. " Readily available computational hardware resources using standard operating systems are fully adequate, e.g., a PC (Intel x86 or Pentium chip- compatible DOS, ™ OS2,™ WINDOWS, ™

WINDOWS NT, ™ WINDOWS95 ™ WINDOWS98,™ LINUX, or even Macintosh, Sun or PCs will suffice) for use in the integrated systems of the invention. Current art in software technology is similarly adequate (i.e., there are a multitude of mature programming languages and source code suppliers) for design, e.g., of an upgradeable open-architecture object-oriented heuristic algorithm, or instruction set for expression analysis, as described herein. For example, software for aligning or otherwise manipulating ,molecular signatures can be constructed by one of skill using a standard programming language such as Visual basic, Fortran, Basic, Java, or the like, according to the methods ) herein.

Various methods and algorithms, including genetic algorithms and neural networks, can be used to perform the data collection, correlation, and storage functions, as well as other desirable functions, as described herein. In addition, digital or analog systems such as digital or analog computer systems can control a variety of other functions such as the display and/or control of input and output files.

For example, standard desktop applications such as word processing software (e.g., Corel :

WordPerfect™ or Microsoft Word™) and database software (e.g., spreadsheet software such as Corel

Quattro Pro™, Microsoft Excel™, or database programs such as Microsoft Access™ or Paradox™) can be adapted to the present invention by inputting one or more character string corresponding, e.g, to an expression pattern or profile, subject medical or historical data, molecular signature, or the like, into the software which is loaded into the memory of a digital system, and carrying out the operations indicated in an instruction set, e.g., as exemplified in Figure 2. For example, systems can include the foregoing software having the appropriate character string information, e.g., used in conjunction with a user interface in conjunction with a standard operating system such as a Windows, Macintosh or

LINUX system. For example, an instruction set for manipulating strings of characters, either by programming the required operations into the applications or with the required operations performed manually by a user (or both). For example, specialized sequence alignment programs such as PILEUP or BLAST can also be incorporated into the systems of the invention, e.g., for alignment of nucleic acids or proteins (or corresponding character strings).

Software for performing the statistical methods required for the invention, e.g., to determine correlations between expression profiles and subsets of members of the diagnostic nucleotide libraries, such as programmed embodiments of the statistical methods described above, are also included in the computer systems of the invention. Alternatively, programming elements for performing such methods as principle component analysis (PCA) or least squares analysis can also be included in the digital system to identify relationships between data. Exemplary software for such methods is provided by

Partek, Inc., St. Peter, Mo; at the web site partek.com.

Any controller or computer optionally includes a monitor which can include, e.g., a flat panel display (e.g., active matrix liquid crystal display, liquid crystal display), a cathode ray tube ("CRT") display, or another display system which serves as a user interface, e.g., to output predictive data.

Computer circuitry, including numerous integrated circuit chips, such as a microprocessor, memory, interface circuits, and the like, is often placed in a casing or box which optionally also includes a hard disk drive, a floppy disk drive, a high capacity removable drive such as a writeable CD-ROM, and other common peripheral elements.

Inputting devices such as a keyboard, mouse, or touch sensitive screen, optionally provide for input from a user and for user selection, e.g., of sequences or data sets to be compared or otherwise manipulated in the relevant computer system. The computer typically includes appropriate software for receiving user instructions, either in the form of user input into a set parameter or data fields (e.g., to input relevant subject data), or in the form of preprogrammed instructions, e.g., preprogrammed for a variety of different specific operations. The software then converts these instructions to appropriate language for instructing the system to carry out any desired operation. © The integrated system may also be embodied within the circuitry of an application specific integrated circuit (ASIC) or programmable logic device (PLD). In such a case, the invention is embodied ina computer readable descriptor language that can be used to create an ASIC or PLD. The integrated system can also be embodied within the circuitry or logic processors of a variety of other digital apparatus, such as PDAs, laptop computer systems, displays, image editing equipment, etc.

The digital system can comprise a learning component where expression profiles, and relevant subject data are compiled and monitored in conjunction with physical assays, and where correlations, e.g., molecular signatures with predictive value for a disease, are established or refined. Successful and unsuccessful combinations are optionally documented in a database to provide justification/preferences for user-base or digital system based selection of diagnostic nucleotide sets with high predictive accuracy for a specified disease or condition.

The integrated systems can also include an automated workstation. For example, such a workstation can prepare and analyze leukocyte RNA samples by performing a sequence of events including: preparing RNA from a human blood sample; labeling the RNA with an isotopic or non- isotopic label; hybridizing the labeled RNA to at least one array comprising all or part of the candidate library; and detecting the hybridization pattern. The hybridization pattern is digitized and recorded in the appropriate database. :

Automated RNA preparation tool

The invention also includes an automated RNA preparation tool for the preparation of mononuclear cells from whole blood samples, and preparation of RNA from the mononuclear cells. In a preferred embodiment, the use of the RNA preparation tool is fully automated, so that the cell separation and RNA isolation would require no human manipulations. Full automation is advantageous because it minimizes delay, and standardizes sample preparation across different laboratories. This standardization increases the reproducibility of the results.

Figure 2 depicts the processes performed by the RNA preparation tool of the invention. A primary component of the device is a centrifuge (A). Tubes of whole blood containing a density gradient solution, transcription/translation inhibitors, and a gel barrier that separates erythrocytes from mononuclear cells and serum after centrifugation are placed in the centrifuge (B). The bamier is permeable to erythrocytes and granulocytes during centrifugation, but does not allow mononuclear cells to pass through (or the barrier substance has a density such that mononuclear cells remain above the level of the barrier during the centrifugation ). After centrifugation, the erythrocytes and granulocytes are trapped beneath the barrier, facilitating isolation of the mononuclear cell and serum layers. A mechanical arm removes the tube and inverts it to mix the mononuclear cell layer and the serum (C). The arm next pours the supernatant into a fresh tube (D), while the erythrocytes and granulocytes remained below the barrier. Alternatively, a needle is used to aspirate the supernatant and : Co 106 SE transfer it to a fresh tube. The mechanical arms of the device opens and closes lids, dispenses PBS to aid in the collection of the mononuclear cells by centrifugation, and moves the tubes in and out of the centrifuge. Following centrifugation, the supernatant is poured off or removed by a vacuum device (E), leaving an isolated mononuclear cell pellet. Purification of the RNA from the cells is performed automatically, with lysis buffer and other purification solutions (F) automatically dispensed and removed before and after centrifugation steps. The result is a purified RNA solution. In another embodiment, RNA isolation is performed using a column or filter method. In yet another embodiment, the invention includes an on-board homogenizer for use in cell lysis.

Other automated systems

Automated and/or semi-automated methods for solid and liquid phase high-throughput sample preparation and evaluation are available, and supported by commercially available devices. For example, robotic devices for preparation of nucleic acids from bacterial colonies, e.g., to facilitate production and characterization of the candidate library include, for example, an automated colony : picker (e.g., the Q-bot, Genetix, U.K.) capable of identifying, sampling, and inoculating up to 10,000/4 hrs different clones into 96 well microtiter dishes. Alternatively, or in addition, robotic systems for liquid handling are available from a variety of sources, e.g., automated workstations like the automated synthesis apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and many robotic systems utilizing robotic arms (Zymate II, Zymark Corporation, Hopkinton, Mass.; Orca, Beckman

Coulter, Inc. (Fullerton, CA)) which mimic the manual operations performed by a scientist. Any of the above devices are suitable for use with the present invention, e.g., for high-throughput analysis of library components or subject leukocyte samples. The nature and implementation of modifications to these devices (if any) so that they can operate as discussed herein will be apparent to persons skilled in the relevant art.

High throughput screening systems that automate entire procedures, e.g., sample and reagent pipetting, liquid dispensing, timed incubations, and final readings of the microplate in detector(s) appropriate for the relevant assay are commercially available. (see, e.g., Zymark Corp., Hopkinton,

MA; Air Technical Industries, Mentor, OH; Beckman Instruments, Inc. Fullerton, CA; Precision

Systems, Inc., Natick, MA, etc.). These configurable systems provide high throughput and rapid start up as well as a high degree of flexibility and customization. Similarly, arrays and array readers are available, e.g., from Affymetrix, PE Biosystems, and others.

The manufacturers of such systems provide detailed protocols the various high throughput.

Thus, for example, Zymark Corp. provides technical bulletins describing screening systems for detecting the modulation of gene transcription, ligand binding, and the like.

A variety of commercially available peripheral equipment, including, e.g., optical and fluorescent detectors, optical and fluorescent microscopes, plate readers, CCD arrays, phosphorimagers, scintillation counters, phototubes, photodiodes, and the like, and software is available for digitizing, storing and analyzing a digitized video or digitized optical or other assay results, e.g., using PC (Intel x86 or pentium chip- compatible DOS™, 0S2™ WINDOWS™,

WINDOWS NT™ or WINDOWS95™ based machines), MACINTOSH™, or UNIX based (e.g.,

SUN™ work station) computers.

Embodiment in a web site. }

The methods described above can be implemented in a localized or distributed computing environment. For example, if a localized computing environment is used, an array comprising a candidate nucleotide library, or diagnostic nucleotide set, is configured in proximity to a detector, which is, in turn, linked to a computational device equipped with user input and output features.

In a distributed environment, the methods can be implemented on a single computer with multiple processors or, altematively, on multiple computers. The computers can be linked, e.g. through a shared bus, but more commonly, the computer(s) are nodes on a network. The network can be generalized or dedicated, at a local level or distributed over a wide geographic area. In certain ‘embodiments, the computers are components of an intra-net or an internet.

The predictive data corresponding to subject molecular signatures (e.g., expression profiles, and related diagnostic, prognostic, or monitoring results) can be shared by a variety of parties. In particular, such information can be utilized by the subject, the subject's health care practitioner or provider, a company or other institution, or a scientist. An individual subject’s data, a subset of the database or the entire database recorded in a computer readable medium can be accessed directly by a user by any method of communication, including, but not limited to, the internet. With appropriate computational devices, integrated systems, communications networks, users at remote locations, as well as users located in proximity to, e.g., at the same physical facility, the database can access the recorded information. Optionally, access to the database can be controlled using unique alphanumeric passwords that provide access to a subset of the data. Such provisions can be used, €.g., to ensure privacy, anonymity, etc.

Typically, a client (e.g., a patient, practitioner, provider, scientist, or the like) executes a Web browser and is linked to a server computer executing a Web server. The Web browser is, for example, a program such as IBM's Web Explorer, Intemet explorer, NetScape or Mosaic, or the like. The Web server is typically, but not necessarily, a program such as IBM's HTTP Daemon or other WWW daemon (e.g., LINUX-based forms of the program). The client computer is bi-directionally coupled with the server computer over a line or via a wireless system. In turn, the server computer is bi- directionally coupled with a website (server hosting the website) providing access to software implementing the methods of this invention.

A user of a client connected to the Intranet or Internet may cause the client to request resources that are part of the web site(s) hosting the application(s) providing an implementation of the methods described herein. Server program(s) then process the request to return the specified resources (assuming they are currently available). A standard naming convention has been adopted, known as a

Uniform Resource Locator ("URL"). This convention encompasses several types of location names, presently including subclasses such as Hypertext Transport Protocol ("http"), File Transport Protocol ("ftp"), gopher, and Wide Area Information Service ("WAIS"). When a resource is downloaded, it may include the URLs of additional resources. Thus, the user of the client can easily learn of the existence of new resources that he or she had not specifically requested.

Methods of implementing Intranet and/or Intranet embodiments of computational and/or data access processes are well known to those of skill in the art and are documented, e.g., in ACM Press, pp.

383-392; ISO-ANSI, Working Draft, "Information Technology-Database Language SQL", Jim

Melton, Editor, International Organization for Standardization and American National Standards

Institute, Jul. 1992; ISO Working Draft, "Database Language SQL-Part 2:Foundation (SQL/Foundation)", CD9075-2:199.chi.SQL, Sep. 11, 1997; and Cluer et al. (1992) A General

Framework for the Optimization of Object-Oriented Queries, Proc SIGMOD Intemational Conference on Management of Data, San Diego, California, Jun. 2-5, 1992, SIGMOD Record, vol. 21, Issue 2,

Jun., 1992; Stonebraker, M., Editor;. Other resources are available, e.g., from Microsoft, IBM, Sun and other software development companies.

Using the tools described above, users of the reagents, methods and database as discovery or diagnostic tools can query a centrally located database with expression and subject data. Each submission of data adds to the sum of expression and subject information in the database. As data is added, a new correlation statistical analysis is automatically run that incorporates the added clinical and expression data. Accordingly, the predictive accuracy and the types of correlations of the recorded molecular signatures increases as the database grows.

For example, subjects, such as patients, can access the results of the expression analysis of their leukocyte samples and any accrued knowledge regarding the likelihood of the patient’s belonging to any specified diagnostic (or prognostic, or monitoring, or risk group), i.e., their expression profiles, and/or molecular signatures. Optionally, subjects can add to the predictive accuracy of the database by providing additional information to the database regarding diagnoses, test results, clinical or other related events that have occurred since the time of the expression profiling. Such information can be provided to the database via any form of communication, including, but not limited to, the internet.

Such data can be used to continually define (and redefine) diagnostic groups. For example, if 1000 patients submit data regarding the occurrence of myocardial infarction over the 5 years since their expression profiling, and 300 of these patients report that they have experienced a myocardial infarction and 700 report that they have not, then the 300 patients define a new “group A.” As the algorithm is used to continually query and revise the database, a new diagnostic nucleotide set that differentiates groups A and B (i.e., with and without myocardial infarction within a five year period) is identified. This newly defined nucleotide set is then be used (in the manner described above) as a test that predicts the occurrence of myocardial infarction over a five-year period. While submission directly by the patient is exemplified above, any individual with access and authority to submit the . relevant data e.g., the patient’s physician, a laboratory technician, a health care or study administrator, or the like, can do so.

As will be apparent from the above examples, transmission of information via the internet (or via an intranet) is optionally bi-directional. That is, for example, data regarding expression profiles, subject data, and the like are transmitted via a communication system to the database, while information regarding molecular signatures, predictive analysis, and the like, are transmitted from the database to the user. For example, using appropriate configurations of an integrated system including a microarray comprising a diagnostic nucleotide set, a detector linked to a computational device can directly transmit (locally or from a remote workstation at great distance, e.g., hundreds or thousands of miles distant from the database) expression profiles and a corresponding individual identifier to a central database for analysis according to the methods of the invention. According to, e.g, the algorithms described above, the individual identifier is assigned to one or more diagnostic (or prognostic, or monitoring, etc.) categories. The results of this classification are then relayed back, via, €.g., the same mode of communication, to a recipient at the same or different internet (or intranet) address.

Kits

The present invention is optionally provided to a user as a kit. Typically, a kit contains one or more diagnostic nucleotide sets of the invention. Alternatively, the kit contains the candidate nucleotide library of the invention. Most often, the kit contains a diagnostic nucleotide probe set, or other subset of a candidate library, e.g., as a cDNA or antibody microarray packaged in a suitable container. The kit may further comprise, one or more additional reagents, e.g., substrates, labels, primers, for labeling expression products, tubes and/or other accessories, reagents for collecting blood samples, buffers, e.g., erythrocyte lysis buffer, leukocyte lysis buffer, hybridization chambers, cover slips, etc., as well as a software package, e.g., including the statistical methods of the invention, e.g., as described above, and a password and/or account number for accessing the compiled database. The kit optionally further comprises an instruction set or user manual detailing preferred methods of using the diagnostic nucleotide sets in the methods of the invention. In one embodiment, the kit may include contents useful for the discovery of diagnostic nucleotide sets using microarrays. The kit may include sterile, endotoxin and RNAse free blood collection tubes. The kit may also include alcohol swabs, tourniquet, blood collection set, and/or PBS (phosphate buffer saline; needed when method of example 2 1s used to derived mononuclear RNA). The kit may also include cell lysis buffer, The kit may include RNA isolation kit, substrates for labeling of RNA (may vary for various expression profiling techniques). The kit may also include materials for fluorescence microarray expression profiling, including one or more of the following: reverse transcriptase and 10x RT buffer, T7(dT)24 primer (primer with T7 promoter at 5’ end), DTT, deoxynucleotides, optionally 100mM each, RNAse inhibitor, second strand cDNA buffer, DNA polymerase, Rnase H, T7 RNA polymerase . ribonucleotides, in vitro transcription buffer, and/or Cy3 and Cys5 labeled ribonucleotides. The kit may also include microarrays containing candidate gene libraries, cover slips for slides, and/or hybridization chambers. The kit may further include software package for identification of diagnostic gene set from data, that contains statistical methods, and/or allows alteration in desired sensitivity and specificity of gene set. The software may further facilitate access to and data analysis by centrally a located database server. The software may further include a password and account number to access central database server. In addition, the kit may include a kit user manual.

In another embodiment, the kit may include contents useful for the application of diagnostic nucleotide sets using microarrays. The kit may include sterile, endotoxin and/or RNAse free blood collection tubes. The kit may also include, alcohol swabs, tourniquet, and/or a blood collection set.

The kit may further include PBS (phosphate buffer saline; needed when method of example 2 is used to derived mononuclear RNA), cell lysis buffer, and/or an RNA isolation kit. In addition, the kit may include substrates for labeling of RNA (may vary for various expression profiling techniques). For fluorescence microarray expression profiling, components may include reverse transcriptase and 10x

RT buffer, T7(dT)24 primer (primer with T7 promoter at 5’ end), DTT, deoxynucleotides (optionally 100mM each), RNAse inhibitor, second strand cDNA buffer, DNA polymerase, Rnase H, T7 RNA polymerase, ribonucleotides, in vitro transcription buffer, and/or Cy3 and CyS labeled ribonucleotides.

The kit may further include microarrays containing candidate gene libraries. The kit may also include cover ships for slides, and/or hybridization chambers. The kit may include a software package for identification of diagnostic gene set from data. The sofiware package may contain statistical methods, allow alteration in desired sensitivity and specificity of gene set, and/or facilitate access to and data analysis by centrally located database server. The software package may include a password and account number to access central database server. In addition, the kit may include a kit user manual.

In another embodiment, the kit may include contents useful for the application of diagnostic nucleotide sets using real-time PCR. This kit may include terile, endotoxin and/or RNAse free blood collection tubes. The kit may further include alcohol swabs, tourniquet, and/or a blood collection set.

The kit may also include PBS (phosphate buffer saline; needed when method of example 2 is used to derived mononuclear RNA). In addition, the kit may include cell lysis buffer and/or an RNA isolation kit. The kit may laso include substrates for real time RT-PCR, which may vary for various real-time

PCR techniques, including poly dT primers, random hexamer primers, reverse Transcriptase and RT buffer, DTT, deoxynucleotides 100 mM, RNase H, primer pairs for diagnostic and control gene set, 10x PCR reaction buffer, and/or Taq DNA polymerase. The kit may also include fluorescent probes for diagnostic and control gene set (alternatively, fluorescent dye that binds to only double stranded

DNA). The kit may further include reaction tubes with or without barcode for sample tracking, 96-well plates with barcode for sample identification, one barcode for entire set, or individual barcode per reaction tube in plate. The kit may also include a software package for identification of diagnostic gene set from data, and /or statistical methods. The software package may allow alteration in desired sensitivity and specificity of gene set, and/or facilitate access to and data analysis by centrally located database server. The kit may include a password and account number to access central database server.

Finally, the kit may include a kit user manual.

This invention will be better understood by reference to the following non-limiting Examples:

LIST OF EXAMPLE TITLES

Example |: Preparation of a leukocyte cONA array comprising a candidate gene library

Example 2: Preparation of RNA from mononuclear cells for expression profiling

Example 3: Preparation of Universal Control RNA Jor use in leukocyte expression profiling

Example 4. RNA Labeling and hybridization to a leukocyte cDNA array of candidate nucleotide sequences.

Example 5: Clinical study for the Identification of diagnostic gene sets useful in diagnosis and treatment of Cardiac allograft rejection

Example 6. Identification of diagnostic nucleotide sets Jor kidney and liver allograft rejection

Example 7: Identification of diagnostic nucleotide sets for diagnosis of cytomegalovirus

Example 8: Design of oligonucleotide probes

Example 9: Production of an array of 8,000 spotted 50 mer oligonucleotides.

Example 10: Identification of diagnostic nucleotide sets for diagnosis of Cardiac Allograft Rejection using microarrays

Example 11: Amplification, labeling, and hybridization of total RNA to an oligonucleotide microarray

Example 12: Real-time PCR validation of array expression results

Example 13: Real-time PCR expression markers of acute allograft rejection

Example 14: Identification of diagnostic nucleotide sets for diagnosis of Cardiac Allograft Rejection using microarrays

Example 15: Correlation and Classification Analysis

Example 16. Acute allograft rejection: biopsy tissue gene expression profiling

Example 17: Microarray and PCR gene expression panels for diagnosis and monitoring of acute allograft rejection

Example 18: Assay sample preparation

Example 19: Allograft rejection diagnostic gene sequence analysis

Example 20: Detection of proteins expressed by diagnostic gene sequences

Example 21: Detecting changes in the rate of hematopoiesis

Examples

Example 1: Preparation of a leukocyte cDNA array comprising a candidate gene library

Candidate genes and gene sequences for leukocyte expression profiling are identified through methods described elsewhere in this document. Candidate genes are used to obtain or design probes for peripheral leukocyte expression profiling in a variety of ways.

A cDNA microarray carrying 384 probes was constructed using sequences selected from the initial candidate library. cDNAs is selected from T-cell libraries, PBMC libraries and buffy coat libraries. 96-Well PCR

Plasmids are isolated in 96-well format and PCR was performed in 96-well format. A master mix is made that contain the reaction buffer, dNTPs, forward and reverse primer and DNA polymerase was made. 99 ul of the master mix was aliquoted into 96-well plate. 1 ul of plasmid (1-2 ng/ul) of plasmid was added to the plate. The final reaction concentration was 10 mM Tris pH 8.3, 3.5 mM MgCI2, 25 mM KCI, 0.4 mM dNTPs, 0.4 uM M13 forward primer, 0.4 M13 reverse primer, and 10 U of Taq Gold (Applied Biosystems). The PCR conditions were:

Step 1 95C for 10 min

Step 2 95C for 15 sec

Step 3 56C for 30 sec

Step 4 72C for 2 min 15 seconds

Step 5 go to Step 2 39 times

Step 6 72C for 10 minutes

Step 7 4C for ever.

PCR Purification

PCR purification is done in a 96-well format. The Arraylt (Telechem International, Inc.) PCR purification kit is used and the provided protocol was followed without modification. Before the sample is evaporated to dryness, the concentration of PCR products was determined using a spectrophotometer. After evaporation, the samples are re-suspended in 1x Micro Spotting Solution (Arraylt) so that the majority of the samples were between 0.2-1.0 ug/ul.

Array Fabrication

Spotted cDNA microarrays are then made from these PCR products by Arraylt using their protocols, which may be found at the Arraylt' website. Each fragment was spotted 3 times onto each array. .

Candidate genes and gene sequences for leukocyte expression profiling are identified through methods described elsewhere in this document. Those candidate genes are used for peripheral leukocyte expression profiling. The candidate libraries can used to obtain or design probes for expression profiling in a variety of ways. ,

Oligonucleotide probes are prepared using the gene sequences of Table 2, Table 8, and the sequence listing. Oligo probes are designed on a contract basis by various companies (for example, Compugen,

Mergen, Affymetrix, Telechem), or designed from the candidate sequences using a variety of parameters and algorithms as indicated at located at the MIT web site. Briefly, the length of the oligonucleotide to be synthesized is determined, preferably greater than 18 nucleotides, generally 18-24 nucleotides, 24-70 nucleotides and, in some circumstances, more than 70 nucleotides. The sequence analysis algorithms and tools described above are applied to the sequences to mask repetitive elements, vector sequences and low complexity sequences. Oligonucleotides are selected that are specific to the candidate nucleotide sequence (based on a Blast n search of the oligonucleotide sequence in question against gene sequences databases, such as the Human Genome Sequence, UniGene, dbEST or the non- redundant database at NCBI), and have <50% G content and 25-70% G+C content. Desired oligonucleotides are synthesized using well-known methods and apparatus, or ordered from a company (for example Sigma). Oligonucleotides are spotted onto microarrays. Alternatively, oligonucleotides are synthesized directly on the array surface, using a variety of techniques (Hughes et al. 2001,

Yershov et al. 1996, Lockhart et al 1996).

Example 2: Preparation of RNA from mononuclear cells for expression profiling

Blood was isolated from the subject for leukocyte expression profiling using the following methods:

Two tubes were drawn per patient. Blood was drawn from either a standard peripheral venous blood draw or directly from a large-bore intra-arterial or intravenous catheter inserted in the femoral artery, femoral vein, subclavian vein or internal jugular vein. Care was taken to avoid sample contamination with heparin from the intravascular catheters, as heparin can interfere with subsequent RNA reactions.

For each tube, 8 ml of whole blood was drawn into a tube (CPT, Becton-Dickinson order #362753) containing the anticoagulant Citrate, 25°C density gradient solution (e.g. Ficoll, Percoll) and a polyester gel barrier that upon centrifugation was permeable to RBCs and granulocytes but not to mononuclear cells. The tube was inverted several times to mix the blood with the anticoagulant. The tubes were centrifuged at 1750xg ina swing-out rotor at room temperature for 20 minutes. The tubes were removed from the centrifuge and inverted 5-10 times to mix the plasma with the mononuclear cells, while trapping the RBCs and the granulocytes beneath the gel barrier. The plasma/mononuclear cell mix was decanted into a 15ml tube and 5m of phosphate-buffered saline (PBS) is added. The 15ml tubes were spun for S minutes at 1750xg to pellet the cells. The supernatant was discarded and

1.8 ml of RLT lysis buffer is added to the mononuclear cell pellet. The buffer and cells were pipetted . up and down to ensure complete lysis of the pellet. The cell lysate was frozen and stored until it is convenient to proceed with isolation of total RNA.

Total RNA was purified from the lysed mononuclear cells using the Qiagen Rneasy Miniprep kit, as

BN directed by the manufacturer (10/99 version) for total RNA isolation, including homogenization (Qiashredder columns) and on-column DNase treatment. The purified RNA was eluted in 50ul of water. The further use of RNA prepared by this method is described in Examples 10 and 11.

Some samples were prepared by a different protocol, as follows:

Two 8 ml blood samples were drawn from a peripheral vein into a tube (CPT, Becton-Dickinson order #362753) containing anticoagulant (Citrate), 25°C density gradient solution (Ficoll) and a polyester gel - barrier that upon centrifugation is permeable to RBCs and granulocytes but not to mononuclear cells.

The mononuclear cells and plasma remained above the barrier while the RBCs and granulocytes were trapped below. The tube was inverted several times to mix the blood with the anticoagulant, and the : tubes were subjected to centrifugation at 1750xg in a swing-out rotor at room temperature for 20 min.

The tubes were removed from the centrifuge, and the clear plasma layer above the cloudy mononuclear cell layer was aspirated and discarded. The cloudy mononuclear cell layer was aspirated, with care taken to rinse all of the mononuclear cells from the surface of the gel barrier with PBS (phosphate buffered saline). Approximately 2 mls of mononuclear cell suspension was transferred to a 2ml microcentrifuge tube, and centrifuged for 3min. at 16,000 rpm in a microcentrifuge to pellet the cells.

The supernatant was discarded and 1.8 ml of RLT lysis buffer (Qiagen) were added to the mononuclear cell pellet, which lysed the cells and inactivated Rnases. The cells and lysis buffer were pipetted up and down to ensure complete lysis of the pellet. Cell lysate was frozen and stored until it was convenient to proceed with isolation of total RNA. :

RNA samples were isolated from 8 mL of whole blood. Yields ranged from 2 ug to 20ug total RNA for 8mL blood. A260/A280 spectrophotometric ratios were between 1.6 and 2.0, indicating purity of sample. 2ul of each sample were run on an agarose gel in the presence of ethidium bromide. No degradation of the RNA sample and no DNA contamination was visible.

In some cases, specific subsets of mononuclear cells were isolated from peripheral blood of human subjects. When this was done, the StemSep cell separation kits (manual version 6.0.0) were used from

StemCell Technologies (Vancouver, Canada). This same protocol can be applied to the isolation of T cells, CD4 T cells, CD8 T cells, B cells, monocytes, NK cells and other cells. Isolation of cell types using negative selection with antibodies may be desirable to avoid activation of target cells by antibodies.

Example 3: Preparation of Universal Control RNA for use in leukocyte expression profiling

Control RNA was prepared using total RNA from Buffy coats and/or total RNA from enriched mononuclear cells isolated from Buffy coats, both with and without stimulation with ionomycin and

PMA. The following control RNAs were prepared:

Control 1: Buffy Coat Total RNA

Control 2: Mononuclear cell Total RNA

Control 3: Stimulated buffy coat Total RNA

Control 4: Stimulated mononuclear Total RNA

Control 5: 50% Buffy coat Total RNA / 50% Stimulated buffy coat Total RNA

Control 6: 50% Mononuclear cell Total RNA / 50% Stimulated Mononuclear Total RNA

Some samples were prepared using the following protocol: Buffy coats from 38 individuals were obtained from Stanford Blood Center. Each buffy coat is derived from ~350 mL whole blood from one individual. 10 ml buffy coat was removed from the bag, and placed into a 50 ml tube. 40 ml of

Buffer EL (Qiagen) was added, the tube was mixed and placed on ice for 15 minutes, then cells were pelleted by centrifugation at 2000xg for 10 minutes at 49°C. The supernatant was decanted and the cell pellet was re-suspended in 10 ml of Qiagen Buffer EL. The tube was then centrifuged at 2000xg for 10 minutes at 4°C. The cell pellet was then re-suspended in 20 ml TRIZOL (GibcoBRL) per Buffy coat sample, the mixture was shredded using a rotary homogenizer, and the lysate was then frozen at ~80°C prior to proceeding to RNA isolation.

Other control RNAs were prepared from enriched mononuclear cells prepared from Buffy coats. Buffy coats from Stanford Blood Center were obtained, as described above. 10 ml buffy coat was added to a 50 ml polypropylene tube, and 10 ml of phosphate buffer saline (PBS) was added to each tube. A polysucrose (5.7 g/dL) and sodium diatrizoate (9.0 g/dL) solution at a 1.077 +/-0.0001 g/ml density solution of equal volume to diluted sample was prepared (Histopaque 1077, Sigma cat. no 1077-1).

This and all subsequent steps were performed at room temperature. 15 ml of diluted buffy coat/PBS was layered on top of 15 ml of the histopaque solution in a 50 ml tube. The tube was centrifuged at 400xg for 30 minutes at room temperature. Afler centrifugation, the upper layer of the solution to within 0.5 cm of the opaque interface containing the mononuclear cells was discarded. The opaque interface was transferred into a clean centrifuge tube. An equal volume of PBS was added to each tube and centrifuged at 350xg for 10 minutes at room temperature. The supernatant was discarded. 5 ml of

Buffer EL (Qiagen) was used to resuspend the remaining cell pellet and the tube was centrifuged at 2000xg for 10 minutes at room temperature. The supernatant was discarded. The pellet was resuspended in 20 mi of TRIZOL (GibcoBRL) for each individual buffy coat that was processed. The sample was homogenized using a rotary homogenizer and frozen at -80C until RNA was isolated.

RNA was isolated from frozen lysed Buffy coat samples as follows: frozen samples were thawed, and 4 ml of chloroform was added to each buffy coat sample. The sample was mixed by vortexing and centrifuged at 2000xg for 5S minutes. The aqueous layer was moved to new tube and then repurified by using the RNeasy Maxi RNA clean up kit, according to the manufacturer's instruction (Qiagen, PN 75162). The yield, purity and integrity were assessed by spectrophotometer and gel electrophoresis.

Some samples were prepared by a different protocol, as follows. The further use of RNA prepared using this protocol is described in Example 11. 50 whole blood samples were randomly selected from consented blood donors at the Stanford Medical

School Blood Center. Each buffy coat sample was produced from ~350 mL of an individual’s donated blood. The whole blood sample was centrifuged at ~4,400 x g for 8 minutes at room temperature, resulting in three distinct layers: a top layer of plasma, a second layer of buffy coat, and a third layer of red blood cells. 25 ml of the buffy coat fraction was obtained and diluted with an equal volume of PBS (phosphate buffered saline). 30 ml of diluted buffy coat was layered onto 15 ml of sodium diatrizoate ns solution adjusted to a density of 1.077+/-0.001 g/ml (Histopaque 1077, Sigma) in a SOmL plastic tube.

The tube was spun at 800 g for 10 minutes at room temperature. The plasma layer was removed to the 30 ml mark on the tube, and the mononuclear cell layer removed into a new tubc and washed with an equal volume of PBS, and collected by centrifugation at 2000 g for 10 minutes at room temperature.

The cell pellet was resuspended in 10 m! of Buffer EL (Qiagen) by vortexing and incubated on ice for minutes to remove any remaining erthythrocytes. The mononuclear cells were spun at 2000 g for 10 minutes at 4 degrees Celsius. The cell pellet was lysed in 25 ml of a phenol/guanidinium thiocyanate solution (TRIZOL Reagent, Invitrogen). The sample was homogenized using a PowerGene 5 rotary homogenizer (Fisher Scientific) and Omini disposable generator probes (Fisher Scientific). The Trizol lysate was frozen at —80 degrees C until the next step. } .

The samples were thawed out and incubated at room temperature for 5S minutes. 5 ml chloroform was added to each sample, mixed by vortexing, and incubated at room temperature for 3 minutes. The aqueous layers were transferred to new 50 ml tubes. The aqueous layer containing total RNA was further purified using the Qiagen RNeasy Maxi kit (PN 75162), per the manufacturer’s protocol (October 1999). The columns were eluted twice with 1 ml Rnase-free water, with a minute incubation before each spin. Quantity and quality of RNA was assessed using standard methods. Generally, RNA was isolated from batches of 10 buffy coats at a time, with an average yield per buffy coat of 870 pg, and an estimated total yield of 43.5 mg total RNA with a 260/280 ratio of 1.56 and a 285/18S ratio of 1.78.

Quality of the RNA was tested using the Agilent 2100 Bioanalyzer using RNA 6000 microfluidics chips. Analysis of the electrophorgrams from the Bioanalyzer for five different batches demonstrated the reproducibility in quality between the batches.

Total RNA from all five batches were combined and mixed in a 50 ml tube, then aliquoted as follows: 2 x 10 ml aliquots in 15 ml tubes, and the rest in 100 pl aliquots in 1.5 ml microcentrifuge tubes. The aliquots gave highly reproducible results with respect to RNA purity, size and integrity. The RNA was : stored at —80°C.

Test hybridization of Reference RNA. :

When compared with BC38 and Stimulated mononuclear reference samples, the R50 performed as well, if not better than the other reference samples as shown in Figure 3. In an analysis of hybridizations, where the R50 targets were fluorescently labeled with Cy-5 using methods described herein and the amplified and labeled aRNA was hybridized (as in example 11) to the olignoucleotide array described in example 9. The R50 detected 97.3% of probes with a Signal to Noise ratio (S/N) of greater than three and 99.9 % of probes with S/N greater than one.

Comparison of Guanine-Silica to Acid-Phenol RNA Purification (GSvsAP)

These data are from a set of 12 hybridizations designed to identify differences between the signal strength from two different RNA purification methods. The two RNA methods used were guanidine- silica (GS, Qiagen) and acid-phenol (AP, Tnzol, Gibco BRL). Ten tubes of blood were drawn from each of four people. Two were used for the AP prep, the other eight were used for the GS prep. The protocols for the leukocyte RNA preps using the AP and GS techniques were completed as described here: }

Guanidine-silica (GS) method:

For each tube, 8ml blood was drawn into a tube containing the anticoagulant Citrate, 25°C density gradient solution and a polyester gel barrier that upon centrifugation is permeable to RBCs and - "granulocytes but not fo mononuclear cells. The mononuclear cells and plasma remained above the ) barrier while the RBCs and granulocytes were trapped below. CPT tubes from Becton-Dickinson (#362753) were used for this purpose. The tube was inverted several times to mix the blood with the anticoagulant. The tubes were immediately centrifuged @1750xg in a swinging bucket rotor at room temperature for 20 min. The tubes were removed from the centrifuge and inverted 5-10 times. This mixed the plasma with the mononuclear cells, while the RBCs and the granulocytes remained trapped beneath the gel barrier. The plasma/mononuclear cell mix was decanted into a 15ml tube and 5Smi of phosphate-buffered saline (PBS) was added. The 15ml tubes are spun for 5 minutes at 1750xg to pellet the cells. The supematant was discarded and 1.8 ml of RLT lysis buffer (guanidine isothyocyanate) was added to the mononuclear cell pellet. The buffer and cells were pipetted up and down to ensure complete lysis of the pellet. The cell lysate was then processed exactly as described in the Qiagen

Rneasy Miniprep kit protocol (10/99 version) for total RNA isolation (including steps for homogenization (Qiashredder columns) and on-column DNase treatment. The purified RNA was eluted in 50ul of water.

Acid-phenol (AP) method:

For each tube, 8ml blood was drawn into a tube containing the anticoagulant Citrate, 25°C density gradient solution and a polyester gel barrier that upon centrifugation is permeable to RBCs and granulocytes but not to mononuclear cells. The mononuclear cells and plasma remained above the barrier while the RBCs and granulocytes were trapped below. CPT tubes from Becton-Dickinson (#362753) were used for this purpose. The tube was inverted several times to mix the blood with the : anticoagulant. The tubes were immediately centrifuged @1750xg in a swinging bucket rotor at room temperature for 20 min. The tubes were removed from the centrifuge and inverted 5-10 times. This mixed the plasma with the mononuclear cells, while the RBCs and the granulocytes remained trapped beneath the gel barrier. The plasma/mononuclear cell mix was decanted into a 15ml tube and Sml of phosphate-buffered saline (PBS) was added. The 15m tubes are spun for 5 minutes @1750xg to pellet the cells. The supernatant was discarded and the cell pellet was lysed using 0.6 mL Phenol/guanidine isothyocyanate (e.g. Trizol reagent, GibcoBRL). Subsequent total RNA isolation proceeded using the manufacturers protocol.

RNA from each person was labeled with either Cy3 or Cy5, and then hybridized in pairs to the mini- array. For instance, the first array was hybridized with GS RNA from one person (Cy3) and GS RNA from a second person (CyS).

Techniques for labeling and hybridization for all experiments discussed here were completed as "detailed above. Arrays were prepared as described in example 1.

RNA isolated from subject samples, or control Buffy coat RNA, were labeled for hybridization to a cDNA array. Total RNA (up to 100 ug) was combined with 2 ul of 100 pM solution of an Oligo

I TVA

! (dT)12-18 (GibcoBRL) and heated to 70°C for 10 minutes and place on ice. Reaction buffer was added to the tube, to a final concentration of IxRT buffer (GibcoBRL), 10 mM DTT (GibcoBRL), 0.1 mM unlabeled dATP, dTTP, and dGTP, and 0.025 mM unlabeled dCTP, 200 pg of CAB (A. thaliana photosystem I chlorophyll a/b binding protein), 200 pg of RCA (A. thaliana RUBISCO activase), 0.25 mM of Cy-3 or Cy-5 dCTP, and 400 U Superscript II RT (GibcoBRL). ~The volumes of each component of the labeling reaction were as follows: 20 pl of SxRT buffer; 10 pl ~ of 100 mM DTT; 1 ul of 10 mM dNTPs without dCTP; 0.5 pl of 5 mM CTP; 13 pl of H20; 0.02 ul of . 10 ng/ul CAB and RCA; 1 pi of 40 Units/ul RNAseOUT Recombinatnt Ribonuclease Inhibitor (GibcoBRLY); 2.5 pul of 1.0 mM Cy-3 or Cy-5 dCTP; and 2.0 ul of 200 Units/ul of Superscript II RT.

The sample was vortexed and centrifuged. The sample was incubated at 4°C for 1 hour for first strand cDNA synthesis, then heated at 70°C for 10 minutes to quench enzymatic activity. 1 ul of 10 mg/ml of

Rnase A was added to degrade the RNA strand, and the sample was incubated at 37°C for 30 minutes.

Next, the Cy-3 and Cy-5 cDNA samples were combined into one tube. Unincorporated nucleotides were removed using QIAquick RCR purification protocol (Qiagen), as directed by the manufacturer.

The sample was evaporated to dryness and resuspended in 5 ul of water. The sample was mixed with hybridization buffer containing 5xSSC, 0.2% SDS, 2 mg/ml Cot-1 DNA (GibcoBRL), 1 mg/ml yeast tRNA (GibcoBRL), and 1.6 ng/u] poly dA40-60 (Pharmacia). This mixture was placed on the microarray surface and a glass cover slip was placed on the array (Corning). The microarray glass slide : was placed into a hybridization chamber (Arrraylt). The chamber was then submerged in a water bath overnight at 62° C. The microarray was removed from the cassette and the cover slip was removed by repeatedly submerging it to a wash buffer containing 1xSSC, and 0.1% SDS. The microarray slide was washed in 1xSSC/0.1% SDS for S minutes. The slide was then washed in 0.1%SSC/0.1% SDS for § minutes. The slide was finally washed in 0.1xSSC for 2 minutes. The slide was spun at 1000 rpm for 2 minutes to dry out the slide, then scanned on a microarray scanner (Axon Instruments, Union City,

CA.).

Six hybridizations with 20 ug of RNA were performed for each type of RNA preparation (GS or AP).

Since both the Cy3 and the CyS labeled RNA are from test preparations, there are six data points for each GS prepped, Cy3-labeled RNA and six for each GS-prepped, Cy5-labeled RNA. The mini array hybridizations were scanned on and Axon Instruments scanner using GenPix 3.0 software. The data presented were derived as follows. First, all features flagged as “not found” by the software were removed from the dataset for individual hybridizations. These features are usually due to high local background or other processing artifacts. Second, the median fluorescence intensity minus the background fluorescence intensity was used to calculate the mean background subtracted signal for each dye for each hybndization. In Figure 3, the mean of these means across all six hybridizations is graphed (n=6 for each column). The error bars are the SEM. This experiment shows that the average signal from AP prepared RNA is 47% of the average signal from GS prepared RNA for both Cy3 and

Cys. oo . : Generation of expression data for leukocyte genes from peripheral leukocyte samples

Six hybridizations were performed with RNA purified from human blood leukocytes using the protocols given above. Four of the six were prepared using the GS method and 2 were prepared using the AP method. Each preparation of leukocyte RNA was labeled with Cy3 and 10 ug hybridized to the mini-array. A contro} RNA was batch labeled with Cy5 and 10 pg hybridized to each mini-array together with the Cy3-labeled experimental RNA.

The control RNA used for these experiments was Control 1: Buffy Coat RNA, as described above.

The protocol for the preparation of that RNA is reproduced here:

Buffy Coat RNA Isolation:

Buffy coats were obtained from Stanford Blood Center (in total 38 individual buffy coats were used.

Each buffy coat is derived from ~350 mL whole blood from one individual. 10 ml buffy coat was taken and placed into a 50 ml tube and 40 ml of a hypoclorous acid (HOC!) solution (Buffer EL from

Qiagen) was added. The tube was mixed and placed on ice for i5 minutes. The tube was then centrifuged at 2000xg for 10 minutes at 4°C. The supernatant was decanted and the cell pellet was re- suspended in 10 ml of hypochlorous acid solution (Qiagen Buffer EL). The tube was then centrifuged at 2000xg for 10 minutes at 4°C. The cell pellet was then re-suspended in 20 ml phenol/guanidine thiocyanate solution ( TRIZOL from GibcoBRL) for each individual buffy coat that was processed.

The mixture was then shredded using a rotary homogenizer. The lysate was then frozen at ~80°C prior to proceeding to RNA isolation.

The arrays were then scanned and analyzed on an Axon Instruments scanner using GenePix 3.0 software. The data presented were derived as follows. First, all features flagged as “not found” by the software were removed from the dataset for individual hybridizations. Second, control features were used to normalize the data for labeling and hybridization variability within the experiment. The control features are cDNA for genes from the plant, Arabidopsis thaliana, that were included when spotting the mini-array. Equal amounts of RNA complementary to two of these cDNAs were added to each of the samples before they were labeled. A third was pre-labeled and equal amounts were added to each hybridization solution before hybridization. Using the signal from these genes, we derived a normalization constant (L;) according to the following formula:

N

>. BGSS, i]

L=—_N ‘ 2,5055 py

K where BGSS; is the signal for a specific feature as identified in the GenePix software as the median background subtracted signal for that feature, N is the number of A. thaliana control features, XK is the number of hybridizations, and L is the normalization constant for each individual hybridization.

Using the formula above, the mean over all'control features of a particular hybridization and dye (eg

Cy3) was calculated. Then these control feature means for all Cyd hybridizations were averaged. The control feature mean in one hybridization divided by the average of all hybridizations gives a normalization constant for that particular Cy3 hybridization. .

The same normalization steps were performed for Cy3 and Cy5 values, both fluorescence and background. Once normalized, the background Cy3 fluorescence was subtracted from the Cy3 fluorescence for each feature. Values less than 100 were eliminated from further calculations since low values caused spurious results. ’

Figure 4 shows the average background subtracted signal for each of nine leukocyte-specific genes on the mini array. This average is for 3-6 of the above-described hybridizations for each gene. The error bars are the SEM.

The ratio of Cy3 to CyS signal is shown for a number of genes. This ratio corrects for variability among hybridizations and allows comparison between experiments done at different times. The ratio is calculated as the Cy3 background subtracted signal divided by the CyS background subtracted signal.

Each bar is the average for 3-6 hybridizations. The error bars are SEM.

Together, these results show that we can measure expression levels for genes that are expressed specifically in sub-populations of leukocytes. These expression measurements were made with only 10 pg of leukocyte total RNA that was labeled directly by reverse transcription. The signal strength can be increased by improved labeling techniques that amplify either the starting RNA or the signal fluorescence. In addition, scanning techniques with higher sensitivity can be used.

Genes in Figures 4 and 5:

GenBank Accession Gene Name

Gene Name/Description Number Abbreviatiol

T cell-specific tyrosine kinase Mma L10717 TKTCS

Interleukin 1 alpha (IL 1) mRNA, complete cds NM_000575 ILIA

T-cell surface antigen CD2 (T11) mRNA, complete cds M14362 CD2

Interleukin-13 (IL-13) precursor gene, complete cds U31120 IL-13

Thymocyte antigen CD1a mRNA, complete cds M28825 CDla

CD6 mRNA for T cell glycoprotein CDS NM_006725 CD6

MHC class IT HLA-DQA1 mRNA, complete cds U77589 HLA-DQA1

Granulocyte colony-stimulating factor M28170 CD19 "| Homo sapiens CD69 antigen © | NM_001781 CD69

Example 5: Clinical study to identify diagnostic gene sets useful in diagnosis and treatment of cardiac "allograft recipients

An observational study was conducted in which a prospective cohort of cardiac transplant recipients were analyzed for associations between clinical events or rejection grades and expression of a leukocyte candidate nucleotide sequence library. Patients were identified at 4 cardiac transplantation centers while on the transplant waiting list or during their routing post-transplant care. All adult cardiac transplant recipients (new or re-transplants) who received an organ at the study center during the study period or within 3 months of the start of the study period were eligible. The first year after transplantation is the time when most acute rejection occurs and it is thus important to study patients during this period. Patients provided informed consent prior to study procedures.

Peripheral blood leukocyte samples were obtained from all patients at the following time points: prior to transplant surgery (when able), the same day as routinely scheduled screening biopsies, upon evaluation for suspected acute rejection (urgent biopsies), on hospitalization for an acute complication of transplantation or immunosuppression, and when Cytomegalovirus (CMV) infection was suspected or confirmed. Samples were obtained through a standard peripheral vein blood draw or through a catheter placed for patient care (for example, a central venous catheter placed for endocardial biopsy).

When blood was drawn from a intravenous line, care was taken to avoid obtaining heparin with the : sample as it can interfere with downstream reactions involving the RNA. Mononuclear cells were prepared from whole blood samples as described in Example 2. Samples were processed within 2 hours of the blood draw and DNA and serum were saved in addition to RNA. Samples were stored at —80° C or on dry ice and sent to the site of RNA preparation in a sealed container with ample dry ice.

RNA was isolated from subject samples as described in Example 2 and hybridized to a candidate library of differentially expressed leukocyte nucleotide sequences, as further described in Examples 9- 10. Methods used for amplification, labeling, hybridization and scanning are described in Example 11.

Analysis of human transplant patient mononuclear cell RNA hybridized to a microarray and identification of diagnostic gene sets is shown in Example 10.

From each patient, clinical information was obtained at the following time points: prior to transplant surgery (when available), the same day as routinely scheduled screening biopsies, upon evaluation for suspected acute rejection (e.g., urgent biopsies), on hospitalization for an acute complication of transplantation or immunosuppression, and when Cytomegalovirus (CMV) infection was suspected or confirmed. Data was collected directly from the patient, from the patient’s medical record, from diagnostic test reports or from computerized hospital databases. It was important to collect all information pertaining to the study clinical correlates (diagnoses and patient events and states to which expression data is correlated) and confounding variables (diagnoses and patient events and states that may result in altered leukocyte gene expression. Examples of clinical data collected are: patient sex, date of birth, date of transplant, race, requirement for prospective cross match, occurrence of pre- transplant diagnoses and complications, indication for transplantation, severity and type of heart disease, history of left ventricular assist devices, all known medical diagnoses, blood type, HLA type, viral serologies (including CMV, Hepatitis B and C, HIV and others), serum chemistries, white and red blood cell counts and differentials, CMV infections (clinical manifestations and methods of diagnosis), occurrence of new cancer, hemodynamic parameters measured by catheterization of the right or left ) heart (measures of graft function), results of echocardiography, results of coronary angiograms, results of intravascular ultrasound studies (diagnosis of transplant vasculopathy), medications, changes in medications, treatments for rejection, and medication levels. Information was also collected regarding the organ donor, including demographics, blood type, HLA type, results of screening cultures, results of viral serologies, primary cause of brain death, the need for inotropic support, and the organ cold ischemia time.

Of great importance was the collection of the results of endocardial biopsy for each of the patients at each visit. Biopsy results were all interpreted and recorded using the international society for heart and lung transplantation (ISHLT) criteria, described below. Biopsy pathological grades were determined by experienced pathologists at each center.

ISHLT Criteria

Grade | Finding Rejection al =

EL LJ

1A Focal (perivascular or interstitial lymphocytic infiltrates without Borderline fy —

I CE Le

One focus only with aggressive lymphocytic infiltrate and/or Mild, focal

Ir 3A Multifocal aggressive lymphocytic infiltrates and/or myocardial Moderate

Cam mmm——— 3B Diffuse inflammatory lymphocytic infiltrates with necrosis Borderline oC rmm—_le

Diffuse aggressive polymorphous lymphocytic infiltrates with

I EE a

Because variability exists in the assignment of ISHLT grades, it was important to have a centralized and blinded reading of the biopsy slides by a single pathologist. This was arranged for all biopsy slides associated with samples in the analysis. Slides were obtained and assigned an encoded number. A single pathologist then read all slides from all centers and assigned an ISHLT grade. Grades from the single pathologist were then compared to the original grades derived from the pathologists at the study centers. For the purposes of correlation analysis of leukocyte gene expression to biopsy grades, the centralized reading information was used in a variety of ways (see Example 10 for more detail). In some analyses, only the original reading was used as an outcome. In other analyses, the result from the centralized reader was used as an outcome. In other analyses, the highest of the 2 grades was used.

For example, if the original assigned grade was 0 and the centralized reader assigned a 1A, then 1A was the grade used as an outcome. In some analyses, the highest grade was used and then samples associated with a Grade 1A reading were excluded from the analysis. In some analyses, only grades with no disagreement between the 2 readings were used as outcomes for correlation analysis.

Clinical data was entered and stored in a database. The database was queried to identify all patients and patient visits that meet desired criteria (for example, patients with > grade II biopsy results, no

CMV infection and time since transplant < 12 weeks). .

The collected clinical data (disease criteria) is used to define patient or sample groups for correlation of expression data. Patient groups are identified for comparison, for example, a patient group that possesses a useful or interesting clinical distinction, versus a patient group that does not possess the distinction. Examples of useful and interesting patient distinctions that can be made on the basis of collected clinical data are listed here: 1. Rejection episode of at least moderate histologic grade, which results in treatment of the patient with additional corticosteroids, anti-T cell antibodies, or total lymphoid irradiation. 2. Rejection with histologic grade 2 or higher. 3. h Rejection with histologic grade <2. ) 4. The absence of histologic rejection and normal or unchanged allograft function (based on hemodynamic measurements from catheterization or on echocardiographic data). 5. The presence of severe allograft dysfunction or worsening allograft dysfunction : during the study period (based on hemodynamic measurements from catheterization or on echocardiographic data). 6. Documented CMV infection by culture, histology, or PCR, and at least one clinical sign or symptom of infection. 7. Specific graft biopsy rejection grades 8. Rejection of mild to moderate histologic severity prompting augmentation of the patient’s chronic immunosuppressive regimen 9. Rejection of mild to moderate severity with allograft dysfunction prompting plasmaphoresis or a diagnosis of “humoral” rejection 10. Infections other than CMV, esp. Epstein Barr virus (EBV) 11. Lymphoproliferative disorder (also called, post-transplant lymphoma) 12. Transplant vasculopathy diagnosed by increased intimal thickness on intravascular ultrasound (IVUS), angiography, or acute myocardial infarction. 13. Graft Failure or Retransplantation 14. All cause mortality 15. Grade 1A or higher rejection as defined by the initial biopsy reading. 16. Grade 1B or higher rejection as defined by the initial biopsy reading. 17. Grade 1A or higher rejection as defined by the centralized biopsy reading. 18. Grade 1B or higher rejection as defined by the centralized biopsy reading. 19. Grade 1A or higher rejection as defined by the highest of the initial and centralized biopsy reading. 20. Grade 1B or higher rejection as defined by the highest of the initial and centralized biopsy reading. 21. Any rejection > Grade 2 occurring in patient at any time in the post-transplant course.

Expression profiles of subject samples are examined to discover sets of nucleotide sequences with differential expression between patient groups, for example, by methods describes above and below.

Non-limiting examples of patient leukocyte samples to obtain for discovery of various diagnostic nucleotide sets are as follows:

Leukocyte set to avoid biopsy or select for biopsy:

Samples : Grade 0 vs. Grades 1-4

Leukocyte set to monitor therapeutic response:

Examine successful vs. unsuccessful drug treatment.

Samples:

Successful: Time 1: rejection, Time 2: drug therapy Time 3: no rejection . Unsuccessful: Time 1: rejection, Time 2: drug therapy; Time 3: rejection - :

Leukocyte set to predict subsequent acutc rejection.

Biopsy may show no rejection, but the patient may develop rejection shortly thereafter. Look at profiles of patients who subsequently do and do not develop rejection.

Samples:

Group 1 (Subsequent rejection): Time 1: Grade 0; Time 2: Grade>0

Group 2 (No subsequent rejection): Time 1: Grade 0; Time 2: Grade 0

Focal rejection may be missed by biopsy. When this occurs the patient may have a Grade 0, but actually has rejection. These patients may go on to have damage to the graft etc.

Samples:

Non-rejectors: no rejection over some period of time

Rejectors: an episode of rejection over same period

Leukocyte set to diagnose subsequent or current graft failure:

Samples:

Echocardiographic or catheterization data to define worsening function over time and correlate to profiles.

Leukocyte set to diagnose impending active CMV:

Samples: .

Look at patients who are CMV IgG positive. Compare patients with subsequent (to a sample) clinical

CMV infection verses no subsequent clinical CMV infection.

Leukocyte set to diagnose current active CMV:

Samples:

Analyze patients who are CMV IgG positive. Compare patients with active current clinical CMV infection vs. no active current CMV infection.

Upon identification of a nucleotide sequence or set of nucleotide sequences that distinguish patient groups with a high degree of accuracy, that nucleotide sequence or set of nucleotide sequences is validated, and implemented as a diagnostic test. The use of the test depends on the patient groups that are used to discover the nucleotide set. For example, if a set of nucleotide sequences is discovered that have collective expression behavior that reliably distinguishes patients with no histological rejection or graft dysfunction from all others, a diagnostic is developed that is used to screen patients for the need for biopsy. Patients identified as having no rejection do not need biopsy, while others are subjected to a biopsy to further define the extent of disease. In another example, a diagnostic nucleotide set that determines continuing graft rejection associated with myocyte necrosis (> grade I) is used to determine . that a patient is not receiving adequate treatment under the current treatment regimen. After increased :

or altered immunosuppressive therapy, diagnostic profiling is conducted to determine whether continuing graft rejection is progressing. In yet another example, a diagnostic nucleotide set(s) that determine a patient’s rejection status and diagnose cytomegalovirus infection is used to balance immunosuppressive and anti-viral therapy.

The methods of this example are also applicable to cardiac xenograft monitoring.

Example 6: Identification of diagnostic nucleotide sets for kidney and liver allograft rejection

Diagnostic tests for rejection are identified using patient leukocyte expression profiles to identify a . molecular signature correlated with rejection of a transplanted kidney or fiver. Blood, or other leukocyte source, samples are obtained from patients undergoing kidney or liver biopsy following liver or kidney transplantation, respectively. Such results reveal the histological grade, i.e., the state and severity of allograft rejection. Expression profiles are obtained from the samples as described above, and the expression profile is correlated with biopsy results. In the case of kidney rejection, clinical data is collected corresponding to urine output, level of creatine clearance, and level of serum creatine (and other markers of renal function). Clinical data collected for monitoring liver transplant rejection includes, biochemical characterization of serum markers of liver damage and function such as SGOT,

SGPT, Alkaline phosphatase, GGT, Bilirubin, Albumin and Prothrombin time.

Leukocyte nucleotide sequence expression profiles are collected and correlated with important clinical states and outcomes in renal or hepatic transplantation. Examples of useful clinical correlates are given here: 1. Rejection episode of at least moderate histologic grade, which results in treatment of the patient with additional corticosteriods, anti-T cell antibodies, or total lymphoid irradiation. 2. The absence of histologic rejection and normal or unchanged allograft function (based on tests of renal or liver function listed above). 3. The presence of severe allograft dysfunction or worsening allograft dysfunction during the study penod (based on tests of renal and hepatic function listed above). 4. Documented CMV infection by culture, histology, or PCR, and at least one clinical sign or symptom of infection. 5. Specific graft biopsy rejection grades 6. Rejection of mild to moderate histologic severity prompting augmentation of the patient’s chronic immunosuppressive regimen 7. Infections other than CMV, esp. Epstein Barr virus (EBV) 8. Lymphoproliferative disorder (also called, post-transplant lymphoma) 9. Graft Failure or Retransplantation 10. Need for hemodialysis or other renal replacement therapy for renal transplant patients. 11. Hepatic encephalopathy for liver transplant recipients. 12. All cause mortality :

Subsets of the candidate library (or of a previously identified diagnostic nucleotide set), are identified, according to the above procedures, that have predictive and/or diagnostic value for kidney or liver allograft rejection.

Example 7: Identification of a diagnostic nucleotide set for diagnosis of cytomegalovirus

Cytomegalovirus is a very important cause of disease in immunocompromised patients, for example, transplant patients, cancer patients, and AIDS patients. The virus can cause inflammation and disease in almost any tissue (particularly the colon, lung, bone marrow and retina). It is increasingly important to identify patients with current or impending clinical CMV disease, particularly when immunosuppressive drugs are to be used in a patient, e.g. for preventing transplant rejection.

Leukocytes are profiled in patients with active CMV, impending CMV, or no CMV. Expression . profiles correlating with diagnosis of active or impending CMV are identified. Subsets of the candidate library (or a previously identified diagnostic nucleotide set) are identified, according to the above procedures that have predictive value for the diagnosis of active or impending CMV. Diagnostic nucleotide set(s) identified with predictive value for the diagnosis of active or impending CMV may be combined, or used in conjunction with, cardiac, liver and/or kidney allograft-related diagnostic gene set(s) (described in Examples 6 and 10).

In addition, or alternatively, CMV nucleotide sequences are obtained, and a diagnostic nucleotide set is designed using CMV nucleotide sequence. The entire sequence of the organism is known and all CMV nucleotide sequences can be isolated and added to the library using the sequence information and the approach described below. Known expressed genes are preferred. Alternatively, nucleotide sequences are selected to represent groups of CMV genes that are coordinately expressed (immediate early genes, early genes, and late genes) (Spector et al. 1990, Stamminger et al. 1990).

Oligonucleotides were designed for CMV genes using the oligo design procedures of Example 8.

Probes were designed using the 14 gene sequences shown here and were included on the array described in example 9:

HCMVTRL2 (IRL2) 1893..2240

HCMVTRL7 (IRL7) complement(6595..6843)

HCMVUL2] complement(26497..27024)

HCMVUL27 complement(32831..34657)

HCMVUL33 43251..44423

HCMVULS4 complement(76903..80631)

Cytomegalovirus HCMVUL7S complement(107901..110132)

MW) HCMVULS3 complement(119352..121037)

Accession #X17403

HCMVULI106 complement(154947..155324)

HCMVUL109 complement(157514..157810)

HCMVULI113 161503..162800

HCMVUL122 complement(169364..170599)

HCMVULI123 (last exon at 3’-end) complement(171006..172225)

HCMVUS28 219200..22017

Diagnostic nucleotide set(s) for expression of CMV genes is used in combination with diagnostic leukocyte nucleotide sets for diagnosis of other conditions, e.g. organ allograft rejection.

Using the techniques described in example 2 mononuclear samples from 180 cardiac transplant recipients (enrolled in the study described in Example 5) were used for expression profiling with the leukocyte arrays. Of these samples 15 were associated with patients who had a diagnosis of primary or reactivation CMV made by culture, PCR or any specific diagnostic test.

After preparation of RNA, amplification, labeling, hybridization, scanning, feature extraction and data processing were done as described in Example | 1 using the oligonucleotide microarrays described in

Example 9.

The resulting log ratio of expression of Cy3 (patient sample)/ CyS (R50 reference RNA) was used for analysis. Significance analysis for microarrays (SAM, Tusher 2001, see Example 15) was applied to determine which genes were most significantly differentially expressed between these 15 CMV patients and the 165 non-CMV patients (Table 12). 12 genes were identified with a 0% FDR and 6 witha 0.1%

FDR and are listed in Table 2. Some genes are represented by more than one oligonucleotide on the array and for 2 genes, multiple oligonucleotides from the same gene are called significant (SEQ IDs: 3061, 3064: eomesodermin and 3031, 3040, 104, 2736: small inducible cytokine Ad).

Clinical variables were also included in the significance analysis. For example, the white blood cell count and the number of weeks post transplant (for the patient at the time the sample was obtained) were available for most of the 180 samples. The log of these variables was taken and the variables were then used in the significance analysis described above with the gene expression data. Both the white blood cell count (0.1% FDR) and the weeks post transplant (0% FDR) appeared to correlate with

CMV status. CMV patients were more likely to have samples associated with later post transplant data and the lower white blood cell counts.

These genes and variables can be used alone or in association with other genes or variables or with ) other genes to build a diagnostic gene set or a classification algorithm using the approaches described herein.

Primers for real-time PCR validation were designed for some of these genes as descnibed in Example 13 and listed in Table 2C and the sequence listing. Using the methods described in example 13, primers for Granzyme B were designed and used to validate expression findings from the arrays. 6 samples were tested (3 from patients with CMV and 3 from patients without CMV). The gene was found to be differentially expressed between the patients with and without CMV (see example 13 for full description). This same approach can be used to validate other diagnostic genes by real-time PCR.

Diagnostic nucleotide sets can also be identified for a variety of other viral diseases (Table 1) using this same approach. cDNA microarrays may be used to monitor viral expression. In addition, these methods may be used to monitor other viruses, such as Epstein-Barr virus, Herpes Simplex 1 and vesicular stomatitis virus.

Example 8- Design of oligonucleotide probes

By way of example, this section describes the design of four oligonucleotide probes using Array

Designer Ver 1.1 (Premier Biosoft International, Palo Alto, CA). The major steps in the process are given first.

Obtain best possible sequence of mRNA from GenBank. Ifa full-length sequence reference sequence is not available, a partial sequence is used, with preference for the 3° end over the 5° end. When the sequence is known to represent the antisense strand, the reverse complement of the sequence is used for probe design. For sequences represented in the subtracted leukocyte expression library that have no significant match in GenBank at the time of probe design, our sequence is used.

Mask low complexity regions and repetitive elements in the sequence using an algorithm such as

RepeatMasker.

Use probe design software, such as Array Designer, version 1.1, to select a sequence of SO residues with specified physical and chemical properties. The 50 residues nearest the 3’ end constitute a search frame. The residues it contains are tested for suitability. If they don’t meet the specified criteria, the search frame is moved one residue closer to the 5” end, and the 50 residues it now contains are tested.

The process is repeated until a suitable 50-mer is found.

If no such 50-mer occurs in the sequence, the physical and chemical criteria are adjusted until a suitable 50-mer is found.

Compare the probe to dbEST, the UniGene cluster set, and the assembled human genome using the

BLASTN search tool at NCBI to obtain the pertinent identifying information and to verify that the probe does not have significant similarity to more than one known gene.

Clone 40H12

Clone 40H12 was sequenced and compared to the nr, dbEST, and UniGene databases at NCBI using the BLAST search tool. The sequence matched accession number NM_002310, a "curated RefSeq project’ sequence, see Pruitt et al. (2000) Trends Genet. 16:44-47, encoding leukemia inhibitory factor receptor (LIFR) mRNA with a reported E value of zero. An E value of zero indicates there is, for all practical purposes, no chance that the similarity was random based on the length of the sequence and . the composition and size of the database. This sequence, cataloged by accession number NM_002310, is much longer than the sequence of clone 40H 12 and has a poly-A tail. This indicated that the sequence cataloged by accession number NM_002310 is the sense strand and a more complete representation of the mRNA than the sequence of clone 40H12, especially at the 3° end. Accession number “NM_002310" was included in a text file of accession numbers representing sense strand mRNAs, and sequences for the sense strand mRNAs were obtained by uploading a text file containing desired accession numbers as an Entrez search query using the Batch Entrez web interface and saving the results locally as a FASTA file. The following sequence was obtained, and the region of alignment of clone 40H12 is outlined:

CTCTCTCCCAGAACGTGTCTCTGCTGCAAGGCACCGGGCCCTTTCGCTCTGCAGAACTGCACTTGCAAGA

CCATTATCAACTCCTAATCCCAGCTCAGAAAGGGAGCCTCTGCGACTCATTCATCGCCCTCCAGGACTGA

CTGCATTGCACAGATGATGGATATTTACGTATGTTTGAAACGACCATCCTGGATGGTGGACAATAAAAGA

ATGAGGACTGCTTCAAATTTCCAGTGGCTGTTATCAACATTTATTCTTCTATATCTAATGAATCAAGTAA

ATAGCCAGAAAAAGGGGGCTCCTCATGATTTGAAGTGTGTAACTAACAATTTGCAAGTGTGGAACTGTTC

TTGGAAAGCACCCTCTGGAACAGGCCGTGGTACTGATTATGAAGTTTGCATTGAAAACAGGTCCCGTTCT

TGTTATCAGTTCGAGAAAACCAGTATTAAAATTCCAGCTCTTTCACATGGTGATTATGAAATAACAATARN

ATTCTCTACATGATTTTGGAAGTTCTACAAGTAAATTCACACTAAATGAACAAAACGTTTCCTTAATTCC

AGATACTCCAGAGATCTTGAATTTGTCTCCTGATTTCTCAACCTCTACATTATACCTAAAGTGGAACGAC

AGGGGTTCAGTTTTTCCACACCGCTCAAATGTTATCTGGGAAATTARAGTTCTACGTARAGAGAGTATGG

AGCTCGTAAAATTAGTGACCCACAACACADACTCTGAATGGCAAAGATACACTTCATCACTGGAGTTGGGC

CTCAGATATGCCCTTGGAATGTGCCATTCATTTTGTGGAAATTAGATGCTACATTGACAATCTTCATTTT

TCTGGTCTCGAAGAGTGGAGTGACTGGAGCCCTGTGAAGAACATTTCTTGGATACCTGATTCTCAGACTA

AGGTTTTTCCTCAAGATAAAGTGATACTTGTAGGCTCAGACATAACATTTTGTTGTGTGAGTCAAGAAAA

AGTGTTATCAGCACTGATTGGCCATACARACTGCCCCTTGATCCATCTTGATGGGGAAMATGTTGCAATC

AAGATTCGTAATATTTCTGTTTCTGCAAGTAGTGGAACAAATGTAGTTTTTACAACCGAAGATAACATAT

TTGGAACCGTTATTTTTGCTGGATATCCACCAGATACTCCTCAACAACTGAATTGTGAGACACATGATTT

ARAAGAAATTATATGTAGTTGGAATCCAGGAAGGGTGACAGCCTTGGTGGGCCCACGTGCTACAAGCTAC

ACTTTAGTTGAAAGTTTTTCAGGAAAATATGTTAGACTTAAAAGAGCTGAAGCACCTACAAACGARAGCT

ATCAATTATTATTTCAARATGCTTCCAAATCARGARATATATAATTTTACTTTGAATGCTCACAATCCGCT

: GGGTCGATCACAATCAACAATTTTAGTTAATATAACTGARAAAGTTTATCCCCATACTCCTACTTCATTC

AAAGTGAAGGATATTAATTCAACAGCTGTTAAACTTTCTTGGCATTTACCAGGCAACTTTGCARAGATTA

ATTTTTTATGTGAAATTGAAATTAAGAAATCTAATTCAGTACAAGAGCAGCGGAATGTCACAATCAAAGG

AGTAGAAAATTCAAGTTATCTTGTTGCTCTGGACAAGT TARATCCATACACTCTATATACTTTTCGGATT

CGTTGTTCTACTGAAACTTTCTGGAAATGGAGCAAATGGAGCAATAAAAAACAACATTTAACAACAGARG

CCAGTCCTTCAAAGGGGCCTGATACT TGGAGAGAGTGGAGTTCTGATGGAAAAAATTTAATAATCTATTG

GAAGCCTTTACCCATTAATGAAGCTAATGGAAAAATACTTTCCTACAATGTATCGTGTTCATCAGATGAG

. GAAACACAGTCCCTTTCTGAAATCCCTGATCCTCAGCACARAGCAGAGATACGACTTGATAAGAATGACT

ACATCATCAGCGTAGTGGCTAAAAATTCTGTGGGCTCATCACCACCTTCCAAAATAGCCAGTATGGARAT

TCCARATGATGATCTCAARATAGAACAAGTTGTTGGGATGGGARAGGGGATTCTCCTCACCTGGCATTAC

GACCCCAACATGACTTGCGACTACGTCATTAAGTGGTGTAACTCGTCTCGGTCGGARCCATGCCTTATGG

ACTGGAGAAAAGTTCCCTCAAACAGCACTGAAACTGTAATAGAATCTGATGAGTTTCGACCAGGTATAAG

ATATAATTTTTTCCTGTATGGATGCAGAAATCAAGGATATCAAT TAT TACGCTCCATGATTGGATATATA

GAAGAATTGGCTCCCATTGTTGCACCARATTTTACTGTTGAGGATACTTCTGCAGATTCGATATTAGTAA

AATGGGAAGACATTCCTGTGGAAGAACTTAGAGGCTTTTTAAGAGGATATTTGTTTTACTTTGGAAAAGG

AGARAGAGACACATCTAAGATGAGGGTTTTAGAATCAGGTCGTTCTGACATAAAAGTTAAGAATATTACT

GACATATCCCAGAAGACACTGAGAATTGCTGATCTTCAAGGTAAAACAAGTTACCACCTGGTCTTGCGAG

CCTATACAGATGGTGGAGTGGGCCCGGAGAAGAGTATGTATGTGG TGACAAAGGAAAATTCTGTGGGATT

AATTATTGCCATTCTCATCCCAGTGGCAGTGGCTGTCAT TGTTCGAGTGGTGACAAGTATCCTTTGCTAT

CGGAAACGAGAATGGATTAAAGAAACCTTCTACCCTGATATTCCARATCCAGAARACTGTAAAGCATTAC

AGTTTCAAAAGAGTGTCTGTGAGGGAAGCAGTGCTCTTAAAACATTGGAAATGAATCCTTGTACCCCARA

TAATGTTGAGGTTCTGGARACTCGATCAGCATTTCCTAAAATAGAAGATACAGARATAATTTCCCCAGTA

GCTGAGCGTCCTGAAGATCGCTCTGATGCAGAGCCTGARAACCATGTGGTTGTGTCCTATTGTCCACCCA

TCATTGAGGAAGAAATACCAAACCCAGCCGCAGATGAAGCTGGAGGGACTGCACAGGTTATTTACATTGA

TGTTCAGTCGATGTATCAGCCTCAAGCAAAACCAGAAGAAGAACAAGAAAATGACCCTGTAGGAGGGGCA

GGCTATAAGCCACAGATGCACCTCCCCATTAATTCTACTGTGGAAGATATAGCTGCAGAAGAGGACTTAG

ATAAAACTGCGGGTTACAGACCTCAGGCCAATGTAAATACATGGAATTTAGTGTCTCCAGACTCTCCTAG

ATCCATAGACAGCAACAGTGAGATTGTCTCATTTGGAAGTCCATGCTCCATTAATTCCCGACAATTTTTG :

ATTCCTCCTAAAGATGAAGACTCTCCTAAATCTAATGGAGGAGGGTGGTCCTTTACARACTTTTTTCAGA

ACAAACCAAACGATTAACAGTGTCACCGTGTCACTTCAGTCAGCCATCTCAATAAGCTCTTACTGCTAGT

GTTGCTACATCAGCACTGGGCATTCTTGGAGGGATCCTGTGAAGTATTGTTAGGAGGTGAACTTCACTAC

ATGTTAAGTTACACTGARAGTTCATGTGCTTTTAATGTAGTCTARAAGCCAAAGTATAGTGACTCAGAAT

CCTCAATCCACAAAACTCAAGATTGGGAGCTCTTTGTGATCAAGCCARAGAATTCTCATGTACTCTACCT

TCARGAAGCATTTCAAGGCTAATACCTACTTGTACGTACATGTAAAACAAATCCCGCCGCAACTGTTTTC

TGTTCTGTTGTTTGTGGTTTTCTCATATGTATACTTGGTGGAATTGTAAGTGGATTTGCAGGCCAGGGAG

AAAATGTCCAAGTAACAGGTGAAGTTTATTTGCCTGACGTTTACTCCTTTCTAGATGAARACCAAGCACA

GATTTTAAAACTTCTAAGATTATTCTCCTCTATCCACAGCATTCACARAAATTAATATAATTTTTAATGT

AGTGACAGCGATTTAGTGTTTTGTTTGATAAAGTATGCTTATTTCTGTGCCTACTGTATAATGGTTATCA

AACAGTTGTCTCAGGGGTACAAACTTTGAAAACAAGTGTGACACTGACCAGCCCAAATICATAATCATGTT

BAAAGCAGAAGGRARMACTARAAAGTCTATCTTGTAT TT ICCC TOCOCTCAGGTTGCCTATGTATTITAC

CTTTTCATATTTAAGGCAAAAGTACTTGAARATTTTAAGTGTCCGAATAAGATATGTCTTTTTTGTTTGT

TTTTTTTGGTTGGTTGTTTGTTTTTTATCATCTGAGATTCTGTAATGTATTTGCAAATAATGGATCAATT

AATTTTTTTTCARGCTCATATTGTATCTTTTTAAAAACCATGTTGTGGAARAAAGCCAGAGTGACARGTG

ACARAATCTATTTAGGAACTCTGTGTATGAATCCTGATTTTARCTGCTAGGATTCAGCTAAATTTCTGAG

CTTTATGATCTGTGGAAATTTGGAATGAAATCGAATTCATTTTGTACATACATAGTATATTAAAACTATA

TAATAGTTCATAGAAATGTTCAGTAATGAAAAAATATATCCAATCAGAGCCATCCCGARAARARARRARAR

AA (SEQ ID NO: 3101)

The FASTA file, including the sequence of NM_002310, was masked using the RepeatMasker web interface (Smit, AFA & Green, P RepeatMasker at http://ftp.genome. washington.edwRM/RepeatMasker.html, Smit and Green). Specifically, during masking, the following types of sequences were replaced with “N's”: SINE/MIR & LINE/L2, LINE/L1 » LTR/MaLR, LTR/Retroviral , Alu, and other low informational content sequences such as simple repeats. Below is the sequence following masking:

CTCTCTCCCAGAACGTGTCTCTGCTGCAAGGCACCGGGCCCTTTCGCTCTGCAGAACTGCACTTGCAAG

ACCATTATCAACTCCTAATCCCAGCTCAGAAAGGGAGCCTCTGCGACTCATTCATCGCCCTCCAGGACT

GACTGCATTGCACAGATGATGGATATTTACGTATGTTTGAAACGACCATCCTGGATGGTGGACAATAAA

AGAATGAGGACTGCTTCAAATTTCCAGTGGCTGTTATCAACATTTATTCTTCTATATCTAATGAATCAA

GTAAATAGCCAGAAAAAGGGGGCTCCTCATGATTTGAAGTGTGTAACTAACAATTTGCAAGTGTGGAAC

TGTTCTTGGARAGCACCCTCTGGAACAGGCCGTGGTACTGATTATGAAGTTTGCATTGAAAACAGGTCC

CGTTCTTGTTATCAGTTGGAGAAAACCAGTATTAAAATTCCAGCTCTTTCACATGGTGATTATGAAATA

ACAATAAATTCTCTACATGATTTTGGAAGTTCTACAAGTAAATTCACACTAAATGAACAAAACGTTTCC

TTAATTCCAGATACTCCAGAGATCTTGAATTTGTCTGCTGATTTCTCAACCTCTACATTATACCTAAAG

TGGAACGACAGGGGTTCAGTTTTTCCACACCGCTCAAATGTTATCTGGGAAATTAAAGTTCTACGTAAA

GAGAGTATGGAGCTCGTAAAATTAGTGACCCACAACACAACTCTGAATGGCAAAGATACACTTCATCAC

TGGAGTTGGGCCTCAGATATGCCCTTGGAATGTGCCATTCATTTTGTGGAAATTAGATGCTACATTGAC

AATCTTCATTTTTCTGGTCTCGAAGAGTGGAGTGACTGGAGCCCTGTGCAAGAACATTTCTTGGATACCT

GATTCTCAGACTAAGGTTTTTCCTCAAGATAAAGTGATACTTGTAGGCTCAGACATAACATTTIGTTGT

GTGAGTCAAGAAARAGTGTTATCAGCACTGATTGGCCATACAAACTGCCCCTTGATCCATCTTGATGGG

GAAAATGTTGCAATCAAGATTCGTAATATTTCTGTTTCTGCAAGTAGTGGAACAAATGTAGTTTTTACA

ACCGAAGATAACATATTTGGAACCGTTATTTTTGCTGGATATCCACCAGATACTCCTCAACAACTGAAT

TGTGAGACACATGATTTARAAGAAATTATATGTAGTTGGAATCCAGGAAGGGTGACAGCGTTGGTGGGC

CCACGTGCTACAAGCTACACTTTAGTTGAAAGTTTTTCAGGAARATATGTTAGACTTAAAAGAGCTGAA

GCACCTACAAACGAAAGCTATCAATTATTATTTCAAATGCTTCCAAATCAAGARATATATAATTTTACT

TTGAATGCTCACAATCCGCTGGGTCGATCACAATCAACAATTTTAGTTAATATAACTGAARAAGTTTAT

CCCCATACTCCTACTTCATTCAAAGTGAAGGATATTAATTCARCAGCTGTTARARCTTTCTTGGCATTTA

CCAGGCAACTTTGCARAGATTAARTTTTTTATGTGAAATTGAAATTAAGAAATCTAATTCAGTACAAGAG

CAGCGGAATGTCACAATCAAAGGAGTAGAAAATTCAAGTTATCTTGTTGCTCTGGACAAGTTAAATCCA

TACACTCTATATACTTTTCGGATTCGTTGTTCTACTGAAACTTTCTGGAAATGGAGCAAATGGAGCAAT

AAAAAACAACATTTAACAACAGAAGCCAGTCCTTCAAAGGGGCCTGATACTTGGAGAGAGTGGAGTTCT

GATGGAAAAAATTTAATAATCTATTGGAAGCCTTTACCCATTAATGAAGCTAATGGAAAAATACTTTCC

TACAATGTATCGTGTTCATCAGATGAGGAAACACAGTCCCTTTCTGAAATCCCTGATCCTCAGCACAAA

GCAGAGATACGACTTGATAAGAATGACTACATCATCAGCGTAGTGGCTAAAAATTCTGTGGGCTCATCA

CCACCTTCCAAAATAGCGAGTATGGAAATTCCAAATGATGATCTCAAAATAGAACAAGTTGTTGGGATG

GGAAAGGGGATTCTCCTCACCTGGCATTACGACCCCAACATGACTTGCGACTACGTCATTAAGTGGTGT

ARCTCGTCTCGGTCGGAACCATGCCTTATGGACTGGAGAAAAGTTCCCTCARACAGCACTGARACTGTA

ATAGAATCTGATGAGTTTCGACCAGGTATAAGATATAATTTTTTCCTGTATGGATGCAGAAATCAAGGA

TATCAATTATTACGCTCCATGATTGGATATATAGAAGAATTGGCTCCCATTGTTGCACCARATTTTACT

GTTGAGGATACTTCTGCAGATTCGATATTAGTAAAATGGGAAGACATTCCTGTGGAAGAACTTAGAGGE

TTTTTAAGAGGATATTTGTTTTACTTTGGAAAAGGAGAAAGAGACACATCTAAGATGAGGGTTTTAGAA

TCAGGTCGTTCTGACATAAAAGTTAAGAATATTACTGACATATCCCAGAAGACACTGAGAATTGCTGAT

CTTCARGGTAARACAAGTTACCACCTGGTCTTGCGAGCCTATACAGATGGTGOAGTGAGCCACEAGARG

AGTATGTATGTGGTGACAAAGGAARATTCTGTGGGATTARTTATTGCCATTCTCATCCCAGTGGCAGTG

GCTGTCATTGTTGGAGTGGTGACAAGTATCCTTTGCTATCGGAAACGAGAATGGATTAAAGAAACCTTC

TACCCTGATATTCCAAATCCAGAAAACTGTAARAGCATTACAGTTTCAAAAGAGTGTCTGTGAGGGAAGE

AGTGCTCTTAAAACATTGGAAATGAATCCTTGTACCCCARATAATCTTGAGGTTCTGGAAACTCGATCA

GCATTTCCTAAAATAGAAGATACAGARATAATTTCCCCAGTAGCTGAGCGTCCTGAAGATCGCTCTCAT

GCAGAGCCTGAAAACCATGTGGTTGTGTCCTATTGTCCACCCATCATTGAGGAAGAAATACCAAACCCA

GCCGCAGATGAAGCTGGAGGGACTGCACAGGTTATTTACATTGATGT TCAGTCGATGTATCAGCCTCAA

GCAAAACCAGAAGAAGAACAAGAAAATGACCCTGTAGGAGGGGCAGGCTATAAGCCACAGATGCACCTC

CCCATTAATTCTACTGTGGAAGATATAGCTGCAGAAGAGGACTTAGATAAAACTGCGGGTTACAGACCT

CAGGCCAATGTAAATACATGGAATTTAGTGTCTCCAGACTCTCCTAGATCCATAGACAGCAACAGTGAG

ATTGTCTCATTTGGAAGTCCATGCTCCATTAATTCCCGACAATTTTTGATTCCTCCTARAGATGAAGAC

TCTCCTAAATCTAATGGAGGAGGGTGGTCCTTTACAAACTTTTTTCAGAACAAACCAAACGATTAACAG

TGTCACCGTGTCACTTCAGTCAGCCATCTCAATAAGCTCTTACTGCTAGTGTTGCTACATCAGCACTGG

GCATTCTTGGAGGGATCCTGTGAAGTATTGTTAGGAGGTGAACTTCACTACATGTTAAGTTACACTGAA

AGTTCATGTGCTTTTAATGTAGTCTAAAAGCCAAAGTATAGTGACTCAGAATCCTCAATCCACAAAACT

CAAGATTGGGAGCTCTTTGTGATCAAGCCARAGAATTCTCATGTACTCTACCTTCAAGAAGCATTTCAA

GGCTAATACCTACTTGTACGTACATGTAAAACAAATCCCGCCGCAACTGTTTTCTGTTCTGTTGTTTGT

GGTTTTCTCATATGTATACTTGGTGGAATTGTAAGTGGATTTGCAGGCCAGGGAGAAAATGTCCAAGTA

ACAGGTGAAGTTTATTTGCCTGACGTTTACTCCTTTCTAGATGAAAACCAAGCACAGATTTTAAAACTT

CTAAGATTATTCTCCTCTATCCACAGCATTCACNNNNNNNNNNNNNNNNNNNNNNGTAGTGACAGCGAT

TTAGTGTTTTGTTTGATAAAGTATGCTTATTTCTGTGCCTACTGTATAATGGTTATCAAACAGTTGTCT

CAGGGGTACAAACTTTGARAACARGTGTGACACTGACCAGCCCARATICATAATCATGTTTICTIGCTGT

AAR CAG AAG GARR AAC TAA AAA TG TA TC TTC TAT TT TCC TOCA TCAGGTIGCC TATGTATTTTAC

CTTTTCATATTTAAGGCAARAGTACTTGAAAATTTTAAGTGTCCGAATAAGATATGTCTTTTTTGTTTG

TTT TTT TTGGTTGGTTGTTTGTTTTTTATCATCTGAGAT TCTGTAATGTATTTGCAAATAATGGATCAA

SE 131

A

TTAATTTTTTTTGAAGCTCATATTGTATCTTTTTAAAARACCATGTTGTGGAARAAAGCCAGAGTGACAA

GTGACAAAATCTATTTAGGAACTCTGTGTATGAATCCTGATTTTAACTGCTAGGATTCAGCTAAATTTC

TGAGCTTTATGATCTGTGGAAATTTGGAATGARATCGAATTCATTTTGTACATACATAGTATATTAAAA

CTATATAATAGTTCATAGAAATGTTCAGTAATGAAAARAATATATCCAATCAGAGCCATCCCGAAAAARA

AAAAAAAA (SEQ ID NO: 3102).

The length of this sequence was determined using batch, automated computational methods and the sequence, as sense strand, its length, and the desired location of the probe sequence near the 3’ end of the mRNA was submitted to Array Designer Ver 1.1 (Premier Biosoft International, Palo Alto, CA).

Search quality was set at 100%, number of best probes set at 1, length range set at 50 base pairs, Target

Tm set at 75 C. degrees plus or minus S degrees, Hairpin max deltaG at 6.0 -kcal/mol., Self dimmer max deltaG at 6.0 —kcal/mol, Run/repeat (dinucleotide) max length set at 5, and Probe site minimum overlap set at 1. When none of the 49 possible probes met the criteria, the probe site would be moved 50 base pairs closer to the 5° end of the sequence and resubmitted to Array Designer for analysis.

When no possible probes met the criteria, the variation on melting temperature was raised to plus and minus 8 degrees and the number of identical basepairs in a run increased to 6 so that a probe sequence was produced.

In the sequence above, using the cntena noted above, Array Designer Ver 1.1 designed a probe corresponding to oligonucleotide number 3037 and is indicated by underlining in the sequence above.

It has a melting temperature of 68.4 degrees Celsius and a max run of 6 nucleotides and represents one of the cases where the criteria for probe design in Array Designer Ver 1.1 were relaxed in order to obtain an oligonucleotide near the 3’ end of the mRNA (Low melting temperature was allowed).

Clone 463D12

Clone 463D12 was sequenced and compared to the nr, dbEST, and UniGene databases at NCBI using the BLAST search tool. The sequence matched accession number AT184553, an EST sequence with the definition line “qd60a05.x1 Soares_testis NHT Homo sapiens cDNA clone IMAGE:1733840 3' similar to gb:M29550 PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT 1 (HUMAN);, mRNA sequence.” The E value of the alignment was 1.00 x 107%. The GenBank sequence begins with a poly-T region, suggesting that it is the antisense strand, read 5° to 3°. The beginning of this sequence is complementary to the 3’ end of the mRNA sense strand. The accession number for this sequence was included in a text file of accession numbers representing antisense sequences. Sequences for antisense strand mRNAs were obtained by uploading a text file containing desired accession numbers as an

Entrez search query using the Batch Entrez web interface and saving the results locally as a FASTA file. The following sequence was obtained, and the region of alignment of clone 463D12 is outlined:

TTTTTTTTTTTTTTCTTAAATAGCATTTATTTTCTCTCAAARAAGCCTATTATGTACTAACAAGTGTTCC

TCTAAATTAGARAGGCATCACTACTAAAATTTTATACATATTTTTTATATAAGAGAAGGAATATTGGGT

TACAATCTGAATTTCTCTTTATGATTTCTCTTAAARGTATAGAACAGCTATTAAAATGACTAATATTGCT

AAAATGAAGGCTACTAAATTTCCCCAAGAATTTCGGTGGAATGCCCAAAAATGGTGTTAAGATATGCAG

ARGGGCCCATTTCAAGCAAAGCAATCTCTCCACCCCTTCATAAAAGATTTAAGCTARAAAARAAANAAN

GGAGTARATGTAACAGTAATAAAACAAATTTTTTTTAAAAATAAAAATTATACCTTTTTCTCCAACAAA

CGGTAAAGACCACGTGAAGACATCCATAAAATTAGGCAACCAGTAAAGATGTGGAGAACCAGTAAACTG

TCGAAATTCATCACATTATTTTCATACTTTAATACAGCAGCTTTAATTATTGGAGAACATCAAAGTAAT

TAGGTGCCGAAAAACATTGTTATTAATGAAGGGAACCCCTGACGTTTGACCTTTTCTGTACCATCTATA

. GCCCTGGACTTGA (SEQ ID NO:3103) Lo

The FASTA file, including the sequence of AA184553, was then masked using the RepeatMasker web interface, as shown below. The region of alignment of clone 463D12 is outlined.

TTTTTTTTTTTTTTCTTAAATAGCATTTATTTTCTCTCARAAAGCCTATTATGTACTAACAAGTGTTCC

TCTAAATTAGAAAGGCATCACTACNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGAAGGAATATTCGGT

TACAATCTGAATTTCTCTTTATGATTTCTCTTAAAGTATAGAACAGCTATTAAAATGACTAATATTGCT

AAAATGAAGGCTACTAAATTTCCCCAAGAATTTCGGTGGAATGCCCAAAAATGGTGTTAAGATATGCAG

AAGGGCCCATTTCAAGCARAGCAATCTCTCCACCCCTTCATAAAAGATTTAAGCTAARAAAARAARAARAA

AA GANS ARAN TCCARCAGC TGA RCAC AT TOGaC TAT TTA TARRTC TTC TCCCAGTCCCCCAGRCAGEET [GGAGTAAATGTAACAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCCTTTTTCTCCAACAAA

CGGTAAAGACCACGTGAAGACATCCATAAAATTAGGCAACCAGTAAAGATGTGGAGAACCAGTAAACTG

TCGAAATTCATCACATTATTTTCATACTTTAATACAGCAGCTTTAATTATTGGAGAACATCAAAGTAAT

TAGGTGCCGAAAAACATTGTTATTAATGAAGGGAACCCCTGACGTTTGACCTTTTCTGTACCATCTATA

GCCCTGGACTTGA Masked version of 463D12 sequence. (SEQ ID NO:3104)

The sequence was submitted to Array Designer as described above, however, the desired location of the probe was indicated at base pair 50 and if no probe met the criteria, moved in the 3’ direction. The complementary sequence from Array Designer was used, because the original sequence was antisense. -

The oligonucleotide designed by Array Designer corresponds to oligonucleotide number 3054 and is complementary to the underlined sequence above. The probe has a melting temperature of 72.7 degrees centigrade and a max run of 4 nucleotides.

Clone 72D4

Clone 72D4 was sequenced and compared to the nr, dbEST, and UniGene databases at NCBI using the

BLAST search tool. No significant matches were found in any of these databases. When compared to the human genome draft, significant alignments were found to three consecutive regions of the reference sequence NT 008060, as depicted below, suggesting that the insert contains three spliced exons of an unidentified gene.

Residue numbers on Matching residue clone 72D4 sequence numbers on NT 008060 1-198 478646 — 478843 a

197 —- 489 479876 — 480168 491 - 585 489271 — 489365

Because the reference sequence contains introns and may represent either the coding or noncoding strand for this gene, BioCardia’s own sequence file was used to design the oligonucleotide. Two complementary probes were designed to ensure that the sense strand was represented. The sequence of the insert in clone 72D4 is shown below, with the three putative exons outlined. :

CCATGACGAGAGCTTIGGCAGAATAAATAACTTCTTTAAACAATTITACGGCATGAAGAAA

TCTGGACCAGTTTATTAAATGGGATTTCIGCCACAAACCTTGGAAGAATCACATCATCTTA

NNCCCAAGIGAAAACTGTGTTGCGTAACAAAGAACATGACTGCGCTCCACACATACATCA

TTGCCCGGCGAGGCGGGACACAAGTCAACGACGGAACACTTGAGACAGGCCTACAACTG:

TGCACGGGTCAGAAGCAAGTTTAAGCCATACTTGCTGCAGTGAGACTACATITCTGTCTAT,

AGARG ATA CCTOACTTGATCTGT TTT CAG CICA TTC CAGA TG TGOG TCT TGTGETC

AAAAAC (SEQ ID NO: 3106)

The sequence was submitted to RepeatMasker, but no repetitive sequences were found. The sequence shown above was used to design the two 50-mer probes using Array Designer as described above. The probes are shown in bold typeface in the sequence depicted below. The probe in the sequence is oligonucleotide number 3020 (SEQ ID NO: 3020) and the complementary probe is oligonucleotide number 318 (SEQ ID NQO:318). A portion of the target sequence is listed below (SEQ ID: 3106).

CAGGTCACACAGCACATCAGTGGCTACATGTGAGCTCAGACCTGGGTCTGCTGCTGTCTGTCTTCCCAA

TATCCATGACCTTGACTGATGCAGGTGTCTAGGGATACGTCCATCCCCGTCCTGCTGGAGCCCAGAGCA

CGGAAGCCTGGCCCTCCGAGGAGACAGRAAGGGAGTGTCGGACACCATGACGAGAGCTTGGCAGAATAAA

TAACTTCTTTAAACAATTTTACGGCATGARAGAAATCTGGACCAGTTTATTARATGGGATTTCTGCCACA

AACCTTGGAAGAATCACATCATCTTANNCCCAAGTGAAAACTGTGTTGCGTAACAAAGAACATGACTGC

GCTCCACACATACATCATTGCCCGGCGAGGCGGGACACAAGTCAACGACGGAACACTTGAGACAGGCCT

ACAACTGTGCACGGGTCAGAAGCAAGTTTAAGCCATACTTGCTGCAGTGAGACTACATTTCTGTCTATA

GAAGATACCTGACTTGATCTGTTTTTCAGCTCCAGTTCCCAGATGTGC

€ - - - -GTCAAGGGTCTACACG

GTGTTGTGGTCCCCAAGTATCACCTTCCAATTTCTGGGAG- - >

CACAACACCAGGGGTTCATAGTGGAAGGTTAAAG-5"

CAGTGCTCTGGCCGGATCCTTEGCCGCGCGGATARAAACT-- - >

C134

Confirmation of probe sequence

Following probe design, each probe sequence was confirmed by comparing the sequence against dbEST, the UniGene cluster set, and the assembled human genome using BLASTn at NCBI.

Alignments, accession numbers, gi numbers, UniGene cluster numbers and names were examined and the most common sequence used for the probe.

Example 9 - Production of an array of 8000 spotted 50mer oligonucleotides

We produced an array of 8000 spotted initial candidate SOmer oligonucleotides. Example 8 exemplifies the design and selection of probes for this array.

Sigma-Genosys (The Woodlands, TX) synthesized un-modified 50-mer oligonucleotides using standard phosphoramidite chemistry, with a starting scale of synthesis of 0.05 umole (see, e.g., R.

Meyers, ed. (1995) Molecular Biology and Biotechnology: A Comprehensive Desk Reference).

Briefly, to begin synthesis, a 3’ hydroxyl nucleoside with a dimethoxytrityl (DMT) group at the 5° end was attached to a solid support. The DMT group was removed with trichloroacetic acid (TCA) in order to free the 5’-hydroxyl for the coupling reaction. Next, tetrazole and a phosphoramidite derivative of the next nucleotide were added. The tetrazole protonates the nitrogen of the phosphoramidite, making it susceptible to nucleophilic attack. The DMT group at the 5’-end of the hydroxyl group blocks further addition of nucleotides in excess. Next, the inter-nucleotide linkage was converted to a phosphotriester bond in an oxidation step using an oxidizing agent and water as the oxygen donor.

Excess nucleotides were filtered out and the cycle for the next nucleotide was started by the removal of the DMT protecting group. Following the synthesis, the oligo was cleaved from the solid support. The oligonucleotides were desalted, resuspended in water at a concentration of 100 or 200 uM, and placed in 96-deep well format. The oligonucleotides were re-arrayed into Whatman Uniplate 384-well polyproylene V bottom plates. The oligonucleotides were diluted to a final concentration 30 pM in 1X

Micro Spotting Solution Plus (Telechemvarrayit.com, Sunnyvale, CA) in a total volume of 15 pl. In total, 8,031 oligonucleotides were arrayed into twenty-one 384-well plates.

Arrays were produced on Telechem/arrayit.com Super amine glass substrates (Telechen/arrayit.com), which were manufactured in 0.1 mm filtered clean room with exact dimensions of 25x76x0.96 mm.

The arrays were printed using the Virtek Chipwriter with a Telechem 48 pin Micro Spotting Printhead.

The Printhead was loaded with 48 Stealth SMP3B TeleChem Micro Spotting Pins, which were used to print oligonucleotides onto the slide with the spot size being 110-115 microns in diameter.

Example 10: Identification of diagnostic nucleotide sets for diagnosis of Cardiac Allograft Rejection

Genes were identified which have expression patterns useful for the diagnosis and monitoring of cardiac allograft rejection. Further, sets of genes that work together in a diagnostic algorithm for allograft rejection were identified. Patients, patient clinical data and patient samples used in the discovery of markers below were derived from a clinical study described in example 5.

The collected clinical data is used to define patient or sample groups for correlation of expression data.

Patient groups are identified for comparison, for example, a patient group that possesses a useful or interesting clinical distinction, verses a patient group that does not possess the distinction. Measures of cardiac allograft rejection are derived from the clinical data described above to divide patients (and patient samples) into groups with higher and lower rejection activity over some period of time or at any _ one point in time. Such data are rejection grade as determined from pathologist reading of the cardiac biopsies and data measuring progression of end-organ damage, including depressed left ventricular dysfunction (decreased cardiac output, decreased ejection fraction, clinical signs of low cardiac output) and usage of inotropic agents (Kobashigawa 1998).

Expression profiles correlating with occurrence of allograft rejection are identified, including expression profiles corresponding to end-organ damage and progression of end-organ damage.

Expression profiles are identified predicting allograft rejection, and response to treatment or likelihood of response to treatment. Subsets of the candidate library (or a previously identified diagnostic nucleotide set) are identified, that have predictive value for the presence of allograft rejection or prediction of allograft rejection or end organ damage.

Mononuclear RNA samples were collected from patients who had recently undergone a cardiac allograft transplantation using the protocol described in example 2. The allograft rejection status at the time of sample collection was determined by examination of cardiac biopsies as described in example 5. 180 samples were included in the analysis. Each patient sample was associated with a biopsy and clinical data collected at the time of the sample. The cardiac biopsies were graded by a pathologist at the local center and by a centralized pathologist who read the biopsy slides from all four local centers in a blinded manner. Biopsy grades included 0, 1A, 1B, 2, 3A, and 3B. No grade 4 rejection was identified. Dependent variables were developed based on these grades using either the local center pathology reading or the higher of the two readings, local or centralized. The dependent variables used for correlation of gene expression profiles with cardiac allograft rejection are shown in Table 4.

Dependent variables are used to create classes of samples corresponding to the presence or absence of rejection.

Clinical data were also used to determine criteria for including samples in the analysis. The strictest inclusion criteria required that samples be from patients who did not have a bacterial or viral infection, were at least two weeks post cardiac transplant and were not currently admitted to the hospital. A second inclusion criteria (inclusion 2) reduced the post-transplant criteria to 1 week and eliminated the hospital admission criteria.

After preparation of RNA (example 2), amplification, labeling, hybridization, scanning, feature extraction and data processing were done as described in Example 11, using the oligonucleotide microarrays described in Example 9. The resulting log ratio of expression of Cy3 (patient sample)/

CyS5 (R50 reference RNA) was used for analysis. This dataset is called the “static” data. A second type of dataset, referenced, was derived from the first. These datasets compared the gene expression log ratio in each sample to a baseline sample from the same patient using the formula: ref log ratio = (log ratio, , )- (log ratio, .;... )

Two referenced datasets were used, named “0 HG” and “Best 0”. The baseline for 0 HG was a Grade 0 sample from the same patient as the sample, using the highest grade between the centralized and local pathologists. The baseline for Best 0 was a Grade 0 sample from the same patient as the sample, using : both the local and centralized reader biopsy grade data. When possible a Grade 0 prior to the sample : was used as the baseline in both referenced datasets.

The datasets were also divided into subsets to compare analysis between two subsets of roughly half of the data. The types of subsets constructed were as follows. First half/second half subsets were the first half of the samples and the second half of the samples from a dataset ordered by sample number.

Odd/even subsets used the same source, a dataset ordered by sample number, but the odd subset consisted of every 2" sample starting with the first and the even subset consisted of every 2" sample starting with the second sample, Center 14/other subsets were the same datasets, divided by transplant hospital. The center 14 subset consisted of all samples from patients at center 14, while the other subset consisted of all samples from the other three centers (12,13, and 15).

Initially, significance analysis for microarrays (SAM, Tusher 2001, Example 15) was used to discover genes that were differentially expressed between the rejection and no-rejection groups. Ninety-six different combinations of dependent variables, inclusion criteria, static/referenced, and data subsets were used in SAM analysis to develop the primary lists of genes significantly differentially expressed between rejection and no-rejection. The most significant of these genes were chosen based on the following criteria. Tier 1 genes were those which appeared with an FDR of less than 20% in identical analyses in two independent subsets. Tier 2 genes were those which appeared in the top 20 genes on . the list with an FDR less than 20% more than 50% of the time over all dependent variables with the inclusion criteria, and static/referenced constant. Tier 3 genes were those that appeared more than 50% of the time with an FDR less than 20% more than 50% of the time over all dependent variables with the inclusion criteria, and static/referenced constant. The genes that were identified by the analysis as statistically differentially expressed between rejection and no rejection are shown in Table 2.

SAM chooses genes as significantly different based on the magnitude of the difference between the groups and the variation among the samples within each group. An example of the difference between some Grade 0 and some Grade 3A samples for 9 genes is shown in Figure 7A.

Additionally, many of these same combinations were used in the Supervised Harvesting of Expression

Trees (SHET, Hastie et al. 2001) algorithm (see example 15) to identify markers that the algorithm chose as the best to distinguish between the rejection and no rejection classes using a bias factor of 0.01. The top 20 or 30 terms were taken from the SHET output and among all comparisons in either the static or referenced data the results were grouped. Any gene found in the top 5 terms in more than 50% of the analyses was selected to be in group B1 (Table 2). The occurrences of each gene were tabulated over all SHET analysis (for either static or referenced data) and the 10 genes that occurred the most were selected to be in group B2 (Table 2).

An additional classification method used was CART (Salford Systems, San Diego, example 15). Either the static or referenced dataset was reduced to only the genes for which expression values (log ratios) were present in at least 80% of the samples. These data were used in CART with the default settings, using the Symmetric Gini algorithm. Each of the dependent variables was used with both the full sample set and the strict inclusion criteria. Two groups of genes were identified. Group C1 were those genes that were a primary splitter (1¥ decision node). Group C2 genes were the 10 genes that occurred as splitters the most often over all these analyses.

Two other classification models were developed and their best genes identified as markers of cardiac allograft rejection. Group D genes were identified from a set of 59 samples, referenced data, local biopsy reading grade, using logistic regression. Group E genes were identified from the primary static dataset using a K-nearest neighbor classification algorithm.

Both hierarchical clustering (Eisen et al. 1998) and CART were used to identify surrogates for each identified marker. Hierarchical clustering surrogates are genes co-expressed in these and were chosen from the nearest branches of the dendrogram. CART surrogates were identified by CART as the surrogates for those genes chosen as primary splitters at decision nodes.

Primers for real-time PCR validation were designed for each of the marker genes as described in

Example 13.

CART was used to build a decision tree for classification of samples as rejection or no-rejection using the gene expression data from the arrays. The analysis identified sets of genes that can be used together to accurately identify samples derived from cardiac allograft transplant patients. The set of genes and the identified threshold expression levels for the decision tree are referred to as a “models”.

This model can be used to predict the rejection state of an unknown sample. The input data were the static expression data (log ratio) and the referenced expression data (log ratio referenced to the best available grade O from either the centralized reader or the local reader) for 139 of our top marker genes.

These two types of expression data were entered into the CART software as independent variables.

The dependent variable was rejection state, defined for this model as no rejection = grade 0 and rejection = grade 3A. Samples were eliminated from consideration in the training set if they were from patients with either bacterial or viral infection or were from patients who were less than two weeks post-transplant. The method used was Symmetric Gini, allowing linear combinations of independent variables. The costs were set to 1 for both false negatives and false positives and the priors were set equal for the two states. No penalties were assessed for missing data, however the marker genes selected have strong representation across the dataset. 10-fold cross validation was used to test the model. Settings not specified remained at the default values.

The model shown in Figure 7B is based on decisions about expression values at three nodes, each a different marker gene. The cost assigned to this model is 0.292, based on the priors being equal, the costs set to 1 for each type of error, and the results from the 10-fold cross validation.

In the training set, no rejection samples were misclassified (sensitivity = 100%) and only 1 no-rejection sample was misclassified (specificity = 94.4%). Following 10-fold cross validation, 2 rejection samples were misclassified (sensitivity = 87.5%) and 3 no-rejection samples were misclassified (specificity = 83.3%). The CART software assigns surrogate markers for each decision node.

These genes can be used alone or in association with other genes or variables to build a diagnostic gene set or a classification algorithm. These genes can be used in association with known gene markers for rejection (such as those identified in the prior art) to provide a diagnostic algorithm.

Example | 1- Amplification, labeling, and hybridization of total RNA to an oligonucleotide microarray

Amplification, labeling, hybridization and scanning

Samples consisting of at least 0.5 to 2 pg of intact total RNA were further processed for array hybridization. When available, 2 pg of intact total RNA is used for amplification. Amplification and labeling of total RNA samples was performed in three successive enzymatic reactions. First, a single- stranded DNA copy of the RNA was made (hereinafter, “ss-cDNA”). Second, the ss-cDNA was used as a template for the complementary DNA strand, producing double-stranded cDNA (hereinafter, “ds- cDNA, or cDNA"). Third, linear amplification was performed by in vitro transcription from a bacterial

T, promoter. During this step, fluorescent-conjugated nucleotides were incorporated into the amplified

RNA (hereinafter, “aRNA”).

The first strand cDNA was produced using the Invitrogen kit (Superscript II). The first strand cDNA was produced in a reaction composed of 50 mM Tris-HCI (pH 8.3), 75 mM KCl, and 3 mM MgCl, (1x

First Strand Buffer, Invitrogen), 0.5 mM dGTP, 0.5 mM dATP, 0.5 mM dTTP, 0.5 mM dCTP, 10 mM

DTT, 200 U reverse transcriptase (Superscript II, Invitrogen, #18064014), 15 U RNase inhibitor : (RNAGuard, Amersham Pharmacia, #27-0815-01), 5 uM T7T24 primer (5'-GGCCAGTGAATTGTAATACGACTCACTATAGGGAGGCGGTTTTITITITITITTITTTITT

TTT-3'), (SEQ ID NO:3105) and 0.5 to 2 pg of selected sample total RNA. Several purified, recombinant control mRNAs from the plant Arabidopsis thaliana were added to the reaction mixture: 2- pg of the following genes CAB, RCA, LTP4, NACI, RCP1,XCP2, RBCL, LTP6, TIM, and PRKase (Stratagene, #252201, #252202, #252204, #252208, #252207, #252206, #252203, #252205, #252209, #252210 respectively). The control RNAs allow the estimate of copy numbers for individual mRNAs in the clinical sample because corresponding sense oligonucleotide probes for each of these plant genes are present on the microarray. The final reaction volume of 20 pl was incubated at 42°C for 90 min.

For synthesis of the second cDNA strand, DNA polymerase and RNase were added to the previous reaction, bringing the final volume to 150 pl. The previous contents were diluted and new substrates were added to a final concentration of 20 mM Tris-HCI (pH 7.0) (Fisher Scientific, Pittsburgh, PA #BP1756-100), 90 mMKCI (Teknova, Half Moon Bay, CA, #0313-500) , 4.6 mM MgCl, (Teknova,

Half Moon Bay, CA, #0304-500), 10 mM(NH,) ,SO, (Fisher Scientific #A702-500)(1x Second Strand buffer, Invitrogen), 0.266 mM dGTP, 0.266 mM dATP, 0.266 mM dTTP, 0.266 mM dCTP, 40 U E. coli DNA polymerase (Invitrogen, #18010-025), and 2 U RNaseH (Invitrogen, #18021-014). The second strand synthesis took place at 16°C for 150 minutes.

Following second-strand synthesis, the ds-cDNA was purified from the enzymes, dNTPs, and buffers before proceeding to amplification, using phenol-chloroform extraction followed by ethanol precipitation of the cDNA in the presence of glycogen.

Alternatively, a silica-gel column is used to purify the cDNA (e.g. Qiaquick PCR cleanup from Qiagen, #28104). The volume of the column purified cDNA was reduced by ethanol precipitation in the

C139 presence of glycogen in which the cDNA was collected by centrifugation at >10,000 xg for 30 minutes, the supernatant is aspirated, and 150 pl of 70% ethanol, 30% water was added to wash the DNA pellet.

Following centrifugation, the supernatant was removed, and residual ethanol was evaporated at room temperature. Alternatively, the volume of the column purified cDNA is reduce in a vacuum evaporator where the supematant is reduce to a final volume of 7.4 ul.

Linear amplification of the cDNA was performed by in vitro transcription of the cDNA. The cDNA pellet from the step described above was resuspended in 7.4 pl of water, and in vitro transcription reaction buffer was added to a final volume of 20 pl containing 7.5 mM GTP, 7.5 mM ATP, 7.5 mM

TTP, 2.25 mM CTP, 1.025 mM Cy3-conjugated CTP (Perkin Elmer; Boston, MA, #NEL-580), 1x reaction buffer (Ambion, Megascript Kit, Austin, TX and #1334) and 1 % T; polymerase enzyme mix (Ambion, Megascript Kit, Austin, TX and #1334). This reaction was incubated at 37°C overnight.

Following in vitro transcription, the RNA was purified from the enzyme, buffers, and excess NTPs using the RNeasy kit from Qiagen (Valencia, CA; # 74106) as described in the vendor’s protocol. A second elution step was performed and the two eluates were combined for a final volume of 60 pl.

RNA is quantified using an Agilent 2100 bioanalyzer with the RNA 6000 nano LabChip. :

Reference RNA was prepared as described above, except CyS-CTP was incorporated instead of

Cy3CTP. Reference RNA from five reactions, each reaction started with 2 ug total RNA, was pooled together and quantitated as described above.

Hybridization to an array

RNA was prepared for hybridization as follows: for an 18mmx5Smm array, 20 pg of amplified RNA (aRNA) was combined with 20 pg of reference aRNA. The combined sample and reference aRNA was concentrated by evaporating the water to 10 pl in a vacuum evaporator. The sample was fragmented by heating the sample at 95°C for 30 minutes to fragment the RNA into 50-200 bp pieces.

Alternatively, the combined sample and reference aBRNA was concentrated by evaporating the water to ul in a vacuum evaporator. Five pl of 20 mM zinc acetate was added to the aRNA and the mix incubated at 60°C for 10 minutes. Following fragmentation, 40 pl of hybridization buffer was added to achieve final concentrations of 5xSSC and 0.20 %SDS with 0.1 pg/ul of Cot-1 DNA (Invitrogen) as a competitor DNA. The final hybridization mix was heated to 98°C, and then reduced to 50°C at 0.1°C per second.

Alternatively, formamide is included in the hybridization mixture to lower the hybridization temperature. :

The hybridization mixture was applied to a pre-heated 65°C microarray, surface, covered with a glass coverslip (Coming, #2935-246), and placed on a pre-heated 65°C hybridization chamber (Telechem, AHC-10). 15 ul of 5xSSC was placed in each of the reservoir in the hybridization chamber and the chamber was sealed and placed in a water bath at 62°C for overnight (16-20 hrs). Following incubation, the slides were washed in 2xSSC, 0.1% SDS for five minutes at 30°C, then in 2xSSC for five minutes at 30°C, then in 2xSSC for another five minutes at 30°C, then in 0.2xSSC for two minutes oo oo at room temperature. The arrays were spun at 1000xg for 2 minutes to dry them. The dry microarrays are then scanned by methods described above. :

The microarrays were imaged on the Agilent (Palo Alto, CA) scanner G2565AA. The scan settings using the Agilent software were as follows: for the PMT Sensitivity (100% Red and 100% Green);

Scan Resolution (10 microns); red and green dye channels; used the default scan region for all slides in the carousel; using the largest scan region; scan date for Instrument ID; and barcode for Slide ID. The full image produced by the Agilent scanner was flipped, rotated, and split into two images (one for each signal channel) using TIFFSplitter (Agilent, Palo Alto, CA). The two channels are the output at 532 nm (Cy3-labeled sample) and 633 nm (CyS5-labeled R50). The individual images were loaded into

GenePix 3.0 (Axon Instruments, Union City, CA) for feature extraction, each image was assigned an excitation wavelength corresponding the file opened; Red equals 633 nm and Green equals 532 nm.

The setting file (gal) was opened and the grid was laid onto the image so that each spot in the grid overlaped with >50% of the feature. Then the GenePix software was used to find the features without setting minimum threshold value for a feature. For features with low signal intensity, GenePix reports “not found”. For all features, the diameter setting was adjusted to include only the feature if necessary.

The GenePix software determined the median pixel intensity for each feature (F;) and the median pixel intensity of the local background for each feature (B;) in both channels. The standard deviation (SDF; and SDB;) for each is also determined. Features for which GenePix could not discriminate the feature from the background were “flagged” as described below.

Following feature extraction into a *“ .gpr” file, the header information of the .gpr file was changed to carry accurate information into the database. An Excel macro was written to include the following information: Name of the onginal .tif image file, SlideID, Version of the feature extraction software, GenePix Array List file, GenePix Settings file, ScanIlD, Name of person who scanned the slide, Green PMT setting, Red PMT setting, ExtractID (date .gpr file was created, formatted as yyyy.mm.dd-hh.mm.ss), Results file name (same as the .gpr file name), StorageCD, and Extraction comments.

Pre-processing with Excel Templates

Following analysis of the image and extraction of the data, the data from each hybridization was pre- processed to extract data that was entered into the database and subsequently used for analysis. The complete GPR file produced by the feature extraction in GenePix was imported into an excel file pre- processing template or processed using a AWK script. Both programs used the same processing logic and produce identical results. The same excel template or AWK script was used to process each GPR file. The template performs a series of calculations on the data to differentiate poor features from others and to combine duplicate or triplicate feature data into a single data point for each probe.

The data columns used in the pre-processing were: Oligo 1D, F633 Median (median value from all the pixels in the feature for the Cy5 dye), B633 Median (the median value of all the pixcls in the local background of the selected feature for Cy5), B633 SD (the standard deviation of the values for the pixels in the local background of the selected feature for Cy5), F532 Median (median value from all the pixels in the feature for the Cy3 dye), B532 Median (the median value of all the pixels in the local background of the selected feature for Cy3), B532 SD (the standard deviation of the values for the pixels in the local background of the selected feature. for Cy3), and Flags. The GenePix Flags column contains the flags set during feature extraction. “-75” indicates there were no features printed on the array in that position, “-50” indicates that GenePix could not differentiate the feature signal from the local background, and “-100" indicates that the user marked the feature as bad.

Once imported, the data associated with features with -75 flags was not used. Then the median of

B633 SD and B532 SD were calculated over all features with a flag value of “0”. The minimum values of B633 Median and B532 Median were identified, considering only those values associated with a flag value of “0”. For each feature, the signal to noise ratio (S/N) was calculated for both dyes by taking the fluorescence signal minus the local background (BGSS) and dividing it by the standard deviation of the local background: sin=E8

SDB,

If the S/N was less than 3, then an adjusted background-subtracted signal was calculated as the fluorescence minus the minimum local background on the slide. An adjusted S/N was then calculated as the adjusted background subtracted signal divided by the median noise over all features for that channel. If the adjusted S/N was greater than three and the original S/N were less than three, a flag of was set for the CyS channel, a flag of 23 was set for the Cy3 channel, and if both met these criteria, then a flag of 28 was set. If both the adjusted S/N and the original S/N were less than three, then a flag of 65 was set for Cy5, 63 set for Cy3, and 68 set if both dye channels had an adjusted S/N less than three. All signal to noise calculations, adjusted background-subtracted signal, and adjusted S/N were calculated for each dye channel. If the BGSS value was greater than or equal to 64000, a flag was set to indicate saturation; 55 for Cy5, 53 for Cy3, 58 for both.

The BGSS used for further calculations was the original BGSS if the original S/N was greater than or equal to three. If the original S/N ratio was less than three and the adjusted S/N ratio was greater than or equal to three, then the adjusted BGSS was used. If the adjusted S/N ratio was less than three, then the adjusted BGSS was used, but with knowledge of the flag status.

To facilitate comparison among arrays, the Cy3 and Cy5 data were scaled. The log of the ratio of

Green/Red was determined for all features. The median log ratio value for good features (Flags 0, 23, 25, 28, 63) was determined. The feature values were scaled using the following formula:

Log_Scaled_Feature_Ratio = Log_Feature_Ratio — Median_Log_Ratio.

The flag setting for each feature was used to determine the expression ratio for each probe, a choice of one, two or three features. If all features had flag settings in the same category (categories=negatives,

0 to 28, 53-58, and 63-68), then the average of the three scaled, anti log feature ratios was calculated If the three features did not have flags in the same category, then the feature or features with the best quality flags were used (0>25>23>28>55>53>58>65>63>68). Features with negative flags were never used. When the best flags were two or three features in the same category, the anti log average was used. If a single feature had a better flag category than the other two then the anti log of that feature ratio was used.

Once the probe expression ratios were calculated from the one, two, or three features, the log of the scaled, averaged ratios was taken as described below and stored for use in analyzing the data.

Whichever features were used to calculate the probe value, the flag from those features was carried forward and stored as the flag value for that probe. 2 different data sets can be used for analysis.

Flagged data uses all values, including those with flags. Filtered data sets are created by removing flagged data from the set before analysis.

Example 12: Real-time PCR validation of array expression results

Leukocyte microarray gene expression was used to discover expression markers and diagnostic gene sets for clinical outcomes. It is desirable to validate the gene expression results for each gene using a more sensitive and quantitative technology such as real-time PCR. Further, it is possible for the diagnostic nucleotide sets to be implemented as a diagnostic test as a real-time PCR panel.

Alternatively, the quantitative information provided by real-time PCR validation can be used to design a diagnostic test using any alternative quantitative or semi-quantitative gene expression technology.

To validate the results of the microarray experiments we used real-time, or kinetic, PCR. In this type of experiment the amplification product is measured during the PCR reaction. This enables the researcher to observe the amplification before any reagent becomes rate limiting for amplification. In kinetic PCR the measurement is of Cy (threshold cycle) or Cp (crossing point). This measurement (C1=Cp) is the point at which an amplification curve crosses a threshold fluorescence value. The threshold is set to a point within the area where all of the reactions were in their linear phase of amplification. When measuring Cr, a lower Cy value is indicative of a higher amount of starting material since an earlier cycle number means the threshold was crossed more quickly.

Several fluorescence methodologies are available to measure amplification product in real-time PCR.

Tagman (Applied BioSystems, Foster City, CA) uses fluorescence resonance energy transfer (FRET) to inhibit signal from a probe until the probe is degraded by the sequence specific binding and Taq 3’ exonuclease activity. Molecular Beacons (Stratagene, La Jolla, CA) also use FRET technology, whereby the fluorescence is measured when a hairpin structure is relaxed by the specific probe binding to the amplified DNA. The third commonly used chemistry is Sybr Green, a DNA-binding dye (Molecular Probes, Eugene, OR). The more amplified product that is produced, the higher the signal.

The Sybr Green method is sensitive to non-specific amplification products, increasing the importance of primer design and selection. Other detection chemistries can also been used, such as ethedium bromide or other DNA-binding dyes and many modifications of the fluorescent dye/quencher dye

Taqman chemistry.

Sample prep and cDNA synthesis

The inputs for real time PCR reaction are gene-specific primers, cDNA from specific patient samples, and standard reagents. The cDNA was produced from mononuclear RNA (prepared as in example 2) or whole blood RNA by reverse transcription using Oligo dT primers (Invitrogen, 18418-012) and random hexamers (Invitrogen, 48190-011) at a final concentration of 0.5ng/ul and 3ng/ul respectively.

For the first strand reaction mix, 0.5 pg of mononuclear total RNA or 2 pg of whole blood RNA and 1 ul of the Oligo dT/ Random Hexamer Mix, were added to water to a final volume of 11.5 pl. The sample mix was then placed at 70°C for 10 minutes. Following the 70°C incubation, the samples were chilled on ice, spun down, and 88.5 pl of first strand buffer mix dispensed into the reaction tube. The final first strand buffer mix produced final concentrations of 1X first strand buffer (Invitrogen, Y00146,

Carlsbad, CA), 10 mM DTT (Invitrogen, Y00147), 0.5 mM dATP (NEB, N0440S, Beverly, MA), 0.5 mM dGTP (NEB, N0442S), 0.5mM dTTP (NEB, N04438S), 0.5 mM dCTP (NEB, N0441S), 200U of reverse transcriptase (Superscript II, Invitrogen, 18064-014), and 18U of RNase inhibitor (RNAGaurd

Amersham Pharmacia, 27-0815-01, Piscataway, NJ). The reaction was incubated at 42°C for 90 minutes. After incubation the enzyme was heat inactivated at 70°C for 15 minutes, 2 U of RNAse H added to the reaction tube, and incubated at 37°C for 20 minutes.

PRIMER DESIGN

Two methods were used to design primers. The first was to use the software, Primer Express™ and recommendations for primer design that are provided with the GeneAmp® 7700 Sequence Detection

System supplied by Applied BioSystems (Foster City, CA). The second method used to design primers was the PRIMER3 ver 0.9 program that is available from the Whitehead Research Institute,

Cambridge, Massachusetts at the Whitehead Research web site. The program can also be accessed on the World Wide Web at the web site at the Massechusetts Institute of Technology website. Primers and Tagman/hybridization probes were designed as described below using both programs.

The Primer Express literature explains that primers should be designed with a melting temperature between 58 and 60 degrees C. while the Tagman probes should have a melting temperature of 68 to 70 under the salt conditions of the supplied reagents. The salt concentration is fixed in the software.

Primers should be between 15 and 30 basepairs long. The primers should produce and amplicon in size between 50 and 150 base pairs, have a C-G content between 20% and 80%, have no more than 4 identical base pairs next to one another, and no more than 2 C's and G’s in the last 5 bases of the 3’ end. The probe cannot have a G on the 5° end and the strand with the fewest G’s should be used for the probe.

Primer3 has a large number of parameters. The defaults were used for all except for melting temperature and the optimal size of the amplicon was set at 100 bases. One of the most critical is salt concentration as it affects the melting temperature of the probes and primers. In order to produce . primers and probes with melting temperatures equivalent to Primer Express, a number of primers and probes designed by Primer Express were examined using PRIMER3. Using a salt concentration of 50 mM these primers had an average melting temperature of 3.7 degrees higher than predicted by Primer

CT

Express. In order to design primers and probes with equivalent melting temperatures as Primer Express using PRIMER3, a melting temperature of 62.7 plus/minus 1.0 degree was used in PRIMER3 for primers and 72.7 plus/minus 1.0 degrees for probes with a salt concentration of 50 mM.

The C source code for Primer3 was downloaded and complied on a Sun Enterprise 250 server using the

GCC complier. The program was then used from the command line using a input file that contained the sequence for which we wanted to design primers and probes along with the input parameters as described by help files that accompany the software. Using scripting it was possible to input a number of sequences and automatically generate a number of possible probes and primers.

Primers for B-Actin (Beta Actin, Genbank Locus: NM_001101)and B-GUS: glucuronidase, beta, (GUSB, Genbank Locus: NM_000181), two reference genes, were designed using both methods and are shown here as examples:

The first step was to mask out repetitive sequences found in the mRNA sequences using RepeatMasker program that can be accessed at: the web site University of Washington Genome Repeatmasker website. (Smit, A.F.A. & Green, P.).

The last 500 basepairs on the last 3° end of masked sequence was then submitted to PRIMER3 using ’ the following exemplary input sequences:

PRIMER_SEQUENCE_ID=>ACTB Beta Actin (SEQID 3083)

SEQUENCE=TTGGCTTGACTCAGGATTTAAAAACTGGAACGGTGAAGGTGACACCAGTCGGTTGGACGA

GCATCCCCCAAAGTTCACAATGTGGCCGAGGACTTTGATTGCACATTGTTGTT TTT TAATAGTCATTCC

AAATATGAGATGCATTGTTACAGGAAGTCCCTTGCCATCCTAAAAGCACCCCACTTCTCTCTAAGGAGA

ATGGCCCAGTCCTCTCCCAAGTCCACACAGGGGAGGGATAGCATTGCTTTCGTGTAAATTATGTAATGC

AAAATTTTTTTAATCTTCGCCTTAATCTTTTTTAT TT TGTTTTATTTTGAATGATGAGCCTTCGTGCCC

CCCCTTCCCCCTTTTTTCCCCCAACTTGAGATGTATGAAGGCTTTTGGTCTCCCTGGGAGTGGETGGAC

GCAGCCGGGCTTACCTGTACACTGACTTGAGACCAGTTGAATAAAAGTGCACACCTTA

PRIMER_SEQUENCE_ID=>GUSB (SEQID 3084)

SEQUENCE=GAAGAGTACCAGAAAAGTCTGCTAGAGCAGTACCATCTGGGTCTGGATCAAAAACGCAGA

AAATATGTGGTTGGAGAGCTCATTTGGAATTTTGCCGATTTCATGACTGAACAGTCACCGACGAGAGTG

CTGGGGAATAAAAAGGGGATCTTCACTCGGCAGAGACAACCAAAAAGTGCAGCGTTCCTTTTGCGAGAG

AGATACTGGAAGATTGCCAATGAAACCAGGTATCCCCACTCAGTAGCCAAGTCACAATGTTTGGAAAAC

AGCCCGTTTACTTGAGCARAGACTGATACCACCTGCGTGTCCCTTCCTCCCCCGAGTCAGGEGCCGACTTCCA

CAGCAGCAGAACAAGTGCCTCCTGGACTGTTCACGGCAGACCAGAACGTTTCTGGCCTGGGTTTTGTGG

TCATCTATTCTAGCAGGGAACACTAAAGGTGGAAATAARAGATTTTCTATTATGGAAATAAAGAGTTGG

CATGAAAGTCGCTACTG

After running PRIMERS, 100 sets of primers and probes were generated for ACTB and GUSB. From this set, nested primers were chosen based on whether both left primers could be paired with both right primers and a single Taqman probe could be used on an insert of the correct size. With more experience we have decided not use the mix and match approach to primer selection and just use several of the top pairs of predicted primers.

For ACTB this turned out to be:

Forward 75 CACAATGTGGCCGAGGACTT(SEQID 3085),

Forward 80 TGTGGCCGAGGACTTTGATT(SEQID 3086),

Reverse 178 TGGCTTTTAGGATGGCAAGG(SEQID 3087), and

Reverse 168 GGGGGCTTAGTTTGCTTCCT(SEQID 3088).

Upon testing, the F75 and R178 pair worked best.

For GUSB the following primers were chosen:

Forward 59 AAGTGCAGCGTTCCTTTTGC(SEQID 3089),

Forward 65 AGCGTTCCTTTTGCGAGAGA (SEQID 3090),

Reverse 158 CGGGCTGTTTTCCAAACATT (SEQID 3091), and

Reverse 197 GAAGGGACACGCAGGTGGTA (SEQID 3092).

No combination of these GUSB pairs worked well.

In addition to the primer pairs above, Primer Express predicted the following primers for GUSB:

Forward 178 TACCACCTGCGTGTCCCTTC (SEQID 3093) and Reverse 242

GAGGCACTTGTTCTGCTGCTG (SEQID 3094). This pair of primers worked to amplify the GUSB mRNA.

The parameters used to predict these primers in Primer Express were:

Primer Tm: min 58, Max=60, opt 59, max difference=2 degrees

Primer GC: min=20% Max =80% no 3’ G/C clamp

Primer: Length: min=9 max=40 opt=20

Amplicon: min Tm=0 max Tm=85 min = 50 bp max = 150 bp

Probe: Tm 10 degrees > primers, do not begin witha G on 5’ end

Other: max base pair repeat = 3 max number of ambiguous residues = 0 secondary structure: max consecutive bp = 4, max total bp = 8

Uniqueness: max consecutive match =9 max % match = 75 max 3’ consecutive match =7

Granzyme B is a marker of transplant rejection.

For Granzyme B the following sequence (NM_004131) (SEQID 3096) was used as input for Primer3 :

GGGGACTCTGGAGGCCCTCTTGTGTGTAACAAGGTGGCCCAGGGCATTGT

CTCCTATGGACGABACAATGGCATGCCTCCACGAGCCTGCACCARAAGTCT

CAAGCTTTGTACACTGGATAAAGAAAACCATGAAACGCTACTAACTACAG .

GAAGCAAACTAAGCCCCCGCTGTAATGAAACACCTTCTCTGGAGCCAAGT

CCAGATTTACACTGGGAGAGGTGCCAGCAACTGAATAAATACCTCTCCCA

GTGTAAATCTGGAGCCAAGTCCAGATTTACACTGGGAGAGGTGCCAGCAA

CTGAATARATACCTCTTAGCTGAGTGG

For Granzyme B the following primers were chosen for testing:

Forward 81 ACGAGCCTGCACCAAAGTCT (SEQID 3097)

Forward 63 AAACAATGGCATGCCTCCAC (SEQID 3098)

Reverse 178 TCATTACAGCGGGGGCTTAG (SEQID 3099)

Reverse 168 GGGGGCTTAGTTTGCTTCCT (SEQID 3100)

Testing demonstrated that F81 and R178 worked well.

Using this approach, primers were designed for all the genes that were shown to have expression patterns that correlated with allograft rejection. These primer pairs are shown in Table 2, Table 8, and are added to the sequence listing. Primers can be designed from any region of a target gene using this approach.

PRIMER ENDPOINT TESTING

Primers were first tested to examine whether they would produce the correct size product without non- specific amplification. The standard real-time PCR protocol was used without the Rox and Sybr green dyes. Each primer pair was tested on cDNA made from universal mononuclear leukocyte reference

RNA that was produced from 50 individuals as described in Example 3 (R50).

The PCR reaction consisted of 1X RealTime PCR Buffer (Ambion, Austin, TX), 2mM MgCi2 (Applied BioSystems, B02953), 0.2mM dATP (NEB), 0.2mM dTTP (NEB), 0.2mM dCTP (NEB), 0.2mM dGTP (NEB), .625U AmpliTaq Gold (Applied BioSystems, Foster City, CA), 0.3uM of each primer to be used (Sigma Genosys, The Woodlands, TX), Spl of the R50 reverse-transcription reaction and water to a final volume of 19ul.

Following 40 cycles of PCR, 10 microliters of each product was combined with Sybr green at a final dilution of 1:72,000. Melt curves for each PCR product were determined on an ABI 7900 (Applied

BioSystems, Foster City, CA), and primer pairs yielding a product with one clean peak were chosen for further analysis. One microliter of the product from these primer pairs was examined by agarose gel electrophoresis on an Agilent Bioanalyzer, DNA 1000 chip (Palo Alto, CA). Results for 2 genes are shown in Figure 9. From the primer design and the sequence of the target gene, one can calculate the expected size of the amplified DNA product. Only primer pairs with amplification of the desired product and minimal amplification of contaminants were used for real-time PCR. Primers that produced multiple products of different sizes are likely not specific for the gene of interest and may amplify multiple genes or chromosomal loci.

PRIMER OPTIMIZATION/EFFICIENCY

Once primers passed the end-point PCR, the primers were tested to determine the efficiency of the reaction in a real-time PCR reaction. cDNA was synthesized from starting total RNA as described above. A set of S serial dilutions of the R50 reverse-transcribed cDNA (as described above) were made in water: 1:10, 1:20, 1:40, 1:80, and 1:160.

The Sybr Green real-time PCR reaction was performed using the Tagman PCR Reagent kit (Applied

BioSystems, Foster City, CA, N808-0228). A master mix was made that consisted of all reagents except the primes and template. The final concentration of all ingredients in the reaction was 1X

Taqman Buffer A (Applied BioSystems), 2mM MgCI2 (Applied BioSystems), 200uM dATP (Applied

BioSystems), 200uM dCTP (Applied BioSystems), 200uM dGTP (Applied BioSystems), 400uM dUTP (Applied BioSystems), 1:400,000 diluted Sybr Green dye (Molecular Probes), 1.25U AmpliTaq

Gold (Applied BioSystems). The PCR master mix was dispensed into two, light-tight tubes. Each -

Actin primer F75 and R178 (Sigma-Genosys, The Woodlands, TX), was added to one tube of PCR master mix and Each 8-GUS primer F178 and R242 (Sigma-Genosys), was added to the other tube of

PCR master mix to a final primer concentration of 300nM. 45pl of the B-Actin or 8-GUS master mix was dispensed into wells, in a 96-well plate (Applied BioSystems). Spl of the template dilution series was dispensed into triplicate wells for each primer. The reaction was run on an ABI 7900 Sequence

Detection System (Applied BioSystems) with the following conditions: 10 mun. at 95°C; 40 cycles of

95°C for 15 sec, 60°C for 1 min; followed by a disassociation curve starting at 50°C and ending at 95°C. .

The Sequence Detection System v2.0 software was used to analyze the fluorescent signal from each well. The high end of the baseline was adjusted to between 8 and 20 cycles to reduce the impact on any data curves, yet be as high as possible to reduce baseline drift. A threshold value was selected that allowed the majority of the amplification curves to cross the threshold during the linear phase of amplification. The disassociation curve for each well was compared to other wells for that marker.

This comparison allowed identification of “bad” wells, those that did not amplify, that amplified the wrong size product, or that amplified multiple products. The cycle number at which each amplification curve crossed the threshold (Cr) was recorded and the file transferred to MS Excel for further analysis.

The Cy values for triplicate wells were averaged. The data were plotted as a function of the log, of the calculated starting concentration of RNA. The starting RNA concentration for each cDNA dilution was determined based on the original amount of RNA used in the RT reaction, the dilution of the RT reaction, and the amount used (5 pl) in the real-time PCR reaction. For each gene, a linear regression line was plotted through all of the dilutions series points. The slope of the line was used to calculate the efficiency of the reaction for each primer set using the equation:

E= 10 Hone) -1 .

Using this equation (Pfaffl 2001, Applied Biosystems User Bulletin #2), the efficiency for these B-actin primers is 1.28 and the efficiency for these B-GUS primers is 1.14 (Figure 10). This efficiency was used when comparing the expression levels among multiple genes and multiple samples. This same method was used to calculate reaction efficiency for primer pairs for each gene studied. A primer pair was considered successful if the efficiency was reproducibly determined to be between 0.7 and 2.4.

SYBR-GREEN ASSAYS

Once markers passed the Primer Efficiency QPCR (as stated above), they were used in real-time PCR assays. Patient RNA samples were reverse-transcribed to cDNA (as described above) and 1:10 dilutions made in water. In addition to the patient samples, a no template control (NTC) and a pooled reference RNA (see example 3) described in were included on every plate.

The Sybr Green real-time PCR reaction was performed using the Taqman Core PCR Reagent kit (Applied BioSystems, Foster City, CA, N808-0228). A master mix was made that consisted of all reagents except the primers and template. The final concentration of all ingredients in the reaction was 1X Tagman Buffer A (Applied BioSystems), 2mM MgCI2 (Applied BioSystems), 200uM dATP (Applied BioSystems), 200uM dCTP (Applied BioSystems), 200uM dGTP (Applied BioSystems), 400uM dUTP (Applied BioSystems), 1:400,000 diluted Sybr Green dye (Molecular Probes), 1.25U

AmpliTaq Gold (Applied BioSystems). The PCR master mix was aliquotted into eight light-tight tubes, one for each marker to be examined across a set of samples. The optimized primer pair for each marker was then added to the PCR master mix to a final primer concentration of 300nM. 18pl of the each marker master mix was dispensed into wells in a 384 well plate (Applied BioSystems). 2ul of the

1:10 diluted control or patient cDNA sample was dispensed into triplicate wells for cach primer pair.

The reaction was run on an ABI 7900 Sequence Detection System (Applied BioSystems) using the cycling conditions described above.

The Sequence Detection System v2.0 software (Applied BioSystems) was used to analyze the fluorescent signal from each well. The high end of the baseline was adjusted to between 8 and 20 cycles to reduce the impact on any data curves, yet be as highas possible to reduce baseline drift. A threshold value was selected that allowed the majority of the amplification curves to cross the threshold during the linear phase of amplification. The disassociation curve for each well was compared to other wells for that marker. This comparison allowed identification of “bad” wells, those that did not amplify, that amplified the wrong size product, or that amplified multiple products. The cycle number at which each amplification curve crossed the threshold (Cr) was recorded and the file transferred to

MS Excel for further analysis. The Cy value representing any well identified as bad by analysis of disassociation curves was deleted. The Cr values for triplicate wells were averaged. A standard deviation (Stdev) and a coefficient of variation (CV) were calculated for the triplicate wells. If the CV was greater than 2, an outlier among the three wells was identified and deleted. Then the average was re-calculated. In each plate, ACy was calculated for each marker-control combination by subtracting the average Cy of the target marker from the average Cr of the control (8-Actin or 3-GUS). The expression relative to the control marker was calculated by taking two to the power of the ACy of the target marker. For example, expression relative to f-Actin was calculated by the equation:

FrA = Cr tein=Cr ger)

All plates were run in duplicate and analyzed in the same manner. The percent variation was determined for each sample-marker combination (relative expression) by taking the absolute value of the value of the RE for the second plate from the RE for the first plate, and dividing that by the average. If more than 25% of the variation calculations on a plate are greater than 50%, then a third plate was run.

TAQMAN PROTOCOL

Real-time PCR assays were also done using Tagman PCR chemistry.

The Tagman real-time PCR reaction was performed using the Tagman Universal PCR Master Mix (Applied BioSystems, Foster City, CA, #4324018). The master mix was aliquoted into eight, light- tight tubes, one for each marker. The optimized primer pair for each marker was then added to the correctly labeled tube of PCR master mix. A FAM/TAMRA dual-labeled Tagman probe (Biosearch

Technologies, Navoto, CA, DLO-FT-2) was then added to the correctly labeled tube of PCR master mix. Alternatively, different combinations of fluorescent reporter dyes and quenchers can be used such that the absorption wavelength for the quencher matches the emission wavelength for the reporter, as shown in Table 5. 18ul of the each marker master mix was dispensed into a 384well plate (Applied

BioSystems). 2ul of the template sample was dispensed into triplicate wells for each primer pair. The final concentration of each reagent was: 1X TagMan Universal PCR Master Mix, 300nM each primer, 0.25nM probe, 2pl 1:10 diluted template. The reaction was run on an ABI 7900 Sequence Detection .

System (Applied Biosystems) using standard conditions (95°C for 10 min., 40 cycles of 95°C for 15 sec, 60°C for 1 mun.).

The Sequence Detector v2.0 software (Applied BioSystems) was used to analyze the fluorescent signal from each well. The high end of the baseline was adjusted to between 8 and 20 cycles to reduce the impact on any data curves, yet be as high as possible to reduce baseline drift. A threshold value was selected that allowed most of the amplification curves to cross the threshold during the linear phase of amplification. The cycle number at which each amplification curve crossed the threshold (Cy) was recorded and the file transferred to MS Excel for further analysis. The Cy values for triplicate wells were averaged. The Cr values for triplicate wells were averaged. A standard deviation (Stdev) and a coefficient of variation (CV) were calculated for the triplicate wells. If the CV was greater than 2, an outlier among the three wells was identified and deleted. Then the average was re-calculated. In each plate, ACy was calculated for each marker-control combination by subtracting the average Cr of the target marker from the average Cy of the control (8-Actin or GUS). The expression relative to the control marker was calculated by taking two to the power of the AC of the target marker. All plates were run in duplicate and analyzed in the same manner. The percent variation was determined for each sample-marker combination (relative expression) by taking the absolute value of the value of the RE for the second plate from the RE for the first plate, and dividing that by the average. If more than 25% of the variation calculations on a plate are greater than 50%, then a third plate was run.

BI-PLEXING

Variation of real-time PCR assays can arise from unequal amounts of RNA starting material between reactions. In some assays, to reduce variation, the control gene amplification was included in the same reaction well as the target gene. To differentiate the signal from the two genes, different fluorescent dyes were used for the control gene. f-Actin was used as the control gene and the TaqMan probe used was labeled with the fluorescent dye VIC and the quencher TAMRA (Biosearch Technologies, Navoto,

CA, DLO-FT-2). Alternatively, other combinations of fluorescent reporter dyes and quenchers (Table 5) can be used as long as the emission wavelength of the reporter for the control gene is sufficiently different from the wavelength of the reporter dye used for the target. The contro} gene primers and probe were used at limiting concentrations in the reaction (150 nM primers and 0.125 nM probe) to ensure that there were enough reagents to amplify the target marker. The plates were run under the same protocol and the data are analyzed in the same way, but with a separate baseline and threshold for the VIC signal. Outliers were removed as above from both the FAM and VIC signal channels. The expression relative to control was calculated as above, using the VIC signal from the control gene.

ABSOLUTE QUANTITATION

Instead of calculating the expression relative to a reference marker, an absolute quantitation can be performed using real-time PCR. To determine the absolute quantity of each marker, a standard curve is constructed using serial dilutions from a known amount of template for each marker on the plate. The standard curve may be made using cloned genes purified from bacteria or using synthetic complimentary oligonucleotides. In either case, a dilution series that covers the expected range of expression 1s used as template in a series of wells in the plate. From the average Cy values for these known amounts of template a standard curve can be plotted. From this curve the Cy values for the unknowns are used to identify the starting concentration of cDNA. These absolute quantities can be compared between disease classes (i.e. rejection vs. no-rejection) or can be taken as expression relative to a control gene to correct for variation among samples in sample collection, RNA purification and quantification, cDNA synthesis, and the PCR amplification.

CELL TYPE SPECIFIC EXPRESSION

Some markers are expressed only in specific types of cells. These markers may be useful markers for differentiation of rejection samples from no-rejection samples or may be used to identify differential expression of other markers in a single cell type. A specific marker for cytotoxic T-lymphocytes (such as CD8) can be used to identify differences in cell proportions in the sample. Otber markers that are known to be expressed in this cell type can be compared to the level of CD8 to indicate differential gene expression within CD8 T-cells.

Control genes for PCR

As discussed above, PCR expression measurements can be made as either absolute quantification of gene expression using a standard curve or relative expression of a gene of interest compared to a control gene. In the latter case, the gene of interest and the control gene are measured in the same sample. This can be done in separate reactions or in the same reaction (biplex format, see above). In either case, the final measurement for expression of a gene is expressed as a ratio of gene expression to control gene expression. It is important for a control gene to be constitutively expressed in the target tissue of interest and have minimal variation in expression on a per cell basis between individuals or between samples derived from an individual. If the gene has this type of expression behavior, the relative expression ratio will help correct for variability in the amount of sample RNA used in an assay.

In addition, an ideal control gene has a high level of expression in the sample of interest compared to the genes being assayed. This is important if the gene of interest and control gene are used in a biplex format. The assay is set up so that the control gene reaches its threshold Ct value early and its amplification is limited by primers so that it does not compete for limiting reagents with the gene of interest.

To identify an ideal control gene for an assay, 2 number of genes were tested for variability between samples and expression in both mononuclear RNA samples and whole blood RNA samples using the

RNA procurement and preparation methods and real-time PCR assays described above. 6 whole-blood and 6 mononuclear RNA samples from transplant recipients were tested. The intensity levels and variability of each gene in duplicate experiments on both sample types are shown in Figure 11.

Based on criteria of low variability and high expression across samples, B-actin, 18s, GAPDH, b2microglobulin were found to be good examples of control genes for the PAX samples. A single control gene may be incorporated as an internal biplex control is assays.

Controlling for variation in real time PCR

Due to differences in reagents, experimenters, and preparation methods, and the variability of pipetting oo steps, there is significant plate-to-plate variation in real-time PCR experiments. This variation can be reduced by automation (to reduce variability and error), reagent lot quality control, and optimal data handling. However, the results on replicate plates are still likely to be different since they are run in the machine at different times.

Variation can also enter in data extraction and analysis. Real-time PCR results are measured as the time (measured in PCR cycles) at which the fluorescence intensity (ORn in Applied Biosystems SDS v2.1 software) crosses a user-determined threshold (CT). When performing relative quantification, the

CT value for the target gene is subtracted from the CT value for a control gene. This difference, called

ACT, is the value compared among experiments to determine whether there is a difference between samples. Variation in setting the threshold can introduce additional error. This is especially true in the duplexed experimental format, where both the target gene and the control gene are measured in the same reaction tube. Duplexing is performed using dyes specific to each of the two genes. Since two different fluorescent dyes are used on the plate, two different thresholds are set. Both of these thresholds contribute to each ACT. Slight differences in the each dye’s threshold settings (relative to the other dye) from one plate to the next can have significant effects on the ACT.

There are several methods for setting the threshold for a PCR plate. Older versions of SDS software (Applied Biosystems) determine the average baseline fluorescence for the plate and the standard deviation of the baseline. The threshold is set to 10x the standard deviation of the baseline. In SDS 2.0 the users must set the baseline by themselves. Software from other machine manufacturers either requires the user to set the threshold themselves or uses different algorithms. The latest version of the

SDS software (SDS 2.1) contains Automatic baseline and threshold setting. The software sets the baseline separately for each well on the plate using the ARn at cycles preceding detectable levels.

Variability among plates is dependent on reproducible threshold setting. This requires a mathematical or experimental data driven threshold setting protocol. Reproducibly setting the threshold according to a standard formula will minimize variation that might be introduced in the threshold setting process.

Additionally, there may be experimental variation among plates that can be reduced by setting the threshold to a component of the data. We have developed a system that uses a set of reactions on each plate that are called the threshold calibrator (TCb). The TCb wells are used to set the threshold on ali plates. 1. The TCb wells contain a template, primers, and probes that are common among all plates within an experiment. 2. The threshold is set within the minimum threshold and maximum threshold determined above. 3. The threshold is set to a value in this range that results in the average CT value for the TCb wells to be the same on all plates.

These methods were used to derive the primers depicted in Table 2C.

Example 13: Real-time PCR expression markers of acute allograft rejection

In examples 14 and 16, genes were identified as useful markers of cardiac and renal allograft rejection using microarrays. Some genes identified through these studies are listed in Table 2. In order to validate these findings, obtain a more precise measurement of expression levels and develop PCR reagents for diagnostic testing, real-time PCR assays were performed on samples from allograft recipients using primers to the identified genes. Some gene specific PCR primers were developed and tested for all genes in Table 2A as described in example 12. Some primers are listed in Table 2C and the sequence listing. These primers were used to measure expression of the genes relative to B-actin or

B-gus in 69 mononuclear RNA samples obtained from cardiac allograft recipients using Sybr green real-time PCR assays as described in example 12. Each sample was associated with an ISHLT cardiac rejection biopsy grade. The samples were tested in 2 phases. In phase I, 14 Grade 0, 1 Grade 1A, 3

Grade 2 and 9 Grade 3A samples were tested. In phase II, 19 Grade 2, 4 Grade 1B, 4 Grade 2 and 15

Grade 3A samples were tested. Data was analyzed for each phase individually and for the combined phase I + Il sample set. These data are summarized in Table 6.

The average fold change in expression between rejection (3A) and no rejection (0) samples was calculated. A t-test was done to determine the significance with which each gene was differentially expressed between rejection and no rejection and a p-value was calculated. Genes with high average fold changes and low p-values are considered best candidates for further development as rejection markers. However, it is important to note that a gene with a low average fold change and a high p- value may still be a useful marker for rejection in some patients and may work as part of a gene expression panel to diagnose rejection. These same PCR data were used to create PCR gene expression panels for diagnosis of acute rejection as discussed in example 17.

Non-parametric tests such as the Fisher Exact Test and Mann-Whitney U test are useful for choosing useful markers. They assess the ability of markers to discrininate between different classes as well as their significance. For example, one could use the median of all samples (including both non-rejector and rejector samples) as a threshold and apply the Fisher Exact test to the numbers of rejectors and non-rejectors above and below the threshold.

These methods were used to generate the data in Table 2D.

Genes were identified which have expression patterns useful for the diagnosis and monitoring of acute cardiac allograft rejection. Further, sets of genes that work together in a diagnostic algorithm for allograft rejection were identified. Acute allograft rejection is a process that occurs in all solid organ transplantation including, heart, lung, liver, kidney, pancreas, pancreatic islet cell, intestine and others.

Gene expression markers of acute cardiac rejection may be useful for diagnosis and monitoring of all allograft recipients. Patients, patient clinical data and patient samples used in the discovery of markers below were derived from a clinical study described in example S.

The collected clinical data was used to define patient or sample groups for correlation of expression data. Patient groups were identified for comparison. For example, a patient group that possesses a useful or interesting clinical distinction, verses a patient group that does not possess the distinction.

Measures of cardiac allograft rejection were derived from the clinical data to divide patients (and patient samples) into groups with higher and lower rejection activity over some period of time or at any one point in time. Such data were rejection grades as determined from histological reading of the cardiac biopsy specimens by a pathologist and data measuring progression of end-organ damage, including depressed left ventricular dysfunction (decreased cardiac output, decreased ejection fraction, clinical signs of low cardiac output) and usage of inotropic agents (Kobashigawa 1998).

Mononuclear RNA samples were collected and prepared from patients who had recently undergone a cardiac allograft transplantation using the protocol described in example 2. The allograft rejection status at the time of sample collection was determined by examination of cardiac biopsies as described in example 5 and as summarized here. 300 patient samples were included in the analysis. Each patient sample was associated with a biopsy and other clinical data collected at the time of the sample. The cardiac biopsies were graded by a pathologist at the local center and by three centralized pathologists who read the biopsy slides from all : four local centers in a blinded manner. Biopsy grades included 0, 1A, 1B, 2, 3A, and 3B. No grade 4 rejection was identified. Dependent variables were developed based on these grades using the local center pathology reading, the reading of a centralized and blinded pathologist, the highest of the readings, local or centralized and a consensus grade derived from all pathological readings. Samples were classified as no rejection or rejection in the following ways: Grade 0 vs. Grades 1-4, Grades 0 and 1A vs. Grades 1B-4, Grade 0 vs. Grade 3A, Grade 0 vs. Grades 1B-4, and Grade 0 vs. Grades 1B and 3A-4. Grade 0 samples were selected such that they were not immediately followed by an episode of acute rejection in the same patient. Comparing Grade 0 samples to Grade 3A samples gives the greatest difference between the rejection and no rejection groups on average.

Taking the highest of all patholdgist readings has the effect of removing any sample from the no rejection class that was not a unanimous Grade 0. It also results in an increase in the number of rejection samples used in an analysis with the assumption that if a pathologist saw features of rejection, the call was likely correct and the other pathologists may have missed the finding. Many leading cardiac pathologists and clinicians believe that ISHLT grade 2 rejection does not represent significant acute rejection. Thus, for correlation analysis, exclusion of Grade 2 samples may be warranted.

Clinical data were also used to determine criteria for including samples in the analysis. For example, a patient with an active infection or in the early post-transplant period (ongoing surgical inflammation) might have immune activation unrelated to rejection and thus be difficult to identify as patients without rejection. The strictest inclusion criteria required that samples be from patients who did not have a bacterial or viral infection, were at least two weeks post cardiac transplant, were asymptomatic and were not currently admitted to the hospital.

After preparation of RNA (example 2), amplification, labeling, hybridization, scanning, feature -extraction and data processing were done as described in Example 11, using the oligonucleotide microarrays described in Example 9. The resulting log ratio of expression of Cy3 (patient sample)/

Cy5 (R50 refererice RNA) was used for analysis.

Significance analysis for microarrays (SAM, Tusher 2001, Example 15) was used to discover genes that were differentially expressed between the rejection and no-rejection groups. Many different combinations of dependent variables, inclusion criteria, static/referenced, and data subsets were used in

SAM analysis to develop the primary lists of genes significantly differentially expressed between rejection and no-rejection. As described in example 15, SAM assigns a false detection rate to each gene identified as differentially expressed. The most significant of these genes were identified.

An exemplary analysis was the comparison of Grade 0 samples to Grade 3A-4 samples using SAM.

Data from the all the pathological readings was used to identify consensus Grade 0 samples and samples with at least one reading of Grade 3A or above. Using this definition of rejection and no rejection, expression profiles from rejection samples were compared to no rejection samples using

SAM. The analysis identified 7 genes with a FDR of 1%, 15 genes @ 1.4%, 35 genes @ 3.9%. Many more genes were identified at higher FDR levels.

In Table 7, a number of SAM analyses are summarized. In each case the highest grade from the 3 pathologists was taken for analysis. No rejection and rejection classes are defined. Samples are either used regardless of redundancy with respect to patients or a requirement is made that only one sample is used per patient or per patient per class. The number of samples used in the analysis is given and the lowest FDR achieved is noted.

Some of the genes identified by SAM as candidate rejection markers are noted in Table 2A and B.

SAM chooses genes as significantly different based on the magnitude of the difference between the : groups and the variation among the samples within each group. It is important to note that a gene which is not identified by SAM as differentially expressed between rejection and no rejection may still be a useful rejection marker because: 1. The microarray technology is not adequately sensitive to detect all genes expressed at low levels. 2. A gene might be a useful member of a gene expression panel in that it is a useful rejection marker only in a subset of patients. This gene may not be significantly differentially expressed between all rejection and no rejection samples.

For the purposes of cross-validation of the results, the datasets were also divided into subsets to compare analysis between two subsets of roughly half of the data. The types of subsets constructed were as follows. First half/second half subsets were the first half of the samples and the second half of the samples from a dataset ordered by sample number. Odd/even subsets used the same source, a dataset ordered by sample number, but the odd subset consisted of every 2™ sample starting with the first and the even subset consisted of every 2™ sample starting with the second sample, Center 14/other subsets were the same datasets, divided by transplant hospital. The center 14 subset consisted of all samples from patients at center 14, while the other subset consisted of all samples from the other three centers (12,13, and 15). When a gene was found to be significantly differentially expressed in both sets of data, a higher priority was put on that gene for development of a diagnostic test. This was reflected in a “Array Score” value (Table 2B) that also considered the false detection rate for the gene and the importance of the gene in classification models (see example 17).

Alternatively one can divide samples into 10 equal parts and do 10-fold cross validation of the results of SAM. )

Microarray data was also used to generate classification models for diagnosis of rejection as described in example 17. Genes identified through classification models as useful in the diagnosis of rejection are noted in in Table 2B in the column “models”.

As genes were identificd as useful rejection markers by microarray significance analysis, classification models, PCR analysis, or through searching the prior art, a varicty of approaches were employed to discover genes that had similar expression behavior (coexpression) to the gene of interest. If a gene is a useful rejection marker, then a gene that is identified as having similar expression behavior is also likely to be a useful rejection marker. Hierarchical clustering (Eisen et al. 1998, see example 15) was used to identify co-expressed genes for established rejection markers. Genes were identified from the nearest branches of the clustering dendrogram. Gene expression profiles generated from 240 samples derived from transplant recipients were generated as described above. Hierarchical clustering was performed and co-expressed genes of rejection markers were identified. An example is shown in

Figure 12. SEQ ID NO:85 was shown to be significantly differentially expressed between rejection and no rejection using both microarrays and PCR. Gene SEQ ID NO:3020 was identified by hierarchical clustering as closely co-expressed with SEQ ID NO:85. In tahle 2B, genes identified as co-expressed with established markers are identified as such by listing the SEQ ID that they are co- : expressed with in the column labeled “clusters”.

Some of the primers for real-time PCR validation were designed for each of the marker genes as described in Example 12 and are listed in Table 2C and the sequence listing. PCR expression measurements using these primers were used to validate array findings, more accurately measure differential gene expression and create PCR gene expression panels for diagnosis of rejection as described in example 17.

These methods were used to identify genes listed in Table 2B.

Example 15: Correlation and Classification Analysis

After generation and processing of expression data sets from microarrays as described in Example 11, a log ratio value is used for most subsequent analysis. This is the logarithm of the expression ratio for each gene between sample and universal reference. The processing algorithm assigns a number of flags to data that are of low signal to noise, saturated signal or are in some other way of low or uncertain quality. Correlation analysis can proceed with all the data (including the flagged data) or can be done on filtered data sets where the flagged data is removed from the set. Filtered data should have

N 156 a less variability and noise and may result in more significant or predictive results. Flagged data contains all information available and may allow discovery of genes that are missed with the filtered data set.

After filtering the data for quality as described above and in example 11, missing data are common in : microarray data sets. Some algorithms don’t require complete data sets and can thus tolerate missing ’ values. ‘Other algorithms are optimal with or require imputed values for missing data. Analysis of data sets with missing values can proceed by filtering all genes from the analysis that have more than 5%, 10%, 20%, 40%, 50%, 60% or other % of values missing across all samples in the analysis. Imputation of data for missing values can be done by a variety of methods such as using the row mean, the column mean, the nearest neighbor or some other calculated number. Except when noted, default settings for filtering and imputation were used to prepare the data for all analytical software packages.

In addition to expression data, clinical data are included in the analysis. Continuous variables, such as the ejection fraction of the heart measured by echocardiography or the white blood cell count can be used for correlation analysis. Any piece of clinical data collected on study subjects can be used in a correlation or classification analysis. In some cases, it may be desirable to take the logarithm of the values before analysis. These variables can be included in an analysis along with gene expression values, in which case they are treated as another “gene”. Sets of markers can be discovered that work to diagnose a patient condition and these can include both genes and clinical parameters. Categorical variables such as male or female can also be used as variables for correlation analysis. For example, the sex of a patient may be an important splitter for a classification tree.

Clinical data are used as supervising vectors (dependent variables) for the significance or classification analysis of expression data. In this case, clinical data associated with the samples are used to divide samples in to clinically meaningful diagnostic categories for correlation or classification analysis, For example, pathologic specimens from kidney biopsies can be used to divide lupus patients into groups with and without kidney disease. A third or more categories can also be included (for example “unknown” or “not reported”). After generation of expression data and definition of supervising vectors, correlation, significance and classification analysis are used to determine which set of genes and set of genes are most appropriate for diagnosis and classification of patients and patient samples.

Two main types of expression data analyses are commonly performed on the expression data with differing results and purposes. The first is significance analyses or analyses of difference. In this case, the goal of the analysis is to identify genes that are differentially expressed between sample groups and to assign a statistical confidence to those genes that are identified. These genes may be markers of the disease process in question and are further studied and developed as diagnostic tools for the indication.

The second major type of analysis is classification analysis. While significance analysis identifies individual genes that are differentially expressed between sample groups, classification analysis identifies gene sets and an algorithm for their gene expression values that best distinguish sample (patient) groups. The resulting gene expression panel and algorithm can be used to create and implement a diagnostic test. The set of genes and the algorithm for their use as a diagnostic tool are often referred to herein as a “model”. Individual markers can also be used to create a gene expression diagnostic model. However, multiple genes (or gene sets) are often more useful and accurate diagnostic tools.

Significance analysis for microarrays (SAM)

Significance analysis for microarrays (SAM) (Tusher 2001) isa method through which genes with a correlation between their expression values and the response vector are statistically discovered and assigned a statistical significance. The ratio of false significant to significant genes is the False

Discovery Rate (FDR). This means that for each threshold there are some number of genes that are called significant, and the FDR gives a confidence level for this claim. 1f a gene is called differentially expressed between two classes by SAM, with a FDR of 5%, there is a 95% chance that the gene is actually differentially expressed between the classes. SAM will identify genes that are differentially expressed between the classes. The algorithm selects genes with low variance within a class and large variance between classes. The algorithm may not identify genes that are useful in classification, but are not differentially expressed in many of the samples. For example, a gene that is a useful marker for . disease in women and not men, may not be a highly significant marker in a SAM analysis, but may be useful as part of a gene set for diagnosis of a multi-gene algorithm.

After generation of data from patient samples and definition of categories using clinical data as supervising vectors, SAM is used to detect genes that are likely to be differentially expressed between the groupings. Those genes with the highest significance can be validated by real-time PCR (Example 13) or can be used to build a classification algorithm as described here.

Classification

Classification algorithms are used to identify sets of genes and formulas for the expression levels of those genes that can be applied as diagnostic and disease monitoring tests. The same classification algorithms can be applied to all types of expression and proteomic data, including microarray and PCR based expression data. Examples of classification models are given in example 17. The discussion below describes the algorithms that were used and how they were used.

Classification and Regression Trees (CART) is a decision tree classification algorithm (Breiman 1984),

From gene expression and or other data, CART can develop a decision tree for the classification of samples. Each node on the decision tree involves a query about the expression level of one or more genes or variables. Samples that are above the threshold go down one branch of the decision tree and samples that are not go down the other branch. Genes from expression data sets can be selected for classification building with CART by significant differential expression in SAM analysis (or other significance test), identification by supervised tree-harvesting analysis, high fold change between sample groups, or known relevance to classification of the target diseases. In addition, clinical data can be used as independent variables for CART that are of known importance to the clinical question or are found to be significant predictors by multivariate analysis or some other technique. CART identifies predictive variables and their associated decision rules for classification (diagnosis). CART also identifies surrogates for each splitter (genes that are the next best substitute for a useful gene in classification). Analysis is performed in CART by weighting misclassification costs to optimize desired performance of the assay. For example, it may be most important that the sensitivity of a test for a given diagnosis be > 90%. CART models can be built and tested using 10 fold cross-validation or v-fold cross validation (see below). CART works best with a smaller number of variables (5-50).

Multiple Additive Regression Trees (Friedman, JH 1999, MART) is similar to CART in that it is a classification algorithm that builds decision trees to distinguish groups. MART builds numerous trees : for any classification problem and the resulting model involves a combination of the multiple trees.

MART can select variables as it build models and thus can be used on large data sets, such as those derived from an 8000 gene microarray. Because MART uses a combination of many trees and does not take too much information from any one tree, it resists over training. MART identifies a set of genes and an algorithm for their use as a classifier.

A Nearest Shrunken Centroids Classifier can be applied to microarray or other data sets by the methods described by Tibshirani et al. 2002. This algorithms also identified gene sets for classification and determines their 10 fold cross validation error rates for each class of samples. The algorithm determines the error rates for models of any size, from one gene to all genes in the set. The error rates for either or both sample classes can are minimized when a particular number of genes are used. When this gene number is determined, the algorithm associated with the selected genes can be identified and employed as a classifier on prospective sample.

For each classification algorithm and for significance analysis, gene sets and diagnostic algorithms that are built are tested by cross validation and prospective validation. Validation of the algorithm by these means yields an estimate of the predictive value of the algorithm on the target population. There are many approaches, including a 10 fold cross validation analysis in which 10% of the training samples are left out of the analysis and the classification algorithm is built with the remaining 90%. The 10% are then used as a test set for the algorithm. The process is repeated 10 times with 10% of the samples being left out as a test set each time. Through this analysis, one can derive a cross validation error which helps estimate the robustness of the algorithm for use on prospective (test) samples. Any % of the samples can be left out for cross validation (v-fold cross validation, LOOCV). When a gene set is established for a diagnosis with an acceptable cross validation error, this set of genes is tested using samples that were not included in the initial analysis (test samples). These samples may be taken from archives generated during the clinical study. Alternatively, a new prospective clinical study can be initiated, where samples are obtained and the gene set is used to predict patient diagnoses.

Example 16: Acute allograft rejection: biopsy tissue gene expression profiling

Acute allograft rejection involves activation of recipient leukocytes and infiltration into the rejecting organ. For example, CD8 T-cells are activated by CD4 T-cells and enter the allograft where they destroy graft tissue. These activated, graft-associated leukocytes may reside in the graft, die or exit the graft. Upon exiting, the cells can find their way into the urine or blood (in the case of renal allografts), bile or blood (liver allografts) or blood (cardiac allografts). These activated cells have specific gene expression patterns that can be measured using microarrays, PCR or other methods.

These gene expression patterns can be measured in the graft tissue (graft associated leukocytes), blood leukocytes, urine leukocytes or stoolbiliary leukocytes. Thus graft associated leukocyte gene expression patterns are used to discover markers of activated leukocytes that can be measured outside the graft for diagnostic testing.

Renal biopsy and cardiac biopsy tissue specimens were obtained for gene expression profiling.

The specimens were obtained at the time of allograft biopsy and were preserved by flash freezing in liquid nitrogen using standard approaches or immersion in an RNA stablization reagent as per the manufacturers recommendation (RNAlater, Qiagen, Valencia, CA). Biopsy allograft pathological evaluation was also obtained and samples were classified as having a particular ISHLT rejection grade (for cardiac) or acute rejection, chronic rejection, acute tubular necrosis or no disease (for renal). 28 renal biopsy tissue samples were transferred to RLT buffer, homogenized and RNA was prepared using RNeasy preparation kits (Qiagen, Valencia, CA). Average total RNA yield was 1.3 ug.

Samples were subjected to on column DNAse digestion. 18 samples were derived from patients with ongoing acute allograft rejection and 10 were from controls with chronic rejection or acute renal failure.

RNA from the samples was used for amplification, labeling and hybridization to leukocyte arrays (example 11). Significance analysis for microarrays (SAM, Tusher 2001, Example 15) was used to identify genes that were differentially expressed between the acute rejection samples and controls.

Leukocyte markers of acute rejection that are associated with the graft should be genes that are expressed at some level in activated leukocytes. Since leukocytes appear in graft tissue with some frequency with acute rejection, leukocyte genes associate with rejection are identified by SAM as upregulated in acute rejection in this experiment. 35 genes were identified as upregulated in acute rejection by SAM with less than a 5% false detection rate and 139 were detected with < 10.0% FDR.

Results of this analysis are shown in Table 8.

For each of these genes, to 50mer oligonucleotide sequence was used to search NCBI databases including Unigene and OMIM. Genes were identified by sequence analysis to be either known leukocyte specific markers, known leukocyte expressed markers, known not to be leukocyte expressed or expression unknown. This information helped selected candidate leukocyte markers from all upregulated genes. This is necessary because some of the upregulated genes may have been expressed by renal tissue. Those genes that are leukocyte specific or leukocyte expressed were selected for evaluation by PCR in urine and blood samples from patients with and without acute allograft rejection (cardiac and renal). These genes are useful expression markers of acute rejection in allograft tissue specimens and may also be useful gene expression markers for the process in circulating leukocytes, or urine leukocytes. Genes with known leukocyte expression are noted in Table 8. In addition, some of the leukocyte expressed genes from this analysis were selected for PCR validation and development for diagnosis of acute cardiac rejection and are noted in Table 2.

Five cardiac rejection markers in the peripheral blood were assayed using real-time PCR in renal biopsy specimens. The average fold change for these genes between acute rejection (n = 6) and controls (n = 6) is given below. Work is ongoing to increase the number of samples tested and the significance of the results.

PCR assays of cardiac rejection peripheral blood markers in renal allograft tissue. R = rejection,

NR = No rejection.

[Gene ~~ Fold change (RINR)_

Granzyme — ES

CD20 1.42 1.74 iL4 1.3

Markers of renal rejection that are secreted from cells may be measured in the urine or serum of patients as a diagnostic or screening assay for rejection. Genes with lower molecular weight are most likely to be filtered into the urine to be measured in this way. Standard immunoassays may be used to measure these proteins. In table 8, genes that are known to be secreted are noted.

Array panels / classification models

Using the methods of the invention, gene expression panels were discovered for screening and diagnosis of acute allograft rejection. Gene expression panels can be implemented for diagnostic testing using any one of a variety of technologies, including, but not limited to, microarrays and real- time PCR.

Using peripheral blood mononuclear cell RNA that was collected and prepared from cardiac allograft recipients as described in examples 2 and 5, leukocyte gene expression profiles were generated and analyzed using microarrays as described in examples 11, 13, and 15. 300 samples were analyzed. ISHLT rejection grades were used to divide patients into classes of rejection and no rejection. Multiple Additive Regression Trees (MART, Friedman, JH 1999, example 15) was used to build a gene expression panel and algorithm for the diagnosis of rejection with high sensitivity.

Default settings for the implementaion of MART called TreeNet 1.0 (Salford Systems, San Diego, CA) were used except where noted. 82 Grade 0 (rejection) samples and 76 Grade 1B-4 (no rejection) samples were divided into training (80% of each class) and testing (20% of each class) sets. A MART algorithm was then developed on the training set to distinguish rejection from no rejection samples using a cost of 1.02:1 for misclassification of rejection as no rejection. The resulting algorithm was then used to classify the test samples. The algorithm correctly classified 51 of 66 (77%) no rejection samples in the training set and 9 of 16 (56%) no rejection samples in the test set. For rejection samples 64 of 64 (100%) were correctly classified in the training set and 12 of 12 were correctly classified in the test set. The algorithm used 37 genes. MART ranks genes by order of importance to the model. In order, the 37 genes were: SEQ IDs: 3058, 3030, 3034, 3069, 3081, 3072, 3041, 3052, 3048, 3045, 3059, 3075, 3024, 279, 3023, 3053, 3022, 3067, 3020, 3047, 3033, 3068, 3060, 3063, 3028, 3032, 3025, 3046, 3065, 3080, 3039, 3058, 49, 3080, 3038, 3071.

Another MART model was built by excluding samples derived from patients in the first month post transplant and from patients with known CMV infection. 20 Grade 0 (rejection) samples and 25

Grade 1B-4 (no rejection) samples were divided into training (80% of each class) and testing (20% of each class) sets. A MART algorithm was then developed on the training set to distinguish rejection from no rejection samples using default settings. The resulting algorithm was then used to classify the test samples. The algorithm correctly classified 100% of samples of both classes in the training and testing sets. However, this model required 169 genes. The sample analysis was done a second time with the only difference being requirement that all decision trees in the algorithm be composed of two nodes (single decision, “stump model”). In this case 15/16 no rejection samples were correctly identified in the training set and 4/4 no rejection samples were correctly identified in the test set. For the rejection samples, 17/19 were correctly identified in the training set and 5/6 were correctly classified in the test set. This model required 23 genes. In order of importance, they were: SEQ [Ds: 3042, 2783, 3076, 3029, 3026, 2751, 3036, 3073, 3035, 3050, 3051, 3027, 3074, 3062, 3044, 3077, 2772, 3049, 3043, 3079, 3070, 3057, 3078.

Real-time PCR panels / classification models

PCR primers were developed for top rejection markers and used in real-time PCR assays on transplant patient samples as described in examples 12 and 13. This data was used to build PCR gene expression panels for diagnosis of rejection. Using MART (example 15) a 10-fold cross validated model was created to diagnose rejection using 12 no rejection samples (grade 0) and 10 rejection samples (grade 3A). Default settings were used with the exception of assigning a 1.02:1 cost for misclassification of rejection as no rejection and requirement that all decision trees be limited to 2 nodes (“stump model”). 20 genes were used in the model, including: SEQ IDs:101, 3021, 102, 2781, 78, 87, 86, 36, 77, 2766, 3018, 80, 3019, 2752, 79, 99, 3016, 2790, 3020, 3056, 88. The 10-fold cross- validated sensitivity for rejection was 100% and the specificity was 85%. Some PCR primers for the genes are listed in Table 2C and the sequence listing.

A different analysis of the PCR data was performed using the nearest shrunken centroids classifier (Tibshirani et al. 2002; PAM version 1.01, see example 15). A 10-fold cross validated model : was created to diagnose rejection using 13 no rejection samples (grade 0) and 10 rejection samples (grade 3A). Default settings were used with the exception of using a prior probability setting of (0.5, 0.5). The algorithm derives algorithms using any number of the genes. A 3-gene model was highly accurate with a 10 fold cross-validated sensitivity for rejection of 90%, and a specificity of 85%.

The 3 genes used in this model were: SEQ IDs 2784, 79, and 2794. Some of the PCR primers used are given in Table 2C and the sequence listing. An ROC curve was plotted for the 3-gene model and is shown in Figure 13.

Example 18: Assay sample preparation

In order to show that XDx’s leukocyte-specific markers can be detected in whole blood, we collected whole blood RNA using the PAXgene whole blood collection, stabilization, and RNA isolation kit (PreAnalytix). Varying amounts of the whole blood RNA were used in the initial RT reaction (1, 2, 4, and 8ug), and varying dilutions of the different RT reactions were tested (1:5, 1:10,

1:20, 1:40, 1:80, 1:160). We did real-time PCR assays with primers specific to XDx’s markers and showed that we can reliably detect these markers in whole blood.

Total RNA was prepared from 14 mononuclear samples (CPT, BD) paired with 14 whole blood samples (PAXgene, PreAnalytix) from transplant recipients. cDNA was prepared from each sample using 2ug total RNA as starting material. Resulting cDNA was diluted 1:10 and Sybr green real-time PCR assays were performed.

For real-time PCR assays, Ct values of 15-30 are desired for each gene. If a gene’s Ct value is much above 30, the result may be variable and non-linear. For PAX sample, target RNA will be more dilute than in CPT samples. cDNA dilutions must be appropriate to bring Ct values to less than 30. Ct values for the first 5 genes tested in this way are shown in the table below for both whole blood RNA {PAX) and mononuclear RNA (CPT).

Gene Joipax lercer

G06 pooosat brsmm )

With one exception, the genes have higher Ct values in whole blood. Using this protocol, all genes can be detected with Cts <35. For genes found to have Ct values above 30 in target samples, less diluted cDNA may be needed.

Example 19: Allograft rejection diagnostic gene sequence analysis

Gene products that are secreted from cells or expressed as surface proteins have special diagnostic utility in that an assay may be developed to detect relative quantities of proteins in blood plasma or serum. Secreted proteins may also be detectable in urine, which may be a useful sample for the detection of rejection in renal allograft recipients. Cell surface markers may be detected using antigen specific antibodies in ELISA assays or using flow srting techniques such as FACS.

Each gene that is found to be differentially regulated in one population of patients has several potential applications. It may be a target for new pharmaceuticals, a diagnostic marker for a condition, a benchmark for titrating drug delivery and clearance, or used in screening small molecules for new therapeutics. Any of these applications may be improved by an understanding of the physiologic function and localization of the gene product in vivo and by relating those functions to known diseases and disorders. Identifying the basic function of each candidate gene helps identify the signaling or metabolic pathways the gene is a part of, leading us to investigate other members of those pathways as potential diagnostic markers or targets of interest to drug developers.

For each of the markers in table 2, we attempted to identify the basic function and subceliular localization of the gene. These results are summarized in Table 9. In addition to initial DNA sequencing and processing, sequence analysis, and analysis of novel clones, information was obtained from the following public resources: Online Mendelian Inheritance in Man at the NCBI, LocusLink at the NCBI, the SWISS-PROT database, and Protein Reviews on the Web. For each marker represented by a curated reference mRNA from the RefSeq project, the corresponding reference protein accession number is listed. Curated sequences are those that have been manually processed by NCBI staff to represent the best estimate of the mRNA sequence as it is transcribed, based on alignments of draft

DNA sequence, predicted initiation, termination and splice sites, and submissions of EST and full- length mRNA sequences from the scientific community.

These methods were used to derive the data in Table 2E.

Example 20: Detection of proteins expressed by diagnostic gene sequences

One of ordinary skill in the art is aware of many possible methods of protein detection. The following example illustrates one possible method.

The designated coding region of the sequence is amplified by PCR with adapter sequences at either end for subcloning. An epitope or other affinity “tag” such as a “His-tag” may be added to facilitate purification and/or detection of the protein. The amplified sequence is inserted into an appropriate expression vector, most typically a shuttle vector which can replicate in either bacteria, most typically E. coli, and the organism/cell of choice for expression such as a yeast or mammalian cell. Such shuttle vectors typically contain origins of replication for bacteria and an antibiotic resistance marker for selection in bacteria, as well as the relevant replication and selection sequences for transformation/transfection into the ultimate expression cell type. In addition, the sequence of interest is inserted into the vector so that the signals necessary for transcription (a promoter) and translation operably linked to the coding region. Said expression could be accomplished in bacteria, fungi, or mammalian cells, or by in vitro translation.

The expression vector would then typically be used to transform bacteria and clones analyzed to ensure that the proper sequence had been inserted into the expression vector in the productive orientation for expression. Said verified expression vector is then transfected into a host cell and transformants selected by a variety of methods including antibiotic resistance or nutritional complementation of an auxotrophic marker. Said transformed cells are then grown under conditions conducive to expression of the protein of interest, the cells and conditioned media harvested, and the protein of interest isolated from the most enriched source, either the cell pellet or media.

The protein is then be isolated by standard of chromatographic or other methods, including immunoaffinity chromatography using the affinity “tag” sequence or other methods, including cell fractionation, ion exchange, size exclusion chromatography, or selective precipitation. The isolated and purified protein is then be used as an antigen to generate specific antibodies. This is accomplished by standard methods including injection into heterologous species with an adjuvant, isolation of monoclonal antibodies from mice, or in vitro selection of antibodies from bacteriophage display antibody libraries. These antibodies are then used to detect the presence of the indicated protein of interest in a complex bodily fluid using standard methods such as ELISA or RIA.

Example 21: Detecting changes in the rate of hematopoiesis

Gene expression profiling of blood cells from cardiac allograft recipients was done using microarrays and real-time PCR as described in other examples herein.

Two of the genes in that were most correlated with cardiac transplant acute rejection with both microarrays and PCR were hemoglobin Beta and 2,3 DPGM. These genes are well know to be specific markers of erythrocyte lineages. This correlation was found using both purified peripheral mononuclear cells and whole blood RNA preparations.

Analysis of the five genes from the PCR data most strongly correlated with rejection showed that their expression levels were extremely highly correlated within each other (R2 > 0.85).

Gene Hs Acc SEQ ID No a

This suggested that they were all elevated as part of a single response or process. When the microarray data was used to cluster these genes with each other and the other genes on the microarray, we found that these five genes clustered reasonably near each and of the other array genes which clustered tightly with them, four of the top 40 or so were platelet related genes. In addition, these a number of these genes clustered closely with CD34. CD34 is a marker of hematopoietic stem cells and 1s seen in the peripheral blood with increased hematopoisis.

CD34, platelet RNA and erythrocyte RNA all mark immature or progenitor blood cells and it is clear that theses marker of acute rejection are part of a coordinated hematopoietic response. A small increase in the rate of production of RBCs and platelets may result in large fold changes in RNA levels.

Immune activation from acute rejection may lead to increased hamatopoiesis in the bone marrow and non-marrow sites. This leads to an increase in many lineages because of the lack of complete specificity of the marrow response. Alternatively, increased hematopoiesis may occur in a transplant recipient due to an infection (viral or other), allergy or other stimulus to the system. This results in production of cells or a critical mass of immune cells that can cause rejection. In this scenario, monitoring for markers of immune activation would provide an opportunity for early diagnosis.

Table 1

Cardiovascular Disease {Atherosclerosis

Unstable angina

Myocardial infarction

Restenosis after angioplasty

Congestive Heart Failure

Myocarditis

Endocarditis

Endothelial Dysfunction

Cardiomyopathy

Cardiovascular drug use

Infectious Disease Hepatitis A,B,C, D,E, G

Malaria

Tuberculosis

HIV

Pneumocystis Carinii

Giardia

Toxoplasmosis

Lyme Disease

Rocky Mountain Spotted Fever

Cytomegalovirus

Epstein Barr Virus

Herpes Simplex Virus

Clostridium Dificile Colitis

Meningitis (all organisms)

Pneumonia (all organisms)

Urinary Tract Infection (al! organisms)

Infectious Diarrhea (all organisms)

Anti-infectious drug use

Angiogenesis Pathologic angiogenesis

Physiologic angiogenesis

Treatment induced angiogenesis

Pro or anti-angiogenic drug use

Transplant Rejection Heart

Lung

Liver

Pancreas

Bowel

Bone Marrow

Stem Cell

Graft versus host disease

Transplant vasculopathy

Skin

Comea

Islet Cells

Kidney

Xenofransplants

Mechanical Organ

Immunosupressive drug use

Hematological Disorders [Anemia — lron Deficiency

Anemia — B12, Folate deficiency

Anemia ~ Aplastic )

Anemia — hemolytic

Anemia — Renal failure

Anemia — Chronic disease

Polycythemia rubra vera

Pernicious anemia : Idiophic Thrrombocytopenic purpura

Thrombotic Thrombocytopenic purpura

Essential thrombocytosis

Leukemia

Cytopenias due to immunosupression

Cytopenias due to Chemotherapy

Myelodysplasia

Table 2A.

A PEO 2 PP =

Gene Name Somer [HS ACC RNA/cDNA

I S— SU CT

XT — C—O VT

TT — SCM LCT TR ER

TPE TT — Cl v1 VIET

EF SSSS— cl ICO TET

A — C—O cor has bows bn

CE titi dN al ll variants

Fr B—— I TT os E— OM XC TCE TE

EE — [VST TT

Ce BS— [CO

CE S— C—O

CT S— TR CC VCC

EE S— 17: ST

SE — TJ 7 VT

RRC Op ses me bo

FCGUR Dt li mae moe

EE S— | TMS

EE — (TW TT 1

EE s— TM C7 EES

SS 177M YL fcr [LN LM STS mS FI TTI VX Ty

EE — || MN TT UL Tr

EE — MS TY TT

CAT oath oon ay 5 oy Jean i fuses pW death

PY — {TITS TS TR

SE S— TA 37 T ER TTR

A S— [ECT ms Jremlobnbeh 1 Jaen i i

Ep Bemodn hms 000

I-III THT

ET W—— (TTT TX Oy ie lemesbin bet] fossa ost Ji

CE ey Sm [Ma Cn ET

HLADG WIIG ds Bol yom ol

BLADE iG desl DRL sur oe 002 [5 jos feos J mum barons ji ———

Cv ia CO vill factor, multiple pm alpha 4 subunit of VLA-4 receptor

Gene Gene Name SOmer ACC RNA/cDNA

ITGAM integrin, alpha M (complement 48 Hs. 172631 NM_000632 380 component receptor 3, alpha; also known as CD11b (p170), macrophage antigen alpha polypeptide

ITGB7 __ lintegrinbeta7 [a9 |Hs1741 [NM 000889 [381 protein (C/EBP), beta motif) ligand 4

CXCL12 chemokine (C-X-C motif) ligand 12 |58 Hs.237356 NM_000609 390 (stromal cell-derived factor 1) (SDF- 1 superfamily, member 4 :

TNFSF4 tumor necrosis factor (ligand) Hs.181097 NM_003326 392 superfamily, member 4 (tax- transcriptionally activated glycoprotein 1, 34kDa

TPT |myptasc,alpha [61 |Hs334455 [NM 003293 [393

CSF2__ [colony stimulating factor, GM-CSF [64 |Hs.1349 [NM 0007582 [396

I ial A A Ml

CRP

GATA3 _ |GATAbindingprotein3 [68 |Hs.169946 [NM 0020511 1400

TL7R [Interleukin 7receptor [69 [Hs362807 [NM 0021851 1401

EKLF kinase

Activator Receptor, CD87, uPAR

TNFSF13B Tumor necrosis factor (ligand) 74 Hs.270737 NM_006573.3 superfamily, member 13b,

BlyS/TALL-1/BAFF

GZMB Granzyme B (granzyme 2, cytotoxic [76 Hs.1051 NM_004131 408 - | T-lymphocyte-associated serine esterase 1 superfamily, member 6

Gene Name S50mer ACC RNA/cDNA

TCIRG1 T-cell, immune regulator 1, ATPase, [78 Hs.46465 NM_006019 410

H+ transporting, lysosomal VO vo protein a isoform 3 [4 |mtedewkind [80 [Hs73017 [NM 000589 [412 |] 113 |imteewlan13 [81 [Hs84s [NM 002188 [413 = protein 4

BYSS Natural killer cell receptor, Hs.81743 NM_007053 416 immunoglobulin superfamily member

HBB |Hemoglobin,beta 186 |Hs155376 [NM 000518 [418

BPGM______[2,3-bisphosphoglycerate mutase __ [87 |Hs.198365 [NM 001724 [419

MTHFD2 Methylene tetrahydrofolate 88 Hs.154672 NM_006636 420 dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase

TAP1 Transporter 1, ATP-binding cassette, Hs.352018 NM_000593 [421 sub-family B (MDR1/TAP) ppm [pp jo 7

OID 4365 [Mitochondrial solute carrier ___ [91 [Hs30049 _ JAlll4652 [423

CXCR4_____ [Chemokine (C-X-C motif) receptor 4 [96 |Hs80414 NM 003467 1428 * lactivation antigen ee pe pee

RANTES, SCYAS [6 literlewkin6 [99 |Ms93013 [NM 000600 [431

Iz imerlewlan2 [100 |Hs89679 [NM 000586 [432 subfamily F, member 1 related oncogene homolog

Rr all

SCYA4

OID 6207 [est [105 |nsopad0 [po0szz [437

FN ec OPO i acetylgalactosaminyltransferase

MIG

BI cl A A ia A

SCYBI10

A I © I PR

Gene Gene Name SO0mer ACC RNA/cDNA 117 Interleukin 17 (cytotoxic T- Hs.41724 NM_002190 [442 lymphocyte-associated serine esterase 8

ICIS |nterlewkinls [i111 |Hs168132 [NM 000585 [443

ILI0_ [iierdewkinl0 [112 |Hs193717 [NM 000572 [444

IFNG [interferon gamma [113 __ |Hs856 [NM 000619 [445

USA = LA Gl i class II, DR beta p37

GPR9

OD 7094 [XDxEST479Giz Jus INA Ina faso |]

OID 7605 [est [119 [Hs109302 [AABOBOI8 [451

CXCL1 Chemokine (C-X-C motif) ligand 1 }120 Hs.789 NM_001511 452 (melanoma growth stimulating activity, alpha

CD47 CD47 antigen (Rh-related antigen, {123 Hs.82685 NM_001777 455 integrin-associated signal transducer) class IL F

PTGS2 Prostaglandin-endoperoxide synthase [128 Hs.196384 NM _000963 460 2 (prostaglandin G/H synthase and cyclooxygenase domain

TNNI3__ |Tropominlcardiac 1132 [Hs351382 [NM 000363 [464

SLC7Al11 Solute carrier family 7, (cationic 135 Hs.6682 NM_014331 467 amino acid transporter, y+ system) member 11 superfamily, member 5; CD40

El ort ll A superfamily, member 7; CD27 2, B7-2 antigen splice variant 2 cMVp67 pps haa [Na [xi7403 Jaa

AU PO J ME PO

Gene Gene Name S0mer ACC RNA/cDNA

CMVIELed [IEl cxond (d0variams) [145 INA [xi7a03 amr] [EBV EBNALP [Short EBNA leader peptide exon _ [149 NA JAJS07700 Jasi cwviel fesse Ina Ixia lm interacting protein eo class I, A

PRO1853 _ |Hypothetical protein PRO1853 [158 |Hs433466 [NM 018607 [490

CDSN |Comeodesmosin [160 [Hs507 [NM 001264 [492

RPS25 ~~ [RibosomalproteinS25 [162 _ |Hs409158 [NM 001028 [494 dehydrogenase /clone=IMAGE:2027701

SLCYA8 Solute carrier family 9 Hs.380978 AB023156 498 (sodium/hydrogen exchanger), isoform 8

OID 1512 |IMAGE:38658615 cloneS' [167 |Hs381302 |BE618004 [499

Nl Gl il pol ypep tide D subunit 3, 21kDa mucin 2 precursor, intestinal chromosome (SMCY

OID 7504 [Hypothetical protein FLI35207 [181 __ |Hs86543 |NM 152312 [513 member 3

OID 7200 [Hypothetical protein FLJ22059 [184 |Hs13323 [NM 022752 [516

Gene Gene Name S50mer ACC RNA/cDNA

SERPINB2 Serine (or cysteine) proteinase 185 Hs.75716 NM_002575 517 inhibitor, clade B (ovalbumin), member 2

ENOI _ |Enolaselalpha [186 |Hs.254105 [NM 001428 [518

OID 7696 |EST3end [187 [Hs438092 |AW297325 [si9

OID 4173 [CMVHCMVIRLZ(IRL2) [188 [NA |x17403 [so

CSF2RB Upstream variant mRNA of colony Hs.285401 AL540399 521 stimulating factor 2 receptor, beta, low-affinity (granulocyte- macrophage

SA ce Gl a 1. T0042 cDNA, mRNA sequence phosphatase, 40kDa

RANT [Immune associated nucleotide {196 |Hs 124675 |BG772661 [528 factor 1 alpha 1 dehydrogenase binding protein 4 calgranulin A

HNRPU HNRPU Heterogeneous nuclear 216 Hs.103804 BM467823 548 ribonucleoprotein U (scaffold attachment factor A

ERCC5 Excision repair cross-complementing [217 Hs.48576 NM 000123 549 rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome)) metallopanstimulin 1 [ACRC___Jacidic repeat containing (ACRC), [219 [Hs135167 [NM 052957 fs51

SS SP J NP

Gene Gene Name S50mer ACC RNA/cDNA 26S subunit, non-ATPase, 11 2

PROTEIN 1s co

OID _4317 ta73c09.x1 3' end 224 Hs.387179 Al318342 556 /clone=IMAGE:2049712 Ribosomal vo

Protein S13 rich protein like 3

SEMA7A Sema domain, immunoglobulin 230 Hs.24640 NM_003612 562 domain (Ig), and GPI membrane co anchor, (semaphorin) 7A

OID 7799 |AlJoFLAMSINE/Al [235 | [JAw837717 [s67

Pll [26serineprotease [236 |Hs997 |NM 006025 [568

TIMM10 translocase of inner mitochondrial [238 Hs.235750 NM_012456 570 membrane 10 (yeast) homolog

TIMM10

FLJ21439

CCNDBPI ’ homolog 1 (Drosophila

IMAGE:565899

SERPINBI11 Serine (or cysteine) proteinase 254 Hs.350958 NM_080475 586 inhibitor, clade B (ovalbumin), member 11

OID 6711 |58G4,IMAGE:43593515' [255 |none |BFO68628 _ [587

RPS16 [ribosomal protein S16 [258 |Hs397609 [NM 001020 {590

Gene Gene Name 50mer |HS ACC RNA/cDNA domain, 1A

OID 5098 |EST3end (260 _ |Hs330268 |AWA68450 soo

ATPSL ATP synthase, H+ transporting, 261 Hs.107476 NM_006476 593 mitochondrial FO complex, subunit g oD 693 ass ez [NA |s2B9 soa |] containing protein RoXaN 2, 20kDa

Ob 6273 |ESTvemd [265 _ |Hsis8976 [AW204774 |s67

HZzF12 zinc finperprotenl? [266 |Hs164284 [NM 033204 [508

CCL3 [Chemokine (C-C motif ligand 3 {267 __ [Hs 73817 _ |Doo144 509

OID 4325 |IMAGE.12837313 [268 |Hs370770 [AA744774 600

OID_S5181 tg93h12.x1 NCI_CGAP_CLL1 269 NA Al400725 cDNA clone IMAGE:2116391 3' similar to contains TAR1.t] MER22

PRDX4 __ |Peroxircdoxind [270 |Hs$3383 [NM 006406 _|602 kinase a 17a A wl Ll A superfamily, member 10a ob 357 |i3sGs_______ Jo76 Na [138Gs_____ les he) al Rial frame 6 acid ceramidase) 1

OD 4230 [EST |»82 _ |Hs177376 |BQo22840 [614

MDM2 Mouse double minute 2, homolog of; (283 Hs.170027 NM_002392 615 p53-binding protein (MDM2), transcript variant MDM2

XRN2 __ |5-3 exoribonuclease2 [284 |Hs268555 |AFO64257 616

OID_6039 Endothelial differentiation, 285 Hs. 122575 BES502246 617 lysophosphatidic acid G-protein- coupled receptor, 4 (EDG4 [OD 4210 |IMAGE:4540096 [286 |Hs374836 JA1300700 [618

OID 7698 |EST3end 287 [Hs118899 [AA243283 [619

PRKRA Protein kinase, interferon-inducible [288 Hs.18571 NM_003690 620 double stranded RNA dependent activator

OID 7384 [ESTs [91 |Hsa4s429 [BF475239 623 protein FLJ20378 n27, Kipl

PLOD Procollagen-lysine, 2-oxoglutarate 5- 294 Hs.75093 NM_000302 626 dioxygenase (lysine hydroxylase, in

Ehlers-Danlos syndrome type VI /clone=IMAGE:2107824

OID S866 |EST3'end ~~ 308 |Hs255649 [BM684739 J640 937202 cDNA clone IMAGE:838756 cDNA clone IMAGE:669292

OID 4891 [Hypothetical protein LOC255488 [314 |Hs.204002 ]AL832320 l646

HADHB Hydroxyacyl-Coenzyme A 315 Hs.146812 NM_000183 647 dehydrogenase/3-ketoacyl-Coenzyme

A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit

RACI Ras-related C3 botulinum toxin 317 Hs.173737 AKO054993 649 substrate 1 (rho family, small GTP binding protein Racl 1 transcript variant 2

Zhangfei like 3

DEFCAP Death effector filament-forming Ced- [326 Hs. 104305 NM 014922 658 4-like apoptosis protein, transcript variant B 122 finterlewkin22(r22) [328 [Hs287369 [NM 020525 [660

A SP J MU PO

Gene Gene Name S0mer |HS ACC RNA/cDNA subunit, alpha type, 4, (PSMA4

CONT |cyelinI(CONI) [330 |Hs79933 |NM 006835 [662

BT il finger domain

Non- [Median

S0mer |Gene Gene Name ACC RNA/cDNA {Score |NR Regulated 152 [OLC__|Charcor-Leyden crystal protein [NM 001828 484 [770 Jas interacting protein complex, class I, A , = cd a protein 157 |DUSPS dual specificity phosphatase S__ [NM 004419 [480 [726 [31225 158 |PRO1853 [Hypothetical protein PRO1853 [NM 0186071490 [725 [a153 159 |OID 6420 |73A7,FLI002%0 protein |AK090404 [491 [725 [70005 [ 160 |CDSN __ [Comeodesmosin [NM 001264 [492 {722 [2732 l61 loD 4269 [EST ~~ |BM727677 [493 1715 |s5985 | ~~ 162 |RPS25 _ |RibosomalproteinS25 [NM 001028494 ~~ |710 i645

Fle Sd ll directed) polypeptide D ll er A ll complex, subunit 3, 21kDa 170 [OID 6282 [EST 3'end [BC041913 [502 [697 [43715 | ~~ 171 |PROI073 |PRO1073 protein |AF001542 |s03 [97 [6754 [

TA ce wl A a el binding ld wl a ll 177 [OID 7595 |DKFZPS66FO546 protein ____|NM 015653 [509 [689 [38825 | ~~ 178 |RNFI9 [Ring fingerprotein19 NM 015435510 689 [77005

Nl A i Al will I chromosome (SMCY 180 [OID 4184 [CMV HCMVUL109 __ |X17403 _ |s12___ le87 [6810.5 181 [OID 7504 |Hypothetical protein FLJ35207 |NM 152312513 686 [6939

J ir a A ll subfamily C, member 3

A a Al ll member U [18¢___ [OID 7200 [Hypothetical protein FLI22050 |NM 022752516 loss [28045 185 SERPINB2 [Serine (or cysteine) proteinase [NM_002575 [517 684 [4690.5 inhibitor, clade B (ovalbumin), member 2 186 [ENOL |Enolase alpha |NM 001428518 esd 307 187 _ [OID 7696 [EST 3end _ |Aw297325 [519 ess Jas7ss

Non- [Median

SEQID SEQ ID Para {Rankin [Down 50mer (Gene Gene Name ACC RNA/cDNA {Score {NR Regulated 188 [OID 4173 [CMV HCMVTRL2 (IRL2) ___[X17403 [520 [683 Ja0i0s 189 CSF2RB |Upstream variant mRNA of ALS540399 [521 683 |3753 colony stimulating factor 2 receptor, beta, low-affinity granulocyte-macrophage 190 OID_7410 | CM2-LT0042-281299-062-¢11 |AW837717 {522 682 |7445

RC ad i A 0 factor 1 alpha ll A il RO 38kDa lc i A ll NO dehydrogenase ll rc ld ll NO binding protein 4 200 [OID 7951 |E2F-like protein (LOC51270) [NM 016521 (541 671 lad67 [

TC ic a al NO 211 [OID 3406 [Hypothetical protein FLJ20356 [NM 018986 [543 [669 [2087 [ 212 [OID 6986 [462H9 EST |AK093608 [s44 [669 Jads4 [1 213 [OD 5962 |EST3'end |AW452467 [545 [668 [58705 {I 214 |OID 5152 |EST3'end |AI1392805 s46 [668 J63s4s

A rl A ll calgranulin A 216 HNRPU HNRPU Heterogeneous nuclear |BM467823 [548 668 14108 ribonucleoprotein U (scaffold attachment factor A 217 ERCCS Excision repair cross- NM_000123 }549 668 6430.5 complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome))

EAA ee i A a metallopanstimulin 1

Non- [Median

SEQ ID SEQ ID Para |Rankin [Down

SOmer [Gene Gene Name ACC RNA/cDNA [Score |NR i CN a 220 PSMD11 |Proteasome (prosome, Al684022 {552 668 4138 macropain) 26S subunit, non- CT

ATPase, 11 221 JOD 1016 [FLIO008 protein [AK024456 [555 [eer [555] 222 OID 1309 JAV706481 DNA [Avi0sa8L [554 esr Jizmos 223 OID_7582 |Weakly similar to ZINC AK027866 |555 667 15003.5 el Yee Cl Gl ll al 224 OID_4317 [ta73c09.x] 3'end Al318342 [556 667 |6499 /clone=IMAGE:2049712 BN

Ribosomal Protein S15 225 OID 5889 |3' end Jclone-IMAGE:3083913_|AW2o7843 [557 Joe Jems TT] 226 JUBLI __|Ubiquitnlike | (sentrin) [NM 003352 [558 ese iors |] 27 oD 3&7 JEST Twososs [59 ese Jssiss 228 JOD 7371 [BSTS — BE7a0s0s [se0 Joes Jrsis acid-rich protein like 3 230 SEMA7A [Sema domain, immunoglobulin {NM _003612 [562 665 [3505.5 domain (Ig), and GPI membrane anchor, (semaphorin) 7A 231 OD 5708 [ESTS'end JAwosisa0 [565 Jess Jemmas |] 232 JOD 5992 [ESTS'end Jawagro%2 [64 Jes [ses |] 23 21 ioerlewkin2l [NM 021803]565 Joes [30365 ee pe

HERC3 235 JOD 7799 [Alulo/FLAM SINE/Al ___ [AWS37717 [567 fees Jose] 236 [P11 [26 serine protease [NM 006025568 feed [rin |] 237 OID 7766 [EST3 end ____— Jawzoarii [so Joes Jos 238 TIMMI10 translocase of inner NM 012456 }570 663 4779.5 mitochondrial membrane 10 east) homolog (TIMM 10 : 229 TEGIN1__ [Eel nine homolog I (C. elegans) [ABI0543 [571 ee J7ias |] 240 [TBC [Tubulin-specific chaperone c [NM 003192 [572 Jeez [3384 241 IRNF3 ___ [Ring fingerprotein NM 006315 [573 Jel _Jdoss i cll GN

FLJ21439

SN ll A ld

CCNDBPI

244 [OID 8063 |MUCI8 gene exons 1&2 [Xew264 [576 Jeo1 [aeons |] pe homolog 1 (Drosophila 246 [HSPC048 |HSPCO4B protein [NM 014148 [578 eso [5981s 247 [OID 5625 EST end from Tells [AWO063780 [579 [eso [aa37 [I

I al lc CN 0 Gl 29 Job 6823 [107H8 [Arsmem [mi [6 Jn 250 Job 7073 [IioFi2__ JaLiososr [ssa eso esis |] pst Job 5339 [EST3'end — Jateosiio [ss ess Jaaias JT]

Rl i) GN ll ll

IMAGE:565899 cl a A

Non- |Median

SEQ ID SEQ ID Para [Rankin |Down

SOmer |Gene Gene Name ACC RNA/eDNA |Score |NR Regulated 254 SERPINBI1 (Serine (or cysteine) proteinase |NM_080475 [586 658 [7535.5 1 inhibitor, clade B (ovalbumin), member 11 255 JOID 6711 |58G4, IMAGE4359351 5° |BF968628 [587 658 [7264 256 [RNFI0 Ring finger protein 10______[NM.014868 [588 Jess [31275 257 |MKRN1 | Makorin, ring finger protein, | _|NM 013446 [589 less [22285 |__ 258 [RPSI6 IribosomalproteinST6 [NM 001020590 les7 [i655 |__ ere Gi I finger domain, 1A 260 JOID 5098 [EST3'end |AwW468459 [592 657 [63395 261 ATPSL ATP synthase, H+ transporting, {NM_006476 [593 657 [1155 mitochondrial FO complex, subunit g 262 [OID 6303 [saB9 — |s7B9 504 les7 [74205 cl 0 a containing protein RoXaN

MER22 270 [PRDX4 [Peroxiredoxin4 NM 006406602 ess [33975

BN co ll osine kinase 272 JOID 6298 [Importin beta subunit mRNA |AI948513 [604 [655 [24335 273 |PGKI __[Phosphoglycerate kinase I_____|NM 0002911605 655 [20595

Bll i ol

A superfamily, member 10a 1 275 JADM ___ Jadrcnomedullin [NM 001124607 654 [4235 276 OID 357 [138Gs ~~ 1138G5 [608 lesa [54275 [1

SA lr dl a reading frame 6 278 |OID 3226 |DKFZP56400823 protein ____ [NM 015393 [610 [653 61875 279 ASAHI N-acylsphingosine NM_004315 |611 653 [1003 amidohydrolase (acid ceramidase) 1

Sd A i

Fl ld wt A al 282 |oD 4239 JEST ~~ 1BQO22840 [614 652 Ja174s 283 MDM2 Mouse double minute 2, homolog|NM_002392 ]615 652 4342 of; p53-binding protein (MDM2), transcript variant MDM2, 284 [XRN2 [5-3 exoribonuclease2 __ |AF064257 [616 [652 [68965

SEQ ID SEQ ID Para |Rankin |Down san Gene Name ACC RNA/cDNA [Score [NR 285 OID_6039 Endothelial differentiation, BES502246 1617 652 |5147 lysophosphatidic acid G-protein- coupled receptor, 4 (EDG4) 286 [OID 4210 [IMAGE:4540096 |AI300700 [618 652 [13305 287 [OID 7698 |EST3end ~~ [AA243283 l619 652 [74325 IT 288 PRKRA Protein kinase, interferon- NM_003690 {620 652 |3512.5 dependent activator - [289 OD 4288 [IMAGE2091815 [AI378046 l621 [651 [e4015 290 |OID 5620 [EST 3'end from Tcells |AWO063678 [622 [651 [6400 201 lob 7384 JESTS' ~~ [BF475239 1623 651 e875 | |]

Rd FO I i hypothetical protein FLJ20378 1 fr pe ro fr 1B (p27, Kip] 294 PLOD Procollagen-lysine, 2- NM_000302 [626 650 }3101 oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-

Elfed al a

Sl el GA complex, class [[ B 299 |OID 5624 |EST3'end from Tecells |AWO063921 [631 [649 [78125 300 |FPRI___ [Formyl peptide receptor I____|NM 0020291632 649 [11565

FE lt id a ll all

HE ll Fer Se dl a /clone=IMAGE:2107824 303 JOD 5639 |EST3'endfromTcells |AWO064243 [635 [648 legos [1 304 [OID 6619 la69At0 _ ~ J469A10 636 le47 [7110 1 305 JOID 6933 |463C7,4 EST hits. Aligned |AI089520 [637 [647 [6880.5 [1 306 JOID 7049 J480E2 ~~ J4s0E2 [638 le47 71285 307 NIL17C__ limterleukin17C ~~ |NM 013278639 [647 [6d115 308 JOM 5866 [EST3'end ~*~ — [BM684739 [640 647 [es32 [1 309 fcpa4 Jepas © JAA91e9%0 641 Jed6 |a7s8

El dw a east 311 OID_4932 {aa%92c¢03.r1 Stratagene fetal AA4S57757 [643 646 ]6057 retina 937202 cDNA clone

IMAGE:838756 312 low 7821 [EST — |AA7a3221 [ead [645 [7507 313 OID_4916 | zr76a03.r1 Soares NhHMPu_S1{AA252909 [645 645 6962.5 cDNA clone IMAGE:669292 fe pr fe

Non- [Median

SEQ ID SEQ ID Para |Rankin |Down

SOmer |Gene Gene Name ACC RNA/cDNA {Score |NR Regulated 315 HADHB Hydroxyacyl-Coenzyme A NM_000183 1647 645 132125 dehydrogenase/3-ketoacyl-

Coenzyme A thiolase/enoyl-

Coenzyme A hydratase (trifunctional protein), beta

DU

316 |FLI22757 |Hypothetical protein FL122757 |NM 024898648 [64s [19655 [1 ~~ 317 RACI1 Ras-related C3 botulinum toxin JAK 054993 644 11533 substrate 1 (rho family, small

GTP binding protein Rac] 318 [OID 6415 |72D4, FLIO02%0 protein ____|CA407201 [650 [644 Ja881

Rl ld specific

Fle fl tumors 1, transcript variant 2 321 [RPS23 [ribosomal proteinS23 [NM 0010251653 fe43 o19.5

I el

Zhangfei

Ced-4-like apoptosis protein, transcript variant B 327 |RPL27A Ribosomal proteinL27a ____ |BF214146 [650 ~~ le42 J6s71 It 328 [1020 [interlenkin22(1L22) [NM 0205250660 |e42 [3891 }1 329 PSMA4 Proteasome (prosome, NM _002789 1934.5 macropain) subunit, alpha type, 4, (PSMA4 330 |CCNI __ [cyclinI(CCND) [NM 006835]662 [641 9805 331 |THBD . |Thiombomodulin [NM 0003610663 le40 a732s

I CA a a finger domain

PCR PCR PCR PCR

Forward Reverse |PCR Forward [Reverse PCR

SEQID [SEQID Primer 1 Primer 1 (Probe 1 Primer 2 |Primer2 {Probe2

Gene S0mer |RNA/cDNA |SEQID SEQID ([SEQID |[SEQID SEQID SEQID

HSRRNI8SYL ~~ [333 66S 1996 ior [

ACTB Jo 3a eee Joy ms

GUSB 3 33s eer Joos iw [i656 [ioos isi]

BM Ja 6 fees Joo m0 (ISN [5 [337 1669 — 11000 [1331 i657 [1965 [2153

CCR7 16 P38 Jero Tol __Jmsz | 1

ILIRZ [7 336 Jerr io02 [1333 [1658 [1906 [isi

AFT Je Pao Jen Tos Jima |]

ALAS? Jo [341 673 i604 [133s

APELIN 110 [342 esa [ioos i336 | | |]

CD80 [11 343 ers ioo6 |337 (169 [1907 [ores]

EPBaI__ 12 [384 Te76 loo ime

CBLB [13 [345 71677 i008 [1339 |1660 __ |1008 [3156

CCRS ~~ T14 — [346 — 71678 [1005 _ ]i340 [1661 [1909 [2157

IMME 115 [347 "71676 Tiolo [1341 [1662 [1910 [2158

KIRCI T1638 71680 [i011 [1342 [1663 hol iso

FCGR3A [17 1329 — 71681 — Jiorz Ji3as | [1

FCGR3B 118 [350 71682 [1013 [1344 |1664 [1912 [2160

LAGS _ T1o [351 — "1683 i014 [1345 [i665 [1913 [2l61

PECAMI 120 [352 ~~ 1684 [i015 [1386 _ |i666 [1914 |ol62 |]

TFRC_ 123 1355 = 7I687 foie i3wy | 1

CMA1 [24 [356 [688 [1019 [1350 [1669 [1917 [2165

KIT Tos [357 J68S Jip Jisst

MPL [26 [358 T1690 lio21 [1352 [1670 [1918 [2166

EphB6 [27 [359 Jeo Jwoz2 Jy

EPOR 128 1360 1662 Jop3 isa

Foxp [29 1361 ~~ 71693 [1024 [1355 i671 [i919 [7167

GATA-1 [30 [362 ~~ 1694 11025 [13s

GNLY 132 [364 "1696 i027 [1358 [1673 [1921 [2160

HBZz [35 1367 1695 11030 [i361 [i676 [1024 [172

HBQ _ 140 [372 — 71704 i035 [1366 [iesl [1929 [2177

IIe [45 J3;7 709 Ttoao 137 [ies [i934 [ois] 1T1GA4_ 47 370 —7it [i423

ITGB7 lao 1381 J713 — Jioas i3ps | | 1

NEE2_ IST [383 Pris foae Jom 1

PDCD1 [52 [384 "1716 [i047 [1378 [1650 [1938 [2186

PRKCQ [54 [386 [718 [1049 1380 ieos [1940 |2188

PPARGCI [55 ~~ [387 710 Jjoso Jissr

PCR PCR PCR PCR

Forward Reverse [PCR Forward |Reverse PCR

SEQ ID |SEQID Primer 1 Primer 1 |Probel Primer2 |Primer2 |Probe2

Gene S0mer |RNA/cDNA |SEQID SEQID |SEQID ([SEQID SEQ ID SEQ ID

RAG [56 [388 [20 [ost [1382 [1693 [1041 [o1g9

RAG: 157 [389 [a1 [i052 [1383 {i694 |io42 2190 [CXCLiz [58 [390 722 _Jios3 [i384 [169s ~ 1943 — {2191 [TNFRSF4 [59 [301 [723 |ios4 [1385 1696 [1944 [2192 [TNFSF4__[60 [302 [724 11055 [1386 [1697 [i945 [2193

TPST [61 [393 1725 [1056 [1387 [1698 — [1946 [2194

ADA leo [394 m6 fios7 [1388 [1609 [i947 [2195

CPM [63 [395 727 [ios [1386 [1700 [1948 [2196

CSF2 [64 [396 728 1059 11390 [1701 1949 [2197 |]

CSF3___ Jes 397 [720 Jio60 [1391 [1702 "11950 [2198

CRP [66 [308 [730 ___[io61 [1392 [1703 T1951 2199

GATA3 _ |68 [400 [732 11063 [1394 [1705 1953 [2201

IC7R [60 [a01 733 [i064 [1395 [1706 {1954 ~~ [2202

CCK [71 [a03 735 [i066 [1397 [1708 1956 [2204

LEFI [72 404 1736 i067 [1398 [1709 ~~ 1957 2205

TNFSFI3B [74 [406 738 i069 11400 [1711 [1959 ~~ [2207

Lg 75 a7 739 hoo Jar | [1

GZMB___ 76 aos J7a0 ior jiao2 | 0] 7]

TNFSF6 [7/7 [409 741 qio72 [1403 [ [~~ [=~

TCIRG1 _|78 [410 [742 Jio73 Jid04 {| | = |]

PRFT___ [79 Jann [743 fo74 Jid05 | 000] 0000} 14 [80 417 744 jis Jiao6 fT 00 is [81 413 [74s fore Tido7 | 00 0000 [CTLA4 [82 [414 q746 [to77 i408 [| 1 ~~

CDsA [83 Jats f747 T0738 Ji409 } 0000 0000] 00]

BYSs [84 |416 [748 Too Jiao} 000] 00000 0000

OID 4460 [55 [417 [749 ios fai [

HBB [86 [418 [750 fio8s1 fi412 | 0000 | 000} 0000]

BPGM [87 [410 [rst Jose Jain

MTHFD2 [88 [420 [752 f1o83 f1ana ] 0001 00000 00]

TAPT [89 421 [753 ~~ Tos [iavs fT 0000 00] [KPNA6 [90 J422 754 qos fae [oF 00 000]

OD 4365 [01 1423 [755 hose far | | =]

IGHM 92 424 [756 fog7 [iat | | 0

OID 573 [93 J425 [757 T1088 11419 [1712 }i1960 [2208

OD 873 (94 426 758 Tog [a0 } 0] 000001 00]

Obs [05 a7 [iso fie tar [ [CXCR4 [96 1428 [760 f1oo1 ft422 [CDed 97 [429 — Per fwoo2 Jtaa3 [00 } 0000 0]

CCLs fo8 1430 [v2 Toss ~~ fia24 | 0] 00000]

Te [99 [431 {763 ~~ Jioe4 Jia2s | 0] 0000 [0]

Tz [00 [42 [eda foes (maze |__| [ [KLRF1__ J1o1 [433 76s fod ~~ fwa27 J 1 00]

CyN 102 434 J7é6 Jioo7 Ta2s | 000} 000 [ 0]

OID 6207 [10s [437 [reo Juoo Just [ [ChGn___ fi0o6 [438 [770 Niwot fia32 | 0] 0 [OD 4281 107 [430 ~~ Ir; fio2 fia33 F000} 000 1 00] [cxcLo_ [io8 [440 [772 Nitos 43a F000] 000] 0]

CXCLio [109 Jaa Irn litoa fuss [

Tir (10 aez [7a ques fms

PCR PCR PCR PCR

Forward Reverse PCR Forward Reverse PCR

SEQID |SEQID Primer 1 Primer 1 |Probe 1 Primer 2 |Primer 2 Probe 2

Gene SOmer |RNA/cDNA |SEQID SEQID |[SEQID |[SEQID SEQ ID SEQ ID

Lis qi jas 77s Nites N47 | CT 1 qLro fi12 Jaea 0 p76 Niwor 8 fT

IENG [113 Jas ~~ J777 [1108 11439 1713 {1961 [7209 (HLA-DRBL 114 Ja46 ~~ |778 i109 — Ti4d0 [1714 {1962 [3210

CDSBI [115 [447 [ro fio far [CD4__ Ji16 Jag 1780 0 Ninil wad}

CXCR3 i117 J449 [781 ~~ [m2 — Nas | I

OID 7004 [118 aso [rez [nid Jam

OID 7605 [110 [asi [res [iia uas | |]

CXCLI__ J120 ~~ Jas2 ~~ |784 ~~ Ninis jade | | ——

OID 253 [121 Jas3 [rss ie iar | |]

GPT [122 Jas4 ~~ [786 iil7 [148

CD47 [123 ass ~~ J787 ~~ Jim [wad [Tp

HLAF [124 Ja56 [78s [iu Jiao | ||]

OID 5350 [125 [457 [789 [i201 | |]

TCRGC2 [126 [458 [70 Jin asa

OID 7016 {127 1459 ~~ J7or ~~ fia | — 1 — 4

PTGS2 [128 Jae0 [ror [nas fms | |]

OID 5847 1129 a61 1993 ~~ fi1o4 — fidss | — 1 — 1

PROMI [130 J462 ~~ [794 — Jri2s —Jias6 | |"

CKB [131 J463 ~~ J795 ~~ Miia [i457 | | 4

TNNI3 1132 Jed ~~ J796 [1127 [i458 | [7

TNNT2 [133 J465 ~~ [797 1128 N49

MB____ 1134 Jae6 [798 [1129 wae0

SLC7AIL 1135 1467 ~~ 1799 ~~ 11130 [1461 | | I]

TNFRSF7 [137 ~~ J469 ~~ [801 ~~ 11132 Ji463 [| J]

CD86 [138 470 [802 [1133 ded | [1]

AlFlva [139 ~ Ja71 [803 1134 ides

EVBCLF-1[140 472 ~~ [804 11135 [1466 [1716 [1964 [2212

EVEBNA-lf146 478 [810 ~~ Nar T1472 N1722 [1970 [2218

EVBZLF-1 [147 1479 ~~ [811 ~~ [1142 [1473 [1723 i971 [2219

EVEBNA-L[149 1481 ~~ [813 — JT144a Nd75 | | 1

CMVIEI [151 [483 ~~ 181s rie [i477 | | | 1.

CLC [15> [asa [816 [1147 [148 [196 [1074 [2322 [TERF2IP [153 [485 ~~ "1817 11148 |1479 [i727 [1975 [2223

OID 5891 [155 [487 ~~ J819 — T1150 |1481 i729 [1977 [2225

OID 6420 [159 aot [so3 Jiis4 [148 [i733 iow [2200

CDSN [160 [492 [goa [ils __ [ia8s [1734 [1982 [2230

RPLPL __ [164 1496 ~~ 1828 ~ |1is9 [1490 [i738 [1986 [2234

OID _si1s [ies J497 [829 [i160 J149T [1739 [i987 [2235

PCR PCR PCR PCR

Forward Reverse PCR Forward [Reverse PCR

SEQID |SEQID Primer 1 Primer 1 |Probel {Primer2 |[Primer2 |Probe2

Gene 50mer |RNA/cDNA |SEQID SEQ ID SEQID |[SEQID SEQID SEQ ID

OID 1512 [167 [499 831 i162 __ 11493 |iy41 [1989 12237

POLR2D [168 [500 1832 [i163 11494 [i742 __ 11990 [2238

ARPC3 [169 [501 [833 ited [1495 [1743 i991 [2239

OID 6282 [170 [502 [834 [i165 |1496 [1744 [1992 [2240

PRO1073 [171 [503 [835 |i166 __ |1497 [1745 11993 [2241 |]

ODD 7222 [172 [504 [836 |1i67 [i498 [1746 [1994 [2242

FPRL1 [173 [505 [837 |ii68 [1499 [1747 11995 [2243

FKBPL __|174 [506 [838 [1169 i500 i748 11996 [2244

OD 7595 |177 [509 sai [i172 [i503 [1751 11999 ~~ 12247

OD 4184 [180 [512 [sad i175 1506 [1754 12002 12250

OID 7504 [181 [513 [sas |1176 [i507 _ |i7ss [2003 — [2251

SERPINB2 [185 [517 [849 quso [sui |] 0 [ENOT__ J186 [sts [850 ier Jisi2 f17s9 [2007 [2255 [CSF2RB__ [189 [521 [853 [iis4 [is15 i762 2010 2258

OID 7410 [190 522 854 i185 Jis16 [1763 [2011 J2259 [OD 4180 [191 [523 [855 i186 [i517 [1764 [2012 [2260

RPS20 [197 [520 [sé |1i92 1523 [1770 12018 [2266

OID 4186 [199 [531 [863 |1194 _ 1525 {1772 {2020 [2268

OID 6086 [212 [544 1876 i207 _ [1538 |1785 ~~ [2033 [2281

OID 5152 [214 [546 1878 i206 [1540 [1787 [2035 ~~ [2283

ANRPU [216 [548 1880 [i211 |is42 [1789 [2037 = [2285 [ERCC5___|217 [549 |881 i212 [1543 ~~ [1790 [2038 [2286

RPS27____ [218 [550 (882 [i213 [i544 [1791 [2039 [2287

PSMDI1__ [220 [552 1884 i215 [i546 {1793 [2041 [2289

PCR PCR PCR PCR

Forward |Reverse (PCR Forward [Reverse PCR

SEQ ID [|SEQID Primer 1 Primer1 |Probel |Primer2 |Primer2 [Probe?2

Gene S0mer |RNA/cDNA |SEQID SEQID (SEQID |[SEQID SEQID SEQID

OID 7371 [228 [560 892 ~~ 1223 i554 [1801 [2049 ~~ J2297

PIT [236 [568 jooo [1231 [1562 [1809 [2057 [2305

OD 7766 [237 [569 01 1232 [i563 i810 [2058 [2306

OID 6451 [242 f574 [oo6 [1237 [1568 [1815 2063 [2311

SUV39HI1 [245 [577 [909 Jiao [1570 [i818 ~~ J2066 [2314

HSPCO48_ [246 [578 |oi0 [12a1 is T1819 2067 [2315

OD 7073 [250 [582 foi4a i245 liste Jiga3 [2071 {2319

OID 4263 [252 (584 [o16 __ lisa7 Ji578 ~ Jigs [2073 [2321

SERPINBI1[254 [586 [018 i249 [1580 iga7 12075 12323

OD 6711 [255 [587 [916 lizs0 [isat [18%® o076 12324

OD 6303 [262 [594 foz6 [izsy piss | —— 1 1

OID 4323 [268 [600 [932 [1263 [1504 [is40 [2088 [2336 |]

Ob sis feo fev { | | |r TT

TNFRSFIOA274 [606 937 ies 11509 Jisas _ |o0o3 Ja3dl

ADM |275 [607 [938 [1269 tbo iga6 [2094 [2342

PCR PCR PCR PCR

Forward Reverse [PCR Forward [Reverse PCR

SEQID (SEQID Primer 1 Primer 1 |Probel Primer2 |Primer2 |Probe2

Gene S0mer |[RNA/cDNA |[SEQID SEQID (SEQID |SEQID SEQID SEQID

OID 357 [276 l608 [930 1270 __ J1601 1847 12095 [2343 |]

Cooofe [277 Je0o [oa0 [1271 [1602 [1888 [2006 [2344

OID 3226 [278 [610 Joa1 [1272 [1603 |iga> 2007 [ass

ASAT [rio fei Joa [1273 [1604 __[igs0 [2098 [2346

ATES [ps0 leiz o43 [174 [i605 [1851 [2000 [2347

OID 4887 281 [613 9a4 [1275 [1606 [1852 [2100 [2348

OID 4239 [282 [614 945 [1776 [1607 [1853 [2101 [2349

MDM2 ass [61s oa 1277 [1608 [1854 [3100 [2350

XRN2 [284 1616 {947 i278 [1609 [1855 [2103 [2351

OID 6039 [285 |617 948 1279 [1610 1856 [2104 [2352

OID 4210 1286 618 1049 [1280 [1611 [1857 [2105 [2353 [OID 7698 [287 610 oso [1281 [i612 [igs J2106 [2354

OID 4288 [289 — J621 1052 [1283 T1614 11860 12108 123%

OID 5620 [290 1622 1953 Jioe4 [1615 i861 [2109 [2357

OD 7384 [291 fe23 os4 [1285 [i616 [1862 |a110 [2358

PLOD [294 |626 Jo57 [1288 1619 J1865s 2113 ~~ 2361

FZD4 1297 [629 ~~ Jo60 ~ [1291 [1622 Jise8 [2116 [2364 [HLA-B 1298 Je30 Jo61 11292 [1623 11865 [2117 12365 [ODF2 301 {633 ~~ Joe4 [1295 Jie26 [1872 [2120 [2368

CD44 1309 1641 Jo72 ~~ [1303 [1634 [1880 [2128 [2376

OID 4891 [314 646 Jo77 [1308 i639 [1885 2133 2381

FLi22757 316 648 ~ J979 ~~ 11310 Ji64l ~~ 11887 [2135 ~~ 2383

RAC [317 Jea0 oso [i3t1 [i642 [1ss8 [oi [2384 [OID 6415 [318 ~ 650 ~~ [o81 11312 [1643 [1889 [2137 [2385

NMEST [319 {esl [082 T1313 [64s [1850 [2138 [336

DMBTI__ [320 [652 983 [1314 [1645 i891 [2139 [2387

IDEFCAP [326 1658 ~~ [o89 ~~ [1320 1651 [1897 ~~ [2145 ~~ [2393 — [RPL27A [327 [659 190 ~~ 11321 lies2 ~~ J1898 ~~ [2146 [2394 — i072 [328 Jee0 oor 1322 [i653 J1899 12147 [2395 — [PSMA4__ [329 [661 1992 [1323 i654 11900 [2148 [2396

CONT [330 le62 [003 [1324 [165s iol |auay [2397

PCR PCR PCR PCR

Forward Reverse PCR Forward |Reverse PCR

SEQ ID [SEQID Primer 1 Primer 1 [Probe 1 Primer 2 |Primer2 {Probe2

Gene S50mer |RNA/cDNA |ISEQID SEQ ID SEQ ID SEQ ID SEQID SEQ ID

THBD [331 Joey (pos ss

CGR19 __ [332 led [99s [i326 1657 1903 2151 2399

Non-

SEQ ID {SEQ ID parametric [Fisher p- [t-test p-

Gene Gene Name S0mer |[RNA/cDNA Odds ratio |value value

HBB [Hemoglobin beta [86 [418 [ss [833 ~~ fooo [0.00 lc A lL carrier

OID 873 |KIAAI8O2 protein [94 [426 [ss [509 ~~ Joor Joor

IL4_ |interlewking [80 Ja1i2 [46 400 ~~ Joo2 foot

OD 4281 [EST ior Ja30 Ise [519 ~~ Joor joo1

Bl cl constant mu

BPGM 2,3-bisphosphoglycerate [87 419 43 7.31 mutase

CTLA4 Cytotoxic T-lymphocyte-|82 414 52 1.84 0.02 associated protein 4

SLC7A11 [Solute carrier family 7, [135 467 2.50 0.15 0.03 (cationic amino acid transporter, y+ system) member 11

OD 6207 [EsT [ros a37 137 [358 ~~ Joao ood

BN A with ZNF domain

LYN v-yes-1 Yamaguchi 102 434 55 1.08 0.08 sarcoma viral related oncogene homolog

I pve l G C importin alpha 7

OID 7094 |XDxEST479G12___ [us laso [35 [113] ~~ 10.09

ILS |interlewkinis Jui 443 si 1378 oos 10.09

OD 4460 [EST Jes lai7 Jaz [273 oud [o.10 |]

MTHFD2 |Methylene 88 420 43 3.50 0.07 0.11 tetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate

ONYAIrQid Sc

TCIRGI T-cell, immune regulator [78 410 57 0.11 . 1, ATPase, H+ transporting, lysosomal

VO protein a isoform 3 cl a Gl lO LA

FLJ32919

CXCR4__ [Chemokine (CX-Cmotif96 [428 156 29 [ foa2

GPT [Glucose phosphate isome{122 1454 |s7 |i4a ~~ foeo ~~ fo2

KLRF1___ |Killer cell lectin like recd101 [433 Jso [ies | ~~ Jo.43

CCLs [Chemokine (C-Cmotifljo8 430 [34 [196 [| = Joa3 [CD47 ____|CD47 antigen (Rherelated123 [455 Iss [14s | fo.a3

IL10_ [interleukin10 112 [444 [33 has | = = Joa3 oD 253 [est roi Jas3 Jo6 Dos | fois

CXCL10__ [Chemokine (C-X-Cmotif109 Ja41 |s3 Tizs | foie |]

Non-

SEQ ID {SEQ ID parametric |Fisher p-

Gene Gene Name 50mer |RNA/cDNA Odds ratio }value value

IFENG Interferon, gamma 1113 fa4s sn 1133 ~~ | To76

PRF1___ |Perforin | (pore forming {79 [411 [48 |120 | T1017 2 [interleukin J100 }432 [33 Jooo |" "fo17

HLA-DRBI [Major histocompatibility[114 [446 142 T150 | —fo1g iL6 [interleukin 99 [431 j49 133 1 ois i a A li alpha

OD 573 [KIAA1486protein [93 J425s ~~ 18 1300 | foto

Fl i A A Ga motif) ligand 9 (MIG om3 Jest los a7 J49 219 | foo

FL polypeptide 1 (p37

CD69 CD69 antigen (p60, 97 429 30 1.71 0.23 early T-cell activation antigen oD 760s [EST N19 jst 147 [311 Joos Jo2qa

TNFSF6 Tumor necrosis factor {77 54 1.36 0.25 (ligand) superfamily, member 6

CXCL1 Chemokine (C-X-C 120 452 20 2.00 0.26 motif) ligand 1 {melanoma growth stimulating activity, alpha

OD 5350 [EST ~~ f125s [457 [49 Jo08 ~~ Jo26 Jo28

FG A A A NO polypeptide (p32

CD4___ [CDAantigen(pss) [116 [448 Iss Jie4a | Joos

PTGS2 Prostaglandin- 128 2.05 0.37 0.29 endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase

GZMB Granzyme B (granzyme }76 408 40 0.33 2, cytotoxic T- lymphocyte-associated serine esterase

SE cd FG ligand 4, SCYA4

ChGn Chondroitin beta 1,4 N- 438 31 2.57 0.36 acetylgalactosaminyltran sferase ll I constant 2

HLA-F Major histocompatibility | 124 456 54 2.36 0.17 0.40 complex, class I, F

TAP1 Transporter 1, ATP- 421 36 1.93 0.45 binding cassette, sub- family B (MDRI1/TAP

SEQ ID [SEQ ID parametric |Fisher p- {t-test p-

Gene Gene Name S0mer ([(RNA/cDNA Odds ratio {value value

CEL TT receptor, immunoglobulin superfamily member

IL8 finterlewlans {75 Jaoz 149 [210 fo26 Jodo

Gene ACC S0mer RNA/cDNA [Accession # SEQ ID Protein

ACIB [Nm oor10l [2 [334 INP 001092 [2400

BoM [NM_004048 |4 [336 [NP 004039 [2402

AFT [NM oodsa7 [8 540 [NP o0As3®s Dave (ALAS? [NM 0000321 [9 [341 INP 000023 [2407

APELIN NM 017413 10 [342 [NP 059109 [2408

KIRCI NM 002259 |16 [348 INP 002250 [2414 ~~ [FCGR3B_______|NM 000570 is [350 [NP 000561 [2416 ~~

CAG3 NM 002286 19 351 INP 002277 2417 ~~

HBQ [NM o00s533t___ la0 [372 [NP 005322 [2437

HLADQ [NM 002122 a2 |374 INP 002113 [2439

PPARGCI [NM 013261 [55 [387 INP 037393 2451

RAG [NM 000448 [56 [388 [Np 000439 [2452

RAG2 [NM 000536 [57 [389 INP OO0S27 [2453

TNFRSF4______ NM 003327 __|56 391 [NP 003318 [2455

Gene ACC SOmer RNA/cDNA |Accession # SEQ ID Protein

TNFSFA_____ [NM 003326 60 [300 [NP 003317 [2456

TPS1 ~~ [NM 003293 Jer [393 ~~ INP 003284 — 12457

CSF2____ [NM 0007582 Jed [39% [NP 000749 [2460

CRP NM 0005671 [66 [398 INP 000558 |pdez

GATA3 [NM 0020511 [68 {400 [NP 002042 [246s

IL7R ~~ [NM 002185.1 69 [401 [NP 002176 [2465

LEFI ~~ [NM 0162692 [72 [404 [NP 057353 12468 [TNFSFI3B ~~ |NM 0065733 [74 ~~ [406 [NP 006564 [2470

I4 ~~ [NM 000589 [80 412 [NP 000580 [2476

Liz NM 002188 [81 [413 INP 002179 [2477

CTLA4 ~~ [NM 005214 [82 1414 INP 005205 {2478 |]

HBB [NM 000518 J86 418 [NP 000509 [2481

TAPI [NM 000593 |89 421 ~~ [NP 000584 [2484

OID 873 ~~ JAK000354 J94 1426 NP 056212 [2485 [CXCR4 [NM 003467 ]96 428 [NP 003458 [2486

CCLs NM 002985 [08 [430 [NP 002976 [2488 lLe ~~ [NM 000600 {99 ]431 [NP 000591 [2489 |]

IL2 ~~ [NM 000586 [100 ~~ [432 INP 000577 [2490

CCL4 INM 002984 J104 ~~ J436 [NP 002975 2494 ~~ |]

ChGn [NM 018371 J106 438 ~~ [NP 060841 12495

CXCL10 [NM 001565 [109 ~~ |441 INP 001556 [2497

IL17 ~~ INM 002190 [110 [442 [NP 002181 12498

Cha NM 000616 [116 J4a8 [NP 000607 [3504

OID 5847 [NM 144588 [129 Ja61 [NP 653189 [asi

Gene ACC SOmer RNA/cDNA [Accession # SEQ ID Protein

TNFRSE7 [NM 00242 [137 Jae0 [Np 002s [sig [CMVIEle3 [NC 001347, compllldd 476 [NP 040060 [2522

RPS25 ~~ INM 001028 [i62 494 INP 001019 [2535

RPLP1 ~~ [NM 001003 Ji64 496 [NP 000994 [2537

ARPC3 ~~ INM 005719 f169 [S01 INP 005710 [2539

OID 7504 [NM 152312 [181 [S13 ~~ INP 689525 [2546

ENO1 [NM 001428 |i86 [518 [NP 001419 [2551

Gene ACC S50mer RNA/cDNA |Accession # SEQ ID Protein

P11 INM 006025 [236 |568 [NP 006016 [2574

TNFRSFIOA ___ |NM 003844 [274 [606 INP 003835 [2505 ~~ [C20orf6 [NM 016649 277 605 ~~ Np 057733 ~~ 2597 ~~

OID 3226 NM 015393 [278 [610 INP 056208 [2508

XRN2___ [AF064257 [284 [616 [NP 036387 [2603

M22 [NM 020525 [328 [660 [NP Os386 [2622

PSMA4 [NM 002789 [329 Je6r [Np 002780 [2623

Gene ACC S0mer RNA/cDNA [Accession # SEQ ID Protein

CCNI NM 006835 [330 1662 INP 006826 |og24

THBD [NM 000361 [331 e63 INP 000352 [2625

CGRTO [NM 006568 [332 Je64 INP 006559 ogo6

HSRRN18S ~~ jx0320s Jn ~~ [333 | ~~~ — [7

HBB ING 000007 136 ~~ [38 1 ~~ 0]

HLADRB | ~~ fa ~~ [3s | ~~

OID 4460 JAF150295 185 ~~ [417 | ~~~ —

KPNA6 [Aw021037 J9%0 ~~ [422 | ~~

OID 436s JAl46s2 Jor [423 ~~ 1 ~~

IGHM _ BCO32249 J92 ~~ 424 | ~~]

OID 573 ~~ [AB040919 [93 ~~ 425 ~~ [ 0

OID 3 ~~ [Aw968s23 ~~ |95 1427 1 0

OID 6207 ~~ [D20s22 _ Jio5 1437 1

OID 4281 ~~ [AA0s3887 [107 a3 ~~ ] ~~ — § om 7094 | Jus aso] 0

OID 7605s [AA808018 mu fast [~~

OID 253 [AK091i2s ~~ J121 fas3 01 0

OID 5350 ~~ [AKO0sS687 ~~ |12s ~~ fas7 | ~~

TCRGC2 ~~ M17323 ~~ J126 fase | ~~ |] —

OID 7016 [Blois6g6 J127 ~~ fas9 ~~ | ~~

EVEBV | Jar ja;3 1

CMVp6? ~~ [NC 001347 J142 Jaya ~~

CMVTRLY ~~ + 00 |13 Jas

EVEBN | 0000 fis Jao 0] 0

EVEBNA-LP ~~} Ji49 ~~ Jar ~~]

OID 5891 ~~ JAW297949 ~~ J155 ~~ Jag7 ~~ | ~~]

OID 6420 ~~ |AK0%0404 ~~ 159 aor [| [7]

OID 4269 ~~ [BM727677 Jiet [493 | ~~ T ]

OID 5115 fAI364926 fis ~~ Jao7 ~~ | ~~ [1]

SLC9A8 ~~ [ABO231s6 fie ~~ [498 1 0]

OID 1512 ~~ |BE618oo4 ~~ J167 ~~ Jao9 | ~~ ~~]

OID 6282 ~~ [BCO41913 ~~ J1i7o [sez

PRO1073 ~~ JAFo0is42 pin [ses ~~ | 1 0]

OID 7222 ~~ |BG260891 172 ~~ [so4 | ~~ I ~~]

OID 1551 ~~ |BE887646 ~~ J176 ~~ [so8 | ~~ 1 ~~]

OID 4184 ~~ IX17403 ~~ hgo ~~ [siz 1 1]

OID 7696 |AW297325 W187 ~~ Is19 [1

OD 4173 ~~ |X17403 ~~ J188 ~~ [s20 ~~ | 0 T ]

CSF2RB_ ~~ |ALS540399 Ties ~~ [sar ~~ 1 ~~ 1 =]

OID 7410 Jawes7zi7 fio fs22 ~~ TF 00]

OID 4180 ~~ |xa7403 for fs23 0 1 1 0

OID 5101 ~~ [BG4e1987 192 fs24 ~~ 1 ~~ ~~ [ hIAN7 __ |BG772661 [196 ~~ fs28 ~~ 1 ~~~ — [

OID 6008 ~~ |Aws92876 Ji98 [so 1 [0] om 4186 ~~ |x17403 fig Iss 0 F010]

OID 4291 ~~ [BCO38439 [203 [53s 0

OID 1366 ~~ JAwssoo41 Jo04 ~~ [s36 | 1 =

OID 6986 JAK093608 [212 [saa 1 ~~ =

OID 59062 |Awasade7 [p13 — fsas — } | 0]

OID 5152 JAI392805 214 ~ — [se6 | [

HNRPU ~~ [BM467823 fot fsa8 ~~

PSMDI1 ~~ JAI684022 ~~ 1220 ss2 ~~ | —

OID 1016 JAKO24456 1221 |ss3 | "1

OID 1309 |Av706481 ~~ J222 ~ [ss¢ | — 1 ~~

OID 7582 ~~ JAK027866 {223 [555 ~~

Gene ACC S0mer RNA/cDNA |Accession # SEQ ID Protein

OID 4317 — JAI318342 [224 ss6 | ~~]

OD 5889 [awaozeas Jes ss |]

OID 3687 _ |wo39ss 227 [sso [

OID 7371 [BE70505 | seo [

OD 5708 — JAwo08i540 [231 [ss [~~ | =]

OID 5992 JAw467992 [232 Ise4

OID 7799 TAwssp7_ Jm3s [ser

OID 7766 |Aw294711 [237 {s¢9 I ~~} [OID 6451 — |AL834168 [242 [s74 [| ~~}

OD 8063 — |x68264 [244 576 | ~~} 0]

OID 5625 |AWO063780 (247 |s79 [| ~~ = }

OID 6823 — |AIB32642 J249 |s&1 [| ~~ |]

OID 7073 JAL705961 (250 Is8&2 | ~~

Om 5339 — JAl625119 Jas [ses | 1

OID 4263 |AAI36584 1252 Is84 | ~~ 0] 000] [MGC26766 |AKO025472 _ |253 s&s [| ~~ ~~

OID 6711 [BF968628 (255 |s&7 [| ~~ | ~~]

OID 5998 [Awd4esds9 J260 [592 [| ~~} 0000]

Om 6393 [5289 ~~ J262 se4 — {| 0

RoxaN __— [BCO04857 [263 ses | | ~~ =]

OID 4323 [AA744774 f268 leo [| ~~]

OID 5181 |Al400725 [269 feo1 [| ~~ ~~ | ~~] [OD 6298 |A1948513 [272 Jeoa ~~ | ~~ oD 357 ~~ |i38Gs 1276 leo | 0} 0]

OID 4235 |BQO22840 [28 fea [0000]

OID 6039 |BES02246 [285 fet7 —

OD 4210 |AI300700 [286 [618 ~~ | ~~} 0]

OD 7698 |AA243283 [287 {619

OID 4288 |A378046 [289 [621 [| ~~ } 0]

OID 5620 |AWo0e3678 [20 ~~ fe22 [

OID 7384 [BRazszse [201 Jes

OID 1209 |Ci4379 a2 [624 | 0 0]

OD 5128 |AKO9784s [305 fear [OD 5877 |Aw297664 1296 [628 ~~ [| ~~}

OD 5624 |AWO063921 [299 ~~ le3t ~~ | ~~

OD 5150 [AI392793 ~~ T302 l63¢ | ~~} |]

OID 5639 |AWoe4243 ~~ f303 63s | ~~} 00000

OD 6619 [469A10 [304 fe36

OID 6933 JAI0S9530 J30s fer

OD 7049 [480E2 136 leas 00}

OID 5866 [|BM684739 308 fea0 | ~~] 00]

CD44 |AAo16990 309 ~~ ear | 000000} 00000]

OID 4932 |AA4s77s7 Bin Jes — 1 00000} 00000000]

OD 7821 [AAsmt Pa jes

OID 4916 |AA252909 [313 [eas ~— [~~] |]

OID 4891 |AL832320 Pia fee [RACI |aK0s4993 317 fea | ~~}

OID 6415 |Cado7201 [318 [eso [~~ J

OID 6205 JAIBsoe07 [335 les

ReLi7A |BF2tatae [327 less

Table 3: Viral genomes were used to design oligonucleotides for the microarrays.

The accession numbers for the viral genomes used are given, along with the gene name and location of the region used for oligonucleotide design.

Ela 1226..1542

Cib_t 3270...3503

E2a 2 complement(24089..25885)

Adenovirus, type 2 E3-1 27609..29792

Accession #J01917 E4 (last exon at 3’-end) complement(33193..32802) 1X 3576..4034

Iva2 complement(4081..5417)

DNA Polymerase complement(5187..5418)

HCMVTRL2 (IRL2) 1893..2240

HCMVTRL7 (IRL7) complement(6595..6843)

HCMVUL21 complement(26497..27024)

HCMVUL27 complement(32831..34657)

HCMVUL33 43251..44423

HCMVULS4 complement(76903..80631)

Cytomegalovirus

CMV) HCMVUL?S complement(107901..110132) . ] HCMVULS3 complement(119352..121037)

Accession #X17403

HCMVUL106 complement(154947..155324)

HCMVUL109 complement(157514..157810)

HCMVUL113 161503..162800

HCMVULI22 complement(169364..170599)

HCMVUL123 (last exon at 3'-end) complement(171006..172225)

HCMVUS28 219200..220171

Exon in EBNA-1 RNA 67477..67649

Exon in EBNA-1 RNA 98364..98730

Epstein-Barr virus

ER BRLF1 complement(103366..105183) ( a BZLF1 (first of 3 exons) complement(102655..103155)

Accession # NC_001345 = BMLF] complement(82743..84059)

BALF2 complement(161384..164770) : U16/U17 complement(26259..27349)

U89 complement(133091..135610)

U0 : complement(135664..135948) uss complement(125989..128136) us3 123528..123821 u22 complement(33739..34347)

Human Herpesvirus 6

DR2 (DR2L}) 791..2653 (HHV6)

DR? (DR7L) 5629..6720

Accession #NC_001664 u9s 142941..146306 u9d complement(141394..142866) u39 complement (59588..62080) u42 complement(69054..70598) ugl complement(121810..122577) u9l 136485..136829

Table 4: Dependent variables for discovery of gene expression markers of cardiac allograft rejection.

Number of Number of

Dependent Rejection No-Rejection

Variable Description Samples Samples lini A LA sO vs 1B-4 HG Stable Grade 0 vs Grades 1B-4, highest 4] 57

El 0-1A vs IB-4 HG | Grades 0 and 1A vs Grades 1B-4, highest 121 58

Sill 0vs 3A HG Grade 0 vs Grade 3A, highest grade. Grades 56 29 rl

Ovs 1B4 Grade 0 vs Grades 1B-4, highest grade. Grade | 57 57

Ei

Table 5: Real-time PCR assay chemistries. Various combinations of reporter and quencher dyes are useful for real-time PCR assays.

Ree [awe]

FAM

BHQ1

TET

BHQ1

TAMRA

JOE

BHQI1

TAMRA

HEX

BHQI1

TAMRA

VIC

BHQ1

BHQ2

TAMRA | BHQ2

Table 6: Real-time PCR results for rejection markers

Array

Faas Phase 1 All Data 0 | Foia | test [NR] R | Foia | Test [NR] R | Fold | tTest [nr] 95] 1003] omsosa| to] 8] | | | Jooss|osteas| 21] 13] rais| ones] 2] wo] TTT Tams] oowss] a2] 10 79] 1822] ooras| 6] 7] oes] oosmms| 19] 15] ora ooseaz| as] 26] soe | 10a oarorr| wo] ao] [1 | | 1001] oagear| 16] 15 75] 084] osesra| 11| 8] os0s|os7es] 16] 13] 062s | 0oma02| sa] 26° 2765 | 1653] 001508] 10] 10] 0.776 | 011082 | 19] 14 | 0956 [037421 | 38] 20] [or] [| I [ornslozeoor] sf slosealormss] 17] 12 [ 2695 | 1553 | 000533] 13] 10] 0.634 [016853] 18] 15] ogee [oasrot | ss] 27] 06 | 1495 [ooeoss| 13] of 1.157] o2eor]| 18] 15] 1455] 0.21006] 33] 25 100 a3] omes| tof s[ [| [| Traoslotate] 12] 8 2766 [ 0956 | 043018] 12] 10] 0089 | o4mors| 19] 1a] oo7efoastor] 31] 24 2r26 | 1037 | oss20s| 11] of 1 1 [| Troasrfoaseos| 11] ol [ ores | 1211 [ooosme| of of | 1 | Ta1211]o0eme] of of oalteor[oooae] wf of | T | Tresrfooooea] a7] 15] 2769 | 1.133 | 023004 | 12] of 1.081] 019632] 10] 15] 1101] 01502 | 31] 24] 2770 | 1730 [oooorr[ sal 10] |] 1 113s1]oomes] 20] 1s] [ 2647 | 1567 | ooaso2| 10] ef | | | | 1557] cossez| 10] 8 2771] 1o9foossral aa] of | 1 1 1 1s2]oatos]| 17] 13] 82] 2009] 000022] 8] 5] 1.287] 013022) 18] 14] 1.256] oossse| 3a] 2] os] 1 I | lore] oa] 19] 15} 0577] oosasz| 19] 14] 36 1605] oooer [ 12] 8) 2618] 001227] 18] 11] 208] 0.00015 | 38] 23] 80[ 5395] 000049] of 6] 4404] 0osaea] 10] 10] 233] 0.02369] 20] 18] sof JT [1 1 | 1 Jozs|oomss] 6] 6 77 | 1894] 00102] 10] 10] 0537 00516] 19] 15] 0863 | 0.21987 | 35] 29] 2772] 1563 [oosere | 10] 6] 074] oa3019] 13] 10] 1436] ozesar| 28] 17] orraf1391looozse | 11] ef } 1 | [1391] 000236] 11] 6] or7a| 1s9looooz2| taf so} |] | | 150] 000022] 13] 10] 102 | 1245[ 005079 11] 10] 1.018 0a2r02] 47} 15] 1.417 | 0.0232 | 32] 28] orrs[orofoteasa] 11] of | 1] 1 loroaoteass| 11] of orre | 1257] ooste| 12] of I 1 | [1257] ooste] 12] of s67| 13afoossos] sa] of | 0 [ 1 | 113]oasee2] 20] 1] 11s| 109026209] mf of 1 1 | [1109loaee09] 11] of e609] 2146] ooosral s2 to] | 0] 1 |1205]o0n4zes| 18] 12] 2777] 11a2 ozone] af a0] J 1 1 [1142] o0z0ms] 13] 10] 78] 1324] 001085] 12] 9] 0.067 0.33851] 18] 14] 1.007 | 0.a686a| 38] 24] 2670] 1assfotr200] sal of | 1 | [13ssoaros] 13] of 2778 | 1a28loneses] 1a of | | | [1428] oteses] 13] of 2770 1991 002513 9] 5 0.642] oos002| 18] 14] oes | 026275] 32] 21)

[271] | 1 | Joseloowas]| 12] 12 0819] 028555] 17] 15]

Table 6: Real-time PCR results for rejection markers

Array

Foo All Data [om [cron [wr [= | rota | crest [ne | & | row | wrest [wr [= or] [1 | Toeseloossnr| 19] 15] 0773] oor] 20] 22] wos r2safosomn | wa] ef TT 1 liasafoww| a] ef [| 2083 | 1508 |oosrza| 8] sl oeasfoosses| tal 10] ose] oserai] 28] 22] er] [1 1 Taserfooeree| 18] 15} ae57| oomsse| a0] 2] ool 0630 ooeer3| 7] 5] osa0fog0z0e] 16] 8) ones] omar] 27] 15] 2602 | 0801 {021236 | 12] e oesalosseor| 18] 15} ors] cosss | as] 2s] 10a] 2202] oowpa| 11] 8] 0621 oos1s2] 19] 15] 0.013] 0a4s06 | 30] 2] 76] 1800] oooeos| o| sl oesaloraoer] 13] sl 1274] oateer| 28] to or | 1960 [oorzeo| 11] 8] 40sr|ooosr2] 19] 13] s.535] ooo0sa| a7] 2] o2{ 2850 [oosess | 11] ef o7eaoosoer| 18] 14 esse] oovez] a7] 24] 85] 09s] oases] 12] sf oes] oorer| 13] 13] 0633] oomes| 33] 24] wos] 1relooeiee| mf wo] TT 1 1 176} oostee] 11] 10] 2783 | 0.045 | oas0zs | 10] 5] ossefozeror| 17] 10] 0.086] ome | 20] 17] [ 2707] 10s osmaas| sal ao] J 1 | lross]osuss) asl tol 2s] aasaomerz | mn] wo] fT | Jamsaloerr] 11] ao se) 1786] 000255] of 6 os2a}oosses| 18] 1a] o7es| orsorel al 22]

[2784] 2.12] 000022 | 12] 10] 0408 oorsza| 18] 13] 0935] oa7sse | a7} 25] [27s] ser] omar] sof of 1 1 1 laser] ossrzl sof tof 12a tass loose] 1] of [TT [rasa]oomza] 11] of oo 1.355] 00zos8| 13] 10] 0073] oawaes| 15] 13] 1125] comer] 28] 23] 27e6 [130s oorma| 12] of | TT [1306] oor] 12] 10 [277 | tose | osears| 12] so] | | 1 Troselosmrel 12] 10) [s0te | 1523 0487] 12] 10] ose o2ron] 18] 13] 1101] osseve] a6] 26] r2s| se loosmez| wu] tof J} | [1252] cose] 1] 10) [zre | 125s] oszn| mi] vo] | FT Tess] oseer| ml v0 27s0| tase ostzs2| of of | | | |iseloswse] ol 6 [3010 | 1268 [021268] 6] 7] ooe1]oasser| 16] 10] 1012] 0aserz] 20] ref 2700 | osst | 017766 | 11] 8] 122] 0425s] 18] 10] osee| osamee| a0] 20

[2701] rear oossa] 13] to | | | [esr] oomssa] 13] 10] 2792 | 1.504 | 0.05006 | 12] 10] 0713] 002079 | 19] 15] 046 | oreoral 31] 25] 2704 | 1.9% | 000176 | 13] 9] 0717 ooeree | 1s 14 0e77] 022205] ao] 25] 2752] 1499 | 0.00077 | 12] 8] 0808 | 015363 | 17] 13] voo4 | oasoos| se] 23] 2795 | 0015] 024734] 8 5] 0965] 041772 | 10] 15] 003s] oozes] so] 22] vo 122 ozo] sol vo] | 1 Trzre[ozeref 10] tol

Table 7: Significance analysis for microarrays for identification of markers of acute rejection. In each case the highest grade from the 3 pathologists was taken for analysis. No rejection and rejection classes are defined. Samples are either used regardless of redundancy with respect to patients or a requirement is made that only one sample is used per patient or per patient per class. The number of samples used in the analysis is given and the lowest FDR achieved is noted.

No Rejection [Rejection # Samples |Low FDR

Ansamples

Grade0 [Grade 3A-4

GradeO [Grade 1B. 3A-4

Non-redundant within class

Grade 0 [Grade 3A-4 EX

GradeO _|Grade 1B, 3A-4

Non-redundant (1 sample/patient

Grade0 [Grade 3A-4

Table 8: Renal rejection tissue gene expression SAM analysis

[2674] glioma pathogenesis-related protein (RT [2.8125 | 2933] ~~ | = 2743|c- nuclear receptor subfamily 1, group! {28125 | } 0 1 326|death effector filament-forming Ced-4-{ [28125 | 2934] ~~ 2716|ESTcDNA,3 end 28125 | 00 |] 2727|c- chemokine (C-X-C motif), receptor 4 13.1316 | 2935]+ —3721]c EST3 endJolonesAGE. [336 |_ 2641] hypothetical protein FLJ20647 (FLJ20647 [3.1316 | 2036] [2671 tumor necrosis factor, alpha-inducedpr [3.525 | 2037] 2752] protein tyrosine phosphatase, receptor [38077 | 2938[+

[2663] phosphodiesterase 4B, cAMP-specific [39 | 2043] ~~ [+ [ 98[small inducible cytokine AS (RANTES) [4.5645 | 2044[+ [+ [2657 tumor necrosis factor receptor superfam [4.8286 | 2045] [ 2683]B-cell lymphomalieukaemia 118 (BCL11B)[4.8286 | 2946{+ ~~ [ 2686 phospholipase A2, group Vil (platelet-a [4.8286 | 2047] [+ 2687 phosphatidylinositol 3-kinase catalytic (4.8286 | 2048] 2644|AV650177 cDNA, 3 end Jaoo28 | | 1 2664 |requiator of G-protein signaling 10 (R___ [50238 | 2949] 1 2747|c- integral membrane protein 2A (TM2A), [5.0238 | 2050] 2744) c interferon consensus sequence binding [5.0238 2678] HSPC022 protein (HSPC022), mRNA 50238 | 2061) 2731]c-x98c03.x1 NCI CGAP Cof8cDNA _ [50238 2713] caspase recruitment domain protein 9 (L_ 15.0238 | 2062] [ 2708] major histocompatbility complex, class [5.15 | 2054] [ oaofciorAs sts 2670[CD72antigen (CD72). mRNA [515 | 2o65)+ [ 2661 [neat shock 70kD protein 6 (HSP70B) [5.15 | 2956] | |] 2680] bridging integrator 2 (BIN2), mRNA eds [515 | 2057] [ 2754[UIH-BWO-aly-b-100-Uls1cDNA 3 end [515 | | [|] oro8|c-EST8O07620DNA [515 | | [ tralpePL sts | oes [ 2742|c-chromoboxhomolog3(OM) 615 | | [ 2668 [basement membrane-induced gene(ICB-1)[5.45 | 2960] ~~ [ [ 2750]Lysosomal-assoc. multispanningmemb__ {5.15 | 2060] [

Table 8: Renal rejection tissue gene expression SAM analysis probe ID SEQ ID | expression

EFZE (ZY |X TN EE EE I orl AVI ONAG end [sds 2627 solute carrier family 17 (sodumphosph [515 | poe1] 2739[c- asparaginyl tRNA synthetase (NARS) [596

[124] major histocompatibility complex, class [595 | 2062] 2647|mRNA for T-cell specific protein /cds [515 | po63]x %628|cEST,3end [52006 [| [ 2638|ExpresscDNAlibrarycONAS 152003 | |] 2725|c 601571679F1 cDNA 5 end 153385 | 2064] 2714]qq78c05x1 CDNA, 3 end/clone 153385 | 2065]

[2635] interleukin 2 receptor gammachain___ 153385 | 20e6l+ 2751|7264, lectin, galactoside-binding, soluble |5.4167 | 2067} + 2629]8. cDNA: FLI21559 fis, clone COL06406_|55296 | 2068]

[2605] mRNA; cDNA DKFZpd34E0516 _ |65588 | 2060] 2741]c-hexokinase2 (HK?) mRNA 155086 41]Similar to major histocompatibility antigen [5.5086 | 2970] 2691|CD5 antigen (p56-62) (CDS) [55986 | 2071] ~~ 2726]c-602650370T1cDNA3 [56014 | | [ 2722|c ESTcDNAclone _ |se014 | | 1 o6Bolinterleukin-2receptor [56014 | 2972) 1 [—2734]c- nuclear receptor subfamily 1, group [56667 2631|pre B-cell colony-enhancing factor [5.7566 | 2073] [+ 2656 postmeiotic segregation increased 5.7756 | 2974] 1 2696] protein tyrosine phosphatase, receptor [6.7756 | 2975] : [2676] butyrophilin, subfamily 3, member A2 [58165 | 2076] — o70f|c-EST3end [seo | [ 2730|EST3 end/clone=IMAGE ____ [se048 | | ~~}

[2710] high affin. immunoglobulin epsilon recept. [5.9048 | 2977] 2632|encoding major histocompatibility comple [5.9048 | 2078] 2r24|cEST3end seo4s | 0] — oeeslest lees | 1 2662] interferon regulatory factor 1 (IRF1), [6.0088 | 2979] ~~ [ 139[allograftinflammatory factor 1 (AIF1), [6.1379 | 2080] 1 2753 | platelet activating receptor homolog (H 16.3182 [| 2081] ~~ 1 2704[c-EST3 end/clone=IMAGE: ~~ J70337 [ | ~~ 2675|pim-2 oncogene (PM2), mRNA |7.1222 | 2982] [+ =] 2700] proteoglycan 1, secretory granule (PRG1_|7.375 | 2983] ~~ [+ 2640|{mRNA for KIAAOB70 protein, partiaicds [7.375 | 2984] 273Jc-EST.5end/dlone=sIMAGE [7375 | | 1 2658|FYN-binding protein (FYB-120/130) (FYB) [7376 | 2985] 2688 | major histocompatiility complex, class [7.375 | 2986] 2735[c-EST.3 end/dlonesMAGE: [7375 | 1 0] 2702[c- hypothetical protein MGC4707 [7634 2681 [hypothetical protein FLJ10652 [8.1117 | 2087] —a7slEST.3ena emp [ 2715|hypothefical protein FLj10842 [8atiz [} 0 [ 2732|c-ESTcDNA, 3 end fsatiz |} 0] 2652|hexokinase2 (HK2) mRNA J84i17 [| | — 2651|colony stimulating factor 3receptor [8.1117 [ 2088] 2718|RNA binding motif protein, Xchrom 182788 2673(Srcilike-adapter (SLA), mRNA 183048 | 2989} 2733|c- major histocompatibilitycomplex [8467 | | 0] 2712] istamine receptor Hz (HRHZ) ____|88563 | 2eso]

Table 8: Renal rejection tissue gene expression SAM analysis probe 1D SEQ ID |expression

207 ! i

Table 9

Array |Gene Gene Name mRNA RefSeq Current Localization [Function

Probe Accession # [Peptide UniGene

SEQ Accession # [Cluster 1D Build 156 111 Interleukin 15 NP_000576 [Hs.168132 Secered heel activation and ) proliferation 79 PRF1 Perforin | (porc [NM _005041 [NP_005032 {Hs 2200 Sccreted CDS, CTL effector; forming protein) channel-forming protein capable of lysing non- specifically a variety of target cells; clearance of virally infected host cells and tumor cells; . 110 |IL17 Interleukin 17 NM_002190 [NP_002181 |Hs.41724 {Secreted Induces stromal cells to (cytotoxic T- produce lymphocyte- proinflammatory and associated serine hematopoietic cytokines; csterase 8) enhances IL6, IL8 and

ICAM-1 expression in fibroblasts; osteoclastic bone resorption in RA; expressed in only in activated CD4+T cells we cytokine 120 |CXCLt Chemokine (C-X- |{NM_001511 [NP_001502 {Hs.789 Secreted Neurogenesis, immunc

C motif) ligand 1 system development, (melanoma growth signaling stimulating activity, alpha ] 113 |IFNG Interferon, gamma Antiviral defense and 1 immune activation and T cells

J GP dua wi vali NS microglobulin

CCLS Chemokine (C-C |[NM_002985 |NP_002976 |Hs.241392 {Secreted Chemoattractant for motif) ligand S monocytes, memory T (RANTES, helper cells and

SCY AS) eosinophils; causes release of histamine from basophils and activates eosinophils;

One of the major HIV- suppressive factors produced by CD8+ cells 112 |IL1O Interleukin 10 NM_000572 {NP_000563 |Hs.193717 {Secreted Chemotactic factor for

CD8+T cells; down- regulates expression of

Th] cytokines, MHC class I Ags, and costimulatory molecules on macrophages; enhances B cell survival, proliferation, and antibody production; . blocks NF kappa B,

JAK-STAT regulation, stimulates CTL lymphoid progenitors

Table 9

Array (Gene Gene Name mRNA RefSeq Current Localization Function

Probe Accession # [Peptide UniGene

SEQ Accession # |Cluster [D) Build 156 109 |CXCLIO Chemokine (C-X- NM_001565 |NP_001556 |Hs.2248 Secreted Stimulation of

C motif) ligand 10, monocytes; NK and T

SCYBI0 cell migration, modulation of adhesion molecule expression motif) ligand 17 trafficking and activation 101 |KLRFI Killer cell lectin- [NM_016523 |NP_057607 |Hs.183125 |Secreted Induction of IgE, I1gG4, like receptor CD23, CD72, surface subfamily F, IgM, and class If MHC member 1 antigen in B cells 95 [its |ImerleukinG [NM 000600 [NP 000591 [93513 [Secreted |B cell maturation 104 |CCL4 Chemokine (C-C {NM_002984 |NP_002975 |Hs.75703 |Secreted Inflammatory and motif) ligand 4 chemokinetic properties; one of the major HIV- suppressive factors produced by CD8+ T cells 76 GZMB Granzyme B NM_004131 |NP_004122 Hs.1051) Secreted Apoptosis; CD8, CTL (granzyme 2, effector cytotoxic T- tymphocyte- associated serine _ esterase 2785 {OID 4789 |KIAA0963 protein|NM_014963 |NP_055778 |Hs.7724 Secreted Proinflammatory; chemoattraction and activation of neutrophils 2791 |XCLI Chemokine (C NM_002995 |NP_002986 |Hs.3195 Secreted Chemotactic factor for motif) ligand 1 lymphocytes but not

SCyC2 monocytes or neutrophils 130 |(PRDMI PR domain NM_001198 {NP_001189 |Hs.388346 Nuclear Transcription factor; containing 1, with promotes B cell

ZNF domain maturation, represses human beta-IFN gene expression 2781 |TBX21 T-box 21 NM_O013351 [NP 037483 Hs.272409 ocr | differentiation, 88 MTHFD2 Methylene NM_006636 |[NP_006627 |Hs.154672 [Mitochondrial |Folate metabolism tetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydr ofolate cyclohydrolase 103 |ILZRA Interleukin 2 NM_000417 {NP_000408 [Hs.1724 Membrane- |T cell mediated immune receptor, alpha bound and response soluble forms 77 TNFSF6 Tumor necrosis |NM_000639 [NP_000630 |Hs.2007 Membrane- |CD8, CTL effector; factor (ligand) bound and proapoptotic superfamily, soluble forms member 6 115 |[CD8BI CDS antigen, beta {NM_004931 |NP_004922 |Hs.2299 Membrane- |CTL mediated killing p37 soluble forms 128 [PTGS2 Prostaglandin- NM_000963 |NP_000954 |Hs.196384 |Membranc- |Angiogencsis, cell endoperoxide associated migration, synthesis of synthase 2 inflammatory (prostaglandin prostaglandins

G/H synthase and cyclooxygenase

Table 9

Array {Gene Gene Name mRNA RefSeq Current Localization [Function

Probe Accession # | Peptide UniGene

SEQ Accession # {Cluster 1D Build 156 89 TAP Transporter 1, NM_000593 |NP_000584 [Hs352018 |ER membrane {Transports antigens into

ATP-binding ER for association with cassctte, sub- MHC class | moleculcs family B

MDRV/TAP : heavy constant mu and secreted forms 122 |GPI Glucose phosphate [NM_000175 {NP_000166 |Hs.409162 |Cytoplasmic Glycolysis and isomerase and secreted gluconeogenesis forms (cytoplasmic); neurotrophic factor (secreted (amyloidosis, and secreted jassembly/disassembly ; Finnish typ . ) ] forms 2780 [STK39 Serine threonine |NM_013233 {NP_037365 {Hs.199263 [Cytoplasmic |Mediator of stress- kinase 39 and nuclear (activated signals; (STE20/SPSI Serine/Thr Kinase, homolog, yeast activated p38 2770 |PSMBS Proteasome AK092738 Hs.180062 [Cytoplasmic [Processing of MHC class (prosome, I antigens macropain) subunit, beta type, 8 (large multifunctional proteasc 7 2667 |LPXN Leupaxin NM _004811 |NP_004802 |Hs.49587 [Cytoplasmic 2669 [ITK [L2-inducible T- [L10717 Hs.211576 [Cytoplasmic [Intracellular kinase, T- cell kinase cell proliferation and differentiation

KPNAG Karyopherin alpha |AW021037 Hs.301553 [Cytoplasmic |Nucleocytoplasmic 6 (importin alpha transport 7 protein 2A transduction 2765 |TNFSFS Tumor necrosis [NM_000074 |NP_000065 {Hs.652 Cellular B-cell proliferation, IgE factor (ligand) membrane production, superfamily, immunoglobulin class member 5 (hyper- switching; expressed on

IgM syndrome CD4+ and CD8+ T cells 97 CD69 CDG9 antigen NM _001781 [NP_001772 {Hs.82401 [Cellular Activation of (p69, early T-cell membranc lymphocytes, activation antigen monocytes, and platelets 2635 |IL2RG Interleukin 2 NM_000206 |NP_000197 Cellular Signalling component of receptor, gamma membrane many interleukin (severe combined receptors immunodeficiency (1L2,IL4,IL7,IL9, and

IL15),

CXCR4 Chemokine (C-X- |NM_003467 [NP_003458 |Hs.89414 [Cellular B-cell lymphopoiesis,

C motif) receptor membrane leukocyte migration, 4 angiogenesis; mediates intracellular calcium flux 2766 {CD19 CD19 antigen NM_001770 |NP_001761 [Hs.96023 |Cellular Signal transduction; B membrane lymphocyte development, activation, and differentiation

Table 9

Array |Gene Gene Name mRNA RefSeq Current Localization [Function

Probe Accession # |Peptide UniGene

SEQ Accession # |Cluster

ID Build 156 : 2769 |ITGBI Integrin, beta | NM 002211 |NP_002202 |Hs.287797 |Celluiar Cell-cell and cell-matrix (fibronectin membrane interactions receptor, beta polypeptide, antigen CD29 includes MDF2, ae MSK12 beta, constant membrane region 82 CTLA4 Cytotoxic T- NM _005214 |NP_005205 [Hs.247824 [Cellular Negative regulation of T lymphocyte- membrane cell activation, expressed associated protein by activated T cells 4 83 CD8A CD8 antigen, NM_001768 [NP_001759 (Hs.85258 |Ccllular CD8 T-cell specific alpha polypeptide membrane marker and class | MHC p32 receptor 114 |HLA-DRBI1 {Major NM _002124 |NP_002115 |Hs.308026 [Cellular Antigen presentation histocompatibility membrane complex, class Il,

DR beta 1 2772 |CD3Z CD3Z antigen, NM_000734 |NP_000725 |Hs.97087 |Cellular T-cell marker; couples zeta polypeptide membrane antigen recognition to (TiT3 complex) several intracellular signal-transduction pathways

Actin, beta - [NM_001101 NP_001052 [Hs 268061 Cr en adhesion and membrane recognition 2774 [ITGAL Integrin, alpha L |NM_002209 {NP_002200 {Hs.174103 Cellular All leukocytes; cell-cell (antigen CDI11A membrane adhesion, signaling (p180), lymphocyte function- associated antigen

I; alpha polypeptide 78 TCIRGI T-cell, immune [NM_0060319 |NP_006010 |Hs.46465 Cellular T cell activation regulator 1, membrane

ATPase, H+ transporting, lysosomal VO protein a isoform 3 membrane 2779 |D12S2489E [DNA segment on |{NM_007360 {NP_031386 |Hs.74085 [Cellular NK cells marker chromosome 12 membrane (unique) 2489 expressed sequence 2692 |MS4Al Membrane- NM_152866 |NP_690605 [Hs.89751 Cellular B-cell activation, plasma spanning 4- membrane cell development domains, subfamily A, member 1, CD20

Fo ll gamma constant 2 membrane 116 |CD4 CD4 antigen (p55) {NM_000616 [NP_000607 |Hs.17483 |Cellular T cell activation, signal membrane transduction, T-B cell adhesion oo

Table 9

Array (Gene Gene Name mRNA RefSeq Current Localization |Function

Probe Accession # |Peptide UniGene

SEQ Accession # | Cluster

ID Build 156 117 |CXCR3 Chemokine (C-X- [NM_001504 |NP_001495 |Hs.198252 [Cellular Integrin activation,

C motif) receptor membrane cytoskeletal changes and 3, GPRY9 chemotactic migration of ] lcukocytes 2707 |CD33 CD33 antigen NM_00t772 |NP_001763 |Hs.83731 Cellular Cell adhesion; receptor (gp67) membrane that inhibits the prolifcration of normal and leukemic myeloid cells 123 |CD47 CD47 antigen (Rh-{NM_001777 {NP_001768 |Hs.82685 Cellular Cell adhesion, related antigen, membrane membrane transport, integrin-associated signaling transduction, } signal transducer permeabili

BYSS5 Natural killer cell |[NM_007053 |NP_008984 |Hs.81743 |Ccllular NK cells and CTLs, receptor, membrane costim with MHC immunoglobulin superfamily member 2784 |KLRD1 Killer cell lectin- |NM_002262 |NP_002253 [Hs.41682 |Cellular NK cell regulation like receptor membrane subfamily D, member 124 |HLA-F Major NM_018950 [NP_061823 {Hs.377850 [Cellular Antigen presentation histocompatibility membrane complex, class I, F 2752 |PTPRCAP [Protein tyrosine |NM_005608 |NP_005599 |Hs.155975 [Cellular T cell activation phosphatase, membrane receptor type, C- associated protein

Table 12: Markers for CMV Infection 1553 FY OR FO IPR =

Probe Sequence FDR 408 cDNA Hs.1051 NM_004131 [7262379 [granzyme B GGAGCCAAGTCCAGATT 0%

TACACTGGGAGAGGTGC

CAGCAACTGAATAAAT

3108 Hs.169824 [NM_002258 [4504878 [killer cell lectin- {1 TGGATCTGCCAAAAAGA 0% like receptor ACTAACACCTGTGAGAA

ATAAAGTGTATCCTGA

3109 [cDNA Hs.170019 |[NM_004350 |4757917 |[runt-related GCTGGGTGGAAACTGCT 0% transcription TTGCACTATCGTTTGCT factor 3 TGGTGTTTGTTTTTAA 433 cDNA Hs.183125 {NM_016523 {7705573 [killer celi lectin- {1 TTCCAGGCTTTTGCTAC 0% like receptor F TCTTCACTCAGCTACAA

TAAACATCCTGAATGT

3110 Hs.2014 X06557 37003 T-cell receptor- GGGGTTTATGTCCTAAC | 0.10% delta TGCTTTGTATGCTGTTT

TATAAAGGGATAGAAG

3111 cDNA Hs.211535 |AI823649 5444320 |EST -1 GAAGCCTTTTCTTTTCT | 0.10%

IMAGE 240014 GTTCACCCTCACCAAGA 8 GCACAACTTAAATAGG 3112 |cDNA Hs.301704 |AW002985 [5849991 |eomesodermin |-1 AACAAGCCATGTTTGCC | 0% (Xenopus CTAGTCCAGGATTGCCT laevis) CACTTGAGACTTGCTA 3112 |Table 3B |Hs.301704 |AW002985 {5849991 |eomesodermin |-1 AACAAGCCATGTTTGCC 0% (Xenopus CTAGTCCAGGATTGCCT laevis) CACTTGAGACTTGCTA 3113 |cDNA Hs.318885 {NM_000636 [10835186 | superoxide TACTTTGGGGACTTGTA | 0.10% dismutase 2 GGGATGCCTTTCTAGTC

CTATTCTATTGCAGTT

3114 [literature |Hs.41682 |NM_007334 [7669498 [killer cell lectin- GGGCAGAGAAGGTGGAG 0% like receptor D AGTAAAGACCCAACATT

ACTAACAATGATACAG

3115 |cDNA Hs. 71245 |AI954499 5746809 |EST TGGTAATAGTGTTTGAC 0%

IMAGE 502221 TCCAGGGAAGAACAGAT

GGGTGCCAGAGTGAAA

3116 |cDNA Hs.75596 |NM_000878 [4504664 |interleukin 2 1 ATGGAAATTGTATTTGC 0% receptor, beta CTTCTCCACTTTGGGAG

GCTCCCACTTCTTGGG

436 cDNA Hs.75703 [NM_002984 [4506844 | small inducible CCACTGTCACTGTTTCT 0% cytokine A4 CTGCTGTTGCAAATACA

TGGATAACACATTTGA

436 cDNA Hs.75703 |NM_002984 }4506844 [small inducible }1 CCACTGTCACTGTTTCT | 0.10% cytokine A4 CTGCTGTTGCAAATACA

TGGATAACACATTTGA

436 cDNA Hs.75703 |NM_002984 [4506844 small inducible GTCCACTGTCACTGTTT | 0% cytokine Ad CTCTGCTGTTGCAAARTA

CATGGATAACACATTT

436 cDNA Hs.75703 |NM_002984 14506844 |small inducible |-1 TGGTCCACTGTCACTGT | 0.10% cytokine A4 TTCTCTGCTGTTGCAAA

TACATGGATAACACAT

415 cDNA |Hs.85258 |BC025715 [19344021 [CD8 antigen CTGAGAGCCCAAACTGC | 0.10%

TGTCCCAAACATGCACT

TCCTTGCTTAAGGTAT

3117 {cDNA AAB06222 12874972 |cDNA 196D7 |-1 TGATTTCTGTAATGTTT 0%

GACCTAATAATAGCCCT

TTTCGTCTCTGACCCA

WBC [NA [NA [NA Ina | WA INA 10.10%

WPT [NA [WA [WA [NA | [WA JNA [ 0%

Claims

© WO 2004/042346 PCT/US2003/012946 We claim:

1. A composition for assessing the immune status of an individual comprising a nucleotide sequence for detecting a gene wherein said gene is expressed at different levels depending upon the rate of hematopoiesis or the distribution of hematopoietic cells along their maturation pathway in said individual.

2. The composition of claim 1 wherein said gene comprises a nucleotide sequence chosen from SEQ ID NO: 52, SEQ ID NO: 67, SEQ ID NO: 19, SEQ ID NO: 39, SEQ ID NO: 63, SEQ ID NO: 26, SEQ ID NO: 68, SEQ ID NO: 13, SEQ ID NO: 200, and SEQ ID NO: 36.

3. The composition of claim 1 wherein said expression level is detected by measuring the RNA level expressed by said gene.

4. The composition of claim 3, wherein said expression level is detected by isolating said RNA from said individual prior to measuring the RNA level expressed by said gene.

5. The composition of claim 3 wherein said RNA level is detected by PCR.

6. The composition of claim 3 wherein said RNA level is detected by hybridization.

7. The composition of claim 6 wherein said RNA level is detected by hybridization to an oligonucleotide.

8. The composition of claim 7 wherein said oligonucleotide comprises DNA, RNA, ¢DNA, PNA, genomic DNA, or synthetic oligonucleotides.

9. The composition of claim 1, wherein said one or more genes comprise a nucleotide selected from a nucleotide sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ 1D NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ 1D NO:40, SEQ ID NO:41, 214 Amended sheet: 25 May 2007

SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78,SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87,SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ 1D NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID NO:183, SEQ ID

215 Amended sheet: 25 May 2007

NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215,SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID NO:319, SEQ ID

216 Amended sheet: 25 May 2007

NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID NO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:270S, SEQ ID NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID

217 Amended sheet: 25 May 2007

NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ 1D NO:2709, SEQ ID NO:2653, SEQ ID NO:2729.

10. The composition of claim 9, wherein said expression level is detected by measuring the RNA level expressed by said one or more genes.

11. The composition of claim 10, wherein said RNA level is detected by PCR.

12. The composition of claim 10, wherein said RNA level is detected by hybridization.

13. The composition of claim 1, wherein said expression level is detected by measuring one or more proteins expressed by said one or more genes.

14. A composition for diagnosing or monitoring transplant rejection in an individual comprising detecting a rate of hematopoiesis.

15. The composition of claim 14, wherein said detecting is applied to a sample isolated from the individual.

16. The composition of claim 14, wherein said detecting is selected from the group consisting of: RNA profiling assay, immunoassay, fluorescent activated cell sorting, protein assay, MRI imaging, bone marrow aspiration, and nuclear imaging.

17. The composition of claim 16, wherein said RNA profiling assay is a PCR based assay.

18. The composition of claim 6, wherein said RNA profile assay is a hybridization based assay.

19. The composition of claim 16, wherein said RNA profiling assay further comprises detecting the expression level of one or more genes in said individual where said one or more genes comprise a nucleotide sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, 218 Amended sheet: 25 May 2007

SEQ ID NO:45,SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63,SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72,SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81,SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ 1D NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID

219 Amended sheet: 25 May 2007

NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ 1D NO:249, SEQ ID NO:250, SEQ 1D NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ 1D NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID

220 Amended sheet: 25 May 2007

NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID NO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID

NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID

NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID

NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID

NO:2705, SEQ ID NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID

NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID NO:2660, SEQ ID

NO:2666, SEQ ID NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID

NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID NO:2630, SEQ ID

NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID

221 Amended sheet: 25 May 2007

NO:2665, SEQ ID NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID NO:2653, SEQ ID NO:2729.

20. The composition of claim 14, wherein said transplant rejection is selected from the group consisting of: heart transplant rejection, kidney transplant rejection, liver transplant rejection, pancreas transplant rejection, pancreatic islet transplant rejection, lung transplant rejection, bone marrow transplant rejection, stem cell transplant rejection, xenotransplant rejection, and mechanical organ replacement rejection.

21. The composition of claim 20, wherein said transplant rejection is heart transplant rejection.

22. The composition of claim 20, wherein said transplant rejection is liver transplant rejection.

23. The composition of claim 20, wherein said transplant rejection is kidney transplant rejection.

24. The composition of claim 20, wherein said transplant rejection is bone marrow transplant rejection. ’ 25. The composition of claim 20, wherein said transplant rejection is pancreatic islet transplant rejection.

26. The composition of claim 20, wherein said transplant rejection is stem cell transplant rejection.

27. A composition for diagnosing or monitoring transplant rejection in an individual comprising a nucleotide sequence for detecting a gene wherein in said gene detects a rate of hematopoiesis or the distribution of hematopoietic cells along their maturation pathway, wherein said detecting is selected from the group consisting of: RNA profiling assay, immunoassay, fluorescent activated cell sorting, protein assay, MRI imaging, bone marrow aspiration, and nuclear imaging.

28. The composition of claim 27, wherein said RNA profile assay is a PCR based assay.

29. The composition of claim 27, wherein said RNA profile assay is a hybridization based assay.

30. The composition of claim 27, wherein said RNA profile assay further comprises detecting the expression level of one or more genes in said individual where said one or more genes comprise a nucleotide sequence 222 Amended sheet: 25 May 2007 selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID

223 Amended sheet: 25 May 2007

NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ 1D NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID

224 Amended sheet: 25 May 2007

NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ 1D NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ 1D NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NQO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID NO:269S, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID NO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID NO:267S, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID

225 Amended sheet: 25 May 2007

NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID NO:2653, SEQ ID NO:2729.

31. The composition of claim 27, wherein said transplant rejection is selected from the group consisting of: heart transplant rejection, kidney transplant rejection, liver transplant rejection, pancreas transplant rejection, pancreatic islet transplant rejection, lung transplant rejection, bone marrow transplant rejection, stem cell transplant rejection, xenotransplant rejection, and mechanical organ replacement rejection.

32. The composition of claim 31, wherein said transplant rejection is heart transplant rejection.

33. The composition of claim 31, wherein said transplant rejection is liver transplant rejection.

34. The composition of claim 31, wherein said transplant rejection is kidney transplant rejection.

3S. The composition of claim 31, wherein said transplant rejection is bone marrow transplant rejection.

36. The composition of claim 31, wherein said transplant rejection is pancreatic islet transplant rejection.

37. The composition of claim 31, wherein said transplant rejection is stem cell transplant rejction.

38. A composition for diagnosing or monitoring transplant rejection in a patient, comprising one or more genes wherein said one or more genes comprise a nucleotide sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID 226 Amended sheet: 25 May 2007

NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ 1D NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53,SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NQO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:114, SEQ ID NO:115,SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID NO:183, SEQ ID

227 Amended sheet: 25 May 2007

NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID NO:319, SEQ ID

228 Amended sheet: 25 May 2007

NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID NO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID 229 Amended sheet: 25 May 2007 ki

NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID NO:2653, SEQ ID NO:2729.

39. The composition of claim 38, further comprising one or more additional genes wherein said one or more additional genes comprise a nucleotide sequence selected from the group consisting of: SEQ ID NO:8, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:89, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151.

40. A composition for diagnosing or monitoring transplant rejection in a patient, comprising one or more genes in said patient to diagnose or monitor transplant rejection in said patient wherein said one or more genes comprise a nucleotide sequence selected from the group consisting of SEQ 1D NO: 36, 87, 94, 107, and 91.

41. The composition of claim 40 wherein said nucleotide sequence is SEQ ID NO: 36.

42. The composition of claim 40 wherein said nucleotide sequence is SEQ ID NO: 87.

43. The composition of claim 40 wherein said nucleotide sequence is SEQ ID NO: 94. 44, The composition of claim 40 wherein said nucleotide sequence is SEQ ID NO: 107.

45. The composition of claim 40 wherein said nucleotide sequence is SEQ ID NO: 91.

46. A composition for diagnosing or monitoring cardiac transplant rejection in a patient, comprising one or more genes wherein said one or more genes comprise a nucleotide sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ 1D NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, 230 Amended sheet: 25 May 2007

SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ 1D NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57,SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID 231 Amended sheet: 25 May 2007

NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ 1D NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID

232 Amended sheet: 25 May 2007

NO:318, SEQ ID NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332.

47. The composition of claim 46, further comprising one or more additional genes wherein said one or more additional genes comprise a nucleotide sequence selected from the group consisting of: SEQ ID NO:8, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:97, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151.

48. A composition for diagnosing or monitoring kidney transplant rejection in a patient, comprising one or more genes selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15,SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID 233 Amended sheet: 25 May 2007

NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID

234 Amended sheet: 25 May 2007

NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:264S5, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID NO:2671, SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID NO:2748, SEQ ID

NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID

235 Amended sheet: 25 May 2007

NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ 1D NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID NO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID NO:2681, SEQ ID NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID NO:2653, SEQ ID NO:2729.

49. The composition of claim 48, further comprising one or more additional genes wherein said one or more additional genes comprise a nucleotide sequence selected from the group consisting of: SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:89, SEQ ID NO:99, SEQ 1D NO:100, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151.

50. A composition for detecting transplant rejection comprising one or more PCR primers wherein said PCR primers consist of nucleotide sequences selected from the group consisting of SEQ ID NO:665, SEQ ID NO:666, SEQ ID NO:667, SEQ ID NO:668, SEQ ID NO:669, SEQ ID NO:670, SEQ ID NO:671, SEQ ID NO:672, SEQ ID NO:673, SEQ ID NO:674, SEQ ID NO:675, SEQ ID NO:676, SEQ ID NO:677, SEQ ID NO:678, SEQ ID NO:679, SEQ ID NO:680, SEQ ID NO:681, SEQ ID NO:682, 236 Amended sheet: 25 May 2007

SEQ ID NO:683, SEQ ID NO:684, SEQ ID NO:685, SEQ ID NO:686, SEQ ID NO:687, SEQ ID NO:688, SEQ ID NO:689, SEQ ID NO:690, SEQ ID NO:691, SEQ ID NO:692, SEQ ID NO:693, SEQ ID NO:694, SEQ ID NO:695, SEQ ID NO:696, SEQ ID NO:697, SEQ ID NO:698, SEQ ID NO:699, SEQ ID NO:700, SEQ ID NO:701, SEQ ID NO:702, SEQ ID NO:703, SEQ ID NO:704, SEQ 1D NO:705, SEQ ID NO:706, SEQ ID NO:707, SEQ ID NO:708, SEQ ID NO:709, SEQ ID NO:710, SEQ ID NO:711, SEQ ID NO:712, SEQ ID NO:713, SEQ ID NO:714, SEQ ID NO:715, SEQ ID NO:716, SEQ ID NO:717, SEQ ID NO:718, SEQ ID NO:719, SEQ ID NO:720, SEQ ID NO:721, SEQ ID NO:722, SEQ ID NO:723, SEQ ID NO:724, SEQ ID NO:725, SEQ ID NO:726, SEQ ID NO:727, SEQ ID NO:728, SEQ ID NO:729, SEQ ID NO:730, SEQ ID NO:731, SEQ ID NO:732, SEQ ID NO:733, SEQ ID NO:734, SEQ ID NO:735, SEQ ID NO:736, SEQ ID NO:737, SEQ ID NO:738, SEQ ID NO:739, SEQ ID NO:740, SEQ ID NO:741, SEQ ID NO:742, SEQ ID NO:743, SEQ ID NO:744, SEQ ID NO:745, SEQ ID NO:746, SEQ ID NO:747, SEQ ID NO:748, SEQ ID NO:749, SEQ ID NO:750, SEQ ID NO:751, SEQ ID NO:752, SEQ ID NO:753, SEQ ID NO:754, SEQ ID NO:755, SEQ ID NO:756, SEQ ID NO:757, SEQ ID NO:758, SEQ ID NO:759, SEQ ID NO:760, SEQ ID NO:761, SEQ ID NO:762, SEQ ID NO:763, SEQ ID NO:764, SEQ ID NO:765, SEQ ID NO:766, SEQ ID NO:767, SEQ ID NO:768, SEQ ID NO:769, SEQ ID NO:770, SEQ ID NO:771, SEQ ID NO:772, SEQ ID NO:773, SEQ ID NO:774,

: SEQ ID NO:775, SEQ ID NO:776, SEQ ID NO:777, SEQ ID NO:778, SEQ ID NO:779, SEQ ID NO:780, SEQ ID NO:781, SEQ ID NO:782, SEQ ID NO:783, SEQ ID NO:784, SEQ ID NO:785, SEQ ID NO:786, SEQ ID NO:787, SEQ ID NO:788, SEQ ID NO:789, SEQ ID NO:790, SEQ ID NO:791, SEQ ID NO:792, SEQ ID NO:793, SEQ ID NO:794, SEQ ID NO:795, SEQ ID NO:796, SEQ ID NO:797, SEQ ID NO:798, SEQ ID NO:799, SEQ ID NO:800, SEQ ID NO:801, SEQ ID NO:802, SEQ ID NO:803, SEQ ID NO:804, SEQ ID NO:805, SEQ ID NO:806, SEQ ID NO:807, SEQ ID NO:808, SEQ ID NO:809, SEQ ID NO:810, SEQ ID NO:811, SEQ ID NO:812, SEQ ID NO:813, SEQ ID NO:814, SEQ ID NO:815, SEQ ID NO:816, SEQ ID NO:817, SEQ ID NO:818,

237 Amended sheet: 25 May 2007

SEQ ID NO:819, SEQ ID NO:820, SEQ ID NO:821, SEQ ID NO:822, SEQ ID NO:823, SEQ ID NO:824, SEQ ID NO:825, SEQ ID NO:826, SEQ ID NO:827, SEQ ID NO:828, SEQ ID NO:829, SEQ ID NO:830, SEQ ID NO:831, SEQ ID NO:832, SEQ ID NO:833, SEQ ID NO:834, SEQ ID NO:835, SEQ ID NO:836, SEQ ID NO:837, SEQ ID NO:838, SEQ ID NO:839, SEQ ID NO:840, SEQ ID NO:841, SEQ ID NO:842, SEQ ID NO:843, SEQ ID NO:844, SEQ ID NO:845, SEQ ID NO:846, SEQ ID NO:847, SEQ ID NO:848, SEQ ID NO:849, SEQ ID NO:850, SEQ ID NO:851, SEQ ID NO:852, SEQ ID NO:853, SEQ ID NO:854, SEQ ID NO:855, SEQ ID NO:856, SEQ ID NO:857, SEQ ID NO:858, SEQ ID NO:859, SEQ ID NO:860, SEQ ID NO:861, SEQ ID NO:862, SEQ ID NO:863, SEQ ID NO:864, SEQ ID NO:865, SEQ ID NO:866, SEQ ID NO:867, SEQ ID NO:868, SEQ ID NO:869, SEQ ID NO:870, SEQ ID NO:871, SEQ ID NO:872, SEQ ID NO:873, SEQ ID NO:874, SEQ ID NO:875, SEQ ID NO:876, SEQ ID NO:877, SEQ ID NO:878, SEQ ID NO:879, SEQ ID NO:880, SEQ ID NO:881, SEQ ID NO:882, SEQ ID NO:883, SEQ ID NO:884, SEQ ID NO:885, SEQ ID NO:886, SEQ ID NO:887, SEQ ID NO:888, SEQ ID NO:889, SEQ ID NO:890, SEQ ID NO:891, SEQ ID NO:892, SEQ ID NO:893, SEQ ID NO:894, SEQ ID NO:895, SEQ ID NO:896, SEQ ID NO:897, SEQ ID NO:898, SEQ ID NO:899, SEQ ID NO:900, SEQ ID NO:901, SEQ ID NO:902, SEQ ID NO:903, SEQ ID NO:904, SEQ ID NO:905, SEQ ID NO:906, SEQ ID NO:907, SEQ ID NO:908, SEQ ID NO:909, SEQ ID NO:910, SEQ ID NO:911, SEQ ID NO:912, SEQ ID NO:913, SEQ ID NO:914, SEQ ID NO:915, SEQ ID NO:916, SEQ ID NO:917, SEQ ID NO:918, SEQ ID NO:919, SEQ ID NO:920, SEQ ID NO:921, SEQ ID NO:922, SEQ ID NO:923, SEQ ID NO:924, SEQ ID NO:925, SEQ ID NO:926, SEQ ID NO:927, SEQ ID NO:928, SEQ ID NO:929, SEQ ID NO:930, SEQ ID NO:931, SEQ ID NO:932, SEQ ID NO:933, SEQ ID NO:934, SEQ ID NO:935, SEQ ID NO:936, SEQ ID NO:937, SEQ ID NO:938, SEQ ID NO:939, SEQ ID NO:940, SEQ ID NO:941, SEQ ID NO:942, SEQ ID NO:943, SEQ ID NO:944, SEQ ID NO:945, SEQ ID NO:946, SEQ ID NO:947, SEQ ID NO:948, SEQ ID NO:949, SEQ ID NO:950, SEQ ID NO:951, SEQ ID NO:952, SEQ ID NO:953, SEQ ID NO:954,

238 Amended sheet: 25 May 2007

SEQ ID NO:955, SEQ ID NO:956, SEQ ID NO:957, SEQ ID NO:958, SEQ ID NO:959, SEQ ID NO:960, SEQ ID NO:961, SEQ ID NO:962, SEQ ID NO:963, SEQ ID NO:964, SEQ ID NO:965, SEQ ID NO:966, SEQ ID NO:967, SEQ ID NO:968, SEQ ID NO:969, SEQ ID NO:970, SEQ ID NO:971, SEQ ID NO:972, SEQ ID NO:973, SEQ ID NO:974, SEQ ID NO:975, SEQ ID NO:976, SEQ ID NO:977, SEQ ID NO:978, SEQ ID NO:979, SEQ ID NO:980, SEQ ID NO:981, SEQ ID NO:982, SEQ ID NO:983, SEQ ID NO:984, SEQ ID NO:985, SEQ ID NO:986, SEQ ID NO:987, SEQ ID NO:988, SEQ ID NO:989, SEQ ID NO:990, SEQ ID NO:991, SEQ ID NO:992, SEQ ID NO:993, SEQ ID NO:994, SEQ ID NO:995, SEQ ID NO:996, SEQ ID NO:997, SEQ ID NO:998, SEQ ID NO:999, SEQ ID NO:1000, SEQ ID NO:1001, SEQ ID NO:1002, SEQ ID NO:1003, SEQ ID NO:1004, SEQ ID NO:1005, SEQ ID NO:1006, SEQ ID NO:1007, SEQ ID NO:1008, SEQ ID NO:1009, SEQ ID NO:1010, SEQ ID NO:1011, SEQ ID NO:1012, SEQ ID NO:1013, SEQ ID NO:1014, SEQ ID NO:1015, SEQ ID NO:1016, SEQ ID NO:1017, SEQ ID NO:1018, SEQ ID NO:1019, SEQ ID NO:1020, SEQ ID NO:1021, SEQ ID NO:1022, SEQ ID NO:1023, SEQ ID NO:1024, SEQ ID NO:1025, SEQ ID NO:1026, SEQ ID NO:1027, SEQ ID NO:1028, SEQ ID NO:1029, SEQ ID NO:1030, SEQ ID NO:1031, SEQ ID NO:1032, SEQ ID NO:1033, SEQ ID NO:1034, SEQ ID NO:1035, SEQ ID NO:1036, SEQ ID NO:1037, SEQ ID NO:1038, SEQ ID NO:1039, SEQ ID NO:1040, SEQ ID NO:1041, SEQ ID NO:1042, SEQ ID NO:1043, SEQ ID NO:1044, SEQ ID NO:1045, SEQ ID NO:1046, SEQ ID NO:1047, SEQ ID NO:1048, SEQ ID NO:1049, SEQ ID NO:1050, SEQ ID NO:1051, SEQ ID NO:1052, SEQ ID NO:1053, SEQ ID NO:1054, SEQ ID NO:1055, SEQ ID NO:1056, SEQ ID NO:1057, SEQ ID NO:1058, SEQ ID NO:1059, SEQ ID NO:1060, SEQ ID NO:1061, SEQ ID NO:1062, SEQ ID NO:1063, SEQ ID NO:1064, SEQ ID NO:1065, SEQ ID NO:1066, SEQ ID NO:1067, SEQ ID NO:1068, SEQ ID NO:1069, SEQ ID NO:1070, SEQ ID NO:1071, SEQ ID NO:1072, SEQ ID NO:1073, SEQ ID NO:1074, SEQ ID NO:1075, SEQ ID NO:1076, SEQ ID NO:1077, SEQ ID NO:1078, SEQ ID NO:1079, SEQ ID NO:1080, SEQ ID NO:1081, SEQ ID NO:1082, SEQ ID NO:1083, SEQ ID NO:1084, SEQ ID NO:1085, SEQ ID NO:1086, SEQ ID NO:1087, SEQ ID NO:1088, SEQ ID NO:1089, SEQ ID NO:1090,

239 Amended sheet: 25 May 2007

SEQ ID NO:1091, SEQ ID NO:1092, SEQ ID NO:1093, SEQ ID NO:1094, SEQ ID NO:1095, SEQ ID NO:1096, SEQ ID NO:1097, SEQ ID NO:1098, SEQ ID NO:1099, SEQ ID NO:1100, SEQ ID NO:1101, SEQ ID NO:1102, SEQ ID NO:1103, SEQ ID NO:1104, SEQ ID NO:1105, SEQ ID NO:1106, SEQ ID NO:1107, SEQ ID NO:1108, SEQ ID NO:1109, SEQ ID NO:1110, SEQ ID NO:1111, SEQ ID NO:1112, SEQ ID NO:1113, SEQ ID NO:1114, SEQ ID NO:1115, SEQ ID NO:1116, SEQ ID NO:1117, SEQ ID NO:1118, SEQ ID NO:1119, SEQ ID NO:1120, SEQ ID NO:1121, SEQ ID NO:1122, SEQ ID NO:1123, SEQ ID NO:1124, SEQ ID NO:1125, SEQ ID NO:1126, SEQ ID NO:1127, SEQ ID NO:1128, SEQ ID NO:1129, SEQ ID NO:1130, SEQ ID NO:1131, SEQ ID NO:1132, SEQ ID NO:1133, SEQ ID NO:1134, SEQ ID NO:1135, SEQ ID NO:1136, SEQ ID NO:1137, SEQ ID NO:1138, SEQ ID NO:1139, SEQ ID NO:1140, SEQ ID NO:1141, SEQ ID NO:1142, SEQ ID NO:1143, SEQ ID NO:1144, SEQ ID NO:1145, SEQ ID NO:1146, SEQ ID NO:1147, SEQ ID NO:1148, SEQ ID NO:1149, SEQ ID NO:1150, SEQ ID NO:1151, SEQ ID NO:1152, SEQ ID NO:1153, SEQ ID NO:1154, SEQ ID NO:1155, SEQ ID NO:1156, SEQ ID NO:1157, SEQ ID NO:1158, SEQ ID NO:1159, SEQ ID NO:1160, SEQ ID NO:1161, SEQ ID NO:1162, SEQ ID NO:1163, SEQ ID NO:1164, SEQ ID NO:1165, SEQ ID NO:1166, SEQ ID NO:1167, SEQ ID NO:1168, SEQ ID NO:1169, SEQ ID NO:1170, SEQ ID NO:1171, SEQ ID NO:1172, SEQ ID NO:1173, SEQ ID NO:1174, SEQ ID NO:1175, SEQ ID NO:1176, SEQ ID NO:1177, SEQ ID NO:1178, SEQ ID NO:1179, SEQ ID NO:1180, SEQ ID NO:1181, SEQ ID NO:1182, SEQ ID NO:1183, SEQ ID NO:1184, SEQ ID NO:1185, SEQ ID NO:1186, SEQ ID NO:1187, SEQ ID NO:1188, SEQ ID NO:1189, SEQ 1D NO:1190, SEQ ID NO:1191, SEQ ID NO:1192, SEQ ID NO:1193, SEQ ID NO:1194, SEQ ID NO:1195, SEQ ID NO:1196, SEQ ID NO:1197, SEQ ID NO:1198, SEQ ID NO:1199, SEQ ID NO:1200, SEQ ID NO:1201, SEQ ID NO:1202, SEQ ID NO:1203, SEQ ID NO:1204, SEQ ID NO:1205, SEQ ID NO:1206, SEQ ID NO:1207, SEQ ID NO:1208, SEQ ID NO:1209, SEQ ID NO:1210, SEQ ID NO:1211, SEQ ID NO:1212, SEQ ID NO:1213, SEQ ID NO:1214, SEQ ID NO:1215, SEQ ID NO:1216, SEQ ID NO:1217, SEQ ID NO:1218, SEQ ID NO:1219, SEQ ID NO:1220, SEQ ID NO:1221, SEQ ID NO:1222, SEQ ID NO:1223, SEQ ID NO:1224, SEQ ID NO:1225, SEQ ID NO:1226,

240 Amended sheet: 25 May 2007

SEQ ID NO:1227, SEQ ID NO:1228, SEQ ID NO:1229, SEQ ID NO:1230, SEQ ID NO:1231, SEQ ID NO:1232, SEQ ID NO:1233, SEQ ID NO:1234, SEQ ID NO:1235, SEQ ID NO:1236, SEQ ID NO:1237, SEQ ID NO:1238, SEQ ID NO:1239, SEQ ID NO:1240, SEQ ID NO:1241, SEQ ID NO:1242, SEQ ID NO:1243, SEQ ID NO:1244, SEQ ID NO:1245, SEQ ID NO:1246, SEQ ID NO:1247, SEQ ID NO:1248, SEQ ID NO:1249, SEQ ID NO:1250, SEQ ID NO:1251, SEQ ID NO:1252, SEQ ID NO:1253, SEQ ID NO:1254, SEQ ID NO:1255, SEQ ID NO:1256, SEQ ID NO:1257, SEQ ID NO:1258, SEQ ID NO:1259, SEQ ID NO:1260, SEQ ID NO:1261, SEQ ID NO:1262, SEQ ID NO:1263, SEQ ID NO:1264, SEQ ID NO:1265, SEQ ID NO:1266, SEQ ID NO:1267, SEQ ID NO:1268, SEQ ID NO:1269, SEQ ID NO:1270, SEQ ID NO:1271, SEQ ID NO:1272, SEQ ID NO:1273, SEQ ID NO:1274, SEQ ID NO:1275, SEQ ID NO:1276, SEQ ID NO:1277, SEQ ID NO:1278, SEQ ID NO:1279, SEQ ID NO:1280, SEQ ID NO:1281, SEQ ID NO:1282, SEQ ID NO:1283, SEQ ID NO:1284, SEQ ID NO:1285, SEQ ID NO:1286, SEQ ID NO:1287, SEQ ID NO:1288, SEQ ID NO:1289, SEQ ID NO:1290, SEQ ID NO:1291, SEQ ID NO:1292, SEQ ID NO:1293, SEQ ID NO:1294, SEQ ID NO:1295, SEQ ID NO:1296, SEQ ID NO:1297, SEQ ID NO:1298, SEQ ID NO:1299, SEQ ID NO:1300, SEQ ID NO:1301, SEQ ID NO:1302, SEQ ID NO:1303, SEQ ID NO:1304, SEQ ID NO:1305, SEQ ID NO:1306, SEQ ID NO:1307, SEQ ID NO:1308, SEQ ID NO:1309, SEQ ID NO:1310, SEQ ID NO:1311, SEQ ID NO:1312, SEQ ID NO:1313, SEQ ID NO:1314, SEQ ID NO:1315, SEQ ID NO:1316, SEQ ID NO:1317, SEQ ID NO:1318, SEQ ID NO:1319, SEQ ID NO:1320, SEQ ID NO:1321, SEQ ID NO:1322, SEQ ID NO:1323, SEQ ID NO:1324, SEQ ID NO:1325, SEQ ID NO:1326, SEQ ID NO:1656, SEQ ID NO:1657, SEQ ID NO:1658, SEQ ID NO:1659, SEQ ID NO:1660, SEQ ID NO:1661, SEQ ID NO:1662, SEQ ID NO:1663, SEQ ID NO:1664, SEQ ID NO:1665, SEQ ID NO:1666, SEQ ID NO:1667, SEQ ID NO:1668, SEQ ID NO:1669, SEQ ID NO:1670, SEQ ID NO:1671, SEQ ID NO:1672, SEQ ID NO:1673, SEQ ID NO:1674, SEQ ID NO:1675, SEQ ID NO:1676, SEQ ID NO:1677, SEQ ID NO:1678, SEQ ID NO:1679, SEQ ID NO:1680, SEQ ID NO:1681, SEQ ID NO:1682, SEQ ID NO:1683, SEQ ID NO:1684, SEQ ID NO:1685, SEQ ID NO:1686, SEQ ID NO:1687, SEQ ID NO:1688, SEQ ID NO:1689, SEQ ID NO:1690, SEQ ID NO:1691,

241 Amended sheet: 25 May 2007

SEQ ID NO:1692, SEQ ID NO:1693, SEQ ID NO:1694, SEQ ID NO:1695, SEQ ID NO:1696, SEQ ID NO:1697, SEQ ID NO:1698, SEQ ID NO:1699, SEQ ID NO:1700, SEQ ID NO:1701, SEQ ID NO:1702, SEQ ID NO:1703, SEQ ID NO:1704, SEQ ID NO:1705, SEQ ID NO:1706, SEQ ID NO:1707, SEQ ID NO:1708, SEQ ID NO:1709, SEQ ID NO:1710, SEQ ID NO:1711, SEQ ID NO:1712, SEQ ID NO:1713, SEQ ID NO:1714, SEQ ID NO:1715, SEQ ID NO:1716, SEQ ID NO:1717, SEQ ID NO:1718, SEQ ID NO:1719, SEQ ID NO:1720, SEQ ID NO:1721, SEQ ID NO:1722, SEQ ID NO:1723, SEQ ID NO:1724, SEQ ID NO:1725, SEQ ID NO:1726, SEQ ID NO:1727, SEQ ID NO:1728, SEQ ID NO:1729, SEQ ID NO:1730, SEQ ID NO:1731, SEQ ID NO:1732, SEQ ID NO:1733, SEQ ID NO:1734, SEQ ID NO:1735, SEQ ID NO:1736, SEQ ID NO:1737, SEQ ID NO:1738, SEQ ID NO:1739, SEQ ID NO:1740, SEQ ID NO:1741, SEQ ID NO:1742, SEQ ID NO:1743, SEQ ID NO:1744, SEQ ID NO:1745, SEQ ID NO:1746, SEQ ID NO:1747, SEQ ID NO:1748, SEQ ID NO:1749, SEQ ID NO:1750, SEQ ID NO:1751, SEQ ID NO:1752, SEQ ID NO:1753, SEQ ID NO:1754, SEQ ID NO:1755, SEQ ID NO:1756, SEQ ID NO:1757, SEQ ID NO:1758, SEQ ID NO:1759, SEQ ID NO:1760, SEQ ID NO:1761, SEQ ID NO:1762, SEQ ID NO:1763, SEQ ID NO:1764, SEQ ID NO:1765, SEQ ID NO:1766, SEQ ID NO:1767, SEQ ID NO:1768, SEQ ID NO:1769, SEQ ID NO:1770, SEQ ID NO:1771, SEQ ID NO:1772, SEQ ID NO:1773, SEQ ID NO:1774, SEQ ID NO:1775, SEQ ID NO:1776, SEQ ID NO:1777, SEQ ID NO:1778, SEQ ID NO:1779, SEQ ID NO:1780, SEQ ID NO:1781, SEQ ID NO:1782, SEQ ID NO:1783, SEQ ID NO:1784, SEQ ID NO:1785, SEQ ID NO:1786, SEQ ID NO:1787, SEQ ID NO:1788, SEQ ID NO:1789, SEQ ID NO:1790, SEQ ID NO:1791, SEQ ID NO:1792, SEQ ID NO:1793, SEQ ID NO:1794, SEQ ID NO:1795, SEQ ID NO:1796, SEQ ID NO:1797, SEQ ID NO:1798, SEQ ID NO:1799, SEQ ID NO:1800, SEQ ID NO:1801, SEQ ID NO:1802, SEQ ID NO:1803, SEQ ID NO:1804, SEQ ID NO:1805, SEQ ID NO:1806, SEQ ID NO:1807, SEQ ID NO:1808, SEQ ID NO:1809, SEQ ID NO:1810, SEQ ID NO:1811, SEQ ID NO:1812, SEQ ID NO:1813, SEQ ID NO:1814, SEQ ID NO:1815, SEQ ID NO:1816, SEQ ID NO:1817, SEQ ID NO:1818, SEQ ID NO:1819, SEQ ID NO:1820, SEQ ID NO:1821, SEQ ID NO:1822, SEQ ID NO:1823, SEQ ID NO:1824, SEQ ID NO:1825, SEQ ID NO:1826, SEQ ID NO:1827,

242 Amended sheet: 25 May 2007

SEQ ID NO:1828, SEQ ID NO:1829, SEQ ID NO:1830, SEQ ID NO:1831, SEQ ID NO:1832, SEQ ID NO:1833, SEQ ID NO:1834, SEQ ID NO:1835, SEQ ID NO:1836, SEQ ID NO:1837, SEQ ID NO:1838, SEQ ID NO:1839, SEQ ID NO:1840, SEQ ID NO:1841, SEQ ID NO:1842, SEQ ID NO:1843, SEQ ID NO:1844, SEQ ID NO:1845, SEQ ID NO:1846, SEQ ID NO:1847, SEQ ID NO:1848, SEQ ID NO:1849, SEQ ID NO:1850, SEQ ID NO:1851, SEQ ID NO:1852, SEQ ID NO:1853, SEQ ID NO:1854, SEQ ID NO:18S55, SEQ ID NO:1856, SEQ ID NO:1857, SEQ ID NO:1858, SEQ ID NO:1859, SEQ ID NO:1860, SEQ ID NO:1861, SEQ ID NO:1862, SEQ ID NO:1863, SEQ ID NO:1864, SEQ ID NO:1865, SEQ ID NO:1866, SEQ ID NO:1867, SEQ ID NO:1868, SEQ ID NO:1869, SEQ ID NO:1870, SEQ ID NO:1871, SEQ ID NO:1872, SEQ ID NO:1873, SEQ ID NO:1874, SEQ ID NO:1875, SEQ ID NO:1876, SEQ ID NO:1877, SEQ ID NO:1878, SEQ ID NO:1879, SEQ ID NO:1880, SEQ ID NO:1881, SEQ ID NO:1882, SEQ ID NO:1883, SEQ ID NO:1884, SEQ ID NO:1885, SEQ ID NO:1886, SEQ ID NO:1887, SEQ ID NO:1888, SEQ ID NO:1889, SEQ ID NO:1890, SEQ ID NO:1891, SEQ ID NO:1892, SEQ ID NO:1893, SEQ ID NO:1894, SEQ ID NO:1895, SEQ ID NO:1896, SEQ ID NO:1897, SEQ ID NO:1898, SEQ ID NO:1899, SEQ ID NO:1900, SEQ ID NO:1901, SEQ ID NO:1902, SEQ ID NO:1903, SEQ ID NO:1904, SEQ ID NO:1905, SEQ ID NO:1906, SEQ ID NO:1907, SEQ ID NO:1908, SEQ ID NO:1909, SEQ ID NO:1910, SEQ ID NO:1911, SEQ ID NO:1912, SEQ ID NO:1913, SEQ ID NO:1914, SEQ ID NO:1915, SEQ ID NO:1916, SEQ ID NO:1917, SEQ ID NO:1918, SEQ ID NO:1919, SEQ ID NO:1920, SEQ ID NO:1921, SEQ ID NO:1922, SEQ ID NO:1923, SEQ ID NO:1924, SEQ ID NO:1925, SEQ ID NO:1926, SEQ ID NO:1927, SEQ ID NO:1928, SEQ ID NO:1929, SEQ ID NO:1930, SEQ ID NO:1931, SEQ ID NO:1932, SEQ ID NO:1933, SEQ ID NO:1934, SEQ ID NO:1935, SEQ ID NO:1936, SEQ ID NO:1937, SEQ ID NO:1938, SEQ ID NO:1939, SEQ ID NO:1940, SEQ ID NO:1941, SEQ ID NO:1942, SEQ ID NO:1943, SEQ ID NO:1944, SEQ ID NO:1945, SEQ ID NO:1946, SEQ ID NO:1947, SEQ ID NO:1948, SEQ ID NO:1949, SEQ ID NO:1950, SEQ ID NO:1951, SEQ ID NO:1952, SEQ ID NO:1953, SEQ ID NO:1954, SEQ ID NO:1955, SEQ ID NO:1956, SEQ ID NO:1957, SEQ ID NO:1958, SEQ ID NO:1959, SEQ ID NO:1960, SEQ ID NO:1961, SEQ ID NO:1962, SEQ ID NO:1963,

243 Amended sheet: 25 May 2007

SEQ ID NO:1964, SEQ ID NO:1965, SEQ ID NO:1966, SEQ ID NO:1967, SEQ ID NO:1968, SEQ ID NO:1969, SEQ ID NO:1970, SEQ ID NO:1971, SEQ ID NO:1972, SEQ ID NO:1973, SEQ ID NO:1974, SEQ ID NO:1975, SEQ ID NO:1976, SEQ ID NO:1977, SEQ ID NO:1978, SEQ ID NO:1979, SEQ ID NO:1980, SEQ ID NO:1981, SEQ ID NO:1982, SEQ ID NO:1983, SEQ ID NO:1984, SEQ ID NO:1985, SEQ ID NO:1986, SEQ ID NO:1987, SEQ ID NO:1988, SEQ ID NO:1989, SEQ ID NO:1990, SEQ ID NO:1991, SEQ ID NO:1992, SEQ ID NO:1993, SEQ ID NO:1994, SEQ ID NO:1995, SEQ ID NO:1996, SEQ ID NO:1997, SEQ ID NO:1998, SEQ ID NO:1999, SEQ ID NO:2000, SEQ ID NO:2001, SEQ ID NO:2002, SEQ ID NO:2003, SEQ ID NO:2004, SEQ ID NO:2005, SEQ ID NO:2006, SEQ ID NO:2007, SEQ ID NO:2008, SEQ ID NO:2009, SEQ ID NO:2010, SEQ ID NO:2011, SEQ ID NO:2012, SEQ ID NO:2013, SEQ ID NO:2014, SEQ ID NO:2015, SEQ ID NO:2016, SEQ ID NO:2017, SEQ ID NO:2018, SEQ ID NO:2019, SEQ ID NO:2020, SEQ ID NO:2021, SEQ ID NO:2022, SEQ ID NO:2023, SEQ ID NO:2024, SEQ ID NO:2025, SEQ ID NO:2026, SEQ ID NO:2027, SEQ ID NO:2028, SEQ ID NO:2029, SEQ ID NO:2030, SEQ ID NO:2031, SEQ ID NO:2032, SEQ ID NO:2033, SEQ ID NO:2034, SEQ ID NO:2035, SEQ ID NO:2036, SEQ ID NO:2037, SEQ ID NO:2038, SEQ ID NO:2039, SEQ ID NO:2040, SEQ ID NO:2041, SEQ ID NO:2042, SEQ ID NO:2043, SEQ ID NO:2044, SEQ ID NO:2045, SEQ ID NO:2046, SEQ ID NO:2047, SEQ ID NO:2048, SEQ ID NO:2049, SEQ ID NO:2050, SEQ ID NO:2051, SEQ ID NO:2052, SEQ ID NO:2053, SEQ ID NO:2054, SEQ ID NO:2055, SEQ ID NO:2056, SEQ ID NO:2057, SEQ ID NO:2058, SEQ ID NO:2059, SEQ ID NO:2060, SEQ ID NO:2061, SEQ ID NO:2062, SEQ ID NO:2063, SEQ ID NO:2064, SEQ ID NO:2065, SEQ ID NO:2066, SEQ ID NO:2067, SEQ ID NO:2068, SEQ ID NO:2069, SEQ ID NO:2070, SEQ ID NO:2071, SEQ ID NO:2072, SEQ ID NO:2073, SEQ ID NO:2074, SEQ ID NO:2075, SEQ ID NO:2076, SEQ ID NO:2077, SEQ ID NO:2078, SEQ ID NO:2079, SEQ ID NO:2080, SEQ ID NO:2081, SEQ ID NO:2082, SEQ ID NO:2083, SEQ ID NO:2084, SEQ ID NO:2085, SEQ ID NO:2086, SEQ ID NO:2087, SEQ ID NO:2088, SEQ ID NO:2089, SEQ ID NO:2090, SEQ ID NO:2091, SEQ ID NO:2092, SEQ ID NO:2093, SEQ ID NO:2094, SEQ ID NO:2095, SEQ ID NO:2096, SEQ ID NO:2097, SEQ ID NO:2098, SEQ ID NO:2099,

244 Amended sheet: 25 May 2007

SEQ ID NO:2100, SEQ ID NO:2101, SEQ ID NO:2102, SEQ ID NO:2103, SEQ ID NO:2104, SEQ ID NO:2105, SEQ ID NO:2106, SEQ ID NO:2107, SEQ ID NO:2108, SEQ ID NO:2109, SEQ ID NO:2110, SEQ ID NO:2111, SEQ ID NO:2112, SEQ ID NO:2113, SEQ ID NO:2114, SEQ ID NO:2115, SEQ ID NO:2116, SEQ ID NO:2117, SEQ ID NO:2118, SEQ ID NO:2119, SEQ ID NO:2120, SEQ ID NO:2121, SEQ ID NO:2122, SEQ ID NO:2123, SEQ ID NO:2124, SEQ ID NO:2125, SEQ ID NO:2126, SEQ ID NO:2127, SEQ ID NO:2128, SEQ ID NO:2129, SEQ ID NO:2130, SEQ ID NO:2131, SEQ ID NO:2132, SEQ ID NO:2133, SEQ ID NO:2134, SEQ ID NO:2135, SEQ ID NO:2136, SEQ ID NO:2137, SEQ ID NO:2138, SEQ ID NO:2139, SEQ ID NO:2140, SEQ ID NO:2141, SEQ ID NO:2142, SEQ ID NO:2143, SEQ ID NO:2144, SEQ ID NO:2145, SEQ ID NO:2146, SEQ ID NO:2147, SEQ ID NO:2148, SEQ ID NO:2149, SEQ ID NO:2150, SEQ ID NO:2151.

51. A composition for detecting transplant rejection comprising one or more PCR primers wherein said PCR primers consist of nucleotide sequences selected from the group consisting of SEQ 1D NO:1327, SEQ ID NO:1328, SEQ ID NO:1329, SEQ ID NO:1330, SEQ ID NO:1331, SEQ ID NO:1332, SEQ ID NO:1333, SEQ ID NO:1334, SEQ ID NO:1335, SEQ ID NO:1336, SEQ ID NO:1337, SEQ ID NO:1338, SEQ ID NO:1339, SEQ ID NO:1340, SEQ ID NO:1341, SEQ ID NO:1342, SEQ ID NO:1343, SEQ ID NO:1344, SEQ ID NO:1345, SEQ ID NO:1346, SEQ ID NO:1347, SEQ ID NO:1348, SEQ ID NO:1349, SEQ ID NO:1350, SEQ ID NO:1351, SEQ ID NO:1352, SEQ ID NO:1353, SEQ ID NO:1354, SEQ ID NO:1355, SEQ ID NO:1356, SEQ ID NO:1357, SEQ ID NO:1358, SEQ ID NO:1359, SEQ ID NO:1360, SEQ ID NO:1361, SEQ ID NO:1362, SEQ ID NO:1363, SEQ ID NO:1364, SEQ ID NO:1365, SEQ ID NO:1366, SEQ ID NO:1367, SEQ ID NO:1368, SEQ ID NO:1369, SEQ ID NO:1370, SEQ ID NO:1371, SEQ ID NO:1372, SEQ ID NO:1373, SEQ ID NO:1374, SEQ ID NO:1375, SEQ ID NO:1376, SEQ ID NO:1377, SEQ ID NO:1378, SEQ ID NO:1379, SEQ ID NO:1380, SEQ ID NO:1381, SEQ ID NO:1382, SEQ ID NO:1383, SEQ ID NO:1384, SEQ ID NO:1385, SEQ ID NO:1386, SEQ ID NO:1387, SEQ ID NO:1388, SEQ ID NO:1389, SEQ ID NO:1390, SEQ ID NO:1391, SEQ ID NO:1392, SEQ ID NO:1393, SEQ ID NO:1394, SEQ ID NO:1395, SEQ ID NO:1396, SEQ ID NO:1397, SEQ ID NO:1398, SEQ ID NO:1399, SEQ ID NO:1400, 245 Amended sheet: 25 May 2007

SEQ ID NO:1401, SEQ ID NO:1402, SEQ ID NO:1403, SEQ ID NO:1404, SEQ ID NO:1405, SEQ ID NO:1406, SEQ ID NO:1407, SEQ ID NO:1408, SEQ ID NO:1409, SEQ ID NO:1410, SEQ ID NO:1411, SEQ ID NO:1412, SEQ ID NO:1413, SEQ ID NO:1414, SEQ ID NO:1415, SEQ ID NO:1416, SEQ ID NO:1417, SEQ ID NO:1418, SEQ ID NO:1419, SEQ ID NO:1420, SEQ ID NO:1421, SEQ ID NO:1422, SEQ ID NO:1423, SEQ ID NO:1424, SEQ ID NO:1425, SEQ ID NO:1426, SEQ ID NO:1427, SEQ ID NO:1428, SEQ ID NO:1429, SEQ ID NO:1430, SEQ ID NO:1431, SEQ ID NO:1432, SEQ ID NO:1433, SEQ ID NO:1434, SEQ ID NO:1435, SEQ ID NO:1436, SEQ ID NO:1437, SEQ ID NO:1438, SEQ ID NO:1439, SEQ 1D NO:1440, SEQ ID NO:1441, SEQ ID NO:1442, SEQ ID NO:1443, SEQ ID NO:1444, SEQ ID NO:1445, SEQ ID NO:1446, SEQ ID NO:1447, SEQ ID NO:1448, SEQ ID NO:1449, SEQ ID NO:1450, SEQ ID NO:1451, SEQ ID NO:1452, SEQ ID NO:1454, SEQ ID NO:1455, SEQ ID NO:1456, SEQ ID NO:1457, SEQ ID NO:1458, SEQ ID NO:1459, SEQ ID NO:1460, SEQ ID NO:1461, SEQ ID NO:1462, SEQ ID NO:1463, SEQ ID NO:1464, SEQ ID NO:1465, SEQ ID NO:1466, SEQ ID NO:1467, SEQ ID NO:1468, SEQ ID NO:1469, SEQ ID NO:1470, SEQ ID NO:1471, SEQ ID NO:1472, SEQ ID NO:1473, SEQ ID NO:1474, SEQ ID NO:1475, SEQ ID NO:1476, SEQ ID NO:1477, SEQ ID NO:1478, SEQ ID NO:1479, SEQ ID NO:1480, SEQ ID NO:1481, SEQ ID NO:1482, SEQ ID NO:1483, SEQ ID NO:1484, SEQ ID NO:1485, SEQ ID NO:1486, SEQ ID NO:1487, SEQ ID NO:1488, SEQ ID NO:1489, SEQ ID NO:1490, SEQ ID NO:1491, SEQ ID NO:1492, SEQ ID NO:1493, SEQ ID NO:1494, SEQ ID NO:1495, SEQ ID NO:1496, SEQ ID NO:1497, SEQ ID NO:1498, SEQ ID NO:1499, SEQ ID NO:1500, SEQ ID NO:1501, SEQ ID NO:1502, SEQ ID NO:1503, SEQ ID NO:1504, SEQ ID NO:1505, SEQ ID NO:1506, SEQ ID NO:1507, SEQ ID NO:1508, SEQ ID NO:1509, SEQ ID NO:1510, SEQ ID NO:1511, SEQ ID NO:1512, SEQ ID NO:1513, SEQ ID NO:1514, SEQ ID NO:1515, SEQ ID NO:1516, SEQ ID NO:1517, SEQ ID NO:1518, SEQ ID NO:1519, SEQ ID NO:1520, SEQ ID NO:1521, SEQ ID NO:1522, SEQ ID NO:1523, SEQ ID NO:1524, SEQ ID NO:1525, SEQ ID NO:1526, SEQ ID NO:1527, SEQ ID NO:1528, SEQ ID NO:1529, SEQ ID NO:1530, SEQ ID NO:1531, SEQ ID NO:1532, SEQ ID NO:1533, SEQ ID NO:1534, SEQ ID NO:1535, SEQ ID NO:1536, SEQ ID NO:1537,

246 Amended sheet: 25 May 2007

SEQ ID NO:1538, SEQ ID NO:1539, SEQ ID NO:1540, SEQ ID NO:1541, SEQ ID NO:1542, SEQ ID NO:1543, SEQ ID NO:1544, SEQ ID NO:1545, SEQ ID NO:1546, SEQ ID NO:1547, SEQ ID NO:1548, SEQ ID NO:1549, SEQ ID NO:1550, SEQ ID NO:1551, SEQ ID NO:1552, SEQ ID NO:1553, SEQ ID NO:1554, SEQ ID NO:1555, SEQ ID NO:1556, SEQ ID NO:1557, SEQ ID NO:1558, SEQ ID NO:1559, SEQ ID NO:1560, SEQ ID NO:1561, SEQ ID NO:1562, SEQ ID NO:1563, SEQ ID NO:1564, SEQ ID NO:1565, SEQ ID NO:1566, SEQ ID NO:1567, SEQ ID NO:1568, SEQ ID NO:1569, SEQ ID NO:1570, SEQ ID NO:1571, SEQ ID NO:1572, SEQ ID NO:1573, SEQ ID NO:1574, SEQ ID NO:1575, SEQ ID NO:1576, SEQ ID NO:1577, SEQ ID NO:1578, SEQ ID NO:1579, SEQ ID NO:1580, SEQ ID NO:1581, SEQ ID NO:1582, SEQ ID NO:1583, SEQ ID NO:1584, SEQ ID NO:1585, SEQ ID NO:1586, SEQ ID NO:1587, SEQ ID NO:1588, SEQ ID NO:1589, SEQ ID NO:1590, SEQ ID NO:1591, SEQ ID NO:1592, SEQ ID NO:1593, SEQ ID NO:15%4, SEQ ID NO:, SEQ ID NO:1595, SEQ ID NO:1596, SEQ ID NO:1597, SEQ ID NO:1598, SEQ ID NO:1599, SEQ 1D NO:1600, SEQ ID NO:1601, SEQ ID NO:1602, SEQ ID NO:1603, SEQ ID NO:1604, SEQ ID NO:1605, SEQ ID NO:1606, SEQ ID NO:1607, SEQ ID NO:1608, SEQ ID NO:1609, SEQ ID NO:1610, SEQ ID NO:1611, SEQ ID NO:1612, SEQ ID NO:1613, SEQ ID NO:1614, SEQ ID NO:1615, SEQ ID NO:1616, SEQ ID NO:1617, SEQ ID NO:1618, SEQ ID NO:1619, SEQ ID NO:1620, SEQ ID NO:1621, SEQ ID NO:1622, SEQ ID NO:1623, SEQ ID NO:1624, SEQ ID NO:1625, SEQ ID NO:1626, SEQ ID NO:1627, SEQ ID NO:1628, SEQ ID NO:1629, SEQ ID NO:1630, SEQ ID NO:1631, SEQ ID NO:1632, SEQ ID NO:1633, SEQ ID NO:1634, SEQ ID NO:1635, SEQ ID NO:1636, SEQ ID NO:1637, SEQ ID NO:1638, SEQ ID NO:1639, SEQ ID NO:1640, SEQ ID NO:1641, SEQ ID NO:1642, SEQ ID NO:1643, SEQ ID NO:1644, SEQ ID NO:1645, SEQ ID NO:1646, SEQ ID NO:1647, SEQ ID NO:1648, SEQ ID NO:1649, SEQ ID NO:1650, SEQ ID NO:1651, SEQ ID NO:1652, SEQ ID NO:1653, SEQ ID NO:1654, SEQ ID NO:1655, SEQ ID NO:1656, SEQ ID NO:1657, SEQ ID NO:2152, SEQ ID NO:, SEQ ID NO:2153, SEQ ID NO:, SEQ ID NO:2154, SEQ ID NO:, SEQ ID NO:, SEQ ID NO: SEQ ID NO:2145, SEQ ID NO:, SEQ ID NO:2156, SEQ ID NO:2157, SEQ ID NO:2158, SEQ ID NO:2159, SEQ ID NO:, SEQ ID NO:2160,

247 Amended sheet: 25 May 2007

SEQ ID NO:2161, SEQ ID NO:2162, SEQ ID NO:2163, SEQ ID NO:2164, SEQ ID NO:, SEQ ID NO:2165, SEQ ID NO:, SEQ ID NO:2166, SEQ ID NO:2167, SEQ ID NO:2168, SEQ ID NO:2169, SEQ ID NO:2170, SEQ ID NO:2171, SEQ ID NO:2172, SEQ ID NO:2173, SEQ ID NO:2174, SEQ ID NO:2175, SEQ ID NO:2176, SEQ ID NO:2177, SEQ ID NO:2178, SEQ ID NO:2179, SEQ ID NO:2180, SEQ ID NO:2181, SEQ ID NO:2182, SEQ ID NO:2183, SEQ ID NO:2184, SEQ ID NO:2185, SEQ ID NO:2186, SEQ ID NO:2187, SEQ ID NO:2188, SEQ ID NO:2189, SEQ ID NO:2190, SEQ ID NO:2191, SEQ ID NO:2192, SEQ ID NO:2193, SEQ ID NO:2194, SEQ ID NO:2195, SEQ ID NO:2196, SEQ ID NO:2197, SEQ ID NO:2198, SEQ ID NO:2199, SEQ ID NO:2200, SEQ ID NO:2201, SEQ 1D NO:2202, SEQ ID NO:2203, SEQ ID NO:2204, SEQ ID NO:2205, SEQ ID NO:2206, SEQ ID NO:2207, SEQ ID NO:2208, SEQ ID NO:2209, SEQ ID NO:2210, SEQ ID NO:2211, SEQ ID NO:2212, SEQ ID NO:2213, SEQ ID NO:2214, SEQ ID NO:2215, SEQ ID NO:2216, SEQ ID NO:2217, SEQ ID NO:2218, SEQ ID NO:2219, SEQ ID NO:2220, SEQ ID NO:2221, SEQ ID NO:2222, SEQ ID NO:2223, SEQ ID NO:2224, SEQ ID NO:2225, SEQ ID NO:2226, SEQ ID NO:2227, SEQ ID NO:2228, SEQ ID NO:2229, SEQ ID NO:2230, SEQ ID NO:2231, SEQ ID NO:2232, SEQ ID NO:2233, SEQ ID NO:2234, SEQ ID NO:2235, SEQ ID NO:2236, SEQ ID NO:2237, SEQ ID NO:2238, SEQ ID NO:2239, SEQ ID NO:2240, SEQ ID NO:2241, SEQ ID NO:2242, SEQ ID NO:2243, SEQ ID NO:2244, SEQ ID NO:2245, SEQ ID NO:2246, SEQ ID NO:2247, SEQ ID NO:2248, SEQ ID NO:2249, SEQ ID NO:2250, SEQ ID NO:2251, SEQ ID NO:2252, SEQ ID NO:2253, SEQ ID NO:2254, SEQ ID NO:2255, SEQ ID NO:2256, SEQ ID NO:2257, SEQ ID NO:2258, SEQ ID NO:2259, SEQ ID NO:2260, SEQ ID NO:2261, SEQ ID NO:2262, SEQ ID NO:2263, SEQ ID NO:2264, SEQ ID NO:2265, SEQ ID NO:2266, SEQ ID NO:2267, SEQ ID NO:2268, SEQ 1D NO:2269, SEQ ID NO:2270, SEQ ID NO:2271, SEQ ID NO:2272, SEQ ID NO:2273, SEQ ID NO:2274, SEQ ID NO:2275, SEQ ID NO:2276, SEQ ID NO:2277, SEQ ID NO:2278, SEQ ID NO:2279, SEQ ID NO:2280, SEQ ID NO:2281, SEQ ID NO:2282, SEQ ID NO:2283, SEQ ID NO:2284, SEQ ID NO:2285, SEQ ID NO:2286, SEQ ID NO:2287, SEQ ID NO:2288, SEQ ID NO:2289, SEQ ID NO:2290, SEQ ID NO:2291, SEQ ID NO:2292, SEQ ID NO:2293, SEQ ID NO:2294, SEQ ID

248 Amended sheet: 25 May 2007

NO:2295, SEQ ID NO:2296, SEQ ID NO:2297, SEQ ID NO:2298, SEQ ID NO:2299, SEQ ID NO:2300, SEQ ID NO:2301, SEQ ID NO:2302, SEQ ID NO:2303, SEQ ID NO:2304, SEQ ID NO:2305, SEQ ID NO:2306, SEQ ID NO:2307, SEQ ID NO:2308, SEQ ID NO:2309, SEQ ID NO:2310, SEQ ID NO:2311, SEQ ID NO:2312, SEQ ID NO:2313, SEQ ID NO:2314, SEQ ID NO:2315, SEQ ID NO:2316, SEQ ID NO:2317, SEQ ID NO:2318, SEQ ID NO:2319, SEQ ID NO:2320, SEQ ID NO:2321, SEQ ID NO:2322, SEQ ID NO:2323, SEQ ID NO:2324, SEQ ID NO:2325, SEQ ID NO:2326, SEQ ID NO:2327, SEQ ID NO:2328, SEQ ID NO:2329, SEQ ID NO:2330, SEQ ID NO:2331, SEQ ID NO:2332, SEQ ID NO:2333, SEQ ID NO:2334, SEQ ID NO:2335, SEQ ID NO:2336, SEQ ID NO:2337, SEQ ID NO:2338, SEQ ID NO:2339, SEQ ID NO:2340, SEQ ID NO:2341, SEQ ID NO:2342, SEQ ID NO:2343, SEQ ID NO:2344, SEQ ID NO:2345, SEQ ID NO:2346, SEQ ID NO:2347, SEQ ID NO:2348, SEQ ID NO:2349, SEQ ID NO:2350, SEQ ID NO:2351, SEQ ID NO:2352, SEQ ID NO:2353, SEQ ID NO:2354, SEQ ID NO:2355, SEQ ID NO:2356, SEQ ID NO:2357, SEQ ID NO:2358, SEQ ID NO:2359, SEQ ID NO:2360, SEQ ID NO:2361, SEQ ID NO:2362, SEQ ID NO:2363, SEQ ID NO:2364, SEQ ID NO:2365, SEQ ID NO:2366, SEQ ID NO:2367, SEQ ID NO:2368, SEQ ID NO:2369, SEQ ID NO:2370, SEQ ID NO:2371, SEQ ID NO:2372, SEQ ID NO:2373, SEQ ID NO:2374, SEQ ID NO:2375, SEQ ID NO:2376, SEQ ID NO:2377, SEQ ID NO:2378, SEQ ID NO:2379, SEQ ID NO:2380, SEQ ID NO:2381, SEQ ID NO:2382, SEQ ID NO:2383, SEQ ID NO:2384, SEQ ID NO:2385, SEQ 1D NO:2386, SEQ ID NO:2387, SEQ ID NO:2388, SEQ ID NO:2389, SEQ ID NO:2390, SEQ ID NO:2391, SEQ ID NO:2392, SEQ ID NO:2393, SEQ ID NO:2394, SEQ ID NO:2395, SEQ ID NO:2396, SEQ ID NO:2397, SEQ ID NO:2398, SEQ ID NO:2399.

52. A composition for detecting transplant rejection comprising one or more PCR primers wherein said PCR primers consist of nucleotide sequences selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ 249 Amended sheet: 25 May 2007

ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115,SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:16S, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ 1D NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, SEQ ID NO:188, SEQ ID NO:189, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:192, SEQ ID NO:193, SEQ ID NO:194, SEQ ID NO:195, SEQ ID NO:196, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:199, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:202, SEQ ID NO:203, SEQ ID NO:204, SEQ ID NO:205, SEQ ID NO:206, SEQ ID NO:207, SEQ ID NO:208, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:212, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:216, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID

250 Amended sheet: 25 May 2007

NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281, SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ 1D NO:307, SEQ 1D NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO:313, SEQ ID NO:314, SEQ ID NO:315, SEQ ID NO:316, SEQ ID NO:317, SEQ ID NO:318, SEQ ID NO:319, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:325, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:2697, SEQ ID NO:2645, SEQ ID NO:2707, SEQ ID NO:2679, SEQ ID NO:2717, SEQ ID NO:2646, SEQ ID NO:2667, SEQ ID NO:2706, SEQ ID NO:2740, SEQ ID NO:2669, SEQ ID NO:2674, SEQ ID NO:2743, SEQ ID NO:2716, SEQ ID NO:2727, SEQ ID NO:2721, SEQ ID NO:2641, SEQ ID NO:2671,SEQ ID NO:2752, SEQ ID NO:2737, SEQ ID NO:2719, SEQ ID NO:2684, SEQ ID NO:2677, SEQ ID NO:2748, SEQ ID NO:2703, SEQ ID NO:2711, SEQ ID NO:2663, SEQ ID NO:2657, SEQ ID NO:2683, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2644, SEQ ID NO:2664, SEQ ID NO:2747, SEQ ID NO:2744, SEQ ID NO:2678, SEQ ID NO:2731, SEQ ID NO:2713, SEQ ID NO:2736, SEQ ID NO:2708, SEQ ID NO:2670, SEQ ID NO:2661, SEQ ID NO:2680, SEQ ID NO:2754, SEQ ID NO:2728, SEQ ID NO:2742, SEQ ID NO:2668, SEQ ID NO:2750, SEQ ID NO:2746, SEQ ID NO:2738, SEQ ID NO:2627, SEQ ID NO:2739, SEQ ID NO:2647, SEQ ID NO:2628, SEQ ID NO:2638, SEQ ID NO:2725, SEQ ID NO:2714, SEQ ID NO:2635, SEQ ID NO:2751, SEQ ID NO:2629, SEQ ID NO:2695, SEQ ID NO:2741, SEQ ID NO:2691, SEQ ID NO:2726, SEQ ID NO:2722, SEQ ID NO:2689, SEQ ID NO:2734, SEQ ID NO:2631, SEQ ID NO:2656, SEQ ID NO:2696, SEQ ID NO:2676, SEQ ID NO:2701, SEQ ID NO:2730, SEQ ID NO:2710, SEQ ID NO:2632, SEQ ID NO:2724, SEQ ID NO:2698, SEQ ID NQO:2662, SEQ ID NO:2753, SEQ ID NO:2704, SEQ ID NO:2675, SEQ ID NO:2700, SEQ ID NO:2640, SEQ ID NO:2723, SEQ ID NO:2658, SEQ ID NO:2688, SEQ ID NO:2735, SEQ ID NO:2702, SEQ ID NO:2681,

251 Amended sheet: 25 May 2007

SEQ ID NO:2755, SEQ ID NO:2715, SEQ ID NO:2732, SEQ ID NO:2652, SEQ ID NO:2651, SEQ ID NO:2718, SEQ ID NO:2673, SEQ ID NO:2733, SEQ ID NO:2712, SEQ ID NO:2659, SEQ ID NO:2654, SEQ ID NO:2636, SEQ ID NO:2639, SEQ ID NO:2690, SEQ ID NO:2705, SEQ ID NO:2685, SEQ ID NO:2692, SEQ ID NO:2693, SEQ ID NO:2648, SEQ ID NO:2650, SEQ ID NO:2720, SEQ ID NO:2660, SEQ ID NO:2666, SEQ ID NO:2699, SEQ ID NO:2633, SEQ ID NO:2672, SEQ ID NO:2642, SEQ ID NO:2682, SEQ ID NO:2655, SEQ ID NO:2630, SEQ ID NO:2745, SEQ ID NO:2643, SEQ ID NO:2694, SEQ ID NO:2749, SEQ ID NO:2665, SEQ ID NO:2649, SEQ ID NO:2637, SEQ ID NO:2634, SEQ ID NO:2709, SEQ ID NO:2653, SEQ ID NO:2729.

53. A composition for detecting transplant rejection comprising one or more antibodies wherein said antibodies detect proteins wherein said proteins comprise an amino acid sequence selected from the group consisting of SEQ ID NO:2400, SEQ ID NO:2401, SEQ ID NO:2402, SEQ ID NO:2403, SEQ ID NO:2404, SEQ ID NO:2405,SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID NO:2410, SEQ ID NO:2411, SEQ ID NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO:2415,SEQ ID NO:2416, SEQ ID NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ ID NO:2421, SEQ ID NO:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID NO:2426, SEQ ID NO:2427, SEQ ID NO:2428, SEQ ID NO:2429, SEQ ID NO:2430, SEQ ID NO:2432, SEQ ID NO:2433, SEQ ID NO:2434,SEQ ID NO:2435, SEQ ID NO:2436, SEQ ID NO:2437, SEQ ID NO:2438, SEQ ID NO:2439, SEQ ID NO:2440, SEQ ID NO:2441, SEQ ID NO:2442, SEQ ID NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID NO:2447, SEQ ID NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID NO:2451, SEQ ID NO:2452, SEQ ID NO:2453, SEQ ID NO:2454, SEQ ID NO:2455, SEQ ID NO:2456, SEQ ID NO:2457, SEQ ID NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461,SEQ ID NO:2462, SEQ ID NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ ID NO:2467, SEQ ID NO:2468, SEQ ID NO:2469, SEQ ID NO:2470,SEQ ID NO:2478, SEQ ID N0O:2479, SEQ ID NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2485, SEQ ID NO:2486, SEQ ID NO:2488, SEQ ID NO:2491, SEQ ID NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID NO:2497, SEQ ID NO:2502, SEQ ID NO:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID NO:2507, SEQ ID NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID NO:2512, SEQ ID NO:2513, SEQ ID NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQ ID NO:2517, SEQ ID NO:2518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NO:2536,SEQ ID NO:2537, SEQ ID N0O:2538, SEQ ID NO:2539, SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID NO:2543, SEQ ID NO:2544, 252 Amended sheet: 25 May 2007

SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID NO:2553, SEQ ID NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID NO:2558, SEQ ID NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ 1D NO:2593, SEQ ID NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID NO:2598, SEQ ID NO:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID NO:2608, SEQ ID NO:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID NO:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID NO:2626, SEQ ID NO:2925, SEQ ID NO:2926, SEQ ID NO:2927, SEQ ID NO:2928, SEQ ID NO:2929, SEQ ID NO:2930, SEQ ID NO:2932, SEQ ID NO:2933, SEQ ID NO:2935, SEQ ID NO:2936, SEQ ID NO:2937, SEQ ID NO:2938, SEQ ID NO:2939, SEQ ID NO:2941, SEQ ID NO:2942, SEQ ID NO:2943, SEQ ID NO:2945, SEQ ID NO:2946, SEQ ID NO:2947, SEQ ID NO:2948, SEQ ID NO:2949, SEQ ID NO:2950, SEQ ID NO:2951, SEQ ID NO:2952, SEQ ID NO:2953, SEQ ID NO:2954, SEQ ID NO:2955, SEQ ID NO:2956, SEQ ID NO:2957, SEQ ID NO:2959, SEQ ID NO:2960, SEQ ID NO:2961, SEQ ID NO:2962, SEQ ID NO:2963, SEQ ID NO:2964, SEQ ID NO:2965, SEQ ID NO:2966, SEQ ID NO:2967, SEQ ID NO:2968, SEQ ID NO:2969, SEQ ID NO:2970, SEQ ID NO:2971, SEQ ID NO:2972, SEQ ID NO:2973, SEQ ID NO:2974, SEQ ID NO:2975, SEQ ID NO:2976, SEQ ID NO:2977, SEQ ID NO:2978, SEQ ID NO:2979, SEQ ID NO:2980, SEQ ID NO:2981, SEQ ID NO:2982, SEQ ID NO:2983, SEQ ID NO:2984, SEQ ID NO:2985, SEQ ID NO:2986, SEQ ID NO:2987, SEQ ID NO:2988, SEQ ID NO:2989, SEQ ID NO:2990, SEQ ID NO:2991, SEQ ID NO:2992, SEQ ID NO:2993, SEQ ID NO:2994, SEQ ID NO:2995, SEQ ID NO:2996, SEQ ID NO:2997, SEQ ID NO:2998, SEQ ID NO:2999, SEQ ID NO:3000, SEQ ID NO:3001, SEQ ID NO:3002, SEQ ID NO:3003, SEQ ID NO:3004, SEQ ID NO:3005, SEQ ID NO:3006, SEQ ID NO:3007, SEQ ID NO:3008, SEQ ID NO:3009, SEQ ID NO:3010, SEQ ID NO:3011, SEQ ID NO:3012, SEQ ID NO:3013, SEQ ID NO:3014, SEQ ID NO:3015.

54. A composition for detecting transplant rejection comprising one or more antibodies wherein said antibodies detect proteins wherein said proteins 253 Amended sheet: 25 May 2007 comprise an amino acid sequence selected from the group consisting of SEQ ID NO:2400, SEQ ID NO:2401, SEQ ID NO:2402, SEQ ID NO:2403, SEQ ID NO:2404, SEQ ID NO:2405, SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID NO:2410, SEQ ID NO:2411, SEQ ID NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO:2415, SEQ ID NO:2416, SEQ ID NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ ID NO:2421, SEQ ID NO:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID NO:2426, SEQ ID NO:2427, SEQ ID NO:2428, SEQ ID NO:2429, SEQ ID NO:2430, SEQ ID NO:2432, SEQ ID NO:2433, SEQ ID NO:2434, SEQ ID NO:2435, SEQ ID NO:2436, SEQ ID NO:2437, SEQ ID NO:2438, SEQ ID NO:2439, SEQ ID NO:2440, SEQ ID NO:2441, SEQ ID NO:2442, SEQ ID NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID NO:2447, SEQ ID NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID NO:2451, SEQ ID NO:2452, SEQ ID NO:2453, SEQ ID NO:2454, SEQ ID NO:2455, SEQ ID NO:2456, SEQ ID NO:2457, SEQ ID NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID NO:2462, SEQ ID NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ ID NO:2467, SEQ ID NO:2468, SEQ ID NO:2469, SEQ ID NO:2470, SEQ ID NO:2478, SEQ ID NO:2479, SEQ ID NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2485, SEQ ID NO:2486, SEQ ID NO:2488, SEQ ID NO:2491, SEQ ID NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID NO:2497, SEQ ID NO:2502, SEQ ID NO:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID NO:2507, SEQ ID NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID NO:2512, SEQ ID NO:2513, SEQ ID NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQ ID NO:2517, SEQ ID NO:2518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID NO:2538, SEQ ID NO:2539, SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID NO:2543, SEQ ID NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID NO:2553, SEQ ID NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID NO:2558, SEQ ID NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID NO:2593, SEQ ID NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID NO:2598,

254 Amended sheet: 25 May 2007

SEQ ID NO:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID NO:2608, SEQ ID NO:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID NO:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID NO:2626, SEQ ID NO:2925, SEQ ID NO:2926, SEQ ID NO:2927, SEQ ID NO:2928, SEQ ID NO:2929, SEQ ID NO:2930, SEQ ID NO:2932, SEQ ID NO:2933, SEQ ID NO:2935, SEQ ID NO:2936, SEQ ID NO:2937, SEQ ID NO:2938, SEQ ID NO:2939, SEQ ID NO:2941, SEQ ID NO:2942, SEQ ID NO:2943, SEQ ID NO:2945, SEQ ID NO:2946, SEQ ID NO:2947, SEQ ID NO:2948, SEQ ID NO:2949, SEQ ID NO:2950, SEQ ID NO:2951, SEQ ID NO:2952, SEQ ID NO:2953, SEQ ID NO:2954, SEQ ID NO:2955, SEQ ID NO:2956, SEQ ID NO:2957, SEQ ID NO:2959, SEQ ID NO:2960, SEQ ID NO:2961, SEQ ID NO:2962, SEQ ID NO:2963, SEQ ID NO:2964, SEQ ID NO:2965, SEQ ID NO:2966, SEQ ID NO:2967, SEQ ID NO:2968, SEQ ID NO:2969, SEQ ID NO:2970, SEQ ID NO:2971, SEQ ID NO:2972, SEQ ID NO:2973, SEQ ID NO:2974, SEQ ID NO:2975, SEQ ID NO:2976, SEQ ID NO:2977, SEQ ID NO:2978, SEQ ID NO:2979, SEQ ID NO:2980, SEQ ID NO:2981, SEQ ID NO:2982, SEQ ID NO:2983, SEQ ID N0O:2984, SEQ ID NO:2985, SEQ ID NO:2986, SEQ ID NO:2987, SEQ ID NO:2988, SEQ ID NO:2989, SEQ ID NO:2990, SEQ ID NO:2991, SEQ ID NO:2992, SEQ ID NO:2993, SEQ ID NO:2994, SEQ ID NO:2995, SEQ ID NO:2996, SEQ ID NO:2997, SEQ ID NO:2998, SEQ ID NO:2999, SEQ ID NO:3000, SEQ ID NO:3001, SEQ ID NO:3002, SEQ ID NO:3003, SEQ ID NO:3004, SEQ ID NO:3005, SEQ ID NO:3006, SEQ ID NO:3007, SEQ ID NO:3008, SEQ ID NO:3009, SEQ ID NO:3010, SEQ ID NO:3011, SEQ ID NO:3012, SEQ ID NO:3013, SEQ ID NO:3014, SEQ ID NO:3015, SEQ ID NO:2406, SEQ ID NO:2431, SEQ ID NO:2471, SEQ ID NO:2472, SEQ ID NO:2473, SEQ ID NO:2474, SEQ ID NO:2475, SEQ ID NO:2476, SEQ ID NO:2477, SEQ ID NO:2484, SEQ ID NO:2487, SEQ ID NO:2489, SEQ ID NO:2490, SEQ ID NO:2498, SEQ ID NO:2499, SEQ ID NO:2500, SEQ ID NO:2501, SEQ ID NO:2522, SEQ ID NO:2523, SEQ 1D NO:2524, SEQ ID NO:2525, SEQ ID NO:2526, SEQ ID NO:2527.SEQ ID NO:2400, SEQ 1D NO:2401, SEQ ID NO:2402, SEQ ID NO:2403, SEQ ID NO:2404, SEQ ID NO:2405, SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID NO:2410, SEQ ID NO:2411, SEQ ID NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO:2415, SEQ ID NO:2416, SEQ ID NO:2417,SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ ID NO:2421, SEQ ID NO:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID NO:2426,SEQ ID NO:2427, SEQ ID NO:2428, SEQ ID NO:2429, SEQ ID NO:2430, SEQ ID NO:2432, SEQ ID NO:2433, SEQ ID NO:2434, SEQ ID NO:2435, SEQ ID NO:2436, SEQ ID NO:2437, SEQ ID NO:2438, SEQ ID NO:2439, SEQ ID NO:2440, SEQ ID NO:2441, SEQ ID NO:2442, SEQ ID NO:2443, SEQ ID NO:2444,

255 Amended sheet: 25 May 2007

SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID NO:2447, SEQ ID NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID NO:2451, SEQ ID NO:2452, SEQ ID NO:2453, SEQ ID NO:2454, SEQ ID NO:2455, SEQ ID NO:2456, SEQ ID NO:2457, SEQ ID NO:2458, SEQ ID N0:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID NO:2462, SEQ ID NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ ID NO:2467, SEQ ID NO:2468, SEQ ID NO:2469, SEQ ID NO:2470, SEQ ID NO:2478, SEQ ID NO:2479, SEQ ID NO:2480, SEQ 1D NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2485, SEQ ID NO:2486, SEQ ID NO:2488, SEQ ID NO:2491, SEQ ID NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID NO:2497, SEQ ID NO:2502, SEQ ID NO:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID NO:2507, SEQ ID NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID NO:2512, SEQ 1D NO:2513, SEQ ID NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQ ID NO:2517, SEQ ID NO:2518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID NO:2538, SEQ ID NO:2539, SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID NO:2543, SEQ ID NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID NO:2553, SEQ ID NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID NO:2558, SEQ ID NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID NO:2593, SEQ ID NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID NO:2598, SEQ ID NO:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID NO:2608, SEQ ID NO:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID NO:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID NO:2626, SEQ ID NO:2925, SEQ ID NO:2926, SEQ ID NO:2927, SEQ ID NO:2928, SEQ ID NO:2929, SEQ ID NO:2930, SEQ ID NO:2932, SEQ ID NO:2933, SEQ ID NO:2935, SEQ ID NO:2936, SEQ ID NO:2937, SEQ ID NO:2938, SEQ ID NO:2939, SEQ ID NO:2941, SEQ ID NO:2942, SEQ ID NO:2943, SEQ ID NO:2945, SEQ ID NO:2946, SEQ ID NO:2947,

256 Amended sheet: 25 May 2007

SEQ ID NO:2948, SEQ ID NO:2949, SEQ ID NO:2950, SEQ ID NO:2951, SEQ ID NO:2952, SEQ ID NO:2953, SEQ ID NO:2954, SEQ ID NO:2955, SEQ ID NO:2956, SEQ ID NO:2957, SEQ ID NO:2959, SEQ ID NO:2960, SEQ ID NO:2961, SEQ ID NO:2962, SEQ ID NO:2963, SEQ ID NO:2964, SEQ ID NO:2965, SEQ ID NO:2966, SEQ ID NO:2967, SEQ ID NO:2968, SEQ ID NO:2969, SEQ ID NO:2970, SEQ ID NO:2971, SEQ ID NO:2972, SEQ ID NO:2973, SEQ ID NO:2974, SEQ ID NO:2975, SEQ ID NO:2976, SEQ ID NO:2977, SEQ ID NO:2978, SEQ ID NO:2979, SEQ ID NO:2980, SEQ ID NO:2981, SEQ ID NO:2982, SEQ ID NO:2983, SEQ ID NO:2984, SEQ ID NO:2985, SEQ ID NO:2986, SEQ ID NO:2987, SEQ ID NO:2988, SEQ ID NO:2989, SEQ ID NO:2990, SEQ ID NO:2991, SEQ ID NO:2992, SEQ ID NO:2993, SEQ ID NO:2994, SEQ ID NO:2995, SEQ ID N0O:2996, SEQ ID NO:2997, SEQ ID NO:2998, SEQ ID NO:2999, SEQ ID NO:3000, SEQ ID NO:3001, SEQ ID NO:3002, SEQ ID NO:3003, SEQ ID NO:3004, SEQ ID NO:3005, SEQ ID NO:3006, SEQ ID NO:3007, SEQ ID NO:3008, SEQ ID NO:3009, SEQ ID NO:3010, SEQ ID NO:3011, SEQ ID NO:3012, SEQ ID NO:3013, SEQ ID NO:3014, SEQ ID NO:3015, SEQ ID NO:2400, SEQ ID NO:2401, SEQ ID NO:2402, SEQ ID NO:2403, SEQ ID NO:2404, SEQ ID NO:2405, SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID NO:2410, SEQ ID NO:2411, SEQ ID NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO:2415, SEQ ID NO:2416, SEQ ID NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ ID NO:2421, SEQ ID NO:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID NO:2426, SEQ ID NO:2427, SEQ ID NO:2428, SEQ ID NO:2429, SEQ ID NO:2430, SEQ ID NO:2432, SEQ ID NO:2433, SEQ ID NO:2434, SEQ ID NO:2435, SEQ ID NO:2436, SEQ ID NO:2437, SEQ ID NO:2438, SEQ ID NO:2439, SEQ ID NO:2440, SEQ ID NO:2441, SEQ 1D NO:2442, SEQ ID NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID NO:2447, SEQ ID NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID NO:2451, SEQ ID NO:2452, SEQ ID NO:2453, SEQ 1D NO:2454, SEQ ID NO:2455, SEQ ID NO:2456, SEQ ID NO:2457, SEQ ID NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID NO:2462, SEQ ID NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ ID NO:2467, SEQ ID NO:2468, SEQ ID NO:2469, SEQ ID NO:2470, SEQ ID NO:2471, SEQ ID NO:2476, SEQ ID NO:2477, SEQ ID NO:2478, SEQ ID NO:2479, SEQ ID NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2484, SEQ ID NO:2485, SEQ ID NO:2486, SEQ ID NO:2488, SEQ ID NO:2489, SEQ ID NO:2490, SEQ ID NO:2491, SEQ ID NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID NO:2497, SEQ ID NO:2498, SEQ ID NO:2499, SEQ ID NO:2500, SEQ ID NO:2501, SEQ ID NO:2502, SEQ ID NO:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID NO:2507, SEQ ID NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID NO:2512, SEQ ID NO:2513, SEQ ID NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQ ID NO:2517, SEQ ID NO:2518, SEQ ID NO:2519, 257 Amended sheet: 25 May 2007

SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID NO:2538, SEQ ID NO:2539, SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID NO:2543, SEQ ID NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID NO:2553, SEQ ID NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID NO:2558, SEQ ID NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID NO:2588, SEQ ID NO:2589, SEQ ID N0O:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID NO:2593, SEQ ID NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID NO:2598, SEQ ID N0O:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID NO:2608, SEQ ID NO:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID NO:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID NO:2626, SEQ ID NO:2406, SEQ ID NO:2431, SEQ ID NO:2472, SEQ ID NO:2473, SEQ ID NO:2474, SEQ ID NO:2475, SEQ ID NO:2487, SEQ ID NO:2522, SEQ ID NO:2523, SEQ ID NO:2524, SEQ ID NO:2525, SEQ ID NO:2526, SEQ ID NO:2527, SEQ ID NO:2400, SEQ ID NO:2401, SEQ ID NO:2402, SEQ ID NO:2403, SEQ ID NO:2404, SEQ ID NO:2405, SEQ ID NO:2406, SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID NO:2410, SEQ ID NO:2411, SEQ ID NO:2412, SEQ ID NO:2413, SEQ ID NO:2414, SEQ ID NO:2415, SEQ ID NO:2416, SEQ ID NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ ID NO:2421, SEQ ID NO:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID NO:2426, SEQ ID NO:2427, SEQ 1D NO:2428, SEQ ID NO:2429, SEQ ID NO:2430, SEQ ID NO:2432, SEQ ID NO:2433, SEQ ID NO:2434, SEQ ID NO:2435, SEQ ID NO:2436, SEQ ID NO:2437, SEQ ID NO:2438, SEQ ID NO:2439, SEQ ID NO:2440, SEQ ID NO:2441, SEQ ID NO:2442, SEQ ID NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID NO:2447, SEQ ID NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID NO:2451, SEQ ID NO:2452, SEQ ID NO:2453, SEQ ID NO:2454, SEQ ID NO:2455, SEQ ID NO:2456, SEQ ID NO:2457, SEQ ID NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID NO:2462, SEQ ID NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466,

258 Amended sheet: 25 May 2007

SEQ ID NO:2467, SEQ ID NO:2468, SEQ ID NO:2469, SEQ ID NO:2470, SEQ ID NO:2474, SEQ ID NO:2478, SEQ ID NO:2479, SEQ ID NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2485, SEQ ID NO:2486, SEQ ID NO:2487, SEQ ID NO:2488, SEQ ID NO:2491, SEQ ID NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID NO:2497, SEQ ID NO:2502, SEQ ID N0:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID NO:2507, SEQ ID NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID NO:2512, SEQ 1D NO:2513, SEQ ID NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQ ID NO:2517, SEQ ID NO:2518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID NO:2528, SEQ ID NO:2529, SEQ 1D NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID NO:2538, SEQ ID NO:2539, SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID NO:2543, SEQ ID NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID NO:2553, SEQ ID NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ 1D NO:2557, SEQ ID NO:2558, SEQ ID NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID NO:2573, SEQ ID NO:2574, SEQ 1D NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID NO:2593, SEQ ID NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID NO:2598, SEQ ID NO:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID NO:2608, SEQ ID NO:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID NO:2623, SEQ ID N0O:2624, SEQ ID NO:2625, SEQ ID NO:2626, SEQ ID NO:2925, SEQ ID NO:2926, SEQ ID NO:2927, SEQ ID NO:2928, SEQ ID NO:2929, SEQ ID NO:2930, SEQ ID NO:2932, SEQ ID NO:2933, SEQ ID NO:2935, SEQ ID NO:2936, SEQ ID NO:2937, SEQ ID NO:2938, SEQ ID NO:2939, SEQ ID NO:2941, SEQ ID NO:2942, SEQ ID NO:2943, SEQ ID NO:2945, SEQ ID NO:2946, SEQ ID NO:2947, SEQ ID NO:2948, SEQ ID NO:2949, SEQ ID NO:2950, SEQ ID NO:2951, SEQ ID NO:2952, SEQ ID NO:2953, SEQ ID NO:2954, SEQ ID NO:2955, SEQ ID NO:2956, SEQ ID NO:2957, SEQ ID NO:2959, SEQ ID NO:2960, SEQ ID NO:2961, SEQ ID NO:2962, SEQ ID NO:2963, SEQ ID NO:2964, SEQ ID NO:2965, SEQ ID NO:2966, SEQ ID NO:2967, SEQ ID NO:2968,

259 Amended sheet: 25 May 2007

SEQ ID NO:2969, SEQ ID NO:2970, SEQ ID NO:2971, SEQ ID NO:2972, SEQ ID NO:2973, SEQ ID NO:2974, SEQ ID NO:2975, SEQ ID NO:2976, SEQ ID NO:2977, SEQ ID NO:2978, SEQ ID NO:2979, SEQ ID NO:2980, SEQ ID NO:2981, SEQ ID NO:2982, SEQ ID NO:2983, SEQ ID NO:2984, SEQ ID NO:2985, SEQ ID NO:2986, SEQ ID NO:2987, SEQ ID NO:2988, SEQ ID NO:2989, SEQ ID NO:2990, SEQ ID NO:2991, SEQ ID NO:2992, SEQ ID NO:2993, SEQ ID NO:2994, SEQ ID NO:2995, SEQ ID NO:2996, SEQ ID NO:2997, SEQ ID NO:2998, SEQ ID NO:2999, SEQ ID NO:3000, SEQ ID NO:3001, SEQ ID NO:3002, SEQ ID NO:3003, SEQ ID NO:3004, SEQ ID NO:3005, SEQ ID NO:3006, SEQ ID NO:3007, SEQ ID NO:3008, SEQ ID NO:3009, SEQ ID NO:3010, SEQ ID NO:3011, SEQ ID NO:3012, SEQ ID NO:3013, SEQ ID NO:3014, SEQ ID NO:3015, SEQ ID NO:2400, SEQ ID NO:2401, SEQ ID NO:2402, SEQ ID NO:2403, SEQ ID NO:2404, SEQ ID NO:2405, SEQ ID NO:2406, SEQ ID NO:2407, SEQ ID NO:2408, SEQ ID NO:2409, SEQ ID NO:2410, SEQ ID NO:2411, SEQ ID NO:2412, SEQ 1D NO:2413, SEQ ID NO:2414, SEQ ID NO:2415, SEQ ID NO:2416, SEQ ID NO:2417, SEQ ID NO:2418, SEQ ID NO:2419, SEQ ID NO:2420, SEQ ID NO:2421, SEQ ID NO:2422, SEQ ID NO:2423, SEQ ID NO:2424, SEQ ID NO:2425, SEQ ID NO:2426, SEQ ID NO:2427, SEQ ID NO:2428, SEQ ID NO:2429, SEQ ID NO:2430, SEQ ID NO:2432, SEQ ID NO:2433, SEQ ID NO:2434, SEQ ID NO:2435, SEQ ID NO:2436, SEQ ID NO:2437, SEQ ID NO:2438, SEQ ID NO:2439, SEQ ID NO:2440, SEQ ID NO:2441, SEQ ID NO:2442, SEQ ID NO:2443, SEQ ID NO:2444, SEQ ID NO:2445, SEQ ID NO:2446, SEQ ID NO:2447, SEQ ID NO:2448, SEQ ID NO:2449, SEQ ID NO:2450, SEQ ID NO:2451, SEQ ID NO:2452, SEQ ID NO:2453, SEQ ID NO:2454, SEQ ID NO:2455, SEQ ID NO:2456, SEQ ID NO:2457, SEQ ID NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID NO:2462, SEQ ID NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ ID NO:2467, SEQ ID NO:2468, SEQ ID NO:2469, SEQ 1D NO:2470, SEQ ID NO:2474, SEQ ID NO:2478, SEQ ID NO:2479, SEQ ID NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2485, SEQ ID NO:2486, SEQ ID NO:2487, SEQ ID NO:2488, SEQ ID NO:2491, SEQ ID NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, SEQ ID NO:2497, SEQ ID NO:2502, SEQ ID NO:2503, SEQ ID NO:2504, SEQ ID NO:2505, SEQ ID NO:2506, SEQ ID NO:2507, SEQ ID NO:2508, SEQ ID NO:2509, SEQ ID NO:2510, SEQ ID NO:2511, SEQ ID NO:2512, SEQ ID NO:2513, SEQ ID NO:2514, SEQ ID NO:2515, SEQ ID NO:2516, SEQ ID NO:2517, SEQ ID NO:2518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID NO:2538, SEQ ID NO:2539, SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID NO:2543, SEQ ID NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, 260 Amended sheet: 25 May 2007

SEQ ID NO:2553, SEQ ID NO:2554, SEQ ID NO:2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID NO:2558, SEQ ID NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID

] . NO:2566, SEQ ID NO:2567, SEQ ID NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ 1D NO:2586, SEQ ID NO:2587, SEQ ID NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID NO:2593, SEQ ID NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID NO:2598, SEQ ID NO:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID NO:2608, SEQ ID NO:2609, SEQ ID NO:2610, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID NO:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID NO:2626, SEQ ID NO:2925, SEQ ID NO:2926, SEQ ID NO:2927, SEQ ID NO:2928, SEQ ID NO:2929, SEQ ID NO:2930, SEQ ID NO:2932, SEQ ID NO:2933, SEQ ID NO:2935, SEQ ID NO:2936, SEQ ID NO:2937, SEQ ID NO:2938, SEQ ID NO:2939, SEQ ID NO:2941, SEQ ID NO:2942, SEQ ID NO:2%43, SEQ ID NO:2945, SEQ ID NO:2946, SEQ ID NO:2947, SEQ ID NO:2948, SEQ ID NO:2949, SEQ ID NO:2950, SEQ ID NO:2951, SEQ ID NO:2952, SEQ ID NO:2953, SEQ ID NO:2954, SEQ ID NO:2955, SEQ ID NO:2956, SEQ ID NO:2957, SEQ ID NO:2959, SEQ ID NO:2960, SEQ ID NO:2961, SEQ ID NO:2962, SEQ ID NO:2963, SEQ ID NO:2964, SEQ ID NO:2965, SEQ ID NO:2966, SEQ ID NO:2967, SEQ ID NO:2968, SEQ ID NO:2969, SEQ ID NO:2970, SEQ ID NO:2971, SEQ ID NO:2972, SEQ ID NO:2973, SEQ ID NO:2974, SEQ ID NO:2975, SEQ ID NO:2976, SEQ ID NO:2977, SEQ ID NO:2978, SEQ ID NO:2979, SEQ ID NO:2980, SEQ ID NO:2981, SEQ ID NO:2982, SEQ ID NO:2983, SEQ ID NO:2984, SEQ ID NO:2985, SEQ ID NO:2986, SEQ ID NO:2987, SEQ ID NO:2988, SEQ ID NO:2989, SEQ ID NO:2990, SEQ ID NO:2991, SEQ ID NO:2992, SEQ ID NO:2993, SEQ ID NO:2994, SEQ ID NO:2995, SEQ ID NO:2996, SEQ ID NO:2997, SEQ ID NO:2998, SEQ ID NO:2999, SEQ ID NO:3000, SEQ ID NO:3001, SEQ ID NO:3002, SEQ ID NO:3003, SEQ ID NO:3004, SEQ ID NO:3005, SEQ ID NO:3006, SEQ ID NO:3007, SEQ ID NO:3008, SEQ ID NO:3009, SEQ ID NO:3010, SEQ ID NO:3011, SEQ ID NO:3012, SEQ ID NO:3013, SEQ ID NO:3014, SEQ ID NO:3015, SEQ ID NO:2431, SEQ ID NO:2471, SEQ ID NO:2472, SEQ ID NO:2473, SEQ ID NO:2475, SEQ ID NO:2476, SEQ ID NO:2477, SEQ ID NO:2484, SEQ ID NO:2489, SEQ ID NO:2490, SEQ ID NO:2498, SEQ ID NO:2499, SEQ ID NO:2500, SEQ ID NO:2501, SEQ ID NO:2522, SEQ ID NO:2523, SEQ ID NO:2524, SEQ ID NO:2525, SEQ ID NO:2526 and SEQ ID NO:2527, 261 Amended sheet: 25 May 2007 \

\

‘ aagaaaaaag ctgagaaaaa gttcattgat atagcagyctg ctaaagaagt cctctetfiat 1380 : ccagaaatga gaaagaagtt tgacgacgga gaagatcctt tggatgcaga gagccagcaa 1440 ggaggcggceg gcaacccttt ccacagaagc tggaactcat ggcaagggtt caatcccttc 1500 agctcaggcg gaccatttag atttaaatte cacttcaatt aa 1542

<210> 51s

<211> 434s

<212> DNA

<213> Homo sapiens

<400> 515 gcgtgggcge cagaaagcgg aacctcccgg gccagtcgeg cggtggtcac cctcttggga 60 gctggggagg aggctgegga ggctggeccg gotccttcgg gegtcegette ccggaccggg 120 tgcgeggggt cccccggaac gtgtgttcca ggtcctccecg cgccagtgtt cgcagtcccecce 180 gcctggtege ggcggegect cgggegeggg tgcaggegeg cggcgcgcag geggggggeg 240 ctgtggtett ggcgcgggga ccgagecgcet cggccagacc cgcctctttt ccctececge 300 cagceccgecc gectgeccge cccccacgeg tcgtgtegec gggaagecgyg gcggagacag 360 agcgcttggg atccacggcg ctcggaccge tgtcctccaa cagcgcaggg cagagcggct 420 ggcgecgecg gagcegcggag ccacdaccct ccctggecge ctttgtctac tggcecgtgcg 480 gcceggaacce gecactctecc agggcegggg acgcgcccdgce agctgteggt gacagctcct 540 ccctaccgca acccteeggg geggagggge ggtegggeeg ggccctgcta gecccgegace 600 gcaagccege gctcgeggat cgatgccccc gcagcagggg gaccccgegt tecccgacceg 660 ctgcgaggcg cctccggtge cgecgegteg ggagegeggt ggacgcegggg gacgcgggcece 720 tggggagceg gggggcecggg ggegtgeggg gggtgeccgag gggcgcggeg tcaagtgcgt 780 gctggtegge gacggcgegg tgggcaagac gagccetggtg gtgagctaca ccaccaacgg 840 ctaccccacc gagtacatcc ctactgcctt cgacaacttc tccgeggtgg tgtctgtgga 900 tgggcggece gtgagactcc aactctgtga cactgccgga caggatgaat ttgacaagcet 960 gaggcctctce tgctacacca acacagacat cttcectgetc tgcttcagtg tcgtgagcce 1020 ctcatccttc cagaacgtca gtgagaaatg ggtgccggag attcgatgce actgtcccaa 1080 agcccccatc atcctagttg gaacgcagtc ggatctcaga gaagatgtca aagtcctcat 1140 tgagttggac aaatgcaaag aaaagccagt gcctgaagag gcggctaage tgtgcgccga 1200 ggaaatcaaa gccgcctect acatcgagtg ttcagccttg actcaaaaaa acctcaaaga 1260 ggtctttgat gcagccatcg tcgctggcat tcaatactcg gacactcage aacagccaaa 1320 gaagtctaaa agcaggactc cagataaaat gaaaaacctc tccaagtcct ggtggaagaa 1380 gtactgctgt ttcgtatgat gctggcaaga cacccagaaa ggctatttte agatgaaatc 1440 gatattagaa gctatattag ctgaaacaac tccttttact gcgtagaacc tatatcgaga 1500 gtgtgtgtat atgtattata ggaggagctc tcaattttat gtattctttc tgcctttaat 1560 tttcttgttt gtttgagett agggatgaga tacttatgca agatattttt gaagtaaatt 1620 aaacattttt cacatctctg gaaatttaga gttctagacc tctggttaat ttatatctaa 1680 tatgaagaag acacctctaa tctggatgtt aagaatgaag ttctgctaca ttataatgta 1740 ’ cagaagagca aaagggagga acactatggt taaccctctc ttgattaagg gctacttaat 1800 gcacagtgca ttatgtacac aggtcaacca tggtaacaat agttcttagc tttgaaactc 1860 catgcaaacc atgccttttt tttaaggagce aaaaatctga gaaaaaaagt gagagacctc 1320 tgcctacaaa acctcaaacc agtcactttt gtcaattgcet aatacccagt tacttatgat 1980 ttaaaaacaa ccaacagaaa acatcccact gactgtatgg cactctgtag tcaaaaaagg 2040 aaacttcctt attgggactt ttctttectta gtccagttgt gttgacacat atgaacacag 2100 acaaagtgct atgcggagga aagcaagtgt tggtcagtag tttcatgttt tagggagtgg 2160 ttcctgtgga gatcagaaag tgacatttge tttcggtact gtaatacgtg caccaaactg 2220 cctcaatcct aggtaacgag ggcaacaggg agcacctgtc tggattgttt ttaaacctcc 2280 atactcaagc tgtctcttcg gcagggaggt gaatactctt gaaaggccaa cagcaagtgt 2340 ttgtgggaca caacacagat aattttttct taagtcggce aagatgtact tctctgtgtg 2400 cacacccatg cacactcatg cacacagata cataggtctg tatggctgta tttgetgttg 2460 attcagactt tcacaccatt aatggggaaa agcgtggcca caaaaacaga tgctaggaag 2520 cttggcttcc tcttcttgtt gacccttttt tgaaccaaca tettttttat tatattcaga 2580 gtatgttttt aagtgtatct taatatatac attttttagg acatcttaaa tctaaacaaa 2640 aaataaaatg aacatctctt gaaacctgtt aaaacaacca gttaaagcca cagatggctt 2700 tcagggcagt agcagcagag gccagtggac tctgaggact cctgaggggce ggggcegtgta 2760 gccagccagg tgcatgcecgg gaccatggcc cccatacttg gctgcttecct gtgacagtga 2820 aatacatcct tcaaggtggc agctgttagg gectgaatctt ctggagaaaa aggtgccatc 2880 tcaggagaat agcttttact ctggtaggaa tgcttccgag acaccacaag gcagcctgaa 25940 cactcagttg cagggtcggg cttgeggtgg gtgacccaga gccaccaaag tcacatccac 3000 aactaatgag ggaaatctgt aaagccagtt agatagaaga attttatttt tctgtgggtt 3060 ttgtgttgtc ttttttatgt taaaaagaaa tccagtttgt gtttttctat agaaaaagta 3120 aaagatcagg ttatacttta ggttaggggt tctatttatt cctgttagta aataaaatta 3180 acaaatttct ttgtttaaca aaagattaat ctttaaacca ctaaaataca tagactgatt 3240 gattattcaa cacattggaa ttgatgtcgg tcatagtttc ctgaagcatt tagttacaac 3300 ctgaaggaat aaaatgattt gtggaaatgc ttaaaataga cctaactgaa tacagtctca 3360 tcttgecegeg cctggettac ctatctgtgg aaagctaggc ttcccagget gggctctgcece 3420 tgtctggtgce ctggaggtgt gggagggaag atgagttatt taactggtaa gcgatttgaa 3480 acactatttt tatattaaag taaatggcat ggagtatagt gcaaattcat ttttaagata 3540 gaacacaaaa cttgaaagaa gttttatgcg tgtgacagtg tatggggctg cagttggtct 3600 ccctggaggg gacttccaca cctcctgect ttaggcatgg gtggaaagtg ctcagtgaag 3660 tacacctgtg tggcccagtt ctgaaagctt tatacagttg aattttaagt ggggttgata 3720 acaccttgga ctgttagtgt taaaaatcta gtgggttgac ctttaaatgc aacagttttt 3780 aaaatatatt gctgcatttt atagaatagt aaaggtacga ttatacttga gattttcctc 3840 catttttatt tcttcgtgaa catagagttt ggggccgaaa atgtttttaa agtatgtgtt 3900 tgagttaaat ataaagttgg ttcacttcaa agctaaaaaa ttgttaaact tgcagcttgg 3960 tattgcagag aagattttat aagaattttg ctttagagaa tgccactttg gctgaactac 4020 aagtgtaggc caccattata atttataaat acagcatact tcaaaactgt ttgttatctc 4080 ttgttaccat gtatgtataa atggaccttt tataaccttg ttctctgctt gacagactca 4140 agagaaacta cccaggtatt acacaagcca aaatgggagc aaggccttct ctccagacta 4200 tcgtaacctg gtgccttace aagttgtgct tttctgtttt caagtgtaaa tgatgttgag 4260 cagaatgttg tacttgaaaa tgctataagt gagatggtat gaaataaatt ctgacttatg 4320 aataaaaaaa aaaaaaaaaa aaaaaa 4346 <210> S516 <211l> 2236 <212> DNA <213> Homo sapiens <400> 516 cccgagtcte aggagcctge cttacagcag gaggtgcagg cctegtcacc tgcagaggtg 60 cctgtgtcte agcctgacce cttgccagect tctgaccaca gttacgagct gcgcaatggt 120 gaagccattg ggcgggatcg ccgggggege agggcccgga ggaacaacag tggagaagca 180 ggcggggcag ccacacagga gctcttetge tcagectgtg accagctcett tctctcacce 240 caccagctac agcagcacct gcggagtcac €gggagggcg tctttaagtg ccccctgtge 300 agtcgtgtct tccctagece ttccagtctg gaccagcace ttggagacca tagcagcgag . 360 tcacacttcc tgtgtgtaga ctgtggcctg gcctteggea cagaggcect cctectggcee 420 caccggcgag cccacacccc gaatcctctg cattcatgte catgtgggaa gaccitueg. tou aaccttacca agttccttta tcaccggcgt actcatgggg tagggggtgt ccctctgecc 540 acaacaccag tcccaccaga ggaacctgtc attggrttcc ctgagccagc cccagcagag 600 actggagagc cagaggcccc tgagccccct gtgtctgagg agacctcagc agggcccgct 660 gccccaggca cctaccgetg cctectgtge agccgtgaat ttggaaaggc cttgcagetg 720 acccggcacce aacgttttgt gcatcggectg gagcggcgec ataaatgcag catttgtgge 780 - aagatgttca agaagaagtc tcacgtgcgt aaccacctgc gcacacacac aggggagcgg 840 cccttecocct gececctgactg cteccaagecce ttcaactcac ctgccaacct ggcccgecac 900 cggctcacac acacaggaga gcggccctac cggtgtgggg actgtggcaa ggctttcacg 960 caaagctcca cactgaggca gcaccgcttg gtgcatgccc agcacttccc ctaccgcectgce 1020 caggaatgtg gggtgcgttt tcaccgtcct taccgcctgc tcatgcaccg ctaccatcac 1080 acaggtgaat acccctacaa gtgtcgcgag tgcccccgect ccttecttgect gegtcggetg 1140 ctggaggtgc accagctcgt ggtccatgcc gggcgecagc cccaccgctg cccatcctgt 1200 ggggctgcct tcccctcctc actgcggctc cgggagcacc gctgtgcage cgctgctgec 1260 caggccccac ggcgctttga gtgtggcacc tgtggcaaga aagtgggctc agctgctcga 1320 ctgcaggcac acgaggcggc ccatgcagct gctgggecctg gagaggtcct ggctaaggag 1380 cccecctgecece ctcgagccecc acgggccact cgtgcaccag ttgectctcc agcagccctt 1440 ggaagcactg ctacagcatc ccctgeggec cctgcccgec geccggggtct agagtgcage 1500 gagtgcaaga agctgttcag cacagagacg tcactgcagg tgcaccggcg catccacaca 1560 ggtgagcggc catacccatg tccagactgt ggcaaagcgt tccgtcagag tacccacctg 1620 aaagaccacc ggcgcctgca cacaggtgag cggccctttg cctgtgaagt gtgtggcaag 1680 gcctttgcca tcectccatgecg cctggcagaa catcgceecgeca tccacacagg cgaacgacce 1740 tactcctgecc ctgactgtgg caagagctac cgctccttct ccaacctctg gaagcaccgc 1800 aagacccatc agcagcagca tcaggcagct gtgcggcagc agctggcaga ggcggaggct 1860 gccgttggec tggccecgtcat ggagactgct gtggaggcge tacccctggt ggaagccatt 1920 gagatctacc ctctggccga ggctgagggg gtccagatca gtggctgact ctgcccgact 1980 tcctetttgg caccteccatt cectgttgct gaaggcecctc cagcatcccec ttaagcatct 2040 gtacatactg tgtceccttcc tcttcccatc cccaccacct tgtaagttct aaattggatt 2100 tattctctcg tgaggggggt gcectctggggt ccttgacaca cataaaggtg ceccccccacce 2160 ttccacctct tagcactggt gaccccaaaa atgaaaccat caataaagac tgggttgcca 2220 aaaaaaaaaa aaaaaa 2236

<210> 517 . <211> 1900 <212> DNA <213> Homo sapiens <400> 517 acaactctca gaggagcatt gcccgtcaga cagcaactca gagaataacc agagaacaac 60 cagattgaaa caatggagga tctttgtgtg gcaaacacac tctttgccct caatttattce 120 aagcatctgg caaaagcaag ccccacccag aacctcttee tctcecccatg gagcatcteg 180 tccaccatgg ccatggtcta catgggctcc aggggcagca ccgaagacca gatggccaag 240 gtgcttcagt ttaatgaagt gggagccaat gcagttaccc ccatgactcc agagaacttt 300 accagctgtg ggttcatgca gcagatccag aagggtagtt atcctgatgc gattttgcag 360 gcacaagctg cagataaaat ccattcatcc ttccgetcte tcagctctge aatcaatgca 420 tccacaggga attatttact ggaaagtgtc aataagctgt ttggtgagaa gtctgcgagce 480 ttccgggaag aatatattcg actctgtcag aaatattact cctcagaacc ccaggcagta 540 gacttcctag aatgtgcaga agaagctaga aaaaagatta attcctgggt caagactcaa 600 accaaaggca aaatcccaaa cttgttacct gaaggttctg tagatgggga taccaggatg 660 gtcctggtga atgctgtcta cttcaaagga aagtggaaaa ctccatttga gaagaaacta 720 aatgggcttt atcctttccg tgtaaactcg gctcagcgca cacctgtaca gatgatgtac 780 ttgcgtgaaa agctaaacat tggatacata gaagacctaa aggctcagat tctagaactc 840 ccatatgctg gagatgttag catgttcttg ttgcttccag atgaaattgc cgatgtgtcc 900 actggcttgg agctgctgga aagtgaaata acctatgaca aactcaacaa gtggaccagc 960 aaagacaaaa tggctgaaga tgaagttgag gtatacatac cccagttcaa attagaagag 1020 cattatgaac tcagatccat tctgagaagc atgggcatgg aggacgcctt caacaaggga 1080 cgggccaatt tctcagggat gtcggagagg aatgacctgt ttctttctga agtgttccac 1140 caagccatgg tggatgtgaa tgaggagggc actgaagcag ccgctggcac aggaggtgtt 1200 atgacaggga gaactggaca tggaggccca cagtttgtgg cagatcatcc ttttcttttt 1260 cttattatgc ataagataac caactgcatt ttatttttcg gcagattttc ctcaccctaa 1320 aactaagcgt gctgcttctg caaaagattt ttgtagatga gectgtgtgecc tcagaattgce 1380 tatttcaaat tgccaaaaat ttagagatgt tttctacata tttctgctct tctgaacaac 1440 ttctgctacc cactaaataa aaacacagaa ataattagac aattgtctat tataacatga 1500 caaccctatt aatcatttgg tcttctaaaa tgggatcatg cccatttaga ttttceccttac 1560 tatcagttta tttttataac attaactttt actttgttat ttattatttt atataatggt 1620 266 gagtttttaa attattgctc actgcctatt taatgtagct aataaagtta tagaagcaga 1680 tgatctgtta atttcctr taataaatgc ctttaattgt tctcataatg aagaataagt 1740 aggtaccctc catgcceol.c tgtaataaat atctggaaaa aacattaaac aataggcaaa 1800 tatatgttat gtacatttct agaaatacat aacacatata tatgtctgta tcttatattc 1860 aattgcaagt atataataaa taaacctgct tccaaacaac “1500 <210> 518 <211> 1812 <212> DNA <213> Homo sapiens <400> 518 tagctaggca ggaagtcggc gcgggeggcg cggacagtat ctgtgggtac ccggagcacg 60 gagatctcgc cggctttacg ttcacctcgg tgtctgcagce accctccget tcctctecta 120 ggcgacgaga cccagtggct agaagttcac catgtctatt ctcaagatcc atgccaggga 180 gatctttgac tctecgecggga atcccactgt tgaggttgat ctcttcacct caaaaggtct 240 cttcagagct gctgtgecca gtggtgcttc aactggtatc tatgaggccc tagagctccg 300 ggacaatgat aagactcgct atatggggaa gggtgtctca aaggctgttg agcacatcaa 360 taaaactatt gcgcctgecec tggttagcaa gaaactgaac gtcacagaac aagagaagat 420 tgacaaactg atgatcgaga tggatggaac agaaaataaa tctaagtttg gtgcgaacgc 480 cattctgggg gtgtcccttg ccgtctgecaa agetggtgec gttgagaagg gggtecccct 540 gtaccgccac atcgctgact tggctggcaa ctctgaagtc atcctgccag tcccggegtt 600 caatgtcatc aatggcggtt ctcatgctgg caacaagctg gccatgcagg agttcatgat 660 cctcccagtc ggtgcagcaa acttcaggga agccatgcgc attggagcag aggtttacca 720 caacctgaag aatgtcatca aggagaaata tgggaaagat gccaccaatg tgggggatga 780 aggcgggttt gctcccaaca tcctggagaa taaagaaggc ctggagctgc tgaagactge 840 tattgggaaa gctggctaca ctgataaggt ggtcatcggc atggacgtag cggcctccga 900 gttcttcagg tctgggaagt atgacctgga cttcaagtct cccgatgacc ccagcaggta 960 catctcgcct gaccagcectgg ctgacctgta ‘caagtccttc atcaaggact acccagtggt 1020 gtctatcgaa gatccctttg accaggatga ctggggagcect tggcagaagt tcacagccag 1080 tgcaggaatc caggtagtgg gggatgatct cacagtgacc aacccaaaga ggatcgccaa 1140 ggccgtgaac gagaagtcct gcaactgect cctgctcaaa gtcaaccaga ttggctecgt 1200 gaccgagtct cttcaggcgt gcaagctggc ccaggccaat ggttggggcg tcatggtgtce 1260 tcatcgttcg ggggagactg aagatacctt catcgctgac ctggttgtgg ggctgtgcac 1320 tgggcagatc aagactggtg ccccttgccg atctgagcge ttggccaagt acaaccagcet 1380 cctcagaatt gaagaggagc tgggcagcaa ggctaagttt gccggcagga acttcagaaa 1440 : cceecttggee aagtaagctg tgggcaggca agceccttcgg tcacctgttg gctacacaga 1500 ccccteccect cgtgtcagect caggcagctc gaggcccccg accaacactt gcaggggtcece 1560 ctgctagtta gcgccccacce geccgtggagt tcgtaccget tecttagaac ttctacagaa 1620 gccaagctcce ctggagccct gttggcagct ctagctttgce agtcgtgtaa ttggcccaag 1680 tcattgtttt tctcgcctca ctttccacca agtgtctaga gtcatgtgag cctcgtgtca 1740 tctececggggt ggccacagge tagatccccg gtggttttgt gctcaaaata aaaagcectca 1800 gtgacccatg ag 1812 <210> 519 <211> 330 <212> DNA <213> Homo sapiens

© <220> <221> misc_feature <222> (113) .. (113) <223> nis a, c, g, t or u <220> <221> misc_feature <222> (270) ..(270) <223> nis a, ¢, g, t or u <400> 519 tttttttttt tttttttgge cagatcaata gctaggtaga aaccttttca actgggacag 60 gagacaccat cctttgggtg ttgttctcta ccttcccatg caaaaggcag tanaagatgt 120 ggaggacaga gaggaagagc tgagagtcct ggaaagccaa aaggctacac acatcacata 180 aactgattgg cctcagggaa aagactgagg ttcaaagagg tgacagactc catcaaggtg 240 acatgactgg ctggttgcct gcagaagtan atgcaggtcc caggtccagc tcectggtctca 300 attacagccc aaagcctatc tccagccaca 330 <210> 520 <211> 348 <212> DNA <213> Homo sapiens <400> 520 acgtccetgg tagacggggt agggggatct accageccag ggdatcgecgtce tttcecgccgec 60 acgctgcttc accgatatcc aataaaccca tccecctcecgec acgacgtctce cgcgtatctt 120 tgtagcctca agaatccgtc cccacgtcca cccatcccga gcactccaca cgccataaca 180 aaccacggac acgacaaatg catgcaaact tctcatttat tgtgtctact actctgtgtt 240 gctacaggga gtgaagaggg tgaaggcaaa gaaaaaaaaa aggaacaaaa taatagatta 300 gcagaaggaa taatccgtgc gaccgagctt gtgcttettt tcttataa 348 <210> 521 <211> 862 <212> DNA 2 <213> Homo sapiens HR <400> 521 agectcectgt caaggtagct agaggcctgg gaaaggagat agccttgctce cggcccecctt 60 gaccttcagc aaatcacttc tcteccctgeg ctcacacaga cacacacaca cacacgtaca 120 tgcacacatt tttectgtea ggttaactta tttgtaggtt ctgcattatt agaactttct 180 agatatactc attccatctc cccctecattt ttttaatcag gtttccttge ttttgecatt 240 tttctteectt cttttttcac tgatttatta tgagagtggg gctgaggtct gagctgagcee 300 ttatcagact gagatgcagc tggttgtgtt gaggacttgt gtgggctgce tgtccecgge 360 agtcgctgat gcacatgaca tgattctcat ctgggtgcag aggtgggagg caccaggtgg 420 gcaccecgtgg gggttagggc ttggaagagt ggcacaggac tgggcacgct cagtgaggct 480 cagggaattc agactagcct cgattgtcac tccgagaaat gggcatggta ttgggggtcg 540 ggggggcggt gcaagggacg cacatgagar actgtttggg agcttctggg gagccctgcet 600 agttgtctca gtkatgtctg tkggacctcc agtcccttga gaccccacgt catgtagaga 660 agttaacggc ccaagtggtg ggcaggctgg cgggacctgg ggaacatcag gagaggagtt 720 cagagcccac gtctactgcg gaaaagtcag gggaaactgc caaacaaagg aaaatgcccc 780 aaaggcatat atkctttagg gecctttggtce caaatggccc gggkgggcac tcttccagat 840 agaccaggca actctcecctce cc 862 <210> 522 <211> 315 <212> DNA <213> Homo sapiens <400> 522 aggtgaatga tgactacaat aacattgcaa ctatttcttt cctggcatag ggaggtaata 60 agaaactaaa tgatcgcatg gtacatgctt gtattatata gatgggttta ggaatctata 120 aagtatggag gtaggaagac accatatgtc caggatcaaa acattcctca tattgaggta 180 gtctagtgaa gctgtttcat gtagctgctt taggaagtgg tttaaggaag cttactccca 240 cttcaagtta agcaccaaag caatcactaa ttctggagca caggaagact gctatctcat 300 cattcacctt tgcag 315 <210> 523 <211> 972 <212> DNA <213> Homo sapiens <400> 523 atgacaccga cgacgacgac cgcggaactc acgacggagt ttgactacga tgaagacgcg 60 actccttgtg ttttcaccga cgtgcttaat cagtcaaagc cagttacgtt gtttctgtac 120 ggcgttgtet ttctettcgg ttccatceggace aacttcttgg tgatcttcac catcacctgg 180 cgacgtcgga ttcaatgctc cggcgatgtt tactttatca acctecgceggdce cgcecgatttg 240 cttttegtet gtacactacc tctgtggatg caatacctcc tagatcacaa ctccctagcc 300 agcgtgecgt gtacgttact cactgectgt ttctacgtgg ctatgtttge cagtttgtgt 360 rttatcacgg agattgcact cgatcgetac tacgctattg tttacatgag atatcggect 420 gtaaaacagg cctgeectttt cagtattttt tggtggatct ttgccgtgat catcgccatt 480 ccacacttta tggtggtgac caaaaaagac aatcaatgta tgaccgacta cgactactta S40 gaggtcagtt acccgatcat cctcaacgta gaactcatgc ttggtgcttt cgtgatcceg 600 ctcagtgtta tcagctactg ctactaccgce atttccagaa tcgttgeggt gtctcagtcd 660 cgccacaaag gtcgcattgt acgggtactt atagcggtcg tgettgtectt tatcatcttt 720 tggctgeegt accacctaac gctgtttgtg gacacgttaa aactcctcaa atggatctcc 780 agcagctgcg agttcgaaag atcgctcaaa cgtgcgetca tcttgaccga gtcgctcgee 840 ttttgtcact gttgtctcaa tcecgetgetg tacgtcttcg tgggcaccaa gtttcgcaag 200 aactacactg tctgctggcece gagtttcgcec agcgactett ttccegegat gtatcctggt 960 accacagcat ga 972 <210> 524

<211> 949

<212> DNA

<213> Homo sapiens

<400> 524 tttectecgecea cggcacaacg ccaccttggg caaacctaat tccagtcttg gatgccacct 60 tgctgacgac aaggcacttc cttacaatga gecctggaatt ctaagcagca gcttcacaat 120 ctgcaattgc acgtttetge cctttacaat aaagaaacac acactttcct ttcaccacce 180 acacccacca aaaataccac cacactccaa cacaccccac gaagaaagceg agaaagcccea 240 aaactgggcc ccccaccaca accgcacece cacgaatctg tcatacatcc acaagacacc 300 cgggccctet gagcaccceac ggcgaacggc cgccaagecg ccaccccect cccaggegge 360 agcccccaca tgcgeccacgt cgtacatcac gtcacccaac gccaccgacc tatgcgcaat 420 cgcgegcata gccccgtact cgggccagca gccccacCccc agccagccac actgctcececc 480 ctcgcacacc acaccaagat cgcgcgaccc aacgcaccca ctccgcacca caccccacac 540 cacccccacc ccgectcgacc agcatgtgtc acaaccccgt acccgcaccce tgagtaccac 600 gaaacggaca ggctaacgac gcgaagtacc tcacccaccc gaccgaacgc gatccacggt 660 cccgtaageg ctaattccag actacaccce catagctcecgc cgcaatggtc tgcacgtcca 720 ccccacacca acagagatca ctacagaaat atgcctccaa ccccgcccac gttaaactce 780 ccactccaca cgcagcaatg tcactcggca ccgcgccttt cacggtgtga caggtcttct 840 ccatagatgt cggatcggcc tccttactac ctccccecctt acgaaagagt acacactcca 900 caaccacaga cctccgccca aggcgccgcc cgcgcgeccc gcgcacgtg 949 <210> 525 <211> 2298 <212> DNA <213> Homo sapiens <400> 525 aatagaagat cgctcgggaa ttcttactct cgataaagat tataacaaca taggaaaatt 60 cttaaataga attttaggca tggaggtgca tcagcagaat gegttatttc agtattttgce 120 ggacacactt actgcagttg ttcaaaatgc caaaaaaaat ggaagatatg atatgggaat 180 cttagatctt ggttctggag atgaaaaagt gcggaaaagt gatgttaaaa agtttctgac 240 tccaggatat tcaacctctg gccacgtaga attatacaca attagtgtag agaggggaat 300 gtcatgggag gaagctacca agatttgggc tgagctgaca ggaccagacg atggctttta 360 cttgtcattg caaataagga acaacaagaa aactgccatc ttagttaaag aagtgaatcc 420 taaaaagaaa cttttcttag tttatcgacc aaatactggg aagcagctca aattagaaat 480 ttatgctgat ctaaaaaaga aatataagaa ggtcgtctca gatgatgccc tgatgcactg 540 gttagatcag tataattcat ctgcagatac ttgtactcat gcttattggc gcggcaattg 600 caaaaaagca agcttggggc tagtttgtga aataggtctt cgttgccgta catattatgt 660 attatgtggt tcagtgctga gtgtctggac aaaagttgag ggtgttctag catctgtcag 720 tggcacaaac gtgaagatgc agatcgtgcg gctaagaacg gaagatgggc aacggattgt 780 aggtttgatc attccggcaa attgtgtgtc tcctcttgta aatctcctat caacttcaga 840 ccagtctcaa cagcttgcgg tccaacagaa acagctatgg caacagcatc accctcagag 900 catcaccaac ttgagcaacg catgaagaac agacaggttt caacatggat ggatctgaaa 960 tgctgttgaa gcatatcatt tgcataaaaa tcagggacag tttccaaaga attatatatt 1020 tttttcagtt gtgctctcta gttagttttt ttgggagtaa ggacaaacct ggaatagata 1080 gcaaaactga aaatcagcag tgctgatggt ggtacatatg tctttccttt agcttctece 1140 ctgataattc ccatctgctt ttacttcggg tgagcagagg dggatgtgtg tgtgcgtgtg 1200. tgtcagtctg tttgtgagtg tgttaaaggc tacagaccac agttggttta aaatgcttgg 1260 aacttcccaa actggcttta ctttatgttt atacagtgct cagggttaac gcagtacatce 1320 catgccattg ctgtgggagg tatccecgga tgcatgtgtt ttgagtctat aaatatagaa 1380 aatatatatt ggtttctttt tccaacttaa taggtttatt aaagcatgaa atgaaaggtt 1440 gcatatcatg cattcaggtt attttctaat ttttgttctg acagtgcatg tctttggaag 1500 catgctgaaa caagattaac acaggagtcg agtaacagag agaaacattt gttagatgta 1560 cagcattggt tattgcattt ttatagtgtt tatacctggg tattgcttca aaccctgcag 1620 acccctcectt ccccttectee ctgccectggg tttctggtceca aggtaatgaa tacatacatt 1680 tttctgtgat aaaactctta aaagttaatt ttaatgtatt aatagtattc ctaatgtgtg 1740 ctgcagaaat ggctatgagc ctcttaaatt tacatttgca acttaaaggt agttttagaa 1800 ggaagtacaa attggctttc atcttgcaaa caatcgtttt ttacttcatt atcttaattt 1860 gctttgtcac tcataaaaag gaaaccatac ctgagttgta gacaatgagg aaacacttga 1920 ggcttctgct gtgtgttett ttgttattgt tgttattgtt gttactcagt aacttgaata 1980 ttgtttaatg tgttgtaaga cgtagagttt atctcaagct gttaaaaatg gtaatgtaca 2040 . aatgtgaata gacacttatc tatataatat gggtaagttt tgtttcgcct ataatagatg 2100 tttataaaaa caagtgaggg gacagttggt ctttttatct tttctttctt tttctttett 2160 ttecttetttt cttttttttc tttotttttt tttttgette cacaggttgc actattgaaa 2220 aatcgagatt gtataaacct ggtaaaaagc tgcaagatgc caaaatcttg tagatgtcaa 2280 ataaaaagtt attatact 2298 <210> 526 <211> 618 <212> DNA <213> Homo sapiens <400> 526 cttttgcggg tggcggcgaa cgcggagagc acgccatgaa ggccteggge acgctacgag 60 agtacaaggt agtgggtcgc tgcctgccca cccccaaatg ccacacgccg cccctctacce 120 gcatgcgaat ctttgcgect aatcatgtcg tcgccaagtc ccgettctgg tactttgtat 180 ctcagttaaa gaagatgaag aagtcttcag gggagattgt ctactgtggg caggtgtttg 240 agaagtcccc cctgegggtg aagaacttcg ggatctgget gegetatgac tcccggagceg 300

PCT/US2003/012946 gcacccacaa catgtaccgg gaataccggg acctgaccac cgcaggcgcet gtcacccagt 360 gctaccgaga catgggtgec c€ggcaccgcg cccgagccca ctccattcag atcatgaagg 420 tggaggagat cgcggccagec aagtgecgec ggecggetgt caagcagttc cacgactcca 480 agatcaagtt cccgctgecc caccgggtcce tgcgccgtca gcacaagcca cgcttcacca 540 CCaagaggcc caacaccttce ttctaggtge agggccctcg tcecgggtgtg ccccaaataa 600 actcaggaac gccccggt 618 <210> 527 <211> 2640 <212> DNA <213> Homo sapiens <400> 527 gggcggccaa cgtgggctcg Cctcttcgacg acccagaaaa cctgcagaag aactggctte 60 gggaatttta ccaggtcgtg cacacacaca agccgcactt catggecttg cactgtcagg 120 agtttggagg gaagaactac gaggcctcca tgtcccacgt ggacaagttc gtcaaagaac 180 tattgtcgag tgatgcgatg aaagaatata acagggctcg agtctacctg gatgaaaact 240 acaaatccca ggagcacttce acggcactag gaagctttta ttttctteat gagtccttaa 300 aaaacatcta ccagtttgac tttaaagcta agaagtatag aaaggtcgct ggcaaagaga 360 tctactcgga taccttagag agcacgccca tgctggagaa ggagaagttt cgcagactac 420 ttcceecgagt gcaaatggtc aagaaaaggc ttcatccgga cgaggtggtg attgcagact 480 gtgcctttga cttggtgaat atccatcttt tccatgatgce ttccaatectg gtcgectggg 540 aaacaagccc ttccgtgtac tegggaatcec ggcacaaggc actgggctac gtgctggaca 600 gaatcattga tcagcgattc gagaaggttt cctactttgt atttggtgat ttcaacttce 660 ggctggattc caagtctgtc gtggagacgc tctcagcaaa accaccgatg cagacggtcc 720 gggccgecga caccaatgaa gtggtgaage tcatatttcg tgagtcggac aacgaccgga 780 aggttatgcet ccagttagaa aagaaactct tcgactactt caaccaggag gttttccgag 840 acaacaacgg caccgcgctce ttggagtttg acaaggagtt gtctgtecttt aaggacagac S00 tgtatgaact ggacatcteg ttcccteecca getacecgta cagtgaggac gcccgceccagg S60 gtgagcagta catgaacacc cggtgcccag cctggtgtga ccgecatccte atgtccecegt 1020 ctgccaagga gctggtgctg cggtcggaga gcgaggagaa ggttgtcacc tatgaccaca 1080 ttgggcccaa cgtctgecatg ggagaccaca agccegtgtt cctggecttce cgaatcatgc 1140 ccggggcagg taaacctcat gcccatgtge acaagtgttg tgtcgtgcecag tgacgtggtg 1200 ggaagagatg ccagcgccac gagaggacac ttcgtgagec tccctgtage cgtggaccga 1260 atacgcactc ttgaaagctg catcgagaac ccgcccaagc gccacctgct agacggccag 1320 ccccacactt cgcttcagce tccggaccat tccggagcag ccccacatac ctcactgtet 1380 cgtctgtcecta tgtgacatta agtagaaata ttggtttttt ttttttttta aataagtcac 1440 agtcctgttg tcaaaactct aatagacagc aaagagggtc tgtaccgtag acttcacagt 1500 tttcagtttt taatgattgc cagtggaggg gcttcttcag cacagagacc ccccactgtg 1560 tccagggacc ccctcectgecca ggtggaggtg tgtccagggg ctggggaagc cgagacgggce 1620 actccctcectg ccggecggca gegtggecct gagcatggca agggggtctg tctcetgecga 1680 tgctcecttecec gecggcactga ctctgecgecg tgtcacatgg tttttgaatc acactgcage 1740 tgctttccat ttttatatat atataaatat atataaatat atacttttta aaaataattt 1800 ataaatctta ccaaaactta tgctaaatat actttccagt atgaacgcac aggagagtcc 1860 catcagcagg cggcattgga gtctaggagc tcagctgtgt gtccatcaac acacaaattc 1920 gtaaaaaaca cacatggcct cgccatcgtg ggtaaaatcg gccccacagc acgtctgcac 1980 cagcgggccg ttactcccat geoccgttcttc tgtgtaatat taagaactga atgtgaagtt 2040 tatagctagc ctgggtgtac cttttaagaa ttttgtaaac cgtttgtctg tcttttgtta 2100 ctgttttatg gtgccaagta tcctacgtta caacaataat atcatgggag aaatagaaat 2160 agcctagttt gcttccaata gaaactgett ttaacatggg ctgtatataa aaatattaaa 2220 gagaaacaaa actgtacatt tcctcattgc tccgctacag acaacccatg tcataacctt 2280 gttgcaaata tttttctcct atagcagtaa gtacagcatt agaaggtgat tagagagtct 2340 gttgatgaaa cacaaatgta tgtttttatt gatttttact ttagaacact acagagttcc 2400 tgggaccggg gtgaaggcat tagctgggtg tttgtgtggg ataaatacta ccactgcaag 2460 tgactgctgt ccgctgecgga atctgttctt ggtggaagca caggtccgtg tcgectgetgt 2520 ggttgccgct gtccgcggtt caacacggag tccgecccgce gggtttcage tgttggtcegt 2580 tctgaggggce ctttggaagt gaccggtctg gttcctaage aataaaattg accgtggtga 2640 <210> 528 <211> 743 <212> DNA <213> Homo sapiens <400> 528 agcgtgggta aaagcaaaag caacagctca agcagcctcc ttggagaaaa cctgaaaatt 60 caacttgttc aagagaaggt cttgtacgtg cctaagttct agagcctcct gacgtgagca 120 tggctgagag tgaggaccgc tccctgagga tcgttctggt agggaaaact ggaagtggga 180 aaagtgcaac agcgaacacc atccttggag aggaaatctt tgattctaga attgetgecc 240 aagctgttac caagaactgt caaaaagcat cccgggaatg gcaggggaga gaccttcttg 300 ttgtagacac tccagggctc tttgacacca aggagagcct ggacaccacc tgcaaggaaa 360 tcagcegetg catcatctce tcctgeccag ggccccatge tattgtccta gttcectgetge 420 tgggccgeta cacagaggag gagcagaaaa ccgttgcatt gatcaaggct gtctttggga 480 agtcagccat gaagcacatg gtcatcttgt tcactcgcaa agaagagttg gagggccaga 540 gcttccatga cttcatagca gatgcggatg tgggcctaaa aagcatcgtce aaggagtgcg 600 ggaaccgctg ctgtgccttt agcaacagca agaaaaccag taaggcagag aacgaaagtc 660 aagtgcagcg agttgggtgg aagctgatag agcaacacat ggtgcagtgc aacgaacggg 720 ccttactttt ctgatgacct ata 743 <210> 529 <211> 346 <212> DNA <213> Homo sapiens <400> 529 cttttacctc gttgcactgc tgagagcaag atgggtcacc agcagctgta ctggagccac 60 ccgcgaaaat tcggccaggg ttctegetet tgtegtgtct gttcaaaccg gcacggtctg 120 atccggaaat atggcctcaa tatgtgcege cagtgtttcec gtcagtacgc gaaggatatc 180 ggtttcatta agttggacta aatgctcttc cttcagagga ttatccgggg catctactca 240 atgaaaaacc atgataattc tttgtatata aaataaacat ttgaaaaaaa aaaaaaaaaa 300 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 346 <210> 530 <211> 397 <212> DNA <213> Homo sapiens <400> 530 ctatgctgcc tgggctagtc tcaaactect tgectcaaat gatcctecca catcagtctc 60 cCaaacagtt caacctacac gaacaggcaa ccatgcctgg tgtatttatt aaaatgtagc 120 tactagaata tttaaaattc acatgtgcct cacatattat ttcttagaga attgcctcat 180 ttttgaaatc tcaggctgcc tgctctaaaa cctggatgtg ccaggaaagt aaaaaatctg 240 aaattttaaa ataattgtca ttatattgct tccatgtatg aataacacat atatattttt 300 cataaataca aataatctta cacacaaatg aaaatgcaag tattttacag tcagggccag 360 tgtccagtgc atgaaggaag ccctgccaga aaaggat 397 <210> 531 :

ry So

<211> 1236 <212> DNA <213> Homo sapiens <400> 531 ttactgagac ttgttcctca ggtcctggat ggctgcctecg atggccaggce tcagggtgtce 60 caggtetteg ggaggggtct cggtgggctg ctcaaactge cccacggcgt aggccttcge 120 ggccgtcectecg tagataggca gcatgaaccc accctggttg gtggagaaga tgcgcaccat 180 gacctgtttg ggaaactttt gcatcagggg caggcacagg ttgagagcgc ccaacaggtce 240 cacgggggtg gcagcgtgga tgatcatgtt gcggtaatcg gaggaacggg ggcataattg 300 gtgggtgtgc aattctttga ggctccacgc ggccttgacg ccttegttac aagcatcgge 360 tgtgcgctge gccacttcgg gtggatgtgt cacgggcatg gtgtgctcca tgaggaaggg 420 agtggagagg gccaggttgc acatggtgcc caggcgacac cgcaccgcat ccacctcact 480 cttcacctca tgattgcggg tgtagataat ctggatgccc ttgttgttca cctgcatggt 540 tttgcaggct ttgatggcct catctaacac ctggtgcata ctgggaatcg tgaagggcag 600 gttcttgtac tcaagagagc gattggtgtt gcggaacatg cggctcacct cgtcaatctt 660 gacgcgacce cgccgagtcet gcacgttggg tgtgcagaag ggggtgttct tatctttcat 720 gatattgcge accttctegt tgtccaactc ggagatgcgt ttgctcttct tcecttgcgggg 780 tcecggtgetce gecccgeccge tgetctgatg goccgcagctce agcagagagg aggaggccgc 840 gccaccaaaa ccgccgcgece catggtgget cgaggtcacg gatgctccte cgecactget 900 gcatttcatec tecctcggact cactctccga gtccgaagcec gaactgcagg aggaggaaga 960 cgaagaggaa ctatcttcat cgggccggcc caagggatcg ggaagaggag ggtggttcat 1020 ctgggagagc gggtgegtgg gagaggtcac tcgecggegtg ccgetgcegg tggaagggga 1080 agacgcggta gcaccgeggg tttcgacttec ttcaccctgt tcecttectcge tatcagagat 1140 cacgatacag ccggcggtat cgataatctt gttgcggtac tggatggtaa agtcgggctce 1200 gggcttgatg tcttectgtt tgatgagggg cagcat 1236 <210> 532 <211> 2034 <212> DNA <213> Homo sapiens <400> 532 aaaccttggc catggtcact tcctctttte caatctcectgt ggcagttttt geccctaataa 60 ccctgecaggt tggtactcag gacagtttta tagctgcagt gtatgaacat gctgtcattt 120 tgccaaataa aacagaaaca ccagtttctc aggaggatgc cttgaatctc atgaacgaga 180 atatagacat tctggagaca gcgatcaagc aggcagctga gcagggtgct cgaatcattg 240

/

tgactccaga agatgcactt tatggatgga aatttaccag ggaaactgtt ttcccttatc 300 tggaggatat cccagaccct caggtgaact ggattccgtg tcaagacccc cacagatttg 360 gtcacacacc agtacaagca agactcagct gcctggccaa ggacaactct atctatgtct 420 tggcaaattt gggggacaaa aagccatgta attcccgtga ctccacatgt cctcctaatg 480 gctactttca atacaatacc aatgtggtgt ataatacaga aggaaaactc gtggcacgtt 540 accataagta ccacctgtac tctgagcctc agtttaatgt ccctgaaaag ccggagttgg 600 tgactttcaa caccgcattt ggaaggtttg gcattttcac gtgctttgat atattcttct 660 atgatcctgg tgttaccctg gtgaaagatt tccatgtgga caccatactg tttcccacag 720 cttggatgaa cgttttgccc cttttgacag ctattgaatt ccattcagct tgggcaatgg 780 gaatgggagt taatcttctt gtggccaaca cacatcatgt cagcctaaat atgacaggaa 840 gtggtattta tgcaccaaat ggtcccaaag tgtatcatta tgacatgaag acagagttgg 900 gaaaacttct cctttcagag gtggattcac atcccctatc ctcgcttgece tacccaacag 960 ctgttaattg gaatgcctac gccaccacca tcaaaccatt tccagtacag aaaaacactt 1020 tcaggggatt tatttccagg gatgggttca acttcacaga actttttgaa aatgcaggaa 1080 accttacagt ctgtcaaaag gagctttgct gtcatttaag ctacagaatg ttacaaaaag 1140 aagagaatga agtatacgtt ctaggagctt ttacaggatt acatggccga aggagaagag 1200 agtactggca ggtctgcaca atgctgaagt gcaaaactac taatttgaca acttgtggac 1260 ggccagtaga aactgcttct acaagatttg aaatgttctc cctcagtggc acatttggaa 1320 cagagtatgt ttttcctgaa gtgctactta ccgaaattca tctgtcacct ggaaaatttg 1380 aggtgctgaa agatgggcgt ttggtaaaca agaatggatc atctgggcct atactaacag 1440 tgtcactctt tgggaggtgg tacacaaagg actcacttta cagctcatgt gggaccagca 1500 attcagcaat aacttacctg ctaatattca tattattaat gatcatagct ttgcaaaata 1560 ttgtaatgtt atagggcgtc tctttatcac tcagcttctg catcatatgc ttggctgaat 1620 gtgtttatcg gcttcccaag tttactaaga aactttgaag ggctatttca gtagtataga 1680 ccagtgagtc ctaaatattt tttctcatca ataattattt tttaagtatt atgataatgt 1740 tgtccatttt tttggctact ctgaaatgtt gcagtgtgga acaatggaaa gagcctgggt 1800 gtttgggtca gataaatgaa gatcaaactc cagctccagcec ctcatttgect tgagactttg 1860 tgtgtatggg ggacttgtat gtatgggagt gaggagtttc agggccattg caaacatagc 1920 tgtgcccttg aagagaatag taatgatggg aatttagagg tttatgactg aattcecttt 1980 gacattaaag actatttgaa ttcaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 2034

<210> 533 <21l> 4500 <212> DNA <213> Homo sapiens <400> 533 c©gggtggttg agtggaagcg gtcgccatgt cecgcggggag cgcgacacat cctggagctg 60 gcgggcgccg cagcaaatgg gaccaaccag ctccagcccce acttctette ctccegecag 120 cggccccagg tggggaggtce accagcagtg ggggaagtcc tgggggcacce acagctgctc 180 cttcaggagc cttggatgct gctgetgetg tggetgccaa gattaatgcc atgctcatgg 240 caaaagggaa gctgaaacca actcagaatg cttctgagaa gcttcaggcet cctggcaaag 300 gcctaactag caataaaagc aaggatgacc tggtggtagce tgaagtagaa attaatgatg 360 tgectctcac atgtaggaac ttgctgactce gaggacagac tcaagacgag atcagccgac 420 . ttagtggggc tgcagtatca actcgaggga ggttcatgac aactgaggaa aaagccaaag 480 tgggaccagg ggatcgtcca ttatatcttc atgttcaggg ccagacacgg gaattagtgg 540 acagagctgt aaaccggatc aaagaaatta tcaccaatgg agtggtaaaa gctgccacag 600 gaacaagtcc aacttttaat ggtgcaacag taactgtcta tcaccagcca gcacccatceg 660 ctcagttgtc tccagetgtt agccagaagc ctcccttcca gtcagggatg cattatgttc 720 aagataaatt atttgtgggt ctagaacatg ctgtacccac ttttaatgtc aaggagaagg 780 tggaaggtcc aggctgctce tatttgcagce acattcagat tgaaacaggt gccaaagtct 840 tcectgegggg caaaggttca ggetgcattg agccagcatc tggccgagaa gcttttgaac 900 ctatgtatat ttacatcagt caccccaaac cagaaggcct ggctgctgcc aagaagcttt 960 gtgagaatct tttgcaaaca gttcatgctg aatactctag atttgtgaat cagattaata 1020 ctgctgtacc tttaccagge tatacacaac cctctgectat aagtagtgtc cctcctcaac 1080 caccatatta tccatccaat ggctatcagt ctggttaccc tgttgttcee cctcctcage 1140 agccagttca acctccctac ggagtaccaa gcatagtgec accagctgtt tcattagcac 1200 ctggagtctt geccggcatta cctactggag tcccacctgt gccaacacaa tacccgataa 1260 cacaagtgca gcctccagct agcactggac agagtccgat gggtggtcct tttattcctg 1320 ctgctcetgt caaaactgce ttgectgetg gececccagec ccageccccag cocccagceeee 1380 cactcccaag tcagccccag gcacagaaga gacgattcac agaggagcta ccagatgaac 1440 gggaatctgg actgcttgga taccagcatg gacccattca tatgactaat ttaggtacag 1500 gcttecteccag tcagaatgag attgaaggtg caggatcgaa gccagcaagt tcctcaggca 1560 aagagagaga gagggacagg cagttgatgc ctccaccagc ctttccagtg actggaataa 1620 aaacagagtc cgatgaaagg aatgggtctg ggaccttaac agggagccat ggtgagtgtg 1680 atatagctgg gggaacagggd gagtggctaa gactggtcta aagctattag ttttctcage 1740 cgggcgcagt ggctcacgecc tgtaatccca gcactttggg aggccgaggt gggcagatca 1800 cctaaggtca ggagttcaag accagcttgg ccaacatagt gaaatcccat ctctactaaa 1860 aatacaaaaa ctagcgggca tggtggtggg cgcctgtaat tccagctact cagggggttg 1920 aggcaggaga atcgcttcaa cctgggaggc agaggttgca gtgagccaag atcagaccac 1980 tgcecctccag cctgggcaat agagcaagac tccatctcat aaataaataa atacataaat 2040 aaagctatta attttctaac ctgatgttca ttcaggtgtt taatccaacc tctataatct 2100 gttggccagt gaaaatactt ttgggctggg cacggtggcet cacgcctgta atcccagcac 2160 tttgggaggc caaggtgggc ggataacctg aggtcaggag tttgagacca gcgtggctaa 2220 cacggtgaaa ccccgtectct actaaaaata gaaaaattaa gctgggcatg gtggtgcatg 2280 cctgtaattc cagcggcttg gaaggctgag gcaggagaat cacttgaact tgggaggtgg 2340 aggttgcagt gggccgagat cacaccactg cattccagcecc tgggcactag agtgagactc 2400 tgtctcaaaa aaaaagaaag agaaagagaa aatagtttct aaaaaattgt atacagacaa 2460 ccttttattt ccaacaaacg tgtgccgaga gagagagaga gaaaatagtt ttaaaaaaat 2520 tgtatacaga caaccttttg tttccaacca acgtgtatct agaaaagagt tagtcgactt 2580 attttataca tagcatcagt gaatagtaat gagtggtagg tcatttcaaa atcctgttgc 2640 ctatattatg tgaataccag gaggtcatct gatacggact taataaaggt tgattttgct 2700 ttatattggg agctgagcca cacctcccct tataactcta ttggtcagta atggtcagtt 2760 tgtggctgtt aggaaaatgt tgccttttag cattccagaa ctctaaatcc tgtagaggta 2820 catgggatat tttattcttt gcctgtactc ataaaaatga acagaagaaa atacgttttt 2880 ttcttttett aacttctttt cttttaacte tttaaaaggt gaaatatcag ccctcaagag 2940 actcacttgc taactttcct ttttttcttt ttttttcttt tttttgtgtt teottttttcet 3000 ttctctgttt tcttacatgg ttctggtgga ttcacatttg ctgatgctgg tgctgttttt 3060 cgtgtgatct tcaacgtttt tgggtgacca ttgaccctgt gacctcaaaa tggtgtccaa 3120 ctaaccactt aaaattaaca tctttttttt aattaacgaa tttatggtat tttttttttt 3180 cccttggecgg ggatggggtt ggggttgttt tttetctatt ctagattatc cagccaagaa 3240 gatgaaaact acagagaagg gatttggctt ggtggcttat gctgcagatt catctgatga 3300 agaggaggaa catggaggtc ataaaaatgc aagtagtttt ccacagggct ggagtttggg 3360 ataccaatat ccttcatcac aaccacgagc taaacaacag atgccattct ggatggctcce 3420 ctaggaaaca gtggaacaga gttttgaccc tcagtgactc ttcttagcaa taatgcatgce 3480 atttgattta acaagactet ggggcctgtg ctgggaacca tctggacctt tgcagaagtt 3540 agagattcag tgcccccectt tcttaaaggg gttccttaac aaccacaaaa atccttattt 3600 ctgcagtggc atagaatctg ttaaaattta attagaatca caaatttatc tcagaagctt 3660 tttaacagtt ggtgaaatgt gcttgtccaa caaagcatcce taacagggtc gttcccatac 3720 acatttgace tggtcagcct tttccaggtg aatagcccca gttetgacat aaagaaagtt 3780 ttatttgtat tttactactg tttggtcaat tttgatatat aactggttac aaacagagcc 3840 ttactattta ttagtgggga aatgatttta agaccgtect tttcagtatt taattctgac 3900 agatctgcat ccctgttttg ttttggatta tttetgtttt ggaaaatgct gtctcattta 3960 aaactgttgg atatagetgg atcctggata ggaaaatgaa attattttee cattgtgtte 4020 tttaattggg gtgatccaaa gctggecacct tcaggcacat tggtctcata gccattactg 4080 tttttattgce ccttctaaga tecctgtcttce agctgggtca gagaaaactt cttgactaaa 4140 actggtcaga actcatcaca gaaatgaaat acagtggtct ctctctcceca gaactggttg 4200 cagctaaaac agagagatct gactgctggc tataggattt tggacttaat gactgaaatt 4260 gcaaattgtc ctttttcttg gcattacaga ttttgccaaa ataacttttt gtatcaaata 4320 ttgatgtgtg aaagtgaagg agctagtctg ctgaaccagg aatagtttga gatattgaac 4380 tgtcattttt gcacatttga atactttgca ggctggcttt gtataaactt atcctctggt 4440 ttcctatatg ttgtaaatat ttagaccata atttcattat aaataaatct ataaatattc 4500 <210> 534 . <211> 594 <212> DNA <213> Homo sapiens

<220> :

<221> misc_feature

<222> (15)..(64)

<223> n is a, c, g, t oru

<400> 534 ggggacatta gtttnnnnnn nnnnnnnnnn nnnnnnnnnn nnAannnnnnn nonnnnannnn 60 :

nnnntgtgtc tcatgaatag gaaagaaagc agatgtaaag agttacataa aagcaaacag 120 cttgctctgg tttctgggte taacaattac gacttaaaca atggagccaa agaaaaatac 180 attagatgat tctcaacctg gaaagcaaga ctgcaaatta taaccacaaa aacaaagatc 240 tactgtctcec cagataccgg aaatggtaac ccggatattt gaggcttcca aggcaggaag 300 ataaaggaga atcagacccce tgagcaggga ctctggagca gcactccagg accctgccta 360 gagactaagc ctcaggtgga gcagtgaggt agacatctgc tcacaccagt ttcctetcac 420 agatgtacac agattggggt gttgggtgag ggcctgatgg gggaaaggaa agagagaact 480 gctataggtg aatctctctg tggettgttg tgggaccectg cgcectttaa attagggcat 540 attttacaaa aacttattat tctacacagce ccttcttggg cctttacaga acga 594 <210> 535 . <211> 1721 <212> DNA <213> Homo sapiens <400> 535 cgggtgtaga tttcacaacc cagggggcgg agccaggatg atgacceccge ccectcececta 60 aataattctc ccgggaggga cacggaagca gcaaccggga tgggacgggg agagaggagg 120 cactactggg gacctaagcet ggttctcaaa tgecctctect ttteccetce aagcctccca 180 ggcttectat ggtccctaag tccegggtte tcagcgtgac attccagagc aaacacagct 240 ccccattact ctataccagg cactggcatg gattaattta tctaatcaca acatcccagt 300 aagatatgcc ctgcctetece tgctcacact ctatggcectgg cattcacctg tggggccagg 360 tcgaaactec tggcttggcece gtcaatgect tactggagcet gctctgctaa ccteetgetg 420 Cttccteteg gacctcgatt cagccatcat gaatttacca gcatagagca tgtgattcca 480 cacctccaag cttttgcaca tgctgctecec tgccagegac cctcttttgg ceggectace 540 ccgggaccct gactactctg tgtcctgect ctactcacct cectcacect ccagcatgtg 600 tttgectget aacatgaagt gtgacaagta ctggggctct tcctcggaca aggctctgga 660 agcgtacage tcactggtcc aggactccag agccagagac cttgggatgc cctgcttctg 720 gggacacagt gaggactgca gactgcaggc cagggtgggg ctcagggcct tcgccacatg 780 aggctgcece ctcccecagt ccagacctgc agaagcagtg ctgtaatgac caggacattt 840 tgaagaggca tcacaacgta tctaagaagc ccttggagac cagctcttece aaagtcaaag S00 ccaagaccat tgtgatgatt cccgactccc agaagctcct gcgatgtgaa cttgagtcac 960 tcaagagcca gttacaggec cagaccaagg ctttcgagtt cctgaaccac tcagtgacca 1020 tgttggagaa ggagagctgc ttgcagcaaa tcaagattca gcagcttgaa gaggtgctga 1080 gccccacagg ccgccaggga gagaaggagg agcacaagtg gggcatggag cagggccgge 1140 aggagctgta tggggccctg acccaaggec ttcagggget ggagaagacc ctgcgtgaca 1200 gtgaggagat gcagcgggcec cgcaccacte gctgcctgea gctgcectggece caggagatcc 1260 gggacagcaa gaagttcctg tgggaggagce tggaactggt gcgggaggag gtgaccttca 1320 tctatcagaa gctccaagcg caggaggatg agatctcaga gaacttggtg aacattcaga 1380 aaatgcagaa aacgcaggtg aaatgccgca aaatcctgac caagatgaag cagcagggtc 1440 atgagacagc cgcctgtccg gagactgaag agataccgca gggagccagt ggctgctgga 1500 aggatgacct ccagaaggaa ctgagtgata tatggtctge tgtgcacgtg ctgcagaact 1560 ccatagacag cctcactttg tgctcggggg cctgtccecaa ggcctcgagce ctaagaggcc 1620 acaaggggca ccagtgcctg agccctccac tccectectg ggactctgac tcegactgtg 1680 accaggacct ctcccagcca cctttcagca agagcggeeg Cc 1721 <210> 536 <211l> 526 <212> DNA <213> Homo sapiens <400> 536 cgcctgeggt cccccaggag ttcaaggctg tggtgagcta tgattgtacc actgcactcg 60 tgcttgagca acagagcaag accgcatctc aaaaacacaa aaacaacace tatcctcttg 120

‘ctttgetgec agaaaagaca aaaagcacaa ataaacaagc acctgacagc gttataggtg 180 gagaccgagt tctatgagtg cagtaaagtg gggcacggca cagagatgga gctgtactct 240 agacagggtg ttctgaatca ggaatggact tacaaaacat ctgcagtcag aaattcacat 300 - acagactata gtagatcaaa agctcatttt aaactatcaa tgaggaaaaa agcaattcat 360 ttacataaca ttctctttcc aactcaaaca tcaggtacaa attgectttct tttagcatat 420 gccagaaatc tgtcattaca caatagctta gcaagtgtga cacaagatac tgccacttte 480 tctacacaaa gacccaccca aacaccagct ttgtttaaaa cattac 526 <210> 537 <211> 1837 <212> DNA <213> Homo sapiens <400> 537 tttttegcaa cgggtttgec gccagaacac aggtgtcgtg aaaactaccc ctaaaagcca 60 aaatgggaaa ggaaaagact catatcaaca ttgtcgtcat tggacacgta gattcgggca 120 agtccaccac tactggccat ctgatctata aatgcggtgg catcgacaaa agaaccattg 180 aaaaatttga gaaggaggct gctgagatgg gaaagggctc cttcaagtat gcctgggtct 240 tggataaact gaaagctgag cgtgaacgtg gtatcaccat tgatatctcc ttgtggaaat 300 ttgagaccag caagtactat gtgactatca ttgatgcccc aggacacaga gactttatca 360 aaaacatgat tacagggaca tctcaggctg actgtgetgt cctgattgtt gctgectggtg 420 ttggtgaatt tgaagctggt atctccaaga atgggcagac ccgagagcat gcccttcetgg 480 cttacacact gggtgtgaaa caactaattg tcggtgttaa caaaatggat tccactgagc 540 caccctacag ccagaagaga tatgaggaaa ttgttaagga agtcagcact tacattaaga 600 aaattggcta caaccccgac acagtagcat ttgtgccaat ttctggttgg aatggtgaca 660 acatgctgga gccaagtgct aacatgcctt ggttcaaggg atggaaagtc acccgtaagg 720 atggcaatgc cagtggaacc acgctgcttg aggctctgga ctgcatccta ccaccaacte 780 gtccaactga caagccettg cgectgecte tccaggatgt ctacaaaatt ggtggtattg 840 gtactgttcc tgttggccga gtggagactg gtgttctcaa acccggtatg gtggtcacct 900 ttgctccagt caacgttaca acggaagtaa aatctgtcga aatgcaccat gaagctttga 960 gtgaagctct tcctggggac aatgtgggct tcaatgtcaa gaatgtgtct gtcaaggatg 1020 ttcgtegtgg caacgttgcet ggtgacagca aaaatgaccc accaatggaa gcagctggct 1080 tcactgctca ggtgattatc ctgaaccatc caggccaaat aagcgcecggc tatgcccctg 1140 tattggattg ccacacggct cacattgcat gcaagtttgc tgagctgaag gaaaagattg 1200 atcgeegtte tggtaaaaag ctggaagatg gccctaaatt cttgaagtct ggtgatgctg 1260 ccattgttga tatggttcct ggcaagccca tgtgtgttga gagcttctca gactatccac 1320 ctttgggtcg ctttgctgtt cgtgatatga gacagacagt tgcggtgggt gtcatcaaag 1380 cagtggacaa gaaggctgct ggagctggca aggtcaccaa gtctgeccag aaagctcaga 1440 aggctaaatg aatattatcc ctaatacctg ccaccccact cttaatcagt ggtggaagaa 1500 cggtctcaga actgtttgtt tcaattggcc atttaagttt agtagtaaaa gactggttaa 1560 tgataacaat gcatcgtaaa accttcagaa ggaaaggaga atgttttgtg gaccactttg 1620 gttttctttt ttgegtgtgg cagttttaag ttattagttt ttaaaatcag tactttttaa 1680 tggaaacaac ttgaccaaaa atttgtcaca gaattttgag acccattaaa aaagttaaat 1740 gagaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1800 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa 1837 <210> 538 <211> 1697 <212> DNA <213> Homo sapiens <400> 538 ggatcgaggg gactctgacc acagcctgtg gctgggaagg gagacagagg cggecggeggce 60 tcaggggaaa cgaggctgca gtggtggtag taggaagatg tcgggcgagg acgagcaaca 120 ggagcaaact atcgctgagg acctggtcgt gaccaagtat aagatggggg gcgacatcgce 180 caacagggta cttcggtcct tggtggaage atctagctca ggtgtgtcgg tactcagect 240 gtgtgagaaa ggtgatgcca tgattatgga agaaacaggg aaaatcttca agaaagaaaa 300 ggaaatgaag aaaggtattg cttttcccac cagcatttcg gtaaataact gtgtatgtca 360 cttctceccet ttgaagagcg accaggatta tattctcaag gaaggtgact tggtaaaaat 420 tgaccttggg gtccatgtgg atggcttcat cgctaatgta gctcacactt ttgtggttga 480 tgtagctcag gggacccaag taacagggag gaaagcagat gttattaagg cagctcacct 540 ttgtgctgaa gctgccctac gecctggtcaa acctggaaat cagaacacac aagtgacaga 600 agcctggaac aaagttgccc actcatttaa ctgcacgcca atagaaggta tgctgtcaca 660 ccagttgaag cagcatgtca tcgatggaga aaaaaccatt atccagaatc ccacagacca 720 gcagaagaag gaccatgaaa aagctgaatt tgaggtacat gaagtatatg ctgtggatgt 780 tctecgtcage tcaggagagg gcaaggccaa ggatgcagga cagagaacca ctatttacaa 840 acgagacccc tctaaacagt atggactgaa aatgaaaact tcacgtgcct tcttcagtga 900 ggtggaaagg cgttttgatg ccatgcegtt tactttaaga gcatttgaag atgagaagaa 960 ggctcggatg ggtgtggtgg agtgcgccaa acatgaactg ctgcaaccat ttaatgttct 1020 ctatgagaag gagggtgaat ttgttgccca gtttaaattt acagttctgc tcatgcccaa 1080 tggccccatg cggataacca gtggtccctt cgagcctgac ctctacaagt ctgagatgga 1140 ggtccaggat gcagagctaa aggccctcct ccagagttct gcaagtcgaa aaacccagaa 1200 aaagaaaaaa aagaaggcct ccaagactgc agagaatccc accagtgggg aaacattaga 1260 agaaaatgaa gctggggact gaggtgcgtc ccatctcccc agettgetge tcctgectca 1320 teccecttece accaaaccec agactctgtg aagtgcagtt cttctceccacc taggaccgcece 1380 agcagagcgg ggggatctcc ctgcccccac cccagttcce caacccactc ccttccaaca 1440 acaaccagct ccaactgact ctggtcttgg gaggtgaggce ttcccaacca cggaagacta 1500 ctttaaacga aaaaaagaaa ttgaataata aaatcaggag tcaaaattca tcgtcttcaa 1560 ggcccctett tctagecttt tctactactc tctgcecttggt caaggtttgt gcocccactac 1620 agaacagggc taaattagcc accaccactg aaaactcagc cgaatttttt tataccactc 1680 tgacgtcagc atttttt 1697 <210> 539

<211> 1283 :

<212> DNA

<213> Homo sapiens

<400> 539 ctctctgectec ctcctgtteg acagtcagecc gecatcttctt ttgegtcgcece agccgagcca 60 catcgctcag acaccatggg gaaggtgaag gtcggagtca acggatttgg tcgtattggg 120 cgcctggtca ccagggctge ttttaactct ggtaaagtgg atattgttge catcaatgac 180 cccttcattg acctcaacta catggtttac atgttccaat atgattccac ccatggcaaa 240 ttccatggca ccgtcaaggce tgagaacggg aagcttgtca tcaatggaaa tcccatcacc 300 atcttccagg agcgagatcc ctccaaaatc aagtggggcg atgctggcgc tgagtacgtce 360 gtggagtcca ctggcgtctt caccaccatg gagaaggctg gggctcattt gcagggggga 420 gccaaaaggg tcatcatctc tgcccectect getgatgcce ccatgttcgt catgggtgtg 480 aaccatgaga agtatgacaa cagcctcaag atcatcagca atgcctectg caccaccaac 540 tgcttagcac ccectggeccaa ggtcatccat gacaactttg gtatcgtgga aggactcatg 600 accacagtcc atgccatcac tgccacccag aagactgtgg atggcccctc cgggaaactg 660 tggcgtgatg gccgegggge tctccagaac atcatcectg cctctactgg cgetgccaag 720 gctgtgggca aggtcatcecc tgagctgaac gggaagctca ctggcatggce cttcegtgte 780 cccactgcca acgtgtcagt ggtggacctg acctgccgtc tagaaaaacc tgccaaatat 840 gatgacatca agaaggtggt gaagcaggcg tcggagggee ccctcaaggg catcctggge 900 tacactgagc accaggtggt ctcctctgac ttcaacagcg acacccactc ctccaccttt 960 gacgctgggg ctggcattgc cctcaacgac cactttgtca agctcatttc ctggtatgac 1020 aacgaatttg gctacagcaa cagggtggtg gacctcatgg cccacatggc ctccaaggag 1080 taagacccct ggaccaccag ccccagcaag agcacaagag gaagagagag accctcactg 1140 ctggggagtc cctgccacac tcagtccccc accacactga atctccecte ctcacagttg 1200 ccatgtagac cccttgaaga ggggaggggce Cctagggagcc gcaccttgtc atgtaccatc 1260 aataaagtac cctgtgctca acc 1283 <210> 540 <211> 6417 <212> DNA <213> Homo sapiens <400> 540 gcggcectcecgg gtgactcggg ccagtgtaga ggtcctcagg ccgceccggecag gagcagetgg 60 gccaattccec tggccgggag cggaagggga tggcgtcggg cctgggetce cegtcccect 120 gctcggeggg cagtgaggag gaggatatgg atgcactttt gaacaacagc ctgcccccac 180 cccacccaga aaatgaagag gacccagaag aggatttgtc agaaacagag actccaaagce 240 tcaagaagaa gaaaaagcct aagaaacctc gggaccctaa aatccctaag agcaagcgcece 300 aaaaaaagga gcgtatgctc ttatgccgge agectggggga cagctctggg gaggggccag 360 agtttgtgga ggaggaggaa gaggtggctc tgcgectcaga cagtgagggce agcgactata 420 ctcctggcaa gaagaagaag aagaagcttg gacctaagaa agagaagaag agcaaatcca 480 agcggaagga ggaggaggag gaggatgatg atgatgatga ttcaaaggag cctaaatcat 540 ctgctcagct cctggaagac tggggcatgg aagacattga ccacgtgtte tcagaggagg 600 attatcgaac cctcaccaac tacaaggcct tecagccagtt tgtcagacce ctcattgctg 660 ccaaaaatcc caagattgct gtctccaaga tgatgatggt tttgggtgceca aaatggcgag 720 agttcagtac caataacccc ttcaaaggca gttctggggc atcagtggca gctgcggcag 780 cagcagcggt agctgtggtg gagagcatgg tgacagccac tgaggttgca ccaccacctce 840 cccectgtgga ggtgectatc cgcaaggcca agaccaagga gggcaaaggt cccaatgcte 300 ggaggaagcce caagggcagc cctcecgtgtac ctgatgccaa gaagcctaaa cccaagaaag 960 tagctcecct gaaaatcaag ctgggaggtt ttggttccaa gcgtaagaga tcctecgagtg 1020 aggatgatga cttagatgtg gaatctgact tcgatgatge cagtatcaat agctattctg 1080 tttctgatgg ttccaccage cgtagtagcc gcagccgcaa gaaactccga accactaaaa 1140 agaaaaagaa aggcgaggag gaggtgactg ctgtggatgg ttatgagaca gaccaccagg 1200 actattgcga ggtgtgccag caaggcggtg agatcatcct gtgtgatacc tgtccccecgtg 1260 cttaccacat ggtctgcectg gatcccgaca tggagaaggc tcccgaggge aagtggaget 1320 gcccacactg cgagaaggaa ggcatccagt gggaagctaa agaggacaat tcggagggtg 1380 aggagatcct ggaagaggtt gggggagacc tcgaagagga ggatgaccac catatggaat 1440 tctgtcgggt ctgcaaggat ggtggggaac tgctctgetg tgatacctgt ccttettect 1500 accacatcca ctgcctgaat cccccacttc cagagatcce caacggtgaa tggctctgtc 1560 cccgttgtac gtgtccagct ctgaagggca aagtgcagaa gatcctaatc tggaagtggg 1620 gtcagccacc atctcccaca ccagtgcctc ggcctccaga tgectgatcce aacacgccct 1680 ccccaaagcc cttggagggg cggccagagc ggcagttctt tgtgaaatgg caaggcatgt 1740 cttactggca ctgctectgg gtttctgaac tgcagctgga gctgcactgt caggtgatgt 1800 tccgaaacta tcagcggaag aatgatatgg atgagccacc ttctggggac tttggtggtg 1860 atgaagagaa aagccgaaag cgaaagaaca aggaccctaa atttgcagag atggaggaac 1920 gcttctatcg ctatgggata aaacccgagt ggatgatgat ccaccgaatc ctcaaccaca 1980 gtgtggacaa gaagggccac gtccactact tgatcaagtg gcgggactta ccttacgate 2040 aggcttcttg ggagagtgag gatgtggaga tccaggatta cgacctgtte aagcagagct 2100 attggaatca cagggagtta atgaggggtg aggaaggccg accaggcaag aagctcaaga 2160 aggtgaagct tcggaagttg gagaggcctc cagaaacgcc aacagttgat ccaacagtga 2220 agtatgagcg acagccagag tacctggatg ctacaggtgg aaccctgcac cecctatcaaa 2280 tggagggcct gaattggttg cgcttctect gggctcaggg cactgacacc atcttggcetg 2340 286 h atgagatggg ccttgggaaa actgtacaga cagcagtctt cctgtattcc ctttacaagg 2400 agggtcattc caaaggcccce ttcctagtga gcgccectet ttctaccatc atcaactggg 2460 agcgggagtt tgaaatgtgg gctccagaca tgtatgtcgt aacctatgtg ggtgacaagg 2520 acagccgtgc catcatccga gagaatgagt tctcectttga agacaatgcc attegtggtg 2580 gcaagaaggc ctccecgcatg aagaaagagg catctgtgaa attccatgtg ctgctgacat 2640 cctatgaatt gatcaccatt gacatggcta ttttgggctc tattgattgg gcctgectcea 2700 tcgtggatga agcccategg ctgaagaaca atcagtctaa gttcttccgg gtattgaatg 2760 gttactcact ccagcacaag ctgttgctga ctgggacacc attacaaaac aatctggaag 2820 agttgtttca tctgctcaac tttctcacce ccgagaggtt ccacaatttg gaaggttttt 2880 tggaggagtt tgctgacatt gccaaggagg accagataaa aaaactgcat gacatgctgg 2940 ggccgcacat gttgeggegg ctcaaagccg atgtgttcaa gaacatgccc tccaagacag 3000 aactaattgt gcgtgtggag ctgagcccta tgcagaagaa atactacaag tacatcctca 3060 ctcgaaattt tgaagcactc aatgcccgag gtggtggcaa ccaggtgtct ctgctgaatg 3120 tggtgatgga tcttaagaag tgctgcaacc atccatacct cttcecctgtg gectgcaatgg 3180 aagctcctaa gatgcctaat ggcatgtatg atggcagtgc cctaatcaga gcatctggga 3240 aattattgct gctgcagaaa atgctcaaga accttaagga gggtgggcat cgtgtactca 3300 tcttttecca gatgaccaag atgctagacc tgctagagga tttcttggaa catgaaggtt 3360 ataaatacga acgcatcgat ggtggaatca ctgggaacat gcggcaagag gcecattgacc 3420 gcttcaatgc accgggtgct cagcagttct gcttcttget ttccactcga gctgggggcece 3480 ttggaatcaa tctggccact getgacacag ttattatcta tgactctgac tggaaccccce 3540 ataatgacat tcaggccttt agcagagctc accggattgg gcaaaataaa aaggtaatga 3600 tctaceggtt tgtgaccegt gcgtcagtgyg aggagcgcat cacgcaggtg gcaaagaaga 3660 aaatgatgct gacgcatcta gtggtgcggce ctgggctggg ctccaagact ggatctatgt 3720 ccaaacagga gcttgatgat atcctcaaat ttggcactga ggaactattc aaggatgaag 3780 ccactgatgg aggaggagac aacaaagagg gagaagatag cagtgttatc cactacgatg 3840 ataaggccat tgaacggctg ctagaccgta accaggatga gactgaagac acagaattgc 3900 agggcatgaa tgaatatttg agctcattca aagtggccca gtatgtggta cgggaagaag 3960 aaatggggga ggaagaggag gtagaacggg aaatcattaa acaggaagaa agtgtggatc 4020 ctgactactg ggagaaattg ctgcggcacc attatgagca gcagcaagaa gatctagccc 4080 gaaatctggg caaaggaaaa agaatccgta aacaggtcaa ctacaatgat ggctcccagg 4140 aggaccgaga ttggcaggac gaccagtccg acaaccagtc cgattactca gtggcttcag 4200 aggaaggtga tgaagacttt gatgaacgtt cagaagctcc ccgtaggcce agtcgtaagg 4260 gcctgecggaa tgataaagat aagccattgc ctcctetgtt ggeccecgtgtt ggtgggaata 4320 ttgaagtact tggttttaat gctcgtcagec gaaaagcctt tcttaatgca attatgcgat 4380 atggtatgcc acctcaggat gcttttacta cccagtggct tgtaagagac ctgcgaggca 4440 aatcagagaa agagttcaag gcatatgtct ctcttttcat gcggcattta tgtgagccgg 4500 gggcagatgg ggctgagacc tttgctgatg gtgtcccccg agaaggcctg tctcgccage 4560 atgtccttac tagaattggt gttatgtctt tgattcgcaa gaaggttcag gagtttgaac 4620 atgttaatgg gcgctggagc atgcctgaac tggctgaggt ggaggaaaac aagaagatgt 4680 cccagccagg gtcaccctece ccaaaaactc ctacacccte cactccaggg gacacgeage 4740 ccaacactcc tgcacctgtc ccacctgctg aagatgggat aaaaatagag gaaaatagcec 4800 tcaaagaaga agagagcata gaaggagaaa aggaggttaa atctacagcc cctgagactg 4860 ccattgagtg tacacaggcc cctgccectg cctcagagga tgaaaaggtc gttgttgaac 4920 cccctgaggg agaggagaaa gtggaaaagg cagaggtgaa ggagagaaca gaggaaccta 4980 tggagacaga gcccaaaggt gctgctgatg tagagaaggt ggaggaaaag tcagcaatag 5040 atctgacccc tattgtggta gaagacaaag aagagaagaa agaagaagaa gagaaaaaag 5100 aggtgatgct tcagaatgga gagaccccca aggacctgaa tgatgagaaa cagaagaaaa 5160 atattaaaca acgtttcatg tttaacattg cagatggtgg ttttactgag ttgcactccce 5220 tttggcagaa tgaagagcgg gcagccacag ttaccaagaa gacttatgag atctggcatc 5280 gacggcatga ctactggctg ctagccggca ttataaacca tggctatgcc cggtggcaag 5340 acatccagaa tgacccacgc tatgccatcc tcaatgagcc tttcaagggt gaaatgaacc 5400 gtggcaattt cttagagatc aagaataaat ttctagctcg aaggtttaag ctcttagaac 5460 aagctctggt gattgaggaa cagctgcgcc gggctgctta cttgaacatg tcagaagacc 5520 cttectcaccce ttccatggcce ctcaacaccc gectttgctga ggtggagtgt ttggcggaaa 5580 gtcatcagca cctgtccaag gagtcaatgg caggaaacaa gccagccaat gcagtcctgce 5640 acaaagttct gaaacagctg gaagaactgc tgagtgacat gaaagctgat gtgactcgac 5700 tcccagctac cattgcccga attcccccag ttgctgtgag gttacagatg tcagagcgta 5760 acattctcag ccgcctggca aaccgggcac ccgaacctac cccacagcag gtagcccagce 5820 agcagtgaag atgcagactg ataccacctc caccgctgag cagtgacctt cctcactttc 5880 tecttgtccca gcttcetecece tgggggectg agagaccctc accttcctte tgeccatctt 5940 ccatgttgta aaggaacagc cccagtgcac tgggggaggg gagggagtga ggggcagtgg 6000

288 - So tgcececttcect gcagaagaga catgcagcag tagcgctggce gccatctgca ggagetggeg 6060 ggctggcctt ctggaccctg gctteteccec actgtaacgc ctgttacaca caaactgttg 6120 tgggttcctg ccaggcttga agaaaatgat ctgaattttt tcctectttt ggttttattt 6180 tgttggttta ttttgtgttt tcttttctcc tttttggggg gtattcagag tgggctgggce 6240 ccctgggecga gacacagcta cctetgttgg catcttttta ataccaggaa cccagcggcet 6300 : ctagccactg agcggctaaa tgaaataaag tggaaaaaaa aaaaaaagga aaaaaccaaa 6360 agcataaaaa accacagcaa atttcttgat gaaaattgaa aataaaagtt tccttgt 6417 <210> 541 <211> 1680 <212> DNA <213> Homo sapiens <400> 541 cacqgcagce ctacactcgg cctggaagaa ttgtttttcect tctctggaaa ggtgaacatt 60 tatagcattt atttcccaaa tctgttaaca tggcaaaata tgtcagtctc actgaagcta 120 acgaagaact caaggtctta atggacgaga accagaccag ccgccccgtg gccgttcaca 180 cctccaccgt gaacccgctc gggaagcagc tcttgccgaa aacctttgga cagtccagtg 240 tcaacattga ccagcaagtg gtaattggta tgcctcagag accagcagca tcaaacatcce 300 ctgtggtagg aagcccaaac ccacccagca ctcactttgc ctctcagaac cagcattcct 360 actcctcacc tcecttgggecc gggcagcaca acaggaaagg agagaagaat ggcatgggec 420 tgtgccgtct ttccatgaag gtctgggaga cggtgcagag gaaagggacc acttcctgece 480 aggaagtggt gggcgagctg gtcgccaagt tcagagctgc cagcaaccac gcctcaccaa 540 acgagtcagc ttatgacgtg aaaaacataa aacggcgcac ctacgatgcc ttaaacgtgce 600 tgatggccat gaatatcatc tccagggaga aaaagaagat caagtggatt ggtctgacca 660 ccaactcggce tcagaactgt cagaacttac gggtggaaag acagaagaga cttgaaagaa 720 taaagcagaa acagtctgaa cttcaacaac ttattctaca gcaaattgct ttcaagaacc 780 tggtgctgag aaaccagtat gtggaggagc aggtcagcca gcggccgctg cccaactcag 840 tcatccacgt gcccttcatc atcatcagca gtagcaagaa gaccgtcatc aactgcagca 900 tctccgacga caaatcagaa tatctgttta agtttaacag ctcctttgaa atccacgatg 960 acacagaagt gctgatgtgg atgggcatga cttttgggct agagtccggg agctgctctg 1020 ccgaagacct taaaatggcc agaaatttgg tcccaaaggc tctggagceccg tacgtgacag 1080 aaatggctca gggaactttt ggaggtgtgt tcacgacggc aggttccagg tctaatggca 1140 cgtggectttc tgccagtgac ctgaccaaca ttgcgattgg gatgctggcc acaagctccg 1200 gtggatctca gtacagtggc tccagggtgg agaccccagc agtcgaggag gaagaggagg 1260 aggacaacaa cgatgacgac ctcagtgaga atgacgagga tgactgacgt cctctecgect 1320 taagattcag cttcaggaaa acatttaggg aaaagaaact tttttttttt ttttaatgtg 1380 aggttttctg tttectttttt gcctactece aagaagatat tggtaagcta tagaatttag 1440 atatgcacet ctgataagca aggattgttt cccgtatgat taagacgtgc tgttgatgtg 1500 tgttttgata ccagtgtgct gacacagaat ctttatttac tttttaggat tttgtgtttt 1560 cattttctat ttttctttaa atgcagagtt cattgttgcc ccttaacagt ttttcctgag 1620 tttactgaag aaattgtact tcatccacat ccatgaaaat aaaatgctct ccttttgtge 1680 <210> 542 <211> 2055 <212> DNA <213> Homo sapiens <400> 542 agcactcaaa aagagtgaat gaaatgtgca gctcagagtg tcatttctga agggaggagt 60 ctttctcttg gagaagagtc ctcaatgagc ctggccgagg cccgggatct gtgtgaagtg 120 gactaaggat taagtaggat gtcaactgag acagaacttc aagtagctgt gaaaaccagc 180 gccaagaaag actccagaaa gaaaggtcag gatcgcagtg aagccacttt gataaagagg 240 tttaaaggtg aaggggtccg gtacaaagcc aaattgatcg ggattgatga agtttecgca 300 gctcggggag acaagttatg tcaagattcc atgatgaaac tcaagggcgt tgttgctgge 360 gctcgttcca aaggagaaca caaacagaaa atctttttaa ccatctcctt tggaggaatc 420 aaaatctttg atgagaagac aggggccctt cagcatcatc atgctgttca tgaaatatcc 480 tacattgcaa aggacattac agatcaccgg gcctttggat atgtttgtgg gaaggaaggg 540 aatcacagat ttgtggccat aaaaacagcc caggcggctg aacctgttat tctggacttg 600 agagatctct ttcaactcat ttatgaattg aagcaaagag aagaattaga aaaaaaggca 660 caaaaggata agcagtgtga acaagctgtg taccagacaa tattggaaga ggatgttgaa 720 gatcctgtgt accagtacat tgtgtttgag gctggacacg agccaatccg tgatcccgaa 780 acggaagaaa acatttatca ggttcccacc agccaaaaga aggaaggtgt ttatgatgtg 840 ccaaaaagtc aacctgctgt gacccaatta gaactttttg gggacatgtc cacaccccct 900 gatataacct ctcccecceccac tcctgcaact ccaggtgatg cctttatcec atcttcatct 260 cagacccttc cagcgagtgc agatgtgttt agttctgtac ctttcggcac tgctgctgta 1020 ccctcaggtt acgttgcaat gggcgctgtc ctccegtect tctggggtca gcagecccte 1080 gtccaacagc agatggtcat gggtgcccag ccaccagtcg ctcaggtgat gcecgggggcet 1140 cagcccatcg catggggcca gccgggtcte tttecctgcca ctcagcagcc ctggccaact 1200 gtggceggge agtttccgec agcegccttc atgcccacac aaactgttat gectttgceca 1260 gctgccatgt tccaaggtcc cctcacccece cttgecaccg tcecccaggcac gagtgactcece 1320 accaggtcaa gtccacagac cgacaagcec aggcagaaaa tgggcaaaga aacgtttaag 1380 gatttccaga tggcccagcc tecgeeegty ccectceccgeca aacccgacca gecctccecte 1440 acctgtacct cagaggcctt ctccagttac ttcaacaaag tcggggtggc acaggataca 1500 gacgactgtg atgactttga catctcccag ttgaatttga cccctgtgac ttctaccaca 1560 ccatcgacca actcacctcc aaccccagec cctagacaga gctctccatc caaatcatct 1620 gcatcccatg ccagtgatcc taccacagat gacatctttg aagagggctt tgaaagtccce 1680 agcaaaagcg aagagcaaga agctcctgat ggatcacagg cctcatccaa cagtgatcca 1740 tttggtgagc ccagtgggga gcccagtggt gataatataa gtccacaggce cggtagctag 1800 atagcgcagg tctgggagcc agagcctctg tacgcgcaga tcaacagacc taagaaatag 1860 catcgatgcg agctegtggt gggtgctcaa gactggcatg gacatcagca tcacgacagg 13920 ctctcttgta ttctttcacc tcttcccaca agaaattcat gattgcccaa tggaactcgce 1980 tcagaagagg gaactaagca tttttggcaa ccaatggcag atatctatgg cagcacacaa 2040 aaaaaaaaaa aaaaa 2055 <210> 543 <211> 4239 <212> DNA <213> Homo sapiens <400> 543 ctgtgggcct gggagctgcc tctgaggaac acgccgcagg gccaggcatg tgaggtctcet 60 gcgggtcatg gagaacctcc ctgeccgtgac cactgaggag ccgaccccca tggggagggg 120 tcctgtggga ccctcaggag gtggcagcac ccgggaccag gtccggactg tggtcatgag 180 gcecctctgtg agctgggaga aagcggggcc cgaggaggcc aaggcgccgg tgagaggcga 240 cgaggctect cctgcecegeg tggctgggec tgctgetggg accectccct gccagatggg 300 ggtttatcce acagacctga ccctgcagcet gectggetgtg cggaggaaga gcagactgceg 360 ggacceccggce ctacagcaga ccctcecgggg ccagcteccge ctgetggaga atgatagecg 420 ggagatggcc cgcgtgcttg gggaattatc agccaggcetg ctgtccatcc acagtgacca 480 ggaccggatc gtggtgacgt ttaagacttt tgaagaaatc tggaagtttt ccacctacca 540 tgctctcgge ttcactcatc actgecctggc aaacctgcte atggaccagg ccttctggcet 600 gctcttgeccc agtgaggagg aggagacggc catccaagte catgtggatg agaacgectt 660 aaggctgacc cacgagagcc tcctcatcca agaagggccc ttctttgtee tgtgtcctga 720 ccaccatgtg agagtgatga cgggtccceg ggatgcagga aatggeccce aggccctceag 780 gcaggettcg ggggcaccece agggagaggc ggccccggaa acagactctt caccgccgag 840 ccccagegtg tcctcecgagg aggtggcagt ggcggccgec ccggagectt tgattccatt 900 tcatcagtgg gctcttagga tcccccagga ccccatcgac gatgccatgg gtggccctgt 960 gatgcccgge aacccgctga tggctgtggg cctggecteg gcattggcag acttccaggg 1020 ctcggggcce gaagagatga ccttccgagg tggecgacctc atcgagatcec ttggggcgea 1080 ggtgcccage ctgccctggt gecgtgggeceg acacgcagcc tcgggccggg tggggtttgt 1140 gcggagcagc ctcatcagca tgcagggccc cgtgtccgag ttggaaagtg cgatttttcet 1200 caatgaggaa gaaaagtcat tcttcagcga gggctgettt tctgaggagg atgccaggca 1260 gttgctgagg cggatgtcgg gcaccgatgt ctgcagcgtg tacagcctgg actcagtaga 1320 ggaagctgag accgagcagc cgcaggaaaa agaaatacct ccaccttgec tgagcccgga 1380 gccacaggag accttgcaga aggtgaagaa tgttctggaa caatgcaaga cctgcccagg 1440 ctgccccecag gagccagegt cctggggtcet ctgtgcggeca tccagcgacg tgagcttgca 1500 ggaccccgag gagccctect tctgettgga agccgaggac gactgggagg acccagaggc 1560 cctgagctca ctgctgetgt tcctgaacge ccctgggtac aaggccagct tccgtggcecet 1620 gtacgatgtg gecgcectgecgt ggctgagcag cgtgttccge agecttcagcg acgaggagga 1680 gctgactggg cgecctggecac aggcccgggg ggcggccaag aaagctggec tectcatgge 1740 cctggccagg ctctgcttee tcetggggeg gctgtgcagec aggaggctca agctgtccca 1800 : ggccegggtyg tactttgagg aagegetggg ggccctggag ggcagcttcg gggacctgtt 1860 cctggtggtyg gctgtgtacyg ccaacctgge cagcatttac cggaagcaga agaaccggga 1920 gaagtgtgca caggtggtgc ccaaagccat ggccecctgcete ctggggacgce ccgaccacat 1380 ctgcagcacc gaggcggagg gggagctcet gcagctggeg ctgcggeggg cggtgggtgg 2040 ccagagcctg caggccgagg cccgggcectg cttectgetg gccaggcacc acgtgcacct 2100 caagcagccc gaggaggccc tgcccttect agagcggcetg ctgcttttgc acagggactce 2160 gggagccecca gaggccgcegt ggcteteaga ctgctaccta ctecctggetg acatctacag 2220 ccgcaagtgce ctgcecccace tggtgctgag ctgtgtcaag gtggcctcat tgcggacacyg 2280 gggctcgetg goccggetege tgaggagtgt gaacctggtg ctccagaacg ccccccagece 2340 ccacagectce cctgcccaaa cttceccacta cctcaggcaa gcgctggecet ccctgaccec 2400 gggcacaggc caggcgctge gecggeccect ctacaccage ttggcccage tgtacagcca 2460 ccatggctge cacggcccgg ccatcacctt catgacgcag gcagtggaag ccagtgctat 2520 tgccggagtc cgtgccatcg tggaccacct ggtggccctg gectggetge acgtgettca 2580 tgggcagagc ccggtggecc tggacatcct gcagtctgtc cgggatgcag tggtggccag 2640 cgaggaccag gagggcgtga ttgccaacat ggtggeccgtg gctctgaaga ggacgggccyg 2700 gacgaggcag gcagctgaga gctactaccg cgccctgegg gtggcteggg acctgggceca 2760 gcaaaggaac caggcagtgg ggctggccaa cttcggggcc ctgtgecctge atgcgggtge 2820 cagcaggctg gcccagcact acctcctgga ggccgtgecgg ctgttctega ggctgcccect 2880 tggggagtgt ggccgggact tcacccacgt gctcctgcag ctgggccatc tctgcacccg 2940 ccagggcccg gcccagcagg gcaagggcta ctacgagtgg gececttetgg tcegcecgtgga 3000 gatgggccac gtggagagcc agctgcgggce cgtccagcgg ctgtgccact tctacagcgce 3060 cgtcatgccc agcgaggecce agtgtgtcat ctaccatgag ctccagctct ccccggcctg 3120 caaggtggcc gacaaggtgc tggaggggca gctcctggag accatcagcec agctctacct 3180 gtccctggge accgagcggg cctacaaatc cgcactggac tacaccaaac gaagtctggg 3240 gattttcatt gacctccaga agaaagagaa ggaggcgcat gcctggctge aagcagggaa 3300 gatctattac atcttgcggc agagcgagct ggtggacctc tacatccagg tggcacagaa 3360 cgtggccctg tacacaggcg accccaacct ggggctggag ctgtttgagg cggctggaga 3420 catcttcttc gacggggcct gggagcggga gaaagetgtg tccttctacc gggaccgggce 3480 cctgccectg gecagtgacta cgggcaaccg caaggcggad ctgcggcetgt gcaacaagcet 3540 ggtggcactg ctggccacgc tggaggagcc ccaggagggce ttggagtttg cccacatgge 3600 cctagcactce agcatcaccc tgggggaccg gctgaacgag cgcgtggect accaccggct 3660 ggccgccetg caacaccgac tgggccatgg cgagctggeca gagcacttct acctcaaggc 3720 cctgtcgete tgcaactcgc cgctggagtt tgacgaggag accctctact acgtgaaggt 3780 gtacctggtg ctcggtgaca tcatcttcta cgacctgaag gacccgtttg atgcagccgg 3840 gtactaccag ctggegctgg cggccgcegt ggacctgggc aacaagaagg cacagctgaa 3900 gatctacacg cggctggcca ccatctacca caacttcctc ctggaccgtg agaagtcgct 3960 cttcttctac cagaaggcca ggaccttcgc cacagagctc aacgtccgca gggtcaacct 4020 gcetectectg ccactectgeg ggtgggcececc ctggttggecc cccagccacc ctcgctgagg 4080 acagcatcca agggagtggg ttttgtgcaa gggctggggg tcteetgect ctectggtgt 4140 cgccggtgge tcattttctg gcaaatggag gcacgaacgc aggggccaaa tagcaataaa 4200 tgggttttgt ttttrttttg caataaaaaa aaaaaaaaa 4239

<210> 544

<211> 2207

<212> DNA

<213> Homo sapiens

<400> 544 atatttctte tatgaatctt ttgtgtacag atttttgtgt agacatatat gtttttatct 60 ctgttgagty tatacctgag agtagaatta ctgggttata tggtaactct atgtttagcc 120 ttttgaggaa ctgctagact gtttcccaaa ggagctgtat cattttacat aaccaccaga 180 tatgtttgag ggttctgatt tctccacagt ctcatgaata cttattattg tctgccattt 240 ttattttagc cagtcaagagg ggtttgaaat ggtacctcat tatggtttca gtttgtgttet 300 ttctaatgag taatgatgtt gagtatcatt ttatattttc tgtgcttatt aaccatttgt 360 atatcatctt tggagaaatg tctgttcata tecctttgectc attttttaaa gattggatta 420 tttgatttct cattattgaa ttgtaagagt tctttatata gtctagctat aagtcatata 480 tatatatgat ttgcacaaat tttcttccat tctataggtt gttctcactt tcatgatggt 540 gagaaccttg ttttttaaac agtttctcac ttgtcttgtg aaagggtact ggataccaac 600 ccecctcatge tggettagece atcaaaagcg tcccattttt acactttgta gattcctctt 660 ggacccactt ttctccaaag aaccctatte cceccaagtt atccttcecag ttctctagca 720 tcaaaacaaa attcgcttte atttggcagt tgttagtcca aactgcacca ttttgtaagt 780 cccccagcat tttgcagacc ttggtcaaag tgacacattc caggcgagtt tgggctgtga 840 gaaacatcct gcctaaccac ctgaccacaa cacacaagaa catccttatc ataccctgct 200 aagcaaaggc ccaactgaag gaacgtccct atcataccct gcaactggaa caaagggcca 960 aaccacctga tcataggaac atcttaatat cctgccggge agcaaaccag acagcccaga 1020 ccecectectge ccatacctat aagtccccag cctgtgaacg gcagtgggct ctggcattaa 1080 gctgcaccce ccacctetgce aggtttttgc aatatacttg tgttgectgta gagcccccce 1140 cccaccccca tetttettta actcccacct tcectttaaa aaaaacctaa cagcaatagc 1200 atggtatgat tcaaaaactc attttgccac taactgacat tgtatcttgg ttaggtcact 1260 taatatcact ggttctcagg ttttettgta aaataaatta atttatttct agtaattcat 1320 gtgagtagca gacttcattc acctgatact tgattttaaa agaaaagttt ttcaacccag 1380 ggaatttata gtgggtgtca gtcgagaaaa atgatgggac aagtctcaat cattttagga 1440 gatttatttg ccaaagttaa ggacgtgccc gggaggcaag tctatgtctt tcttcgaaga 1500 tgattttgag gtctccaaat ttaaagggga aagggcagga tgttgagaag tacacaattg 1560 tcatgtaaga ggtgggtagg ggcaaatagt tatttatgcc tttggctceag tgaatctgca 1620 ttttttacgt aagatgacat aaaaggggca gaggaaaata ttaggggaat ctgcatttta 1680 cataagataa cagacaaaat ggggtagggg aacaatcaga tttgcattta tgtctggtgg 1740 gccaggggta actgcacctg taagctgtca attgacattg ccatgatgaa attttagctc 1800 actgggaatt tccctgtggg caaaatacag gggaggtgtg tagcttttca tecttgtagee 1860 atcctattta gaaaccaaaa ggggggagac aggtttgcat gacccagttc ccagcttgac 1920 ttcttecectt tggectaaatg agtttggggt cccaaaattt aatttccttt cacatttcec 1980 ttcttttttc tgtaaaatct tttggagaaa gcattttaaa aggaagacga gttcctggec 2040 tcaggttggt ttttcctcece ttttttgage tgctttctta ttgctaggat ggtttattce 2100 tagaagttca ggtccccagt ctctaggaag gctcatttcect aagaggtcat gtcccatgaa 2160 ggttaaaaaa aaaaaatagg aagaggaaag aagtaaaaaa ggaaagg 2207 <210> 545 <211> 467 <212> DNA : <213> Homo sapiens <400> 545 cggccgcaga gtcccaccge caccaggcga cccccaccca gagagggaca gacatgcggg 60 gagccagcac cgggcaagat ggctctgggg atcctcattcec tgtgaagaca ccaactcatt 120 tctcaaacac aggatccagg agacagatgg ctcctaaatg gagatggcac atgectccgtg © 180 gggtccctca tagaggagtg ccaccctcca cactggccac gctgggetge cccagagegg 240 ccagaaagga aggtgggagc tagccccatc ctcactcaga ggccggaagg aggaagatgg 300 catctecgcca acttcagagc cgaatggcct ctagccacac tgcttccaga ccccagacgg 360 ggcagcagca gcagttccca gatgagcacc cattgttgca gctaggaccc accaaggatg 420 ggactcctgg agtcaggtge acaccaggta acccaggacc acgectc 467 <210> 546 <211> 459

<212> DNA <213> Homo sapiens

<400> 546 gtcatgaact atttttaaca tttccgaaag cctcctggaa attattatgce agccagccac 60 aacagggctg caacaaaatg ccagtatctt cgcttttcte tggagtccca tcagctcagt 120 gccgtcacac tgatcaaagg cactgcctgg cagtcatcta tgttagtgat gagtaaagta 180 gacaggaaat tcattgttgc ttgataaatg tcctctccaa gtcaccccat cttgggaaac 240 acaccaccta tttacccagt tgcccaagtc aaatgcagga gtcacccctg gttcttctcet 300 ttctgtcact ctgtctcccec aaccccaatc cagctcatca gcaagtcccc caagcctgge 360

0 12946 atggcacagg ggctccacaa ttatttgttg actgaatgac Ctccatctga taagtgaact 420 tgaatgtgcce cagaaaataa gaaaataacg aaaagcctg 459 <210> 547 <211> 428 <212> DNA <213> Homo sapiens <400> 547 atgtctcttg tcagctgtct ttcagaagac ctggtgggge aagtccgtgg gcatcatgtt 60 gaccgagctg gagaaagcct tgaactctat catcgacgte taccacaagt actccctgat 120 aaaggggaat ttccatgecg tctacaggga tgacctgaag aaattgctag agaccgagtg 180 tcctcagtat atcaggaaaa agggtgcaga cgtctggttc aaagagttgg atatcaacac 240 tgatggtgca gttaacttcc aggagttcct cattctggtg ataaagatgg gcgtggcage 300 ccacaaaaaa agccatgaag aaagccacaa agagtagctg agttactggg cccagaggct 360 gggccectgg acatgtacct gcagaataat aaagtcatca atacctcaaa aaaaaaaaaa 420 aaaaaaaa 428 <210> 548 : <211> 1131 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (33)..(33) <223> nis a, ¢, g, t or u <220> <221> misc_feature <222> (624) ..(624) <223> nis a, c, g, t or u <220> <221> misc_feature <222> (84B).. (848) <223> nis a, ¢, g, t or u <400> 548 ttcecgaatat cgtecgaccac gcgtccgtag aanataaaac tgctatgaga tagaaatgat 60 gtaaaattat gtggaaagtt ttccctcata tactcacata cagcctttga agggctctgg 120 ctctgaccgg ttgatggect tgagcgagat gaaatcatga aattgagtca aatcaatttg 180 acattgaaat gacaagagga aactcttaaa tacataaaaa caagctctca tttgcctagg 240 atagatactg tcttaaaaat aaagactgaa cctagatgtt ctgagcacta gcaacaaggt 300 attttaacaa gtttaaagga attctctgaa aaagttataa aattattcta ggaaacataa 360 ccataatagt gttttaaggg actttcacct ggggatttta tattcatgaa cagagtgtat 420 tctgtattta aaatgtctca tttgtgggaa ttggatgaca tgttttttga taaatttatt 480 cacaatataa attgactttt tattctagga ccatgtgaat aatgggttcc attgcacaaa 540 tacaaatatt ttaatagctt cttaggcagt ggtgtagaca tcttggatat aaataattgt 600 agatcttgta tatttgattt ttanaaaact agaataaaca gagaggcata aacatatctt 660 agagtccaag tggtagtgtt tagcattgga tataataaat ggatgtttta caaagtgttt 720 ccataattct cttcctatac ataaatgtct tgttttcaaa agtggatgga acttggctgg 780 gtgtggtggc tcacgcctgt aatcctagca ctttgggaag ccaggccggg aggatcactt 840 gagctcanga gtttgagaca tcctgggcca catagtgaga cctggtctcc tgaaaaaaaa 200 aagtggatgg gacttgtacc agagatttta tctacttctc caactgcttc agaataccca 960 ttgagatgtt ccccctggaa agatgaccec atactgectc ttgagccatt tcttcccacc 1020 taacattctt aaatgataaa ggcccaactt ttggcattct tcccaatttc gggaacctga 1080 gtttgagggg gttccaaatt tggggaaaaa aatggggttt aaggtttaac t 1131 <210> 549 <211> 3854 <212> DNA <213> Homo sapiens <400> 549 gccagagtct ctccgecttta atgegctccc attagtgccg tcccccactg gaaaaccgtg 60 gcttctgtat tatttgccat ctttgttgty taggagcagg gagggcttcc tcccggggtce 120 ctaggcggcg gtgcagtccg tcgtagaaga attagagtag aagttgtcgg ggtccgctcet 180 taggacgcag ccgcctcatg ggggtccagg ggctctggaa gctgetggag tgctccggge 240 ggcaggtcag ccccgaagcg ctggaaggga agatcctgge tgttgatatt agcatttggt 300 taaaccaagc acttaaagga gtccgggatc gccatgggaa ctcaatagaa aatcctcatce 360 ttctcacttt gtttcatcgg ctctgcaaac tcttattttt tcgaattcgt cctatttttg 420 tgtttgatgg ggatgctcca ctattgaaga aacagacttt ggtgaagaga aggcagagaa 480 aggacttagc gtccagtgac tccaggaaaa cgacagagaa gcttctgaaa acatttttga 540 aaagacaagc catcaaaact gccttcagaa gcaaaagaga tgaagcacta cccagtctta 600 cccaagttcg aagagaaaac gacctctatg ttttgcctcc tttacaagag gaagaaaaac 660 acagttcaga agaggaagat gaaaaagaat ggcaagaaag aatgaatcaa aaacaagcat 720 tacaggaaga gttctttcat aatcctcaag cgatagatat tgagtctgag gacttcagca 780 gcctgeccce tgaagtaaag catgaaatct tgactgatat gaaagagttc accaagcgca 840 gaagaacatt atttgaagca atgccagagg agtctgatga cttttcacag taccaactca 900 aaggcttgct taaaaagaac tatctgaacc agcatataga acatgtccaa aaggaaatga 960 atcagcaaca ttcaggacac atccgaaggc agtatgaaga tgaagggggc tttctgaagg 1020 aggtagagtc aaggagagtg gtctctgaag acacttcaca ttacatcttg ataaaaggta 1080 ttcaagctaa gacagttgca gaagtggatt cagagtctct tccttecttec agcaaaatgc 1140 acggcatgtc ttttgacgtg aagtcatctc catgtgaaaa actgaagaca gagaaagagc 1200 ctgatgctac cectccttcet ccaagaactt tactagctat gcaagctgcc ctgctgggaa 1260 gtagctcaga agaggagctg gagagtgaaa atcgaaggca ggcccgtggg aggaacgcac 1320 ctgctgectgt agacgaaggc tccatatcac cccggactct ttcagccatt aagagagctc 1380 ttgacgatga cgaagatgta aaagtgtgtg ctggggatga tgtgcagacg ggagggccag 1440 gagcagaaga aatgcgtata aacagctcca ccgagaacag tgatgaagga cttaaagtga 1500 gagatggaaa aggaataccg tttactgcaa cacttgcgtc atctagtgtg aactctgcag 1560 aggagcacgt agccagcact aatgagggga gagagcccac agactcagtt ccaaaagaac 1620 aaatgtcact tgttcacgtg gggactgaag ccttteccgat aagtgatgag tctatgatta 1680 aggacagaaa agatcggctg cctctggaga gtgcagtggt tagacatagt gacgcacctg 1740 ggctcccgaa tggaagggaa ctgacaccgg catctccaac ttgtacaaat tctgtgtcaa 1800 agaatgaaac acatgctgaa gtgcttgagc agcagaacga actttgccca tatgagagta 1860 aattcgatte ttectettett tcaagtgatg atgaaacaaa atgtaaaccg aattctgett 1920 ctgaagtcat tggccctgte agtttgcaag aaacaagtag catagtaagt gtcccttcag 1980 aggcagtaga taatgtggaa aatgtggtgt catttaatgc taaagagcat gagaattttc 2040 tggaaaccat ccaagaacag cagaccactg aatctgcagg ccaggattta atttccatte 2100 caaaggccgt ggaaccaatg gaaattgact €ggaagaaag tgaatctgat ggaagtttca 2160 ttgaagtgca aagtgtgatt agtgatgagg aacttcaagc agaattcect gaaacttcca 2220 aacctcccte agaacaaggc gaagaggaac tggtaggaac tagggaggga gaagcccctg 2280 ctgagtccga gagcctcectg agggacaact ctgagaggga cgacgtggat ggtgagccac 2340 aggaagctga gaaagatgcg gaagattcgc tccatgaatg gcaagatatt aatttggaqgg 2400 agttggaaac tctggagage aacctcttag cacagcagaa ttcactgaaa gctcaaaaac 2460 agcagcaaga acggatcgct gctactgtca ccggacagat gttcctggaa agccaggaac 2520 tcecctgegeet gttcggecatt cectacatec aggctcccat ggaagcagag gcgcagtgcg 2580 ccatcctgga cctgactgat cagacttceg gaaccatcac tgatgacagt gatatctggc 2640 tgtttggagce gcggcatgtc tatagaaact tttttaataa aaacaagttt gtagaatatt 2700 atcaatatgt ggactttcac aatcaattgg gattggaccg gaataagtta ataaatttgg 2760 cttatttgct tggaagtgat tataccgaag gaataccaac tgtgggttgt gtaaccgcca 2820 tggaaattct caatgaattc cctgggcatg gcctggaacc tctcctaaaa ttctcagaat 2880 ggtggcatga agctcaaaaa aatccaaaga taagacctaa tcetcatgac accaaagtga 2940 daaaaaaatt acggacattg caactcacce ctggctttece taacccagct gttgccgagg 3000 cctacctcaa accecgtggtg gatgactcga agggatcctt tctgtggggg aaacctgatc 3060 tcgacaaaat tagagaattt tgtcagcggt atttcggctg gaacagaacg aagacagatg 3120 aatctctgtt tcctgtatta aagcaactcg atgcccagca gacacagctce cgaattgatt 3180 Ccttctttag attagcacaa caggagaaag aagatgctaa acgtattaag agccagagac 3240 taaacagagce tgtgacatgt atgctaagga aagagaaaga agcagcagcc agcgaaatag 3300 aagcagtttc tgttgccatg gagaaagaat ttgagctact tgataaggca aaacgaaaaa 3360 cCccagaagag aggcataaca aataccttag aagagtcatc aagcctgaaa agaaagaggc 3420 tttcagattc taaacgaaag aatacatgcg gtggattttt gggggagacc tgcctcteag 3480 aatcatctga tggatcttca agtgaacatg ctgaaagttc atctttaatg aatgtacaaa 3540 ggagaacagc tgcgaaagag ccaaaaacca gtgcttcaga ttcgcagaac tcagtgaagg 3600 aagctcccgt gaagaatgga ggtgcgacca ccagcagctce tagtgatagt gatgacgatg 3660 gagggaaaga gaagatggtc ctcgtgaccg ccagatctgt gtttgggaag aaaagaagga 3720 aactaagacg tgcgagggga agaaaaagga aaacctaatt aaaaaatatg tatcctctat 3780 aattagttat gacagccatt tgtaatgaat ttgtcgcaaa gacgtaataa aattaactgg 3840 tggeacggtc aaaa 3854 <210> 550

<211> 344

<212> DNA

<213> Homo sapiens

<400> 550 cctttcegge ggtgacgace tacgcacacg agaacatgcc tctcgcaaag gatctcecttce 60 atccctctee agaagaggag aagaggaaac acaagaagaa acgcctggtg cagagcccca 120 attcctactt catggatgtg aaatgcccag gatgctataa aatcaccacg gtctttagec 180 atgcacaaac ggtagttttg tgtgttggcet gctccactgt cctctgccag cctacaggag 240 gaaaagcaag gcttacagaa ggatgttcct tcaggaggaa gcagcactaa aagcactctg 300 agtcaagatg agtgggaaac catctcaata aacacatttt ggat 344

299 P

<210> 551 <211> 2692 <212> DNA <213> Homo sapiens <400> 551 acatggatgg gtgcaaaaaa gagctgcccc gecttgcaaga gccggaggag gacgaggatt 60 gttacatcct taatgttcag tcaagcagtg atgacaccag tgggtcttct gtggccagaa 120 gagctccgaa gagacaggcg agttgcatcce ttaatgtcca gtcaaggagt ggtgacacca 180 gtgggtcttc tgtggccaga agagctccga agagacaggce gagctccgtg gtagtgattg 240 actctgattc tgatgaggaa tgtcacaccc atgaagagaa gaaagctaag ttattggaaa 300 taaacagcga cgatgagagt ccggagtgtt gtcatgtgaa gcctgccatc caggaacctc 360 caatagttat tagtgatgat gacaatgacg atgacaacgg taatgatttg gaagttccceg 420 acgacaacag tgatgattca gaagctcccg acgacaacag tgatgattcg gaagctcctg 480 acgacaacag tgatgattcg gaagctcccg acgacaacag tgatgattcg gaagctcecg 540 acgacaatag tgatgattcg gatgttcccg acgacaacag tgatgattca tccgacgaca 600 acagtgatga ttcatccgac gacaacagtg atgattcgga tgttcccgac gacaagagtg 660 atgattcgga tgttcccgac gacagcagtg atgattcgga tgttccecgac gacagcagtg 720 atgattcgga agcteccgac gacagcagtg atgattcgga agctcccgac gacagcagtg 780 atgattcgga agcteccgac gacagcagtg atgattcgga agctcccgac gacagcagtg 840 atgattcgga agcttccgac gacagcagtg atgattcgga agecttccgac gacagcagtg 900 atgattcgga agctcccgac gacaagagtg atgattecgga tgttcccgaa gacaagagtg 960 atgattcgga tgttceccgat gacaatagtg atgatttgga agttcctgtg ccagcagaag 1020 atttgtgtaa tgaaggccaa attgcttcag atgaagaaga gctggttgag gctgctgetg 1080 ctgtctccca gecatgattca tcectgatgatg ctggtgagca ggatcttggt gagaatctca 1140 gcaaaccacc aagtgatcct gaggctaacc ctgaagtttc agagagaaag ctgccaactg 1200 aggaagagcc tgcacctgtg gtggaacaat cagggaaaag gaagtcaaaa accaaaacta 1260 ttgtggagcc accgaggaaa aggcagacaa agaccaaaaa tatagtggag ccaccaagga 1320 aaaggcagac aaagaccaaa aatatagtgg agccactgag gaagaggaag gcgaaaacca 1380 aaaatgtatc tgtgacacct ggacataaga agcgtgggcce ttcaaagaag aaacccggtg 1440 cagcaaaagt tgaaaaacgc aagactagga ctcctaaatg caaagtccct ggatgtttet 1500 tgcaagacct tgaaaagtca aagaaatact ctggaaaaaa tttaaagcga aataaggatg 1560 aattggttca gagaatctac gacctgttta acagatccgt ctgtgataaa aagctgccag 1620 agaaactacg cataggctgg aataacaaga tggtgaaaac tgctggctta tgcagcactg 1680 gtgagatgtg gtacccaaag tggcggcgct ttgccaagat ccagattggce ttgaaagtct 1740 gcgactctge agaccgaatc cgggatacct tgatccatga aatgtgccat gectgectect 1800 ggctgattga tggtatccat gattctcatg gtgacgcatg gaagtattat gccaggaaat 1860 Ccaacaggat acacccggag ctgcccaggg tcacccgttg ccataactat aagattaact 1920 acaaggtcca ttatgaatgt actggatgca aaacgaggat tggctgctac accaaatcgt 1980 tggacaccag ccgcttcatc tgtgccaaat gcaaggggtc tctggtcatg gtgccattaa 2040 Ctcagaaaga tgggacccgt attgtgecccc acgtgtgacc atttgctgtg tatgtgcaga 2100 agtattatag aaaaattatg caggagatgg ctaggattag ccttggggat gtgatgaaaa 2160 cacttggcag gaattacaag gcaatgaaga attcttaagg ttatcttaga gtatattaat 2220 gtgagctata tcctttactg gtaagaagtt ttagaaaagt ttgttttgtg aagttaggaa 2280 tattagaatt taggtactgt taagtaagta atgttagaat ttaagattca tgttattaac 2340 gatgattgac cttaaatagg gactctattg ctaaccattc tgtgcccttg acagggtatt 2400 tctgaagcece ttgggatcta ccttgggtcect tacttgagtt ccatattttt cacatgtaga 2460 acaaaatgca aaagaaaagt gagttttcaa gagtggcagg ttgagagagg agaatgctgg 2520 aaagaggaca agtttgagag gcaacactta aacactaggg ctactgtggc atctatgtag 2580 acaggaaaga caaacgtgtt tcataaaatt cgttgttgat ggtattgatt gaaactatct 2640 gagccatgta atcaaaaaat aaaagttttc tgcatcaaaa aaaaaaaaaa aa 2692 <210> 552 <211> 390 <212> DNA <213> Homo sapiens } <400> 552 ttettttttt tttttttttt tttttttttt ttccttttac aaaatataaa tttattatga 60 aaacctggaa ggataatcca aggaaggtaa aaaaagaaaa aaggaggcca ccaaaaaaag 120 gcaggaagga gaggaaaaga aaaaaagaca aagaggagat gagagaaaaa aatccagttc 180 agcacaacaa aagtgcaaaa gctcacctac ccaaatggca ttaaagccte gttgtgtaat 240 cgtgtcagaa aacaaagcat actgacacat agggctttac ttcccatcca cttgagtttt 300 aagaggtaaa ttaaaaagct ccttgggaag gggacatgag gttgttcaaa aacccaacaa 360 agaaaattaa aaaaaaaaga gagagagaaa 390 <210> 553 <211> 4314 <212> DNA

301

<213> Homo sapiens <400> 553 gaacagattc atgggtgatt tagcctatct gtcccaggecc agcecgtggetg agtgtgctgg 60 ctggaggcct ctctectetge ttcgagggta gectgagatce accccggaaa ccggcaggat 120 gaagggggca agtgaggaga agctggcatce tgtgtccaac ctggtcactg tgtttgagaa 180 tagcaggtat gggcagctgg ggtgggaggg tcaccatggt gggctggcag ccaccctcca 240 gcctttctgg cagctctcte cctgggecct geecccggacce ctcectectge aggggcagcece 300 cegegttcet cggtcacgga ttcecttggag catgggagag tgtcggtggg acaccaggag 360 ccaggcaggg gtgagagtgc cagtgtgtgt tgggagagtc cagacaggtg tggttacgag 420 caagcatggg cagaccaaag cctgtgtgtg ggcacaggac cccacccadt gcctgccage 480 acctctcaga aaaggtagct gatactcacc aagaatttac gccctatgat taggataacc 540 atataattta tcattcagca cacaattgaa actgaaagta aatgccaaat aaaatgtggt 600 ggttgtgggg gaggcattac aggtaaagct gggaccgtat gaggcaaacc aggatgtacg 660 ggcagcatcc tgatggggta ctccctactc taagttcatg tccttactta tttaatttag 720 tcatcgaaca gecctaacagg ggtagattct gtttctgttc ccgtcttata gatgaggaaa 780 tggagacaca gagaggtgag gatgccaagt gctttaagta tctggggcaa tgctggggeg 840 tctgtctgga gggaaaagge tgggccagat gcgtggagtc attggtagcc ctgggagcat 900 gtgtgtttgt gtgtgtgege gtgtgtgtat gtgtgtgttg tgtgttatgt gtggcatcaa 960 tccattcectge aggcatttct taagctcagg actgtgttag gggctgtcecc aggtagggtt 1020 ttctggaaat agactcagac agaggtttgc ctcaggtgat ttatcaggga gagcttttgg 1080 gaacaacagc tgtgggtgtg agggaagcag ggccgggcag ggggagatgce tgaactgcag 1140 tgcacctgcc acagaggect cagcctgtcc cagggagctc tggagctggg atgcctcetceg 1200 gttgttccag ctgaggaaga gggctgggta tttgtatctce catgtggact ggacaagaga 1260 ctctgggtga ggcagctctce tcttecagag agtgattccc agagagggac tcagccaata 1320 aattacccgg cageccccag tactaccagt agctggtggg gatggtgtgg ggaggcctca 1380 ttcctgaagg agggacatgg gtggcacagc acagcatcct acaggaactg tagaggatga 1440 agaagggttt cagtatttgg atgctgagct catcgaataa ctatgatgca aggtcataga 1500 cagtagatgt cctaggaatg gccecggatgc tgtattgagg gcactcatgg caggcaatgt 1560 ttcctgtagg cttcagggtg gagatggcat agatgtagac ctagaagtct tcaacttcct 1620 gagctgggtg attctccect gectcteceg ggatctttge caagetegte ctgttcageca 1680 ccaaagacag ctcttgggtg ccgecttcct ggcccaccac ceccttgggt gtgggtggat 1740 ggtaccacct cactcaacat gcttgacgtg gactaggcac acctgggtgg agcccctcag 1800 catgctgtge tctgcccagg caataaccct ggcaggagtg ggcagccctt agacgggagt 1860 taggtcccag Caggcatcaa gagggtgaga gccactcctt actgagtgag gggacccata 1920 c€caactgcct tggcctggge ttccttatga ggtctccage acctcagctg atctgaaact 1980 gaggggcaaa gaggaaacag aagctggcca ggggccctag aacagaaatg cagaacctga 2040 aaccaaatgt agaacagaaa gcctgagaac cagctacgcec catgagctgc agacccatgg 2100 gctgagaaac cagggactgg ggtgccaggg aggggtggga gagcctggga gtagccacac 2160 agcactaggt cccaatgett tcgctgeccac aaacccaatt gtgtcacttg gggcaagtca 2220 ctttgactcc gcggacctgt ttctccttta ctcaaatggyg gaggggcagyg ttagagtgaa 2280 ggctcaggaa gcagtcgect gatttgaatc ccacctctgce cacttccgag ccgcatgtta 2340 Ctcatcctgt ccagacctca gtttccttga gtgcaaaata tgggtaatga aaacctttct 2400 cacggagttt tggagatttc gtatttgttt ggccttccat ttecctggect gtetttctea 2460 taaggatgcc tgcectgttce tgtcatcaca agcccttcca caccaagggc aacgttgggt 2520 gtattcatca agggtgggcc ctgttgtcta aggaatttga ctggcttgca gaacccagta 2580 cacagggtaa taaaggtgac ctacgaaggc ccgtcecctgg gagaacagag catctgctgc 2640 tgggctgget ctccctgett ctggacgtgt ggaggatgtc gatcccattg agaagcccca 2700 gcttttgcag geoctgctcte actttatatt gttctgtggc tcctaccttce ccttgatgta 2760 taggttactg atgtggaaac tgaaaacaga ggtgaggtcc aaaggtgagg ataatccagg 2820 . gggtaccact caaaaacccc tatatacaga aaggattcct ggacactgtg gcttcatttt 2880 aaacaaggaa gtatgcagtt ccccagaaaa taaaatatag tccaccctga ctcattttga 2540 acactgagtt ccctccaaga atgtgttggg agagaagtga aagtcttact cagcatgttc 3000 CCaaagaaag ccaggcaccc aggggcccct gcactgggga tttgcaccag gcaacccaaa 3060 tccacaccag ggacttgetg ctgttttcee tgttctccag ggaggaagce ctcaggtctg 3120 tctettetee tcaggacccece agaagcagca cccagaggcc agaggctaga ggacgtgcat 3180 caccgccctg agtgcaggece tcccgagtcc ccaggaccac gggagaagac gaatgtcggg 3240 gaggccgtgg ggtctgagcc caggacagtc agcaggaggt acctgaactc cctgaagaac 3300 aagctgteca gcgaagcecctg gaggaaatct tgccageetg tgacectctce aggatcggqgg 3360 acgcaggtgc ctgagggctg aggtagaggt gtggggtgct ggggtgggga gctctecectg 3420 acctcaccte cacacatgct ttcctageca gagccagcag ttccccaggt gggggtatgg 3480 tgtgatcaga ggtcagctgg gagctagatt tccececatget taatggeoctt tgattcacta 3540 actgcctget acgcaccgtg ctggattact tcgcgagteec ctecgtgtagg agttttttgg 3600 acaaggaagt tgaaacacag ttttaaggaa cttattcaag gccacacagc ttggaacagt 3660 ctccatcttg tgaacctaat actcttctca ggtggggcct cagtttaccce actggaggag 3720 acaacaatct caacctagaa atagaggtct gagtgtgaac tgtcetgeece ttagactaaa 3780 gcececagtetg atctcttectg tggcttgcag ttttectcatc tgcagagttce aagggttggc 3840 atgcagatac tgtgcaccca aattccctgg agtcacatcc cagcacgtct gcttactaac 3900 tgtgtgtcect tgggecaagtc acttgagtct ctttgtgcca gtttectcat ttgtaaaatg 3960 gggatagtgg ttatagtaat gcgtcctggt tttcaatcge tgectgaacaa acetatcaaa 4020 aatgtagcgg ctggccgggt gcagtaactc acgcctgtaa tcccagcact ttgggaggcec 4080 gaggtgggca gatcacctga ggtcaggagt tcaagaccag cctggccaac atagggaaac 4140 actgtctcaa ctaaaaatac aaaaattagt tgggcatggt ggtgggcgcc tgtaatccca 4200 gctactcagt aggctgagac aggagaatca cttgaatcca ggaggaggag gttgcagtga 4260 gccgagattg cgecacteca ctctagcetg ggtgacagag cgagactctg tctce 4314 <210> 554 <211> 689 <212> DNA <213> Homo sapiens <400> 554 aacgtctcaa ctgtaaactc tgggcacgeg gctagegeca ggtcetctec agccctaaca 60 ttctgtgatt ctaaacttgt ctgatttgtc tcatatgttg caaggctcgt agcaaaaaga 120 aaaaaatact ccataactat ttaacaggaa ttagctaaag cacagctcta gagagagaga 180 cacacacaca cgtttcaaat aacccgaaca ctagaaccta gtgaatttta tacctttact 240 aaactttagc gattatttgt ttctttcgta acaaaggtta ttgattagat ttagtgctga 300 aaaaaaccaa caacgtgcgc ttcggtcatt tgtcttatgg aggaaacata aatctataaa 360 tcttectect gtctctaaga aataaaactc tcttcatttc caaagtaaaa aaaaaaaaat 420 tggcaaaata ccaaaaaggt caaaaaaaaa actcgagggg gggcccggta cccaattcge 480 cctataggga gtcgtattac aattcactgg ccgtegtttt acaacgtcgt gactgggaaa 540 accctggcgt tacccaactt aatcgecttg gagcacattc ccectttegge agctggcegta 600 atagcgaaaa ggcccgcacc gatcgcectt tccaacagtt gggcaccctg aatggcaaat 660 ggcaaatttg gagcgctaat aatttgtta 689 <210> 555 <211> 4828 <212> DNA <213> Homo sapiens

<400> 555 cactgttcct acagcaatcg gtcagttgtg ggagtgettg tccactacca gaaaagacac 60 ccagaaataa aggttactgc caaatatatc agacaggctc ctcccacage tgcaatgatg 120 agaggggtcg aagggcccca aggctcccce cggccacccg cccccataca acagctgaac 180 cgaagcagct ctgagagaga tggccctcct gtggagaatg agatgttctt ttgccageac 240 tgtgattatg ggaaccggac ggtcaaaggg gtactcattc attatcagaa gaagcaccga 300 gacttcaagg ccaatgcaga tgtgatccgg cagcatacgg ccaccattcg aagecctctge 360 gaccgaaatc ggaagaagcc tgccagctgce gtgcttatct cccectctaa tctggagegg 420 gacaaaacga aactccgagc actcaaatgt aggcagtgct catatacctc ccecctactte 480 tatgcactga ggaagcatat caagaaagac caccccgccc tgaaagccac agtcacgtcec 540 atcatgcgat gggcatttct agatggcttg atagaagctg gctaccactg cgagtggtge 600 atctactcce atacggagcc caacggtttg ctcctgecatt accgacggag gcatccagaa 660 cactatgttg attacaccta catggctact aaactgtggg ctgggccaga cccatcccct 720 ccctctctca caatgccagc cgaagccaaa acctacagat gcagggactg tgttttcgaa 780 gctgtttcca tctgggacat cactaatcac taccaagcat tccacccetg ggccatgaat 840 ggtgatgagt cagtgctact ggacatcatc aaggagaaag atgctgtgga gaagcccatt S00 ctttcatccg aagagttgac aggccctgtyg aattgtgcaa acagtatacc caccccttte 960 ccggagcagg aagctgaatg tccagaggat gcaagactgt cccctgagaa aagcctgcag 1020 ctagcttcag ccaaccecgce catatcctecc accccatacc agtgcacggt atgccaatct 1080 gagtataaca acttgcacgg ccttctcact cattatggga agaagcaccc tggcatgaaa 1140 gtgaaggctg ctgactttgc ccaggacatt gacatcaacc caggtgccgt ctacaaatgce 1200 aggcattgcc catacatcaa cacccgcatc cacggcgtac tgacccacta ccagaagcga 1260 cacccgtcca tcaaggtgac cgctgaggac tttgtgcacg acgtagagca gtctgetgac 1320 atatcccaga atgacgtgga ggagacgagc aggatcttca agcaagggta tggcgcctac 1380 . cggtgcaaac tgtgtcecgta cacacacggc actttggaga aactaaaaat ccactacgag 1440 aagtatcaca atcagcctga atttgatgtc ttttcccagt cgcccccgaa gctgccagtce 1500 cccctcgage ccgagatgac cactgaagtg agcccttccc aagtctccat cactgaggag 1560 gaggtgggag aggagcccgt gtccacttct cacttctcta cctcccacct ggtctceccac 1620 actgtgttcc ggtgccagct ctgcaagtac ttctgetcca cgaggaaggg gatcgccagg 1680 cactaccgca tcaagcacaa taatgtccga gcccagccag aaggcaagaa caacctcttce 1740 aagtgtgccc tgtgtgccta caccaacccec atccgcaaag gtctggcage ccactaccag 1800 aagcgccacyg acattgatgec gtattacact cactgcttgg cagcctccag gaccatcagc 1860 gacaagccca acaaagtgat catcccatce ccgcccaagg acgactccce tcagetgage 1920 gaggaactcc ggcgggcagt ggagaagaaa aagtgctect tgtgcetcttt ccagtegttc 1980 agcaagaagg gcatcgtgtc ccattacatg aaacgccacc caggggtgtt cccaaagaag 2040 cagcacgcca gcaagttggg gggctacttc acggccgtct atgcagatga gcatgagaag 2100 cccacactga tggaagaaga ggagagaggc aactttgaga aagccgaggt ggagggtgaa 2160 gctcaggaaa tcgagtggct cccattccge tgcatcaaat gettcaagcect gtcctttage 2220 actgcagagc tgctgtgcat gcattacact gaccaccaca gtcgggacct aaagagggac 2280 ttcatcatac tgggcaacgg ccceccgettg cagaactcca cctaccagtg taagcactgt 2340 gatagcaaac tgcaaagcac agccgagctg acctcacact tgaacattca caatgaggaa 2400 ttccagaagc gtgccaaacg tcaggagagg aggaaacagce ttttgagcaa gcaggaatat 2460 gcagatggtg cttttgcaga tttcaaacaa gagaggcctt ttggtcactt agaagaggtg 2520 ccaaagatca aggagaggaa agtggtgggc tacaaatgta aattctgtgt ggaagtgcac 2580 ccaacgctcc gagccatctg caatcacctc cgaaagcacg tccagtatgg caatgtccca 2640 gctgtgtcag ctgctgtgaa ggaggcggat gaccctgccc acttattect ggatggattg 2700 gaagcagcca aagacgcaag tggcgccctg gtgggcececggyg tggatggtga acactgcettg 2760 cttgatggaa tgttggagga tgaaacccgg ccggggggat accattgcag tcaatgtgac 2820 agagtcctga tgteccatgca ggggctgcgt tctcatgaga ggagccacct ggccctggcece 2880 atgtttaccc gcgaggacaa gtacagctgc cagtatagct cgtttgtttc tgctttcagg 2940 . cacaatttgg atcgccatat gcaaacccac cacggacacc ataaaccatt ccgatgcaaa 3000 ctctgctcet tcaagtecctc ctataacagc cggctgaaaa cacatatact caaagctcat 3060 gctggtgagc atgcctacaa gtgttcttgg tgctcattct ccaccatgac aatcagccag 3120 ctgaaggaac actccctcaa ggtccacgga aaagccctga ccctccccag gccacggatce 3180 gtcagtctcc tctcctcaca ctcccaccac tcctcccaaa aagctacccc ggctgaagaa 3240 gtggaagact ccaatgactc atcatattca gagcccccag atgttcagca gcagttgaac 3300 cactatcagt cagctgccct ggcaaggaac aacagccgtg ttageccctgt gecctetttcet 3360 ggggctgetg ctggcactga gcagaaaact gaagccgtgce ttcactgecga attctgtgaa | 3420 ttctcetecg gctacatcca gagcatcagg cgtcattacc gggacaagca tggtgggaag 3480 aagcttttca agtgcaaaga ctgctccttt tacacaggct ttaaatctgc ttttactatg 3540 cacgtggaag ctgggcactc agcagttccc gaggagggcc ccaaagatct tcgcectgtcct 3600 ctctgcetct atcacaccaa atacaagcgc aacatgattg accacatcgt gctgcactga 3660 gaagagcgtg ttgtccccat tgaagtttgc cggtccaaac tgtccaaata cttgcaggga 3720 gtagttttcc gctgtgataa gtgtaccttc acctgctcca gtgatgagag cctceccagcaa 3780 catatagaaa agcacaatga actgaaacct tacaaatgcc agctctgcta ctatgagacc 3840 aagcacacgg aggaactgga cagccacctt cgggatgagc ataaggtaag ccgtaacttt 3900 gagctggttg gacgggttaa cttggatcag ctggaacaga tgaaggagaa aatggagagc 3960 tccagcageg atgatgagga caaggaagaa gaaatgaaca gcaaggctga agacagagag 4020 ctgatgagat tttctgacca cggggctgct cttaacactg agaagcgttt tccatgtgaa 4080 ttttgtggac gggecgttttc acagggctct gagtgggaaa gacatgtgct gagacacggc 4140 atggcattga atgacaccaa gcaggtgagc agagaagaaa tccacccaaa agagatcatg 4200 gagaacagtg ttaaaatgcc ctccatagag gaaaaggaag atgacgaggc cattgggata 4260 gacttttccc taaagaatga aacagtagcc atctgtgtag taactgccga caaatctctce 4320 ctggagaatg cagaggccaa aaaagaatga gcgtttggtg aaattcttaa tcaaacctta 4380 cttgaacagt gatgaaaaag tgggagggct ggctttggect gagaagggag ggacagaaaa 4440 gagaagacag aacaaagctg ctttttagga ctgaacaatc tattttcaaa gcactggtac 4500 ctgtgtgagt gagtatgtaa attaaagtta tttaaatggt tggaatatgt ggctcctttt 4560 ccatcactac atcttttctt ccggatcttc atcatggaag tttcatttgt tgcggaatat 4620 ggaagcacct cccaatggta cggtgcaccc tgtggtggtc ttggacagta tgtggaaaca 4680 gaagctccat gacggtagaa gacttctcat tggggagcaa cttttttacg cacaactttt 4740 ggtgegtttt tctagtttta ataccttaag ctttttcaag acctaactge agccgctttg 4800 ggaaaaaaaa acaaaaaaca aaaaacag , 4828 <210> 556 <211> 279 <212> DNA <213> Homo sapiens <400> 556 gggggcgccg tccatggaga agccggatgt ggcgaataca caccctgggg cacattgatc 60 agtgctacgc atgagatggg gggcagcgtg ggggccgtat acaacggcga gacactttaa 120 ccaggtgtag atcaagaccg agatgatcgg ccactacctg ggcgagatct ccatcaccta 180 ctagcccgga aagcatggec ggcccgtgat cacggccacc cacttgtcecca gcttcatccce 240 tctgaagtaa tggctcagct aataaaggct cacatgact 279 <210> 557

<211> 390 <212> DNA <213> Homo sapiens <400> 557 ttettetttt tttttttget ctgectggecaa ttccaagaac atcactgcta cattgagcaa 60 ctatccatct ttaaagagcc agcagagcaa aacaaaataa atctctttte caaagccagg 120 ataaccaaga agacttcctt caaaaagcag gggactggga aaaggggaaa agggaaggaa 180 agagataaag taaagctttt ccaaattttg gectttttget cctattcccet ctgcctgttt 240 tgaaaactta aggataagca atgacattag cagtgtcttt ggtatctaaa ccaaatccca 300 cttaagttct gtgggatcat ttatttaaaa aaatagcctt tctagagata cagtctatat 360 ccaaactcag ggagccaaga aagtttgtcc 390 <210> 558 <211l> 1227 <212> DNA <213> Homo sapiens <400> 558 cgtagcggaa gttactgcag ccgeggtgtt gtgctgtggg gaagggagaa ggatttgtaa 60 accccggage gaggttcectge ttacccgagg cegetgetgt geggagacce ccgggtgaag 120 ccaccgtcat catgtctgac caggaggcaa aaccttcaac tgaggacttg ggggataaga 180 aggaaggtga atatattaaa ctcaaagtca ttggacagga tagcagtgag attcacttca 240 aagtgaaaat gacaacacat ctcaagaaac tcaaagaatc atactgtcaa agacagggtg 300 ttccaatgaa ttcactcagg tttctetttg agggtcagag aattgctgat aatcatactc 360 caaaagaact gggaatggag gaagaagatg tgattgaagt ttatcaggaa caaacggggg 420 gtcattcaac agtttagata ttctttttat ttttttttet tttcecctcaa tcctttttta 480 tttttaaaaa tagttctttt gtaatgtggt gttcaaaacg gaattgaaaa ctggcaccce 540 atctctttga aacatctggt aatttgaatt ctagtgctca ttattcatta ttgtttgttt 600 tcattgtgct gatttttggt gatcaagcct cagtcccectt catattaccce tctecttttt 660 aaaaattacg tgtgcacaga gaggtcacct ttttcaggac attgcatttt caggcttgtg 720 gtgataaata agatcgacca atgcaagtgt tcataatgac tttccaattg gccctgatgt 780 tctagcatgt gattacttca ctcctggact gtgactttca gtgggagatg gaagtttttc 840 agagaactga actgtggaaa aatgaccttt ccttaacttg aagctacttt taaaatttga 900 gggtctggac caaaagaaga ggaatatcag gttgaagtca agatgacaga taaggtgaga 960 gtaatgacta actccaaaga tggcttcact gaagaaaagg cattttaaga ttttttaaaa 1020 atcttgtcag aagatcccag aaaagttcta attttcatta gcaattaata aagctataca 1080 tgcagaaatg aatacaacag aacactgctc tttttgattt tatttgtact ttttggcectg 1140 ggatatgggt tttaaatgga cattgtctgt accagcttca ttaaaataaa caatatttgt 1200 aaaaatcaaa aaaaaaaaaa aaaaaaa 1227 <210> 559 <211> 452 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (1)..(1) <223> nis a, ¢c, g, t or u ) <220> <221> misc_feature <222> (340)..(340) <223> n is a, ¢, g, t or u <400> 559 ngacaaatag actcgcctaa gagggccttt ctctccaagc cctcgecage acaggctgtg 60 tcactttctt aggtggcacc taccgtctgt tgcacacttg ctgcagatga tttggcacag 120 gatgtcgctt cagaaaacct tgtaggaagc cgtgagtegt taccgtccec atttcacaga 180 caggaaagtg caggccttag atgcactgec tgataccctg tggcccececge gttcectagac 240 agatacactg cctggtacac tgtaccccce caccecccget atcgtttgca agctggggtt 300 gaacccctge aattcaatag acaaggttcc ceccttgagtn agccccccat ctgcttaact 360 gagggcttgt cctceggttat aaatgtctgg gtgggggtgg gcactgctgg ctgcagctgt 420 caggactggg aatgctgaac ctgcactgag gg ] 452 <210> 560 <211> 1197 <212> DNA <213> Homo sapiens <400> S60 gtagcgggaa ccatatacgg ctaggtacga ggctgggtgg ctaggcgecat ggctcccege 60 gggaggaagc gtaaggctga ggccgcggtg gtcgecgtag ccgagaagcg agagaagctg 120 gcgaacggcg gggagggaat ggaggaggcg accgttgtta tcgagcattg cactagctga 180 cgcgtctatg ggcgcaacgce cgcggcectg agccaggcgc tgcgcecctgga ggccccagag 240 cttccagtaa aggtgaaccc gacgaagccc cggaggggca gcttcgaggt gacgctgctg 300 cgecegggac ggcagcagtg cggagetcectg gactggggat taagaagggg cccccatgcea 360 aactcaaatt ccctgagect caagaggtgg tggaagagtt gaacgcaagt acctgtcgat 420

309 - — uM agggagcatt gggtagaagc cctcattgct gagctttgtg ttcectggtg atgtgggacc 480 attaatgatg gaacatggcc aaatttcagt cattgatcct gaagccatgg tttcttcecg 540 tgccagaaat gacaggctca gttatgaggc aaccctctta gtagggcatt gtaaaacgta 600 cctggattgg ggtttactac caccgtttga cacttacggt acacacaaac acacaaaaaa 660 aaacgttggg gggcactcta tagtgccgag gggcgcggac aacaccgcgg ttacatgaac 720 gtggcacatt ggggccaata gggtgttccc ctggacgcac agtttctttg gtacacaggg 780 tggggtaaac tctggcgggg acacccctta atagggagag ggcgagaata aattttcgga 840 : taaacgcagg gttaccttgt atagacatct tgactgtaca acaagagggg aacgaaaacg 900 aaagcacaaa acaaaggaga aaaacgacga ctgggagaaa aggaggagga gagggaggag 960 gagagggaga gcagaagaag cgagaggagc aggaaaagag gaggaccacc caaagagacg 1020 aggaaacaag agaggagaga gaacagagga taacgcgaaa gaaaggaaga agcacgatgce 1080 aaacagaaac aagacgagac agagtgagcg agcaggagag aggggagaaa agaaggagag 1140 gagaggagag aggagaagaa agcaagagga aggggacgca gacagaagdg caggacg 1197 <210> 561 <211l> 764 <212> DNA <213> Homo sapiens <400> 561 ggcacgagcc cggcagtgca gctgccgeta ccgececgcect ctgcccgececg gececgtcetgt 60 ctacccccag catgagecgge ctgcgegtct acagcacgtc ggtcaccggc tcccgcgaaa 120 tcaagtccca gcagagcgag gtgacccgaa tcctggatgg gaagcgcatc caataccagce 180 tagtggacat ctcccaggac aacgccctga gggatgagat gcgagcettg gcaggcaacce 240 ccaaggccac cccaccccag attgtcaacg gggaccagta ctgtggggac tatgagctct 300 tcgtggaggc tgtggaacaa aacacgctgc aggagttcct gaagectggct tgagtcaage 360 ctgtccagag ttcccctget ggactccatc accacactcc ccccagectt cacctggceca 420 tgaaggacct tttgaccaac tccctgtcat tcctaaccta accttagagt ccctcecccccce 480 aatgcaggce acttctccte cctececttete taaatgtagt cccctctect ccatgtaaag 540 gcaacattcc ttacccatta gtctcagaaa ttgtcttaag caacagcccc aaatgctggce 600 tgceccccage caagcattgg ggccgccatc ctgectggea ctggctgatg ggecacctctg 660 ttggttccat cagccagage tctgccaaag gccecgecagt ccctctecca ggaggaccect 720 agaggcaatt aaatgatgtc ctgttcaaaa aaaaaaaaaa aaaa 764

<210> 562

<211> 2661

<212> DNA

<213> Homo sapiens

<400> 562 gctccecgggg ccacgggatg acgcctcctc cgccecggacg tgccgeececce agegecaccge 60 gcgccegegt ccctggeccg ccggctecggt tggggcttece gctgeggetg cggcetgetge 120 tgctgctcetg ggcggccgece gectcecgece agggccacct aaggagcgga ccccgcatct 180 tcgecegtcetg gaaaggccat gtagggcagg accgggtgga ctttggccag actgagccge 240 acacggtgct tttccacgag ccaggcagct cctctgtgtg ggtgggagga cgtggcaagg 300 tctacctett tgacttccce gagggcaaga acgcatctgt gcgcacggtg aatatcggct 360 ccacaaaggg gtcctgtctg gataagcggg actgcgagaa ctacatcact ctcctggaga 420 ggcggagtga ggggcetgetg gecectgtggea ccaacgcceg gcaccccage tgctggaace 480 tggtgaatgg cactgtggtg ccacttggcg agatgagagg ctacgccccc ttecagcccgg 540 acgagaactc cctggttctg tttgaagggg acgaggtgta ttccaccatc cggaagcagg 600 aatacaatgg gaagatccct cggttccgeec gcatecgggg cgagagtgag ctgtacacca 660 gtgatactgt catgcagaac ccacagttca tcaaagccac catcgtgcac caagaccagg 720 cttacgatga caagatctac tacttcttcc gagaggacaa tcctgacaag aatcctgagg 780 ctcctetcaa tgtgtcecegt gtggcccagt tgtgcagggg ggaccagggt ggggaaagtt |. 840 cactgtcagt ctccaagtgg aacacttttc tgaaagccat gctggtatge agtgatgctg 900 ccaccaacaa gaacttcaac aggctgcaag acgtcttect getcectgac cccagcggec 960 agtggaggga caccagggtc tatggtgttt tctccaaccc ctggaactac tcagccgtcet 1020 gtgtgtattc cctcggtgac attgacaagg tcttccgtac ctcctcacte aagggctacc 1080 actcaagcct tcccaacccg cggecctggeca agtgcctece agaccagcag ccgataccca 1140 cagagacctt ccaggtggct gaccgtcacc cagaggtggc gcagagggtg gagcccatgg 1200 ggcctctgaa gacgccattg ttccactcta aataccacta ccagaaagtg gccgtccacce 1260 gcatgcaagc cagccacggg gagacctttc atgtgcttta cctaactaca gacaggggca 1320 ctatccacaa ggtggtggaa ¢cgggggagc. aggagcacag cttcgectte aacatcatgg 1380 agatccagcc cttcecgecge gecggctgeca tccagaccat gtcgctggat gctgagegga 1440 ggaagctgta tgtgagctce cagtgggagg tgagccaggt gcccctggac ctgtgtgagg 1500 tctatggcgg gggctgccac ggttgectca tgtcccgaga ccectactge ggctgggacc 1560 aaggccgcetg catctccate tacagetccg aacggtcagt gctgcaatcce attaatccag 1620 ccgagccaca caaggagtgt cccaacccca aaccagacaa ggccccactg cagaaggttt 1680 ccctggccec aaactctcgce tactacctga gectgccccat ggaatcceccge cacgcecacct 1740 actcatggcg ccacaaggag aacgtggagc agagctgcga acctggtcac cagagcccca 1800 actgcatcct gttcatcgag aacctcacgg cgcagcagta cggccactac ttctgcgagg 1860 cccaggaggg ctcctacttc cgcgaggctce agcactggca gctgctgccc gaggacggcea 1920 tcatggccga gcacctgctg ggtcatgect gtgecectgge cgecteectce tggctggggg 1980 tgctgcccac actcactctt ggcttgctgg tccactaggg cctcccgagg ctgggcatgc 2040 ctcaggcttc tgcagcccag ggcactagaa cgtctcacac tcagagccgg ctggecceggg 2100 agctccttge ctgccacttc ttccagggga cagaataacc cagtggagga tgccaggcct 2160 ggagacgtcc agccgcaggc ggcetgctggg ccccaggtge gcacggatgg tgaggggetg 2220 agaatgaggg caccgactgt gaagctgggg catcgatgac ccaagacttt atcttctgga 2280 aaatattttt cagactccct caaacttgac taaatgcagc gatgctccca gcccaagagce 2340 ccatgggtcg gggagtgggt ttggatagga gagctgggac tccatctcga cecctgggget 2400 gaggcctgag tcecttctgga ctcecttggtac ccacattgecc tcecttcecececct ccctctctea 2460 tggetgggtg gctggtgttc ctgaagacce agggctacce tetgtcecage cctgtcectcet 2520 gcagctccct ctctggtcct gggtcccaca ggacagccge cttgcatgtt tattgaagga 2580 tgtttgettt ccggacggaa ggacggaaaa agctctattt ttatgttagg cttatttcat 2640 gtatagctac ttccgactge c 2661 <210> 563 <211> 507 <212> DNA <213> Homo sapiens <400> 563 ttctccagge tggccctcag cctggegecece cttceccgcaga catcecctaga aaaagaacta 60 acgecggcectt ctccgagccc agggctggag taggaagtac ccgccctcce gaacgcgagg 120 tcctggetge gecattggctg cgaaggceegt cagtactccg gagggcggag cctcccggea 180 cccagcggaa tttcaggccce gecaccteccgg gagggtcecte cgggecteccg ggettcottte 240 ctcceecctta acactaccec cgecacacaca ccggccccga gaaggcaact agcctcectea 300 aacggttcct ttgccecttttt atttcgcagg ccttcctcte accccataca gttactgecce 360 ctttgactcc tccgagagge saagettitt caaagctcta acacctctcce cctaccccag 420 caagttccce gtgcgagacc aaatagagga tgccgetgtt ctaagagtga agcaagctgt 480 ggactggatc tcgccgaggg agagaga 507

<210> 564 <211> 430 <212> DNA <213> Homo sapiens <400> 564 gctttaaaag ttatctttta ttaatatatt gtgtgtgcac cttgtcttcc tcaggcttag 60 aattccccag gtgctgggaa cttgagectg cttcectttce ctctgtette cataattcat 120 tccttaatge aacatctcect gagggcctac tttgtgtcag aaactacatt atttgctagg 180 ggtgcagagc ccaggaaggc acaggtgctt ccctcaagca gttctgaaat gaatagggta 240 cagataagta aaccccectc tcctatccag tgagtagagt tgtgtacaag gggacacaaa 300 atgagctctg gagacttgct cccccaaaat gggagccatg gaccatcagc attggcatca 360 cctgggagat caatagagat gcagacccct gtacccattc agttggagtg tgcatttgaa 420 ataagatccc 430 <210> 565 <211> 642 <212> DNA <213> Homo sapiens <400> 6565 gctgaagtga aaacgagacc aaggtctagc tctactgttg gtacttatga gatccagtcc 60 tggcaacatg gagaggattg tcatctgtct gatggtcatc ttcttgggga cactggtcca 120 caaatcaagc tcccaaggtc aagatcgcca catgattaga atgcgtcaac ttatagatat 180 tgttgatcag ctgaaaaatt atgtgaatga cttggtccct gaatttctgc cagctccaga 240 agatgtagag acaaactgtg agtggtcagc tttttcctgt tttcagaagg cccaactaaa 300 gtcagcaaat acaggaaaca atgaaaggat aatcaatgta tcaattaaaa agctgaagag 360 gaaaccacct tccacaaatg cagggagaag acagaaacac agactaacat gcccttcatg 420 tgattcttat gagaaaaaac cacccaaaga attcctagaa agattcaaat cacttctcca 480 aaagatgatt catcagcatc tgtcctctag aacacacgga agtgaagatt cctgaggatc 540 taacttgcag ttggacacta tgttacatac tctaatatag tagtgaaagt catttctttg 600 tattccaagt ggaggagccc tattaaatta tataaagaaa ta 642 <210> 566 <211> 4894 <212> DNA <213> Homo sapiens <400> 566 cgaaaacgga gaaaccccgg gtccggegag aggggctgtg acagtcggag tcccaagcetg 60 cggttcggct gctgccgaga actgcaaggt gtggaatatt tctggcttct agtccaatge 120 caagtgtgtg acctgtggct acatgattece ctgaaagata agaacaatgt tatgttgggg 180 atattggtct ctgggccaac ctggtatcag caccaacctg cagggaattg tggctgagcece 240 ccaggtgtgt gggttcatat ctgacagaag tgtcaaggaa gtggcectgtg ggggaaacca 300 ctctgtgttc ctgctggaag atggggaagt ttacacatgt ggtttgaaca ccaaggggca 360 actgggccat gagagggaag gaaacaagcc agaacaaatt ggagctctgg cagatcagca 420 tatcattcat gtggcatgtg gcgagtccca cagtctggcc ctcagtgacce gaggccagct 480 gttttcttgg ggtgcaggga gtgatggtca gctaggactc atgactactg aggattctgt S40 ggcagtgccc aggttaatac aaaagctgaa ccagcaaaca atattacaag tttcctgtgg 600 caactggcat tgcttggctc ttgcggctga tggccagttce ttcacctggg gaaagaacag 660 ceatgggcag cttggcttag ggaaggagtt cccctececcaa gccageccac agagggtgag 720 gtccctggag gggatcccac tggctcaggt ggctgccgga ggggctcaca gctttgeccect 780 gtctctetea ggagetgttt ttggctgggg gatgaataat gccgggcagce tagggctcag 840 tgatgaaaaa gatcgagaat ctccatgcca tgtaaaactc ttacgcacgce aaaaagttgt S00 ctatattagt tgtggagaag aacacacagc agttctcaca aagagtggag gtgtgtttac 960 ctttggcgect ggttcctgtg ggcaacttgg acacgactcce atgaatgatg aggttaaccc 1020 tagaagagtt ctagagctga tgggtagtga agtaactcaa attgcttgtg gcagacaaca 1080 taccctagee ttegtgectt cttetggact catctatgca tttggttgtg gagcaagagg 1140 tcaattagga actgggcaca cttgtaatgt taagtgccca tctcctgtca agggttactg 1200 ggctgceccac agtggecage tttcagccecg agctgatcge tttaaatate atatcgttaa 1260 gcagatcttc tctggaggag accagacttt tgtactttgec tccaaatacg agaattattc 1320 tcetgetgtt gacttcagga ctatgaacca agcacattat accagtttaa taaatgatga 1380 aaccatagca gtttggagac aaaaactctce agaacacaac aatgcaaata caatcaatgg 1440 tgttgttcag atattatctt ctgcagcctg ttggaatgga agttttcttg aaaaaaaaat 1500 tgatgaacat tttaaaacga gtcccaaaat ccetgggatt gacctgaact caactagggt 1560 gttatttgag aagttaatga actctcagca ctccatgatt ctagaacaga ttttgaacag 1620 ttttgaaagt tgtctgatte cccagttgtc aagctcacca ccagatgttg aagccatgag 1680 aatctattta atactacctg agtttcccct actccaggat tccaagtatt atataacatt 1740 gactattccc ttggctatgg ccattcttcg gctggataca aaccccagca aagtactaga 1800 taactggtgg tctecaggtat gcccgaaata tttcatgaag ctggtaaacc tctataaagg 1860 tgcagtcctt tatctactga gdggaagaaa gacattctta attcccgtac tgtttaacaa 1920 ttatatcaca gcagctctca aactcttgga gaagttatat aaggtaaatc ttaaagtgaa 1980 gcatgtggaa tatgatacat tttacattcc tgagatttcc aatctegtgg acattcagga 2040 agactacctec atgtggttct tgcatcaagc agggatgaag gctagaccat caataataca 2100 ggatactgta acactttgtt cctacccttt catctttgat gecccaagecca agaccaaaat 2160 gttacagaca gatgctgaac tacagatgca ggtggcagtc aatggagcca acctgcagaa 2220 tgtcttcatg cttctcaccc tggagcctct gotggecaga agccccttcce tggtccttca 2280 cgttcgcagg aacaaccttg ttggagatgc cctaagagag ctgagcattc attctgatat 2340 tgatttgaaa aagcctctca aagtaatctt tgatggtgaa gaagcagtgg atgccggtgg 2400 tgttacaaag gaattttttc ttttgctgtt aaaagaactt ttgaatccca tctatggaat 2460 gtttacctac tatcaagatt caaatctctt gtggttttca gacacgtgtt ttgtagagca 2520

) caactggttt cacttgattg gtataacctg tggactagct atctacaact ccactgtggt 2580 cgatctccac ttcccattgg ctctctacaa gaagttactc aatgtaaagc ctggcttgga 2640 agacttaaag gagttgtcac ccactgaagg aaggagtctc caagagcttt tagattaccc 2700 cggggaggat gtggaggaga ctttctgcct caacttcacg atctgecgag aaagctatgg 2760 agtgattgaa cagaagaagc tgatacctgg gggagataat gtaactgtgt gcaaggataa 2820 caggcaggaa tttgtggatg cttatgtgaa ttatgtcttc caaatctcag ttcatgaatg 2880 gtacacagcc ttctctagtg gecttcctaaa ggtgtgtggt ggcaaagtac ttgagctctt 2940 ccagccttca gaactgaggg ctatgatggt ggggaacagce aactacaact gggaagaact 3000 ggaagagact gccatctaca agggagatta ctcggccaca catcccactyg taaaactatt 3060 ttgggaaaca tttcatgagt ttccattgga aaagaagaag aagtttctct tgttectgac 3120 aggcagcgat cggattcceca tctacggcat ggccagtctg cagattgtca tccagtcecac 3180 agccagcggg gaggagtact tgecggtggc ccacacttge tacaacctte ttgacctccec 3240 caagtacagc agcaaagaga ttctgagtgc ccggctgacc caggcccttg acaactatga 3300 agggtttagt ttggcctgag gcttctcage ttgteccagta tttcecctteg ttectcagtg 3360 tccacattga ggcctataca gaaaatcatg gggagtgatt tctatttttt tattgtctaa 3420 gtgggttggg acttttaaat actgagcctg gttgatgtgt ttctgggatt gtatagcagt 3480 aaacaacctt tttgaaaaat tagaggttgg ggatggggtg aaaaattggc ccttgtatgg 3540 gaggtgtttt tgtttttgtt ttaaaccaaa ctacccagta ttccttgcac ttgtgaatgt 3600 gttgcactet gctggatgaa atggcagtgg atttttaaac tttaatttcc caaatgtctc 3660 tctcagcecet gatgttttet cacagtgctt ccttgtectt ctcttaactt ctcattcectce 3720 tataagaatg atttagactg acctgtcctt ttttatctgc gcatgcgaga acatcacctt 3780

315 Co cctctgtaca cttggaaatg cctetggett gttgcagcecc tcctttaacc caaaggagga 3840 aaggactgct tcagaaactc ccaattccaa aaagctgagt ctgggtccat tattttggca 3900 gaactcctaa gaatttatgg gagcctatat aaacatatct tgcttttaaa aagttcttga 33960 gggaatagca actttcccat ggctgtgcecct atttcctaga ccttttaaaa gatgtgcaga 4020 gcagcttagc attcgttgca gctgagecta attttttcett gctcatecctt gtccctttga 4080 caataaggtt aattgataga cccaccacct cttgcactct cgcttttgga gcaagttgca 4140 ttaactattt tgagtctcta tattgtccaa gaaaagtaga aataataaat ttactttccc 4200 tttttctatc accttatgtc ctctaccatt ttcteccttcec tececcttecet tattttctcece 4260 ttttcgtacc ctgtgtcecte cctgatttte ctttegttte ttctttattt tatcccattce 4320 tctgttactt gactcagtgc tcccttecte tcecctctcectt ctagtggatg catgcagect 4380 ttttttcaat ttttatttaa attgcaaaat ttttactcag attttttttec ctcttecccta 4440 attgctaaga tttaaggacg ttctttatta tgaaacttta tcacattcga aatgtttgtt 4500 tacagtggga ttttaggggg gattgtgttt aaatcaaata tatgtatttt aaaaataatg 4560 acatgctcaa ccttcctcat catggagtaa gaaaattcta catgattaaa gaatccatgt 4620 aagtctaatt ttaaattcct agtaactaga gaaaagactt atttatataa aatgaagtat 4680 ttatgaactg tgataaagca tcaaatcttg atgaaggatt gtagattttt gctttttctt 4740 tttgttttta aaacttattc caattgctaa attggtagtt tttcagtctt tataaataca 4800 ggattaaaaa tatatataca gttatatgaa atgtttattt tctatgtgtg tgcatatagt 4860 tcaatattat gcaataaatt tggtgtttta actt 4894 <210> 567 <211> 315 <212> DNA <213> Homo sapiens <400> 567 aggtgaatga tgactacaat aacattgcaa ctatttcttt cctggcatag ggaggtaata 60 agaaactaaa tgatcgcatg gtacatgctt gtattatata gatgggttta ggaatctata 120 aagtatggag gtaggaagac accatatgtc caggatcaaa acattcctca tattgaggta 180 gtctagtgaa gctgtttcat gtagctgctt taggaagtgg tttaaggaag cttactccca 240 cttcaagtta agcaccaaag caatcactaa ttctggagca caggaagact gctatctcat 300 cattcacctt tgcag 31S <210> 568 <211> 2321

<212> DNA <213> Homo sapiens <400> 568 cttcctgaaa ggatctggag acaccagectc cacaagtcct ggtgtcttta aaaggatcag 60 cttgaggaat aaggctcgte tgagagetgt gacattcatc tgactctagt gaaagtccaa 120 cagccactcc ctttttggece tccaactggg caccatgagg gectgcatct ccctggtatt 180 ggcecgtgetg tgtggectgg cctgggctga ggaccacaaa gagtcagagc cattgccaca 240 gctggaggaa gagacagaag aggccctcge cagcaacttg tactcggcac ccacctcctg 300 ccagggccge tgctacgaag cctttgacaa gcaccaccaa tgtcactgca atgcccgctg 360 ccaagagttt gggaactgct gcaaggattt tgagagcctg tgtagtgacc acgaggtctc 420 ccacagcagt gatgccataa caaaagagga gattcagagc atctctgaga agatctacag 480 ggcagacacéc aacaaagccc agaaggaaga catcgttctc aatagccaaa actgcatctc 540 cccgtcagag accagaaacc aagtggatcg ctgcccaaag ccactcttca cttatgtcaa 600 tgagaagctg ttctccaagc ccacctatgc ageccttcatc aacctcctca acaactacca 660 gcgggcaaca ggccatgggg agcacttcag tgcccaggag ctggccgage aggacgectt 720 cctcagagag atcatgaaga cagcagtcat gaaggagctc tacagcttcc tccatcacca 780 gaatcgctat ggctcagagc aagagtttgt cgatgacttg aagaacatgt ggtttgggct 840 ctattcaaga ggcaatgaag agggggactc gagtggcttt gaacatgtct tctcaggtga 900 ggtaaaaaaa ggcaaggtta ctggcttcca taactggatc cgcttctacc tggaggagaa 960 ggagggtctg gttgactatt acagtcacat ctacgatggg ccttgggatt cttaccccga 1020 tgtgctggca atgcagttca actgggacgg ctactataag gaagtgggct ctgctttcat 1080 cggcagcagc cctgagtttyg agtttgcact ctactcectg tgetteateg ccaggccagg 1140 caaagtgtgc cagttaagcc tgggaggata tcccttagcet gtcecggacat atacctggga 1200 caagtccacc tatgggaatg gcaagaagta catcgccaca gcctacatag tgtcttccac 1260 ctaatagaac ttcgagccag aaaggggcat gagggctctt gcgagactga agtgctatct 1320 tctctggact agagagaaga gggagaggac tggaagggat caccaaatct caaagcaatg 1380 agaagcattc ctaaatccca aagtgcccac atgggaaaga gataaaatgt acaaattaga 1440 aaaatgtgga taaacagtca aacctttatc ctctagaatt ttggcaatgt tgactaagaa 1500 acagagtcca agcagagaag gtaggaaccc tccatagctc tctgccctga tgtgtggggg 1560 aactaggaag aagtcctttg acctcaccag gcctcatgct tccctttaat gtaaagggaa 1620 ggggtttgec cactttccte tttttggggt tggtgagagg gcaaaccctg atatttttac 1680 tgtgaaggtg ttttcagttg ttcttaggaa gaacagctga tagaaattca agattactat 1740 317

EE aatggctgtt attatacaca gctctgtaaa ctaccactca gccctgtgtt ggggtcctca 1800 aagaagtaag gccacagtaa tcaagcaagg gcectttggtt ttttccagag ttagatccte 1860 tcagaacaga gtctgggaga actccaatgc tgaatggaga agggtaatag gttggtgcag 1920 tgaatgggct gggggtgggg tggcecttcte caggcctgag tgtttttgtg tccagctcag 1580 tatctgcaac aagaagtttc ccacttgtgg atgtttagtg cagccacaga cttgtatttt 2040 gatccccaat tteetettga aagagttctc ctcataggag gatgattcag catcagaaga 2100 agaaggaacc catagcttgg tgtcattaac ataattattt taagccttat ccagcagcca 2160 taatttgaat aactctacga gaccagagag actgtagttc cctattttaa cctcaattat 2220 gcatttgtce cccaacccca ctgagaacta aatgctgtac cacagagccg ggtgtgaact 2280 atggtttaga aggttcaagt ttccaattaa agtcattgaa g 2321 <210> 569 <211> 497 <212> DNA <213> Homo sapiens <400> 569 tttrtttttt tttttttgag gggaggaagt ggaggagaga tgataggaaa ctcctcectta 60 aggttgccga ctcctaactt tctgaaaatg actaaggaag agaaattcca agggaagaga 120 aacatgtttc tttcttggtc tctggttatc ccacctgagg agagaggcct ctgatgacca 180 gacatggaca acagggaggt gctggtttct ggaaatgtgt aaccaagttg gagcaccagc 240 agggatggat tacacccacg ggccacctct catttcagat gattcgcatt gattctcaac 300

© tcattaggga aacccgectt gcatctccaa gggcttcgaa atttgataca ggaaataaga 360 tgtggaggta ggggtgatgt ttcatccctt cttctagttg taggccataa ctttagaaaa 420 gaaaagcatg tatggaaatt taacaggata ccatttagat gcccgcaatg agcaggattt 480 gttttgctaa attatgg 497 <210> 570 <211> 658 <212> DNA <213> Homo sapiens <400> 570 ggagcctcac grgagcgkgg taacgttata gtatttgtca gaagttgggg tcteccgtggg 60 cattgtgatc cgtcccaggc agtggattag gaggccagaa ggagatccct tccacggtgce 120 taggctgaga tggatcctct cagggcccaa cagctggetg cggagctgga ggtggagatg 180 atggccgata tgtacaacag aatgaccagt gcctgccacc ggaagtgtgt gectcectcac 240 tacaaggaag cagagctctc caagggcgag tctgtgtgec tggaccgatg tgtctctaag 300 tacctggaca tccatgagcg gatgggcaaa aagttgacag agttgtctat gcaggatgaa 360 gagctgatga agagggtgca gcagagctct gggcctgcat gaggtccctg tcagtataca 420 ccectggggtg taccccaccee ctteccactt taataaacgt gectcecectgtt gggtgtcatce 480 tgtgaagact gccaggccta ggctctctgt agagagtctt caagatcccg gagtggtage 540 gctgtctect ggtgaaggag tatttgtcac actggaatgt gactgtgtgt gtatgtatgt 600 gtatatatat atatatatat atatataaac aagtttgttg acacctacaa aaaaaaaa 658 <210> 571 <211> 4045 <212> DNA <213> Homo sapiens <400> 571 atctctctece ccgcteccca gectegggeg aggccgtecg geccgcectaccece ctectgcetceg 60 gccgecgecag tcgecgtcge cgcecgecgec gccgccatgg ccaatgacag cggcgggccea 120 ggcgggccga gecccgagcega gcgagaccgyg cagtactgeg agctgtgcgg gaagatggag 180 aacctgetge gctgcagceg ctgecgcage tcecttctact gctgcaagga gcaccagcegt 240 caggactgga agaagcacaa gctcgtgtgc cagggcagcg agggcgccct cggccacgga 300 gtgggcccac accagcattc cggccccgeg ccgeocggctg cagtgccgcc gcccagggcece 360 ggggccecggg agcccaggaa ggcagcggceg cgccgggaca acgcctececgg ggacgcggec 420 aagggaaaag taaaggccaa gcccccggcec gacccagcgg cggccgcecgte gecgtgtcegt 480 gcggcecgeeg gcggccaggg ctecggceggtg getgecgaag ccgagcccgg caaggaggag 540 ccgecggece gctcatcget gttccaggag aaggcgaacc tgtacccccc aagcaacacyg 600 cccggggatg cgctgagecce cggeggcggce ctgcggccca acgggcagac gaagcccctg 660 ccggcgctga agctggcget cgagtacatc gtgeccgtgca tgaacaagca cggcatctgt 720 gtagtggacg acttcctcgg caaggagacc ggacagcaga tcggcgacga ggtgcgcgcec 780 ctgcacgaca ccgggaagtt cacggacggg cagctggtca gccagaagag tgactcgtce 840 aaggacatcc gaggcgataa gatcacctgg atcgagggca aggagcccgg ctgcgaaacc 900 attgggctgc tcatgagcag catggacgac ctgatacgcc actgtaacgg gaagctgggc 960 agctacaaaa tcaatggccg gacgaaagcc atggttgcectt gttatceggg caatggaacg 1020 ggttatgtac gtcatgttga taatccaaat ggagatggaa gatgtgtgac atgtatatat 1080 tatcttaata aagactggga tgccaaggta agtggaggta tacttcgaat ttttccagaa 1140 ggcaaagccc agtttgctga cattgaaccc aaatttgata gactgcectgtt tttctggtcect 1200 gaccgtcgca accctcatga agtacaacca gcatatgcta caaggtacge aataactgtt 1260 tggtattttg atgcagatga gagagcacga gctaaagtaa aatatctaac aggtgaaaaa 1320 ggtgtgaggg ttgaactcaa taaacctteca gattcggtcg gtaaagacgt cttctagage 1380 ctttgatcca gcaatacccc acttcaccta caatattgtt aactatttgt taacttgtga 1440 atacgaataa atgggataaa gaaaaataga caaccagttc gcattttaat aaggaaacag 1500 aaacaacttt ttgtgttgca tcaaacagaa gattttgact gctgtgactt tgtactgceat 1560 gatcaacttc aaatctgtga ttgcttacag gaggaagata agctactaat tgaaaatggt 1620 ttttacatct ggatatgaaa taagtgccct gtgtagaatt tttttcattce ttatattttg 1680 ccagatctgt tatctagectg agttcatttc atctctccct tttttatatc aagtttgaat 1740 ttgggataat ttttctatat taggtacaat ttatctaaac tgaattgaga aaaaattaca 1800 gtattattcc tcaaaataac atcaatctat ttttgtaaac ctgttcatac tattaaattt 1860 tgccctaaaa gacctcttaa taatgattgt tgccagtgac tgatgattaa ttttatttta 1920 cttaaaataa gaaaaggagc actttaatta caactgaaaa atcagattgt tttgtagtcc 1980 tteccttacac taatttgaac tgttaaagat tgctgctttt tttttgacat tgtcaataac 2040 gaaacctaat tgtaaaacag tcaccattta ctaccaataa cttttagtta atgttttaca 2100 aggaaaaaga cacaagaaga gtttaaattt ttttgttttg ttttgttttt ttgagacagt 2160 cttgctctgt tacccaggct ggaggggagt ggtgcattct tggctcactg caacctccge 2220 cttccaggtt caagcaatcc tcccacctca gcctcccaac tagctgggac tgcaggcaca 2280 caccaccatg cctgactaat ttttgtatgt ttagtagaga cggggttttg ccatgttgcc 2340 taggctgggg tttaagttaa attttttaaa aaactaaagt gactggcact aagtgaactt 2400 gagattatcc tcagcttcaa gttcctaaga taagggettt cttaagcttt caggtgtatg 2460 tatcctctag atgtagacaa taatgtccca tttctaagtc ttttcctttt gcttctecett 2520 aaattgattg tacttccaaa tttgctgtta tgtttttttc ctaatactgt gatctatctg 2580 atctgcagac aagaaccttg tctctgttga agagcatcaa ggggagatta tgtacacatt 2640 gaaactgaag tgtggtgtta ctgacggaat gtgcagtaac tcctcagata tctgttaagg 2700 catttcccag atgtgatgcc ageccttetta cctgtactga aagatgctta gcttagaaaa 2760 aaacaaaaca gatgcaaaat cagataattt tattttgttt catgggtttt cttatttact 2820 ttttaaacaa gggaaggaat attagaaaat cacacaaggc ctcacataca tgttatttaa 2880 agaatgaatt gggacggatg tcttagactt cactttccta ggctttttag ccaaaaccta 2940 aagggtggta tccatatttt gcgtgaatta tgggtgtaag accttgcecca cttaggtttt 3000 ctatctctgt ccttgatctt cttgccaaaa tgtgagtata cagaaatttt ctgtatattt 3060

Caacttaaga catttttagc atctgtatag ttgtattcaa tttgagacct tttctatggg 3120 aagctcagta atttttatta aaagattgcc attgctattc atgtaaaaca tggaaaaaaa 3180 attgtgtagt gaagccaaca gtggacttag gatgggattg aatgttcagt atagtgatct 3240 cacttaggag aatttgcagg agaaagtgat agtttattgt tttttcctcg cccatattca 3300 gttttgttet acttecctece cttectteca gatgataaca tcacatctct acagtaagtg 3360 cctctgecag cccaacccag gagcgcaagt tgtetttgec atctggtcta tagtacagtg 3420 ¢gcggcgtta ggccacaact caaaagcatt atctttttta gggttagtag aaattgtttt 3480 atgttgatgg gaggtttgtt tgattgtcaa aatgtacagc cacagccttt taatttggga 3540 gccectgttg tcattcaaat gtgtacctet acagttgtaa aaagtattag attctactat 3600 ctgtgggttg tgcttgccag acaggtctta aattgtatat tttttggaaa agtttatata 3660 Ctctcttagg aatcattgtg aaaagatcaa gaaatcagga tggccattta tttaatatcc 3720 attcatttca tgttagtggg actattaact tgtcaccaag caggactcta tttcaaacaa 3780 aatttaaaac tgtttgtgge ctatatgtgt ttaatcctgg ttaaagataa agcttcataa 3840 tgctgtetet attcaacaca ttaaccagct gtaaaacaca gacctttatc aagagtaggc 3900 aaagattttc aggattcata tacagataga ctataaagtc atgtaatttg aaaagcagtg 3960 tttcattatg aaagagctct caagttgctt gtaaagctaa tctaattaaa aagatgtata 4020 aatgttgttg aaacaaaaaa aaaaa 4045 <210> 572 <211> 1575 <212> DNA : <213> Homo sapiens <400> 572 gagagaggaa gcttgaagcc aatatggagt ccgtcagttg ctcegetget gctgtcagga 60 ccggagacat ggagtcccag cgggacctga gcctggtgece tgageggctt cagagacgcg 120 aacaagaacg gcagctggaa gttgaaaggc ggaaacaaaa gcggcagaac caggaggtag 180 agaaggagaa cagccacttt ttcgtcgcca cctttgctcg ggagcgagcg gccgtggaag 240 agcttctgga gecgegcggag tcggtcegage ggctggagga ggcggcctcet cggctccagg 300 ggctgcagaa actaatcaac gactcagttt ttttcctage cgcttacgac ctgcggcagg 360 gacaagaggc gctggegegg ctgcaggegg ccttggecga geggegecgg gggctgcagce 420 ccaagaagcg tttcgctttc aagacceggg gaaaggatgc tgcttcgtct accaaagtag 480 acgcggctcc tggcatccce ccggcagttg aaagcataca ggactccecg ctgcccaaga 540 aggcggaagg agacctcggce cccagetggg tctgeggttt ctccaacctg gagtcccaag 600 321 EO,

tcttggagaa gagagecage gagttgcacc agegecgacgt tcttttgacc gaactgagcea 660 actgcacggt cagactgtat ggaaatccca acaccctgeg gctaaccaag gcccacagct 720 gcaagctgcet ctgcggtcecg gtgtctacct ctgttttect ggaggactge agtgactgcg 780 tgctggcagt ggcctgccaa cagctccgca tacacagtac gaaagacacce cgcatcttec 840 tgcaggtgac cagcagggcc atcgtggagg actgcagtgg gatccagtte gccccttaca 900 cctggagcta cccggagatc gacaaggact tcgagagctc tggtttagat aggagcaaaa 960 ataactggaa cgatgttgac gattttaact ggctggccecg ggatatggece tccccaaact 1020 ggagtattct tcctgaagag gagcgaaata tccagtggga ctaagcagtt gtcactctgt 1080 tcttcactcc taccaaatac tttccacgtt ggactttcce ccttattggg tctegaagtt 1140 tacttattgt cacactgtgt atgttttcag cattttaagg ctagagattg taatgggctc 1200 ctacttgtaa tttccattaa attcgtaaca ggtataacac taaagcattt ttgctatttt 1260 cgtcatgcct ttgagactga gtcttactcc gtecceccage gtggtggege gctgggatta 1320 caggcgcgeg ccaccacgcg aactcgtatt tttagtagag acggggtttc gccatgttgt 1380 ccgggectget ctcgaactcoe tgacctcagg tgatccacce gettcagett cccaaagtgce 1440 tggcattaca ggcgtgagcc accacgccag ggctttattt atttattttt accacaatag 1500 tttgaagcag taagggggaa ggagggtgat tatattgctt tgtaatggtt tgtgatactt 1560 gaaacatcac ggtgc 1575 <210> 573 <211> 995 <212> DNA <213> Homo sapiens <400> 573 tttgggggty ataaaaaggg gggcccaaaa aacgdggdag cggagatttt tttgggaaat 60 tttetttttt ttcectttgga tatatgacca gcagtgggat tgctggatct tacgatggaa 120 ttceccaaaga tgttgaccag gaagatcaag ctgtgggaca tcaacgccca catcacctgc 180 cgcetgtgea gegggtaccet catcgacgce accacggtga ccgagtgtet geacacctte 240 tgcaggagct gcctggtgaa gtacctggag gagaacaaca cctgccccac ctgcaggatt 300 gtgatccacc agagccaccc cctgcagtac atcggtcatg acagaaccat gcaagatatt 360 gtttacaaat tggtaccagg cctccaagaa gcggaaatga gaaagcagag ggagttctat 420 cacaaattgg gcatggaggt gccgggagac atcaaggggg agacctgctc tgcaaaacag 480 cacttagatt cccatcggaa tggtgaaacc aaagcagacg acagttcaaa caaagaggcc 540 gcggaggaga agccggagga ggacaacgac taccaccgca gcgacgagca ggtgagcatc 600 tgcttggagt gtaacagcag caaactgcge gggctgaagc ggaagtggat ccgctgctca 660 gcccaggcga ccgtcecttgca tctgaagaag ttcatcgcca aaaaactcaa cctttecatcce 720 tttaacgagc tggacatttt atgcaacgag gagatcctgg gcaaggacca cacactcaag 780 ttcgtggttg tcactaggtg gagattcaag aaggcgccgc tcctgectgca ctacagaccce 840 aagatggact tgctgtgaat ggtgccacac agcgcccaca gactgggetce gcacccttgg S00 gtgctcececgg ccgeegeget taagaacatt gcctctgggt gtcatgtgga ccagacttct 960 gaatagagaa tatttataac ttttgtatga gagag 995 <210> 574 <211> 3367 <212> DNA <213> Homo sapiens <400> 574 ccttectggea ctttctatgg gaggattcte gtaacagcag cacaccaact gaaaagccca 60 aactgetcge tcttggtgaa aattatgaac tgcttatcta tgaatttaat ttgaaagatg 120 gaagatgtga tgcaaccatt ttgtatagct gtagtaggga ggcattgcaa aagctcattg 180 acgatcaaga tatcagtatt tccttattgt ctttgagaat cctgtcattt cacaataaca 240 catcattact gttcatcaac aaatgtgtca tcctacatat tatatttcct gaaagagatg 300 ctgcaattag agtactcaac tgtttcacac ttccecttgec tgcacaggeca gtggacatga 360 ttattgacac gcagctctgec agaggaattc tttttgtttt gagtagttta ggctggatct 420 acatttttga tgttgtggat ggtacatatg tagctcatgt ggatttagca cttcacaaag 480 aagacatgtg taatgagcag caacaggagc cagccaagat ttcttcattt acttcactga 540 aagtttctca agacctcgat gttgcagtga ttgtcagcte ctccaactcec gcagttgctce 600 ttaacttaaa tttgtatttc aggcaacacc caggacacct actgtgtgaa agaatactag 660 aagatcttcc tattcaagga cctaagggcg tagatgaaga tgatcctgtt aactctgcct 720 acaacatgaa actggccaag ttttccttcc aaattgatag gtcttggaaa gcccagctat 780 catcattgaa tgaaacaata aagaactcca aactggaggt ttcctgttgt gctccatggt 840 tccaggatat tttgcatttg gagtcacctg aatctggtaa ccacagtaca agtgtgcaga 900 gctgggectt cattccacag gacataatgec atgggcaata taatgttcta cagaaagatc 960 atgccaagac cagtgatcca ggaagatcat ggaaaataat gcacatcagt gaacaagagg 1020 aacccataga gcttaaatgt gtgtctgtga caggattcac tgcactgttt acttgggaag 1080 tggaaaggat gggctatacc attaccctct gggatttgga gacccagggce atgcagtgtt 1140 tttcccttgg cacaaagtgt attcctgtag acagtagtgg agaccagcag ctgtgctttg 1200 ttttgacaga gaatggactc tctctgattt tgtttggttt gactcaagaa gagtttttaa 1260 acagactcat gatccatgga agtgccagca ctgtggacac tctttgtcat ctcaatggct 1320 ggggaaggtg ctcaattccc atacatgcac tagaggccgg gatagaaaat cgtcagectgg 1380 acacagtaaa tttctttttg aagagcaagg aaaatctttt taatccatcc tcaaaatctt 1440 ctgtatctga tcagtttgat cacttgtcat cccatttata tttaagaaat gtggaagagc 1500 tgataccagc attggattta ctttgctecgg caattagaga aagttattct gaaccccaaa 1560 gcaaacactt ttcagaacaa ttgcttaatc ttacactgtc tttccttaac aaccaaataa 1620 aggagctttt cattcacact gaagaactag atgaacatct gcaaaaagga gtgaacattt 1680 tgactagcta cattaatgaa cttcgaacct tcatgataaa gtttccttgg aagctaacag 1740 atgctataga tgaatatgat gtacatgaaa atgtccccaa agtaaaggag agcaatatat 1800 ggaagaaact cagctttgag gaagttattg ccagcgccat tttaaacaac aaaataccag 1860 aggcacagac tttcttcagg attgatagtc attctgctca aaaacttgag gagcttattg 1920 ’ gcataggect aaatttggte tttgacaatt taaaaaagaa caatataaag gaagcctctg 1980 aacttttgaa gaatatgggg tttgatgtaa aaggccaatt gctcaagatc tgcttctata 2040 caactaataa aaatatacgt gactttttgg ttgaaatttt aaaagaaaaa aattattttt 2100 ctgaaaaaga gaaaagaact atagacttcg tgcatcaagt tgagaagctt tatttgggac 2160 atttccaaga aaatatgcaa atccagtcat ttcccaggta ctggataaag gaacaagatt 2220 tttcaagcac aagtctgttt tggactcatt cctgaaatat gattgtaaag atgaatttaa 2280 caaacaggac catagaattg tgttaaattg ggctctgtgg tgggatcaac taacacaaga 2340 atccatcctt ctccccagga taagtccaga agaatacaaa tcatattccce ctgaagccct 2400 ctggagatac ctcacagctc gccatgattg gttaaacatt atcttatgga ttggagaatt 2460 tcaaacccag catagttatg cttcacttca gcagaacaaa tggccecectte tgactgttga 2520 tgttattaac cagaatactt cctgtaacaa ctacatgagg aatgaaattt tagataagct 2580 ggccaggaat ggggtttttt tggcatctga actggaagac tttgaatgct tcctcecctaag 2640 actgagccgt attggaggtg taatacagga taccctccct gttcaaaact acaagaccaa 2700 agaaggttgg gatttccatt ctcaattcat tctctattgt ttggagcaca gtctgcagca 2760 tcttetttat gtctaccttg actgttacaa acttagtcct gaaaattgtc cctttttgga 2820 aaaaaaagag ttacatgaag cacacccttg gtttgaattt ttagttcagt gtcgacaagt 2880 tgccagtaac ttaacagatc ccaaactgat cttccaggct agccttgcaa atgctcagat 2940 tttgattcce accaatcagg ccagtgtaag cagtatgcta ttggaaggac ataccctect 3000 ggcccttget actacaatgt attctcctgg gggtgtcagt caggttgttc agaatgaaga 3060 aaatgaaaac tgtttgaaga aagtggatcc ccagctattg aagatggcat taactcctta 3120 ccccaagcta aaaactgctc tcttcccaca gtgcactect cctagtgtcc tgccatctga 3180 tattacaatc taccacctta ttcagtcatt atcacccttt gatcctagca gattgtttgg 3240 ctggcagtct gctaacacac tagctatagg agatgcatgg agtcatctcc cacatttctc 3300 tagccctgac ctggttaata aatatgctat agtggaacgt ctgaattttg cttattattt 3360 acataaa 3367 <210> 575 <211> 1615 <212> DNA <213> Homo sapiens <400> 575 gggaggaggc agggcagggce ctctgggacg gggctggacg gcttgttgac ggaaacgagce 60 ccttgacgct gtggcccgga agtggagcgg ctgtcgcagt gcggctecgg cagtggcagc 120 ggaggcctgt gtttgcggcec ttcggcaage gactgagatg gcgagcgcaa ctgcacctge 180 agccgcagtc cccaccctgg cttecgecttt ggagcagctc cggcacttgg cggaggagct 240 gcggttgete ctgcctcgag tgecgggtecgg cgaagcccag gagaccaccg aggagtttaa 300 tcgagagatg ttctggagaa gactcaatga ggcagctgtg actgtgtcaa gggaagccac 360 gactctgacc atagtcttct ctcagcttce actgccgtct ccacaggaaa cccagaagtt 420 ctgtgaacaa gtccatgctg ccatcaaggc atttattgca gtgtactatt tgcttccaaa 480 ggatcagggg atcaccctga gaaagctggt acggggcgcc accctggaca tcgtggatgg 540 catggctcag ctcatggaag tactttccgt cactccaact cagagccectg agaacaatga 600 ccttatttcec tacaacagtg tctgggttgc gtgccagcag atgcctcaga taccaagaga 660 taacaaagct gcagctcttt tgatgctgac caagaatgtg gattttgtga aggatgcaca 720 tgaagaaatg gagcaggctg tggaagaatg tgacccttac tctggcctct tgaatgatac 780 tgaggagaac aactctgaca accacaatca tgaggatgat gtgttggggt ttcccagcaa 840 tcaggacttg tattggtcag aggacgatca agagctcata atcccatgcc ttgecgectggt 900 gagagcatcc aaagcctgcc tgaagaaaat tcggatgtta gtggcagaga atgggaagaa 960 ggatcaggtg gcacagatgg ctgacattgt ggatatttct gatgaaatca gccctagtgt 1020 ggatgatttg gctctgagca tatatccacc tatgtgtcac ctgaccgtgce gaatcaattc 1080 tgcgaaactt gtatctgttt taaagaaggc acttgaaatt acaaaagcaa gtcatgtgac 1140 ccctcagcca gaagatagtt ggatcccttt acttattaat gccattgatc attgcatgaa 1200 tagaatcaag gagctcacte agagtgaact tgaattatga cttttcagge tcatttgtac 1260 tctcttecece tctceatcgte atggtcagge tctgatacct gecttttaaaa tggagctaga 1320 atgcttgectg gattgaaagg gagtgcctat ctatatttag caagagacac tattaccaaa 1380 gattgttggt taggccagat tgacacctat ttataaacca tatgcgtata tttttctgtg 1440 ctatatatga aaaataattg catgatttct cattcctgag tcatttctca gagatteccta 1500 ggaaagctgc cttattctct ttttgcagta aagtatgttg ttttcattgt aaagatgttg 1560 atggtctcaa taaaatgcta acttgccagt gattaaaaaa aaaaaaaaaa aaaaa 1615 <210> 576 <211> 2882 <212> DNA <213> Homo sapiens <400> 6576 ctgcaggtaa cggatcagcg ctgccgggat cctttcaatc atcaggaaca gcaacaggtt 60 tgcagggtca ggctggggac cctcgcccat taactctttce ttctececetgt ttctttcetet 120 taggtgaggg gaaactgagt tccagggtag gctccagagt gaagagggaa gaaacatgat 180 tctcaaggcec aggtctggac aagtgtgaac accttgggce tgcgaattca gcccecctect 240 tcctttctcect ggtcaaagge tagacttgca ggagcttgcg tttgaaggga cagcccagaa 300 ggcatcgtct gcactcccca tacaggtact tctgggtcetg tgggactggce gcagggttct 360 tctecccaaag ctgccagcac tgaggctgag gcagtgtcag gccggcggca gcggcagtgg 420 tgcaatcgtt ctgggaagga tagtggccgg cctgaattct ctgtggcaag ggaggggagc 480 ccaagtggga ggccccttgg ggacaccgag gaccaggtcec gctactgctc ctceccccagg 540 aggtccccta ggggctacat tggctggcag gggctgagca gcggtgagcce tggectggcett 600 cgaccecgggg cgactceggg catccgggac agcettctect cgetgccacce tcggccagte 660 agaccccgag acacctgtca ctacccectc agccttccca ageccaggagce ctgggagtcc 720 ggctctggece tacctecgge agegctceccta ggegcacgtce ccgggctgge ggcgccgggg 780 cccgeccect agggetgegg cgcgegggge gggggctggg ggetgegegg ggeggggcgg 840 gccegggege tccgggecec cteccccgec ccectgacgt cageccccgg cagcctcegag 900 ctgctcactt gcgtctcgee ctececggeccaa gcatggggct tcccaggctg gtctgegect 960 tettgctecge cgeetgetge tgetgtecte gecgtcgeggg tgagttcgect tcgctcgcag 1020 gggcecgegec ccggetaggg gtetgeggtg gagcgtgeca gggagcagag ccageggcge 1080 ggcgggtcgg ggcgttgegt ctgggaggac gagcctecte cctgggtecec cgatcceccgg 1140 gceccttgecge gcgagcaact cttctttgca geccagtttge agccgggatt ctagagtatc 1200

326 3 So oo ccgggagcag cactcggaag gcggggagga ggctgcttct gggaacgaga aggggtggag 1260 ctcagccttt cgggatgetg gggggtgggt ggtccctgag gtgctcactc tgggggcccg 1320 caattgaagc cgggcaggag gcgcagctgg ggegcatcct caaagcctga attccgegcec 1380 cggctgttge tggaaaaggc agcttcctte getggagggg gtgcgccgac ccaccccttce 1440 ccecttectge ctgggcatca cgccaggctg gaggtgagcg agagcgggag gttcggeggce 1500 tccegeeccga gectgggegtt ggcaggggtt gecggggeggt gtgggtcgoc tcgcegectcec 1560 ccgagtgatg ggatcatagg ggacagagat gagggatgga ggattcccat actggacgcec 1620 cgctggctta ttttggggac cacattcagg tgggaagtgc gcccgggcac ctcggagegt 1680 ttctceggat ccgeoctggta gcagggtget ctegggtecce gctgcecttg tatggeccge 1740 gcagcggtgt cgcgtgttte tcttggctee cattccgecg tccegetgtc cggetgggga 1800 aggggagggc taggcaatac cagctcgctg gectcatgee cagtgccaac catgtcctgg 1860 ggtattccag ctactgcctc ccaggctgac tttatttctg ggaaagggct aaatcgggcet 1920 ccacagttgc agccggtcca gctccaccct gececctgctct tctagtctcg ggaggagtca 1980 ggggtctgag gctctgggtt ggagacccca ccttccacct gecctcettg tccgagagcece 2040 aaggtaacaa cccaggactc ccagagteccc aggcagatgg tgtcgagtga catcacctcc 2100 tcacagggct ggcagcacgc tggcaccact gacgtcactc ctgcccactg cctggcectt 2160 gccctgacce ctgggggaga ctctgacctc tccatcctta ccagctaccet agggtggggt 2220 ccgegggtgt gtgcggagtg ttcatggcegg tgcagctgag ggagggagca tgagaccgga 2280 acttccgcca gagttagccce gctggggagt gagggcaggg attttggagg gcagaggggt 2340 agagcagtgg tgtcttcctg gcggtggtga cacaaaaggc ctgttggecc cagectggea 2400 catcgtttge attcccacac tctgagctca cccggagaggd agggggcctg gaaggaaagg 2460 cgttcctctt goccccgagec tagttgccce tttetgccec tctacagect cagctggage 2520 tgtcggtget cagtctctge tcaatctetg cttggctcecca aggacctggg atctcetggt 2580 acggggagag ggctggccca ggtggggtgg cgggtcgggg tgggggtaga gcegttcagag 2640 acagggccct ctgcagaccc tctgagtggc aggaaaaaca gctcgacgag cgctgcgagg 2700 ggaggggcgg acacgacgcg gacgtgacac agecctgggec ccgectccct cccccaggtg 2760 tgccecggaga ggctgagcag cctgcgectg agcetggtgga ggtggaagtg ggcagcacag 2820 cccttctgaa gtgcggcctce tcccagtccc aaggcaacct cagccatgtc gactggtttt 2880 ct 2882 <210> 577 <211> 2733

<212> DNA <213> Homo sapiens <400> 577 ctcgcgagge cggctaggcc cgaatgtcgt tagccgtggg gaaagatggc ggaaaattta 60 aaaggctgca gcgtgtgttg caagtcttct tggaatcage tgcaggacct gtgccgectg 120 gccaagctct cctgcectge cctcecggtatc tctaagagga acctctatga ctttgaagtc 180 gagtacctgt gcgattacaa gaagatccgc gaacaggaat attacctggt gaaatggegt 240 ggatatccag actcagagag cacctgggag ccacggcaga atctcaagtg tgtgcgtatc 300 ctcaagcagt tccacaagga cttagaaagg gagctgctcc ggeggcacca ccggtcaaag 360 acccececgge acctggaccc aagcttggec aactacctgg tgcagaaggc caagcagagg 420 cgggcgetece gtecgetggga gcaggagctc aatgccaage gcagccatct gggacgcatce 480 actgtagaga atgaggtgga cctggacggc cctccgeggg ccttcgtgta catcaatgag S40 taccgtgttg gtgagggcat caccctcaac caggtggctg tgggctgcga gtgccaggac 600 tgtctgtggg cacccactgg aggctgctgc ccgggggegt cactgcacaa gtttgectac 660 aatgaccagg gccaggtgcg gcttcgagee gggctgccca tctacgagtg caactcccgce 720 tgccgetgeg getatgactg cccaaatcgt gtggtacaga agggtatccg atatgacctc 780 tgcatcttce ggacggatga tgggegtgge tggggcgtce gcaccctgga gaagattcge 840 aagaacagct tcgtcatgga gtacgtggga gagatcatta cctcagagga ggcagagcgg S00 cggggccaga tctacgaccg tcagggcgcec acctacctct ttgacctgga ctacgtggag 960 gacgtgtaca ccgtggatgc cgcctactat ggcaacatct cccactttgt caaccacagt 1020 tgtgacccca acctgcaggt gtacaacgtc ttcatagaca accttgacga gcggctgcce 1080 cgcatcgett tctttgccac aagaaccatc cgggcaggcg aggagctcac ctttgattac 1140 aacatgcaag tggaccccgt ggacatggag agcacccgca tggactccaa ctttggcctg 1200 gctgggetee ctggectcece taagaagegg gtecgtattg aatgcaagtg tgggactgag 1260 tcctgecgeca aatacctctt ctagccctta gaagtctgag gccagactga ctgagggggce 1320 ctgaagctac atgcacctcc cccactgctg ccctcoctgtc gagaatgact gccagggcect 1380 cgcetgectce cacctgecce cacctgctec tacctgctct acgttcaggg ctgtggccgt 1440 ggtgaggacc gactccagga gtccccttte cctgtcccag ccccatctgt gggttgcact 1500 tacaaacccc cacccacctt cagaaatagt ttttcaacat caagactctc tgtcgttggg 1560 attcatggcc tattaaggag gtccaagggg tgagtcccaa cccagcccca gaatatattt 1620 gtttttgcac ctgcttctge ctggagattg aggggtctgc tgcaggccte ctccctgctg 1680 ccccaaaggt atggggaagc aaccccagag caggcagaca tcagaggcca gagtgcctag 1740 cccgacatga agctggttcc ccaaccacag aaactttgta ctagtgaaag aaaggggtcc 1800 ctggcctacg ggctgaggct ggtttctget cgtgcttaca gtgctgggta gtgttggcce 1860 taagagctgt agggtctctt cttcagggct gcatatctga gaagtggatg cccacatgcce 1920 actggaaggg aagtgggtgt ccatgggcca ctgagcagtg agaggaaggc agtgcagagce 1980 tggccagecece tggaggtagg ctgggaccaa gctctgectt cacagtgcag tgaaggtacc 2040 tagggctctt gggagctctg cggttgctag gggccctgac ctggggtgtc atgaccgctg 2100 acaccactca gagctggaac caagatctag atagtccgta gatagcactt aggacaagaa 2160 tgtgcattga tggggtggtg atgaggtgec aggcactagg tagagcacct ggtccacgtg 2220 gattgtctca gggaagcctt gaaaaccacg gaggtggatg ccaggaaagg gcccatgtgg 2280 cagaaggcaa agtacaggcc aagaattggg ggtgggggag atggettcecc cactatggga 2340 tgacgaggcg agagggaagc ccttgctgee tgccattcce agaccccagc cctttgtgcet 2400 caccctggtt ccactggtct caaaagtcac ctgcctacaa atgtacaaaa ggcgaaggtt 2460 ctgatggctg ccttgctecet tgctccccea ccccectgtga ggacttctct aggaagtcect 2520 tcctgactac ctgtgcecag agtgccecta catgagactg tatgccctge tatcagatge 2580 . cagatctatg tgtctgtctg tgtgtccatc cecgeccggecc cccagactaa cctccaggea 2640 tggactgaat ctggttctcc tcttgtacac ccctcaacce tatgecagect ggagtgggca 2700 tcaataaaat gaactgtcga ctgaaaaaaa aaa 2733 <210> 578 <211> 710 <212> DNA <213> Homo sapiens <400> 578 gagaggtgga ggcgctttga aaggtgagag €gcgagggcg gtgcggggct gtctccegge 60 tgggactcge tcgcgctece ggtgctaatg gtttatgaga gggcggggga agccgtgcect 120 cctcgcggac taagagaaaa attcccgegg gcgctetttg ggtgggccgg agaacgccce 180 tcagcecttt gcecgectctaa ccetectcag ctgagctgca gtgggcgcgg tgceegttat 240 ttccgeecttg gggaggtget tggaactgat gtagggagct cggttggtga tttctcgggt 300 ttctggectt tccagaccct tgtaattgtt ttctcggtge agagetcttt tggggtctgg 360 gggtttccgt cgtectgcge gegtcatege gaagcttggc ctgagggtcec ggtttcctag 420 ctactgtgcc cctccctect ggaggcagag tgacggacta gtgggctagce gggcgctggg 480 ttcctgcgte ccgccaaaga ggtttgtaat catgaaagtt cacccttceg ggtgttaatt 540 cctgagagga tctactccac tgtctaccac tcattcctge tgcattaacce ttcattgtta 600 acggatttta atgaataata tagttatccc ggataccatg ctggcaggat ccactttgeg 660 aaattgtgga ctgttggact gtgattctaa gtgggggaaa taggctttag 710 <210> 579

<211> 287

<212> DNA

<213>" Homo sapiens

<220>

<221> misc_feature

<222> (235)..(235) . <223> nis a, c, g, t or u

<400> 579 caccatctecc tgcgtctege gggggtaggc acgcacgaag aacatcecggce tatggcacag 60 ccgcatatgc gcgaccttceca ccgtcgtegt cacgccggece agcaccacga cctcatggcet 120 ccagtcgaac tggtaagcct cgcceggete aaagctcagc ggcacgaacg cggtcgccgt 180 gcggeccact tcectecgegect gccagcggeg ggcatggcgg cgaacggtat catanccgcc 240 ctcgtatecet tgcgcecgcea gcgtctcgaa caggcggatc agcgtca 287 <210> 580

<211> 2693

<212> DNA

<213> Homo sapiens

<400> 580 Cgaaaaaaga ggggaagagt attaaagacc atttctggct gggcagggca ctctcagcag 60 ctcaactgce cagecgtgacc agtggccacce tctgcagtgt cttccacaac ctggtcttga 120 ctcgtctget gaacaaatce tctgacctca ggccggetgt gaacgtagtt cctgagagat 180 agcaaacatg cccaacagtg agcccgcatc tctgctggag ctgttcaaca gcatcgcceac 240 acaaggggag ctcgtaaggt ccctcaaagc gggaaatgcg tcaaaggatg aaattgattc 300 tgcagtaaag atgttggtgt cattaaaaat gagctacaaa gctgcecgegg gggaggatta 360 caaggctgac tgtcctecag ggaacccage acctaccagt aatcatggcc cagatgecac 420 agaagctgaa gaggattttg tggacccatg gacagtacag acaagcagtg caaaaggcat 480 agactacgat aagctcattg ttcggtttgg aagtagtaaa attgacaaag agctaataaa 540 ccgaatagag agagccaccyg gccaaagacc acaccacttc ctgcgcagag gcatcttcett 600 ctcacacaga gatatgaatc aggttcttga tgcctatgaa aataagaage cattttatct 660 gtacacgggc cggggcccct cttctgaage aatgcatgta ggtcacctca ttccatttat 720 tttcacaaag tggctccagg atgtatttaa cgtgccecttg gtcatccaga tgacggatga 780

Cgagaagtat ctgtggaagg acctgaccct ggaccaggcc tatggcgatg ctgttgagaa 840 tgccaaggac atcatcgect gtggectttga catcaacaag actttcatat tctctgacct S00 ggactacatg gggatgagct caggtttcta caaaaatgtg gtgaagattc aaaagcatgt 960 taccttcaac caagtgaaag gcattttcgg cttcactgac agcgactgca ttgggaagat 1020 cagttttcct gccatccagg ctgctcccte cttcagecaac tcatteccac agatcttccg 1080 agacaggacg gatatccagt gccttatcce atgtgccatt gaccaggatc cttactttag 1140 aatgacaagg gacgtcgccc ccaggatcgg ctatcctaaa ccagccctgt tgcactccac 1200 cttcttcecca gcectgcagg gegcccagac caaaatgagt gccagcgace caaactcecte 1260 catcttcetc accgacacgg ccaagcagat caaaaccaag gtcaataagc atgcgtttte 1320 tggagggaga gacaccatcg aggagcacag gcagtttggg ggcaactgtg atgtggacgt 1380 gtctttcatg tacctgacct tcttcctcga ggacgacgac aagctcgagc agatcaggaa 1440 ggattacacc agcggagcca tgctcaccgg tgagctcaag aaggcactca tagaggttct 1500 gcagcecttg atcgcagage accaggcccg gcgcaaggag gtcacggatg agatagtgaa 1560 agagttcatg actccccgga agctgtcctt cgactttcag tagcactcgt tttacatatg 1620 cttataaaag aagtgatgta tcagtaatgt atcaataatc ccagcccagt caaagcaccg 1680 ccacctgtag gcttctgtet catggtaatt actgggcctg gectctgtaa gcctgtgtat 1740 gttatcaata ctgtttcttc ctgtgagttc cattatttct atctcttatg ggcaaagcat 1800 tgtgggtaat tggtgctggc taacattgca tggtcggata gagaagtcca gctgtgagtc 1860 tctceccaaa gcagceccac agtggagcct tcggctggaa gtccatgggc caccctgttce 1920 ttgtccatgg aggacttccg agggttccaa gtatactctt aagacccact ctgtttaaaa 1980 atatatattc tatgtatgcg tatatggaat tgaaatgtca ttattgtaac ctagaaagtg 2040 ctttgaaata ttgatgtggg gaggtttatt gagcacaaga tgtatttcag cccatgccce 2100 ctcccaaaaa gaaattgata agtaaaagct tcgttataca tttgactaag aaatcaccca 2160 gctttaaage tgcttttaac aatgaagatt gaacagagtt cagcaatttt gattaaatta 2220 agacttgggg gtgaaacttt ccagtttact gaactccaga ccatgcatgt agtccactce 2280 agaaatcatg ctcgcttccc ttggcacacc agtgttctce tgccaaatga ccctagacce 2340 tctgtectge agagtcaggg tggcttttcc cctgactgtg tecgatgeca aggagtcctg 2400 gcctccgecag atgcttcatt ttgacccettg gctgcagtgg aagtcagcac agagcagtge 2460 cctggetgtg tecctggacgg gtggacttag ctagggagaa agtcegaggca gcagccctcg 2520 aggccctcac agatgtctag gecaggcctca tttcatcacg cagcatgtgc aggcctggaa 2580 gagcaaagcc aaatctcagg gaagtccttg gttgatgtat ctgggtctec tctggagcac 2640 tctgcectec tgtcacccag tagagtaaat aaacttcctt ggctcctaaa aaa 2693 <210> 581 <211> 4633 <212> DNA <213> Homo sapiens <400> 581 tacggctgcg agaagacgac agaaggggag aagaaagcca gtgcgtctcet gggcgcaggg 60 gccagtgggg ctcggaggca caggcacecc gcgacactcc aggttccceg acccacgtec 120 ctggcagecece cgattattta cagcctcage agagcacggg gecgggggcag aggggcccge 180 ccgggaggge tgctacttct taaaacctct gecgggcetgct tagtcacagce cccecettget 240 tgggtgtgtc cttcgectege tcccteccte cgtottaggt cactgttttce aacctcgaat 300 aaaaactgca gccaacttec gaggcagcct cattgcccag cggaccccag cctctgcecag 360 gttcggtceeg ccatcectegt cccgtectee gecggecect gcecccecgcegece cagggatcect 420 ccagctcctt tcgccecgege cctcecegtteg cteccggacac catggacaag ttttggtgge 480 acgcagcctg gggactctge ctegtgecge tgagcctggc gcagatcgat ttgaatataa 540 cctgecgett tgcaggtgta ttccacgtgg agaaaaatgg tcgctacage atctctcgga 600 €ggaggcege tgacctctge aaggetttca atagcacctt gecccacaatg gcccagatgg 660 agaaagctct gagcatcgga tttgagacct gcaggtatgg gttcatagaa gggcacgtgg 720 tgattccceg gatccaccce aactccatct gtgcagcaaa caacacaggg gtgtacatcc 780 tcacatccaa cacctceccag tatgacacat attgcttcaa tgcttcaget ccacctgaag 840 aagattgtac atcagtcaca gacctgccca atgcetttga tggaccaatt accataacta 900 ttgttaaccg tgatggcacc cgctatgtcc agaaaggaga atacagaacg aatcctgaag 960 acatctaccc cagcaacccet actgatgatg acgtgagcag cggctcctec agtgaaagga 1020 gcagcacttc aggaggttac atcttttaca ccttttctac tgtacacccc atcccagacg 1080 aagacagtcc ctggatcacc gacagcacag acagaatcce tgctaccaga gaccaagaca 1140 cattccaccc cagtgggggg tcccatacca ctcatggatce tgaatcagat ggacactcac 1200 atgggagtca agaaggtgga gcaaacacaa cctetggtcee tataaggaca ccccaaattce 1260 cagaatggct gatcatcttg gcatccctet tggecttgge tttgattcett gcagtttgca 1320 ttgcagtcaa cagtcgaaga aggtgtgggc agaagaaaaa gctagtgatc aacagtggca 1380 atggagctgt ggaggacaga aagccaagtg gactcaacgg agaggccage aagtctcagg 1440 aaatggtgca tttggcgaac aaggagtcgt cagaaactcc agaccagttt atgacagctg 1500 atgagacaag gaacctgcag aatgtggaca tgaagattqg ggtgtaacac ctacaccatt 1560 atcttggaag gaaacaaccg ttggaaacat aaccattaca gggagctggg acacttaaca 1620 gatgcaatgt gctactgatt gtttcattgc gaatcttttt tagcataaaa ttttctactc 1680 tttttgtttt ttgtgttttg ttctttaaag tcaggtccaa tttgtaaaaa cagcattgct 1740 ttctgaaatt agggcccaat taataatcag caagaatttg atcgttccag ttcccacttg 1800 gaggcctttc atcccteggg tgtgctatgg atggcttcta acaaaaacta cacatatgta 1860 ttcctgatcg ccaacctttc cecccaccage taaggacatt tcccagggtt aatagggcct 1920 ggtccctggg aggaaatttg aatgggtcca ttttgeccctt ccatagccta atccctgggce 1980 attgctttce actgaggttg ggggttgggg tgtactagtt acacatctte aacagacccce 2040 ctctagaaat ttttcagatg cttctgggag acacccaaag ggtgaagcta tttatctgta 2100 gtaaactatt tatctgtgtt tttgaaatat taaaccctgg atcagtcctt tgatcagtat 2160 aattttttaa agttactttg tcagaggcac aaaagggttt aaactgattc ataataaata 2220 tctgtactte ttcgatcttc accttttgtg ctgtgattct tcagtttcta aaccagcact 2280 gtctgggtce ctacaatgta tcaggaagag ctgagaatgg taaggagact cttctaagtc 2340 ttcatctcag agaccctgag ttcccactca gacccactca gecaaatctc atggaagacce 2400 aaggagggca gcactgtttt tgttttttgt tttttgtttt tttttttttg acactgtcca 2460 aaggttttcc atcctgtect ggaatcagag ttggaagctg aggagcttca gectetttta 2520 tggtttaatg gccacctgtt ctctectgtg aaaggctttg caaagtcaca ttaagtttgc 2580 atgacctgtt atccctgggg ccctatttca tagaggctgg ccctattagt gatttccaaa 2640 aacaatatgg aagtgccttt tgatgtectta caataagaga agaagccaat ggaaatgaaa 2700 gagattggca aaggggaagg atgatgccat gtagatcctg tttgacattt ttatggctgt 2760 atttgtaaac ttaaacacac- cagtgtectgt tcttgatgca gttgctattt aggatgagtt 2820 aagtgcctgg ggagtccctc aaaaggttaa agggattccc atcattggaa tcttatcacce 2880 agataggcaa gtttatgacc aaacaagaga gtactggctt tatcctctaa cctcatattt 2940 tctcccactt ggcaagtcct ttgtggcatt tattcatcag tcagggtgtc cgattggtcce 3000 tagaacttcc aaaggctgct tgtcatagaa gccattgcat ctataaagca acggctcctg 3060 ttaaatggta tctcctttet gaggctccta ctaaaagtca tttgttacct aaacttatgt 3120 gcttaacagg caatgcttct cagaccacaa agcagaaaga agaagaaaag ctcctgacta 3180 aatcagggct gggcttagac agagttgatc tgtagaatat ctttaaagga gagatgtcaa 3240 ctttctgcac tattcccage ctctgctect ccctgectac cctecteccect cectctctec 3300 ctccacttca ccccacaatc ttgaaaaact tcctttctct tctgtgaaca tcattggeca 3360

- gatccatttt cagtggtctg gatttetttt tattttcttt tcaacttgaa agaaactgga 3420 cattaggcca ctatgtgttg ttactgccac tagtgttcaa gtgcctcttg ttttcecaga 3480 gatttcctgg gtctgccaga ggcccagaca ggctcactca agctctttaa ctgaaaagca 3540 acaagccact ccaggacaag gttcaaaatg gttacaacag cctctacctg tcgccccagg 3600 gagaaagggg tagtgataca agtctcatag ccagagatgg ttttccactc cttctagata 3660 ttcccaaaaa gaggctgaga caggaggtta ttttcaattt tattttggaa ttaaatactt 3720 ttttcecttt attactgttg tagtccctca cttggatata cctctgtttt cacgatagaa 3780 ataagggagg tctagagctt ctattccttg gccattgtca acggagagct ggccaagtcet 3840 tcacaaaccc ttgcaacatt gcctgaagtt tatggaataa gatgtattct cactcecttg 3900 atctcaaggg cgtaactctg gaagcacagc ttgactacac gtcattttta ccaatgattt 3960 tcaggtgacc tgggctaagt catttaaact gggtctttat aaaagtaaaa ggccaacatt 4020 taattatttt gcaaagcaac ctaagagcta aagatgtaat ttttcttgca attgtaaatc 4080 ttttgcgtct cctgaagact tcccttaaaa ttagctctga gtgaaaaatc aaaagagaca 4140 aaagacatct tcgaatccat atttcaagcecc tggtagaatt ggcttttcta gcagaacctt 4200 tccaaaagtt ttatattgag attcataaca acaccaagaa ttgattttgt agccaacatt 4260 cattcaatac tgttatatca gaggagtagg agagaggaaa catttgactt atctggaaaa 4320 gcaaaatgta cttaagaata agaataacat ggtccattca cctttatgtt atagatatgt 4380 ctttgtgtaa atcatttgtt ttgagttttc aaagaatagc ccattgttca ttcttgtgct 4440 gtacaatgac cactgttatt gttactttga cttttcagag cacacccttc ctctggtttt 4500 tgcatattta ttgatggatc aataataatg aggaaagcat gatatgtata ttgctgagtt 4560 gaaagcactt attggaaaat attaaaaggc taacattaaa agactaaagg aaacagaaaa 4620 aaaaaaaaaa aaa 4633 <210> 582 <211> 770 <212> DNA <213> Homo sapiens <400> 582 : ccaattagtg tcctaactct gtcttcccat agtaccaccc aaaaagtgct ccatgctcaa 60 gtaagtttgg ttaaatgaag tagattgtca gaaagacaga aagattctca gtcttttaat 120 acactgatat gcattttgaa atatgtagtt aattctcaat tttattgcag aattctgcaa 180 acagtggtta acattgctta cagattttct gcatgttaat ttgaatcttt aatcatatta 240 aaatgcaaat actcctggga aggataatga acttcttaac ttgtaactga aaacattcac 300

334 3 Co

012946 acattttctc atagtgtcgt tgtttcaatt acttacctga aaagaacttt ttgtacggta 360 cagcacttgg ctgggttaat actcaccaac tttgagaagg ttggtctctg ctcttctgta 420 tactttttat gaggcagtat cacttagggc ttaaggttta aactttcttt ttctctctgt 480 gttcatttca tattgagatt atggataaaa agtttgttct gacattgctt aacattttte 540 tttaatcatg tgattacaga aattcaatga cttacaaaac aataaatgta ccttagaatg 600 aaaaatgcat cagtaaggtc tgtatttaaa tgtggatgta gacatcataa ttaccaagac 660 aagaaattgt tttgagaaat tctctgatgt ttttettectt caggtttcac gtgccacgat 720 catggtgcca cggtactgca gtatgcaccc aaacagcaac tcctaatctc 770 <210> 583 <211> 391 <212> DNA <213> Homo sapiens <400> 583 tttttttttg tacatgactc tcattttatt gtttcttaga catttagaaa cctgggagta 60 agagcaaaaa ctcacggccet aattatgttt acactgatag tttaaagata ttttagcact 120 aaccagcatc aattcectaat attcattcaa aatgttagca cttggtataa agaaggaaac 180 aggttgagca aggtggctca tgcctgtaat cccagtactt tggcaggctg aggtgggcag 240 atcacttgag cccaggagtt tgagaccaga ctgggcaaca tggcaaaacc ctgtctctac 300 aaacaataca aaaattagct gggtttggtg gtgtatgcct atagtcccag ctacttggga 360 ggctgaggca ggagaatcgc ttgaacctgg g 391 <210> 584 <211> 407 <212> DNA <213> Homo sapiens : <220> <221> misc_feature <222> (289).. (289) <223> nis a, ¢, g, t or u <400> 584 gtttcctgct tggggaaatg ttcacaccce cttgtggata cattgtccag cccagagttt 60 gtcctceetg gatatgtttt gaattaatga cggccgcacce tcctttectg tatttatttg 120 gaattgcctg gtggaaggag gactctgetg cactcactga ctgtgtgatc tttggtaaat 180 atcttaccect ctctgggctt agtttcccta gtggtaaagt ggaaatagtg ataactatct 240 tagatagctg ttgtgatgcc cacatgagat agcatctggg ctttaccent tccecteggt 300 ctgggcaata acgggttacc ttgcaaggat tgggcagaaa gccttagagg tatggtgett 360 tgcagatggt caccgttgtg attaatgtgg gtgagttcca tgagaga 407 <210> 58$% ) <211> 2324 <212> DNA <213> Homo sapiens <400> 585 gatgtggacc gtagtcggac cgttctaagce tccaaaagct gcggaattcc tcgagcactg 60 ttggcctact ggtctgctta aaattctgtt tttaaaaccce agtttcctag ttttccagge 120 aaatagctac ctccgggaaa gttgctgggg gggcctgaag cacaatgtag cgcagatgct 180 tccttteccag geccattctect cacccagect gcacggagga gatgggagat gctgggggtc 240 ctgccctecag tctttttggyg ccttaggegt ttcgttcatc ctgctaaggg gatgaagcaa 300 acacgaggtg attcctttge ctttcagagt ggaagccctg gagtttgttt tgaaggccag 360 gaggctgaag gatctctaag ctacggtgtg ggcttaatag cagcaggctt tgtcctcctg 420 tctecctccaa geccagtgtcet gattcettgg Caacacaggt cttagtctgt ggagtggctce 480 tgctgtggcce ttcctectgge cgggcaggea ctgtccagcc atagccaget cctgagaata 540 ggtcagcctc tecctttetgt ctcccaggge acatccagec cgtgectgtg ttcactgtge 600 cccgaagtgc aattacccat accccttctc agcctgggga ccccaggcaa ccacagactg 660 tccactcagg ggagctgaat cccaggtcag ccctgccaat gtcccttagg aactgeccag 720 gcaaggccce tggttttgta tacttgttce tgccacccag cagtagatga gtgtttcagg 780 tgaagaccag gatagatttt ctaagtgtga atccccactt cacatatgga accccttatg 840 Cctgaacttga aaagcaccaa gacttcctgt agacaagaaa gtgcttaggt agggacagcc 900 cctgggcatc ccacccaatg tagctggcac cccactatgg caaaggtgcc ttgataactg 960 agccctgtat ccctceccatg cccagecaga ttctcatggg aagccctctce ccttetttte 1020 tgcctaacac catctcatcg tttectggect cactgtggac aatccacaca cattcttett 1080 tcctcectectg geggggcaca gagccacccee cttgcctttt cttttecttga aggttctagt 1140 tcagctectg attcatcaga ceccttctage cccctgcate tagcagtgaa gcatgaagcc 1200 tggtggggat gtggtactcc catctggtgt ggccaccagc tctgccaatg ttcctgtage 1260 cttggaaaac ttgctctctc ggttcttttg ggtgctgtgt actccccagce ttcccccectt 1320 ccccccccat tttgcacctg ggtttagtga aaggatggca tttggttgac ccatatagaa 1380 acccagaatg aggtctcagg gccaggagge ctggtatttg taggccaggg aaggggaaga 1440 ggcaagtggt ctggggtatc accagccagce cctctctgat ttggectcta ctccccataa 1500 gtcacagtac cataagcagg cttctggect cagcaatttg gtctttgtgc ccaagtttat 1560 tgtgagaatt tcctgaaaac tctataaaag gtctcttect actgtaggec tctaatgttt 1620 ctceceectttt tgettcagtc Ccactcttcag tcttgtaggc ctagttttca aacctgcaca 1680 tgtgtcctac ctggccacag gcatgcaggc ctcaggcagc tgggccagtt tgggagcctce 1740 gggtgatgtc tgcacgatct ggggctgcct ctgcaceccct getgtggget tcagggttgg 1800 agaagggctg ggaccaaccg ggtgagatcc acaagtctct ggatgtggct gaaggcaaat 1860 acacaattga agtactttct gttttgaagt gectttcecctt ttgaatctgg tttgaaacat 1920 gcagcttctg tctctagcce aaggaaagac Caaaacatag ggaaataaaa gcatttatct 1980 ttgtcttgga agtaattgtt gaagttgtge agttgatcag tgcacagtta ggtgcaatgt 2040 ttatagaaat tgattgttaa accaaattta cactggcatg tgtggtgtag tttctaaaag 2100 gcacttcaca tttgaaattt ttcttacctt agaaagtttce tagtgatcta aatgtctagt 2160 tttgtattct tttgtgtgtg ttcactgttt ctcagtatta ccacttgaat aattctctgt 2220 acaggggggt ttgtgctata cactgggatg tctaattgeca gcaataaage ctttctttaa 2280 daaggaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 2324 <210> 586 <211> 1179 <212> DNA <213> Homo sapiens <400> 586 atgggttcte tcagcacagc taacgttgaa ttttgccttg atgtgttcaa agagctgaac 60 agtaacaaca taggagataa catcttcttt tcttecgetga gtectgettta tgctctaage 120 atggtcctee ttggtgccag gggagagact gcagagcaat tggagaaggt gcttcatttt 180 agtcatactg tagactcatt aaaaccaggg ttcaaggact cacctaagtg cagccaagct 240 ggaagaattc attccgagtt tggtgtcgaa ttctetcaaa tcaaccagcec agactctaac 300 tgtaccctca gcattgeccaa caggctctac gggacaaaga cgatggcatt tcatcagcaa 360 tatttaagct gttctgagaa atggtatcaa gccaggttgc aaactgtgga ttttgaacag 420 tctacagaag aaacgaggaa aatgattaat gcttgggttg aaaataaaac taatggaaaa 480 gtcgcaaatc tctttggaaa gagcacaatt gacccttcat ctgtaatggt cctggtgaat 540 accatatatt tcaaaggaca aaggcaaaat aaatttcaag taagagagac agttaaaagt 600 ccttttcagc taagtgaagg taaaaatgta actgtggaaa tgatgtatca aattggaaca 660 tttaaactgg cctttgtaaa ggagccgcag atgcaagtte ttgagcetgece ctacgttaac 720 aacaaattaa gcatgattat tctgcttcca gtaggcatag ctaatctgaa acagatagaa 780 aagcagctga attcggggac gtttcatgag tggacaagct cttctaacat gatggaaaga 840 gaagttgaag tacacctccc cagattcaaa cttgaaatta agtatgagct aaattccctg 900 ttaaaacctc taggggtgac agatctcttc aaccaggtca aagctgatct ttctggaatg 960 tcaccaacca agggcctata tttatcaaaa gccatccaca agtcatacct ggatgtcage 1020 gaagagggca cggaggcagc agcagccact ggggacagca tcgctgtaaa aagcctacca 1080 atgagagctc agttcaaggc gaaccacccc ttcctgttct ttataaggca cactcatacce 1140 aacacgatcc tattctgtgg caagcttgce tctccctaa 1179 <210> 587 <211> 822 <212> DNA <213> Homo sapiens <400> 587 gatcctcttt ccctcecttecee caccctcatt ataggctgeg aagectecte tctgcacctg 60 ataacaaaac gtcatatgag aagcatggta gatccttagc atcaaaggtt gaggactctt 120 attctgatta taagtagtgg ctcttgacta caatcaagtc tcaaataata gtgtaagaga 180 ataaagcaga ataataagac taagttaaca gtttaggctt ctttggaatc atgcgggcect 240 agatgaaaat cccaacactg tcctttacta gctaagtgac cttgagcaac tgattacacce 300 ctttgatgece tcagttttcect cctcectgtgtt gtggggtaat agtaatatct acttcctggg 360 gttgttcgtg aagattaatt aacaattata cttgtcaaag ctttagcaca gtgcectgta 420 tgttatttcc ttggccaaac tttcttactc tgccatttgt tcaatgtcct aatgagcatg 480 aacactacat taggtatcat gcagaacact ctaaagataa gtattatgat ctctatttca 540 cagataagga aatttaaact gggagaggct aaagggctga cttgcccaag gtcacttgaa 600 actaatatgc cagcagagac agaattagga gccaagtata tttaagagcc aagtgtattg 660 aacctaaaat ctgggctcct aaataccaag cttcactggc tctctggtcc cagtgagagt 720 tggtgctaaa aagtattccg gaatgaaaag ttctcttcca gagaccctgg ccttccaaag 780 cggtcacctg atagggaagt cttacggcta ggaagttaca aa 822 <210> 588 <211> 31289 : <212> DNA <213> Homo sapiens <400> 588 cgactcgtcg ccatteccegg agcaggtegg ccteggecca ggggcgagta tccgttgctg 60 tgtcggagac actagtcccc gacaccgaga cagccagccc tctceccectge ctegeggegd 120 gagagcgtgt ccggeccggec ggccggeggg gectcgcgcaa cctececctecge ctccecttcee 180 cccgecagecct cecgccccgcec aggcccggece cggactcccg agccccggec tcctcegtect 240 cggtcgeccgce tgeccgccggg cttaacagece ccgteccgecyg cttetcettece tagtttgaga 300 agccaaggaa ggaaacaggg aaaaatgtcg ccatgaaggc cgagaaccgc tgeccgeccgec 360 gacccccgec ggccctgaac gccatgagce tgggtccccg ccgegeccge tccgctccga 420 ctgccgtege cgeccgaggcc cccogttgatg ccgctgagct cccccaacgc cgccgcecace 480 gcctccgaca tggacaagaa cagcggctcc aacagctcct ccgcectctte gggcagcagce 540 aaagggcaac agccgccccg ctccgecteg geggggccag ccggcgagtc taaacccaag 600 agcgatggaa agaactccag tggatccaag cgttataatc gcaaacgtga actttcectac 660 cccaaaaatg aaagttttaa caaccagtcc cgtcgctcca gttcacagaa aagcaagact 720 tttaacaaga tgcctcctca aaggggcggc ggcagcagca aactctttag ctcttcotttt 780 aatggtggaa gacgagatga ggtagcagag gctcaacggg cagagtttag ccctgcccag 840 ttctctggtc ctaagaagat caacctgaac cacttgttga atttcacttt tgaaccccgt 900 ggccagacgg gtcactttga aggcagtgga catggtagct ggggaaagag gaacaagtgg 960 ggacataagc cttttaacaa ggaactcttt ttacaggcca actgccaatt tgtggtgtct 1020 gaagaccaag actacacagc tcattttgct gatcctgata cattagttaa ctgggacttt 1080 gtggaacaag tgcgcatttg tagccatgaa gtgccatctt gcccaatatg cctctatcca 1140 cctactgcag ccaagataac ccgttgtgga cacatcttct gctgggcatg catcctgceac 1200 tatctttcac tgagtgagaa gacgtggagt aaatgtccca tctgttacag ttcetgtgcat 1260 aagaaggatc tcaagagtgt tgttgccaca gagtcacatc agtatgttgt tggtgatacc 1320 attacgatgc agctgatgaa gagggagaaa ggggtgttgg tggctttgcc caaatccaaa 1380 tggatgaatg tagaccatcc cattcatcta ggagatgaac agcacagcca gtactccaag 1440 tttctgctgg cctctaagga gcaggtgcetg caccgggtag ttctggagga gaaagtagca 1500 ctagagcagc agctggcaga ggagaagcac actcccgagt cctgctttat tgaggcagcet 1560 atccaggagc tcaagactcg ggaagaggct ctgtcgggat tggccggaag cagaagggag 1620 gtcactggtg ttgtggctgc tctggaacaa ctggtgctga tggctccctt ggcgaaggag 1680 tctgtttttec aacccaggaa gggtgtgctg gagtatctgt ctgccttcga tgaagaaacc 1740 acggaagttt gttctctgga cactccttct agacctcttg ctctccctect ggtagaagag 1800 gaggaagcag tgtctgaacc agagcctgag gggttgeccag aggcctgtga tgacttggag 1860 ttagcagatg acaatcttaa agaggggacc atttgcactg agtccagcca gcaggaaccce 1920 atcaccaagt caggcttcac acgcctcagc agctctectt gttactactt ttaccaagcg 1980 gaagatggac agcatatgtt cctgcaccect gtgaatgtgc gctgcctegt gecgggagtac 2040 oo ggcagectag agaggagccc cgagaagatc tcagcaactg tggtggagat tgctggctac 2100 tccatgtctg aggatgttcg acagcgtcac agatatctet ctcacttgece actcacctgt 2160 gagttcagca tctgtgaact ggctttgcaa cctcoctgtgg tctctaagga aaccctagag 2220 atgttctcag atgacattga gaagaggaaa cgtcagcgcc aaaagaaggc tcgggaggaa 2280 cgccgcecgag agcgcaggat tgagatagag gagaacaaga aacagggcaa gtacccagaa 2340 gtccacattc ccctcgagaa tctacagcag tttcctgect tcaattctta tacctgetce 2400 tctgattctg ctttgggtcc caccagcacc gagggccatg gggcecctcte catttctect 2460 ctcagcagaa gtccaggttc ccatgcagac tttctgctga cccctetgtc acccactgce 2520 agtcagggca gtccctcatt ctgegttggg agtctggaag aagactcetee cttcecttcee 2580 tttgcccaga tgctgagggt tggaaaagca aaagcagatg tgtggcccaa aactgctcca 2640 aagaaagatg agaacagctt agttcctcct gccectgtgg acagcgacgg ggagagtgat 2700 aattcagacc gtgttcctgt gcccagtttt caaaattcct tcagccaage tattgaagca 2760 gccttecatga aactggacac accagctact tcagatccee tctctgaaga gaaaggagga 2820 aagaaaagaa aaaaacagaa acagaagctc ctgttcagca cctcagtcgt ccacaccaag 2880 tgacactact ggcccaggct accttctcca tectggttttt gtttttgttt tttttteccc 2940 catgcttttg tttggctget gtaattttta agtatttgag tttgaacaga ttagctetgg 3000 ggggaggggg tttccacaat gtgaggggga accaagaaaa ttttaaatac agtgtatttt 3060 ccagcttcct gtctttacac caaaataaag tattgacaca agagaaaaaa aaaaaaaaaa 3120 aaaaaaaaa 3129 <210> 589 <211> 3116 <212> DNA <213> Homo sapiens <400> 589 agcgectcaga tacgcgacgce gtagcaggceg gggaccgaac gggtgectca gtgtccttece 60 cctccecteg cctggecteg cegtectcecte ccecgecagecg gaccggaact atgtgatcec 120 ggaagttccg gggcctttge tgtgtgggat aaacagtaat ggcggaggect gcaactcccg 180 gaacaacagc cacaacatca ggagcaggag cggcagcggce gacggcggca gcagcctcce 240 ccaccccgat ccccacagtc accgecceccgt ccectggggge gggoggaggg ggcggcggcea 300 gcgacggcag cggcggdgcggc tggactaaac aggtcacctg caggtatttt atgcatgggg 360 tttgtaagga aggagacaac tgtcgctact cgcatgacct ctctgacagt ccgtatagtg 420 tagtgtgcaa gtattttcag cgagggtact gtatttatgg agaccgctgc agatatgaac 480 atagcaaacc attgaaacag gaagaagcaa ctgctacaga gctaactaca aagtcatcce 540 ttgctgctte ctcaagtctc tcatcgatag ttggaccact tgttgaaatg aatacaggcg 600 aagctgagtc aagaaattca aactttgcaa ctgtaggagc aggttcagag gactgggtga 660 atgctattga gtttgttcct gggcaaccct actgtggccg tactgcgect tcctgcactg 720 aagcacccct gcagggctca gtgaccaagg aagaatcaga gaaagagcaa accgcegtgg 780 agacaaagaa gcagctgtgc ccctatgetg cagtgggaga gtgccgatac ggggagaact 840 gtgtgtatct ccacggagat tcttgtgaca tgtgtgggct gcagctectg catccaatgg 900 atgctgccca gagatcgcag catatcaaat cgtgcattga ggcccatgag aaggacatgg 960 agctctcatt tgcecgtgcag cgcagcaagg acatggtgtg tgggatctgce atggaggtgg 1020 tctatgagaa agccaacccc agtgagecgec gcttcgggat cctctccaac tgcaaccaca 1080 cctactgtct caagtgcatt cgcaagtgga ggagtgctaa gcaatttgag agcaagatca 1140 taaagtcctg cccagaatgc cggatcacat ctaactttgt cattccaagt gagtactggg 1200 tggaggagaa agaagagaag cagaaactca ttctgaaata caaggaggca atgagcaaca 1260 aggcgtgcag gtattttgat gaaggacgtg ggagctgccc atttggaggg aactgttttt 1320 acaagcatgc gtaccctgat ggccgtagag aggagccaca gagacagaaa gtgggaacat 1380 caagcagata ccgggcccaa cgaaggaacc acttctggga actcattgag gaaagagaga 1440 acagcaaccc ctttgacaac gatgaagaag aggttgtcac ctttgagctg ggcgagatgt 1500 tgcttatgct tttggctgca ggtggggacg acgaactaac agactctgaa gatgagtggg 1560 acttgtttca tgatgagctg gaagattttt atgacttgga tctatagcaa ccttgegtgg 1620 cgtgtgaact ggtctgctga cctcagacag cagctgtcce ctgtggtggt gtggcagtgc 1680 ctgtgttctc tcctaggcag gcctctcaac tccaggtgct gtcctaagaa tttttaccca 1740 gggcctgtct tctcaaccec tcacctttece ctgaggagtg tgttgttttec cctgttgaaa 1800 aaagttacaa aaataaatct taaagttagt tttttgtaac acgaatttaa ctgtcagaca 1860 gttagtgtag gtgtgttgcg tcatctgttt tcaaccagat tgcatttatg gacttttcac 1920 acactcattt tgaggacccc aggttcaaaa gtaaaagcag tggccctgct ttggggtcca 1580 agaataggag tgatgggtga agggacctaa gctggccaat agccctcetge cccagacatg 2040 ggatgtggat ccttgaggtt tctggtgaaa tctgcacatc tgtgttttta tatctgttcc 2100 ctaccctgta atccctacca cgtgcacttg ttctgtggtt ttggtctctt gtttaattge 2160 acacaagtaa tactactggg taaccagaat caggtgtgaa tgtgttgaga ttttttactg 2220 ttttgcatga taggaaaatt gagaaagaat acgtataaaa gatagagagg cataacatca 2280

+ --- atgcagagtt ggaagttggc tcccadggge tgacatggtg tgagtgtgtg ggtgtgtgat 2340 aagcttctca tccctgcata gatgcagtat tcttagcctt agtagaaaaa cctggtttag 2400 tggtttaagc cttgtgtggc agatagatct taaagggcaa agcagtatat tggtagttgt 2460 caatatagca gtgctagctc tgtctatata aatagagaaa tggggttagce catagaggtt 2520 aaaactacct ggttatccca tataataaca caaactgggt cttggataca cagttgtatt 2580 taatgtttta cgatctagcc tttccagtac aggcactttc tgagaaacct ttgtcctcac 2640 ttgaggcatt ttgttgtcgg gtttttgtgt ttgtttttgt gggtatttge ctcattccac 2700 ccctgagett tcaggtagac agacgtgatt caaaactctg ttctaaggtg tttattgtag 2760 tggagtaatg ggtttgcagt gataagtcat acttttccac cgaaagggag ggcttgggaa 2820 tccctgagat tagctaaagt taagttgttg gaagaattcc ttgattggaa attgtacctt 2880 tgtgttttgt tgctctgttt cctgaaaata actcggggat gctcetggtt tgtccatcta 2940 ctgctttgat tccttggatc ccacccatte tttcacttta agaaaaaaca aataattgtt 3000 gcagaggtct ctgtattttg cagctgceccct tttgtaagaa gcacttttecc caaataaaac 3060 aattaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 3116

<210> 580

<211> 570

<212> DNA

<213> Homo sapiens

<400> 590 ttttecggtt gcggecgecge geggtgaggt tgtctagtce acgctcggag ccatgecgte 60 caagggcccg ctgcagtctg tgcaggtctt cggacgcaag aagacagcga cagctgtgge 120 gcactgcaaa cgcggcaatg gtctcatcaa ggtgaacggg cggcccctgg agatgattga 180 gccgegcacg ctacagtaca agctgctgga gceccagttctg cttcteggeca aggagcgatt 240 tgctggtgta gacatccgtg tccgtgtaaa gggtggtggt cacgtggccc agatttatge 300 tatcecgtcag tccatctcca aageccctggt ggectattac cagaaatatg tggatgaggce 360 ttccaagaag gagatcaaag acatcctcat ccagtatgac cggaccctge tggtagctga 420 ccctegtege tgcgagtcca aaaagtttgg aggccctggt geccgegctc gcectaccagaa 480 atcctaccga taagcccatc gtgactcaaa actcacttgt ataataaaca gtttttgagg 540 gattttaaag tttcaaaaaa aaaaaaaaaa 570

<210> 591

<211> 5925

<212> DNA

<213> Homo sapiens

<220> <221> misc_feature <222> (5402)..(5402) <223> nis a, c, g, t or u <400> 591 cttttcccat cgtgtagtca agagtctgtg ccagacttga aggctttact ttgttagcca 60 tgtgtttatg aacccccage gctttececta gatcttttgg ctgataatct caaacatgga 120 ggatgcttct gaatcttcac gaggggttge tccattaatt aataatgtag ttctcccagg 180 ctctcegetg tctetteoctg tatcagtgac aggctgtaaa agtcatcgag tagccaataa 240 aaaggtagaa gcgaggagtg aaaagctcct cccaacagct cttcctectt cagagccgaa 300 agtagatcag aaacttccca ggagctecga gaggcgggga agtggcggtg ggacgcaatt 360 ccecgegegg agtegggcag tggcageggg agaagcggca gccaggggeg cggeggggec 420 ggagagaggc agtcccctgg gaagacgggt ctccectegt tgectttgta gtggagaagg 480 tggacaagtg gcagtcggcg tgatcgcagg gaagcgggge cggcgcggdgce gcgacgggtce 540 caggcgagcec ccgggcggac gggagatgcce gctgctacac cgaaagecgt ttgtgagaca 600 gaagccgece gecggacctge ggcccgacga ggaagttttc tactgtaaag tcaccaacga 660 gatctteccge cactacgatg acttttttga acgaaccatt ctgtgcaaca gecttgtgtg 720 gagttgtgct gtgacgggta gacctggact gacgtatcag gaagcacttg agtcagaaaa 780 aaaagcaaga cagaatcttc agagttttcec agaaccacta attattccag ttttatactt 840 gaccagcctt accecatcgtt cgcgcttaca tgaaatttgt gatgatatct ttgcatatgt 900 caaggatcga tattttgtcg aagaaactgt ggaagtcatt aggaacaatg gtgcaaggtt 960 gcagtgtacg attttggaag tcctcecctee atcacatcaa aatggttttg ctaatggaca 1020 tgttaacagt gtggatggag aaactattat catcagtgat agtgatgatt cagaaacaca 1080 aagctgttct tttcaaaatg ggaagaaaaa agatgcaatt gatcccttac tattcaagta 1140 taaagtgcaa cccactaaaa aagaattaca tgagtctgct attgttaaag caacacaaat 1200 cagccggaga aaacacctat tttctcgtga taaactaaag ctttttctga agcaacactg 1260 tgaaccacaa gaaggagtca ttaaaataaa ggcatcatct ctttcaacgt ataaaatagc 1320 agaacaagat ttttcttatt tcttccctga tgatccaccc acatttatct tcagtcctge 1380 taacagacga agagggagac ctcccaaacg aatacatatt agtcaagagg acaatgttgc 1440 taataaacag actcttgcaa gttataggag caaagctact aaagaaagag ataaactttt 1500 gaaacaagaa gaaatgaagt cactggcttt tgaaaaggct aaattaaaaa gagaaaaagc 1560 agatgcccta gaagcgaaga aaaaagaaaa agaagataaa gagaaaaaga gggaagaatt 1620

__. .. 9aaaaaaatt gttgaagaag agagactaaa -gaaaaaagaa gaaaaagaga dgcttaaagt 1680 oo agaaagagaa aaggaaagag agaagttacg tgaagaaaag cgaaagtatg tggaatactt 1740 aaaacagtgg agtaaaccta gagaagatat ggaatgtgat gaccttaagg aacttccaga 1800 accaacacca gtgaaaacta gactacctecc tgaaatcttt ggtgatgctc tgatggtttt 1860 -ggagttcctt aatgcatttg gggaactttt tgatcttcaa gatgagtttc ctgatggagt 1920 aaccctagaa gtattagagg aagctcttgt tggaaatgac agtgaaggcec cactgtgtga 1980 attgcttttt ttcttecctga ctgcaatctt ccaggcaata gctgaagaag aagaggaagt 2040 agccaaagag caactaactg atgctgacac caaaggctgc agtttgaaaa gtttggatct 2100 tgatagctgc actctttcag aaatcctcag actgcacatc ttagcttcag gtgctgatgt 2160 aacatcagca aatgcaaagt atagatatca aaaacgagga ggatttgatg ctacagatga 2220 tgcttgtatg gagcttegtt tgagcaatcc cagtctagtg aagaaactgt caagcacctc 2280 agtgtatgat ttgacaccag gagaaaaaat gaagatactc catgctctct gtggaaagct 2340 actgacccta gtttcaacta gggattttat tgaagattat gttgatatat tacgacaggc 2400 aaagcaggag ttccgggaat taaaagcaga acaacatcga aaagagagag aagaagcagce 2460 tgccagaatt cgtaaaagga aggaagaaaa acttaaggag caagaacaaa aaatgaaaga 2520 gaaacaagaa aaactgaaag aagatgagca aagaaattca acggcagata tatctattgg 2580 ggaggaagaa agggaagatt ttgatactag cattgagagc aaagacacag agcaaaagga 2640 attagatcaa gatatgttca ctgaagatga agatgaccca ggatcacata aaagaggcag 2700 aagggggaaa agaggacaaa atggatttaa agaatttaca aggcaagaac agatcaactg 2760 tgtaacaaga gagcttctta ctgctgatga ggaagaagca ttaaaacagg aacaccaacg 2820 aaaagagaaa gagctcttag aaaaaatcca aagtgccata gecctgtacca atatctttec 2880 cttgggtcge gaccgceatgt atagacgata ctggattttc ccttctatte ctggactctt 2940 tattgaagag gattattctg gtcttactga agacatgctg ttgcctagac cttcatcatt 3000 tcagaataat gtacagtctc aagatcctca ggtatccact aaaactggag agcctttgat 3060 gtctgaatct acctccaaca ttgaccaagg tccacgtgac cattctgtgec agctgccaaa 3120 accagtgcat aagccaaatc ggtggtgctt ttacagttct tgtgaacagc tagaccagct 3180 tattgaagct cttaattcta gaggacatag agaaagtgcc ttaaaagaaa ctttgttaca 3240 agagaaaagc agaatatgtg cacagctagc ccgtttttct gaagagaaat ttcatttttc 3300 agacaaacct cagcctgata gcaaaccaac atatagtcgg ggaagatctt ccaatgcata 3360 tgatccatct cagatgtgtg cagaaaagca acttgaacta aggctgagag attttctttt 3420 agatattgaa gatagaatct accaaggaac attaggagec atcaaggtta cagatcgaca 3480 tatctggaga tcagcattag aaagtggacg gtatgagctg ttaagtgagg aaaacaagga 3540 aaatgggata attaaaactg tgaatgaaga cgtagaagag atggaaattg atgaacaaac 3600 aaaggtcata gtaaaagaca gacttttggg gataaaaaca gaaactccaa gtactgtate 3660 aacaaatgca agtacaccac aatcagtgag cagtgtggtt cattatctgg caatggcact 3720 Ctttcaaata gagcagggca ttgagcggeg ttttctgaaa gctccacttyg atgccagtga 3780 cagtgggcgt tcttataaaa cagttctgga ccgttggaga gagtctcectce tttettetge 3840 tagtctatec caagtttttec ttcacctatc caccttggat cgtagcgtga tatggtctaa 3500 atctatactg aatgcgcgtt gcaagatatg tcgaaagaaa ggcgatgctg aaaacatggt 3960 tctttgtgat ggctgtgata ggggtcatca tacctactgt gttcgaccaa agctcaagac 4020 tgtgcctgaa ggagactggt tttgtccaga atgtcgacca aagcaacgtt gtagaagact 4080 gtcctttaga cagagaccat ccttggaaag tgatgaagat gtggaagaca gtatgggagg 4140 tgaggatgat gaagttgatg gcgatgaaga agaaggtcaa agtgaggagg aagagtatga 4200 ggtagaacaa gatgaagatg actctcaaga agaggaagaa gtcagcctac ccaaacgagg 4260 aagaccacaa gttagattgc cagttaaaac aagagggaaa cttagctctt ctttctcaag 4320 tcgtggccaa caacaagaac ctggaagata cccttccagg agtcagcaga gcacacccaa 4380 aacaactgtt tcttctaaaa ctggtagaag cctaagaaag ataaactctg ctcctcectac 4440 agaaacaaaa tctttaagaa ttgccagtcg ttctactege cacagtcatg gcccactgca 4500 agcagatgta tttgtggaat tgcttagtcc tcgtagaaaa cgcagaggca ggaaaagtgc 4560 taataataca ccagaaaata gtcccaactt ccctaacttc agagtcattg ccacaaagtc 4620 aagtgaacag tcaagatctg taaatattgc ttcaaaactt tctctccaag agagtgaatce 4680 caaaagaaga tgcagaaaaa gacaatctcc agagccatcg cctgtgacac tgggtcgaag 4740 gagttctggc cgacagggag gagttcatga attgtctgct tttgaacaac ttgttgtaga 4800 attggtacga catgatgaca gctggccttt tttgaaactt gtttctaaaa tccaggtccce 4860 agactactat gacatcatca aaaagcccat tgccttaaat ataattcgtg aaaaagtgaa 4920 taagtgtgaa tataaattag catctgagtt tattgatgac attgagttaa tgttttcgaa 4980 ctgctttgaa tacaacccte gtaacacaag tgaagcaaaa gctggaacta ggcttcaagce 5040 attttttcat attcaggctc aaaagcttgg actccacgtc acacccagta atgtggacca 5100 agttagcaca ccaccggctg cgaaaaagtc acgaatctga ctttgtcctt ctaaaggata 5160 tatttgaaga aaaacaaatt gttcatgaaa atggaacatt aaatcatgct gtataaagca 5220 ataacaaaca attgattgac cacatgaaag tgtggcctge actatattct caattttaat 5280 attaagcact caggagaatg taggaaagat atcctttgct acagttttgt tcagtatcta 5340 ataagtttga tagatgtatt ggatacagta ctggtttaca gaggtttttg tacatttttg 5400 anatcattca tgtgtccaga gatcttggaa aatatttttt cacccacgat ttattttgtt 5460 attgatgatt tatttttaaa gtggtggtat taagggagag ttatctacat ggatgagtct 5520 tccgetatag cacagtttag aaaaggtgtt tatgtcttaa ttaattgttt gagtacattc 5580 tttcaacact acacatgaat gaatccaatc ttataacctt gaagtgctgt accagtgctg 5640 gctgcaggta ttaagtccaa gtttattaac tagatattta tttagtattg agagtaattt 5700 gtgaatttgt tttgtattta taaaatttat acctggaaaa tgttccttaa tgttttaaac 5760 cttttactgt gtttttattc ctctaactte cttaatgatc aatcaaaaaa agtaacaccc 5820 tcccttttte ctgacagtte tttcagettt acagaactgt attataagtt ctatgtataa 5880 } ttttaactgt tcaaataaaa tacatttttc caataaaaaa aaaaa 5925 <210> 592 <211> 468 <212> DNA <213> Homo sapiens <400> 592 tttttttttt tttttttaaa tgtacacctce ctttaatctg atttttctec tttttgaaac 60 agggtctecec tgtcacccag gctggagtge agcagtgcaa tcacagctca ctgcagcctt 120 gacatcccag ggttcaagcg atcctcecegt ctcagectec cgagtagccg ggaccacagg 180 - agcgcaccac cacacccgga taattttttg tagagatggg gtttcaccgt gttgcccagg 240 tcactctcaa actectggge tcaagcgatc tgcctgectt, ggtcttccaa agtcctggga 300 ttataggecgt gagccaccat gcccagectt aatcatttta agtggaaatg taaccatttt 360 aggataatgt cctacaaaaa cgtgagtaca agcaagcaaa gacatttgca gaaagatttt 420 cacagatgat gtgagtctaa tgccaaaaaa ctaaacacag ccttttgg 468 <210> 593 <211> 1154 <212> DNA <213> Homo sapiens <400> 593 gggggecette cggcgggtga cattcagecg gcggttcggg gcgacggact ctccattcca 60 gaaccatggc ccaatttgtc cgtaaccttg tggagaagac cccggcgectg gtgaacgctg 120 ctgtgactta ctcgaagcct cgattggcca cattttggta ctacgccaag gttgagctgg 180 ttcecteeccac ceetgctgag atccctagag ctattcagag cctgaaaaaa atagccaata 240 gtgctcagac tggtagcttc aaacagctca cagttaagga agctgtgctg aatggtttgg 300 tggccactga ggtgttgatg tggttttatg tcggagagat tataggcaag cggggcatca 360 ttggctatga tgtttgaaga ccaatcttta acatctgatt atatttgatt tattatttga 420 gtgttgttgg accatgtgtg atcagactgc tatctgaata aaataagatt tgtcaaaact 480 cagtgttttc tccatcagat actccatgaa aggtcacaat ttctcttgat attaagctgg 540 gttgtcttta aacaacccta aatacacgtce tgtttagccc gcaattggaa aggatatatg 600 tggcaatatt aacctggtac atgaatatat ggggataaca ttttaatttg aaggtttgga 660 atatatatat ttaagcttta tttccagaac agtgagggtt aggtcttggg aaaactataa 720 cttgccaaag tagaagaaat agtagtacca tatgccaaag tgatagagat gaatcatgtce 780 agtagttaga ataacatttc aactgttttc tttgctaaaa tcacagaaag accctattga 840 caacatctat gtctgtaaaa atgttagagt acttgtcatc ttgaatatag cctccccaag 900 agagaacagg gtggtattct aagtatgttt ctttgtaaca tctttagcag taggacagag 960 ccatacatgt gaaatctgat ttttatgtgt gttattcgtt tgtctggttt tactaccttt 1020 gcaaaaacaa aataccccaa agatatttaa acaaggttat aatttagcat cttccctgga 1080 tctaaatagt atattatatc ctgaaataaa tgaaatgatt gctcaaaaaa aaaaaaaaaa 1140 aaaaaaaaaa aaaa 1154 <210> 594 <211> 434 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (8).. (44) <223> n is a, ¢, g, t or u <220> <221> misc_feature <222> (263) ..(372) <223> n is a, ¢, g, toru <220> <221> misc_feature <222> (408) ..(408) <223> mn is a, ¢c, g, t or u <220> <221> misc_feature <222> (423)..(423) <223> n is a, ¢, g, tor u <400> 594 tacaagcnnn nnnnnnnnnn NnNnnnnnnn nnnnnnnnnn nnnpaaagaa gtaaaatctt 60

_ tatcatgaaa tttatatgta aaagaatcac tcagtaaaga caatttccat aaaataaaaa 120 tggatatgga tactatttaa ctatgttgta ttaaaaaaaa ctgatcaaag aattggttta 180 atggaaaatg ctctggaaaa ttcttttgca acagttcatc gctgttgata taatcctaat 240 taaaattatc ggactccagt ttnnnnnnnn nnnnnnnnnn onNnnnnnnn nnnnnnnnnn 300 nnnnnnnnnn nnnnnonnnn nANNNNNnAn nONnnnnonnn nnonnnonnn nAnnnnonnn 360 nnnnnnnnnn nnagagaaag ttgcacgtgt gcacgtttce ttgcecgenga aggtaaaaaa 420 aanaaaaaag agga 434 <210> 595 <211> 1424 <212> DNA <213> Homo sapiens <400> 595 ggcacgaggg ccacatggac ggagctgccg gggcggegge gccgggagea ggatgcggcc 60 gcccgtaatt aaatagcatt tactcttatt attactaata ataataacgt aatcatacct 120 ctagtcatag cataccattt atcgggctcg gecgcaggece gcggggagcg cagcccggceg 180 gaggtctecce tctgatgeccg agccgaaget ggacggtact getgecatet cggctcactg 240 caacctccect gectgattcet cctgcectcag cectgeccgagt gcectgcgatt gaaggcegtge 300 gccgccacge ctgactggtt ttcgtatttt tttggtggag acggggtttc gctgtgttgg 360 ccgggetggt ctccagectece taaccgcgag tgatgcacca gcctecggect cccogaggtge 420 cgggattgca gacggagtct cgttcactca gtgctcaatg gtgccaaggc tggagtgcag 480 tggcgtgatce tcggctegect acaacctcca cctceccagca gectgecttg gecctcccaaa 540 gtgccgagat tgcagcctct gcceggecege cacccegtcet gggaagtgag gagcgtcetct 600 gecectggecge ccategtetyg ggatgtgagg agccectcectg cctggetgece cagtctggaa 660 agtgaggagc gtctctgece agccgccatce ccatctagga agtgaggagc gcctcttcce 720 ggccgeccatc ccatctggga agtgaggagc gtctctgcce ggecgeccat cgtctgagat 780 gtggggagca cctctgccct gccacceccgt ccgggatgtg aggagcgtct ctgcceggec 840 gccccatctg agaagtgagg agcccctccg cceggcagec gccecgtcetg agaagtgagyg 900 agcccctecg cccagcagce acccegtcetg ggaagtgagg agegtctccg cccggcagece 960 acctcgtceg ggagggaggt cggggggtca gccccececgece cggccageccg ccccgtccag 1020 gaggaaactc ttggatgatg tactgaccaa aacagggaat aacctaacag agaggaagac 1080 agggatttta ggaaaccgga gatcacacag gaaggaggta aagggaaatc ccaggatgat 1140 ggcaaaggga agtccccaaa caacagctgt gcaacaagaa taaagaacaa tcagaggacc 1200 tcttgagcece agaggtcaag gctgcggtga gccaaqgtcg tgccactaca ctgaagcctg 1260 ggcaacagag tgagaccctg tctcaaaaca gaaaaggacc tatcagcccc aagtggagca 1320 gaacagaggg atttgggagg aatgtcctca gaaaaagata ttaaaacaca gttatctgaa 1380 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1424 <210> 596 <211> 2120 <212> DNA <213> Homo sapiens <400> 596 cgcattgtgg tccgcttctc tgcactatgt cgggtggect cctgaaggcg ctgcgecageg 60 actcctacgt ggagctgagc cagtaccggg accagcactt ccggggtgac aatgaagaac 120 aagaaaaatt actgaagaaa agctgtacgt tatatgttgg aaatctttct ttttacacaa 180 ctgaagaaca aatctatgaa ctcttcagca aaagtggtga cataaagaaa atcattatgg 240 gtctggataa aatgaagaaa acagcatgtg gattctgttt tgtggaatat tactcacgcg 300 cagatgcgga aaacgccatg cggtacataa atgggacgcg tctggatgac cgaatcattc 360 gcacagactg ggacgcaggc tttaaggagg gcaggcaata cggcegtggg cgatctgggg 420 gccaggtteg ggatgagtat cggcaggact acgatgctgg gagaggaggc tatggaaaac 480. tggcacagaa ccagtgagtg gtgagagctc tgtcagtgac aaacactcct ttggcectgtt 540 gaatttgctg aagaacatca cctaaagtct gcacacgagc ccatttttac caagatttga 600 tcagtgtctt tactgagctg gaagcctctg aaagttatta aaggacagaa tccaaaagaa 660 tgectttaat tcttgtctga gaatcttgge catgtgtcag attatcagaa caattttgtt 720 accaggtcag aaattgtgtt ctttgacaac agattggatc tgtaatgttg attagtcttt 780 agccataacc actacacttt tagaaagaca gaaaaatgta agaatttgtt tttaccataa 840 tgagtcttaa gtaggttcat gatctacatt ggggcctggg attatttttt taattttaag 900 tttgcatgag atagcctaat aaatggaggt ggggccaggc atggtggctc acacgtgtaa 960 tcccaacact ttgggaggcet gaggaggaag gatagcttga ggccaggagt ttgagactag 1020 actgggcaac atagcaagac cccgtctcta caaagcacaa cgaaaaacaa caaatggagt 1080 tgtgctatgt tgtattgctt tgcacaaaat taggaacagg tgtttgacaa ttgaatttgt 1140 tttctgtgaa ttctaacctc taaaggcatg cttagaggtc aaggaccttc ctgtgtagtt 1200 ggtgcaaaag caatctccac aggacagcac tgcttccatg cttcatacat caggaaatga 1260 ggccagaact tgagtattta ctaacacgtt tttcaaaaga tgtcagtgtt atacctaaag 1320 ctaaaaaaaa gcaagggttt gtcatagagg gaacctctaa ataatttcag gggtagggga 1380 gatgttgtca ataggaaatg ggataaaata tcaagagaca atgaaaacac tgccttgaca © 1440 tgaggaccag caagtttatt cttttcattt tcagtgatgt tgggaatgga ctgggtttta 1500 aaagggagct tgaagaggga atgtttgaca gtcacagaag gttcctgcag cagatgcectce 1560 ttttagccat ttctcatttt tttcctcaaa ttttacctac tgaggctcaa gccttcacag 1620 tgagctgatg gtctctacag ggaggggagt ctagggaatt tatttggtat ttgtaaggca 1680 agaggtgatt tctctctaat atatctgagt tattgctcat ttaaaactgt taagtccagt 1740 ataattttce ctgatatgaa aaaatgtgca tttttttcac ttagcaacaa agtaccttct 1800 aatttccaat agtccgtgaa agttggggct gaagtaccta agtgtgaatg tctctccegt 1860 taaactgagt gtagaaatct gaatttttaa aagagctgta actagttgta agtgcttagg 1920 aagaaacttt gcaaacattt aatgaggata cactgttcat ttttaaaatt ccttcacact 1980 gtaatttaat gtgttttata ttcttttgta gtaaaacaac ataactcaga tttctacagg 2040 agacagtggt tttatttgga ttgtcttctg taataggttt caataaagct ggatgaactt 2100 aaaaaaaaaa aaaaaaaaaa 2120 <210> 597 <211> 551 <212> DNA <213> Homo sapiens <400> 597 tttttttttt tttttttgca cacacatatc tttttatttg agagtttaaa aggaaatctg 60 aggtccagag gatcacagag cctcttgttc tgctatcaaa ggaccaataa gaagcaaact 120 gatattacag ggcaaatgtt cccagacagc ccagcctgct ccccttagga atgagtgtcec 180 ctggaggggg agagcctgga accaaagccc cgccaggaac tgcttcccct aaactgaggt 240 tctctgaaaa aaatgttecgce ctggctgata aageccgcctc ttaacagagce ccagacactt 300 ctgtgettec cctgggttge taattgagga cactaaagcc ctaagagata ccccaggtcg 360 ggggaagggg ccccaagacc tagacctceccg gtggcgacca tgcccttgag aggatgggag 420 ctgaattgga gcacgagatt atttatcatc gctggatgaa gcttccagct agagctcagt 480 atttcctectt tttctgggct cagacagaca cagactggaa ggaatcctgt ccgtttggcet 540 gtgggagtgt t 551 <210> 598 <211> 1458 <212> DNA <213> Homo sapiens <400> 598 ttagttcctc ggggagcccc tggtgccccg gatacggctg attttgtcegt gtgggacctg 60

350 ttctggctge teccagcccca ggaaggaccc aggacacccg gaagccggaa atggactcag 120 tggectttga ggatgtgget gtgaacttca cccaggagga gtgggctttg ctgagtcctt 180 cccagaagaa tctctacaga gatgtgacgc tggaaacctt ¢aggaacctg gccteggteg 240 gaatccaatg gaaagaccag gacattgaga atctgtacca aaacctgggg attaagctaa 300 gaagtctggt ggagagactc tgtggacgta aagaagggaa tgaacacaga gaaactttca 360 gccagattce tgattgtcac ctgaacaaga aaagtcaaac tggagtgaaa ccatgcaaat 420 gcagcgtgtg tgggaaagtc ttcctecgte attcattcecet ggacaggcac atgagagctce 480 atgctggaca caaacgatct gagtgtggtg gggaatggag agagacgccec cgtaaacaga 540 aacaacatgg gaaagcctcc atttcccceca gtagtggtge acggcgcaca gtaacaccaa 600 ctcgaaagag accttatgaa tgcaaggtgt gcgggaaage ctttaattct cccaatttat 660 ttcaaatcca tcaaagaact cacactggaa agaggtccta taaatgtagg gaaatagtga 720 gagccttcac agtttccagt ttctttcgaa aacatggaaa aatgcatact ggagaaaaac 780 gctatgaatg taaatactgt ggaaaaccta tcgattatce cagtttattt caaattcatg 840 ttagaactca cactggagaa aaaccttaca aatgtaaaca atgtggtaaa gccttcattt 900 ccgcaggtta ccttcggaca catgaaatca gatctcacgc gctggagaaa tcccaccaat S60 gtcaggaatg tgggaaaaaa ctcagttgtt ccagttccct tcacagacat gaaagaactc 1020 atagtggagg aaaactctac gaatgtcaaa aatgtgccaa agtctttaga tgtcccacgt 1080 cccttcaagc acatgaaaga gctcacactg gagaaagacc ttatgaatgt aataaatgtg 1140 gtaaaacctt caattatccc agttgtttte gaagacataa aaaaactcat agtggagaaa 1200 agccatatga atgtacaagg tgtggtaaag cctttgggtg gtgcagttce ctccgaagac 1260 atgaaatgac tcacactgga gaaaaaccct ttgattgtaa acagtgtggt aaagtcttta 1320 ctttttcaaa ttaccttaga cttcatgaaa gaactcattt ggccgggegt agccagtgcet 1380 ttggcaggag gcagggggat cacctgagec caggagtttg agaccagcct gggcaacata 1440 agaaggcccc cggaattc 1458 <210> 599 <211> 3176 <212> DNA <213> Homo sapiens

<400> 599 acccagggac ctatcacaca aatataagaa ctattcattce tttaaggcat gtatttccaa 60 gcctttgtat ttttttccat gecttagggtt ggcaaggaat atatatatat ttgtacaaat 120 atatatgtgt atatgtacaa atacatgtat atatagtaca aatatatata tatatttgta 180 caattcttca gactttgtag aatttgtata atgtcgtatc ttgctttttt taaccactga 240 tgttataagc atatttatgc cacttcattc attttagaga cttaataata aatgatctag 300 tggataattt atcattccct gatggagaaa aatttagctt tgtttatttt agagttataa 360 acgatgctgg gtcaggtatc tttatgtttg aagatggctc catatttggg ttgtttccac 420 agaactcttt cctagaaatg ctttttctag gttaatggct acagatattt ctaggcacct 480 gacatattga cacccacctc taaagtattt ttatgatcca caactagcgt ttaacacagc 540 gccctagtca ctacatgact aataaataga caaatgactg aaacatgacc tcatgetttce 600 tattcctcca gctttcattc agttctttge ctctgggagg aggaagggtt gtgcagcect 660 ccacagcatc agcccatcaa ccctatccct gtggttatag cagctgagga agcagaattg 720 cagctctgtg ggaaggaatg gggctggaga gttcatgcac agaccagttc ttatgagaag 780 ggactgacta agaatagcct tgggttgaca tatacccctce ttcacactca caggagaaac 840 catttcccta tgaaactata acaagtcatg agttgagagc tgagagttag agaatagcetc S00 aaagatgcta ttcttggata tcctgagccc ctgtggtcac cagggaccct gagttgtgca 960 acttagcatg acagcatcac tacgcttaaa aatttccctc ctcaccccca gattccattt 1020 cceccateccge cagggctgec tataaagagg agagctggtt tcagacttca gaaggacacg 1080 ggcagcagac agtggtcagt cctttcttgg ctctgctgac actcgagccc acattccgtc 1140 acctgctcag aatcatgcag gtctccactg ctgcccttge tgtcctectc tgcaccatgg 1200 ctctctgcaa ccagttctet gcatcacgtg agtctgagtt tcgttgtggg tatcaccact 1260 ctctggccat ggttagacca catcaatctt ttcttgtgge ctaaaagccc ccaagagaaa 1320 agagaacttc ttaaagggct gccaaacatc ttggtctttc tctttaagac ttttattttt 1380 atctctagaa ggggtcttag cccecctagtc tccaggtatg agaatctagg caggggcagg 1440 ggagttacag tcccttttac agatagaaaa acagggttcg aaacgaatca gttagcaaga 1500 ggcagaatcc agggctgctt acttcccagt ggggtatgtt gttcactctc cagctcactce 1560 taggtctcecc aggagctctg tcccttggat gtcttatgag agatgtccaa ggcttcectcett 1620 gggttggggt atgacttctt gaaccagaca aaattccctg aagagaactg agataagaga 1680 acagtccgtt caggtatctg gatcacacag agaaacagag aacccactat gaagagtcaa 1740 ggagaaagaa ggatacagac agaaacaaag agacatttct cagcaaaaat gcccaaatgc 1800 cttccagtca cttggtctga gcaagcctgc cttcctcaac tgctcgggga tcagaagcetg 1860 cctggccttt tcttctgage tgtgactcag gctcattctc ttcectttcte cacagttget 1920 gctgacacgc cgaccgcctg ctgcttcagc tacacctccc ggcagattcec acagaatttce 1980 atagctgact actttgagac gagcagccag tgctccaagc ccggtgtcat gtaagtgcca 2040 gtcttectge tcacctctat ggaggtaggg agggtcaggg ttggggcaga gacaggccag 2100 aaggctatcc tggaaaggcc cagccttcag gagcecctatcg gggatacagg acgcagggct 2160 ccgaggtgtg acctgacttg gagctggagt gaggcatgtg ttacagagtc aggaagggct 2220 gccccagccoce agaggaaagg gacaggaaga aggaggcagc gggacactct gagggccacce 2280 cctactgagt cactgagaga agctctctag acagagatag gcagggggcc cctgaaagag 2340 gagcaagcce tgagctgcecce aggacagaga gcagaatggt ggggccatgg tgggcccagg 2400 attcccectge tggattccece agtgcttaac tcttecctceccce ttctccacag cttectaacce 2460 aagcgaagcc ggcaggtctg tgctgacccc agtgaggagt gggtccagaa atatgtcagce 2520 gacctggagc tgagtgcctg aggggtccag aagcttcgag gcccagcgac cteggtgggce 2580 ccagtgggga ggagcaggag cctgagcctt gggaacatgc gtgtgacctc cacagctacc 2640 tcttctatgg actggttgtt gccaaacagc cacactgtgg gactcttctt aacttaaatt’ 2700 ttaatttatt tatactattt agtttttgta atttattttc gatttcacag tgtgtttgtg 2760 attgtttget ctgagagttc ccctgtcccc tcccecttecec ctcacaccge gtctggtgac 2820 aaccgagtgg ctgtcatcag cctgtgtagg cagtcecatgge accaaageca ccagactgac 2880 aaatgtgtat cggatgcttt tgttcagggc tgtgatcggc ctggggaaat aataaagatg 2940 ctcttttaaa aggtaaacca gtattgagtt tggttttgtt tttctggcaa atcaaaatca 3000 ctggttaaga ggaatcatag gcaaagatta ggaagaggtg aaatggaggg aaattgggag 3060 agatggggag ggctaccaca gagttatcca ctttacaacg gagacacagt tctggaacat 3120 tgaaactacg aatatgttat aactcaaatc ataacatgca tgctctagga gaattc 3176 <210> 600 <211> 130 <212> DNA <213> Homo sapiens <400> 600 gtaactagaa atggcagggt aaggagtgtt tgcctgacat cgtctcgttt ttacggaaga 60 gggcecctca cgatgtgccc atcagcccca cctgaaatag caagaaatct tcttcagcag 120 agagcgaata 130 <210> 601 <211> 200 <212> DNA <213> Homo sapiens <400> 601 tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tettttttee 60 ttttttettt tttttetttt ggggeccceeg gettttttta taaaaaccag ggggaaggtt 120 tgggccaaac cccccaggcet ttgggtttte ccccccccec ccgggaaagg gggoccccceco 180 cccecccccaa aaaaaaccca 200 «210> 602 <211> 921 <212> DNA <213> Homo sapiens <400> 602 gcggcgecteg cgccaaggga cgtgtttctg cgctegegtg gtcatggagg cgctgecget 60 gctagccgeg acaactccgg accacggccg ccaccgaagg ctgcttctge tgecgctact 120 gctgttecctg ctgecggetg gagctgtgeca gggctgggag acagaggaga ggccccggac 180 tcgcgaagag gagtgccact tctacgeggg tggacaagtg tacccgggag aggcatcccg 240 ggtatcggtc gccgaccact ccctgcacct aagcaaagcg aagatttcca agccagcgce 300 ctactgggaa ggaacagctg tgatcgatgg agaatttaag gagctgaagt taactgatta 360 tcgtgggaaa tacttggttt tcttcttcta cccacttgat ttcacatttg tgtgtccaac 420 tgaaattatc gcttttggcg acagacttga agaattcaga tctataaata ctgaagtggt 480 agcatgctct gttgattcac agtttaccca tttggecctgg attaatacce ctegaagaca 540 aggaggactt gggccaataa ggattccact tctttcagat ttgacccatc agatctcaaa 600 ggactatggt gtatacctag aggactcagg ccacactctt agaggtctct tcattattga 660 tgacaaagga atcctaagac aaattactct gaatgatctt cctgtgggta gatcagtgga 720 tgagacacta cgtttggttc aagcattcca gtacactgac aaacacggag aagtctgccc 780 tgctggctgg aaacctggta gtgaaacaat aatcccagat ccagctggaa agctgaagta 840 tttcgataaa ctgaattgag aaatacttct tcaagttatg atgcttgaaa gttctcaata 900 aagttcacgg tttcattacc a 921 <210> 603 <211> 2591 <212> DNA <213> Homo sapiens <400> 603 ctcagactgt ccttectcetc tggactgtaa gaatatgtct ccagggccag tgtctgctge 60 gatcgagtcc caccttccaa gtcectggcat ctcaatgcat ctgggaagct acctgcatta 120 agtcaggact gagcacacag gtgaactcca gaaagaagaa gctatggccg cagtgattct 180 ggagagcatc tttctgaagc gatcccaaca gaaaaagaaa acatcacctc taaacttcaa 240 gaagecgectg tttctcttga ccgtgcacaa actctcctac tatgagtatg actttgaacg 300 tgggagaaga ggcagtaaga agggttcaat agatgttgag aagatcactt gtgttgaaac 360 agtggttcct gaaaaaaatc ctcctccaga aagacagatt ccgagaagag gtgaagagtc 420 cagtgaaatg gagcaaattt Caatcattga aaggttccct tatceccttec aggttgtata 480 tgatgaaggg cctctctacg tcttetecce aactgaagaa ctaaggaagc ggtggattca S40 ccagctcaaa aacgtaatcc ggtacaacag tgatctggtt cagaaatatc acccttgett 600 ctggatcgat gggcagtatc tctgctgete tcagacagecec aaaaatgcta tgggctgcca 660 aattttggag aacaggaatg gaagcttaaa acctgggagt tctcaccgga agacaaaaaa 720 gcctcttcee ccaacgectg aggaggacca gatcttgaaa aagccactac cgcctgagec 780 agcagcagca ccagtctcca caagtgagct gaaaaaggtt gtggeccttt atgattacat 840 gccaatgaat gcaaatgatc tacagctgcg gaagggtgat gaatatttta tcttggagga 900 . aagcaactta ccatggtgga gagcacgaga taaaaatggg caggaaggct acattcctag 960 taactatgtc actgaagcag aagactccat agaaatgtat gagtggtatt ccaaacacat 1020 gactcggagt caggctgagce aactgctaaa gcaagagggg aaagaaggag gtttcattgt 1080 : cagagactcc agcaaagctg gcaaatatac agtgtctgtg tttgctaaat ccacagggga 1140 ccctcaaggg gtgatacgte attatgttgt gtgttccaca cctcagagcc agtattacct 1200 ggctgagaag caccttttca gcaccatccee tgagctcatt aactaccatc agcacaactc 1260 tgcaggactc atatccaggc tcaaatatcce agtgtctcaa caaaacaaga atgcaccttce 1320 cactgcaggc ctgggatacg gatcatggga aattgatcca aaggacctga ccttcttgaa 1380 ggagctgggg actggacaat ttggggtagt gaagtatggg aaatggagag gccagtacga 1440 cgtggccatc aagatgatca aagaaggctc catgtctgaa gatgaattca ttgaagaagc 1500 caaagtcatg atgaatcttt cccatgagaa gctggtgeag ttgtatggeg tetgcaccaa 1560 gcagegccce atcttcatca tcactgagta catggccaat ggctgcctcc tgaactacct 1620 gagggagatg cgccaccgct tccagactca gcagctgcta gagatgtgca aggatgtctg 1680 tgaagccatg gaatacctgg agtcaaagca gttccttcac cgagacctag cagctcgaaa 1740 ctgtttggta aacgatcaag gagttgttaa agtatctgat ttcggectgt ccaggtatgt 1800 cctggatgat gaatacacaa gctcagtagg ctccaaattt ccagtccggt ggtcecccacce 1860 ggaagtcctg atgtatagca agttcagcag caaatctgac atttgggctt ttggggtttt 1920 gatgtgggaa atttactccc tggggaagat gccatatgag agatttacta acagtgagac 1980 tgctgaacac attgcccaag gectacgtet ctacaggcct catctggctt cagagaaggt 2040 atataccatc atgtacagtt gttggcatga gaaagcagat gagcgtccca ctttcaaaat 2100 tcttctgage aatattctag atgtcatgga tgaagaatcc tgagctcgecc aataagcttce 2160 ttggttctac ttctcttctc cacaagcccce aatttcactt tctcagagga aatcccaagc 2220 ttaggagccc tggagccttt gtgctcccac tcaatacaaa aaggccccete tctacatctg 2280 gggatgcacc tcttctttga ttccctggga tagtggcttc tgagcaaagg ccaaaaaatt 2340 attgtgcctg aaatttcccg agagaattaa gacagactga atttgcgatg aaaatatttt 2400 ttaggaggga ggatgtaaat agccgcacaa aggggtccaa cagctctttg agtaggcatt 2460 tggtagagct tgggggtgtg tgtgtggggg tggaccgaat ttggcaagaa tgaaatggtg 2520 tcataaagat gggaggggag ggtgttttga taaaataaat tctagaaagc ttaaaaaaaa 2580 aaaaaaaaaa a 2591 <210> 604 <211> 594 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (520) .. (520) <223> nis a, ¢, g, t or u <400> 604 tttttttttt tttttgtact tttgttcata gatcggcact tgactttgaa cctggcacca 60 aaaggcacaa tatctgatac cctgtacaag agctattaga gatgctgecca tatggatggg 120 caaaactgag ccaatcccac ttaggaatgg aaggcttgga catggaaggg aggatataaa 180 cgaggagttg gagaaaaacg caagcccagt ttttgctaga gtggaaatga aagtgggaat 240 gagggtcttg tttttagtcc tctaaggacc aggaagcaat tttaaaactt ccttggtett 300 tctgaaagca gcatattcaa aatgccagca aaaactccta acaactgcaa aaccaaaaga 360 : ggatcaaagc tcaccaacat cccttcttat tgctgaaagg ctctaaaatt caggatgccc 420 tgttccecttg taaaagggaa aataattaag tctgatttat ggtaatcata ccacatcaca 480 cttctaaaaa aatattcaag tgtgtgacca ggggacgttn gacaccattt tattaacctt 540 caacttcagt ggaaaaataa aaccttttcc aagtgccatt ttcatcacaa gact 554

<210> 605

<211> 2338

<212> DNA }

<213> Homo sapiens

<400> 605 agcgcacgtc ggcagtcggc tccctcgttg accgaatcac cdacctctct ccccagetgt 60 atttccaaaa tgtcgctttc taacaagctg acgctggaca agctggacgt taaagggaag 120 cgggtcgtta tgagagtcga cttcaatgtt cctatgaaga acaaccagat aacaaacaac 180 cagaggatta aggctgctgt cccaagcatc aaattctgct tggacaatgg agccaagtcg 240 gtagtcctta tgagccacct aggccggcct gatggtgtgc ccatgcctga caagtactcce 300 ttagagccag ttgctgtaga actcaaatct ctgctgggca aggatgttct gttcttgaag 360 gactgtgtag gcccagaagt ggagaaagcc tgtgccaacc cagctgctgg gtctgtcatc 420 ctgctggaga acctcegctt tcatgtggag gaagaaggga agggaaaaga tgcttctggg 480 aacaaggtta aagccgagee agccaaaata gaagctttcc gagcttcact ttccaageta 540 ggggatgtct atgtcaatga tgcttttggc actgctcaca gagcccacag ctccatggta 600 ggagtcaatc tgccacagaa ggctggtggg tttttgatga agaaggagct gaactacttt 660 gcaaaggcct tggagagccc agagcgaccc ttecctggcca tcctgggcgg agctaaagtt 720 gcagacaaga tccagctcat caataatatg ctggacaaag tcaatgagat gattattggt 780 ggtggaatgg cttttacctt ccttaaggtg ctcaacaaca tggagattgg cacttctctg 840 tttgatgaag agggagccaa gattgtcaaa gacctaatgt ccaaagctga gaagaatggt S00 gtgaagatta ccttgcctgt tgactttgtc actgctgaca agtttgatga gaatgccaag 960 actggccaag ccactgtggc ttctggcata cctgetggect ggatgggett ggactgtggt 1020 cctgaaagca gcaagaagta tgctgaggct gtcactcggg ctaagcagat tgtgtggaat 1080 ggtectgtgg gggtatttga atgggaagct tttgcccggg gaaccaaagc tctcatggat 1140 gaggtggtga aagccacttc taggggctgc atcaccatca taggtggtgg agacactgcec 1200 acttgctgtyg ccaaatggaa cacggaggat aaagtcagcc atgtgagcac tgggggtggt 1260 gccagtttgg agctcctgga aggtaaagtc cttcctgggg tggatgctct cagcaatatt 1320 tagtactttc ctgecctttta gttcctgtge acagccccta agtcaactta gcattttctg 1380 catctccact tggcattagc taaaaccttc catgtcaaga ttcagctagt ggccaagaga 1440 tgcagtgcca ggaaccctta aacagttgca cagcatctca gctcatcttc actgcaccct 1500 ggatttgcat acattcttca agatcccatt tgaatttttt agtgactaaa ccattgtgca 1560 ttctagagtyg catatattta tattttgcct gttaaaaaga aagtgagcag tgttagctta 1620 gttctctttt gatgtaggtt attatgatta gctttgtcac tgtttcacta ctcagcatgg 1680 aaacaagatg aaattccatt tgtaggtagt gagacaaaat tgatgatcca ttaagtaaac 1740 aataaaagtg tccattgaaa ccgtgatttt tttttttttc ctgtcatact ttgttaggaa 1800 gggtgagaat agaatcttga ggaacggatc agatgtctat attgctgaat gcaagaagtg 1860 gggcagcagc agtggagaga tgggacaatt agataaatgt ccattcttta tcaagggcct 1920

TT Tactttatggc agacattgtg ctagtgottt tattctaact tttattttra tcagttacac 1980 atgatcataa tttaaaaagt caaggcttat aacaaaaaag ccccagccca ttcctcoccat 2040 tcaagattcc cactccccag aggtgaccac tttcaactct tgagtttttc aggtatatac 2100 ctccatgttt ctaagtaata tgcttatatt gttcacttcc ttttttttta ttttttaaag 2160 aaatctattt cataccatgg aggaaggctc tgttccacat atatttccac ttcttcatte 2220 tctcggtata gttttgtcac aattatagat tagatcaaaa gtctacataa ctaatacage 2280 tgagctatgt agtatgctat gattaaattt acttatgtaa aaaaaaaaaa aaaaaaaa 2338 <210> 606 <211> 1723 <212> DNA <213> Homo sapiens <400> 606 actccgaatg cgaagttctg tcttgtcata gccaagcacg ctgcttcettg gattgacctg 60 gcaggatggc gccaccacca gctagagtac atctaggtgc gttecctggca gtgactccga 120 atccecgggag cgcagegagt gggacagagg cagccgcgge cacacccagc aaagtgtggg 180 gctcttececge ggggaggatt gaaccacgag gcgggggccg aggagcgctc cctacctcca 240 tgggacagca cggacccagt gcccgggecce gggcagggcg cgccccagga cecaggcecgg 300 c€gcgggaagc cagccctcgg ctccgggtec acaagacctt caagtttgtc gtegtcgggg 360 . tcectgectgeca ggtcgtaccet agctcagctg caaccatcaa acttcatgat caatcaattg 420 gcacacagca atgggaacat agccctttgg gagagttgtg tccaccagga tctcatagat 480 cagaacatcc tggagcctgt aaccggtgca cagagggtgt gggttacacc aatgcttcca 540 acaatttgtt tgcttgcctc ccatgtacag cttgtaaatc agatgaagaa gagagaagtc 600 cctgcaccac gaccaggaac acagcatgtc agtgcaaacc aggaacttte cggaatgaca 660 attctgctga gatgtgcegg aagtgcagca gagggtgccc cagagggatg gtcaaggtca 720 aggattgtac gccctggagt gacatcgagt gtgtccacaa agaatcaggc aatggacata 780 atatatgggt gattttggtt gtgactttgg ttgttccgtt gctgttggtg getgtgctga 840 ttgtctgttg ttgcatcgge tcaggttgtg gaggggaccc caagtgcatg gacagggtgt 900 gtttctggeg cttgggtete ctacgagggc ctggggctga ggacaatgct cacaacgaga 960 ttctgagcaa cgcagactcg ctgtccactt tcgtctetga gcagcaaatg gaaagccagg 1020 agccggcaga tttgacaggt gtcactgtac agtccccagg ggaggcacag tgtctgectgg 1080 gaccggcaga agctgaaggg tctcagagga ggaggctget ggttccagea aatggtgctg 1140 accccactga gactctgatg ctgttctttg acaagtttgc aaacatcgtg ccctttgact 1200 cctgggacca gctcatgagg cagctggacc tcacgaaaaa tgagatcgat gtggtcagag 1260 ctggtacagc aggcccaggg gatgccttgt atgcaatgct gatgaaatgg gtcaacaaaa 1320 ctggacggaa cgcctcgate cacaccctge tggatgcctt ggagaggatg gaagagagac 1380 atgcaaaaga gaagattcag gacctcttgg tggactctgg aaagttcatc tacttagaag 1440 atggcacagg ctctgcecgtg tccttggagt gaaagactct ttttaccaga ggtttcctcect 1500 taggtgttag gagttaatac atattaggtt tttttttttt ttaacatgta tacaaagtaa 1560 attcttagecc aggtgtagtg gctcatgcet gtaatcccag cactttggga ggctgaggceg 1620 ggtggatcac ttgaggtcag aagttcaaga ccagcctgac caacatcgtg aaatgccgtc 1680 tttacaaaaa aatacaaaaa ttaactggaa aaaaaaaaaa aaa 1723 <210> 607 <211> 1449 <212> DNA <213> Homo sapiens <400> 607 ctggatagaa cagctcaagc cttgccactt cgggcttete actgcagctg ggcttggact 60 tcggagtttt gccattgecca gtgggacgtc tgagactttc tccttcaagt acttggcaga 120 tcactctctt agcagggtct gcgcttegea gccgggatga agctggtttc cgtcgecctg 180 atgtacctgg gttcgctege .cttectaggce gctgacaccg ctcggttgga tgtcgegtceg 240 gagtttcgaa agaagtggaa taagtgggct ctgagtcgtg ggaagaggga actgcggatg 300 tccagcaget accccaccgg gctegctgac gtgaaggccg ggcctgccca gacccttatt 360 cggccccagg acatgaaggg tgcctctega agccccgaag acagcagtcc ggatgccgec 420 cgcatccgag tcaagcgcta ccgccagagc atgaacaact tccagggcct ccggagettt 480 ggctgccget tcgggacgtg cacggtgcag aagetggcac accagatcta ccagttcaca 540 gataaggaca aggacaacgt cgcccccagg agcaagatca gcccccaggg ctacggccge 600 cggcgeccgge gctccctgee cgaggecgge ccgggtcgga ctctggtgte ttctaageca 660 Caagcacacg gggctccagc ccccccgagt ggaagtgctc cccactttet ttaggattta 720 ggcgcccatg gtacaaggaa tagtcgcgca agcatcccge tggtgectce cgggacgaag 780 gacttcccga gecggtgtggg gaccgggctce tgacagccct gcggagaccce tgagtcecggg 840 aggcaccgtc cggcggcgag ctctggcettt gcaagggcce ctcecttetgg gggetteget 900 tccttagect tgctcaggtg caagtgccce agggggcggg gtgcagaaga atccgagtgt 960 ttgccaggct taaggagagg agaaactgag aaatgaatgc tgagaccccc ggagcagggg 1020 tctgagccac agccgtgctc geccacaaac tgatttctca cggegtgtca ccccaccagg 1080 gcgcaagect cactattact tgaactttcc aaaacctaaa gaggaaaagt gcaatgcgtg 1140 ttgtacatac agaggtaact atcaatattt aagtttgttg ctgtcaagat tttttttgta 1200 acttcaaata tagagatatt tttgtacgtt atatattgta ttaagggcat tttaaaagca 1260 attatattgt cctcccctat tttaagacgt gaatgtctca gcgaggtgta aagttgttceg 1320 ccgecgtggaa tgtgagtgtg tttgtgtgca tgaaagagaa agactgatta cctcctgtgt 1380 ggaagaagga aacaccgagt ctctgtataa tctatttaca taaaatgggt gatatgcgaa 1440 cagcaaacc 1449 <210> 608 <211> 498 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (11)..(39)

«223> nis a, ¢c, g, t or u

<220>

<221> misc_feature

<222> (380) ..(475)

«223> nis a, ¢, g, t or u

<400> 608 aggtacaagC nnnnnnnonn NNNNonnnnn nnonnnnnna gatcaaataa agactaatga 60 tattgatttg gatacggtga ataagctgga caagatgttg aggagagggg gtaaaacaag 120 tttacattaa atatactaac aataacgatt gggtacagat ttgtaagtga tggtgatgga 180 taaaaactga ataagaatac aaacctaaaa tataatgaaa atgaaaaaaa tatcttttat 240 cttttttaat aaagaagggg gacggggtct tggattagta taaatataac aataatggaa 300 aagttgaata tgttaaggaa taagaattaa tctcatttaa agcctcaaaa caaccatgaa 360 aaggattaga aacattttan nnnnnnnnnn NNNNNANNNNN NONONDONGNN ODONDNNNNDNn 420

NNNANNNNNN NNONNNONANN NONONNDNNNN NNNNNNDNNNn nnnnnnnnnn nannngattt 480 aaaaaaaaaa aaaataga 498

<210> 609

<211> 3216

<212> DNA

<213> Homo sapiens

<400> 609 gcggacggtg agtggggatg gactggagtt gaagagctcg agatgaaggg cttgagggcg 60 tgtgttattt gttttcttca agcatttggt cgagattaag aattaaaaat gtcatccaaa 120 caagaaataa tgagtgacca gcggtttaga cgggttgcaa aggacccgag attttgggaa 180 atgccagaaa aggatcgaaa agtcaaaatt gacaagagat ttcgagccat gtttcatgac 240 dadgaagttca agttgaacta tgccgtggat aaaagagggc gccccattag ccatagcact 300 acagaggatt tgaagcgttt ttacgacctt tcagattctg attccaatct ctctggtgaa 360 gatagcaaag cattgagtca aaagaaaata aagaagaaaa aaacccagac taaaaaagaa 420 atcgattcaa aaaatctagt tgagaaaaag aaagaaacca agaaggctaa tcacaagggt 480 tctgaaaata aaactgattt agataattct ataggaatta aaaaaatgaa aacctcatgt 540 aaatttaaga tagattcaaa cataagtccg aagaaggata gcaaagaatt tacacaaaaa 600 aataagaaag agaaaaaaaa cattgttcaa catactacag actcttctct cgaagaaaaa 660 caaaggacat tagactcagg cacctctgaa attgtgaaat ctcccagaat cgagtgttcet 720 dagacaagaa gagaaatgca atcagtggtt caactcataa tgacaagaga cagtgatggt 780 tatgaaaact caacagatgg tgaaatgtgt gacaaagatg ctctggagga agattcagaa 840 agcgttagtg aaataggaag tgatgaggaa tctgaaaatg aaattacaag tgttggtaga 900 gcttcaggtg atgacgatgg aagtgaagat gatgaagagg aggatgaaga tgaagaggag 960 gatgaagatg aggatagtga ggatgatgat aaaagtgaca gtggccctga tcttgcaagg 1020 ggtaaaggaa atatagaaac tagttctgaa gatgaagatg atacggcaga tttgtttcca 1080 gaagaatctg gttttgagca tgcttggaga gaattagata aagatgctcc tcgtgctgat 1140 gagattacac gtcgattagc agtttgtaac atggactggg atagattaaa ggcaaaagat 1200 ttgctggete tgttcaattc atttaaaccc aaaggaggtg taatattete cgtcaagata 1260 tatccttcag aatttggaaa ggagaggatg aaggaagagc aagttcaagg accagtagag 1320 ctattaagta ttcctgaaga tgccccagaa aaagactgga cgtctagaga aaaattgaga 1380 gattatcaat tcaaacgact gaagtactat tatgcagtag tagactgtga ttctccggaa 1440 acagctagta aaatttatga ggattgtgat gacctggaat ttgaaagtag ttgttctttc 1500 atagatctaa ggtttatacc agatgatatt acttttgatg atgagcctaa ggatgtagcc 1560 tcagaagtga atttaacagc atataaacca aaatatttca cttctgctgec aatgggaaca 1620 tcaacggtgg aaatcacttg guatgagact gatcatgaaa gaattacaat gctcaacagg 1680 aagtttaaaa aggaagagct tttggacatg gattttcaag cctacttagc ttecctctagt 1740 gaagatgaag aggagataga agaggagcta caaggtgatg atggagtcaa tgtagaagaa 1800 gatgggaaaa caaagaaaag tcagaaggat gatgaagaac aaattgctaa atacaggcag 1860 ctcttgcagg ttattcaaga aaaagaaaag aaaggcaaag aaaatgatat ggaaatggaa 1920

© attaaatggg ttccaggtct taaagaaagt gcagaagaga tggtcaaaaa caaattggaa 1980 ggaaaggata aactgacccc ttgggaacaa tttttagaga agaagaaaga gaaaaaaaga 2040 ctgaaaagga aacagaaggc tcttgctgaa gaggccagtg aagaggaact tcecctetgat 2100 gttgatttga atgacccata ctttgctgaa gaagttaaac aaataggtat aaataaaaaa 2160 tcggtaaaat ctgcaaaaga tggcacatct ccagaagaag aaattgaaat agaaagacaa 2220 aaggctgaaa tggctttgct tatgatggat gaggacgagg acagtaagaa acacttcaat 2280 tacaacaaga ttgtggagca ccagaatctg agcaaaaaga agaaaaagca gctcatgaaa 2340 aagaaggaat taatagagga tgactttgag gtaaatgtta acgatgcacg gtttcaggca 2400 atgtacactt cccacttgtt caatttggac ccctcagatc ccaatttcaa daaaacaaaa 2460 gctatggaaa aaatccttga ggagaaggcc cggcaaagag aacggaaaga acaagaactt © 2520 actcaggcaa taaagaaaaa agagagtgag attgaaaagg aatcacaaag gaagtccatt 2580 gatcctgctt tgtcaatgtt gattaaatct ataaaaacca aaacagagca gtttcaagca 2640 agaaaaaagc aaaaagtcaa ataactggat gttacttatt tttgaactga atacatcttt 2700 tcctaaaatg tacaaaaata ataggaggga atatttattg ggaacaaagc tatctttcaa 2760 gaacatgaat aaaatctttt tctggacata gtaaaatttt tctccataaa taattgtact 2820 taattgtgga tgactgacaa atttttattg tatattccta cagatcagtc ataattaaat 2880 tacctgcatt atagggttta taaaattttt atattttaca atgttcagtt ctaactagtg 2540 gaaagttact ctagcttttt aaaaggctgt ttacaattct gtgtaaaaat agagcagtat 3000 ctactcaagt ttgtgtaaat gttagggata atttgaaaaa tatatatatt taatacatta 3060 atttctctgg aagcaggagg catgtttaaa taactattaa aataatttat ttttctagcec 3120 ataaaggatg gaagtcaaga actttttgtt gtttagtcat gttaagtata gtttatgaaa 31890 ttaacttgta aataaaagtg taaaatattt tcatta 3216 <210> 610 <211> 2155 <212> DNA <213> Homo sapiens

<400> 610 tgggggcgtt cgcctegttt gectegegec ctccactgga gctgttcgeg ccteccggcet 60 cccaccgcag cccaccecgge agaggagtcg ctaccagege ccagtgcgect ctgtcagtcec 120 gcaaactcct tgccgcccge ccecgggetgg gegeccaaata ccaggctacce atggtctaca 180 agactctctt cgctctttge atcttaactg caggatggag ggtacagagt ctgcctacat 240 cagctccttt gtctgtttct cttcecgacaa acattgtacc accgactacc atctggacta 300 gctctccaca aaacactgat gcagacactg cctccccatc caacggcact cacaacaact 360 ¢ggtgctcece agttacagca tcagccccaa catctctget tcctaagaac atttccatag 420 agtccagaga agaggagatc accagcccag gttcgaattg ggaaggcaca aacacagacce 480 cctcaccttc tgggttctceg tcaacaagcg gtggagtcca cttaacaacc acgttggagg 540 aacacagctt gggcactcct gaagcaggcg tggcagetac actgtcgcag tccgetgetg 600 agcctcccac actcatetce cctcaagctc cagcctcatc accctcatcc ctatcaacct 660 caccacctga ggtcttttct gcctecgtta ctaccaacca tagctccact gtgaccagca 720 cccaacccac tggagctcca actgcaccag agtccccaac agaggagtce agetctgace 780 acacacccac ttcacatgcc acagctgage cagtgcccca ggagaaaaca cccccaacaa 840 ctgtgtcagg caaagtgatg tgtgagctca tagacatgga gacaccacca cctttcccag 900 ggtgatcatg caggaagtag aacatgcatt aagttcaggc agcatcgccg ccattaccgt 960 gacagtcatt gccgtggtgc tgctggtgtt tggagttgca gcoctacctaa aaatcaggca 1020 ttcctectat ggaagacttt tggacgacca tgactacggg tcctggggaa actacaacaa 1080 ccctectgtac gatgactect aacaatggaa tatggcctgg gatgaggatt aactgttctt 1140 tatttataag tgcttatcca gtagaattaa taagtacctg atgcgcattg aacgacaatc 1200 ttaagccctg ttttgttggt atggttgttt ttgttttect cectctecte tggctgctac 1260 aacttccect ttctggtaca agaagaacca ttctttaaag gtgagtggag gctgatttgce 1320 agctgaagtg ggccagcctt gcaccagcca ggccagacca ccatggtgaa ggettcttte 1380 cccactgcag gacccacttt gagaaggacc gaggaggagg atttgggttg ttttgttagg 1440 ggttactttc aggggaacat ttcatttgtg ttatttctta aacttctatt taggaaatta 1500 cattaagtat taatgagggg aaaggaaatg agctctacga ggatttcacc ctgcatggga 1560 . . gagagcaggg ttttctcaga ttccttttta atctctattt atctggttgt ttctgacagg 1620 atgctgcctg cttggctecta caagetggaa agcagcttct tagctgccta attaatgaaa 1680 gatgaaaata ggaagtgccc tggagggggc cagcaggtca cggggcagaa tctctcaggt 1740 tgctgtggga tctcagtgtg cccctacctg ttctececte caggccacct gtctctgtaa 1800 aggatgtcetg ctctgttcaa aaggcagctg ggatcccagce ccacaagtga tcagcagagt 1860 tgcatttcca aagaaaaagg ctatgagatg agctgagtta tagagagaaa gggagaggca 1920 tgtacggtgt ggggaagtgg aagggaagct ggcgggggag aaggaggcta acctgcactg 1980 agtacttcat taggacaagt gagaatcagc tattgataat ggccagagat atccacagct 2040 tggaggagcc cagagaccgt ttgctttata Ccccacacagc aactggtcca ctgctttact 2100 gtctgttgga taatggctgt aaaatgttta aaaacaaaaa aaaaaaaaaa aaaaa 2155

<210> 611 <211> 2333 . <212> DNA <213> Homo sapiens <400> 611 : ggcacgaggc tagagcgatg ccgggccgga gttgegtcecge cttagtectc ctggetgeceg 60 ccgtcagectg tgcegtecgeg cagcacgcgce cgecgtggac agaggactge agaaaatcaa 120 cctatcectce ttcaggacca acgtacagag gtgcagttcc atggtacacc ataaatcttg 180 acttaccacc ctacaaaaga tggcatgaat tgatgcttga caaggcacca atgctaaagg 240 ttatagtgaa ttctctgaag aatatgataa atacattcgt gccaagtgga aaagttatgc 300 aggtggtgga tgaaaaattg cctggcctac ttggcaactt tcctggcecect tttgaagagg 360 aaatgaaggg tattgccgct gttactgata tacctttagg agagattatt tcattcaata 420 ttttttatga attatttacc atttgtactt caatagtagc agaagacaaa aaaggtcatc 480 taatacatgg gagaaacatg gattttggag tatttcttgg gtggaacata aataatgata 540 cctgggtcat aactgagcaa ctaaaacctt taacagtgaa tttggatttc caaagaaaca 600 acaaaactgt cttcaaggct tcaagctttg ctggctatgt gggcatgtta acaggattca 660 aaccaggact gttcagtctt acactgaatg aacgtttcag tataaatggt ggttatctgg 720 gtattctaga atggattctg ggaaagaaag atgccatgtg gatagggttc ctcactagaa 780 cagttctgga aaatagcaca agttatgaag aagccaagaa tttattgacc aagaccaaga 840 tattggcccc agcctacttt atcctgggag gcaaccagtc tggggaaggt tgtgtgatta 900 cacgagacag aaaggdaatca ttggatgtat atgaactcga tgctaagcag ggtagatggt 960 atgtggtaca aacaaattat gaccgttgga aacatccctt cttccttgat gatcgcagaa 1020 cgcctgcaaa gatgtgtctg aaccgcacca geccaagagaa tatctcattt gaaaccatgt 1080 atgatgtcct gtcaacaaaa cctgtcctca acaagctgac cgtatacaca accttgatag 1140 atgttaccaa aggtcaattc gaaacttacc tgcgggactg ccctgaccct tgtataggtt 1200 ggtgagcaca cgtctggcct acagaatgcg gcctctgaga catgaagaca ccatctccat 1260 gtgaccgaac actgcagctg tctgaccttc caaagactaa gactcgcggec aggttctctt 1320 tgagtcaata gcttgtcttc gtccatctgt tgacaaatga cagatctttt tttttttccc 1380 cctatcagtt gatttttctt atttacagat aacttcttta ggggaagtaa aacagtcatc 1440 tagaattcac tgagttttgt ttcactttga catttggagga tctggtgggc agtcgaacca 1500 tggtgaactc cacctccgtg gaataaatgg agattcageg tgggtgttga atccagcacg 1560 tctgtgtgag taacgggaca gtaaacactc cacattcttc agtttttcac ttctacctac 1620 atatttgtat gtttttctgt ataacagcct tttccttetg gttctaactg ctgttaaaat 1680 taatatatca ttatctttgc tgttattgac agcgatatta ttttattaca tatcattaga 1740 gggatgagac agacattcac ctgtatattt cttttaatgg gcacaaaatg ggcccttgce 1800 tctaaatagc actttttggg gttcaagaag taatcagtat gcaaagcaat cttttataca 1860 ataattgaag tgttcecettt ttcataatta ctctacttec cagtaaccct aaggaagttg 1920 ctaacttaaa aaactgcatc ccacgttctg ttaatttagt aaataaacaa gtcaaagact 1980 tgtggaaaat aggaagtgaa cccatatttt aaattctcat aagtagcatt gatgtaataa 2040 acaggttttt agtttgttct tcagattgat agggagtttt aaagaaattt tagtagttac 2100 taaaattatg ttactgtatt tttcagaaat caaactgctt atgaaaagta ctaatagaac 2160 ttgttaacct ttctaacctt cacgattaac tgtgaaatgt acgtcatttg tgcaagaccg 2220 tttgtccact tcattttgta taatcacagt tgtgttcctg acactcaata aacagtcact 2280 ggaaagagtg ccagtcagca gtcatgcacg ctgataaaaa aaaaaaaaaa aaa 2333 <210> 612 <211l> 2010 <212> DNA <213> Homo sapiens <400> 612 attcattccce tgtectecgga tcacagtctc ttctcactac agtgtcgceg cctctgectg 60 cgtagccccg gccatggete tgtagectcg acccetttgt gccecccggece cgtctecgeg 120 ctcaccacgc ctgcgctcte cgctcccace ttctttettc agcecgaggece gccgccgcect 180 ctcettgetg cageccatgga gtcttccact ttcgecttgg tgecctgtett cgeccacctg 240 agcatcctcc agagectegt gccagctgct ggtgcagect ctecectgttge catcagtgcee 300 cagcacctgt gctacagcca tgtcactcct ggcgaccctg gggctggage tggacagggce 360 cctgctccca gectagtggge tgggatgget cgtagactat gggaaactcece cccecggeecee 420

. tgcceccectg gectecctatg aggtccttgg gggagccctg gagggcgggce ttccagtggg 480 gggagagcce ctggcaggtg atggcttctc tgactggatg actgagcgag ttgatttcac 540 agctctccte cctctggage ctcecctace cceccggcace ctcccccaac cttocccaac 600 cccacctgac ctggaagcta tggcctccect cctcaagaag gagctggaac agatggaaga 660 cttcttecta gatgeccecge cecteccace acccteecececg ccgccactac caccaccace 720 actaccacca gcccectece tececctgte cctececctec tttgacctec cccagccccce 780 tgtcttggat actctggact tgctggccat ctactgccge aacgaggccg ggcaggagga 840 agtggggatg ccgcctctge cccecgecaca gcagccccet cctccttcote cacctcaace 900 ttctcgectg gccccecctace cacatectgc caccacccga ggggaccgca agcaaaagaa 960 gagagaccag aacaagtcgg cggctctgag gtaccgccag cggaagceggg cagagggtga 1020 ggccctggag ggcgagtgcc aggggctgga ggcacggaat cgcgagctga aggaacgggce 1080 agagtccgtg gagcgcgaga tccagtacgt caaggacctg ctcatcgagg tttacaagge 1140 ccggagccag aggacccegta gctgctagaa gggcaggggt gtggcttctg ggggctggtce 1200 ttcagctctg gcgcecttcat ccccctgect ctaccttcat tccaaaccce tctcggcegg 1260 gtgcagtggce ttatgcttgt aatcccagca ctttgggagg ccaaggcagg aggatcgttt 1320 gaggccagga ggtcaatacc agcctgggca acatagtaag accctgtctc tattaaaaaa 1380 aaaaaatcaa cccttcttec ccaccaaacc acccaactcc tctctactct tatcctttta 1440 tccteotgtet ctgcttatca cctctcttge gtatttetgg atctcecttece ctectttcte 1500 gtccaaatca tgaaatgttt ggeccttagtc aatgtctatg cccgtcacat aacagccgag 1560 gcaccgaggc ccacagggaa gcagctggga gcttggaaac ctggtctctt gaatttcaaa 1620 cctggtttct tacaggtggt tgtctggggt gggtggagtg gcgacaggat agagctgaag 1680 gactatgcaa atgaggaagt aagtcagggc gggctttgag aaggggaccc atatcctaca 1740 ggcaaaaagc aggctaggtg accttgggac actacgctaa gggagggagg ctaaaggcgg 1800 ccaggtttgc agtgcgggaa gatgagcagg ccagtgggag gaggggcadyg gcagggctgt 1860 agttggtgac tgggtgttca ttttagctct aagaaaaaaa atcagtgttt cgtgaaggtg 1920 ttggagaggg gctgtgtctg ggtgagggat ggcggggtac tgattttttt gggaggttat 1980 gagcaaaaat aaaacgaaac atttcctctg 2010 <210> 613 <211> 1263 <212> DNA <213> Homo sapiens <400> 613 ggcacgaggt agagaagcag gggatagact cataggctgc aacaaaggtg actctgtccc 60 tggacactgc ctcegtactt tctccttget tcactggcca cagcatctcc ctccagccet 120 cgctatgtge ctctgecate ttcacccatc atggagcaga ggtgaggaga ggcagcctgg 180 gaatatggag accagtgaag gaccaggcct ggagagcaca gggtcctacc tgggcatcca 240 gcagaggagc ccctaaaggc caggagcacc ccaagaggag ggagggcagce cagcctccat 300 tgacggcgag cctccagcce tctcctactt tgatcaccat ttctctecag getttctgec 360 tccgagatgt ggcaccatag tgcggtgccc tgtggettca cegccctact tccacctecg 420 cccagcctgt aatgtttata taagcagcct caaggaccaa gaaccatctg cgaaaggaca 480 cacacaggaa attcataaaa gaaatctgaa tggataaaac catgaaaaaa agtatgcettce 540 attagtaatt aaagaaaggc aaatagagct ggaagcattt ttcccttage aaaccataac 600 agaaaaaaat aagacccaat attggcaaag agactactga aaaaacattc Ccatacattg 660 cgtgtgggag tatacatcgg tgcaggcttce ctggatgaca gttgggtgat atgtgtcatg 720 tggcctaaaa gcctccatgt catttgacct acgaattcta tctttgggaa tttatcctaa 780 gaaaatactt aaggatttag ttagtgataa gatgttcatc ccagcattgc aatggagaaa 840 aatgggaagc aatggtttgg ttgggaattt attcctttte tgctgtaacg aaagtttgca S00 ataggggatt gcttaagtaa attattgtat ctccatccag atggtggagt accgcgcaga 960 cattaaaagt catgtaaaag aacatctgac tgaaagaaaa atgctccttg aatattaaaa 1020 ggttgtaaaa atagtgcatg ttatgtgatt tcaattttgt tttttaaaat atgggtgtat 1080 gcttgtatac gtagagcaga taaaaaagac ggaaggcata ctaaaaaatg ttgagtggtt 1140 atctttgtat ggtggaacaa agtcactgta attttecatct ttggtttttc tgtaatttcce 1200 aaattttcca cattttgtat ttcatataat aaatataatt taagaaaaaa aaaaaaaaaa 1260 aaa 1263 <210> 614 <211> 447 <212> DNA <213> Homo sapiens <400> 614 tttttttttt ttetettttgg tgaaacaatt tattagccat ggttcagaat aatacaaaaa 60 taaaggtgtg gctttattta cacacactct tgaagctett ggeattcagce ggacagcaaa 120 caccatactc agagtgatgg aattaatagc atttagggta agcaaggacc agtgtgagac 180 tgggceccagg aaatggggag ggaatgtgag gagaaacagg gaatgacatt aaagaagaaa 240 cagacacctt ggagaattta tgactccttt ctctatgtca tgtccagaag aggcaagtct 300 acagagatca aagtagccta ggggtgccta gggatgggga ggttggggtg gcgactaagg 360 ggggctggat ttcttttggg ggtagtcaac tctaagacgg actgtgctga tggctgetga 420 actgtgacta tactaaaccg gcatcaa 447

<210> 615

<211> 2372

<212> DNA

<213> Homo sapiens

<400> 615 gcaccgegeg agecttggetyg cttetgggge ctgtgtggce ctgtgtgteg gaaagatgga 60 i 367 gcaagaagcc gagcccgagg ggcggeegeg accectctga ccgagatcect gctgcttteg 120 cagccaggag caccgteccct cccecggatta gtgcgtacga gcgceccagtg ccectggeeeg 180 gagagtggaa tgatccccga ggcccaggge gtegtgette cgeagtagtce agtccccgtg 240 aaggaaactg gggagtcttg agggaccccc gactccaage gcgaaaacce cggatggtga 300 ggagcaggca aatgtgcaat accaacatgt ctgtacctac tgatggtgct gtaaccacct 360 cacagattcc agcttcggaa caagagaccc tggttagacc aaagccattg cttttgaagt 420 tattaaagtc tgttggtgca caaaaagaca cttatactat gaaagaggtt cttttttate 480 ttggccagta tattatgact aaacgattat atgatgagaa gcaacaacat attgtatatt 540 gttcaaatga tcttctagga gatttgtttg gcgtgccaag cttctctgtg aaagagcaca 600 ggaaaatata taccatgatc tacaggaact tggtagtagt caatcagcag gaatcatcgg 660 actcaggtac atctgtgagt gagaacaggt gtcaccttga aggtgggagt gatcaaaagg 720 accttgtaca agagcttcag gaagagaaac cttcatctte acatttggtt tctagaccat 780 ctacctcatc tagaaggaga gcaattagtg agacagaaga aaattcagat gaattatctg 840 gtgaacgaca aagaaaacgc cacaaatctg atagtatttec ccttteccttt gatgaaagcc s00 tggctctgtg tgtaataagg gagatatgtt gtgaaagaag cagtagcagt gaatctacag 960 ggacgccatc gaatccggat cttgatgctg gtgtaagtga acattcaggt gattggttgg 1020 atcaggattc agtttcagat cagtttagtg tagaatttga agttgaatct ctcgactcag 1080 aagattatag ccttagtgaa gaaggacaag aactctcaga tgaagatgat gaggtatatc 1140 aagttactgt gtatcaggca ggggagagtyg atacagattc atttgaagaa gatcctgaaa 1200 tttccttage tgactattgg aaatgcactt catgcaatga aatgaatccc ccccttecat 1260 cacattgcaa cagatgttgg gccettegtg agaattgget tcctgaagat aaagggaaag 1320 ataaagggga aatctctgag aaagccaaac tggaaaactc aacacaagct gaagagggct 1380 ttgatgttce tgattgtaaa aaaactatag tgaatgattc cagagagtca tgtgttgagg 1440 asaatgatga taaaattaca caagcttcac aatcacaaga aagtgaagac tattctcagc 1500 catcaacttc tagtagcatt atttatagca gccaagaaga tgtgaaagag tttgaaaggg 1560 aagaaaccca agacaaadaa gagagtgtgg aatctagttt gcecccttaat gccattgaac 1620 cttgtgtgat ttgtcaaggt cgacctaaaa atggttgcat tgtccatgge aaaacaggac 1680 atcttatggc ctgctttaca tgtgcaaaga agctaaagaa aaggaataag ccctgcccag 1740 tatgtagaca accaattcaa atgattgtgc taacttattt ccecectagttyg acctgtctat 1800 aagagaatta tatatttcta actatataac cctaggaatt tagacaacct gaaatttatt 1860 cacatatatc aaagtgagaa aatgcctcaa ttcacataga tttcttetct ttagtataat 1920 tgacctactt tggtagtgga atagtgaata cttactataa tttgacttga atatgtagct 1980 catcctttac accaactcct aattttaaat aatttctact ctgtcttaaa tgagaagtac 2040 ttggtttttt ttttcttaaa tatgtatatg acatttaaat gtaacttatt attttttttg 2100 agaccgagtc ttgctctgtt acccaggctg gagtgcagtg ggtgatcttg gctcactgca 2160 agctctgecc tecceccgggtt cgcaccatte tcctgcctca gectcccaat tagcttggce 2220 tacagtcatc tgccaccaca cctggctaat tetttgtact tttagtagag acagggtttc 2280 accgtgttag ccaggatggt ctcgatctcc tgacctecgtg atccgecccac ctcggectcec 2340 caaagtgctg ggattacagg catgagccac cg 2372 <210> 616 <211> 3198 <212> DNA <213> Homo sapiens <400> 616 ccgcatgcte ccgtatcttt ggttacgctc gtcageccggt cggecgecge ctccagccgt 60 gtgccgctat gggagtcccg gegttcttcoe getggctcag cegcaagtac ccgtccatca 120 tagtcaactg cgtggaagag aagccaaaag aatgcaatgg tgtaaagatt ccagttgatg 180 ccagtaaacc taatccaaat gatgtggagt ttgataatct gtatttggat atgaatggaa 240 tcatccatcc ctgtactcat cctgaagaca aaccagcacc aaaaaatgaa gatgaaatga 300 tggttgcaat ttttgagtac attgacagac ttttcagtat tgtaagacca agaagacttc 360 tctacatggc aatagatgga gtggcaccac gtgtaaaaat gaaccagcag cgttcaagga 420 ggttcagggc catcaaaaga ggaatggaag cagcagtcga gaagcagcga gtcagggaag 480 aaatattggc aaaaggtggc tttcttcctc cagaagaaat aaaagaaaga tttgacagca 540 actgtattac accaggaact gaattcatgg acaatcttgc taaatgcctt cgctattaca 600 tagctgatcg tttaaataat gaccctgggt ggaaaaattt gacagttatt ttatctgatg 660 ctagtgctcc tggtgaagga gaacataaaa tcatggatta cattagaagg caaagagccc 720 agcctaacca tgacccaaat actcatcatt gtttatgtgg agctgatgct gatctcatta 780 tgcttggcct tgccacacat gaaccgaact ttaccattat tagagaagaa ttcaaaccaa 840 acaggcccaa accatgtggt ctttgtaatc agtttggaca tgaggtcaaa gattgtgaag 900 gtttgtcaag agaaaagaag ggaaagcatg atgaacttgc cgatagtctt ccttgtgcag 960 aaggagagtt tatcttcctt cggcttaatg ttcttegtga gtatttggaa agagaactca 1020 caatggccag cctaccattc acatttgatg ttgagaggag cattgatgac tgggttttca 1080 tgtgcttctt tgtgggaaat gacttcctec ctcatttgec atcgttagag attagggaaa 1140 atgcaattga ccgtttggtt aacatataca aaaatgtggt acacaaaact gggggttacc 1200 ttacagaaag tggttatgtc aatctgcaaa gagtacagat gatcatgtta gcagttggtg 1260 aagttgagga tagcattttt aaaaagagaa aggatgatga ggacagtttt agaagacgac 1320 agaaagaaaa aagaaagaga atgaagagag atcaaccagc tttcactcct agtggaatat 1380 taactcctca tgccttgggt tcaagaaatt caccaggttce tcaagtagec agtaatccga 1440 gacaagcagc ctatgacatg aggatgcaga ataactctag tccttcgata tctectaata 1500 cgagtttcac atctgatggc tccccgtctc cattaggagg aattaagcga aaagcagaag 1560 acagtgacag tgaacctgag ccagaggata atgtcaggtt atgggaagct ggctggaagc 1620 agcggtacta caagaacaaa tttgatgtgg atgcagctga tgagaaattc cgtcggaaag 1680 ttgtgcagtc gtacgttgaa ggactttgct gggttcttag atattattac cagggctgtg 1740 cttcctggaa gtggtattat ccatttcatt atgcaccatt tgcttcagac tttgaaggca 1800 ttgcagacat gccatctgaa tttgaaaagg gtacgaaacc gtttaaacca ctagaacaac 1860 ttatgggggt atttccagct gcaagtggta attttctacc tccatcatgg cggaagctca 1820 tgagtgatcc tgattctagt ataattgact tctatcctga agattttget attgatttga 1980 atgggaagaa atatgcatgg caaggtgttg ctctcttgee attcgtggat gagcgaaggce 2040 tacgagctgc cctagaagag gtatacccag acctcactce agaagagacc agaagaaaca 2100 gccttggagg tgatgtctta tttgtgggga aacatcaccc actccatgac ttcattttag 2160 agctgtacca gacaggttcc acagagccag tggaggtacc ccctgaacta tgtcatggga 2220 ttcaaggaaa gttttctttg gatgaagaag ccattcttce agatcaaata gtatgtgctc 2280 ctgttcctat gttaagggat ctgacacaga acactgtagt cagtattaat tttaaagacc 2340 cacagtttgc tgaagattac atttttaaag ctgtaatgct tccaggagca agaaagccag 2400 cagcagtact gaaacctagt gactggggaa aatccagcaa tggacggcag tggaagcctc 2460 agcttggett taaccgtgac cggaggcctg tgcacctgga tcaggcagcec ttcaggactt 2520 tgggccatgt gatgccaaga ggctcaggaa ctggcattta cagcaatgct gcaccaccac 2580 ctgtgactta ccagggaaac ttatacaggc cgcttttgag aggacaagcc cagattccaa 2640 aacttatgtc aaatatgagg ccccaggatt cctggcgagg tcctectcee cttttecage 2700 agcaaaggtt tgacagaggc gttggggctg aacctctgct cccatggaac cggatgctgc 2760 aaacccagaa tgcagccttc cagccaaacc agtaccagat gctagetggg cctggtgggt 2820 atccacccag acgagatgat cgtggaggga gacagggata tcccagagaa ggaaggaaat 2880 accctttgee accaccctca ggaagataca attggaatta agettttgta aagctttcce 2940 aaatcctttc atcattctac agttttatgce tatttgtgga aagatttctt tctcaagtag 3000 tagtttttaa taaaactaca gtactttgtg tatttctttt aactgtgtat atttctactg 3060 atctgatctc actgtttatg ttgctttcca aagatgtatg ttgcataata cagtggatct 3120 gaatttatta atgcttataa acacatttga ggaataggag gtccgggttt tccataatgg 3180 gtaaaatgga accagctg 3198 <210> 617 <211l> 422 <212> DNA <213> Homo sapiens <400> 617 tgagtgtaaa gaaaggttta ctccttgtat catcccctce ccgtggactg cttcaattct 60 atcggggaca ggccagtccc tggaggctgc aaggagccac aaacctttcc cagctcacac 120 tctgcaccee tcagtcectctg ctgctaaaga atcagactca ggtagatggg gtgtccacag 180 tctgtcectca ttacccagtce ataccgggta gcatggceccecg agagagcccet tatctctccee 240 caccttaaaa ccctcagcat cacacagcag gaaccagtcc acagggctta ccaaggatac 300 gcagtgaaaa cagaataatg tctgttacaa accccctaaa cctgagatgg ctgaagagcec 360 agattcctge accccatctg actcccccag gcagtgggag atgacccaaa gcccccattc 420 cc 422 <210> 618 <211> 287 <212> DNA <213> Homo sapiens <400> 618 tttttttttt tttttcatca gcaatttcaa ttttatgttt tctacttatt tttatataaa 60 aatacaatgc aacaaaatat tcatatattg cacaaacagg gatgtgcata caaagatgct 120 aacaacattg gctggtaata ggctttacca tgttatgatc taaatgcttg ttcatcaaaa 180 aatgtacaaa attctaagtt tggcatccaa aagggggctt acagttattg aatatttttc 240 ccagccctat tttaaatcaa attcaagttt gcctatgaca aagactg 287 <210> 619 <211> 515 <212> DNA <213> Homo sapiens <400> 619 tttttttttt tttttttttt tttttttttt tctgcttaat ggcatgagag ctccatgaag 60 gaatttatta gatacaccct gattctccac tgccctaaca cacgatactg agttgctaat 120 gtccacattc agcaccaggg gaaattcgtg catcacatga catcgcctca ttaaagctgt 180 cagcataact ttaccaaaca agttatataa caaccaagaa gccactggta caggataata 240 ttcagaatgt gacatgtaaa aattgcaata agtagaatat attttttatg ttgttgaaca 300 aaagaaaatt gaaagaatta aagcaatcca agggcctaga agcaagtgaa ttctctgata 360 cctgtgagta AggEtactLt aggacagccc atgaatccat tcctcgggtt gttctgaget 420 ccttgagaaa tggccccaac tgggtttttg gagtgaacct ggttcaatac agattgectt 480 aggatgttca ctgaaagttt cggcttgctc tggac 515 <210> 620 <211> 1843 <212> DNA <213> Homo sapiens <400> 620 ggaggaggtg gcggegetgg agctcectccc ggggaccage gacccgggga gcgagcacgt 60 cgctccgcac cgctcttect ccagcegetg agcegtceect tetcgecatyg tcccagagca 120 ggcaccgcege cgaggdccccg ccgetggagc gcgaggacag tgggacctte agtttgggga 180 agatgataac agctaagcca gggaaaacac cgattcaggt attacacgaa tacggcatga 240 agaccaagaa catcccagtt tatgaatgtg aaagatctga tgtgcaaata cacgtgccca 300 ctttcacctt cagagtaacc gttggtgaca taacctgcac aggtgaaggt acaagtaaga 360 agctggcgaa acatagagct gcagaggctg ccataaacat tttgaaagcc aatgcaagta 420 tttgetttge agttcctgac cecttaatge ctgaccctte caagcaacca aagaaccage 480 ttaatcctat tggttcatta caggaattgg ctattcatca tggctggaga cttcctgaat 540 ataccctttc ccaggaggga ggacctgctc ataagagaga atatactaca atttgcaggce 600 tagagtcatt tatggaaact ggaaaggggg catcaaaaaa gcaagccaaa aggaatgctg 660 ctgagaaatt tcttgccaaa tttagtaata tttctecaga gaaccacatt tctttaacaa 720 atgtagtagg acattcttta ggatgtactt ggcattcctt gaggaattct cctggtgaaa 780 agatcaactt actgaaaaga agcctcctta gtattccaaa tacagattac atccagctgce 840 ttagtgaaat tgccaaggaa caaggtttta atataacata tttggatata gatgaactga 900 gcgccaatgg acaatatcaa tgtcttgectg aactgtccac cagccccatce acagtctgtce 960 atggctccgg tatctcctgt ggcaatgcac aaagtgatge agctcacaat getttgcagt 1020 atttaaagat aatagcagaa agaaagtaaa tctggagcaa cttaaaaaat ctttcagtag 1080 cacataaaaa gttccectet ggccecttee caagtaaaac ttttaccgta gtgtttatgt 1140 cttgtttcta aatctcttca tagattccat caacactcca gatttaatta tctcctcata 1200

372 Co gttgttatta agctcttttt aatggcttca actttgtatc agtatactgt atttataaac 1260 tttgtaccac aagagagagt gtagcaccca ttttacagtg ccatgcacat cagagaaaga 1320 aactgcatgt ttgttgttga tgatgaaata aaaatgctag cgacagtctt tcttactggt 1380 gcttaagctc ttctttgcac aaagetttat aaagggaatt caaaggaagc cctttagaat 1440 tagagtcttg agggacagca ctaacaggcc tttattaagt atgattgatt gttaaatttc 1500 agggaacatg attggtctgc tgtgtatttg aattcatgta acaaagaact gttacgatgg 1560 gattctgctc attttattaa aaagctactg acttgactgt catcctgttc ttgttagcca 1620 ttgtgaataa gattttaatg ttgataattc tgttatttac atatctctaa tttactttga 1680 aattcaaagg tgaaaataaa aaatgatggc ctaagtaaaa tttaaaaaaa aaaaaaaaaa 1740 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1800 daaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaccccc ggg 1843 <210> 621 <211> 267 <212> DNA <213> Homo sapiens <400> 621 ttttttettt tttttgecte ttccacttgg tctgcagtct gattcactcc tttactttcc 60 tccaatatac tgacccttgg gacttgggta ttgctggect gctttgggcecc ctcaggctcect 120 ttgcctgectg gtttctgagec tttccatagt cacagtctgg ttttaggcag aaactgtacc 180 tccatttgca atcaaccctt ttgcagctgt gecttacgcet tcttactgtg tttttaccaa 240 ttcatctgga acaaactaga aaaggaa 267 <210> 622 <211> 363 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (316) .. (316) <223> n is a, ¢, g, t or u <400> 622 ctttgccatc aggtggtggt caacgaaggg gcccttcttce agcgaacgag tcatggccta 60 gcccttactt cttgcgacge gagacgatga acgtctgegt gcgcttgttg ttgcgagtgce 120 ggtagccett cgtcagggtg ttccacggeg acacagggac ctggccctecg ccggtgecggce 180 cttcgccacc accgtgcggg tgatccaccyg ggttcatgge aacgccacga acggtcggge 240 ggatgccett ccagcggatc gegeceggect tgeccgtactg gegcaggetg tgctettegt 300 tgctcacttc accganggtg gcgecggcagt cgatgtgcac gecggcggact tcgeeggage 360 gca 363 <210> 623 <211> 345 ‘<212> DNA <213> Homo sapiens <400> 623 acaatttcac acaggagatc tcagacagat gactatatcc ttccctgggt acttgcaggg 60 taagcacatc ccctcgaaat agcagcagct ctaaacatga aattcttcct ggaggatttt 120 cttactcttg agttctattc taccaaattt tttgagcact tactgtcagg cattcagaat 180 gtgagcaatg acaataattt acctacactt ttgcacttac agtatgctgg gcccagttga 240 ttctcaaaac agttctggga attagctata aaaatgcccce catcttacag atgaggaagc 300 tcaggctcag aaaggcaaaa aaaaaaaagc cctatagtga gtcgt 345 <210> 624 <211> 417 <212> DNA <213> Homo sapiens <400> 624 gcaaaggaaa atgaatattw attcaatgtc cagattgggg aggggtctgt gtgtttaaca 60 ggaaaagwta cagaaaaama cctatcacam aggaaaagat aaatatgtyt gaytatytha 120 mmaggtgaaa cccataacca aaatttaaag gcaaattcac acaagtggaa atacagatgc 180 ccaactatcg tacaaagrga accatgwtca aggtcactaa caagcaaaga attttmagtt 240 tttbbtgttt ttbgttgttt ttyatttgrg acggrgtytc gytctgtcac ccaggctggr 300 gtscagtggc gcgatcttgg ytcactgcaa cctccgectc ctgggttcaa gcaattetct 360 gcctcagect cccaagtagce tgggdttaca ggcgccegec accacgecccg getaatt 417 <210> 625 <21l> 2422 <212> DNA <213> Homo sapiens <400> 625 gtcagcctee cttccaccge catattggge cactaaaaaa agggggctceg tcttttcggg 60 gtgtttttct ccececteecee tgtecceget tgectcacgge tctgecgacte cgacgccgge 120 aaggtttgga gagcggctgg gttcgeggga ccegeggget tgecacccgce cagactcgga 180 cgggctttge caccctctce gettgectgg teccctetce tctecegeect cecgetegee 240 agtccatttg atcagcggag actcggcgge cgggccgggg ctteccccgeca goceccctgcge 300 gctcctagag ctecgggecgt ggctcgtegg ggtetgtgte ttttggctec gagggcagtc 360 gctgggecttc cgagaggggt tcgggecegeg taggggcgct ttgttttgtt cggttttgtt 420 tttttgagag tgcgagagag gecggtegtge agacccggga gaaagatgtc aaacgtgcga 480 gtgtctaacg ggagccctag cctggagcgg atggacgcca ggcaggcgga gcaccccaag 540 cccteggect gecaggaacct cttcggeccg gtggaccacg aagagttaac ccgggacttg 600 gagaagcact gcagagacat ggaagaggcg agccagcgca agtggaattt cgattttcag 660 aatcacaaac ccctagaggg Caagtacgag tggcaagagg tggagaaggg cagcttgecce 720 gagttctact acagaccccce gcggecccce aaaggtgcct gcaaggtgec ggcgcaggag 780 agccaggatg tcagcgggag ccgceceggcg gegocctttaa ttggggctce ggctaactcet 840 gaggacacgc atttggtgga cccaaagact gatccgtcgg acagccagac ggggttageg S00 gagcaatgcg caggaataag gaagcgacct gcaaccgacg attcttctac tcaaaacaaa 960 agagccaaca gaacagaaga aaatgtttca gacggttcce caaatgccgg ttctgtggag 1020 cagacgccca agaagectgg cctcagaaga cgtcaaacgt aaacagctcg aattaagaat 1080 atgtttcctt gtttatcaga tacatcactg cttgatgaag Caaggaagat atacatgaaa 1140 attttaaaaa tacatatcgc tgacttcatg gaatggacat cctgtataag cactgaaaaa 1200 caacaacaca ataacactaa aattttaggc actcttaaat gatctgcctc taaaagcgtt 1260 ggatgtagca ttatgcaatt aggtttttcc ttatttgctt cattgtacta cctgtgtata 1320 tagtttttac cttttatgta gcacataaac tttggggaag ggagggcagg gtggggctga 1380 ggaactgacg tggagcgggg tatgaagagc ttgctttgat ttacagcaag tagataaata 1440 tttgacttge atgaagagaa gcaattttgg ggaagggttt gaattgtttt ctttaaagat 1500 gtaatgtccc tttcagagac agctgatact tcatttaaaa Aaatcacaaa aatttgaaca 1560 ctggctaaag ataattgcta tttattttta Ccaagaagttt attctcattt gggagatctg 1620 gtgatctccc aagctatcta aagtttgtta gatagctgca tgtggetttt ttaaaaaagc 1680 aacagaaacc tatcctcact gcccteccca gtctctetta aagttggaat ttaccagtta 1740 attactcagc agaatggtga tcactccagg tagtttgggg Caaaaatccg aggtgcttgg 1800 gagttttgaa tgttaagaat tgaccatctg cttttattaa atttgttgac aaaattttct 1860 cattttcttt tcacttcggg ctgtgtaaac acagtcaaaa taattctaaa tcectegata 1920 tttttaaaga tctgtaagta acttcacatt aaaaaatgaa atatttttta atttaaagct 1980 tactctgtcec atttatccac aggaaagtgt tatttttaaa ggaaggttca tgtagagaaa 2040 agcacacttg taggataagt gaaatggata ctacatcttt aaacagtatt tcattgcctg 2100 tgtatggaaa aaccatttga agtgtacctg tgtacataac tctgtaaaaa cactgaaaaa 2160 ttatactaac ttatttatgt taaaagattt tttttaatct agacaatata caagccaaag 2220 tggcatgttt tgtgcatttg taaatgctgt gttgggtaga ataggttttc ccetettttg 2280 ttaaataata tggctatgct taaaaggttg catactgagc caagtataat tttttgtaat 2340 gtgtgaaaaa gatgccaatt attgttacac attaagtaat caataaagaa aacttccata 2400 gctaaaaaaa aaaaaaaaaa aa 2422 <210> 626 <211> 3115 <212> DNA <213> Homo sapiens <400> 626 ccaccatatc ggtccecgtat ttcacattga taaggtcctg tttcatttct cgtgacattg 60 ggtagaatga ggatcctgtt ttcaatgggt cgctttaccce tgggactgac agggaggctc 120 tgaccattta gccaccaaat gtaggtgtag ttctcactct taggttcacc ccgcggccga 180 tcgtecececca taccteggece atgcggccecce tgctgetact ggecctgetg ggctggcetge 240 tgctggecga agcecgaaggge gacgccaagce cggaggacaa ccttttagtce ctcacggtgg 300 ccactaagga gaccgaggga ttccgtcgcect tcaagcgctc agetcagttc ttcaactaca 360 agatccaggc gcttggccta ggggaggact ggaatgtgga gaaggggacg tcggcaggtg 420 gagggcagaa ggtccggctg ctgaagaaag ctctggagaa gcacgcagac aaggaggatc 480 tggtcattct cttcacagac agctatgacg tgctgtttgc atcggggccc cgggagctcce 540 tgaagaagtt ccggcaggcc aggagccagg tggtcttctc tgectgaggag ctcatctace 600 cagaccgcag gctggagacc aagtatccgg tggtgtccga tggcaagagg ttcctggget 660 ctggaggctt catcggttat gcccccaacc tcagcaaact ggtggccgag tgggagggcc 720 aggacagcga cagcgatcag ctgttttaca ccaagatctt cttggacccg gagaagaggg 780 agcagatcaa tatcaccctg gaccaccgct geccgtatctt ccagaacctg gatggagcct 840 tggatgaggt cgtgctcaag tttgaaatgg gccatgtgag agcgaggaac ctggcctatg 900 acaccctcec ggtectgatc catggcaacg ggccaaccaa gctgcagttg aactacctgg 960 gcaactacat cccgcgcttc tggacctteg aaacaggctg caccgtgtgt gacgaaggct 1020 tgcgcagcecct caagggcatt ggggatgaag ctctgcccac ggtcctggtc ggecgtgttca 1080 tcgaacagcc cacgcecgttt gtgtcccectgt tcttecageg gctcctgegg ctceccactace 1140 cccagaaaca catgcgactt ttcatccaca accacgagca gcaccacaag gctcaggtgg 1200 aagagttcct ggcacagcat ggcagcgagt accagtctgt gaagectggtg ggccctgagg 1260 tgcggatggec gaatgcagat gccaggaaca tgggcgcaga cctgtgececgg caggaccgcea 1320 gctgcaccta ctacttcage gtggatgctg acgtggccct gaccgagcecc aacagcctgce 1380 ggctgctgat ccaacagaac aagaatgtca ttgcccecget gatgacccgg catgggaggc 1440 tgtggtcgaa cttctggggg gctctcagtg cagatggcta ctatgcccgt tccgaggact 1500 acgtggacat tgtgcagggg cggcgtgttg gtgtctggaa tgtgccctat atttcaaaca 1560 tctacttgat caagggcagt gccctgecggg gtgagctgea gtcctcagat ctcttccacc 1620 acagcaagct ggaccccgac atggccttct gtgccaacat ccggcagcag gatgtgttca 1680 tgttcctgac caaccggcac acccttggee atctgctcte cctagacage taccgcacca 1740 cccacctgca caacgacctc tgggaggtgt tcagcaaccc cgaggactgg aaggagaagt 1800 acatccacca gaactacacc aaagccctgg cagggaagct ggtggagacg ccctgcccgg 1860 atgtctattg gttccccatc ttcacggagg tggcctgtga tgagectggtg gaggagatgg 1920 agcactttgg ccagtggtcet ctgggcaaca acaaggacaa ccgcatccag ggtggctacg 1980 agaacgtgcc gactattgac atccacatga accagatcgg ctttgagcgg gagtggcaca 2040 aattcctgct ggagtacatt gcgcccatga cggagaagct ctaccccgge tactacacca 2100 gggcccagtt tgacctggce tttgtcgtce gctacaagcc tgatgagcag ccctcactga 2160 tgccacacca tgatgcctcc accttcacca tcaacatcgc cctgaaccga gtcgggatyg 2220 attacgaggg cgggggctgt cggttcctge gctacaactg ttccatccga gccccaagga 2280 agggctggac cctcatgcac cctggacgac tcacgcatta ccatgagggg ctccccacca 2340 ccaggggcac ccgctacatc gcagtctcet tcgtegatcc ctaattggecc aggcctgacc 2400 ctcttggacc tttcttettt gccgacaace actgcccagce agcctctggg acctcggggt 2460 cccagggaac ccagtccagce ctcctggetg ttgacttecce attgctcttg gagccaccaa 2520 tcaaagagat tcaaagagat tcctgcaggce cagaggccgg aacacacctt tatggctggg 2580 gctcteegtg gtgttectgga cccagccect ggagacacca ttcactttta ctgctttgta 2640 gtgactcgtg ctctccaacc tgtcttcetg aaaaaccaag gcccccttec cccacctcett 2700 ccatggggtyg agacttgagc agaacagggg cttccccaag ttgcccagaa agactgtcetg 2760 ggtgagaagc catggccaga gcttctceccca ggcacaggtg ttgcaccagg gacttctgct 2820 tcaagttttg gggtaaagac acctggatca gactccaagg gctgccctga gtctgggact 2880 tctgccteca tggcectggtca tgagagcaaa ccgtagtcce ctggagacag ccactccaga 2940 gaacctcttg ggagacagaa gaggcatctg tgcacagctc gatcttctac ttgcctgtgg 3000 ggaggggagt gacaggtcca cacaccacac tgggtcaccc tgtcctggat gcctctgaag 3060 agagggacag accgtcagaa actggagagt ttctattaaa ggtcatttaa accac 3115

<210> 627 <211> 2883 <212> DNA <213> Homo sapiens <400> 627 agatcctgtg gttcactgtg agaccteccge ctctctegtce tgectcacge tgcccccteg 60 : cacccccaag gtatgacggc atttgaacaa tgcacgtgcc catctagagc cttggggtgg 120 gcctgtgaga gagtggccgc ccaccccagt ccccaccagg tgecatagtce tgcggectaag 180 tcagggcggt tgtaacaaag gctcagaccc tccaactacc aggetgtgtt gtgacgagge 240 tgetggagec ccaggcacca tgacgggaat gggtgaatcc acccacagtg ggtgactcte 300 aatgtgatac tagcccggta cacttagaca cccaaaaatc aacgcggcag acgttgtatce 360 cccaggagaa ggacccccce gaacagacac gtgggacaat ggcaagcatg gcecatccctg 420 aggacaatgg caggacccag agtgcctctc tcctcctcaa ggcatgaact ggcccctcca 480 gatacaggga caaccttttc ttcccacctc ggcctgtaac agacacgaca caggccatac 540 ccttggctag agtcactgca acatgatcca gagggtgact gtgaaaggag ccagcggggce 600 tgctgtgteg gttttectgg agacacggaa atgggtacaa acttaaaaca tctgggcaga 660 ggtctttggg ataaagtcca gaaaatcaca gctggctcca tcattcagga attgatttcce 720 cccatgacac catcggatgc aaccttgtcc ctgcecgccte cagectctccect tgatttceccce 780 tctgagctca caaaaagaaa caaaagctca gagaggctga ataactttcc cagcttacac 840 ggaggagctg ggtttgaatc cagacatcac actgatcagc acgcagaccc gcagggtttce 900 atactcttcc ggcatttcac gtacacctct ctccatctca ccgcctcacc ataggaggtg 960 aggcctattc ctatccgcac aatctgacag ggaaattgag actcagagag gttaagtaac 1020 ttgcctaagg ccacataget cgtaatcagg gcagcaggga ttccaggecg agcaggcagg 1080 cccctgatce aggctcectag cctgctgeccc agggaggtca gagctggaaa ccacttccac 1140 agcacaagga gactctgctt ggactgtgct tggcctcacg tgacctctga cctecectgge 1200 cctecctgtga cccoctgacagg tgtgctgage ttcectgaaggg tgggaaggec tgcaagggge 1260 ctgcgtgcat tctgtgtgca tcgacccagg acaccacggt tggtgcctct gagttcatca 1320 cgtcgatcat ccccgtcttc tttctgetca agtacttgat ttgtcaacat gcacagaagg 1380 gtgagacctg gccatggtgc tgcttgaatc ttgttaacag ttaggctctg attcaatagt 1440 ctgggtgggg cccaagactc tgcatttett tttettttct tttttetttt ttgagacgga 1500 gtcttgctct gttgcccagg ctggagtgca gtggtgcaat ctcagctcac tgcaacctec 1560 ccctectggg ttcatgcaat tctcttgect cagecctccca agtagectggg actataggca 1620 378 y cgcgccacca tgectggcecta atttttgtat ttttagtaga gatagggttt caccatgceceg 1680 gccaggetgg tctcaaactc ctgacctcaa gtgatctgcece cgecttggec tcccaaagtg 1740 ctgggattcc aggcatgagc ccccgcaccc gccagactct gcatctctaa agtgctggga 1800 ttccgggtgt gagcccccac gecccgccaga ctctgcatct ctaaagcgct cccagggatg 1860 ctgatgctgc catctggggg accacgcttg gagtactgcg gccctggcaa accatctcett 1920 ccaggaaget gcatcttgcect ctgeccttcet ccecctgeccag cagctcagcce ctgatcatct 1980 ctcacctgag gcccttaaaa gcctcccaat cagcctctct gecccccgacc cccaggcctg 2040 cacccggtee tcteccgcac tgcagecccag cgctgtctaa ctgagcecgacce tgggttacat 2100 ttcagcatcc cccatgtgat tecctgctgt ccacaccagc aagtctctga gtgcaacceg 2160 cagccacgtg catcataatc agctgagctg ctggtgaagg ggtagattcc tgggcctcac 2220 ccctgacaga tcctatccca geccectgegg gaggggccca ggaatgcage cagttcacca 2280 gctgccectge caaagcctgg caatctetgg gecctagagge ttgagaacgg tcaagcagcet 2340 cgccctggcect ccecctgggag ccaccctage ctggaacgct gcacaccaga caggggtagt 2400 agagctcctg gccattccca aatgccccac acccagcagc gcctggaatg tgctcatgcea 2460 ggttcctcgt gacatggaca caccccctte cccatcctac ccacatgtce ccagcccagg 2520 cctcegttecee actcccccag gatgcoccccaa cecctccaagg gaacaaagag aatgctcttce 2580 cctttctcecca gaagcccage acccgggcca catagtcaag cgctttgtct ttgaaacata 2640 aaaatagcta tagaagggct ccgttagctg gcatcggcca gagagagaac atttccatat 2700 aattagagct taccctttca tatggaaagt tagacatttc tctgtctaag gcgcctacgt 2760 agaatatgta atttgacctt ctttggggga aattttggat tgtctttggg atgataatat 2820 aggaaatccc tcgagggctt ttaaaatgta aagaacagag gtcccataaa ctaagtgacc 2880 ccagaatgc 2888 <210>_ 628 <211> 449 <212> DNA <213> Homo sapiens <400> 628 tttttttttt tttttttcaa gcagtaaaat tccatcagaa aagaaaagct ctttagacta 60 gcaatgtatg tatgaggcac ttatgggtta gaaacacatt cactgagaaa catttatttg 120 gaaccttttc tgggctcagc actgagttag gttctaggga ttcggagata aataaaacca 180 gttccagccc tcaaggcact cagggaggca gagacataga gcagcaatca cattccagtg 240 aagaaagtgt caggtgaaag aatggtctgg cagccaataa gggcgctaac gggacctgac 300 cccatgtget ggcccagage acaggcecctg ctctagactg ctttgggttc aaactcttte 360 tcttcactta ctagctgtgt gtccttggge atttttcttg acctctetgt gcctgagttt 420 cctcttctgt aaaatgaaaa ttataacag 449 <210> 629 : <211> 7391 <212> DNA : <213> Homo sapiens <400> 629 gctgcgcage gectggctget ggctggectc gocggagacgc cgaacggacg cggccggcgce 60 cggcttgtgg gctcgeccgec tgcagccatg accctegcag cctgtececte ggecteggece 120 cgggacgtct aaaatcccac acagtcgcgc gcagctgcetg gagagccggce cgctgccccece 180 tcgtcgecge atcacactec cgtceccggga gectgggagca gcgcgggcag ccggcgccce 240 cgtgcaaact gggggtgtct gccagagcag ccccagccge tgcegctget acccccgatg 300 ctggccatgg cctggcgggg cgcagggccg agcegtcccgg — gggcgtceggt 360 ctcagtctgg ggttgctcct gcagttgectg ctgctecetgg ggccagegeg gggcttcgqgg 420 gacgaggaag agcggcgetg cgaccccatc cgcatcteca tgtgccagaa cctcggctac 480 aacgtgacca agatgcccaa cctggttggg cacgagctgc agacggacgc cgagctgecag 540 ctgacaactt tcacaccgct catccagtac ggctgctcca gccagctgca gttcttcecett 600 tgttctgttt atgtgccaat gtgcacagag aagatcaaca tcceccattgg cccatgcggce 660 ggcatgtgtc tttcagtcaa gagacgctgt gaacccgtcc tgaaggaatt tggatttgcc 720 tggccagaga gtctgaactg cagcaaattc ccaccacaga acgaccacaa ccacatgtge 780 atggaagggc caggtgatga agaggtgcce ttacctcaca RAACEIEIac ccagcctggg 840 gaagagtgtc actctgtggg aaccaattct gatcagtaca tctgggtgaa aaggagcctg 900 aactgtgtgc tcaagtgtgg ctatgatgct ggcttataca gcecgctcagce caaggagttc 960 actgatatct ggatggctgt gtgggccage ctgtgtttca tctcecactge cttcacagta 1020 ctgaccttce tgatcgattc ttctaggttt tectaccctg agcgccccat catatttctce 1080 agtatgtgct ataatattta tagcattget tatattgtca ggctgactgt aggccgggaa 1140 aggatatcct gtgattttga agaggcagca gaacctgttc tcatccaaga aggacttaag 1200 aacacaggat gtgcaataat tttcttgctg atgtactttt ttggaatggc cagctccatt 1260 tggtgggtta ttctgacact cacttggttt ttggcagcag gactcaaatg gggtcatgaa 1320 gccattgaaa tgcacagctce ttatttccac attgcagect gggccatcec cgcagtgaaa 1380 accattgtca tcttgattat gagactggtg gatgcagatg aactgactgg cttgtgctat 1440

380 Co gttggaaacc aaaatctcga tgccctcacc gggttcgtgg tggctcccct ctttacttat 1500 ttggtcattg gaactttgtt cattgctgca ggtttggtgg ccttgttcaa aattcggtca 1560 aatcttcaaa aggatgggac aaagacagac aagttagaaa gactgatggt caagattggg 1620 gtgttctcag tactgtacac agttcctgca acgtgtgtga ttgcctgtta tttttatgaa 1680 atctccaact gggcactttt tcggtattct gcagatgatt ccaacatggc tgttgaaatg 1740 ttgaaaattt ttatgtcttt gttggtgggc atcacttcag gcatgtggat ttggtctgcc 1800 aaaactcttc acacgtggca gaagtgttcc aacagattgg tgaattctgg aaaggtaaag 1860 agagagaaga gaggaaatgg ttgggtgaag cctggaaaag gcagtgagac tgtggtataa 1920 ggctagtcag I ttcttcattt tgaagggggg aatgccagca ttttggagga 1980 aattctacta aaagttttat gcagtgaatc tcagtttgaa caaactagca acaattaagt 2040 gacccccegte aacccactgce ctcccacccc gaccccagca tcaaaaaacc aatgattttg 2100 ctgcagactt tggaatgatc caaaatggaa aagccagtta gaggctttca aagctgtgaa 2160 aaatcaaaac gttgatcact ttagcaggtt gcagcttgga gcgtggaggt cctgcctaga 2220 ttccaggaag tccagggcga tactgttttce ccctgcaggg tgggatttga gctgtgagtt 2280 ggtaactagc agggagaaat attaactttt ttaacccttt accattttaa atactaactg 2340 ggtctttcag atagcaaagc aatctataaa cactggaaac gctgggttca gaaaagtgtt 2400 acaagagttt tatagtttgg ctgatgtaac ataaacatct tctgtggtgc gctgtcetgct 2460 gtttagaact ttgtggactg cactcccaag aagtggtgtt agaatctttc agtgcctttg 2520 tcataaaaca gttatttgaa caaacaaaag tactgtactc acacacataa ggtatccagt 2580 ggatttttet tctctgtctt cctetcttaa atttcaacat ctcectcttett ggetgetget 2640 gttttcttca ttttatgtta atgactcaaa aaaggtattt ttatagaatt tttgtactgc 2700 agcatgctta aagaggggaa aaggaagggt gattcacttt ctgacaatca cttaattcag 2760 aggaaaatga gatttactaa gttgacttac ctgacggacc ccagagacct attgcattga 2820 gcagtgggga cttaatatat tttacttgtg tgattgcatc tatgcagacg ccagtctgga 2880 agagctgaaa tgttaagttt cttggcaact ttgcattcac acagattagc tgtgtaattt 2940 ttgtgtgtca attacaatta aaagcacatt gttggaccat gacatagtat actcaactga 3000 ctttaaaact atggtcaact tcaacttgca ttctcagaat gatagtgcct ttaaaaattt 3060 ttttattttt taaagcataa gaatgttatc agaatctggt ctacttagga caatggagac 3120 tttttcagtt ttataaaggg aactgaggac agctaatcca actacttggt gcgtaattgt 3180 ttcctagtaa ttggcaaagg ctccttgtaa gatttcactg gaggcagtgt ggcctggagt 3240 atttatatgg tgcttaatga atctccagaa tgccagccag aagectgatt ggttagtagg 3300 gaataaagtg tagaccatat gaaatgaact gcaaactcta atagcccagg tcttaattgce 3360 ctttagcaga ggtatccaaa gcttttaaaa tttatgcata cgttcttcac aagggggtac 3420 ccccagcage ctctcgaaaa ttgcacttct cttaaaactg taactggcect ttctettace 3480 ttgccttagg ccttctaatc atgagatctt ggggacaaat tgactatgtce acaggttget 35490 ctccttgtaa ctcatacctg tctgcttcag caactgcttrt gcaatgacat ttatttatta 3600 attcatgcct taaaaaaata ggaagggaag cttttttttt tctttttttt tttttcaate 3660 acactttgtyg gaaaaacatt tccagggact caaaattcca aaaaggtggt caaattctgg 3720 aagtaagcat ttcctctttt ttaaaaattt ggtttgagcc ttatgcccat agtttgacat 3780 ttcecctttet tetttecttt ttgtttttgt gtggttcttg agctctctga catcaagatg 3840 catgtaaagt cgattgtatg ttttggaagg caaagtcttg gcttttgaga ctgaagttaa 39500 gtgggcacag gtggcccctg ctgctgtgec cagtctgagt accttggcta gactctaggt 3960 caggctccag gagcatgaga attgatcccc agaagaacca ttttaactcce atctgatact 4020 ccattgccta tgaaatgtaa aatgtgaact cectgtgetg cttgtagaca gttcccataa © 4080 ctgtccacgg ccctggageca cgcacccagg ggcagagect gcccttactc acgetctgcet 4140 ctggtgtctt gggagttgtg cagggactct ggcccaggca ggggaaggaa gaccaggcgg 4200 taggggactg gtcttgctgt tagagtatag aggtttgtaa tgcagttttce ttcataatgt 4260 gtcagtgatt gtgtgaccaa ggcagcatct agcagaaagc caggcatgga gtaggtgatc 4320 gatacttgtc aatgactaaa taataacaat aaaagagcac ttgggtgaat ctgggcacct 4380 gatttctgag ttttgagttc tggagctagt gttttgacaa tgectttgggt tttgacatgce 4440 } cttttccaca aatctcttge cttttcaggg caaagtgtat ttgatcagaa gtggccattt 4500 ggattagtag ccttagcaat gctacagggt rataggeete tecectttcaca ttccagacaa 4560 tggagagtgt ttatggtttc aggaaaagaa ctttgtggct gaggggtcag ttaccagtga 4620 ccttcaatca actccatcac ttcttaaatc ggtatttgtt aaaaaaatca gttattttat 4680 ttattgagtg ccgactgtag taaagccctg aaatagataa tctectgttet tctaactgat 4740 ctaggatggg gacgcaccca ggtctgctga actttactgt tectetggga aaggagcagg 4800 gacctctgga attcccatct gtttcactgt ctccattcca taaatctctt cctgtgtgag 4860 ccaccacacc cagcctgggt ctctctactt ttaacacatc tctcatcect tteccaggat 4920 tccttccaag tcagttacag gtggttttaa cagaaagcat cagctctgct tcgtgacagt 4980 ctctggagaa atcccttagg aagactatga gagtaggcca caaggacatg ggcccacaca 5040 tctgetttgg ctttgcegge aattcaggge ttggggtatt cceatgtgact tgtataggta 5100 tatttgagga cagcatcttg ctagagaaaa ggtgagggtt gtttttcttt ctctgaaacc 5160 tacagtaaat gggtatgatt gtagcttcct cagaaatccc ttggcctcca gagattaaac 5220 atggtgcaat ggcacctctg tccaacctcc tttctggtag attcctttct cctgcttcat 5280 ataggccaaa cctcagggca agggaacatg ggggtagagt ggtgctggcc agaaccatct 5340 gcttgagcta cttggttgat tcatatcctce tttcctttat ggagacccat ttcctgatct 5400 ctgagactgt tgctgaactg gcaacttact tgggcctgaa actggagaag gggtgacatt 5460 tttttaattt cagagatgct ttcetgatttt cctctcccag gtcactgtct cacctgcact 5520 ctccaaactc aggttccggg aagcttgtgt gtctagatac tgaattgaga ttctgttcag 5580 caccttttag ctctatactc tctggctccc ctcatcctca tggtcactga attaaatgct 5640 tattgtattg agaaccaaga tgggacctga ggacacaaag atgagctcaa cagtctcagc 5700 cctagaggaa tagactcagg gatttcacca ggtcggtgca gtatttgatt tctggtgagg 5760 tgaccacagc tgcagttagg gaagggagcc attgagcaca gactttggaa ggaacctttt 5820 ttttgttgtt tgtttgtttg tttgtttgtt tgtttgtttg agacagggtc ttgctctgtc 5880 acccaggctg gggcgcaatg gcacgatctt ggctcactgc aacctctgce tcectgggttce 5940 aagtgattct cctgccacag cctcctgagg agctgggact acaggtgcgt gctaccacgce 6000 ccagctactt ctgtattttt agtagagacg gggtttcact gtgttggcca ggctggtctce 6060 gaactcctga cctcatgate tgecccgecte agectcccaa agtgectggga ttacaagtgt 6120 gagccaccac acctggcecctg gaaggaacct cttaaaatca gtttacgtct tgtattttgt 6180 tctgtgatgg aggacactgg agagagttgc tattccagtc aatcatgtcg agtcactgga 6240 ctctgaaaat cctattggtt cctttatttt atttgagttt agagttccct tctgggtttg 6300 tattatgtct ggcaaatgac ctgggttatc acttttcctc cagggttaga tcatagatct 6360 tggaaactcc ttagagagca ttttgctcct accaaggatc agatactgga gccccacata 6420 atagatttca tttcactcta gcctacatag agctttctgt tgctgtctct tgccatgceac 6480 ttgtgcggtg attacacact tgacagtacc aggagacaaa tgacttacag atcccccgac 6540 atgcctctte cccttggcaa getcagttge cctgatagta gecatgtttct gtttctgatg 6600 tacctttttt ctcttcttct ttgcatcagec caattcccag aatttcccca ggcaatttgt 6660 agaggacctt tttggggtcc tatatgagcc atgtcctcaa agcttttaaa cctccttget 6720 ctcctacaat attcagtaca tgaccactgt catcctagaa ggcttctgaa aagaggggca 6780 agagccactc tgcgccacaa aggttgggte catcttctct ccgaggttgt gaaagttttce 6840 aaattgtact aataggctgg ggccctgact tggctgtggg ctttgggagg ggtaagctgce 6900 tttctagatc tctcccagtg aggcatggag gtgtttctga attttgtceta cctcacaggg 6960 atgttgtgag gcttgaaaag gtcaaaaaat gatggcccct tgagctcttt gtaagaaagg 7020 tagatgaaat atcggatgta atctgaaaaa aagataaaat gtgacttcecc ctgctectgtg 7080 cagcagtcgg getggatget ctgtggectt tettgggtcece tcatgccacc ccacagctce 7140 aggaaccttg aagccaatct gggggacttt cagatgtttg acaaagaggt accaggcaaa 7200 cttcctgcta cacatgccct gaatgaattg ctaaatttca aaggaaatgg accctgcttt 7260 taaggatgta caaaagtatg tctgcatcga tgtctgtact gtaaatttct aatttatcac 7320 tgtacaaaga aaaccccttg ctatttaatt ttgtattaaa ggaaaataaa gttttgtttg 7380 ttaaaaaaaa a 7391 <210> 630 <211> 1310 <212> DNA <213> Homo sapiens <400> 630 agacgccgag atgctggtca tggcgcccceg aaccgtcctce ctgctgetect cggcggccct 60 ggccctgacc gagacctggg ccggctccca ctccatgagg tatttctaca cctececgtgtce 120 ccggeccgge cgcggggagce cccgcttcat ctcagtggge tacgtggacg acacccagtt 180 cgtgaggttc gacagcgacg ccgcgagtcc gagagaggag ccgcgggcegce cgtggataga 240 gcaggagggg ccggdagtatt gggaccggaa cacacagatc tacaaggccce aggcacagac 300 tgaccgagag agcctgcgga acctgcgcgg ctactacaac cagagcgagg ccgggtctca 360 caccctccag agcatgtacg gctgegacgt ggggccggac gggegcctcec tccgegggcea 420 tgaccagtac gcctacgacg gcaaggatta catcgccctg aacgaggacce tgcgetcectg 480 gaccgccgcg gacacggegg ctcagatcac ccagcgcaag tgggaggegg cccgtgagge 540 ggagcagecgg agagcctacc tggagggcga gtgcgtggag tggctccgeca gatacctgga 600 gaacgggaag gacaagctgg agcgcgctga ccccccaaag acacacgtga cccaccacce 660 catctctgac catgaggcca ccctgaggtg ctgggccctg ggtttctacc ctgeggagat 720 cacactgacc tggcagcggg atggcgagga ccaaactcag gacactgagc ttgtggagac 780 cagaccagca ggagatagaa ccttccagaa gtgggcagcet gtggtggtgc cttctggaga 840 agagcagaga tacacatgcc atgtacagca tgaggggctg ccgaagcccc tcaccctgag 900 atgggagccg tcttcccagt ccaccgtcce catcgtggge attgttgetg gectggetgt 960 cctagcagtt gtggtcatcg gagctgtggt cgctgctgtg atgtgtagga ggaagagttc 1020 aggtggaaaa ggagggagct actctcaggc tgegtgcagc gacagtgccc agggctctga 1080 tgtgtctcte acagcttgaa aagcctgaga cagctgtctt gtgagggact gagatgcagg 1140 atttcttcac gectcceett tgtgacttca agagcctctg gcatctecttt ctgcaaagge 1200 acctgaatgt gtctgcgtce ctgttagecat aatgtgagga ggtggagaga cagcccacce 1260 ttgtgtccac tgtgacccect gttcgcatgc tgacctgtgt ttcctcccca 1310 <210> 631 <211> 320 <212> DNA <213> Homo sapiens <400> 631 gcggggctca tgcccagtca cttcggaaac gagagcgcge ccaccaccag caactggaac 60 tacacccacg cgctegtege cgacgggacg ccgtattacg tctcecggegt geggggegtyg 120 tacaagccgt ccgacacgtt ttegttcacg ctcgtcgect acaacgggtg gaacgccctce 180 ggaaacccga acccgtacaa gtcgggtggg tatcgegtcg ALYEERICE CagIgEERTy 240 gtggccgtceg ccaacgecge gcacgtcgge atcgtcgggt ctacaaggac cttcgcatcet 300 tcgaagacct ggtggtcacc 320 <210> 632 <211> 1281 <212> DNA <213> Homo sapiens <400> 632 cccagaccta gaactaccca gagcaagacc acagctggtg aacagtccag gagcagacaa 60 gatggagaca aattcctctc tccccacgaa catctctgga gggacacctg ctgtatctgce 120 tggctatctc ttectggata tcatcactta tctggtattt gcagtcacct ttgtcctcegg 180 ggtcctggge aacgggcttg tgatctgggt ggetggattc cggatgacac acacagtcac 240 caccatcagt tacctgaacc tggcegtggc tgacttctgt ttcacctcca ctttgccatt 300 cttcatggtc aggaaggcca tgggaggaca ttggccttte ggctggttcc tgtgcaaatt 360 cgtctttacc atagtggaca tcaacttgtt cggaagtgtc ttcctgatecg cectcattge 420 tctggaccge tgtgtttgeg tcectgcatcec agtctggacc cagaaccacc gcaccgtgag 480 cctggccaag aaggtgatca ttgggccetg ggtgatgget ctgctcctca cattgccagt 540 tatcattcgt gtgactacag tacctggtaa aacggggaca gtagcctgca cttttaactt 600 ttcgecectgg accaacgacc ctaaagagag gataaatgtg gccgttgcca tgttgacggt 660 gagaggcatc atccggttca tcattggctt cagcgcaccce atgtccatcg ttgctgtcag 720 ttatgggctt attgccacca agatccacaa gcaaggcttg attaagtcca gtegtcecctt 780 acgggtcctc tcctttgtcg cagcagectt ttttctctge tggtccccat atcaggtggt 840 ggcccttata gccacagtca gaatccgtga gttattgcaa ggcatgtaca aagaaattgg 900 tattgcagtg gatgtgacaa gtgccctgge cttcttcaac agctgcctca accccatgcet 960 ctatgtettc atgggccagg acttccggga gaggctgatc cacgceccttc ccgeccagtcet 1020 ggagagggcc ctgaccgagg actcaaccca aaccagtgac acagctacca attctacttt 1080 accttctgca gaggtggagt tacaggcaaa gtgaggaggg agctggggga cactttegag 1140 ctcccagete cagcttcgtc tcaccttgag ttaggctgag cacaggcatt tcctgcttat 1200 tttaggatta cccactcatc agaaaaaaaa aaaaaagcct ttgtgtcccc tgatttgggg 1260 agaataaaca gatatgagtt t 1281 <210> 633 <211> 2298 <212> DNA <213> Homo sapiens <400> 633 cgagcggttc tcacccgeece tctecgcacg tcecgccggeg cctcaggttt cccccggaca 60 gttgctgtgc gacttggaca gtagaggagc gcctcccaag ttttcatcca actgecaacce 120 ccaaagcttc cacccttcte ccctcagaga ggacgtttga tgccgggccc cttgagaggce 180 tcattgacaa gcctgcccct ctgggtccce ctgagcagag cctgctgacc caattgccca 240 cctttgcgge tttgatgect agccatgtct gectcatcct caggeggctc ccccaggttt 300 ccatcgtgtg ggaagaacgg agtaacgagt ctcacgcaga aaaaggtctt gagagcacct 360 tgtggcgcac ccagtgtaac tgtgacgaaa tctcacaagc gaggaatgaa aggggacact 420 gtgaatgtgc ggcggagtgt ccgggtgaaa accaagaatc cacctcattg cctggagatc 480 acgccaccat cttcagaaaa gctggtctca gtgatgcggt taagtgacct ctctacagaa 540 gatgatgact caggtcactg taaaatgaac cgttatgata agaagattga tagtctaatg 600 aatgecggttg gttgtctgaa gtctgaggtc aagatgcaaa aaggtgagcg ccagatggcce 660 aaaaggttcc tggaggaacg gaaggaagad ctggaggagg tggcccacga actggctgag 720 actgagcacg agaacacggt gttgaggcac aacatcgagc gcatgaagga ggagaaggac 780 ttcaccatac ttcagaagaa acacctacaa caggagaagg agtgcctcat gtccaagctg 840 gtggaggcgg aaatggatgg ggctgcggct gccaagcagg tcatggectt gaaggatacce 900 atcgggaagc tgaaaacgga gaaacaaatg acctgcacgg acatcaacac cctgacaagg 960 cagaaggaac ttctcctgca gaagctgagc acatttgagg agaccaaccg caccctccga 1020 gacctcctga gggaacagca ctgcaaagag gattctgaaa gactaatgga gcaacaagga 1080 gcactgctga aacggctgge ggaggccgac tcagagaaag cgcgcctget gttactgetg 1140 caagacaagg acaaggaggt ggaagagctc cttcaggaaa tacaatgtga gaaggctcaa 1200 gcaaagacag cctctgagct ttctaaatcc atggagtcca tgcgtgagca tttgcaggca 1260 cagcttcggt ccaaagaggce tgagaacagt cgcctgtgca tgcagattaa gaatctggag 1320 c¢gcagcggga atcagcataa ggcagaagtg gaggccatca tggagcaget gaaggagttg 1380 aagcagaagg gagaccgaga caaagagagc ttgaagaagg ccatccgage ccagaaggag 1440 ¢gagccgaga agagcgagga gtatgctgag cagctacacg tgcaactcge tgacaaggat 1500 ctttatgtcg ctgaagcttt atccactctg gaatcctgga ggagccgcta caaccaagtt 1560 gtaaaagaaa agggagacct tgagctggaa attattgtcc tgaatgaccg ggtaacagat 1620 cttgtaaacc aacaacaaac cctggaggag aagatgcggg aagaccggga tagcctggtg 1680 gagagactac accgtcagac tgctgagtat tcecgecattca agctggagaa tgagaggctg 1740 aaggccagct ttgctccaat ggaggacaaa Ctcaaccagg cacacctcga ggtccagcag i800 ctgaaggcct cagtgaagaa ctatgagggg atgattgaca actataagag tcaggtgatg 1860 aagaccagat tggaggctga tgaagtagct gcccagctag aacgctgtga caaagagaac 1920 aagatcctta aagatgagat gaacaaagag attgaggcgg cacgaaggca gttccagtcet 1980 ’ cagctggctg acctgcagca getccctgac atcctgaaga tcacggaggc gaagctgget 2040 gagtgccaag accaactgca dgggctatgag cggaagaaca tcgacctcac agccatcata 2100 tcagacctge gcagccgggt aagggactgg cagaaagggt cccacgaact gacccgagca 2160 ggggccecgca taccaagatg agctgcacgce cccccaaggg aggactactt cctttttcectt 2220 ggctgctget ttttaaaagg agtgagctat catcagtgct gtgaaataaa agtctggtgt 2280 gccaaaaaaa aaaaaaaa 2298 <210> 634 <211> 359 <212> DNA <213> Homo sapiens <400> 634 tttttttttt tttttttttt ttttttttet tttttttttt taaaacaaaa agggctttat 60 taaaaccccc aaaaaaaact tttaacaaaa ggggacccat accattcccc aaaaaagttt 120 agctgaaaaa tggcaaacaa aaagggcaag gcttttttta aaccecccaaa aataaggttc 180 Cacaaaaaag gacccgccaa aaccaaatta tagcggcaaa ttttttttgg ccataaatag 240 ggatcccctt aaaaatcett ggaaactcect tggcagtttt aaggcccaaa ctaacccttg 300 tgggccagtg gctcaccttc atcaaaaaaa ggaacccatt tggcaaaaaa attttggtt 359

<210> 635 <211> 240 <212> DNA <213> Homo sapiens <400> 635 cgtcttcgac aagaccggca ccctcaccaa gggggagecec gaggtcacgg acgtcattgt 60 cggcgacttc gatcgcgatc gggtcctgge gectcgeggge gcactcgaac gagagtccga 120 acatcctctc gectcaggeeg tcgtgecgcca cgtcgatgca accgatgtgc cgcgcttgceg 180 cgccacegeg ttcecgcaacg tcacgggcat cggcgeecte gccgaggtceg acggccacca 240 <210> 636 <211> 498 . <212> DNA <213> Homo sapiens ) <220> <221> misc_feature <222> (384) ..(489) <223> n is a, ¢, g, t or u <400> 636 tgccctteoee ttcocgectggag agceccccttt cceccctttee tgecctcttcc ccatggcccce 60 gagcatcttc cagcagaccce cagtgtatga cteccttecta cctccccaaa gaatggggag 120 agggaacgag cagagcctgt gcctgagcca tctegttcaa cgecttcaac gecggggettg 180 gagtcctgge ttggcactcc cttgctggtg atcttgggca aaccatgctg ggcctcgatt 240 ttcctactgg caccagagag agcaggacga cttcttcaaa ttcttgtgca aatacggcga 300 gaagaagtgc atgagaaagt gctttataag ctgtatagct ctcttgccta tgagagtatc 360 attgtagttc atctcacata accnnnnnnn nNNNNNONNN NNNNNDONNN NNnONNQNNNnn 420 NNNNNNNNNN NNNNNNNNNNn nnonnnnnnn nonnnonnninn nnnnonnnnn nnnnnnnnnn 480 nnnnnnnnnc agaggaaa : 498 <210> 637 <211> 443 <212> DNA <213> Homo sapiens <400> 637 tttttttttg gaagagatct ttattaatag agtgctttta ttaataattc ataccttgtc 60 taagcggtaa aaacccagca gaggattaac ccatgcccat ggtatttgaa actataaaga 120 ataaagtttt ctcctgtatt tgttaggaat tgctcttgge tgcaagtaac agagaactga 180 aataacagtc atttaacaca agacacaaat ttctttctgt ctcatgtaaa agaaacccaa 240 gcagcagtcc tgggccccca agtatcatca gtgactgtgg ctccttettt ctttctgatc 300 tgccatcecte caagtggggt ttccaccctc acagtcacct caagatgcaa gaacactgct 360 ggtgctccag ccattgcgtc tgcatccgca gcagaaaact ggaggaagcg ccatttgtct 420 ctcceccaaa ctteccectta cat 443 <210> 638 <21l1l> 450 <212> DNA <213> Homo sapiens <400> 638 caccttgaga gagcactttg cagatgactc taatgaacaa tccttgaaca aagaatttta 60 aaagatttaa tctagttcat aacacagctt tatagctata gataagtcat ttaagccttc 120 tgagccttat cagtcaaaga ggaatgttaa tatgtaatag gaaatgaaga attggtgaaa 180 atactttgtg aaagaaacat aactttaaga tagtactata tctgaatccc ttgctgttcce 240 ctatatggtg ccttacacat cataagccag caaatacctt ggtctgattg aatggtaatg 300 ggatatattt tattaaaatc aaagttttgc tagggctggg aagctctacc aaaagaagaa 360 aaaattatct ttcttggtca tgtttccctc tttactccac gacagtttca ttattgtaac 420 cagggatcaa tgaaagaaga aagcagggtt 450 <210> 639 <211l> 1048 <212> DNA <213> Homo sapiens <400> 639 gccaggtgtg caggccgctc caagcccage ctgecceget geccgecacca tgacgctcecct 60 ccceggecte ctgtttetga cectggectgeca cacatgcctg geccaccatg accectecct 120 cagggggcac ccccacagtc acggtaccecc acactgctac tcggctgagg aactgccccet 180 €ggccaggcec cccccacacce tgctggctcg aggtgccaag tgggggcagg ctttgectgt 240 agccetggtg tccagectgg aggcagcaag ccacaggggg aggcacgaga ggccctcage 300 tacgacccag tgcccggtge tgcggcecgga ggaggtgttg gaggcagaca cccaccagceg 360 ctccatctca ccctggagat accgtgtgga cacggatgag gaccgctatce cacagaagcet 420 ggccttcgee gagtgcctgt gcagaggctg tatcgatgca cggacgggcc gcgagacagc 480 tgcgctcaac tcegtgegge tgctccagag cctgectggtg ctgecgecgec ggccctgete 540 ccgcgacggce tcggggctce ccacacctgg ggectttgec ttccacaccg agttcatcca 600 cgtceccecgtc ggetgcacct gegtgetgec ccgttcagtg tgaccgeccga ggccgtgggg 660 cccctagact ggacacgtgt gctccccaga gggcaccecc tatttatgtg tatttattgt 720 tatttatatg cctecccccaa cactaccctt ggggtctggg cattcecccgt gtcectggagga 780 cagcccccca ctgttctcct catctccage ctcagtagtt gggggtagaa ggagctcage 840 acctcttcca gcecttaaag ctgcagaaaa ggtgtcacac ggctgcctgt accttggctce 900

: cctgtectge teceggcttce ccttacccta tcactggect caggcccecg caggctgect 960 cttceccaacc tccttggaag tacccctgtt tcttaaacaa ttatttaagt gtacgtgtat 1020 tattaaactg atgaacacat ccccaaaa 1048 <210> 640 <211> 633 <212> DNA <213> Homo sapiens <400> 640 tttttttttt ttttttttac ataactagaa taaaatttaa tgtaaatgtg ccaaagagga 60 gaagaaatca catgagattt acaaaactta catgaaataa gaaaatgttc agctatgtaa 120 taaccaaagc ttccttaact tgggaatctt gggaacctag aaagtgaggt aacccaagcc 180 aaattcctct ggtgtcacag ttcctectat accaggecag gcacttgcca atgacactgg 240 agtaggggta agccctgggt gtgttgtgta gtgtgtgacg tagtaggtga aaaacagcaa 300 agaggtaatt ctttattctc gagagcttcc tegtgcacat gatcagcttt tgcacatget 360 tgaaggaaaa acaacactat taaaatgtct ttttaaaagt caaagctaaa tgagtatgca 420 ataaagcttt gagaaatgga aaagaaaatc tatgaggaaa acgtcagctt gcttatccag 480 ggaatgagca ggacttaatt ctcatgccgg catggggctg ccgggcacce agctecttte 540 ctgtgggtag aaaacaagtc cccaagttgc tactgagcca aactgtaaag gccagtcagg 600 aaatgagcag cagtgctgaa tgggcctcgt gcc 633

<210> 641

<211> 306

<212> DNA

<213> Homo sapiens

<400> 641 gacactgtcc aaaggttttc catcctgtcc tggaatcaga gttggaagct gaggagcttc 60 agcctctttt atggtttaat ggccacctgt tctctcctgt gaaaggcttt gcaaagtcac 120 attaagtttg catgacctgt tatccctggg geectattte atagaggctg gcectattag 180 tgatttccaa aaacaatatg gaagtgcctt ttgatgtctt acaataagag aagaagccaa 240 tggaaatgaa agagattggc aaaggggaag gatgatgcca tgtagatcct gtttgacatt 300 tttatg 306

390

<210> 642 <«211> 2311 <212> DNA <213> Homo sapiens <400> 642 tagccagaaa agggggcggg aagggctgta gggtacttgt caattcgeccg ccatgaacgt 60 ggtttttgct gtgaagcagt acatttccaa aatgatagag gacagcgggc ctggtatgaa 120 agtacttctc atggataaag agacgactgg catagtgagt atggtataca cacaatcgga 180 gattctacag aaggaagtgt acctctttga acgcattgat tctcaaaatc gagagatcat 240 gaaacacctg aaggcaattt gttttcttcg acctacaaag gagaatgtgg attatattat 300 tcaggagctc cgaagaccca aatacactat atatttcatt tatttcagta atgtgatcag 360 caagagtgac gtgaagtcat tggctgaagc tgatgaacag gaagttgtgg ctgaggttca 420 ggaattttat ggtgattaca ttgctgtgaa cccacatttg ttttccctca atattttggg 480 ttgctgccag ggtcgaaatt gggatccage ccagctatct agaacaactc aagggcettac 540 agctctceccett ttatctctga agaagtgtcce catgattcgt tatcagctct catcagagge 600 agcaaagaga cttgcagagt gcgttaagca agtgataact aaagaatatg aactgtttga 660 attccgtcgg acagaggttc ctccattgect cecttatttta gatcgctgtg atgatgccat 720 caccccattg ctaaaccagt ggacatatca ggccatggtc cacgaactac taggcataaa 780 caacaatcgg attgatcttt ccagagtgcc gggaatcagt aaagacttaa gagaagtggt 840 cctatctget gaaaatgatg aattctatgce taataatatg tacctgaact ttgctgagat 900 tggtagcaat ataaagaatc tcatggaaga ttttcagaag aagaaaccaa aagaacagca 960 aaaactagaa tcaatagcag acatgaaggc gtttgttgag aattatccac agttcaagaa 1020 aatgtctggg actgtttcaa agcatgtgac agtggttgga gaactgtctc gattggtcag 1080 tgaacggaat ctgctggagg tttcagaggt tgagcaagaa ctggcctgtc aaaatgacca 1140 ttctagtgct ctccagaata taaaaaggct tctgcagaac cccaaagtga cagagtttga 1200 tgectgccecge ctggtgatge tttatgecttt acattatgag cgacacagca gcaatagcct 1260 gccaggacta atgatggacc tcaggaataa aggtgtttct gagaagtatc gaaagctcgt 1320 gtctgcagtt gttgaatatg gtggtaaacg agtcagagga agtgacctct tcagccccaa 1380 agatgctgtg gctatcacca aacaattcct caaaggactg aagggagtag aaaatgtata 1440 tacacagcat caacctttcc tacatgaaac cctggatcat ctcatcaaag gaaggcttaa 1500 ggaaaaccta tatccttatt taggccccag cacactcaga gacagacctc aggatatcat 1560 tgtgtttgta attggaggag ccacctatga agaggctcta acagtttata acctgaaccg 1620 caccactcct ggagtgagga ttgtcctggg aggcaccaca gtgcacaaca cgaaaagttt 1680 cctagaggaa gttctggcett ctggactgca cagccgaagce aaggagagct ctcaagtcac 1740 atcaaggtca gcgagcagaa gatgaaacgg tggttggggg aagggcacag cttcctctct 1800 tgtccccact acaggtttte cctactaaac aaaggtgttg gagagcagct ttgggttctg 1860 tgctagttgt tagaactcat ctccaggtag cccacggata cgtggttgge acagacacaa 1920 gactcccaga gttgtcctaa caataagtct gagcccatct caacccactt ttcteccggta 1980 gtctttatgt atctgttagc acaatcactt cagttactga tgaattttgt tgggatctga 2040 cttggggaaa gggttatcag agcctagagg ggcttaaaaa gtaatcattt gatgtacata 2100 ccacactcct tggcttcctt tctcttcect taacccttte tgecttttcat taaccacatt 2160 cctgcacaac tcatttctga aaacctacca tgtttcttta cagagccatc caaaaatttt 2220 ttgtcectac atagcaattt tctgtggcac tgagaaacca tgtatgacca caataaaaat 2280 ccattttgtg aaaggaaaaa aaaaaaaaaa a 2311 <210> 643 <21l> 329 <212> DNA <213> Homo sapiens <400> 643 ttcttgggat gaggtccaaa tttactaata aggcctgaaa ccctgtgtaa ttttgctcct 60 agttatggct ggcatctgca ccacaactac agccactgcc acctccccecct gccacacaca 120 cattttaaaa gtaacaatag tagtgttttc tgtgttttge atatacagtc ttttctcatc 180 tcccagectt cttgagettt tcctctgect gagatacgct cccactcaca tagacattgg 240 gggcactaaa taaaaatagc tgtttaattg aattggaatc gttccacttg gaacccaagt 300 ttggaaattt tgctacttct tagttaagct 329 <210> 644 <211> 373 <212> DNA <213> Homo sapiens <400> 644 ttttettttt ttctgtttat attataatct ttattgcatc tgatggtect gtctcatttt 60 tgctgtctca tcagtaaacc attgcaaacc acagtgccag cccttgtgtce cccacatttt 120 tgacacaata atttcctcca ggtgtggctg agtcagaatt cecgtccgegt ccatccetgt 180 gcgtcctgta tgggtgacag tgcaagggta agaacagtgg gtgtattcag tggggaaata 240 acatgtgtgc tgtgaaagaa aatgagaaaa acacagcgtc tccattaaaa aactgtatgt 300 cctcgagtee acaaaagagt tggaaaaaaa ccactcgggc catctgggca tctgttcaga 360 tgaacgatct tgt 373 <210> 645 <211> 351 <212> DNA <213> Homo sapiens <400> 645 cacagtcaca cctcagggtg agccagctct gcaataggat gcactgecttt gtctgcagcec 60 tcacagacct gaaatgcact ctcatgtcct gtgcctcagt gctggctggg ccttggtcect 120 attacatctt gaactcaagg taatacatca gtggccggga ttcacactca gaaccacctt 180 gaaagtctgt gctgttacca ccatgtcaca gaggtagaag tagatgtctg tataaacaac 240 ctttgggtag caggtggtca gttaggcagg aaaaatagtt ctgctacatt atatatatca 300 ggagtatatt gacaggaaca tgtgtgttgg gaatatatat gtcagtaaca g 351 <210> 646 <21l> 4692 <212> DNA <213> Homo sapiens <400> 646 agaatggaag agctcctgtc cggtgtgcca gcagcccgga ctggcggtga gcgcgaggga 60 ggctactgag aagcccggcg acggaggaac gcaggtctge tgccagggat tgaggagact 120 gaagaacgct gaagacaggc tgatgggctc agctggtagg ctccactatc tcgccatgac 180 tgctgaaaat cccactcctg gagacctgge tccggcccce ctcatcactt gcaaactctg 240 cctgtgtgag cagtctctgg acaagatgac cacactccag gaatgccagt gcatcttttg 300 cacagcttgc ctgaaacagt acatgcagct ggcaatccga gaaggatgtg ggtctcccat 360 cacttgccect gacatggtgt gcctaaacca cgggaccctg caggaagctg agattgcctg 420 tttggtacct gtggaccagt ttcaacttta tcagaggtta aaatttgaaa gagaagttca 480 tctggacccc taccgaacat ggtgtcctgt tgcagactgt cagacagtgt gccctgttge 540 ctcgagtgac ccaggacagc ctgtgctggt ggaatgccct tcttgeccacc tgaaattctg 600 ctcgtgttge aaggatgcett ggcatgcaga ggtctcctgt agagacagtc agcctattgt 660 cctgeccaaca gagcaccgag ccctctttgg gacagatgca gaagccccca ttaagcagtg 720 cccagtttgc cgggtttata tcgaacgcaa tgaaggctgc gctcagatga tgtgcaaaaa 780 ctgcaagcat acattttgct ggtactgcct ccagaacttg gataatgaca ttttcctcag 840 acattatgac aaagggccat gcaggaataa acttggccac tcaagagcat cagtgatgtg 900 gaaccgaaca caggtggtgg ggattcccgt aggcttgggce atcattgcecct tggttacttce 960 acccttgtta ctecctggect ccccatgtat aatctgttgt gtctgcaagt cctgtcgggg 1020 caagaagaaa aagcacgace catccacaac ctaaagatct crgtgttcat acgccccaga 1080 tatgtgagtt acatgagatg gcacagtgat aaagcccecat ttagtgacct tgcctceettc 1140 recttgccaa ctttgaaagt gcctccgtgt ccagactttg aacttgcctg ccagecttca 1200 gcatcaggaa aggccaagte ctgggtgtga gtgttcetgt gtaacaagaa ctgggctcaa 1260 cggtccagcet gtttctatad agctttgggds ttccttgaga tgaatgaaca tatcatttta 1320 tcatccaaag gatctcactg gactgttcaa ctteccagcecea aattcaagga gcttgeggga 1380 acatttgata taacaaatgt gttgtcattg ttggcaacat acaagataac caagaagctg 1440 gagtctgtte tgtgttgatt tgactaccat gagaaacaca ggggaaacct gatgaggaga 1500 aggataagac tgcgtaagga gaaatcctca taggagctat aaagcagget gctgatctea 1560 gcagttgata tggtggttgt gcctetgetd gctactgggt gtgctgtece catgttcccd 1620 ctgtgatttg gcagaaacac aataggcttc rccttgtatg atctcagcett caagcaggtg 1680 aaactgctgt gcagagggag ttgccccttce ccagtaaaag agttgcagec tgttaaacaa 1740 tgtggtctaa tttagtgtct ctcecttggc aaatgtaagt trtctaagtt ggccaacttg 1800 tectettacag ccagtggctdg tggtctacag aattgtttca rataaaatac gggtagagtg 1860 gtagagtttc aaaactttcg tcatagatat ctgggacctt tctcaggatc tgtgttcgcea 1920 cagccaatag atttggaatc aggcctaaga gtacacatgg agggtaaata ttaaagtgcd 1980 tattatgtac atctagaatc catgtgactt gcagcectace tgtaatttct atccattgag 2040 catgcatgga tatacccaat agtacacaca aaataaatgt ttacttaaga gccattctat 2100 cctrttgtga ctgaaatggt trattgtaaa tctgectaaa gattttttgc atattatata 2160 tgtgaatttt ggttgtaagt tcataactta cccaagggta tagactcata COCELELRS 2220 aacagtgett agtacaatat cotgecatcet ctgtaaaaac gctaattgat aaccgagtca 2280 tttacatgtt ttcgaacaca gaatagctct tttctcagcea tcattattgc tctttcagca 2340 tctgttagga cagtctgaat actttctgtt tcaaggcact gataaaaccg caacaaaaac 2400 atgtaagaaa taaaatagaa gtgctttata rattttagtt taaatttatg tatcacctca 2460 ttgtgactta trtrttccat tataccatta gtcagatttg aataacgadg tcttgaaags 2520 ataaaacctt ttctccaatg acaggattat ataattgcta ttggcaatgt agcctggtac 2580 ttcatgagac ctatgctaaa tgttactgga gagttcttga agccagggat accatatcag 2640 gaactattca ggatctatga tattttctga ggtaactggs taatagaata tcaaattgct 2700 gctatctcgg acctattgtt aaaggacgat gctttgeeta tgtaatagga ratatcctaa 2760 gtagggatgt gtatatttea ggaactttaa rtcacaagta tatattgata tctgatgtgt 2820 gtatagtaca tctgttggtt atgtacattt taatttacat gttgtgtaga acatagatga 2880 gaactctggg aaaacttggg aatggcaacc aaccaaaatc atttttaatc atttattaga 2940 aatttctcaa tattgtgtct ttttcttttg aaactctaaa cacttcagaa aaaaacacta 3000 tcagtgtagt tcatgttagt ataattatag atttacatat atttgaatag ttaatttgct 3060 ttgttttaca cgtagcccac tgcctcatta taggtaaaag gcatttataa ctgctcaggg 3120 gattacgaga actcaactga aactgaattt ttgtaacaag aatgttaata gtggcaaagt 3180 cctctgtcag taaactcttt aagcttggtg ccgcaaagag tctttaaatg ggggctgatt 3240 tcaagtaacc taaaagactg tgttatcaga ggaagaggtc ccaaatttgg agtaaagatg 3300 ggagaaaata aatatgtgct atttccttgg cgagttgggt gaatttgcca ccttacagag 3360 tttgtatcac tgaattagct gecttttgttt tttttttttt ttttttttge cagggctatg 3420 gagtgggggt tgtttgtcaa actgattttc aataattgga tttaattttt tttaacattg 3480 aaaagtgcct gaaaaatggt aaattcttaa atgtgtgtga gattgtcaga atcaacaaaa 3540 ctaggttggt taaacatatc tctggtacat caaggggcat gatacaaacc agtctaaaga 3600 ctgtttataa aggagagagc tggcgactta tttttatttt ttttttttgg acagagtctc 3660 cctttgtcac ccaggccgga gtgcagtgge atgatcatgg ttcacttcaa cccctacctc 3720 ctgggctcaa gtgttcctet caccttatce tcctgagcag ctgggactac aggcacacac 3780 caccacacct ggctaagttt tgtatttttt gtagagatgg ggtttctctg tgttgeceag 3840 tcttgtctca aactcctggg ctcaagegat ctacccacct tgggctccca aagtgtcggg 3900 attacaggtg tgtgtcactg tgcctgacag ctgacagttt taactgacaa ctttgataac 3960 agaggctgct atttttgttt tagataattg gccagtgaca gagtttaccc ttgcctcctt 4020 tcttggtctg ccagctttgt cctttctgag tgattctctt tctgtattga gaggaagtgt 4080 gggtctacat agggatgttt ggatgctatg gcaagaatct ttttgtgttt ggagtgtagt 4140 ccatttgcaa tagaaataaa aaaatccgtc accaaattgt aacctggatg ttatagccca 4200 gcatctagaa atcctatgaa atgtattagc acaatatctt gccattgtcc catctaggaa 4260 attttttctt gttgtgaggt agggaagtga ggaggaaagc catgccgaag caaatgttag 4320 aatcttaggc atcctatttg ttcatgccat gggtatttgc tttggacttg gagtctgtac 4380 tttgaaagag gcctttgaaa aacaaataat tctgtgtgaa ttttcttgta gcgtgcttca 4440 tgaaaatatc tacttatcca ggtttgcaaa tgtacatgtt catttgaatg taaatcacca 4500 tttcttggaa ccccacgttt tttcttaaaa attattctga attaaatgta tatttcttta 4560 gccttecocta cacagtacta ataaaagact tttctttctg ttcaaaaaaa aaaaaaaaaa 4620 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aagaaaaaaa 4680 aaaaaaaaaa aa 4692 <210> 647 <211> 1991 <212> DNA '<213> Homo sapiens <400> 647 cttgctccga gagggagtcece tcgeggacgt cagccaagat tccagaatga ctatcttgac 60 ttacceccttt aaaaatcttc ccactgcatc aaaatgggcc ctcagatttt ccataagacc 120 tctgagctgt tcctcccage tacgagcectge cccagcetgtc cagaccaaaa cgaagaagac 180 gttagccaaa cccaatataa ggaatgttgt ggtggtggat ggtgttcgca cteccattttt 240 getgtctgge acttcatata aagacctgat gccacatgat ttggctagag cagcgcttac 300 gggtttgttg catcggacca gtgtccctaa ggaagtagtt gattatatca tctttggtac 360 agttattcag gaagtgaaaa caagcaatgt ggctagagag gctgcccttg gagctggctt 420 . ctctgacaag actecctgcte acactgtcac catggcttgt atctctgcca accaagccat 480 gaccacaggt gttggcttga ttgcttctgg ccagtgtgat gtgatcgtgg caggtggtgt 540 tgagttgatg tccgatgtcc ctattcgtca ctcaaggaaa atgagaaaac tgatgcttga 600 tctcaataag gccaaatcta tgggccageg actgtcttta atctctaaat tccgatttaa 660 tttcctageca cctgagctce ctgcggttte tgagttctcc accagtgaga ccatgggcca 720 ctctgcagac cgactggeccg ctgcctttge tgtttcetegg ctggaacagg atgaatatgc 780 actgcgctct cacagtctag ccaagaaggc acaggatgaa ggactccttt ctgatgtggt 840 acccttcaaa gtaccaggaa aagatacagt taccaaagat aatggcatcc gtccttcctce 900 actggagcag atggccaaac taaaacctgc attcatcaag ccctacggca cagtgacagc 960 tgcaaattct tctttcttga ctgatggtge atctgcaatg ttaatcatgg cggaggaaaa 1020 ggctctggce atgggttata agccgaaggc atatttgagg gattttatgt atgtgtctea 1080 ggatccaaaa gatcaactat tacttggacc aacatatgct actccaaaag ttctagaaaa 1140 ggcaggattg accatgaatg atattgatgc ttttgaattt catgaagctt tctegggtca 1200 gattttggca aattttaaag ccatggattc tgattggttt gcagaaaact acatgggtag 1260 aaaaaccaag gttggattgc ctcctttgga gaagtttaat aactggggtg gatctctgtc 1320 : cctgggacac ccatttggag ccactggctg caggttggtc atggctgctg ccaacagatt 1380 acggaaagaa ggaggccagt atggcttagt ggctgcgtgt gcagctggag ggcagggcca 1440 tgctatgata gtggaagctt atccaaaata atagatccag aagaagtgac ctgaagttte 1500 tgtgcaacac tcacactagg caatgccatt tcaatgcatt actaaatgac atttgtagtt 1560 cctagctect cttaggaaaa cagttcttgt ggccttctat taaatagttt gcacttaagce 1620 cttgccagtg ttctgagctt ttcaataatc agtttactgc tctttcaggg atttctaagce 1680 caccagaatc tcacatgaga tgtgtgggtg gttgtttttg gtctctgttg tcactaaaga 1740 ctaaatgagg gtttgcagtt gggaaagagg tcaactgaga tttggaaatc atctttgtaa i800 tatttgcaaa ttatacttgt tcttatctgt gtcctaaaga tgtgttctct ataaaataca 1860 aaccaacgtg cctaattaat tatggaaaaa taattcagaa tctaaacacc actgaaaact 1920 tataaaaaat gtttagatac ataaatatgg tggtcagcgt taataaagtg gagaaatatt 1980 ggaaaaaaaa a 1991 <210> 648 <211> 2811 <212> DNA . <213> Homo sapiens <400> 648 . acacaggaag ctgagccggc ttggggccca gcatacacag gcccccagga cccctgggga 60 gagggccceg ctgggctggce cctgcaggga ccatggaatc cagagctgaa gggggctccc 120 ctgctgtgtt tgattggttc ttcgaagcgg cctgecctge ctccctgcag gaggatcccc 180 ccatecctgcg gcagttccct ccagacttca gggaccagga agctatgcag atggtgccta 240 aattctgctt cccttttgat gtggaaaggg agccccccag ccccgeccgtg cagecatttca 300 ccttecgeecet cacagacctt geccggcaacc gcagatttgg tttctgccge ctgcgggcgg 360 gtacccagag ctgtctctge atcctcagcc acctgeccttg gttcgaggtg ttttacaage 420 tattgaacac agtgggagac ctcctagccc aggaccaagt caccgaggca gaggaacttc 480 ttcaaaatct gtttcagcag tcectgtctg ggccccagge ctcagtgggg cttgagcectgg 540 gcagcggagt gacggtctcc agecgggcagg gtatccccece ccctacccgg gggaatagca 600 agccgcettte ctgcecttegtg geccceggact ccggeccgect gecatccatc cctgagaaca 660 ggaacctaac ggagctggtg gtggccgtga ctgacgagaa catcgtgggg ctgttegegg 720 cgctcctgge cgagagaaga gtcctgctca ccgccagcaa actcagcacce ctgacctcegt 780 gcgtccacge gtcctgegeg ctcctgtace ccatgegetg ggagcacgtg ctgatcccca 840 cgctgececce acacctgctg gactactgct gcgcgcccat gccctaccte attggagtge 900 acgccagtct cgccgagaga gtacgagaaa aagccctgga ggacgtcgtg gtgctgaacg 960 tggacgccaa taccttggag acgaccttta acgacgtgca ggcgctgcct ccagacgtgg 1020 tgtccctget gaggctcecgg ctcaggaagg tcgccctgge ccccggggaa ggggtgtcec 1080 gtctctteet caaagcccag geccctgctect tcggggggta ccgcgacgca ctcgtctgea 1140 gcccgggcca gccagtgacce ttcagtgagg aagtcttctt ggcccagaag cctggggcac 1200 ctctgcagge cttccaccgg cgggctgtgc acctgcagct gttcaaacag ttcatcgaag 1260 cccggctgga gaagctcaac aagggggagg gcttctcaga tcaattcgag caggagatca 1320 ctggctgcgg ggcctccecca ggggeccttc gatcctatca gctctgggcc gacaatctaa 1380 agaaaggtgg tggcgccctc ctgcactcag tcaaggccaa gacccaacca gccgtcaaga 1440 acatgtaccg ctcggccaag agtggcttga agggggtgca gagccttcta atgtataagg 1500 atggggactc tgtcctgcag aggggggget ctctgaggge cccagecctc cccageceget 1560 cagaccgcct gcagcaacgc ctcccaatca ctcagcactt tggaaagaac cggccccttce 1620 gccccagcag gagacgccag ctggaagagg gaacttccga gcccccaggg geggggacac 1680 ccccactgag ccctgaggat gaggggtgcc cgtgggcaga agaagctctg gacagcagcet 1740 tcttggggtc tggagaagaa ctggatttgt tgagcgagat tctggacagt cttagcatgg 1800 gagccaagag cgcaggcagc ctgagaccga gccagagttt agactgctgt cacagaggag 1860 acctggacag ctgcttcagc ctgcccaaca tactaagatg gcaaccagac gataagaaac 1920 taccagagcc ggagccccag cccctttece tgeccatcecct gcaaaatgec tcgtctttgg 1980 atgccaccag ctcttcaaag gactccaggt cccagctgat accctcagag tccgaccaag 2040 aagtcacgtc tccatcccag tcctcaacag cttctgcaga cccaagcatc tggggggacce 2100 ccaaaccctc tcctctcaca gagcccctaa ttcttcatct caccecttcec cacaaggcag 2160 ctgaagattt tacagcccag gaaaacccca ctccctgget ctccactgca cccactgagce 2220 ccagccctcc agaaagcccec caaattctgg cccccacaaa gcccaacttt gatatagcct 2280 ggacgtccca geccccttgat ccttcecctcag accccagtte tctggaggac cccagagcecce 2340 ggecctcccaa agccctgetg gcagagegeg ctcacctcca gccacgggag gaaccaggag 2400 ccctgaatte ccctgctaca cccaccagca actgtcaaaa gtcccagccc agcaagccdgg 2460 cccagagtcg ctgatcttaa gaagtgcttt gagggttaag aatcaggggt ccaagagaga 2520 ccccagtccc tcaataaagec cacaagagcc caaaaaagct ggtttttttc ctggtgaatt 2580 tctctggtge cctcactctg ctcggaaatc catcccaccc acctctgtcecc ctccaagggce 2640 agcctctcta actggctcct agcagggaat tccaggaage ctcctggtcet tctagaatcce 2700 tggcaacctt acaattcctc tcggcatttg tcacttccat ctcagctaat gcacccacca 2760 gctcaaacac accaataaag cttttgttac tctcaaaaaa aaaaaaaaaa a 2811 <210> 649

<211l> 2315

<212> DNA :

<213> Homo sapiens <400> 649 ttttttcctg tttctctgca gttttcctca gctttgggtg gtggccgcetg ccgggcatceg 60 gcttccagte cgcggagggce gaggcggegt ggacagegge cccggecacce agcgccccge 120 cgcccgcaag ccgcgcgecce gtccgeccgeg ccccgagcecc gccgecttect atctcagcgce 180 cctgccgeccg ccgccgcggce ccagcgagceg gcectgatge agdgccatcaa gtgtgtggtg 240 gtgggagacg gagctgtagg taaaacttgce ctactgatca gttacacaac caatgcattt 300 cctggagaat atatccctac tgtctttgac aattattctg ccaatgttat ggtagatgga 360 aaaccggtga atctgggctt atgggataca gctggacaag aagattatga cagattacgc 420 ccecectatecct atccgcaaac agatgtgttc ttaatttgcet tttceccttgt gagtcctgca 480 tcatttgaaa atgtccgtgc aaagtggtat cctgaggtgc ggcaccactg tcccaacact 540 cccatcatce tagtgggaac taaacttgat cttagggatg ataaagacac gatcgagaaa 600 . ectgaaggaga agaagctgac tcccatcacc tatccgcagg gtctagccat ggctaaggag 660 attggtgctg taaaatacct ggagtgctcg gcgctcacac agcgaggcct caagacagtg 720 tttgacgaag cgatccgagc agtcctctge ccgeccteccecg tgaagaagag gaagagaaaa 780 tgcectgetgt tgtaaatgtce tcagcccctc gttcttggtc ctgtcecttg gaacctttgt 840 acgctttget caaaaaaaaa caaaaaaaaa aaacaaaaaa aaaaaacaac ggtggagcct 900 tcgcactcaa tgccaacttt ttgttacaga ttaatttttc cataaaacca ttttttgaac S60 caatcagtaa ttttaaggtt ttgtttgttc taaatgtaag agttcagact cacattctat 1020 taaaatttag ccctaaaatg acaagccttc ttaaagcctt atttttcaaa agcgcccccce 1080 ccattcttgt tcagattaag agttgccaaa ataccttctg aactacactg cattgttgtg 1140 ccgagaacac cgagcactga actttgcaaa gaccttcgtc tttgagaaga cggtagcttce 1200 tgcagttagg aggtgcagac acttgctctc ctatgtagtt ctcagatgcg taaagcagaa 1260 cagcctcccg aatgaagcgt tgccattgaa ctcaccagtg agttagcagce acgtgttccc 1320 gacataacat tgtactgtaa tggagtgagc gtagcagctc agctctttgg atcagtcttt 1380 gtgatttcat agcgagtttt ctgaccagct tttgcggaga ttttgaacag aactgctatt 1440 tcctctaatg aagaattctg tttagctgtg ggtgtgcegg gtggggtgtg tgtgatcaaa 1500 ggacaaagac agtattttga caaaatacga agtggagatt tacactacat tgtacaagga 1560 atgaaagtgt cacgggtaaa aactctaaaa ggttaatttc tgtcaaatgc agtagatgat 1620 gaaagaaagg ttggtattat caggaaatgt tttcttaagc ttttecectttc tcttacacct 1680 gccatgcctec cccaaattgg gcatttaatt catctttaaa ctggttgttc tgttagtcgc 1740 taacttagta agtgcttttc ttatagaacc ccttectgact gagcaatatg cctcettgta 1800 ttataaaatc tttctgataa tgcattagaa ggtttttttg tcgattagta aaagtgcttt 1860 ccatgttact ttattcagag ctaataagtg ctttccttag ttttctagta actaggtgta 1920 aaaatcatgt gttgcagctt tatagttttt aaaatatttt agataattct taaactatga 1980 accttcttaa catcactgtc ttgccagatt accgacactg tcacttgacc aatactgacc 2040 ctctttacct cgcccacgcg gacacacgcec tcctgtagtc gectttgecta ttgatgttcee 2100 tttgggtctg tgaggttctg taaactgtgc tagtgctgac gatgttctgt acaacttaac 2160 tcactggcga gaatacagcg tgggaccctt cagccactac aacagaattt tttaaattga 2220 cagttgcaga attgtggagt gtttttacat tgatcttttg ctaatgcaat tageattatg 2280 ttttgcatgt atgacttaat aaatccttga atcat 2315 <210> 650 <211> 636 <212> DNA «213> Homo sapiens <400> 650 ggcaacaccce tgtgataatt ccaggtgatt ctctacatct gcagcttgag gtgggaagtc 60 tgaagctcag agagcctggg ccaatggtac aggtcacaca gcacatcagt ggctacatgt 120 gagctcagac ctgggtctge tgctgtctgt cttcccaata tccatgacct tgactgatgce 180 aggtgtctag ggatacgtcc atcceccgtcc tgetggagcc cagagcacgg aagcctggec 240 ctccgaggag acagaaggga gtgtcggaca ccatgacgag agcttggcag aataaataac 300 ttctttaaac aattttacgg catgaagaaa tctggaccag tttattaaat gggatttctg 360 : ccacaaacct tggaagaatc acatcatctt agcccaaggt gaaaactgtg ttgcgtaaca 420 aagaacatga ctgcgctcca cacatacatc attgcccggc gaggcgggac acaagtcaac 480 gacggaacac ttgagacagg cctacaactg tgcacggttc aaaagcaggt ttaagccata 540 cttgctgcag tgagactaca tttctgtcta aagaagatgt ccctgacttg atctgttttt 600 caactccagt tcccagatgt gegtgttgtg gtcccec 636 <210> 651

<211> 886

<212> DNA

<213> Homo sapiens

<400> 651 gtcggtteceg ggcgttacca tcgtcoccgtge gcaccgcccg gegtccaggt gagtctccca 60 tctgcagaga cgcggacgcg ccggcccgca gttggectge ggagegeggt ggacggtttg 120 gcgcccacca gdcgatcaat actttggatt tttaatttct agatttggca attcttcgct 180 gaagtcatca tgagcttttt ccaactcctg atgaaaagga aggaactcat tcccttggtg 240 gtgttcatga ctgtggcggc gggtggagcc tcatcttteg ctgtgtattc tctttggaaa 300 accgatgtga tccttgatcg aaaaaaaaat ccagaacctt gggaaactgt ggaccctact 360 gtacctcaaa agcttataac aatcaaccaa caatggaaac ccattgaaga gttgcaaaat 420 gtccaaaggg tgaccaaatg acgagccctc gecctctttcect tctgaagagt actctataaa 480 tctagtggaa acatttctgc acaaactaga ttctggacac cagtgtgcgg aaatgcttct 540 gctacatttt tagggtttgt ctacattttt tgggctctgg ataaggaatt aaaggagtgc 600 agcaataact gcactgtcta aaagtttgtg cttattttct tgtaaatttg aatattgcat 660 attgaaattt ttgtttatga tctatgaatg tttttcttaa aatttacaaa gctttgtaaa 720 ttagattttc tttaataaaa tgccatttgt gcaagatttc tcaaagatta ggtatatatt 780 taaatggaag agaaaatatt tttatgggag aaaaatacat ttgaaccatg aaatttcatc 840 ttttaaataa catccagtac agatatctgt gtaaaaaaaa aaaaaa 886 <210> 652 <211> 7686 <212> DNA <213> Homo sapiens <400> 652 tttatagcag cagcagaaat ataccaccct agaggacaca cctcctttta gctaggtacce 60 tataaatgtc caggattttc tattcaattg agaagaaccc agcaaaatgg ggatctccac 120 agtcatcctt gaaatgtgtc ttttatgggg acaagttcta tctacaggtg ggtggatccc 180 aaggactaca gactacgctt cactgattce CLogaaggty ccecttggatec aaactgtage 240 agaaggttct ccatttccct cggagtcgac cctggagtca actgcagcag aaggttctce 300 gatttccttg gagtcaaccc tggagtcaac tgtagcagaa ggttctctga ttccctcaga 360 gtcaaccctg gagtcaactg tagcagaagg atctgattct ggtttggccc tgaggctggt 420 gaatggagat ggcaggtgtc agggccgagt ggagatccta taccgaggct cctggggcac 480 cgtgtgtgat gacagctggg acaccaatga tgccaacgtg gtctgtaggc agctgggttg 540 tggctgggec atgtcagctc caggaaatgc ctggtttggc cagggctcag gacccattgce 600 cctggatgat gtgcgctgct caggacacga atcctacctg tggagctgcc cccacaatgg 660 ctggctctece cataactgtg gecatggtga agatgctggt gttatctgct cagctgccca 720 gcctcagtca acactcagge cagaaagttg gcctgtcagg atatcaccac ctgtacccac 780 agaaggatct gaatccagtt tggccctgag gctggtgaat ggaggcgaca ggtgtcgagg 840 ccgagtggag gtcctatacc gaggctcctg gggcaccgtg tgtgatgact actgggacac 900 caatgatgcc aatgtggtct gcaggeaget gggctgtggce tgggccatgt cagccccagg 960 aaatgcccag tttggccagg gctcaggacc cattgtcctg gatgatgtge gotgctcagg 1020 acacgagtcc tacctgtgga gctgccecca caatggctgg ctcacccaca actgtggeca 1080 tagtgaagac gctggtgtca tctgctcagc tccccagtec cggccgacac ccagcccaga 1140 tacttggccg acctcacatg catcaacagc aggacctgaa tccagtttgg ccctgaggct 1200 ggtgaatgga ggtgacaggt gtcagggccg agtggaggtc ctataccgag gctcctgggg 1260 caccgtgtgt gatgatagct gggacaccag tgacgccaat gtggtctgcc ggcagctggg 1320 ctgtggctgg gccacgtcag ccccaggaaa tgcccggttt ggccagggtt caggacccat 1380 tgtcctggat gacgtgcgct gctcaggcta tgagtcctac ctgtggagct gcccccacaa 1440 tggctyygcte tcccataact gtcagcacag tgaagacgct ggtgtcatct getcagetge 1500 ccactcctgg tcgacgccca gtccagacac gttgecgacc atcaccttac ctgcatcgac 1560 agtaggatct gaatccagtt tggccctgag gctggtgaat ggaggtgaca ggtgtcaggg 1620 ccgagtggag gtcctatacc gaggctcctg gggcaccgtg tgtgatgaca gctgggacac 1680 caatgatgcc aatgtggtct gcaggcagct gggctgtgge tgggccatgt tggccccagg 1740 aaatgcccgg tttggtcagg gctcaggacc cattgtcctg gatgacgtgc gctgctcagg 1800 gaatgagtce tacttgtgga gctgccccca caatggetgg ctctcccata actgtggcca 1860 tagtgaagac gctggtgtca tctgctcagg acctgaatcce agtttggccc tgaggctggt 1920 gaatggaggt gacaggtgtc agggccgagt ggaggteccta taccgaggct cttggggcac 1980 cgtgtgtgat gacagctggg acaccaatga tgccaatgtg gtctgcaggce agctgggctg 2040 tggctgggcc atgtcagccc caggaaatgc ccggtttggt cagggctcag gacccattgt 2100 cctggatgat gtgecgctget caggacatga gtectacctg tggagctgcec ccaacaatgg 2160 ctggctctec cacaactgtg gccatcatga agatgctggt gtcatctgct cagctgccca 2220 gtccecggteg acgcccaggc cagacacgtt gtcgaccatc acgttacctce catcgacagt 2280 aggatctgaa tccagtttga ccctgaggct ggtgaatgga agtgacaggt gtcagggecg 2340 agtagaggtc ctataccgag gctcctgggg caccgtgtgt gatgacagcet gggataccaa 2400 tgatgccaat gtggtctgca ggcagctggg ctgtggetgg gccatgtcag ccccaggaaa 2460 tgceceggttt ggccagggct caggacccat tgttctggat gatgtgcgct gctcaggaca 2520 cgagtcctac ctgtggagct gcccccacaa tggctggctc tcccacaact gtggccatca 2580 tgaagatgct ggtgtcatct gctcagtttc ccagtcccgg ccgacaccca gtccagatac 2640 ttggccgacc tcacatgcat caacagcagg atctgaatcc agtttggcce tgaggetggt 2700 gaatggaggt gacaggtgtc agggccgagt ggaggtccta taccgaggct cctggggcac 2760 cgtgtgtgat gatagctggg acaccagtga cgccaatgtg gtctgcecgge agctgggetg 2820 tggctgggee acgtcagccc caggaaatgc ccggtttggc cagggttcag gacccattgt 2880 cctggatgac gtgcgctget caggctatga gtcctacctg tggagctgec cccacaatgg 2940 ctggctctce cataactgtc agcacagtga agacgctggt gtcatctgct cagctgccca 3000 ctcetggteg acgeccagte cagacacatt geccgaccatc accttgecctg catcgacagt 3060 aggatctgaa tccagtttgg ccctgaggect ggtgaatgga ggtgacaggt gtcagggccg 3120 agtggaggtc ctataccaag gctcctgggg caccgtgtgc gatgacagct gggacaccaa 3180 tgatgccaat gtcgtctgca ggcaaccggg ctgtggctgg gccatgtcag ccccaggaaa 3240 tgcceggttt ggtcaggget caggacccat tgtcctggat gatgtgcget gctcaggaca 3300 cgagtcttac ccgtggagct gceccccacaa tggctggctc tcccacaact gtggccatag 3360 tgaagacgct ggtgtcatct gctcagcttc ccagtcccgg ccaacaccta gtccagacac 3420 ttggccaacc tcacatgcat caacagcagg atctgaatcc agtttggeccc tgaggctggt 3480 gaatggaggt gacaggtgtc agggccgagt ggaggtccta taccgaggct cctggggcac 3540 ’ cgtgtgtgat gactactggg acaccaatga tgccaatgtg gtttgcaggc agctgggctg 3600 tggctgggcc atgtcagccc caggaaatge ccggtttggce cagggttcag gacccattgt 3660 cctggatgat gtgcgectgcet caggacatga gtcctatctg tggagctgcec cccacaatgg 3720 ctggctcteec cacaactgtg gccatcatga agacgctggt gtcatctget cagcttccca 3780 gtcccagcecg acacccadcc cagacacttg gccaacctca catgcatcaa cagcaggatc 3840 tgaatccagt ttggccctga ggctggtgaa tggaggtgac aggtgtcagg gccgagtgga 3900 ggtcctatac cgaggctect ggggcaccgt gtgtgatgac tactgggaca ccaatgatgc 3960 : caatgtggtt tgcaggcagc tgggctgtgg ctgggccacg tcagccccag gaaatgcccg 4020 gtttggccag ggttcaggac ccattgtcct ggatgatgtg cgectgctcag gacatgagtce 4080 ctatctgtgg agctgccccc acaatggctg gctctcccac aactgtggcc atcatgaaga 4140 cgetggtgte atctgetcag cttcccagtc ccagccgaca cccagcccag acacttggcce 4200 aacctcacat gcatcaacag caggatctga atccagtttg gccctgaggce tggtgaatgg 4260 aggtgacagg tgtcagggcc gagtggaggt cctataccga ggctcctggg gcaccgtgtg 4320 tgatgactac tgggacacca atgatgccaa tgtggtttgc aggcagctgg gctgtggctg 4380 ggccacgtca gccccaggaa atgccecggtt tggccagggt tcaggaccca ttgtcctgga 4440 tgatgtgcge tgctcaggac atgagtccta tctgtggagce tgcccccaca atggctggct 4500 ctcccacaac tgtggccatc atgaagacgc tggtgtcatc tgctcagctt cccagtccca 4560 gccgacacce agcccagaca cttggceccaac ctcectcgtgca tcaacagcag gatctgaatc 4620 cactttggcc ctgagactgg tgaatggagg tgacaggtgt cgaggccgag tggaggtccet 4680 ataccaaggc tcctggggca ccgtgtgtga tgactactgg gacaccaatg atgccaacgt 4740 ggtctgcagg cagctgggct gtggctgggc catgtcagcc ccaggaaatg cccagtttgg 4800 ccagggetea ggacccattg tcctggatga tgtgcgctge tcaggacacg agtcttacct 4860 gtggagctgc ccccacaatg gctggctctcec ccacaactgt ggccatcatg aagatgctgg 4920 tgtcatctge tcagctgctc agtcccagtc aacgcccagg ccagatactt ggctgaccac 4980 caacttaccg gcattgacag taggatctga atccagtttg gctctgaggc tggtgaatgg 5040 aggtgacagg tgtcgaggcc gagtggaggt cctgtatcga ggctcctggg gaaccgtgtg 5100 tgatgacagc tgggacacca atgatgccaa tgtggtctgc aggcagctgg gctgtggctg S160 ggccatgtcg gccccaggaa atgccceggtt tggcecaggge tcaggaccca ttgtcctgga 5220 tgatgtgcgc tgctcaggga atgagtccta cctgtggagc tgecccccaca aaggectggcet 5280 cacccacaac tgtggccatc acgaagacgc tggtgtcatc tgctcagcca cccaaataaa 5340 ttctactacg acagattggt ggcatccaac aactacaacc actgcaagac cctcttcaaa 5400 ttgtggtgge ttettattct atgccagtgg gacattctcc agcccatcect accctgcata 5460 ctaccccaac aatgctaagt gtgtttggga aatagaagtg aattctggtt atcgcataaa 5520 cctgggcttec agtaatctga aattggaggce acaccataac tgcagttttg attatgttga 5580 aatctttgat ggatcattga atagcagtct cctgctgggg aaaatctgta atgataccag 5640 gcaaatattt acatcttctt acaaccgaat gaccattcac tttcgaagtg acatcagttt 5700 ccaaaacact ggctttttgg cttggtataa ctccttccca agcgatgcca ccttgaggtt 5760 ggtcaattta aattcatcct atggtctatg tgccgggcgt gtagaaattt accatggtgg 5820 cacctggggg acagtttgtg atgactcctg gaccattcag gaagctgagg tggtctgcag 5880 acagctaggg tgtggacgtg cagtttcagc ccttggaaat gcatattttg gctctggctce 5940 tggccccatc accctggacg atgtagagtg ctcagggacg gaatccactc tctggcagtg 6000 ccggaaccga ggctggttct cccacaactg taatcatcgt gaagatgctg gtgtcatctg 6060 ctcaggaaac catctatcga cacctgctec ttttctcaac atcacccgtc caaacacaga 6120 ttattcctge ggaggcttcce tatcccaacc atcaggggac ttttccagcec cattctatce 6180 cgggaactat ccaaacaatg ccaagtgtgt gtgggacatt gaggtgcaaa acaactaccg 6240 tgtgactgtg atcttcagag atgtccagct tgaaggtggc tgcaactatg attatattga 6300 agttttcgat ggcccctacc gcagttccecc tctcattget cgagtttgtg atggggccag 6360 aggctcctte acttcttcct ccaacttcat gtccattcgc ttcatcagtg accacageat 6420 cacaaggaga gggttccggg ctgagtacta ctccagtccc tccaatgaca gcaccaacct 6480 gctctgtctg ccaaatcaca tgcaagccag tgtgagcagg agctatctcc aatccttggg 6540 cttttctgeec agtgaccttg tcatttccac ctggaatgga tactacgagt gtcggcccca 6600 gataacgccg aacctggtga tattcacaat tccctactca ggctgeggca ccttcaagca 6660 ggcagacaat gacaccatcg actattccaa cttcctcaca gcagctgtct caggtggcat 6720 catcaagagg aggacagacc tccgtattca cgtcagctgc agaatgcttc agaacacctg 6780 ggtcgacacc atgtacattg ctaatgacac catccacgtt gctaataaca ccatccaggt 6840 cgaggaagtc cagtatggca attttgacgt gaacatttcc ttttatactt cctcatcttt 6900 cttgtatcct gtgaccagcc gcccttacta cgtggacctg aaccaggact tgtacgttca 6960 ggctgaaatc ctccattetg atgctgtact gaccttgttt gtggacacct gecgtggcatce 7020 accatactcc aatgacttca cgtctttgac ttatgatcta atccggagtg gatgcgtgag 7080 ggatgacacc tacggaccct actcctegee gtctcttecge attgecccget tccggttcag 7140 ggccttccac ttectgaacc gcecttccecte cgtgtacctg cgttgtaaaa tggtggtgtg 7200 cagagcgtat gacccctctt cccgectgecta ccgaggetgt gtgttgaggt cgaagaggga 7260 tgtgggctcc taccaggaaa aggtggacgt cgtcctgggt cccatccage tgcagacccce 7320 cccacgccga gaagaggagc ctcggtaggt ggtcgctctc agaccccact gtccaccggg 7380 gcgcagaccc ctgactcggg gacttgggat gttcctcttg gtgtcatatt ccaactcaga 7440 ttgagcccta cattgtgctg cacctggtca tacggagttg aatcagacct ggttcccgcc 7500 tccceccaagg ctcatggtcce ttggaggacc cgttgcaggg cgaggtcaag agagttctga 7560 cctggatggc ccatagacct gacgtcccag aatccatgct tctcatctgc aaaatgaaaa 7620 tgtcaatact tacttcttag cactgttgag agggttactt acataaagga attttggtga 7680 aactgc 7686 <210> 653 <211> 506 <212> DNA <213> Homo sapiens <400> 653 ctctttcgect caggcccgtg gcgccgacag gatgggcaag tgtegtggac ttegtactge 60 taggaagctc cgtagtcacc gacgagacca gaagtggcat gataaacagt ataagaaagc 120 tcatttgggc acagccctaa aggccaaccc ttttggaggt gcttctcatg caaaaggaat 180 cgtgctggaa aaagtaggag ttgaagccaa acagccaaat tctgccatta ggaagtgtgt 240

TTT.

aagggtccag ctgatcaaga atggcaagaa aatcacagcc tttgtaccca atgacggttg 300 cttgaacttt attgaggaaa atgatgaagt tctggttgct ggatttggtc gcaaaggtca 360 tgctgttggt gatattcctg gagtccgett taaggttgtc aaagtagcca atgtttctcet 420 tttggcecta tacaaaggca agaaggaaag accaagatca taaatattaa tggtgaaaac 480 actgtagtaa taaattttca tatgcc 506 <210> 654 - <211> 2952 <212> DNA <213> Homo sapiens <400> 654 ggcgcggtcg agtcatcgca gggcectcacce gcttcecgttet ccecgtecccte ceccgegectt 60 ggctcgacta gccaagtgag gcgggaggcg actcggacct ttccctgcat ttegtttegg 120 ccagtgcecgg ggctaccege cctggggect gggatccttg gggeccegtga gccactctta 180 gcggecgggg ctaccgegge cegeegtgge cctcatgagg catagcectgac caagcetgetg 240 gcagcctcgg gcagcaactc cccaacccge agtgagagcc cggagcecggc tgcaacttgt 300 tcgctgecect ctgacctgac ccgggcectgca gcgggggagg aggagacgge ggcggcgatce 360 tceccggecge aagcagcagt ttggcgacga aggagagttg gaagccggga gggggagccg 420 cggcggcegtg gcegtgcgeg cgccctcecce cgaggagatg gaggaggagg cgatcgccag 480 cctcccgggg gaagagacgg aggatatgga ctttectgtct gggctggaac tggcggatct 540 cctggaccce aggcaaccgq actggcacct ggaccccggg cttagctcgce cggggcectct 600 ctcectegtect ggcggagget cggatagcgg cggcecctgtgg agaggggacg atgacgatga 660 ggccgcggct gcectgaaatgc agcgcttcete tgacctgetg caaaggctgt taaacggtat 720 cggaggctgce agcagcagca gtgacagtgg cagcgccgaa aagaggcgga gaaagtcccec 780 aggaggaggc ggcggtggcg gcagcggtaa cgacaacaac caggcggcga caaagagtcec 840 ccggaaggcg gcggcggccg ctgcccgect taatcgactg aagaagaagg agtacgtgat 900 ggggctggag agtcgagtcc ggggtctgge agccgagaac caggagctgc gggccgagaa 960 tcgggagctg ggcaaacgceg tacaggcact gcaggaggag agtcgctacc tacgggcagt 1020 cttagccaac gagactggac tggctcgctt gctgagccgg ctgagcggcg tgggactgeg 1080 gctgaccacc tcgctcttca gagactcgec cgccggtgac cacgactacg ctctgccagt 1140 gggaaagcag aagcaggacc tgctggaaga ggacgactcqg gcgggaggag tctgtctcca 1200 tgtggacaag gataaggtgt cggtggagtt ctgctcggeg tgcgcccgga aggcgtcgtce 1260 ttctcttaaa atgtagggtc aagtaatctg ctctttatcec gcgtttacce ctttcaactce 1320 ccttacacca tgtcaaactt accttagtgg gacatcttca ccggacacat ttcagaggag 1380 agaaaaaaag taatattgaa tcttaaagtg tttagctaaa agcatgaatg tgacacagta 1440 accaactcct aatgataaca tgtgactatt aaatctctct gacagtttct tttttaggtg 1500 atttccttce tgccaggctce cgttgtaggg gttacagaac agtcgttccc gcctcacaac 1560 ctgtggatac agctgttggg gcagaagaga cgggaccagc tgctggccac atttccectgcet 1620 ttattttaaa aggtagtata agaatgagga aaaagaggta atatcagggc ttctgetgtt 1680 ttttattttt aacatgttca taattaaaaa gtattttcca gcagtccaaa gatgtaagtt 1740 atcttacaca taatatgttt tattttgtta tttggttatg aaaatggaat ccttgttctt 1800 gcacaactgt aaatgttttg ttgctagata atacgatttg agacctgaat tggtctttgg 1860 tttccagtge atcacagcat attttgtaaa atcatgtact actgcacttg agcatgaatg 1920 ggtagtagcc aaactcacaa attggagtga tgaacctgct tatacctaag ggcaggagca 1980 agceccctcac aatgcagctg catgggtttt tagtgcctac tgaattatat atatatatac 2040 atatatatat atatatataa accaaaagta gttggaaaga ttatttgaaa tgactaactt 2100 tgtgctatct ttatgaaata tgttaaatgt agcttttttg aaacagaagc cttgaattga 2160 aatttaacta atacttgaac attttgtata tatttctttg tatataattt tgtgcagtac 2220 caatgacaaa aatatggtgt cataataaaa ccaggtttgt tgatctttta gttatgggct 2280 caaagaattt attcatctct aacatgatat tggaaaataa tggatgaaaa taggaaaaat 2340 gattgttaat gctgactgtg ggtcttaaaa ggttctggaa agcagtaagt tcatttttct 2400 aaaaactata acattctgtt ggagtatttt cttccttacg tcaatacttt tcctgcatta 2460 tttgaaattg tgggctgggg agaaacagta gtcaaagctt tetgaattga gatactttga 2520 aattccaagt gtagattttt agaatgtcat tttataaatg gccgtttttg gaattacttg 2580 ataagaactt ttgaaaatgg aaggattagt atggcctatt tttaaagctg ctttgttagg 2640 tteccttatgt tttattaact gtettttctc agtttccatt tcattttttt ttttctagtt 2700 ttggtgactt agtgattttg tcatttttta catcaacttc atggtcttgt ttttacatgg 2760 taattgcatg tacttaggat ctatctaata ggggctttaa ataaatttgg tcatatttat 2820 gtgtaagcac attttactgt aaatgtttgg gtttctgaat ttaaacagat ctgtttattt 2880 cagtatgtag taaacaatat cttaaagtgt ccgattcact acttgttaat taaaaaagtt 2940 atgattaatg tg 2852 <210> 655 <211> 2618 <212> DNA <213> Homo sapiens

<400> 655 atgaagcacc tgaagcggtg gtggtcggec ggecggeggece tcctgcacct caccctccetg 60 ctgagcttgg cggggctceceg cgtagaccta gatctttacce tgctgctgec geocgeccace 120 ctgctgcagg acgagctgct gttcctggge ggcccggceca gctceccgccta cgcegctcage 180 cecttetegg cctcgggagg gtgggggcgc gcgggccact tgcaccccaa gggccgggag 240 ctggaccctg ccgecgccgec cgagggccag ctgctecggg aggtgcgcge gctcggggtce 300 cccttcgtece ctecgraccag cgtggatgca tggctggtge acagcgtggce tgccgggage 360 gcggacgagg cccacgggct gctcggecgec gecgecgcect cgtccaccgg aggagccggce 420 gccagegtgg acggcggcag ccaggctgtg caggggggcd gcggggacce ccgagcggcet 480 cggagtggcc ccttggacgc cggggaagag gagaaggcac ccgcggaacc gacggctcag 540 gtgccggacg ctggcggatg tgcgagcgag gagaatgggg tactaagaga aaagcacgaa 600 gctgtggatc atagttccca gcatgaggaa aatgaagaaa gggtgtcagc ccagaaggag 660 aactcacttc agcagaatga tgatgatgaa aacaaaatag cagagaaacc tgactgggag 720 gcagaaaaga ccactgaatc tagaaatgag agacatctga atgggacaga tacttctttc 780 tctctggaag acttattcca gttgctttca tcacagcctg aaaattcact ggagggcatce 840 tcattgggag atattcctct tccaggcagt atcagtgatg gcatgaattc ttcagcacat 900 tatcatgtaa acttcagcca ggctataagt caggatgtga atcttcatga ggccatcttg 960 ctttgtcecca acaatacatt tagaagagat ccaacagcaa ggacttcaca gtcacaagaa 1020 ccatttctgc agttaaattc tcataccacc aatcctgagc aaacccttce tggaactaat 1080 ttgacaggat ttctttcacc ggttgacaat catatgagga atctaacaag ccaagaccta 1140 ctgtatgacc ttgacataaa tatatttgat gagataaact taatgtcatt ggccacagaa 1200 gacaactttg atccaatcga tgtttctcag ctttttgatg aaccagattc tgattctggce 1260 ctttectttag attcaagtca caataatacc tctgtcatca agtctaattc ctctcactct 1320 gtgtgtgatg aaggtgctat aggttattgc actgaccatg aatctagttc ccatcatgac 1380 ttagaaggtg ctgtaggtgg ctactaccca gaacccagta agctttgtca cttggatcaa 1440 agtgattctg atttccatgg agatcttaca tttcaacacg tatttcataa ccacacttac 1500 cacttacagc caactgcacc agaatctact tctgaacctt ttceccgtggcece tgggaagtca 1560 cagaagataa ggagtagata ccttgaagac acagatagaa acttgagccg tgatgaacag 1620 cgtgctaaag ctttgcatat ccctttttct gtagatgaaa ttgtcggcat gcctgttgat 1680 tctttcaata gcatgttaag tagatattat ctgacagacc tacaagtctc acttatccgt 1740 gacatcagac gaagagggaa aaataaagtt gctgcgcaga actgtcgtaa acgcaaattg 1800 gacataattt tgaatttaga agatgatgta tgtaacttgc aagcaaagaa ggaaactctt 1860 aagagagagc aagcacaatg taacaaagct attaacataa tgaaacagaa actgcatgac 1920 ctttatcatg atatttttag tagattaaga gatgaccaag gtaggccagt caatcccaac 1980 cactatgctc tccagtgtac ccatgatgga agtatcttga tagtacccaa agaactggtg 2040 gcctcaggee acaaaaagga aacccaaaag ggaaagagaa agtgagaaga aactgaagat 2100 ggactctatt atgtgaagta gtaatgttca gaaactgatt atttggatca gaaaccattg 2160 aaactgcttc aagaattgta tctttaagta ctgctacttg aataactcag ttaacgctgt 2220 tttgaagctt acatggacaa atgtttagga cttcaagatc acacttgtgg gcaatctggg 2280 ggagccacaa cttttcatga agtgcattgt atacaaaatt catagttatg tccaaagaat 2340 aggttaacat gaaaacccag taagactttc catcttggca gccatccttt ttaagagtaa 2400 gttggttact tcaaaaagag caaacactgg ggatcaaatt attttaagag gtatttcagt 2460 tttaaatgca aaatagcctt attttcattt agtttgttag cactatagtg agcttttcaa 2520 acactatttt aatctttata tttaacttat aaattttgct ttctatggaa ataaattttg 2580 tatttgtatt aaaaattaac tttteccttt tatacaga 2618 <210> 656 <211> 2128 <212> DNA <213> Homo sapiens <400> 656 gggccggcag gggeggtgeg cgggaaggga ccccggacce ggaggtcegeg gagagetggg 60 cagtgttggc cgctggcgga gegetgggge agcatgaagt gcctggtcac gggcggcaac 120 gtgaaggtgc tcggcaaggc cgtccactcc ctgtcecgeca tecggggacga gctctacctg 180 gaacccttgg aggacgggct cteccteegg acggtgaact cctceegete tgcctatgece 240 tgctttctect ttgecccget ctteottccag caataccagg cagccacccce tggtcaggac 300 ctgctgcget gtaagatcct gatgaagtct ttcctgtetg tctteegetce actggcgatg 360 ctggagaaga cggtggaaaa atgctgcate tccctgaatg gccggadcag cecgectggtg 420 gtccagetge attgcaagtt cggggtgcgyg aagactcaca acctgtcctt ccaggactgt 480 gagtccctge aggccgtctt cgacccagcc tcgtgceccce acatgctccg cgcceccagea 540 cgggttctgg gggaggctgt tctgcccette tctcctgecac tggctgaagt gacgetggge 600 attggcecgtg geccgeagggt catcctgcge agctaccacg aggaggaggce agacagcact 660 gccaaagcca tggtgactga gatgtgcett ggagaggagg atttccagca getgcaggcece 720 caggaagggg tggccatcac tttctgectc aaggaattcce gggggctcct gagctttgca 780 gagtcagcaa acttgaatct tagcattcat tttgatgctc caggcaggcc cgccatcttce 840 accatcaagg actctttgct ggacggccac tttgtcttgg ccacactctc agacaccgac 900 tcgcactcce aggacctggg ctccccagag cgtcaccage cagtgcctca gctecagget S60 cacagcacac cccacccgga cgactttgece aatgacgaca ttgactctta catgatcgece 1020 atggaaacca ctataggcaa tgagggctcg cgggtgctgc cctccatttc cctttcaccet 1080 ggcecccage cccccaagag ccecccggtceccee cactccgagg aggaagatga ggctgagccoce 1140 agtacagtgc ctgggactcc cccacccaag aagttccget cactgttett cggctccatc 1200 ctggececctg tacgcteccce ccagggecce agecctgtge tggcocggaaga cagtgagggt 1260 gaaggctgaa ccaagaacct gaagcctgta cccagaggcce ttggactaga cgaagcccca 1320 gccagtggea gaactgggtc tctcagecct ggggatcaga aaggtgggct tgctggaget 1380 gagctgtttce actgcctcte gcaggcccca gctggctgtc actgtaaagc tgtcccacag 1440 cggtcgggec tgggccgtta tctceccccaca acccccagec aatcaggact ttccagactt 1500 ggccectgaac tactgacgtt cctacctcett atttctcatt gagcctcagg ctatactcca 1560 gctggccaag gctggaaacce tgtcectcectce aggctcacct tcctaaggaa aatgtcatag 1620 taggtgctge tggcccctgg tgatccaget tctctgccaa tcatgacctg ttccttectg 1680 aagtcctggg catgcatctg ggacccecccgt ggagctgaca agttttcecctt gctttectga 1740 tactctttgg cgctgacttg gaattctaag agccttggac ccgagtgtgt ggctagggtt 1800 gcecetggetg gggeccggtg ccgagactcecce caagcggctce tgtgcagaag agcetgcecagyg 1860 cagtgtctta gatgtgagac ggaggccatg gcgagaatcc agctttgacc tttattcaag 1520 agaccagatg ggttgcccca ggatccggct gcoccagccctg aggccaagca cggctggaga 1980 cccacgacct ggcctgcegt tgccctgagc tgcagccteg gccccaggat cctgctcaca 2040 gtcaccgcag gtgcaggcag gaagcagcecce tgggggactg gacgctgeta ttgattcatt 2100 aaaaaaagaa aagaaaaata caaaaaaa 2128 <210> 657 <211> 500 <212> DNA <213> Homo sapiens <400> 657 tttccaattec acttcaattt tttatttcag caagcagcag tgggcctgtg aagttttcaa 60 agtgccccag gcatttettt ctggactcaa tatattaagt caaagaaagt agcaggtctt 120 aggtgccaat gaagtggcat taagctattt ctctttgcaa ggccteccttc tctgtgaagce 180 aaatcccagc cactcactca cttaaagcaa tgcagaacgt ctggtcagca aacagaaaaa 240 ggataaaaat tcctcagttc ctcacctgta ttattaccat tccctcccece agggaaaggce 300 aggctagtag aaattctaca gaggtcagta aacataggtg gttatttgca aaagtagtta 360 gtacttttct caggctataa aagcaatggc atttgggggt cacaatgcta accatacact 420 gcccecetctg atgactttta ttecttgagg ttcgctcatt ggatgcccca ctcectatagce 480 agatcgcatc acacagcctc 500 <210> 658 <211l> 65458 <212> DNA <213> Homo sapiens <400> 658 gccccagggce ctggagaggt ctgaagaaac ctgggagcca gcagcccggg gctccactcet 60 gggttctgaa agcccattcc ctgectctgeg gctcecteccca ccccacctcet tctcagectt 120 gcagctcaag ggttgatctc aggagtccag gacccaggag agggaagaat ctgaggaaca 180 cagaacagtg agcgttgccc acaccccatc tcccgtcacce acatctccce tcaccctcac 240 cctcectgee tggeccctgga ccccatccca ggacctcecct atcagctgac ttcttecagt 300 gtcttgcagg cccctctggg ctecctceccte cectggettt tectaccact cccecctctat 360 cggegtctat ctgtaggtgc cctgggattt ataaaactgg gttccgaatg ctgaataaga 420 gacggtaaga gccaaggcaa aggacagcac tgttctctge ctgcctgata ccctcaccac 480 ctgggaacat cccccagaca ccctcttaac tcecgggacag agatggctgg cggagcctgg 540 ggccgectgg cctgttactt ggagttcctg aagaaggagg agctgaagga gttccagctt 600 ctgctcgecca ataaagcgca ctccaggagce tcttcgggtg agacacccge tcagccagag 660 aagacgagtg gcatggaggt ggcctcgtac ctggtggctc agtatgggga gcagcgggcce 720 tgggacctag ccctccatac ctgggagcag atggggctga ggtcactgtg cgcccaagcce 780 caggaagggg caggccactc tccctcatte ccctacagec caagtgaacc ccacctgggg 840 tctceccagec aacccacctce caccgcagtg ctaatgccct ggatccatga attgecggceg 900 gggtgcaccc agggctcaga gagaagggtt ttgagacagc tgcctgacac atctggacgce 960 cgctggagag aaatctctgc ctcactccte taccaagctc ttccaagcetce cccagaccat 1020 gagtctccaa gccaggagtc acccaacgcc cccacatcca cagcagtget ggggagctgg 1080 ggatccccac ctcagcccag cctagcaccc agagagcagg aggctcctgg gacccaatgg 1140 cctctggatg aaacgtcagg aatttactac acagaaatca gagaaagaga gagagagaaa 1200 tcagagaaag gcaggccccc atgggcagcg gtggtaggaa cgcccccaca ggcgcacacce 1260 agcctacagc cccaccacca cccatgggag ccttetgtga gagagagcect ctgttccaca 1320 tggccctgga aaaatgagga ttttaaccaa aaattcacac agctgctact tctacaaaga 1380 cctecacccca gaagccaaga tcccctggtc aagagaagct ggectgatta tgtggaggag 1440 aatcgaggac atttaattga gatcagagac ttatttggcc caggcctgga tacccaagaa 1500 cctecgeatag £ORLACLYES gggggctgct ggaattggga agtcaacact ggccaggcag 1560 gtgaaggaag cctgggggag aggccagctg tatggggacc gcttccagca tgtcttctac 1620 ttcagctgca gagagctgge ccagtccaag gtggtgagtc tcgctgagct catcggaaaa 1680 gatgggacag ccactccggc tcccattaga cagatcctgt ctaggccaga gcggetgctc 1740 ttcatcctcg atggtgtaga tgagccagga tgggtcttgce aggagccgag ttctgagcetce 1800 tgtctgcact ggagccagcece acagccggcg gatgcactge tgggcagttt gctggggaaa 1860 actatacttc ccgaggcate cttecctgatc acggctegga ccacagctct gcagaacctce 1920 attcctrctt tggagcaggce acgttgggta gaggtcctgg ggttctctga gtccagcagg 1980 aaggaatatt tctacagata tttcacagat gaaaggcaag caattagagc ctttaggttg 2040 gtcaaatcaa acaaagagct ctgggccctg tgtcttgtge cctgggtgtc ctggectggec 2100 tgcacttgec tgatgcagca gatgaagcgg aaggaaaaac tcacactgac ttccaagacc 2160 accacaaccc tctgtctaca ttaccttgce caggctctcc aagctcagcce attgggaccce 2220 cagctcagag acctctgctc tctggectgcect gagggcatct ggcaaaaaaa gacccttttce 2280 agtccagatg acctcaggaa gcatgggtta gatggggcca tcatctccac cttcttgaag 2340 atgggtattc ttcaagagca ccccatcect ctgagctaca gcttcattca cctctgtttc 2400 caagagttct ttgcagcaat gtcctatgtc ttggaggatg agaaggggag aggtaaacat 2460 tctaattgca tcatagattt ggaaaagacg ctagaagcat atggaataca tggcctgttt 2520 ggggcatcaa ccacacgttt cctattgggc ctgttaagtg atgaggggga gagagagatg 2580 gagaacatct ttcactgccg gectgtctcag gggaggaacc tgatgcagtg ggtccegtcece 2640 ctgcagectge tgctgcagce acactectetg gagtccctec actgettgta cgagactcegg 2700 aacaaaacgt tcctgacaca agtgatggcc catttcgaag aaatgggcat gtgtgtagaa 2760 acagacatgg agctcttagt gtgcactttc tgcattaaat tcagccgcca cgtgaagaag 2820 cttcagctga ttgagggcag gcagcacaga tcaacatgga gccccaccat ggtagtcctg 2880 ttcaggtggg tcccagtcac agatgcctat tggcagattc tcttctecegt cctcaaggtce 2940 accagaaacc tgaaggagct ggacctaagt ggaaactcgc tgagccactc tgcagtgaag 3000 agtctttgta agaccctgag acgccctege tgcctcecctgg agaccctgeg gttggectggce 3060 tgtggcctca cagctgagga ctgcaaggac cttgcectttg ggctgagagc caaccagacce 3120

412 _ y ctgaccgagc tggacctgag cttcaatgtg ctcacggatg ctggagccaa acacctttgce 3180 cagagactga gacagccgag ctgcaagcta cagcgactgc agctggtcag ctgtggectce 3240 acgtctgact gctgccagga cctggectct gtgcttagtg ccagccccag cctgaaggag 3300 ctagacctgc agcagaacaa cctggatgac gttggcgtgc gactgctctg tgaggggcetce 3360 aggcatcctg cctgcaaact catacgcctg gggctggacc agacaactct gagtgatgag 3420 atgaggcagg aactgagggc cctggagcag gagaaacctc agctgctcat cttcagcaga 3480 cggaaaccaa gtgtgatgac ccctactgag ggcctggata cgggagagat gagtaatagc 3540 acatcctcac tcaagcggca gagactcgga tcagagaggg cggcttccca tgttgctcag 3600 : gctaatctca aactcctgga cgtgagcaag atcttcccaa ttgctgagat tgcagaggaa 3660 agctccccag aggtagtacc ggtggaactce ttgtgegtge cttcectcctge ctctcaaggg 3720 gacctgcata cgaagccttt ggggactgac gatgacttct ggggccccac ggggcctgtg 3780 gctactgagg tagttgacaa agaaaagaac ttgtaccgag ttcacttccc tgtagctggce 3840 tcctaccgct ggcccaacac gggtctetge tttgtgatga gagaagceggt gaccgttgag 3900 attgaattct gtgtgtggga ccagttectg ggtgagatca acccacagca cagctggatg 3860 gtggcagggc ctctgctgga catcaaggct gagecctggag ctgtggaagc tgtgcacctc 4020 cctcactttg tggctctcecca agggggccat gtggacacat ccctgttcca aatggcccac 4080 tttaaagagg aggggatgct cctggagaag ccagccaggg tggagctgca tcacatagtt 4140 ctggaaaacc ccagcttctc cceccttggga gtcctcctga aaatgatcca taatgccctg 4200 cgcttcattc cecgtcacctc tgtggtgttg ctttaccacc gecgtccatcc tgaggaagtc 4260 accttccacce tctacctgat cccaagtgac tgctccattc ggaaggaact ggagctctgce 4320 tatcgaagcc ctggagaaga ccagctgttc tcggagttct acgttggcca cttgggatca 4380 gggatcaggc tgcaagtgaa agacaagaaa gatgagactc tggtgtggga ggccttggtg 4440 aaaccaggag atctcatgcc tgcaactact ctgatcectc cagcccgcat agccgtacct 4500 tcacctctgg atgccccgea gttgectgecac tttgtggacc agtatcgaga gcagctgata 4560 gcccgagtga catcggtgga ggttgtcttg gacaaactgce atggacaggt gctgagccag 4620 gagcagtacg agagggtgct ggctgagaac acgaggccca gccagatgeg gaagctgttce 4680 agcttgagcc agtcctggga ccggaagtgc aaagatggac tctaccaagec cctgaaggag 4740 acccatcctcec acctcattat ggaactctgg gagaagggca gcaaaaaggg actcctgcca 4800 ctcagcagct gaagtatcaa caccagccct tgacccttga gtcectggett tggctgaccce 4860 ttctttgggt ctcagtttct ttctctgcaa acaagttgcc atctggtttg ccttecagea 4920 ctaaagtaat ggaactttga tgatgccttt gctgggcatt atgtgtccat gccagggatg 4980

413 y ccacaggggg ccccagtcca ggtggcctaa cagcatctca gggaatgtcc atctggaget 5040 ggcaagaccc ctgcagacct catagagcct catctggtgg ccacagcagc caagcctaga 5100 gcccteocgga tcccatccag gcgcaaagag gaataggagg gacatggaac catttgectce 5160 tggctgtgtc acagggtgag ccccaaaatt ggggttcagc gtgggaggcc acgtggattc 5220 ttggctttgt acaggaagat ctacaagage aagccaacag agtaaagtgg aaggaagttt 5280 attcagaaaa taaaggagta tcacagctct tttagaattt gtctagcagg ctttccagtt 5340 tttaccagaa aacccctata aattaaaaat tttttactta aatttaagaa ttaaaaaaat 5400 acaaaaaaga aaaaatgaaa ataaaggaat aagaagttac ctactccaaa aaaaaaaa 5458 <210>. 659 <211> 1373

.. <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (241)..(241) <223> n is a, ¢, g, t or u <400> 659 cttttttttt ttegtectggg ctgccaacat gccatccaga ctgaggaaga cccggaaact 60 taggggccac gtgagccacg gccacggcgc ataggcaagc accggaagca ccccggcggce 120 cgcggtaatg ctggtggtct gcatcaccac cggatcaact tcgacaaata ccacccaggc 180 tacttgggga aagtgggtat gaagcattac cacttaaaga ggaaccagag cttctgccca 240 natgtcaacc ttgacaaatg tgtgggactt gggtcagtga acagacacgg gtgaatgctg 300 ctaaaaacaa gactggggct gctcccatca ttgatgtggt gecgatcgggce tactataaag 360 ttctgggaaa gggaaagctc ccaaagcagc ctgtcatcgt gaaggccaaa ttcttcagcea 420 gaagagctga ggagaagatt acgagtgtgg ggggggcctg tgtcctggtg gcttgaagcce 480 acatggaggg agttcataaa tggtatacca aaaaaaaaga aaaaaaaaaa attgtttggg 540 gcggggccca gaaaattcaa accacggtgc gggcgggcca gagatggcaa cgggccgagg 600 gcgcagagac cgggacgaca ggggggttcc acaaaaaagc gcgggceccggg tgaagaacag 660 ggtccgecag ggtcgcagge acggatcatc ccccgccgeg gecccacacac gacgacacag 720 acaaacgaag agacaagacc catctgatgt cctcagtctc aggcgacgac gtgccaggag 780 aggcgcgcag aaacactgca aaaaactgac accgcagcag gcccagccac ccacaaggca 840 aaagtgccac cgacgcgcege aaccggagcg ccaaagccga gccaagacga gaagaaccga 900 cacgagcagc acaagggcgg cgacgcggaa ggagacagga gccacggcag acggaccaga 960 cacgatgcaa cacacgcaaa dacgcaccca agacagaacg gacagacaca aacaaggaga 1020 aagcaggaga actaccgacC gcgacgcaag agacacagaa aacagagggg aacgaggcag 1080 agaaaagaga acgagcgcga acgcgacgga tcaaggcgag cagaccagac acagaacagc 1140 ggggacacag cagaagaacg aagaacaaca gagacgcgac agaaagacaa agaaccgcag 1200 agcagacacc aggccaagag caagagggga gaacacacag cgagggaacg agcgagagag 1260 : agatgagaaa tacagacatg aaggaagacg agcaaggaca cagcgagagt ccaggaacag 1320 gcagacaagc gagaaagagg agaagcgcaa cacgaacaga aaaccagagc gag 1373 <210> 660 <211> 690 <212> DNA <213> Homo sapiens <400> 660 tgcacaagca gaatcttcag aacaggttct ccttccccag tcaccagttg ctcgagttag 60 aattgtctgc aatggccgcc ctgcagaaat ctgtgagctc tttccttatg gggaccctgg 120 ccaccagctg cctecttete ttggecctet tggtacaggg aggagcagct gcgeccatca 180 gctcccactg caggcttgac aagtccaact tccagcagec ctatatcace aaccgcacct 240 tcatgctgge taaggagdct agcttggctg ataacaacac agacgttegt ctcattgggg 300 agaaactgtt ccacggagtc agtatgagtg agcgctgcta tctgatgaag caqggtgctga 360 acttcaccct tgaagaagtg ctgttccctc aatctgatag gttccagect tatatgcagg 420 aggtggtgcc cttectggec aggctcagca acaggctaag cacatgtcat attgaaggtg 480 atgacctgca tatccagagg aatgtgcaaa agctgaagga cacagtgaaa aagcttggag 540 agagtggaga gatcaaagca attggagaac tggatttgct gtttatgtct ctgagaaatg 600 cctgcatttg accagagcaa agctgaaaaa tgaataacta accccctttc cctgctagaa 660 ataacaatta gatgccccaa agcgattttt 690 <210> 661

<211> 1189

<212> DNA

<213> Homo sapiens

<400> 661 gcgcatgege gggggccata ttagcagcgg ttattcggtg agcggtggtg gtttattett 60 ccgtggagtt aagggctccg tggacatctc aggtcttcag ggtcttccat ctggaactat 120 ataaagttca gaaaacatgt ctcgaagata tgactccagg accactatat tttctccaga 1890 aggtcgctta taccaagttg aatatgccat ggaagctatt ggacatgcag gcacctgttt 240 gggaatttta gcaaatgatg gtgttttget tgcagcagag agacgcaaca tccacaagcet 300 tcttgatgaa gtcttttttt ctgaaaaaat ttataaactc aatgaggaca tggcttgeag 360 tgtggcaggc ataacttctg atgctaatgt tctgactaat gaactaaggc tcattgctca 420 aaggtattta ttacagtatc aggagccaat accttgtgag cagttggtta cagcgctgtg 480 tgatatcaaa caagcttata cacaatttgg aggaaaacgt ccctttggtg tttcattget 540 gtacattggc tgggataagc actatggctt tcagctctat cagagtgacc ctagtggaaa 600 ttacggggga tggaaggcca catgcattgg aaataatagc gctgcagctg tgtcaatgtt 660 gaaacaagac tataaagaag gagaaatgac cttgaagtca gcacttgctt tagctatcaa 720 agtactaaat aagaccatgg atgttagtaa actctctgcect gaaaaagtgg aaattgcaac 780 actaacaaga gagaatggaa agacagtaat cagagttctc aaacaaaaag aagtggagca 840 gttgatcaaa aaacatgagg aagaagaagc caaagctgag cgtgagaaga aagaaaaaga 900 acagaaagaa aaggataaat agaatcagag attttattac tcatttgggg caccatttca 960 gtgtaaaagc agtecctactce ttccacacta ggaaggettt acttttttta actggtgcag 1020 tgggaaaata ggacattaca tactgaattg ggtccttgtc atttctgtec aattgaatac 1080 tttattgtaa cgatgatggt tacccttcat ggacgtctta atcttccaca cacatccceet 1140 ttttttggaa taaaatttgg aaaatggaaa tgaaaaaaaa aaaaaaaaa 1189 <210> 662 <211> 1890 <212> DNA <213> Homo sapiens <400> 662 cccgegageg gacgeggceag cgcctetgte tcgetttttc ttatttttec ccectttcee 60 ctttecttttt ttttttttct tttcttttet cecceteccee cetttcacca tttcecectceg 120 gaggcgcettt cccecgggeag gggcagagcc ggtctcacce ccecgectcte ccecggeccece 180 gccgccectat ggcgagaggg agccccctec caacccgggce tcgagcggeg gcggcctcag 240 gccgggggte atcatggaac taattcgctg accgacccag cggcecgcagce cgtgecgtccc 300 gctcgagege cagcgeecge gecccgegece cccgatceege ttececttte tccctectea 360 gttggccegag tcgtecegeg cgeacegeet €cgcgegect atgagaatga ggtggtaacg 420 ggccccegga tgacccecgeg tcaccactgt gaggcctaca gctctgcecgg ggaggaggag 480 gaggaggaag aggaggagaa ggtagctaca gcaagctggg tagcaggcag atccaaagga 540 tatcatgaag tttccaggge ctttggaaaa Ccagagattg tctttcctgt tggaaaaggce 600 aatcactagg gaagcacaga tgtggaaagt gaatgtgcgg aaaatgcctt caaatcagaa 660 tgtttctcca tcccagagag atgaagtaat tcaatggctg gccaaactca agtaccaatt 720 caacctttac ccagaaacat ttgctctgge tagcagtctt ttggataggt ttttagctac 780 cgtaaaggct catccaaaat acttgagttg tattgcaatc agctgttttt tcctagetgce 840 caagactgtt gaggaagatg agagaattcc agtactaaag gtattggcaa gagacagttt 900 ctgtggatgt tcctcatctg aaattttgag aatggagaga attattctgg ataagttgaa 960 ttgggatctt cacacagcca caccattgga ttttcttcat attttccatg ccattgcagt 1020 gtcaactagg cctcagttac ttttcagttt gcccaaattg agcccatctc aacatttggc 1080 agtccttacc aagcaactac ttcactgtat ggcctgcaac caacttctgc aattcagagg 1140 atccatgctt gctctggcca tggttagtct ggaaatggag aaactcattc ctgattggct 1200 ttctecttaca attgaactgc ttcagaaagc acagatggat agctcccagt tgatccattg 1260 tcgggagctt gtggecacatc acctttctac tctgcagtet tccctgectce tgaattccgt 1320 ttatgtctac cgtcccctca agcacaccct ggtgacctgt gacaaaggag tgttcagatt 1380 acatccctcc tctgtcccag gcecccagactt ctccaaggac aacagcaagc cagaagtgcc 1440 agtcagaggt acagcagcct tttaccatca tctcccagct gccagtgggt gcaagcagac 1500 ctctactaaa cgcaaagtag aggaaatgga agtggatgac ttctatgatg gaatcaaacyg 1560 gctctataat gaagataatg tctcagaaaa tgtgggttct gtgtgtggca ctgatttatc 1620 aagacaagag ggacatgctt ccccttgtec acctttgcag cctgtttctg tcatgtagtt 1680 tcaacaagtg ctacctttga gtgtaaacta aggtagacta ctttgggaat gagaacatgc 1740 aaaatcagga aaggctgtag aaggaaatat accttaacag gctgatttgg agtgagccag 1800 aaaaaaaaaa taaaactctc attatttgtg tggctaatta taattcagcg ttatttaagc 1860 acataaagac caaaaaaaaa aaaaaaaaaa 1880 «210> 663 <211> 4050 <212> DNA <213> Homo sapiens <400> 663 cttgcaatcc aggctttcct tggaagtggc tgtaacatgt atgaaaagaa agaaaggagg 60 accaagagat gaaagagggc tgcacgcgtg ggggcccgag tggtgggcgg ggacagtcegt 120 cttgttacag gggtgctgge cttcectgge gectgecect gtcggecccg cccgagaacce 180 tccctgegec agggcagggt ttactcatcce cggcgaggtg atcccatgcg cgagggcggg 240 cgcaagggcg gccagagaac ccagcaatcc gagtatgegg catcagccect tcecaccagg 300 cacttcctte cttttcccga acgtccaggg agggagggcc gggcacttat aaactcgage 360 cctggeccgat ccgcatgtca gaggctgect cgcagggget gecgcgcacgg caagaagtgt 420 ctgggctggg acggacagga gaggctgteg ccatcggegt cctgtgccce tcetgctecgg 480 cacggccectg tcgcagtgee cgcgetttece cecggcgectg cacgcggcge gectgggtaa 540 catgcttggg gtcctagtece ttggegeget ggeectggece ggectggggt tecccgcacc 600 cgcagagccg cagccgggtg gcagccagtg cgtcgagcac gactgctteg cgctctacce 660 gggccececgeg accttectca atgccagtca gatctgcgac ggactgeggg gceccacctaat 720 gacagtgcge tceteggtgg ctgecgatgt catttecttg ctactgaacg gegacggcegg 780 cgttggcege cggecgcectct ggatcggcect gcagctgcca ceccggctgcg gcgaccccaa 840 gcgectecggyg ccocctgegeg gottccagtg ggttacggga gacaacaaca ccagctatag 300 caggtgggca cggctcgacc tcaatggggce tcccctetge ggccocegttgt gegtegetgt 960 ctecgectgect gaggccactg tgcccagcga gccgatctgg gaggagcagc agtgcgaagt 1020 gaaggccgat ggcttcctct gecgagttcca cttcccagec acctgcaggce cactggetgt 1080 ggagccecgge gecgeggcetg ccgeegtetce gatcacctac ggecaccecgt tcgeggcecg 1140 cggagcggac ttccaggcgce tgeccocggtggg cagctecgec geggtggcetc ccctceggett 1200 acagctaatg tgcaccgecgce cgeccggagce ggtccagggg cactgggcca gggaggegcec 1260 gggcgcttgg gactgecagcg tggagaacgg cggctgcgag cacgcgtgceca atgcgatccc 1320 tggggctcce cgctgccagt gcccagecgg cgccgceccctg caggcagacg ggcgcectcctg 1380 caccgcatce gcgacgcagt cctgcaacga cctcectgecgag cacttctgeg ttcccaacce 1440 cgaccagcecg ggctcctact cgtgcatgtg cgagaccgge taccggctgg cggccgacca 1500 acaccggtgc gaggacgtgg atgactgcat actggagccce agteccgtgtc cgcagcgctg 1560 tgtcaacaca cagggtggct tcgagtgcca ctgctaccct aactacgacc tggtggacgg 1620 cgagtgtgtg gagcccgtgg acccgtgcett cagagccaac tgcgagtacc agtgccagcec 1680 cctgaaccaa actagctacc tctgcgtctg cgeccgagggce ttcgcgcecca ttcceccacga 1740 gcecgecacagg tgccagatgt tttgcaacca gactgcctgt ccagccgact gcgaccccaa 1800 cacccaggct agctdgtgagt gccctgaagg ctacatcctg gacgacggtt tcatctgceac 1860 ggacatcgac gagtgcgaaa acggcggctt ctgctccggg gtgtgccaca acctccccgg 1920 taccttecgag tgcatctgeg ggcccgactc ggcccttgec cgccacattg gcaccgactg 1980 tgactccgge aaggtggacg gtggcgacag cggdctctggc gagcccccge ccagcccgac 2040 gceccggectee accttgactc ctccggecgt ggggctegtg cattecggget tgctcatagg 2100 catctccatc gcgagcetgt gecctggtggt ggcgettttg gecgectcctet geccacctgeg 2160 caagaagcag gdggcgccgcca gggccaagat ggagtacaag tgecgeggecce cttccaagga 2220 ggtagtgctg cagcacgtgc ggaccgagcg gacgccgcag agactctgag cggcctccgt 2280 ccaggagcct ggctccgtcoc aggagctgtg cctcectcacc cccagctttg ctaccaaagc 2340 accttagctg gcattacagc tggagaagac cctccccgca ccccccaage tgttttctte 2400 tattccatgg ctaactggcg agggggtgat tagagggagg agaatgagcc tcggcctctt 2460 ccgtgacgtc actggaccac tgggcaatga tggcaatttt gtaacgaaga cacagactgc 2520 gatttgtcce aggtcctcac taccgggcege aggagggtga gcgttattgg tcggcagcct 2580 tctgggcaga ccttgacctc gtgggctagg gatgactaaa atatttattt tttttaagta 2640 tttaggtttt tgtttgtttc ctttgttctt acctgtatgt ctccagtatc cactttgcac 2700 agctctccgg tctctctete tctacaaact cccacttgtce atgtgacagg taaactatct 2760 tggtgaattt ttttttccta gccctctcac atttatgaag caagccccac ttattcccca 2820 ttcttcctag ttttctccte ccaggaactg ggccaactca cctgagtcac cctacctgtg 2880 cctgacccta cttcttttge tcatctaget gtctgctcag acagaacccc tacatgaaac 2940 agaaacaaaa acactaaaaa taaaaatggc catttgcttt ttcaccagat ttgctaattt 3000 atcctgaaat ttcagattcc cagagcaaaa taattttaaa caaagggttg agatgtaaaa 3060 ggtattaaat tgatgttgct ggactgtcat agaaattaca cccaaagagg tatttatctt 3120 tacttttaaa cagtgagcct gaattttgtt gctgttttga tttgtactga aaaatggtaa 3180 ttgttgctaa tcttcttatg caatttcctt ttttgttatt attacttatt tttgacagtg 3240 ttgaaaatgt tcagaaggtt gctctagatt gagagaagag acaaacacct cccaggagac 3300 agttcaagaa agcttcaaac tgcatgattc atgccaatta gcaattgact gtcactgttc 3360 cttgtcactg gtagaccaaa ataaaaccag ctctactggt cttgtggaat tgggagcttg 3420 ggaatggatc ctggaggatg cccaattagg gcctagectt aatcaggtcc tcagagaatt 3480 tctaccattt cagagaggcc ttttggaatg tggcccctga acaagaattg gaagctgcce 3540 tgcccatggg agctggttag aaatgcagaa tcctaggctce caccccatcc agttcatgag 3600 aatctatatt taacaagatc tgcagggggt gtgtctgctc agtaatttga ggacaaccat 3660 tccagactgc ttccaatttt ctggaataca tgaaatatag atcagttata agtagcaggc 3720 caagtcaggc ccttattttc aagaaactga ggaattttct ttgtgtagct ttgctctttg 3780 _ gtagaaaagg ctaggtacac agctctagac actgccacac agggtctgca aggtctttgg 3840 ttcagctaag ctaggaatga aatcctgctt cagtgtatgg aaataaatgt atcatagaaa 3900 tgtaactttt gtaagacaaa ggttttcctc ttctattttg taaactcaaa atatttgtac 33960 atagttattt atttattgga gataatctag aacacaggca aaatccttgc ttatgacatc 4020 acttgtacaa aataaacaaa taacaatgtg 4050 <210> 664 <211l> 1258 <212> DNA <213> Homo sapiens <400> 664 ccgggctceta cccagagcaa gaccctgatg gotgeggtgt ttctggtaac gctttatgaa 60 tactcgccge ttttctacat cgeggtggtc tttacctget tcatcgtgac caccggectg 120 gtattgggat ggtttggttg ggatgttcca gtaattctga gaaattcaga agagacccag 180 ttcagcacaa gagttttcaa aaagcaaatg agacaagtca agaatccttt tggcttagag 240 atcactaatc catcttcagc ttcaattaca actggcataa ccttgacaac agattgcctt 300 gaagatagcc tccttacatg ctactggggg tgcagtgttce aaaaattata tgaagctctg 360 cagaagcatg tttattgctt cagaataagc actccccaag cattagaaga tgctctgtat 420 agtgaatatc tctatcagga acagtatttt attaaaaagg atagcaaaga agaaatatat 480 tgccagttac caagagatac taaaattgaa gactttggta cagtacccag atctcgctat 540 ccattggtag cgctattgac cttagctgat gaggatgacc gggaaattta tgatattatt 600 tccatggtgt cagtgattca tattcctgat aggacttata aactatcctg cagaatattg 660 tatcaatatt tactcttggc tcaaggtcaa tttcatgatc ttaagcaact tttcatgtct 720 gcaaataata atttcactcc ctccaacaat tcctcttcag aagaaaaaaa cacagacaga 780 agtttgttgg aaaaggtggg actctctgaa agtgaagttg agccatcgga agagaacagc 840 aaggactgtg ttgtttgcca gaatgggact gtgaactggg tactcttacc atgcagacac 900 acatgcctgt gtgatggctg tgtgaagtat tttcagcagt gcccaatgtg caggcagttt 960 gttcaggaat cttttgcact ttgcagtcaa aaagagcaag ataaagacaa accgaagact 1020 ctttgaagac atcgtaacac tgaaaagtac actttctact aaagatgcag aaattgatga 1080 tcttggaatt catcataaca tggaatctac agtactgacc atcaatgaaa attatatttt 1140 aacttcatat ttgtatggta cttggatgat aaaaattaat tattcctttc tgcttagtga 1200 atgaatactg gaatccatct gtgttgatac aataaaaatt cattcaactc ttgaaaag 1258

<210> 665

<21l1l> 21

<212> DNA

<213> Homo sapiens

<400> 665 gtaaccecgtt gaaccccatt © 21

<210> 666 <211> 20 <212> DNA <213> Homo sapiens <400> 666 cacaatgtgg ccgaggactt 20 <210> 667 <211> 20 <212> DNA. <213> Homo sapiens <400> 667 caccgatcte aggggttctg 20 <210> 668 <211> 23 <212> DNA <213> Homo sapiens <400> 668 tccaacatca acatcttggt cag 23 <210> 669 <211> 21 <212> DNA <213> Homo sapiens <400> 6689 ccaaaagaca ccagccactc a 21 <210> 670 <211> 20 <212> DNA <213> Homo sapiens <400> 670 ccctceccteec ategttttcet 20 <210> 671 <211> 21 <212> DNA <213> Homo sapiens <400> 671 : tggagtcaag actgacaatc c 21 <210> 672 <211> 23 «212> DNA <213> Homo sapiens <400> 672 gaggaaaaag cgagagaaaa gga 23

<210> 673 <211> 20 <212> DNA <213> Homo sapiens <400> 673 ccecctccagg atgtgtcectgt 20 <210> 674 <211> 20 <212> DNA <213> Homo sapiens <400> 674 caagagcctg atgcccaact 20 <210> 675 <211> 20 <212> DNA <213> Homo sapiens <400> 675 cctactgctt tgccccaaga 20 <210> 676 <211> 20 <212> DNA <213> Homo sapiens <400> 676 gacctccect ggtgaagaca 20 <210> 677 <211> 20 <212> DNA <213> Homo sapiens <400> 677 caacaggacg ccctctgatt 20 <210> 678 <211> 20 <212> DNA <213> Homo sapiens <400> 678 ctgtcagcag gaagcaacga 20 <210> 679 <211l> 20 <212> DNA <213> Homo sapiens

<400> 679 . caaagggttg ggagctgatg 20 <210> 680 <211> 21 <212> DNA <213> Homo sapiens <400> 680 agtttgctgg cctgtacttc g . 21 <210> 681 <211> 20 <212> DNA <213> Homo sapiens <400> 681 ccaaccacaa gcacacadga 20 <210> 682 <211> 20 <212> DNA <213> Homo sapiens <400> 682 tccacattcc aaaagccaca 20 <210> 683 <211l> 20 <212> DNA <213> Homo sapiens <400> 683 gccacctcct gctgtttcte 20 <210> 684 <211> 20 <212> DNA <213> Homo sapiens <400> 684 ccecctgtecece ctctatgacc 20 <210> 685 <211> 20 <212> DNA <213> Homo sapiens <400> 685 ggaccaggtc ttggagctga 20 <210> 686 <211> 20 <212> DNA

<213> Homo sapiens <400> €86 ctgccctgta ggaaggcaga 20 <210> 687 <211> 20 <212> DNA <213> Homo sapiens <400> 687 ttcctggtte gggtgttacg 20 <210> 688 <211l> 20 <212> DNA <213> Homo sapiens <400> 688 ggcaatccca ggaagacaaa 20 <210> 6889 <21l1l> 25 <212> DNA <213> Homo sapiens <400> 689 tcaggtatgt tgcctttatg gtttc 25 <«210> 690 <211> 20 <212> DNA <213> Homo sapiens <400> 690 tgctgtacca cccacattge 20 <210> 691 <211> 20 <212> DNA <213> Homo sapiens <400> 691 cacatccagc tccttcagca 20 <210> 692 <211> 20 <212> DNA <213> Homo sapiens <400> 692 cctaccccac cccacctaaa 20 <210> 693

<211> 20 <212> DNA <213> Homo sapiens

<400> 693 gactgggatg gcctcaagtg 20 <210> 694

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 694 ggcaggtact cagtgcacca 20 <210> 695

<211> 20

<212> DNA

<213> Homo sapiens

<400> 695 ggagagggcc attccaatct 20 <210> 696

<211> 20

<212> DNA

<213> Homo sapiens

<400> 696 cacctgecgtg atgaggagaa 20 <210> 697

<211l> 20

<212> DNA

<213> Homo sapiens ’

<400> 697 ctggaagccc tttgttgtgce 20 <210> 698

<211> 20

<212> DNA

<213> Homo sapiens

<400> 698 ctcctgeccga caagaccaac 20 <210> 699

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 699 tacttccege acttcgacct 20

<210> 700 <211> 21 <212> DNA <213> Homo sapiens <400> 700 aggcagaatc cagatgctca a 21 <210> 701 <211s> 20 <212> DNA <213> Homo sapiens <400> 701 ggcagaagcc atacccttga 20 <210> 702 <211l> 20 <212> DNA <213> Homo sapiens <400> 702 gtggaagagg ctggaggtga 20 <210> 703 <211> 20 <212> DNA <213> Homo sapiens <400> 703 cagctttggc aacctgtcct 20 <210> 704 <211> 20 <212> DNA <213> Homo sapiens <400> 704 gcactacccc ggagacttca 20 <210> 705 <211> 20 <212> DNA <213> Homo sapiens <400> 705 tatgactgca gggtggagca 20 <210> 706 <211> 20 <212> DNA <213> Homo sapiens <400> 706 agtgaccatc tccccatceca 20 <210> 707 <211> 20 <212> DNA <213> Homo sapiens <400> 707 tacacctgcc aagtggagca 20 <210> 708 «211> 20 <212> DNA . <213> Homo sapiens <400> 708 ctgtgtgtgg ggtggggtat 20 <210> 709 <211> 20 <212> DNA <213> Homo sapiens <400> 709 gaccaaggaa atcggcectct 20 <210> 710 <211> 20

<212> DNA <213> Homo sapiens <400> 710 cacgcgacat ccaatccata 20 <210> 711 <211> 21 <212> DNA <213> Homo sapiens <400> 711 ggctgtgttc caacaaccat t 21 <210> 712 <211> 20 <212> DNA <213> Homo sapiens <400> 712 gtaggtgacg gcagcgtagc 20 <210> 713 <211> 20 <212> DNA <213> Homo sapiens

<400> 713 cctecgettte aagaggcaga 20 <210> 714 <211> 20 <212> DNA <213> Homo sapiens <400> 714 gcgtgtgtac acgggactga 20 <210> 715 <211> 20 <212> DNA <213> Homo sapiens <400> 715 ctgaagagta cgcgctgcaa 20 <210> 716 <211> 20 <212> DNA <213> Homo sapiens <400> 716 gtgttgggag ggcagaagtg 20 <210> 717 <211> 20 <212> DNA <213> Homo sapiens <400> 717 tgaagaccac ctcccaggtc 20 <210> 718 <211> 20 <212> DNA <213> Homo sapiens <400> 718 cegtgtgtet cgtctectga 20 <210> 719 : <211> 21 <212> DNA <213> Homo sapiens <400> 719 tcaaagcagc agagagggaa c 21 <210> 720 <211> 21

<212> DNA <213> Homo sapiens <400> 720 ggttgagagt gtgggtcttg c 21 <210> 721 <211> 26 i’ <212> DNA <213> Homo sapiens <400> 721 gccaataaag aaattaacac ccaaaa 26 <210> 722 <211> 20 <212> DNA <213> Homo sapiens <400> 722 tggagcagag gggctgaata 20 <210> 723 <211l> 20 <212> DNA <213> Homo sapiens <400> 723 . atcctgctgg ccctgtacct 20 <210> 724 <211l> 22 <212> DNA <213> Homo sapiens <400> 724 cctcagccat ctttgtgagt cc 22 <210> 725 <211> 20 <212> DNA <213> Homo sapiens <400> 725 ggcgatgtgg acaatgatga 20 <210> 726 <211> 20 <212> DNA <213> Homo sapiens <400> 726 gccgcgtcac ttctctgatt 20

<210> 727 <211> 22 «212> DNA <213> Homo sapiens <400> 727 agtgggacct tgactggaga aa 22 <210> 728 <211> 20 <212> DNA <213> Homo sapiens <400> 728 tcatcttgga gggaccaaggd 20 <210> 729 <211> 20 <212> DNA <213»> Homo sapiens <400> 729 atgtgggagg gagcagacag 20 <210> 730 - <211> 20 <212> DNA <213> Homo sapiens <400> 730 ggagggactgd cgtggtattg 20 <210> 731 <21l> 21 <212> DNA <213> Homo sapiens <400> 731 gggataggtg gagggatgas 9 21 <210> 732 <211> 21 <212> DNA <213> Homo sapiens <400> 732 tcaaacaact gtggccagtg @ 21 <210> 733 <211> 20 <212> DNA <213> Homo sapiens <400> 733 accctgagca actgggttca 20

<210> 734 <211> 20 <212> DNA <213> Homo sapiens <400> 734 ccegtgtgtt tceggtagtg 20 <210> 735 <211> 20 <212> DNA <213> Homo sapiens <400> 735 ctggtactgg ccctctgtgg 20 <210> 736 <211> 20 <212> DNA <213> Homo sapiens <400> 736 accaacagag tggggtttgg 20 <210> 737 <211> 20 <212> DNA <213> Homo sapiens <400> 737 cggcagattt tcaagctcca 20 <210> 738 <211> 20 <212> DNA <213> Homo sapiens <400> 738 gcaatgccag ctgaatagca 20 <210> 739 <211l> 24 <212> DNA <213> Homo sapiens <400> 739 tgatactccc agtcttgtca ttgce 24 <210> 740 <211> 20 <212> DNA <213> Homo sapiens

<400> 740 acgagcctgc accaaagtct 20 <210> 741 <211> 23 <212> DNA <213> Homo sapiens <400> 741 ctacctcaag ggggactgtc ttt 23 <210> 742 <21l1> 189 <212> DNA <213> Homo sapiens <400> 742 gcacgggcta caagctgag 19 <210> 743 <211> 21 <212> DNA <213> Homo sapiens <400> 743 agcaccgtgt gggacaataa c 21 <210> 744 <211> 20 <212> DNA <213> Homo sapiens <400> 744 gactgtgctc cggcagttct 20 <210> 745 <211> 20 <212> DNA <213> Homo sapiens <400> 745 ctgaggcaga cagcagctca 20 <210> 746 <211> 20 <212> DNA <213> Homo sapiens <400> 746 ttcgatggge ccaattctta 20 <210> 747 <211l> 20 <212> DNA . .

<213> Homo sapiens <400> 747 aattgttgga gagcccctca 20 <210> 748 <211> 24 <212> DNA <213> Homo sapiens <400> 748 agtgattgac ttggcatgaa aatg 24 <210> 749 <211> 22 <212> DNA <213> Homo sapiens <400> 749 ctggtgggag gtctccataa ac 22 <210> 750 <211> 20 <212> DNA <213> Homo sapiens <400> 750 ctggctcacc tggacaacct 20 <210> 751 <211> 21 <212> DNA <213> Homo sapiens <400> 751 ggccacaaga ataagcagca a 21 <210> 752 <211> 20 <212> DNA <213> Homo sapiens <400> 752 tttgggcagc ttgggtaagt 20 <210> 753 <211> 29 <212> DNA <213> Homo sapiens <400> 753 ttcaaagtta aaagcaaaca cttacagaa 29 <210> 754

<211> 20 <212> DNA <213> Homo sapiens <400> 754 acgagtggag ttgggtgtcg 20 <210> 755 <21l1l> 20 <212> DNA <213> Homo sapiens

<400> 755 tgtgtgtgct tgtgcgtgte 20 <210> 756

<21ll1l> 20

<212> DNA

<213> Homo sapiens

<400> 756 agccgaggac tggaagaagg 20 <210> 757

<211> 20

<212> DNA

<213> Homo sapiens

<400> 757 gggggatgag ttctggcagt 20 <210> 758

<211> 21

<212> DNA

<213> Homo sapiens

<400> 758 ggggctactg gagaggagag a 21 <210> 759

<211> 20

<212> DNA

<213> Homo sapiens

<400> 759 tcaatgcagg cgdtccaagta 20 <210> 760

<21ll> 24

<212> DNA

<213> Homo sapiens

<400> 760 acgtgatttt gctgtagaag atgg 24

<210> 761 <211> 31 <212> DNA <213> Homo sapiens <400> 761 gactatgagg aatatttgca agacatagaa t 31 <210> 762 <211> 20 <212> DNA <213> Homo sapiens <400> 762 ctgagctctg gectttgectt 20 <210> 763 <211> 20 <212> DNA <213> Homo sapiens <400> 763 agtccagcet gagggctctt 20 <210> 764 <211> 20 <212> DNA <213> Homo sapiens <400> 764 tgcagatgag acagcaacca 20 <210> 765 <211> 22 <212> DNA <213> Homo sapiens <400> 765 tgccaaaatc tcttctcect te 22 <210> 766 <211> 20 <212> DNA <213> Homo sapiens <400> 766 acagggagac ccgtccattt 20 <210> 767 <211> 21 <212> DNA <213> Homo sapiens <400> 767 435 h aaacagaggc catggcagaa t 21 <210> 768 <211> 25 <212> DNA <213> Homo sapiens <400> 768 tgccgtgtta ttgtattagg tgtca 25 <210> 769 <211> 20 <212> DNA <213> Homo sapiens <400> 768 gtccaccact tgctgggttt 20 <210> 770 <211> 20 <212> DNA <213> Homo sapiens <400> 770 aagccagaag ccaggaggag 20 <210> 771 <211> 24 <212> DNA : <213> Homo sapiens <400> 771 tgctgtactc aggtggcact aact 24 <210> 772 <211> 22 <212> DNA <213> Homo sapiens <400> 772 tcccaaattg aatcactgct ca 22 <210> 773 <211l> 18 <212> DNA <213> Homo sapiens <400> 773 tccactgcca tcctccca 18 <210> 774 <211l> 20 <212> DNA <213> Homo sapiens

436 y

<400> 774 tagggcctgg cttctgtctg 20 <210> 775 <211> 25 <212> DNA <213> Homo sapiens <400> 775 caaacatcac tctgctgctt agaca 25 <210> 776 <211l> 25 <212> DNA <213> Homo sapiens <400> 776 gattaattca ccttccagtg tctcecg 25 <210> 777 <211> 22 <212> DNA <213> Homo sapiens <400> 777 tggcatgtca gacagaactt ga 22 <210> 778 . <211> 20 <212> DNA <213> Homo sapiens <400> 778 . ttgtggcttc ctcagctcct 20 <210> 779 <211> 20 <212> DNA <213> Homo sapiens <400> 779 gctgaccttc ctcgcagaga 20 <210> 780 . <211> 21 ‘ <212> DNA <213> Homo sapiens <400> 780 tccctcagte ccaactectt t 21 <210> 781 <211> 19

<212> DNA . <213> Homo sapiens <400> 781 ttcatcttcec ccaagtgcg 19 <210> 782 <211> 19 <212> DNA <213> Homo sapiens <400> 782 cttgtectec gcactgcecac 19 <210> 783 <211> 23 <212> DNA <213> Homo sapiens <400> 783 tgggagtttt gctgattcct tct 23 <210> 784 <211> 28 <212> DNA <213> Homo sapiens <400> 784 ctaagccaga aacactgtaa aactacca 28 <210> 785 <211> 21 <212> DNA <213> Homo sapiens <400> 785 cccatcccca catcatattcec a 21 <210> 1786 <211> 21 <212> DNA <213> Homo sapiens <400> 786 cctctcacga cgcttctacc a 21 <210> 787 <211> 20 <212> DNA <213> Homo sapiens <400> 787 ttgcggcgtg tataccaatg 20

<210> 788 <211> 20 <212> DNA <213> Homo sapiens <400> 788 gtggtgcctt ctggagagga 20 <210> 789 <211> 20 <212> DNA <213> Homo sapiens <400> 789 tgttgtgcca gggaaggttt 20 <210> 790 <211> 22 <212> DNA <213> Homo sapiens <400> 790 cattcttcat cctcacccag ga 22 <210> 791 <211> 27 <212> DNA <213> Homo sapiens <400> 791 catgctttga gagtgattat ttccttt 27 <210> 792 <21ll> 24 <212> DNA <213> Homo sapiens <400> 792 tctcattagc ctgaatgtgc cata 24 <210> 793 <211> 20 <212> DNA <213> Homo sapiens <400> 793 cggaggagat tttcggacct 20 <210> 754 <211> 21 <212> DNA <213> Homo sapiens <400> 794 ccttggaaga tctgacccga a i 21

<210> 795 <211> 20 <212> DNA <213> Homo sapiens <400> 795 gaggtggagc tggtgcagat 20 <210> 796 <211> 20 <212> DNA <213> Homo sapiens <400> 796 gcccagccta ggatctgaca 20 <210> 797 . <211> 20 <212> DNA <213> Homo sapiens <400> 797 gcagactgag cgggaaaaga 20 <210> 798 <211> 20 <212> DNA <213> Homo sapiens <400> 798 tcccaaccga acttcttcca 20 <210> 799 <211> 32 <212> DNA <213> Homo sapiens <400> 799 tctacatgca atgttagtaa ttctgaagtt tt 32 <210> 800 <211> 20 <212> DNA <213> Homo sapiens <400> 800 ccaggaggat ggcaaagaga 20 <210> 801 <211> 20 <212> DNA : <213> Homo sapiens

<400> 801 cgaccatcca agggagagtg 20 <210> 802 <211> 20 <212> DNA <213> Homo sapiens <400> 802 gggctccagg actccctcta 20 <210> 803 <211> 20 <212> DNA <213> Homo sapiens <400> 803 gcctecttece atctcaacca 20 <210> 804 ’ <211> 20 <212> DNA <213> Homo sapiens <400> 804 ggtggatcag gccgttattg 20 <210> 805 <211> 20 <212> DNA . <213> Homo sapiens <400> 805 aggggagacc gaagtgaagg 20 <210> 806 <211> 23 <212> DNA <213> Homo sapiens <400> 806 aaaaccgtat ccttccectgt tgt 23 <210> 807 <211> 20 <212> DNA <213> Homo sapiens <400> 807 aagaggcagc cgagagaatg 20 <210> 808 <211> 20 <212> DNA

<213> Homo sapiens <400> 808 acccgectgtt tccagagttg 20 <210> 809 <211> 24 <212> DNA <213> Homo sapiens <400> 809 tgggctaact atgcagagca tgta 24 <210> 810 <211> 20 <212> DNA <213> Homo sapiens <400> 810 tggggcttct gagagattgg ’ 20 <210> 811 <211> 20 <212> DNA <213> Homo sapiens <400> 811 cttaaacttg gcccggcatt 20 <210> 812 <211> 20 <212> DNA <213> Homo sapiens <400> 812 cggtgccttc ttaggagetg 20 <210> 813 <211> 21 <212> DNA <213> Homo sapiens <400> 813 cctaggggag accgaagtga a 21 <210> 814 <211> 20 <212> DNA <213> Homo sapiens <400> 814 tgectgcggca tagaatcaag 20 <210> 815 442 A

<211> 19 <212> DNA <213> Homo sapiens <400> 81S tcgttgcaat cctcggtca 19 <210> 81s6 <211> 20 <212> DNA <213> Homo sapiens <400> 816 agcagcaggt ggaatccaag 20 <210> 817 <211l> 20 <212> DNA <213> Homo sapiens <400> 817 ggccatttca ggcagcataa 20 <210> 818 <211s> 21 <212> DNA <213> Homo sapiens <400> 818 ttctaccctg cggagatcac a 21 <210> 819 <211> 20 <212> DNA <213> Homo sapiens <400> 819 gcttgtgcat gaccctgatg 20 <210> 820 <211> 20 <212> DNA <213> Homo sapiens <400> 820 ttgecctete ctcacacgta 20 <210> 821 <211> 20 <212> DNA <213> Homo sapiens <400> 821 cccectggagg ttgtcttcaa 20

<210> 822 <211> 22 <212> DNA <213> Homo sapiens <400> 822 tgcecttgcta cctcatcaga ga 22 <210> 823 <211> 20 <212> DNA <213> Homo sapiens <400> 823 agagagggcc tgccttaacc 20 <210> 824 <211> 19 <212> DNA <213> Homo sapiens <400> 824 tcccattcca ccacagtgce 19 <210> 825 <211> 22 <212> DNA <213> Homo sapiens <400> 825 tcaaggatca gtttcaccca ca 22 <210> 826 <211> 19 <212> DNA <213> Homo sapiens <400> 826 ttctccgage ttcgcaatg 19 <210> 827 <211> 20 <212> DNA <213> Homo sapiens <400> 827 ggcatcctgg gctacactga 20 <210> 828 <211l> 20 <212> DNA <213> Homo sapiens

<400> 828 gcacgacgat gaggtgacag 20 <210> 829 <211> 20 <212> DNA <213> Homo sapiens <400> 829 ccaaccaaaa ttgccccttt 20 <210> B30 <211> 20 <212> DNA <213> Homo sapiens <400> 830 tgttaggccc ctgtttcctg 20 <210> 831 <211> 19 <212> DNA <213> Homo sapiens <400> 831 ctcatcatcec tggccgtca 19 <210> 832 <211> 20 <212> DNA <213> Homo sapiens <400> 832 tgttcactge agcccatttg 20 <210> 833 <211> 21 <212> DNA <213> Homo sapiens <400> 833 ttccaaaagc caaggtgaga a 21 <210> 834 <211i> 21 <212> DNA

<213> Homo sapiens <400> 834 aaagttgctg tggttggttg c 21 <210> 835 <211l> 21 <212> DNA <213> Homo sapiens

<400> 835 gaccatccca aaatgcttca a 21 <210> 836 <211> 21 <212> DNA <213> Homo sapiens <400> 836 tggcgccaac tttaaacatt c¢ 21 <210> 837 <211> 20 <212> DNA <213> Homo sapiens <400> 837 cctcaacccc atgctttacg 20 <210> 838 <211> 20 <212> DNA <213> Homo sapiens <400> 838 tcttcggectg ctcctgactt 20 <210> 839 <211> 20 <212> DNA <213> Homo sapiens <400> 839 tttctectee tececectcage 20 <210> 840 <211> 20 <212> DNA <213> Homo sapiens <400> 840 ttgagggccc ttgacaaaag 20 <210> 841 <211> 24 <212> DNA <213> Homo sapiens <400> 841 ccattatggt gctactgagc gttt 24 <210> 842 <21l> 22

<212> DNA <213> Homo sapiens <400> 842 aggggaagtt tgtaccccat tg 22 <210> 843 <211> 21 <212> DNA <213> Homo sapiens <400> 843 ggctcttcag ctgecttgtee t 21 <210> 844 <211> 20 <212> DNA <213> Homo sapiens <400> 844 tcgtegtggt ggttttgttg 20 <210> 845 <211> 20 <212> DNA <213> Homo sapiens <400> 845 tccgececatce ctgectattta 20 <210> 846 <211> 20 <212> DNA <213> Homo sapiens : <400> 846 gatgcagaga gccagcaagg 20 <210> 847 <211> 23 <212> DNA <213> Homo sapiens <400> 847 cccaggtatt acacaagcca aaa 23 <210> 848 <211> 20 <212> DNA <213> Homo sapiens <400> 848 ctgactctgc ccgacttcct 20

<210> 849 <211> 32 <212> DNA <213> Homo sapiens <400> 849 ttcctatcta ataaatgecct ttaattgttc tc 32 <210> 850 <211> 21

<212> DNA

<213> Homo sapiens

<400> 850 gcgtcatggt gtctcatcgt t 21 <210> 851

<211> 20

<212> DNA

<213> Homo sapiens

<400> 851 tgacatgact ggctggttgc 20 <210> 852

<211> 20

<212> DNA

<213> Homo sapiens

<400> 852 cacgacgtct ccgcgtatct 20 <210> 853

<211> 20

<212> DNA

<213> Homo sapiens

<400> 853 agttaacggc ccaagtggtg 20 <210> 854

<211> 25

<212> DNA

<213> Homo sapiens

<400> 854 agctgtttca tgtagctgct ttagg 25 <210> 855

<21l1l> 19

<212> DNA

<213> Homo sapiens

<400> 855 gaaacacagc ccgatggtg 19

<210> 856 <211> 20 <212> DNA <213> Homo sapiens <400> 856 ttcctttcac cacccacacc 20 <210> 857 <211> 19 <212> DNA <213> Homo sapiens <400> 857 gacccctect tceccttcet 19 <210> 858 <211> 20 <212> DNA <213> Homo sapiens <400> 858 cacccagtgc taccgagaca 20 <210> 859 <211> 18 <212> DNA <213> Homo sapiens <400> 859 tgtcgctgct gtggttge 18 <210> 860 <211> 20 <212> DNA <213> Homo sapiens <400> 860 . agccatgaag cacatggtca 20 <210> 861 <211> 20 <212> DNA <213> Homo sapiens <400> 861 caatatgtgc cgccagtgtt 20 <210> 862 <211> 28 <212> DNA <213> Homo sapiens

<400> 862 aatcttacac acaaatgaaa atgcaagt 28 <210> 863 <211> 20 <212> DNA <213> Homo sapiens <400> 863 atgttgcggt aatcggagga 20 <210> 864 ’ <211> 20 <212> DNA <213> Homo sapiens <400> 864 cctgggtgtt tgggtcagat 20 <210> 865 <211> 22 <212> DNA <213> Homo sapiens <400> 865 ctgtcttcag ctgggtcaga ga 22 <210> 866 <211> 20 <212> DNA <213> Homo sapiens <400> 866 gagcagggac tctggagcag 20 <210> 867 <211l> 21 <212> DNA <213> Homo sapiens <400> 867 cagaaaacgc aggtgaaatg c 21 <210> 868 <211> 22 <212> DNA <213> Homo sapiens <400> 868 gcgttatagg tggagaccga gt 22 <210> 869 <211> 19 . <212> DNA

<213> Homo sapiens <400> 869 tccacctttg ggtcgcttt 19 <210> 870 <211> 20 <212> DNA <213> Homo sapiens <400> 870 tctggtettg ggaggtgagg 20 <210> 871 <211> 20 <212> DNA <213> Homo sapiens <400> 871 gcaccaggtg gtctcctctg 20 <210> 872 <211> 20 <212> DNA <213> Homo sapiens <400> 872 ctaccccaca gcaggtagcc 20 <210> 873 <211> 20 <212> DNA <213> Homo sapiens <400> 873 cctgaccaac attgcgattg 20 <210> 874 <211> 20 <212> DNA <213> Homo sapiens <400> 874 cccatgccag tgatcctacce 20 <210> 875 <211> 20 <212> DNA <213> Homo sapiens <400> 875 tcctecctgga ccgtgagaag 20 <210> 876

<211> 23 <212> DNA <213> Homo sapiens <400> 876 gattcctctt ggacccactt ttc 23 <210> 877 <211> 20 <212> DNA <213> Homo sapiens <400> 877 gctagcccca tcctcactca 20 <210> 878 <211> 21 <212> DNA <213> Homo sapiens <400> 878 ccgaaagcct cctggaaatt a 21 <210> 879 <211> 20 <212> DNA <213> Homo sapiens <400> 879 gcatcatgtt gaccgagctg 20 <210> 880 <211> 27 <212> DNA <213> Homo sapiens <400> 880 tgtggaaagt tttccctcat atactca 27 <210> 881 <211> 21 . <212> DNA <213> Homo sapiens <400> 881 gggagacctg cctctcagaa t 21 <210> 882 <211> 20 <212> DNA <213> Homo sapiens <400> 882 tgcagagcce caattcectac 20

<210> 883 <211> 18 <212> DNA <213> Homo sapiens <400> 883 gccccacgtg tgaccatt 18 <210> B84 <211> 24 <212> DNA <213> Homo sapiens <400> 884 tcgttgtgta atcgtgtcag aaaa 24 <210> 885 <211> 20 <212> DNA <213> Homo sapiens <400> 885 aacaagctgt ccagcgaagc 20 <210> 886 <211> 20 <212> DNA <213> Homo sapiens <400> 886 cggtacccaa ttcgccctat 20 <210> 887 <211> 20 <212> DNA <213> Homo sapiens <400> 887 accectgtggt ggtcttggac 20 <210> 888 <211> 20 <212> DNA <213> Homo sapiens <400> 888 gccgtataca acggcgagac 20 <210> 889 <211l> 21 <212> DNA <213> Homo sapiens <400> 889 aagagccagc agagcaaaac a 21 <210> 890 <211> 22 <212> DNA : <213> Homo sapiens <400> 890 ttacgtgtgc acagagaggt ca 22 <210> 891 <211> 20 <212> DNA <213> Homo sapiens <400> 891 ggtggcacct accgtctgtt 20 <210> 892 <211> 20 <212> DNA <213> Homo sapiens <400> 892 tgtgttccct ggtgatgtgg 20 <210> 893 <211> 20 <212> DNA <213> Homo sapiens <400> 893 cttcgtggag gctgtggaac 20 <210> 894 <211> 20 <212> DNA <213> Homo sapiens <400> 8954 tgaggcctga gtcettetgg 20 <210> 895 <211> 20 <212> DNA <213> Homo sapiens <400> 895 atttcgcagg ccttcctete 20 <210> 896 <211> 21 <212> DNA <213> Homo sapiens

<400> 896 tgtgtgtgca ccttgtcttc ¢ 21 <210> 897 <211> 20 <212> DNA ’ <213> Homo sapiens <400> 897 gtcctggcaa catggagagg 20 <210> 898 <211> 27 <212> DNA <213> Homo sapiens <400> 898 ccctaattge taagatttaa ggacgtt 27 <210> 899 <211> 25 <212> DNA <213> Homo sapiens <400> 899 ttgagggagt agtggaatga aaaca 25 <210> 900 <211> 20 <212> DNA <213> Homo sapiens <400> 900 tgggagaact ccaatgctga 20 <210> 901 <211> 20 <212> DNA <213> Homo sapiens <400> 901 gcaccagcag ggatggatta 20 <210> 902 <211> 20 <212> DNA <213> Homo sapiens <400> 902 gcctggaccg atgtgtctct 20 <210> 903 <211> 22

<212> DNA <213> Homo sapiens <400> 903 cagccacagc cttttaattt gg 22 <210> 904 <211> 20 ‘ <212> DNA

<213> Homo sapiens

<400> 904 aagacacccg catcttcctg 20 <210> 905

<211> 20

<212> DNA

<213> Homo sapiens

<400> 905 gggagacctg ctctgcaaaa 20 <210> 906

<211> 22

<212> DNA

<213> Homo sapiens

<400> 906 cccaaactga tcttccaggce ta 22 <210> 907

<211> 20

<212> DNA

<213> Homo sapiens

<400> 907 . ttccecctcte atcgtcatgg 20 <210> 908

<211> 20

<212> DNA

<213> Homo sapiens

<400> 908 ccaaggacct gggatctcct 20 <210> 909

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 909 gaaaaccacg gaggtggatg 20

456 p

<210> 910 <21l> 20 <212> DNA <213> Homo sapiens <400> 910 tggaggcaga gtgacggact 20 <210> 911 <211> 20 <212> DNA <213> Homo sapiens '<400> 3911 gtaggcacgc acgaagaaca 20 : <210> 912 <211> 20 <212> DNA <213> Homo sapiens <400> 912 cctccgcaga tgcttcattt 20 <210> 913 <211> 27 <212> DNA <213> Homo sapiens <400> 913 tttgttttga gttttcaaag aatagcc 27 <210> 914 <211> 22 <212> DNA <213> Homo sapiens <400> 914 ggtacagcac ttggctgggt ta 22 <210> 915 <211> 31 <212> DNA <213> Homo sapiens <400> 915 tttgtacatg actctcattt tattgtttct t 31 <210> 916 <211> 20 <212> DNA <213> Homo sapiens <400> 916 cctgcttggg gaaatgttca 20

<210> 917 <211> 19 <212> DNA <213> Homo sapiens <400> 917 gtgggcttca gggttggag 19 <210> 918 <211> 20 <212> DNA <213> Homo sapiens <400> 918 cctggatgtc agcgaagagg . 20 <210> 919 <211> 21 <212> DNA <213> Homo sapiens <400> 919 caagcttcac tggctctctg g 21 <210> 920 <211> 20 <212> DNA <213> Homo sapiens <400> 920 gcccaaaact gctccaaaga . 20 <210> 921 <211> 22 <212> DNA <213> Homo sapiens <400> 921 gccttteccag tacaggcact tt 22 <210> 922 <211> 20 <212> DNA <213> Homo sapiens <400> 922 gcgcggtgag gttgtctagt 20 <210> 923 <211> 26 <212> DNA <213> Homo sapiens

<400> 923 tcaacactac acatgaatga atccaa 26 <210> 924 <211> 29 <212> DNA <213> Homo sapiens <400> 924 tggaaatgta accattttag gataatgtc 29 <210> 925 <211> 21 <212> DNA <213> Homo sapiens <400> 925 cccaagagag aacagggtgg t 21 <210> 926 <211> 32 <212> DNA <213> Homo sapiens <400> 926 cactcagtaa agacaatttc cataaaataa aa 32 <210> 927 <211> 20 <212> DNA <213> Homo sapiens <400> 927 ccgcccgtaa ttaaatagca 20 <210> 928 <211> 20 <212> DNA <213> Homo sapiens <400> 928 cctgcagcag atgcctcettt ’ 20 <210> 929 <211l> 20 <212> DNA <213> Homo sapiens <400> 929 tcccctgggt tgctaattga 20 <210> 930 <211> 20 <212> DNA

<213> Homo sapiens <400> 930 gccttcattt ccgcaggtta 20 <210> 931 <211> 20 <212> DNA <213> Homo sapiens

<400> 931 cgtctggtga caaccgagtg 20 <210> 932

<211l> 21

<212> DNA

<213> Homo sapiens

<400> 932 tggcagggta aggagtgttt g 21 <210> 933

<211> 20

<212> DNA

<213> Homo sapiens

<400> 933 atcgcttttg gcgacagact 20 <210> 934

<211> 20

<212> DNA

<213> Homo sapiens

<400> 934 tcctgagete gccaataagce 20 <210> 935

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 935 tggcaccaaa aggcacaata 20 <210> 936

<211> 20

<212> DNA

<213> Homo sapiens

<400> 936 caagagatgc agtgccagga 20 <210> 937

460 N

<211> 20 <212> DNA <213> Homo sapiens <400> 937 agaggaggag gctgctggtt 20 <210> 938 <211> 20 <212> DNA <213> Homo sapiens <400> 938 gctecgecccac aaactgattt 20 <210> 939 <211> 25 <212> DNA <213> Homo sapiens <400> 939 tgatttggat acggtgaata agctg 25 <210> 940 <211> 20 <212> DNA <213> Homo sapiens <400> 940 cggcaaagag aacggaaaga 20 <210> 941 <211> 20 <212> DNA <213> Homo sapiens <400> 941 gatcccagec cacaagtgat 20 <210> 942 <211> 27 <212> DNA <213> Homo sapiens <400> 942 acttgttaac ctttctaacc ttcacga : 27 <210> 943 <211> 20 <212> DNA <213> Homo sapiens <400> 943 agtaagtcag ggcgggcttt 20

<210> 944 : <211> 20 <212> DNA <213> Homo sapiens <400> 944 tcttcaccca tcatggagca 20 <210> 945 <211> 20 <212> DNA <213> Homo sapiens <400> 945 cattcagcgg acagcaaaca 20 <210> 946 <211> 20 <212> DNA <213> Homo sapiens <400> 946 ttgtccatgg caaaacagga 20 <210> 947 : <211> 20 <212> DNA <213> Homo sapiens <400> 947 aggtcctect ccecttttec 20 <210> 948 <211> 20 <212> DNA <213> Homo sapiens <400> 948 tcacactetg caccecteag 20 <210> 949 <21l1l> 24 <212> DNA <213> Homo sapiens <400> 949 caacattggc tggtaatagg cttt 24 <210> 950 . <211> 20 <212> DNA <213> Homo sapiens <400> 950 462 W tccactgeccec taacacacga 20 <210> 951 <211> 21 <212> DNA <213> Homo sapiens : <400> 951 acccatttta cagtgccatg c 21 <210> 952 <211> 20 <212> DNA <213> Homo sapiens <400> 952 gctctttgee tgectggttte : 20 <210> 953 <211> 20 <212> DNA <213> Homo sapiens <400> 953 cgaacgagtc atggcctagc 20 <210> 954 <211> 20 <212> DNA <213> Homo sapiens <400> 954 ggtaagcaca tcccctcgaa 20 <210> 955 <21l1l> 25 <212> DNA <213> Homo sapiens <400> 955 cccataacca aaatttaaag gcaaa 25 <210> 956 <211> 21 <212> DNA : <213> Homo sapiens <400> 956 tggcatgttt tgtgcatttg t 21 <210> S957 <211> 20 <212> DNA <213> Homo sapiens

<400> 957 ccatggggtg agacttgagc 20 <210> 958 <211> 20 <212> DNA <213> Homo sapiens <400> 958 tttctccaga agcccagcac 20 <210> 959 <211> 25 <212> DNA <213> Homo sapiens <400> 959 ttttttttca agcagtaaaa ttcca 25 <210> 960 <211> 20 <212> DNA <213> Homo sapiens <400> 960 cactctgcgc cacaaaggtt 20 <210> 961 <211> 20 <212> DNA <213> Homo sapiens <400> 961 gaagcccctc accctgagat 20 <210> 962 <211> 20 <212> DNA <213> Homo sapiens <400> 962 ccgtacaagt cgggtgggta 20 <210> 963 <211> 20 <212> DNA <213> Homo sapiens <400> 963 : gcaaagtgag gagggagctg 20 <210> 964 <211> 20 464 i

<212> DNA <213> Homo sapiens <400> 964 cagggctatg agcggaagaa 20 <210> 965 <211> 20 <212> DNA <213> Homo sapiens <400> 965 gacccgccaa aaccaaatta 20 <210> 966 <211> 20 <212> DNA <213> Homo sapiens <400> 966 gacgtcattg tcggcgactt 20 <210> 967 <211> 20 <212> DNA <213> Homo sapiens <400> 967 cttccagcag accccagtgt 20 <210> 968 <211> 20 <212> DNA <213> Homo sapiens <400> 968 : cctctgetgg gttgttaccg ’ 20 <210> 969 <211> 21 <212> DNA <213> Homo sapiens <400> 969 tgaatccctt gctgttcect a 21 <210> 970 <211> 20 <212> DNA <213> Homo sapiens <400> 970 taccttgget ccctgtcctg 20

<«210> 971 <211> 20 <212> DNA <213> Homo sapiens <400> 971 taggggtaag ccctgggtgt 20 <210> 972

<211> 21

<212> DNA

<213> Homo sapiens

<400> 972 ttccatcctg tcctggaatc a 21 <210> 973

<211> 20

<212> DNA

<213> Homo sapiens

<400> 973 gggcacagct tcctctcettg 20 <210> 974

<211> 20

<212> DNA

<213> Homo sapiens

<400> 974 ccctgceccaca cacacatttt 20 <210> 975

<211> 20

<212> DNA

<213> Homo sapiens

<400> 975 cccttgtgte cccacatttt 20 <210> 976

<211> 20

<212> DNA

<213> Homo sapiens

<400> 976 ctgcagcctc acagacctga 20 <210> 977

<211> 21

<212> DNA

<213> Homo sapiens

<400> 977 tgccattgtc ccatctagga a 21

466

<210> 978 <211> 21 <212> DNA <213> Homo sapiens <400> 978 tcagggattt ctaagccacc a 21 <210> 979

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 979 agcagggaat tccaggaagc 20 <210> 980

<211> 20 : <212> DNA

<213> Homo sapiens

<400> 980 gcctectgta gtegetttge 20 <210> 981 ’

<211> 20

<212> DNA

<213> Homo sapiens

<400> 981 gcacggttca aaagcaggtt 20 <210> 982

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 982 gagccctcge ctctttctte 20 <210> 983

<211> 20

<212> DNA

<213> Homo sapiens

<400> 983 ggtggtgtgc agagcgtatg 20 <210> 984

<211> 20

<212> DNA

<213> Homo sapiens

<400> 984 accgacgaga ccagaagtgg 20 <210> 985 <211l> 27 <212> DNA <213> Homo sapiens <400> 98S ttctgttgga gtattttctt ccttacg 27 <210> 986 <211> 20 <212> DNA <213> Homo sapiens <400> 986 cacacttgtg ggcaatctgg 20 <210> 987 <211> 20 <212> DNA <213> Homo sapiens <400> 987 cccgtggage tgacaagttt 20 <210> 988 <211> 20 <212> DNA <213> Homo sapiens <400> 988 agtgccccag gcatttettt 20 <210> 989 <211> 20 <212> DNA <213> Homo sapiens <400> 989 gcctttgectg ggcattatgt 20 <210> 950 <211l> 20 <212> DNA <213> Homo sapiens <400> 990 ccgagccaag acgagaagaa 20 <210> 981 <21l> 20 <212> DNA 468 L

<213> Homo sapiens <400> 991 cctgcatttg accagagcaa 20 <210> 992 <211> 25 <212> DNA <213> Homo sapiens . <400> 992 tgcaacacta acaagagaga atgga 25 <210> 993 <211l> 20 <212> DNA <213> Homo sapiens <400> 993 aggcccagac ttctccaagg 20 <210> 994 <211> 20 <212> DNA <213> Homo sapiens <400> 994 aggccaagtc aggcccttat 20 <210> 985 <211i> 20 <212> DNA <213> Homo sapiens <400> 995 ttgccagaat gggactgtga 20 <210> 996 <211l> 20 <212> DNA <213> Homo sapiens <400> 996 gcaagcttat gacccgcact 20 <210> 997 <211> 20 <212> DNA <213> Homo sapiens <400> 997 tggcttttag gatggcaagg 20 <210> 998

<211> 19 <212> DNA <213> Homo sapiens <400> 998 ccgataaggg cgaggtctg 19 <210> 999 <211> 22 <212> DNA <213> Homo sapiens <400> 999 tttccceccaa attctaagca ga 22 <210> 1000 <211> 20 <212> DNA <213> Homo sapiens <400> 1000 ’ ccagagccca ggtttctcaa 20 <210> 1001 <211> 20 <212> DNA <213> Homo sapiens <400> 1001 ggcaagtgag gggatgagtg 20 <210> 1002 <211> 20 <212> DNA <213> Homo sapiens <400> 1002 ggcgctetcect atgtgggtgt 20 <210> 1003

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1003 gggtcattag aagccccttc a 21

<210> 1004

<211l> 20

<212> DNA :

<213> Homo sapiens

<400> 1004 cccatgttcc cgaagtagga 20 470 I

<210> 100S <211> 20 <212> DNA

<213> Homo sapiens

<400> 1005 ggggaggtgg ataggcaaac 20 <210> 1006

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1006 ttttcagccc cttgcttctg 20 <210> 1007

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1007 ggacgtcttt ggttgggatt t 21 <210> 1008

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1008 gaaggagggg tgggttgttc 20 <210> 1009

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1009 ttgacttggc ccagagggta 20 <210> 1010

<21l1> 20

<212> DNA

<213> Homo sapiens

<400> 1010 actcgaacac tgcagcatgg 20 <210> 1011

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1011 cccatggatg atgactgctg 20 <210> 1012 <211> 22 <212> DNA <213> Homo sapiens <400> 1012 ggtggtttta cagtccctgc at 22 <210> 1013 <211> 20 <212> DNA <213> Homo sapiens <400> 1013 tgccaaacct tgagtgatgg 20 <210> 1014 <211> 20 <212> DNA <213> Homo sapiens <400> 1014 atcgtcttgg tcgccactgt 20 <210> 1015

<211l> 20 <212> DNA <213> Homo sapiens <400> 1015 tgtgecgttgc ctgaatgaac 20 <210> 1016 <211> 20 <212> DNA <213> Homo sapiens <400> 1016 ggaggaagcc atggagatca 20 <210> 1017 <211l> 20 <212> DNA : <213> Homo sapiens <400> 1017 tctceccact tgaagcegtct 20 <210> 1018 <211l> 20 <212> DNA <213> Homo sapiens

<400> 1018 tgcaaaatgc atgccctgta 20 <210> 1019 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 1019 ccgaccgtcc ataggatacg 20 <210> 1020 <211> 20 ’ <212> DNA <213> Homo sapiens <400> 1020 ctttggaaag gtgcgagagc 20 <210> 1021 <211> 20 <212> DNA <213> Homo sapiens <400> 1021 tccagggaac tgggagtgag 20 <210> 1022 <211> 20 <212> DNA <213> Homo sapiens <400> 1022 tcccttctecg gaccagtgtce 20 <210> 1023 <211> 20 <212> DNA <213> Homo sapiens <400> 1023 gtaggggcca tcggataagc 20 <210> 1024 <211> 20 <212> DNA <213> Homo sapiens <400> 1024 accaccaaca acccacatcc 20 <210> 1025 <211> 20

<212> DNA <213> Homo sapiens <400> 1025 ggatccccac tggcatttcet 20 <210> 1026 <211> 20 <212> DNA <213> Homo sapiens <400> 1026 gaagaagccg accttccaca 20 <210> 1027 <211> 20 <212> DNA <213> Homo sapiens <400> 1027 ctgtagtcac ggcccagcte 20 <210> 1028 <211> 20 <212> DNA <213> Homo sapiens <400> 1028 atagacacca ggcccacgag : 20 <210> 1029 <211> 20 <212> DNA <213> Homo sapiens <400> 1029 ggggaaggac aggdaacatcc 20 <210> 1030 . <211> 20 <212> DNA <213> Homo sapiens <400> 1030 tgtecgtcgat gctcttcacc 20 <210> 1031 <211> 20 <212> DNA <213> Homo sapiens <400> 1031 ccctggcecca caagtatcac 20

<«210> 1032 <211> 20 <212> DNA <213> Homo sapiens <400> 1032 gccctggete acaagtacca 20 <210> 1033 <21l> 20 <212> DNA <213> Homo sapiens <400> 1033 atggcagagg gagacgacag 20 <210> 1034 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 1034 gctttgtgge atctcccaag 20 <210> 1035 <211l> 20 <212> DNA <213> Homo sapiens <400> 1035 ttcagcggta ctcggaaacc 20 <210> 1036 <211> 20 <212> DNA <213> Homo sapiens <400> 1036 caggcatctg gattggctct 20 <210> 1037 <211l> 20 <212> DNA <213> Homo sapiens <400> 1037 attccgaaac caccggactt 20 <210> 1038 <211> 21 <212> DNA <213> Homo sapiens <400> 1038 cgactccact cagcatcttg ¢ 21

<210> 1039 <211> 20 <212> DNA <213> Homo sapiens <400> 1039 tgggatgagg atgtgtcgag 20 <210> 1040

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1040 gccatacctc taggctggct atc 23 <210> 1041

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 1041 ctgegcatte tcaagggttt 20 <210> 1042

<211> 23

<212> DNA ’

<213> Homo sapiens

<400> 1042 ttcecggaagt catttcacta agc 23 <210> 1043

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1043 aggattgacc gtcccctcte 20 <210> 1044

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1044 caccctccag ttcccactgt 20 <210> 1045

<211> 20

<212> DNA )

<213> Homo sapiens

\

<400> 1045S tcaacagcaa caagcccgta 20 <210> 1046 <211> 19 <212> DNA ‘ <213> Homo sapiens <400> 1046 agcagttcca ccecctctgg 18 <210> 1047 <211> 20 <212> DNA <213> Homo sapiens <400> 1047 ccggccaacc cctttaaata 20 <210> 1048 <211> 20 <212> DNA <213> Homo sapiens <400> 1048 tcagcgtgge tatcagttgg 20 <210> 1049 <211> 20 <212> DNA <213> Homo sapiens <400> 1049 caagtgcgga gacccatctt 20 <210> 1050 <211> 22 <212> DNA <213> Homo sapiens <400> 1050 acagccatca agaaaggaca ca 22 <210> 1051 <211> 21 <212> DNA <213> Homo sapiens <400> 1051 ccacctgcat ccaaataatg g 21 <210> 1052 <211> 20 : <212> DNA

<213> Homo sapiens

<400> 1052 tccaaagggt tgcttgaagg 20 <210> 1053

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1053 ccatggaagg gtccaatgag 20 <210> 1054 <211> 19

<212> DNA

<213> Homo sapiens

<400> 1054 gcectgctect cttggatgg 19 <210> 1055

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1055 aaatagggga cctgccecagt 20 <210> 1056

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1056 tgtaggcgce aaggtggtat 20 <210> 1057

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1057 gttgccacag aaggagggtt t 21 <210> 1058

<211> 22

<212> DNA

<213> Homo sapiens

<400> 1058 tccattcacc gtcaagactg aa 22 <210> 1059

<211> 22 <212> DNA <213> Homo sapiens <400> 1059 tattcccatt cttctgeccat gc 22 <210> 1060 <211> 20 . <212> DNA <213> Homo sapiens <400> 1060 ggtgaagagg tggagggtga 20 <210> 1061 <211> 20° <212> DNA <213> Homo sapiens <400> 1061 ggtgtctggt ttgggtccag 20 <210> 1062 <211> 20 <212> DNA <213> Homo sapiens <400> 1062 aacaggcgac ctttcagcag 20 <210> 1063 <211> 20 <212> DNA <213> Homo sapiens <400> 1063 aggcatgaag gatgccaaga 20 <210> 1064 <211> 20 '<212> DNA <213> Homo sapiens . <400> 1064 ccaggacctc ctgcttagec 20 <210> 1065 <21l> 20 <212> DNA <213> Homo sapiens <400> 1065 cacaggggag aagccatacg 20

<210> 1066 <211> 20 <212> DNA <213> Homo sapiens <400> 1066 tcatgaggct gtgctggaag 20 <210> 1067 <211l> 22 <212> DNA <213> Homo sapiens <400> 1067 ggcttctctg tgaattgcect gt 22 <210> 1068 <211> 20 <212> DNA <213> Homo sapiens <400> 1068 ggctccaatg gtttccacaa 20 <210> 1069 : <211> 20 <212> DNA <213> Homo sapiens <400> 1069 ggtccatgtc tttggggatg 20 <210> 1070 <211> 24 <212> DNA <213> Homo sapiens <400> 1070 gactgtggag ttttggctgt ttta 24 <210> 1071 <211> 20 <212> DNA <213> Homo sapiens <400> 1071 tcattacage gggggcttag 20 <210> 1072 <211> 21 <212> DNA <213> Homo sapiens <400> 1072 ttggcctett tcagcctctt t 21 <«210> 1073 <211> 19 <212> DNA <213> Homo sapiens <400> 1073 cctgcagtgg geccctagtce 19 <210> 1074 <211> 20 <212> DNA <213> Homo sapiens <400> 1074 gagcacatcc ccaaaatcca 20 <210> 1075 <211> 20 <212> DNA <213> Homo sapiens <400> 1075 gatcagctgc ttgtgcctgt 20 <210> 1076 <211> 20 <212> DNA <213> Homo sapiens <400> 1076 cagccacagt cttccccaat 20 <210> 1077 <211> 20 <212> DNA <213> Homo sapiens <400> 1077 aaccttcatg caccccattc 20 <210> 1078 <211> 20 <212> DNA <213> Homo sapiens <400> 1078 agtgcatgtt tgggacagca 20 <210> 1079 <211> 20 <212> DNA <213> Homo sapiens

<400> 1079 ctgtggtgct cttggtctge 20 <210> 1080 <211> 23 <212> DNA <213> Homo sapiens <400> 1080 agttcaaccc aaatgatcag gaa 23 <210> 1081 <211> 20 <212> DNA <213> Homo sapiens <400> 1081 gcccaggagc ctgaagttct 20 <210> 1082 <211> 23 <212> DNA <213> Homo sapiens <400> 1082 accaaaatga gaacctcaac agc 23 <210> 1083 <21l1l> 27 <212> DNA <213> Homo sapiens <400> 1083 aatttctgga aaagtcaaca ggataca 27 <210> 1084 <211l> 25 <212> DNA <213> Homo sapiens <400> 1084 ttgatgatgt ctctcactct gttece 25 <210> 1085 <211> 20 <212> DNA <213> Homo sapiens <400> 1085 ttgagtggct gggactccat 20 <210> 1086 <211> 20

<212> DNA <213> Homo sapiens

<400> 1086 ccggccacat tcactgattt 20 <210> 1087

<21ll> 20

<212> DNA

<213> Homo sapiens

<400> 1087 aagcggtcga tggtcttctg 20 <210> 1088

<211> 24

<212> DNA

<213> Homo sapiens

<400> 1088 gatggaaacc agagacaaaa acga 24 <210> 1089

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1089 gagaattccg gaacctgtgg 20 <210> 1050

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1090 cccaacttecc tgacggttca 20 <210> 1091

<21l> 21

<212> DNA

<213> Homo sapiens

<400> 1091 ggtgctgaaa tcaacccact ¢ 21 <210> 1092

<211l> 28

<212> DNA

<213> Homo sapiens

<400> 1092 agaattgatt taggaaagtc acaaacct 28

483 F

<210> 10893 <211l> 20 <212> DNA <213> Homo sapiens <400> 1093 tgcagtgttec ctcccttect 20 <210> 1094 <211> 20 <212> DNA <213> Homo sapiens <400> 1094 gcccagtgga caggtttctg 20 <210> 10955 <21l1l> 25 <212> DNA <213> Homo sapiens <400> 1055 cctgatatgt tttaagtggg aagca 25 <210> 1096 <211l> 25 <212> DNA <213> Homo sapiens <400> 1096 tgatcacatg aagtcacatt ggttt 25 <210> 1097 <211> 19 <212> DNA <213> Homo sapiens <400> 1097 agatgatccc cgcacatga 15 <210> 1098 <211> 20 <212> DNA <213> Homo sapiens <400> 1098 ctgcctggga cctcattcat 20 <210> 109% <211> 23 <212> DNA <213> Homo sapiens <400> 109% ccatgtattt gcaacagcag aga 23

<210> 1100 <211> 20 ! <212> DNA <213> Homo sapiens <400> 1100 gccaaacctg caaacaaaca 20 <210> 1101 <211> 21 <212> DNA <213> Homo sapiens <400> 1101 gggaccgctt tcttacctgt t 21 <210> 1102 <211> 23 <212> DNA <213> Homo sapiens <400> 1102 cagtcattgg tgtctttgga gtg 23 <210> 1103 <211> 20 <212> DNA <213> Homo sapiens <400> 1103 gatctccacc ggacagcact 20 <210> 1104 <211> 30 <212> DNA <213> Homo sapiens <400> 1104 cacatacatt ttcagatatt tctaccttcce 30 <210> 1105 <211> 20 <212> DNA <213> Homo sapiens <400> 1105 gttcattctg ccccatcage 20 <210> 1106 <211> 24 <212> DNA <213> Homo sapiens

<400> 1106 : tccaaggtct gatcatcttce ttga 24 <210> 1107 <211> 23 <212> DNA <213> Homo sapiens <400> 1107 gctttcaaga atgaagtggt tgg 23 <210> 1108 <211> 24 <212> DNA <213> Homo sapiens <400> 1108 gtcaacaata tttggaagca ccag 24 <210> 1109 <211> 20 ) <212> DNA <213> Homo sapiens <400> 1109 tttaggcaaa ggggagcaca 20 <210> 1110 <211> 20 <212> DNA <213> Homo sapiens <400> 1110 ccaaaggaag ccctcagaga 20 <210> 1111 <211> 21 <212> DNA <213> Homo sapiens <400> 1111 gggcacaaat gcaaagtaag c 21 <210> 1112 <211> 18 . <212> DNA <213> Homo sapiens <400> 1112 cctgggctgt ggcttcat 18 <210> 1113 <211> 21 <212> DNA 486 q

<213> Homo sapiens <400> 1113 caggtggatt cgtggtgcta a 21 <210> 1114 <211> 21 . <212> DNA <213> Homo sapiens <400> 1114 gttttggggt gttgagggag t 21 <210> 111% <211> 24 <212> DNA <213> Homo sapiens <400> 1115 ttcacagtgt gtggtcaaca tttc 24 <210> 1116 <21i> 20 <212> DNA <213> Homo sapiens <400> 1116 ccctctcatec tagcccacca 20 <210> 1117 <211> 20 <212> DNA <213> Homo sapiens <400> 1117 cacagaggag gctgcagatg 20 <210> 1118 <211> 22 <212> DNA <213> Homo sapiens <400> 1118 tgattggaag ccacaaattt ca 22 <210> 1119 <211> 20 <212> DNA <213> Homo sapiens <400> 1118 gggagactgc tcccatctca 20 <210> 1120

<211> 20 <212> DNA <213> Homo sapiens <400> 1120 tgacctcaga cgtggagcag 20 <210> 1121 <211> 20 <212> DNA . <213> Homo sapiens <400> 1121 tggggttgga gctcaatctt 20 <210> 1122 <211> 27 <212> DNA <213> Homo sapiens <400> 1122 ctgttgatect gtttcttgaa ctttect 27 <210> 1123 <211> 23 <212> DNA <213> Homo sapiens <400> 1123 taaaacccac agtgcttgac aca 23 <210> 1124 <211> 20 <212> DNA <213> Homo sapiens <400> 1124 ggagcagggg tagagccact 20 <210> 1125 <21ll1l> 21 <212> DNA <213> Homo sapiens <400> 1125 ggccagaatt tecttctcca © 21 <210> 1126 <211> 19 <212> DNA <213> Homo sapiens <400> 1126 catttctggg caggcatga 19

<210> 1127 <211l> 20 <212> DNA <213> Homo sapiens <400> 1127 gagacacccce agcccctagt 20 <210> 1128 <211l> 20 <212> DNA <213> Homo sapiens <400> 1128 gatgctctge cacagctcct 20 <210> 1129 <211> 20 <212> DNA <213> Homo sapiens <400> 1129 ctgtcttcaa ggggccagtg 20 <210> 1130 <211> 29 } . <212> DNA <213> Homo sapiens <400> 1130 aattaatctg gacagtttca tctgaagag 29 : <210> 1131 <211> 20 <212> DNA <213> Homo sapiens <400> 1131 ctctggccaa ctgectgttt 20 <210> 1132 ° <211> 20 <212> DNA <213> Homo sapiens <400> 1132 tccectgecag tctcgaaaag 20 <210> 1133 <211> 20 <212> DNA <213> Homo sapiens <400> 1133 gcttggccca taagtgtgcet 20 <210> 1134 <211l> 20 <212> DNA <213> Homo sapiens

<400> 1134 agccccttca atcccatcat 20 <210> 1135 <211> 20 <212> DNA <213> Homo sapiens <400> 1135 tcctcaaacc cgtggatcat 20 <210> 1136

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1136 cggtgeccttc ttaggagctg 20 <210> 1137

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1137 aaaaggagga caagtctaac ggaat 25 <210> 1138

<211s> 21

<212> DNA

<213> Homo sapiens

<400> 1138 tgatggttat tcgctggttc g 21 <210> 1139

<211> 21

<212> DNA :

<213> Homo sapiens

<400> 1139 tctgccagga catctttctc g 21 <210> 1140

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1140 cacatcatgc agctccttaa tacaa 25 <210> 1141

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1141 gctgcatcca gcctctgttt 20 <210> 1142

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1142 aacagccaga atcgctggag 20 <210> 1143

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1143 aggggagacc gaagtgaagg 20 <210> 1144

<211l> 17

<212> DNA

<213> Homo sapiens :

<400> 1144 ctctggccecg ataccgg 17 <210> 1145

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1145 ctgcaaacat cctcccatca 20 <210> 1146

<211> 20

«212> DNA

<213> Homo sapiens

<400> 1146 ggccgaagaa tccctcaaaa 20 <210> 1147

<211> 21 :

<212> DNA <213> Homo sapiens <400> 1147 ttggccattg accattacct g 21 <210> 1148

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1148 tttggggata atccgtgttc a 21 <210> 1149

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1149 gtgtcctggg tctggtcecte 20 <210> 1150

<211> 26

<212> DNA

<213> Homo sapiens

<400> 1150 cttagggaat tttggaacag aacatt 26 <210> 1151

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1151 gccgtcecect cctctetcta 20 <210> 1152

<211> 22

<212> DNA

<213> Homo sapiens

<400> 1152 :

aattattgecc ttttccectg ga 22 <210> 1153

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1153 ccagctacaa cggatgcaaa 20

<210> 1154 <211> 20 <212> DNA <213> Homo sapiens <400> 1154 tcccggtcca ctgcttaaaa 20 <210> 1158S <211l> 20 <212> DNA <213> Homo sapiens <400> 1155 tcaggggttt cccagttgag 20 <210> 1156 <211l> 20 <212> DNA <213> Homo sapiens <400> 1156 atcatcacgg tatggcgttg 20 <210> 1157 <21ll> 19 <212> DNA <213> Homo sapiens <400> 1157 ccceggattt gttcactgg 19 <210> 1158 <211l> 20 <212> DNA <213> Homo sapiens <400> 1158 agtggtcgtt gagggcaatg 20 <210> 1159 <211> 19 <212> DNA <213> Homo sapiens <400> 1159 : cagggccttt gcaaacaag 19 <210> 1160 <211> 21 <212> DNA <213> Homo sapiens <400> 1160 ttttggaacc cttagccctg t 21

<210> 1161 <211> 198 <212> DNA <213> Homo sapiens <400> 1161 ccatctctga cccgecttce 19 <210> 1162 <211> 20 <212> DNA <213> Homo sapiens «400> 1162 ggaccatggt ggaggtgaaa 20 «210> 1163 <211> 20 «<212> DNA <213> Homo sapiens <400> 1163 ctgactgctg cggcctctac 20 <210> 1164 <211> 23 <212> DNA : <213> Homo sapiens <400> 1164 gtttgcaggt ttggcataaa ttg 23 <210> 1165 <211> 31 <212> DNA <213> Homo sapiens <400> 1165 actaggtgac cagatacatg agtcttattt t 31 <210> 1166 <211s> 20 <212> DNA <213> Homo sapiens <400> 1166 ccattggaga aatggctggt 20 <210> 1167 <211l> 20 <212> DNA <213> Homo sapiens

<400> 1167 ttttetggag cggccatatce 20 <210> 1168 <211> 20 <212> DNA <213> Homo sapiens <400> 1168 gggctgagtc ctcagacagg 20 <210> 1169 <211> 20 <212> DNA ' <213> Homo sapiens <400> 1169 aactgaggct gccctagcaa 20 <210> 1170 <211> 20 <212> DNA <213> Homo sapiens <400> 1170 ccttcctgec ctaacagcaa 20 <210> 1171 <211> 19 <212> DNA <213> Homo sapiens <400> 1171 caccgtcagt cgtgggtgt 19 <210> 1172 <211> 22 <212> DNA <213> Homo sapiens <400> 1172 cctggtaggg aaaagtgatg ga 22 <210> 1173 <211> 23 <212> DNA <213> Homo sapiens <400> 1173 tggaaaacaa cacagcaaaa tcc 23 <210> 1174 <211> 21 <212> DNA

<213> Homo sapiens <400> 1174 aaatgacctt tggtgccact g 21 <210> 1175S «211> 21 <212> DNA <213> Homo sapiens <400> 1175 tggaggagag gaaaacggag a 21 <210> 1176 <211l> 21 <212> DNA <213> Homo sapiens <400> 1176 aatagcagca aggggaagac C 21 <210> 1177 <211> 21 <212> DNA <213> Homo sapiens <400> 1177 atctaaatgg tccgcecctgag c© 21 <210> 1178 <211> 21 <212> DNA <213> Homo sapiens <400> 1178 gcacaacttg gtaaggcacc a 21 <210> 1178 <211> 20 <212> DNA <213> Homo sapiens <400> 1179 tgggaagagg aagggacaca 20 <210> 1180 <211> 29 <212> DNA <213> Homo sapiens <400> 1180 tgcacataac atatatttgc ctattgttt 29 <210> 1181

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1181 caaggggcac cagtcttgat 20 <210> 1182

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1182 tggctggaga taggctttgg 20 <210> 1183

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1183 tttgtegtgt ccgtggtttg 20 <210> 1184

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1184 ttggcagttt cccectgactt 20 <210> 1185 <211> 21

<212> DNA

<213> Homo sapiens

<400> 1185 agcagtcttc ctgtgctcca g 21 <210> 1186

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1186 acactgctac cctgcgcetcet : 20 <210> 1187

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1187 gcccagtttt gggcectttcetce 20

<210> 1188 <211> 22 <212> DNA <213> Homo sapiens <400> 1188 catagccatt tctgcagcac ac 22 <210> 1189 <211> 20

<212> DNA

<213> Homo sapiens

<400> 1189 tcgtggaact gcttgacagce 20 <210> 1190

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1190 aaccagaccg gtcacttcca 20 <210> 1191

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1191 cccacatceg catctgctat 20 <210> 1192

<21l1l> 20

<212> DNA

<213> Homo sapiens

<400> 1182 gatgccccgg ataatcctcet 20 <210> 1183

<211> 19

<212> DNA

<213> Homo sapiens

<400> 1193 ccttttctgg cagggcttc 19 <210> 1194

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 1194 gcacagccga tgcttgtaac 20 <210> 1195 <211> 20 <212> DNA <213> Homo sapiens <400> 1195 tggccctgaa actcctcact 20 <210> 1196 <211l> 21 <212> DNA <213> Homo sapiens <400> 1196 tgcaaccagt tctgggagag a 21 <210> 1197 <211> 20 <212> DNA <213> Homo sapiens <400> 1197 cacccaacac cccaatctgt 20 <210> 1198 <211l> 2¢ <212> DNA <213> Homo sapiens <400> 1198 ggctccctge ggtatctett 20 <210> 1199 <211> 24 <212> DNA <213> Homo sapiens <400> 1199 agtccattcc tgattcagaa cacc 24 <210> 1200 <211l> 19 <212> DNA <213> Homo sapiens <400> 1200 gtgaccttgc cagctccag 19 <210> 1201 <211l> 19 <212> DNA <213> Homo sapiens }

<400> 1201 aggggccttg aagacgatg 19 <210> 1202 <211> 20 <212> DNA <213> Homo sapiens <400> 1202 agtggtcgtt gagggcaatg 20 <210> 1203 <211> 20 <212> DNA <213> Homo sapiens <400> 1203 aggggagaag ctgggacaag 20 <210> 1204 <211> 21 <212> DNA <213> Homo sapiens <400> 1204 cctectette cteectegact g 21 <210> 1205 <211> 21 <212> DNA <213> Homo sapiens <400> 1205 tccatcagga gcttcttgct c 21 <210> 1206 <211> 20 <212> DNA <213> Homo sapiens <400> 1206 agtggcagag gaggcaggtt 20 <210> 1207 <21l1l> 22 <212> DNA <213> Homo sapiens <400> 1207 actgccaaat gaaagcgaat tt 22 <210> 1208 <211> 20

<212> DNA <213> Homo sapiens <400> 1208 ctggggtctg gaagcagtgt 20 <210> 1209 <211> 20 <212> DNA <213> Homo sapiens <400> 1209 agtgtgacgg cactgagctg 20 <210> 1210 <211> 19 <212> DNA <213> Homo sapiens <400> 1210 ccctgtagac ggcatggaa 19 <210> 1211 <211> 22 «<212> DNA <213> Homo sapiens <400> 1211 catgatttca tctcgctcaa gg 22 <210> 1212 <211> 20 <212> DNA <213> Homo sapiens <400> 1212 ggctcttteg cagctgttcect 20 <210> 1213 <211> 20 <212> DNA <213> Homo sapiens <400> 1213 gacagtggag cagccaacac 20 <210> 1214 <211> 22 <212> DNA <213> Homo sapiens <400> 1214 cctgccaagt gttttcatca ca 22

<210> 1215

<211> 19

<212> DNA

<213> Homo sapiens

<400> 1215 ccccttececca aggagettt 19

<210> 1216

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1216 accccacacc tctacctcag c 21

<210> 1217

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1217 gttgggtaac gccagggttt 20

<210> 1218

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1218 cgcaccaaaa gttgtgcgta 20

<210> 1219

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 1219 tccgggectag taggtgatgg 20 «<210> 1220

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1220 ttttcecectt ttecccagtec 20

<210> 1221

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1221 catcagggcc aattggaaag 20

<210> 1222 <211> 20 <212> DNA <213> Homo sapiens <400> 1222 atggggacgg taacgactca 20 <210> 1223 <211> 20 <212> DNA <213> Homo sapiens <400> 1223 gtcatttctg gcacgggaag 20 <210> 1224 <211> 20 <212> DNA

. <213> Homo sapiens <400> 1224 ggggagtgtg gtgatggagt 20 <210> 1225 <211> 20 <212> DNA <213> Homo sapiens <400> 1225 agccctgggt cttcaggaac 20 <210> 1226 <211> 20 <212> DNA <213> Homo sapiens <400> 1226 ctggggtagg ggagaggtgt 20 <210> 1227 <211l> 21 <212> DNA <213> Homo sapiens <400> 1227 gaaagggaag caggctcaag t 21 <210> 1228 <211> 21 <212> DNA <213> Homo sapiens le ee

<400> 1228 tcatgtggcg atcttgacct t 21 <210> 1229

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1229 ccatgatgag gaaggttgag c } 21 <210> 1230

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1230 ttgagggagt agtggaatga aaaca 25 <210> 1231

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1231 acactcaggc ctggagaagg 20 <210> 1232

<21l1l> 20

<212> DNA

<213> Homo sapiens

<400> 1232 tttcgaagec cttggagatg 20 <210> 1233

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1233 tgctgcacce tcttecatcag 20 <210> 1234

<211> 20

<212> DNA

<213> Homo sapiens <400> 1234 ggcaagcaca acccacagat 20 <210> 1235 <211> 20 <212> DNA

<213> Homo sapiens <400> 1235 . tccttgtcga tcteccgggta 20 <210> 1236 <211> 20 <212> DNA <213> Homo sapiens <400> 1236 gttgtcetec teceggettet 20 <210> 1237 <211> 20 <212> DNA <213> Homo sapiens <400> 1237 ggccaggagg gtatgtcectt 20 <210> 1238 <211l> 20 <212> DNA <213> Homo sapiens <400> 1238 } ccctttcaat ccagcaagca 20 <210> 1239 <211> 20 } <212> DNA <213> Homo sapiens <400> 1239 cagagggccc tgtctctgaa 20 <210> 1240 <211> 20 <212> DNA <213> Homo sapiens <400> 1240 tcatcccata gtggggaagc 20 <210> 1241 <211> 20 <212> DNA <213> Homo sapiens <400> 1241 ttaacacccg gaagggtgaa 20 <210> 1242

<211> 20 <212> DNA <213> Homo sapiens <400> 1242 gactggagcc atgaggtcgt 20 <210> 1243

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1243 gctgectgect cgactttcte 20 <210> 1244

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1244 ccagaggaag ggtgtgctct 20 <210> 1245

<211l> 25

<212> DNA

<213> Homo sapiens

<400> 1245 ttaagcccta agtgatactg cctca 25 <210> 1246

<21l1l> 25

<212> DNA

<213> Homo sapiens

<400> 1246 ttaggaattg atgctggtta gtgct 25 <210> 1247

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1247 gcggeccgtca ttaattcaaa 20 <210> 1248

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1248 atttgccttc agccacatcce 20

<210> 1249 <211l> 20 <212> DNA <213> Homo sapiens <400> 12469 ggtggttcgc cttgaactga 20 <210> 1250 <211> 20 <212> DNA <213> Homo sapiens <400> 1250 atcaggtgac cgctttggaa 20 <210> 1251 <211> 20 <212> DNA <213> Homo sapiens <400> 1251 gcacaggaac acggtctgaa 20 <210> 1252 <211> 20 <212> DNA <213> Homo sapiens <400> 1252 aggggtggaa tgaggcaaat 20 <210> 1253 <211l> 20 <212> DNA <213> Homo sapiens <400> 1253 ccacagctgt cgctgtcette 20 «<210> 1254 <211> 32 <212> DNA <213> Homo sapiens <400> 1254 aaatacaaaa caaattcaca aattactctc aa 32 <210> 1255 <211> 25 <212> DNA <213> Homo sapiens <400> 1255 :

ttggcattag actcacatca tctgt 25 <210> 1256 <21l1l> 25 <212> DNA <213> Homo sapiens <400> 1256 aaaccagaca aacgaataac acaca 25 <210> 1257 <211> 26 <212> DNA <213> Homo sapiens <400> 1257 aggattatat caacagcgat gaactg 26 <210> 1258 <211l> 19 <212> DNA <213> Homo sapiens <400> 1258 ccgagcccga taaatggta 19 <210> 12589 <211l> 20 <212> DNA <213> Homo sapiens ' <400> 1259 tcccecteecct gtagagacca 20 <210> 1260 <211l> 20 <212> DNA <213> Homo sapiens <400> 1260 catcctctca agggcatggt 20 <210> 1261 <211> 21 <212> DNA <213> Homo sapiens . <400> 1261 tcccacattec ctgacattgg t 21 <210> 1262 <21i> 20 <212> DNA <213> Homo sapiens S08

<400> 1262 cacagccctg aacaaaagca 20 <210> 1263 <211> 20 <212> DNA <213> Homo sapiens <400> 1263 gctatttcag gtggggctga 20 <210> 1264 <211l> 21 <212> DNA <213> Homo sapiens <400> 1264 aatccaggcc aaatgggtaa a 21 <210> 1265 <211l> 20 <212> DNA <213> Homo sapiens <400> 1265 aaaggctcca gggctcctaa 20 <210> 1266 <211> 20 <212> DNA <213> Homo sapiens <400> 1266 tccatgtcca agccttccat 20 <210> 1267 <211> 20 <212> DNA <213> Homo sapiens <400> 1267 atgcaaatcc agggtgcagt 20 <210> 1268 : <211> 20 <212> DNA <213> Homo sapiens <400> 1268 caggagtcaa agggcacgat 20 <210> 1269 <211> 20

<212> DNA <213> Homo sapiens <400> 1268 cacgcattgc acttttectc 20 <210> 1270 <«211> 27 <212> DNA <213> Homo sapiens : <400> 1270 acaaatctgt acccaatcgt tattgtt 27 <210> 1271 <211> 23 <212> DNA <213> Homo sapiens <400> 1271 tcaacattga caaagcagga tca 23 <210> 1272 <211> 20 <212> DNA <213> Homo sapiens <400> 1272 cccacaccgt acatgcctct 20 <210> 1273 <211> 23 <212> DNA <213> Homo sapiens <400> 1273 tggcactctt tccagtgact gtt 23 <210> 1274 <211> 20 <212> DNA <213> Homo sapiens <400> 1274 agcctcectc ccttagegta 20 <210> 1275 <211> 20 <212> DNA <213> Homo sapiens <400> 1275 atgcccaggt aggaccctgt 20

<210> 1276 <211> 20 <212> DNA <213> Homo sapiens <400> 1276 Cctcacattc cctcceccatt 20 <210> 1277 <211> 20 <212> DNA <213> Homo sapiens <400> 1277 ctgggcaggg cttattcctt 20 <210> 1278 <211> 20 <212> DNA <213> Homo sapiens <400> 1278 aaggctgcat tctgggtttg 20 <210> 1279 <21l> 20 <212> DNA <213> Homo sapiens . <400> 1279 gccatgctac ccggtatgac 20 <210> 1280 <211> 24 <212> DNA <213> Homo sapiens <400> 1280 : tgatttaaaa tagggctggg aaaa 24 <210> 1281 <211> 20 <212> DNA <213> Homo sapiens <400> 1281 cgatgtcatg tgatgcacga 20 <210> 1282 <211> 23 <212> DNA <213> Homo sapiens <400> 1282 gcaaagaaga gcttaagcac cag 23

<210> 1283 <211> 20 <212> DNA <213> Homo sapiens <400> 1283 cgtaaggcac agctgcaaaa 20 <210> 1284 <211> 20 <212> DNA <213> Homo sapiens <400> 1284 gtggaacacc ctgacgaagqg 20 <210> 1285 <211> 23 <212> DNA <213> Homo sapiens <400> 1285 tgectgacag taagtgctca aaa 23 <210> 1286 <211> 27 <212> DNA <213> Homo sapiens <400> 1286 aaattctttg cttgttagtg accttga 27 <210> 1287 <211> 23 <212> DNA <213> Homo sapiens <400> 1287 cttggctcag tatgcaacct ttt 23 <210> 1288 <211> 20 <212> DNA <213> Homo sapiens <400> 1288 acacctgtgc ctgggagaag 20 <210> 1289 <211> 20 ’ <212> DNA <213> Homo sapiens 512

<400> 1289 gttctctete tggeccgatge 20 <210> 1290 ’ <21l> 24 <212> DNA <213> Homo sapiens <400> 1290 tgtttctaac ccataagtgc ctca 24 <210> 1291 <211> 20 <212> DNA <213> Homo sapiens <400> 1291 aaagcccaca gccaagtcag 20 <210> 1292 <211> 20 <212> DNA <213> Homo sapiens <400> 1292 cacagctccg atgaccacaa 20 <210> 1293 <211> 20 <212> DNA <213> Homo sapiens <400> 1293 ggtccttgta gacccgacga 20 <210> 1294 <211> 20 <212> DNA <213> Homo sapiens <400> 1294 agcaggaaat gcctgtgctc 20 <210> 1295 <211> 20 : <212> DNA <213> Homo sapiens <400> 1295 tcagttcgtg ggaccctttce 20 <210> 1296 <211> 20 <212> DNA

<213> Homo sapiens <400> 1296 gggccttaaa actgccaagg 20 <210> 1297 <211> 20 <212> DNA <213> Homo sapiens <400> 1297 gcctgagcga gaggatgtte 20 <210> 1298 <211> 20 <212> DNA <213> Homo sapiens <400> 1298 gaaggcgttg aacgagatgg 20 <210> 1299 <211> 28 <212> DNA <213> Homo sapiens <400> 1299 tcccaatcta atttaaaccc tcataaca 28 <210> 1300 <211> 20 <212> DNA <213> Homo sapiens <400> 1300 agcttecccag ccctagcaaa 20 <210> 1301 <211> 20 <212> DNA <213> Homo sapiens <400> 1301 Cccaaggaggt tgggaagagg 20 <210> 1302 <21l> 20 <212> DNA <213> Homo sapiens <400> 1302 tcatgtgcac gaggaagctc 20 <210> 1303 514 x:

<211> 20 <212> DNA <213> Homo sapiens <400> 1303 ttgcaaagcc tttcacagga 20 <210> 1304 <211> 290 <212> DNA <213> Homo sapiens <400> 1304 accagcacag aacccaaagc 20 <210> 1305 <211ls> 20 <212> DNA <213> Homo sapiens <400> 1305 gggagcgtat ctcaggcaga 20 <210> 1306 <211> 20 <212> DNA <213> Homo sapiens <400> 1306 cacccataca ggacgcacag 20 <210> 1307 <211> 20 <212> DNA <213> Homo sapiens <400> 1307 gaatccecgge cactgatgta 20 <210> 1308 <211s> 20 <212> DNA <213> Homo sapiens <400> 1308 taacatttgc ttcggcatgg 20 <210> 1308 <211> 20 <212> DNA <213> Homo sapiens <400> 1308 tcccaactgce aaaccctcat 20

<210> 1310 <211> 20 . <212> DNA : <213> Homo sapiens ’ <400> 1310 ttgagctggt gggtgcatta 20 <210> 1311 <211> 20 <212> DNA <213> Homo sapiens <400> 1311 cgctgtattc tcgccagtga 20 <210> 1312 <211> 20 <212> DNA <213> Homo sapiens <400> 1312 ) caacacgcac atctgggaac 20 <210> 1313 <211> 19 <212> DNA <213> Homo sapiens <400> 1313 aagcatttcc gcacactgg 19 <210> 1314 <211> 20 <212> DNA <213> Homo sapiens <400> 1314 acgacgtcca cctttteetg 20 <210> 1315 <211> 20 <212> DNA <213> Homo sapiens <400> 1315 ttgcatgaga agcacctcca 20 <210> 1316 <211> 27 <212> DNA <213> Homo sapiens <400> 1316 tcagaaagct ttgactactg tttctecc 27 <210> 1317 <211> 20 <212> DNA <213> Homo sapiens <400> 1317 atggctgcca agatggaaag 20 <210> 1318 <211> 20 <212> DNA <213> Homo sapiens <400> 1318 ggcaacccta gccacacact 20 <210> 1319 <211> 20 <212> DNA <213> Homo sapiens <400> 1319 cacagagaag gaggccttgce 20 <210> 1320 <211> 20 <212> DNA <213> Homo sapiens <400> 1320 gccagctcca gatggacatt 20 <210> 1321 <211> 20 <212> DNA <213> Homo sapiens <400> 1321 cgtgtgttgc atcgtgtctg 20 <210> 1322 <21l1> 20 <212> DNA <213> Homo sapiens <400> 1322 cgctttgggg catctaattg 20 <210> 1323 <211> 20 <212> DNA <213> Homo sapiens

<400> 1323 cgctcagett tggcttctte 20 <«210> 1324 <211> 20 <212> DNA <213> Homo sapiens <400> 1324 gaggtctgct tgcacccact 20 <210> 1325 <211> 20 <212> DNA <213> Homo sapiens <400> 1325 cagaccctgt gtggcagtgt } 20 <210> 1326 <211> 20 ’ <212> DNA <213> Homo sapiens <400> 1326 cacattgggc actgctgaaa 20 <210> 1327 <211ls> 21 <212> DNA <213> Homo sapiens <400> 1327 tgatggggat cggggattge a 21 <210> 1328 <21ll> 32 <212> DNA <213> Homo sapiens <400> 1328 tectgtaaca atgcatctca tatttggaat ga 32 <210> 1329 <211> 20 <212> DNA ’ <213> Homo sapiens <400> 1329 cgtccagcet gggteggggt 20 <210> 1330 <211> 32

<212> DNA

<213> Homo sapiens

<400> 1330 tgaactcttc aatctcttgc actcaaagct tg 32 <210> 1331

<211> 35

<212> DNA

<213> Homo sapiens

<400> 1331 ccaatcaagg tataacacac aaatgttatc tgcgc 35 <210> 1332

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1332 tgeccattecee getggettgg 20 © <«210> 1333

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1333 ggccgtccac cacagcatgg t 21 <210> 1334

<211l> 27

<212> DNA

<213> Homo sapiens

<400> 1334 tgcecectgatt tgaagggaaa agggatg 27 <210> 1335

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1335 ggacggcgac agaaattgca ggc 23 <210> 1336

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1336 ccctgactee cccgteccceca 20

<210> 1337 <211> 30 <212> DNA <213> Homo sapiens ’ <400> 1337 gggcgtacac tttcccttct caatctctca 30 <210> 1338 <211> 30 <212> DNA <213> Homo sapiens <400> 1338 tcacagcatt ggcattatct gagatggtga 30 <210> 1339 «211> 34 <212> DNA <213> Homo sapiens <400> 1339 aaggtttcaa cctaatggag ggatgagaag atca 34 <210> 1340 . <211> 30 <212> DNA <213> Homo sapiens <400> 1340 gggtcctatg ctactgttgc actctccaca 30 <210> 1341 <211l> 26 <212> DNA <213> Homo sapiens <400> 1341 ggcagactcc ttgccaacgg gtattg 26 <210> 1342 <211> 28 <212> DNA <213> Homo sapiens <400> 1342 ccaatccatg aggatggtga aatgatgg 28 <210> 1343 <211l> 27 <212> DNA <213> Homo sapiens <400> 1343 ggccaagaaa gcattttcac ctectgce 27

<210> 1344 <211> 22 <212> DNA <213> Homo sapiens <400> 1344 tcccaacaag cccecctgcag aa 22 <210> 1345 <211> 25 <212> DNA" <213> Homo sapiens <400> 1345 tgaaagccaa aggctccagt cacca 25 <210> 1346 <211> 24 <212> DNA <213> Homo sapiens <400> 1346 ggttttceca tttgtggagg gecga 24 <210> 1347 <211> 28 <212> DNA <213> Homo sapiens / <400> 1347 ccagcctcag aggaagagga tttttcgg 28 <210> 1348 <211> 24 <212> DNA <213> Homo sapiens <400> 1348 gcagtgcege acttggagat ttgg 24 <210> 13459 <211l> 32 <212> DNA <213> Homo sapiens <400> 1349 gtgttatacg atgaacatgc cacatgcttt ca 32 <210> 1350 <211> 20 <212> DNA <213> Homo sapiens

<400> 1350 cctgggccac cccagcacac 20 <210> 1351 <211> 29 <212> DNA <213> Homo sapiens <400> 1351 tgcaaatggt tacttccaga taacggcca 29 <210> 1352 <21ll1l> 22 <212> DNA <213> Homo sapiens <400> 1352 gcctgtcctec aaggectgcectg cc 22 : <210> 1353 <211> 22 <212> DNA <213> Homo sapiens <400> 1353 tccactgage cctgctgect ca 22 <210> 1354 <211> 20 <212> DNA <213> Homo sapiens <400> 1354 tgggctcccect gggagtcccce 20 <210> 135% <211> 20 <212> DNA <213> Homo sapiens <400> 1355 agcccagacc caggcectgece 20 <210> 1356 <211> 22 <212> DNA <213> Homo sapiens <400> 1356 ccgccacagt gtcgtggtgg tc 22 <210> 1357 <211> 20 <212> DNA 522 ie

<213> Homo sapiens <400> 1357 gcaggccacc cagcacaccce 20 <210> 1358 <211> 20 <212> DNA <213> Homo sapiens <400> 1358 tcaccectggg ggecectectg 20 <210> 1359 <211> 23 <212> DNA <213> Homo sapiens <400> 1359 ggccaaagga agtgacccct cgg 23 <210> 1360 <211> 20 <212> DNA <213> Homo sapiens <400> 1360 tctccaggge ctecgcacca 20 <210> 1361 <211> 20 <212> DNA <213> Homo sapiens <400> 1361 accaccttgg agccgtgcegce : 20 <210> 1362 <211> 34 <212> DNA <213> Homo sapiens <400> 1362 ccaactacta aactggggga tattatgaag ggcc 34 <210> 1363 <211> 34 <212> DNA ' <213> Homo sapiens <400> 1363 cctggactgt ttcctgataa ccataagaag acce 34 <210> 1364

<211> 25 <212> DNA <213> Homo sapiens <400> 1364 tgggtccagg ggtaaacaac gagga 25 <210> 1365 <211> 20 <212> DNA <213> Homo sapiens

<400> 1365 tggggttgcc catgatggcea 20 <210> 1366

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1366 tgtccagcga cgcctgcagce 20 <210> 1367

<21l1ls> 22

<212> DNA <213> Homo sapiens

<400> 1367 cagccgctcce tcaagcactg gg 22 <210> 1368

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1368 ggccctcaac caccacaacc tgce 23 <210> 1369

<211> 26

<212> DNA

<213> Homo sapiens

<400> 1369 gcectctcac agtggaatgg agagca 26

<210> 1370

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 1370 caaccaggcc aggtgggcca 20

<210> 1371 <211l> 29 <212> DNA <213> Homo sapiens <400> 1371 tggtcecgggg tgcattatct ctacagtca 29 <210> 1372 <211> 25 <212> DNA <213> Homo sapiens <400> 1372 cctccggaat tcattccagt caccg 25 <210> 1373 <211l> 29 <212> DNA <213> Homo sapiens <400> 1373 tgttcagtct gaagtttgce agtttggec 29 <210> 1374 <211> 20 <212> DNA <213> Homo sapiens <400> 1374 cccacgcaca agggagccca 20 <210> 137% <211> 26 <212> DNA <213> Homo sapiens <400> 1375 tgtcectecce tecttcagag agtggg 26 <210> 1376 <211> 22 <212> DNA <213> Homo sapiens <400> 1376 gcgattactc agggecccgge tg 22 <210> 1377 <211l> 20 <212> DNA <213> Homo sapiens <400> 1377 cccceggggce acaaggaaga 20 <210> 1378 <211l> 20 <212> DNA <213> Homo sapiens <400> 1378 tcccagggtg ggcacatggg 20 «<210> 1379 <211> 20 <212> DNA <213> Homo sapiens <400> 1379 cagtggggca gtggggtccg 20 <210> 1380 <211> 32 <212> DNA <213> Homo sapiens <400> 1380 tgacctaact tcaggagcgt ctgtgagaca tg 32 <210> 1381 <211l> 29 <212> DNA <213> Homo sapiens <400> 1381 tgacccaaac atcatacccc aatagtgca 29 <210> 1382 <211> 29 <212> DNA <213> Homo sapiens <400> 1382 tttattecte ccaactacca ctggcgett 29 <210> 1383 <211l> 27 <212> DNA <213> Homo sapiens <400> 1383 tgcttttaag ttttggccaa ctgccga 27 <210> 1384

<211> 22 <212> DNA <213> Homo sapiens

<400> 1384 tgggggaggt gcaaccttct gc 22 <210> 1385 <211> 20 <212> DNA <213> Homo sapiens <400> 1385 gcctececececa gggggettgt 20 <210> 1386 <211> 27 <212> DNA <213> Homo sapiens <400> 1386 tggatcggga ttggaatcce ttaagea 27 <210> 1387 <211s> 27 <212> DNA <213> Homo sapiens <400> 1387 ccattatggg gaccttcacc tgcttca 27 <210> 1388 <211> 20 <212> DNA <213> Homo sapiens <400> 1388 atgcccatgt gcaagggcgc 20 <210> 1389 <211> 32 <212> DNA <213> Homo sapiens <400> 1389 catccatttc tcttcttcag gaagatcgtg ga 32 <210> 1390 <211> 20 <212> DNA <213> Homo sapiens <400> 1390 tceccaccatg gctgtggecc 20 <210> 13381 <211> 26 a ——

<212> DNA <213> Homo sapiens <400> 1391 ggagcttecet ttcacacaca ggectg 26 <210> 1392 <211> 21 <212> DNA <213> Homo sapiens <400> 1392 tcaggagacc tgggcecage a 21 <210> 1393 <211> 23 <212> DNA <213> Homo sapiens <400> 1393 ttcgacctga gcctgcggag aga 23 <210> 1394 <211> 31 <212> DNA <213> Homo sapiens <400> 1394 ggaaacaaaa ctggcagttt gtccatttga a 31 <210> 1395 <211> 20 <212> DNA <213> Homo sapiens <400> 1395 tggagggggc agcgtgctgt 20 <210> 1396 <211l> 20 <212> DNA <213> Homo sapiens <400> 1396 ccgagegege gaatctecag 20 <210> 1397 <211> 20 <212> DNA <213> Homo sapiens <400> 1397 aggtgggccy gtoctctagg 20

<210> 1388 <211l> 26 <212> DNA <213> Homo sapiens <400> 1398 aacaccttac aagggcggag aagcca 26 <210> 1399 <211> 22 <212> DNA <213> Homo sapiens <400> 1399 tgggceccteg ttgcatttgg tg 22 <210> 1400 <21l1l> 35 <212> DNA <213> Homo sapiens <400> 1400 tgggtagtgt ttcaggcata ttttgaatac atcga 35 <210> 1401 <21l> 32 <212> DNA <213> Homo sapiens <400> 1401 tcattattcc gtaattcaac acagcactac ca 32 <210> 1402 <211> 31 <212> DNA <213> Homo sapiens . <400> 1402 tgtacactgg ataaagaaaa ccatgaaacg ¢ 31 <210> 1403 <21l> 29 <212> DNA <213> Homo sapiens <400> 1403 ccatccctta aatcctcagg tcacaacca 29 <210> 1404 <211> 22 <212> DNA <213> Homo sapiens <400> 1404 tcccttcacc ttecgectgceca ca : 22

<210> 1405 <211> 22 <212> DNA <213> Homo sapiens <400> 1405 aaccccatct ggtcagtgecg gc 22 <210> 1406 <211> 20 <212> DNA <213> Homo sapiens <400> 1406 cgectgectgg gtgcgactge 20 <210> 1407 <21l> 24 <212> DNA <213> Homo sapiens <400> 1407 ccccaacggt gacaaacaca ctca 24 <210> 1408 <21l> 24 <212> DNA <213> Homo sapiens <400> 1408 tgccatggac agaagaaggc agca 24 <210> 1409 <211> 24 <212> DNA <213> Homo sapiens <400> 1409 cacagccctg gecctetgete aact 24 <210> 1410 <211l> 28 <212> DNA <213> Homo sapiens <400> 1410 tccatacagc actgctggag gaagagga 28 <210> 1411 <21l1l> 32 <212> DNA <213> Homo sapiens

<400> 1411 caagatccca aaatccaaac tgattgactg ag 32 <210> 1412 <211> 24 <212> DNA <213> Homo sapiens <400> 1412 tgcactgtga caagctgcac gtgg 24 <210> 1413 <211> 28 <212> DNA <213> Homo sapiens <400> 1413 tcectectttgg ccacaagaat aagcagca 28 <210> 1414 <211> 26 <212> DNA <213> Homo sapiens <400> 1414 ccaccaaaga actgtcagca gctgcec 26 <210> 1415 <211> 34 <212> DNA <213> Homo sapiens <400> 1415 tcctcagtca agttcagagt cttcagagac ttcg 34 <210> 1416 <21ll> 26 <212> DNA <213> Homo sapiens <400> 1416 caaaggcaat tcccacaaaa gctgge 26 <210> 1417 <211> 24 <212> DNA <213> Homo sapiens <400> 1417 aaaacagctg gagagtccca gccg 24 <210> 1418 <211l> 20 <212> DNA :

<213> Homo sapiens <400> 1418 acattgacat gggtgggttt 20 <210> 1419 <211> 31 <212> DNA

<213> Homo sapiens

<400> 1418 tccttgtgat tggtggtgaa actttctttg c 31 <210> 1420

<211> 31

<212> DNA

<213> Homo sapiens

<400> 1420 tgctgtgtaa caagttaggg tggacttget g 31 <210> 1421

<211> 32

<212> DNA

<213> Homo sapiens

<400> 1421 tgagaaaaat tcaaaagaat cgaaaggttg ca 32 <210> 1422

<211> 31

<212> DNA

<213> Homo sapiens

<400> 1422 ccagcatttc tataccactt tgggctttgg t 31 <210> 1423

<211> 29

<212> DNA

<213> Homo sapiens

<400> 1423 tggaaaatgt gcaatatgtg atgtggcaa 29 <210> 1424

<211l> 26

<212> DNA

<213> Homo sapiens

<400> 1424 tgcaagggct ctgtgacaag gaagga 26

<210> 1425

<211> 22 «212> DNA <213> Homo sapiens <400> 1425 cggcaaatgt agcatgggca cc 22 <210> 1426 <211> 33 <212> DNA <213> Homo sapiens <400> 1426 tggattacct tttgtcaaag catcatctca aca 33 <210> 1427 <211> 27 <212> DNA <213> Homo sapiens <400> 1427 ccctccatca tcgacactgg tctagece 27 <210> 1428 <211> 21 <212> DNA <213> Homo sapiens <400> 1428 tggcaggggt ggctgcctca t 21 <210> 1429 <211> 20 <212> DNA <213> Homo sapiens <400> 1429 tcatgggttt ggctgccceg 20 <210> 1430 <211> 25 <212> DNA <213> Homo sapiens <400> 1430 ccecctatggg gatggtccac tgtca : 25 <210> 1431 <211l> 32 <212> DNA <213> Homo sapiens <400> 1431 ggcaagagac tggactgaga ctttgtgaga aa 32

<210> 1432 <211> 32 <212> DNA <213> Homo sapiens <400> 1432 ccgtgtgaac caaacaatct cttttcaaaa ca 32 <210> 1433 <21l> 27 <212> DNA <213> Homo sapiens <400> 1433 catctgcagc cagttagtgc cacctga 27 <210> 1434 <211> 28 <212> DNA <213> Homo sapiens <400> 1434 gctgatgatt tagagtgctg tccggtgg 28 <210> 1435 <211l> 20 <212> DNA <213> Homo sapiens <400> 1435S cccaaattct ttcagtggct 20 <210> 1436 <211> 26 <212> DNA <213> Homo sapiens <400> 1436 caaggcacca cacaacccag aaagga 26 <210> 1437 <211ls> 31 <212> DNA <213> Homo sapiens <400> 1437 cactcggcat ttaaaatgtg ctgtcaaaac a 31 <210> 1438 <211> 26 <212> DNA <213> Homo sapiens <400> 1438 gggattccec taacctcatt ccccaa 26 <210> 1439 <211> 31 <212> DNA . <213> Homo sapiens <400> 1439 tgtgtcaggt gaccctgatg aaaacatagc a 31 <210> 1440 <211> 22 <212> DNA <213> Homo sapiens <400> 1440 gcccttggec tgaagtcceca gc 22 <210> 1441 <211> 25 <212> DNA <213> Homo sapiens <400> 1441 caagcctcat tcccaacctg cacct 25 <210> 1442 <«211> 20 <212> DNA <213> Homo sapiens <400> 1442 tgctggggect ccccatttgce 20 <210> 1443 <211> 24 <212> DNA <213> Homo sapiens <400> 1443 caaggcatgg cgtagagggt gctg 24 <210> 1444 <211> 20 <212> DNA : <213> Homo sapiens <400> 1444 acaaccccct cctecggecec 20 <210> 1445 <211> 34 <212> DNA <213> Homo sapiens

<400> 1445 caggggtaac tccagaaagg attgatatct gtga 34 <210> 1446 <21l> 34 <212> DNA <213> Homo sapiens <400> 1446 tgccttacaa gaaagacata aaatgtccaa ggga 34 <210> 1447

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1447 ccactggggt tcaggcccca 20 <210> 1448

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1448 ctggcectecge gectgetgett 20 <210> 1449

<211> 29

<212> DNA

<213> Homo sapiens

<400> 1449 ctcaaacctg aaatcagaag agggccatg 29 <210> 1450

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1450 gcagcccctc gtgctgcaca 20 <210> 1451

<211> 28

<212> DNA

<213> Homo sapiens

<400> 1451 tceccgtggga tactatttca gacgtgea 28 <210> 1452

<211> 29

<212> DNA <213> Homo sapiens <400> 1452 tcctgtaccect getcccaatc tgtgttcect 29 <210> 1453 <211> 28 <212> DNA <213> Homo sapiens } : <400> 1453 acgaagcatc cacagatccc tcaaaaca 28 <210> 1454 <211> 20 <212> DNA <213> Homo sapiens <400> 1454 cccggatgaa cgccgctect 20 <210> 1455 <211> 22 <212> DNA <213> Homo sapiens <400> 1455 ccggectcgag gacgtggagg at 22 <210> 1456 <211> 20 <212> DNA <213> Homo sapiens <400> 1456 tegtgatggce ctggccecctge 20 <210> 1457 <211ls> 20 <212> DNA <213> Homo sapiens <400> 1457 gcctgggaac aagggggcca 20 <210> 1458 <211> 23 <212> DNA <213> Homo sapiens <400> 1458 tcaggtggtc aatggccagc acc 23

«210> 1459

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1459 tggcttggat ttggggttac agcca 25 <210> 1460

<211> 34 a

<212> DNA

<213> Homo sapiens

<400> 1460 gaaaatgcac aaactgtcaa aattcatcat cgtg 34 <210> 1461

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1461 tcectgggtgyg gtgcagectce a 21 <210> 1462

<211> 22

<212> DNA

<213> Homo sapiens

<400> 1462 gggactgcag ttgtggctge ca 22 <210> 1463

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1463 tcttggcata cggagcagag ctgga 25 <210> 1464

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1464 gggggcctgt tggcttttee tttte 25 <210> 1465

<211> 29

<212> DNa

<213> Homo sapiens

<400> 1465 ggcagtgtca taggcagtat cctgcacag 29

<210> 1466 <211> 20 <212> DNA <213> Homo sapiens <400> 1466 gaggggaccc tctggcccga 20 <210> 1467 <211> 34 <212> DNA <213> Homo sapiens <400> 1467 tggagggata tcaggtcatc attgtgtatc aaaa 34 <210> 1468 <211> 28 <212> DNA <213> Homo sapiens <400> 1468 tgtgtctgeg atggtecgtct cttactgg 28 <210> 1469 <211> 25 <212> DNA <213> Homo sapiens : <400> 14689 gggttctegt tgcaatcctc ggtca 25 <210> 1470 <211> 26 <212> DNA <213> Homo sapiens <400> 1470 gccatccaca tctccegett atcecte 26 <210> 1471 <211> 20 <212> DNA <213> Homo sapiens <400> 1471 tcacccctge tttgcceccca 20 <210> 1472 <211> 26 <212> DNA <213> Homo sapiens

<400> 1472 tggaagccac ccgattcttg tatcgc 26 <210> 1473 <211l> 20 <212> DNA <213> Homo sapiens <400> 1473 ’ gaggggaccc tctggcccga 20 <210> 1474 <211> 19 <212> DNA <213> Homo sapiens <400> 1474 ccctggacca acccggecc 19 <210> 1475 <211> 26 <212> DNA <213> Homo sapiens <400> 1475 gacggaagag aaattcactg gcgcct 26 <210> 1476 <211> 27 <212> DNA <213> Homo sapiens <400> 1476 tcaaattctt ggccatcctg aaagggc 27 <210> 1477 <211l> 29 <212> DNA <213> Homo sapiens <4 00> 1477 cccaatctaa aggagcttct gccaaagga 29 <210> 1478 <21l> 20 “ <212> DNA <213> Homo sapiens : . <400> 1478 cccatcccge tgccaggtca 20 <210> 1478 <211> 33 <212> DNA ) 540 L

<213> Homo sapiens

<400> 1479 cagtggccaa ttttcatacc ctaagaagaa tga 33

<210> 1480

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1480 cattggggag cagagggccc a 21

<210> 1481

<211> 26

<212> DNA

<213> Homo sapiens

<400> 1481 ccacgttgca aaatctgcaa atccca 26

<210> 1482

<211> 28

<212> DNA

<213> Homo sapiens

<400> 1482 gggttttgac tgacgtgcat tcctctga 28

<210> 1483

<21l> 27

<212> DNA

<213> Homo sapiens

<400> 1483 tggaattgtc caagtcagca ccacagg 27 <210> 1484

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1484 aggggtggtg atctggctga ggg 23

<210> 1485

<211> 33

<212> DNA

<213> Homo sapiens

<400> 1485 ccaaagtcca tttactcgag acagaaatga gtc : 33

<210> 1486

<211> 30 : <212> DNA <213> Homo sapiens <400> 1486 gcgtcecttet tcttcttgte gtccttaggc 30 <210> 1487 <211> 26 <212> DNA <213> Homo sapiens <400> 1487 tgggtgtcgce tgttgaagtc agagga ’ 26 <210> 1488 <211> 25 <212> DNA <213> Homo sapiens <400> 1488 ccggetgett taatgagggc attga 25 <210> 1489 <211> 26 <212> DNA <213> Homo sapiens <400> 1489 caaaggatgt gaggggaaaa aggggdg 26 <210> 1490 <211> 20 <212> DNA <213> Homo sapiens <400> 1450 cctcccagec caaagcccca 20 <210> 1491 : <211> 22 <212> DNA <213> Homo sapiens <400> 1491 catgggggtg tggaggtggg ag 22 <210> 1492 <211> 26 <212> DNA <213> Homo sapiens <400> 1492 } gccttgtcat tgggcacaca acaacc 26

<210> 1493 <211l> 26 <212> DNA <213> Homo sapiens <400> 1493 ggaaaaccag gctctccagg aatggg 26 <210> 1494 ’ <211> 32 <212> DNA <213> Homo sapiens <400> 1494 tcacgtgagg tagaggacag ttttctgtgt ca 32 <210> 1495 <211> 31 <212> DNA <213> Homo sapiens <400> 1495 : ccccaccccc ttaatcagac tttaaaagtg c 31 <210> 1496 <211> 20 <212> DNA <213> Homo sapiens <400> 1496 cgcgtctgec ccgcgaacta 20 <210> 1497 <211> 22 <212> DNA <213> Homo sapiens <400> 1497 gccctctecca gactggtggg ca 22 <210> 1498 <211> 20 <212> DNA - <213> Homo sapiens <400> 1498 tctggaggge caggtggggg 20 <210> 1499 <211> 20 <212> DNA . <213> Homo sapiens <400> 1499 ccccagcaaa tgccaggggce 20 <210> 1500 <211> 28 <212> DNA <213> Homo sapiens = <400> 1500 ggccgttaat ttaatggggc caactttg 28 <210> 1501 <211> 28 <212> DNA <213> Homo sapiens <400> 1501 gcagcccatg gcatttttct ttttacca 28 <210> 1502 <211> 23 <212> DNA <213> Homo sapiens <400> 1502 tggtgccttt gggatcgact ggg 23 <210> 1503 <211> 33 <212> DNA <213> Homo sapiens <400> 1503 gctcatcaga gtaggagagt tgtagcaaag gca 33 <210> 1504 <211> 33 <212> DNA <213> Homo sapiens

<400> 1504 aactcatcgt gatgatggaa acaagaatga tga 33 <210> 1505 <211> 21 <212> DNA <213> Homo sapiens <400> 1505 tgccccagece cttcccagag a 21 <210> 1506 <211> 26 ’ <212> DNA <213> Homo sapiens

<400> 1506 gggattgaac ccttgccatg agttcce 26 <210> 1507 <211> 25 <212> DNA <213> Homo sapiens <400> 1507 gtctggagag aaggccttgc tccca 25 <210> 1508 <211> 21 <212> DNA <213> Homo sapiens <400> 1508 . ggggatgctg gagggecttc a 21 <210> 1509 <211> 34 <212> DNA <213> Homo sapiens <400> 1509 cagaagggca tggagggtac ctacttattc ttca 34 <210> 1510 <211> 20 <212> DRA <213> Homo sapiens <400> 1510 ctgcccagtg cacagcccca 20 <210> 1511 <211> 23 <212> DNA <213> Homo sapiens <400> 1511 ccagagectgg acctgggacc tgc 23 <210> 1512 <211> 20 <212> DNA <213> Homo sapiens <400> 1512 tcgggatggg tggacgtggg 20 <210> 1513 <211l> 20

<212> DNA <213> Homo sapiens <400> 1513 gttccccagg tccecgccagce 20 <210> 1514 <211> 31 <212> DNA <213> Homo sapiens <400> 1514 tgattgcttt ggtgcttaac ttgaagtggg a 31 <210> 1515 <211> 20 <212> DNA <213> Homo sapiens <400> 1515 actggctgga acgtcggege 20 <210> 1516 <211l> 24 <212> DNA <213> Homo sapiens <400> 1516 cgtggggtgt gttggagtgt ggtg 24 <210> 1517 <211> 23 <212> DNA <213> Homo sapiens <400> 1517 ttgaccagaa acccagggca ggg 23 <210> 1518 : <211> 20 <212> DNA <213> Homo sapiens <400> 1518 aatggagtgg gctcgggegce 20 <210> 1519 <211> 20 . <212> DNA <213> Homo sapiens <400> 1519 acagctgaaa cccgcggggce 20

<210> 1520 <21l1l> 24 <212> DNA <213> Homo sapiens <400> 1520 tggccctcca actcttettt gega 24 <210> 1521 <211> 28 <212> DNA <213> Homo sapiens <400> 1521 aaaccgatat ccttcgegta ctgacgga 28 <210> 1522 <211> 23 <212> DNA <213> Homo sapiens <400> 1522 catgcactgg acactggccc tga 23 <210> 1523 <211> 20 <212> DNA <213> Homo sapiens <400> 1523 gaaggcgtca aggccgegtg 20 <210> 1524 <211> 25 <212> DNA <213> Homo sapiens <400> 1524 tcaagcaaat gaggctggag ctgga 25 <210> 1525 <211> 35 <212> DNA <213> Homo sapiens <400> 1525 ccactgtatt tcatttctgt gatgagttet gacca 35 <210> 1526 <211> 27 <212> DNA <213> Homo sapiens <400> 152¢ gcctcaggtg gagcagtgag gtagaca 27

<210> 1527 <211> 21 <212> DNA <213> Homo sapiens <400> 1527 tccggacagg cggetgtctce a 21 <210> 1528 <211> 21 <212> DNA <213> Homo sapiens <400> 1528 ccatctctgt gccgtgeccec a 21 <210> 1529 <211> 23 : <212> DNA <213> Homo sapiens <400> 1529 tgctttgatg acacccaccg caa 23 <210> 1530 <211> 34 ’ <212> DNA <213> Homo sapiens <400> 1530 tttttcgttt aaagtagtct tccgtggttg ggaa 34 <210> 1531 <211> 24 <212> DNA <213> Homo sapiens <400> 1531 tggaggagtg ggtgtcgetg ttga 24 <210> 1532 <21ll> 22 <212> DNA <213> Homo sapiens <400> 1532 cactgctcag cggtggaggt gg 22 <210> 1533 <211> 21 <212> DNA <213> Homo sapiens

<400> 1533 caccggagct tgtggccage a 21 <210> 1534 <211> 26 <212> DNA <213> Homo sapiens <400> 1534 tcgettttge tgggactttc aaagcec 26 <210> 1535 <211l> 22 <212> DNA <213> Homo sapiens <400> 1535 tgcggacgtt gagctctgtg gc 22 <210> 1536 <211> 32 <212> DNA <213> Homo sapiens <400> 1536 gatgctagag aactggaagg ataacttggg gg 32 <210> 1537 <211> 22 <212> DNA : <213> Homo sapiens . <400> 1537 tgccatctte ctcectteegg cc 22 <210> 1538 <211> 21 <212> DNA <213> Homo sapiens <400> 1538 gcectgttgt ggctggetge a 21 <210> 1539 <211> 33 : ’ <212> DNA <213> Homo sapiens <400> 1539 ccctttatca gggagtactt gtggtagacg tcg 33 <210> 1540 <211> 23 <212> DNA :

<213> Homo sapiens <400> 1540 tcaaccggtc agagccagag ccc 23 <210> 1541 <211> 32 <212> DNA <213> Homo sapiens <400> 1541 ttcagcatgt tcacttgaag atccatcaga tg 32 <210> 1542 <21l1l> 28 <212> DNA <213> Homo sapiens <400> 1542 ccgtggtgat tttatagcat cctgggca 28 <210> 1543 <21l1> 28 <212> DNA <213> Homo sapiens <400> 1543 cccaaggcta atcctagcca tctcctge 28 <210> 1544 <211> 32 <212> DNA <213> Homo sapiens <400> 1544 caagtggatg ggaagtaaag ccctatgtgt ca 32 <210> 1545 <211> 20 <212> DNA <213> Homo sapiens <400> 1545 ctcaggcacc tgcgtccccg 20 <210> 1546 <211l> 25 <212> DNA <213> Homo sapiens <400> 1546 tcacgacgtt gtaaaacgac ggcca 25 <210> 1547

<211l> 29 <212> DNA <213> Homo sapiens <400> 1547 tctaccgtcea tggagcttct gtttccaca 29 <210> 1548 <211> 22 <212> DNA <213> Homo sapiens <400> 1548 tcgcecaggt agtggcecgat ca 22 <210> 1549 <211> 32 <212> DNA <213> Homo sapiens <400> 1549 ggaagtcttc ttggttatcc tggectttgga aa 32 <210> 1550 <211> 27 <212> DNA <213> Homo sapiens <400> 1550 ccacaagcct gaaaatgcaa tgtcctg 27 <210> 1551 <211> 25 <212> DNA <213> Homo sapiens <400> 1551 tcctgtgcca aatcatctge agcaa 25 <210> 1552 <211> 29 <212> DNA <213> Homo sapiens <400> 1552 tcaggatcaa tgactgaaat ttggccatg 29 <210> 1553 <211> 24 <212> DNA <213> Homo sapiens <400> 15853 ccagcagggg aactctggac aggce 24

«210> 1554 <211> 23 <212> DNA <213> Homo sapiens <400> 1554 ggaggggaag gaggcaatgt ggg 23 <210> 1558 . <211> 24 <212> DNA <213> Homo sapiens <400> 1555 gcctetegga ggagtcaaag gggce 24 <210> 1556 <211> 25 <212> DNA <213> Homo sapiens <400> 1556 cccagcacct ggggaattct aagcc 25 <210> 1557 <211l> 26 <212> DNA <213> Homo sapiens <400> 1557 gcttgatttg tggaccagtg tcccca 26 <210> 1558 <211> 33 <212> DNA <213> Homo sapiens <400> 1558 cceccctaaaa tecccactgta aacaaacatt tcg 33 <210> 1559 <211> 36 <212> DNA <213> Homo sapiens <400> 1559 gacaaatgtt tttacatgtg gaatgtcaca tcaacc . 36 <210> 1560 <211> 20 <212> DNA <213> Homo sapiens <400> 1560 .

caccccacce ccagcccatt : 20 <210> 1561 <211> 23 <212> DNA <213> Homo sapiens <400> 1561 tgaaatgaga ggtggcccgt ggg 23 <210> 1562 <211> 22 <212> DNA <213> Homo sapiens <400> 1562 gcccateccge tcatggatgt cc 22 <210> 1563 <211> 31 <212> DNA <213> Homo sapiens <400> 1563 gaggtacaca tttgaatgac aacaggggct c 31 <210> 1564 <21il> 21 <212> DNA <213> Homo sapiens <400> 1564 ccacgatggc cctgetggtce a 21 <210> 1565 <211> 23 <212> DNA <213> Homo sapiens <400> 1565 cctcegegge ctetttgttt gaa 23 <210> 1566 <211> 25 <212> DNA <213> Homo sapiens <400> 1566 tgcttacact ggcctgattg gtggg 25 <210> 1567 <211> 36 <212> DNA <213> Homo sapiens

<400> 1567 tcaggctctg atacctgctt ttaaaatgga gctaga 36 <210> 1568 <211> 20 <212> DNA <213> Homo sapiens <400> 1568 tctaccccca ccccgacced 20 <210> 15689

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1569 ccccacccec aattcttgge © 21 <210> 1570

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1570 ccagcgceccg ctagcccact 20 <210> 1571

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1571 gcgcatatgc ggctgtgcca } 20 <210> 1572

<211l> 21

<212> DNA

<213> Homo sapiens

<400> 1572 cgtccaggac acagccaggg © 21 <210> 1573

<211l> 34

<212> DNA

<213> Homo sapiens

<400> 1573 cagtggtcat tgtacagcac aagaatgaac aatg 34

<210> 1574

<211> 31

<212> DNA <213> Homo sapiens <400> 1574 gagcagagac caaccttctc aaagttggtg a 31 <210> 1575 <211> 28 <212> DNA <213> Homo sapiens <400> 1575 gcecgtgagtt tttgctctta ctcccagg 28 <210> 1576 <211l> 25 <212> DNA <213> Homo sapiens <400> 1576 cagggaggac aaactctggg ctgga 25 <210> 1577 <211> 20 <212> DNA <213> Homo sapiens <400> 1577 caccecggttg gtcccagcecc 20 <210> 1578 <211> 20 <212> DNA <213> Homo sapiens <400> 1578 tggctgctge tgcctccgtg 20 <210> 1579 <211> 29 <212> DNA <213> Homo sapiens <400> 1579 ggccagggtc tctggaagag aacttttca : 29 <210> 1580 <211> 20 <212> DNA <213> Homo sapiens <400> 1580 ccgtcgetgt ccacaggggce 20

<210> 1581 <211l> 27 <212> DNA <213> Homo sapiens <400> 1581 cccgacaaca aaatgcctca agtgagg 27 <210> 1582

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1582 ggcccttgga cggcatggct 20 <210> 1583

<211> 24

<212> DNA

<213> Homo sapiens

<400> 1583 cctgcagcca gcactggtac agca 24 <210> 1584

<211> 30

<212> DNA

<213> Homo sapiens

<400> 1584 tgcaaatgtc tttgcttgct tgtactcacg 30 <210> 1585

<211l> 34

<212> DNA

<213> Homo sapiens

<400> 1585 tcagatttca catgtatggc tctgtcctac tgct 34 <210> 1586

<211> 35

<212> DNA

<213> Homo sapiens

<400> 1586 : :

ccagagcatt ttccattaaa ccaattcttt gatca 35 . <210> 1587

<211> 27

<212> DNA

<213> Homo sapiens

<400> 1587 aacgtaatca tacctctagt catagca 27

<210> 1588 <211> 27 <212> DNA <213> Homo sapiens <400> 1588 cagctcactg tgaaggcttg agcctca 27 <210> 1589 <211l> 20 <212> DNA <213> Homo sapiens <400> 1589 cccttcececce gacctggggt 20 <210> 1590 <211> 26 <212> DNA <213> Homo sapiens <400> 1590 ggatttctcc agcgcgtgag atctga 26 <210> 1591 <211> 23 <212> DNA <213> Homo sapiens <400> 1591 tggctttggt gccatgactg cct 23 <210> 1592 <211> 20 <212> DNA <213> Homo sapiens <400> 1592 tgggcacatc gtgaggggcc 20 <210> 1593 <211> 33 <212> DNA <213> Homo sapiens ‘ <400> 1593 ctgtgaatca acagagcatg ctaccacttc agt 33 <210> 1554 <211> 29 <212> DNA <213> Homo sapiens

<400> 1594 . tgagaaagtg aaattggggc ttgtggaga 29 <210> 1595 <211> 24 <212> DNA <213> Homo sapiens

<400> 1595 gtgggattgg ctcagttttg ccca 24 <210> 1596

<211> 30

<212> DNA

<213> Homo sapiens

<400> 15896 gagctgagat gctgtgcaac tgtttaaggg 30 <210> 1597 '

<211l> 23 ’

<212> DNA

<213> Homo sapiens

<400> 1597 gtggggtcag caccatttgc tgg 23 <210> 1598

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 1598 gcecctggtgg ggtgacacge 20 <210> 1599

<211> 34

<212> DNA

<213> Homo sapiens

<400> 1599 aacttgtttt accccctctc ctcaacatct tgtc 34 <210> 18600

<211> 35

<212> DNA

<213> Homo sapiens

<400> 1600 tggacttcct ttgtgattcc ttttcaatct cactc 35

<210> 1601

<211> 30

<212> DNA

558 “, hy Nn au Co

<213> Homo sapiens

<400> 1601 gcctttttet ttggaaatge aactctgetg 30 <210> 1602

<211> 27

<212> DNA

<213> Homo sapiens

<400> 1602 tggacaaacg gtcttgcaca aatgacg 27 <210> 1603

<211l> 27

<212> DNA

<213> Homo sapiens

<400> 1603 ccaaggtcac ctagecctget ttttgece 27 <210> 1604

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1604 ttceccagget gectetecte ace 23 <210> 1605

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1605 tcctgggece agtctcacac tgg 23 <210> 1606

<211> 28

<212> DNA

<213> Homo sapiens

<400> 1606 agcttctttg cacatgtaaa gcaggcca 28 <210> 1607

<211> 22

<212> DNA

<213> Homo sapiens <400> 1607 tgggagcaga ggttcagcce ca 22 <210> 1608

<21l1l> 27 <212> DNA <213> Homo sapiens <400> 1608 tgaggacaga ctgtggacac cccatct 27 <210> 16095 <211> 26 <212> DNA . . <213> Homo sapiens <400> 1608S ctgtaagccc ccttttggat gccaaa 26 <210> 1610 <211> 24 <212> DNA <213> Homo sapiens <400> 1610 ttcececctggt gctgaatgtg gaca 24 <210> 1611 <211l> 34 <212> DNA <213> Homo sapiens <400> 1611 tcatcaacaa caaacatgca gtttctttct ctga 34 <210> 1612 . <211> 31 <212> DNA <213> Homo sapiens : <400> 1612 ttgattgcaa atggaggtac agtttctgcc t 31 <210> 1613 <211> 20 <212> DNA <213> Homo sapiens <400> 1613 cgcaacaaca agcgcacgca 20 <210> 1614 ’ <21l> 32 <212> DNA <213> Homo sapiens <400> 1614 tccaggaaga atttcatgtt tagagctgct ge 32

<210> 1615 <211> 33 <212> DNA <213> Homo sapiens <400> 1615 Cgatagttgg gcatctgtat ttccacttgt gtg 33 <210> 1616 <211> 32 <212> DNA <213> Homo sapiens <400> 1616 agaggggaaa acctattcta cccaacacag ca 32 <210> 1617 <211> 22 <212> DNA <213> Homo sapiens <400> 1617 tgggcaactt ggggaagccc ct 22 <210> 1618 <211> 23 <212> DNA <213> Homo sapiens <400> 1618 aagcgcttga ctatgtggcc cgg 23 <210> 1619 <211> 32 <212> DNA <213> Homo sapiens <400> 1619 } tcagaaaaga aaagctcttt agactagcaa tg 32 <210> 1620 <211> 27 <212> DNA <213> Homo sapiens <400> 1620 tcacaacctc ggagagaaga tggaccc 27 <210> 1621 <211l> 22 <212> DNA <213> Homo sapiens <400> 1621 aggccagcaa caatgcccac ga 22 <210> 1622 <211l> 18 <212> DNA <213> Homo sapiens <400> 1622 tggggtgcca ctcgacgeg 19 <210> 1623 <21l> 22 <212> DNA <213> Homo sapiens <400> 1623 cgaagctgga gctgggagct cg 22 <210> 1624 <211> 20 <212> DNA <213> Homo sapiens <400> 1624 acccggctge gcaggtctga 20 <210> 1625 <211> 33 <212> DNA <213> Homo sapiens <400> 1625 ggatttttaa ggggatccct atttatggcc aaa 33 <210> 1626 <211> 20 <212> DNA <213> Homo sapiens <400> 1626 ccaggacccg atcgcgatcg 20 <210> 1627 <211> 24 <212> DNA <213> Homo sapiens <400> 1627 aggctctgct cgttcectet cece 24 <210> 1628 <211> 21 <212> DNA <213> Homo sapiens

<400> 1628 tgcgggecgea agcttatgtc c 21 <210> 1629 <211> 29 <212> DNA <213> Homo sapiens <400> 1625 tttgctggct tatgatgtgt aaggcacca 29 <210> 1630 <211> 19 <212> DNA <213> Homo sapiens <400> 1630 cgggggcctg aggccagtg 19 <210> 1631 <211> 34 <212> DNA <213> Homo sapiens <400> 1631 cctectttget gtttttcacc tactacgtca caca 34 <210> 1632 <211> 29 <212> DNA <213> Homo sapiens <400> 1632 agaggctgaa gctcctcagc ttccaactce 29 <210> 1633 <211> 34 <212> DNA <213> Homo sapiens <400> 1633 tgctctccaa cacctttgtt tagtagggaa aacc 34 <210> 1634 <21ll> 28 <212> DNA <213> Homo sapiens <400> 1634 ggaaaagctc aagaaggdctg ggagatga 28 <210> 1635 <211> 23

<212> DNA <213> Homo sapiens <400> 1635 ggatggacgc ggacggaatt ctg 23 <210> 1636 <211> 21 <212> DNA <213> Homo sapiens <400> 1636 aggaccaagg cccagccage a 21 <210> 1637 <211> 31 <212> DNA <213> Homo sapiens <400> 1637 tcctectcac tteecctaccet cacaacaaga a 31 <210> 1638 <211> 29 <212> DNA <213> Homo sapiens <400> 1638 tgacaacaga gaccaaaaac aaccaccca 29 <210> 1639 <211l> 26 <212> DNA <213> Homo sapiens <400> 1639 tgccgagagg aattgtaagg ttgcca 26 <210> 1640 <211> 30 <212> DNA <213> Homo sapiens <400> 1640 cagaacctca cagacccaaa ggaacatcaa 30 <210> 1641 <211> 33 <212> DNA <213> Homo sapiens <400> 1641 tggagttgaa aaacagatca agtcagggac atc 33

PCT/US2003/012946

<210> 1642 <211> 34 <212> DNA <213> Homo sapiens <400> 1642 tgtccagaat ctagtttgtg cagaaatgtt tcca 34 <210> 1643 <211s> 22 <212> DNA <213> Homo sapiens <400> 1643 cacagccteg gtagcagegg ga 22 : <210> 1644 <211> 23 <212> DNA <213> Homo sapiens <400> 1644 gttggecttt agggctgtge cca 23 <210> 1645 <211> 29 <212> DNA <213> Homo sapiens <400> 1645 Cccagcccaca atttcaaata atgcaggaa 29 <210> 1646 <211> 29 <212> DNA <213> Homo sapiens <400> 1646 aatgcacttc atgaaaagtt gtggctccc 29 <210> 1647 <211> 28 <212> DNA <213> Homo sapiens <400> 1647 gcgccaaaga gtatcaggaa agcaagga 28 <210> 1648 <211> 27 <212> DNA <213> Homo sapiens <400> 1648 tgccacttca ttggcaccta agacctg 27

<210> 1649 : <211l> 20 <212> DNA <213> Homo sapiens <400> 16489 cccctgtgge atccctggea 20 <210> 1650 <211> 19

<212> DNA

<213> Homo sapiens

<400> 1650 cgccgecectt gtgctgcetce 19 <210> 1651

<211> 35

<212> DNA

<213> Homo sapiens

<400> 1651 gcagggaaag ggggttagtt attcattttt cagcet 35 <210> 1652

<211> 35

<212> DNA

<213> Homo sapiens

<400> 1652 caactgctce acttcttttt gtttgagaac tctga 35 <210> 1653 :

<211> 28

<212> DNA

<213> Homo sapiens

<400> 1653 ggcagctggg agatgatggt aaaaggct 28 <210> 1654

<211> 35

<212> DNA

<213> Homo sapiens

<400> 1654 ccaaagagca aagctacaca aagaaaattc ctcag 35 <210> 1655

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1655 cacacaggca tgtgtgtctg catgg 25

<210> 1656

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1656 aagtgcagcg ttccttttge 20

<210> 1657

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1657 ccggggtgac aagcagatac 20

<210> 1658

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1658 aaggaagcct cctccacgtt 20

<210> 1659

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1659 cagaagcaag gggctgaaaa 20 © <210> 1660

«211s 20

<212> DNA

<213> Homo sapiens

<400> 1660 caacccacce ctceccttettt 20

<210> 1661

<211> 22

<212> DNA

<213> Homo sapiens )

<400> 1661 tcagggaatg aaggtgtcag aa 22

<210> 1662

<211> 22

<212> DNA

<213> Homo sapiens <400> 1662 tggctgagtt ctggtcaaag aa 22 <210> 1663 <211> 22 «212> DNA <213> Homo sapiens <400> 1663 tctgtccatc atttcaccat cc 22 <210> 1664 <211> 20 <212> DNA <213> Homo sapiens <400> 1664 ctcggtgggt gttcaaggag 20 <210> 1665 <211> 20 <212> DNA <213> Homo sapiens <400> 1665 tgctecctttt ggtgactgga 20 <210> 1666 <211> 20 <212> DNA <213> Homo sapiens <400> 1666 ggcctggtta gaggctggtt 20 <210> 1667 <211> 20 <212> DNA <213> Homo sapiens <400> 1667 ctgtctetge ctecetcacc 20 <210> 1668 <211> 20 oo <212> DNA <213> Homo sapiens <400> 1668 ggagaagcgg cgataccata 20 <210> 1669

<211> 20 <212> DNA <213> Homo sapiens <400> 1669 gtcccacctg ggagaatgtg 20 <210> 1670 <211> 20 <212> DNA <213> Homo sapiens <400> 1670 tcactcccag ttccctggac 20 <210> 1671 <211> 20 <212> DNA <213> Homo sapiens <400> 1671 atccgccaca acctgagtct 20 <210> 1672 <211> 20 <212> DNA <213> Homo sapiens <400> 1672 gtgtcctcecc tceccectatge 20 <210> 1673 <211l> 20 <212> DNA <213> Homo sapiens <400> 1673 ctgggccgtg actacaggac 20 <210> 1674 <211> 20 <212> DNA <213> Homo sapiens <400> 1674 tcgtgcaatg gagattctgg 20 <210> 1675 <211> 20 <212> DNA <213> Homo sapiens <400> 1675 ctaagccact gcctgctggt 20

<210> 1676 <211> 20 <212> DNA .<213> Homo sapiens <400> 1676 atgtgggcca agatctccac 20 <210> 1677 <211> 22 <212> DNA <213> Homo sapiens ! <400> 1677 gcccttcata atatccceca gt 22 <210> 1678 <21l> 21 <212> DNA <213> Homo sapiens <400> 1678 ggcattgtgt tcccaagttc a 21 <210> 1679 <211> 19 <212> DRA <213> Homo sapiens <400> 1679 cgtctececte tgcecatceet 19 <210> 1680 <211l> 20 <212> DNA <213> Homo sapiens <400> 1680 gggaaggctc ctggttgtct 20 <210> 1681 <211> 20 <212> DNA <213> Homo sapiens <400> 1681 acagaggccc tggaaaggac 20 <210> 1682 <21l1l> 21 <212> DNA <213> Homo sapiens <400> 1682 tacctgacct ttgtgccctc a 21 <210> 1683 <211> 20 <212> DNA <213> Homo sapiens <400> 1683 aagtccggtg gtttcggaat 20 <210> 1684 <211> 20 <212> DNA <213> Homo sapiens <400> 1684 ggaatggaga gcacggtctg 20 <210> 1685 <211> 20 <212> DNA <213> Homo sapiens <400> 1685 tttgcacagg tgttccctga 20 <210> 1686 <211> 2€ <212> DNA <213> Homo sapiens <400> 1686 tttgaatgac caagttctct tcattg 26 <210> 1687 <211> 20 <212> DNA <213> Homo sapiens <400> 1687 cacctttgcec tttgctggac 20 <210> 1688 <211> 20 <212> DNA <213> Homo sapiens <400> 1688 ctecccttgtg cgtgggtaag 20 <210> 1689 <211> 20 <212> DNA <213> Homo sapiens

<400> 1689 cttctececte tgeccctetce 20 <210> 1690 <211> 20 <212> DNA <213> Homo sapiens <400> 1690 gggagaggga catcctacgg 20 <210> 1691 <211> 20 <212> DNA <213> Homo sapiens <400> 1691 ccagcectgga ggtgatcaag 20 <210> 1692 <211> 20 <212> DNA <213> Homo sapiens <400> 1692 aagatgggtc tccgcacttg 20 <210> 1693 <211> 20 <212> DNA <213> Homo sapiens <400> 1693 gccagtggta gttgggagga 20 <210> 1694 <211> 26 <212> DNA <213> Homo sapiens <400> 1694 gccaataaag aaattaacac ccaaaa 26 <210> 1695 : <211> 20 <212> DNA <213> Homo sapiens BE <400> 1695 acccttccat ggtgtgatcg 20 <210> 1696 <211> 20

<212> DNA <213> Homo sapiens <400> 1696 acctcacagg gaccctccac 20 <210> 1697 <211> 24 <212> DNA <213> Homo sapiens <400> 1697 ctggacaagc ttacatcttc ctca 24 <210> 1698 <211> 20 <212> DNA : <213> Homo sapiens <400> 1698 atccgtgacg acatgctgtg 20 <210> 1699 <211> 20 <212> DNA <213> Homo sapiens <400> 1699 gatgccacct tcagcctctg 20 <210> 1700 <21l> 20 <212> DNA <213> Homo sapiens <400> 1700 ccacctggaa tcagggattg 20 <210> 1701 <211l> 20 <212> DNA <213> Homo sapiens <400> 1701 tcatcttgga gggaccaagg 20 <210> 1702 <211> 19 <212> DNA <213> Homo sapiens <400> 1702 ggacatttgc cttgctgga 1°

<210> 1703 <211l> 20 <212> DNA <213> Homo sapiens <400> 1703 gggcccagca gttctatgac 20 <210> 1704 <211> 20 . <212> DNA <213> Homo sapiens <400> 1704 cctgccttgt gacaggatga 20 <210> 1705 <211l> 21 <212> DNA <213> Homo sapiens <400> 1705 ggcaactggt gaacggtaac a 21 <210> 1706 <211s> 20 <212> DNA <213> Homo sapiens <400> 1706 cccaaggcta agcaggaggt 20 <210> 1707 <211> 20 <212> DNA <213> Homo sapiens <400> 1707 gggtcccaaa caactcagga 20 <210> 1708 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 1708 cccaagtcag gctggagaga 20 <210> 1709 <211> 22 <212> DNA <213> Homo sapiens <400> 17089 aacaattcaa gtgctggget tt 22

<«210> 1710 «211> 20 <212> DNA <213> Homo sapiens <400> 1710 cggtggctac cagacattga 20 <210> 1711 <211> 21 <212> DNA <213> Homo sapiens <400> 1711 cagcagtttc aatgcaccaa a 21 <210> 1712 <21l> 26 <212> DNA <213> Homo sapiens <400> 1712 gacaactttc gcatttgectt ttattt 26 <210> 1713 : <211> 25 <212> DNA <213> Homo sapiens <400> 1713 gctttaatgg catgtcagac agaac 25 <210> 1714 <211> 21 <212> DNA <213> Homo sapiens <400> 1714 agtcccagca ttgatgacag c 21 <210> 1715 <211> 20 <212> DNA <213> Homo sapiens : <400> 1715 cctgtttgee atcctcttgg 20 <210> 1716 <211> 20 <212> DNA <213> Homo sapiens

<400> 1716 caccggctaa tggtgggtaa 20 <210> 1717 <211> 20 <212> DNA <213> Homo sapiens

<400> 1717 gtcgececcagt cctaccagag 20 <210> 1718

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1718 attccgttag acttgtcctc ctttt 25 <210> 1719

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1719 gacgaccatc gcagacacag 20 <210> 1720

<211> 19

<212> DNA

<213> Homo sapiens

<400> 1720 ctgggagacc cgctgtttc 19 <210> 1721

<211> 24

<212> DNA

<213> Homo sapiens

<400> 1721 tgggctaact atgcagagca tgta 24 <210> 1722

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1722 cgacaatgag cggggagata 20 <210> 1723

<211l> 20

<212> DNA

576 i P—

<213> Homo sapiens

<400> 1723 accactgctg ctgctgtttg 20

<210> 1724

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1724 ccctgaaggt gaaccgctta 20

<210> 1725

<211> 25 :

<212> DNA

<213> Homo sapiens

<400> 1725 .

gtcaaacaga ttaaggttcg agtgg 25

<210> 1726

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1726 gcctgaggect gtgaagatgg 20

<210> 1727

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1727 aggaggcata ggccatttca g 21

<210> 1728

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1728 gaggaccaga cccaggacac 20

<210> 1729

<211> 20 3

<212> DNA

<213> Homo sapiens

<400> 1728 .

gcttgtgcat gaccctgatg 20 . <210> 1730

<211> 19 <212> DNA <213> Homo sapiens <400> 1730 caggagaacg tggccctcet 19 <210> 1731 <211> 20 <212> DNA <213> Homo sapiens <400> 1731 tgcetgtect tctgtgtget 20 <210> 1732 <211> 22 <212> DNA <213> Homo sapiens <400> 1732 gaggaatgca cgtcagtcaa aa 22 <210> 1733 <211> 19 <212> DNA <213> Homo sapiens <400> 1733 gcaaggctga cgdagagctg 19 <210> 1734 <211> 20 <212> DNA <213> Homo sapiens <400> 1734 ccatcecggga tatcctagcce 20 <210> 1735 <211> 20 <212> DNA <213> Homo sapiens <400> 1735 ccctgtetet ccccaccttt 20 <210> 1736 <21l> 18 <212> DNA <213> Homo sapiens <400> 1736 gacgaggctg cggtgtcet 18

<210> 1737 <211> 19 <212> DNA <213> Homo sapiens <400> 1737 gggaaactgt ggcgtgatg 1s <210> 1738 <211l> 21 <212> DNA <213> Homo sapiens : <400> 1738 cagccggtgt aaatgttgag c 21 <210> 1739 <211l> 19 <212> DNA <213> Homo sapiens <400> 1739 ttaaaattcc gggeccttgg 18 <210> 1740 <211l> 21 <212> DNA <213> Homo sapiens <400> 1740 gtgcatccgt ggtcaaaagt c 21 <210> 1741 <211> 18

<212> DNA <213> Homo sapiens <400> 1741 tcctgtcecat gtgecctggt 19 <210> 1742 <211> 20 <212> DNA <213> Homo sapiens <400> 1742 gcagcagtca gcgatgtttc 20 <210> 1743 <211> 21 <212> DNA <213> Homo sapiens <400> 1743 ccaaacctgc aaacaaacag g 21 <210> 1744 <21ll> 26 <212> DNA <213> Homo sapiens <400> 1744 tgccaatgat gtacagtttt atggtt 26 <210> 1745 <211> 22 <212> DNA <213> Homo sapiens <400> 1745 agccatttect ccaatggaca tc 22 <210> 1746 <211> 21 <212> DNA <213> Homo sapiens <400> 1746 attcatgtcc agtggcttee a 21 <210> 1747 <211> 19 <212> DNA <213> Homo sapiens <400> 1747 actcecctgec caccagtct 19 <210> 1748 <211> 20 <212> DNA <213> Homo sapiens <400> 1748 aaggagctgc ccgatgctat 20 <210> 1749 <211> 20 <212> DNA <213> Homo sapiens <400> 1749 gccatactcc ctgcectectt 20 <210> 1750 <211> 21 <212> DNA <213> Homo sapiens

580 i

<400> 1750 ttgacaccac cctctttgga a 21 <210> 1751 } <211> 22 <212> DNA <213> Homo sapiens <400> 1751 ctccaaccat gaaatcaaag ca 22 <210> 1752 <211> 21 <212> DNA <213> Homo sapiens <400> 1752 gaaatcaaag cacggtgcag a 21 <210> 1753 <211> 20 <212> DNA <213> Homo sapiens <400> 1753 ccccgatgct cagaagtgtce 20 <210> 1754 <211> 21 <212> DNA <213> Homo sapiens <400> 1754 ggggacaacd aaaacaagag g 21 <210> 1755 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 1755 ccgctatgat cctcgetttg 20 <210> 1756 <211> 22 <212> DNA <213> Homo sapiens <400> 1756 ggagaagatc ctttggatgc ag 22 <210> 1757 <211> 20

«<212> DNA <213> Homo sapiens <400> 1757 caagccaaaa tgggagcaag 20 <210> 1758 <211> 19 <212> DNA . <213> Homo sapiens <400> 1758 ctggccgtca tggagactg 19 <210> 1759 <211> 20 <212> DNA <213> Homo sapiens <400> 1758 agtcctgcaa ctgcctcectg 20 <210> 1760 <211> 20 .- <212> DNA <213> Homo sapiens <400> 17690 tggcctcagg gaaaagactg 20 <210> 1761 <211l> 20 <212> DNA <213> Homo sapiens <400> 1761 tccctggtag acggggtagg 20 <210> 1762 <211> 20 <212> DNA <213> Homo sapiens <400> 1762 gcggaaaagt caggggaaac 20 <210> 1763 <211> 22 <212> DNA <213> Homo sapiens <400> 1763 tccaggatca aaacattcct ca 22

<210> 1764 <211> 20 <212> DNA <213> Homo sapiens <400> 1764 cagacgcaga gcatggatga 20 <210> 1765 <211> 20 <212> DNA <213> Homo sapiens <400> 1765 cccgtaageg ctaattccag 20 <210> 1766 <211> 25 <212> DNA <213> Homo sapiens <400> 1766 catgctgaaa caagattaac acagg 25 <210> 1767 <211> 20 <212> DNA . <213> Homo sapiens <400> 1767 ttgcgcctaa tcatgtcegtce 20 <210> 1768 <211> 19 <212> DNA <213> Homo sapiens <400> 1768 gaagcacagg tccgtgtceg 19 <210> 1769 <211> 20 <212> DNA <213> Homo sapiens <400> 1769 gcagaaaacc gttgcattga 20 <210> 1770 <211> 20 <212> DNA <213> Homo sapiens <400> 1770 cgccagtgtt tccgtcagta . 20

<210> 1771 <211> 32 <212> DNA <213> Homo sapiens <400> 1771 atacaaataa tcttacacac aaatgaaaat gc 32 <210> 1772

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1772 ccgtctcgta gataggcagce a 21 <210> 1773

<211l> 20

<212> DNA

<213> Homo sapiens

<4Q00> 1773 gctccagect catttgettg 20 <210> 1774

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1774 ttttaattgg ggtgatccaa age 23 <210> 1775

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1775 aagcctcagg tggagcagtg 20 <210> 1776

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 1776 gcectgtcegg agactgaaga 20

<210> 1777

<211> 19

<212> DNA

<213> Homo sapiens

<400> 1777 cggcacagag atggagctg 19 <210> 1778 <211> 19 . <212> DNA <213> Homo sapiens <400> 1778 tccacetttg ggtegettt 19 <210> 1779 <211> 189 <212> DNA <213> Homo sapiens <400> 1779 tcccaccaaa ccccagact 19 <210> 1780 <211> 20 <212> DNA <213> Homo sapiens <400> 1780 gccctcaacg accactttgt 20 <210> 1781 <211> 20 <212> DNA <213> Homo sapiens <400> 1781 accgctgagc agtgaccttce 20 <210> 1782 <211> 20 <212> DNA <213> Homo sapiens <400> 1782 cacaagctcc ggtggatctce 20 <210> 1783 <211> 20 <212> DNA <213> Homo sapiens <400> 1783 accccagccc ctagacagag 20 <210> 1784 <211> 20 <212> DNA

<213> Homo sapiens . <400> 1784 aacctgccte ctctgecact 20 <210> 1785 <211> 24 <212> DNA <213> Homo sapiens <400> 1785 gtgaaagggt actggatacc aacc 24 <210> 1786

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1786 cgaatggcct ctagccacac 20 <210> 1787

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1787 cacaacaggg ctgcaacaaa 20 <210> 1788

<211l> 23

<212> DNA

<213> Homo sapiens

<400> 1788 gacgtctggt tcaaagagtt gga 23 <210> 1789

<211> 19

<212> DNA

<213> Homo sapiens

<400> 1789 tggctctgac cggttgatg 19 <210> 1790

<211> 19

<212> DNA

<213> Homo sapiens

<400> 1790 gcgaccacca gcagctcta 19

<210> 1781

<21l1> 19 <212> DNA <213> Homo sapiens <400> 1791 tgtgaaatgc ccaggatgc 18 <210> 1792 <211> 22 <212> DNA <213> Homo sapiens <400> 1792 gcccttgaca gggtatttct ga 22 <210> 1793 <211> 2S <212> DNA <213> Homo sapiens <400> 1793 cgtgtcagaa aacaaagcat actga 25 <210> 1794 <211> 1S <212> DNA <213> Homo sapiens <400> 1794 ggggagectct ccctgacct 19 <210> 1795 <211> 20 <212> DNA <213> Homo sapiens <400> 17385 acaattcact ggccgtegtt 20 <210> 1796 <211> 20 . <212> DNA <213> Homo sapiens <400> 1796 ggagaatgca gaggccaaaa 20 <210> 1797 : <211> 20 <212> DNA <213> Homo sapiens <400> 1797 cgagatgatc ggccactacc 20

<210> 1798 <211> 20 <212> DNA <213> Homo sapiens <400> 1798 aagcagggga ctgggaaaag 20 <210> 179° <211l> 20 . <212> DNA <213> Homo sapiens <400> 1799 ttgcattttc aggcttgtgg : 20 <210> 1800 <211l> 20 <212> DNA <213> Homo sapiens <400> 1800 ctcgcctaag agggecttte 20 <210> 1801 <211> 20 <212> DNA <213> Homo sapiens <400> 1801 gcggggacac cccttaatag 20 <210> 1802 <211> 20 <212> DNA <213> Homo sapiens <400> 1802 taagcaacag ccccaaatgce 20 <210> 1803 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 1803 ggggagtggg tttggatagg 20 = <210> 1804 . <211> 20 <212> DNA <213> Homo sapiens <400> 1804 .

gcctcecctcaa acggttcecett 20 <210> 1805 <211> 31 <212> DNA <213> Homo sapiens <400> 1805 Cttttattaa tatattgtgt gtgcaccttg t 31 <210> 1806 <211> 21 <212> DNA <213> Homo sapiens <400> 1806 tccacaaatc aagctcccaa g 21 <210> 1807 <211> 32 <212> DNA <213> Homo sapiens <400> 1807 aggacgttct ttattatgaa actttatcac at 32 <210> 1808 <211> 25 <212> DNA <213> Homo sapiens <400> 1808 ttaaatgtca aaatgaaagg ggaca 25 <210> 1809 <211> 21 <212> DNA <213> Homo sapiens <400> 1809 ccttctecag gectgagtgt t 21 <210> 1810 <211> 21 <212> DNA <213> Homo sapiens <400> 1810 gaggcctctg atgaccagac a 21 <210> 1811 <211> 20 <212> DNA <213> Homo sapiens

<400> 1811 gctccetgtt gggtgtcatce 20 <210> 1812 <211> 19

<212> DNA

<213> Homo sapiens

<400> 1812 gtgggttgtg cttgccaga 19 <210> 1813

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1813 tacccggaga tcgacaagga 20 <210> 1814

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1814 cggaatggtg aaaccaaagc 20 <210> 1815

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1815 acataccctc ctggcccttg 20 <210> 1816

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1816 acctgaccgt gcgaatcaat 20 <210> 1817 . <211> 20

<212> DNA

<213> Homo sapiens

<400> 1817 ctcttgecece gagcctagtt 20 <210> 1818

<211> 20

590 lt Co Co

<212> DNA

<213> Homo sapiens

<400> 1818 ccccactatg ggatgacgag 20

<210> 1819

<211l> 21

<212> DNA

<213> Homo sapiens :

<400> 1819 cagagctctt ttggggtctg g 21

«<210> 1820

<21l1l> 19

<212> DNA

<213> Homo sapiens

<400> 1820 caccatctcc tgecgtcteg 19

<210> 1821

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1821 ttggcacacc agtgttctcc 20

<210> 1822

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1822 gcccattgtt cattcttgtg © 21 <210> 1823

<211> 26

<212> DNA :

<213> Homo sapiens

<400> 1823 ccaagacaag aaattgtttt gagaaa 26

<210> 1824

<211> 31

<212> DNA

<213> Homo sapiens

<400> 1824 tttgtacatg actctcattt tattgtttet t 31

<210> 1825 <211l> 18 <212> DNA <213> Homo sapiens <400> 1825 ccctcggtct gggcaataa 19 <210> 1826 . <21l1> 20 <212> DNA <213> Homo sapiens <400> 1826 ccgggtgaga tccacaagtc 20 <210> 1827 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 1827 gagccgcaga tgcaagttct 20 <210> 1828 <211> 23 <212> DNA <213> Homo sapiens <400> 1828 gggctcctaa ataccaagct tea 23 <210> 1828 <211> 20 <212> DNA <213> Homo sapiens <400> 1829 tcagcacctc agtcgtccac 20 <210> 1830 <21l1l> 22 <212> DNA <213> Homo sapiens <400> 1830 cacttgaggc attttgttgt cg 22 <210> 1831 <211> 20 <212> DNA <213> Homo sapiens <400> 1831 agccctggtg gcectattacce 20

<210> 1832 <211> 31 <212> DNA <213> Homo sapiens <400> 1832 tgtttgagta cattctttca acactacaca t 31 <210> 1833 <211> 29 <212> DNA <213> Homo sapiens <400> 1833 ttttaagtgg aaatgtaacc attttagga 29 <210> 1834 <211> 22 <212> DNA <213> Homo sapiens <400> 1834 tagcctcceec aagagagaac ag 22 <210> 1835 <211> 21 <212> DNA <213> Homo sapiens <400> 1835 ccgcecgtaa ttaaatagca t 21 <210> 1836 <211> 21 <212> DNA <213> Homo sapiens <400> 1836 agggagcttg aagagggaat g 21 <210> 1837 <211> 20 <212> DNA <213> Homo sapiens <400> 1837 aaaatgttcg cctggctgat 20 <210> 1838 <211l> 20 <212> DNA <213> Homo sapiens

<400> 1838 tcccaccaat gtcaggaatg 20 <210> 1839

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1839 gctctgagag ttccecctgte © 21 <210> 1840

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1840 tttgcctgac atcgtectegt 20 <210> 1841

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1841 ttgggccaat aaggattcca 20 <210> 1842

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1842 gcagatgagc gtcccacttt 20 <210> 1843

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1843 ’ aatggaaggc ttggacatgg 20 <210> 1844

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1844 aaaagtgtcc attgaaaccg tga 23 <210> 1845

<211> 20

<212> DNA : .

<213> Homo sapiens <400> 1845 tgccttggag aggatggaag 20 <210> 1846 <211> 20 <212> DNA <213> Homo sapiens <400> 1846 tgccaggctt aaggagagga 20 <210> 1847 <211l> 28 <212> DNA <213> Homo sapiens <400> 1847 ctaatgatat tgatttggat acggtgaa 28 <210> 1848 <211> 20 <212> DNA <213> Homo sapiens <400> 1848 cccctcagat cccaatttca 20 . <210> 1849 <211> 20 <212> DNA <213> Homo sapiens <400> 1849 gctgtgggat ctcagtgtge 20 <210> 1850 <211> 27 <212> DNA <213> Homo sapiens <400> 1850 acttgttaac ctttctaacc ttcacga 27 <210> 1851 : <21l> 20 I. . <212> DNA <213> Homo sapiens <400> 1851 ggaagatgag caggccagtg 20 <210> 1852

<21l1l> 20 <212> DNA <213> Homo sapiens <400> 1852 tgtgecctctg ccatctteac 20 <210> 1853 <211> 21 <212> DNA <213> Homo sapiens <400> 1853 ttgaagctct tggcattcag c 21 <210> 1854 <211> 23 <212> DNA <213> Homo sapiens <400> 1854 gcagccaaga agatgtgaaa gag 23 <210> 1855 <211> 20 <212> DNA : <213> Homo sapiens <400> 1855 ggatgctgca aacccagaat 20 <210> 1856 <211> 20 <212> DNA <213> Homo sapiens <400> 1856 cccgtggact gettcaattce 20 <210> 1857 <211> 27 <212> DNA <213> Homo sapiens <400> 1857 Ccatgttatg atctaaatgc ttgtteca 27 <210> 1858 : <211> 20 <212> DNA <213> Homo sapiens <400> 1858 ttgagaaatg gccccaactg 20

<210> 1859 <211> 21 <212> DNA <213> Homo sapiens <400> 1859 gggaacatga ttggtctgct g 21 <210> 1860 <211> 20 <212> DNA <213> Homo sapiens <400> 1860 gecctctteca cttggtctge 20 <210> 1861 <211> 20 <212> DNA <213> Homo sapiens <400> 1861 cccttcttca gecgaacgagt 20 <210> 1862 <211l> 25 <212> DNA <213> Homo sapiens <400> 1862 tttcacacag gagatctcag acaga 25 <210> 1863 <211> 27 <212> DNA _ <213> Homo sapiens <400> 1863 taaccaaaat ttaaaggcaa attcaca 27 <210> 1864 <211> 21 <212> DNA <213> Homo sapiens <400> 1864 caagccaaag tggcatgttt t 21 <210> 1865 <211> 21 <212> DNA <213> Homo sapiens <400> 1865 597 i tcgtgctcte caacctgtet t 21 <210> 1866 <211> 20 <212> DNA <213> Homo sapiens <400> 1866 cctegtgaca tggacacacce 20 <210> 1867 <211> 23 <212> DNA <213> Homo sapiens <400> 1867 ttttttcaag cagtaaaatt cca 23 <210> 1868 <211> 20 <212> DNA <213> Homo sapiens <400> 1868 gtggcctttc ttgggteccte 20 <210> 1869 <211> 20 <212> DNA <213> Homo sapiens <400> 1869 gcctggctgt cctagcagtt 20 <210> 1870 <211> 19 <212> DNA <213> Homo sapiens <400> 1870 gtacaagccg tccgacacyg 19 <210> 1871 <211l> 20 <212> DNA <213> Homo sapiens <400> 1871 gaccgaggac tcaacccaaa 20 <210> 1872 <211> 20 <212> DNA <213> Homo sapiens

<400> 1872 gcggaagaac atcgacctca 20 <210> 1873 <211> 21 <212> DNA <213> Homo sapiens <400> 1873 tggcagtttt aaggcccaaa c 21 <210> 1874 <211> 19 <212> DNA <213> Homo sapiens <400> 1874 acaagaccgg caccctcac 19 <210> 1875 <211> 20 <212> DNA <213> Homo sapiens <400> 1875 aagaatgggg agagggaacg 20 <210> 1876 <211> 35 <212> DNA <213> Homo sapiens ] <400> 1876 ggagaaaact ttattcttta tagtttcaaa tacca 35 <210> 1877 <211> 21 <212> DNA <213> Homo sapiens <400> 1877 ggctgggaag ctctaccaaa a 21 <210> 1878 <211> 20 <212> DNA . <213> Homo sapiens ’ <400> 1878 ggagctcagc acctcttcca 20 <210> 1878 <211> 20

<212> DNA <213> Homo sapiens <400> 1879 cacccagctc ctttcetgtg 20 <210> 1880 <211l> 20 <212> DNA <213> Homo sapiens <400> 1880 ccctggggec ctatttcata 20 <210> 1881 <211> 20 <212> DNA <213> Homo sapiens <400> 1881 ctccaggtag cccacggata 20 <210> 1882 <211> 20 <212> DNA <213> Homo sapiens <400> 1882 ctggcatctg caccacaact 20 <210> 1883 <211> 20 <212> DNA <213> Homo sapiens <400> 1883 tccteccaggt gtggctgagt 20 <210> 1884 <211> 21 <212> DNA <213> Homo sapiens <400> 1884 cgggattcac actcagaacc a 21 <210> 1885 . <211> 19 <212> DNA <213> Homo sapiens <400> 1885 : aagccatgcc gaagcaaat 19

<210> 1886 <21l1l> 21 <212> DNA <213> Homo sapiens <400> 1886 catgagatgt gtgggtggtt g 21 <210> 1887 <211l> 20 . <212> DNA <213> Homo sapiens <400> 1887 ctctggtgcc ctcactctgce 20 <210> 1888 ~ <211> 21 <212> DNA <213> Homo sapiens <400> 1888 tgttcectttg ggtctgtgag g 21 <210> 1889 <211> 20 <212> DNA <213> Homo sapiens <400> 1889 ctgggccaat ggtacaggtc 20 <210> 1890 <211> 23 <212> DNA <213> Homo sapiens <400> 1880 acaatcaacc aacaatggaa acc 23 <210> 1891 <211> 20 <212> DNA <213> Homo sapiens <400> 1891 gggctcctac caggaaaagg 20 <210> 18892 <211> 20 <212> DNA <213> Homo sapiens <400> 1892 atgggcaagt gtcgtggact 20

<210> 1893 <211l> 28 <212> DNA <213> Homo sapiens <400> 1893 ttttecttect tacgtcaata cttttect 28 <210> 1894 <21ll1l> 25 <212> DNA <213> Homo sapiens <400> 18594 catgaaaacc cagtaagact ttcca 25 <210> 1885 : <211> 20 <212> DNA <213> Homo sapiens <400> 1895 gaagtcctgg gcatgcatct 20 <210> 1896 <211> 21 <212> DNA <213> Homo sapiens <400> 1856 gtgggcctgt gaagttttca a 21 <210> 1897 <211> 20 <212> DNA <213> Homo sapiens <400> 1887 agcccttgac ccttgagtcce 20 <210> 1898 <211> 20 <212> DNA <213> Homo sapiens <400> 1898 - ggggacacag cagaagaacg 20 <210> 1899 <211l> 20 <212> DNA <213> Homo sapiens

<400> 1899 atcaccaacc gcaccttcat 20 <210> 1900

<211> 20

«212> DNA

<213> Homo sapiens

<400> 1900 tggggcacca tttcagtgta } 20

<210> 1901

<211l> 21

<212> DNA

<213> Homo sapiens

<400> 1901 cctttgecage ctgtttetgt c 21 <210> 1902

<21l> 24

<212> DNA

<213> Homo sapiens

<400> 1902 gggtgtgtcect gctcagtaat ttga 24 <210> 1903

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1903 agccatcgga agagaacage 20 <210> 1904

<211> 20

<212> DNA <213> Homo sapiens

<400> 1904 gaagggacac gcaggtggta 20 : <210> 1905

<211> 24

<212> DNA

<213> Homo sapiens

<400> 1905 tgacttttaa ttccccaatc aagg 24 <210> 1906 <211> 21 <212> DNA

<213> Homo sapiens <400> 1906 ccgtctgtge atccatattce ¢ 21 <210> 1907 <211> 20 <212> DNA <213> Homo sapiens <400> 1907 atgatcccca cgatccatgt 20 <210> 1908 <211> 20 <212> DNA <213> Homo sapiens <400> 1908 gcacctggag aacccattca 20 <210> 1909 <211> 20 <212> DNA <213> Homo sapiens <400> 1909 tttcecetteg ttgettcetg 20 <210> 1910 <211> 20 <212> DNA <213> Homo sapiens <400> 1910 tecttgccaa cgggtattgt 20 <210> 1811 <211> 21 <212> DNA <213> Homo sapiens <400> 1511 gccaaaccat tcattgtcac ¢ 21 <210> 18912 <211> 20 <212> DNA <213> Homo sapiens <400> 1912 tgtggctttt ggaatgtgga 20 <210> 1913

<211> 20 <212> DNA <213> Homo sapiens <400> 1913 ggagggtgaa tcccttgcte 20 <210> 1914 <211l> 21 <212> DNA <213> Homo sapiens <400> 1914 aggctgtctg gtcagcactg t 21 <210> 1915 <211> 20 <212> DNA <213> Homo sapiens <400> 1915 ccacagaaga ggcagctggt 20 <210> 1916 <211> 23 <212> DNA <213> Homo sapiens <400> 18516 gagagcagcg tatcctgaag cta 23 <210> 1917 <211> 20 <212> DNA <213> Homo sapiens <400> 18917 ggggatccat gagtctcagc 20 <210> 1918 <211> 20 <212> DNA <213> Homo sapiens <400> 1918 gtgaggtctg gggtgcttgt oe 20 <210> 1919 <211> 20 <212> DNA <213> Homo sapiens <400> 1919 cttgcggaac tccagctcat 20

<210> 1920 <211> 20 <212> DNA <213> Homo sapiens <400> 1920 attggaatgg ccctctecte 20 <210> 1921 <211> 20 <212> DNA <213> Homo sapiens <400> 1921 tcgcagcatt ggaaacactt 20 <210> 1922 <21l> 20 <212> DNA <213> Homo sapiens <400> 1922 cacgagggtc tccgcattta 20 <210> 1923 <211> 21 <212> DNA <213> Homo sapiens <400> 1923 gtgctcacag aagccaggaa c 21 <210> 1924 <211> 20 <212> DNA <213> Homo sapiens <400> 1924 Cgaagtgcgg gaagtaggtc 20 <210> 1925 <211l> 18 <212> DNA <213> Homo sapiens <400> 1925 ggtggctggt gtggctaa 18 <210> 1926 <211> 20 <212> DNA <213> Homo sapiens <400> 1926 agaaggtggt ggctggtgtg 20 <210> 1927 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 1927 gggcttgagg ttgtccatgt 20 <210> 1928 <211> 20 <212> DNA <213> Homo sapiens <400> 1928 gtgccttgac tttggggttg 20 <210> 1929 <211> 20 <212> DNA <213> Homo sapiens <400> 1929 tgggctctga cttgtgagga 20 <210> 1930 <211> 20 <212> DNA <213> Homo sapiens <400> 1930 cgttgtctca ggcatctgga 20 <210> 1931 <211> 20 <212> DNA

© <213> Homo sapiens <400> 1931 tggggagtca tttccagcat 20 <210> 1932 <211> 18 <212> DNA : <213> Homo sapiens } <400> 1932 ggccccaagg aagagcag 18 <210> 1933 <211l> 19 «212> DNA <213> Homo sapiens

<400> 1933 ggcacagctt ggacaacca 19 <210> 1934

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1934 atatggtcecg gggtgcatta 20 <210> 1935

<211> 20

<212> DNA

<213> Homo sapiens .

<400> 1935 cctgttgaat gcctccaggt 20 <210> 1936’

<211l> 21

<212> DNA

<213> Homo sapiens

<400> 1936 tgctgetgtg tttcectcte © 21 <210> 1937

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1937 tacacgtggg ttgcgtcagt 20 <210> 1938

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1938 cacttctgec ctcccaacac . 20 <210> 1939

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 1939 gcttgcaggt ccaagcaaat 20 <210> 1940 <211> 20

<212> DNA <213> Homo sapiens <400> 1940 gcccctgatt caacaagcat 20 <210> 1941 <211> 26 <212> DNA <213> Homo sapiens <400> 1941 tcatacaatc actgaagaca cacaca 26 <210> 1942 © <211l> 21 <212> DNA <213> Homo sapiens <400> 1942 ggcataatcc aaagggttge t 21 <210> 1943 <211> 21 <212> DNA <213> Homo sapiens <400> 1943 cagctggaaa agggtgtagce a 21 <210> 1944 <211> 20 <212> DNA <213> Homo sapiens <400> 1944 aggtacaggg ccagcaggat 20 <210> 1945 <211> 20 <212> DNA <213> Homo sapiens <400> 1945 gatttggatc gggattggaa 20 <210> 1946 <211> 20 <212> DNA <213> Homo sapiens <400> 1946 gtgccattca ccttgcacac 20

So

<210> 1947

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1947 aatgttgctc agccccacag 20 <210> 1948

<211l> 23

<212> DNa

<213> Homo sapiens

<400> 1948 tgtggaattt ggaaacatcc att 23 <210> 1849

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 19459 ccatgcctgt atcagggtca 20 <210> 1950

«211s 21

<212> DNA

<213> Homo sapiens

<400> 1950 gggtgacagt ggagcttect t 21 <210> 1951

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1951 cccacattca cagggctctt 20 <210> 1952

<211> 22

<212> DNA

<213> Homo sapiens

<400> 1952 tcaactgctg cttcaccaga ct : 22 <210> 1953

<211> 20

<212> DNA <213> Homo sapiens <400> 1953 ttcaaagctg ttggcectcet 20

<210> 1954 <211> 21 <212> DNA <213> Homo sapiens <400> 1954 tgacgccect attctctect c 21 <210> 1955 <211> 20 <212> DNA <213> Homo sapiens <400> 1955 agggcacttc cagctcttcc 20 <210> 1956 <21l> 20 <212> DNA <213> Homo sapiens <400> 1956 ggacttcttc acggccacag 20 <210> 19857 <211> 20 <212> DNA <213> Homo sapiens <400> 1957 tgcgttcagc agactggttt 20 <210> 1958 <211l> 20 <212> DNA <213> Homo sapiens <400> 1858 agaatggccg ccagtgttac 20 <210> 1959 <21l> 20 <212> DNA <213> Homo sapiens <400> 1958 ctggcattgec aaaactggaa 20 <210> 18960 <21l1l> 22 <212> DNA <213> Bomo sapiens

<400> 1960 tcaccaccaa tcacaaggaa ga 22 <210> 1961

<21l> 20

<212> DNA

<213> Homo sapiens

<400> 1961 gcaccaggca tgaaatctcce 20 <210> 1962

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 1962 gggaggccat acggtttagg 20 <210> 1963

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1963 gatctcctgg ggttcctgcet 20 <210> 1964

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1964 cagagatgtg gcggtctcaa 20 <210> 1965

<211> 20

<212> DNA

<213> Homo sapiens

<400> 1965 ccctgaaggt gaaccgctta 20 <210> 1966

<211> 22

<212> DNA

<213> Homo sapiens

<400> 1966 aacggaaagt ccgaatccta ca 22 <210> 1967 <211l> 24 <212> DNA

<213> Homo sapiens <400> 1867 tcatgagatt ctgctgtacg tgtg 24 <210> 1968 <211l> 20 <212> DNA <213> Homo sapiens } <400> 1968 catctttctc ggggttctecg 20 <210> 1969 <211> 29 <212> DNA <213> Homo sapiens <400> 196% k cagagcatgt atgagaacta cattgtacc 29 <210> 1970 <211> 20 <212> DNA <213> Homo sapiens <400> 1970 : ctctcagaag ccccactgga 20 <210> 1971 <211> 20 <212> DNA <213> Homo sapiens <400> 1971 gcacctcagc tgttcccagt 20 <210> 19872 <211> 20 <212> DNA <213> Homo sapiens <400> 1972 gtcgcccagt cctaccagag 20 <210> 1973 <211l> 29 . <212> DNA <213> Homo sapiens <400> 1973 taagatatct aaggcattct gcaaacatc 29 <210> 1974

<211l> 21 <212> DNA <213> Homo sapiens <400> 1974 agacagggat tccttggcaa c 21 <210> 1975 <211> 21 <212> DNA . <213> Homo sapiens <400> 1975 tccgtgttca aggcctcata a 21 <210> 1976 <211l> 22 <212> DNA <213> Homo sapiens <400> 1976 ctgcacatgg caggtgtatc tc 22 <210> 1977 <211> 28 <212> DNA <213> Homo sapiens <400> 1877 tttagcttaa cttgettagg gaattttg 28 <210> 1978 <211> 20 <212> DNA <213> Homo sapiens <400> 1978 aggccgttga gctggtacac 20 <210> 1979 <21ll> 22 <212> DNA <213> Homo sapiens <400> 1979 gcaaaatctg caaatcccag aa : 22 <210> 1980 <211> 21 <212> DNA <213> Homo sapiens <400> 1980 ggccgactga agggtaaaat g 21

<210s 1981 <211s> 20 <212> DNA <213> Homo sapiens <400> 1981 acttgggcac tgcctcattc 20 <210> 1982 «211s 21 <212> DNA <213> Homo sapiens <400> 1982 ggcatgcaca cacacaacag t 21 <210> 1983 <211> 22 <212> DNA <213> Homo sapiens <400> 1983 caagccccaa gttgtctcat tt 22 <210> 1984 <211> 22 <212> DNA <213> Homo sapiens <400> 1584 tctttgtctt tcttggccga ct 22 <210> 1985 <211l> 20 <212> DNA <213> Homo sapiens <400> 1985 cagctcaggg atgaccttgce 20 <210> 18586 <211> 18 <212> DNA <213> Homo sapiens <400> 1986 gtccaccgge ccctacat 18. <210> 1987 <211> 20 <212> DNA <213> Homo sapiens <400> 1987 :

aaaggggcaa ttttggttgg 20 <210> 1988 <211> 19 <212> DNA <213> Homo sapiens <400> 1988 accatgcagg tggaagcag 19 «210> 1989 <211> 20 <212> DNA <213> Homo sapiens <400> 1989 } ggtgtggagg tgggagtcag 20 <210> 1990 <211> 21 <212> DNA <213> Homo sapiens <400> 1990 tgtgctgtga atggcacaac t 21 <210> 1981 <211> 23 <212> DNA <213> Homo sapiens <400> 1991 ttgctgggtt tatcattctg agg 23 <210> 1992 <211> 27 <212> DNA <213> Homo sapiens <400> 1992 atttatttca cgtgaggtag aggacag 27 <210> 1993 <211> 23 <212> DNA <213> Homo sapiens <400> 1993 } caggataatc agaccaccac agg 23 <210> 1994 <211> 20 <212> DNA <213> Homo sapiens

<400> 1994 . ccccgegaac tagatttgaa 20 <210> 1995 <211> 20 <212> DNA <213> Homo sapiens <400> 1995 tctctgcagg aggtgaagca 20 <210> 1996 <211l> 20 <212> DNA <213> Homo sapiens <400> 1996 gccagattgg catgaaggac 20 <210> 1997 <211> 20 <212> DNA <213> Homo sapiens <400> 1997 aaggacagca gtgcctccag 20 <210> 1998 <211> 21 <212> DNA <213> Homo sapiens <400> 1998 ttgggtagtt gctccagttg c¢ 21 <210> 1999 <211> 25 <212> DNA <213> Homo sapiens <400> 1999 tgtcagctga acattgtcca taaac . 25 <210> 2000 : <21l1l> 24 <212> DNA <213> Homo sapiens <400> 2000 cagtattttg gccaacttct gctt 24 <210> 2001 <211> 22

<212> DNA <213> Homo sapiens <400> 2001 taaaggtacg cacttgggct tc 22 <210> 2002 <211> 21 <212> DNA <213> Homo sapiens <400> 2002 aaaccaccac gacgatgaaa c 21 <210> 2003 <211> 21 <212> DNA <213> Homo sapiens <400> 2003 agctcatatt cctgggcatc c 21 <210> 2004 <211l> 20 <212> DNA <213> Homo sapiens <400> 2004 gcctgagectg aagggattga 20 <210> 2005 <211> 27 <212> DNA <213> Homo sapiens <400> 2005 acaacattct gctcaacatc atttaca 27 <210> 2006 <21l> 20 <212> DNA <213> Homo sapiens <400> 2006 gggcagagtc agccactgat 20 <210> 2007 . <211> 18 <212> DNA <213> Homo sapiens <400> 2007 catgacgecc caaccatt 18

<210> 2008 <211> 19 <212> DNA <213> Homo sapiens <400> 2008 ctggacctgg gacctgcat 19 <210> 20089 <211l> 20 <212> DNA <213> Homo sapiens <400> 2008 gcgaggggat gggtttattg 20 <210> 2010 <211> 20 <212> DNA ’ <213> Homo sapiens <400> 2010 ggagggagag ttgcctggtc 20 <210> 2011 <211l> 25 <212> DNA <213> Homo sapiens <400> 2011 agtgattgect ttggtgctta acttg 25 <210> 2012 <211> 21 <212> DNA <213> Homo sapiens <400> 2012 accctgatgce tggtcatggt a 21 <210> 2013 <211l> 20 <212> DNA <213> Homo sapiens <400> 2013 cggggttgga ggcatattte 20 <210> 2014 <211> 20 <212> DNA <213> Homo sapiens <400> 2014 agaaggggaa ggaggggtct 20

<210> 2015 <211> 21 <212> DNA <213> Homo sapiens <400> 2015 cttctcaaac acctgcccac a 21 <210> 2016 <211> 19 <212> DNA <213> Homo sapiens <400> 2016 caaaggccce tcagaacga 18 <210> 2017 <211> 20 <212> DNA <213> Homo sapiens <400> 2017 gaagctctgg ccctccaact 20 <210> 2018 <211l> 22 <212> DNA <213> Homo sapiens <400> 2018 cattgagtag atgccccgga ta 22 <210> 20189 <211> 18 <212> DNA <213> Homo sapiens <400> 2019 ctggcagggc ttccttea 18 <210> 2020 <211> 20 <212> DNA <213> Homo sapiens <400> 2020 ctgccectga tgcaaaagtt : 20 <210> 2021 <211l> 22 <212> DNA <213> Homo sapiens

<400> 2021 ttcaagggca cagctatgtt tg 22 <210> 2022 <211> 20 <212> DNA <213> Homo sapiens <400> 2022 tgacccagct gaagacagga : 20 <210> 2023 <211> 20 <212> DNA <213> Homo sapiens ’ <400> 2023 . tcccacaaca agccacagag 20 <210> 2024 <211> 189 <212> DNA <213> Homo sapiens <400> 2024 cagcacgtgc acagcagac 19 <210> 2025 <211> 25 <212> DNA <213> Homo sapiens <400> 2025 tgaatttctg actgcagatg ttttg 25 <210> 2026 <211> 21 <212> DNA <213> Homo sapiens <400> 2026 agctccagca gccttecttgt c 21 <210> 2027 <211> 19 <212> DNA <213> Homo sapiens } } <400> 2027 gagtgggttg gggaactgg 19 <210> 2028 <211> 22 <212> DNA

<213> Homo sapiens <400> 2028 cttactcctt ggaggccatg tg 22 <210> 2029 <21l> 21 <212> DNA <213> Homo sapiens <400> 2029 caacatggaa gatgggcaga a 21 <210> 2030 <211l> 21 <212> DNA <213> Homo sapiens <400> 2030 ggtcgtcatc gttgttgtce t 21 <210> 2031 <211> 20 <212> DNA <213> Homo sapiens <400> 2031 cgcttttgect gggactttca 20 <210> 2032 <211> 20 <212> DNA <213> Homo sapiens <400> 2032 cccttgcaca aaacccactce 20 <210> 2033 <211> 22 <212> DNA <213> Homo sapiens <400> 2033 tttggagaaa agtgggtcca ag 22 <210> 2034 <211> 20 <212> DNA <213> Homo sapiens <400> 2034 catccttggt gggtcctage 20 <210> 2035

<211> 21 <212> DNA <213> Homo sapiens <400> 2035 ggcagtgcct ttgatcagtg t 21 <210> 2036 <211> 20 <212> DNA <213> Homo sapiens <400> 2036 ctgccacgece catctttatc 20 <210> 2037 <211> 28 <212> DNA <213> Homo sapiens <400> 2037 acagtatcta tcctaggcaa atgagagc 28 <210> 2038 <211> 20 <212> DNA <213> Homo sapiens <400> 2038 tcttceccte gcacgtcectta 20 <210> 2039 <211> 20 <212> DNA <213> Homo sapiens <400> 2039 tcctectgta ggctggcaga 20 <210> 2040 <211> 21 <212> DNA <213> Homo sapiens <400> 2040 tcectectcteca acctgccact © 21 <210> 2041 <211l> 19 <212> DNA <213> Homo sapiens 1 <400> 2041 catgtccecect tcccaagga 19

<210> 2042 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 2042 agctcccage tgacctctga 20 <210> 2043 <211> 21 <212> DNA <213> Homo sapiens <400> 2043 gaatgtgctc caaggcgatt a 21 <210> 2044 <211l> 20 <212> DNA <213> Homo sapiens : <400> 2044 cecctecctte tcagccaaag 20 <210> 2045 <211> 21 <212> DNA <213> Homo sapiens <400> 2045 cagagggatg aagctggaca a 21 <210> 2046 <211> 22 <212> DNA <213> Homo sapiens <400> 2046 tttcaaaaca ggcagaggga at 22 <210> 2047 <211> 22 <212> DNA <213> Homo sapiens <400> 2047 tceccactgaa agtcacagte ca 22 <210> 2048 <211> 20 <212> DNA <213> Homo sapiens <400> 2048

T/US2003/012946 tgcagcaagt gtgcaacaga 20 <210> 2049 <211> 20 <212> DNA <213> Homo sapiens <400> 2049 tegttttegt teccctettg 20 <210> 2050 <211> 20 <212> DNA <213> Homo sapiens <400> 2050 gagctctgge tgatggaacce 20 <210> 2051 <211ls> 20 <212> DNA <213> Homo sapiens <400> 2051 ggaaggaggc aatgtgggta 20 <210> 2052 <211> 20 <212> DNA <213> Homo sapiens <400> 2052 gctttgecte tcggaggagt 20 <210> 2053 <21l1l> 22 <212> DNA <213> Homo sapiens <400> 2053 ggaagacaga ggaaagggaa gc 22 <210> 2054 <211s> 20 <212> DNA ’ <213> Homo sapiens <400> 2054 ggcagaaatt cagggaccaa 20 <210> 2055 <211> 29 <212> DNA <213> Homo sapiens

<400> 2085 atgtagaatt ttcttactcc atgatgagg 29 <210> 2056 <211> 25 <212> DNA <213> Homo sapiens <400> 2056 tgttttcatt ccactactce ctcaa 25 <210> 2057 <211> 21 <212> DNA <213> Homo sapiens <400> 2057 tggctgcact aaacatccac a 21 <210> 2058 <211> 19 <212> DNA <213> Homo sapiens <400> 2058 gccecgtgggt gtaatccat 18 <210> 2059 <211> 20 <212> DNA <213> Homo sapiens <400> 2059 accaggagac agcgctacca 20 <210> 2060 <211> 24 <212> DNA <213> Homo sapiens <400> 2060 tcccactaac atgaaatgaa tgga 24 <210> 2061 <211> 20 <212> DNA <213> Homo sapiens <400> 2061 agtttgggga ggeccatatcc 20 <210> 2062 <211l> 20 :

<212> DNA <213> Homo sapiens <400> 2062 cagatgctca cctgctegte 20 <210> 2063 <211> 21 <212> DNA <213> Homo sapiens . <400> 2063 tggggatcca ctttcttcaa a 21 <210> 2064 <211> 20 <212> DNA <213> Homo sapiens <400> 2064 ttctggctga ggggtcacat 20 <210> 2065 ’ <211> 20 <212> DNA <213> Homo sapiens <400> 2065S gtccttggag ccaagcagag 20 <210> 2066 <211> 20 <212> DNA <213> Homo sapiens <400> 2066 . accagtggaa ccagggtgag 20 <210> 2067 «211s 20 <212> DNA <213> Homo sapiens <400> 2067 aggagggagg ggcacagtag 20 <210> 2068 <211> 20 <212> DNA <213> Homo sapiens <400> 2068 gtgccatagc cggatgttct 20

<210> 20639 } <211> 20 <212> DNA <213> Homo sapiens <400> 2069 gactccttgg catcggacac 20 <210> 2070 <211> 27 <212> DNA <213> Homo sapiens <400> 2070 tcatgctttc ctcattatta ttgatce 27 <210> 2071 <211> 21 <212> DNA <213> Homo sapiens <400> 2071 ttgctgtttg ggtgcatact g 21 <210> 2072 <211> 28 <212> DNA <213> Homo sapiens <400> 2072 tttgaatgaa tattaggaat tgatgctg 28 <210> 2073 <211> 20 <212> DNA <213> Homo sapiens <400> 2073 : acaacggtga ccatctgcaa 20 <210> 2074 <211> 22° . <212> DNA <213> Homo sapiens <400> 2074 accagattca aaagggaaag ca 22 <210> 2075 <211l> 20 <212> DNA <213> Homo sapiens <400> 2075 ctcatgaaac gtccccgaat 20 628

<210> 2076 <211> 20 <212> DNA <213> Homo sapiens <400> 2076 aggccagggt ctctggaaga 20 <210> 2077 <211> 20 <212> DNA <213> Homo sapiens <400> 2077 acagcagcca aacaaaagca 20 <210> 2078 . <211> 20 <212> DNA <213> Homo sapiens <400> 2078 ctgaaagctc aggggtggaa 20 <210> 2079 <211> 20 <212> DNA <213> Homo sapiens <400> 2079 cagcagggtc cggtcatact 20 <210> 2080 <211> 32 «212> DNA <213> Homo sapiens <400> 2080 acaaaacaaa ttcacaaatt actctcaata ct 32 <210> 2081 <211> 26 <212> DNA <213> Homo sapiens <400> 2081 tctgtgaaaa tctttctgca aatgtc 26 <210> 2082 <211> 28 <212> DNA <213> Homo sapiens

<400> 2082 agtaaaacca gacaaacgaa taacacac . 28 <210> 2083 <211> 18 <212> DNA <213> Homo sapiens <400> 2083 ccgagcecga taaatggt : 18 <210> 2084 <211> 20 <212> DNA <213> Homo sapiens <400> 2084 tccecteceect gtagagacca 20 <210> 2085 <21l> 20 <212> DNA <213> Homo sapiens <400> 2085 cccgacctgg ggtatctett 20 <210> 2086 <211> 20 <212> DNA <213> Homo sapiens <400> 2086 cttgaaggga cgtgggacat 20 <210> 2087 <211> 20 <212> DNA <213> Homo sapiens <400> 2087 tttggtgcca tgactgccta 20 <210> 2088 <211> 23 <212> DNA <213> Homo sapiens <400> 2088 ttcgctectet gctgaagaag att 23 <210> 2089 <211> 22 <212> DNA . :

<213> Homo sapiens <400> 2089 aagagtgtgg cctgagtcct ct 22 <210> 2090 <211l> 20 <212> DNA <213> Homo sapiens <400> 2090 ttggggcttyg tggagaagag 20 <210> 2091 <211> 22 <212> DNA <213> Homo sapiens v <400> 2091 aagaccctca tteccacttt ca 22 <210> 2092 <211l> 20 <212> DNA <213> Homo sapiens <400> 2092 ccccacttct tgcattcagce 20 <210> 2083 <211> 20 <212> DNA <213> Homo sapiens <400> 2093 actccaagga cacggcagag 20 <210> 2094 <211> 20 <212> DNA <213> Homo sapiens <400> 2094 . cgccgtgaga aatcagtttg 20 <210> 2095 <211> 28 <212> DNA <213> Homo sapiens <400> 2095 accatcactt acaaatctgt acccaatc 28 <210> 2096

<211> 27

<212> DNA

<213> Homo sapiens

<400> 2096 tgagtaagtt cttgttcttt cegttcet 27 <210> 2097

<211> 20 :

<212> DNA

<213> Homo sapiens

<400> 2097 gatcccaget gecttttgaa 20 <210> 2098

<211> 28

<212> DNA

<213> Homo sapiens

<400> 2098 tgtgattata caaaatgaag tggacaaa 28 <210> 209%

<21l1l> 20

<212> DNA

<213> Homo sapiens

<400> 2099 ccctcteccaa caccttceacg 20 <210> 2100

<211> 20

<212> DNA

<213> Homo sapiens

<400> 2100 aggcctggte cttcactggt 20 <210> 2101

<211l> 22

<212> DNA

<213> Homo sapiens

<400> 2101 cagtctcaca ctggtecttg ct 22 <210> 2102 2

<211> 20

<212> DNA

<213> Homo sapiens <400> 2102 caatggcatt aaggggcaaa 20

RE 2

<210> 2103

<211> 20

<212> DNA

<213> Homo sapiens

<400> 2103 , tccacgatca tctegtectgg 20 <210> 2104

«211s 20

<212> DNA

<213> Homo sapiens

<400> 2104 ctgaggggtg cagagtgtga 20 <210> 2105

<211l> 25

<212> DNA

<213> Homo sapiens

<400> 2105 cagtctttgt cataggcaaa cttga 25 <210> 2106

<211l> 20

<212> DNA

<213> Homo sapiens

<400> 2106 tccagagcaa gccgaaactt 20 <210> 2107

<211> 24

<212> DNA

<213> Homo sapiens

<400> 2107 ttcacaatgg ctaacaagaa cagg 24 <210> 2108

<21l1l> 20

<212> DNA

<213> Homo sapiens

<400> 2108 ccaaagcagg ccagcaatac 20 <210> 2109

<211> 19

<212> DNA

<213> Homo sapiens <400> 2109 gacgaagggc taccgcact 19 <210> 2110 <21l1l> 21 <212> DNA <213> Homo sapiens <400> 2110 gctatttcga ggggatgtge t 21 <210> 2111 <211> 27 <212> DNA <213> Homo sapiens <400> 2111 aaattctttg cttgttagtg accttga 27 <210> 2112 <211l> 24 <212> DNA <213> Homo sapiens <400> 2112 tgcaaccttt taagcatagc cata 24 <210> 2113 <211> 20 <212> DNA <213> Homo sapiens <400> 2113 gaagccecctg ttctgctcaa 20 <210> 2114 <211> 20 «212> DNA <213> Homo sapiens <400> 2114 tttgttcect tggagggttg 20 <210> 2115 <211> 23 <212> DNA <213> Homo sapiens <400> 2115 ctaacccata agtgcctcat aca 23 <210> 2116 <21l1l> 20 <212> DNA <213> Homo sapiens ]

634

- Cael eg held . AE co .

<400> 2116 cagggcatgt gtagcaggaa 20 <210> 2117 <211> 22 <212> DNA <213> Homo sapiens <400> 2117 gcctgagagt agctcectec tt 22 <210> 2118 <21l1l> 21 <212> DNA <213> Homo sapiens <400> 2118 gacttgtacg ggttcgggtt t 21 <210> 2119 ’ <211ls> 20 <212> DNA <213> Homo sapiens <400> 2119 ggagctggga gctcgaaagt 20 <210> 2120 <211> 20 <212> DNA <213> Homo sapiens <400> 2120 gcgtgecaget catcttggta 20 <210> 2121 <211> 21 <212> DNA <213> Homo sapiens <400> 2121 ttttgccaaa tgggttcctt t 21 <210> 2122 <211> 19 <212> DNA <213> Homo sapiens <400> 2122 atcgaagtcg ccgacaatg 19 <210> 2123 <211> 20

~~ & CsA

<212> DNA

<213> Homo sapiens

<400> 2123 gatcaccagc aagggagtge 20 <210> 2124

<211> 35

<212> DNA

<213> Homo sapiens

<400> 2124 ttaataattc atacctagta ctaagcggta acaac 35 <210> 2125

<211> 24

<212> DNA

<213> Homo sapiens

<400> 212%

cctgctttct tetttcattg atec 24 <210> 2126

<211> 22

<212> DNA

<213> Homo sapiens

<400> 2126 cctgaggcca gtgatagggt aa 22 <210> 2127

<211> 20

<212> DNA

<213> Homo sapiens

<400> 2127 gcactgctge tcatttectyg 20 <210> 2128

<211> 20

<212> DNA

<213> Homo sapiens

<400> 2128 .

teccttecect ttgeccaatcet 20 <210> 2129

<211> 21

<212> DNA

<213> Homo sapiens

<400> 2129 accggagaaa agtgggttga g 21

<210> 2130 <21l> 21 . <212> DNA <213> Homo sapiens <400> 2130 aagctcaaga aggctgggag a 21 <210> 2131 <211l> 22 <212> DNA <213> Homo sapiens <400> 2131 cacccactgt tcttaccctt gc 22 <210> 2132 <211l> 21 <212> DNA <213> Homo sapiens <400> 2132 tcctgectaa ctgaccacct g 21 <210> 2133 <211> 23 <212> DNA <213> Homo sapiens <400> 2133 cagactccaa gtccaaagca aat 23 <210> 2134 <211> 25 <212> DNA <213> Homo sapiens <400> 2134 tgatttccaa atctcagttg acctc 25 <210> 2135 <21lls> 20 <212> DNA <213> Homo sapiens <400> 2135 gcttcctgga attcectget 20 <210> 2136 <211> 20 <212> DNA <213> Homo sapiens <400> 2136 tgaagggtcc cacgctgtat 20

«210> 2137 <211l> 21 <212> DNA <213> Homo sapiens <400> 2137 tgcatcagtc aaggtcatgg a 21 <210> 2138 <211> 219 <212> DNA <213> Homo sapiens <400> 2138 cgagggctcg tcatttggt 19 <210> 2139 <211> 20 <212> DNA . <213> Homo sapiens <400> 2139 ctgagagcga ccacctaccg 20 <210> 2140 <211l> 20 <212> DNA <213> Homo sapiens <400> 2140 gctgtgeccca aatgagcettt 20 <210> 2141 <211s 31 <212> DNA <213> Homo sapiens <400> 2141 gtatctcaat tcagaaagct ttgactactg t 31 <210> 2142 , <211> 21 <212> DNA <213> Homo sapiens <400> 2142 tttgatccece agtgtttget c 21 <210> 2143 <211> 20 <212> DNA <213> Homo sapiens 638

<400> 2143 attccaagtc agcgccaaag 20 <210> 2144 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 2144 atgccacttc attggcacct 20 <210> 2145 <211> 20 <212> DNA <213> Homo sapiens <400> 2145 tgctggaagg caaaccagat 20 <210> 2146 <21l> 29 <212> DNA <213> Homo sapiens <400> 2146 tcccagaaga gatgacggag gctaccttce 29 <210> 2147 <211> 20 <212> DNA <213> Homo sapiens <400> 2147 . cgctgtgtgt tctcccectcet 20 <210> 2148 <211> 21 «<212> DNA <213> Homo sapiens <400> 2148 tggaacagtt tcteccccaat g 21 <210> 2149 <21l> 24 <212> DNA <213> Homo sapiens <400> 2149 tcaattggac agaaatgaca agga 24 <210> 2150 <211> 21 <212> DNA

<213> Homo sapiens <400> 2150 tctggctcac tccaaatcag © 21 <210> 2151 <211> 20 <212> DNA <213> Homo sapiens <400> 2151 gcctgacttg gectgcectact 20 <210> 2152 <211l> 20 <212> DNA <213> Homo sapiens <400> 2152 tcacacagecc atcacacagg 20 <210> 2153 <211l> 24 <212> DNA <213> Homo sapiens <400> 2153 tgccaatgaa accaggtatc ccca 24 <210> 2154 <211> 33 <212> DNA <213> Homo sapiens <400> 2154 tgagtggctg gtgtcttttg gttagtgtaa cca 33 <210> 2155 <211> 20 <212> DNA ’ <213> Homo sapiens <400> 2155 ggccagcaca atgccccagg 20 <210> 2156 <211> 29 <212> DNA <213> Homo sapiens <400> 2156 tcaggcaaat tcacaaccca gtgagtctg 23 <210> 2157 -

<211> 25 <212> DRA <213> Homo sapiens <400> 2157 tgacagccac aatgctcace gttca 25 <210> 2158 <21l1l> 26 <212> DNA <213> Homo sapiens <400> 2158 cagctcccaa ccetttgtgt ctcage 26 <210> 2159 <211> 30 <212> DNA <213> Homo sapiens <400> 2159 ggatgatgac tgctgttacg aaacacacca 30 <210> 2160 <211l> 27 <212> DNA <213> Homo sapiens <400> 2160 tgcagagcag tgttcttcca gctgtga 27 <210> 2161 <211> 24 <212> DNA <213> Homo sapiens <400> 2161 ggcagaaaat cgtcttggtc gcca 24 <210> 2162 <211> 32 <212> DNA <213> Homo sapiens <400> 2162 ccaaaactac aagcctttga aggaccaaag ga 32 <210> 2163 <211l> 22 <212> DNA <213> Homo sapiens <400> 2163 gggtgcagag caaggaaggg gc 22 641 i

ESE SX CIS . ~

<210> 2164 <211> 30 <212> DNA <213> Homo sapiens <400> 2164 tcaggaaggt aaagcaaatc tctggaggca 30 <210> 2165 <211> 20 <212> DNA <213> Homo sapiens <400> 2165 cttccccage cagecacecg 20 <210> 2166 <211> 28 <212> DNA <213> Homo sapiens <400> 2166 ttgtgggggt agggtaggga agttcaca 28 <210> 2167 <211> 20 <212> DNA «<213> Homo sapiens <400> 2167 ccacggtcca cacagccccec 20 <210> 2168 <211> 20 <212> DNA <213> Homo sapiens <400> 2168 cttcececteg gggcaggcetg 20 <210> 2169 <211> 28 <212> DNA <213> Homo sapiens <400> 2169 tgggtgggct tatccaccat cttcttcea 28 <210> 2170 <211l> 22 <212> DNA <213> Homo sapiens <400> 2170 ccccteggaa aacaccctceg ca 22 <210> 2171 <211> 20 <212> DNA <213> Homo sapiens <400> 2171 gaactcggeg gggaggtggg 20 <210> 2172 <211> 20 <212> DNA <213> Homo sapiens <400> 2172 ggtgccgatg gtgtcggect 20 <210> 2173 <211> 27 <212> DNA <213> Homo sapiens <400> 2173 tgccctggec cacaagtatc actaagce 27 <210> 2174 <211> 27 <212> DNA <213> Homo sapiens <400> 2174 tgccctggct cacaagtacc attgaga 27 <210> 2175 <211> 21 <212> DNA <213> Homo sapiens <400> 2175 gccatgggcc ttgaccttgg g 21 <210> 2176 <211> 23 <212> DNA <213> Homo sapiens <400> 2176 cccatgatgg cagaggcaga gga 23 <210> 2177 <211> 20 <212> DNA <213> Homo sapiens

. . ee

<400> 2177 gcecggggcte aggtccaggt 20 . <210> 2178 <211> 20 <212> DNA <213> Homo sapiens <400> 2178 gcagggtgga gcactggggc 20 <210> 2179 <211> 26 <212> DNA <213> Homo sapiens <400> 2179 tggtgactgg accttccaga tcectgg 26 <210> 2180 <211> 23 <212> DNA <213> Homo sapiens <400> 2180 : gatgctgagt ggagtcgggg gct 23 <210> 2181 <211> 20 <212> DNA <213> Homo sapiens <400> 2181 ggccaggtgg gccaccatga 20 <210> 2182 <211> 35 <212> DNA <213> Homo sapiens <400> 2182 cagtcatatc ttcaaataga ggccgatttc cttgg 35 <210> 2183 : <211> 28 <212> DNA <213> Homo sapiens <400> 2183 ttccatcaga atgtcttggt cttcccca 28 <210> 2184 <211> 20

<212> DNA <213> Homo sapiens <400> 2184 ccgtecccte teccggagga 20 <210> 2185 <211> 20 <212> DNA <213> Homo sapiens <400> 2185 acttcgaaac cggcccgcec 20 <210> 2186 <211> 20 <212> DNA <213> Homo sapiens <400> 2186 caaccccagc cctgeectcec 20 <210> 2187 <211> 20 <212> DNA <213> Homo sapiens <400> 2187 cagtggggca gtggggtccg 20 <210> 2188 <211l> 20 <212> DNA <213> Homo sapiens <400> 2188 ggcgcccagg tgaagagcca 20 <210> 2189 <211> 26 <212> DNA <213> Homo sapiens <400> 2189 tgcaatcaaa aaccacctgc atccaa 26 <210> 2190 <211> 27 <212> DNA <213> Homo sapiens <400> 2180 tgcttttaag ttttggccaa ctgccga 27

<210> 2191 <211> 21 <212> DNA <213> Homo sapiens <400> 2181 tcccagtcag ggagcccacg gd 21 <210> 2192 <211> 20 . <212> DNA <213> Homo sapiens <400> 2182 ’ aggcccagga tggcggcaac 20 <210> 21893 <211l> 34 <212> DNA <213> Homo sapiens <400> 2193 tgataactge tcttgaagga ctcacaaaga tggce 34 <210> 2194 <211> 20 . <212> DNA <213> Homo sapiens <400> 2194 ccctetgget gttcccggca 20 <210> 2195 <211> 23 <212> DNA <213> Homo sapiens <400> 2195 ggtgaaggct tggaggagtg gcg 23 <210> 2196 <21ll> 27 <212> DNA <213> Homo sapiens <400> 2196 ’ cgtggagttt ctccagtcaa ggtccca 27 <210> 2187 <21ll> 20 <212> DNA <213> Homo sapiens <400> 2197 tceccaccatg getgtggece . 20

A © WO 2004/042346 eo. ..PCT/US2003/012946 <210> 2198 <211> 22 <212> DNA <213> Homo sapiens <400> 2198 tceccteeccac atcceccagte cc 22 <210> 2198 <211> 23 <212> DNA <213> Homo sapiens <400> 2199 ggacccaaac cagacacctg gcc 23 <210> 2200 : <21l> 30 <212> DNA <213> Homo sapiens <400> 2200 cctttgaaaa caagagtaaa cgcagacggc 30 <210> 2201 . <211> 30 <212> DNA <212> Homo sapiens <400> 2201 ctgattgecc agaactggta tttcecctttge 30 <210> 2202 <211> 24 <212> DNA <213> Homo sapiens <400> 2202 ggcccattcet tgccactcte cctg 24 <210> 2203 <211l> 19 <212> DNA <213> Homo sapiens <400> 2203 } agggggacgt ggcgggacc 19 <210> 2204 <211> 20 <212> DNA <213> Homo sapiens

<400> 2204 gggggagaac cccagggcect 20 <210> 2205 <211> 34 <212> DNA <213> Homo sapiens <400> 2205 gggggtgata aggaaagaaa tgaaaattca ctgc 34 <210> 2206 <211> 20 <212> DNA <213> Homo sapiens <400> 2206 tcatggggcc tcggcagtca 20 <210> 2207 <211> 31 <212> DNA <213> Homo sapiens <400> 2207 tgtgacatct ccatccagtg atatttgtge a 31 <210> 2208 <211> 20 <212> DNA <213> Homo sapiens <400> 2208 tgggttaggg gatgcggggg 20 <210> 2209 <211> 30 <212> DNA <213> Homo sapiens <400> 2209 tgaatgtgtc aggtgaccct gatgaaaaca 30 <210> 2210 <211l> 289 <212> DNA <213> Homo sapiens <400> 2210 gcctcatctt caacttttgt geteccett 29 <210> 2211 <21ll> 26 <212> DNA

<213> Homo sapiens <400> 2211 tggttggctt cttggccacc tttttg 26 <210> 2212 <211l> 20 <212> DNA <213> Homo sapiens <400> 2212 aatgcagctg gggccagggg : 20 <210> 2213 <211> 23 <212> DNA <213> Homo sapiens <400> 2213 cggactcgtc tgggttcttg gcc 23 <210> 2214 <211> 21 <212> DNA <213> Homo sapiens <400> 2214 tggtcatggc ggtggtggtec a 21 <210> 2215 <211> 35 <212> DNA <213> Homo sapiens <400> 2215 tggttattcg ctggttcgtt ctaagatgag tatcg 35 <210> 2216 <211> 28 <212> DNA <213> Homo sapiens <400> 2216 gttttgaggg attcttcggce caactctg 28 <210> 2217 <211> 26 oo <212> DNA <213> Homo sapiens <400> 2217 gccatccaca tctcccgett atcecte 26 <210> 2218

<211> 20 <212> DNA <213> Homo sapiens <400> 2218 cccggeeccag ggtectgatce 20 <210> 2219 <211> 21 . <212> DNA <213> Homo sapiens <400> 2218 . ggtgcttctc ccececggettg g 21 <210> 2220 <211> 23 <212> DNA <213> Homo sapiens <400> 2220 . cggactcgte tgggttcttg gece 23 <210> 2221 <21l1l> 25 <212> DNA <213> Homo sapiens <400> 2221 tgctgeggeca tagaatcaag gagca 25 <210> 2222 <211> 30 <212> DNA <213> Homo sapiens <400> 2222 tggtcaggga gatatctctc cacacttgca 30 <210> 2223 <211> 29 <212> DNA <213> Homo sapiens <400> 2223 cccaatctaa aggagcttct gccaaagga 29 <210> 2224 ’ <211> 21 <212> DNA <213> Homo sapiens <400> 2224 ccatccecctg caggcetggt c 21

<210> 2228 <211> 33 <212> DNA <213> Homo sapiens <400> 2225 gaacagaaca ttcagtggcc aattttcata ccc 33 <210> 2226 oo <211> 20 : <212> DNA - <213> Homo sapiens <400> 2226 cgtccggaag gcattggcca 20 <210> 2227 <211> 22 <212> DNA <213> Homo sapiens <400> 2227 caacctccag gggcagggag ga 22 <210> 2228 <211> 26 <212> DNA <213> Homo sapiens <400> 2228 aacccagcta caacggatgc aaaggg 26 <210> 2229 <211> 221 <212> DNA <213> Homo sapiens <400> 2229 tggctacgct cccagcagcec © 21 <210> 2230 <211> 28 <212> DNA <213> HBomo sapiens <400> 2230 gaaaacttca gggtcagcta gctggage 28 <210> 2231 <211l> 32 <212> DNA <213> Homo sapiens

. <400> 2231

Cll ARTE ccttgctcca tcttgacaaa tcacttttct ge 32 <210> 2232 <211> 27 <212> DNA

<213> Homo sapiens

<400> 2232 gcattgcgaa gctcggagaa tagcagc 27 <210> 2233

<211> 20

<212> DNA

<213> Homo sapiens

<400> 2233 gttctggaga gccccgcggce 20 <210> 2234

<21ll> 23

<212> DNA

<213> Homo sapiens

<400> 2234 ccagggcctt tgcaaacaag cca 23 <210> 2235

<211> 28

<212> DNA

<213> Homo sapiens

<400> 2235 tttcaagcag gggtttectt ggctttet 28 <210> 2236

<211s> 20

<212> DNA

<213> Homo sapiens

<400> 2236 ggcctccecca tcccagectg 20 <210> 2237

<21l1l> 23

<212> DNA

<213> Homo sapiens

<400> 2237 tgacggccag gatgatgagc agg 23 <210> 2238

<21ll> 24

<212> DNA

<213> Homo sapiens

<400> 2238 tccagectgg gaagtacaca ggcg 24

<210> 2239

<211l> 33

<212> DNA

<213> Homo sapiens

<400> 2239 tcacaaagtc tcagtccagt ctcttgectt agc 33

<210> 2240

<211> 29

<212> DNA

<213> Homo sapiens

<400> 2240 tgtgtcatgt aatgcaacca accacagca 29

«210> 2241

<211> 29

<212> DNA

<213> Homo sapiens

<400> 2241 gcagttctca cgttgaggtc tgtggaaga 29

<210> 2242

<211> 21

<212> DNA

<213> Homo sapiens

<400> 2242 tggcgccaac accggtacgt t 21

<210> 2243

<211> 24

<212> DNA

<213> Homo sapiens

<400> 2243 tggcagccgt gtcattagtt gggg 24

<210> 2244

<211> 20

<212> DNA

<213> Homo sapiens

<400> 2244 )

tctggagggc caggtggggg 20 } <210> 2245

<211> 27

<212> DNA <213> Homo sapiens <400> 2245 gctcaactct ggagcctctg gtaggca 27 <210> 2246 <21l1l> 22 <212> DNA <213> Homo sapiens <400> 2246 ggtgccttaa gtgagggccg cc 22 <210> 2247 <211> 33 <212> DNA <213> Homo sapiens <400> 2247 ggaccttttg tacttggtac aagttctgca ccg 33 <210> 2248 <211l> 32 <212> DNA <213> Homo sapiens <400> 2248 tgcttttgtt tatggacaat gttcagctga ca 32 <210> 2249 <211> 28 <212> DNA <213> Homo sapiens <400> 2249 cctgtatgcect agcaggaatg ttgctggc 28 <210> 2250 <211> 19 <212> DNA <213> Homo sapiens <400> 2250 ctacgcatcc gtggccgceg 19 <210> 2251 . . <21l> 22 <212> DNA <213> Homo sapiens <400> 2251 tgggccactt tgttccagec ga 22

<210> 2252 <211l> 19 <212> DNA <213> Homo sapiens <400> 2252 cgeccgectee ttgectggcet 19 <210> 2253 <211> 25 <212> DNA <213> Homo sapiens <400> 2253 gcacaacttg gtaaggcacc aggttacga 29 <210> 2254 <211> 20 <212> DNA <213> Homo sapiens <400> 2254 accccctcag cctecggecag 20 <210> 2255 <211l> 20 <212> DNA <213> Homo sapiens <400> 2255 ctgggccage ttgcacgcct 20 <210> 2256 <211> 24 <212> DNA <213> Homo sapiens <400> 2256 tctgcaggca accagccagt catg 24 <210> 2257 <211> 20 <212> DNA <213> Homo sapiens <400> 2257 agcagcgtgg cggcgaaaga 20 <210> 2258 <211> 24 <212> DNA <213> Homo sapiens <400> 2258 tggggcattt tcctttgttt ggca 24

<210> 2258 <211> 34 <212> DNA <213> Homo sapiens <400> 2259 ccacttccta aagcagctac atgaaacagc ttca 34 <210> 2260

<211l> 21

: <212> DNA

<213> Homo sapiens

<400> 2260 tccgtgtcca ccatecggget g 21 <210> 2261

<211> 20

<212> DNA

<213> Homo sapiens

<400> 2261 tgeggegage tatgggggtg 20 <210> 2262

<211> 34

<212> DNA

<213> Homo sapiens

<400> 2262 gcagggtttg aagcaatacc caggtataaa cact 34 <210> 2263

<211> 31

<212> DNA

<213> Homo sapiens

<400> 2263 gagatacaaa gtaccagaag cgggacttgg c 31 . <210> 2264

<211> 20

<212> DNA

<213> Homo sapiens .

<400> 2264 acagctgaaa cccgcecggggce 20 <210> 2265 <21l> 26

<212> DNA

<213> Homo sapiens

<400> 2265 tcatggctga cttcccaaag acagcc 26 <210> 2266 <211> 30 <212> DNA <213> Homo sapiens <400> 2266 tccaacttaa tgaaaccgat atccttcgcg 30 <210> 2267 <21l> 24 <212> DNA <213> Homo sapiens <400> 2267 tgcactggac actggccctg actg 24 <210> 2268 <21ll> 22 <212> DNA <213> Homo sapiens <400> 2268 cccaaacagg tcatggtgcg ca 22 <210> 2269 <21ll> 24 <212> DNA <213> Homo sapiens <400> 2269 tggccctgaa actcctcact ccca 24 <210> 2270 <211l> 25 <212> DNA <213> Homo sapiens <400> 2270 gagaccaatg tgcctgaagg tgcca 25 <210> 2271 <21l1l> 20 <212> DNA <213> Homo sapiens . <400> 2271 gggtgaggge ctgatggggg 20 <210> 2272 <211> 20 <212> DNA :

<213> Homo sapiens <400> 2272 cagccactgg cteccctgegg 20 <210> 2273 <211> 34

<212> DNA

<213> Homo sapiens

<400> 2273 aagtccattc ctgattcaga acaccctgtce taga 34 <210> 2274

<211l> 23

<212> DNA

<213> Homo sapiens

<400> 2274 tgectttgatg acacccaccg caa 23 <210> 2275

<211> 20

<212> DNA

<213> Homo sapiens

<400> 2275 ccegetetge tggeggtcct 20 <210> 2276

<211> 24

<212> DNA

<213> Homo sapiens

<400> 2276 tccaccacce tgttgetgta gecca 24 <210> 2277

<211> 21

<212> DNA

<213> Homo sapiens

<400> 2277 cccccagggg agaagcetggg a 21 <210> 2278

<211> 21

«212> DNA

<213> Homo sapiens

<400> 2278 ggggtctcca ccctggagec a 21 <210> 2279

658 i

<211l> 24 <212> DNA <213> Homo sapiens <400> 2279 tggcatggga tgcagatgat ttgg 24 <210> 2280 <211> 20 <212> DNA <213> Homo sapiens <400> 2280 gagggtggct gggggccaac 20 <210> 2281 <211> 25 <212> DNA <213> Homo sapiens <400> 2281 tgggacgctt ttgatggcta agcca 25 <210> 2282 <211> 20 <212> DNA <213> Homo sapiens <400> 2282 tgcccecgtct ggggtctgga 20 <210> 2283 <211> 24 <212> DNA <213> Homo sapiens <400> 2283 acggcactga gctgatggga ctcc 24 <210> 2284 <211> 31 <212> DNA <213> Homo sapiens <400> 2284 tcctggaagt taactgcacc atcagtgttg a 31 <210> 2285 <211> 30 <212> DNA <213> Homo sapiens <400> 2285 tcaatttcat gatttcatct cgctcaaggc 30

<210> 2286 <211> 23 <212> DNA <213> Homo sapiens ’ <400> 2286 tggcggtcac gaggaccatc ttc 23 <210> 2287 «211s 26 <212> DNA <213> Homo sapiens <400> 2287 ggacagtgga gcagccaaca cacaaa 26 <210> 2288 <211> 30 <212> DNA <213> Homo sapiens <400> 2288 caagtaagac ccaaggtaga tcccaagggc 30 <210> 2289 <211> 33 <212> DNA <213> Homo sapiens <400> 2289 aactcaagtg gatgggaagt aaagccctat gtg 33 <210> 2280 <211> 21 <212> DNA <213> Homo sapiens <400> 2290 cccacctggg gaactgctgg © 21 <210> 2291 <211> 22 <212> DNA <213> Homo sapiens <400> 2291 cgccagggtt ttcccagtca cg oo .22 <210> 2292 <21l1l> 28 <212> DNA <213> Homo sapiens <400> 2292 660 i &

Ccagcecctce cactttttca tcactgtt 28 <210> 2293 <211> 20 <212> DNA <213> Homo sapiens <400> 2293 tggaggcaga gtgacggact 20 <210> 2294 <21ll> 32 <212> DNA <213> Homo sapiens <400> 2294 aggagcaaaa agccaaaatt tggaaaagct tt 32 <210> 2285 <211> 30 <212> DNA <213> Homo sapiens <400> 2295 tcagggccaa ttggaaagtc attatgaaca 30 <210> 2296 <211l> 20 <212> DNA <213> Homo sapiens <400> 2296 cagcctgtgc tggcgagggc : 20 <210> 2297 <211> 30 <212> DNA <213> Homo sapiens <400> 2297 tgcgtttatc cgaaaattta ttctcgccct 30 <210> 2298 <211> 20 . <212> DNA <213> Homo sapiens <400> 2298 ccaatgcttg gctgggggceca 20 <210> 22989 <211> 20 <212> DNA <213> Homo sapiens

<400> 2299 aggcctcagc cccagggtceg 20 <210> 2300 <211> 22 <212> DNA <213> Homo sapiens <400> 2300 ggggtgagag gaaggcctgc ga 22 <210> 2301 <211> 23 <212> DNA <213> Homo sapiens <400> 2301 gctcaagttc ccagcacctg ggg 23 <210> 2302 <211> 29 <212> DNA <213> Homo sapiens <400> 2302 tgacgcattc taatcatgtg gcgatcttg 29 <210> 2303 <211l> 33 <212> DNA <213> Homo sapiens <400> 2303 cccecctaaaa tcccactgta aacaaacatt teg 33 <210> 2304 <211> 36 <212> DNA <213> Homo sapiens <400> 2304 agctgcaact ttacagggac ttgaaaagaa agaaaa 36 <210> 2305 <211> 32 <212> DNA ] <213> Homo sapiens <400> 2305 gggaaacttc ttgttgcaga tactgagctg ga 32 <210> 2306 <211l> 26 }

<212> DNA <213> Homo sapiens <400> 2306 ttccagaaac cagcacctcc ctgttg 26 <210> 2307 <211> 27 <212> DNA <213> Homo sapiens <400> 2307 cagagagcct aggcctggca gtcttca 27 <210> 2308 <211l> 30 <212> DNA <213> Homo sapiens <400> 2308 tggccatecet gatttettga tcttttcaca 30 <210> 2309 <211l> 25 <212> DNA <213> Homo sapiens <400> 2309 ¢gggccagcc agttaaaatc gtcaa 25 1 <210> 2310 <211> 20 <212> DNA <213> Homo sapiens <400> 2310 ctccggette tectecgegg 20 <210> 2311 <211l> 26 <212> DNA <213> Homo sapiens <400> 2311 tgaacaacct gactgacacc cccagg 26 <210> 2312 <211> 36 <212> DNA <213> Homo sapiens <400> 2312 tgcgaaactt gtatctgttt taaagaaggc acttga 36

<210> 2313 <211> 23 <212> DNA <213> Homo sapiens <400> 2313 tgagcaccga cagctccagc tga 23 <210> 2314 <211> 21 <212> DNA <213> Homo sapiens <400> 2314 ggggtctggg aatggcaggc a 21 <210> 2315 ) <211> 20 <212> DNA <213> Homo sapiens <400> 2315 gcgcgcagga cgacggaaac 20 <210> 2316 <211> 19 <212> DNA <213> Homo sapiens <400> 2316 tcgtgegtge ctaccccecg 19 <210> 2317 <211l> 24 <212> DNA <213> Homo sapiens <400> 2317 gaggaaaagc caccctgact ctgce 24 <210> 2318 <211> 27 <212> DNA <213> Homo sapiens <400> 2318 : tgcaaaaacc agaggaaggg tgtgctc 27 <210> 2319 <211> 21 <212> DNA <213> Homo sapiens <400> 2319 tggcaccatg atcgtggcac g 21 664 W :

<210> 2320 <211> 28 <212> DNA <213> Homo sapiens <400> 2320 gccgtgagtt tttgctcectta ctcccagg 28 <210> 2321 © <211l> 24 <212> DNA <213> Homo sapiens <400> 2321 gcccaatcct tgcaaggtaa cccg 24 <210> 2322 <211> 28 <212> DNA <213> Homo sapiens <400> 2322 tgtgtatttg ccttcagcca catccaga 28 <210> 2323 <21l> 34 <212> DNA <213> Homo sapiens <400> 2323 catgcttaat ttgttgttaa cgtagggcag ctca 34 <210> 2324 <211l> 27 <212> DNA <213> Homo sapiens <400> 2324 ccaactctca ctgggaccag agagcca 27 <210> 2325 <211> 25 <212> DNA <213> Homo sapiens <400> 2325 ccagatggag aaggtagcct gggcc 25 <210> 2326 <211l> 32 <212> DNA <213> Homo sapiens

<400> 2326 tgaggcaaat acccacaaaa acaaacacaa aa 32 <210> 2327 <211> 29 <212> DNA <213>" Homo sapiens <400> 2327 tttgatctcc ttecttggaag cctcatcca 29 <210> 2328 <211> 24 : <212> DNA <213> Homo sapiens <400> 2328 cctgcagcecca gcactggtac agca 24 <210> 2329 <211> 35 <212> DNA <213> Homo sapiens <400> 2329 tttgcttget tgtactcacg tttttgtagg acatt 35 <210> 2330 <211> 34 <212> DNA <213> Homo sapiens <400> 2330 tcagatttca catgtatgge tctgtectac tgcet 34 <210> 2331 <211l> 27 <212> DNA <213> Homo sapiens <400> 2331 aacgtaatca tacctctagt catagca 27 <210> 2332 <21l1> 26 : <212> DNA <213> Homo sapiens <400> 2332 ggcatctgect gcaggaacct tctgtg 26 <210> 2333 <211> 25 <212> DNA

<213> Homo sapiens <400> 2333 gcaacccagg ggaagcacag aagtg 25 <210> 2334 <211> 31 <212> DNA <213> Homo sapiens <400> 2334 tcatgtctgt gaagggaact ggaacaactg a 31 <210> 2335 <211l> 20 <212> DNA <213> Homo sapiens <400> 2335 cgcggtgtga gggaaggggg 20 <210> 2336 <21lls> 20 <212> DNA <213> Homo sapiens <400> 2336 tgggcacatc gtgaggggcc 20 <210> 2337 <211> 33 <212> DNA <213> Homo sapiens <400> 2337 acaccatagt cctttgagat ctgatgggtc aaa 33 <210> 2338 <211> 25 <212> DNA <213> Homo sapiens <400> 2338 tggcgagctc aggattcttc atcca 25 <210> 2339 <211> 25 ] <212> DNA <213> Homo sapiens <400> 2339 tgggcttgcg tttttctcecca actec 25 <210> 2340 :

<211> 32 <212> DNA <213> Homo sapiens <400> 2340 tccgttectc aagattctat tctcaccectt cc 32 <210> 2341 <211> 29 <212> DNA <213> Homo sapiens <400> 2341 ttccagagtc caccaagagg tcctgaatc 29 <210> 2342 <211> 20 <212> DNA <213> Homo sapiens <400> 2342 gcgagcacgg ctgtggcetceca 20 <210> 2343 <21l1l> 27 <212> DNA <213> Homo sapiens <400> 2343 cccectectec tcaacatctt gtccage 27 <210> 2344 <21l> 21 <212> DNA <213> Homo sapiens <400> 2344 tgccgggect tetectcaag g 21 <210> 2345 <211> 23 <212> DNA <213> Homo sapiens <400> 2345 caggtggcct ggaggggaga aca 23 <210> 2346 <211> 30 <212> DNA <213> Homo sapiens <400> 2346 cggtcttgca caaatgacgt acatttcaca 30

<210> 2347 <211> 20 <212> DNA <213> Homo sapiens <400> 2347 agccctgeee tgeecctect 20 <210> 2348 <211> 23 : <212> DNA <213> Homo sapiens <400> 2348 ‘ ttcccagget gectectcecte acc 23 <210> 2349 <211> 31 <212> DNa . <213> Homo sapiens <400> 2349 tccatcacte tgagtatggt gtttgectgte c 31 <210> 2350 <211> 33 <212> DNA <213> Homo sapiens <400> 2350 tccacactct cttetttgte ttgggtttet tee 33 <210> 2351 <211> 24 <212> DNA <213> Homo sapiens <400> 2351 ccaccaggcce cagctagcat ctgg 24 «210> 2352 <211> 21 <212> DNA <213> Homo sapiens <400> 2352 cagggactgg cctgtceceg a 21 <210> 2353 <211> 26 <212> DNA <213> Homo sapiens <400> 2353 ctgtaagccc ccttttggat gccaaa 26 <210> 2354 <211> 33 <212> DNA <213> Homo sapiens <400> 2354 catcctaagg caatctgtat tgaaccaggt tca 33 <210> 2355 <211> 35 <212> DNA <213> Homo sapiens <400> 2355 tgagcagaat cccatcgtaa cagttctttg ttaca 35 <210> 2356 <211> 31 <212> DNA <213> Homo sapiens <400> 2356 ccaagtccca agggtcagta tattggagga a 31 <210> 2357 <211> 20 <212> DNA <213> Homo sapiens <400> 2357 cgcaacaaca agcgcacgca 20

<210> 2358 <211> 31 <212> DNA <213> Homo sapiens <400> 2358 ccctgcaagt acccagggaa ggatatagtc a 31 <210> 2359 <211> 35 <212> DNA <213> Homo sapiens <400> 2359 tttgtacgat agttgggcat ctgtatttcc acttg 35 <210> 2360 <211> 32 <212> DNA <213> Homo sapiens 670 i y

<400> 2360 agaggggaaa acctattcta cccaacacag ca 32 <210> 2361 <211> 20 <212> DNA <213> Homo sapiens <400> 2361 tgggggaagg gggccttggt 20 <210> 2362 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 2362 aacgaggcct gggctgggga 20 <210> 2363 <211l> 32 <212> DNA <213> Homo sapiens <400> 2363 tcagaaaaga aaagctcttt agactagcaa tg 32 <210> 2364 <211> 21 <212> DNA <213> Homo sapiens <400> 2364 tcctggagct gtggggtgge a 21 <210> 2365 <211> 23 <«212> DNA <213> Homo sapiens <400> 2365 agcgaccaca gctccgatga cca 23 <210> 2366 <211> 20 <212> DNA <213> Homo sapiens <400> 2366 ccgagggcgt tccacccecgtt 20 <210> 2367 <211> 24

<212> DNA <213> Homo sapiens <400> 2367 tcceeccaget ccctcoctcac tttg 24 <210> 2368 <211> 20 <212> DNA : <213> Homo sapiens : <400> 2368 acccggetge gcaggtctga 20 <210> 2369 <211> 21 <212> DNA <213> Homo sapiens <400> 2369 tgagccactg geccacaagg g 21 <210> 2370 ’ <211> 20 <212> DNA <213> Homo sapiens <400> 2370 tcecgtgacct cgggctcccce 20 <210> 2371 <211> 20 <212> DNA <213> Homo sapiens <400> 2371 ccecegegttg aaggegttga 20 <210> 2372 <211> 24 <212> DNA <213> Homo sapiens <400> 2372 tgggcatggg ttatcctcectg ctgg 24 <210> 2373 <211> 30 : <212> DNA <213> Homo sapiens <400> 2373 tgtcgtggag taaagaggga aacatgacca 30 672 Ro So oo

<210> 2374 <211> 21 <212> DNA <213> Homo sapiens <400> 2374 c¢gggagcagg acagggagcc a 21 <210> 2375 <211> 30 <212> DNA <213> Homo sapiens <400> 2375 . tggctcagta gcaacttggg gacttgtttt 30 <210> 2376 <21l1l> 32 <212> DNA <213> Homo sapiens <400> 2376 tgtttttgga aatcactaat agggccagcc tc 32 <210> 2377 <211l> 26 ’ <212> DNA <213> Homo sapiens <400> 2377 tgggagtctt gtgtctgtgc caacca ’ 26 <210> 2378 <21l1l> 21 <212> DNA <213> Homo sapiens <400> 2378 agggggaggt ggcagtggct g 21 <210> 2379 <211> 20 <212> DNA <213> Homo sapiens <400> 2379 acgcacaggg atggacgcgg 20 <210> 2380 <211> 29 <212> DNA <213> Homo sapiens <400> 2380 cctctgtgac atggtggtaa cagcacaga 29

<210> 2381 <211> 27 <212> DNA <213> Homo sapiens <400> 2381 cccatggcat gaacaaatag gatgcct : 27 <210> 2382 <211> 34 <212> DNA <213> Homo sapiens <400> 2382 tcccaactge aaaccctcat ttagtcttta gtga 34 <210> 2383 <211l> 22 <212> DNA <213> Homo sapiens <400> 2383 tggagggaca gaggtgggtg gg 22 <210> 2384 <211> 33 <212> DNA <213> Homo sapiens <400> 2384 cgccagtgag ttaagttgta cagaacatcg tca 33 <210> 2385 <211> 25 <212> DNA <213> Homo sapiens <400> 2385 gggaagacag acagcagcag accca 25 <210> 2386 <211> 31 <212> DNA <213> Homo sapiens <400> 2386 oo caccetttgg acattttgca actcttcaat g 31 Co oT <210> 2387 <211s> 21 <212> DNA <213> Homo sapiens

<400> 2387 tgggacccag gacgacgtcc a 21 <210> 2388 <211> 24 <212> DNA <213> Homo sapiens <400> 2388 tgccacttct ggtctegtcg gtga 24 <210> 2389 <211> 28 <212> DNA <213> Homo sapiens <400> 2389 ctccccagec cacaatttca aataatgce 28 <210> 2390 <211> 34 <212> DNA <213> Homo sapiens <400> 2390 accaacttac tcttaaaaag gatggctgcc aaga 34 <210> 2391 <211> 21 <212> DNA <213> Homo sapiens <400> 2391 tgtcagctcec acgggggtcc © 21 <210> 2392 <211> 26 <212> DNA <213> Homo sapiens <400> 2392 gagtccagaa agaaatgcct ggggca 26 <210> 2393 <211l> 25 <212> DNA <213> Homo sapiens <400> 2393 cccaaagaag ggtcagccaa agcca 25 <210> 2394 <211> 21 <212> DNA

PCT/US2003/012946 <213> Homo sapiens <400> 2394 ggcctggtgt ctgctetgeg g 21 <210> 2395 <211> 27 <212> DNA <213> Homo sapiens . <400> 2395 tcagccaagc tagcctectt agccagc 27 <210> 2396 <211> 34 <212> DNA <213> Homo sapiens <400> 2396 tcagtatgta atgtcctatt ttccecactge acca 34 <210> 2397 <211> 30 <212> DNA <213> Homo sapiens <400> 2397 ttcectgattt tgcatgttct cattcccaaa 30 <210> 2398 <211l> 29 <212> DNA <213> Homo sapiens <400> 2398 tccagaaaat tggaagcagt ctggaatgg 29 <210> 2399 <211> 25 <212> DNA <213> Homo sapiens <400> 2399 cccagttcac agtcccattc tggca 25 <210> 2400 <211> 37% <212> PRT - <213> Homo sapiens <400> 2400 Met Asp Asp Asp Ile Ala Ala Leu Val Val Asp Asn Gly Ser Gly Met 1 5 10 15 676 i. -

Cys Lys Ala Gly Phe Ala Gly Asp Asp Ala Pro Arg Ala Val Phe Pro

Ser Ile val Gly Arg Pro Arg His Gln Gly Val Met val Gly Met Gly 40 45 Gln Lys Asp Ser Tyr Val Gly Asp Glu Ala Gln Ser Lys Arg Gly Ile 50 55 60 Leu Thr Leu Lys Tyr Pro Ile Glu His Gly Ile Val Thr Asn Trp Asp 65 70 75 80 Asp Met Glu Lys Ile Trp His His Thr Phe Tyr Asn Glu Leu Arg Val 8S 90 95 Ala Pro Glu Glu His Pro Val Leu Leu Thr Glu Ala Pro Leu Asn Pro 100 105 110 Lys Ala Asn Arg Glu Lys Met Thr Gln Ile Met Phe Glu Thr Phe Asn 115 120 125 Thr Pro Ala Met Tyr Val Ala Ile Gln Ala Val Leu Ser Leu Tyr Ala 130 135 140 Ser Gly Arg Thr Thr Gly Ile Val Met Asp Ser Gly Asp Gly Val Thr 145 150 155 160 His Thr Val Pro Ile Tyr Glu Gly Tyr Ala Leu Pro His Ala Ile Leu 165 170 175 Arg Leu Asp Leu Ala Gly Arg Asp Leu Thr Asp Tyr Leu Met Lys lle 180 185 190 Leu Thr Glu Arg Gly Tyr Ser Phe Thr Thr Thr Ala Glu Arg Glu Ile 195 200 205 Val Arg Asp Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu Asp Phe Glu 210 215 220 Gln Glu Met Ala Thr Ala Ala Ser Ser Ser Ser Leu Glu Lys Ser Tyr 225 230 235 240 Glu Leu Pro Asp Gly Gln Val Ile Thr Ile Gly Asn Glu Arg Phe Arg 245 250 255

PCT/US2003/012946

Cys Pro Glu Ala Leu Phe Gln Pro Ser Phe Leu Gly Met Glu Ser Cys 260 265 270 Gly Ile His Glu Thr Thr Phe Asn Ser Ile Met Lys Cys Asp Val Asp 275 280 285 ’ Ile Arg Lys Asp Leu Tyr Ala Asn Thr Val Leu Ser Gly Gly Thr Thr 290 295 300 Met Tyr Pro Gly Ile Ala Asp Arg Met Gln Lys Glu Ile Thr Ala Leu 305 310 315 320 Ala Pro Ser Thr Met Lys Ile Lys Ile Ile Ala Pro Pro Glu Arg Lys 325 330 33s Tyr Ser Val Trp Ile Gly Gly Ser Ile Leu Ala Ser Leu Ser Thr Phe 340 345 350 Gln Gln Met Trp Ile Ser Lys Gln Glu Tyr Asp Glu Ser Gly Pro Ser 355 360 365 Ile Val His Arg Lys Cys Phe 370 375 <210> 2401 <211> 651 <212> PRT <213> Homo sapiens <400> 2401 Met Ala Arg Gly Ser ala Val Ala Trp Ala Ala Leu Gly Pro Leu Leu 1 5 10 1S Trp Gly Cys Ala Leu Gly Leu Gln Gly Gly Met Leu Tyr Pro Gln Glu

Ser Pro Ser Arg Glu Cys Lys Glu Leu Asp Gly Leu Trp Ser Phe Arg 40 45 Ala Asp Phe Ser Asp Asn Arg Arg Arg Gly Phe Glu Glu Gln Trp Tyr 50 55 60 Arg Arg Pro Leu Trp Glu Ser Gly Pro Thr Val Asp Met Pro Val Pro 65 70 75 80 Ser Ser Phe Asn Asp Ile Ser Gln Asp Trp Arg Leu Arg His Phe Val 85 90 95

Gly Trp val Trp Tyr Glu Arg Glu Val Ile Leu Pro Glu Arg Trp Thr 100 105 110 . Gln Asp Leu Arg Thr Arg Val Val Leu Arg Ile Gly Ser Ala His Ser 115 120 125 Tyr Ala Ile Val Trp Val Asn Gly Val Asp Thr Leu Glu His Glu Gly 130 135 140 Gly Tyr Leu Pro Phe Glu Ala Asp Ile Ser Asn Leu Val Gln Val Gly 145 150 155 160 Pro Leu Pro Ser Arg Leu Arg Ile Thr Ile Ala Ile Asn Asn Thr Leu 165 170 175 Thr Pro Thr Thr Leu Pro Pro Gly Thr Ile Gln Tyr Leu Thr Asp Thr 180 185 190 Ser Lys Tyr Pro Lys Gly Tyr Phe Val Gln Asn Thr Tyr Phe Asp Phe 195 200 205 Phe Asn Tyr Ala Gly Leu Gln Arg Ser Val Leu Leu Tyr Thr Thr Pro 210 215 220 Thr Thr Tyr Ile Asp Asp Ile Thr Val Thr Thr Ser Val Glu Gln Asp 225 230 235 240 Ser Gly Leu Val Asn Tyr Gln Ile Ser Val Lys Gly Ser Asn Leu Phe 245 .250 255 Lys Leu Glu Val Arg Leu Leu Asp Ala Glu Asn Lys Val Val Ala Asn 260 265 270 Gly Thr Gly Thr Glin Gly Gln Leu Lys Val Pro Gly Val Ser Leu Trp 275 280 285 Trp Pro Tyr Leu Met His Glu Arg Pro Ala Tyr Leu Tyr Ser Leu Glu 290 295 300 Val Gln Leu Thr Ala Gln Thr Ser Leu Gly Pro Val Ser Asp Phe Tyr 305 310 315 320 Thr Leu Pro Val Gly Ile Arg Thr Val Ala Val Thr Lys Ser Gln Phe 325 330 335

Leu Ile Asn Gly Lys Pro Phe Tyr Phe His Gly Val Asn Lys His Glu 340 345 350 Asp Ala Asp Ile Arg Gly Lys Gly Phe Asp Trp Pro Leu Leu Val Lys 355 360 365 Asp Phe Asn Leu Leu Arg Trp Leu Gly Ala Asn Ala Phe Arg Thr Ser 370 375 380 His Tyr Pro Tyr Ala Glu Glu Val Met Gln Met Cys Asp Arg Tyr Gly 385 3590 3395 400 Ile Val Val Ile Asp Glu Cys Pro Gly Val Gly Leu Ala Leu Pro Gln 405 410 415 Phe Phe Asn Asn Val Ser Leu His His His Met Gln Val Met Glu Glu 420 425 430 val Val Arg Arg Asp Lys Asn His Pro Ala Val Val Met Trp Ser Val 435 440 445 Ala Asn Glu Pro Ala Ser His Leu Glu Ser Ala Gly Tyr Tyr Leu Lys 450 455 460 Met Val Ile Ala His Thr Lys Ser Leu Asp Pro Ser Arg Pro Val Thr 465 470 475 480 Phe Val Ser Asn Ser Asn Tyr Ala Ala Asp lys Gly Ala Pro Tyr Val 485 490 4395 Asp Val Ile Cys Leu Asn Ser Tyr Tyr Ser Trp Tyr His Asp Tyr Gly 500 505 510 His Leu Glu Leu Ile Gln Leu Gln Leu Ala Thr Gln Phe Glu Asn Trp 515 520 525 Tyr Lys Lys Tyr Gln Lys Pro Ile Ile Gln Ser Glu Tyr Gly Ala Glu 530 535 540 Thr Ile Ala Gly Phe His Gln Asp Pro Pro Leu Met Phe Thr Glu Glu 545 S50 555 560 Tyr Gln Lys Ser Leu Leu Glu Gln Tyr His Leu Gly Leu Asp Gln Lys 565 570 575

Arg Arg Lys Tyr Val Val Gly Glu Leu Ile Trp Asn Phe Ala Asp Phe 580 585 590 Met Thr Glu Gln Ser Pro Thr Arg Val Leu Gly Asn Lys Lys Gly Ile 595 600 605 Phe Thr Arg Gln Arg Gln Pro Lys Ser Ala Ala Phe Leu Leu Arg Glu 610 615 620 Arg Tyr Trp Lys Ile Ala Asn Glu Thr Arg Tyr Pro His Ser Val Ala 625 630 635 640 Lys Ser Gln Cys Leu Glu Asn Ser Pro Phe Thr 645 650 <210> 2402 <211> 119 <212> PRT <213> Homo sapiens <400> 2402 Met Ser Arg Ser Val Ala Leu Ala Val Leu Ala Leu Leu Ser Leu Ser 1 5 10 15 Gly Leu Glu Ala Ile Gln Arg Thr Pro Lys Ile Gln Val Tyr Ser Arg

His Pro Ala Glu Asn Gly Lys Ser Asn Phe Leu Asn Cys Tyr Val Ser 40 45 Gly Phe His Pro Ser Asp Ile Glu Val Asp Leu Leu Lys Asn Gly Glu 50 55 60 Arg Ile Glu Lys Val Glu His Ser Asp Leu Ser Phe Ser Lys Asp Trp 65 70 75 80 Ser Phe Tyr Leu Leu Tyr Tyr Thr Glu Phe Thr Pro Thr Glu Lys Asp 85 90 95 Glu Tyr Ala Cys Arg Val Asn His Val Thr Leu Ser Gln Pro Lys Ile 100 105 110 Val Lys Trp Asp Arg Asp Met 115 <210> 2403 <21ll> 228

<212> PRT <213> Homo sapiens <400> .2403 Met Ser Val Ser Glu Ile Phe Val Glu Leu Gln Gly Phe Leu Ala Ala 1 S 10 15 Glu Gln Asp Ile Arg Glu Glu Ile Arg Lys Val Val Gln Ser Leu Glu

Gln Thr Ala Arg Glu Ile Leu Thr Leu Leu Gln Gly Val His Gln Gly 40 45 Ala Gly Phe Gln Asp Ile Pro Lys Arg Cys Leu Lys Ala Arg Glu His 50 55 60 Phe Gly Thr Val Lys Thr His Leu Thr Ser Leu Lys Thr Lys Phe Pro 65 70 75 80 Ala Glu Gln Tyr Tyr Arg Phe His Glu His Trp Arg Phe Val Leu Gln 85 90 95 Arg Leu Val Phe Leu Ala Ala Phe Val Val Tyr Leu Glu Thr Glu Thr 100 105 110 Leu Val Thr Arg Glu Ala Val Thr Glu Ile Leu Gly Ile Glu Pro Asp 115 120 125 Arg Glu Lys Gly Phe His Leu Asp Val Glu Asp Tyr Leu Ser Gly Val 130 135 140 Leu Ile Leu Ala Ser Glu Leu Ser Arg Leu Ser Val Asn Ser Val Thr 145 150 155 160 Ala Gly Asp Tyr Ser Arg Pro Leu His Ile Ser Thr Phe Ile Asn Glu 165 170 175 Leu Asp Ser Gly Phe Arg Leu Leu Asn Leu Lys Asn Asp Ser Leu Arg 180 185 190 Lys Arg Tyr Asp Gly Leu Lys Tyr Asp Val Lys Lys Val Glu Glu Val 195 200 205 Val Tyr Asp Leu Ser Ile Arg Gly Phe Asn Lys Glu Thr Ala ala ala 210 215 220

PCT/US2003/012946

Cys val Glu Lys 225 <210> 2404 <211> 378 <212> PRT <213> Homo sapiens <400> 2404 Met Asp Leu Gly Lys Pro Met Lys Ser val Leu Val Val Ala Leu Leu 1 5 10 15 Val Ile Phe Gln Val Cys Leu Cys Gln Asp Glu Val Thr Asp Asp Tyr

Ile Gly Asp Asn Thr Thr Val Asp Tyr Thr Leu Phe Glu Ser Leu Cys 40 45 Ser Lys Lys Asp Val Arg Asn Phe Lys Ala Trp Phe Leu Pro Ile Met 50 55 60 Tyr Ser Ile Ile Cys Phe Val Gly Leu Leu Gly Asn Gly Leu val val 65 70 75 80 Leu Thr Tyr Ile Tyr Phe Lys Arg Leu Lys Thr Met Thr Asp Thr Tyr 85 S90 9s Leu Leu Asn Leu Ala Val Ala Asp Ile Leu Phe Leu Leu Thr Leu Pro 100 105 110 Phe Trp Ala Tyr Ser Ala Ala Lys Ser Trp Val Phe Gly Val His Phe 115 120 125 Cys Lys Leu Ile Phe Ala Ile Tyr Lys Met Ser Phe Phe Ser Gly Met 130 135 140 Leu Leu Leu Leu Cys Ile Ser Ile Asp Arg Tyr Val Ala Ile val Gln 145 150 155 160 Ala Val Ser Ala His Arg His Arg Ala Arg Val Leu Leu Ile Ser Lys 165 170 178 Leu Ser Cys Val Gly Ile Trp Ile Leu Ala Thr Val Leu Ser Ile Pro 180 185 1590 Glu Leu Leu Tyr Ser Asp Leu Gln Arg Ser Ser Ser Glu Gln Ala Met 185 200 205

Arg Cys Ser Leu Ile Thr Glu His Val Glu Ala Phe Ile Thr Ile Gln 210 215 220 Val Ala Gln Met Val Ile Gly Phe Leu Val Pro Leu Leu Ala Met Ser 225 230 235 240 Phe Cys Tyr Leu Val Ile Ile Arg Thr Leu Leu Gln Ala Arg Asn Phe 245 250 255 Glu Arg Asn Lys Ala Ile Lys Val Ile Ile Ala Val Val Val Val Phe . 260 265 270 Ile Val Phe Gln Leu Pro Tyr Asn Gly Val Val Leu Ala Gln Thr Val 275 280 285 Ala Asn Phe Asn Ile Thr Ser Ser Thr Cys Glu Leu Ser Lys Gln Leu 290 295 300 Asn Ile Ala Tyr Asp Val Thr Tyr Ser Leu Ala Cys Val Arg Cys Cys 305 310 315 320 Val Asn Pro Phe Leu Tyr Ala Phe Ile Gly Val Lys Phe Arg Asn Asp 325 330 335 Leu Phe Lys Leu Phe Lys Asp Leu Gly Cys Leu Ser Gln Glu Gln Leu 340 345 350 Arg Gln Trp Ser Ser Cys Arg His Ile Arg Arg Ser Ser Met Ser Val 355 360 365 Glu Ala Glu Thr Thr Thr Thr Phe Ser Pro 370 375 <210> 2405 <21l1l> 398 <212> PRT <213> Homo sapiens <400> 2405 Met Leu Arg Leu Tyr Val Leu Val Met Gly Val Ser Ala Phe Thr Leu 0 oo 1 5 10 15 Gln Pro Ala Ala His Thr Gly Ala Ala Arg Ser Cys Arg Phe Arg Gly

Arg His Tyr Lys Arg Glu Phe Arg Leu Glu Gly Glu Pro Val Ala Leu 40 45 Arg Cys Pro Gln Val Pro Tyr Trp Leu Trp Ala Ser Val Ser Pro Arg 50 5% 60 Ile Asn Leu Thr Trp His Lys Asn Asp Ser Ala Arg Thr Val Pro Gly 65 70 75 80 Glu Glu Glu Thr Arg Met Trp Ala Gln Asp Gly Ala Leu Trp Leu Leu 85 90 95 Pro Ala Leu Gln Glu Asp Ser Gly Thr Tyr Val Cys Thr Thr Arg Asn 100 105 110 Ala Ser Tyr Cys Asp Lys Met Ser Ile Glu Leu Arg Val Phe Glu Asn 115 120 125 Thr Asp Ala Phe Leu Pro Phe Ile Ser Tyr Pro Gln Ile Leu Thr Leu 130 135 140 Ser Thr Ser Gly Val Leu Val Cys Pro Asp Leu Ser Glu Phe Thr Arg 145 150 155 160 Asp Lys Thr Asp Val Lys Ile Gln Trp Tyr Lys Asp Ser Leu Leu Leu 165 170 175 Asp Lys Asp Asn Glu Lys Phe Leu Ser Val Arg Gly Thr Thr His Leu 180 185 150 Leu val His Asp Val Ala Leu Glu Asp Ala Gly Tyr Tyr Arg Cys Val 195 200 205 Leu Thr Phe Ala His Glu Gly Gln Gln Tyr Asn Ile Thr Arg Ser Ile 210 215 220 Glu Leu Arg Ile Lys Lys Lys Lys Glu Glu Thr Ile Pro Val Ile Ile 225 230 235 240 Ser Pro Leu Lys Thr Ile Ser Ala Ser Leu Gly Ser Arg Leu Thr Ile 245 250 255 Pro Cys Lys Val Phe Leu Gly Thr Gly Thr Pro Leu Thr Thr Met Leu 260 265 270 Trp Trp Thr Ala Asn Asp Thr His Ile Glu Ser Ala Tyr Pro Gly Gly

PCT/US2003/012946

275 280 285 Arg Val Thr Glu Gly Pro Arg Gln Glu Tyr Ser Glu Asn Asn Glu Asn 290 295 300 Tyr Ile Glu Val Pro Leu Ile Phe Asp Pro Val Thr Arg Glu Asp Leu 305 310 315 320 His Met Asp Phe Lys Cys Val Val His Asn Thr Leu Ser Phe Gln Thr 325 330 335 Leu Arg Thr Thr Val Lys Glu Ala Ser Ser Thr Phe Ser Trp Gly Ile 340 345 350 Val Leu Ala Pro Leu Ser Leu Ala Phe Leu Val Leu Gly Gly Ile Trp 355 360 365 Met His Arg Arg Cys Lys His Arg Thr Gly Lys Ala Asp Gly Leu Thr 370 375 380 Val Leu Trp Pro His His Gln Asp Phe Gln Ser Tyr Pro Lys 385 390 385 <210> 2406 <211> 132 <212> PRT <213> Homo sapiens <400> 2406 Met Glu Phe Asp Leu Asn Gly Asn Gly Asp Ile Gly Glu Lys Arg val 1 5 10 15 Ile Cys Gly Gly Arg Val val Cys Arg Pro Lys Lys Thr Glu Val Ser

Pro Thr Cys Ser Ile Pro His Asp Leu Gly Gly Gly Pro Pro Thr Thr 40 45 Val Gly Gly Arg Arg Met Gly Met Arg Lys Trp Glu Arg Arg Glu Arg 50 5S 60 Val Ser-Pro Pro Ser Pro His Pro His Pro Leu Pro Pro Asp Ile Met 65 70 75 80 Ser Leu Lys Arg Met Leu Glu Lys Leu Gly Val Pro Lys Thr His Leu 85 90 95 686 Ie

Glu Leu Lys Lys Leu Ile Gly Glu Val Ser Ser Gly Ser Gly Glu Thr 100 105 110 Phe Ser Tyr Pro Asp Phe Leu Arg Met Met Leu Gly Lys Arg Ser Ala 115 120 125 Ile Leu Lys Met 130 <210> 2407 <211> 587 <212> PRT <213> Homo sapiens <400> 2407 Met Val Thr Ala Ala Met Leu Leu Gln Cys Cys Pro Val Leu Ala Arg 1 5 10 15 Gly Pro Thr Ser Leu Leu Gly Lys Val Val Lys Thr His Gln Phe Leu

Phe Gly Ile Gly Arg Cys Pro Ile Leu Ala Thr Gln Gly Pro Asn Cys 40 45 Ser Gln Ile His Leu Lys Ala Thr Lys Ala Gly Gly Asp Ser Pro Ser 50 55 60 Trp Ala Lys Gly His Cys Pro Phe Met Leu Ser Glu Leu Gln Asp Gly 65 70 75 80 Lys Ser Lys Ile Val Gln Lys Ala Ala Pro Glu Val Gln Glu Asp Val 85 90 95 Lys Ala Phe Lys Thr Asp Leu Pro Ser Ser Leu Val Ser Val Ser Leu 100 105 110 Arg Lys Pro Phe Ser Gly Pro Gln Glu Gln Glu Gln Ile Ser Gly Lys 115 120 125 Val Thr His Leu Ile Gln Asn Asn Met Pro Gly Asn Tyr Val Phe Ser 130 135 140 Tyr Asp Gln Phe Phe Arg Asp Lys Ile Met Glu Lys Lys Gln Asp His 145 150 155 160 Thr Tyr Arg Val Phe Lys Thr Val Asn Arg Trp Ala Asp Ala Tyr Pro

PCT/US2003/012946

165 170 175 Phe Ala Gln His Phe Phe Glu Ala Ser Val Ala Ser Lys Asp Val Ser 180 185 180 Val Trp Cys Ser Asn Asp Tyr Leu Gly Met Ser Arg His Pro Gln val 19% 200 205 Leu Gln Ala Thr Gln Glu Thr Leu Gln Arg His Gly Ala Gly Ala Gly 210 215 220 Gly Thr Arg Asn Ile Ser Gly Thr Ser Lys Phe His Val Glu Leu Glu 225 230 235 240 Gln Glu Leu Ala Glu Leu His Gln Lys Asp Ser Ala Leu Leu Phe Ser 245 250 255 Ser Cys Phe val Ala Asn Asp Ser Thr Leu Phe Thr Leu Ala Lys Ile 260 265 270 Leu Pro Gly Cys Glu Ile Tyr Ser Asp Ala Gly Asn His Ala Ser Met 275 280 285 Ile Gln Gly Ile Arg Asn Ser Gly Ala Ala Lys Phe Val Phe Arg His 290 295 300 Asn Asp Pro Asp His Leu Lys Lys Leu Leu Glu Lys Ser Asn Pro Lys 305 310 315 320 Ile Pro Lys Ile Val Ala Phe Glu Thr Val His Ser Met Asp Gly Ala 325 330 335 Ile Cys Pro Leu Glu Glu Leu Cys Asp Val Ser His Gln Tyr Gly Ala 340 345 350 Leu Thr Phe Val Asp Glu Val His Ala Val Gly Leu Tyr Gly Ser Arg 355 360 365 Gly Ala Gly Ile Gly Glu Arg Asp Gly Ile Met His Lys Ile Asp Ile 370 375 380 Ile Ser Gly Thr Leu Gly Lys Ala Phe Gly Cys Val Gly Gly Tyr Ile 385 390 385 400 Ala Ser Thr Arg Asp Leu Val Asp Met Val Arg Ser Tyr Ala Ala Gly 405 410 415

Phe Ile Phe Thr Thr Ser Leu Pro Pro Met Val Leu Ser Gly Ala Leu 420 425 430 Glu Ser val Arg Leu Leu Lys Gly Glu Glu Gly Gln Ala Leu Arg Arg 435 440 445 Ala His Gln Arg Asn Val Lys His Met Arg Gln Leu Leu Met Asp Arg 450 455 460 Gly Leu Pro val Ile Pro Cys Pro Ser His Ile Ile Pro Ile Arg Val 465 470 475 480 Gly Asn Ala Ala Leu Asn Ser Lys Leu Cys Asp Leu Leu Leu Ser Lys 485 490 ° 495 His Gly Ile Tyr Val Gln Ala Ile Asn Tyr Pro Thr Val Pro Arg Gly 500 505 510 Glu Glu Leu Leu Arg Leu Ala Pro Ser Pro His His Ser Pro Gln Met 518 520 525 Met Glu Asp Phe Val Glu Lys Leu Leu Leu Ala Trp Thr Ala val Gly 530 535 540 Leu Pro Leu Gln Asp Val Ser Val Ala ala Cys Asn Phe Cys Arg Arg 545 550 555 S60 Pro Val His Phe Glu Leu Met Ser Glu Trp Glu Axg Ser Tyr Phe Gly 565 570 575% Asn Met Gly Pro Gln Tyr Val Thr Thr Tyr Ala 580 585 <210> 2408 <211> 122 <212> PRT <213> Homo sapiens <400> 2408 Met Ser Ala Thr Trp Cys Ser Pro Glu Gly Gln Gly Met Gly Gln Gly - 1 5 10 15 Pro Gly Arg Glu Val Gly Gly Asn Ser Ala Ala Ser Gly Pro Ala Ser

Pro Ile Arg Asp Pro Cys Leu Ser Glu Ala Gly Leu Lys Gly Pro Pro 35 40 45 Ser Ala His Pro Arg Arg Leu Cys Leu Leu His Arg Leu Val Cys Phe 50 55 60 Ser Gly Gly Leu Thr Ser Ile Gln Leu Ser Pro Axg Thr Cys Cys Ser 65 70 75 80 His Gln Trp Ala Gln Leu Phe Ser Pro Ala Cys Phe Pro Gln Trp Arg 85 90 95 Ala Pro Gly Cys Ser Leu Asp Asp Ser Arg Ser Leu Thr Arg Ile Arg 100 10S 110 Pro Val His Leu Pro Gly Pro Ser Leu Asp 115 120 <210> 2409 <211> 288 <212> PRT <213> Homo sapiens <400> 2409 Met Gly His Thr Arg Arg Gln Gly Thr Ser Pro Ser Lys Cys Pro Tyr 1 5 10 15 Leu Asn Phe Phe Gln Leu Leu Val Leu Ala Gly Leu Ser His Phe Cys

Ser Gly Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu 40 45 Ser Cys Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile 50 55 60 . Tyr Trp Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp 65 70 75 80 Met Asn Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr 85 90 95 Asn Asn Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly 100 105 110 Thr Tyr Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg 115 120 125

Glu His Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr 130 135 140 Pro Ser Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile 145 150 155 160 Ile Cys Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu 165 170 175 Glu Asn Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr val Ser Gln Asp 180 185 190 Pro Glu Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met 185 200 205 Thr Thr Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg 210 2185 220 Val Asn Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro 225 230 235 240 y Asp Asn Leu Leu Pro Ser Trp Ala Ile Thr Leu Ile ser Val Asn Gly 245 250 255 Ile Phe Val Ile Cys Cys Leu Thr Tyr Cys Phe Ala Pro Arg Cys Arg 260 265 270 Glu Arg Arg Arg Asn Glu Arg Leu Arg Arg Glu Ser Val Arg Pro val 275 280 285 <210> 2410 <21l> 6588 <212> PRT <213> Homo sapiens <400> 2410 Met His Cys Lys Val Ser Leu Leu Asp Asp Thr Val Tyr Glu Cys Val 1 5 10 15 Val Glu Lys His Ala Lys Gly Gln Asp Leu Leu Lys Arg Val Cys Glu )

His Leu Asn Leu Leu Glu Glu Asp Tyr Phe Gly Leu Ala Ile Trp Asp 40 45

Asn Ala Thr Ser Lys Thr Trp Leu Asp Ser Ala Lys Glu Ile Lys Lys 50 55 60 Gln Val Arg Gly val Pro Trp Asn Phe Thr Phe Asn Val Lys Phe Tyr 65 70 75 80 Pro Pro Asp Pro Ala Gln Leu Thr Glu Asp Ile Thr Arg Tyr Tyr Leu 85 90 95 Cys Leu Gln Leu Arg Gln Asp Ile Val Ala Gly Arg Leu Pro Cys Ser 100 105 110 Phe Ala Thr Leu Bla Leu Leu Gly Ser Tyr Thr Ile Gln Ser Glu Leu 115 120 125 Gly Asp Tyr Asp Pro Glu Leu His Gly Val Asp Tyr Val Ser Asp Phe 130 135 140 Lys Leu Ala Pro Asn Gln Thr Lys Glu Leu Glu Glu Lys Val Met Glu 145 150 155 160 Leu His Lys Ser Tyr Arg Ser Met Thr Pro Ala Gln Ala Asp Leu Glu 165 170 175 Phe Leu Glu Asn Ala Lys Lys Leu Ser Met Tyr Gly Val Asp Leu His 180 185 190 Lys Ala Lys Asp Leu Glu Gly Val Asp Ile Ile Leu Gly Val Cys Ser 195 200 205 Ser Gly Leu Leu Val Tyr Lys Asp Lys Leu Arg Ile Asn Arg Phe Pro 210 215 220 Trp Pro Lys Val Leu Lys Ile Ser Tyr Lys Arg Ser Ser Phe Phe Ile 225 230 235 240 Lys Ile Arg Pro Gly Glu Gln Glu Gln Tyr Glu Ser Thr Ile Gly Phe 245 250 255 Lys Leu Pro Ser Tyr Arg Ala Ala Lys Lys Leu Trp Lys Val Cys val 260 265 270 Glu His His Thr Phe Phe Arg Leu Thr Ser Thr Asp Thr Ile Pro Lys 275 280 285 Ser Lys Phe Leu Ala Leu Gly Ser Lys Phe Arg Tyr Ser Gly Arg Thr

T/US2003/012946

290 295 300 Gln Ala Gln Thr Arg Gln Ala Ser Ala Leu Ile Asp Arg Pro Ala Pro 30S 310 315 320 His Phe Glu Arg Thr Ala Ser Lys Arg Ala Ser Arg Ser Leu Asp Gly 325 330 335 Ala Ala Ala val Asp Ser Ala Asp Arg Ser Pro Arg Pro Thr Ser Ala 340 345 350 Pro Ala Ile Thr Gln Gly Gln Val Ala Glu Gly Gly Val Leu Asp Ala 355 360 365 Ser Ala Lys Lys Thr Val Val Pro Lys Ala Gln Lys Glu Thr val Lys 370 375 380 Ala Glu Val Lys Lys Glu Asp Glu Pro Pro Glu Gln Ala Glu Pro Glu 385 390 398 400 Pro Thr Glu Ala Trp Lys Lys Lys Arg Glu Arg Leu Asp Gly Glu Asn 405 410 415 Ile Tyr Ile Arg His Ser Asn Leu Met Leu Glu Asp Leu Asp Lys Ser 420 425 430 Gln Glu Glu Ile Lys Lys His His Ala Ser Ile Ser Glu Leu Lys Lys 435 440 445 Asn Phe Met Glu Ser Val Pro Glu Pro Arg Pro Ser Glu Trp Asp Lys 450 455 460 Arg Leu Ser Thr His Ser Pro Phe Arg Thr Leu Asn Ile Asn Gly Gln 465 470 475 480 Ile Pro Thr Gly Glu Gly Pro Pro Leu Val Lys Thr Gln Thr Val Thr 485 490 495 Ile Ser Asp Asn Ala Asn Ala Val Lys Ser Glu Ile Pro Thr Lys Asp 500 505 510 Val Pro Ile Val His Thr Glu Thr Lys Thr Ile Thr Tyr Glu Ala Ala 515 520 525 Gln Thr Val Lys Gly Gly Ile Ser Glu Thr Arg Ile Glu Lys Arg Ile 530 535 540

Val Ile Thr Gly Asp Ala Asp Ile Asp His Asp Gln Val Leu Val Gln 545 S50 555 560 Ala Ile Lys Glu Ala Lys Glu Gln His Pro Asp Met Ser Val Thr Lys 565 570 575 Val Val val His Gln Glu Thr Glu Ile Ala Asp Glu 580 585 <210> 2411 <21l1> 982 <212> PRT <213> Homo sapiens <400> 2411 Met Ala Asn Ser Met Asn Gly Arg Asn Pro Gly Gly Arg Gly Gly Asn 1 5 10 15 Pro Arg Lys Gly Arg Ile Leu Gly Ile Ile Asp Ala Ile Gln Asp Ala

Val Gly Pro Pro Lys Gln Ala Ala Ala Asp Arg Arg Thr Val Glu Lys 40 45 Thr Trp Lys Leu Met Asp Lys Val Val Arg Leu Cys Gln Asn Pro Lys 50 55 60 Leu Gln Leu Lys Asn Ser Pro Pro Tyr Ile Leu Asp Ile Leu Pro Asp 65 70 75 80 Thr Tyr Gin His Leu Arg Leu Ile Leu Ser Lys Tyr Asp Asp Asn Gln 85 20 95 Lys Leu Ala Gln Leu Ser Glu Asn Glu Tyr Phe Lys Ile Tyr Ile Asp 100 105 110 Ser Leu Met Lys Lys Ser Lys Arg Ala Ile Arg Leu Phe Lys Glu Gly 115 120 125 Lys Glu Arg Met Tyr Glu Glu Gln Ser Gln Asp Arg Arg Asn Leu Thr 130 135 140 Lys Leu Ser Leu Ile Phe Ser His Met Leu Ala Glu Ile Lys Ala Ile 145 150 155 160

Phe Pro Asn Gly Gln Phe Gln Gly Asp Asn Phe Arg Ile Thr Lys Ala 165 170 175 Asp Ala Ala Glu Phe Trp Arg Lys Phe Phe Gly Asp Lys Thr Ile Val 180 185 190 Pro Trp Lys Val Phe Arg Gln Cys Leu His Glu Val His Gln Ile Ser 195 200 205 Ser Gly Leu Glu Ala Met Ala Leu Lys Ser Thr Ile Asp Leu Thr Cys 210 215 220 Asn Asp Tyr Ile Ser Val Phe Glu Phe Asp Ile Phe Thr Arg Leu Phe 225 230 235 240 Gln Pro Trp Gly Ser Ile Leu Arg Asn Trp Asn Phe Leu Ala Val Thr 245 250 255 His Pro Gly Tyr Met Ala Phe Leu Thr Tyr Asp Glu Val Lys Ala Arg 260 265 270 Leu Gln Lys Tyr Ser Thr Lys Pro Gly Ser Tyr Ile Phe Arg Leu Ser 275 280 285 Cys Thr Arg Leu Gly Gln Trp Ala Ile Gly Tyr Val Thr Gly Asp Gly 290 295 300 Asn Ile Leu Gln Thr Ile Pro His Asn Lys Pro Leu Phe Gln Ala Leu 305 310 315 320 Ile Asp Gly Ser Arg Glu Gly Phe Tyr Leu Tyr Pro Asp Gly Arg Ser 325 330 335 Tyr Asn Pro Asp Leu Thr Gly Leu Cys Glu Pro Thr Pro His Asp His 340 345 350 Ile Lys Val Thr Gln Glu Gln Tyr Glu Leu Tyr Cys Glu Met Gly Ser 355 360 365 Thr Phe Gln Leu Cys Lys Ile Cys Ala Glu Asn Asp Lys Asp Val Lys 370 375 380 : Ile Glu Pro Cys Gly His Leu Met Cys Thr Ser Cys Leu Thr Ala Trp 385 390 385 400. Gln Glu Ser Asp Gly Gln Gly Cys Pro Phe Cys Arg Cys Glu Ile Lys

PCT/US20 2946

405 410 415 Gly Thr Glu Pro Ile Ile Val Asp Pro Phe Asp Pro Arg Asp Glu Gly 420 425 430 Ser Arg Cys Cys Ser Ile Ile Asp Pro Phe Gly Met Pro Met Leu Asp 435 440 445 Leu Asp Asp Asp Asp Asp Arg Glu Glu Ser Leu Met Met Asn Arg Leu 450 455 460 Ala Asn Val Arg Lys Cys Thr Asp Arg Gln Asn Ser Pro Val Thr Ser 465 470 475 480 Pro Gly Ser Ser Pro Leu Ala Gln Arg Arg Lys Pro Gln Pro Asp Pro 485 490 4385 Leu Gln Ile Pro His Leu Ser Leu Pro Pro Val Pro Pro Arg Leu Asp 500 505 510 Leu Ile Gln Lys Gly Ile Val Arg Ser Pro Cys Gly Ser Pro Thr Gly 515 520 525 Ser Pro Lys Ser Ser Pro Cys Met Val Arg Lys Gln Asp Lys Pro Leu S30 535 540 Pro Ala Pro Pro Pro Pro Leu Arg Asp Pro Pro Pro Pro Pro Pro Glu 545 550 555 560 Arg Pro Pro Pro Ile Pro Pro Asp Asn Arg Leu Ser Arg His Ile His 565 570 575 His Val Glu Ser Val Pro Ser Lys Asp Pro Pro Met Pro Leu Glu Ala 580 S85 580 Trp Cys Pro Arg Asp Val Phe Gly Thr Asn Gln Leu Val Gly Cys arg 595 600 605 Leu Leu Gly Glu Gly Ser Pro Lys Pro Gly Ile Thr Ala Ser Ser Asn 610 615 620 Val Asn Gly Arg His Ser Arg Val Gly Ser Asp Pro Val Leu Met Arg 625 630 635 640 Lys His Arg Arg His Asp Leu Pro Leu Glu Gly Ala Lys Val Phe Ser 645 650 655 AY

Asn Gly His Leu Gly Ser Glu Glu Tyr Asp Val Pro Pro Arg Leu Ser 660 665 670 Pro Pro Pro Pro Val Thr Thr Leu Leu Pro Ser Ile Lys Cys Thr Gly 675 680 685 Pro Leu Ala Asn Ser Leu Ser Glu Lys Thr Arg Asp Pro Val Glu Glu 690 695 700 Asp Asp Asp Glu Tyr Lys Ile Pro Ser Ser His Pro Val Ser Leu Asn 705 710 715 720 Ser Gln Pro Ser His Cys His Asn Val Lys Pro Pro Val Arg Ser Cys 725 730 735 Asp Asn Gly His Cys Met Leu Asn Gly Thr His Gly Pro Ser Ser Glu 740 745 750 Lys Lys Ser Asn Ile Pro Asp Leu Ser Ile Tyr Leu Lys Gly Asp Val 755 760 765 Phe Asp Ser Ala Ser Asp Pro Val Pro Leu Pro Pro Ala Arg Pro Pro 770 775 780 Thr Arg Asp Asn Pro Lys His Gly Ser Ser Leu Asn Arg Thr Pro Ser 785 790 795 800 Asp Tyr Asp Leu Leu Ile Pro Pro Leu Gly Glu Asp Ala Phe Asp Ala 805 810 815 Leu Pro Pro Ser Leu Pro Pro Pro Pro Pro Pro Ala Arg His Ser Leu 820 825 830 Ile Glu His Ser Lys Pro Pro Gly Ser Ser Ser Arg Pro Ser Ser Gly 835 840 845 Gln Asp Leu Phe Leu Leu Pro Ser Asp Pro Phe Val Asp Leu Ala Ser 850 855 860 Gly Gln Val Pro Leu Pro Pro Ala Arg Arg Leu Pro Gly Glu Asn Val 865 870 875 880 Lys Thr Asn Arg Thr Ser Gln Asp Tyr Asp Gln Leu Pro Ser Cys Ser 885 890 895

PCT/US2003/012946

Asp Gly Ser Gln Ala Pro Ala Arg Pro Pro Lys Pro Arg Pro Arg Arg 900 205 S10 Thr Ala Pro Glu Ile His His Arg Lys Pro His Gly Pro Glu Ala Ala 915 S20 825 Leu Glu Asn val Asp Ala Lys Ile Ala Lys Leu Met Gly Glu Gly Tyr 930 935 940 Ala Phe Glu Glu Val Lys Arg Ala Leu Glu Ile Ala Gln Asn Asn Val 945s 950 955 960 Glu Val Ala Arg Ser Ile Leu Arg Glu Phe Ala Phe Pro Pro Pro Val 965 S70 875 Ser Pro Arg Leu Asn Leu 980 <210> 2412 <211> 352 <212> PRT <213> Homo sapiens <400> 2412 Met Asp Tyr Gln Val Ser Ser Pro Ile Tyr Asp Ile Asn Tyr Tyr Thr 1 5 10 15 Ser Glu Pro Cys Gln Lys Ile Asn Val Lys Gln Ile Ala Ala Arg Leu

Leu Pro Pro Leu Tyr Ser Leu Val Phe Ile Phe Gly Phe val Gly Asn 3S 40 45 Met Leu Val Ile Leu Ile Leu Ile Asn Cys Lys Arg Leu Lys Ser Met 50 5S 60 Thr Asp Ile Tyr Leu Leu Asn Leu Ala Ile Ser Asp Leu Phe Phe Leu 65 70 75 80 Leu Thr Val Pro Phe Trp Ala His Tyr Ala Ala Ala Gln Trp Asp Phe 85 90 85 Gly Asn Thr Met Cys Gln Leu Leu Thr Gly Leu Tyr Phe Ile Gly Phe 100 105 110 Phe Ser Gly Ile Phe Phe Ile Ile Leu Leu Thr Ile Asp Arg Tyr Leu

. 115 120 125 Ala Val val His Ala Val Phe Ala Leu Lys Ala Arg Thr Val Thr Phe 130 135 140 Gly Val val Thr Ser val Ile Thr Trp Val Val Ala val Phe Ala Ser 145 150 155 160 Leu Pro Gly Ile Ile Phe Thr Arg Ser Gln Lys Glu Gly Leu His Tyr 165 170 175 Thr Cys Ser Ser His Phe Pro Tyr Ser Gln Tyr Gln Phe Trp Lys Asn 180 185 190 Phe Gln Thr Leu Lys Ile Val Ile Leu Gly Leu Val Leu Pro Leu Leu 195 200 205 Val Met Val Ile Cys Tyr Ser Gly Ile Leu Lys Thr Leu Leu Arg Cys 210 215 220 Arg Asn Glu Lys Lys Arg His Arg Ala Val Arg Leu Ile Phe Thr Ile 225 230 235 240 Met Ile Val Tyr Phe Leu Phe Trp Ala Pro Tyr Asn Ile Val Leu Leu 245 250 255 Leu Asn Thr Phe Gln Glu Phe Phe Gly Leu Asn Asn Cys Ser Ser Ser 260 265 270 Asn Arg Leu Asp Gln Ala Met Gln Val Thr Glu Thr Leu Gly Met Thr 275 280 285 His Cys Cys Ile Asn Pro Ile Ile Tyr Ala Phe val Gly Glu Lys Phe 290 295 300 Arg Asn Tyr Leu Leu Val Phe Phe Gln Lys His Ile Ala Lys Arg Phe 305 310 315 320 Cys Lys Cys Cys Ser Ile Phe Gln Gln Glu Ala Pro Glu Arg Ala Ser 325 330 335 Ser Val Tyr Thr Arg Ser Thr Gly Glu Gln Glu Ile Ser Val Gly Leu 340 345 350 <210> 2413 <211> 750

PCT/US2003/012946

<212> PRT <213> Homo sapiens <400> 2413 Met Gly Lys Ser Glu Ser Gln Met Asp Ile Thr Asp Ile Asn Thr Pro 1 5 10 15 Lys Pro Lys Lys Lys Gln Arg Trp Thr Arg Leu Glu Ile Ser Leu Ser val Leu Val Leu Leu Leu Thr Ile Ile Ala Val Arg Met Ile Ala Leu 40 45 Tyr Ala Thr Tyr Asp Asp Gly Ile Cys Lys Ser Ser Asp Cys Ile Lys 50 55 60 Ser Ala Ala Arg Leu Ile Gln Asn Met Asp Ala Thr Thr Glu Pro Cys 65 70 75 80 Arg Asp Phe Phe Lys Tyr Ala Cys Gly Gly Trp Leu Lys Arg Asn Val 85 90 S5 Ile Pro Glu Thr Ser Ser Arg Tyr Gly Asn Phe Asp Ile Leu Arg Asp 100 105 110 Glu Leu Glu Val val Leu Lys Asp Val Leu Gln Glu Pro Lys Thr Glu 115 120 125 Asp Ile Val Ala Val Gln Lys Ala Lys Ala Leu Tyr Arg Ser Cys Ile 130 135 140 Asn Glu Ser Ala Ile Asp Ser Arg Gly Gly Glu Pro Leu Leu Lys Leu 145 150 155 160 Leu Pro Asp Ile Tyr Gly Trp Pro Val Ala Thr Glu Asn Trp Glu Gln 165 170 175 Lys Tyr Gly Ala Ser Trp Thr Ala Glu Lys Ala Ile Ala Gln Leu Asn 180 185 190 Ser Lys Tyr Gly Lys Lys Val Leu Ile Asn Leu Phe Val Gly Thr Asp : 195 200 208 Asp Lys Asn Ser Val Asn His Val Ile His Ile Asp Gln Pro Arg Leu 210 215 220

PCT/US2003/012946

Gly Leu Pro Ser Arg Asp Tyr Tyr Glu Cys Thr Gly Ile Tyr Lys Glu 225 230 235 240 Ala Cys Thr ala Tyr Val Asp Phe Met Ile Ser val Ala Arg Leu Ile 245 250 255 Arg Gln Glu Glu Arg Leu Pro Ile Asp Glu Asn Gln Leu Ala Leu Glu 260 265 270 Met Asn Lys Val Met Glu Leu Glu Lys Glu Ile Ala Asn Ala Thr Ala 275 280 285 Lys Pro Glu Asp Arg Asn Asp Pro Met Leu Leu Tyr Asn Lys Met Arg 290 295 300 Leu Ala Gln Ile Gln Asn Asn Phe Ser Leu Glu Ile Asn Gly Lys Pro 305 310 315 320 Phe Ser Trp Leu Asn Phe Thr Asn Glu Ile Met Ser Thr Val Asn Ile 325 330 335 Ser Ile Thr Asn Glu Glu Asp Val val Val Tyr ala Pro Glu Tyr Leu 340 345 350 Thr Lys Leu Lys Pro Ile Leu Thr Lys Tyr Ser Ala Arg Asp Leu Gln 355 360 365 Asn Leu Met Ser Trp Arg Phe Ile Met Asp Leu Val Ser Ser Leu Ser 370 375 380 Arg Thr Tyr Lys Glu Ser Arg Asn Ala Phe Arg Lys Ala Leu Tyr Gly 385 390 395 400 Thr Thr Ser Glu Thr Ala Thr Trp Arg Arg Cys Ala Asn Tyr Val Asn 405 410 415 Gly Asn Met Glu Asn Ala Val Gly Arg Leu Tyr Val Glu Ala Ala Phe 420 425 430 Ala Gly Glu Ser Lys His Val Val Glu Asp Leu Ile Ala Gln Ile Arg 435 440 445 Glu val Phe Ile Gln Thr Leu Asp Asp Leu Thr Trp Met Asp Ala Glu 450 455 460 Thr Lys Lys Arg Ala Glu Glu Lys Ala Leu Ala Ile Lys Glu Arg Ile

465 470 475 480 Gly Tyr Pro Asp Asp Ile Val Ser Asn Asp Asn Lys Leu Asn Asn Glu

485 490 495 Tyr Leu Glu Leu Asn Tyr Lys Glu Asp Glu Tyr Phe Glu Asn Ile Tle 500 505 510 Gln Asn Leu Lys Phe Ser Gln Ser Lys Gln Leu Lys Lys Leu Arg Glu 515 520 525 Lys Val Asp Lys Asp Glu Trp Ile Ser Gly Ala Ala val Val Asn Ala 530 535 540 Phe Tyr Ser Ser Gly Arg Asn Gln Ile Val Phe Pro Ala Gly Ile Leu 545 550 555 560 Gln Pro Pro Phe Phe Ser Ala Gln Gln Ser Asn Ser Leu Asn Tyr Gly 565 570 575 Gly Ile Gly Met Val Ile Gly His Glu Ile Thr His Gly Phe Asp Asp 580 585 5390 Asn Gly Arg Asn Phe Asn Lys Asp Gly Asp Leu Val Asp Trp Trp Thr 595 600 60S Gln Gln Ser Ala Ser Asn Phe Lys Glu Gln Ser Gln Cys Met val Tyr 610 615 620 Gln Tyr Gly Asn Phe Ser Trp Asp Leu Ala Gly Gly Gln His Leu Asn 625 630 635 640 Gly Ile Asn Thr Leu Gly Glu Asn Ile Ala Asp Asn Gly Gly Leu Gly 645 650 655 Gln Ala Tyr Arg Ala Tyr Gln Asn Tyr Ile Lys Lys Asn Gly Glu Glu 660 665 670 Lys Leu Leu Pro Gly Leu Asp Leu Asn His Lys Gln Leu Phe Phe Leu 675 680 685 Asn Phe Ala Gln Val Trp Cys Gly Thr Tyr Arg Pro Glu Tyr Ala Val 690 695 700 Asn Ser Ile Lys Thr Asp Val His Ser Pro Gly Asn Phe Arg Ile Ile 705 710 715 720 ’ 702 : [ JE . _

Gly Thr Leu Gln Asn Ser Ala Glu Phe Ser Glu Ala Phe His Cys Arg 725 730 735 Lys Asn Ser Tyr Met Asn Pro Glu Lys Lys Cys Arg Val Trp 740 745 750 <210> 2414 <211> 233 <212> PRT <213> Homo sapiens <400> 2414 Met Asp Asn Gln Gly val Ile Tyr Ser Asp Leu Asn Leu Pro Pro Asn 1 5 10 15 Pro Lys Arg Gln Gln Arg Lys Pro Lys Gly Asn Lys Ser Ser Ile Leu

Ala Thr Glu Gln Glu Ile Thr Tyr Ala Glu Leu Asn Leu Gln Lys Ala 40 45 Ser Gln Asp Phe Gln Gly Asn Asp Lys Thr Tyr His Cys Lys Asp Leu 50 55 60 Pro Ser Ala Pro Glu Lys Leu Ile Val Gly Ile Leu Gly Ile Ile Cys 65 70 75 80 Leu Ile Leu Met Ala Ser Val Val Thr Ile val Val Ile Pro Ser Thr 85 90 95 Leu Ile Gln Arg His Asn Asn Ser Ser Leu Asn Thr Arg Thr Gln Lys 100 105 110 Ala Arg His Cys Gly His Cys Pro Glu Glu Trp Ile Thr Tyr Ser Asn 115 120 128 Ser Cys Tyr Tyr Ile Gly Lys Glu Arg Arg Thr Trp Glu Glu Ser Leu 130 135 140 Leu Ala Cys Thr Ser Lys Asn Ser Ser Leu Leu Ser Ile Asp Asn Glu Co ) 145 150 155 160 Glu Glu Met Lys Phe Leu Ser Ile Ile Ser Pro Ser Ser Trp Ile Gly 165 170 175

Val Phe Arg Asn Ser Ser His His Pro Trp Val Thr Met Asn Gly Leu 180 185 150 Ala Phe Lys His Glu Ile Lys Asp Ser Asp Asn Ala Glu Leu Asn Cys 195 200 205 Ala Val Leu Gln Val Asn Arg Leu Lys Ser Ala Gln Cys Gly Ser Ser 210 215 220 Ile Ile Tyr His Cys Lys His Lys Leu 225 230 <210> 2415 <211l> 290 <212> PRT <213> Homo sapiens <400> 2415 . Met Gly Gly Gly Ala Gly Glu Arg Leu Phe Thr Ser Ser Cys Leu Val 1 5 10 15 Gly Leu Val Pro Leu Gly Leu Arg Ile Ser Leu Val Thr Cys Pro Leu

Gln Cys Gly Ile Met Trp Gln Leu Leu Leu Pro Thr Ala Leu Leu Leu 40 45 Leu Val Ser Ala Gly Met Arg Thr Glu Asp Leu Pro Lys Ala Val val 50 55 60 Phe Leu Glu Pro Gln Trp Tyr Arg Val Leu Glu Lys Asp Ser Val Thr 65 70 75 80 Leu Lys Cys Gln Gly Ala Tyr Ser Pro Glu Asp Asn Ser Thr Gln Trp 85 90 95 Phe His Asn Glu Ser Leu Ile Ser Ser Gln Ala Ser Ser Tyr Phe Ile 100 105 110 Asp Ala Ala Thr Val Asp Asp Ser Gly Glu Tyr Arg Cys Gln Thr Asn 115 120 125 Leu Ser Thr Leu Ser Asp Pro Val Gln Leu Glu Val His Ile Gly Trp 130 13s 140 Leu Leu Leu Gln Ala Pro Arg Trp Val Phe Lys Glu Glu Asp Pro Ile 145 150 155 160

PCT/US2003/012946

His Leu Arg Cys His Ser Trp Lys Asn Thr Ala Leu His Lys val Thr 165 170 175 Tyr Leu Gln Asn Gly Lys Gly Arg Lys Tyr Phe His His Asn Ser Asp 180 185 190 Phe Tyr Ile Pro Lys Ala Thr Leu Lys Asp Ser Gly Ser Tyr phe Cys 1385 200 205 Arg Gly Leu Val Gly Ser Lys Asn Val Ser Ser Glu Thr Val Asn Ile 210 215 220 Thr Ile Thr Gln Gly Leu Ala Val Ser Thr Ile Ser Ser Phe Phe Pro 225 230 235 240 Pro Gly Tyr Gln Val Ser Phe Cys Leu Val Met Val Leu Leu Phe Ala 245 250 255 Val Asp Thr Gly Leu Tyr Phe Ser Val Lys Thr Asn Ile Arg Ser Ser 260 265 270 Thr Arg Asp Trp Lys Asp His Lys Phe Lys Trp Arg Lys Asp Pro Gln 275 280 285 Asp Lys 290 <210> 2416 <211l> 233 <212> PRT <213> Homo sapiens <400> 2416 Met Trp Gln Leu Leu Leu Pro Thr Ala Leu Leu Leu Leu Val Ser Ala 1 5 10 15 Gly Met Arg Thr Glu Asp Leu Pro Lys Ala Val Val Phe Leu Glu Pro

Gln Trp Tyr Ser Val Leu Glu Lys Asp Ser Val Thr Leu Lys Cys Gln 40 45 Gly Ala Tyr Ser Pro Glu Asp Asn Ser Thr Gin Trp Phe His Asn Glu 50 55 60 ser Leu Ile Ser Ser Gln Ala Ser Ser Tyr Phe Ile Asp Ala Ala Thr 65 70 75 80 val Asn Asp Ser Gly Glu Tyr Arg Cys Gln Thr Asn Leu Ser Thr Leu

85 90 95 Ser Asp Pro Val Gln Leu Glu Val His Ile Gly Trp Leu Leu Leu Gln 100 105 110 Ala Pro Arg Trp Val Phe Lys Glu Glu Asp Pro Ile His Leu Arg Cys 115 120 125 His Ser Trp Lys Asn Thr Ala Leu His Lys Val Thr Tyr Leu Gln Asn 130 135 140 Gly Lys Asp Arg Lys Tyr Phe His His Asn Ser Asp Phe His Ile Pro 145 150 155 160 Lys Ala Thr Leu Lys Asp Ser Gly Ser Tyr Phe Cys Arg Gly Leu Val 165 170 17S Gly Ser Lys Asn Val Ser Ser Glu Thr Val Asn Ile Thr Ile Thr Gln 180 185 190 Gly Leu Ala Val Ser Thr Ile Ser Ser Phe Ser Pro Pro Gly Tyr Gln 195 200 205 Val Ser Phe Cys Leu Val Met Val Leu Leu Phe Ala Val Asp Thr Gly 210 215 220 Leu Tyr Phe Ser Val Lys Thr Asn Ile 225 230 <210> 2417 <211> 525 <212> PRT <213> Homo sapiens <400> 2417 Met Trp Glu Ala Gln Phe Leu Gly Leu Leu Phe Leu Gln Pro Leu Trp 1 S 10 15 val Ala Pro Val Lys Pro Leu Gln Pro Gly Ala Glu Val Pro Val Val

Trp Ala Gln Glu Gly Ala Pro Ala Gln Leu Pro Cys Ser Pro Thr Ile 40 45

Pro Leu Gln Asp Leu Ser Leu Leu Arg Arg Ala Gly val Thr Trp Gln 50 55 60 His Gln Pro Asp Ser Gly Pro Pro Ala Ala Ala Pro Gly His Pro Leu €5 70 75 80 Ala Pro Gly Pro His Pro Ala Ala Pro Ser Ser Trp Gly Pro Arg Pro 85 90 95 Arg Arg Tyr Thr Val Leu Ser Val Gly Pro Gly Gly Leu Arg Ser Gly 100 105 110 Arg Leu Pro Leu Gln Pro Arg Val Gln Leu Asp Glu Arg Gly Arg Gln 115 120 125 Arg Gly Asp Phe Ser Leu Trp Leu Arg Pro Ala Arg Arg Ala Asp Ala 130 135 140 Gly Glu Tyr Arg Ala Ala Val His Leu Arg Asp Arg Ala Leu Ser Cys 145 150 155 160 Arg Leu Arg Leu Arg Leu Gly Gln Ala Ser Met Thr Ala Ser Pro Pro 165 170 175 Gly Ser Leu Arg Ala Ser Asp Trp Val Ile Leu Asn Cys Ser Phe Ser 180 185 150 Arg Pro Asp Arg Pro Ala Ser Val His Trp Phe Arg Asn Arg Gly Gln 195 200 205 Gly Arg Val Pro Val Arg Glu Ser Pro His His His Leu Ala Glu Ser 210 215 220 Phe Leu Phe Leu Pro Gln Val Ser Pro Met Asp Ser Gly Pro Trp Gly 225 230 235 240 Cys Ile Leu Thr Tyr Arg Asp Gly Phe Asn Val Ser Ile Met Tyr Asn 245 250 255 Leu Thr Val Leu Gly Leu Glu Pro Pro Thr Pro Leu Thr Val Tyr Ala 260 265 270 Gly Ala Gly Ser Arg Val Gly Leu Pro Cys Arg Leu Pro Ala Gly Val 275 280 285

Gly Thr Arg Ser Phe Leu Thr Ala Lys Trp Thr Pro Pro Gly Gly Gly 290 . 295 300 Pro Asp Leu Leu Val Thr Gly Asp Asn Gly Asp Phe Thr Leu Arg Leu 305 310 315 320 Glu Asp Val Ser Gln Ala Gln Ala Gly Thr Tyr Thr Cys His Ile His 325 330 33S Leu Gln Glu Gln Gln Leu Asn Ala Thr Val Thr Leu Ala Ile Ile Thr 340 345 350 Val Thr Pro Lys Ser Phe Gly Ser Pro Gly Ser Leu Gly Lys Leu Leu 355 360 365 Cys Glu Val Thr Pro Val Ser Gly Gln Glu Arg Phe Val Trp Ser Ser 370 ’ 375 - 380 Leu Asp Thr Pro Ser Gln Arg Ser Phe Ser Gly Pro Trp Leu Glu Ala 385 380 395 400 Gln Glu Ala Gln Leu Leu Ser Gln Pro Trp Gln Cys Gln Leu Tyr Gln 405 410 415 Gly Glu Arg Leu Leu Gly Ala Ala Val Tyr Phe Thr Glu Leu Ser Ser 420 425 430 Pro Gly Ala Gln Arg Ser Gly Arg Ala Pro Gly Ala Leu Pro Ala Gly 435 440 445 His Leu Leu Leu Phe Leu Thr Leu Gly val Leu Ser Leu Leu Leu Leu 450 455 460 val Thr Gly Ala Phe Gly Phe His Leu Trp Arg Arg Gln Trp Arg Pro 465 470 475 480 Arg Arg Phe Ser Ala Leu Glu Gln Gly Ile His Pro Pro Gln Ala Gln 485 490 495 Ser Lys Ile Glu Glu Leu Glu Gln Glu Pro Glu Pro Glu Pro Glu Pro 500 505 510 Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu Gln Leu 515 520 525

<210> 2418 <211> 738 <212> PRT <213> Homo sapiens <400> 2418 Met Gln Pro Arg Trp Ala Gln Gly Ala Thr Met Trp Leu Gly Val Leu 1 5 10 15 Leu Thr Leu Leu Leu Cys Ser Ser Leu Glu Gly Gln Glu Asn Ser Phe

Thr Ile Asn Ser Val Asp Met Lys Ser Leu Pro Asp Trp Thr Val Gln 40 45 Asn Gly Lys Asn Leu Thr Leu Gln Cys Phe Ala Asp Val Ser Thr Thr 50 55 60 Ser His Val Lys Pro Gln His Gln Met Leu Phe Tyr Lys Asp Asp Val 65 70 75 80 Leu Phe Tyr Asn Ile Ser Ser Met Lys Ser Thr Glu Ser Tyr Phe Ile 85 90 95 Pro Glu Val Arg Ile Tyr Asp Ser Gly Thr Tyr Lys Cys Thr Val Ile 100 105 110 Val Asn Asn Lys Glu Lys Thr Thr Ala Glu Tyr Gln Val Leu Val Glu 115 120 125 Gly Val Pro Ser Pro Arg Val Thr Leu Asp Lys Lys Glu Ala Ile Gln 130 135 140 Gly Gly Ile Val Arg Val Asn Cys Ser Val Pro Glu Glu Lys Ala Pro 145 150 155 160 Ile His Phe Thr Ile Glu Lys Leu Glu Leu Asn Glu Lys Met Val Lys 165 170 175 Leu Lys Arg Glu Lys Asn Ser Arg Asp Gln Asn Phe Val Ile Leu Glu 180 18S 190 Phe Pro Val Glu Glu Gln Asp Arg Val Leu Ser Phe Arg Cys Gln Ala 195 200 205 Arg Ile Ile Ser Gly Ile His Met Gln Thr Ser Glu Ser Thr Lys Ser 210 215 220

Glu Leu Val Thr val Thr Glu Ser Phe Ser Thr Pro Lys Phe His Ile 225 230 235 240 Ser Pro Thr Gly Met Ile Met Glu Gly Ala Gln Leu His Ile Lys Cys

245 250 255 Thr Ile Gln Val Thr His Leu Ala Gln Glu Phe Pro Glu Ile Ile Ile 260 265 270 Gln Lys Asp Lys Ala Ile Val Ala His Asn Arg His Gly Asn Lys Ala 275 280 285 Val Tyr Ser Val Met Ala Met Val Glu His Ser Gly Asn Tyr Thr Cys 290 295 300 Lys Val Glu Ser Ser Arg Ile Ser Lys Val Ser Ser Ile Val Val Asn 305 310 315 320 Ile Thr Glu Leu Phe Ser Lys Pro Glu Leu Glu Ser Ser Phe Thr His 325 330 335 Leu Asp Gln Gly Glu Arg Leu Asn Leu Ser Cys Ser Ile Pro Gly Ala 340 345 350 Pro Pro Ala Asn Phe Thr Ile Gln Lys Glu Asp Thr Ile Val Ser Gln 355 360 365 Thr Gln Asp Phe Thr Lys Ile Ala Ser Lys Ser Asp Ser Gly Thr Tyr 370 375 380 Ile Cys Thr Ala Gly Ile Asp Lys Val Val Lys Lys Ser Asn Thr Val 385 390 395 : 400 Gln Ile Val val Cys Glu Met Leu Ser Gln Pro Arg Ile Ser Tyr Asp 405 410 415 Ala Gln Phe Glu Val Ile Lys Gly Gln Thr Ile Glu Val Arg Cys Glu 420 425 430 Ser Ile Ser Gly Thr Leu Pro Ile Ser Tyr Gln Leu Leu Lys Thr Ser 435 440 445 Lys Val Leu Glu Asn Ser Thr Lys Asn Ser Asn Asp Pro Ala Val Phe 450 455 460

Lys Asp Asn Pro Thr Glu Asp Val Glu Tyr Gln Cys Val Ala Asp Asn 465 470 475 480 Cys His Ser His Ala Lys Met Leu Ser Glu Val Leu Arg Val Lys val 485 490 495 Ile Ala Pro val Asp Glu Val Gln Ile Ser Ile Leu Ser Ser Lys Val 500 505 510 Val Glu Ser Gly Glu Asp Ile Val Leu Gln Cys Ala Val Asn Glu Gly 515 520 525 Ser Gly Pro Ile Thr Tyr Lys Phe Tyr Arg Glu Lys Glu Gly Lys Pro 530 535 540 Phe Tyr Gln Met Thr Ser Asn Ala Thr Gln Ala Phe Trp Thr Lys Gln 545 550 555 560 Lys Ala Asn Lys Glu Gln Glu Gly Glu Tyr Tyr Cys Thr Ala Phe Asn 565 570 575 Arg Ala Asn His Ala Ser Ser Val Pro Arg Ser Lys Ile Leu Thr Val 580 585 590 Arg Val Ile Leu Ala Pro Trp Lys Lys Gly Leu Ile Ala Val val Ile 595 600 605 Ile Gly Val Ile Ile Ala Leu Leu Ile Ile Ala Ala Lys Cys Tyr Phe 610 615 620 Leu Arg Lys Ala Lys Ala Lys Gln Met Pro Val Glu Met Ser Arg Pro 625 630 635 640 Ala Val Pro Leu Leu Asn Ser Asn Asn Glu Lys Met Ser Asp Pro Asn 645 650 655 Met Glu Ala Asn Ser His Tyr Gly His Asn Asp Asp Val Gly Asn His 660 665 670 Ala Met Lys Pro Ile Asn Asp Asn Lys Glu Pro Leu Asn Ser Asp Val 675 680 685 Gln Tyr Thr Glu Val Gln Val Ser Ser Ala Glu Ser His Lys Asp Leu €90 695 700

Gly Lys Lys Asp Thr Glu Thr Val Tyr Ser Glu val Arg Lys Ala val 705 710 715 720 Pro Asp Ala Val Glu Ser Arg Tyr Ser Arg Thr Glu Gly Ser Leu Asp 725 730 735

Gly Thr

<210> 2419 .

<211> 328

<212> PRT

<213> Homo sapiens

<400> 2419

Met Leu Val Arg Arg Gly Ala Arg Ala Gly Pro Arg Met Pro Arg Gly 1 5 10 15

Trp Thr Ala Leu Cys Leu Leu Ser Leu Leu Pro Ser Gly Phe Met Ser

Leu Asp Asn Asn Gly Thr Ala Thr Pro Glu Leu Pro Thr Gln Gly Thr 40 45 Phe Ser Asn Val Ser Thr Asn Val Ser Tyr Gln Glu Thr Thr Thr Pro 50 55 60 Ser Thr Leu Gly Ser Thr Ser Leu His Pro Val Ser Gln His Gly Asn 65 70 75 80 Glu Ala Thr Thr Asn Ile Thr Glu Thr Thr Val Lys Phe Thr Ser Thr 8S 90 95 Ser Val Ile Thr Ser Val Tyr Gly Asn Thr Asn Ser Ser Val Gln Ser 100 105 110 Gln Thr Ser Val Ile Ser Thr val Phe Thr Thr Pro Ala Asn Val Sex 115 120 125 Thr Pro Glu Thr Thr Leu Lys Pro Ser Leu Ser Pro Gly Asn Val Ser 130 135 140 Asp Leu Ser Thr Thr Ser Thr Ser Leu Ala Thr Ser Pro Thr Lys Pro 145 150 155 160 Tyr Thr Ser Ser Ser Pro Ile Leu Ser Asp Ile Lys Ala Glu Ile Lys 165 170 175

PCT/US2003/012946

Cys Ser Gly Ile Arg Glu Val Lys Leu Thr Gln Gly Ile Cys Leu Glu 180 185 190 Gln Asn Lys Thr Ser Ser Cys Ala Glu Phe Lys Lys Asp Arg Gly Glu 195 200 205 Gly Leu Ala Arg Val Leu Cys Gly Glu Glu Gln Ala Asp Ala Asp Ala 210 215 220 Gly Ala Gln Val Cys Ser Leu Leu Leu Ala Gln Ser Glu Val Arg Pro 225 230 235 240 Gln Cys Leu Leu Leu Val Leu Ala Asn Arg Thr Glu Ile Ser Ser Lys 245 250 255 Leu Gln Leu Met Lys Lys His Gln Ser Asp Leu Lys Lys Leu Gly Ile 260 265 270 Leu Asp Phe Thr Glu Gln Asp Val Ala Ser His Gln Ser Tyr Ser Gln 275 280 285 Lys Thr Leu Ile Ala Leu Val Thr Ser Gly Ala Leu Leu Ala Val Leu 290 295 300 Gly Ile Thr Gly Tyr Phe Leu Met Asn Arg Arg Ser Trp Ser Pro Thr 305 310 315 320 Gly Glu Arg Leu Glu Leu Glu Pro 325 <210> 2420 <211> 374 <212> PRT <213> Homo sapiens <400> 2420 Met Trp Phe Leu Thr Thr Leu Leu Leu Trp Val Pro Val Asp Gly Gln 1 5 10 15 Val Asp Thr Thr Lys Ala Val Ile Thr Leu Gln Pro Pro Trp Val Ser

Val Phe Gln Glu Glu Thr Val Thr Leu His Cys Glu val Leu His Leu 40 45 - T13

PCT/US2003/012946

Pro Gly Ser Ser Ser Thr Gln Trp Phe Leu Asn Gly Thr Ala Thr Gln 50 SS 60 Thr Ser Thr Pro Ser Tyr Arg Ile Thr Ser Ala Ser Val Asn Asp Ser 65 70 75 80 Gly Glu Tyr Arg Cys Gln Arg Gly Leu Ser Gly Arg Ser Asp Pro Ile 85 90 95 Gln Leu Glu Ile His Arg Gly Trp Leu Leu Leu Gln Val Ser Ser Arg 100 105 110 Val Phe Thr Glu Gly Glu Pro Leu Ala Leu Arg Cys His Ala Trp Lys 115 120 125 Asp Lys Leu Val Tyr Asn Val Leu Tyr Tyr Arg Asn Gly Lys Ala Phe 130 135 140 Lys Phe Phe His Trp Asn Ser Asn Leu Thr Ile Leu Lys Thr Asn Ile 145 150 155 160 Ser His Asn Gly Thr Tyr His Cys Ser Gly Met Gly Lys His Arg Tyr 165 170 175 Thr Ser Ala Gly Ile Ser Val Thr Val Lys Glu Leu Phe Pro Ala Pro 180 185 190 Val Leu Asn Ala Ser Val Thr Ser Pro Leu Leu Glu Gly Asn Leu Val 195 200 205 Thr Leu Ser Cys Glu Thr Lys Leu Leu Leu Gln Arg Pro Gly Leu Gln 210 215 220 Leu Tyr Phe Ser Phe Tyr Met Gly Ser Lys Thr Leu Arg Gly Arg Asn 225 230 235 240 Thr Ser Ser Glu Tyr Gln Ile Leu Thr Ala Arg Arg Glu Asp Ser Gly 245 250 255 Leu Tyr Trp Cys Glu Ala Ala Thr Glu Asp Gly Asn Val Leu Lys Arg 260 265 270 Ser Pro Glu Leu Glu Leu Gln Val Leu Gly Leu Gln Leu Pro Thr Pro 275 280 28S Val Trp Phe His Val Leu Phe Tyr Leu Ala Val Gly Ile Met Phe Leu

2380 295 300 Val Asn Thr val Leu Trp Val Thr Ile Arg Lys Glu Leu Lys Arg Lys 305 310 315 320 Lys Lys Trp Asp Leu Glu Ile Ser Leu Asp Ser Gly His Glu Lys Lys 325 330 335 Val Ile Ser Ser Leu Gln Glu Asp Arg His Leu Glu Glu Glu Leu Lys 340 345 350 Cys Gln Glu Gln Lys Glu Glu Gln Leu Gln Glu Gly val His Arg Lys 355 360 365 Glu Pro Gln Gly Ala Thr 370 <210> 2421 <211> 760 <212> PRT <213> Homo sapiens <400> 2421 Met Met Asp Gln Ala Arg Ser Ala Phe Ser Asn Leu Phe Gly Gly Glu 1 5 10 15 Pro Leu Ser Tyr Thr Arg Phe Ser Leu Ala Arg Gln Val Asp Gly Asp

Asn Ser His Val Glu Met Lys Leu Ala Val Asp Glu Glu Glu Asn Ala 40 45 Asp Asn Asn Thr Lys Ala Asn Val Thr Lys Pro Lys Arg Cys Ser Gly 50 55 60 Ser Ile Cys Tyr Gly Thr Ile Ala Val Ile Val Phe Phe Leu Ile Gly 65 70 75 80 Phe Met Ile Gly Tyr Leu Gly Tyr Cys Lys Gly Val Glu Pro Lys Thr 85 90 95 Glu Cys Glu Arg Leu Ala Gly Thr Glu Ser Pro Val Arg Glu Glu Pro 100 105 110 Gly Glu Asp Phe Pro Ala Ala Arg Arg Leu Tyr Trp Asp Asp Leu Lys 115 120 125 715

Arg Lys Leu Ser Glu Lys Leu Asp Ser Thr Asp Phe Thr Ser Thr Ile 130 138 140 Lys Leu Leu Asn Glu Asn Ser Tyr Val Pro Arg Glu Ala Gly Ser Gln 145 150 155 160 Lys Asp Glu Asn Leu Ala Leu Tyr Val Glu Asn Gln Phe Arg Glu Phe 16S 170 175 Lys Leu Ser Lys Val Trp Arg Asp Gln His Phe Val Lys Ile Gln Val 180 185 150 Lys Asp Ser Ala Gln Asn Ser Val Ile Ile Val Asp Lys Asn Gly Arg 19S 200 205 Leu Val Tyr Leu Val Glu Asn Pro Gly Gly Tyr val Ala Tyr Ser Lys 210 21s 220 Ala Ala Thr Val Thr Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys 225 230 23s 240 Lys Asp Phe Glu Asp Leu Tyr Thr Pro Val Asn Gly Ser Ile Val Ile 245 250 2585 Val Arg Ala Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu 260 265 270 Ser Leu Asn Ala Ile Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe 275 280 285% Pro Ile Val Asn Ala Glu Leu Ser Phe Phe Gly His Ala His Leu Gly 290 285 300 Thr Gly Asp Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln 305 310 315 320 Phe Pro Pro Ser Arg Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr 325 330 335 Ile Ser Arg Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp 340 345 350 Cys Pro Ser Asp Trp Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser 358 360 365

T/US2003/012946

Glu Ser Lys Asn val Lys Leu Thr Val Ser Asn val Leu Lys Glu Ile 370 375 380

Lys Ile Leu Asn Ile Phe Gly val Ile Lys Gly Phe val Glu Pro Asp

38S 380 385 400

His Tyr val val val Gly Ala Gln Arg Asp Ala Trp Gly Pro Gly Ala

405 410 415 Ala Lys Ser Gly Val Gly Thr Ala Leu Leu Leu Lys Leu Ala Gln Met 420 425 430 Phe Ser Asp Met Val Leu Lys Asp Gly Phe Gln Pro Ser Arg Ser Ile 435 440 445 Ile Phe Ala Ser Trp Ser Ala Gly Asp Phe Gly ser val Gly Ala Thr 450 455 . 460

Glu Trp Leu Glu Gly Tyr Leu Ser Ser leu His Leu Lys Ala Phe Thr

465 470 475 480 . Tyr Ile Asn Leu Asp Lys Ala Val Leu Gly Thr Ser Asn Phe Lys val ’

485 490 495 Ser Ala Ser Pro Leu Leu Tyr Thr Leu Ile Glu Lys Thr Met Gln Asn 500 S05 510 Val Lys His Pro Val Thr Gly Gln Phe Leu Tyr Gln Asp Ser Asn Trp 515 520 525 Ala Ser Lys val Glu Lys Leu Thr Leu Asp Asn Ala Ala Phe Pro Phe 530 535 540

Leu Ala Tyr Ser Gly Ile Pro Ala Val Ser Phe Cys Phe Cys Glu Asp

545 550 555 560

Thr Asp Tyr Pro Tyr Leu Gly Thr Thr Met Asp Thr Tyr Lys Glu Leu

565 570 575 Ile Glu Arg Ile Pro Glu Leu Asn Lys Val Ala Arg Ala Ala Ala Glu 580 585 590 Val Ala Gly Gln Phe Val Ile Lys Leu Thr His Asp Val Glu Leu Asp 5385 600 605 Leu Asp Tyr Glu Arg Tyr Asn Ser Gln Leu Leu Ser Phe Val Arg Asp 717

610 615 620 Leu Asn Gln Tyr Arg Ala Asp Ile Lys Glu Met Gly Leu Ser Leu Gln 625 630 635 640 Trp Leu Tyr Ser Ala Arg Gly Asp Phe Phe Arg Ala Thr Ser Arg Leu 645 650 655 Thr Thr Asp Phe Gly Asn Ala Glu Lys Thr Asp Arg Phe Val Met Lys 660 665 670 Lys Leu Asn Asp Arg Val Met Arg Val Glu Tyr His Phe Leu Ser Pro 675 680 685 Tyr Val Ser Pro Lys Glu Ser Pro Phe Arg His Val Phe Trp Gly Ser 690 695 700 Gly Ser His Thr Leu Pro Ala Leu Leu Glu Asn Leu Lys Leu Arg Lys 705 710 715 720 Gln Asn Asn Gly Ala Phe Asn Glu Thr Leu Phe Arg Asn Gln Leu Ala 725 730 735 Leu Ala Thr Trp Thr Ile Gln Gly Ala Ala Asn Ala Leu Ser Gly Asp 740 745 750 Val Trp Asp Ile Asp Asn Glu Phe 755 760 <210> 2422 <211> 247 <212> PRT <213> Homo sapiens <400> 2422 Met Leu Leu Leu Pro Leu Pro Leu Leu Leu Phe Leu Leu Cys Ser Arg 1 5 10 15 Ala Glu Ala Gly Glu Ile Ile Gly Gly Thr Glu Cys Lys Pro His Ser

Arg Pro Tyr Met Ala Tyr Leu Glu Ile Val Thr Ser Asn Gly Pro Ser 40 45 Lys Phe Cys Gly Gly Phe Leu lle Arg Arg Asn Phe val Leu Thr Ala 50 55 60

Ala His Cys Ala Gly Arg Ser Ile Thr Val Thr Leu Gly Ala His Asn 65 70 75 80 Ile Thr Glu Glu Glu Asp Thr Trp Gln Lys Leu Glu val Ile Lys Gln 85 90 9s Phe Arg His Pro Lys Tyr Asn Thr Ser Thr Leu His His Asp Ile Met 100 105 110 Leu Leu Lys Leu Lys Glu Lys Ala Ser Leu Thr Leu Ala Val Gly Thr 115 120 125 Leu Pro Phe Pro Ser Gln Phe Asn Phe Val Pro Pro Gly Arg Met Cys 130 135 140 Arg Val Ala Gly Trp Gly Arg Thr Gly Val Leu Lys Pro Gly Ser Asp 145 150 155 160 Thr Leu Gln Glu Val Lys Leu Arg Leu Met Asp Pro Gln Ala Cys Ser 165 170 175 His Phe Arg Asp Phe Asp His Asn Leu Gln Leu Cys Val Gly Asn Pro 180 185 150 Arg Lys Thr Lys Ser Ala Phe Lys Gly Asp Ser Gly Gly Pro Leu Leu : 1395 200 205 Cys Ala Gly Val Ala Gln Gly Ile Val Ser Tyr Gly Arg Ser Asp Ala 210 215 220 Lys Pro Pro Ala Val Phe Thr Arg Ile Ser His Tyr Arg Pro Trp Ile 225 230 235 240 Asn Gln Ile Leu Gln Ala Asn 245 <210> 2423 <211l> 976 <212> PRT <213> Homo sapiens <400> 2423 Met Arg Gly Ala Arg Gly Ala Trp Asp Phe Leu Cys Val Leu Leu Leu 1 5 10 15 Leu Leu Arg Val Gln Thr Gly Ser Ser Gln Pro Ser Val Ser Pro Gly

Glu Pro Ser Pro Pro Ser Ile His Pro Gly Lys Ser Asp Leu Ile val 40 45 Arg Val Gly Asp Glu Ile Arg Leu Leu Cys Thr Asp Pro Gly Phe val 50 55 60 Lys Trp Thr Phe Glu Ile Leu Asp Glu Thr Asn Glu Asn Lys Gln Asn 65 70 75 80 Glu Trp Ile Thr Glu Lys Ala Glu Ala Thr Asn Thr Gly Lys Tyr Thr 85 90 95 Cys Thr Asn Lys His Gly Leu Ser Asn Ser Ile Tyr Val Phe Val Arg 100 105 110 Asp Pro Ala Lys Leu Phe Leu Val Asp Arg Ser Leu Tyr Gly Lys Glu 115 120 125 Asp Asn Asp Thr Leu Val Arg Cys Pro Leu Thr Asp Pro Glu Val Thr 130 135 140 Asn Tyr Ser Leu Lys Gly Cys Gln Gly Lys Pro Leu Pro Lys Asp Leu 145 150 155 160 Arg Phe Ile Pro Asp Pro Lys Ala Gly Ile Met Ile Lys Ser Val Lys 165 170 175 Arg Ala Tyr His Arg Leu Cys Leu His Cys Ser Val Asp Gln Glu Gly 180 185 150 Lys Ser Val Leu Ser Glu Lys Phe Ile Leu Lys Val Arg Pro Ala Phe 185 200 205 Lys Ala Val Pro Val Val Ser Val Ser Lys Ala Ser Tyr Leu Leu Arg 210 215 220 Glu Gly Glu Glu Phe Thr val Thr Cys Thr Ile Lys Asp Val Ser Ser 225 230 235 240 Ser Val Tyr Ser Thr Trp Lys Arg Glu Asn Ser Gln Thr Lys Leu Gln 245 250 255 Glu Lys Tyr Asn Sex Trp His His Gly Asp Phe Asn Tyr Glu Arg Gln 260 265 270

012946

Ala Thr Leu Thr Ile Ser Ser Ala Arg Val Asn Asp Ser Gly Val Phe 275% 280 285 Met Cys Tyr Ala Asn Asn Thr Phe Gly Ser Ala Asn val Thr Thr Thr 290 295 300 Leu Glu Val val Asp Lys Gly Phe Ile Asn Ile Phe Pro Met Ile Asn 305 310 315 320 Thr Thr Val Phe Val Asn Asp Gly Glu Asn Val Asp Leu Ile Val Glu 325 330 335 Tyr Glu Ala Phe Pro Lys Pro Glu His Gln Gln Trp Ile Tyr Met Asn 340 345 350 Arg Thr Phe Thr Asp Lys Trp Glu Asp Tyr Pro Lys Ser Glu Asn Glu 355 360 365 Ser Asn Ile Arg Tyr Val Ser Glu Leu His Leu Thr Arg Leu Lys Gly 370 375 380 Thr Glu Gly Gly Thr Tyr Thr Phe Leu Val Ser Asn Ser Asp Val Asn 385 390 395 400 Ala Ala Ile Ala Phe Asn Val Tyr Val Asn Thr Lys Pro Glu Ile Leu 405 410 415 Thr Tyr Asp Arg Leu Val Asn Gly Met Leu Gln Cys Val Ala Ala Gly 420 425 430 Phe Pro Glu Pro Thr Ile Asp Trp Tyr Phe Cys Pro Gly Thr Glu Gln 435 440 445 A Arg Cys Ser Ala Ser Val Leu Pro val Asp Val Gln Thr Leu Asn Ser 450 455 460 Ser Gly Pro Pro Phe Gly Lys Leu Val Val Gln Ser Ser Ile Asp Ser 465 470 475 480 Ser Ala Phe Lys His Asn Gly Thr Val Glu Cys Lys Ala Tyr Asn Asp 485 490 495 Val Gly Lys Thr Ser Ala Tyr Phe Asn Phe Ala Phe Lys Gly Asn Asn 500 505 510

Lys Glu Gln Ile His Pro His Thr Leu Phe Thr Pro Leu Leu Ile Gly 515 520 525 Phe Val Ile val Ala Gly Met Met Cys Ile Ile Val Met Ile Leu Thr 530 535 540 Tyr Lys Tyr Leu Gln Lys Pro Met Tyr Glu Val Gln Trp Lys Val val 545 550 555 560 Glu Glu Ile Asn Gly Asn Asn Tyr Val Tyr Ile Asp Pro Thr Gln Leu 565 570 575 Pro Tyr Asp His Lys Trp Glu Phe Pro Arg Asn Arg Leu Ser Phe Gly 580 585 580 Lys Thr Leu Gly Ala Gly Ala Phe Gly Lys Val Val Glu Ala Thr Ala 595 600 605 Tyr Gly Leu Ile Lys Ser Asp Ala Ala Met Thr Val Ala Val Lys Met 610 615 620 Leu Lys Pro Ser Ala His Leu Thr Glu Arg Glu Ala Leu Met Ser Glu 625 630 635 640 Leu Lys Val Leu Ser Tyr Leu Gly Asn His Met Asn Ile Val Asn Leu 645 650 655 Leu Gly Ala Cys Thr Ile Gly Gly Pro Thr Leu Val Ile Thr Glu Tyr 660 665 670 Cys Cys Tyr Gly Asp Leu Leu Asn Phe Leu Arg Arg Lys Arg Asp Ser 675 680 685 Phe Ile Cys Ser Lys Gln Glu Asp His Ala Glu Ala Ala Leu Tyr Lys 690 695 700 Asn Leu Leu His Ser Lys Glu Ser Ser Cys Ser Asp Ser Thr Asn Glu 705 710 715 720 Tyr Met Asp Met Lys Pro Gly Val Ser Tyr Val Val Pro Thr Lys Ala 725 730 735 Asp Lys Arg Arg Ser Val Arg Ile Gly Ser Tyr Ile Glu Arg Asp Val 740 745 750

Thr Pro Ala Ile Met Glu Asp Asp Glu Leu Ala Leu Asp Leu Glu Asp 755 760 765 Leu Leu Ser Phe Ser Tyr Gln Val Ala Lys Gly Met Ala Phe Leu Ala 770 775 780 Ser Lys Asn Cys Ile His Arg Asp Leu Ala Ala Arg Asn Ile Leu Leu 785 790 795 800 Thr His Gly Arg Ile Thr Lys Ile Cys Asp Phe Gly Leu Ala Arg Asp 805 810 815 Ile Lys Asn Asp Ser Asn Tyr Val Val Lys Gly Asn Ala Arg Leu Pro 820 825 830 Val Lys Trp Met Ala Pro Glu Ser Ile Phe Asn Cys Val Tyr Thr Phe 835 840 845 Glu Ser Asp Val Trp Ser Tyr Gly Ile Phe Leu Trp Glu Leu Phe Ser 850 855 860 Leu Gly Ser Ser Pro Tyr Pro Gly Met Pro Val Asp Ser Lys Phe Tyr 865 870 875 880 Lys Met Ile Lys Glu Gly Phe Arg Met Leu Ser Pro Glu His Ala Pro 885 890 895 Ala Glu Met Tyr Asp Ile Met Lys Thr Cys Trp Asp Ala Asp Pro Leu 900 905 910 Lys Arg Pro Thr Phe Lys Gln Ile Val Gln Leu Ile Glu Lys Gln Ile 915 920 925 Ser Glu Ser Thr Asn His Ile Tyr Ser Asn Leu Ala Asn Cys Ser Pro 930 935 940 Asn Arg Gln Lys Pro Val Val Asp His Ser Val Arg Ile Asn Ser Val 945 950 955 960 Gly Ser Thr Ala Ser Ser Ser Gln Pro Leu Leu Val His Asp Asp Val 965 970 975 <210> 2424 <211> 635 <212> PRT <213> Homo sapiens 723

<400> 2424 Met Pro Ser Trp Ala Leu Phe Met Val Thr Ser Cys Leu Leu Leu Ala 1 5 10 15 Pro Gln Asn Leu Ala Gln Val Ser Ser Gln Asp Val Ser Leu Leu Ala

Ser Asp Ser Glu Pro Leu Lys Cys Phe Ser Arg Thr Phe Glu Asp Leu 40 45 Thr Cys Phe Trp Asp Glu Glu Glu Ala Ala Pro Ser Gly Thr Tyr Gln 50 SS 60 Leu Leu Tyr Ala Tyr Pro Arg Glu Lys Pro Arg Ala Cys Pro Leu Ser 65 70 75 80 Ser Gln Ser Met Pro His Phe Gly Thr Arg Tyr Val Cys Gln Phe Pro 85 90 95 Asp Gln Glu Glu Val Arg Leu Phe Phe Pro Leu His Leu Trp Val Lys 100 105 110 Asn Val Phe Leu Asn Gln Thr Arg Thr Gln Arg Val Leu Phe Val Asp 115 120 125 Ser Val Gly Leu Pro Ala Pro Pro Ser Ile Ile Lys Ala Met Gly Gly 130 135 140 Ser Gln Pro Gly Glu Leu Glm Ile Ser Trp Glu Glu Pro Ala Pro Glu 145 150 155 160 Ile Ser Asp Phe Leu Arg Tyr Glu Leu Arg Tyr Gly Pro Arg Asp Pro 165 170 175 Lys Asn Ser Thr Gly Pro Thr Val Ile Gln Leu Ile Ala Thr Glu Thr 180 185 190 Cys Cys Pro Ala Leu Gln Arg Pro His Ser Ala Ser Ala Leu Asp Gln 19S 200 205 Ser Pro Cys Ala Gln Pro Thr Met Pro Trp Gln Asp Gly Pro Lys Gln 210 215 220 Thr Ser Pro Ser Arg Glu Ala Ser Ala Leu Thr Ala Glu Gly Gly Ser 225 230 235 240

Cys Leu Ile Ser Gly Leu Gln Pro Gly Asn Ser Tyr Trp Leu Gln Leu 245 250 255 Arg Ser Glu Pro Asp Gly Ile Ser Leu Gly Gly Ser Trp Gly Ser Trp 260 265 270 Ser Leu Pro Val Thr val Asp Leu Pro Gly Asp Ala Val Ala Leu Gly } 27% 280 285 Leu Gln Cys Phe Thr Leu Asp Leu Lys Asn Val Thr Cys Gln Trp Gln 2590 295 300 Gln Gln Asp His Ala Ser Ser Gln Gly Phe Phe Tyr His Ser Arg Ala 305 310 31s 320 Arg Cys Cys Pro Arg Asp Arg Tyr Pro Ile Trp Glu Asn Cys Glu Glu 325% 330 335 Glu Glu Lys Thr Asn Pro Gly Leu Gln Thr Pro Gln Phe Ser Arg Cys 340 345 350 His Phe Lys Ser Arg Asn Asp Ser Ile Ile His Ile Leu Val Glu Val 355 360 365 Thr Thr Ala Pro Gly Thr Val His Ser Tyr Leu Gly Ser Pro Phe Trp 370 375 380 Ile His Gln Ala Val Arg Leu Pro Thr Pro Asn Leu His Trp Arg Glu 385 390 385 400 Ile Ser Ser Gly His Leu Glu Leu Glu Trp Gln His Pro Ser Ser Trp 405 410 415 Ala Ala Gln Glu Thr Cys Tyr Gln Leu Arg Tyr Thr Gly Glu Gly His 420 425 430 Gln Asp Trp Lys Val Leu Glu Pro Pro Leu Gly Ala Arg Gly Gly Thr 435 440 445 Leu Glu Leu Arg Pro Arg Ser Arg Tyr Arg Leu Gln Leu Arg Ala Arg 450 455 460 Leu Asn Gly Pro Thr Tyr Gln Gly Pro Trp Ser Ser Trp Ser Asp Pro 465 470 475 480

Thr Arg Val Glu Thr Ala Thr Glu Thr Ala Trp Ile Ser Leu Val Thr 485 490 495 Ala Leu His Leu Val Leu Gly Leu Ser Ala Val Leu Gly Leu Leu Leu 500 505 510 Leu Arg Trp Gln Phe Pro Ala His Tyr Arg Arg Leu Arg His Ala Leu 515 520 525 Trp Pro Ser Leu Pro Asp Leu His Arg Val Leu Gly Gln Tyr Leu Arg 530 535 540 Asp Thr Ala Ala Leu Ser Pro Pro Lys Ala Thr Val Ser Asp Thr Cys 545 550 555 560 Glu Glu Val Glu Pro Ser Leu Leu Glu Ile Leu Pro Lys Ser Ser Glu 565 570 575 Arg Thr Pro Leu Pro Leu Cys Ser Ser Gln Ala Gln Met Asp Tyr Arg 580 585 590 Arg Leu Gln Pro Ser Cys Leu Gly Thr Met Pro Leu Ser Val Cys Pro 595 600 605 Pro Met Ala Glu Ser Gly Ser Cys Cys Thr Thr His Ile Ala Asn His 610 615 620 Ser Tyr Leu Pro Leu Ser Tyr Trp Gln Gln Pro 625 630 635 <210> 2425 <21ll> 1006 <212> PRT <213> Homo sapiens <400> 2425 Met val Cys Ser Leu Trp Val Leu Leu Leu Val Ser Ser Val Leu Ala 1 5 10 15 Leu Glu Glu Val Leu Leu Asp Thr Thr Gly Glu Thr Ser Glu Ile Gly

Trp Leu Thr Tyr Pro Pro Gly Gly Trp Asp Glu Val Ser Val Leu Asp 40 45 Asp Gln Arg Arg Leu Thr Arg Thr Phe Glu Ala Cys His Val Ala Gly 50 SS 60

Ala Pro Pro Gly Thr Gly Gln Asp Asn Trp Leu Gln Thr His Phe val 65 70 75 80 Glu Arg Arg Gly Ala Gln Arg Ala His Ile Arg Leu His Phe Ser Val

85 20 Ss Arg Ala Cys Ser Ser Leu Gly Val Ser Gly Gly Thr Cys Arg Glu Thr 100 105 110 Phe Thr Leu Tyr Tyr Arg Gln Ala Glu Glu Pro Asp Ser Pro Asp Ser 115 120 125 Val Ser Ser Trp His Leu Lys Arg Trp Thr Lys Val Asp Thr Ile Ala 130 135 140 Ala Asp Glu Ser Phe Pro Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser 145 150 155 160 Ser Ala Ala Trp Ala Val Gly Pro His Gly Ala Gly Gln Arg Ala Gly 165 170 175 Leu Gln Leu Asn Val Lys Glu Arg Ser Phe Gly Pro Leu Thr Gln Arg 180 185 190 Gly Phe Tyr Val Ala Phe Gln Asp Thr Gly Ala Cys Leu Ala Leu Val 195 200 205 Ala Val Arg Leu Phe Ser Tyr Thr Cys Pro Ala Val Leu Arg Ser Phe 210 215 220 Ala Ser Phe Pro Glu Thr Gln Ala Ser Gly Ala Gly Gly Ala Ser Leu 225 230 235 240 Val Ala Ala Val Gly Thr Cys Val Ala His Ala Glu Pro Glu Glu Asp 245 250 255 Gly val Gly Gly Gln Ala Gly Gly Ser Pro Pro Arg Leu His Cys Asn 260 265 270 Gly Glu Gly Lys Trp Met Val Ala Val Gly Gly Cys Arg Cys Gln Pro 275 280 285 Gly Tyr Gln Pro Ala Arg Gly Asp Lys Ala Cys Gln Ala Cys Pro Arg 290 295 300 } 727 y

Gly Leu Tyr Lys Ser Ser Ala Gly Asn Ala Pro Cys Ser Pro Cys Pro 305 310 31s 320 Ala Arg Ser His Ala Pro Asn Pro Ala Ala Pro Val Cys Pro Cys Leu

325 330 335 Glu Gly Phe Tyr Arg Ala Ser Ser Asp Pro Pro Glu Ala Pro Cys Thr 340 345 350 Gly Pro Pro Ser Ala Pro Gln Glu Leu Trp Phe Glu Val Gln Gly Ser 355 360 365 Ala Leu Met Leu His Trp Arg Leu Pro Arg Glu Leu Gly Gly Arg Gly 370 375 380 Asp Leu Leu Phe Asn Val Val Cys Lys Glu Cys Glu Gly Arg Gln Glu 385 390 395 400 Pro Ala Ser Gly Gly Gly Gly Thr Cys His Arg Cys Arg Asp Glu Val 405 410 415 His Phe Asp Pro Arg Gln Arg Gly Leu Thr Glu Ser Arg Val Leu Val 420 425 430 Gly Gly Leu Arg Ala His Val Pro Tyr Ile Leu Glu Val Gln Ala Val 435 440 445 Asn Gly Val Ser Glu Leu Ser Pro Asp Pro Pro Gln Ala Ala Ala Ile

- 450 455 460 Asn Val Ser Thr Ser His Glu Val Pro Ser Ala val Pro Val Val His 465 470 475 480 Gln Val Ser Arg Ala Ser Asn Ser Ile Thr Val Ser Trp Pro Gln Pro

485 490 495 Asp Gln Thr Asn Gly Asn Ile Leu Asp Tyr Gln Leu Arg Tyr Tyr Asp 500 505 510 Gln Ala Glu Asp Glu Ser His Ser Phe Thr Leu Thr Ser Glu Thr Asn 515 520 525 Thr Ala Thr val Thr Gln Leu Ser Pro Gly His Ile Tyr Gly Phe Gln 530 535 540

Val Arg Ala Arg Thr Ala Ala Gly His Gly Pro Tyr Gly Gly Lys Val 545 550 555 560 Tyr Phe Gln Thr Leu Pro Gln Gly Glu Leu Ser Ser Gln Leu Pro Glu 565 570 575 Arg Leu Ser Leu Val Ile Gly Ser Ile Leu Gly Ala Leu Ala Phe Leu 580 585 5380 Leu Leu Ala Ala Ile Thr Val Leu Ala Val Val Phe Gln Arg Lys Arg 595 600 605 Arg Gly Thr Gly Tyr Thr Glu Gln Leu Gln Gln Tyr Ser Ser Pro Gly 610 615 620 Leu Gly Val Lys Tyr Tyr Ile Asp Pro Ser Thr Tyr Glu Asp Pro Cys 625 630 635 640 Gln Ala Ile Arg Glu Leu Ala Arg Glu Val Asp Pro Ala Tyr Ile Lys 645 650 655 Ile Glu Glu Val Ile Gly Thr Gly Ser Phe Gly Glu val Arg Gln Gly 660 665 670 Arg Leu Gln Pro Arg Gly Arg Arg Glu Gln Thr Val Ala Ile Gln Ala 675 680 685 Leu Trp Ala Gly Gly Ala Glu Ser Leu Gln Met Thr Phe Leu Gly Arg 690 695 700 Ala Ala Val Leu Gly Gln Phe Gln His Pro Asn Ile Leu Arg Leu Glu 705 710 715 720 Gly Val Val Thr Lys Ser Arg Pro Leu Met Val Leu Thr Glu Phe Met 725 730 735 Glu Leu Gly Pro Leu Asp Ser Phe Leu Arg Gln Arg Glu Gly Gln Phe 740 745 750 Ser Ser Leu Gln Leu Val Ala Met Gln Arg Gly Val Ala Ala Ala Met 755 760 765 Gln Tyr Leu Ser Ser Phe Ala Phe Val His Arg Ser Leu Ser Ala His 770 775 780 Ser Val Leu Val Asn Ser His Leu Val Cys Lys Val Ala Arg Leu Gly 729

2003 946

785 790 795 800 His Ser Pro Gln Gly Pro Ser Cys Leu Leu Arg Trp Ala Ala Pro Glu 805 810 815 Val Ile Ala His Gly Lys His Thr Thr Ser Ser Asp Val Trp Ser Phe 820 825 830 Gly Ile Leu Met Trp Glu Val Met Ser Tyr Gly Glu Arg Pro Tyr Trp 835 840 845 Asp Met Ser Glu Gln Glu Val Leu Asn Ala Ile Glu Gln Glu Phe Arg 850 855 860 Leu Pro Pro Pro Pro Gly Cys Pro Pro Gly Leu His Leu Leu Met Leu 865 870 875 880 Asp Thr Trp Gln Lys Asp Arg Ala Arg Arg Pro His Phe Asp Gln Leu 885 890 895 Val Ala Ala Phe Asp Lys Met Ile Arg Lys Pro Asp Thr Leu Gln Ala S00 905 910 Gly Gly Asp Pro Gly Glu Arg Pro Ser Gln Ala Leu Leu Thr Pro val 915 920 925 Ala Leu Asp Phe Pro Cys Leu Asp Ser Pro Gln Ala Trp Leu Ser Ala 930 835 940 Ile Gly Leu Glu Cys Tyr Gln Asp Asn Phe Ser Lys Phe Gly Leu Cys 945 950 955 960 Thr Phe Ser Asp Val Ala Gln Leu Ser Leu Glu Asp Leu Pro Ala Leu 965 970 975 Gly Ile Thr Leu Ala Gly His Gln Lys Lys Leu Leu His His Ile Gln 980 985 990 Leu Leu Gln Gln His Leu Arg Gln Gln Gly Ser val Glu Val 995 1000 1005S <210> 2426 <211> 508 <212> PRT <213> Homo sapiens <400> 2426

PCT/US2003/012946

Met Asp His Leu Gly Ala Ser Leu Trp Pro Gln val Gly Ser Leu Cys 1 5 10 15 Leu Leu Leu Ala Gly Ala Ala Trp Ala Pro Pro Pro Asn Leu Pro Asp

Pro Lys Phe Glu Ser Lys Ala Ala Leu Leu Ala Ala Arg Gly Pro Glu 3S 40 45 Glu Leu Leu Cys Phe Thr Glu Arg Leu Glu Asp Leu Val Cys Phe Trp 50 85 60 Glu Glu Ala Ala Ser Ala Gly val Gly Pro Gly Asn Tyr Ser Phe Ser 65 70 75 80 Tyr Gln Leu Glu Asp Glu Pro Trp Lys Leu Cys Arg Leu His Gln Ala 85 20 95 Pro Thr Ala Arg Gly Ala val Arg Phe Trp Cys Ser Leu Pro Thr Ala 100 105 110 Asp Thr Ser Ser Phe Val Pro Leu Glu Leu Arg Val Thr Ala Ala Ser 115 120 125 Gly Ala Pro Arg Tyr His Arg Val Ile His Ile Asn Glu Val Val Leu 130 135 140 Leu Asp Ala Pro Val Gly Leu Val Ala Arg Leu Ala Asp Glu Ser Gly 145 150 155 160 His val Val Leu Arg Trp Leu Pro Pro Pro Glu Thr Pro Met Thr Ser 165 170 175 His Ile Arg Tyr Glu Val Asp Val Ser Ala Gly Asn Gly Ala Gly ser 180 185 150 Val Gln Arg Val Glu Ile Leu Glu Gly Arg Thr Glu Cys val Leu Ser 195 200 205 Asn Leu Arg Gly Arg Thr Arg Tyr Thr Phe Ala Val Arg Ala Arg Met 210 215 220 Ala Glu Pro Ser Phe Gly Gly Phe Trp Ser Ala Trp Ser Glu Pro Val 225 230 235 240 731 y

Ser Leu Leu Thr Pro Ser Asp Leu Asp Pro Leu Ile Leu Thr Leu Ser 245 250 255 Leu Ile Leu Val val Ile Leu Val Leu Leu Thr Val Leu Ala Leu Leu : 260 265 270 Ser His Arg Arg Ala Leu Lys Gln Lys Ile Trp Pro Gly Ile Pro Ser 275 280 285 . Pro Glu Ser Glu Phe Glu Gly Leu Phe Thr Thr His Lys Gly Asn Phe 280 295 300 Gln Leu Trp Leu Tyr Gln Asn Asp Gly Cys Leu Trp Trp Ser Pro Cys 305 310 315 320 Thr Pro Phe Thr Glu Asp Pro Pro Ala Ser Leu Glu Val Leu Ser Glu 325 330 335 Arg Cys Trp Gly Thr Met Gln Ala Val Glu Pro Gly Thr Asp Asp Glu 340 345 350 Gly Pro Leu Leu Glu Pro Val Gly Ser Glu His Ala Gln Asp Thr Tyr 355 360 365 Leu val Leu Asp Lys Trp Leu Leu Pro Arg Asn Pro Pro Ser Glu Asp 370 375 380 Leu Pro Gly Pro Gly Gly Ser Val Asp Ile Val Ala Met Asp Glu Gly 385 390 385 400 Ser Glu Ala Ser Ser Cys Ser Ser Ala Leu Ala Ser Lys Pro Ser Pro 405 410 415 Glu Gly Ala Ser Ala Ala Ser Phe Glu Tyr Thr Ile Leu Asp Pro Ser 420 425 430 Ser Gln Leu Leu Arg Pro Trp Thr Leu Cys Pro Glu Leu Pro Pro Thr 435 4490 445 Pro Pro His Leu Lys Tyr Leu Tyr Leu Val Val Ser Asp Ser Gly Ile 450 4585 460 Ser Thr Asp Tyr Ser Ser Gly Asp Ser Gln Gly Ala Gln Gly Gly Leu 465 470 475 480 Ser Asp Gly Pro Tyr Ser Asm Pro Tyr Glu Asn Ser Leu Ile Pro Ala

PCT/US2003/012946

485 490 495 Ala Glu Pro Leu Pro Pro Ser Tyr val Ala Cys Ser 500 505 <210> 2427 <211> 441 <212> PRT . <213> Homo sapiens <400> 2427 Met Ser Pro Ile Ser Gly Ala Ser Pro Ser Trp Arg Ala Ala Pro Lys 1 5 10 15 Ala Ser Asp Leu Leu Gly Ala Arg Gly Pro Gly Gly Thr Phe Gln Gly

Arg Asp Leu Arg Gly Gly Ala His Ala Ser Ser Ser Ser Leu Asn Pro 40 45 Met Pro Pro Ser Gln Leu Gln Leu Ser Thr val Asp Ala His Ala Arg 50 55 60 Thr Pro Val Leu Gln Val His Pro Leu Glu Ser Pro Ala Met Ile Ser 65 70 75 80 Leu Thr Pro Pro Thr Thr Ala Thr Gly Val Phe Ser Leu Lys Ala Arg 85 20 95 Pro Gly Leu Pro Pro Gly Ile Asn Val Ala Ser Leu Glu Trp val Ser 100 105 110 Arg Glu Pro Ala Leu Leu Cys Thr Phe Pro Asn Pro Ser Ala Pro Arg 115 120 125 Lys Asp Ser Thr Leu Ser Ala Val Pro Gln Ser Ser Tyr Pro Leu Leu 130 135 140 Ala Asn Gly Val Cys Lys Trp Pro Gly Cys Glu Lys Val Phe Glu Glu 145 150 155 160 Pro Glu Asp Phe Leu Lys His Cys Gln Ala Asp His Leu Leu Asp Glu 165 170 175 Lys Gly Arg Ala Gln Cys Leu Leu Gln Arg Glu Met Val Gln Ser Leu 180 185 190 733 i

2003 46

Glu Gln Gln Leu Val Leu Glu Lys Glu Lys Leu Ser Ala Met Gln Ala 1398 200 205 His Leu Ala Gly Lys Met Ala Leu Thr Lys Ala Ser Ser Val Ala Ser 210 215 220 Ser Asp Lys Gly Ser Cys Cys Ile val Ala Ala Gly Ser Gln Gly Pro 225 230 235 240 Val val Pro Ala Trp Ser Gly Pro Arg Glu Ala Pro Asp Ser Leu Phe 245 250 255 Ala Val Arg Arg His Leu Trp Gly Ser His Gly Asn Ser Thr Phe Pro 260 265 270 Glu Phe Leu His Asn Met Asp Tyr Phe Lys Phe His Asn Met Arg Pro 275 280 285 Pro Phe Thr Tyr Ala Thr Leu Ile Arg Trp Ala Ile Leu Glu Ala Pro 290 295 300 Glu Lys Gln Arg Thr Leu Asn Glu Ile Tyr His Trp Phe Thr Arg Met 305 310 315 320 Phe Ala Phe Phe Arg Asn His Pro Ala Thr Trp Lys Val Ser Ser Ser 325 330 33S Glu Val Ala Val Thr Gly Met Ala Ser Ser Ala Ile Ala Ala Gln Ser 340 345 350 Gly Gln Ala Trp Val Trp Ala His Arg His Ile Gly Glu Glu Arg Asp 355 360 365 Val Gly Cys Trp Trp Trp Leu Leu Ala Ser Glu Val Asp Ala His Leu 370 375 380 Leu Pro Val Pro Gly Leu Pro Gln Asn Ala Ile Arg His Asn Leu Ser 385 390 395 400 Leu His Lys Cys Phe Val Arg Val Glu Ser Glu Lys Gly Ala Val Trp 405 410 415 Thr Val Asp Glu Leu Glu Phe Arg Lys Lys Arg Ser Gln Arg Pro Ser 420 425 430

Arg Cys Ser Asn Pro Thr Pro Gly Pro 435 440 <210> 2428 <211l> 413 <212> PRT <213> Homo sapiens <400> 2428 Met Glu Phe Pro Gly Leu Gly Ser Leu Gly Thr Ser Glu Pro Leu Pro 1 5 10 15 Gln Phe Val Asp Pro Ala Leu Val Ser Ser Thr Pro Glu Ser Gly val

Phe Phe Pro Ser Gly Pro Glu Gly Leu Asp Ala Ala Ala Ser Ser Thr 40 45 Ala Pro Ser Thr Ala Thr Ala Ala Ala Ala Ala Leu Ala Tyr Tyr Arg 50 55 60 Asp Ala Glu Ala Tyr Arg His Ser Pro Val Phe Gln Val Tyr Pro Leu 65 70 75 80 Leu Asn Cys Met Glu Gly Ile Pro Gly Gly Ser Pro Tyr Ala Gly Trp 8S 90 95 Ala Tyr Gly Lys Thr Gly Leu Tyr Pro Ala Ser Thr Val Cys Pro Thr 100 105 110 Arg Glu Asp Ser Pro Pro Gln Ala Val Glu Asp Leu Asp Gly Lys Gly 115 120 125 Ser Thr Ser Phe Leu Glu Thr Leu Lys Thr Glu Arg Leu Ser Pro Asp 130 135 140 Leu Leu Thr Leu Gly Pro Ala Leu Pro Ser Ser Leu Pro Val Pro Asn 145 150 155 160 Ser Ala Tyr Gly Gly Pro Asp Phe Ser Ser Thr Phe Phe Ser Pro Thr 165 170 175 Gly Ser Pro Leu Asn Ser Ala Ala Tyr Ser Ser Pro Lys Leu Arg Gly 180 185 190 Thr Leu Pro Leu Pro Pro Cys Glu Ala Arg Glu Cys Val Asn Cys Gly 185 200 205

Ala Thr Ala Thr Pro Leu Trp Arg Arg Asp Arg Thr Gly His Tyr Leu 210 215 220 Cys Asn Ala Cys Gly Leu Tyr His Lys Met Asn Gly Gln Asn Arg Pro 225 230 235 240 Leu Ile Arg Pro Lys Lys Arg Leu Ile Val Ser Lys Arg Ala Gly Thr 245 250 255 Gln Cys Thr Asn Cys Gln Thr Thr Thr Thr Thr Leu Trp Arg Arg Asn 260 265 270 Ala Ser Gly Asp Pro Val Cys Asn Ala Cys Gly Leu Tyr Tyr Lys Leu 275 280 285 His Gln Val Asn Arg Pro Leu Thr Met Arg Lys Asp Gly Ile Gln Thr 290 295 300 Arg Asn Arg Lys Ala Ser Gly Lys Gly Lys Lys Lys Arg Gly Ser Ser 305 310 315 320 Leu Gly Gly Thr Gly Ala Ala Glu Gly Pro Ala Gly Gly Phe Met Val 325 330 335 val Ala Gly Gly Ser Gly Ser Gly Asn Cys Gly Glu Val Ala Ser Gly 340 345 350 Leu Thr Leu Gly Pro Pro Gly Thr Ala His Leu Tyr Gln Gly Leu Gly 355 360 365 Pro Val Val Leu Ser Gly Pro Val Ser His Leu Met Pro Phe Pro Gly 370 375 380 Pro Leu Leu Gly Ser Pro Thr Gly Ser Phe Pro Thr Gly Pro Met Pro 385 390 395 400 Pro Thr Thr Ser Thr Thr val Val Ala Pro Leu Ser Ser 405 410 <210> 24289 <211> 1039 <212> PRT <213> Homo sapiens <400> 2429

Met Ala Arg Ala Leu Cys Pro Leu Gln Ala Leu Trp Leu Leu Glu Trp 1 Ss 10 15 Val Leu Leu Leu Leu Gly Pro Cys Ala Ala Pro Pro Ala Trp Ala Leu

Asn Leu Asp Pro Val Gln Leu Thr Phe Tyr Ala Gly Pro Asn Gly Ser 40 45 Gln Phe Gly Phe Ser Leu Asp Phe His Lys Asp Ser His Gly Arg Val 50 55 60 Ala Ile val val Gly Ala Pro Arg Thr Leu Gly Pro Ser Gln Glu Glu 65 70 75 80 Thr Gly Gly Val Phe Leu Cys Pro Trp Arg Ala Glu Gly Gly Gln Cys 85 S0 95 Pro Ser Leu Leu Phe Asp Leu Arg Asp Glu Thr Arg Asn Val Gly Ser 100 105 110 Gln Thr Leu Gln Thr Phe Lys ala Arg Gln Gly Leu Gly Ala Ser Val 115 120 125 Val Ser Trp Ser Asp Val Ile val Ala Cys Ala Pro Trp Gln His Trp 130 135 140 Asn Val Leu Glu Lys Thr Glu Glu Ala Glu Lys Thr Pro val Gly Ser 145 150 155 160 Cys Phe Leu Ala Gln Pro Glu Ser Gly Arg Arg Ala Glu Tyr Ser Pro 165 170 175 Cys Arg Gly Asn Thr Leu Ser Arg Ile Tyr Val Glu Asn Asp Phe Ser 180 185 1g0 Trp Asp Lys Arg Tyr Cys Glu Ala Gly Phe Ser Ser Val val Thr Gln 195 200 205 Ala Gly Glu Leu Val Leu Gly Ala Pro Gly Gly Tyr Tyr Phe Leu Gly 210 215 220 Leu Leu Ala Gln Ala Pro val Ala Asp Ile Phe Ser Ser Tyr Arg Pro 225 230 235 240 Gly Ile Leu Leu Trp His Val Ser Ser Gln Ser Leu Ser Phe Asp Ser

245 250 255 Ser Asn Pro Glu Tyr Phe Asp Gly Tyr Trp Gly Tyr Ser Val Ala val 260 265 270 Gly Glu Phe Asp Gly Asp Leu Asn Thr Thr Glu Tyr Val Val Gly Ala 275 280 285 Pro Thr Trp Ser Trp Thr Leu Gly Ala Val Glu Ile Leu Asp Ser Tyr 290 295 300 Tyr Gln Arg Leu His Arg Leu Arg Ala Glu Gln Met Ala Ser Tyr Phe 305 310 315 320 Gly His Ser val Ala Val Thr Asp Val Asn Gly Asp Gly Arg His Asp 325 330 338 Leu Leu Val Gly Ala Pro Leu Tyr Met Glu Ser Arg Ala Asp Arg Lys 340 345 350 Leu Ala Glu val Gly Arg Val Tyr Leu Phe Leu Gln Pro Arg Gly Pro 355 360 365 His Ala Leu Gly Ala Pro Ser Leu Leu Leu Thr Gly Thr Gln Leu Tyr 370 375 380 Gly Arg Phe Gly Ser Ala Ile Ala Pro Leu Gly Asp Leu Asp Arg Asp 38S 390 395 400 Gly Tyr Asn Asp Ile Ala Val Ala Ala Pro Tyr Gly Gly Pro Ser Gly 405 410 415 Arg Gly Gln Val Leu Val Phe Leu Gly Gln Ser Glu Gly Leu Arg Ser 420 425 430 Arg Pro Ser Gln Val Leu Asp Ser Pro Phe Pro Thr Gly Ser Ala Phe 435 440 445 Gly phe Ser Leu Arg Gly Ala Val Asp Ile Asp Asp Asn Gly Tyr Pro 450 455 460 Asp Leu Ile Val Gly Ala Tyr Gly Ala Asn Gln Val Ala Val Tyr Arg 465 470 475 480 Ala Gln Pro Val Val Lys Ala Ser Val Gln Leu Leu Val Gln Asp Ser 485 490 485

Leu Asn Pro Ala Val Lys Ser Cys Val Leu Pro Gln Thr Lys Thr Pro 500 505 510 Val Ser Cys Phe Asn Ile Gln Met Cys Val Gly Ala Thr Gly His Asn 515 520 525 Ile Pro Gln Lys Leu Ser Leu Asn Ala Glu Leu Gln Leu Asp Arg Gln 530 535 540 Lys Pro Arg Gln Gly Arg Arg Val Leu Leu Leu Gly Ser Gln Gln Ala 545 550 555 560 Gly Thr Thr Leu Asn Leu Asp Leu Gly Gly Lys His Ser Pro Ile Cys 565 570 575 His Thr Thr Met Ala Phe Leu Arg Asp Glu Ala Asp Phe Arg Asp Lys 580 585 590 Leu Ser Pro Ile Val Leu Ser Leu Asn Val Ser Leu Pro Pro Thr Glu 585 600 605 Ala Gly Met Ala Pro Ala Val Val Leu His Gly Asp Thr His Val Gln 610 615 620 Glu Gln Thr Arg Ile Val Leu Asp Ser Gly Glu Asp Asp Val Cys Val 625 630 635 640 Pro Gln Leu Gln Leu Thr Ala Ser Val Thr Gly Ser Pro Leu Leu Val 645 650 655 Gly Ala Asp Asn Val Leu Glu Leu Gln Met Asp Ala Ala Asn Glu Gly 660 665 670 Glu Gly Ala Tyr Glu Ala Glu Leu Ala Val His Leu Pro Gln Gly Ala 675 680 685 His Tyr Met Arg Ala Leu Ser Asn Val Glu Gly Phe Glu Arg Leu Ile 690 695 700 Cys Asn Gln Lys Lys Glu Asn Glu Thr Arg Val Val Leu Cys Glu Leu 705 710 715 720 Gly Asn Pro Met Lys Lys Asn Ala Gln Ile Gly Ile Ala Met Leu Val 725 730 735

T/US2003/012946

Ser Val Gly Asn Leu Glu Glu Ala Gly Glu Ser val Ser Phe Gln Leu 740 745 750 Gln Ile Arg Ser Lys Asn Ser Gln Asn Pro Asn Ser Lys Ile Val Leu 755 760 765 Leu Asp Val Pro Val Arg Ala Glu Ala Gln Val Glu Leu Arg Gly Asn 770 775 780 Ser Phe Pro Ala Ser Leu Val Val Ala Ala Glu Glu Gly Glu Arg Glu 785 790 795 800 Gln Asn Ser Leu Asp Ser Trp Gly Pro Lys Val Glu His Thr Tyr Glu 805 810 815 Leu His Asn Asn Gly Pro Gly Thr Val Asn Gly Leu His Leu Ser Ile 820 825 830 His Leu Pro Gly Gln Ser Gln Pro Ser Asp Leu Leu Tyr Ile Leu Asp 835 840 845 Ile Gln Pro Gln Gly Gly Leu Gln Cys Phe Pro Gln Pro Pro Val Asn 850 855 860 Pro Leu Lys Val Asp Trp Gly Leu Pro Ile Pro Ser Pro Ser Pro Ile 865 870 875 880 His Pro Ala His His Lys Arg Asp Arg Arg Gln Ile Phe Leu Pro Glu 88s 890 895 Pro Glu Gln Pro Ser Arg Leu Gln Asp Pro Val Leu Val Ser Cys Asp 200 905 910 Ser Ala Pro Cys Thr Val Val Gln Cys Asp Leu Gln Glu Met Ala Arg 915 920 925 Gly Gln Arg Ala Met Val Thr Val Leu Ala Phe Leu Trp Leu Pro Ser 930 935 S40 Leu Tyr Gln Arg Pro Leu Asp Gln Phe Val Leu Gln Ser His Ala Trp 945 950 955 860 Phe Asn Val Ser Ser Leu Pro Tyr Ala Val Pro Pro Leu Ser Leu Pro 965 970 975

Arg Gly Glu Ala Gln Val Trp Thr Gln Leu Leu Arg Ala Leu Glu Glu 980 985 930 Arg Ala Ile Pro Ile Trp Trp Val Leu Val Gly Val Leu Gly Gly Leu 985 1000 1005 Leu Leu Leu Thr Ile Leu Val Leu Ala Met Trp Lys Val Gly Phe 1010 1015 1020 Phe Lys Arg Asn Arg Pro Pro Leu Glu Glu Asp Asp Glu Glu Gly 1025 1030 1035 Glu <210> 2430 <211> 145 <212> PRT <213> Homo sapiens <400> 2430 Met Ala Thr Trp Ala Leu Leu Leu Leu Ala Ala Met Leu Leu Gly Asn 1 5 10 15 Pro Gly Leu Val Phe Ser Arg Leu Ser Pro Glu Tyr Tyr Asp Leu Ala

Arg Ala His Leu Arg Asp Glu Glu Lys Ser Cys Pro Cys Leu Ala Gln 40 45 Glu Gly Pro Gln Gly Asp Leu Leu Thr Lys Thr Gln Glu Leu Gly Arg 50 55 60 Asp Tyr Arg Thr Cys Leu Thr Ile Val Gln Lys Leu Lys Lys Met Val 65 70 75 80 Asp Lys Pro Thr Gln Arg Ser Val Ser Asn Ala Ala Thr Arg Val Cys 85 90 95 Arg Thr Gly Arg Ser Arg Trp Arg Asp Val Cys Arg Asn Phe Met Arg 100 105 110 Arg Tyr Gln Ser Arg Val Thr Gln Gly Leu Val Ala Gly Glu Thr Ala 115 120 125 Gln Gln Ile Cys Glu Asp Leu Arg Leu Cys Ile Pro Ser Thr Gly Pro 130 135 140

Leu

<210> 2431 <21l1l> 262 <212> PRT <213> Homo sapiens <400> 2431 ) Met Arg Asn Ser Tyr Arg Phe Leu Ala Ser Ser Leu Ser Val Val Val 1 5 10 15 Ser Leu Leu Leu Ile Pro Glu Asp Val Cys Glu Lys Ile Ile Gly Gly

Asn Glu Val Thr Pro His Ser Arg Pro Tyr Met Val Leu Leu Ser Leu 40 45 Asp Arg Lys Thr Ile Cys Ala Gly Ala Leu Ile Ala Lys Asp Trp val 50 55 60 Leu Thr Ala Ala His Cys Asn Leu Asn Lys Arg Ser Gln Val Ile Leu 65 70 75 80 Gly Ala His Ser Ile Thr Arg Glu Glu Pro Thr Lys Gln Ile Met Leu 85 S0 95 Val Lys Lys Glu Phe Pro Tyr Pro Cys Tyr Asp Pro Ala Thr Arg Glu 100 105 110 Gly Asp Leu Lys Leu Leu Gln Leu Thr Glu Lys Ala Lys Ile Asn Lys 115 120 125 Tyr Val Thr Ile Leu His Leu Pro Lys Lys Gly Asp Asp Val Lys Pro 130 135 140 Gly Thr Met Cys Gln Val Ala Gly Trp Gly Arg Thr His Asn Ser Ala 145 150 155 160 Ser Trp Ser Asp Thr Leu Arg Glu Val Asn Ile Thr Ile Ile Asp Arg 165 170 175 Lys Val Cys Asn Asp Arg Asn His Tyr Asn Phe Asn Pro Val Ile Gly 180 185 190

Met Asn Met val Cys Ala Gly Ser Leu Arg Gly Gly Arg Asp Ser Cys 195 200 20S . Asn Gly Asp Ser Gly Ser Pro Leu Leu Cys Glu Gly Val Phe Arg Gly 210 215 220 Val Thr Ser Phe Gly Leu Glu Asn Lys Cys Gly Asp Pro Arg Gly Pro 225 230 235 240 Gly Val Tyr Ile Leu Leu Ser Lys Lys His Leu Asn Trp Ile Ile Met 245 250 255 Thr Ile Lys Gly Ala Val 260 <210> 2432 <21l> 142 <212> PRT <213> Homo sapiens <400> 2432 Met Val Leu Ser Pro Ala Asp Lys Thr Asn Val Lys Ala Ala Trp Gly 1 5 10 15 Lys Val Gly Ala His Ala Gly Glu Tyr Gly Ala Glu Ala Leu Glu Arg

Met Phe Leu Ser Phe Pro Thr Thr Lys Thr Tyr Phe Pro His Phe Asp 40 45 Leu Ser His Gly Ser Ala Gln val Lys Gly His Gly Lys Lys Val Ala 50 55 60 Asp Ala Leu Thr Asn Ala Val Ala His Val Asp Asp Met Pro Asn Ala 65 70 75 80 Leu Ser Ala Leu Ser Asp Leu His Ala His Lys Leu Arg Val Asp Pro 85 90 95 Val Asn Phe Lys Leu Leu Ser His Cys Leu Leu Val Thr Leu Ala Ala 100 105 110 His Leu Pro Ala Glu Phe Thr Pro Ala Val His Ala Ser Leu Asp Lys 115 120 125 Phe Leu Ala Ser Val Ser Thr Val Leu Thr Ser Lys Tyr Arg 130 135 140

<210> 2433 <211> 142 <212> PRT <213> Homo sapiens <400> 2433 . Met Ser Leu Thr Lys Thr Glu Arg Thr Ile Ile Val Ser Met Trp Ala 1 5 10 1s Lys Ile Ser Thr Gln Ala Asp Thr Ile Gly Thr Glu Thr Leu Glu Arg

Leu Phe Leu Ser His Pro Gln Thr Lys Thr Tyr Phe Pro His Phe Asp 40 45 Leu His Pro Gly Ser Ala Gln Leu Arg Ala His Gly Ser Lys Val val 50 55 60 Ala Ala Val Gly Asp Ala Val Lys Ser Ile Asp Asp Ile Gly Gly Ala 65 70 75 80 Leu Ser Lys Leu Ser Glu Leu His Ala Tyr Ile Leu Arg Val Asp Pro 85 90 95 Val Asn Phe Lys Leu Leu Ser His Cys Leu Leu Val Thr Leu Ala Ala 100 105 110 Arg Phe Pro Ala Asp Phe Thr Ala Glu Ala His Ala Ala Trp Asp Lys 118 120 125 Phe Leu Ser Val Val Ser Ser Val Leu Thr Glu Lys Tyr Arg 130 135 ~ 140 <210> 2434 <211> 147 <212> PRT <213> Homo sapiens <400> 2434 Met val His Leu Thr Pro Glu Glu Lys Thr Ala Val Asn Ala Leu Trp 1 S 10 1S Gly Lys Val Asn Val Asp Ala Val Gly Gly Glu Ala Leu Gly Arg Leu 20 25 30 Leu Val Val Tyr Pro Trp Thr Gln Arg Phe Phe Glu Ser Phe Gly Asp

35 40 45 Leu Ser Ser Pro Asp Ala Val Met Gly Asn Pro Lys Val Lys Ala His 50 ss 60 Gly Lys Lys Val Leu Gly Ala Phe Ser Asp Gly Leu Ala His Leu Asp 65 70 75 80 Asn Leu Lys Gly Thr Phe Ser Gln Leu Ser Glu Leu His Cys Asp Lys 85 90 95 Leu His Val Asp Pro Glu Asn Phe Arg Leu Leu Gly Asn Val Leu Val 100 105 110 Cys Val Leu Ala Arg Asn Phe Gly Lys Glu Phe Thr Pro Gln Met Gln 115 120 125 Ala Ala Tyr Gln Lys Val Val Ala Gly Val Ala Asn Ala Leu Ala His 130 135 140 Lys Tyr His 145 <210> 2435S <211> 147 <212> PRT <213> Homo sapiens <400> 2435 Met val His Phe Thr Ala Glu Glu Lys Ala Ala Val Thr Ser Leu Trp 1 5 10 15 Ser Lys Met Asn Val Glu Glu Ala Gly Gly Glu Ala Leu Gly Arg Leu

Leu Val Val Tyr Pro Trp Thr Gln Arg Phe Phe Asp Ser Phe Gly Asn 40 45 Leu Ser Ser Pro Ser Ala Ile Leu Gly Asn Pro Lys Val Lys Ala His 50 55 60 Gly Lys Lys Val Leu Thr Ser Phe Gly Asp Ala Ile Lys Asn Met Asp 65 70 75 80 Asn Leu Lys Pro Ala Phe Ala Lys Leu Ser Glu Leu His Cys Asp Lys 85 90 95

Leu His Val Asp Pro Glu Asn Phe Lys Leu Leu Gly Asn Val Met val 100 105 110 Ile Ile Leu Ala Thr His Phe Gly Lys Glu phe Thr Pro Glu Val Gln 115 120 125 Ala Ala Trp Gln Lys Leu Val Ser Ala Val Ala Ile Ala Leu Ala His 130 135 140 Lys Tyr His 145 <210> 2436 <211> 147 <212> PRT <213> Homo sapiens <400> 2436 Met Gly His Phe Thr Glu Glu Asp Lys Ala Thr Ile Thr Ser Leu Trp 1 5 10 15 Gly Lys Val Asn Val Glu Asp Ala Gly Gly Glu Thr Leu Gly Arg Leu

Leu Val val Tyr Pro Trp Thr Gln Arg Phe Phe Asp Ser Phe Gly Asn 40 45 Leu Ser Ser Ala Ser Ala Ile Met Gly Asn Pro Lys val Lys Ala His 50 55 60 Gly Lys Lys Val Leu Thr Ser Leu Gly Asp Ala Thr Lys His Leu Asp 65 70 75 80 Asp Leu Lys Gly Thr Phe Ala Gln Leu Ser Glu Leu His Cys Asp Lys 8S So 95 Leu His Val Asp Pro Glu Asn Phe Lys Leu Leu Gly Asn Val Leu val 100 105 110 Thr Val Leu Ala Ile His Phe Gly Lys Glu Phe Thr Pro Glu Val Gln 115 120 125 Ala Ser Trp Gln Lys Met Val Thr Ala Val Ala Ser Ala Leu Ser Ser 130 135 140 Arg Tyr His

<210> 2437

<211> 142

<212> PRT

<213> Homo sapiens -

<400> 2437

Met Ala Leu Ser Ala Glu Asp Arg Ala Leu Val Arg Ala Leu Trp Lys

1 5 10 1S

Lys Leu Gly Ser Asn Val Gly Val Tyr Thr Thr Glu Ala Leu Glu Arg

Thr Phe Leu Ala Phe Pro Ala Thr Lys Thr Tyr Phe Ser His Leu Asp

40 45 Leu Ser Pro Gly Ser Ser Gln Val Arg Ala His Gly Gln Lys Val Ala 50 5S 60

Asp Ala Leu Ser Leu Ala Val Glu Arg Leu Asp Asp Leu Pro His Ala

65 70 75 80

Leu Ser Ala Leu Ser His Leu His Ala Cys Gln Leu Arg Val Asp Pro

85 90 95

Ala Ser Phe Gln Leu Leu Gly His Cys Leu Leu Val Thr Leu Ala Arg 100 105 110

His Tyr Pro Gly Asp Phe Ser Pro Ala Leu Gln Ala Ser Leu Asp Lys

115 120 125 Phe Leu Ser His Val Ile Ser Ala Leu Val Ser Glu Tyr Arg 130 135 140

<210> 2438

<21l> 260

<212> PRT ’

<213> Homo sapiens

<400> 2438

Met Arg Pro Glu Asp Arg Met Phe His Ile Arg Ala Val Ile Leu Arg

1 5 10 15

Ala Leu Ser Leu Ala Phe Leu Leu Ser Leu Arg Gly Ala Gly Ala Ile 20 25 30

Lys Ala Asp His Val Ser Thr Tyr Ala Ala Phe val Gln Thr His Arg 40 45 Pro Thr Gly Glu Phe Met Phe Glu Phe Asp Glu Asp Glu Met Phe Tyr 50 55 60 Val Asp Leu Asp Lys Lys Glu Thr Val Trp His Leu Glu Glu Phe Gly €5 70 75 80 Gln Ala Phe Ser Phe Glu Ala Gln Gly Gly Leu Ala Asn Ile Ala Ile 85 90 95 Leu Asn Asn Asn Leu Asn Thr Leu Ile Gln Arg Ser Asn His Thr Gln 100 105 110 Ala Thr Asn Asp Pro Pro Glu Val Thr Val Phe Pro Lys Glu Pro Val 115 120 125 Glu Leu Gly Gln Pro Asn Thr Leu Ile Cys His Ile Asp Lys Phe Phe 130 135 140 Pro Pro Val Leu Asn Val Thr Trp Leu Cys Asn Gly Glu Leu Val Thr 145 150 155 160 Glu Gly Val Ala Glu Ser Leu Phe Leu Pro Arg Thr Asp Tyr Ser Phe 165 170 175 His Lys Phe His Tyr Leu Thr Phe Val Pro Ser Ala Glu Asp Phe Tyr 180 185 190 Asp Cys Arg Val Glu His Trp Gly Leu Asp Gln Pro Leu Leu Lys His 195 200 205 Trp Glu Ala Gln Glu Pro Ile Gln Met Pro Glu Thr Thr Glu Thr Val 210 215 220 Leu Cys Ala Leu Gly Leu Val Leu Gly Leu Val Gly Ile Ile val Gly 225 230 235 240 Thr Val Leu Ile Ile Lys Ser Leu Arg Ser Gly His Asp Pro Arg Ala 245 250 25% Gln Gly Thr Leu 260 <210> 2439

<211> 255 <212> PRT <213> Homo sapiens <400> 2439 Met Ile Leu Asn Lys Ala Leu Leu Leu Gly Ala Leu Ala Leu Thr Thr 1 5 10 15 Val Met Ser Pro Cys Gly Gly Glu Asp Ile Val Ala Asp His Val Ala

Ser Cys Gly Val Asn Leu Tyr Gln Phe Tyr Gly Pro Ser Gly Gln Tyr 40 45 Thr His Glu Phe Asp Gly Asp Glu Gln Phe Tyr Val Asp Leu Glu Arg 50 55 60 Lys Glu Thr Ala Trp Arg Trp Pro Glu Phe Ser Lys Phe Gly Gly Phe €5 70 75 80 Asp Pro Gln Gly Ala Leu Arg Asn Met Ala Val Ala Lys His Asn Leu 85 90 95 Asn Ile Met Ile Lys Arg Tyr Asn Ser Thr Ala Ala Thr Asn Glu Val 100 105 110 Pro Glu Val Thr Val Phe Ser Lys Ser Pro Val Thr Leu Gly Gln Pro 115 120 125 Asn Thr Leu Ile Cys Leu Val Asp Asn Ile Phe Pro Pro Val Val Asn 130 135 140 Ile Thr Trp Leu Ser Asn Gly Gln Ser Val Thr Glu Gly Val Ser Glu 145 150 155 160 Thr Ser Phe Leu Ser Lys Ser Asp His Ser Phe Phe Lys Ile Ser Tyr 165 170 175 Leu Thr Phe Leu Pro Ser Ala Asp Glu Ile Tyr Asp Cys Lys Val Glu 180 185 190 His Trp Gly Leu Asp Gln Pro Leu Leu Lys His Trp Glu Pro Glu Ile 195 200 205 Pro Ala Pro Met Ser Glu Leu Thr Glu Thr Val Val Cys Ala Leu Gly 210 215 220

Leu Ser Val Gly Leu Met Gly Ile Val Val Gly Thr val Phe Ile Ile 225 230 235 240 Gln Gly Leu Arg Ser Val Gly Ala Ser Arg His Gln Gly Pro Leu

245 250 255 <210> 2440 <211> 199 <212> PRT <213> Homo sapiens <400> 2440 Met Lys Ser Gly Leu Trp Tyr Phe Phe Leu Phe Cys Leu Arg Ile Lys 1 5 10 15 Val Leu Thr Gly Glu Ile Asn Gly Ser Ala Asn Tyr Glu Met Phe Ile

Phe His Asn Gly Gly val Gln Ile Leu Cys Lys Tyr Pro Asp Ile Val 40 45 Gln Gln Phe Lys Met Gln Leu Leu Lys Gly Gly Gln Ile Leu Cys Asp 50 55 60 Leu Thr Lys Thr Lys Gly Ser Gly Asn Thr Val Ser Ile Lys Ser Leu 65 70 75 80 Lys Phe Cys His Ser Gln Leu Ser Asn Asn Ser Val Ser Phe Phe Leu 85 S50 95 Tyr Asn Leu Asp His Ser His Ala Asn Tyr Tyr Phe Cys Asn Leu Ser 100 105 110 Ile Phe Asp Pro Pro Pro Phe Lys Val Thr Leu Thr Gly Gly Tyr Leu 115 120 125 His Ile Tyr Glu Ser Gln Leu Cys Cys Gln Leu Lys Phe Trp Leu Pro 130 138 140 Ile Gly Cys Ala Ala Phe Val Val Val Cys Ile Leu Gly Cys Ile Leu 145 150 155 160 Ile Cys Trp Leu Thr Lys Lys Lys Tyr Ser Ser Ser Val His Asp Pro 165 170 175 Asn Gly Glu Tyr Met Phe Met Arg Ala Val Asn Thr Ala Lys Lys Ser

180 185 190 Arg Leu Thr Asp val Thr Leu 195 <210> 2441 <211> 193 <212> PRT <213> Homo sapiens <400> 2441 Met Ala Ala Glu Pro Val Glu Asp Asn Cys Ile Asn Phe Val Ala Met 1 5 10 15 Lys Phe Ile Asp Asn Thr Leu Tyr Phe Ile Ala Glu Asp Asp Glu Asn

Leu Glu Ser Asp Tyr Phe Gly Lys Leu Glu Ser Lys Leu Ser Val Ile 40 45 Arg Asn Leu Asn Asp Gln Val Leu Phe Ile Asp Gln Gly Asn Arg Pro 50 55 60 Leu Phe Glu Asp Met Thr Asp Ser Asp Cys Arg Asp Asn Ala Pro Arg 65 70 75 80 Thr Ile Phe Ile Ile Ser Met Tyr Lys Asp Ser Gln Pro Arg Gly Met 85 90 SS Ala Val Thr Ile Ser Val Lys Cys Glu Lys Ile Ser Thr Leu Ser Cys 100 105 110 Glu Asn Lys Ile Ile Ser Phe Lys Glu Met Asn Pro Pro Asp Asn Ile 115 120 125 Lys Asp Thr Lys Ser Asp Ile Ile Phe Phe Gln Arg Ser Val Pro Gly 130 135 140 His Asp Asn Lys Met Gln Phe Glu Ser Ser Ser Tyr Glu Gly Tyr Phe 145 150 155 160 Leu Ala Cys Glu Lys Glu Arg Asp Leu Phe Lys Leu Ile Leu Lys Lys 165 170 175 Glu Asp Glu Leu Gly Asp Arg Ser Ile Met Phe Thr Val Gln Asn Glu 180 185 190

Asp <210> 2442 <211l> 152 <212> PRT <213> Homo sapiens <400> 2442 Met Ser Arg Leu Pro Val Leu Leu Leu Leu Gln Leu Leu Val Arg Pro 1 5 10 15 Gly Leu Gln Ala Pro Met Thr Gln Thr Thr Pro Leu Lys Thr Ser Trp

Val Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln 40 45 Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln 50 55 60 Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe 65 70 75 80 Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile 85 90 95 Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr 100 105 110 Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg 115 120 125 Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 130 135 140 Thr Thr Leu Ser Leu Ala Ile Phe 145 150 <210> 2443 <211> 1038 oo <212> PRT <213> Homo sapiens <400> 2443 Met Phe Pro Thr Glu Ser Ala Trp Leu Gly Lys Arg Gly Ala Asn Pro 1 s 10 15

Gly Pro Glu Ala Ala Val Arg Glu Thr Val Met Leu Leu Leu Cys Leu

Gly val Pro Thr Gly Arg Pro Tyr Asn Val Asp Thr Glu Ser Ala Leu 40 45 Leu Tyr Gln Gly Pro His Asn Thr Leu Phe Gly Tyr Ser Val Val Leu 50 55 60 His Ser His Gly Ala Asn Arg Trp Leu Leu Val Gly Ala Pro Thr Ala 65 70 75 80 Asn Trp Leu Ala Asn Ala Ser Val Ile Asn Pro Gly Ala Ile Tyr Arg 85 90 85 Cys Arg Ile Gly Lys Asn Pro Gly Gln Thr Cys Glu Gln Leu Gln Leu 100 105 110 Gly Ser Pro Asn Gly Glu Pro Cys Gly Lys Thr Cys Leu Glu Glu Arg 115 120 125 Asp Asn Gln Trp Leu Gly Val Thr Leu Ser Arg Gln Pro Gly Glu Asn 130 135 140 Gly Ser Ile Val Thr Cys Gly His Arg Trp Lys Asn Ile Phe Tyr Ile 145 150 155 160 Lys Asn Glu Asn Lys Leu Pro Thr Gly Gly Cys Tyr Gly Val Pro Pro 165 170 175 Asp Leu Arg Thr Glu Leu Ser Lys Arg Ile Ala Pro Cys Tyr Gln Asp 180 185 150 Tyr Val Lys Lys Phe Gly Glu Asn Phe Ala Ser Cys Gln Ala Gly Ile 195 200 205 Ser Ser Phe Tyr Thr Lys Asp Leu Ile Val Met Gly Ala Pro Gly Ser 210 215 220 Ser Tyr Trp Thr Gly Ser Leu Phe Val Tyr Asn Ile Thr Thr Asn Lys 225 230 235 240 Tyr Lys Ala Phe Leu Asp Lys Gln Asn Gln Val Lys Phe Gly Ser Tyr .. 245 250 255

Leu Gly Tyr Ser val Gly Ala Gly His Phe Arg Ser Gln His Thr Thr 260 265 270 Glu Val val Gly Gly Ala Pro Gln His Glu Gln Ile Gly Lys Ala Tyr 275 280 285 Ile Phe Ser Ile Asp Glu Lys Glu Leu Asn Ile Leu His Glu Met Lys 290 295 300 Gly Lys Lys Leu Gly Ser Tyr Phe Gly Ala Ser Val Cys Ala Val Asp 305 : 310 315 320 Leu Asn Ala Asp Gly Phe Ser Asp Leu Leu Val Gly Ala Pro Met Gln 325 330 335 Ser Thr Ile Arg Glu Glu Gly Arg Val Phe Val Tyr Ile Asn Ser Gly 340 345 350 Ser Gly Ala Val Met Asn Ala Met Glu Thr Asn Leu Val Gly Ser Asp 355 360 365 Lys Tyr Ala Ala Arg Phe Gly Glu Ser Ile Val Asn Leu Gly Asp Ile 370 375 380 Asp Asn Asp Gly Phe Glu Asp Val Ala Ile Gly Ala Pro Gln Glu Asp 385 350 395 400 Asp Leu Gln Gly Ala Ile Tyr Ile Tyr Asn Gly Arg Ala Asp Gly Ile 405 410 415 Ser Ser Thr Phe Ser Gln Arg Ile Glu Gly Leu Gln Ile Ser Lys Ser 420 425 430 Leu Ser Met Phe Gly Gln Ser Ile Ser Gly Gln Ile Asp Ala Asp Asn 435 440 445 Asn Gly Tyr Val Asp Val Ala Val Gly Ala Phe Arg Ser Asp Ser Ala 450 455 460 Val Leu Leu Arg Thr Arg Pro Val Val Ile Val Asp Ala Ser Leu Ser 465 470 475 480 His Pro Glu Ser Val Asn Arg Thr Lys Phe Asp Cys Val Glu Asn Gly 485 490 495

Trp Pro Ser val Cys Ile Asp Leu Thr Leu Cys Phe Ser Tyr Lys Gly 500 505 510 Lys Glu val Pro Gly Tyr Ile Val Leu Phe Tyr Asn Met Ser Leu Asp 515 520 525 Val Asn Arg Lys Ala Glu Ser Pro Pro Arg Phe Tyr Phe Ser Ser Asn 530 535 540 Gly Thr Ser Asp Val Ile Thr Gly Ser Ile Gln Val Ser Ser Arg Glu 545 550 555 560 Ala Asn Cys Arg Thr His Gln Ala Phe Met Arg Lys Asp Val Arg Asp 565 570 575 Ile Leu Thr Pro Ile Gln Ile Glu Ala Ala Tyr His Leu Gly Pro His 580 585 590 Val Ile Ser Lys Arg Ser Thr Glu Glu Phe Pro Pro Leu Gln Pro Ile 595 600 605 Leu Gln Gln Lys Lys Glu Lys Asp Ile Met Lys Lys Thr Ile Asn Phe 610 615 620 Ala Arg Phe Cys Ala His Glu Asn Cys Ser Ala Asp Leu Gln Val Ser 625 630 635 6490 Ala Lys Ile Gly Phe Leu Lys Pro His Glu Asn Lys Thr Tyr Leu Ala 645 650 655 Val Gly Ser Met Lys Thr Leu Met Leu Asn Val Ser Leu Phe Asn Ala 660 665 670 Gly Asp Asp Ala Tyr Glu Thr Thr Leu His Val Lys Leu Pro Val Gly 675 680 685 Leu Tyr Phe Ile Lys Ile Leu Glu Leu Glu Glu Lys Gln Ile Asn Cys 690 695 700 Glu Val Thr Asp Asn Ser Gly Val Val Gln Leu Asp Cys Ser Ile Gly 705 710 715 720 Tyr Ile Tyr Val Asp His Leu Ser Arg Ile Asp Ile Ser Phe Leu Leu 725 730 735 Asp Val Ser Ser Leu Ser Arg Ala Glu Glu Asp Leu Ser Ile Thr Val

740 745 . 750 His Ala Thr Cys Glu Asn Glu Glu Glu Met Asp Asn Leu Lys His Ser 755 760 765 Arg Val Thr Val Ala Ile Pro Leu Lys Tyr Glu Val Lys Leu Thr Val 770 7175 780 His Gly Phe Val Asn Pro Thr Ser Phe Val Tyr Gly Ser Asn Asp Glu 785 790 795 800 Asn Glu Pro Glu Thr Cys Met Val Glu Lys Met Asn Leu Thr Phe His 805 810 815 Val Ile Asn Thr Gly Asn Ser Met Ala Pro Asn Val Ser Val Glu Ile 820 825 830 Met Val Pro Asn Ser Phe Ser Pro Gln Thr Asp Lys Leu Phe Asn Ile 835 840 845 Leu Asp Val Gln Thr Thr Thr Gly Glu Cys His Phe Glu Asn Tyr Gln 850 B55 860 Arg Val Cys Ala Leu Glu Gln Gln Lys Ser Ala Met Gln Thr Leu Lys 865 870 875 880 Gly Ile Val Arg Phe Leu Ser Lys Thr Asp Lys Arg Leu Leu Tyr Cys 885 890 895 Ile Lys Ala Asp Pro His Cys Leu Asn Phe Leu Cys Asn Phe Gly Lys 800 905 910 Met Glu Ser Gly Lys Glu Ala Ser Val His Ile Gln Leu Glu Gly Arg 915 920 925 Pro Ser Ile Leu Glu Met Asp Glu Thr Ser Ala Leu Lys Phe Glu Ile 930 935 940 Arg Ala Thr Gly Phe Pro Glu Pro Asn Pro Arg Val Ile Glu Leu Asn 945 950 855 960 Lys Asp Glu Asn Val Ala His Val Leu Leu Glu Gly Leu His His Gln 965 970 975 Arg Pro Lys Arg Tyr Phe Thr Ile Val Ile Ile Ser Ser Ser Leu Leu 980 985 990

Leu Gly Leu Ile Val Leu Leu Leu Ile Ser Tyr Val Met Trp Lys Ala 995 1000 1005 Gly Phe Phe Lys Arg Gln Tyr Lys Ser Ile Leu Gln Glu Glu Asn 1010 1015 1020 Arg Arg Asp Ser Trp Ser Tyr Ile Asn Ser Lys Ser Asn Asp Asp 1025 1030 1035 <210> 2444 <211> 1152 <212> PRT <213> Homo sapiens <400> 2444 Met Ala Leu Arg Val Leu Leu Leu Thr Ala Leu Thr Leu Cys His Gly 1 5 10 15 Phe Asn Leu Asp Thr Glu Asn Ala Met Thr Phe Gln Glu Asn Ala Arg

Gly Phe Gly Gln Ser Val Val Gln Leu Gln Gly Ser Arg Val Val Val 40 45 Gly Ala Pro Gln Glu Ile Val Ala Ala Asn Gln Arg Gly Ser Leu Tyr 50 55 60 Gln Cys Asp Tyr Ser Thr Gly Ser Cys Glu Pro Ile Arg Leu Gln Val 65 70 75 80 Pro Val Glu Ala Val Asn Met Ser Leu Gly Leu Ser Leu Ala Ala Thr 85 90 95 Thr Ser Pro Pro Gln Leu Leu Ala Cys Gly Pro Thr Val His Gln Thr 100 108 110 Cys Ser Glu Asn Thr Tyr Val Lys Gly Leu Cys Phe Leu Phe Gly Ser 115 120 125 Asn Leu Arg Gln Gln Pro Gln Lys Phe Pro Glu Ala Leu Arg Gly Cys 130 135 140 Pro Gln Glu Asp Ser Asp Ile Ala Phe Leu Ile Asp Gly Ser Gly Ser 145 150 155 160

Ile Ile Pro His Asp Phe Arg Arg Met Lys Glu Phe Val Ser Thr Val 165 170 175 Met Glu Gln Leu Lys Lys Ser Lys Thr Leu Phe Ser Leu Met Gln Tyr 180 185 150 . Ser Glu Glu Phe Arg Ile His Phe Thr Phe Lys Glu Phe Gln Asn Asn 185 200 205 Pro Asn Pro Arg Ser Leu Val Lys Pro Ile Thr Gln Leu Leu Gly Arg 210 215 220 Thr His Thr Ala Thr Gly Ile Arg Lys Val val Arg Glu Leu Phe Asn 225 230 235 240 Ile Thr Asn Gly Ala Arg Lys Asn Ala Phe Lys Ile Leu Val Val Ile 245 250 255 Thr Asp Gly Glu Lys Phe Gly Asp Pro Leu Gly Tyr Glu Asp Val Ile 260 265 270 Pro Glu Ala Asp Arg Glu Gly Val Ile Arg Tyr Val Ile Gly Val Gly 275 280 285 Asp Ala Phe Arg Ser Glu Lys Ser Arg Gln Glu Leu Asn Thr Ile Ala 290 295 300 Ser Lys Pro Pro Arg Asp His Val Phe Gln Val Asn Asn Phe Glu Ala 305 310 315 320 Leu Lys Thr Ile Gln Asn Gln Leu Arg Glu Lys Ile Phe Ala Ile Glu 325 330 335 Gly Thr Gln Thr Gly Ser Ser Ser Ser Phe Glu His Glu Met Ser Gln 340 345 350 Glu Gly Phe Ser Ala Ala Ile Thr Ser Asn Gly Pro Leu Leu Ser Thr 355 360 365 ) Val Gly Ser Tyr Asp Trp Ala Gly Gly Val Phe Leu Tyr Thr Ser Lys 370 375 380 - Glu Lys Ser Thr Phe Ile Asn Met Thr Arg Val Asp Ser Asp Met Asn 385 390 395 400 Asp Ala Tyr Leu Gly Tyr Ala Ala Ala Ile Ile Leu Arg Asn Arg Val

405 410 415 Gln Ser Leu Val Leu Gly Ala Pro Arg Tyr Gln His Ile Gly Leu Val 420 425 430 Ala Met Phe Arg Gln Asn Thr Gly Met Trp Glu Ser Asn Ala Asn Val 435 440 445 Lys Gly Thr Gln Ile Gly Ala Tyr Phe Gly Ala Ser Leu Cys Ser Val 450 455 460 Asp Val Asp Ser Asn Gly Ser Thr Asp Leu Val Leu Ile Gly Ala Pro 4€5 470 475 480 His Tyr Tyr Glu Gln Thr Arg Gly Gly Gln Val Ser Val Cys Pro Leu 485 490 495 Pro Arg Gly Arg Ala Arg Trp Gln Cys Asp Ala Val Leu Tyr Gly Glu 500 505 510 Gln Gly Gln Pro Trp Gly Arg Phe Gly Ala Ala Leu Thr Val Leu Gly 515 520 525 Asp Val Asn Gly Asp Lys Leu Thr Asp Val Ala Ile Gly Ala Pro Gly 530 535 540 Glu Glu Asp Asn Arg Gly Ala Val Tyr Leu Phe His Gly Thr Ser Gly 545 550 555 560 Ser Gly Ile Ser Pro Ser His Ser Gln Arg Ile Ala Gly Ser Lys Leu 565 570 575 Ser Pro Arg Leu Gln Tyr Phe Gly Gln Ser Leu Ser Gly Gly Gln Asp 580 585 530 Leu Thr Met Asp Gly Leu Val Asp Leu Thr Val Gly Ala Gln Gly His 595 600 605 Val Leu Leu Leu Arg Ser Gln Pro Val Leu Arg Val Lys Ala Ile Met 610 61S 620 Glu Phe Asn Pro Arg Glu Val Ala Arg Asn Val Phe Glu Cys Asn Asp 625 630 635 640 Gln Val Val Lys Gly Lys Glu Ala Gly Glu Val Arg Val Cys Leu His 645 650 655

Val Gln Lys Ser Thr Arg Asp Arg Leu Arg Glu Gly Gln Ile Gln Ser 660 665 670 Val val Thr Tyr Asp Leu Ala Leu Asp Ser Gly Arg Pro His Ser Arg 675 680 685 Ala Val Phe Asn Glu Thr Lys Asn Ser Thr Arg Arg Gln Thr Gln Val 690 695 700 Leu Gly Leu Thr Gln Thr Cys Glu Thr Leu Lys Leu Gln Leu Pro Asn 705 710 715 720 Cys Ile Glu Asp Pro Val Ser Pro Ile Val Leu Arg Leu Asn Phe Ser 725 730 735 Leu Val Gly Thr Pro Leu Ser Ala Phe Gly Asn Leu Arg Pro Val Leu 740 745 750 : Ala Glu Asp Ala Gln Arg Leu Phe Thr Ala Leu Phe Pro Phe Glu Lys 755 760 765 Asn Cys Gly Asn Asp Asn Ile Cys Gln Asp Asp Leu Ser Ile Thr Phe 770 775 780 Ser Phe Met Ser Leu Asp Cys Leu Val Val Gly Gly Pro Arg Glu Phe 785 790 795 800 Asn Val Thr Val Thr Val Arg Asn Asp Gly Glu Asp Ser Tyr Arg Thr 805 810 815 Gln Val Thr Phe Phe Phe Pro Leu Asp Leu Ser Tyr Arg Lys Val Ser 820 825 830 Thr Leu Gln Asn Gln Arg Ser Gln Arg Ser Trp Arg Leu Ala Cys Glu 835 840 845 Ser Ala Ser Ser Thr Glu Val Ser Gly Ala Leu Lys Ser Thr Ser Cys : 850 855 860 Ser Ile Asn His Pro Ile Phe Pro Glu Asn Ser Glu Val Thr Phe Asn 865 870 875 880 Ile Thr Phe Asp Val Asp Ser Lys Ala Ser Leu Gly Asn Lys Leu Leu 885 890 895

Leu Lys Ala Asn Val Thr Ser Glu Asn Asn Met Pro Arg Thr Asn Lys

900 905 S10 Thr Glu Phe Gln Leu Glu Leu Pro Val Lys Tyr Ala Val Tyr Met Val 915 920 925

Val Thr Ser His Gly Val Ser Thr Lys Tyr Leu Asn Phe Thr Ala Ser 930 935 940

Glu Asn Thr Ser Arg Val Met Gln His Gln Tyr Gln Val Ser Asn Leu

545 950 S55 960

Gly Gln Arg Ser Pro Pro Ile Ser Leu Val Phe Leu Val Pro Val Arg

965 970 975 Leu Asn Gln Thr Val Ile Trp Asp Arg Pro Gln Val Thr Phe Ser Glu 980 985 990 Asn Leu Ser Ser Thr Cys His Thr Lys Glu Arg Leu Pro Ser His Ser 995 1000 1005S

Asp Phe Leu Ala Glu Leu Arg Lys Ala Pro Val Val Asn Cys Ser 1010 1015 1020

Ile Ala Val Cys Gln Arg Ile Gln Cys Asp Ile Pro Phe Phe Gly 1025 1030 1035

Ile Gln Glu Glu Phe Asn Ala Thr Leu Lys Gly Asn Leu Ser Phe 1040 1045 1050

Asp Trp Tyr Ile Lys Thr Ser His Asn His Leu Leu Ile Val Ser 1055 1060 1065

Thr Ala Glu Ile Leu Phe Asn Asp Ser Val Phe Thr Leu Leu Pro 1070 1075 1080

Gly Gln Gly Ala Phe Val Arg Ser Gln Thr Glu Thr Lys Val Glu 1085 1090 1095

Pro Phe Glu Val Pro Asn Pro Leu Pro Leu Ile val Gly Ser Ser 1100 1105 1110

Val Gly Gly Leu Leu Leu Leu Ala Leu Ile Thr Ala Ala Leu Tyr 1115 112¢C 1125

Lys Leu Gly Phe Phe Lys Arg Gln Tyr Lys Asp Met Met Ser Glu 1130 1135 1140 Gly Gly Pro Pro Gly Ala Glu Pro Gln 1145 1150 <210> 2445. <211> 798 <212> PRT <213> Homo sapiens . <400> 2445 Met Val Ala Leu Pro Met Val Leu Val Leu Leu Leu Val Leu Ser Arg 1 S 10 15 Gly Glu Ser Glu Leu Asp Ala Lys Ile Pro Ser Thr Gly Asp Ala Thr

Glu Trp Arg Asn Pro His Leu Ser Met Leu Gly Ser Cys Gln Pro Ala 40 45 Pro Ser Cys Gln Lys Cys Ile Leu Ser His Pro Ser Cys Ala Trp Cys 50 55 60 Lys Gln Leu Asn Phe Thr Ala Ser Gly Glu Ala Glu Ala Arg Arg Cys 65 70 75 80 Ala Arg Arg Glu Glu Leu Leu Ala Arg Gly Cys Pro Leu Glu Glu Leu 85 90 95 Glu Glu Pro Arg Gly Gln Gln Glu Val Leu Gln Asp Gln Pro Leu Ser 100 105 110 Gln Gly Ala Arg Gly Glu Gly Ala Thr Gln Leu Ala Pro Gln Arg val 115 120 125 Arg Val Thr Leu Arg Pro Gly Glu Pro Gln Gln Leu Gln Val Arg Phe 130 135 140 Leu Arg Ala Glu Gly Tyr Pro Val Asp Leu Tyr Tyr Leu Met Asp Leu 145 150 155 160 Ser Tyr Ser Met Lys Asp Asp Leu Glu Arg Val Arg Gln Leu Gly His 165 170 175 Ala Leu Leu Val Arg Leu Gln Glu Val Thr His Ser val Arg Ile Gly 180 185 190

Phe Gly Ser Phe val Asp Lys Thr Val Leu Pro Phe Val Ser Thr val 195 200 205 Pro Ser Lys Leu Arg His Pro Cys Pro Thr Arg Leu Glu Arg Cys Gln 210 215 220 Ser Pro Phe Ser Phe His His Val Leu Ser Leu Thr Gly Asp Ala Gln 225 230 235 240 Ala Phe Glu Arg Glu Val Gly Arg Gln Ser Val Ser Gly Asn Leu Asp 245 250 255 Ser Pro Glu Gly Gly Phe Asp Ala Ile Leu Gln Ala Ala Leu Cys Gln 260 265 270 Glu Gln Ile Gly Trp Arg Asn Val Ser Arg Leu Leu Val Phe Thr Ser 275 280 285 Asp Asp Thr Phe His Thr Ala Gly Asp Gly Lys Leu Gly Gly Ile Phe 290 295 300 Met Pro Ser Asp Gly His Cys His Leu Asp Ser Asn Gly Leu Tyr Ser 305 310 315 320 Arg Ser Thr Glu Phe Asp Tyr Pro Ser Val Gly Gln Val Ala Gln Ala 325 330 335 Leu Ser Ala Ala Asn Ile Gln Pro Ile Phe Ala Val Thr Ser Ala Ala 340 345 350 Leu Pro Val Tyr Gln Glu Leu Ser Lys Leu Ile Pro Lys Ser Ala Val 355 360 365 Gly Glu Leu Ser Glu Asp Ser Ser Asn Val Val Gln Leu Ile Met Asp 370 375 380 Ala Tyr Asn Ser Leu Ser Ser Thr Val Thr Leu Glu His Ser Ser Leu 385 390 3985 400 Pro Pro Gly Val His Ile Ser Tyr Glu Ser Gln Cys Glu Gly Pro Glu 405 410 415 Lys Arg Glu Gly Lys Ala Glu Asp Arg Gly Gln Cys Asn His Val Arg 420 425 430

Ile Asn Gln Thr Val Thr Phe Trp Val Ser Leu Gln Ala Thr His Cys 435 440 445 Leu Pro Glu Pro His Leu Leu Arg Leu Arg Ala Leu Gly Phe Ser Glu 450 455 460 Glu Leu Ile Val Glu Leu His Thr Leu Cys Asp Cys Asn Cys Ser Asp 465 470 475 480 Thr Gln Pro Gln Ala Pro His Cys Ser Asp Gly Gln Gly His Leu Gln 485 490 495 Cys Gly Val Cys Ser Cys Ala Pro Gly Arg Leu Gly Arg Leu Cys Glu 500 505 510 Cys Ser Val Ala Glu Leu Ser Ser Pro Asp Leu Glu Ser Gly Cys Arg 515 520 525 Ala Pro Asn Gly Thr Gly Pro Leu Cys Ser Gly Lys Gly His Cys Gln S30 S35 540 Cys Gly Arg Cys Ser Cys Ser Gly Gln Ser Ser Gly His Leu Cys Glu 545 550 555 560 Cys Asp Asp Ala Ser Cys Glu Arg His Glu Gly Ile Leu Cys Gly Gly 565 570 575 Phe Gly Arg Cys Gln Cys Gly Val Cys His Cys His Ala Asn Arg Thr 580 585 590 Gly Arg Ala Cys Glu Cys Ser Gly Asp Met Asp Ser Cys Ile Ser Pro 595 600 605 Glu Gly Gly Leu Cys Ser Gly His Gly Arg Cys Lys Cys Asn Arg Cys 610 615 620

Gln Cys Leu Asp Gly Tyr Tyr Gly Ala Leu Cys Asp Gln Cys Pro Gly

625 630 635 640

Cys Lys Thr Pro Cys Glu Arg His Arg Asp Cys Ala Glu Cys Gly Ala

645 650 655 Phe Arg Thr Gly Pro Leu Ala Thr Asn Cys Ser Thr Ala Cys Ala His 660 665 670

Thr Asn val Thr Leu Ala Leu Ala Pro Ile Leu Asp Asp Gly Trp Cys 675 680 685 Lys Glu Arg Thr Leu Asp Asn Gln Leu Phe Phe Phe Leu Val Glu Asp 690 695 700 Asp Ala Arg Gly Thr Val Val Leu Arg Val Arg Pro Gln Glu Lys Gly 705 710 715 720 Ala Asp His Thr Gln Ala Ile Val Leu Gly Cys Val Gly Gly Ile Val 725 730 735 Ala Val Gly Leu Gly Leu Val Leu Ala Tyr Arg Leu Ser Val Glu Ile 740 745 750 Tyr Asp Arg Arg Glu Tyr Ser Arg Phe Glu Lys Glu Gln Gln Gln Leu 75S 760 765 Asn Trp Lys Gln Asp Ser Asn Pro Leu Tyr Lys Ser Ala Ile Thr Thr 770 775 780 Thr Ile Asn Pro Arg Phe Gln Glu Ala Asp Ser Pro Thr Leu 785 730 795 <210> 2446 <211> 345 <212> PRT <213> Homo sapiens <400> 2446 Met Gln Arg Leu Val Ala Trp Asp Pro Ala Cys Leu Pro Leu Pro Pro 1 5 10 15 Pro Pro Pro Ala Phe Lys Ser Met Glu Val Ala Asn Phe Tyr Tyr Glu Ala Asp Cys Leu Ala Ala Ala Tyr Gly Gly Lys Ala Ala Pro Ala Ala 38 40 45 Pro Pro Ala Ala Arg Pro Gly Pro Arg Pro Pro Ala Gly Glu Leu Gly 50 55 60 Ser Ile Gly Asp His Glu Arg Ala Ile Asp Phe Ser Pro Tyr Leu Glu 65 70 75 80 Pro Leu Gly Ala Pro Gln Ala Pro Ala Pro Ala Thr Ala Thr Asp Thr

85 . 90 95

Phe Glu Ala Ala Pro Pro Ala Pro Ala Pro Ala Pro Ala Ser Ser Gly 100 105 110 Gln His His Asp Phe Leu Ser Asp Leu Phe Ser Asp Asp Tyr Gly Gly 115 120 125 Lys Asn Cys Lys Lys Pro Ala Glu Tyr Gly Tyr Val Ser Leu Gly Arg 130 135 140 Leu Gly Ala Ala Lys Gly Ala Leu His Pro Gly Cys Phe Ala Pro Leu 145 150 155 160 His Pro Pro Pro Pro Pro Pro Pro Pro Pro Ala Glu Leu Lys Ala Glu 165 170 175 Pro Gly Phe Glu Pro Ala Asp Cys Lys Arg Lys Glu Glu Ala Gly Ala 180 185 190 Pro Gly Gly Gly Ala Gly Met Ala Ala Gly Phe Pro Tyr Ala Leu Arg 195 200 205 Ala Tyr Leu Gly Tyr Gln Ala Val Pro Ser Gly Ser Ser Gly Ser Leu 210 215 220 Ser Thr Ser Ser Ser Ser Ser Pro Pro Gly Thr Pro Ser Pro Ala Asp 225 230 235 240 Ala Lys Ala Pro Pro Thr Ala Cys Tyr Ala Gly Ala Ala Pro Ala Pro 245 250 255 Ser Gln Val Lys Ser Lys Ala Lys Lys Thr Val Asp Lys His Ser Asp 260 265 270 Glu Tyr Lys Ile Arg Arg Glu Arg Asn Asn Ile Ala Val Arg Lys Ser 275 280 285 Arg Asp Lys Ala Lys Met Arg Asn Leu Glu Thr Gln His Lys Val Leu 290 295 300 Glu Leu Thr Ala Glu Asn Glu Arg Leu Gln Lys Lys Val Glu Gln Leu 305 310 31s 320 Ser Arg Glu Leu Ser Thr Leu Arg Asn Leu Phe Lys Gln Leu Pro Glu 325 330 335

Pro Leu Leu Ala Ser Ser Gly His Cys 340 345 <210> 2447 <211> 373 <212> PRT <213> Homo sapiens <400> 2447 Met Ser Pro Cys Pro Pro Gln Gln Ser Arg Asn Arg Val Ile Gln Leu 1 5 10 15 Ser Thr Ser Glu Leu Gly Glu Met Glu Leu Thr Trp Gln Glu Ile Met

Ser Ile Thr Glu Leu Gln Gly Leu Asn Ala Pro Ser Glu Pro Ser Phe 40 45 Glu Pro Gln Ala Pro Ala Pro Tyr Leu Gly Pro Pro Pro Pro Thr Thr 50 55 60 Tyr Cys Pro Cys Ser Ile His Pro Asp Ser Gly Phe Pro Leu Pro Pro 65 70 75 80 Pro Pro Tyr Glu Leu Pro Ala Ser Thr Ser His Val Pro Asp Pro Pro 85 90 95 Tyr Ser Tyr Gly Asn Met Ala Ile Pro Val Ser Lys Pro Leu Ser Leu 100 105 110 Ser Gly Leu Leu Ser Glu Pro Leu Gln Asp Pro Leu Ala Leu Leu Asp 115 120 125 Ile Gly Leu Pro Ala Gly Pro Pro Lys Pro Gln Glu Asp Pro Glu Ser 130 135 140 Asp Ser Gly Leu Ser Leu Asn Tyr Ser Asp Ala Glu Ser Leu Glu Leu 145 150 155 160 Glu Gly Thr Glu Ala Gly Arg Arg Arg Ser Glu Tyr Val Glu Met Tyr 165 170 175 Pro Val Glu Tyr Pro Tyr Ser Leu Met Pro Asn Ser Leu Ala His Ser 180 185 190 Asn Tyr Thr Leu Pro Ala Ala Glu Thr Pro Leu Ala Leu Glu Pro Ser

195 200 205 Ser Gly Pro Val Arg Ala Lys Pro Thr Ala Arg Gly Glu Ala Gly Ser 210 215 220 Arg Asp Glu Arg Arg Ala Leu Ala Met Lys Ile Pro Phe Pro Thr Asp 225 230 235 240 Lys Ile Val Asn Leu Pro Val Asp Asp Phe Asn Glu Leu Leu Ala Arg 245 250 255 Tyr Pro Leu Thr Glu Ser Gln Leu Ala Leu Val Arg Asp Ile Arg Arg 260 265 270 Arg Gly Lys Asn Lys Val Ala Ala Gln Asn Cys Arg Lys Arg Lys Leu 275 280 285 Glu Thr Ile val Gln Leu Glu Arg Glu Leu Glu Arg Leu Thr Asn Glu 2590 295 300 Arg Glu Arg Leu Leu Arg Ala Arg Gly Glu Ala Asp Arg Thr Leu Glu 305 310 315 320 Val Met Arg Gln Gln Leu Thr Glu Leu Tyr Arg Asp Ile Phe Gln His 325 330 335 Leu Arg Asp Glu Ser Gly Asn Ser Tyr Ser Pro Glu Glu Tyr Ala Leu 340 345 350 Gln Gln Ala Ala Asp Gly Thr Ile Phe Leu Val Pro Arg Gly Thr Lys 355 360 365 Met Glu Ala Thr Asp 370 <210> 2448 <211> 288 <212> PRT <213> Homo sapiens <400> 2448 . Met Gln Ile Pro Gln Ala Pro Trp Pro Val val Trp Ala Val Leu Gln 1 5 10 15 Leu Gly Trp Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp

Asn Pro Pro Thr Phe Phe Pro Ala Leu Leu Val Val Thr Glu Gly Asp 40 45 Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val 50 55 60 Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala 65 70 75 80 Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg 85 90 95 Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg 100 105 110 Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu 115 120 125 Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val 130 135 140 Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro 145 150 155 160 Arg Pro Ala Gly Gln Phe Gln Thr Leu Val Val Gly Val Val Gly Gly 165 170 175 Leu Leu Gly Ser Leu Val Leu Leu Val Trp Val Leu Ala Val Ile Cys 180 185 190 Ser Arg Ala Ala Arg Gly Thr Ile Gly Ala Arg Arg Thr Gly Gln Pro 195 200 205 Leu Lys Glu Asp Pro Ser Ala Val Pro Val Phe Ser Val Asp Tyr Gly 210 215 220 Glu Leu Asp Phe Gln Trp Arg Glu Lys Thr Pro Glu Pro Pro Val Pro 225 230 : 235 240 Cys Val Pro Glu Gln Thr Glu Tyr Ala Thr Ile Val Phe Pro Ser Gly 245 250 255 Met Gly Thr Ser Ser Pro Ala Arg Arg Gly Ser Ala Asp Gly Pro Arg 260 265 270

Ser Ala Gln Pro Leu Arg Pro Glu Asp Gly His Cys Ser Trp Pro Leu 275 280 285 <210> 2449 <211> 101 <212> PRT : <213> Homo sapiens <400> 2449 Met Ser Ser Ala Ala Gly Phe Cys Ala Ser Arg Pro Gly Leu Leu Phe 1 5 10 15 Leu Gly Leu Leu Leu Leu Pro Leu Val Val Ala Phe Ala Ser Ala Glu

Ala Glu Glu Asp Gly Asp Leu Gln Cys Leu Cys Val Lys Thr Thr Ser 40 45 Gln Val Arg Pro Arg His Ile Thr Ser Leu Glu Val Ile Lys Ala Gly 50 55 60 Pro His Cys Pro Thr Ala Gln Leu Ile Ala Thr Leu Lys Asn Gly Arg 65 70 75 80 Lys Ile Cys Leu Asp Leu Gln Ala Pro Leu Tyr Lys Lys Ile Ile Lys 85 90 95 Lys Leu Leu Glu Ser 100 <210> 2450 <211> 706 <212> PRT <213> Homo sapiens <400> 2450 Met Ser Pro Phe Leu Arg Ile Gly Leu Ser Asn Phe Asp Cys Gly Ser 1 S 10 15 Cys Gln Ser Cys Gln Gly Glu Ala Val Asn Pro Tyr Cys Ala Val Leu 20 25 30 Val Lys Glu Tyr Val Glu Ser Glu Asn Gly Gln Met Tyr Ile Gln Lys 35 40 45 Lys Pro Thr Met Tyr Pro Pro Trp Asp Ser Thr Phe Asp Ala His Ile 50 55 60

PCT/US2003/012946 © WO 2004/042346 Asn Lys Gly Arg Val Met Gln Ile Ile val Lys Gly Lys Asn Val Asp 65 70 75 80 Leu Ile Ser Glu Thr Thr Val Glu Leu Tyr Ser Leu Ala Glu Arg Cys 85 SO 95 Arg Lys Asn Asn Gly Lys Thr Glu Ile Trp Leu Glu Leu Lys Pro Gln 100 105 110 Gly Arg Met Leu Met Asn Ala Arg Tyr Phe Leu Glu Met Ser Asp Thr 115 120 125 Lys Asp Met Asn Glu Phe Glu Thr Glu Gly Phe Phe Ala Leu His Gln 130 135 140 Arg Arg Gly Ala Ile Lys Gln Ala Lys Val His His Val Lys Cys His 145 150 155 160 Glu Phe Thr Ala Thr Phe Phe Pro Gln Pro Thr Phe Cys Ser val Cys 165 170 175 His Glu Phe Val Trp Gly Leu Asn Lys Gln Gly Tyr Gln Cys Arg Gln 180 185 190 Cys Asn Ala Ala Ile His Lys Lys Cys Ile Asp Lys val Ile Ala Lys 195 200 205 Cys Thr Gly Ser Ala Ile Asn Ser Arg Glu Thr Met Phe His Lys Glu 210 215 220 Arg Phe Lys Ile Asp Met Pro His Arg Phe Lys Val Tyr Asn Tyr Lys 225 230 235 240 Ser Pro Thr Phe Cys Glu His Cys Gly Thr Leu Leu Trp Gly Leu Ala 245 250 255 Arg Gln Gly Leu Lys Cys Asp Ala Cys Gly Met Asn Val His His Arg 260 265 270 Cys Gln Thr Lys Val Ala Asn Leu Cys Gly Ile Asn Gln Lys Leu Met : 275 280 285 Ala Glu Ala Leu Ala Met Ile Glu Ser Thr Gln Gln Ala Arg Cys Leu 290 285 300

Arg Asp Thr Glu Gln Ile Phe Arg Glu Gly Pro Val Glu Ile Gly Leu 305 310 315 320 Pro Cys Ser Ile Lys Asn Glu Ala Arg Pro Pro Cys Leu Pro Thr Pro 325 330 3358 Gly Lys Arg Glu Pro Gln Gly Ile Ser Trp Glu Ser Pro Leu Asp Glu 340 345 350 Val Asp Lys Met Cys His Leu Pro Glu Pro Glu Leu Asn Lys Glu Arg 355 360 365 Pro Ser Leu Gln Ile Lys Leu Lys Ile Glu Asp Phe Ile Leu His Lys 370 375 380 Met Leu Gly Lys Gly Ser Phe Gly Lys Val Phe Leu Ala Glu Phe Lys 385 390 395 400 Lys Thr Asn Gln Phe Phe Ala Ile Lys Ala Leu Lys Lys Asp Val Val 405 410 415 Leu Met Asp Asp Asp Val Glu Cys Thr Met Val Glu Lys Arg Val Leu 420 425 430 Ser Leu Ala Trp Glu His Pro Phe Leu Thr His Met Phe Cys Thr Phe 435 440 445 Gln Thr Lys Glu Asn Leu Phe Phe Val Met Glu Tyr Leu Asn Gly Gly 450 455 460 Asp Leu Met Tyr His Ile Gln Ser Cys His Lys Phe Asp Leu Ser Arg 465 470 475 480 Ala Thr Phe Tyr Ala Ala Glu Ile Ile Leu Gly Leu Gln Phe Leu His 485 430 495 Ser Lys Gly Ile Val Tyr Arg Asp Leu Lys Leu Asp Asn Ile Leu Leu 500 505 510 Asp Lys Asp Gly His Ile Lys Ile Ala Asp Phe Gly Met Cys Lys Glu 515 520 525 ’ Asn Met Leu Gly Asp Ala Lys Thr Asn Thr Phe Cys Gly Thr Pro Asp 530 535 540 Tyr Ile Ala Pro Glu Ile Leu Leu Gly Gln Lys Tyr Asn His Ser Val : 772 i

545 550 555 560 Asp Trp Trp Ser Phe Gly Val Leu Leu Tyr Glu Met Leu Ile Gly Gln 565 570 575 Ser Pro Phe His Gly Gln Asp Glu Glu Glu Leu Phe His Ser Ile Arg 580 585 590 Met Asp Asn Pro Phe Tyr Pro Arg Trp Leu Glu Lys Glu Ala Lys Asp 595 600 605 Leu Leu Val Lys Leu Phe Val Arg Glu Pro Glu Lys Arg Leu Gly Val 610 615 620 Arg Gly Asp Ile Arg Gln His Pro Leu Phe Arg Glu Ile Asn Trp Glu 625 630 635 640 Glu Leu Glu Arg Lys Glu Ile Asp Pro Pro Phe Arg Pro Lys Val Lys 645 650 655 Ser Pro Phe Asp Cys Ser Asn Phe Asp Lys Glu Phe Leu Asn Glu Lys 660 665 670 Pro Arg Leu Ser Phe Ala Asp Arg Ala Leu Ile Asn Ser Met Asp Gln 675 680 685 Asn Met Phe Arg Asn Phe Ser Phe Met Asn Pro Gly Met Glu Arg Leu 690 695 700 Ile Ser 705 <210> 2451 <211> 798 <212> PRT <213> Homo sapiens <400> 2451 Met Ala Trp Asp Met Cys Asn Gln Asp Ser Glu Ser Val Trp Ser Asp 1 5 10 15 Ile Glu Cys Ala Ala Leu Val Gly Glu Asp Gln Pro Leu Cys Pro Asp

Leu Pro Glu Leu Asp Leu Ser Glu Leu Asp Val Asn Asp Leu Asp Thr 40 45

Asp Ser Phe Leu Gly Gly Leu Lys Trp Cys Ser Asp Gln Ser Glu Ile 50 55 60 Ile Ser Asn Gln Tyr Asn Asn Glu Pro Ser Asn Ile Phe Glu Lys Ile 65 70 75 80 Asp Glu Glu Asn Glu Ala Asn Leu Leu Ala Val Leu Thr Glu Thr Leu 85 90 95 Asp Ser Leu Pro Val Asp Glu Asp Gly Leu Pro Ser Phe Asp Ala Leu 100 105 110 Thr Asp Gly Asp Val Thr Thr Asp Asn Glu Ala Ser Pro Ser Ser Met 115 120 125 Pro Asp Gly Thr Pro Pro Pro Gln Glu Ala Glu Glu Pro Ser Leu Leu 130 135 140 Lys Lys Leu Leu Leu Ala Pro Ala Asn Thr Gln Leu Ser Tyr Asn Glu 145 150 155 160 Cys Ser Gly Leu Ser Thr Gln Asn His Ala Asn His Asn His Arg Ile 165 170 175 Arg Thr Asn Pro Ala Ile Val Lys Thr Glu Asn Ser Trp Ser Asn Lys 180 185 190 Ala Lys Ser Ile Cys Gln Gln Gln Lys Pro Gln Arg Arg Pro Cys Ser 195 200 205 Glu Leu Leu Lys Tyr Leu Thr Thr Asn Asp Asp Pro Pro His Thr Lys 210 215 220 Pro Thr Glu Asn Arg Asn Ser Ser Arg Asp Lys Cys Thr Sex Lys Lys 225 230 235 240 Lys Ser His Thr Gln Ser Gln Ser Gln His Leu Gln Ala Lys Pro Thr 245 250 255 Thr Leu Ser Leu Pro Leu Thr Pro Glu Ser Pro Asn Asp Pro Lys Gly 260 265 270 Ser Pro Phe Glu Asn Lys Thr Ile Glu Arg Thr Leu Ser Val Glu Leu 275 280 285

Ser Gly Thr Ala Gly Leu Thr Pro Pro Thr Thr Pro Pro His Lys Ala 290 295 300 Asn Gln Asp Asn Pro Phe Arg Ala Ser Pro Lys Leu Lys.

Ser Ser Cys 305 310 315 320 Lys Thr val Val Pro Pro Pro Ser Lys Lys Pro Arg Tyr Ser Glu Ser 325 330 335 Ser Gly Thr Gln Gly Asn Asn Ser Thr Lys Lys Gly Pro Glu Gln Ser 340 345 350 Glu Leu Tyr Ala Gln Leu Ser Lys Ser Ser Val Leu Thr Gly Gly His 355 360 365 Glu Glu Arg Lys Thr Lys Arg Pro Ser Leu Arg Leu Phe Gly Asp His 370 375 380 Asp Tyr Cys Gln Ser Ile Asn Ser Lys Thr Glu Ile Leu Ile Asn Ile 385 390 395 400 Ser Gln Glu Leu Gln Asp Ser Arg Gln Leu Glu Asn Lys Asp Val Ser 405 410 415 Ser Asp Trp Gln Gly Gln Ile Cys Ser Ser Thr Asp Ser Asp Gln Cys 420 425 430 Tyr Leu Arg Glu Thr Leu Glu Ala Ser Lys Gln Val Ser Pro Cys Ser 435 440 445 Thr Arg Lys Gln Leu Gln Asp Gln Glu Ile Arg Ala Glu Leu Asn Lys 450 455 460 His Phe Gly His Pro Ser Gln Ala Val Phe Asp Asp Glu Ala Asp Lys 465 470 475 480 Thr Gly Glu Leu Arg Asp Ser Asp Phe Ser Asn Glu Gln Phe Ser Lys 485 480 495 Leu Pro Met Phe Ile Asn Ser Gly Leu Ala Met Asp Gly Leu Phe Asp. __ 500 505 510 Asp Ser Glu Asp Glu Ser Asp Lys Leu Ser Tyr Pro Trp Asp Gly Thr 515 520 525 Gln Ser Tyr Ser Leu Phe Asn Val Ser Pro Ser Cys Ser Ser Phe Asn

530 535 540 Ser Pro Cys Arg Asp Ser Val Ser Pro Pro Lys Ser Leu Phe Ser Gln 545 S50 555 560 Arg Pro Gln Arg Met Arg Ser Arg Ser Arg Ser Phe Ser Arg His Arg 565 S70 575 Ser Cys Ser Arg Ser Pro Tyr Ser Arg Ser Arg Ser Arg Ser Pro Gly 580 585 5380 Ser Arg Ser Ser Ser Arg Ser Cys Tyr Tyr Tyr Glu Ser Ser His Tyr 595 600 605 Arg His Arg Thr His Arg Asn Ser Pro Leu Tyr Val Arg Ser Arg Ser 610 615 620 Arg Ser Pro Tyr Ser Arg Arg Pro Arg Tyr Asp Ser Tyr Glu Glu Tyr 625 630 635 640 Gln His Glu Arg Leu Lys Arg Glu Glu Tyr Arg Arg Glu Tyr Glu Lys 645 650 655 Arg Glu Ser Glu Arg Ala Lys Gln Arg Glu Arg Gln Arg Gln Lys Ala 660 665 670 : Ile Glu Glu Arg Arg Val Ile Tyr Val Gly Lys Ile Arg Pro Asp Thr 675 680 685 Thr Arg Thr Glu Leu Arg Asp Arg Phe Glu Val Phe Gly Glu Ile Glu 690 695 700 Glu Cys Thr Val Asn Leu Arg Asp Asp Gly Asp Ser Tyr Gly Phe Ile 705 710 715 720 Thr Tyr Arg Tyr Thr Cys Asp Ala Phe Ala Ala Leu Glu Asn Gly Tyr 725 730 735 Thr Leu Arg Arg Ser Asn Glu Thr Asp Phe Glu Leu Tyr Phe Cys Gly 740 745 750 Arg Lys Gln Phe Phe Lys Ser Asn Tyr Ala Asp Leu Asp Ser Asn Ser 755 760 765 Asp Asp Phe Asp Pro Ala Ser Thr Lys Ser Lys Tyr Asp Ser Leu Asp 770 775 780

Phe Asp Ser Leu Leu Lys Glu Ala Gln Arg Ser Leu Arg Arg 785 790 795 <210> 2452 <211> 1043 <212> PRT <213> Homo sapiens <400> 2452 Met Ala Ala Ser Phe Pro Pro Thr Leu Gly Leu Ser Ser Ala Pro Asp 1 S 10 15 Glu Ile Gln His Pro His Ile Lys Phe Ser Glu Trp Lys Phe Lys Leu

Phe Arg Val Arg Ser Phe Glu Lys Thr Pro Glu Glu Ala Gln Lys Glu 40 45 Lys Lys Asp Ser Phe Glu Gly Lys Pro Ser Leu Glu Gln Ser Pro Ala S50 55 60 Val Leu Asp Lys Ala Asp Gly Gln Lys Pro Val Pro Thr Gln Pro Leu €5 70 75 80 : Leu Lys Ala His Pro Lys Phe Ser Lys Lys Phe His Asp Asn Glu Lys 85 90 85 Ala Arg Gly Lys Ala Ile His Gln Ala Asn Leu Arg His Leu Cys Arg 100 105 110 Ile Cys Gly Asn Ser Phe Arg Ala Asp Glu His Asn Arg Arg Tyr Pro 1158 120 125 Val His Gly Pro Val Asp Gly Lys Thr Leu Gly Leu Leu Arg Lys Lys 130 135 140 Glu Lys Arg Ala Thr Ser Trp Pro Asp Leu Ile Ala Lys Val Phe Arg 145 150 155 160 Ile Asp Val Lys Ala Asp Val Asp Ser Ile His Pro Thr Glu Phe Cys 165 170 175 His Asn Cys Trp Ser Ile Met His Arg Lys Phe Ser Ser Ala Pro Cys 180 185 190

Glu Val Tyr Phe Pro Arg Asn Val Thr Met Glu Trp His Pro His Thr 195 200 205 Pro Ser Cys Asp Ile Cys Asn Thr Ala Arg Arg Gly Leu Lys Arg Lys 210 215 220 Ser Leu Gln Pro Asn Leu Gln Leu Ser Lys Lys Leu Lys Thr Val Leu 225 230 235 240 Asp Gln Ala Arg Gln Ala Arg Gln Arg Lys Arg Arg Ala Gln Ala Arg 245 250 255 Ile Ser Ser Lys Asp Val Met Lys Lys Ile Ala Asn Cys Ser Lys Ile 260 265 270 His Leu Ser Thr Lys Leu Leu Ala Val Asp Phe Pro Glu His Phe Val 275 280 285 Lys Ser Ile Ser Cys Gln Ile Cys Glu His Ile Leu Ala Asp Pro Val 290 295 300 Glu Thr Asn Cys Lys His Val Phe Cys Arg Val Cys Ile Leu Arg Cys 305 310 315 320 Leu Lys Val Met Gly Ser Tyr Cys Pro Ser Cys Arg Tyr Pro Cys Phe 325 330 335 Pro Thr Asp Leu Glu Ser Pro Val Lys Ser Phe Leu Ser Val Leu Asn 340 345 350 Ser Leu Met Val Lys Cys Pro Ala Lys Glu Cys Asn Glu Glu Val Ser 355 360 365 Leu Glu Lys Tyr Asn His His Ile Ser Ser His Lys Glu Ser Lys Glu 370 375 380 Ile Phe Val His Ile Asn Lys Gly Gly Arg Pro Arg Gln His Leu Leu 385 390 395 400 Ser Leu Thr Arg Arg Ala Gln Lys His Arg Leu Arg Glu Leu Lys Leu 405 410 415 Gln Val Lys Ala Phe Ala Asp Lys Glu Glu Gly Gly Asp Val Lys Ser 420 425 430 Val Cys Met Thr Leu Phe Leu Leu Ala Leu Arg Ala Arg Asn Glu His

435 440 445 Arg Gln Ala Asp Glu Leu Glu Ala Ile Met Gln Gly Lys Gly Ser Gly 450 455 460 Leu Gln Pro Ala Val Cys Leu ARla Ile Arg Val Asn Thr Phe Leu Ser 465 470 475 480 Cys Ser Gln Tyr His Lys Met Tyr Arg Thr Val Lys Ala Ile Thr Gly 485 490 495 Arg Gln Ile Phe Gln Pro Leu His Ala Leu Arg Asn Ala Glu Lys Val 500 505 510 Leu Leu Pro Gly Tyr His His Phe Glu Trp Gln Pro Pro Leu Lys Asn 515 520 525 Val Ser Ser Ser Thr Asp Val Gly Ile Ile Asp Gly Leu Ser Gly Leu 530 535 540 Ser Ser Ser Val Asp Asp Tyr Pro Val Asp Thr Ile Ala Lys Arg Phe 545 550 555 560 Arg Tyr Asp Ser Ala Leu Val Ser Ala Leu Met Asp Met Glu Glu Asp 565 570 575 Ile Leu Glu Gly Met Arg Ser Gln Asp Leu Asp Asp Tyr Leu Asn Gly 580 585 590 Pro Phe Thr val val Val Lys Glu Ser Cys Asp Gly Met Gly Asp Val 595 600 605 Ser Glu Lys His Gly Ser Gly Pro Val Val Pro Glu Lys Ala Val Arg 610 615 620 Phe Ser Phe Thr Ile Met Lys Ile Thr Ile Ala His Ser Ser Gln Asn 625 630 635 640 Val Lys Val Phe Glu Glu Ala Lys Pro Asn Ser Glu Leu Cys Cys Lys 645 650 655 Pro Leu Cys Leu Met Leu Ala Asp Glu Ser Asp His Glu Thr Leu Thr 660 665 670 Ala Ile Leu Ser Pro Leu Ile Ala Glu Arg Glu Ala Met Lys Ser Ser 675 680 685

Glu Leu Met Leu Glu Leu Gly Gly Ile Leu Arg Thr Phe Lys Phe Ile 690 695 700 Phe Arg Gly Thr Gly Tyr Asp Glu Lys Leu Val Arg Glu Val Glu Gly 705 710 715 720 Leu Glu Ala Ser Gly Ser Val Tyr Ile Cys Thr Leu Cys Asp Ala Thr 725 730 735 Arg Leu Glu Ala Ser Gln Asn Leu Val Phe His Ser Ile Thr Arg Ser 740 745 750 His Ala Glu Asn Leu Glu Arg Tyr Glu Val Trp Arg Ser Asn Pro Tyr 755 760 765 His Glu Ser Val Glu Glu Leu Arg Asp Arg Val Lys Gly Val Ser Ala 770 775 780 Lys Pro Phe Ile Glu Thr Val Pro Ser Ile Asp Ala Leu His Cys Asp 785 790 795 800 Ile Gly Asn Ala Ala Glu Phe Tyr Lys lle Phe Gln Leu Glu Ile Gly 805 810 815 Glu Val Tyr Lys Asn Pro Asn ARla Ser Lys Glu Glu Arg Lys Arg Trp 820 825 830 Gln Ala Thr Leu Asp Lys His Leu Arg Lys Lys Met Asn Leu Lys Pro 835 840 845 Ile Met Arg Met Asn Gly Asn Phe Ala Arg Lys Leu Met Thr Lys Glu 850 855 860 Thr Val Asp Ala Val Cys Glu Leu Ile Pro Ser Glu Glu Arg His Glu 865 870 875 880 Ala Leu Arg Glu Leu Met Asp Leu Tyr Leu Lys Met Lys Pro val Trp 885 890 835 Arg Ser Ser Cys Pro Ala Lys Glu Cys Pro Glu Ser Leu Cys Gln Tyr 900 90s 910 Ser Phe Asn Ser Gln Arg Phe Ala Glu Leu Leu Ser Thr Lys Phe Lys 915 920 925 780 ic - —_— UE

Tyr Arg Tyr Glu Gly Lys Ile Thr Asn Tyr Phe His Lys Thr Leu Ala 930 935 940 His Val Pro Glu Jle Ile Glu Arg Asp Gly Ser Ile Gly Ala Trp Ala 945 950 955 S60 Ser Glu Gly Asn Glu Ser Gly Asn Lys Leu Phe Arg Arg Phe Arg Lys 965 870 975 Met Asn Ala Arg Gln Ser Lys Cys Tyr Glu Met Glu Asp Val Leu Lys 980 985 990 His His Trp Leu Tyr Thr Ser Lys Tyr Leu Gln Lys Phe Met Asn Ala 995 1000 1005 His Asn Ala Leu Lys Thr Ser Gly Phe Thr Met Asn Pro Gln Ala 1010 1015 1020 Ser Leu Gly Asp Pro Leu Gly Ile Glu Asp Ser Leu Glu Ser Gln 1025 1030 1035 Asp Ser Met Glu Phe 1040 <210> 2453 <21l> 527 } <212> PRT <213> Homo sapiens <400> 2453 Met Ser Leu Gln Met Val Thr Val Ser Asn Asn Ile Ala Leu Ile Gln 1 5 10 15 Pro Gly Phe Ser Leu Met Asn Phe Asp Gly Gln Val Phe Phe Phe Gly

Gln Lys Gly Trp Pro Lys Arg Ser Cys Pro Thr Gly Val Phe His Leu 40 45 Asp Val Lys His Asn His Val Lys Leu Lys Pro Thr Ile Phe Ser Lys 50 55 60 Asp Ser Cys Tyr Leu Pro Pro Leu Arg Tyr Pro Ala Thr Cys Thr Phe 65 70 75 80 Lys Gly Ser Leu Glu Ser Glu Lys His Gln Tyr Ile Ile His Gly Gly

85 90 95 Lys Thr Pro Asn Asn Glu Val Ser Asp Lys Ile Tyr Val Met Ser Ile 100 105 110 Val Cys Lys Asn Asn Lys Lys Val Thr Phe Arg Cys Thr Glu Lys Asp 115 120 125 Leu Val Gly Asp Val Pro Glu Ala Arg Tyr Gly His Ser Ile Asn Val 130 135 140 val Tyr Ser Arg Gly Lys Ser Met Gly Ala Leu Phe Gly Gly Arg Ser 145 150 155 160 Tyr Met Pro Ser Thr His Arg Thr Thr Glu Lys Trp Asn Ser Val Ala 165 170 175 Asp Cys Leu Pro Cys Val Phe Leu Val Asp Phe Glu Phe Gly Cys Ala 180 185 190 Thr Ser Tyr Ile Leu Pro Glu Leu Gln Asp Gly Leu Ser Phe His Val 195 200 205 Ser Ile Ala Lys Asn Asp Thr Ile Tyr Ile Leu Gly Gly His Ser Leu 210 215 220 Ala Asn Asn Ile Arg Pro Ala Asn Leu Tyr Arg Ile Arg Val Asp Leu 225 230 235 240 Pro Leu Gly Ser Pro Ala Val Asn Cys Thr Val Leu Pro Gly Gly Ile 245 250 255 Ser Val Ser Ser Ala Ile Leu Thr Gln Thr Asn Asn Asp Glu Phe Val 260 265 270 Ile Val Gly Gly Tyr Gln Leu Glu Asn Gln Lys Arg Met Ile Cys Asn 275 280 285 Ile Ile Ser Leu Glu Asp Asn Lys Ile Glu Ile Arg Glu Met Glu Thr 290 295 300 Pro Asp Trp Thr Pro Asp Ile Lys His Ser Lys Ile Trp Phe Gly Ser 305 310 315 320 Asn Thr Gly Asn Gly Thr Val Phe Leu Gly Ile Pro Gly Asp Asn Lys 325 330 335

Gln val Val Ser Glu Gly Phe Tyr Phe Tyr Met Leu Lys Cys Ala Glu 340 345 350 Asp Asp Thr Asn Glu Glu Gln Thr Thr Phe Thr Asn Ser Gln Thr Ser 355 360 365 Thr Glu Asp Pro Gly Asp Ser Thr Pro Phe Glu Asp Ser Glu Glu Phe 370 375 380 Cys Phe Ser Ala Glu Ala Asn Ser Phe Asp Gly Asp Asp Glu Phe Asp 38S 390 395 400 Thr Tyr Asn Glu Asp Asp Glu Glu Asp Glu Ser Glu Thr Gly Tyr Trp 405 410 415 Ile Thr Cys Cys Pro Thr Cys Asp Val Asp Ile Asn Thr Trp Val Pro 420 425 430 Phe Tyr Ser Thr Glu Leu Asn Lys Pro Ala Met Ile Tyr Cys Ser His 435 440 445 Gly Asp Gly His Trp Val His Ala Gln Cys Met Asp Leu Ala Glu Arg 450 455 460 Thr Leu Ile His Leu Ser Ala Gly Ser Asn Lys Tyr Tyr Cys Asn Glu 465 470 475 480 His val Glu Ile Ala Arg Ala Leu His Thr Pro Gln Arg Val Leu Pro 485 490 495 Leu Lys Lys Pro Pro Met Lys Ser Leu Arg Lys lys Gly Ser Gly Lys 500 505 510 Ile Leu Thr Pro Ala Lys Lys Ser Phe Leu Arg Arg Leu Phe Asp 515 520 525 <210> 2454 <211> 93 <212> PRT <213> Homo sapiens <400> 2454 Met Asn Ala Lys Val Val val val Leu Val Leu Val Leu Thr Ala Leu 1 5 10 15

Cys Leu Ser Asp Gly Lys Pro Val Ser Leu Ser Tyr Arg Cys Pro Cys

Arg Phe Phe Glu Ser His Val Ala Arg Ala Asn Val Lys His Leu Lys 3s 40 45 Ile Leu Asn Thr Pro Asn Cys Ala Leu Gln Ile Val Ala Arg Leu Lys 50 55 60 Asn Asn Asn Arg Gln Val Cys Ile Asp Pro Lys Leu Lys Trp Ile Gln 65 70 75 80 Glu Tyr Leu Glu Lys Ala Leu Asn Lys Arg Phe Lys Met 85 90

<210> 2455 )

<211l> 277

<212> PRT

<213> Homo sapiens

<400> 2455

Met Cys Val Gly Ala Arg Arg Leu Gly Arg Gly Pro Cys Ala Ala Leu 1 5 10 15

Leu Leu Leu Gly Leu Gly Leu Ser Thr Val Thr Gly Leu His Cys Val

20 25 30 Gly Asp Thr Tyr Pro Ser Asn Asp Arg Cys Cys His Glu Cys Arg Pro 40 45 Gly Asn Gly Met Val Ser Arg Cys Ser Arg Ser Gln Asn Thr Val Cys sO 55 60 Arg Pro Cys Gly Pro Gly Phe Tyr Asn Asp Val Val Ser Ser Lys Pro 65 70 75 80 Cys Lys Pro Cys Thr Trp Cys Asn Leu Arg Ser Gly Ser Glu Arg Lys 85 90 95 Gln Leu Cys Thr Ala Thr Gln Asp Thr Val Cys Arg Cys Arg Ala Gly 100 105 110 Thr Gln Pro Leu Asp Ser Tyr Lys Pro Gly Val Asp Cys Ala Pro Cys 115 120 125 Pro Pro Gly His Phe Ser Pro Gly Asp Asn Gln Ala Cys Lys Pro Trp 130 - 135 140

Thr Asn Cys Thr Leu Ala Gly Lys His Thr Leu Gln Pro Ala Ser Asn 145 150 155 160 Ser Ser Asp Ala Ile Cys Glu Asp Arg Asp Pro Pro Ala Thr Gln Pro 165 170 175 Gln Glu Thr Gln Gly Pro Pro Ala Arg Pro Ile Thr Val Gln Pro Thr 180 185 190 Glu Ala Trp Pro Arg Thr Ser Gln Gly Pro Ser Thr Arg Pro Val Glu 195 200 205 Val Pro Gly Gly Arg Ala Val Ala Ala Ile Leu Gly Leu Gly Leu Val 210 215 220 Leu Gly Leu Leu Gly Pro Leu Ala Ile Leu Leu Ala Leu Tyr Leu Leu 225 230 235 240 Arg Arg Asp Gln Arg Leu Pro Pro Asp Ala His Lys Pro Pro Gly Gly 245 250 255 Gly Ser Phe Arg Thr Pro Ile Gln Glu Glu Gln Ala Asp Ala His Ser 260 265 270 Thr Leu Ala Lys Ile 275 <210> 2456 <211> 183 <212> PRT <213> Homo sapiens <400> 2456 Met Glu Arg Val Gln Pro Leu Glu Glu Asn Val Gly Asn Ala Ala Arg 1 LS) 10 15 Pro Arg Phe Glu Arg Asn Lys Leu Leu Leu Val Ala Ser Val Ile Gln : 30 Gly Leu Gly Leu Leu Leu Cys Phe Thr Tyr Ile Cys Leu His Phe Ser 40 45 Ala Leu Gln Val Ser His Arg Tyr Pro Arg Ile Gln Ser Ile Lys Val

50 . 55 60

Gln Phe Thr Glu Tyr Lys Lys Glu Lys Gly Phe Ile Leu Thr Ser Gln 65 70 75 80 Lys Glu Asp Glu Ile Met Lys Val Gln Asn Asn Ser val Ile Ile Asn 85 90 95 Cys Asp Gly Phe Tyr Leu Ile Ser Leu Lys Gly Tyr Phe Ser Gln Glu 100 105 110 val Asn Ile Ser Leu His Tyr Gln Lys Asp Glu Glu Pro Leu Phe Gln 115 120 125 Leu Lys Lys Val Arg Ser Val Asn Ser Leu Met Val Ala Ser Leu Thr 130 135 140 Tyr Lys Asp Lys Val Tyr Leu Asn Val Thr Thr Asp Asn Thr Ser Leu 145 150 155 160 Asp Asp Phe His Val Asn Gly Gly Glu Leu Ile Leu Ile His Gln Asn 165 170 175 Pro Gly Glu Phe Cys Val Leu 180 <210> 2457 <21ll> 275 <212> PRT <213> Homo sapiens <400> 2457 Met Leu Ser Leu Leu Leu Leu Ala Leu Pro Val Leu Ala Ser Arg Ala 1 5 10 15 Tyr Ala Ala Pro Ala Pro Val Gln Ala Leu Gln Gln Ala Gly Ile Val

Gly Gly Gln Glu Ala Pro Arg Ser Lys Trp Pro Trp Gln Val Ser Leu 40 45 Arg Val Arg Asp Arg Tyr Trp Met His Phe Cys Gly Gly Ser Leu Ile 50 55 60 His Pro Gln Trp Val Leu Thr Ala Ala His Cys Leu Gly Pro Asp Val 65 70 } 75 80 Lys Asp Leu Ala Thr Leu Arg Val Gln Leu Arg Glu Gln His Leu Tyr 85 90 85

Tyr Gln Asp Gln Leu Leu Pro Val Ser Arg Ile Ile Val His Pro Gln 100 105 110 Phe Tyr Ile Ile Gln Thr Gly Ala Asp Ile Ala Leu Leu Glu Leu Glu 115 120 125 Glu Pro Val Asn Ile Ser Ser Arg Val His Thr Val Met Leu Pro Pro 130 135 140 Ala Ser Glu Thr Phe Pro Pro Gly Met Pro Cys Trp Val Thr Gly Trp 145 150 155 160 Gly Asp Val Asp Asn Asp Glu Pro Leu Pro Pro Pro Phe Pro Leu Lys 165 170 175 Gln Val Lys Val Pro Ile Met Glu Asn His Ile Cys Asp Ala Lys Tyr 180 185 190 His Leu Gly Ala Tyr Thr Gly Asp Asp Val Arg Ile Ile Arg Asp Asp 195 200 205 Met Leu Cys Ala Gly Asn Ser Gln Arg Asp Ser Cys Lys Gly Asp Ser 210 215 220 Gly Gly Pro Leu Val Cys Lys Val Asn Gly Thr Trp Leu Gln Ala Gly 225 230 235 240 Val val Ser Trp Asp Glu Gly Cys Ala Gln Pro Asn Arg Pro Gly Ile 245 250 255 Tyr Thr Arg val Thr Tyr Tyr Leu Asp Trp Ile His His Tyr Val Pro 260 265 270 Lys Lys Pro 275 <210> 2458 <211> 363 <212> PRT <213> Homo sapiens <400> 2458 Met Ala Gln Thr Pro Ala Phe Asp Lys Pro Lys Val Glu Leu His Val 1 5 10 15

Co

His Leu Asp Gly Ser Ile Lys Pro Glu Thr Ile Leu Tyr Tyr Gly Arg

Arg Arg Gly Ile Ala Leu Pro Ala Asn Thr Ala Glu Gly Leu Leu Asn 40 45 Val Ile Gly Met Asp Lys Pro Leu Thr Leu Pro Asp Phe Leu Ala Lys 50 55 60 Phe Asp Tyr Tyr Met Pro Ala Ile Ala Gly Cys Arg Glu Ala Ile Lys 65 70 75 80 Arg Ile Ala Tyr Glu Phe Val Glu Met Lys Ala Lys Glu Gly Val Val 85 90 95 Tyr Val Glu Val Arg Tyr Ser Pro His Leu Leu Ala Asn Ser Lys Val 100 105 110 Glu Pro Ile Pro Trp Asn Gln Ala Glu Gly Asp Leu Thr Pro Asp Glu 115 120 125 Val Val Ala Leu Val Gly Gln Gly Leu Gln Glu Gly Glu Arg Asp Phe 130 135 140 Gly Val Lys Ala Arg Ser Ile Leu Cys Cys Met Arg His Gln Pro Asn 145 150 . 155 160 Trp Ser Pro Lys Val Val Glu Leu Cys Lys Asn Tyr Gln Gln Gln Thr 165 170 175 Val Val Ala Ile Asp Leu Ala Gly Asp Glu Thr Ile Pro Gly Ser Ser 180 185 190 Leu Leu Pro Gly His Val Gln Ala Tyr Gln Glu Ala Val Lys Ser Gly 195 200 205 Ile His Arg Thr Val His Ala Gly Glu Val Gly Ser Ala Glu Val Val 210 215 220 Lys Glu Ala Val Asp Ile Leu Lys Thr Glu Arg Leu Gly His Gly Tyr 225 230 235 240 His Thr Leu Glu Asp Gln Ala Leu Tyr Asn Arg Leu Arg Gln Glu Asn 245 250 255 Met His Phe Glu Ile Cys Pro Trp Ser Ser Tyr Leu Thr Gly Ala Trp

260 265 270 Lys Pro Asp Thr Glu His Ala Val Ile Arg Leu Lys Asn Asp Gln Ala 275 280 285 Asn Tyr Ser Leu Asn Thr Asp Asp Pro Leu Ile Phe Lys Ser Thr Leu 290 295 300 Asp Thr Asp Tyr Gln Met Thr Lys Arg Asp Met Gly Phe Thr Glu Glu 305 310 315 320 Glu Phe Lys Arg Leu Asn Ile Asn Ala Ala Lys Ser Ser Phe Leu Pro 325 330 335 Glu Asp Glu Lys Arg Glu Leu Leu Asp Leu Leu Tyr Lys Ala Tyr Gly 340 345 350 Met Pro Pro Ser Ala Ser Ala Gly Gln Asn Leu ‘ 355 360 <210> 2459 <211> 443 <212> PRT <213> Homo sapiens <400> 2459 Met Asp Phe Pro Cys Leu Trp Leu Gly Leu Leu Leu Pro Leu Val Ala 1 5 10 15 Ala Leu Asp Phe Asn Tyr His Arg Gln Glu Gly Met Glu Ala Phe Leu

Lys Thr Val Ala Gln Asn Tyr Ser Ser Val Thr His Leu His Ser Ile 40 45 Gly Lys Ser Val Lys Gly Arg Asn Leu Trp Val Leu Val Val Gly Arg 50 55 60 Phe Pro Lys Glu His Arg Ile Gly Ile Pro Glu Phe Lys Tyr Val Ala 65 70 75 80 Asn Met His Gly Asp Glu Thr Val Gly Arg Glu Leu Leu Leu His Leu 85 90 95 Ile Asp Tyr Leu Val Thr Ser Asp Gly Lys Asp Pro Glu Ile Thr Asn 100 105 110

Leu Ile Asn Ser Thr Arg Ile His Ile Met Pro Ser Met Asn Pro Asp 115 120 125 Gly Phe Glu Ala val Lys Lys Pro Asp Cys Tyr Tyr Ser Ile Gly Arg 130 135 140 Glu Asn Tyr Asn Gln Tyr Asp Leu Asn Arg Asn Phe Pro Asp Ala phe 145 150 155 160 Glu Tyr Asn Asn Val Ser Arg Gln Pro Glu Thr Val Ala Val Met Lys 165 170 175 Trp Leu Lys Thr Glu Thr Phe Val Leu Ser Ala Asn Leu His Gly Gly 180 185 190 Ala Leu Val Ala Ser Tyr Pro Phe Asp Asn Gly Val Gln Ala Thr Gly 195 200 205 Ala Leu Tyr Ser Arg Ser Leu Thr Pro Asp Asp Asp Val Phe Gln Tyr 210 215 220 Leu Ala His Thr Tyr Ala Ser Arg Asn Pro Asn Met Lys Lys Gly Asp 225 230 235 240 Glu Cys Lys Asn Lys Met Asn Phe Pro Asn Gly Val Thr Asn Gly Tyr 245 250 255 Ser Trp Tyr Pro Leu Gln Gly Gly Met Gln Asp Tyr Asn Tyr Ile Trp 260 265 270 Ala Gln Cys Phe Glu Ile Thr Leu Glu Leu Ser Cys Cys Lys Tyr Pro 275 280 285 Arg Glu Glu Lys Leu Pro Ser Phe Trp Asn Asn Asn Lys Ala Ser Leu 290 295 300 Ile Glu Tyr Ile Lys Gln Val His Leu Gly Val Lys Gly Gln val Phe 305 310 315 320 Asp Gln Asn Gly Asn Pro Leu Pro Asn Val Ile Val Glu Val Gln Asp 325 330 335 Arg Lys His Ile Cys Pro Tyr Arg Thr Asn Lys Tyr Gly Glu Tyr Tyr 340 345 350 790

Fe. oo So

Leu Leu Leu Leu Pro Gly Ser Tyr Ile Ile Asn Val Thr Val Pro Gly 355 360 365 His Asp Pro His Ile Thr Lys Val Ile Ile Pro Glu Lys Ser Gln Asn 370 375 380 Phe Ser Ala Leu Lys Lys Asp Ile Leu Leu Pro Phe Gln Gly Gln Leu 385 390 395 400 Asp Ser Ile Pro Val Ser Asn Pro Ser Cys Pro Met Ile Pro Leu Tyr 405 410 415 Arg Asn Leu Pro Asp His Ser Ala Ala Thr Lys Pro Ser Leu Phe Leu 420 425 430 Phe Leu Val Ser Leu Leu His Ile Phe Phe Lys 435 440 <210> 2460 ) <211> 144 <212> PRT <213> Homo sapiens <400> 2460 Met Trp Leu Gln Ser Leu Leu Leu Leu Gly Thr Val Ala Cys Ser Ile 1 5 10 15 Ser Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp Glu His val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu Ser Arg Asp 40 45 Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile Ser Glu Met Phe 50 55 60 Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys 65 70 75 80 Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu Thr Met 85 90 SS Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr Pro Glu Thr Ser 100 105 110 Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu Asn Leu Lys 115 120 125

Asp Phe Leu Leu Val Ile Pro Phe Asp Cys Trp Glu Pro Val Gln Glu 130 135 140 <210> 2461 <211> 204 <212> PRT <213> Homo sapiens <400> 2461 Met Ala Gly Pro Ala Thr Gln Ser Pro Met Lys Leu Met Ala Leu Gln 1 5 10 15 Leu Leu Leu Trp His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro

Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu 40 45 Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys 50 55 60 Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu 65 70 75 80 Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser 85 90 95 Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu 100 105 110 Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu 115 120 125 Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala 130 135 140 Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu 145 150 155 160 Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg 165 170 175 Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu 180 185 190

Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro 195 200 <210> 2462 <211> 224 , <212> PRT <213> Homo sapiens <400> 2462 Met Glu Lys Leu Leu Cys Phe Leu Val Leu Thr Ser Leu Ser His Ala 1 5 10 15 Phe Gly Gln Thr Asp Met Ser Arg Lys Ala Phe Val Phe Pro Lys Glu

Ser Asp Thr Ser Tyr Val Ser Leu Lys Ala Pro Leu Thr Lys Pro Leu 40 45 Lys Ala Phe Thr Val Cys Leu His Phe Tyr Thr Glu Leu Ser Ser Thr 50 55 60 Arg Gly Thr Val Phe Ser Arg Met Pro Pro Arg Asp Lys Thr Met Arg 65 70 75 80 Phe Phe Ile Phe Trp Ser Lys Asp Ile Gly Tyr Ser Phe Thr Val Gly 85 90 95 Gly Ser Glu Ile Leu Phe Glu Val Pro Glu Val Thr Val Ala Pro Val 100 105 110 His Ile Cys Thr Ser Trp Glu Ser Ala Ser Gly Ile Val Glu Phe Trp 115 120 125 Val Asp Gly Lys Pro Arg Val Arg Lys Ser Leu Lys Lys Gly Tyr Thr 130 135 140 Val Gly Ala Glu Ala Ser Ile Ile Leu Gly Gln Glu Gln Asp Ser Phe 145 150 155 160 Gly Gly Asn Phe Glu Gly Ser Gln Ser Leu Val Gly Asp Ile Gly Asn 165 170 175 Val Asn Met Trp Asp Phe val Leu Ser Pro Asp Glu Ile Asn Thr Ile 180 185 180 Tyr Leu Gly Gly Pro Phe Ser Pro Asn Val Leu Asn Trp Arg Ala Leu 195 200 205

Lys Tyr Glu Val Gln Gly Glu Val Phe Thr Lys Pro Gln Leu Trp Pro 210 215 220 <210> 2463 <211> 993 <212> PRT <213> Homo sapiens <400> 2463 Met Pro Ala Leu Ala Arg Asp Ala Gly Thr Val Pro Leu Leu Val val 1 5 10 is Phe Ser Ala Met Ile Phe Gly Thr Ile Thr Asn Gln Asp Leu Pro Val

Ile Lys Cys Val Leu Ile Asn His Lys Asn Asn Asp Ser Ser Val Gly 40 45 Lys Ser Ser Ser Tyr Pro Met Val Ser Glu Ser Pro Glu Asp Leu Gly 50 55 60 Cys Ala Leu Arg Pro Gln Ser Ser Gly Thr Val Tyr Glu Ala Ala Ala 65 70 75 80 Val Glu Val Asp Val Ser Ala Ser Ile Thr Leu Gln Val Leu Val Asp 85 90 9s Ala Pro Gly Asn Ile Ser Cys Leu Trp Val Phe Lys His Ser Ser Leu 100 105 110 Asn Cys Gln Pro His Phe Asp Leu Gln Asn Arg Gly Val Val Ser Met 115 120 125 val Ile Leu Lys Met Thr Glu Thr Gln Ala Gly Glu Tyr Leu Leu Phe 130 135 140 Ile Gln Ser Glu Ala Thr Asn Tyr Thr Ile Leu Phe Thr Val Ser Ile 145 150 155 160 Arg Asn Thr Leu Leu Tyr Thr Leu Arg Arg Pro Tyr Phe Arg Lys Met 165 170 175 Glu Asn Gln Asp Ala Leu Val Cys Ile Ser Glu Ser Val Pro Glu Pro 180 185 190

Ile val Glu Trp val Leu Cys Asp Ser Gln Gly Glu Ser Cys Lys Glu 195 200 205 Glu Ser Pro Ala val Val Lys Lys Glu Glu Lys Val Leu His Glu Leu 210 218 220 Phe Gly Thr Asp Ile Arg Cys Cys Ala Arg Asn Glu Leu Gly Arg Glu 225 230 235 240 Cys Thr Arg Leu Phe Thr Ile Asp Leu Asn Gln Thr Pro Gln Thr Thr 245 ’ 250 255 Leu Pro Gln Leu Phe Leu Lys Val Gly Glu Pro Leu Trp Ile Arg Cys 260 265 270 Lys Ala Val His Val Asn His Gly Phe Gly Leu Thr Trp Glu Leu Glu 275 280 285 Asn Lys Ala Leu Glu Glu Gly Asn Tyr Phe Glu Met Ser Thr Tyr Ser 290 295 300 Thr Asn Arg Thr Met Ile Arg Ile Leu Phe Ala Phe Val Ser Ser Val 305 310 315 320 Ala Arg Asn Asp Thr Gly Tyr Tyr Thr Cys Ser Ser Ser Lys His Pro 325 330 335 Ser Gln Ser Ala Leu Val Thr Ile val Gly Lys Gly Phe Ile Asn Ala 340 345 350 Thr Asn Ser Ser Glu Asp Tyr Glu Ile Asp Gln Tyr Glu Glu Phe Cys 358 360 365 Phe Ser Val Arg Phe Lys Ala Tyr Pro Gln Ile Arg Cys Thr Trp Thr 370 375 380 Phe Ser Arg Lys Ser Phe Pro Cys Glu Gln Lys Gly Leu Asp Asn Gly 385 390 385 400 Tyr Ser Ile Ser Lys Phe Cys Asn His Lys His Gln Pro Gly Glu Tyr 405 410 415 Ile Phe His Ala Glu Asn Asp Asp Ala Gln Phe Thr Lys Met Phe Thr 420 425 430 Leu Asn Ile Arg Arg Lys Pro Gln Val Leu Ala Glu Ala Ser Ala Ser

435 440 445 Gln Ala Ser Cys Phe Ser Asp Gly Tyr Pro Leu Pro Ser Trp Thr Trp 450 455 460 Lys Lys Cys Ser Asp Lys Ser Pro Asn Cys Thr Glu Glu Ile Thr Glu 465 470 475 480 Gly Val Trp Asn Arg Lys Ala Asn Arg Lys Val Phe Gly Gln Trp Val 485 490 495 Ser Ser Ser Thr Leu Asn Met Ser Glu Ala Ile Lys Gly Phe Leu Val 500 505 510 Lys Cys Cys Ala Tyr Asn Ser Leu Gly Thr Ser Cys Glu Thr Ile Leu 515 520 525 Leu Asn Ser Pro Gly Pro Phe Pro Phe Ile Gln Asp Asn Ile Ser Phe 530 53% 540 Tyr Ala Thr Ile Gly Val Cys Leu Leu Phe Ile Val Val Leu Thr Leu 545 550 555% 560 Leu Ile Cys His Lys Tyr Lys Lys Gln Phe Arg Tyr Glu Ser Gln Leu 565 570 575 Gln Met Val Gln Val Thr Gly Ser Ser Asp Asn Glu Tyr Phe Tyr Val 580 585 590 Asp Phe Arg Glu Tyr Glu Tyr Asp Leu Lys Trp Glu Phe Pro Arg Glu 595 600 605 Asn Leu Glu Phe Gly Lys Val Leu Gly Ser Gly Ala Phe Gly Lys Val 610 615 620 Met Asn Ala Thr Ala Tyr Gly Ile Ser Lys Thr Gly Val Ser Ile Gln 625 630 635 640 Val Ala Val Lys Met Leu Lys Glu Lys Ala Asp Ser Ser Glu Arg Glu 645 650 655 Ala Leu Met Ser Glu Leu Lys Met Met Thr Gln Leu Gly Ser His Glu 660 665 670 Asn Ile Val Asn Leu Leu Gly Ala Cys Thr Leu Ser Gly Pro Ile Tyr 675 680 685 -

Leu Ile Phe Glu Tyr Cys Cys Tyr Gly Asp Leu Leu Asn Tyr Leu Arg 690 695 700 Ser Lys Arg Glu Lys Phe His Arg Thr Trp Thr Glu Ile Phe Lys Glu 705 710 715 720 His Asn Phe Ser Phe Tyr Pro Thr Phe Gln Ser His Pro Asn Ser Ser 725 730 735 Met Pro Gly Ser Arg Glu Val Gln Ile His Pro Asp Ser Asp Gln Ile 740 P 745 750 Ser Gly Leu His Gly Asn Ser Phe His Ser Glu Asp Glu Ile Glu Tyr 755 760 765 Glu Asn Gln Lys Arg Leu Glu Glu Glu Glu Asp Leu Asn Val Leu Thr 770 775 780 Phe Glu Asp Leu Leu Cys Phe Ala Tyr Gln Val Ala Lys Gly Met Glu 785 790 795 800 Phe Leu Glu Phe Lys Ser Cys Val His Arg Asp Leu Ala Ala Arg Asn 805 810 815 Val Leu Val Thr His Gly Lys Val Val Lys Ile Cys Asp Phe Gly Leu 820 825 830 Rla Arg Asp Ile Met Ser Asp Ser Asn Tyr Val Val Arg Gly Asn Ala 835 840 845 Arg Leu Pro Val Lys Trp Met Ala Pro Glu Ser Leu Phe Glu Gly Ile 850 855 860 Tyr Thr Ile Lys Ser Asp Val Trp Ser Tyr Gly Ile Leu Leu Trp Glu 865 870 87S 880 Ile Phe Ser Leu Gly Val Asn Pro Tyr Pro Gly Ile Pro Val Asp Ala 885 890 895 Asn Phe Tyr Lys Leu Ile Gln Asn Gly Phe Lys Met Asp Gln Pro Phe 500 905 910 Tyr Ala Thr Glu Glu Ile Tyr Ile Ile Met Gln Ser Cys Trp Ala Phe 915 920 925

Asp Ser Arg Lys Arg Pro Ser Phe Pro Asn Leu Thr Ser Phe Leu Gly 930 935 940

Cys Gln Leu Ala Asp Ala Glu Glu Ala Met Tyr Gln Asn Val Asp Gly

945 950 955 960

Arg Val Ser Glu Cys Pro His Thr Tyr Gln Asn Arg Arg Pro Phe Ser

965 970 975

Arg Glu Met Asp Leu Gly Leu Leu Ser Pro Gln Ala Gln Val Glu Asp $80 985 990

Ser

<210> 2464

<211> 443

<212> PRT

<213> Homo sapiens

<400> 2464

Met Glu Val Thr Ala Asp Gln Pro Arg Trp Val Ser His His His Pro

1 5 10 15

Ala Val Leu Asn Gly Gln His Pro Asp Thr His His Pro Gly Leu Ser

His Ser Tyr Met Asp Ala Ala Gln Tyr Pro Leu Pro Glu Glu Val Asp

40 45 Val Leu Phe Asn Ile Asp Gly Gln Gly Asn His Val Pro Pro Tyr Tyr 50 SS 60

Gly Asn Ser Val Arg Ala Thr Val Gln Arg Tyr Pro Pro Thr His His

65 70 75 80

Gly Ser Gln Val Cys Arg Pro Pro Leu Leu His Gly Ser Leu Pro Trp

85 90 85

Leu Asp Gly Gly Lys Ala Leu Gly Ser His His Thr Ala Ser Pro Trp 100 105 110

Asn Leu Ser Pro Phe Ser Lys Thr Ser Ile His His Gly Ser Pro Gly

115 120 125 Pro Leu Ser Val Tyr Pro Pro Ala Ser Ser Ser Ser Leu Ser Gly Gly

130 135 140 His Ala Ser Pro His Leu Phe Thr Phe Pro Pro Thr Pro Pro Lys Asp 145 150 155 160 Val Ser Pro Asp Pro Ser Leu Ser Thr Pro Gly Ser Ala Gly Ser Ala 165 170 175 Arg Gln Asp Glu Lys Glu Cys Leu Lys Tyr Gln Val Pro Leu Pro Asp 180 185 180 Ser Met Lys Leu Glu Ser Ser His Ser Arg Gly Ser Met Thr Ala Leu 195 200 205 Gly Gly Ala Ser Ser Ser Thr His His Pro Ile Thr Thr Tyr Pro Pro 210 215 220 / Tyr Val Pro Glu Tyr Ser Ser Gly Leu Phe Pro Pro Ser Ser Leu Leu 225 230 235 240 Gly Gly Ser Pro Thr Gly Phe Gly Cys Lys Ser Arg Pro Lys Ala Arg 245 250 255 Ser Ser Thr Gly Arg Glu Cys Val Asn Cys Gly Ala Thr Ser Thr Pro 260 265 270 Leu Trp Arg Arg Asp Gly Thr Gly His Tyr Leu Cys Asn Ala Cys Gly 275 280 285 Leu Tyr His Lys Met Asn Gly Gln Asn Arg Pro Leu Ile Lys Pro Lys 290 295% 300 Arg Arg Leu Ser Ala Ala Arg Arg Ala Gly Thr Ser Cys Ala Asn Cys 308 310 315 320 Gln Thr Thr Thr Thr Thr Leu Trp Arg Arg Asn Ala Asn Gly Asp Pro 325 330 335 Val Cys Asn Ala Cys Gly Leu Tyr Tyr Lys Leu His Asn Ile Asn Arg 340 345 350 Pro Leu Thr Met Lys Lys Glu Gly Ile Gln Thr Arg Asn Arg Lys Met 355 360 365 Ser Ser Lys Ser Lys Lys Cys Lys Lys Val His Asp Ser Leu Glu Asp 370 375 380

Phe Pro Lys Asn Ser Ser Phe Asn Pro Ala Ala Leu Ser Arg His Met 385 390 395 . 400 Ser Ser Leu Ser His Ile Ser Pro Phe Ser His Ser Ser His Met Leu : 405 410 415 Thr Thr Pro Thr Pro Met His Pro Pro Ser Ser Leu Ser Phe Gly Pro 420 425 430 His His Pro Ser Ser Met Val Thr Ala Met Gly 435 440 <210> 2465 <211> 459 <212> PRT <213> Homo sapiens <400> 2465 Met Thr Ile Leu Gly Thr Thr Phe Gly Met Val Phe Ser Leu Leu Gln 1 S 10 15 Val val Ser Gly Glu Ser Gly Tyr Ala Gln Asn Gly Asp Leu Glu Asp

Ala Glu Leu Asp Asp Tyr Ser Phe Ser Cys Tyr Ser Gln Leu Glu Val 40 45 Asn Gly Ser Gln His Ser Leu Thr Cys Ala Phe Glu Asp Pro Asp Val 50 55 60 Asn Ile Thr Asn Leu Glu Phe Glu Ile Cys Gly Ala Leu Val Glu Val 65 70 75 80 Lys Cys Leu Asn Phe Arg Lys Leu Gln Glu Ile Tyr Phe Ile Glu Thr 85 90 95 Lys Lys Phe Leu Leu Ile Gly Lys Ser Asn Ile Cys Val Lys Val Gly 100 105 110 Glu Lys Sex Leu Thr Cys Lys Lys Ile Asp Leu Thr Thr Ile Val Lys 115 120 125 Pro Glu Ala Pro Phe Asp Leu Ser Val Val Tyr Arg Glu Gly Ala Asn 130 135 140 800 k; 1 :

Asp Phe Val Val Thr Phe Asn Thr Ser His Leu Gln Lys Lys Tyr Val 145 150 15% 160 Lys Val Leu Met His Asp val Ala Tyr Arg Gln Glu Lys Asp Glu Asn 165 170 175 Lys Trp Thr His Val Asn Leu Ser Ser Thr Lys Leu Thr Leu Leu Gln 180 185 190 Arg Lys Leu Gln Pro Ala Ala Met Tyr Glu Ile Lys Val Arg Ser Ile 185 200 205 Pro Asp His Tyr phe Lys Gly Phe Trp Ser Glu Trp Ser Pro Ser Tyr 210 215 220 Tyr Phe Arg Thr Pro Glu Ile Asn Asn Ser Ser Gly Glu Met Asp Pro 225 230 235 240 Ile Leu Leu Thr Ile Ser Ile Leu Ser Phe Phe Ser Val Ala Leu Leu 245 250 255 Val Ile Leu Ala Cys Val Leu Trp Lys Lys Arg Ile Lys Pro Ile Val 260 265 270 Trp Pro Ser Leu Pro Asp His Lys Lys Thr Leu Glu His Leu Cys Lys 275 280 285 Lys Pro Arg Lys Asn Leu Asn Val Ser Phe Asn Pro Glu Ser Phe Leu 290 295 300 Asp Cys Gln Ile His Arg val Asp Asp Ile Gln Ala Arg Asp Glu Val 305 310 315 320 Glu Gly Phe Leu Gln Asp Thr Phe Pro Gln Gln Leu Glu Glu Ser Glu 325 330 335 Lys Gln Arg Leu Gly Gly Asp Val Gln Ser Pro Asn Cys Pro Ser Glu 340 345 350 Asp Val Val Ile Thr Pro Glu Ser Phe Gly Arg Asp Ser Ser Leu Thr . 355 360 365 Cys Leu Ala Gly Asn Val Ser ala Cys Asp Ala Pro Ile Leu Ser Ser 370 375 380 Ser Arg Ser Leu Asp Cys Arg Glu Ser Gly Lys Asn Gly Pro His val

385 390 395 400 Tyr Gln Asp Leu Leu Leu Ser Leu Gly Thr Thr Asn Ser Thr Leu Pro

405 410 415 Pro Pro Phe Ser Leu Gln Ser Gly Ile Leu Thr Leu Asn Pro Val Ala 420 425 430 Gln Gly Gln Pro Ile Leu Thr Ser Leu Gly Ser Asn Gln Glu Glu Ala 435 440 445 Tyr Val Thr Met Ser Ser Phe Tyr Gln Asn Gln 450 455 <210> 2466 <211> 362 <212> PRT <213> Homo sapiens <400> 2466 Met Ala Thr Ala Glu Thr Ala Leu Pro Ser Ile Ser Thr Leu Thr Ala 1 5 10 15 Leu Gly Pro Phe Pro Asp Thr Gln Asp Asp Phe Leu Lys Trp Trp Arg

Ser Glu Glu Ala Gln Asp Met Gly Pro Gly Pro Pro Asp Pro Thr Glu 40 45 Pro Pro Leu His Val Lys Ser Glu Asp Gln Pro Gly Glu Glu Glu Asp ’ 50 55 60 ) Asp Glu Arg Gly Ala Asp Ala Thr Trp Asp Leu Asp Leu Leu Leu Thr 65 70 75 80 Asn Phe Ser Gly Pro Glu Pro Gly Gly Ala Pro Gln Thr Cys Ala Leu 85 90 95 Ala Pro Ser Glu Ala Ser Gly Ala Gln Tyr Pro Pro Pro Pro Glu Thr 100 105 110 Leu Gly Ala Tyr Ala Gly Gly Pro Gly Leu Val Ala Gly Leu Leu Gly 1158 120 125 Ser Glu Asp His Ser Gly Trp Val Arg Pro Ala Leu Arg Ala Arg Ala 130 135 140 802

Pro Asp Ala Phe Val Gly Pro Ala Leu Ala Pro Ala Pro Ala Pro Glu 145 150 155 160 Pro Lys Ala Leu Ala Leu Gln Pro Val Tyr Pro Gly Pro Gly Ala Gly 165 170 175 Ser Ser Gly Gly Tyr Phe Pro Arg Thr Gly Leu Ser Val Pro Ala Ala 180 185 190 Ser Gly Ala Pro Tyr Gly Leu Leu Ser Gly Tyr Pro Ala Met Tyr Pro 185 200 205 Ala Pro Gln Tyr Gln Gly His Phe Gln Leu Phe Arg Gly Leu Gln Gly 210 215 220 Pro Ala Pro Gly Pro Ala Thr Ser Pro Ser Phe Leu Ser Cys Leu Gly 225 230 235 240 Pro Gly Thr Val Gly Thr Gly Leu Gly Gly Thr Ala Glu Asp Pro Gly 245 250 255 Val Ile Ala Glu Thr Ala Pro Ser Lys Arg Gly Arg Arg Ser Trp Ala 260 265 270 Arg Lys Arg Gln Ala Ala His Thr Cys Ala His Pro Gly Cys Gly Lys 275 280 285 Ser Tyr Thr Lys Ser Ser His Leu Lys Ala His Leu Arg Thr His Thr 290 285 300 Gly Glu Lys Pro Tyr Ala Cys Thr Trp Glu Gly Cys Gly Trp Arg Phe 305 310 315 320 Ala Arg Ser Asp Glu Leu Thr Arg His Tyr Arg Lys His Thr Gly Gln 325 330 335 Arg Pro Phe Arg Cys Gln Leu Cys Pro Arg Ala Phe Ser Arg Ser Asp 340 345 350 His Leu Ala Leu His Met Lys Arg His Leu 355 360 <210> 2467 <211> 509 <212> PRT <213> Homo sapiens

<400> 2467 Met Gly Cys Gly Cys Ser Ser His Pro Glu Asp Asp Trp Met Glu Asn 1 5 10 15 Ile Asp Val Cys Glu Asn Cys His Tyr Pro Ile Val Pro Leu Asp Gly

Lys Gly Thr Leu Leu Ile Arg Asn Gly Ser Glu Val Arg Asp Pro Leu 40 45 Val Thr Tyr Glu Gly Ser Asn Pro Pro Ala Ser Pro Leu Gln Asp Asn 50 55 60 Leu Val Ile Ala Leu His Ser Tyr Glu Pro Ser His Asp Gly Asp Leu 65 70 75 80 Gly Phe Glu Lys Gly Glu Pro Leu Arg Ile Leu Glu Gln Ser Gly Glu 85 90 8S Trp Trp Lys Ala Gln Ser Leu Thr Thr Gly Gln Glu Gly Phe Ile Pro 100 105 110 Phe Asn Phe Val Ala Lys Ala Asn Ser Leu Glu Pro Glu Pro Trp Phe 115 120 125 Phe Lys Asn Leu Ser Arg Lys Asp Ala Glu Arg Gln Leu Leu Ala Pro 130 135 140 Gly Asn Thr His Gly Ser Phe Leu lle Arg Glu Ser Glu Ser Thr Ala 145 150 155 160 Gly Ser Phe Ser Leu Ser Val Arg Asp Phe Asp Gln Asn Gln Gly Glu 165 170 175 Val Val Lys His Tyr Lys Ile Arg Asn Leu Asp Asn Gly Gly Phe Tyr 180 185 150 Ile Ser Pro Arg Ile Thr Phe Pro Gly Leu His Glu Leu Val Arg His 195 200 205 Tyr Thr Asn Ala Ser Asp Gly Leu Cys Thr Arg Leu Ser Arg Pro Cys 210 215 220 Gln Thr Gln Lys Pro Gln Lys Pro Trp Trp Glu Asp Glu Trp Glu Val 225 230 235 240 804 i Mi

Pro Arg Glu Thr Leu Lys Leu Val Glu Arg Leu Gly Ala Gly Gln Phe 245 250 255 Gly Glu Val Trp Met Gly Tyr Tyr Asn Gly His Thr Lys Val Ala val 260 265 270 Lys Ser Leu Lys Gln Gly Ser Met Ser Pro Asp Ala Phe Leu Ala Glu 275 280 285 Ala Asn Leu Met Lys Gln Leu Gln His Gln Arg Leu Val Arg Leu Tyr 290 285 300 Ala Val Val Thr Gln Glu Pro Ile Tyr Ile Ile Thr Glu Tyr Met Glu 305 310 315 320 Asn Gly Ser Leu Val Asp Phe Leu Lys Thr Pro Ser Gly Ile Lys Leu 325 330 335 Thr Ile Asn Lys Leu Leu Asp Met Ala Ala Gln Ile Ala Glu Gly Met 340 345 350 Ala Phe Ile Glu Glu Arg Asn Tyr Ile His Arg Asp Leu Arg Ala Ala 355 360 365 Asn Ile Leu Val Ser Asp Thr Leu Ser Cys Lys Ile Ala Asp Phe Gly 370 375 380 Leu Ala Arg Leu Ile Glu Asp Asn Glu Tyr Thr Ala Arg Glu Gly Ala 385 390 395 400 Lys Phe Pro Ile Lys Trp Thr Ala Pro Glu Ala Ile Asn Tyr Gly Thr 405 410 415 Phe Thr Ile Lys Ser Asp Val Trp Ser Phe Gly Ile Leu Leu Thr Glu 420 425 430 Ile Val Thr His Gly Arg Ile Pro Tyr Pro Gly Met Thr Asn Pro Glu 435 440 445 Val Ile Gln Asn Leu Glu Arg Gly Tyr Arg Met Val Arg Pro Asp Asn 450 455 460 Cys Pro Glu Glu Leu Tyr Gln Leu Met Arg Leu Cys Trp Lys Glu Arg 465 470 475 480

Pro Glu Asp Arg Pro Thr Phe Asp Tyr Leu Arg Ser Val Leu Glu Asp 485 490 495 Phe Phe Thr Ala Thr Glu Gly Gln Tyr Gln Pro Gln Pro 500 505 <210> 2468 <211> 399 ) <212> PRT <213> Homo sapiens <400> 2468 Met Pro Gln Leu Ser Gly Gly Gly Gly Gly Gly Gly Gly Asp Pro Glu 1 5 10 15 Leu Cys Ala Thr Asp Glu Met Ile Pro Phe Lys Asp Glu Gly Asp Pro

Gln Lys Glu Lys Ile Phe Ala Glu Ile Ser His Pro Glu Glu Glu Gly 40 45 Asp Leu Ala Asp Ile Lys Ser Ser Leu Val Asn Glu Ser Glu Ile Ile 50 55 60 Pro Ala Ser Asn Gly His Glu val Ala Arg Gln Ala Gln Thr Ser Gln 65 70 75 80 Glu Pro Tyr His Asp Lys Ala Arg Glu His Pro Asp Asp Gly Lys His 85 90 95 Pro Asp Gly Gly Leu Tyr Asn Lys Gly Pro Ser Tyr Ser Ser Tyr Ser 100 105 110 Gly Tyr Ile Met Met Pro Asn Met Asn Asn Asp Pro Tyr Met Ser Asn 115 120 125 Gly Ser Leu Ser Pro Pro Ile Pro Arg Thr Ser Asn Lys Val Pro Val 130 135 140 Val Gln Pro Ser His Ala Val His Pro Leu Thr Pro Leu Ile Thr Tyr 145 150 155 160 Ser Asp Glu His Phe Ser Pro Gly Ser His Pro Ser His Ile Pro Ser 165 170 175 Asp Val Asn Ser Lys Gln Gly Met Ser Arg His Pro Pro Ala Pro Asp

180 185 190 Ile Pro Thr Phe Tyr Pro Leu Ser Pro Gly Gly val Gly Gln Ile Thr 195 200 205 Pro Pro Leu Gly Trp Gln Gly Gln Pro Val Tyr Pro Ile Thr Gly Gly 210 215 220 Phe Arg Gln Pro Tyr Pro Ser Ser Leu Ser Val Asp Thr Ser Met Ser 225 230 235 240 Arg Phe Ser His His Met Ile Pro Gly Pro Pro Gly Pro His Thr Thr 245 250 255 Gly Ile Pro His Pro Ala Ile Val Thr Pro Gln Val Lys Gln Glu His 260 265 270 Pro His Thr Asp Ser Asp Leu Met His Val Lys Pro Gln His Glu Gln 275 280 28S Arg Lys Glu Gln Glu Pro Lys Arg Pro His Ile Lys Lys Pro Leu Asn 290 295 300 Ala Phe Met Leu Tyr Met Lys Glu Met Arg Ala Asn Val val ala Glu 305 310 315 320 Cys Thr Leu Lys Glu Ser Ala Ala Ile Asn Gln Ile Leu Gly Arg Arg 325 330 335 Trp His Ala Leu Ser Arg Glu Glu Gln Ala Lys Tyr Tyr Glu Leu Ala 340 345 350 Arg Lys Glu Arg Gln Leu His Met Gln Leu Tyr Pro Gly Trp Ser Ala 355 360 365 Arg Asp Asn Tyr Gly Lys Lys Lys Lys Arg Lys Arg Glu Lys Leu Gln 370 375 380 Glu Ser Ala Ser Gly Thr Gly Pro Arg Met Thr Ala Ala Tyr Ile 385 390 395 <210> 2469 <21l> 335 <212> PRT <213> Homo sapiens <400> 2468

Met Gly His Pro Pro Leu Leu Pro Leu Leu Leu Leu Leu His Thr Cys 1 5 10 15 Val Pro Ala Ser Trp Gly Leu Arg Cys Met Gln Cys Lys Thr Asn Gly

Asp Cys Arg Val Glu Glu Cys Ala Leu Gly Gln Asp Leu Cys Arg Thr 40 45 Thr Ile val Arg Leu Trp Glu Glu Gly Glu Glu Leu Glu Leu Val Glu 50 55 60 Lys Ser Cys Thr His Ser Glu Lys Thr Asn Arg Thr Leu Ser Tyr Arg 65 70 75 80 Thr Gly Leu Lys Ile Thr Ser Leu Thr Glu Val Val Cys Gly Leu Asp 85 SO 95 Leu Cys Asn Gln Gly Asn Ser Gly Arg Ala Val Thr Tyr Ser Arg Ser 100 105 110 Arg Tyr Leu Glu Cys Ile Ser Cys Gly Ser Ser Asp Met Ser Cys Glu 115 120 125 Arg Gly Arg His Gln Ser Leu Gln Cys Arg Ser Pro Glu Glu Gln Cys 130 135 140 Leu Asp Val Val Thr His Trp Ile Gln Glu Gly Glu Glu Gly Arg Pro 145 150 155 160 Lys Asp Asp Arg His Leu Arg Gly Cys Gly Tyr Leu Pro Gly Cys Pro 165 170 175 Gly Ser Asn Gly Phe His Asn Asn Asp Thr Phe His Phe Leu Lys Cys 180 185 190 Cys Asn Thr Thr Lys Cys Asn Glu Gly Pro Ile Leu Glu Leu Glu Asn 195 200 205 Leu Pro Gln Asn Gly Arg Gln Cys Tyr Ser Cys Lys Gly Asn Ser Thr 210 215 220 His Gly Cys Ser Ser Glu Glu Thr Phe Leu Ile Asp Cys Arg Gly Pro 225 230 238s 240

Met Asn Gln Cys Leu Val Ala Thr Gly Thr His Glu Pro Lys Asn Gln 245 250 255 Ser Tyr Met Val Arg Gly Cys Ala Thr Ala Ser Met Cys Gln His Ala 260 265 270 His Leu Gly Asp Ala Phe Ser Met Asn His Ile Asp Val Ser Cys Cys 275 280 285 Thr Lys Ser Gly Cys Asn His Pro Asp Leu Asp Val Gln Tyr Arg Ser 290 295 300 Gly Ala Ala Pro Gln Pro Gly Pro Ala His Leu Ser Leu Thr Ile Thr 305 310 315 320 Leu Leu Met Thr Ala Arg Leu Trp Gly Gly Thr Leu Leu Trp Thr 325 330 335 <210> 2470 <211> 285 <212> PRT <213> Homo sapiens <400> 2470 Met Asp Asp Ser Thr Glu Arg Glu Gln Ser Arg Leu Thr Ser Cys Leu 1 5 10 15 Lys Lys Arg Glu Glu Met Lys Leu Lys Glu Cys Val Ser Ile Leu Pro

Arg Lys Glu Ser Pro Ser Val Arg Ser Ser Lys Asp Gly Lys Leu Leu 40 45 Ala Ala Thr Leu Leu Leu Ala Leu Leu Ser Cys Cys Leu Thr val val 50 55 60 Ser Phe Tyr Gln Val Ala Ala Leu Gln Gly Asp Leu Ala Ser Leu Arg 65 70 75 80 Ala Glu Leu Gln Gly His His Ala Glu Lys Leu Pro Ala Gly Ala Gly 85 90 85 Ala Pro Lys Ala Gly Leu Glu Glu Ala Pro Ala Val Thr Ala Gly Leu 100 105 110 Lys Ile Phe Glu Pro Pro Ala Pro Gly Glu Gly Asn Ser Ser Gln Asn 115 120 125

Ser Arg Asn Lys Arg Ala Val Gln Gly Pro Glu Glu Thr Val Thr Gln 130 135 140 Asp Cys Leu Gln Leu Ile Ala Asp Ser Glu Thr Pro Thr Ile Gln Lys 145 150 155 160 Gly Ser Tyr Thr Phe Val Pro Trp Leu Leu Ser Phe Lys Arg Gly Ser 165 170 175 Ala Leu Glu Glu Lys Glu Asn Lys Ile Leu Val Lys Glu Thr Gly Tyr 180 185 190 Phe Phe Ile Tyr Gly Gln Val Leu Tyr Thr Asp Lys Thr Tyr Ala Met 195 200 205 Gly His Leu Ile Gln Arg Lys Lys Val His Val Phe Gly Asp Glu Leu 210 215 220 Ser Leu Val Thr Leu Phe Arg Cys Ile Gln Asn Met Pro Glu Thr Leu 225 230 235 240 Pro Asn Asn Ser Cys Tyr Ser Ala Gly Ile Ala Lys Leu Glu Glu Gly 245 250 255 Asp Glu Leu Gln Leu Ala Ile Pro Arg Glu Asn Ala Gln Ile Ser Leu 260 265 270 Asp Gly Asp Val Thr Phe Phe Gly Ala Leu Lys Leu Leu 275 280 285 <210> 2471 <211l> 99 <212> PRT <213> Homo sapiens <400> 2471 Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu Ile Ser 1 S 10 15 Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu Arg Cys Gln Cys Ile Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe 40 45 810

Le.

Ile Lys Glu Leu Arg Val Ile Glu Ser Gly Pro His Cys Ala Asn Thr 50 55 60

Glu Ile Ile val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro

65 70 75 80

Lys Glu Asn Trp Val Gln Arg Val val Glu Lys Phe Leu Lys Arg Ala

85 SO 95

Glu Asn Ser

<210> 2472

<211> 247

<212> PRT

<213> Homo sapiens

<400> 2472

Met Gln Pro Ile Leu Leu Leu Leu Ala Phe Leu Leu Leu Pro Arg Ala

1 5 10 15

Asp Ala Gly Glu Ile Ile Gly Gly His Glu Ala Lys Pro His Ser Arg

Pro Tyr Met Ala Tyr Leu Met Ile Trp Asp Gln Lys Ser Leu Lys Arg 40 45

Cys Gly Gly Phe Leu Ile Gln Asp Asp Phe Val Leu Thr Ala Ala His 50 55 60

Cys Trp Gly Ser Ser Ile Asn Val Thr Leu Gly Ala His Asn Ile Lys

65 70 75 80

Glu Gln Glu Pro Thr Gln Gln Phe Ile Pro Val Lys Arg Pro Ile Pro

85 90 95 His Pro Ala Tyr Asn Pro Lys Asn Phe Ser Asn Asp Ile Met Leu Leu 100 105 110 Gln Leu Glu Arg Lys Ala Lys Arg Thr Arg Ala Val Gln Pro Leu Arg 115 120 125

Leu Pro Ser Asn Lys Ala Gln Val Lys Pro Gly Gln Thr Cys Ser Val 130 135 140

Ala Gly Trp Gly Gln Thr Ala Pro Leu Gly Lys His Ser His Thr Leu

145 150 155 160

Gln Glu val Lys Met Thr Val Gln Glu Asp Arg Lys Cys Glu Ser Asp 165 170 175 Leu Arg His Tyr Tyr Asp Ser Thr Ile Glu Leu Cys Val Gly Asp Pro 180 185 190 Glu Ile Lys Lys Thr Ser Phe Lys Gly Asp Ser Gly Gly Pro Leu Val ’ 195 200 205 Cys Asn Lys Val Ala Gln Gly Ile Val Ser Tyr Gly Arg Asn Asn Gly 210 215 220 Met Pro Pro Arg Ala Cys Thr Lys Val Ser Ser Phe Val His Trp Ile 225 230 235 240 Lys Lys Thr Met Lys Arg Tyr 245 <210> 2473 <211> 281 <212> PRT <213> Homo sapiens <400> 2473 Met Gln Gln Pro Phe Asn Tyr Pro Tyr Pro Gln Ile Tyr Trp Val Asp 1 5 10 15 Ser Ser Ala Ser Ser Pro Trp Ala Pro Pro Gly Thr Val Leu Pro Cys

Pro Thr Ser Val Pro Arg Arg Pro Gly Gln Arg Arg Pro Pro Pro Pro 40 45 Pro Pro Pro Pro Pro Leu Pro Pro Pro Pro Pro Pro Pro Pro Leu Pro 50 55 60 Pro Leu Pro Leu Pro Pro Leu Lys Lys Arg Gly Asn His Ser Thr Gly 65 70 75 80 Leu Cys Leu Leu Val Met Phe Phe Met Val Leu Val Ala Leu Val Gly 85 90 95 Leu Gly Leu Gly Met Phe Gln Leu Phe His Leu Gln Lys Glu Leu Ala 100 105 110

Glu Leu Arg Glu Ser Thr Ser Gln Met His Thr Ala Ser Ser Leu Glu 115 120 125 Lys Gln Ile Gly His Pro Ser Pro Pro Pro Glu Lys Lys Glu Leu Arg 130 135 140 Lys Val Ala His Leu Thr Gly Lys Ser Asn Ser Arg Ser Met Pro Leu 145 150 155 160 Glu Trp Glu Asp Thr Tyr Gly Ile val Leu Leu Ser Gly Val Lys Tyr 165 170 175 Lys Lys Gly Gly Leu Val Ile Asn Glu Thr Gly Leu Tyr Phe Val Tyr 180 185 150 Ser Lys Val Tyr Phe Arg Gly Gln Ser Cys Asn Asn Leu Pro Leu Ser 185 200 205 His Lys Val Tyr Met Arg Asn Ser Lys Tyr Pro Gln Asp Leu Val Met 210 215 220 Met Glu Gly Lys Met Met Ser Tyr Cys Thr Thr Gly Gln Met Trp Ala 225 230 235 240 Arg Ser Ser Tyr Leu Gly Ala Val Phe Asn Leu Thr Ser Ala Asp His 245 250 255 Leu Tyr Val Asn Val Ser Glu Leu Ser Leu Val Asn Phe Glu Glu Ser 260 265 270 Gln Thr Phe .Phe Gly Leu Tyr Lys Leu 275 280 <210> 2474 <211> 830 <212> PRT <213> Homo sapiens <400> 2474 Met Gly Ser Met Phe Arg Ser Glu Glu Val Ala Leu Val Gln Leu Phe 1 5 10 15 Leu Pro Thr Ala Ala Ala Tyr Thr Cys Val Ser Arg Leu Gly Glu Leu

Gly Leu Val Glu Phe Arg Asp Leu Asn Ala Ser Val Ser Ala Phe Gln 3% 40 . 45

Arg Arg Phe Val Val Asp Val Arg Arg Cys Glu Glu Leu Glu Lys Thr 50 55 60 Phe Thr Phe Leu Gln Glu Glu Val Arg Arg Ala Gly Leu Val Leu Pro 65 70 75 80 Pro Pro Lys Gly Arg Leu Pro Ala Pro Pro Pro Arg Asp Leu Leu Arg 85 90 95 Ile Gln Glu Glu Thr Glu Arg Leu Ala Gln Glu Leu Arg Asp Val Arg 100 105 110 Gly Asn Gln Gln Ala Leu Arg Ala Gln Leu His Gln Leu Gln Leu His 115 120 128 Ala Ala val Leu Arg Gln Gly His Glu Pro Gln Leu Ala Ala Ala His 130 135 140 Thr Asp Gly Ala Ser Glu Arg Thr Pro Leu Leu Gln Ala Pro Gly Gly 145 150 155 160 Pro His Gln Asp Leu Arg Val Asn Phe Val Ala Gly Ala Val Glu Pro 165 170 175 His Lys Ala Pro Ala Leu Glu Arg Leu Leu Trp Arg Ala Cys Arg Gly 180 185 190 Phe Leu Ile Ala Ser Phe Arg Glu Leu Glu Gln Pro Leu Glu His Pro 195 200 205 val Thr Gly Glu Pro Ala Thr Trp Met Thr Phe Leu Ile Ser Tyr Trp 210 215 220 Gly Glu Gln Ile Gly Gln Lys Ile Arg Lys Ile Thr Asp Cys Phe His 225 230 235 240 Cys His Val Phe Pro Phe Leu Gln Gln Glu Glu Ala Arg Leu Gly Ala 245 250 255 Leu Gln Gln Leu Gln Gln Gln Ser Gln Glu Leu Gln Glu Val Leu Gly 260 265 270 Glu Thr Glu Arg Phe Leu Ser Gln Val Leu Gly Arg Val Leu Gln Leu 275 280 285 814 i

Leu Pro Pro Gly Gln Val Gln Val His Lys Met Lys Ala Val Tyr Leu 290 295 300 Ala Leu Asn Gln Cys Ser Val Ser Thr Thr His Lys Cys Leu Ile Ala 305 310 315 320 Glu Ala Trp Cys Ser Val Arg Asp Leu Pro Ala Leu Gln Glu Ala Leu 325 330 335 Arg Asp Ser Ser Met Glu Glu Gly Val Ser Ala Val Ala His Arg Ile 340 345 350 Pro Cys Arg Asp Met Pro Pro Thr Leu Ile Arg Thr Asn Arg Phe Thr 355 360 365 Ala Ser Phe Gln Gly Ile Val Asp Ala Tyr Gly Val Gly Arg Tyr Gln 370 375 380 Glu Val Asn Pro Ala Pro Tyr Thr Ile Ile Thr Phe Pro Phe Leu Phe 385 390 395 400 Ala Val Met Phe Gly Asp Val Gly His Gly leu Leu Met Phe Leu Phe 405 410 415 Ala Leu Ala Met Val Leu Ala Glu Asn Arg Pro Ala Val Lys Ala Ala 420 425 430 Gln Asn Glu Ile Trp Gln Thr Phe Phe Arg Gly Arg Tyr Leu Leu Leu 435 440 445 Leu Met Gly Leu Phe Ser Ile Tyr Thr Gly Phe Ile Tyr Asn Glu Cys 450 455 460 Phe Ser Arg Ala Thr Ser Ile Phe Pro Ser Gly Trp Ser Val Ala Ala 465 470 475 480 Met Ala Asn Gln Ser Gly Trp Ser Asp Ala Phe Leu Ala Gin His Thr 485 490 495 Met Leu Thr Leu Asp Pro Asn Val Thr Gly Val Phe Leu Gly Pro Tyr 500 505 510 Pro Phe Gly Ile Asp Pro Ile Trp Ser Leu Ala Ala Asn His Leu Ser 51S 520 525

Phe Leu Asn Ser Phe Lys Met Lys Met Ser Val Ile Leu Gly Val val 530 535 540 His Met Ala Phe Gly Val Val Leu Gly Val Phe Asn His Val His Phe 545 550 555 560 Gly Gln Arg His Arg Leu Leu Leu Glu Thr Leu Pro Glu Leu Thr Phe 565 570 575 Leu Leu Gly Leu Phe Gly Tyr Leu Val Phe Leu Val Ile Tyr Lys Trp 580 585 590 Leu Cys Val Trp Ala Ala Arg Ala Ala Ser Ala Pro Ser Ile Leu Ile 585 600 605 His Phe Ile Asn Met Phe Leu Phe Ser His Ser Pro Ser Asn Arg Leu 610 615 620 Leu Tyr Pro Arg Gln Glu Val Val Gln Ala Thr Leu Val Val Leu Ala 625 630 635 640 Leu Ala Met Val Pro Ile Leu Leu Leu Gly Thr Pro Leu His Leu Leu 645 650 655 His Arg His Arg Arg Arg Leu Arg Arg Arg Pro Ala Asp Arg Gln Glu 660 665 670 Glu Asn Lys Ala Gly Leu Leu Asp Leu Pro Asp Ala Ser Val Asn Gly 675 680 685 Trp Ser Ser Asp Glu Glu Lys Ala Gly Gly Leu Asp Asp Glu Glu Glu 690 695 700 Ala Glu Leu Val Pro Ser Glu Val Leu Met His Gln Ala Ile His Thr 705 710 715 720 Ile Glu Phe Cys Leu Gly Cys Val Ser Asn Thr Ala Ser Tyr Leu Arg 725 730 735 Leu Trp Ala Leu Ser Leu Ala His Ala Gln Leu Ser Glu Val Leu Trp 740 745 750 Ala Met Val Met Arg Ile Gly Leu Gly Leu Gly Arg Glu Val Gly Val 755 760 765 Ala Ala val Val Leu Val Pro Ile Phe Ala Ala Phe Ala Val Met Thr 816

770 775 780 Val Ala Ile Leu Leu Val Met Glu Gly Leu Ser Ala Phe Leu His Ala 785 790 795 800 Leu Arg Leu His Trp Val Glu Phe Gln Asn Lys Phe Tyr Ser Gly Thr 805 810 815 Gly Tyr Lys Leu Ser Pro Phe Thr Phe Ala Ala Thr Asp Asp 820 825 830 <210> 2475 <211> 555 <212> PRT <213> Homo sapiens <400> 2475 Met Ala Ala Arg Leu Leu Leu Leu Gly Ile Leu Leu Leu Leu Leu Pro 1 S 10 15 Leu Pro Val Pro Ala Pro Cys His Thr Ala Ala Arg Ser Glu Cys Lys

Arg Ser His Lys Phe Val Pro Gly Ala Trp Leu Ala Gly Glu Gly Val 40 45 Asp Val Thr Ser Leu Arg Arg Ser Gly Ser Phe Pro Val Asp Thr Gln 50 55 60 Arg Phe Leu Arg Pro Asp Gly Thr Cys Thr Leu Cys Glu Asn Ala Leu 65 70 75 80 Gln Glu Gly Thr Leu Gln Arg Leu Pro Leu Ala Leu Thr Asn Trp Arg 85 80 95 Ala Gln Gly Ser Gly Cys Gln Arg His val Thr Arg Ala Lys Val Ser 100 105 110 Ser Thr Glu Ala Val Ala Arg Asp Ala Ala Arg Ser Ile Arg Asn Asp 115 120 125 Trp Lys Val Gly Leu Asp Val Thr Pro Lys Pro Thr Ser Asn Val His 130 135 140 Val Ser Val Ala Gly Ser His Ser Gln Ala Ala Asn Phe Ala Ala Gln 145 150 155 160

Lys Thr His Gln Asp Gln Tyr Ser Phe Ser Thr Asp Thr Val Glu Cys 165 170 175 Arg Phe Tyr Ser Phe His Val Val His Thr Pro Pro Leu His Pro Asp 180 185 190 Phe Lys Arg Ala Leu Gly Asp Leu Pro His His Phe Asn Ala Ser Thr 195 200 205 Gln Pro Ala Tyr Leu Arg Leu Ile Ser Asn Tyr Gly Thr His Phe Ile 210 215 220 Arg Ala Val Glu Leu Gly Gly Arg Ile Ser Ala Leu Thr Ala Leu Arg 225 230 235 240 Thr Cys Glu Leu Ala Leu Glu Gly Leu Thr Asp Asn Glu Val Glu Asp 245 250 255 Cys Leu Thr val Glu Ala Gln Val Asn Ile Gly Ile His Gly Ser Ile 260 265 270 Ser Ala Glu Ala Lys Ala Cys Glu Glu Lys Lys Lys Lys His Lys Met 275 280 285 Thr Ala Ser Phe His Gln Thr Tyr Arg Glu Arg His Ser Glu Val Val 290 295 300 Gly Gly His His Thr Ser Ile Asn Asp Leu Leu Phe Gly Ile Gln Ala 305 310 315 320 Gly Pro Glu Gln Tyr Ser Ala Trp Val Asn Ser Val Pro Gly Ser Pro 325 330 335 Gly Leu Val Asp Tyr Thr Leu Glu Pro Leu His Val Leu Leu Asp Ser 340 345 350 Gln Asp Pro Arg Arg Glu Ala Leu Arg Arg Ala Leu Ser Gln Tyr Leu 355 360 365 Thr Asp Arg Ala Arg Trp Arg Asp Cys Ser Arg Pro Cys Pro Pro Gly 370 375 380 Arg Gln Lys Ser Pro Arg Asp Pro Cys Gln Cys Val Cys His Gly Ser 385 390 395 400 818 Bh

PCT/US2003/012946

Ala val Thr Thr Gln Asp Cys Cys Pro Arg Gln Arg Gly Leu Ala Gln 405 410 415 Leu Glu val Thr Phe Ile Gln Ala Trp Ser Leu Trp Gly Asp Trp Phe 420 425 430 Thr Ala Thr Asp Ala Tyr Val Lys Leu Phe Phe Gly Gly Gln Glu Leu 435 440 445 Arg Thr Ser Thr val Trp Asp Asn Asn Asn Pro Ile Trp Ser Val Arg 450 455 460 Leu Asp Phe Gly Asp Val Leu Leu Ala Thr Gly Gly Pro Leu Arg Leu 465 470 475 480 Gln val Trp Asp Gln Asp Ser Gly Arg Asp Asp Asp Leu Leu Gly Thr 485 490 495 Cys Asp Gln Ala Pro Lys Ser Gly Ser His Glu Val Arg Cys Asn Leu 500 505 510 Asn His Gly His Leu Lys Phe Arg Tyr His Ala Arg Cys Leu Pro His 515 520 525 Leu Gly Gly Gly Thr Cys Leu Asp Tyr Val Pro Gln Met Leu Leu Gly 530 535 540 Glu Pro Pro Gly Asn Arg Ser Gly Ala Val Trp 545 550 555 <210> 2476 <211> 153 <212> PRT <213> Homo sapiens <400> 2476 Met Gly Leu Thr Ser Gln Leu Leu Pro Pro Leu Phe Phe Leu Leu Ala 1 5) 10 15 Cys Ala Gly Asn Phe Val His Gly His Lys Cys Asp Ile Thr Leu Gln

Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys 40 45 Thr Glu Leu Thr val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr 50 55 60

PCT/US2003/012946

Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr val Leu Arg Gln Phe Tyr 65 70 75 80 Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln 85 90 S95 Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg 100 105 110 Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala 115 120 125 Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met 130 135 140 Arg Glu Lys Tyr Ser Lys Cys Ser Ser 145 150 <210> 2477 <21l1l> 146 <212> PRT <213> Homo sapiens <400> 2477 Met His Pro Leu Leu Asn Pro Leu Leu Leu Ala Leu Gly Leu Met Ala 1 5 10 15 Leu Leu Leu Thr Thr Val Ile Ala Leu Thr Cys Leu Gly Gly Phe Ala

Ser Pro Gly Pro Val Pro Pro Ser Thr Ala Leu Arg Glu Leu Ile Glu 40 45 Glu Leu val Asn Ile Thr Gln Asn Gln Lys Ala Pro Len Cys Asn Gly 50 55 60 Ser Met Val Trp Ser Ile Asn Leu Thr Ala Gly Met Tyr Cys Ala Ala 65 70 : 75 BO Leu Glu Ser Leu Ile Asn Val Ser Gly Cys Ser Ala Ile Glu Lys Thr 85 90 95 Gln Arg Met Leu Ser Gly Phe Cys Pro His Lys Val Ser ala Gly Gin 100 105 110

Phe Ser Ser Leu His Val Arg Asp Thr Lys Ile Glu Val Ala Gln Phe 11S 120 125 Val Lys Asp Leu Leu Leu His Leu Lys Lys Leu Phe Arg Glu Gly Gln 130 135 140 Phe Asn 145 <210> 2478 <211> 223 <212> PRT <213> Homo sapiens <400> 2478 Met Ala Cys Leu Gly Phe Gln Arg His Lys Ala Gln Leu Asn Leu Ala 1 5 10 15 Thr Arg Thr Trp Pro Cys Thr Leu Leu Phe Phe Leu Leu Phe Ile Pro

Val Phe Cys Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala 40 45 Ser Ser Arg Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly 50 SS 60 Lys Ala Thr Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln 65 70 75 80 Val Thr Glu Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr 85 90 95 Phe Leu Asp Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val 100 105 110 Asn Leu Thr Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile 115 120 125 Cys Lys Val Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly 130 135 140 . Asn Gly Thr Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser 145 150 155 160 Asp Phe Leu Leu Trp Ile Leu Ala Ala Val Ser Ser Gly Leu Phe Phe 165 170 175

Tyr Ser Phe Leu Leu Thr Ala Val Ser Leu Ser Lys Met Leu Lys Lys 180 185 190 Arg Ser Pro Leu Thr Thr Gly Val Tyr Val Lys Met Pro Pro Thr Glu 185 200 205 Pro Glu Cys Glu Lys Gln Phe Gln Pro Tyr Phe Ile Pro Ile Asn 210 215 220 <210> 2479 <211> 23S <212> PRT <213> Homo sapiens <400> 2479 Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 1 5 10 15 His Ala Ala Arg Pro Ser Gln Phe Arg Val Ser Pro Leu Asp Arg Thr

Trp Asn Leu Gly Glu Thr Val Glu Leu Lys Cys Gln Val Leu Leu Ser 40 45 Asn Pro Thr Ser Gly Cys Ser Trp Leu Phe Gln Pro Arg Gly Ala Ala 50 55 60 Ala Ser Pro Thr Phe Leu Leu Tyr Leu Ser Gln Asn Lys Pro Lys Ala 65 70 75 80 Ala Glu Gly Leu Asp Thr Gln Arg Phe Ser Gly Lys Arg Leu Gly Asp 85 S80 95 Thr Phe val Leu Thr Leu Ser Asp Phe Arg Arg Glu Asn Glu Gly Tyr 100 105 110 Tyr Phe Cys Ser Ala Leu Ser Asn Ser Ile Met Tyr Phe Ser His Phe 115 120 ’ 125 Val Pro Val Phe Leu Pro Ala Lys Pro Thr Thr Thr Pro Ala Pro Arg 130 135 140 Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg 145 150 155 160

Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly 165 170 175 Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr 180 185 190 Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Asn His 195 200 205 Arg Asn Arg Arg Arg Val Cys Lys Cys Pro Arg Pro Val Val Lys Ser 210 215 220 Gly Asp Lys Pro Ser Leu Ser Ala Arg Tyr val 225 230 235 <210> 2480 <211> 181 <212> PRT <213> Homo sapiens <400> 2480 Met Leu Leu Glu Pro Gly Arg Gly Cys Cys Ala Leu Ala Ile Leu Leu 1 5 10 15 Ala Ile Val Asp Ile Gln Ser Gly Gly Cys Ile Asn Ile Thr Ser Ser

Ala Ser Gln Glu Gly Thr Arg Leu Asn Leu Ile Cys Thr val Trp His 40 45 Lys Lys Glu Glu Ala Glu Gly Phe Val Val Phe Leu Cys Lys Asp Arg 50 55 60 Ser Gly Asp Cys Ser Pro Glu Thr Ser Leu Lys Gln Leu Arg Leu Lys 65 70 75 80 Arg Asp Pro Gly Ile Asp Gly Val Gly Glu Ile Ser Ser Gln Leu Met 85 90 95 Phe Thr Ile Ser Gln Val Thr Pro Leu His Ser Gly Thr Tyr Gln Cys 100 105 110 Cys Ala Arg Ser Gln Lys Ser Gly Ile Arg Leu Gln Gly His Phe Phe 115 120 125 Ser Ile Leu Phe Thr Glu Thr Gly Asn Tyr Thr Val Thr Gly Leu Lys 130 135 140

Gln Arg Gln His Leu Glu Phe Ser His Asn Glu Gly Thr Leu Ser Ser 145 150 155 160 Gly Phe Leu Gln Glu Lys Val Trp Val Met Leu Val Thr Ser Leu Val 165 170 175 Ala Leu Gln Ala Leu 180 <210> 2481 <211> 147 «212> PRT <213> Homo sapiens <400> 2481 Met Val His Leu Thr Pro Glu Glu lys Ser Ala Val Thr Ala Leu Trp 1 5 10 15 Gly Lys Val Asn Val Asp Glu Val Gly Gly Glu Ala Leu Gly Arg Leu

Leu Val val Tyr Pro Trp Thr Gln Arg Phe Phe Glu Ser Phe Gly Asp 40 45 Leu Ser Thr Pro Asp Ala Val Met Gly Asn Pro Lys Val Lys Ala His 50 5S 60 Gly Lys Lys Val Leu Gly Ala Phe Ser Asp Gly Leu Ala His Leu Asp 65 70 75 80 Asn Leu Lys Gly Thr Phe Ala Thr Leu Ser Glu Leu His Cys Asp Lys BS 90 85 Leu His Val Asp Pro Glu Asn Phe Arg Leu Leu Gly Asn Val Leu Val 100 105 110 Cys Val Leu Ala His His Phe Gly Lys Glu Phe Thr Pro Pro Val Gln 115 120 : 125 Ala Ala Tyr Gln Lys Val Val Ala Gly Val Ala Asn Ala Leu Ala His 130 135 140 Lys Tyr His 145 824

<210> 2482 <211> 259 <212> PRT <213> Homo sapiens <400> 2482 Met Ser Lys Tyr Lys Leu Ile Met Leu Arg His Gly Glu Gly Ala Trp 1 5 10 15 Asn Lys Glu Asn Arg Phe Cys Ser Trp Val Asp Gln Lys Leu Asn Ser

Glu Gly Met Glu Glu Ala Arg Asn Cys Gly Lys Gln Leu Lys Ala Leu 40 45 Asn Phe Glu Phe Asp Leu Val Phe Thr Ser Val Leu Asn Arg Ser Ile 50 55 60 His Thr Ala Trp Leu Ile Leu Glu Glu Leu Gly Gln Glu Trp Val Pro 65 70 75 80 Val Glu Ser Ser Trp Arg Leu Asn Glu Arg His Tyr Gly Ala Leu Ile 85 90 95 Gly Leu Asn Arg Glu Gln Met Ala Leu Asn His Gly Glu Glu Gln Val 100 105 110 Arg Leu Trp Arg Arg Ser Tyr Asn Val Thr Pro Pro Pro Ile Glu Glu 115 120 125 Ser His Pro Tyr Tyr Gln Glu Ile Tyr Asn Asp Arg Arg Tyr Lys Val 130 135 140 Cys Asp Val Pro Leu Asp Gln Leu Pro Arg Ser Glu Ser Leu Lys Asp 145 150 155 160 Val Leu Glu Arg Leu Leu Pro Tyr Trp Asn Glu Arg Ile Ala Pro Glu 165 170 175 Val Leu Arg Gly Lys Thr Ile Leu Ile Ser Ala His Gly Asn Ser Ser 180 185 130 Arg Ala Leu Leu Lys His Leu Glu Gly Ile Ser Asp Glu Asp Ile Ile 195 200 205 Asn Ile Thr Leu Pro Thr Gly Val Pro Ile Leu Leu Glu Leu Asp Glu 210 215 220

Asn Leu Arg Ala Val Gly Pro His Gln Phe Leu Gly Asp Gln Glu Ala 225 230 235 240 Ile Gln Ala Ala Ile Lys Lys Val Glu Asp Gln Gly Lys Val Lys Gln

245 250 255

Ala Lys Lys

<210> 2483

«211> 344

<212> PRT

<213> Homo sapiens

<400> 2483

Met Ser Ala Leu Ala Ala Arg Leu Leu Gln Pro Ala His Ser Cys Ser 1 5 10 15 Leu Arg Leu Arg Pro Phe His Leu Ala Ala Val Arg Asn Glu Ala Val

Val Ile Ser Gly Arg Lys Leu Ala Gln Gln Ile Lys Gln Glu Val Arg 40 45 Gln Glu Val Glu Glu Trp Val Ala Ser Gly Asn Lys Arg Pro His Leu 50 S5 60 Ser Val Ile Leu Val Gly Glu Asn Pro Ala Ser His Ser Tyr Val Leu 65 70 75 80 Asn Lys Thr Arg Ala Ala Ala Val Val Gly Ile Asn Ser Glu Thr Ile 85 80 95 Met Lys Pro Ala Ser Ile Ser Glu Glu Glu Leu Leu Asn Leu Ile Asn 100 105 110 Lys Leu Asn Asn Asp Asp Asn Val Asp Gly Leu Leu Val Gln Leu Pro 115 120 125 Leu Pro Glu His Ile Asp Glu Arg Arg Ile Cys Asn Ala Val Ser Pro 130 135 140 Asp Lys Asp Val Asp Gly Phe His Val Ile Asn Val Gly Arg Met Cys 145 150 155 160

Leu Asp Gln Tyr Ser Met Leu Pro Ala Thr Pro Trp Gly Val Trp Glu 165 170 175 Ile Ile Lys Arg Thr Gly Ile Pro Thr Leu Gly Lys Asn Val val Val 180 185 190 Ala Gly Arg Ser Lys Asn Val Gly Met Pro Ile Ala Met Leu Leu His 195 200 205 Thr Asp Gly Ala His Glu Arg Pro Gly Gly Asp Ala Thr Val Thr Ile 210 215 220 Ser His Arg Tyr Thr Pro Lys Glu Gln Leu Lys Lys His Thr Ile Leu 225 230 235 240 Ala Asp Ile Val Ile Ser Ala Ala Gly Ile Pro Asn Leu Ile Thr Ala 245 250 255 Asp Met Ile Lys Glu Gly Ala Ala Val Ile Asp Val Gly Ile Asn Arg 260 265 270 Val His Asp Pro Val Thr Ala Lys Pro Lys Leu Val Gly Asp val Asp 275 280 285 Phe Glu Gly Val Arg Gln Lys Ala Gly Tyr Ile Thr Pro Val Pro Gly . 290 295 300 Gly Val Gly Pro Met Thr Val Ala Met Leu Met Lys Asn Thr Ile Ile 305 310 31s 320 Ala Ala Lys Lys Val Leu Arg Leu Glu Glu Arg Glu Val Leu Lys Ser 325 330 335 Lys Glu Leu Gly Val Ala Thr Asn 340 <210> 2484 <211> 808 <212> PRT : <213> Homo sapiens <400> 2484 : ) Met Ala Glu Leu Leu Ala Ser Ala Gly Ser Ala Cys Ser Trp Asp Phe 1 5 10 15 Pro Arg Ala Pro Pro Ser Phe Pro Pro Pro Ala Ala Ser Arg Gly Gly

Leu Gly Gly Thr Arg Ser Phe Arg Pro His Arg Gly Ala Glu Ser Pro 40 45 Arg Pro Gly Arg Asp Arg Asp Gly Val Arg Val Pro Met Ala Ser Ser 50 55 60 Arg Cys Pro Ala Pro Arg Gly Cys Arg Cys Leu Pro Gly Ala Ser Leu 65 70 75 80 Ala Trp Leu Gly Thr val Leu Leu Leu Leu Ala Asp Trp Val Leu Leu 85 20 95 Arg Thr Ala Leu Pro Arg Ile Phe Ser Leu Leu Val Pro Thr Ala Leu 100 105 110 Pro Leu Leu Arg Val Trp Ala Val Gly Leu Ser Arg Trp Ala Val Leu 115 120 125 Trp Leu Gly Ala Cys Gly Val Leu Arg Ala Thr Val Gly Ser Lys Ser ! 130 135 140 Glu Asn Ala Gly Ala Gln Gly Trp Leu Ala Ala Leu Lys Pro Leu Ala 145 150 155 160 Ala Ala Leu Gly Leu Ala Leu Pro Gly Leu Rla Leu Phe Arg Glu Leu 165 170 175 Ile Ser Trp Gly Ala Pro Gly Ser Ala Asp Ser Thr Arg Leu Leu His 180 185 190 Trp Gly Ser His Pro Thr Ala Phe Val Val Ser Tyr Ala Ala Ala Leu 195 200 205 Pro ala Ala Ala Leu Trp His Lys Leu Gly Ser Leu Trp Val Pro Gly 210 215 220 Gly Gln Gly Gly Ser Gly Asn Pro Val Arg Arg Leu Leu Gly Cys Leu 225 230 235 240 Gly Ser Glu Thr Arg Arg Leu Ser leu Phe Leu Val Leu Val Val Leu 245 250 255 Ser Ser Leu Gly Glu Met Ala Ile Pro Phe Phe Thr Gly Arg Leu Thr 260 265 270

Asp Trp Ile Leu Gln Asp Gly Ser Ala Asp Thr Phe Thr Arg Asn Leu 275 280 285 Thr Leu Met Ser Ile Leu Thr Ile Ala Ser Ala Val Leu Glu Phe Val 290 295 300 Gly Asp Gly Ile Tyr Asn Asn Thr Met Gly His Val His Ser His Leu 305 310 315 320 Gln Gly Glu val Phe Gly Ala Val Leu Arg Gln Glu Thr Glu Phe Phe 325 330 335 Gln Gln Asn Gln Thr Gly Asn Ile Met Ser Arg Val Thr Glu Asp Thr 340 345 350 Ser Thr Leu Ser Asp Ser Leu Ser Glu Asn Leu Ser Leu Phe Leu Trp 355 360 365 Tyr Leu Val Arg Gly Leu Cys Leu Leu Gly Ile Met Leu Trp Gly Ser 370 375 380 Val Ser Leu Thr Met Val Thr Leu Ile Thr Leu Pro Leu Leu Phe Leu 385 330 395 400 Leu Pro Lys Lys Val Gly Lys Trp Tyr Gln Leu Leu Glu Val Gln Val 405 410 415 Arg Glu Ser Leu Ala Lys Ser Ser Gln Val Ala Ile Glu Ala Leu Ser 420 425 430 Ala Met Pro Thr Val Arg Ser Phe Ala Asn Glu Glu Gly Glu Ala Gln 435 440 445 Lys Phe Arg Glu Lys Leu Gln Glu Ile Lys Thr Leu Asn Gln Lys Glu 450 455 460 Ala Val Ala Tyr Ala Val Asn Ser Trp Thr Thr Ser Ile Ser Gly Met 465 470 475 480 Leu Leu Lys Val Gly Ile Leu Tyr Ile Gly Gly Gln Leu Val Thr Ser 485 490 495 Gly Ala Val Ser Ser Gly Asn Leu Val Thr Phe Val Leu Tyr Gln Met 500 505 510

Gln Phe Thr Gln Ala Val Glu Val Leu Leu Ser Ile Tyr Pro Arg val 515 520 525 Gln Lys Ala Val Gly Ser Ser Glu Lys Ile Phe Glu Tyr Leu Asp Arg 530 535 540 Thr Pro Arg Cys Pro Pro Ser Gly Leu Leu Thr Pro Leu His Leu Glu 545 550 555 560 Gly Leu Val Gln Phe Gln Asp Val Ser Phe Ala Tyr Pro Asn Arg Pro 565 570 575 Asp Val Leu Val Leu Gln Gly Leu Thr Phe Thr Leu Arg Pro Gly Glu 580 585 590 Val Thr Ala Leu Val Gly Pro Asn Gly Ser Gly Lys Ser Thr val Ala 595 600 605 Ala Leu Leu Gln Asn Leu Tyr Gin Pro Thr Gly Gly Gln Leu Leu Leu 610 615 620 Asp Gly Lys Pro Leu Pro Gln Tyr Glu His Arg Tyr Leu His Arg Gln 625 630 635 640 Val Ala Ala Val Gly Gln Glu Pro Gln Val Phe Gly Arg Ser Leu Gln 645 650 655 Glu Asn Ile Ala Tyr Gly Leu Thr Gln Lys Pro Thr Met Glu Glu Ile 660 665 670 Thr Ala Ala Ala Val Lys Ser Gly Ala His Ser Phe Ile Ser Gly Leu 675 680 685 Pro Gln Gly Tyr Asp Thr Glu Val Asp Glu Ala Gly Ser Gln Leu Ser 690 695 700 Gly Gly Gln Arg Gln Ala Val Ala Leu Ala Arg Ala Leu Ile Arg Lys 705 710 715 720 Pro Cys Val Leu Ile Leu Asp Asp Ala Thr Ser Ala Leu Asp Ala Asn 725 730 735 Ser Gln Leu Gln Val Glu Gln Leu Leu Tyr Glu Ser Pro Glu Arg Tyr 740 745 750 Ser Arg Ser Val Leu Leu Ile Thr Gln His Leu Ser Leu Val Glu Gln

755 760 765 Ala Asp His Ile Leu Phe Leu Glu Gly Gly Ala Ile Arg Glu Gly Gly 770 775 780 Thr His Gln Gln Leu Met Glu Lys Lys Gly Cys Tyr Trp Ala Met Val 785 790 785 800 Gln Ala Pro Ala Asp Ala Pro Glu 805 <210> 2485 <211> 453 <212> PRT <213> Homo sapiens <400> 2485 Met Ala Arg Lys Val Val Ser Arg Lys Arg Lys Ala Pro Ala Ser Pro 1 5 10 15 Gly Ala Gly Ser Asp Ala Gln Gly Pro Gln Phe Gly Trp Asp His Ser

Leu His Lys Arg Lys Arg Leu Pro Pro Val Lys Arg Ser Leu Val Tyr 40 45 Tyr Leu Lys Asn Arg Glu Val Arg Leu Gln Asn Glu Thr Ser Tyr Ser 50 55 60 Arg Val Leu His Gly Tyr Ala Ala Gln Gln Leu Pro Ser Leu Leu Lys 65 70 75 80 Glu Arg Glu Phe His Leu Gly Thr Leu Asn Lys Val Phe Ala Ser Gln 85 50 95 Trp Leu Asn His Arg Gln Val Val Cys Gly Thr Lys Cys Asn Thr Leu 100 10S 110 Phe Val val Asp Val Gln Thr Ser Gln Ile Thr Lys Ile Pro Ile Leu 115 120 125 Lys Asp Arg Glu Pro Gly Gly Val Thr Gln Gln Gly Cys Gly Ile His 130 135 140 Ala Ile Glu Leu Asn Pro Ser Arg Thr Leu Leu Ala Thr Gly Gly asp 145 150 155 160

Asn Pro Asn Ser Leu Ala Ile Tyr Arg Leu Pro Thr Leu Asp Pro val 165 170 175 Cys Val Gly Asp Asp Gly His Lys Asp Trp Ile Phe Ser Ile Ala Trp 180 185 190 Ile Ser Asp Thr Met Ala Val Ser Gly Ser Arg Asp Gly Ser Met Gly 195 200 205 Leu Trp Glu val Thr Asp Asp Val Leu Thr Lys Ser Asp Ala Arg His 210 215 220 Asn Val Ser Arg Val Pro Val Tyr Ala His Ile Thr His Lys Ala Leu 225 230 235 240 Lys Asp Ile Pro Lys Glu Asp Thr Asn Pro Asp Asn Cys Lys Val Arg 245 250 255 Ala Leu Ala Phe Asn Asn Lys Asn Lys Glu Leu Gly Ala Val Ser Leu 260 265 270 Asp Gly Tyr Phe His Leu Trp Lys Ala Glu Asn Thr Leu Ser Lys Leu 275 280 285 Leu Ser Thr Lys Leu Pro Tyr Cys Arg Glu Asn Val Cys Leu Ala Tyr 290 295 300 Gly Ser Glu Trp Ser Val Tyr Ala Val Gly Ser Gln Ala His Val Ser 305 310 315 320 Phe Leu Asp Pro Arg Gln Pro Ser Tyr Asn Val Lys Ser Val Cys Ser 328 330 335 Arg Glu Arg Gly Ser Gly Ile Arg Ser Val Ser Phe Tyr Glu His Ile 340 345 350 Ile Thr Val Gly Thr Gly Gln Gly Ser Leu Leu Phe Tyr Asp Ile Arg 355 360 365 Ala Gln Arg Phe Leu Glu Glu Arg Leu Ser Ala Cys Tyr Gly Ser Lys 370 375 380 Pro Arg Leu Ala Gly Glu Asn Leu Lys Leu Thr Thr Gly Lys Gly Trp 385 390 395 400

Leu Asn His Asp Glu Thr Trp Arg Asn Tyr Phe Ser Asp Ile Asp Phe 405 410 415 Phe Pro Asn Ala Val Tyr Thr His Cys Tyr Asp Ser Ser Gly Thr Lys 420 425 430 Leu Phe Val Ala Gly Gly Pro Leu Pro Ser Gly Leu His Gly Asn Tyr 435 440 445 Ala Gly Leu Trp Ser 450 <210> 2486 <211> 352 <212> PRT <213> Homo sapiens <400> 2486 Met Glu Gly Ile Ser Ile Tyr Thx Ser Asp Asn Tyr Thr Glu Glu Met 1 5 10 15 Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys Phe Arg Glu Glu

Asn Ala Asn Phe Asn Lys Ile Phe Leu Pro Thr Ile Tyr Ser Ile Ile 40 45 Phe Leu Thr Gly Ile Val Gly Asn Gly Leu Val Ile Leu Val Met Gly 50 55 60 Tyr Gln Lys Lys Leu Arg Ser Met Thr Asp Lys Tyr Arg Leu His Leu 65 70 75 80 Ser Val Ala Asp Leu Leu Phe Val Ile Thr Leu Pro Phe Trp Ala Val 85 90 95 Asp Ala Val Ala Asn Trp Tyr Phe Gly Asn Phe Leu Cys Lys Ala Val 100 105 110 His Val Ile Tyr Thr Val Asn Leu Tyr Ser Ser Val Leu Ile Leu Ala 115 120 125 Phe Ile Ser Leu Asp Arg Tyr Leu Ala Ile Val His Ala Thr Asn Ser 130 135 140 Gln Arg Pro Arg Lys Leu Leu Ala Glu Lys Val Val Tyr Val Gly val 145 150 155 160

Trp Ile Pro Ala Leu Leu Leu Thr Ile Pro Asp Phe Ile Phe Ala Asn 165 170 175 Val Ser Glu Ala Asp Asp Arg Tyr Ile Cys Asp Arg Phe Tyr Pro Asn 180 185 190 Asp Leu Trp Val Val Val Phe Gln Phe Gln His Ile Met Val Gly Leu 195 200 205 Ile Leu Pro Gly Ile Val Ile Leu Ser Cys Tyr Cys Ile Ile Ile Ser ) 210 215 220 Lys Leu Ser His Ser Lys Gly His Gln Lys Arg Lys Ala Leu Lys Thr 225 230 235 240 Thr Val Ile Leu Ile Leu Ala Phe Phe Ala Cys Trp Leu Pro Tyr Tyr 245 250 255 Ile Gly Ile Ser Ile Asp Ser Phe Ile Leu Leu Glu Ile Ile Lys Gln 260 265 270 ’ Gly Cys Glu Phe Glu Asn Thr val His Lys Trp Ile Ser Ile Thr Glu 275 280 285 Ala Leu Ala Phe Phe His Cys Cys Leu Asn Pro Ile Leu Tyr Ala Phe 290 295 300 Leu Gly Ala Lys Phe Lys Thr Ser Ala Gln His Ala Leu Thr Ser Val 305 310 315 320 Ser Arg Gly Ser Ser Leu Lys Ile Leu Ser Lys Gly Lys Arg Gly Gly 325 330 335 His Ser Ser Val Ser Thr Glu Ser Glu Ser Ser Ser Phe His Ser Ser 340 345 350 <210> 2487 <211> 199 <212> PRT <213> Homo sapiens <400> 2487 Met Ser Ser Glu Asn Cys Phe Val Ala Glu Asn Ser Ser Leu His Pro 1 5 10 15

Glu Ser Gly Gln Glu Asn Asp Ala Thr Ser Pro His Phe Ser Thr Arg

His Glu Gly Ser Phe Gln Val Pro Val Leu Cys Ala Val Met Asn Val 40 45 Val Phe Ile Thr Ile Leu Ile Ile Ala Leu Ile Ala Leu Ser Val Gly 50 5S 60 Gln Tyr Asn Cys Pro Gly Gln Tyr Thr Phe Ser Met Pro Ser Asp Ser 65 70 75 80 His Val Ser Ser Cys Ser Glu Asp Trp Val Gly Tyr Gln Arg Lys Cys 85 90 95 Tyr Phe Ile Ser Thr Val Lys Arg Ser Trp Thr Ser Ala Gln Asn Ala 100 105 110 Cys Ser Glu His Gly Ala Thr Leu Ala val Ile Asp Ser Glu Lys Asp 115 120 125 Met Asn Phe Leu Lys Arg Tyr Ala Gly Arg Glu Glu His Trp val Gly 130 135 140 Leu Lys Lys Glu Pro Gly His Pro Trp Lys Trp Ser Asn Gly Lys Glu 145 150 155 160 Phe Asn Asn Trp Phe Asn Val Thr Gly Ser Asp Lys Cys Val Phe Leu 165 170 175 Lys Asn Thr Glu Val Ser Ser Met Glu Cys Glu Lys Asn Leu Tyr Trp 180 185 190 Ile Cys Asn Lys Pro Tyr Lys 195 <210> 2488 <211> 91 <212> PRT <213> Homo sapiens <400> 2488 Met Lys Val Ser Ala Ala Ala Leu Ala Val Ile Leu Ile Ala Thr Ala 1 5 10 15 Leu Cys Ala Pro Ala Ser Ala Ser Pro Tyr Ser Ser Asp Thr Thr Pro 20 25 30

Cys Cys Phe Ala Tyr Ile Ala Arg Pro Leu Pro Arg Ala His Ile Lys 35 40 45 Glu Tyr Phe Tyr Thr Ser Gly Lys Cys Ser Asn Pro Ala Val Val Phe 50 55 60 Val Thr Arg Lys Asn Arg Gln Val Cys Ala Asn Pro Glu Lys Lys Trp 65 70 75 80 Val Arg Glu Tyr Ile Asn Ser Leu Glu Met Ser 85 20 <210> 2489 <211> 212 <212> PRT <213> Homo sapiens <400> 2489 Met Asn Ser Phe Ser Thr Ser Ala Phe Gly Pro Val Ala Phe Ser Leu 1 5 10 15 Gly Leu Leu Leu Val Leu Pro Ala Ala Phe Pro Ala Pro Val Pro Pro

Gly Glu Asp Ser Lys Asp Val Ala Ala Pro His Arg Gln Pro Leu Thr 40 45 Ser Ser Glu Arg Ile Asp Lys Gln Ile Arg Tyr Ile Leu Asp Gly Ile 50 Ss 60 Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys Ser Asn Met Cys Glu Ser 65 70 75 80 Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu Pro Lys Met Ala 85 S0 95 Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu Glu Thr Cys Leu 100 105 110 Val Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val Tyr Leu Glu Tyr 115 120 125 Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala Arg Ala Val Gln 130 135 140 836 B a

Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln Lys Lys Ala Lys Asn 145 150 155 160 Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn Ala Ser Leu Leu 165 170 175 Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp Met Thr Thr His 180 185 190 Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser Ser Leu Arg Ala 195 200 205 Leu Arg Gln Met } 210 <210> 2480 <211> 153 <212> PRT <213> Homo sapiens <400> 24%0 Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu 1 5 10 15 Val Thr Asn Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu 2S 30 Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile 40 45 . Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe 50 5% 60 Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu 65 70 75 80 Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys 85 90 95 Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile 100 105 110 Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala 115 120 125 Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe 130 135 140

Cys Gln Ser Ile Ile Ser Thr Leu Thr 145 150 <210> 2491 <211> 231 <212> PRT <213> Homo sapiens <400> 2491 Met Gln Asp Glu Glu Arg Tyr Met Thr Leu Asn Val Gln Ser Lys Lys 1 5 10 15 Arg Ser Ser Ala Gln Thr Ser Gln Leu Thr Phe Lys Asp Tyr Ser Val

Thr Leu His Trp Tyr Lys Ile Leu Leu Gly Ile Ser Gly Thr Val Asn 40 45 Gly Ile Leu Thr Leu Thr Leu Ile Ser Leu Ile Leu Leu Val Ser Gln 50 55 60 Gly val Leu Leu Lys Cys Gln Lys Gly Ser Cys Ser Asn Ala Thr Gln 65 70 75 80 Tyx Glu Asp Thr Gly Asp Leu Lys Val Asn Asn Gly Thr Arg Arg Asn 85 20 95 Ile Ser Asn Lys Asp Leu Cys Ala Ser Arg Ser Ala Asp Gln Thr Val 100 105 110 Leu Cys Gln Ser Glu Trp Leu Lys Tyr Gln Gly Lys Cys Tyr Trp Phe 115 120 125 Ser Asn Glu Met Lys Ser Trp Ser Asp Ser Tyr Val Tyr Cys Leu Glu 130 135 140 Arg Lys Ser His Leu Leu Ile Ile His Asp Gln Leu Glu Met Ala Phe 145 150 155 160 Ile Gln Lys Asn Leu Arg Gln Leu Asn Tyr Val Trp Ile Gly Leu Asn 165 170 17% Phe Thr Ser Leu Lys Met Thr Trp Thr Trp Val Asp Gly Ser Pro Ile 180 185 190

Asp Ser Lys Ile Phe Phe Ile Lys Gly Pro Ala Lys Glu Asn Ser Cys 195 200 205 Ala Ala Ile Lys Glu Ser Lys Ile Phe Ser Glu Thr Cys Ser Ser val 210 215 220 Phe Lys Trp Ile Cys Gln Tyr 225 230 <210> 2492 <211> 512 <212> PRT <213> Homo sapiens <400> 2492 } Met Gly Cys Ile Lys Ser Lys Gly Lys Asp Ser Leu Ser Asp Asp Gly 1 5 10 15 Val Asp Leu Lys Thr Gln Pro Val Arg Asn Thr Glu Arg Thr Ile Tyr

Val Arg Asp Pro Thr Ser Asn Lys Gln Gln Arg Pro Val Pro Glu Ser 40 45 Gln Leu Leu Pro Gly Gln Arg Phe Gln Thr Lys Asp Pro Glu Glu Gln 50 55 60 Gly Asp Ile Val Val Ala Leu Tyr Pro Tyr Asp Gly Ile His Pro Asp 65 70 75 80 Asp Leu Ser Phe Lys Lys Gly Glu Lys Met Lys Val Leu Glu Glu His 85 90 95 Gly Glu Trp Trp Lys Ala Lys Ser Leu Leu Thy Lys Lys Glu Gly Phe 100 10S 110 Ile Pro Ser Asn Tyr Val Ala Lys Leu Asn Thr Leu Glu Thr Glu Glu 115 120 125 Trp Phe Phe Lys Asp Ile Thr Arg Lys Asp Ala Glu Arg Gln Leu Leu 130 135 140 Ala Pro Gly Asn Ser Ala Gly Ala Phe Leu Ile Arg Glu Ser Glu Thr 145 150 155 160 Leu Lys Gly Ser Phe Ser Leu Ser val Arg Asp Phe Asp Pro Val His 165 170 175

Gly Asp val Ile Lys His Tyr Lys Ile Arg Ser Leu Asp Asn Gly Gly 180 185 190 Tyr Tyr Ile Ser Pro Arg Ile Thr Phe Pro Cys Ile Ser Asp Met Ile 195 200 205 Lys His Tyr Gln Lys Gln Ala Asp Gly Leu Cys Arg Arg Leu Glu Lys 210 215 220 Ala Cys Ile Ser Pro Lys Pro Gln Lys Pro Trp Asp Lys Asp Ala Trp 225 230 235% 240 Glu Ile Pro Arg Glu Ser Ile Lys Leu val Lys Arg Leu Gly Ala Gly 245 250 255 Gln Phe Gly Glu Val Trp Met Gly Tyr Tyr Asn Asn Ser Thr Lys Val 260 265 270 Ala val Lys Thr Leu Lys Pro Gly Thr Met Ser val Gln Ala Phe Leu 275 280 285 Glu Glu Ala Asn Leu Met Lys Thr Leu Gln His Asp Lys Leu Val Arg 290 295 300 Leu Tyr Ala Val Val Thr Arg Glu Glu Pro Ile Tyr Ile Ile Thr Glu 305 310 315 320 Tyr Met Ala Lys Gly Ser Leu Leu Asp Phe Leu Lys Ser Asp Glu Gly 325 330 3358 Gly Lys Val Leu Leu Pro Lys Leu Ile Asp Phe Ser Ala Gln Ile Ala 340 345 350 Glu Gly Met Ala Tyr Ile Glu Arg Lys Asn Tyr Ile His Arg Asp Leu 355 360 365 Arg Ala Ala Asn Val Leu Val Ser Glu Ser Leu Met Cys Lys Ile Ala 370 375 380 Asp Phe Gly Leu Ala Arg val Ile Glu Asp Asn Glu Tyr Thr Ala Arg 385 390 395 400 Glu Gly Ala Lys Phe Pro Ile Lys Trp Thr Ala Pro Glu Ala Ile Asn 405 410 41S

Phe Gly Cys Phe Thr Ile Lys Ser Asp Val Trp Ser Phe Gly Ile Leu 420 425 430 Leu Tyr Glu Ile val Thr Tyr Gly Lys Ile Pro Tyr Pro Gly Arg Thr 435 440 445 Asn Ala Asp Val Met Thr Ala Leu Ser Gln Gly Tyr Arg Met Pro Arg . 450 455 460 val Glu Asn Cys Pro Asp Glu Leu Tyr Asp Ile Met Lys Met Cys Trp 465 470 47S 480 Lys Glu Lys Ala Glu Glu Arg Pro Thr Phe Asp Tyr Leu Gln Ser Val 485 490 495 Leu Asp Asp Phe Tyr Thr Ala Thr Glu Gly Gln Tyr Gln Gln Gln Pro 500 505 510 <210> 2493 <211l> 272 <212> PRT <213> Homo sapiens <400> 2493 Met Asp Ser Tyr Leu Leu Met Trp Gly Leu Leu Thr Phe Ile Met Val 1 1) 10 15 Pro Gly Cys Gln Ala Glu Leu Cys Asp Asp Asp Pro Pro Glu Ile Pro

25 . 30 His Ala Thr Phe Lys Ala Met Ala Tyr Lys Glu Gly Thr Met Leu Asn 40 45 Cys Glu Cys Lys Arg Gly Phe Arg Arg Ile Lys Ser Gly Ser Leu Tyr 50 55 60 Met Leu Cys Thr Gly Asn Ser Ser His Ser Ser Trp Asp Asn Gln Cys 65 70 75 80 Gln Cys Thr Ser Ser Ala Thr Arg Asn Thr Thr Lys Gln Val Thr Pro 85 90 95 Gln Pro Glu Glu Gln Lys Glu Arg Lys Thr Thr Glu Met Gln Ser Pro 100 105 110 Met Gln Pro Val Asp Gln Ala Ser Leu Pro Gly His Cys Arg Glu Pro

PCT/US2003/012946

115 120 125 Pro Pro Trp Glu Asn Glu Ala Thr Glu Arg Ile Tyr His Phe Val Val 130 135 140 Gly Gln Met val Tyr Tyr Gln Cys Val Gln Gly Tyr Arg Ala Leu His 145 150 155 160 Arg Gly Pro Ala Glu Ser val Cys Lys Met Thr His Gly Lys Thr Arg 165 170 175 Trp Thr Gln Pro Gln Leu Ile Cys Thr Gly Glu Met Glu Thr Ser Gin 180 185 190 Phe Pro Gly Glu Glu Lys Pro Gln Ala Ser Pro Glu Gly Arg Pro Glu 185 200 205 Ser Glu Thr Ser Cys Leu Val Thr Thr Thr Asp Phe Gln Ile Gln Thr 210 215 220 Glu Met Ala Ala Thr Met Glu Thr Ser Ile phe Thr Thr Glu Tyr Gln 225 230 235 240 val Ala Val Ala Gly Cys Val Phe Leu Leu Ile Ser Val Leu Leu Leu 245 250 255 Ser Gly Leu Thr Trp Gln Arg Arg Gln Arg Lys Ser Arg Arg Thr Ile 260 265 270 <210> 2494 <211> 92 <212> PRT <213> Homo sapiens <400> 2494 Met Lys Leu Cys Val Thr Val Leu Ser Leu Leu Met Leu Val Ala Ala 1 5) 10 15 Phe Cys Ser Pro Ala Leu Ser Ala Pro Met Gly Ser Asp Pro Pro Thr

Ala Cys Cys Phe Ser Tyr Thr Ala Arg Lys Leu Pro Arg Asn Phe Val 3s 40 45 Val Asp Tyr Tyr Glu Thr Ser Ser Leu Cys Ser Gln Pro Ala val val 50 55 60

Phe Gln Thr Lys Arg Ser Lys Gln Val Cys Ala Asp Pro Ser Glu Ser 65 70 75 80 Trp Val Gln Glu Tyr Val Tyr Asp Leu Glu Leu Asn 85 90 <210> 2495 <211> 532 <212> PRT <213> Homo sapiens <400> 2495 Met Met Met Val Arg Arg Gly Leu Leu Ala Trp Ile Ser Arg Val Val 1 5 10 15 Val Leu Leu Val Leu Leu Cys Cys Ala Ile Ser Val Leu Tyr Met Leu }

Ala Cys Thr Pro Lys Gly Asp Glu Glu Gln Leu Ala Leu Pro Arg Ala 40 45 Asn Ser Pro Thr Gly Lys Glu Gly Tyr Gln Ala Val Leu Gln Glu Trp 50 55 60 Glu Glu Gln His Arg Asn Tyr Val Ser Ser Leu Lys Arg Gln Ile Ala €5 70 75 80 Gln Leu Lys Glu Glu Leu Gln Glu Arg Ser Glu Gln Leu Arg Asn Gly 85 90 85 Gln Tyr Gln Ala Ser Asp Ala Ala Gly Leu Gly Leu Asp Arg Ser Pro 100 105 110 Pro Glu Lys Thr Gln Ala Asp Leu Leu Ala Phe Leu His Ser Gln Val 115 120 125 Asp Lys Ala Glu Val Asn Ala Gly Val Lys Leu Ala Thr Glu Tyr Ala 130 138 140 Ala Val Pro Phe Asp Ser Phe Thr Leu Gln Lys Val Tyr Gln Leu Glu 145 150 155 160 Thr Gly Leu Thr Arg His Pro Glu Glu Lys Pro Val Arg Lys Asp Lys 165 170 175 Arg Asp Glu Leu Val Glu Ala Ile Glu Ser Ala Leu Glu Thr Leu Asn 843 ] J JE

180 185 190 Asn Pro Ala Glu Asn Ser Pro Asn His Arg Pro Tyr Thr Ala Ser Asp 185 200 205 Phe Ile Glu Gly Ile Tyr Arg Thr Glu Arg Asp Lys Gly Thr Leu Tyr 210 215 220 Glu Leu Thr Phe Lys Gly Asp His Lys His Glu Phe Lys Arg Leu Ile 225 230 235 240 Leu Phe Arg Pro Phe Gly Pro Ile Met Lys Val Lys Asn Glu Lys Leu 245 250 255 Asn Met Ala Asn Thr Leu Ile Asn Val Ile Val Pro Leu Ala Lys Arg 260 265 270 Val Asp Lys Phe Arg Gln Phe Met Gln Asn Phe Arg Glu Met Cys Ile 275 280 285 Glu Gln Asp Gly Arg Val His Leu Thr Val Val Tyr Phe Gly Lys Glu 290 295 300 Glu Ile Asn Glu Val Lys Gly Ile Leu Glu Asn Thr Ser Lys Ala Ala 305 310 315 320 Asn Phe Arg Asn Phe Thr Phe Ile Gln Leu Asn Gly Glu Phe Ser Arg 325 330 335 Gly Lys Gly Leu Asp Val Gly Ala Arg Phe Trp Lys Gly Ser Asn Val 340 345 350 Leu Leu Phe Phe Cys Asp Val Asp Ile Tyr Phe Thr Ser Glu Phe Leu 358 360 365 Asn Thr Cys Arg Leu Asn Thr Gln Pro Gly Lys Lys Val Phe Tyr Pro 370 375 380 Val Leu Phe Ser Gln Tyr Asn Pro Gly Ile Ile Tyr Gly His His Asp 385 390 395 400 Ala Val Pro Pro Leu Glu Gln Gln Leu Val Ile Lys Lys Glu Thr Gly 405 410 415 Phe Trp Arg Asp Phe Gly Phe Gly Met Thr Cys Gln Tyr Arg Ser Asp 420 425 430

Phe Ile Asn Ile Gly Gly Phe Asp Leu Asp Ile Lys Gly Trp Gly Gly

435 440 445 Glu Asp val His Leu Tyr Arg Lys Tyr Leu His Ser Asn Leu Ile Val

450 455 460 Val Arg Thr Pro Val Arg Gly Leu Phe His Leu Trp His Glu Lys Arg 465 470 475 480 Cys Met Asp Glu Leu Thr Pro Glu Gln Tyr Lys Met Cys Met Gln Ser 485 490 495 Lys Ala Met Asn Glu Ala Ser His Gly Gln Leu Gly Met Leu Val Phe 500 505 510

Arg His Glu Ile Glu Ala His Leu Arg Lys Gln Lys Gln Lys Thr Ser

515 520 525 Ser Lys Lys Thr

530 <210> 2496 <211> 125 <212> PRT . <213> Homo sapiens <400> 2496 Met Lys Lys Ser Gly Val Leu Phe Leu Leu Gly Ile Ile Leu Leu Val 1 5 10 15 Leu Ile Gly Val Gln Gly Thr Pro Val Val Arg Lys Gly Arg Cys Ser

Cys Ile Ser Thr Asn Gln Gly Thr Ile His Leu Gln Ser Leu Lys Asp

40 45 Leu Lys Gln Phe Ala Pro Ser Pro Ser Cys Glu Lys Ile Glu Ile Ile

50 55 60 Ala Thr Leu Lys Asn Gly Val Gln Thr Cys Leu Asn Pro Asp Ser Ala 65 70 75 80 , Asp Val Lys Glu Leu Ile Lys Lys Trp Glu Lys Gln Val Ser Gln Lys . 85 90 95

PCT/US2003/012946

Lys Lys Gln Lys Asn Gly Lys Lys His Gln Lys Lys Lys Val Leu Lys 100 105 110 Val Arg Lys Ser Gln Arg Ser Arg Gln Lys Lys Thr Thr 115 120 125 <210> 2497 <211> 98 <212> PRT <213> Homo sapiens <400> 2497 Met Asn Gln Thr Ala Ile Leu Ile Cys Cys Leu Ile Phe Leu Thr Leu 1 5 10 15 Ser Gly Ile Gln Gly Val Pro Leu Ser Arg Thr Val Arg Cys Thr Cys

Ile Ser Ile Ser Asn Gln Pro Val Asn Pro Arg Ser Leu Glu Lys Leu 40 45 Glu Ile Ile Pro Ala Ser Gln Phe Cys Pro Arg Val Glu Ile Ile Ala 50 55 60 Thr Met Lys Lys Lys Gly Glu Lys Arg Cys Leu Asn Pro Glu Ser Lys 65 70 75 80 Ala Ile Lys Asn Leu Leu Lys Ala Val Ser Lys Glu Met Ser Lys Arg 85 90 95 Ser Pro <210> 2498 <211> 155 <212> PRT <213> Homo sapiens <400> 2498 Met Thr Pro Gly Lys Thr Ser Leu Val Ser Leu Leu Leu Leu Leu Ser 1 S 10 15 Leu Glu Ala Ile Val Lys Ala Gly Ile Thr Ile Pro Arg Asn Pro Gly 20 25 30 Cys Pro Asn Ser Glu Asp Lys Asn Phe Pro Arg Thr val Met Val Asn 35 40 45

Leu Asn Ile His Asn Arg Asn Thr Asn Thr Asn Pro Lys Arg Ser Ser 50 55 60 Asp Tyr Tyr Asn Arg Ser Thr Ser Pro Trp Asn Leu His Arg Asn Glu €5 70 75 80 Asp Pro Glu Arg Tyr Pro Ser Val Ile Trp Glu Ala Lys Cys Arg His ’ 85 90 95 Leu Gly Cys Ile Asn Ala Asp Gly Asn Val Asp Tyr His Met Asn Ser 100 105 110 val Pro Ile Gln Gln Glu Ile Leu Val Leu Arg Arg Glu Pro Pro His 115 120 125 Cys Pro Asn Ser Phe Arg Leu Glu Lys Ile Leu Val Ser Val Gly Cys 130 135 140 Thr Cys Val Thr Pro Ile val His His Val Ala 145 150 155 <210> 2499 <211l> 162 <212> PRT <213> Homo sapiens <400> 2499 Met Arg Ile Ser Lys Pro His Leu Arg Ser Ile Ser Ile Gln Cys Tyr 1 5 10 15 Leu Cys Leu Leu Leu Asn Ser His Phe Leu Thr Glu Ala Gly Ile His

Val Phe Ile Leu Gly Cys Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala 40 45 Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 50 55 60 Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 65 70 75 80 Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 85 90 95 val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu

100 105 110 Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn val 115 120 125 : Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 130 135 140

Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 145 150 155 160 Thr Ser

<210> 2500

<211l> 178

<212> PRT

<213> Homo sapiens

<400> 2500

Met His Ser Ser Ala Leu Leu Cys Cys Leu Val Leu Leu Thr Gly Val 1 5 10 15

Arg Ala Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His

Phe Pro Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe 40 45 Ser Arg Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu 50 55 60 Leu Leu Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys 65 70 75 80 Gln Ala Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro 85 90 95 Gln Ala Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu 100 105 110 Gly Glu Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg 115 120 125 Phe Leu Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn 130 135 140

Ala Phe Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu 145 150 155 160 Phe Asp Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile 165 170 175 Arg Asn <210> 2501 <211l> 166 <212> PRT <213> Homo sapiens <400> 2501 Met Lys Tyr Thr Ser Tyr Ile Leu Ala Phe Gln Leu Cys Ile Val Leu 1 5 10 15 Gly Ser Leu Gly Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu ' Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn 40 45 Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp 50 55 60 Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe 65 70 75 80 Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile 85 90 95 Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg 100 105 110 Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val 115 120 125 Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser . i 130 135 140 Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Gln 145 150 155 160 Gly Arg Arg Ala Ser Gln

<210> 2502 <21l> 266 <212> PRT <213> Homo sapiens <400> 2502 Met Val Cys Leu Lys Leu Pro Gly Gly Ser Cys Met Thr Ala Leu Thr 1 5 10 15 Val Thr Leu Met Val Leu Ser Ser Pro Leu Ala Leu Ala Gly Asp Thr

Arg Pro Arg Phe Leu Trp Gln Leu Lys Phe Glu Cys His Phe Phe Asn 40 45 Gly Thr Glu Arg Val Arg Leu Leu Glu Arg Cys Ile Tyr Asn Gln Glu 50 55 60 Glu Ser Val Arg Phe Asp Ser Asp Val Gly Glu Tyr Arg Ala Val Thr 65 70 75 80 Glu Leu Gly Arg Pro Asp Ala Glu Tyr Trp Asn Ser Gln Lys Asp Leu 85 90 95 Leu Glu Gln Arg Arg Ala Ala Val Asp Thr Tyr Cys Arg His Asn Tyr 100 105 110 Gly Val Gly Glu Ser Phe Thr Val Gln Arg Arg Val Glu Pro Lys Val 115 . 120 125 Thr Val Tyr Pro Ser Lys Thr Gln Pro Leu Gln His His Asn Leu Leu 130 135 140 Val Cys Ser Val Ser Gly Phe Tyr Pro Gly Ser Ile Glu Val Arg Trp 145 150 155 160 Phe Arg Asn Gly Gln Glu Glu Lys Ala Gly Val Val Ser Thr Gly Leu 165 170 175 Ile Gln Asn Gly Asp Trp Thr Phe Gln Thr Leu Val Met Leu Glu Thr 180 185 150 Val Pro Arg Ser Gly Glu Val Tyr Thr Cys Gln Val Glu His Pro Ser 195 200 205

Val Thr Ser Pro Leu Thr Val Glu Trp Arg Ala Arg Ser Glu Ser Ala 210 215 220 Gln Ser Lys Met Leu Ser Gly Val Gly Gly Phe Val Leu Gly Leu Leu 225 230 235 240 Phe Leu Gly Ala Gly Leu Phe Ile Tyr Phe Arg Asn Gln Lys Gly His 245 250 255 Ser Gly Leu Gln Pro Thr Gly Phe Leu Ser 260 265 <210> 2503 <211> 210 <212> PRT <213> Homo sapiens <400> 2503 Met Arg Pro Arg Leu Trp Leu Leu Leu Ala Ala Gln Leu Thr Val Leu 1 5 10 15 His Gly Asn Ser Val Leu Gln Gln Thr Pro Ala Tyr Ile Lys Val Gln

Thr Asn Lys Met Val Met Leu Ser Cys Glu Ala Lys Ile Ser Leu Ser 40 45 Asn Met Arg Ile Tyr Trp Leu Arg Gln Arg Gln Ala Pro Ser Sex Asp 50 55 60 Ser His His Glu Phe Leu Ala Leu Trp Asp Ser Ala Lys Gly Thr Ile 65 70 75 80 His Gly Glu Glu Val Glu Gln Glu Lys Ile Ala Val Phe Arg Asp Ala 85 90 95 Ser Arg Phe Ile Leu Asn Leu Thr Ser Val Lys Pro Glu Asp Ser Gly 100 105 110 Ile Tyr Phe Cys Met Ile Val Gly Ser Pro Glu Leu Thr Phe Gly Lys 11s 120 125 Gly Thr Gln Leu Ser Val Val Asp Phe Leu Pro Thr Thr Ala Gln Pro 130 135 140 Thr Lys Lys Ser Thr Leu Lys Lys Arg Val Cys Arg Leu Pro Arg Pro

145 150 155 160 Glu Thr Gln Lys Gly Pro Leu Cys Ser Pro Ile Thr Leu Gly Leu Leu 165 170 175 val Ala Gly val Leu Val Leu Leu Val Ser Leu Gly Val Ala Ile His 180 185 190 Leu Cys Cys Arg Arg Arg Arg Ala Arg Leu Arg Phe Met Lys Gln Phe 195 200 205 Tyr Lys 210 <210> 2504 <211> 458 <212> PRT <213> Homo sapiens <400> 2504 Met Asn Arg Gly Val Pro Phe Arg His Leu Leu Leu Val Leu Gln Leu 1 5 10 15 Ala Leu Leu Pro Ala Ala Thr Gln Gly Lys Lys Val Val Leu Gly Lys

Lys Gly Asp Thr Val Glu Leu Thr Cys Thr Ala Ser Gln Lys Lys Ser 40 45 Ile Gln Phe His Trp Lys Asn Ser Asn Gln Ile Lys Ile Leu Gly Asn 50 55 60 Gln Gly Ser Phe Leu Thr Lys Gly Pro Ser Lys Leu Asn Asp Arg Ala 65 70 75 80 Asp Ser Arg Arg Ser Leu Trp Asp Gln Gly Asn Phe Pro Leu Ile Ile 85 90 95 \ Lys Asn Leu Lys Ile Glu Asp Ser Asp Thr Tyr Ile Cys Glu Val Glu 100 105 110 Asp Gln Lys Glu Glu Val Gln Leu Leu Val Phe Gly Leu Thr Ala Asn 115 120 125 Ser Asp Thr His Leu Leu Gln Gly Gln Ser Leu Thr Leu Thr Leu Glu 130 135 140

Ser Pro Pro Gly Ser Ser Pro Ser Val Gln Cys Arg Ser Pro Arg Gly 145 150 155 160 Lys Asn Ile Gln Gly Gly Lys Thr Leu Ser Val Ser Gln Leu Glu Leu

165 170 175 Gln Asp Ser Gly Thr Trp Thr Cys Thr Val Leu Gln Asn Gln Lys Lys 180 185 190 Val Glu Phe Lys Ile Asp Ile Val Val Leu Ala Phe Gln Lys Ala Ser 185 200 205 Ser Ile val Tyr Lys Lys Glu Gly Glu Gln Val Glu Phe Ser Phe Pro

210 215 220 Leu Ala Phe Thr Val Glu Lys Leu Thr Gly Ser Gly Glu Leu Trp Trp 225 230 235 240 Gln Ala Glu Arg Ala Ser Ser Ser Lys Ser Trp Ile Thr Phe Asp Leu

245 250 255 Lys Asn Lys Glu Val Ser val Lys Arg Val Thr Gln Asp Pro Lys Leu 260 265 270 Gln Met Gly Lys Lys Leu Pro Leu His Leu Thr Leu Pro Gln Ala Leu 275 280 285 Pro Gln Tyr Ala Gly Ser Gly Asn Leu Thr Leu Ala Leu Glu Ala Lys 290 285 300 Thr Gly Lys Leu His Gln Glu Val Asn Leu Val Val Met Arg Ala Thr 305 310 315 320 Gln Leu Gln Lys Asn Leu Thr Cys Glu Val Trp Gly Pro Thr Ser Pro 325 330 335 Lys Leu Met Leu Ser Leu Lys Leu Glu Asn Lys Glu Ala Lys Val Ser 340 345 350 Lys Arg Glu Lys Ala Val Trp Val Leu Asn Pro Glu Ala Gly Met Trp 355 360 365 Gln Cys Leu Leu Ser Asp Ser Gly Gln Val Leu Leu Glu Ser Asn Ile 370 375 380

Lys Val Leu Pro Thr Trp Ser Thr Pro Val Gln Pro Met Ala Leu Ile 385 390 395 400 Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile 405 410 415 Phe Phe Cys Val Arg Cys Arg His Arg Arg Arg Gln Ala Glu Arg Met 420 425 430 Ser Gln Ile Lys Arg Leu Leu Ser Glu Lys Lys Thr Cys Gln Cys Pro 435 440 445 His Arg Phe Gln Lys Thr Cys Ser Pro Ile 450 455 <210> 2505 <211> 368 <212> PRT <213> Homo sapiens <400> 2508S Met Val Leu Glu Val Ser Asp His Gln Val Leu Asn Asp Ala Glu Val 1 5 10 15 Ala Ala Leu Leu Glu Asn Phe Ser Ser Ser Tyr Asp Tyr Gly Glu Asn

Glu Ser Asp Ser Cys Cys Thr Ser Pro Pro Cys Pro Gln Asp Phe Ser 40 45 Leu Asn Phe Asp Arg Ala Phe Leu Pro Ala Leu Tyr Ser Leu Leu Phe 50 55 60 Leu Leu Gly Leu Leu Gly Asn Gly Ala Val Ala Ala Val Leu Leu Ser 65 70 75 80 Arg Arg Thr Ala Leu Ser Ser Thr Asp Thr Phe Leu Leu His Leu Ala 85 90 95 Val Ala Asp Thr Leu Leu Val Leu Thr Leu Pro Leu Trp Ala Val Asp 100 105 110 Ala Ala Val Gln Trp Val Phe Gly Ser Gly Leu Cys Lys val Ala Gly 115 120 125 Ala Leu Phe Asn Ile Asn Phe Tyr Ala Gly Ala Leu Leu Leu Ala Cys 130 135 140

PCT/US2003/012946

Ile Ser phe Asp Arg Tyr Leu Asn Ile Val His Ala Thr Gln Leu Tyr 145 150 155 160 Arg Arg Gly Pro Pro Ala Arg Val Thr Leu Thr Cys Leu Ala Val Trp 165 170 175 Gly Leu Cys Leu Leu Phe Ala Leu Pro Asp Phe Ile Phe Leu Ser Ala 180 185 1390 His His Asp Glu Arg Leu Asn Ala Thr His Cys Gln Tyr Asn Phe Pro 195 200 205 Gln Val Gly Arg Thr Ala Leu Arg Val Leu Gln Leu Val Ala Gly Phe 210 215 220 Leu Leu Pro Leu Leu Val Met Ala Tyr Cys Tyr Ala His Ile Leu Ala 225 230 235 240 Val Leu Leu Val Ser Arg Gly Gln Arg Arg Leu Arg Ala Met Arg Leu 245 250 255 Val Val val val Val Val Ala Phe Ala Leu Cys Trp Thr Pro Tyr His 260 265 270 Leu Val val Leu Val Asp Ile Leu Met Asp Leu Gly Ala Leu Ala Arg 275 280 285 Asn Cys Gly Arg Glu Ser Arg Val Asp Val Ala Lys Ser val Thr Ser 290 2895 300 Gly Leu Gly Tyr Met His Cys Cys Leu Asn Pro Leu Leu Tyr Ala Phe 305 310 315 320 Val Gly Val Lys Phe Arg Glu Arg Met Trp Met Leu Leu Leu Arg Leu 325 330 335 Gly Cys Pro Asn Gln Arg Gly Leu Gln Arg Gln Pro Ser Ser Ser Arg 340 345 350 Arg Asp Ser Ser Trp Ser Glu Thr Ser Glu Ala Ser Tyr Ser Gly Leu 355 360 365 <210> 2506 <211> 107 <212> PRT :

PCT/US2003/012946

<213> Homo sapiens <400> 2506 . Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu 1 S 10 15 Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg ala

Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr 40 45 Leu Gln Gly Ile His Pro Lys Asn Ile Gln Ser Val Asn Val Lys Ser 50 55 60 Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn 65 70 75 80 Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro Ile Val Lys Lys Ile 85 90 95 Ile Glu Lys Met Leu Asn Ser Asp Lys Ser Asn 100 105 <210> 2507 <211> 558 <212> PRT <213> Homo sapiens <400> 2507 Met Ala Ala Leu Thr Arg Asp Pro Gln Phe Gln Lys Leu Gln Gln Trp 1 5 10 15 Tyr Arg Glu His Arg Ser Glu Leu Asn Leu Arg Arg Leu Phe Asp Ala 20 25 30 Asn Lys Asp Arg Phe Asn His Phe Ser Leu Thr Leu Asn Thr Asn His 35 40 45 Gly His Ile Leu Val Asp Tyr Ser Lys Asn Leu val Thr Glu Asp Val S50 55 60 Met Arg Met Leu Val Asp Leu Ala Lys Ser Arg Gly val Glu Ala Ala 65 70 75 80 Arg Glu Arg Met Phe Asn Gly Glu Lys Ile Asn Tyr Thr Glu Gly Arg 85 _ 80 85

PCT/US2003/012946

Ala Val Leu His Val Ala Leu Arg Asn Arg Ser Asn Thr Pro Ile Leu 100 105 110 Val Asp Gly Lys Asp Val Met Pro Glu val Asn Lys Val Leu Asp Lys 115 120 125 Met Lys Ser Phe Cys Gln Arg Val Arg Ser Gly Asp Trp Lys Gly Tyr 130 135 140 Thr Gly Lys Thr Ile Thr Asp Val Ile Asn Ile Gly Ile Gly Gly ser 145 150 155 160 Asp Leu Gly Pro Leu Met Val Thr Glu Ala Leu Lys Pro Tyr Ser Ser 165 170 175 Gly Gly Pro Arg val Trp Tyr Val Ser Asn Ile Asp Gly Thr His Ile 180 185 190 Ala Lys Thr Leu Ala Gln Leu Asn Pro Glu Ser Ser Leu Phe Ile Ile 185 200 205 Ala Ser Lys Thr Phe Thr Thr Gln Glu Thr Ile Thr Asn Ala Glu Thr 210 215 220 Ala Lys Glu Trp Phe Leu Gln Ala Ala Lys Asp Pro Ser Ala Val ala 225 230 235 240 Lys His Phe Val Ala Leu Ser Thr Asn Thr Thr Lys Val Lys Glu Phe 245 250 255 Gly Ile Asp Pro Gln Asn Met Phe Glu Phe Trp Asp Trp Val Gly Gly 260 265 270 Arg Tyr Ser Leu Trp Ser Ala Ile Gly Leu Ser Ile Ala Leu His Val 275 280 285 Gly Phe Asp Asn Phe Glu Gln Leu Leu Ser Gly Ala His Trp Met Asp 290 295 300 Gln His Phe Arg Thr Thr Pro Leu Glu Lys Asn Ala Pro val Leu Leu 305 310 315 320 Ala Leu Leu Gly Ile Trp Tyr Ile Asn Cys Phe Gly Cys Glu Thr His 325 330 335

Ala Met Leu Pro Tyr Asp Gln Tyr Leu His Arg Phe Ala Ala Tyr Phe 340 345 350 Gln Gln Gly Asp Met Glu Ser Asn Gly Lys Tyr Ile Thr Lys Ser Gly 355 360 365 Thr Arg Val Asp His Gln Thr Gly Pro Ile Val Trp Gly Glu Pro Gly 370 375 380 Thr Asn Gly Gln His Ala Phe Tyr Gln Leu Ile His Gln Gly Thr Lys 385 3590 395 400 Met Ile Pro Cys Asp Phe Leu Ile Pro Val Gln Thr Gln His Pro Ile 405 410 415 Arg Lys Gly Leu His His Lys Ile Leu Leu Ala Asn Phe Leu Ala Gln 420 425 430 Thr Glu Ala Leu Met Arg Gly Lys Ser Thr Glu Glu Ala Arg Lys Glu 435 440 445 Leu Gln Ala Ala Gly Lys Ser Pro Glu Asp Leu Glu Arg Leu Leu Pro 450 455 460 His Lys Val Phe Glu Gly Asn Arg Pro Thr Asn Ser Ile Val Phe Thr 465 470 475 480 Lys Leu Thr Pro Phe Met Leu Gly Ala Leu Val Ala Met Tyr Glu His 485 490 495 Lys Ile Phe Val Gln Gly Ile Ile Trp Asp Ile Asn Ser Phe Asp Gln 500 505 510 Trp Gly Val Glu Leu Gly Lys Gln Leu Ala Lys Lys Ile Glu Pro Glu 515 520 525 Leu Asp Gly Sex Ala Gln Val Thr Ser His Asp Ala Ser Thr Asn Gly 530 535 540 Leu Ile Asn Phe Ile Lys Gln Gln Arg Glu Ala Arg Val Gln 545 550 555 <210> 2508 <211> 323 <212> PRT <213> Homo sapiens

PCT/US2003/012946

<400> 2508 Met Trp Pro Leu Val Ala Ala Leu Leu Leu Gly Ser Ala Cys Cys Gly 1 5 10 15 Ser Ala Gln Leu Leu Phe Asn Lys Thr Lys Ser Val Glu Phe Thr Phe

Cys Asn Asp Thr Val val Ile Pro Cys Phe Val Thr Asn Met Glu Ala 40 45 Gln Asn Thr Thr Glu val Tyr Val Lys Trp Lys Phe Lys Gly Arg Asp 50 55 60 Ile Tyr Thr Phe Asp Gly Ala Leu Asn Lys Ser Thr Val Pro Thr Asp 65 70 75 80 Phe Ser Ser Ala Lys Ile Glu Val Ser Gln Leu Leu Lys Gly Asp Ala 85 S0 95 Ser Leu Lys Met Asp Lys Ser Asp Ala Val Ser His Thr Gly Asn Tyr 100 105 110 Thr Cys Glu Val Thr Glu Leu Thr Arg Glu Gly Glu Thr Ile Ile Glu 115 120 125 Leu Lys Tyr Arg Val Val Ser Trp Phe Ser Pro Asn Glu Asn Ile Leu 130 135 140 Ile val Ile Phe Pro Ile Phe Ala Ile Leu Leu Phe Trp Gly Gln Phe 145 150 155 160 Gly Ile Lys Thr Leu Lys Tyr Arg Ser Gly Gly Met Asp Glu Lys Thr 165 170 175 Ile Ala Leu Leu Val Ala Gly Leu Val Ile Thr Val Ile Val Ile val 180 185 1s0 Gly Ala Ile Leu Phe Val Pro Gly Glu Tyr Ser Leu Lys Asn Ala Thr 195 200 205 Gly Leu Gly Leu Ile Val Thr Ser Thr Gly Ile Leu Ile Leu Leu His 210 215 220 Tyr Tyr Val Phe Ser Thr Ala Ile Gly Leu Thr Ser Phe Val Ile Ala 225 230 235 240

Ile Leu Val Ile Gln Val Ile Ala Tyr Ile Leu Ala Val Val Gly Leu 245 250 255 Ser Leu Cys Ile Ala Ala Cys Ile Pro Met His Gly Pro Leu Leu Ile 260 265 270 Ser Gly Leu Ser Ile Leu Ala Leu Ala Gln Leu Leu Gly Leu Val Tyr 275 280 285 Met Lys Phe Val Ala Ser Asn Gln Lys Thr Ile Gln Pro Pro Arg Lys 290 295 300 Ala Val Glu Glu Pro Leu Asn Ala Phe Lys Glu Ser Lys Gly Met Met 305 310 315 320 Asn Asp Glu <210> 2509 «211l> 362 <212> PRT <213> Homo sapiens <400> 2509 Met Ala Pro Arg Ser Leu Leu Leu Leu Leu Ser Gly Ala Leu Ala Leu 1 5 10 15 Thr Asp Thr Trp Ala Gly Ser His Ser Leu Arg Tyr Phe Ser Thr Ala Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Tyr Ile Ala Val Glu Tyr 40 ) 45 Val Asp Asp Thr Gln Phe Leu Arg Phe Asp Ser Asp Ala Ala Ile Pro

. 50 55 60 Arg Met Glu Pro Arg Glu Pro Trp Val Glu Gln Glu Gly Pro Gln Tyr 65 70 75 BO Trp Glu Trp Thr Thr Gly Tyr Ala Lys Ala Asn Ala Gln Thr Asp Arg 85 S0 95 Val Ala Leu Arg Asn Leu Leu Arg Arg Tyr Asn Gln Ser Glu Ala Gly 100 105 110 ) 860 B _

PCT/US2003/012946

Ser His Thr Leu Gln Gly Met Asn Gly Cys Asp Met Gly Pro Asp Gly 115 120 125 Arg Leu Leu Arg Gly Tyr His Gln His Ala Tyr Asp Gly Lys Asp Tyr 130 135 140 Ile Ser Leu Asn Glu Asp Leu Arg Ser Trp Thr Ala Ala Asp Thr Val 145 150 155 160 Ala Gln Ile Thr Gln Arg Phe Tyr Glu Ala Glu Glu Tyr Ala Glu Glu 165 170 175 Phe Arg Thr Tyr Leu Glu Gly Glu Cys Leu Glu Leu Leu Arg Arg Tyr 180 185 190 Leu Glu Asn Gly Lys Glu Thr Leu Gln Arg Ala Asp Pro Pro Lys Ala 195 200 205 His val Ala His His Pro Ile Ser Asp His Glu Ala Thr Leu Arg Cys 210 215 220 Trp Ala Leu Gly Phe Tyr Pro Ala Glu Ile Thr Leu Thr Trp Gln Arg 225 230 235 240 Asp Gly Glu Glu Gln Thr Gln Asp Thr Glu Leu Val Glu Thr Arg Pro 245 250 255 Ala Gly Asp Gly Thr Phe Gln Lys Trp Ala Ala Val Val Val Pro Ser 260 265 270 Gly Glu Glu Gln Arg Tyr Thr Cys His Val Gln His Glu Gly Leu Pro 27s 280 285 Gln Pro Leu Ile Leu Arg Trp Glu Gln Ser Pro Gln Pro Thr Ile Pro 290 295 300 Ile Val Gly Ile val Ala Gly Leu Val val Leu Gly Ala Val val Thr 305 310 315 320 Gly Ala Val Val Ala Ala val Met Trp Arg Lys Lys Ser Ser Asp Arg 325 330 335 Asn Arg Gly Ser Tyr Ser Gln Ala Ala Val Thr Asp Ser Ala Gln Gly 340 345 350 Ser Gly Val Ser Leu Thr Ala Asn Lys Val

355 360 <210> 2510 <211l> 604 <212> PRT <213> Homo sapiens <400> 2510 Met Leu Ala Arg Ala Leu Leu Leu Cys Ala Val Leu Ala Leu Ser His 1 5 10 15 Thr Ala Asn Pro Cys Cys Ser His Pro Cys Gln Asn Arg Gly Val Cys Met Ser Val Gly Phe Asp Gln Tyr Lys Cys Asp Cys Thr Arg Thr Gly 40 45 Phe Tyr Gly Glu Asn Cys Ser Thr Pro Glu Phe Leu Thr Arg Ile Lys 50 55 60 Leu Phe Leu Lys Pro Thr Pro Asn Thr Val His Tyr Ile Leu Thr His 65S 70 75 80 Phe Lys Gly Phe Trp Asn Val Val Asn Asn Ile Pro Phe Leu Arg Asn 85 90 95 Ala Ile Met Ser Tyr Val Leu Thr Ser Arg Ser His Leu Ile Asp Ser 100 105 110 Pro Pro Thr Tyr Asn Ala Asp Tyr Gly Tyr Lys Ser Trp Glu Ala Phe 115 120 125 Ser Asn Leu Ser Tyr Tyr Thr Arg Ala Leu Pro Pro Val Pro Asp Asp 130 135 140 Cys Pro Thr Pro Leu Gly Val Lys Gly Lys Lys Gln Leu Pro Asp Ser 145 150 155 160 Asn Glu Ile Val Glu Lys Leu Leu Leu Arg Arg Lys Phe Ile Pro Asp 165 170 175 Pro Gln Gly Ser Asn Met Met Phe Ala Phe Phe Ala Gln His Phe Thr 180 185 150 His Gln Phe Phe Lys Thr Asp His Lys Arg Gly Pro Ala Phe Thr Asn 195 200 205 862 i.

T/US2003/012946

Gly Leu Gly His Gly val Asp Leu Asn His Ile Tyr Gly Glu Thr Leu 210 215 220 Ala Arg Gln Arg Lys Leu Arg Leu Phe Lys Asp Gly Lys Met Lys Tyr 225 230 235 240 Gln Ile Ile Asp Gly Glu Met Tyr Pro Pro Thr Val Lys Asp Thr Gln 245 . 250 255 Ala Glu Met Ile Tyr Pro Pro Gln Val Pro Glu His Leu Arg Phe Ala 260 265 270 val Gly Gln Glu Val phe Gly Leu Val Pro Gly Leu Met Met Tyr Ala 275 280 285 Thr Ile Trp Leu Arg Glu His Asn Arg Val Cys Asp Val Leu Lys Gln 2380 295 300 Glu His Pro Glu Trp Gly Asp Glu Gln Leu Phe Gln Thr Ser Arg Leu 305 310 315 320 Ile Leu Ile Gly Glu Thr Ile Lys Ile val Ile Glu Asp Tyr Val Gln 325 330 335 His Leu Ser Gly Tyr His Phe Lys Leu Lys Phe Asp Pro Glu Leu Leu 340 345 350 Phe Asn Lys Gln Phe Gln Tyr Gln Asn Arg Ile Ala Ala Glu Phe Asn 355 360 365 Thr Leu Tyr His Trp His Pro Leu Leu Pro Asp Thr Phe Gln Ile His 370 375 380 Asp Gln Lys Tyr Asn Tyr Gln Gln Phe Ile Tyr Asn Asn Ser Ile Leu 385 380 395 400 Leu Glu His Gly Ile Thr Gln Phe Val Glu Ser Phe Thr Arg Gln Ile 405 410 415 Ala Gly Arg Val Ala Gly Gly Arg Asn Val Pro Pro Ala Val Gln Lys 420 425 430 Val Ser Gln Ala Ser Ile Asp Gln Ser Arg Gln Met Lys Tyr Gln Ser 435 440 445 phe Asn Glu Tyr Arg Lys Arg Phe Met Leu Lys Pro Tyr Glu Ser Phe 450 455 460 Glu Glu Leu Thr Gly Glu Lys Glu Met Ser Ala Glu Leu Glu Ala Leu 465 470 475 480 Tyr Gly Asp Ile Asp Ala Val Glu Leu Tyr Pro Ala Leu Leu Val Glu 485 490 495 Lys Pro Arg Pro Asp Ala Ile Phe Gly Glu Thr Met Val Glu Val Gly 500 505 510 Ala Pro Phe Ser Leu Lys Gly Leu Met Gly Asn Val Ile Cys Ser Pro 515 520 525 Ala Tyr Trp Lys Pro Ser Thr Phe Gly Gly Glu Val Gly Phe Gln Ile 530 535 540 Ile Asn Thr Ala Ser Ile Gln Ser Leu Ile Cys Asn Asn Val Lys Gly 545 550 555 560 Cys Pro Phe Thr Ser Phe Ser Val Pro Asp Pro Glu Leu Ile Lys Thr 565 570 575 Val Thr Ile Asn Ala Ser Ser Ser Arg Ser Gly Leu Asp Asp Ile Asn : 580 585 590 Pro Thr Val Leu Leu Lys Glu Arg Ser Thr Glu Leu 595 600 <210> 2511 <211l> 343 <212> PRT <213> Homo sapiens <400> 2511 Met Pro Leu Cys Ser Leu Leu Thr Cys Leu Gly Leu Asn Val Leu Phe 1 5 10 15 Leu Thr Leu Asn Glu Gly Ala Trp Tyr Ser Val Gly Ala Leu Met Ile

Ser Val Pro Ala Leu Leu Gly Tyr Leu Gln Glu Val Cys Arg Ala Arg 40 45 Leu Pro Asp Ser Glu Leu Met Arg Arg Lys Tyr His Ser Val Arg Gln 50 55 60 864 ke

Glu Asp Leu Gln Arg Val Arg Leu Ser Arg Pro Glu Ala Val Ala Glu 65 70 75 80 Val Lys Ser Phe Leu lle Gln Leu Glu Ala Phe Leu Ser Arg Leu Cys 85 S0 95 Cys Thr Cys Glu Ala Ala Tyr Arg Val Leu His Trp Glu Asn Pro Val 100 105 110 val Ser Ser Gln Phe Tyr Gly Ala Leu Leu Gly Thr Val Cys Met Leu 115 120 125 Tyr Leu Leu Pro Leu Cys Trp Val Leu Thr Leu Leu Asn Ser Thr Leu 130 135 140 Phe Leu Gly Asn Val Glu Phe Phe Arg Val Val Ser Glu Tyr Arg Ala 145 150 155 160 Ser Leu Gln Gln Arg Met Asn Pro Lys Gln Glu Glu His Ala Phe Glu 165 170 175 Ser Pro Pro Pro Pro Asp Val Gly Gly Lys Asp Gly Leu Met Asp Ser 180 185 190 ~ Thr Pro Ala Leu Thr Pro Thr Glu Asp Leu Thr Pro Gly Ser Val Glu 195 200 205 Glu Ala Glu Glu Ala Glu Pro Asp Glu Glu Phe Lys Asp Ala Ile Glu 210 215 220 ’ Glu Thr His Leu Val Val Leu Glu Asp Asp Glu Gly Ala Pro Cys Pro 225 230 235 240 Ala Glu Asp Glu Leu Ala Leu Gln Asp Asn Gly Phe Leu Ser Lys Asn 245 250 255 Glu val Leu Arg Ser Lys Val Ser Arg Leu Thr Glu Arg Leu Arg Lys 260 265 : 270 Arg Tyr Pro Thr Asn Asn Phe Gly Asn Cys Thr Gly Cys Ser Ala Thr 275 280 285 Phe Ser Val Leu Lys Lys Arg Arg Ser Cys Ser Asn Cys Gly Asn Ser 290 295 300

Phe Cys Ser Arg Cys Cys Ser Phe Lys Val Pro Lys Ser Ser Met Gly 305 310 31s 320 Ala Thr Ala Pro Glu Ala Gln Arg Glu Thr val Phe Val Cys Ala Ser 325 330 335 Cys Asn Gln Thr Leu Ser Lys 340 <210> 2512 <211> 789 <212> PRT <213> Homo sapiens <400> 2512 Met Lys Met Asp Met Glu Asp Ala Asp Met Thr Leu Trp Thr Glu Ala 1 5 10 15 Glu Phe Glu Glu Lys Cys Thr Tyr Ile Val Asn Asp His Pro Trp Asp

Ser Gly Ala Asp Gly Gly Thr Ser Val Gln Ala Glu Ala Ser Leu Pro 40 45 Arg Asn Leu Leu Phe Lys Tyr Ala Thr Asn Ser Glu Glu Val Ile Gly 50 55 60 Val Met Ser Lys Glu Tyr lle Pro Lys Gly Thr Arg Phe Gly Pro Leu 65 70 75 80 Ile Gly Glu Ile Tyr Thr Asn Asp Thr Val Pro Lys Asn Ala Asn Arg 85 90 95 Lys Tyr Phe Trp Arg Ile Tyr Ser Arg Gly Glu Leu His His Phe Ile 100 105 110 Asp Gly Phe Asn Glu Glu Lys Ser Asn Trp Met Arg Tyr Val Asn Pro 115 120 125 Ala His Ser Pro Arg Glu Gln Asn Leu Ala Ala Cys Gln Asn Gly Met . . 130 135 140 Asn Ile Tyr Phe Tyr Thr Ile Lys Pro Ile Pro Ala Asn Gln Glu Leu 145 150 155 160 Leu Val Trp Tyr Cys Arg Asp Phe Ala Glu Arg Leu His Tyr Pro Tyr 866 E a Co I I

PCT/US2003/012946

165 170 175 Pro Gly Glu Leu Thr Met Met Asn Leu Thr Gln Thr Gln Ser Ser Leu 180 185 190 Lys Gln Pro Ser Thr Glu Lys Asn Glu Leu Cys Pro Lys Asn Val Pro 185 200 205 Lys Arg Glu Tyr Ser val Lys Glu Ile Leu Lys Leu Asp Ser Asn Pro 210 215 220 Ser Lys Gly Lys Asp Leu Tyr Arg Ser Asn Ile Ser Pro Leu Thr Ser 225 230 235 240 Glu Lys Asp Leu Asp Asp Phe Arg Arg Arg Gly Ser Pro Glu Met Pro 245 250 255 Phe Tyr Pro Arg Val Val Tyr Pro Ile Arg Ala Pro Leu Pro Glu Asp 260 265 270 Phe Leu Lys Ala Ser Leu Ala Tyr Gly Ile Glu Arg Pro Thr Tyr Ile 275 280 285 Thr Arg Ser Pro Ile Pro Ser Ser Thr Thr Pro Ser Pro Ser Ala Arg 290 295 300 Ser Ser Pro Asp Gln Ser Leu Lys Ser Ser Ser Pro His Ser Ser Pro 305 310 315 320 Gly Asn Thr Val Ser Pro val Gly Pro Gly Ser Glan Glu His Arg Asp 325 330 335 Ser Tyr Ala Tyr Leu Asn Ala Ser Tyr Gly Thr Glu Gly Leu Gly Ser 340 345 350 Tyr Pro Gly Tyr Ala Pro Leu Pro His Leu Pro Pro Ala Phe Ile Pro 355 360 365 Ser Tyr Asn Ala His Tyr Pro Lys Phe Leu Leu Pro Pro Tyr Gly Met 370 375 380 Asn Cys Asn Gly Leu Ser Ala Val Ser Ser Met Asn Gly Ile Asn Asn 385 390 395 400 Phe Gly Leu Phe Pro Arg Leu Cys Pro Val Tyr Ser Asn Leu Leu Gly 405 - 410 415

Gly Gly Ser Leu Pro His Pro Met Leu Asn Pro Thr Ser Leu Pro Ser 420 425 430 Ser Leu Pro Ser Asp Gly Ala Arg Arg Leu Leu Gln Pro Glu His Pro 435 440 445 Arg Glu val Leu Val Pro Ala Pro His Ser Ala Phe Ser Phe Thr Gly 450 455 460 Ala Ala Ala Ser Met Lys Asp Lys Ala Cys Ser Pro Thr Ser Gly Ser 465 470 475 480 Pro Thr Ala Gly Thr Ala Ala Thr Ala Glu His Val Val Gln Pro Lys 485 450 495 Ala Thr Ser Ala Ala Met Ala Ala Pro Ser Ser Asp Glu Ala Met Asn 500 505 510 Leu Ile Lys Asn Lys Arg Asn Met Thr Gly Tyr Lys Thr Leu Pro Tyr 515 520 525 Pro Leu Lys Lys Gln Asn Gly Lys Ile Lys Tyr Glu Cys Asn Val Cys 530 535 540 Ala Lys Thr Phe Gly Gln Leu Ser Asn Leu Lys Val His Leu Arg Val 545 550 555 560 His Ser Gly Glu Arg Pro Phe Lys Cys Gln Thr Cys Asn Lys Gly Phe 565 570 575 Thr Gln Leu Ala His Leu Gln Lys His Tyr Leu Val His Thr Gly Glu 580 585 $90 Lys Pro His Glu Cys Gln Val Cys His Lys Arg Phe Ser Ser Thr Ser 595 600 605 Asn Leu Lys Thr His Leu Arg Leu His Ser Gly Glu Lys Pro Tyr Gln 610 615 620 Cys Lys Val Cys Pro Ala Lys Phe Thr Gln Phe Val His Leu Lys Leu 625 630 635 640 His Lys Arg Leu His Thr Arg Glu Arg Pro His Lys Cys Ser Gln cys 645 650 655

PCT/US2003/012946

His Lys Asn Tyr Ile His Leu Cys Ser Leu Lys Val His Leu Lys Gly 660 665 670 Asn Cys Ala Ala Ala Pro Ala Pro Gly Leu Pro Leu Glu Asp Leu Thr 675 680 685 Arg Ile Asn Glu Glu Ile Glu Lys Phe Asp Ile Ser Asp Asn Ala Asp 690 695 700 Arg Leu Glu Asp Val Glu Asp Asp Ile Ser Val Ile Ser val val Glu 705 710 715 720 Lys Glu Ile Leu Ala Val Val Arg Lys Glu Lys Glu Glu Thr Gly Leu © 725 730 735 Lys Val Ser Leu Gln Arg Asn Met Gly Asn Gly Leu Leu Ser Ser Gly 740 745 750 Cys Ser Leu Tyr Glu Ser Ser Asp Leu Pro Leu Met Lys Leu Pro Pro 755 760 765 Ser Asn Pro Leu Pro Leu Val Pro Val Lys Val Lys Gln Glu Thr Val . 770 775 780 Glu Pro Met Asp Pro 785 <210> 2513 <211> 381 <212> PRT <213> Homo sapiens <400> 2513 Met Pro Phe Ser Asn Ser His Asn Ala Leu Lys Leu Arg Phe Pro Ala 1 5 10 15 Glu Asp Glu Phe Pro Asp Leu Ser Ala His Asn Asn His Met Ala Lys

Val Leu Thr Pro Glu Leu Tyr Ala Glu Leu Arg ala Lys Ser Thr Pro 40 45 Ser Gly Phe Thr Leu Asp Asp Val Ile Gln Thr Gly Val Asp Asn Pro 50 55 60 Gly His Pro Tyr Ile Met Thr val Gly Cys val Ala Gly Asp Glu Glu

65 70 75 : 80 Ser Tyr Glu Val Phe Lys Asp Leu Phe Asp Pro Ile Ile Glu Asp Arg 85 90 95 His Gly Gly Tyr Lys Pro Ser Asp Glu His Lys Thr Asp Leu Asn Pro 100 105 110 Asp Asn Leu Gln Gly Gly Asp Asp Leu Asp Pro Asn Tyr Val Leu Ser 115 120 125 Ser Arg Val Arg Thr Gly Arg Ser Ile Arg Gly Phe Cys Leu Pro Pro 130 135 140 - His Cys Ser Arg Gly Glu Arg Arg Ala Ile Glu Lys Leu Ala Val Glu 145 150 155 160 Ala Leu Ser Ser Leu Asp Gly Asp Leu Ala Gly Arg Tyr Tyr Ala Leu 165 170 175 Lys Ser Met Thr Glu Ala Glu Gln Gln Gln Leu Ile Asp Asp His Phe 180 185 190 Leu Phe Asp Lys Pro Val Ser Pro Leu Leu Leu Ala Ser Gly Met Ala 185 200 205 Arg Asp Trp Pro Asp Ala Arg Gly Ile Trp His Asn Asp Asn Lys Thr 210 215 220 Phe Leu Val Trp Val Asn Glu Glu Asp His Leu Arg Val Ile Ser Met 225 230 235 240 Gln Lys Gly Gly Asn Met Lys Glu Val Phe Thr Arg Phe Cys Thr Gly 245 250 255 Leu Thr Gln Ile Glu Thr Leu Phe Lys Ser Lys Asp Tyr Glu Phe Met 260 265 270 Trp Asn Pro His Leu Gly Tyr Ile Leu Thr Cys Pro Ser Asn Leu Gly 275 280 285 Thr Gly Leu Arg Ala Gly Val His Ile Lys Leu Pro Asn Leu Gly Lys 290 295 300 His Glu Lys Phe Ser Glu Val Leu Lys Arg Leu Arg Leu Gln Lys Arg 305 310 315 320

PCT/US2003/012946

Gly Thr Gly Gly val Asp Thr Ala Ala Val Gly Gly val Phe Asp Val 325 330 335 Ser Asn Ala Asp Arg Leu Gly Phe Ser Glu Val Glu Leu Val Gln Met 340 345 350 Val val Asp Gly val Lys Leu Leu Ile Glu Met Glu Gln Arg Leu Glu 355 360 365 Gln Gly Gln Ala Ile Asp Asp Leu Met Pro Ala Gln Lys 370 375 380 <210> 2514 <211> 541 <212> PRT <213> Homo sapiens <400> 2514 Met Thr Thr Pro ala Gly Ser Gly Ser Gly Phe Gly Ser val ser Trp 1 5 10 15 Trp Gly Leu Ser Pro Ala Leu Asp Leu Gln Ala Glu Ser Pro Pro val

Asp Pro Asp Ser Gln Ala Asp Thr Val His Ser Asn Pro Glu Leu Asp 40 45 Val Leu Leu Leu Gly Ser val asp Gly Arg His Leu Leu Arg Thr Leu 50 55 60 Ser Arg Ala Lys Phe Trp Pro Arg Arg Arg Phe Asn Phe Phe Val Leu 65 70 75 80 Glu Asn Asn Leu Glu Ala Val Ala Arg His Met Leu Ile Phe Ser Leu 85 90 95 Ala Leu Glu Glu Pro Glu Lys Met Gly Leu Gln Glu Arg Ser Glu Thr 100 105 110 Phe Leu Glu Val Trp Gly Asn Ala Leu Leu Arg Pro Pro val Ala ala 115 120 125 Phe Val Arg Ala Gln Ala Asp Leu Leu Ala His Leu Val Pro Glu Pro 130 135 140

Asp Arg Leu Glu Glu Gln Leu Pro Trp Leu Ser Leu Arg Ala Leu Lys 145 150 155 160 Phe Arg Glu Arg Asp Ala Leu Glu Ala Val Phe Arg Phe Trp Ala Gly

165 170 175 Gly Glu Lys Gly Pro Gln Ala Phe Pro Met Ser Arg Leu Trp Asp Ser 180 185 150 Arg Leu Arg His Tyr Leu Gly Ser Arg Tyr Asp Ala Arg Arg Gly Val 195 200 205 Ser Asp Trp Asp Leu Arg Met Lys Leu His Asp Arg Gly Ala Gln Val 210 215 220 Ile His Pro Gln Glu Phe Arg Arg Trp Arg Asp Thr Gly Val Ala Phe 225 230 235 240 Glu Leu Arg Asp Ser Ser Ala Tyr His Val Pro Asn Arg Thr Leu Ala 245 250 255 Ser Gly Arg Leu Leu Ser Tyr Arg Gly Glu Arg Val Ala Ala Arg Gly 260 265 270 Tyr Trp Gly Asp Ile Ala Thr Gly Pro Phe Val Ala Phe Gly Ile Glu 275 280 285 Ala Asp Asp Glu Ser Leu Leu Arg Thr Ser Asn Gly Gln Pro Val Lys 290 295 300 Thr Ala Gly Glu Ile Thr Gln His Asn Val Thr Glu Leu Leu Arg Asp 305 310 315 320 Val Ala Ala Trp Gly Arg Ala Arg Ala Thr Gly Gly Asp Leu Glu Glu 325 330 335 Gln Gln His Ala Glu Gly Ser Pro Glu Pro Gly Thr Pro Ala Ala Pro 340 345 350 Thr Pro Glu Ser Phe Thr Val His Phe Leu Pro Leu Asn Ser Ala Gln 355 360 365 Thr Leu His His Lys Ser Cys Tyr Asn Gly Arg Phe Gln Leu Leu Tyr 370 375 380 Val Ala Cys Gly Met Val His Leu Leu Ile Pro Glu Leu Gly Ala Cys 872 h

385 390 395 400 Val Ala Pro Gly Gly Asn Leu Ile val Glu Leu Ala Arg Tyr Leu Val 405 410 415 Asp Val Arg Gln Glu Gln Leu Gln Gly Phe Asn Thr Arg Val Arg Glu 420 425 430 Leu Ala Gln Ala Ala Gly Phe Ala Pro Gln Thr Gly Ala Arg Pro Ser 435 440 445 Glu Thr Phe Ala Arg Phe Cys Lys Ser Gln Glu Ser Ala Leu Gly Asn 450 455 460 Thr Val Pro Ala Val Glu Pro Gly Thr Pro Pro Leu Asp Ile Leu Ala 465 470 475 480 Gln Pro Leu Glu Ala Ser Asn Pro Ala Leu Glu Gly Leu Thr Gln Pro 485 490 4385 Leu Gln Gly Gly Thr Pro His Cys Glu Pro Cys Gln Leu Pro Ser Glu 500 505 510 Ser Pro Gly Ser Leu Ser Glu Val Leu Ala Gln Pro Gln Gly Ala Leu 515 520 525 Ala Pro Pro Asn Cys Glu Ser Asp Ser Lys Thr Gly Val 530 535 540 <210> 2515 <211> 288 <212> PRT <213> Homo sapiens <400> 2515 Met Ser Asp Ile Glu Glu Val Val Glu Glu Tyr Glu Glu Glu Glu Gln 1 S 10 15 Glu Glu Ala Ala Val Glu Glu Gln Glu Glu Ala Ala Glu Glu Asp Ala

Glu Ala Glu Ala Glu Thr Glu Glu Thr Arg Ala Glu Glu Asp Glu Glu 40 45 Glu Glu Glu Ala Lys Glu Ala Glu Asp Gly Pro Met Glu Glu Ser Lys 50 S55 60

Pro Lys Pro Arg Ser Phe Met Pro Asn Leu Val Pro Pro Lys Ile Pro 65 70 75 80 Asp Gly Glu Arg Val Asp Phe Asp Asp Ile His Arg Lys Arg Met Glu 85 S0 95 Lys Asp Leu Asn Glu Leu Gln Ala Leu Ile Glu Ala His Phe Glu Asn 100 105 110 Arg Lys Lys Glu Glu Glu Glu Leu Val Ser Leu Lys Asp Arg Ile Glu 115 120 125 Arg Arg Arg Ala Glu Arg Ala Glu Gln Gln Arg Ile Arg Asn Glu Arg 130 135 140 Glu Lys Glu Arg Gln Asn Arg Leu Ala Glu Glu Arg Ala Arg Arg Glu 145 150 155 160 : Glu Glu Glu Asn Arg Arg Lys Ala Glu Asp Glu Ala Arg Lys Lys Lys 165 170 175 Ala Leu Ser Asn Met Met His Phe Gly Gly Tyr Ile Gln Lys Gln Ala 180 185 190 Gln Thr Glu Arg Lys Ser Gly Lys Arg Gln Thr Glu Arg Glu Lys Lys 185 200 205 Lys Lys Ile Leu Ala Glu Arg Arg Lys Val Leu Ala Ile Asp His Leu 210 215 220 Asn Glu Asp Gln Leu Arg Glu Lys Ala Lys Glu Leu Trp Gln Ser Ile 225 230 235 240 Tyr Asn Leu Glu Ala Glu Lys Phe Asp Leu Gln Glu Lys Phe Lys Gln 245 250 255 Gln Lys Tyr Glu Ile Asn Val Leu Arg Asn Arg Ile Asn Asp Asn Gln 260 265 270 Lys Val Ser Lys Thr Arg Gly Lys Ala Lys Val Thr Gly Arg Trp Lys 275 280 285 <210> 2516 <21ll> 154 <212> PRT <213> Homo sapiens .

<400> 2516 Met Gly Leu Ser Asp Gly Glu Trp Gln Leu Val Leu Asn Val Trp Gly 1 5 10 15 Lys Val Glu Ala Asp Ile Pro Gly His Gly Gln Glu Val Leu Ile Arg

Leu Phe Lys Gly His Pro Glu Thr Leu Glu Lys Phe Asp Lys Phe Lys 40 45 His Leu Lys Ser Glu Asp Glu Met Lys Ala Ser Glu Asp Leu Lys Lys 50 55 60 His Gly Ala Thr Val Leu Thr Ala Leu Gly Gly Ile Leu Lys Lys Lys 65 70 75 80 Gly His His Glu Ala Glu Ile Lys Pro Leu Ala Gln Ser His Ala Thr 85 90 95 Lys His Lys Ile Pro Val Lys Tyr Leu Glu Phe Ile Ser Glu Cys Ile 100 105 110 Ile Gln Val Leu Gln Ser Lys His Pro Gly Asp Phe Gly Ala Asp Ala 115 120 125 Gln Gly Ala Met Asn Lys Ala Leu Glu Leu Phe Arg Lys Asp Met Ala 130 135 140 Ser Asn Tyr Lys Glu Leu Gly Phe Gln Gly 145 150 <«210> 2517 <211> 501 <212> PRT <213> Homo sapiens <400> 2517 Met Val Arg Lys Pro Val Val Ser Thr Ile Ser Lys Gly Gly Tyr Leu 1 S 10 15 Gln Gly Asn Val Asn Gly Arg Leu Pro Ser Leu Gly Asn Lys Glu Pro 20 25 30 Pro Gly Gln Glu Lys Val Gln Leu Lys Arg Lys Val Thr Leu Leu Arg 35 40 45 875 _ — J -

PCT/US2003/012946 Gly Val Ser Ile Ile Ile Gly Thr Ile Ile Gly Ala Gly Ile Phe Ile 50 55 60 Ser Pro Lys Gly Val Leu Gln Asn Thr Gly Ser val Gly Met Ser Leu 65 70 75 80 Thr Ile Trp Thr Val Cys Gly Val Leu Ser Leu Phe Gly Ala Leu Ser

85 . 90 85 Tyr Ala Glu Leu Gly Thr Thr Ile Lys Lys Ser Gly Gly His Tyr Thr 100 105 110 Tyr Ile Leu Glu Val rhe Gly Pro Leu Pro Ala phe Val Arg Val Trp 115 120 125 Val Glu Leu Leu Ile Ile Arg Pro Ala Ala Thr Ala Val Ile Ser Leu 130 135 140 Ala Phe Gly Arg Tyr Ile Leu Glu Pro Phe Phe Ile Gln Cys Glu Ile 145 150 155 160 Pro Glu Leu Ala Ile Lys Leu Ile Thr Ala Val Gly Ile Thr val val 165 170 175 Met Val Leu Asn Ser Met Ser val Ser Trp Ser Ala Arg Ile Gln Ile 180 185 190 Phe Leu Thr Phe Cys Lys Leu Thr Ala Ile Leu Ile Ile Ile val Pro 195 200 205 Gly val Met Gln Leu Ile Lys Gly Gln Thr Gln Asn Phe Lys Asp Ala 210 215 220 Phe Ser Gly Arg Asp Ser Ser Ile Thr Arg Leu Pro Leu Ala Phe Tyr 225 230 235 240 Tyr Gly Met Tyr Ala Tyr Ala Gly Trp Phe Tyr Leu Asn Phe Val Thr 245 : 250 255 Glu Glu Val Glu Asn Pro Glu Lys Thr Ile Pro Leu Ala Ile Cys Ile 260 265 270 Ser Met Ala Ile Val Thr Ile Gly Tyr Val Leu Thr Asn Val Ala Tyr 275 280 285

Phe Thr Thr Ile Asn Ala Glu Glu Leu Leu Leu Ser Asn Ala Val Ala 290 285 300 Val Thr Phe Ser Glu Arg Leu Leu Gly Asn Phe Ser Leu Ala Val Pro 305 310 315 320 Ile Phe val Ala Leu Ser Cys Phe Gly Ser Met Asn Gly Gly Val Phe 325 330 335 Ala Val Ser Arg Leu Phe Tyr Val Ala Ser Arg Glu Gly His Leu Pro 340 345 350 Glu Ile Leu Ser Met Ile His Val Arg Lys His Thr Pro Leu Pro Ala 355 360 365 Val Ile Val Leu His Pro Leu Thr Met Ile Met Leu Phe Ser Gly Asp 370 375 380 Leu Asp Ser Leu Leu Asn Phe Leu Ser Phe Ala Arg Trp Leu Phe Ile 385 3380 395 400 Gly Leu Ala val Ala Gly Leu Ile Tyr Leu Arg Tyr Lys Cys Pro Asp 405 410 415 Met His Arg Pro Phe Lys Val Pro Leu Phe Ile Pro Ala Leu Phe Ser 420 425 430 Phe Thr Cys Leu Phe Met Val Ala Leu Ser Leu Tyr Ser Asp Pro Phe 435 440 445 Ser Thr Gly Ile Gly Phe Val Ile Thr Leu Thr Gly Val Pro Ala yx 450 455 460 Tyr Leu Phe Ile Ile Trp Asp Lys Lys Pro Arg Trp Phe Arg Ile Met 465 470 475 480 Ser Glu Lys Ile Thr Arg Thr Leu Gln Ile Ile Leu Glu Val Val Pro 485 490 495 Glu Glu Asp Lys Leu 500 <210> 2518 <211> 277 <212> PRT <213> Homo sapiens

<400> 2518 Met Val Arg Leu Pro Leu Gln Cys Val Leu Trp Gly Cys Leu Leu Thr 1 S 10 15 Ala Val His Pro Glu Pro Pro Thr Ala Cys Arg Glu Lys Gln Tyr Leu

Ile Asn Ser Gln Cys Cys Ser Leu Cys Gln Pro Gly Gln Lys Leu Val 40 45 Ser Asp Cys Thr Glu Phe Thr Glu Thr Glu Cys Leu Pro Cys Gly Glu 50 55 60 Ser Glu Phe Leu Asp Thr Trp Asn Arg Glu Thr His Cys His Gln His 65 70 75 80 Lys Tyr Cys Asp Pro Asn Leu Gly Leu Arg Val Gln Gln Lys Gly Thr 85 90 95 Ser Glu Thr Asp Thr Ile Cys Thr Cys Glu Glu Gly Trp His Cys Thr 100 105 110 Ser Glu Ala Cys Glu Ser Cys Val Leu His Arg Ser Cys Ser Pro Gly 115 120 125 Phe Gly val Lys Gln Ile Ala Thr Gly Val Ser Asp Thr Ile Cys Glu 130 135 140 Pro Cys Pro Val Gly Phe Phe Ser Asn Val Ser Ser Ala Phe Glu Lys 145 150 155 160 Cys His Pro Trp Thr Ser Cys Glu Thr Lys Asp Leu Val Val Gln Gln 165 170 175 Ala Gly Thr Asn Lys Thr Asp Val Val Cys Gly Pro Gln Asp Arg Leu 180 185 180 Arg Ala Leu Val Val Ile Pro Ile Ile Phe Gly Ile Leu Phe Ala Ile 195 200 205 Leu Leu Val Leu Val Phe Ile Lys Lys Val Ala Lys Lys Pro Thr Asn 210 218 220 Lys Ala Pro His Pro Lys Gln Glu Pro Gln Glu Ile Asn Phe Pro Asp 225 230 235 240

Asp Leu Pro Gly Ser Asn Thr Ala Ala Pro Val Gln Glu Thr Leu His 245 250 255 Gly Cys Gln Pro Val Thr Gln Glu Asp Gly Lys Glu Ser Arg Ile Ser 260 265 270 Val Gln Glu Arg Gln 275 <210> 2519 <211l> 260 <212> PRT <213> Homo sapiens <400> 2519 Met Ala Arg Pro His Pro Trp Trp Leu Cys Val Leu Gly Thr Leu Val 1 S 10 15 Gly Leu Ser Ala Thr Pro Ala Pro Lys Ser Cys Pro Glu Arg His Tyr

Trp Ala Gln Gly Lys Leu Cys Cys Gln Met Cys Glu Pro Gly Thr Phe 40 45 Leu Val Lys Asp Cys Asp Gln His Arg Lys Ala Ala Gln Cys Asp Pro 50 55 60 Cys Ile Pro Gly Val Ser Phe Ser Pro Asp His His Thr Arg Pro His 65 70 75 80 Cys Glu Ser Cys Arg His Cys Asn Ser Gly Leu Leu Val Arg Asn Cys 85 90 95 Thr Ile Thr Ala Asn Ala Glu Cys Ala Cys Arg Asn Gly Trp Gln Cys 100 105 110 Arg Asp Lys Glu Cys Thr Glu Cys Asp Pro Leu Pro Asn Pro Ser Leu 115 120 125 Thr Ala Arg Ser Ser Gln Ala Leu Ser Pro His Pro Gln Pro Thr His . 130 135 140 Leu Pro Tyr Val Ser Glu Met Leu Glu Ala Arg Thr Ala Gly His Met 145 150 155 160 Gln Thr Leu Ala Asp Phe Arg Gln Leu Pro Ala Arg Thr Leu Ser Thr

165 170 175 His Trp Pro Pro Gln Arg Ser Leu Cys Ser Ser Asp Phe Ile Arg Ile 180 185 150 Leu Val Ile Phe Ser Gly Met Phe Leu Val Phe Thr Leu Ala Gly Ala 185 200 205 Leu Phe Leu His Gln Arg Arg Lys Tyr Arg Ser Asn Lys Gly Glu Ser 210 215 220 Pro Val Glu Pro Ala Glu Pro Cys Arg Tyr Ser Cys Pro Arg Glu Glu 225 230 235 240 Glu Gly Ser Thr Ile Pro Ile Gln Glu Asp Tyr Arg Lys Pro Glu Pro 245 250 255 Ala Cys Ser Pro 260 <210> 2520 <211> 329 <212> PRT <213> Homo sapiens <400> 2520 Met Asp Pro Gln Cys Thr Met Gly Leu Ser Asn Ile Leu Phe Val Met 1 5 10 15 Ala Phe Leu Leu Ser Gly Ala Ala Pro Leu Lys Ile Gln Ala Tyr Phe

Asn Glu Thr Ala Asp Leu Pro Cys Gln Phe Ala Asn Ser Gln Asn Gln 40 45 Ser Leu Ser Glu Leu Val Val Phe Trp Gln Asp Gln Glu Asn Leu Val 50 S5 60 Leu Asn Glu Val Tyr Leu Gly Lys Glu Lys Phe Asp Ser val His Ser 65 70 75 80 Lys Tyr Met Gly Arg Thr Ser Phe Asp Ser Asp Ser Trp Thr Leu Arg 85 80 S5 Leu His Asn Leu Gln Ile Lys Asp Lys Gly Leu Tyr Gln Cys Ile Ile 100 108 110 880 ry

His His Lys Lys Pro Thr Gly Met Ile Arg Ile His Gln Met Asn Ser 115 120 125 Glu Leu Ser Val Leu Ala Asn Phe Ser Gln Pro Glu Ile Val Pro Ile 130 135 140 Ser Asn Ile Thr Glu Asn Val Tyr Ile Asn Leu Thr Cys Ser Ser Ile 145 150 155 160 His Gly Tyr Pro Glu Pro Lys Lys Met Ser Val Leu Leu Arg Thr Lys 165 170 175 Asn Ser Thr Ile Glu Tyr Asp Gly Ile Met Gln Lys Ser Gln Asp Asn 180 185 190 val Thr Glu Leu Tyr Asp Val Ser Ile Ser Leu Ser Val Ser Phe Pro 195 200 205 Asp Val Thr Ser Asn Met Thr Ile Phe Cys Ile Leu Glu Thr Asp Lys 210 215 220 Thr Arg Leu Leu Ser Ser Pro Phe Ser Ile Glu Leu Glu Asp Pro Gln 225 230 235 240 Pro Pro Pro Asp His Ile Pro Trp Ile Thr Ala Val Leu Pro Thr Val 245 250 255 _ Ile Ile Cys Val Met Val Phe Cys Leu Ile Leu Trp Lys Trp Lys Lys 260 265 270 Lys Lys Arg Pro Arg Asn Ser Tyr Lys Cys Gly Thr Asn Thr Met Glu 275 280 285 Arg Glu Glu Ser Glu Gln Thr Lys Lys Arg Glu Lys Ile His Ile Pro 290 2595 300 Glu Arg Ser Asp Glu Ala Gln Arg Val Phe Lys Ser Ser Lys Thr Ser 305 310 315 320 Ser Cys Asp Lys ser Asp Thr Cys Phe 325 <210> 2521 <211> 132 <212> PRT <213> Homo sapiens

T/US2003/012946

<400> 2521 Met Glu Phe Asp Leu Asn Gly Asn Gly Asp Ile Gly Glu Lys Arg val 1 5 10 15 Ile Cys Gly Gly Arg Val Val Cys Arg Pro Lys Lys Thr Glu Val Ser

Pro Thr Cys Ser Ile Pro His Asp Leu Gly Gly Gly Pro Pro Thr Thr 40 45 Val Gly Gly Arg Arg Met Gly Met Arg Lys Trp Glu Arg Arg Glu Arg 50 55 60 Val Ser Pro Pro Ser Pro His Pro His Pro Leu Pro Pro Asp Ile Met 65 70 75 80 Ser Leu Lys Arg Met Leu Glu Lys Leu Gly val Pro Lys Thr His Leu 85 S0 95 Glu Leu Lys Lys Leu Ile Gly Glu Val Ser Ser Gly Ser Gly Glu Thr 100 105 110 Phe Ser Tyr Pro Asp Phe Leu Arg Met Met Leu Gly Lys Arg Ser Ala 115 120 125 Ile Leu Lys Met 130 <210> 2522 <211> 491 <212> PRT <213> Homo sapiens <400> 2522 Met Glu Ser Ser Ala Lys Arg Lys Met Asp Pro Asp Asn Pro Asp Glu 1 5 10 15 Gly Pro Ser Ser Lys Val Pro Arg Pro Glu Thr Pro Val Thr Lys Ala 20 25 30 Thr Thr Phe Leu Gln Thr Met Leu Arg Lys Glu Val Asn Ser Gln Leu 35 40 45 Ser Leu Gly Asp Pro Leu Phe Pro Glu Leu Ala Glu Glu Ser Leu Lys 50 55 60

Thr Phe Glu Gln Val Thr Glu Asp Cys Asn Glu Asn Pro Glu Lys Asp 65 70 75 80 Val Leu Ala Glu Leu Val Lys Gln Ile Lys Val Arg Val Asp Met Val

85 90 95 Arg His Arg Ile Lys Glu His Met Leu Lys Lys Tyr Thr Gln Thr Glu 100 105 110 Glu Lys Phe Thr Gly Ala Phe Asn Met Met Gly Gly Cys Leu Gln Asn 115 120 125 Ala Leu Asp Ile Leu Asp Lys Val His Glu Pro Phe Glu Glu Met Lys 130 135 140 Cys Ile Gly Leu Thr Met Gln Ser Met Tyr Glu Asn Tyr Ile Val Pro 145 150 155 160 Glu Asp Lys Arg Glu Met Trp Met Ala Cys Ile Lys Glu Leu His Asp 165 170 175 Val Ser Lys Gly Ala Ala Asn Lys Leu Gly Gly Ala Leu Gln Ala Lys 180 185 190 Ala Arg Ala Lys Lys Asp Glu Leu Arg Arg Lys Met Met Tyr Met Cys 185 200 205 Tyr Arg Asn Ile Glu Phe Phe Thr Lys Asn Ser Ala Phe Pro Lys Thr 210 215 220 Thr Asn Gly Cys Ser Gln Ala Met Ala Ala Leu Gln Asn Leu Pro Gln 225 230 235 240 Cys Ser Pro Asp Glu Ile Met Ala Tyr Ala Gln Lys Ile Phe Lys Ile 245 250 255 Leu Asp Glu Glu Arg Asp Lys Val Leu Thr His Ile Asp His Ile Phe 260 265 270 Met Asp Ile Leu Thr Thr Cys Val Glu Thr Met Cys Asn Glu Tyr Lys oo 275 280 285 Val Thr Ser Asp Ala Cys Met Met Thr Met Tyr Gly Gly Ile Ser Leu 290 295 300

Leu Ser Glu Phe Cys Arg Val Leu Cys Cys Tyr val Leu Glu Glu Thr 305 310 315 320 Ser Val Met Leu Ala Lys Arg Pro Leu Ile Thr Lys Pro Glu Val Ile

325 330 335 Ser Val Met Lys Arg Arg Ile Glu Glu Ile Cys Met Lys Val Phe Ala 340 345 350 Gln Tyr Ile Leu Gly Ala Asp Pro Leu Arg Val Cys Ser Pro Ser val 355 360 365 Asp Asp Leu Arg Ala Ile Ala Glu Glu Ser Asp Glu Glu Glu Ala Ile 370 375 380 Val Ala Tyr Thr Leu Ala Thr Ala Gly Val Ser Ser Ser Asp Ser Leu 385 390 3985 400 Val Ser Pro Pro Glu Ser Pro Val Pro Ala Thr Ile Pro Leu Ser Ser 405 410 415 Val Ile Val Ala Glu Asn Ser Asp Gln Glu Glu Ser Glu Gln Ser Asp 420 425 430 Glu Glu Glu Glu Glu Gly Ala Gln Glu Glu Arg Glu Asp Thr Val ser 435 440 445 Val Lys Ser Glu Pro Val Ser Glu Ile Glu Glu Val Ala Pro Glu Glu 450 455 460 Glu Glu Asp Gly Ala Glu Glu Pro Thr Ala Ser Gly Gly Lys Ser Thr 465 470 475 480 His Pro Met Val Thr Arg Ser Lys Ala Asp Gln 485 490 <210> 2523 <211> 481 <212> PRT <213> Homo sapiens <400> 2523 Met Glu Ser Ser Ala Lys Arg Lys Met Asp Pro Asp Asn Pro Asp Glu 1 5 10 15 Gly Pro Ser Ser Lys Val Pro Arg Pro Glu Thr Pro Val Thr Lys Ala

Thr Thr Phe Leu Gln Thr Met Leu Arg Lys Glu Val Asn Ser Gln Leu 40 45 Ser Leu Gly Asp Pro Leu Phe Pro Glu Leu Ala Glu Glu Ser Leu Lys 50 55 60 Thr Phe Glu Gln val Thr Glu Asp Cys Asn Glu Asn Pro Glu Lys Asp 65 70 75 80 Val Leu Ala Glu Leu Val Lys Gln Ile Lys Val Arg Val Asp Met Val 85 90 95 Arg His Arg Ile Lys Glu His Met Leu Lys Lys Tyr Thr Gln Thr Glu 100 105 110 : Glu Lys Phe Thr Gly Ala Phe Asn Met Met Gly Gly Cys Leu Gln Asn 115 120 125 Ala Leu Asp Ile Leu Asp Lys Val His Glu Pro Phe Glu Glu Met Lys 130 135 140 Cys Ile Gly Leu Thr Met Gln Ser Met Tyr Glu Asn Tyr Ile Val Pro 145 150 155 160 Glu Asp Lys Arg Glu Met Trp Met Ala Cys Ile Lys Glu Leu His Asp 165 170 175 Val Ser Lys Gly Ala Ala Asn Lys Leu Gly Gly Ala Leu Gln Ala Lys 180 185 180 Ala Arg Ala Lys Lys Asp Glu Leu Arg Arg Lys Met Met Tyr Met Cys 195 200 205 Tyr Arg Asn Ile Glu Phe Phe Thr Lys Asn Ser Ala Phe Pro Lys Thr 210 215 220 Thr Asn Gly Cys Ser Gln Ala Met ‘Ala Ala Leu Gln Asn Leu Pro Gln 225 230 235 240 Cys Ser Pro Asp Glu ‘Ile Met Ala Tyr Ala Gln Lys Ile Phe Lys Ile - 245 250 255 Leu Asp Glu Glu Arg Asp Lys Val Leu Thr His Ile Asp His Ile Phe 260 265 270

Met Asp Ile Leu Thr Thr Cys Val Glu Thr Met Cys Asn Glu Tyr Lys 27S 280 285 Val Thr Ser Asp Ala Cys Met Met Thr Met Tyr Gly Gly Ile Ser Leu 290 295 300 Leu Ser Glu Phe Cys Arg Val Leu Cys Cys Tyr Val Leu Glu Glu Thr 305 310 . - 315 320 Ser Val Met Leu Ala Lys Arg Pro Leu Ile Thr Lys Pro Glu Val Ile 325 330 335 Ser Val Met Lys Arg Arg Ile Glu Glu Ile Cys Met Lys Val Phe Ala 340 345 350 Gln Tyr Ile Leu Gly Ala Asp Pro Leu Arg Val Cys Ser Pro Ser Val 355 360 365 Asp Asp Leu Arg Ala Ile Ala Glu Glu Ser Asp Glu Glu Glu Ala Ile 370 375 380 . Val Ala Tyr Thr Leu Ala Thr Ala Gly Val Ser Ser Ser Asp Ser Leu 385 390 395 400 Val Ser Pro Pro Glu Ser Pro Val Pro Ala Thr Ile Pro Leu Ser Ser 405 410 415 val Ile Val Ala Glu Asn Ser Asp Gln Glu Glu Ser Glu Gln Ser Asp 420 425 430 Glu Glu Glu Glu Glu Gly Ala Gln Glu Glu Arg Glu Asp Thr Val Ser 435 440 445 Val Lys Ser Glu Pro Val Ser Glu Ile Glu Glu Val Ala Pro Glu Glu 450 455 460 Glu Glu Asp Gly Ala Glu Glu Pro Thr Ala Ser Gly Gly Lys Ser Thr 465 470 475 480 Hie Pro Met Val Thr Arg Ser Lys Ala Asp Gln 485 490 <210> 2524 <211l> 641 <212> PRT <213> Homo sapiens

<400> 2524 Met Ser Asp Glu Gly Pro Gly Thr Gly Pro Gly Asn Gly Leu Gly Glu 1 5 10 15 Lys Gly Asp Thr Ser Gly Pro Glu Gly Ser Gly Gly Ser Gly Pro Gln

Arg Arg Gly Gly Asp Asn His Gly Arg Gly Arg Gly Arg Gly Arg Gly 40 45 Arg Gly Gly Gly Arg Pro Gly Ala Pro Gly Gly Ser Gly Ser Gly Pro 50 55 60 Arg His Arg Asp Gly Val Arg Arg Pro Gln Lys Arg Pro Ser Cys Ile 65 70 75 80 Gly Cys Lys Gly Thr His Gly Gly Thr Gly Ala Gly Ala Gly Ala Gly 85 90 95 Gly Ala Gly Ala Gly Gly Ala Gly Ala Gly Gly Gly Ala Gly Ala Gly 100 105 110 Gly Gly Ala Gly Gly Ala Gly Gly Ala Gly Gly Ala Gly Ala Gly Gly 115 120 125 Gly Ala Gly Ala Gly Gly Gly Ala Gly Gly Ala Gly Gly Ala Gly Ala 130 135 140 Gly Gly Gly Ala Gly Ala Gly Gly Gly Ala Gly Gly Ala Gly Ala Gly 145 150 155 160 Gly Gly Ala Gly Gly Ala Gly Gly Ala Gly Ala Gly Gly Gly Ala Gly 165 170 175 Ala Gly Gly Gly Ala Gly Gly Ala Gly Ala Gly Gly Gly Ala Gly Gly 180 185 190 Ala Gly Gly Ala Gly Ala Gly Gly Gly Ala Gly Ala Gly Gly Ala Gly 195 200 205 Gly Ala Gly Gly Ala Gly Ala Gly Gly Ala Gly Ala Gly Gly Gly Ala 210 215 220 Gly Gly Ala Gly Gly Ala Gly Ala Gly Gly Ala Gly Ala Gly Gly Ala 225 230 235 240

Gly Ala Gly Gly Ala Gly ala Gly Gly Ala Gly Gly Ala Gly Ala Gly 245 250 255 Gly Ala Gly Gly Ala Gly Ala Gly Gly Ala Gly Gly Ala Gly Ala Gly 260 265 270 Gly Gly Ala Gly Gly Ala Gly Ala Gly Gly Gly Ala Gly Gly Ala Gly 275 280 285 Ala Gly Gly Ala Gly Gly Ala Gly Ala Gly Gly Ala Gly Gly Ala Gly 290 2895 300 Ala Gly Gly Ala Gly Gly Ala Gly Ala Gly Gly Gly Ala Gly Ala Gly 305 310 315 320 Gly Ala Gly Ala Gly Gly Gly Gly Arg Gly Arg Gly Gly Ser Gly Gly 325 . 330 335 Arg Gly Arg Gly Gly Ser Gly Gly Arg Gly Arg Gly Gly Ser Gly Gly 340 345 350 Arg Arg Gly Arg Gly Arg Glu Arg Ala Arg Gly Gly Ser Arg Glu Arg 355 360 365 Ala Arg Gly Arg Gly Arg Gly Arg Gly Glu Lys Arg Pro Arg Ser Pro 370 375 380 Ser Ser Gln Ser Ser Ser Ser Gly Ser Pro Pro Arg Arg Pro Pro Pro 385 350 395 400 Gly Arg Arg Pro Phe Phe His Pro Val Gly Glu Ala Asp Tyr Phe Glu 405 410 415 Tyr His Gln Glu Gly Gly Pro Asp Gly Glu Pro Asp Val Pro Pro Gly 420 425 430 Ala Ile Glu Gln Gly Pro Ala Asp Asp Pro Gly Glu Gly Pro Ser Thr 435 440 445 Gly Pro Arg Gly Gln Gly Asp Gly Gly Arg Arg Lys Lys Gly Gly Trp 450 455 460 Phe Gly Lys His Arg Gly Gln Gly Gly Ser Asn Pro Lys Phe Glu Asn 465 470 475 480

Ile Ala Glu Gly Leu Arg Ala Leu Leu Ala Arg Ser His Val Glu Arg 485 490 495 Thr Thr Asp Glu Gly Thr Trp Val Ala Gly val Phe Val Tyr Gly Gly S00 505 510 Ser Lys Thr Ser Leu Tyr Asn Leu Arg Arg Gly Thr Ala Leu Ala Ile 515 520 525 Pro Gln Cys Arg Leu Thr Pro Leu Ser Arg Leu Pro Phe Gly Met Ala 530 535 540 Pro Gly Pro Gly Pro Gln Pro Gly Pro Leu Arg Glu Ser Ile Val Cys 545 550 555 560 : Tyr Phe Met Val Phe Leu Gln Thr His Ile Phe Ala Glu Val Leu Lys 565 570 575 Asp Ala Ile Lys Asp Leu Val Met Thr Lys Pro Ala Pro Thr Cys Asn 580 585 590 Ile Arg Val Thr Val Cys Ser Phe Asp Asp Gly Val Asp Leu Pro Pro 595 600 605 Trp Phe Pro Pro Met Val Glu Gly Ala Ala Ala Glu Gly Asp Asp Gly 610 615 620 Asp Asp Gly Asp Glu Gly Gly Asp Gly Asp Glu Gly Glu Glu Gly Gln 625 630 635 640 Glu <210> 2525 <211> 245 <212> PRT <213> Homo sapiens <400> 2525 Met Met Asp Pro Asn Ser Thr Ser Glu Asp Val Lys Phe Thr Pro Asp 1 5 10 15 Pro Tyr Gln Val Pro Phe Val Gln Ala Phe Asp Gln Ala Thr Arg Val

Tyr Gln Asp Leu Gly Gly Prec Ser Gln Ala Pro Leu Pro Cys Val Leu

40 45 Trp Pro Val Leu Pro Glu Pro Leu Pro Gln Gly Gln Leu Thr Ala Tyr 50 55 60 His Val Ser Thr Ala Pro Thr Gly Ser Trp Phe Ser Ala Pro Gln Pro 65 70 75 80 ala Pro Glu Asn Ala Tyr Gln Ala Tyr Ala Ala Pro Gln Leu Phe Pro 85 90 95 Val Ser Asp Ile Thr Gln Asn Gln Gln Thr Asn Gln Ala Gly Gly Glu 100 105 110 Ala Pro Gln Pro Gly Asp Asn Ser Thr Val Gln Thr Ala Ala Ala Val 115 120 125 Val Phe Ala Cys Pro Gly Ala Asn Gln Gly Gln Gln Leu Ala Asp Ile 130 135 140 Gly Val Pro Gln Pro Ala Pro Val Ala Ala Pro Ala Arg Arg Thr Arg 145 150 155 160 Lys Pro Gln Gln Pro Glu Ser Leu Glu Glu Cys Asp Ser Glu Leu Glu 165 170 175 Ile Lys Arg Tyr Lys Asn Arg Val Ala Ser Arg Lys Cys Arg Ala Lys 180 185 190 Phe Lys Gln Leu Leu Gln His Tyr Arg Glu Val Ala Ala Ala Lys Ser 195 200 205 Ser Glu Asn Asp Arg Leu Arg Leu Leu Leu Lys Gln Met Cys Pro Ser 210 215 220 Leu Asp Val Asp Ser Ile Ile Pro Arg Thr Pro Asp Val Leu His Glu 225 230 235 240 Asp Leu Leu Asn Phe 245 <210> 2526 <211> 491 <212> PRT <213> Bomo sapiens <400> 2526

Met Glu Ser Ser Ala Lys Arg Lys Met Asp Pro Asp Asn Pro Asp Glu 1 5 10 15 Gly Pro Ser Ser Lys Val Pro Arg Pro Glu Thr Pro Val Thr Lys Ala

Thr Thr Phe Leu Gln Thr Met Leu Arg Lys Glu Val Asn Ser Gln Leu 40 45 Ser Leu Gly Asp Pro Leu Phe Pro Glu Leu Ala Glu Glu Ser Leu Lys

50 55 60 Thr Phe Glu Gln Val Thr Glu Asp Cys Asn Glu Asn Pro Glu Lys Asp 65 70 75 80 Val Leu Ala Glu Leu Val Lys Gln Ile Lys Val Arg Val Asp Met Val

85 90 95 Arg His Arg Ile Lys Glu His Met Leu Lys Lys Tyr Thr Gln Thr Glu 100 105 110 Glu Lys Phe Thr Gly Ala Phe Asn Met Met Gly Gly Cys Leu Gln Asn 115 120 125 ala Leu Asp Ile Leu Asp Lys Val His Glu Pro Phe Glu Glu Met Lys 130 135 140 Cys Ile Gly Leu Thr Met Gln Ser Met Tyr Glu Asn Tyr Ile Val Pro 145 150 155 160 Glu Asp Lys Arg Glu Met Trp Met Ala Cys Ile Lys Glu Leu His Asp 165 170 175 Val Ser Lys Gly Ala Ala Asn Lys Leu Gly Gly Ala Leu Gln Ala Lys 180 185 150 Ala Arg Ala Lys Lys Asp Glu Leu Arg Arg Lys Met Met Tyr Met Cys 185 200 205 Tyr Arg Asn Ile Glu Phe Phe Thr Lys Asn Ser Ala Phe Pro Lys Thr 210 215 220 Thr Asn Gly Cys Ser Gln Ala Met Ala Ala Leu Gln Asn Leu Pro Gln 225 230 235 240

Cys Ser Pro Asp Glu Ile Met Ala Tyr Ala Gln Lys Ile Phe Lys Ile 245 250 255 : Leu Asp Glu Glu Arg Asp Lys Val Leu Thr His Ile Asp His Ile Phe 260 265 270 Met Asp Ile Leu Thr Thr Cys Val Glu Thr Met Cys Asn Glu Tyr Lys 275 280 285 val Thr Ser Asp Ala Cys Met Met Thr Met Tyr Gly Gly lle Ser Leu 290 295 300 Leu Ser Glu Phe Cys Arg Val Leu Cys Cys Tyr Val Leu Glu Glu Thr 305 310 315 320 Ser Val Met Leu Ala Lys Arg Pro Leu Ile Thr Lys Pro Glu Val Ile 325 330 335 Ser Val Met Lys Arg Arg Ile Glu Glu Ile Cys Met Lys Val Phe Ala 340 345 350 Gln Tyr Ile Leu Gly Ala Asp Pro Leu Arg Val Cys Ser Pro Ser Val 355 360 365 Asp Asp Leu Arg Ala Ile Ala Glu Glu Ser Asp Glu Glu Glu Ala Ile 370 375 380 Val Ala Tyr Thr Leu Ala Thr Ala Gly Val Ser Ser Ser Asp Ser Leu 385 350 395 400 val Ser Pro Pro Glu Ser Pro Val Pro Ala Thr Ile Pro Leu Ser Ser 405 410 415 Val Ile Val Ala Glu Asn Ser Asp Gln Glu Glu Ser Glu Gln Ser Asp 420 425 430 Glu Glu Glu Glu Glu Gly Ala Gln Glu Glu Arg Glu Asp Thr Val Ser 435 440 445 val Lys Ser Glu Pro Val Ser Glu Ile Glu Glu Val Ala Pro Glu Glu 450 455 460 Glu Glu Asp Gly Ala Glu Glu Pro Thr Ala Ser Gly Gly Lys Ser Thr 465 470 475 480 His Pro Met Val Thr Arg Ser Lys Ala Asp Gln

PCT/US2003/012946

485 4950 <210> 2527 <211> 491 <212> PRT <213> Homo sapiens <400> 2527 Met Glu Ser Ser Ala Lys Arg Lys Met Asp Pro Asp Asn Pro Asp Glu 1 Ss 10 15 Gly Pro Ser Ser Lys Val Pro Arg Pro Glu Thr Pro Val Thr Lys Ala

Thr Thr Phe Leu Gln Thr Met Leu Arg Lys Glu Val Asn Ser Gln Leu 40 45 Ser Leu Gly Asp Pro Leu Phe Pro Glu Leu Ala Glu Glu Ser Leu Lys 50 55 60 Thr Phe Glu Gln Val Thr Glu Asp Cys Asn Glu Asn Pro Glu Lys Asp 65 70 75 80 Val Leu Ala Glu Leu Val Lys Gln Ile Lys val Arg val Asp Met Val 85 90 95 Arg His Arg Ile Lys Glu His Met Leu Lys Lys Tyr Thr Gln Thr Glu 100 105 110 Glu Lys Phe Thr Gly Ala Phe Asn Met Met Gly Gly Cys Leu Gln Asn 115 120 125 Ala Leu Asp Ile Leu Asp Lys Val His Glu Pro Phe Glu Glu Met Lys 130 135 140 Cys Ile Gly Leu Thr Met Gln Ser Met Tyr Glu Asn Tyr Ile Val Pro 145 150 155 160 Glu Asp Lys Arg Glu Met Trp Met Ala Cys Ile Lys Glu Leu His Asp 165 170 175 Val Ser Lys Gly Ala Ala Asn Lys Leu Gly Gly Ala Leu Gln Ala Lys 180 185 190 Ala Arg Ala Lys Lys Asp Glu Leu Arg Arg Lys Met Met Tyr Met Cys 195 200 205

Tyr Arg Asn Ile Glu Phe Phe Thr Lys Asn Ser Ala Phe Pro Lys Thr 210 215 220 Thr Asn Gly Cys Ser Gln Ala Met Ala Ala Leu Gln Asn Leu Pro Gln 225 230 235 240 Cys Ser Pro Asp Glu Ile Met Ala Tyr Ala Gln Lys Ile Phe Lys Ile 245 .250 255 Leu Asp Glu Glu Arg Asp Lys Val Leu Thr His Ile Asp His Ile Phe 260 265 270 Met Asp Ile Leu Thr Thr Cys Val Glu Thr Met Cys Asn Glu Tyr Lys 275 280 285 Val Thr Ser Asp Ala Cys Met Met Thr Met Tyr Gly Gly Ile Ser Leu 290 295 300 Leu Ser Glu Phe Cys Arg Val Leu Cys Cys Tyr Val Leu Glu Glu Thr 305 310 315 320 Ser Val Met Leu Ala Lys Arg Pro Leu Ile Thr Lys Pro Glu val Ile 325 330 335 Ser Val Met Lys Arg Arg Ile Glu Glu Ile Cys Met Lys Val Phe Ala 340 3458 350 Gln Tyr Ile Leu Gly Ala Asp Pro Leu Arg Val Cys Ser Pro Ser Val 355 360 365 Asp Asp Leu Arg Ala Ile Ala Glu Glu Ser Asp Glu Glu Glu Ala Ile 370 375 380 Val Ala Tyr Thr Leu Ala Thr Ala Gly val Ser Ser Ser Asp Ser Leu 385 350 395 400 Val Ser Pro Pro Glu Ser Pro Val Pro Ala Thr Ile Pro Leu Ser Ser 405 410 415 Val Ile val Ala Glu Asn Ser Asp Gln Glu Glu Ser Glu Gln Ser Asp 420 425 430 Glu Glu Glu Glu Glu Gly Ala Gln Glu Glu Arg Glu Asp Thr val Ser 435 440 445

03/012946

Val Lys Ser Glu Pro Val Ser Glu Ile Glu Glu val Ala Pro Glu Glu 450 455 460 Glu Glu Asp Gly Ala Glu Glu Pro Thr Ala Ser Gly Gly Lys Ser Thr 465 470 475 480 : His Pro Met val Thr Arg Ser Lys Ala Asp Gln 485 490 <210> 2528 <211> 142 <212> PRT <213> Homo sapiens <400> 2528 Met Ser Leu Leu Pro Val Pro Tyr Thr Glu Ala Ala Ser Leu Ser Thr 1 5 10 15 Gly Ser Thr Val Thr Ile Lys Gly Arg Pro Leu Ala Cys Phe Leu Asn

Glu Pro Tyr Leu Gln Val Asp Phe His Thr Glu Met Lys Glu Glu Ser 40 45 Asp Ile Val Phe His Phe Gln Val Cys Phe Gly Arg Arg Val val Met 50 55 60 Asn Ser Arg Glu Tyr Gly Ala Trp Lys Gln Gln val Glu Ser Lys Asn 65 70 75 80 Met Pro Phe Gln Asp Gly Gln Glu Phe Glu Leu Ser Ile Ser Val Leu 85 20 95 Pro Asp Lys Tyr Gln Val Met Val Asn Gly Gln Ser Ser Tyr Thr Phe 100 105 110 Asp His Arg Ile Lys Pro Glu Ala Val Lys Met Val Gln Val Trp Arg 115 120 125 Asp Ile Ser Leu Thr Lys Phe Asn Val Ser Tyr Leu Lys Arg 130 135 140 <210> 2529 <211l> 298 <212> PRT <213> Homo sapiens <400> 2529

Met Ala Glu Ala Met Asp Leu Gly Lys Asp Pro Asn Gly Pro Thr His 1 ) 10 15 Ser Ser Thr Leu Phe Val Arg Asp Asp Gly Ser Ser Met Ser Phe Tyr

Val Arg Pro Ser Pro Ala Lys Arg Arg Leu Ser Thr Leu Ile Leu His 40 45 Gly Gly Gly Thr Val Cys Arg Val Gln Glu Pro Gly Ala Val Leu Leu 50 58 60 Ala Gln Pro Gly Glu Ala Leu Ala Glu Ala Ser Gly Asp Phe Ile Ser 65 70 75 80 Thr Gln His Ile Leu Asp Cys Val Glu Arg Asn Glu Arg Leu Glu Leu 85 90 95 Glu Ala Tyr Arg Leu Gly Pro Ala Ser Ala Ala Asp Thr Gly Ser Glu 100 105 110 Ala Lys Pro Gly Ala Leu Ala Glu Gly Ala Ala Glu Pro Glu Pro Gln 115 120 125 Arg His Ala Gly Arg Ile Ala Phe Thr Asp Ala Asp Asp Val Ala Ile 130 135 140 Leu Thr Tyr Val Lys Glu Asn Ala Arg Ser Pro Ser Ser Val Thr Gly 145 150 155 160 Asn Ala Leu Trp Lys Ala Met Glu Lys Ser Ser Leu Thr Gln His Ser 165 170 175 Trp Gln Ser Leu Lys Asp Arg Tyr Leu Lys His Leu Arg Gly Gln Glu 180 185 180 His Lys Tyr Leu Leu Gly Asp Ala Pro Val Ser Pro Ser Ser Gln Lys 195 200 205 Leu Lys Arg Lys Ala Glu Glu Asp Pro Glu Ala Ala Asp Ser Gly Glu 210 215 220 Pro Gln Asn Lys Arg Thr Pro Asp Leu Pro Glu Glu Glu Tyr Val Lys 225 230 235 240

Glu Glu Ile Gln Glu Asn Glu Glu Ala val Lys Lys Met Leu val Glu 245 250 255 Ala Thr Arg Glu Phe Glu Glu Val Val Val Asp Glu Ser Pro Pro Asp 260 265 270 Phe Glu Ile His Ile Thr Met Cys Asp Asp Asp Pro Pro Thr Pro Glu 275 280 285 Glu Asp Ser Glu Thr Gln Pro Asp Glu Glu 290 295 <210> 2530 <211> 365 <212> PRT <213> Homo sapiens <400> 2530 Met Ala Val Met Ala Pro Arg Thr Leu Leu Leu Leu Leu Ser Gly Ala 1 Ss 10 15 Leu Ala Leu Thr Gln Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe

Phe Thr Ser Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala 40 45 Val Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ala 50 S55 60 Ala Ser Gln Arg Met Glu Pro Arg Ala Pro Trp Ile Glu Gln Glu Gly 65 70 75 80 Pro Glu Tyr Trp Asp Gln Glu Thr Arg Asn Val Lys Ala Gln Ser Gln 85 90 95 Thr Asp Arg Val Asp Leu Gly Thr Leu Arg Gly Tyr Tyr Asn Gln Ser 100 105 110 Glu Ala Gly Ser His Thr Ile Gln Ile Met Tyr Gly Cys Asp val Gly 115 120 125 Ser Asp Gly Arg Phe Leu Arg Gly Tyr Arg Gln Asp Ala Tyr Asp Gly 130 135 140 Lys Asp Tyr Ile Ala Leu Asn Glu Asp Leu Arg Ser Trp Thr Ala Ala 145 150 1558 160

Asp Met Ala Ala Gln Ile Thr Lys Arg Lys Trp Glu Ala Ala His Glu 165 170 175 Ala Glu Gln Leu Arg Ala Tyr Leu Asp Gly Thr Cys Val Glu Trp Leu 180 185 190 Arg Arg Tyr Leu Glu Asn Gly Lys Glu Thr Leu Gln Arg Thr Asp Pro 195 200 205 Pro Lys Thr His Met Thr His His Pro Ile Ser Asp His Glu Ala Thr 210 215 220 Leu Arg Cys Trp Ala Leu Gly Phe Tyr Pro Ala Glu Ile Thr Leu Thr 225 230 235 240 Trp Gln Arg Asp Gly Glu Asp Gln Thr Gln Asp Thr Glu Leu Val Glu 245 250 255 Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp Ala Ala Val Val 260 265 270 Val Pro Ser Gly Glu Glu Gln Arg Tyr Thr Cys His Val Gln His Glu 275 280 285 Gly Leu Pro Lys Pro Leu Thr Leu Arg Trp Glu Leu Ser Ser Gln Pro 2590 295 300 Thr Ile Pro Ile Val Gly Ile Ile Ala Gly Leu Val Leu Leu Gly Ala 305 310 315 320 Val Ile Thr Gly Ala Val val Ala Ala Val Met Trp Arg Arg Lys Ser 325 330 335 Ser Asp Arg Lys Gly Gly Ser Tyr Thr Gln Ala Ala Ser Ser Asp Ser 340 345 350 Ala Gln Gly Ser Asp Val Ser Leu Thr Ala Cys Lys Val 355 360 365 <210> 2531 <211> 155 <212> PRT <213> Homo sapiens <400> 2531

PCT/US2003/012946

Met Glu Leu Arg Ser Gly Ser val Gly Ser Gln Ala val Ala Arg Arg 1 5 10 15 Met Asp Gly Asp Ser Arg Asp Gly Gly Gly Gly Lys Asp Ala Thr Gly

Ser Glu Asp Tyr Glu Asn Leu Pro Thr Ser Ala Ser Val Ser Thr His 40 45 Met Thr Ala Gly Ala Met Ala Gly Ile Leu Glu His Ser val Met Tyr 50 55 60 Pro Val Asp Ser val Lys Thr Arg Met Gln Ser Leu Ser Pro Asp Pro €5 70 75 80 Lys Ala Gln Tyr Thr Ser Ile Tyr Gly Ala Leu Lys Lys Ile Met Arg 85 50 95 Thr Glu Gly Phe Trp Arg Pro Leu Arg Gly Val Asn Val Met Ile Met 100 10S 110 Gly Ala Gly Pro Ala His Ala Met Tyr Phe Ala Cys Tyr Glu Asn Met 115 120 125 Lys Arg Thr Leu Asn Asp Val Phe His His Gln Gly Asn Ser His Leu 130 135 140 Ala Asn Gly Ile Leu Lys Ala Phe Val Trp Ser 145 150 155 <210> 2532 <211> 384 <212> PRT <213> Homo sapiens <400> 2532 Met Lys Val Thr Ser Leu Asp Gly Arg Gln Leu Arg Lys Met Leu Arg 1 S 10 15 Lys Glu Ala Ala Ala Arg Cys Val val Leu Asp Cys Arg Pro Tyr Leu 20 25 30 Ala Phe Ala Ala Ser Asn Val Arg Gly Ser Leu Asn Val Asn Leu Asn 35 40 45 Ser Val Val Leu Arg Arg Ala Arg Gly Gly Ala Val Ser Ala Arg Tyr 50 55 60

PCT/US2003/012946

Val Leu Pro Asp Glu Ala Ala Arg Ala Arg Leu Leu Gln Glu Gly Gly 65 70 75 80 Gly Gly Val Ala Ala Val Val Val Leu Asp Gln Gly Ser Arg His Trp 85 S0 95 Gln Lys Leu Arg Glu Glu Ser Ala Ala Arg Val Val Leu Thr Ser Leu 100 105 110 Leu Ala Cys Leu Pro Ala Gly Pro Arg Val Tyr Phe Leu Lys Gly Gly 115 120 125 Tyr Glu Thr Phe Tyr Ser Glu Tyr Pro Glu Cys Cys Val Asp Val Lys 130 135 140 Pro Ile Ser Gln Glu Lys Ile Glu Ser Glu Arg Ala Leu Ile Ser Gln 145 150 155 160 Cys Gly Lys Pro Val Val Asn Val Ser Tyr Arg Pro Ala Tyr Asp Gln 165 170 175 Gly Gly Pro Val Glu Ile Leu Pro Phe Leu Tyr Leu Gly Ser Ala Tyr 180 185 150 His Ala Ser Lys Cys Glu Phe Leu Ala Asn Leu His Ile Thr Ala Leu 195 200 205 } Leu Asn Val Ser Arg Arg Thr Ser Glu Ala Cys Met Thr His Leu His 210 215 220 Tyr Lys Trp Ile Pro Val Glu Asp Ser His Thr Ala Asp Ile Ser Ser 225 230 235 240 His Phe Gln Glu Ala Ile Asp Phe Ile Asp Cys Val Arg Glu Lys Gly 245 250 255 Gly Lys Val Leu Val His Cys Glu Ala Gly Ile Ser Arg Ser Pro Thr 260 265 270 Ile Cys Met Ala Tyr Leu Met Lys Thr Lys Gln Phe Arg Leu Lys Glu 275 280 285 Ala Phe Asp Tyr Ile Lys Gln Arg Arg Ser Met Val Ser Pro Asn Phe 290 295 300

Gly Phe Met Gly Gln Leu Leu Gln Tyr Glu Ser Glu Ile Leu Pro Ser 305 310 315 320 Thr Pro Asn Pro Gln Pro Pro Ser Cys Gln Gly Glu Ala Ala Gly Ser 325 330 335 Ser Leu Ile Gly His Leu Gln Thr Leu Ser Pro Asp Met Gln Gly Ala 340 34S 350 Tyr Cys Thr Phe Pro Ala Ser Val Leu Ala Pro Val Pro Thr His Ser 355 360 365 Thr Val Ser Glu Leu Ser Arg Ser Pro Val Ala Thr Ala Thr Ser Cys 370 375 380 <210> 2533 <211> 899 <212> PRT <213> Homo sapiens <400> 2533 ’ Met Ala Gln Gly Lys Val Ala Ser Leu Gly Pro Ile Lys Gln His Thr 1 Ss 10 15 Phe Leu Lys Asn Met Gly Ile Asp Val Arg Leu Lys Val Leu Leu Asp

Lys Ser Asn Glu Pro Ser Val Arg Gln Gln Leu Leu Gln Gly Tyr Asp 40 45 Met Leu Met Asn Pro Lys Lys Met Gly Glu Arg Phe Asn Phe Phe Ala 50 55 60 Leu Leu Pro His Gln Arg Leu Gln Gly Gly Arg Tyr Gln Arg Asn Ala €5 70 75 80 Arg Gln Ser Lys Pro Phe Ala Ser val Val Ala Gly Phe Ser Glu Leu 85 ‘ 90 95 Ala Trp Gln . <210> 2534 <211> 529 <212> PRT <213> Homo sapiens

<400> 2534 Met Gly Ser Ser Arg Ala Pro Trp Met Gly Arg val Gly Gly His Gly 1 1) 10 15 Met Met Ala Leu Leu Leu Ala Gly Leu Leu Leu Pro Gly Thr Leu Ala

Lys Ser Ile Gly Thr Phe Ser Asp Pro Cys Lys Asp Pro Thr Arg Ile 40 45 Thr Ser Pro Asn Asp Pro Cys Leu Thr Gly Lys Gly Asp Ser Ser Gly 50 55 60 Phe Ser Ser Tyr Ser Gly Ser Ser Ser Ser Gly Ser Ser Ile Ser Ser 65 70 75 80 Ala Arg Ser Ser Gly Gly Gly Ser Ser Gly Ser Ser Ser Gly Ser Ser 85 90 95 Ile Ala Gln Gly Gly Ser Ala Gly Ser Phe Lys Pro Gly Thr Gly Tyr 100 "105 110 Ser Gln Val Ser Tyr Ser Ser Gly Ser Gly Ser Ser Leu Gln Gly ala 115 120 125 Ser Gly Ser Ser Gln Leu Gly Ser Ser Ser Ser His Ser Gly Ser Ser 130 135 140 Gly Ser His Ser Gly Ser Ser Ser Ser His Ser Ser Ser Ser Ser Ser 145 150 155 160 Phe Gln Phe Ser Ser Ser Ser Phe Gln Val Gly Asn Gly Ser Ala Leu 165 170 175 Pro Thr Asn Asp Asn Ser Tyr Arg Gly Ile Leu Asn Pro Ser Gln Pro 180 185 180 Gly Gln Ser Ser Ser Ser Ser Gln Thr Ser Gly Val Ser Ser Ser Gly 195 200 205 Gln Ser Val Ser Ser Asn Gln Arg Pro Cys Ser Ser Asp Ile Pro Asp 210 215 220 Ser Pro Cys Ser Gly Gly Pro Ile Val Ser His Ser Gly Pro Tyr Ile 225 230 235 240

Pro Ser Ser His Ser Val Ser Gly Gly Gln Arg Pro val Val Val val 245 250 255 Val Asp Gln His Gly Ser Gly Ala Pro Gly Val Val Gln Gly Pro Pro 260 265 270 Cys Ser Asn Gly Gly Leu Pro Gly Lys Pro Cys Pro Pro Ile Thr Ser 275 280 285 Val Asp Lys Ser Tyr Gly Gly Tyr Glu Val val Gly Gly Ser Ser Asp 290 295 300 Ser Tyr Leu Val Pro Gly Met Thr Tyr Ser Lys Gly Lys Ile Tyr Pro 305 310 315 320 Val Gly Tyr Phe Thr Lys Glu Asn Pro Val Lys Gly Ser Pro Gly val 325 330 335 Pro Ser Phe Ala Ala Gly Pro Pro Ile Ser Glu Gly Lys Tyr Phe Ser 340 345 350 Ser Asn Pro Ile Ile Pro Ser Gln Ser Ala Ala Ser Ser Ala Ile Ala 355 360 365 Phe Gln Pro Val Gly Thr Gly Gly Val Gln Leu Cys Gly Gly Gly Ser 370 375 380 Thr Gly Ser Lys Gly Pro Cys Ser Pro Ser Ser Ser Arg Val Pro Ser 385 390 395 400 Ser Ser Ser Ile Ser Ser Ser Ser Gly Ser Pro Tyr His Pro Cys Gly 405 410 415 Ser Ala Ser Gln Ser Pro Cys Ser Pro Pro Gly Thr Gly Ser Phe Ser 420 425 430 Ser Ser Ser Ser Ser Gln Ser Ser Gly Lys Ile Ile Leu Gln Pro Cys 435 440 445 Gly Ser Lys Ser Ser Ser Ser Gly His Pro Cys Met Ser Val Ser Ser 450 455 460 Leu Thr Leu Thr Gly Gly Pro Asp Gly Ser Pro His Pro Asp Pro Ser 465 470 475 480

Ala Gly Ala Lys Pro Cys Gly Ser Ser Ser Ala Gly Lys Ile Pro Cys 485 490 495 Arg Ser Ile Arg Asp Ile Leu Ala Gln Val Lys Pro Leu Gly Pro Gln 500 505 510 Leu Ala Asp Pro Glu Val Phe Leu Pro Gln Gly Glu Leu Leu Asp Ser 515 520 525 Pro <210> 2535 <211> 125 <212> PRT <213> Homo sapiens <400> 2535 Met Pro Pro Lys Asp Asp Lys Lys Lys Lys Asp Ala Gly Lys Ser Ala 1 5 10 15 Lys Lys Asp Lys Asp Pro Val Asn Lys Ser Gly Gly Lys Ala Lys Lys

Lys Lys Trp Ser Lys Gly Lys Val Arg Asp Lys Leu Asn Asn Leu Val 38 40 45 Leu Phe Asp Lys Ala Thr Tyr Asp Lys Leu Cys Lys Glu Val Pro Asn 50 1) 60 Tyr Lys Leu Ile Thr Pro Ala Val Val Ser Glu Arg Leu Lys Ile Arg 65 70 75 80 Gly Ser Leu Ala Arg Ala Ala Leu Gln Glu Leu Leu Ser Lys Gly Leu 85 90 95 Ile Lys Leu Val Ser Lys His Arg Ala Gln Val Ile Tyr Thr Arg Asn 100 105 110 Thr Lys Gly Gly Asp Ala Pro Ala Ala Gly Glu Asp Ala 115 120 125 <210> 2536 <211> 335 <212> PRT <213> Homo sapiens <400> 2536 .

PCT/US2003/012946

Met Gly Lys Val Lys Val Gly Val Asn Gly Phe Gly Arg Ile Gly Arg 1 S 10 15 Leu Val Thr Arg Ala Ala Phe Asn Ser Gly Lys Val Asp Ile val Ala

Ile Asn Asp Pro Phe Ile Asp Leu Asn Tyr Met Val Tyr Met Phe Gln 40 45 Tyr Asp Ser Thr His Gly Lys Phe His Gly Thr Val Lys Ala Glu Asn 50 55 60 Gly Lys Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe Gln Glu Arg 65 70 75 80 Asp Pro Ser Lys Ile Lys Trp Gly Asp Ala Gly Ala Glu Tyr Val val 85 90 95 Glu Ser Thr Gly Val Phe Thr Thr Met Glu Lys Ala Gly Ala His Leu 100 105 110 Gln Gly Gly Ala Lys Arg Val Ile Ile Ser Ala Pro Ser Ala Asp Ala 115 120 125 Pro Met Phe Val Met Gly Val Asn His Glu Lys Tyr Asp Asn Ser Leu 130 135 140 Lys Ile Ile Ser Asn Ala Ser Cys Thr Thr Asn Cys Leu Ala Pro Leu - 145 150 155 160 Ala Lys Val Ile His Asp Asn Phe Gly Ile Val Glu Gly Leu Met Thr 165 170 175 Thr Val His Ala Ile Thr Ala Thr Gln Lys Thr val Asp Gly Pro Ser 180 185 190 Gly Lys Leu Trp Arg Asp Gly Arg Gly Ala Leu Gln Asn Ile Ile Pro 185 200 205 Ala ser Thr Gly Ala Ala Lys Ala Val Gly Lys Val Ile Pro Glu Leu 210 215 220 Asn Gly Lys Leu Thr Gly Met Ala Phe Arg Val Pro Thr Ala Asn Val 225 230 235 240

Ser Val Val Asp Leu Thr Cys Arg Leu Glu Lys Pro Ala Lys Tyr Asp 245 250 255 Asp Ile Lys Lys val Val Lys Gln Ala Ser Glu Gly Pro Leu Lys Gly 260 . 265 270 Ile Leu Gly Tyr Thr Glu His Gln Val Val Ser Ser Asp Phe Asn Ser 275 280 285 Asp Thr His Ser Ser Thr Phe Asp Ala Gly Ala Gly Ile Ala Leu Asn 290 295 300 Asp His Phe Val Lys Leu lle Ser Trp Tyr Asp Asn Glu Phe Gly Tyr 305 310 315 320 Ser Asn Arg Val Val Asp Leu Met Ala His Met Ala Ser Lys Glu 325 330 335 <210> 2537 <211> 114 <«212> PRT <213> Homo sapiens <400> 2537 Met Ala Ser Val Ser Glu Leu Ala Cys Ile Tyr Ser Ala Leu Ile Leu 1 5 10 15 His Asp Asp Glu Val Thr Val Thr Glu Asp Lys Ile Asn Ala Leu Ile

Lys Ala Ala Gly Val Asn Val Glu Pro Phe Trp Pro Gly Leu Phe Ala 40 45 Lys Ala Leu Ala Asn Val Asn Ile Gly Ser Leu Ile Cys Asn val Gly 50 55 60 Ala Gly Gly Pro Ala Pro Ala Ala Gly Ala Ala Pro Ala Gly Gly Pro 65 70 75 80 Ala Pro Ser Thr Ala Ala Ala Pro Ala Glu Glu Lys Lys Val Glu Ala 85 90 95 Lys Lys Glu Glu Ser Glu Glu Ser Asp Asp Asp Met Gly Phe Gly Leu 100 105 110 Phe Asp

<210> 2538

<211> 142

<212> PRT

<213> Homo sapiens

<400> 2538

Met Ala Ala Gly Gly Ser Asp Pro Arg Ala Gly Asp Val Glu Glu Asp

1 5 10 15 hla Ser Gln Leu Ile Phe Pro Lys Glu Phe Glu Thr Ala Glu Thr Leu

Leu Asn Ser Glu Val His Met Leu Leu Glu His Arg Lys Gln Gln Asn

40 45 Glu Ser Ala Glu Asp Glu Gln Glu Leu Ser Glu Val Phe Met Lys Thr 50 55 60

Leu Asn Tyr Thr Ala Arg Phe Ser Arg Phe Lys Asn Arg Glu Thr Ile

€5 70 75 80

Ala Ser Val Arg Ser Leu Leu Leu Gln Lys Lys Leu His Lys Phe Glu

85 80 95

Leu Ala Cys Leu Ala Asn Leu Cys Pro Glu Thr Ala Glu Glu Ser Lys 100 105 110

Ala Leu Ile Pro Ser Leu Glu Gly Arg Phe Glu Asp Glu Glu Leu Gln

115 120 125 Gln Ile Leu Asp Asp Ile Gln Thr Lys Arg Ser Phe Gln Tyr 130 135 140

<210> 2539

<21l> 178

<212> PRT

<213> Homo sapiens

<400> 2539

Met Pro Ala Tyr His Ser Ser Leu Met Asp Pro Asp Thr Lys Leu Ile

1 5 10 15

Gly Asn Met Ala Leu Leu Pro Ile Arg Ser Gln Phe Lys Gly Pro Ala 20 25 30

Pro Arg Glu Thr Lys Asp Thr Asp Ile Val Asp Glu Ala Ile Tyr Tyr

35 40 45 Phe Lys Ala Asn Val Phe Phe Lys Asn Tyr Glu Ile Lys Asn Glu Ala 50 55 60 Asp Arg Thr Leu Ile Tyr Ile Thr Leu Tyr Ile Ser Glu Cys Leu Lys €5 70 75 80 Lys Leu Gln Lys Cys Asn Ser Lys Ser Gln Gly Glu Lys Glu Met Tyr 85 S90 95 . Thr Leu Gly Ile Thr Asn Phe Pro Ile Pro Gly Glu Pro Gly Phe Pro 100 105 110 Leu Asn Ala Ile Tyr Ala Lys Pro Ala Asn Lys Gln Glu Asp Glu Val 115 120 125 Met Arg Ala Tyr Leu Gln Gln Leu Arg Gln Glu Thr Gly Leu Arg Leu 130 135 140 Cys Glu Lys Val Phe Asp Pro Gln Asn Asp Lys Pro Ser Lys Trp Trp 145 150 155 160 Thr Cys Phe Val Lys Arg Gln Phe Met Asn Lys Ser Leu Ser Gly Pro 165 170 175 Gly Gln . <210> 2540 <211l> 351 <212> PRT <213> Homo sapiens <400> 2540 Met Glu Thr Asn Phe Ser Thr Pro Leu Asn Glu Tyr Glu Glu Val Ser 1 5 10 15 Tyr Glu Ser Ala Gly Tyr Thr Val Leu Arg Ile Leu Pro Leu Val val

Leu Gly Val Thr Phe Val Leu Gly Val Leu Gly Asn Gly Leu Val Ile 40 45 Trp Val Ala Gly Phe Arg Met Thr Arg Thr val Thr Thr Ile Cys Tyr 50 55 60

Leu Asn Leu Ala Leu Ala Asp Phe Ser Phe Thr Ala Thr Leu Pro Phe €5 70 75 80 Leu Ile Val Ser Met Ala Met Gly Glu Lys Trp Pro Phe Gly Trp Phe } 85 90 95 Leu Cys Lys Leu Ile His Ile Val Val Asp Ile Asn Leu Phe Gly Ser 100 105 110 Val Phe Leu Ile Gly Phe Ile Ala Leu Asp Arg Cys Ile Cys Val Leu 115 120 125 His Pro Val Trp Ala Gln Asn His Arg Thr Val Ser Leu Ala Met Lys 130 135 140 Val Ile Val Gly Pro Trp Ile Leu Ala Leu Val Leu Thr Leu Pro Val 145 150 155 160 Phe Leu Phe Leu Thr Thr Val Thr Ile Pro Asn Gly Asp Thr Tyr Cys 165 170 175 Thr Phe Asn Phe Ala Ser Trp Gly Gly Thr Pro Glu Glu Arg Leu Lys 180 185 190 Val Ala Ile Thr Met Leu Thr Ala Arg Gly Ile Ile Arg Phe Val Ile 195 200 205 Gly Phe Ser Leu Pro Met Ser Ile Val Ala Ile Cys Tyr Gly Leu Ile 210 215 220 Ala Ala Lys Ile His Lys Lys Gly Met Ile Lys Ser Ser Arg Pro Leu 225 230 235 240 Arg Val Leu Thr Ala Val Val Ala Ser Phe Phe Ile Cys Trp Phe Pro 245 250 255 Phe Gln Leu Val Ala Leu Leu Gly Thr Val Trp Leu Lys Glu Met Leu 260 265 270 Phe Tyr Gly Lys Tyr Lys Ile Ile Asp Ile Leu Val Asn Pro Thr Ser 275 280 285 Ser Leu Ala Phe Phe Asn Ser Cys Leu Asn Pro Met Leu Tyr Val Phe 290 295 300

Val Gly Gln Asp Phe Arg Glu Arg Leu Ile His Ser Leu Pro Thr Ser 305 310 315 320 Leu Glu Arg Ala Leu Ser Glu Asp Ser Ala Pro Thr Asn Asp Thr Ala 325 330 335 Ala Asn Ser Ala Ser Pro Pro Ala Glu Thr Glu Leu Gln Ala Met 340 345 350 <210> 2541 <211l> 349 <212> PRT <213> Homo sapiens <400> 2541 Met Glu Thr Pro Pro Val Asn Thr Ile Gly Glu Lys Asp Thr Ser Gln 1 S 10 15 Pro Gln Gln Glu Trp Glu Lys Asn Leu Arg Glu Asn Leu Asp Ser Val Ile Gln Ile Arg Gln Gln Pro Arg Asp Pro Pro Thr Glu Thr Leu Glu 40 45 Leu Glu Val Ser Pro Asp Pro Ala Ser Gln Ile Leu Glu His Thr Gln 50 55 60 Gly Ala Glu Lys Leu Val Ala Glu Leu Glu Gly Asp Ser His Lys Ser €5 70 75 80 His Gly Ser Thr Ser Gln Met Pro Glu Ala Leu Gln Ala Ser Asp Leu 85 90 8S Trp Tyr Cys Pro Asp Gly Ser Phe Val Lys Lys Ile Val Ile Arg Gly 100 105 110 His Gly Leu Asp Lys Pro Lys Leu Gly Ser Cys Cys Arg Val Leu Ala 115 120 125 Leu Gly Phe Pro Phe Gly Ser Gly Pro Pro Glu Gly Trp Thr Glu Leu 130 135 140 Thr Met Gly Val Gly Pro Trp Arg Glu Glu Thr Trp Gly Glu Leu Ile 145 150 155 160 Glu Lys Cys Leu Glu Ser Met Cys Gln Gly Glu Glu Ala Glu Leu Gln 165 170 175 910 k. ~

‘ 003/012946

Leu Pro Gly His Ser Gly Pro Pro Val Arg Leu Thr Leu Ala Ser Phe 80 185 150 Thr Gln Gly Arg Asp Ser Trp Glu Leu Glu Thr Ser Glu Lys Glu Ala 195 200 205 Leu Ala Arg Glu Glu Arg Ala Arg Gly Thr Glu Leu Phe Arg Ala Gly 210 218 220 Asn Pro Glu Gly Ala Ala Arg Cys Tyr Gly Arg Ala Leu Arg Leu Leu 225 230 235 240 Leu Thr Leu Pro Pro Pro Gly Pro Pro Glu Arg Thr Val Leu His Ala 245 250 255 Asn Leu Ala Ala Cys Gln Leu Leu Leu Gly Gln Pro Gln Leu Ala Ala 260 265 270 Gln Ser Cys Asp Arg Val Leu Glu Arg Glu Pro Gly His Leu Lys Ala 275 280 285 Leu Tyr Arg Arg Gly Val Ala Gln Ala Ala Leu Gly Asn Leu Glu Lys 290 29S 300 Ala Thr Ala Asp Leu Lys Lys Val Leu Ala Ile Asp Pro Lys Asn Arg 305 310 315 320 Ala Ala Gln Glu Glu Leu Gly Lys Val val Ile Gin Gly Lys Asn Gln 325 330 335 Asp Ala Gly Leu Ala Gln Gly Leu Arg Lys Met Phe Gly 340 345 <210> 2542 <211i> 417 <212> PRT <213> Homo sapiens <400> 2542 Met Gly Arg Arg Arg Ala Pro Glu Leu Tyr Arg Ala Pro Phe Pro Leu 1 5 10 15 Tyr Ala Leu Gln Val Asp Pro Ser Thr Gly Leu Leu Ile Ala Ala Gly

Gly Gly Gly Ala Ala Lys Thr Gly Ile Lys Asn Gly Val His Phe Leu 40 45 Gln Leu Glu Leu Ile Asn Gly Arg Leu Ser Ala Ser Leu Leu His Ser 50 55 60 His Asp Thr Glu Thr Arg Ala Thr Met Asn Leu Ala Leu Ala Gly Asp 65 70 78 80 Ile Leu Ala Ala Gly Gln Asp Ala His Cys Gln Leu Leu Arg Phe Gln 85 So 95 Ala His Gln Gln Gln Gly Asn Lys Ala Glu Lys Ala Gly Ser Lys Glu 100 105 110 Gln Gly Pro Arg Gln Arg Lys Gly Ala Ala Pro Ala Glu Lys Lys Cys 115 120 125 Gly Ala Glu Thr Gln His Glu Gly Leu Glu Leu Arg Val Glu Asn Leu 130 135 140 Gln Ala Val Gln Thr Asp Phe Ser Ser Asp Pro Leu Gln Lys Val Val 145 150 155 160 Cys Phe Asn His Asp Asn Thr Leu Leu Ala Thr Gly Gly Thr Asp Gly 165 170 175% Tyr Val Arg Val Trp Lys Val Pro Ser Leu Glu Lys Val Leu Glu Phe 180 185 190 Lys Ala His Glu Gly Glu Ile Glu Asp Leu Ala Leu Gly Pro Asp Gly 195 200 205 Lys Leu Val Thr Val Gly Arg Asp Leu Lys Ala Ser Val Trp Gln Lys 210 215 220 Asp Gln Leu Val Thr Gln Leu His Trp Gln Glu Asn Gly Pro Thr Phe 225 230 235 240 Ser Ser Thr Pro Tyr Arg Tyr Gln Ala Cys Arg Phe Gly Gln Val Pro 245 250 255 Asp Gln Pro Ala Gly Leu Arg Leu Phe Thr val Gln Ile Pro His Lys 260 265 270 Arg Leu Arg Gln Pro Pro Pro Cys Tyr Leu Thr Ala Trp Asp Gly Ser

275 280 285 Asn Phe Leu Pro Leu Arg Thr Lys Ser Cys Gly His Glu Val Val Ser 290 295 300 Cys Leu Asp Val Ser Glu Ser Gly Thr Phe Leu Gly Leu Gly Thr Val 305 310 315 320 Thr Gly Ser val Ala Ile Tyr Ile Ala Phe Ser Leu Gln Cys Leu Tyr 325 330 335 Tyr Val Arg Glu Ala His Gly Ile Val Val Thr Asp Val Ala Phe Leu 340 345 350 Pro Glu Lys Gly Arg Gly Pro Glu Leu Leu Gly Ser His Glu Thr Ala . 355 360 365 Leu Phe Ser Val Ala Val Asp Ser Arg Cys Gln Leu His Leu Leu Pro 370 375 380 Ser Arg Arg Ser Val Pro Val Trp Leu Leu Leu Leu Leu Cys Val Gly 385 390 395 400 Leu Ile Ile Val Thr Ile Leu Leu Leu Gln Ser Ala Phe Pro Gly Phe 405 410 415 Leu <210> 2543 <211> 308 <212> PRT <213> Homo sapiens <400> 2543 Met Arg Gln Asn Asp Lys Ile Met Cys Ile Leu Glu Asn Arg Lys Lys 1 5 10 15 Arg Asp Arg Lys Asn Leu Cys Arg Ala Ile Asn Asp Phe Gln Gln Ser

Phe Gln Lys Pro Glu Thr Arg Arg Glu Phe Asp Leu Ser Asp Pro Leu 40 45 Ala Leu Lys Lys Asp Leu Pro Ala Arg Gln Ser Asp Asn Asp Val Arg 50 55 60

Asn Thr Ile Ser Gly Met Gln Lys Phe Met Gly Glu Asp Leu Asn Phe 65 70 75 80 His Glu Arg Lys Lys Phe Gln Glu Glu Gln Asn Arg Glu Trp Ser Leu

85 90 95 Gln Gln Gln Arg Glu Trp Lys Asn Ala Arg Ala Glu Gln Lys Cys Ala 100 } 105 110 Glu Ala Leu Tyr Thr Glu Thr Arg Leu Gln Phe Asp Glu Thr Ala Lys 115 120 125 His Leu Gln Lys Leu Glu Ser Thr Thr Arg Lys Ala Val Cys Ala Ser 130 135 140 Val Lys Asp Phe Asn Lys Ser Gln Ala Ile Glu Ser Val Glu Arg Lys 145 150 155 160 Lys Gln Glu Lys Lys Gln Glu Gln Glu Asp Asn Leu Ala Glu Ile Thr 165 170 175 Asn Leu Leu Arg Gly Asp Leu Leu Ser Glu Asn Pro Gln Gln Ala Ala 180 185 190 Ser Ser Phe Gly Pro His Arg Val Val Pro Asp Arg Trp Lys Gly Met 185 200 205 Thr Gln Glu Gln Leu Glu Gln Ile Arg Leu Val Gln Lys Gln Gln Ile 210 215 220 Gln Glu Lys Leu Arg Leu Gln Glu Glu Lys Arg Gln Arg Asp Leu Asp 225 230 235 240 Trp Asp Arg Arg Arg Ile Gln Gly Ala Arg Ala Thr Leu Leu Phe Glu 245 250 255 Arg Gln Gln Trp Arg Arg Gln Arg Asp Leu Arg Arg Ala Leu Asp Ser 260 265 270 Ser Asn Leu Ser Leu Ala Lys Glu Gln His Leu Gln Lys Lys Tyr Met 275 280 285 Asn Glu Val Tyr Thr Asn Gln Pro Thr Gly Asp Tyr Phe Thr Gln Phe 2580 295 300

Asn Thr Gly Ser Arg

<210> 2544 <211> 838 <212> PRT <213> Homo sapiens <400> 2544 Met Gln Glu Gln Glu Ile Gly Phe Ile Ser Lys Tyr Asn Glu Gly Leu 1 5 10 15 Cys Val Asn Thr Asp Pro Val Ser Ile Leu Thr Ser Ile Leu Asp Met

Ser Leu His Arg Gln Met Gly Ser Asp Arg Asp Leu Gln Ser Ser Ala 40 45 Ser Ser Val Ser Leu Pro Ser Val Lys Lys Ala Pro Lys Lys Arg Arg S50 55 60 Ile Ser Ile Gly Ser Leu Phe Arg Arg Lys Lys Asp Asn Lys Arg Lys 65 70 75 80 Ser Arg Glu Leu Asn Gly Gly Val Asp Gly Ile Ala Ser Ile Glu Ser 85 90 95 Ile His Ser Glu Met Cys Thr Asp Lys Asn Ser Ile Phe Ser Thr Asn 100 105 110 Thr Ser Ser Asp Asn Gly Leu Thr Ser Ile Ser Lys Gln Ile Gly Asp 115 120 125 : Phe Ile Glu Cys Pro Leu Cys Leu Leu Arg His Ser Lys Asp Arg Phe 130 135 140 Pro Asp Ile Met Thr Cys His His Arg Ser Cys Val Asp Cys Leu Arg 145 150 155 160 Gln Tyr Leu Arg Ile Glu Ile Ser Glu Ser Arg Val Asn Ile Ser Cys 165 170 175 Pro Glu Cys Thr Glu Arg Phe Asn Pro His Asp Ile Arg Leu Ile Leu 180 18S 190 Ser Asp Asp Val Leu Met Glu Lys Tyr Glu Glu Phe Met Leu Arg Arg 195 200 205

Trp Leu Val Ala Asp Pro Asp Cys Arg Trp Cys Pro Ala Pro Asp Cys 210 215 220 Gly Tyr Ala val Ile Ala Phe Gly Cys Ala Ser Cys Pro Lys Leu Thr 225 230 235 240 Cys Gly Arg Glu Gly Cys Gly Thr Glu Phe Cys Tyr His Cys Lys Gln 245 250 255 Ile Trp His Pro Asn Gln Thr Cys Asp Ala Ala Arg Gln Glu Arg Ala 260 265 270 Gln Ser Leu Arg Leu Arg Thr Ile Arg Ser Ser Ser Ile Ser Tyr Ser 275 280 285 Gln Glu Ser Gly Ala Ala Ala Asp Asp Ile Lys Pro Cys Pro Arg Cys 290 295 300 Ala Ala Tyr Ile Ile Lys Met Asn Asp Gly Ser Cys Asn His Met Thr 305 310 315 320 Cys Ala Val Cys Gly Cys Glu Phe Cys Trp Leu Cys Met Lys Glu Ile 325 330 335 Ser Asp Leu His Tyr Leu Ser Pro Ser Gly Cys Thr Phe Trp Gly Lys 340 345 350 Lys Pro Trp Ser Arg Lys Lys Lys Ile Leu Trp Gln Leu Gly Thr Leu 355 360 365 val Gly Ala Pro Val Gly Ile Ala Leu Ile Ala Gly Ile Ala Ile Pro 370 375 380

Ala Met Ile Ile Gly Ile Pro Val Tyr Val Gly Arg Lys Ile His Asn

385 390 395 400

Arg Tyr Glu Gly Lys Asp Val Ser Lys His Lys Arg Asn Leu Ala Ile

405 410 415 Ala Gly Gly Val Thr Leu Ser Val Ile Val Ser Pro Val val Ala Ala 420 425 430 val Thr Val Gly Ile Gly val Pro Ile Met Leu Ala Tyr val Tyr Gly 435 440 445

Val Val Pro Ile Ser Leu Cys Arg Ser Gly Gly Cys Gly Val Ser Ala 450 455 460 Gly Asn Gly Lys Gly Val Arg Ile Glu Phe Asp Asp Glu Asn Asp Ile 465 470 47S 480 Asn Val Gly Gly Thr Asn Thr Ala Val Asp Thr Thr Ser Val Ala Glu 485 ) 490 495 Ala Arg His Asn Pro Ser Ile Gly Glu Gly Ser val Gly Gly Leu Thr 500 505 510 Gly Ser Leu Ser Ala Ser Gly Ser His Met Asp Arg Ile Gly Ala Ile 515 520 525 Arg Asp Asn Leu Ser Glu Thr Ala Ser Thr Met Ala Leu Ala Gly Ala S30 535% 540 Ser Ile Thr Gly Ser Leu Ser Gly Ser Ala Met Val Asn Cys Phe Asn 545 550 555 560 Arg Leu Glu Val Gln Ala Asp Val Gln Lys Glu Arg Tyr Ser Leu Ser 565 570 575 Gly Glu Ser Gly Thr Val Ser Leu Gly Thr Val Ser Asp Asn Ala Ser 580 585 590 Thr Lys Ala Met Ala Gly Ser Ile Leu Asn Ser Tyr Ile Pro Leu Asp 595 600 605 Lys Glu Gly Asn Ser Met Glu Val Gln Val Asp Ile Glu Ser Lys Pro 610 615 620 Ser Lys Phe Arg His Asn Ser Gly Ser Ser Ser Val Asp Asp Gly Ser 625 630 635 640 Ala Thr Arg Ser Tyr Ala Gly Gly Ser Ser Ser Gly Leu Pro Glu Gly 645 650 655 Lys Ser Ser Ala Thr Lys Trp Ser Lys Glu Ala Thr Ala Gly Lys Lys 660 665 670 Ser Lys Ser Gly Lys Leu Arg Lys Lys Gly Asn Met Lys Ile Asn Glu 675 680 685

Thr Arg Glu Asp Met Asp Ala Gln Leu Leu Glu Gln Gln Ser Thr Asn 630 695 700 . Ser Ser Glu Phe Glu Ala Pro Ser Leu Ser Asp Ser Met Pro Ser Val 705 710 715 720 Ala Asp Ser His Ser Ser His Phe Ser Glu Phe Ser Cys Ser Asp Leu 725 730 © 73S Glu Ser Met Lys Thr Ser Cys Ser His Gly Ser Ser Asp Tyr His Thr 740 745 750 Arg Phe Ala Thr Val Asn Ile Leu Pro Glu Val Glu Asn Asp Arg Leu 755 760 765 Glu Asn Ser Pro His Gln Cys Ser Ile Ser Val Val Thr Gln Thr Ala 770 ) 775 780 Ser Cys Ser Glu Val Ser Gln Leu Asn His Ile Ala Glu Glu His Gly 785 790 795 800 Asn Asn Gly Ile Lys Pro Asn Val Asp Leu Tyr Phe Gly Asp Ala Leu 805 810 815 Lys Glu Thr Asn Asn Asn His Ser His Gln Thr Met Glu Leu Lys Val 820 825 830 Ala Ile Gln Thr Glu Ile B35 <210> 2545 <211> 15389 <212> PRT <213> Homo sapiens <400> 2545 Met Glu Pro Gly Cys Asp Glu Phe Leu Pro Pro Pro Glu Cys Pro Val 1 5 10 15 Phe Glu Pro Ser Trp Ala Glu Phe Gln Asp Pro Leu Gly Tyr Ile Ala

20 . 25 30 Lys Ile Arg Pro Ile Ala Glu Lys Ser Gly Ile Cys Lys Ile Arg Pro 40 45 Pro Ala Asp Trp Gln Pro Pro Phe Ala Val Glu Val Asp Asn Phe Arg 50 55 60

Phe Thr Pro Arg Val Gln Arg Leu Asn Glu Leu Glu Ala Gln Thr Arg 65 70 75 80 Val Lys Leu Asn Tyr Leu Asp Gln Ile Ala Lys Phe Trp Glu Ile Gln 85 90 95 Gly Ser Ser Leu Lys Ile Pro Asn Val Glu Arg Lys Ile Leu Asp Leu 100 105 110 Tyr Ser Leu Ser Lys Ile Val Ile Glu Glu Gly Gly Tyr Glu Ala Ile 115 120 125 Cys Lys Asp Arg Arg Trp Ala Arg Val Ala Gln Arg Leu His Tyr Pro 130 135 140 Pro Gly Lys Asn Ile Gly Ser Leu Leu Arg Ser His Tyr Glu Arg Ile 145 150 155 160 Ile Tyr Pro Tyr Glu Met Phe Gln Ser Gly Ala Asn His Val Gln Cys 165 170 175 Asn Thr His Pro Phe Asp Asn Glu Val Lys Asp Lys Glu Tyr Lys Pro 180 185 150 His Ser Ile Pro Leu Arg Gln Ser Val Gln Pro Ser Lys Phe Ser Ser 195 200 205 Tyr Ser Arg Arg Ala Lys Arg Leu Gln Pro Asp Pro Glu Pro Thr Glu 210 215 220 Glu Asp Ile Glu Lys His Pro Glu Leu Lys Lys Leu Gln Ile Tyr Gly 225 230 235 240 Pro Gly Pro Lys Met Met Gly Leu Gly Leu Met Ala Lys Asp Lys Asp 245 250 255 Lys Thr Val His Lys Lys Val Thr Cys Pro Pro Thr Val Thr Val Lys 260 265 270 Asp Glu Gln Ser Gly Gly Gly Asn Val Ser Ser Thr Leu Leu Lys Gln 275 280 285 His Leu Ser Leu Glu Pro Cys Thr Lys Thr Thr Met Gln Leu Arg Lys 250 285 300

Asn His Ser Ser Ala Gln Phe Ile Asp Ser Tyr Ile Cys Gln Val Cys 305 310 315 320 Ser Arg Gly Asp Glu Asp Asn Lys Leu Leu Phe Cys Asp Gly Cys Asp

325 330 335 Asp Asn Tyr His Ile Phe Cys Leu Leu Pro Pro Leu Pro Glu Ile Pro 340 . 345 350 Arg Gly Ile Trp Arg Cys Pro Lys Cys Ile Leu Ala Glu Cys Lys Gln 355 360 365 Pro Pro Glu Ala Phe Gly Phe Glu Gln Ala Thr Gln Glu Tyr Ser Leu

370 375 380 Gln Ser Phe Gly Glu Met Ala Asp Ser Phe Lys Ser Asp Tyr Phe Asn 385 390 395 400 Met Pro Val His Met Val Pro Thr Glu Leu Val Glu Lys Glu Phe Trp

405 410 415 Arg Leu Val Ser Ser Ile Glu Glu Asp Val Thr Val Glu Tyr Gly Ala 420 425 430 Asp Ile His Ser Lys Glu Phe Gly Ser Gly Phe Pro Val Ser Asn Ser 435 440 445 Lys Gln Asn Leu Ser Pro Glu Glu Lys Glu Tyr Ala Thr Ser Gly Trp

450 455 460 Asn Leu Asn Val Met Pro Val Leu Asp Gln Ser Val Leu Cys His Ile 465 470 475 480 Asn Ala Asp lle Ser Gly Met Lys Val Pro Trp Leu Tyr Val Gly Met

485 490 495 Val Phe Ser Ala Phe Cys Trp His Ile Glu Asp His Trp Ser Tyr Ser 500 © 505 510 Ile Asn Tyr Leu His Trp Gly Glu Pro Lys Thr Trp Tyr Gly Val Pro 515 520 525 Ser Leu Ala Ala Glu His Leu Glu Glu Val Met Lys Met Leu Thr Pro 530 535 540

Glu Leu Phe Asp Ser Gln Pro Asp Leu Leu His Gln Leu Val Thr Leu 545 550 555 560 Met Asn Pro Asn Thr Leu Met Ser His Gly Val Pro Val Val Arg Thr 565 570 575 Asn Gln Cys Ala Gly Glu Phe val Ile Thr Phe Pro Arg Ala Tyr His 580 585 580 Ser Gly Phe Asn Gln Gly Tyr Asn Phe Ala Glu Ala Val Asn Phe Cys 595 600 605 Thr Ala Asp Trp Leu Pro Ala Gly Arg Gln Cys Ile Glu His Tyr Arg 610 615 . 620 Arg Leu Arg Arg Tyr Cys Val Phe Ser His Glu Glu Leu Ile Cys Lys £25 630 635 640 Met Ala Ala Phe Pro Glu Thr Leu Asp Leu Asn Leu Ala Val Ala Val 645 650 655 His Lys Glu Met Phe Ile Met Val Gln Glu Glu Arg Arg Leu Arg Lys 660 665 670 ’ Ala Leu Leu Glu Lys Gly Val Thr Glu Ala Glu Arg Glu Ala Phe Glu 675 680 685 Leu Leu Pro Asp Asp Glu Arg Gln Cys Ile Lys Cys Lys Thr Thr Cys 690 695 700 Phe Leu Ser Ala Leu Ala Cys Tyr Asp Cys Pro Asp Gly Leu Val Cys 705 710 715 720 Leu Ser His Ile Asn Asp Leu Cys Lys Cys Ser Ser Ser Arg Gln Tyr 725 730 735 Leu Arg Tyr Arg Tyr Thr Leu Asp Glu Leu Pro Thr Met Leu His Lys 740 745 750 Leu Lys Ile Arg Ala Glu Ser Phe Asp Thr Trp Ala Asn Lys Val Arg 755 760 765 val Ala Leu Glu Val Glu Asp Gly Arg Lys Arg Ser Phe Glu Glu Leu 770 775 780 Arg Ala Leu Glu Ser Glu Ala Arg Glu Arg Arg Phe Pro Asn Ser Glu

785 790 795 800 Leu Leu Gln Arg Leu Lys Asn Cys Leu Ser Glu Val Glu Ala Cys Ile 805 810 815 Ala Gln Val Leu Gly Leu Val Ser Gly Gln Val Ala Arg Met Asp Thr 820 825 830 Pro Gln Leu Thr Leu Thr Glu Leu Arg Val Leu Leu Glu Gln Met Gly 835 B40 845 Ser Leu Pro Cys Ala Met His Gln Ile Gly Asp Val Lys Asp Val Leu 850 855 860 Glu Gln Val Glu Ala Tyr Gln Ala Glu Ala Arg Glu Ala Leu Ala Thr 865 870 875 880 Leu Pro Ser Ser Pro Gly Leu Leu Arg Ser Leu Leu Glu Arg Gly Gln 885 890 895 Gln Leu Gly Val Glu Val Pro Glu Ala His Gln Leu Gln Gln Gln Val 500 905 910 Glu Gln Ala Gln Trp Leu Asp Glu Val Lys Gln Ala Leu Ala Pro Ser 915 920 925 Ala His Arg Gly Ser Leu Val Ile Met Gln Gly Leu Leu Val Met Gly 930 935 940 Ala Lys Ile Ala Ser Ser Pro Ser Val Asp Lys Ala Arg Ala Glu Leu 945 950 955 960 Gln Glu Leu Leu Thr Ile Ala Glu Arg Trp Glu Glu Lys Ala His Phe 965 870 975 Cys Leu Glu Ala Arg Gln Lys His Pro Pro Ala Thr Leu Glu Ala Ile 980 98S 990 Ile Arg Glu Thr Glu Asn Ile Pro Val His Leu Pro Asn Ile Gln Ala 995 1000 1005 Leu Lys Glu Ala Leu Thr Lys Ala Gln Ala Trp Ile Ala Asp Val 1010 1018 1020 Asp Glu Ile Gln Asn Gly Asp His Tyr Pro Cys Leu Asp Asp Leu 1025 1030 1035S

Glu Gly Leu val Ala Val Gly Arg Asp Leu Pro Val Gly Leu Glu 1040 1045 1050 Glu Leu Arg Gln Leu Glu Leu Gln Val Leu Thr Ala His Ser Trp 1055 1060 1065 Arg Glu Lys Ala Ser Lys Thr Phe Leu Lys Lys Asn Ser Cys Tyr 1070 1075 1080 Thr Leu Leu Glu Val Leu Cys Pro Cys Ala Asp Ala Gly Ser Asp 1085 1090 1085 Ser Thr Lys Arg Ser Arg Trp Met Glu Lys Ala Leu Gly Leu Tyr 1100 1105 1110 Gln Cys Asp Thr Glu Leu Leu Gly Leu Ser Ala Gln Asp Leu Arg 1115 1120 1125 Asp Pro Gly Ser Val Ile Val Ala Phe Lys Glu Gly Glu Gln Lys 1130 1135 1140 Glu Lys Glu Gly Ile Leu Gln Leu Arg Arg Thr Asn Ser Ala Lys 1145 1150 1155 Pro Ser Pro Leu Ala Pro Ser Leu Met Ala Ser Ser Pro Thr Ser 1160 1165 1170 Ile Cys Val Cys Gly Gln Val Pro Ala Gly Val Gly Leu Leu Gln : 1175 1180 1185 Cys Asp Leu Cys Gln Asp Trp Phe His Gly Gln Cys Val Ser Val 1190 1195 1200 Pro His Leu Leu Thr Ser Pro Lys Pro Ser Leu Thr Ser Ser Pro 1205 1210 1215 Leu Leu Ala Trp Trp Glu Trp Asp Thr Lys Phe Leu Cys Pro Leu 1220 1225 1230 Cys Met Arg Ser Arg Axg Pro Arg Leu Glu Thr Ile Leu Ala Leu 1235 1240 1245 Leu Val Ala Leu Gln Arg Leu Pro Val Arg Leu Pro Glu Gly Glu 1250 1255 1260

Ala Leu Gln Cys Leu Thr Glu Arg Ala Ile Gly Trp Gln Asp Arg 1265 1270 1275 ala Arg Lys Ala Leu Ala Phe Glu Asp Val Thr Ala Leu Leu Arg 1280 1285 1290 Gln Leu Ala Glu Leu Arg Gln Gln Leu Gln Ala Lys Pro Arg Pro 1285 1300 1305 Glu Glu Ala Ser Val Tyr Thr Ser Ala Thr Ala Cys Asp Pro Ile 1310 1315 1320 Arg Glu Gly Ser Gly Asn Asn Ile Ser Lys Val Gln Gly Leu Leu 1325 1330 1335 Glu Asn Gly Asp Ser Val Thr Ser Pro Glu Asn Met Ala Pro Gly 1340 1345 1350 Lys Gly Ser Asp Leu Glu Leu Leu Ser Ser Leu Leu Pro Gln Leu 1355 1360 1365 Thr Gly Pro Val Leu Glu Leu Pro Glu Ala Ile Arg Ala Pro Leu 1370 1375 1380 Glu Glu Leu Met Met Glu Gly Gly Leu Leu Glu Val Thr Leu Asp 1385 1390 1395 Glu Asn His Ser Ile Trp Gln Leu Leu Gln Ala Gly Gln Pro Pro 1400 1405 1410 Asp Leu Asp Arg Ile Arg Thr Leu Leu Glu Leu Glu Lys Phe Glu 1415 1420 1425 His Gln Gly Ser Arg Thr Arg Ser Arg Ala Leu Glu Arg Arg Arg 1430 1435 1440 Arg Arg Gln Lys Val Asp Gln Gly Arg Asn Val Glu Asn Leu Val 1445 1450 : 1455 Gln Gln Glu Leu Gln Ser Lys Arg Ala Arg Ser Ser Gly Ile Met 1460 1465 1470 Ser Gln Val Gly Arg Glu Glu Glu His Tyr Gln Glu Lys Ala Asp 1475 1480 1485

Arg Glu Asn Met Phe Leu Thr Pro Ser Thr Asp His Ser Pro Phe 1490 1495 1500 Leu Lys Gly Asn Gln Asn Ser Leu Gln His Lys Asp Ser Gly Ser 1505 1510 1515 Ser Bla Ala Cys Pro Ser Leu Met Pro Leu Leu Gln Leu Ser Tyr 1520 1525 1530 Ser Asp Glu Gln Gln Leu 1535 <210> 2546 <211> 274 <212> PRT <213> Homo sapiens <400> 2546 Met Gly Val Ser Ala Gln Asp Ile Phe Asn Ala Val Ile Lys Glu His 1 5 10 15 Pro Gly Leu Val Gln Arg Leu Pro Cys Val Trp Asn Val Gln Leu Ser

Asp His Thr Leu Ala Glu Arg Cys Tyr Ser Glu Ala Ser Asp Leu Lys 40 45 val Ile His Trp Asn Ser Pro Lys Lys Leu Arg Val Lys Asn Lys His 50 55 60 val Glu Phe Phe Arg Asn Phe Tyr Leu Thr Phe Leu Glu Tyr Asp Gly 65 70 75 80 Asn Leu Leu Arg Arg Glu Leu Phe Val Cys Pro Ser Gln Pro Pro Pro 85 90 95 Gly Ala Glu Gln Leu Gln Gln Ala Leu Ala Gln Leu Asp Gly Glu Asp 100 105 110 Pro Cys Phe Glu Phe Arg Gln Gln Gln Leu Thr Val His Arg Val His 115 120 125 val Thr Phe Leu Pro His Glu Pro Pro Pro Pro Arg Pro His Asp Val 130 135 140 Thr Leu Val Ala Gln Leu Ser Met Asp Arg Leu Gln Met Leu Glu Ala 145 150 155 160 .

Leu Cys Arg His Trp Pro Gly Pro Met Ser Leu Ala Leu Tyr Leu Thr 165 170 175

Asp Ala Glu Ala Gln Gln Phe Leu His Phe Val Glu Ala Ser Pro Val 180 185 190

Leu Ala Ala Arg Gln Asp Val Ala Tyr His Val val Tyr Arg Glu Gly

195 200 205 Pro Leu Tyr Pro Val Asn Gln Leu Arg Asn Val Ala Leu Ala Gln Ala 210 215 220

Leu Thr Pro Tyr Val Phe Leu Ser Asp Ile Asp Phe Leu Pro Ala Tyr

225 230 235 240

Ser Leu Tyr Asp Tyr Leu Arg Glu Ala Arg Ala Gly Phe Asn Ser Ser

245 250 255

Ser Thr Cys Gly Cys Ala His Pro Ser His Gln Ala Arg Trp Pro Met 260 265 270 val val

<210> 2547

<21l1l> 504

<212> PRT

<213> Homo sapiens

<400> 2547

Met Val Ala Pro Gly Ser Val Thr Ser Arg Leu Gly Ser Val Phe Pro

1 5 10 15

Phe Leu Leu Val Leu Val Asp Leu Gln Tyr Glu Gly Ala Glu Cys Gly

Val Asn Ala Asp Val Glu Lys His Leu Glu Leu Gly Lys Lys Leu Leu

40 45 Ala Ala Gly Gln Leu Ala Asp Ala Leu Ser Gln Phe His Ala Ala Val 50 55 60 Asp Gly Asp Pro Asp Asn Tyr Ile Ala Tyr Tyr Arg Arg Ala Thr val 65 70 75 80

Phe Leu Ala Met Gly Lys Ser Lys Ala Ala Leu Pro Asp Leu Thr Lys 85 90 95 Val Ile Gln Leu Lys Met Asp Phe Thr Ala Ala Arg Leu Gln Arg Gly 100 105 110 His Leu Leu Leu Lys Gln Gly Lys Leu Asp Glu Ala Glu Asp Asp Phe 115 120 125 Lys Lys Val Leu Lys Ser Asn Pro Ser Glu Asn Glu Glu Lys Glu Ala 130 135 140 Gln Ser Gln Leu Ile Lys Ser Asp Glu Met Gln Arg Leu Arg Ser Gln 145 150 155 160 Ala Leu Asn Ala Phe Gly Ser Gly Asp Tyr Thr Ala Ala Ile Ala Phe 165 170 175 Leu Asp Lys Ile Leu Glu Val Cys Val Trp Asp Ala Glu Leu Arg Glu 180 185 190 Leu Arg Ala Glu Cys Phe Ile Lys Glu Gly Glu Pro Arg Lys Ala Ile 195 200 205 Ser Asp Leu Lys Ala Ala Ser Lys Leu Lys Asn Asp Asn Thr Glu Ala 210 215 220 Phe Tyr Lys Ile Ser Thr Leu Tyr Tyr Gln Leu Gly Asp His Glu Leu 225 230 235 240 Ser Leu Ser Glu Val Arg Glu Cys Leu Lys Leu Asp Gln Asp His Lys 245 250 255 Arg Cys Phe Ala His Tyr Lys Gln Val Lys Lys Leu Asn Lys Leu Ile 260 265 270 Glu Ser Ala Glu Glu Leu Ile Arg Asp Gly Arg Tyr Thr Asp Ala Thr 275 280 285 Ser Lys Tyr Glu Ser Val Met Lys Thr Glu Pro Ser Ile Ala Glu Tyr 290 295 300 Thr val Arg Ser Lys Glu Arg Ile Cys His Cys Phe Ser Lys Asp Glu 305 310 315 320 Lys Pro Val Glu Ala Ile Arg Val Cys Ser Glu Val Leu Gln Met Glu

325 330 335 Pro Asp Asn Val Asn Ala Leu Lys Asp Arg Ala Glu Ala Tyr Leu Ile 340 345 350 Glu Glu Met Tyr Asp Glu Ala Ile Gln Asp Tyr Glu Thr Ala Gln Glu 355 360 365 His Asn Glu Asn Asp Gln Gln Ile Arg Glu Gly Leu Glu Lys Ala Gln 370 375 380 Arg Leu Leu Lys Gln Ser Gln Lys Arg Asp Tyr Tyr Lys Ile Leu Gly 385 390 395 400 val Lys Arg Asn Ala Lys Lys Gln Glu Ile Ile Lys Ala Tyr Arg Lys 405 410 415 Leu Ala Leu Gln Trp His Pro Asp Asn Phe Gln Asn Glu Glu Glu Lys 420 425 430 Lys Lys Ala Glu Lys Lys Phe Ile Asp Ile Ala Ala Ala Lys Glu Val 435 440 445 Leu Ser Asp Pro Glu Met Arg Lys Lys Phe Asp Asp Gly Glu Asp Pro 450 455 460 Leu Asp Ala Glu Ser Gln Gln Gly Gly Gly Gly Asn Pro Phe His Arg 465 470 475 480 Ser Trp Asn Ser Trp Gln Gly Phe Asn Pro Phe Ser Ser Gly Gly Pro 485 490 495 Phe Arg Phe Lys Phe His Phe Asn 500 . <210> 2548 <21l1l> 258 <212> PRT <213> Homo sapiens <400> 2548 R Met Pro Pro Gln Gln Gly Asp Pro Ala Phe Pro Asp Arg Cys Glu Ala 1 S 10 15 Pro Pro Val Pro Pro Arg Arg Glu Arg Gly Gly Arg Gly Gly Arg Gly

Pro Gly Glu Pro Gly Gly Arg Gly Arg Ala Gly Gly Ala Glu Gly Arg 40 45 Gly val Lys Cys Val Leu Val Gly Asp Gly Ala Val Gly Lys Thr Ser SO 55 60 Leu Val Val Ser Tyr Thr Thr Asn Gly Tyr Pro Thr Glu Tyr Ile Pro 65 70 75 80 Thr Ala Phe Asp Asn Phe Ser Ala Val Val Ser Val Asp Gly Arg Pro 85 90 95 Val Arg Leu Gln Leu Cys Asp Thr Ala Gly Gln Asp Glu Phe Asp Lys 100 105 110 Leu Arg Pro Leu Cys Tyr Thr Asn Thr Asp Ile Phe Leu Leu Cys Phe 115 120 125 Ser Val Val Ser Pro Ser Ser Phe Gln Asn Val Ser Glu Lys Trp Val 130 135 140 Pro Glu Ile Arg Cys His Cys Pro Lys Ala Pro Ile Ile Leu val Gly 145 150 155 160 Thr Gln Ser Asp Leu Arg Glu Asp Val Lys Val Leu Ile Glu Leu Asp 165 170 175 Lys Cys Lys Glu Lys Pro Val Pro Glu Glu Ala Ala Lys Leu Cys Ala 180 185 190 Glu Glu Ile Lys Ala Ala Ser Tyr Ile Glu Cys Ser Ala Leu Thr Gln 185 200 205 Lys Asn Leu Lys Glu Val Phe Asp Ala Ala Ile Val Ala Gly Ile Gln 210 215 220 Tyr Ser Asp Thr Gln Gln Gln Pro Lys Lys Ser Lys Ser Arg Thr Pro 225 230 235 240 Asp Lys Met Lys Asn Leu Ser Lys Ser Trp Trp Lys Lys Tyr Cys Cys 245 250 255 Phe Val

<210> 2549 <211l> 394 <212> PRT <213> Homo sapiens <400> 2548 Met Phe Lys Lys Lys Ser His Val Arg Asn His Leu Arg Thr His Thr 1 5 10 15 Gly Glu Arg Pro Phe Pro Cys Pro Asp Cys Ser Lys Pro Phe Asn Ser

Pro Ala Asn Leu Ala Arg His Arg Leu Thr His Thr Gly Glu Arg Pro 40 45 Tyr Arg Cys Gly Asp Cys Gly Lys Ala Phe Thr Gln Ser Ser Thr Leu 50 55 60 Arg Gln His Arg Leu Val His Ala Gln His Phe Pro Tyr Arg Cys Gln 65 70 75 80 Glu Cys Gly Val Arg Phe His Arg Pro Tyr Arg Leu Leu Met His Arg 85 90 95 Tyr His His Thr Gly Glu Tyr Pro Tyr Lys Cys Arg Glu Cys Pro Arg 100 105 110 Ser Phe Leu Leu Arg Arg Leu Leu Glu Val His Gln Leu Val Val His 115 120 125 Ala Gly Arg Gln Pro His Arg Cys Pro Ser Cys Gly Ala Ala Phe Pro 130 135 140 Ser Ser Leu Arg Leu Arg Glu His Arg Cys Ala Ala Ala Ala Ala Gin 145 150 155 160 Ala Pro Arg Arg Phe Glu Cys Gly Thr Cys Gly Lys Lys Val Gly Ser 165 170 175 Ala Ala Arg Leu Gln Ala His Glu Ala Ala His Ala Ala Ala Gly Pro 180 185 190 . Gly Glu Val Leu Ala Lys Glu Pro Pro Ala Pro Arg Ala Pro Arg Ala 185 200 205 Thr Arg Ala Pro Val Ala Ser Pro Ala Ala Leu Gly Ser Thr Ala Thr 210 215 220

Ala Ser Pro Ala Ala Pro Ala Arg Arg Arg Gly Leu Glu Cys Ser Glu 225 230 235 240 Cys Lys Lys Leu Phe Ser Thr Glu Thr Ser Leu Gln Val His Arg Arg 245 250 255 Ile His Thr Gly Glu Arg Pro Tyr Pro Cys Pro Asp Cys Gly Lys Ala 260 265 270 Phe Arg Gln Ser Thr His Leu Lys Asp His Arg Arg Leu His Thr Gly 275 280 285 Glu Arg Pro Phe Ala Cys Glu Val Cys Gly Lys Ala Phe Ala Ile Ser 290 295 300 Met Arg Leu Ala Glu His Arg Arg Ile His Thr Gly Glu Arg Pro Tyr 305 310 315 320 Ser Cys Pro Asp Cys Gly Lys Ser Tyr Arg Ser Phe Ser Asn Leu Trp 325 330 335 Lys His Arg Lys Thr His Gln Gln Gln His Gln Ala Ala Val Arg Gln 340 345 350 Gln Leu Ala Glu Ala Glu Ala Ala Val Gly Leu Ala Val Met Glu Thr 355 360 365 Ala Val Glu Ala Leu Pro Leu Val Glu Ala Ile Glu Ile Tyr Pro Leu 370 375 380 Ala Glu Ala Glu Gly Val Gln Ile Ser Gly 385 3390 <210> 2550 <211> 415 <212> PRT <213> Homo sapiens <400> 2550 Met Glu Asp Leu Cys Val Ala Asn Thr Leu Phe Ala Leu Asn Leu Phe 1 5 10 15 Lys His Leu Ala Lys Ala Ser Pro Thr Gln Asn Leu Phe Leu Ser Pro

Trp Ser Ile Ser Ser Thr Met Ala Met val Tyr Met Gly Ser Arg Gly 40 45 Ser Thr Glu Asp Gln Met Ala Lys Val Leu Gln Phe Asn Glu Val Gly 50 55 60 Ala Asn Ala Val Thr Pro Met Thr Pro Glu Asn Phe Thr Ser Cys Gly 65 70 75 80 Phe Met Gln Gln Ile Gln Lys Gly Ser Tyr Pro Asp Ala Ile Leu Gln 85 90 9s Ala Gln Ala Ala Asp Lys Ile His Ser Ser Phe Arg Ser Leu Ser Ser 100 105 110 Ala Ile Asn Ala Ser Thr Gly Asn Tyr Leu Leu Glu Ser Val Asn Lys 115 120 125 Leu Phe Gly Glu Lys Ser Ala Ser Phe Arg Glu Glu Tyr Ile Arg Leu 130 135 140 Cys Gln Lys Tyr Tyr Ser Ser Glu Pro Gln Ala Val Asp Phe Leu Glu 145 150 155 160 Cys Ala Glu Glu Ala Arg Lys Lys Ile Asn Ser Trp Val Lys Thr Gln 165 170 175 Thr Lys Gly Lys Ile Pro Asn Leu Leu Pro Glu Gly Ser Val Asp Gly 180 185 190 } Asp Thr Arg Met Val Leu Val Asn Ala Val Tyr Phe Lys Gly Lys Trp 195 200 205 Lys Thr Pro Phe Glu Lys Lys Leu Asn Gly Leu Tyr Pro Phe Arg Val 210 215 220 Asn Ser Ala Gln Arg Thr Pro Val Gln Met Met Tyr Leu Arg Glu Lys 225 230 235 240 Leu Asn Ile Gly Tyr Ile Glu Asp Leu Lys Ala Gln Ile Leu Glu Leu 245 250 255 Pro Tyr Ala Gly Asp Val Ser Met Phe Leu Leu Leu Pro Asp Glu Ile 260 265 270 Ala Asp Val Ser Thr Gly Leu Glu Leu Leu Glu Ser Glu Ile Thr Tyr

275 280 285 Asp Lys Leu Asn Lys Trp Thr Ser Lys Asp Lys Met Ala Glu Asp Glu 290 295 300 val Glu Val Tyr Ile Pro Gln Phe Lys Leu Glu Glu His Tyr Glu Leu 305 310 315 320 Arg Ser Ile Leu Arg Ser Met Gly Met Glu Asp Ala Phe Asn Lys Gly 325 330 335 Arg Ala Asn Phe Ser Gly Met Ser Glu Arg Asn Asp Leu Phe Leu Ser 340 345 350 Glu Val Phe His Gln Ala Met Val Asp Val Asn Glu Glu Gly Thr Glu 355 360 365 ala Ala Ala Gly Thr Gly Gly Val Met Thr Gly Arg Thr Gly His Gly 370 375 380 Gly Pro Gln Phe Val Ala Asp His Pro Phe Leu Phe Leu Ile Met His 385 390 395 400 Lys Ile Thr Asn Cys Ile Leu Phe Phe Gly Arg Phe Ser Ser Pro 405 410 415 <210> 2551 <211> 434 <212> PRT <213> Homo sapiens <400> 2551 Met Ser Ile Leu Lys Ile His Ala Arg Glu Ile Phe Asp Ser Arg Gly 1 S 10 15 Asn Pro Thr Val Glu Val Asp Leu Phe Thr Ser Lys Gly Leu Phe Arg

Ala Ala Val Pro Ser Gly Ala Ser Thr Gly Ile Tyr Glu Ala Leu Glu 40 45 Leu Arg Asp Asn Asp Lys Thr Arg Tyr Met Gly Lys Gly val Ser Lys 50 55 60 Ala Val Glu His Ile Asn Lys Thr Ile Ala Pro Ala Leu Val Ser Lys 65 70 75 80

Lys Leu Asn Val Thr Glu Gln Glu Lys Ile Asp Lys Leu Met Ile Glu 85 90 95 Met Asp Gly Thr Glu Asn Lys Ser Lys Phe Gly Ala Asn Ala Ile Leu 100 105 110 Gly Val Ser Leu Ala Val Cys Lys Ala Gly Ala val Glu Lys Gly Val 115 120 125 Pro Leu Tyr Arg His Ile Ala Asp Leu Ala Gly Asn Ser Glu Val Ile 130 135 140 Leu Pro Val Pro Ala Phe Asn Val Ile Asn Gly Gly Ser His Ala Gly 145 150 155 160 Asn Lys Leu Ala Met Gln Glu Phe Met Ile Leu Pro Val Gly Ala Ala 165 170 175 Asn Phe Arg Glu Ala Met Arg Ile Gly Ala Glu Val Tyr His Asn Leu 180 185 190 Lys Asn Val Ile Lys Glu Lys Tyr Gly Lys Asp Ala Thr Asn Val Gly 195 200 205 Asp Glu Gly Gly Phe Ala Pro Asn Ile Leu Glu Asn Lys Glu Gly Leu 210 215 220 Glu Leu Leu Lys Thr Ala Ile Gly Lys Ala Gly Tyr Thr Asp Lys Val 225 230 235 240 Val Ile Gly Met Asp Val Ala Ala Ser Glu Phe Phe Arg Ser Gly Lys 245 250 255 Tyr Asp Leu Asp Phe Lys Ser Pro Asp Asp Pro Ser Arg Tyr Ile Ser 260 265 270 Pro Asp Gln Leu Ala Asp Leu Tyr Lys Ser Phe Ile Lys Asp Tyr Pro 275 280 285 Val val Ser Ile Glu Asp Pro Phe Asp Gln Asp Asp Trp Gly Ala Trp 290 295 300 Gln Lys Phe Thr Ala Ser Ala Gly Ile Gln Val Val Gly Asp Asp Leu 305 310 315 320

Thr Val Thr Asn Pro Lys Arg Ile Ala Lys Ala Val Asn Glu Lys Ser 325 330 335 Cys Asn Cys Leu Leu Leu Lys Val Asn Gln Ile Gly Ser Val Thr Glu 340 345 350 Ser Leu Gln Ala Cys Lys Leu Ala Gln Ala Asn Gly Trp Gly Val Met 355 360 365 val Ser His Arg Ser Gly Glu Thr Glu Asp Thr Phe Ile Ala Asp Leu 370 375 380 val Val Gly Leu Cys Thr Gly Gln Ile Lys Thr Gly Ala Pro Cys Arg 385 390 385 400 Ser Glu Arg Leu Ala Lys Tyr Asn Gln Leu Leu Arg Ile Glu Glu Glu 405 410 415 Leu Gly Ser Lys Ala Lys Phe Ala Gly Arg Asn Phe Arg Asn Pro Leu 420 425 430 Ala Lys ~~ <210> 2552 <211> 281 <212> PRT <213> Homo sapiens <400> 2552 Met Glu Val His Gln Gln Asn Ala Leu Phe Gln Tyr Phe Ala Asp Thr 1 5 10 15 Leu Thr Ala Val Val Gln Asn Ala Lys Lys Asn Gly Arg Tyr Asp Met

Gly Ile Leu Asp Leu Gly Ser Gly Asp Glu Lys Val Arg Lys Ser Asp 40 45 Val Lys Lys Phe Leu Thr Pro Gly Tyr Ser Thr Ser Gly His Val Glu 50 55 60 Leu Tyr Thr Ile Ser Val Glu Arg Gly Met Ser Trp Glu Glu Ala Thr 65 70 75 80 Lys 1le Trp Ala Glu Leu Thr Gly Pro Asp Asp Gly Phe Tyr Leu Ser 85 90 95

Leu Gln Ile Arg Asn Asn Lys Lys Thr Ala Ile Leu Val Lys Glu Val 100 105 110 Asn Pro Lys Lys Lys Leu Phe Leu Val Tyr Arg Pro Asn Thr Gly Lys 115 120 125 . Gln Leu Lys Leu Glu Ile Tyr Ala Asp Leu Lys Lys Lys Tyr Lys Lys 130 135 140 Val Val Ser Asp Asp Ala Leu Met His Trp Leu Asp Gln Tyr Asn Ser 145 150 155 160 Ser Ala Asp Thr Cys Thr His Ala Tyr Trp Arg Gly Asn Cys Lys Lys 165 170 175 Ala Ser Leu Gly Leu Val Cys Glu Ile Gly Leu Arg Cys Arg Thr Tyr 180 185 190 Tyr Val Leu Cys Gly Ser val Leu Ser Val Trp Thr Lys Val Glu Gly 195 200 205 Val Leu Ala Ser Val Ser Gly Thr Asn Val Lys Met Gln Ile Val Arg 210 215 220 Leu Arg Thr Glu Asp Gly Gln Arg Ile Val Gly Leu Ile Ile Pro Ala 225 230 235 240 Asn Cys Val Ser Pro Leu Val Asn Leu Leu Ser Thr Ser Asp Gln Ser 245 250 255 Gln Gln Leu Ala Val Gln Gln Lys Gln Leu Trp Gln Gln His His Pro 260 265 270 Gln Ser Ile Thr Asn Leu Ser Asn Ala 275 280 <210> 2553 <211> 176 <212> PRT <213> Homo sapiens <400> 2563 Met Lys Ala Ser Gly Thr Leu Arg Glu Tyr Lys Val Val Gly Arg Cys 1 5 10 15

Leu Pro Thr Pro Lys Cys His Thr Pro Pro Leu Tyr Arg Met Arg Ile

Phe Ala Pro Asn His Val Val Ala Lys Ser Arg Phe Trp Tyr Phe Val 40 45 Ser Gln Leu Lys Lys Met Lys Lys Ser Ser Gly Glu Ile Val Tyr Cys 50 55 60 Gly Gln Val Phe Glu Lys Ser Pro Leu Arg Val Lys Asn Phe Gly Ile 65 70 75 80 Trp Leu Arg Tyr Asp Ser Arg Ser Gly Thr His Asn Met Tyr Arg Glu 85 90 95 Tyr Arg Asp Leu Thr Thr Ala Gly Ala Val Thr Gln Cys Tyr Arg Asp 100 105 110 Met Gly Ala Arg His Arg Ala Arg Ala His Ser Ile Gln Ile Met Lys 115 120 125 val Glu Glu Ile Ala Ala Ser Lys Cys Arg Arg Pro Ala Val Lys Gln 130 135 140 Phe His Asp Ser Lys Ile Lys Phe Pro Leu Pro His Arg Val Leu Arg 145 150 155 160 Arg Gln His Lys Pro Arg Phe Thr Thr Lys Arg Pro Asn Thr Phe Phe 165 170 175 <210> 2554 <211> 363 <212> PRT <213> Homo sapiens <400> 2554 Met Ala Leu His Cys Gln Glu Phe Gly Gly Lys Asn Tyr Glu Ala Ser 1 5 10 15 Met Ser His Val Asp Lys Phe Val Lys Glu Leu Leu Sex Ser Asp Ala 20 25 30 Met Lys Glu Tyr Asn Arg Ala Arg Val Tyr Leu Asp Glu Asn Tyr Lys 35 40 45 Ser Gln Glu His Phe Thr Ala Leu Gly Ser Phe Tyr Phe Leu His Glu 50 55 60

Ny

Ser Leu Lys Asn Ile Tyr Gln Phe Asp Phe Lys Ala Lys Lys Tyr Arg 65 70 75 80 Lys Val Ala Gly Lys Glu Ile Tyr Ser Asp Thr Leu Glu Ser Thr Pro 85 20 95 Met Leu Glu Lys Glu Lys Phe Arg Arg Leu Leu Pro Arg Val Gln Met 100 105 110 Val Lys Lys Arg Leu His Pro Asp Glu Val Val Ile Ala Asp Cys Ala 115 120 125 Phe Asp Leu Val Asn Ile His Leu Phe His Asp Ala Ser Asn Leu Val 130 135 140 Ala Trp Glu Thr Ser Pro Ser Val Tyr Ser Gly Ile Arg His Lys Ala 145 150 155 160 Leu Gly Tyr Val Leu Asp Arg Ile Ile Asp Gln Arg Phe Glu Lys Val 165 170 175 Ser Tyr Phe val Phe Gly Asp Phe Asn Phe Arg Leu Asp Ser Lys Ser 180 185 130 Val Val Glu Thr Leu Ser Ala Lys Pro Pro Met Gln Thr Val Arg Ala 195 200 205 Ala Asp Thr Asn Glu Val Val Lys Leu Ile Phe Arg Glu Ser Asp Asn 210 215 220 Asp Arg Lys Val Met Leu Gln Leu Glu'Lys Lys Leu Phe Asp Tyr Phe 225 230 235 240 Asn Gln Glu Val Phe Arg Asp Asn Asn Gly Thr Ala Leu Leu Glu Phe 245 250 255 Asp Lys Glu Leu Ser Val Phe Lys Asp Arg Leu Tyr Glu Leu Asp Ile 260 265 270 Ser Phe Pro Pro Ser Tyr Pro Tyr Ser Glu Asp Ala Arg Gln Gly Glu 275 280 285 Gln Tyr Met Asn Thr Arg Cys Pro Ala Trp Cys Asp Arg Ile Leu Met 290 295 300 938 L

Ser Pro Ser Ala Lys Glu Leu Val Leu Arg Ser Glu Ser Glu Glu Lys 305 310 318 320 val Val Thr Tyr Asp His Ile Gly Pro Asn Val Cys Met Gly Asp His 325 330 335 Lys Pro Val Phe Leu Ala Phe Arg Ile Met Pro Gly Ala Gly Lys Pro 340 345. 350 His Ala His val His Lys Cys Cys Val Val Gln 355 360 <210> 2555 <211l> 56 <212> PRT <213> Homo sapiens <400> 2555 Met Gly His Gln Gln Leu Tyr Trp Ser His Pro Arg Lys Phe Gly Gln 1 5 10 15 Gly Ser Arg Ser Cys Arg Val Cys Ser Asn Arg His Gly Leu Ile Arg

Lys Tyr Gly Leu Asn Met Cys Arg Gln Cys Phe Arg Gln Tyr Ala Lys 40 45 Asp Ile Gly Phe Ile Lys Leu Asp 50 SS <210> 2556 <211l> 520 <212> PRT <213> Homo sapiens <400> 2556 Met Val Thr Ser Ser Phe Pro Ile Ser Val Ala Val Phe Ala Leu Ile 1 5 10 15 Thr Leu Gln Val Gly Thr Gln Asp Ser Phe Ile Ala Ala Val Tyr Glu 20 25 30 . His Ala Val Ile Leu Pro Asn Lys Thr Glu Thr Pro Val Ser Gln Glu 35 40 45 Asp Ala Leu Asn Leu Met Asn Glu Asn Ile Asp Ile Leu Glu Thr Ala 50 55 60

A

Ile Lys Gln Ala Ala Glu Gln Gly Ala Arg Ile Ile Val Thr Pro Glu 65 70 75 BO Asp Ala Leu Tyr Gly Trp Lys Phe Thr Arg Glu Thr Val Phe Pro Tyr 85 90 95 Leu Glu Asp Ile Pro Asp Pro Gln Val Asn Trp Ile Pro Cys Gln Asp 100 _ 105 110 Pro His Arg Phe Gly His Thr Pro val Gln Ala Arg Leu Ser Cys Leu 115 120 125 Ala Lys Asp Asn Ser Ile Tyr Val Leu Ala Asn Leu Gly Asp Lys Lys 130 135 140 Pro Cys Asn Ser Arg Asp Ser Thr Cys Pro Pro Asn Gly Tyr Phe Gln 145 150 155 160 Tyr Asn Thr Asn Val Val Tyr Asn Thr Glu Gly Lys Leu Val Ala Arg 165 170 175 Tyr His Lys Tyr His Leu Tyr Ser Glu Pro Gln Phe Asn Val Pro Glu : 180 185 190 Lys Pro Glu Leu Val Thr Phe Asn Thr Ala Phe Gly Arg Phe Gly Ile 195 200 205 Phe Thr Cys Phe Asp Ile Phe Phe Tyr Asp Pro Gly Val Thr Leu Val 210 215 220 Lys Asp Phe His Val Asp Thr Ile Leu Phe Pro Thr Ala Trp Met Asn 225 230 235 240 Val Leu Pro Leu Leu Thr Ala Ile Glu Phe His Ser Ala Trp Ala Met 245 250 255 Gly Met Gly Val Asn Leu Leu Val Ala Asn Thr His His Val Ser Leu 260 265 270 Asn Met Thr Gly Ser Gly Ile Tyr Ala Pro Asn Gly Pro Lys Val Tyr 275 280 285 His Tyr Asp Met Lys Thr Glu Leu Gly Lys Leu Leu Leu Ser Glu Val 230 295 300

PCT/US2003/012946

Asp Ser His Pro Leu Ser Ser Leu Ala Tyr Pro Thr Ala Val Asn Trp 305 310 315 320 Asn Ala Tyr Ala Thr Thr Ile Lys Pro Phe Pro Val Gln Lys Asn Thr 325 330 33s Phe Arg Gly Phe Ile Ser Arg Asp Gly Phe Asn Phe Thr Glu Leu Phe 340 345 350 Glu Asn Ala Gly Asn Leu Thr Val Cys Gln Lys Glu Leu Cys Cys His 355 360 365 Leu Ser Tyr Arg Met Leu Gln Lys Glu Glu Asn Glu Val Tyr Val Leu ) 370 375 380 Gly Ala Phe Thr Gly Leu His Gly Arg Arg Arg Arg Glu Tyr Trp Gln 385 380 395 400 Val Cys Thr Met Leu Lys Cys Lys Thr Thr Asn Leu Thr Thr Cys Gly 405 410 415 Arg Pro Val Glu Thr Ala Ser Thr Arg Phe Glu Met Phe Ser Leu Ser 420 425 430 Gly Thr Phe Gly Thr Glu Tyr Val Phe Pro Glu Val Leu Leu Thr Glu 435 440 445 Ile His Leu Ser Pro Gly Lys Phe Glu Val Leu Lys Asp Gly Arg Leu 450 455 460 Val Asn Lys Asn Gly Ser Ser Gly Pro Ile Leu Thr Val Ser Leu Phe 465 470 475 480 Gly Arg Trp Tyr Thr Lys Asp Ser Leu Tyr Ser Ser Cys Gly Thr Ser 485 490 495 Asn Ser Ala Ile Thr Tyr Leu Leu Ile Phe Ile Leu Leu Met Ile Ile 500 505 510 Ala Leu Gln Asn Ile Val Met Leu 515 520 «210> 2557 <211> 564 <212> PRT <213> Homo sapiens

PCT/US2003/012946

<400> 2557 Met Ser Ala Gly Ser Ala Thr His Pro Gly Ala Gly Gly Arg Arg Ser 1 5 10 15 Lys Trp Asp Gln Pro Ala Pro Ala Pro Leu Leu Phe Leu Pro Pro Ala

Ala Pro Gly Gly Glu Val Thr Ser Ser Gly Gly Ser Pro Gly Gly Thr 40 45 Thr Ala Ala Pro Ser Gly Ala Leu Asp Ala Ala Ala Ala Val Ala Ala 50 55 60 Lys Ile Asn Ala Met Leu Met Ala Lys Gly Lys Leu Lys Pro Thr Gln 65 70 75 80 Asn Ala Ser Glu Lys Leu Gln Ala Pro Gly Lys Gly Leu Thr Ser Asn 85 90 95 Lys Ser Lys Asp Asp Leu Val val Ala Glu Val Glu Ile Asn Asp Val 100 105 110 Pro Leu Thr Cys Arg Asn Leu Leu Thr Arg Gly Gln Thr Gln Asp Glu 115 120 125 Ile Ser Arg Leu Ser Gly Ala Ala Val Ser Thr Arg Gly Arg Phe Met 130 135 140 Thr Thr Glu Glu Lys ala Lys Val Gly Pro Gly Asp Arg Pro Leu Tyr 145 150 155 160 Leu His Val Gln Gly Gln Thr Arg Glu Leu Val Asp Arg Ala Val Asn 165 170 175 Arg Ile Lys Glu Ile Ile Thr Asn Gly val Val Lys Ala Ala Thr Gly 180 185 190 Thr Ser Pro Thr Phe Asn Gly Ala Thr val Thr val Tyr His Gln Pro 195 200 205 Ala Pro Ile Ala Gln Leu Ser Pro Ala val Ser Gln Lys Pro Pro Phe 210 215 220 Gln Ser Gly Met His Tyr Val Gln Asp Lys Leu Phe val Gly Leu Glu 2258 230 235 240

PCT/US2003/012946

His Ala Val Pro Thr Phe Asn Val Lys Glu Lys val Glu Gly Pro Gly 245 250 255 Cys Ser Tyr Leu Gln His Ile Gln Ile Glu Thr Gly Ala Lys Val Phe 260 265 270 leu Arg Gly Lys Gly Ser Gly Cys Ile Glu Pro Ala Ser Gly Arg Glu 27s 280 285 Ala Phe Glu Pro Met Tyr Ile Tyr Ile Ser His Pro Lys Pro Glu Gly 290 295 300 Leu Ala Ala Ala Lys Lys Leu Cys Glu Asn Leu Leu Gln Thr val His 305 310 315 320 Ala Glu Tyr Ser Arg Phe Val Asn Gln Ile Asn Thr Ala val Pro Leu 328 330 335 Pro Gly Tyr Thr Gln Pro Ser Ala Ile Ser Ser Val Pro Pro Gln Pro 340 345 350 Pro Tyr Tyr Pro Ser Asn Gly Tyr Gln Ser Gly Tyr Pro Val Val Pro 355 360 365 Pro Pro Gln Gln Pro Val Gln Pro Pro Tyr Gly val Pro Ser Ile val 370 375 380 Pro Pro Ala Val Ser Leu Ala Pro Gly Val Leu Pro Ala Leu Pro Thr 385 390 395 400 Gly Val Pro Pro Val Pro Thr Gln Tyr Pro Ile Thr Gln Val Gln Pro 405 410 415 Pro Ala Ser Thr Gly Gln Ser Pro Met Gly Gly Pro Phe Ile Pro Ala 420 425 430 Ala Pro Val Lys Thr Ala Leu Pro Ala Gly Pro Gln Pro Gln Pro Gln 435 440 445 Pro Gln Pro Pro Leu Pro Ser Gln Pro Gln Ala Gln Lys Arg Arg Phe 450 455 460 Thr Glu Glu Leu Pro Asp Glu Arg Glu Ser Gly Leu Leu Gly Tyr Gln 465 470 475 480

==="

His Gly Pro Ile His Met Thr Asn Leu Gly Thr Gly Phe Ser ser Gln 485 490 495 Asn Glu Ile Glu Gly Ala Gly ser Lys pro Ala Ser Ser ser Gly Lys 500 505 510 glu Arg Glu Arg Asp Arg Gln Leu Met Pro pro Pro Ala Phe Pro Val 515 520 525 Thr Gly Tle Lys Thr Glu Ser Asp Glu Arg Asn Gly Ser gly Thr Leu 530 53% 540 Thr Gly Ser His Gly Glu Cys ASP 11e Ala Gly Gly Thr Gly Glu TIP 545 550 555 560 Leu Arg Leu val <210> 2558 <211> 462 <212> PRT <213> Homo sapiens <400> 2558 Met Gly Llvys glu Lys Thr His Ile Asn Ile val val ile Gly His val 1 5 10 15 Asp Ser Gly Lys ser Thr Thr Thr Gly His Leu Ile TYT Lys Cys Gly

Gly lle Asp Lys Arg Thr Ile Glu Lys Phe Glu Lys Glu Ala Ala Glu 40 45 met Gly LYS Gly Ser phe Lys TYT ala Trp yal Leu Asp Lys Leu Lys 50 55 60 ala Glu Arg glu Arg Gly Ile Thr Ile Asp 11e Ser Leu Trp Lys Phe 65 70 75 80 Glu Thr Ser Lys Tyr TYY val Thr Ile 1le Asp Ala Pro Gly His AYg. - 85 90 95 Asp Phe Tle Lys Asn Met Ile Thr Gly Thr Ser Gln hla Asp cys Ala 100 105 110 val Leu Ile val Ala Ala Gly yal Gly Glu phe Glu Ala Gly Ile Ser 944 Fa

1S2003/012946

115 120 125 Lys Asn Gly Gln Thr Arg Glu His Ala Leu Leu Ala Tyr Thr Leu Gly 130 135 140 Val Lys Gln Leu Ile Val Gly Val Asn Lys Met Asp Ser Thr Glu Pro 145 150 155 160 Pro Tyr Ser Gln Lys Arg Tyr Glu Glu Ile Val Lys Glu val Ser Thr 165 170 175 Tyr Ile Lys Lys Ile Gly Tyr Asn Pro Asp Thr val Ala Phe Val Pro 180 185 190 Ile Ser Gly Trp Asn Gly Asp Asn Met Leu Glu Pro Ser Ala Asn Met 195 200 205 Pro Trp Phe Lys Gly Trp Lys Val Thr Arg Lys Asp Gly Asn Ala Ser 210 215 220 Gly Thr Thr Leu Leu Glu Ala Leu Asp Cys Ile Leu Pro Pro Thr Arg 225 230 235 240 Pro Thr Asp Lys Pro Leu Arg Leu Pro Leu Gln Asp Val Tyr Lys Ile 245 250 255 Gly Gly Ile Gly Thr Val Pro Val Gly Arg Val Glu Thr Gly Val Leu 260 265 270 Lys Pro Gly Met Val Val Thr Phe Ala Pro Val Asn Val Thr Thr Glu 275 280 285 Val Lys Ser Val Glu Met His His Glu Ala Leu Ser Glu Ala Leu Pro 290 295 300 Gly Asp Asn Val Gly Phe Asn Val Lys Asn Val Ser val Lys Asp Val 305 310 315 320 Arg Arg Gly Asn Val Ala Gly Asp Ser Lys Asn Asp Pro Pro Met Glu 325 330 335 Ala Ala Gly Phe Thr Ala Gln Val Ile Ile Leu Asn His Pro Gly Gln 340 345 . 350 Ile Ser Ala Gly Tyr Ala Pro Val Leu Asp Cys His Thr Ala His Ile 3588 360 365

PCT/US2003/012946

Ala Cys Lys Phe Ala Glu Leu Lys Glu Lys Ile Asp Arg Arg ser Gly 370 37s 380 Lys Lys Leu Glu Asp Gly Pro Lys Phe Leu Lys Ser Gly Asp Ala ala 385 390 395 400 Ile Val Asp Met Val Pro Gly Lys Pro Met Cys Val Glu Ser Phe Ser : 405 410 415 Asp Tyr Pro Pro Leu Gly Arg Phe Ala Val Arg Asp Met Arg Gln Thr 420 425 430 Val Ala val Gly val Ile Lys Ala Val Asp Lys Lys Ala Ala Gly Ala 435 440 445 Gly Lys Val Thr Lys Ser Ala Gln Lys Ala Gln Lys Ala Lys 450 455 460 <210> 2559 <21ll> 394 <212> PRT <213> Homo sapiens <400> 2559 Met Ser Gly Glu Asp Glu Gln Gln Glu Gln Thr Ile Ala Glu Asp Leu 1 S 10 15 Val val Thr Lys Tyr Lys Met Gly Gly Asp Ile Ala Asn Arg Val Leu

Arg Ser Leu Val Glu Ala Ser Ser Ser Gly Val Ser Val Leu Ser Leu 40 45 Cys Glu Lys Gly Asp Ala Met Ile Met Glu Glu Thr Gly Lys Ile Phe 50 55 60 Lys Lys Glu Lys Glu Met Lys Lys Gly Ile Ala Phe Pro Thr Ser Ile 65 70 75 80 Ser Val Asn Asn Cys Val Cys His Phe Ser Pro Leu Lys Ser Asp Gln 85 90 95 Asp Tyr Ile Leu Lys Glu Gly Asp Leu Val Lys Ile Asp Leu Gly val 100 105 110

PCT/US2003/012946

His Val Asp Gly Phe Ile Ala Asn Val Ala His Thr Phe val Val Asp 115 120 125 Val Ala Gln Gly Thr Gln Val Thr Gly Arg Lys Ala Asp Val Ile Lys 130 135 140 Ala Ala His Leu Cys Ala Glu Ala Ala Leu Arg Leu Val Lys Pro Gly 145 150 155 160 Asn Gln Asn Thr Gln Val Thr Glu Ala Trp Asn Lys Val Ala His Ser 165 170 175 Phe Asn Cys Thr Pro Ile Glu Gly Met Leu Ser His Gln Leu Lys Gln 180 185 190 His Val Ile Asp Gly Glu Lys Thr Ile Ile Gln Asn Pro Thr Asp Gln 155 200 205 Gln Lys Lys Asp His Glu Lys Ala Glu Phe Glu Val His Glu Val Tyr 210 215 220 Ala val Asp Val Leu Val Ser Ser Gly Glu Gly Lys Ala Lys Asp Ala 225 230 235 240 Gly Gln Arg Thr Thr Ile Tyr Lys Arg Asp Pro Ser Lys Gln Tyr Gly 245 250 255 Leu Lys Met Lys Thr Ser Arg Ala Phe Phe Ser Glu val Glu Arg Arg 260 265 270 Phe Asp Ala Met Pro Phe Thr Leu Arg Ala Phe Glu Asp Glu Lys Lys 275 280 285 Ala Arg Met Gly Val Val Glu Cys Ala Lys His Glu Leu Leu Gln Pro 290 285 300 Phe Asn Val Leu Tyr Glu Lys Glu Gly Glu Phe Val Ala Gin Phe Lys 30S 310 315 320 Phe Thr Val Leu Leu Met Pro Asn Gly Pro Met Arg Ile Thr Ser Gly 325 330 335 Pro Phe Glu Pro Asp Leu Tyr Lys Ser Glu Met Glu Val Gln Asp Ala 340 345 350 Glu Leu Lys Ala Leu Leu Gln Ser Ser Ala Ser Arg Lys Thr Gln Lys 947 o

355 360 365 Lys Lys Lys Lys Lys Ala Ser Lys Thr Ala Glu Asn Pro Thr Ser Gly 370 375 380 Glu Thr Leu Glu Glu Asn Glu Ala Gly Asp 385 390 <210> 2560 <211> 335 <212> PRT <213> Homo sapiens <400> 2560 Met Gly Lys Val Lys Val Gly Val Asn Gly Phe Gly Arg Ile Gly Arg 1 5 10 15 : Leu Val Thr Arg Ala Ala Phe Asn Ser Gly Lys Val Asp Ile Val Ala

Ile Asn Asp Pro Phe Ile Asp Leu Asn Tyr Met Val Tyr Met Phe Gln 40 45 Tyr Asp Ser Thr His Gly Lys Phe His Gly Thr Val Lys Ala Glu Asn 50 55 60 Gly Lys Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe Gln Glu Arg 65 70 75 80 Asp Pro Ser Lys Ile Lys Trp Gly Asp Ala Gly Ala Glu Tyr Val Val 85 90 95 Glu Ser Thr Gly Val Phe Thr Thr Met Glu Lys Ala Gly Ala His Leu 100 105 110 Gln Gly Gly Ala Lys Arg Val Ile Ile Ser Ala Pro Ser Ala Asp Ala 115 120 125 Pro Met Phe Val Met Gly Val Asn His Glu Lys Tyr Asp Asn Ser Leu 130 135 140 Lys Ile Ile Ser Asn Ala Ser Cys Thr Thr Asn Cys Leu Ala Pro Leu 145 150 155 160 Ala Lys Val Ile His Asp Asn Phe Gly Ile Val Glu Gly Leu Met Thr 165 170 175

Thr Val His ala Ile Thr Ala Thr Gln Lys Thr Val Asp Gly Pro Ser 180 185 150 Gly Lys Leu Trp Arg Asp Gly Arg Gly Ala Leu Gln Asn Ile Ile Pro 185 200 205 Ala Ser Thr Gly Ala Ala Lys Ala val Gly Lys Val Ile Pro Glu Leu 210 215 220 Asn Gly Lys Leu Thr Gly Met Ala Phe Arg Val Pro Thr Ala Asn Val 225 230 235 240 Ser Val Val Asp Leu Thr Cys Arg Leu Glu Lys Pro Ala Lys Tyr Asp 245 250 255 Asp Ile Lys Lys Val Val Lys Gln Ala Ser Glu Gly Pro Leu Lys Gly 260 265 270 Ile Leu Gly Tyr Thr Glu His Gln Val Val Ser Ser Asp Phe Asn Ser 275 280 285 Asp Thr His Ser Ser Thr Phe Asp Ala Gly Ala Gly Ile Ala Leu Asn 290 2985 300 Asp His Phe Val Lys Leu Ile Ser Trp Tyr Asp Asn Glu Phe Gly Tyr 305 310 315 320 Ser Asn Arg Val Val Asp Leu Met Ala His Met Ala Ser Lys Glu 325 330 335 <210> 2561 <211l> 1912 <212> PRT <213> Homo sapiens <400> 2561 Met Ala Ser Gly Leu Gly Ser Pro Ser Pro Cys Ser Ala Gly Ser Glu 1 5 10 15 Glu Glu Asp Met Asp Ala Leu Leu Asn Asn Ser Leu Pro Pro Pro His .

Pro Glu Asn Glu Glu Asp Pro Glu Glu Asp Leu Ser Glu Thr Glu Thr 40 45 Pro Lys Leu Lys Lys Lys Lys Lys Pro Lys Lys Pro Arg Asp Pro Lys

50 55 60 ‘ Ile Pro Lys Ser Lys Arg Gln Lys Lys Glu Arg Met Leu Leu Cys Arg 65 70 75 80 Gln Leu Gly Asp Ser Ser Gly Glu Gly Pro Glu Phe Val Glu Glu Glu 85 90 9s Glu Glu Val Ala Leu Arg Ser Asp Ser Glu Gly Ser Asp Tyr Thr Pro 100 105 110 Gly Lys Lys Lys Lys Lys Lys Leu Gly Pro Lys Lys Glu Lys Lys Ser 115 120 125 Lys Ser Lys Arg Lys Glu Glu Glu Glu Glu Asp Asp Asp Asp Asp Asp 130 135 140 Ser Lys Glu Pro Lys Ser Ser Ala Gln Leu Leu Glu Asp Trp Gly Met 145 150 155 ‘ 160 Glu Asp Ile Asp His Val Phe Ser Glu Glu Asp Tyr Arg Thr Leu Thr 165 170 175 Asn Tyr Lys Ala Phe Ser Gln Phe Val Arg Pro Leu Ile Ala Ala Lys 180 185 190 Asn Pro Lys Ile Ala Val Ser Lys Met Met Met Val Leu Gly Ala Lys 195 200 205 Trp Arg Glu Phe Ser Thr Asn Asn Pro Phe Lys Gly Ser Ser Gly Ala 210 215 220 Ser Val Ala Ala Ala Ala Ala Ala Ala Val Ala Val Val Glu Ser Met 225 230 235 240 Val Thr Ala Thr Glu Val Ala Pro Pro Pro Pro Pro Val Glu Val Pro 245 250 255 Ile Arg Lys Ala Lys Thr Lys Glu Gly Lys Gly Pro Asn Ala Arg Arg 260 . 265 270 Lys Pro Lys Gly Ser Pro Arg Val Pro Asp Ala Lys Lys Pro Lys Pro 275 280 285 Lys Lys Val Ala Pro Leu Lys Ile Lys Leu Gly Gly Phe Gly Ser Lys 290 295 300

Arg Lys Arg Ser Ser Ser Glu Asp Asp Asp Leu Asp Val Glu Ser Asp 305 310 31s 320 Phe Asp Asp Ala Ser Ile Asn Ser Tyr Ser Val Ser Asp Gly Ser Thr

325 330 335 Ser Arg Ser Ser Arg Ser Arg Lys Lys Leu Arg Thr Thr Lys Lys Lys 340 345 350 Lys Lys Gly Glu Glu Glu Val Thr Ala Val Asp Gly Tyr Glu Thr Asp 355 360 365 His Gln Asp Tyr Cys Glu Val Cys Gln Gln Gly Gly Glu Ile Ile Leu 370 375 380 Cys Asp Thr Cys Pro Arg Ala Tyr His Met Val Cys Leu Asp Pro Asp 385 390 395 400 Met Glu Lys Ala Pro Glu Gly Lys Trp Ser Cys Pro His Cys Glu Lys 405 410 415 Glu Gly Ile Glm Trp Glu Ala Lys Glu Asp Asn Ser Glu Gly Glu Glu 420 425 430 Ile Leu Glu Glu Val Gly Gly Asp Leu Glu Glu Glu Asp Asp His His 435 440 445 Met Glu Phe Cys Arg Val Cys Lys Asp Gly Gly Glu Leu Leu Cys Cys 450 455 460 Asp Thr Cys Pro Ser Ser Tyr His Ile His Cys Leu Asn Pro Pro Leu 465 470 475 480 Pro Glu Ile Pro Asn Gly Glu Trp Leu Cys Pro Arg Cys Thr Cys Pro 485 490 495 Ala Leu Lys Gly Lys Val Gln Lys Ile Leu Ile Trp Lys Trp Gly Gln 500 505 510 Pro Pro Ser Pro Thr Pro Val Pro Arg Pro Pro Asp Ala Asp Pro Asn 515 520 525 Thr Pro Ser Pro Lys Pro Leu Glu Gly Arg Pro Glu Arg Gln Phe Phe 530 535 540

PCT/US2003/012946

Val Lys Trp Gln Gly Met Ser Tyr Trp His Cys Ser Trp Val Ser Glu 545 550 555 560 Leu Gln Leu Glu Leu His Cys Gln Val Met phe Arg Asn Tyr Gln Arg 565 570 575 Lys Asn Asp Met Asp Glu Pro Pro Ser Gly Asp Phe Gly Gly Asp Glu 580 585 590 Glu Lys Ser Arg Lys Arg Lys Asn Lys Asp Pro Lys Phe Ala Glu Met 585 600 605 Glu Glu Arg Phe Tyr Arg Tyr Gly Ile Lys Pro Glu Trp Met Met Ile 610 615 620 His Arg Ile Leu Asn His Ser Val Asp Lys Lys Gly His Val His Tyr 625 630 635 640 Leu Ile Lys Trp Arg Asp Leu Pro Tyr Asp Gln Ala Ser Trp Glu Ser 645 650 655 Glu Asp Val Glu Ile Gln Asp Tyr Asp Leu Phe Lys Gln Ser Tyr Trp 660 665 670 Asn His Arg Glu Leu Met Arg Gly Glu Glu Gly Arg Pro Gly Lys Lys 675 680 685 Leu Lys Lys Val Lys Leu Arg Lys Leu Glu Arg Pro Pro Glu Thr Pro 690 695 700 Thr Val Asp Pro Thr Val Lys Tyr Glu Arg Gln Pro Glu Tyr Leu Asp 705 710 715 720 Ala Thr Gly Gly Thr Leu His Pro Tyr Gln Met Glu Gly Leu Asn Trp 725 730 735 Leu Arg Phe Ser Trp Ala Gin Gly Thr Asp Thr Ile Leu Ala Asp Glu 740 745 750 Met Gly Leu Gly Lys Thr Val Gln Thr Ala Val Phe Leu Tyr Ser Leu 755 760 765 Tyr Lys Glu Gly His Ser Lys Gly Pro Phe Leu Val Ser Ala Pro Leu 770 775 780 952 w

PCT/US2003/012946 .

Ser Thr Ile Ile Asn Trp Glu Arg Glu Phe Glu Met Trp Ala Pro Asp 785 790 795 800 Met Tyr val Val Thr Tyr Val Gly Asp Lys Asp Ser Arg Ala Ile Ile 80S 810 815 Arg Glu Asn Glu Phe Ser Phe Glu Asp Asn Ala Ile Arg Gly Gly Lys 820 825 830 Lys Ala Ser Arg Met Lys Lys Glu Ala Ser val Lys Phe His Val Leu 835 840 845 Leu Thr Ser Tyr Glu Leu Ile Thr Ile Asp Met Ala Ile Leu Gly Ser 850 855 860 Ile Asp Trp Ala Cys Leu Ile Val Asp Glu Ala His Arg Leu Lys Asn 865 870 875 880 Asn Gln Ser Lys Phe Phe Arg Val Leu Asn Gly Tyr Ser Leu Gln His 885 890 895 Lys Leu Leu Leu Thr Gly Thr Pro Leu Gln Asn Asn Leu Glu Glu Leu S00 905 910 Phe His Leu Leu Asn Phe Leu Thr Pro Glu Arg Phe His Asn Leu Glu 915 920 925 Gly Phe Leu Glu Glu Phe Ala Asp Ile Ala Lys Glu Asp Gln Ile Lys 930 935 940 Lys Leu His Asp Met Leu Gly Pro His Met Leu Arg Arg Leu Lys Ala 945 950 855 960 Asp Val Phe Lys Asn Met Pro Ser Lys Thr Glu Leu Ile Val Arg Val 965 $70 975 Glu Leu Ser Pro Met Gln Lys Lys Tyr Tyr Lys Tyr Ile Leu Thr Arg 980 985 990 Asn Phe Glu Ala Leu Asn Ala Arg Gly Gly Gly Asn Gln Val Ser Leu 985 1000 1005 Leu Asn Val Val Met Asp Leu Lys Lys Cys Cys Asn His Pro Tyr 1010 1015 1020 Leu Phe Pro Val Ala Ala Met Glu Ala Pro Lys Met Pro Asn Gly

1025 1030 1035 Met Tyr Asp Gly Ser Ala Leu Ile Arg Ala Ser Gly Lys Leu Leu 1040 1045 1050 Leu Leu Gln Lys Met Leu Lys Asn Leu Lys Glu Gly Gly His Arg 1055 1060 1065 Val Leu Ile Phe Ser Gln Met Thr Lys Met Leu Asp Leu Leu Glu 1070 1075 1080 Asp Phe Leu Glu-His Glu Gly Tyr Lys Tyr Glu Arg Ile Asp Gly 1085 1090 1095 Gly Ile Thr Gly Asn Met Arg Gln Glu Ala Ile Asp Arg Phe Asn 1100 1105 1110 Ala Pro Gly Ala Gln Gln Phe Cys Phe Leu Leu Ser Thr Arg Ala 1115 1120 : 1125 Gly Gly Leu Gly Ile Asn Leu Ala Thr Ala Asp Thr Val Ile Iie 1130 1135 1140 Tyr Asp Ser Asp Trp Asn Pro His Asn Asp Ile Gln Ala Phe Ser 1145 1150 1155 Arg Ala His Arg Ile Gly Gln Asn Lys Lys Val Met Ile Tyr Arg 1160 1165 1170 Phe Val Thr Arg Ala Ser val Glu Glu Arg Ile Thr Gln Val Ala 1175 1180 1185 Lys Lys Lys Met Met Leu Thr His Leu Val Val Arg Pro Gly Leu 1190 1195 1200 Gly Ser Lys Thr Gly Ser Met Ser Lys Gln Glu Leu Asp Asp Ile 1205 1210 1215 Leu Lys DPhe Gly Thr Glu Glu Leu Phe Lys Asp Glu Ala Thr Asp 1220 1225 1230 Gly Gly Gly Asp Asn Lys Glu Gly Glu Asp Ser Ser Val Ile His 1235 1240 1245 Tyr Asp Asp Lys Ala Ile Glu Arg Leu Leu Asp Arg Asn Gln Asp 1250 1255 1260

PCT/US2003/012946

Glu Thr Glu Asp Thr Glu Leu Gln Gly Met Asn Glu Tyr Leu Ser 1265 1270 1275 Ser Phe Lys Val Ala Gln Tyr val Val Arg Glu Glu Glu Met Gly 1280 1285 1290 Glu Glu Glu Glu val Glu Arg Glu Ile Ile Lys Gln Glu Glu Ser 1295 1300 1305 Val Asp Pro Asp Tyr Trp Glu Lys Leu Leu Arg His His Tyr Glu 1310 1315 1320 Gln Gln Gln Glu Asp Leu Ala Arg Asn Leu Gly Lys Gly Lys Arg 1325 1330 1335 Ile Arg Lys Gln Val Asn Tyr Asn Asp Gly Ser Gln Glu Asp Arg 1340 1345 1350 Asp Trp Gln Asp Asp Gln Ser Asp Asn Gln Ser Asp Tyr Ser Val 1355 1360 1365 Ala ser Glu Glu Gly Asp Glu Asp Phe Asp Glu Arg Ser Glu Ala 1370 1375 1380 Pro Arg Arg Pro Ser Arg Lys Gly Leu Arg Asn Asp Lys Asp Lys 1385 1390 1395 Pro Leu Pro Pro Leu Leu Ala Arg Val Gly Gly Asn Ile Glu Val 1400 1405 1410 Leu Gly Phe Asn Ala Arg Gln Arg Lys Ala Phe Leu Asn Ala Ile 1415 1420 1425 Met Arg Tyr Gly Met Pro Pro Gln Asp Ala Phe Thr Thr Gln Trp 1430 1435 1440 Leu val Arg Asp Leu Arg Gly Lys Ser Glu Lys Glu Phe Lys Ala 1445 1450 1455 Tyr Val ‘Ser Leu Phe Met Arg His Leu Cys Glu Pro Gly ala Asp 1460 1465 1470 Gly Ala Glu Thr Phe Ala Asp Gly Val Pro Arg Glu Gly Leu Ser 1475 1480 1485

PCT/US2003/012946

Arg Gln His Val Leu Thr Arg Ile Gly Val Met Ser Leu Ile Arg 1490 14895 1500 Lys Lys Val Gln Glu Phe Glu His Val Asn Gly Arg Trp Ser Met 1505 1510 1515 Pro Glu Leu Ala Glu Val Glu Glu Asn Lys Lys Met Ser Gln Pro 1520 1525 1530 Gly Ser Pro Ser Pro Lys Thr Pro Thr Pro Ser Thr Pro Gly Asp 15358 1540 1545 Thr Gln Pro Asn Thr Pro Ala Pro Val Pro Pro Ala Glu Asp Gly 1550 1555 1560 Ile Lys Ile Glu Glu Asn Ser Leu Lys Glu Glu Glu ser Ile Glu 1565 1570 1575 Gly Glu Lys Glu Val Lys Ser Thr Ala Pro Glu Thr Ala Ile Glu 1580 1585 1580 Cys Thr Gln Ala Pro Ala Pro Ala Ser Glu Asp Glu Lys val val 1585 1600 1605 Val Glu Pro Pro Glu Gly Glu Glu Lys val Glu Lys Ala Glu val 1610 1615S 1620 Lys Glu Arg Thr Glu Glu Pro Met Glu Thr Glu Pro Lys Gly Ala 1625 1630 1635 Ala Asp Val Glu Lys Val Glu Glu Lys Ser Ala Ile Asp Leu Thr 1640 1645 1650 Pro Ile val val Glu Asp Lys Glu Glu Lys Lys Glu Glu Glu Glu 1655 1660 1665 Lys Lys Glu Val Met Leu Gln Asn Gly Glu Thr Pro Lys Asp Leu 1670 1675 : 1680 Asn Asp Glu Lys Gln Lys Lys Asn Ile Lys Gln Arg Phe Met Phe 1685 1690 1695 Asn Ile Ala Asp Gly Gly Phe Thr Glu Leu His Ser Leu Trp Gln 1700 1705 1710

PCT/US2003/012946

Asn Glu Glu Arg Ala Ala Thr Val Thr Lys Lys Thr Tyr Glu Ile 1718 1720 1725 Trp His Arg Arg His Asp Tyr Trp Leu Leu Ala Gly Ile Ile Asn 1730 1735 1740 His Gly Tyr Ala Arg Trp Gln Asp Ile Gln Asn Asp Pro Arg Tyr 1745 1750 1755 Ala Ile Leu Asn Glu Pro Phe Lys Gly Glu Met Asn Arg Gly Asn 1760 1765 1770 Phe Leu Glu Ile Lys Asn Lys Phe Leu Ala Arg Arg Phe Lys Leu 1775 1780 1785 Leu Glu Gln Ala Leu Val Ile Glu Glu Gln Leu Arg Arg Ala Ala 1790 1795S 1800 Tyr Leu Asn Met Ser Glu Asp Pro Ser His Pro Ser Met Ala Leu 1805 1810 1818 Asn Thr Arg Phe Ala Glu Val Glu Cys Leu Ala Glu Ser His Gln 1820 1825 1830 His Leu Ser Lys Glu Ser Met Ala Gly Asn Lys Pro Ala Asn Ala 1835 1840 1845 Val Leu His Lys Val Leu Lys Gln Leu Glu Glu Leu Leu Ser Asp 1850 1855 1860 Met Lys Ala Asp Val Thr Arg Leu Pro Ala Thr Ile Ala Arg Ile 1865 1870 1875 Pro Pro Val Ala Val Arg Leu Gln Met Ser Glu Arg Asn Ile Leu 1880 1885 1890 Ser Arg Leu Ala Asn Arg Ala Pro Glu Pro Thr Pro Gln Gln Val 1895 1500 1905 > Ala Gln Gln Gln 1910 <210> 2562 <211> 345 <212> PRT <213> Homo sapiens

<400> 2562 . Met Pro Gln Arg Pro Ala Ala Ser Asn Ile Pro val Val Gly ser Pro 1 5 10 15 Asn Pro Pro Ser Thr His Phe Ala Ser Gln Asn Gln His Ser Tyr Ser

Ser Pro Pro Trp Ala Gly Gln His Asn Arg Lys Gly Glu Lys Asn Gly 40 45 Met Gly Leu Cys Arg Leu Ser Met Lys Val Trp Glu Thr val Gln Arg S50 55 60 Lys Gly Thr Thr Ser Cys Gln Glu Val Val Gly Glu Leu Val Ala Lys 65 70 75 80 Phe Arg Ala Ala Ser Asn His Ala Ser Pro Asn Glu Ser Ala Tyr Asp 85 90 95 Val Lys Asn Ile Lys Arg Arg Thr Tyr Asp Ala Leu Asn Val Leu Met 100 105 110 Ala Met Asn Ile Ile Ser Arg Glu Lys Lys Lys Ile Lys Trp Ile Gly 115 120 125 Leu Thr Thr Asn Ser Ala Gln Asn Cys Gln Asn Leu Arg Val Glu Arg 130 135 140 Gln Lys Arg Leu Glu Arg Ile Lys Gln Lys Gln Ser Glu Leu Gln Gln 145 150 158 160 Leu Ile Leu Gln Gln Ile Ala Phe Lys Asn Leu Val Leu Arg Asn Gln 165 170 175 Tyr Val Glu Glu Gln Val Ser Gln Arg Pro Leu Pro Asn Ser Val Ile 180 185 180 His val Pro Phe Ile Ile Ile Ser Ser Ser Lys Lys Thr Val Ile Asn 195 200 205 Cys Ser Ile Ser Asp Asp Lys Ser Glu Tyr Leu Phe Lys Phe Asn Ser 210 21s 220 Ser Phe Glu Ile His Asp Asp Thr Glu Val Leu Met Trp Met Gly Met 225 230 235 240 958

012946

Thr Phe Gly Leu Glu Ser Gly Ser Cys Ser Ala Glu Asp Leu Lys Met 245 250 255 Ala Arg Asn Leu Val Pro Lys Ala Leu Glu Pro Tyr Val Thr Glu Met 260 265 270 Ala Gln Gly Thr Phe Gly Gly Val Phe Thr Thr Ala Gly Ser Arg Ser 275 280 285 Asn Gly Thr Trp Leu Ser Ala Ser Asp Leu Thr Asn Ile Ala Ile Gly 290 295 300 Met Leu Ala Thr Ser Ser Gly Gly Ser Gln Tyr Ser Gly Ser Arg Val 305 310 315 320 Glu Thr Pro Ala Val Glu Glu Glu Glu Glu Glu Asp Asn Asn Asp Asp 325 330 335 Asp Leu Ser Glu Asn Asp Glu Asp Asp 340 345 <210> 2563 <211> 553 <212> PRT <213> Homo sapiens <400> 2563 Met Ser Thr Glu Thr Glu Leu Gln Val Ala Val Lys Thr Ser Ala Lys 1 5 10 15 Lys Asp Ser Arg Lys Lys Gly Gln Asp Arg Ser Glu Ala Thr Leu Ile

Lys Arg Phe Lys Gly Glu Gly Val Arg Tyr Lys Ala Lys Leu Ile Gly 40 45 Ile Asp Glu Val Ser Ala Ala Arg Gly Asp Lys Leu Cys Gln Asp Ser 50 55 60 Met Met Lys Leu Lys Gly Val Val Ala Gly Ala Arg Ser Lys Gly Glu 65 70 © 75 80 His Lys Gln Lys Ile Phe Leu Thr Ile Ser Phe Gly Gly Ile Lys Ile 85 90 85 Phe Asp Glu Lys Thr Gly Ala Leu Gln His His His Ala Val His Glu 959 y

100 105 110 Ile Ser Tyr Ile Ala Lys Asp Ile Thr Asp His Arg Ala Phe Gly Tyr 115 120 125 Val Cys Gly Lys Glu Gly Asn His Arg Phe Val Ala Ile Lys Thr Ala 130 135 140 Gln Ala Ala Glu Pro Val Tle Leu Asp Leu Arg Asp Leu Phe Gln Leu 145 150 155 160 Ile Tyr Glu Leu Lys Gln Arg Glu Glu Leu Glu Lys Lys Ala Gln Lys 165 170 175 Asp Lys Gln Cys Glu Gln Ala val Tyr Gln Thr Ile Leu Glu Glu Asp 180 185 190 Val Glu Asp Pro Val Tyr Gln Tyr Ile Val Phe Glu Ala Gly His Glu 185 200 205 Pro Ile Arg Asp Pro Glu Thr Glu Glu Asn Ile Tyr Gln Val Pro Thr 210 215 220 Ser Gln Lys Lys Glu Gly Val Tyr Asp Val Pro Lys Ser Gln Pro Ala 225 230 235 240 Val Thr Gln Leu Glu Leu Phe Gly Asp Met Ser Thr Pro Pro Asp Ile 245 250 255 Thr Ser Pro Pro Thr Pro Ala Thr Pro Gly Asp Ala Phe Ile Pro Ser 260 265 270 . Ser Ser Gln Thr Leu Pro Ala Ser Ala Asp Val Phe Ser Ser Val Pro 275 280 285 Phe Gly Thr Ala Ala Val Pro Ser Gly Tyr Val Ala Met Gly Ala val 290 295 300 Leu Pro Ser Phe Trp Gly Gln Gln Pro Leu Val Gln Gln Gln Met val 305 310 315 320 Met Gly Ala Gln Pro Pro Val Ala Gln Val Met Pro Gly Ala Gln Pro 325 330 335 Ile Ala Trp Gly Gln Pro Gly Leu Phe Pro Ala Thr Gln Gln Pro Trp 340 345 350

PCT/US2003/012946

Pro Thr val Ala Gly Gln Phe Pro Pro Ala Ala Phe Met Pro Thr Gln 355 360 365 Thr Val Met Pro Leu Pro Ala Ala Met Phe Gln Gly Pro Leu Thr Pro 370 375 380 Leu Ala Thr Val Pro Gly Thr Ser Asp Ser Thr Arg Ser Ser Pro Gln 385 390 388 400 Thr Asp Lys Pro Arg Gln Lys Met Gly Lys Glu Thr phe Lys Asp Phe 405 410 415 Gln Met Ala Gln Pro Pro Pro Val Pro Ser Arg Lys Pro Asp Gln Pro 420 425 430 Ser Leu Thr Cys Thr Ser Glu Ala Phe Ser Ser Tyr Phe Asn Lys Val 435 440 445 Gly Val Ala Gln Asp Thr Asp Asp Cys Asp Asp Phe Asp Ile Ser Gln 450 455 460 Leu Asn Leu Thr Pro Val Thr Ser Thr Thr Pro Ser Thr Asn Ser Pro 465 470 475 480 Pro Thr Pro Ala Pro Arg Gln Ser Ser Pro Ser Lys Ser Ser Ala Ser 485 490 495 His Ala Ser Asp Pro Thr Thr Asp Asp Ile Phe Glu Glu Gly Phe Glu 500 505 510 Ser Pro Ser Lys Ser Glu Glu Gln Glu Ala Pro Asp Gly Ser Gln Ala 515 520 525 Ser Ser Asn Ser Asp Pro Phe Gly Glu Pro Ser Gly Glu Pro Ser Gly 530 535 540 Asp Asn Ile Ser Pro Gln Ala Gly Ser 545 550 . <210> 2564 <211> 1336 <212> PRT <213> Homo sapiens <400> 2564

Met Glu Asn Leu Pro Ala Val Thr Thr Glu Glu Pro Thr Pro Met Gly 1 5 10 1s Arg Gly Pro Val Gly Pro Ser Gly Gly Gly ser Thr Arg Asp Gln Val

Arg Thr Val Val Met Arg Pro Ser Val Ser Trp Glu Lys Ala Gly Pro 40 45 Glu Glu Ala Lys Ala Pro Val Arg Gly Asp Glu Ala Pro Pro Ala Arg 50 55 60 Val Ala Gly Pro Ala Ala Gly Thr Pro Pro Cys Gln Met Gly val Tyr 65 70 75 80 Pro Thr Asp Leu Thr Leu Gln Leu Leu Ala Val Arg Arg Lys Ser Arg 85 90 95 Leu Arg Asp Pro Gly Leu Gln Gln Thr Leu Arg Gly Gln Leu Arg Leu 100 105 110 Leu Glu Asn Asp Ser Arg Glu Met Ala Arg Val Leu Gly Glu Leu Ser 115 120 125 Ala Arg Leu Leu Ser Ile His Ser Asp Gln Asp Arg Ile Val Val Thr 130 135 140 Phe Lys Thr Phe Glu Glu Ile Trp Lys Phe Ser Thr Tyr His Ala Leu 145 150 155 160 Gly Phe Thr His His Cys Leu Ala Asn Leu Leu Met Asp Gln Ala phe 165 170 175 Trp Leu Leu Leu Pro Ser Glu Glu Glu Glu Thr Ala Ile Gln Val His 180 185 190 Val Asp Glu Asn Ala Leu Arg Leu Thr His Glu Ser Leu Leu Ile Gln 195 200 205 Glu Gly Pro Phe Phe Val Leu Cys Pro Asp His His Val Arg Val Met 210 215 220 ’ Thr Gly Pro Arg Asp Ala Gly Asn Gly Pro Gln Ala Leu Arg Gln Ala 225 230 235 240 Ser Gly Ala Pro Gln Gly Glu Ala Ala Pro Glu Thr Asp Ser Ser Pro

245 250 255 R Pro Ser Pro Ser Val Ser Ser Glu Glu Val Ala Val Ala Ala Ala Pro 260 265 270 Glu Pro Leu Ile Pro Phe His Gln Trp Ala Leu Arg Ile Pro Gln Asp 275 280 28S Pro Ile Asp Asp Ala Met Gly Gly Pro Val Met Pro Gly Asn Pro Leu 290 295 300 Met Ala Val Gly Leu Ala Ser Ala Leu Ala Asp Phe Gln Gly Ser Gly : 305 310 315 320 Pro Glu Glu Met Thr Phe Arg Gly Gly Asp Leu Ile Glu Ile Leu Gly 325 330 335 Ala Gln Val Pro Ser Leu Pro Trp Cys Val Gly Arg His Ala Ala Ser 340 345 350 Gly Arg Val Gly Phe Val Arg Ser Ser Leu Ile Ser Met Gln Gly Pro 355 360 365 Val Ser Glu Leu Glu Ser Ala Ile Phe Leu Asn Glu Glu Glu Lys Ser 370 375 380 Phe Phe Ser Glu Gly Cys Phe Ser Glu Glu Asp Ala Arg Gln Leu Leu 385 390 395 400 Arg Arg Met Ser Gly Thr Asp Val Cys Ser Val Tyr Ser Leu Asp Ser 405 410 415 Val Glu Glu Ala Glu Thr Glu Gln .Pro Gln Glu Lys Glu Ile Pro Pro 420 425 430 Pro Cys Leu Ser Pro Glu Pro Gln Glu Thr Leu Gln Lys Val Lys Asn 435 440 445 Val Leu Glu Gln Cys Lys Thr Cys Pro Gly Cys Pro Gln Glu Pro Ala 450 455 460 Ser Trp Gly Leu Cys Ala Ala Ser Ser Asp Val Ser Leu Gln Asp Pro 465 470 475 480 Glu Glu Pro Ser Phe Cys Leu Glu Ala Glu Asp Asp Trp Glu Asp Pro 485 490 495

Glu Ala Leu Ser Ser Leu Leu Leu Phe Leu Asn Ala Pro Gly Tyr Lys 500 508 510 Ala Ser Phe Arg Gly Leu Tyr Asp Val Ala Leu Pro Trp Leu Ser Ser 515 520 525 Val Phe Arg Ser Phe Ser Asp Glu Glu Glu Leu Thr Gly Arg Leu Ala 530 535 540 Gln Ala Arg Gly Ala ala Lys Lys Ala Gly Leu Leu Met Ala Leu Ala 545 550 555 560 Arg Leu Cys Phe Leu Leu Gly Arg Leu Cys Ser Arg Arg Leu Lys Leu 565 570 575 Ser Gln Ala Arg Val Tyr Phe Glu Glu Ala Leu Gly Ala Leu Glu Gly 580 585 590 Ser Phe Gly Asp Leu Phe Leu Val Val Ala Val Tyr Ala Asn Leu Ala 585 600 605 Ser Ile Tyr Arg Lys Gln Lys Asn Arg Glu Lys Cys Ala Gln Val val 610 615 620 Pro Lys Ala Met Ala Leu Leu Leu Gly Thr Pro Asp His Ile Cys Ser 625 630 635 640 Thr Glu Ala Glu Gly Glu Leu Leu Gln Leu Ala Leu Arg Arg Ala Val 645 650 655 Gly Gly Gln Ser Leu Gln Ala Glu Ala Arg Ala Cys Phe Leu Leu Ala 660 665 670 Arg His His Val His Leu Lys Gln Pro Glu Glu Ala Leu Pro Phe Leu 675 680 685 Glu Arg Leu Leu Leu Leu His Arg Asp Ser Gly Ala Pro Glu Ala Ala 690 695 700 Trp Leu Ser Asp Cys Tyr Leu Leu Leu Ala Asp Ile Tyr Ser Arg Lys 705 710 715 720 Cys Leu Pro His Leu Val Leu Ser Cys Val Lys val Ala Ser Leu Arg 725 730 735

: PCT/US2003/012946

Thr Arg Gly Ser Leu Ala Gly Ser Leu Arg Ser Val Asn Leu Val Leu 740 745 750 Gln Asn Ala Pro Gln Pro His Ser Leu Pro Ala Gln Thr Ser His Tyr 755 760 765 Leu Arg Gln Ala Leu Ala Ser Leu Thr Pro Gly Thr Gly Gln Ala Leu 770 775 780 Arg Gly Pro Leu Tyr Thr Ser Leu Ala Gln Leu Tyr Ser His His Gly 785 790 785 800 Cys His Gly Pro Ala Ile Thr Phe Met Thr Gln Ala Val Glu Ala Ser 80S 810 818 Ala Ile Ala Gly Val Arg Ala Ile Val Asp His Leu Val Ala Leu Ala 820 825 830 Trp Leu His Val Leu His Gly Gln Ser Pro Val Ala Leu Asp Ile Leu 835 840 845 Gln Ser Val Arg Asp Ala Val Val Ala Ser Glu Asp Gln Glu Gly val 850 855 860 Ile Ala Asn Met Val Ala Val Ala Leu Lys Arg Thr Gly Arg Thr Arg 865 870 875 880 Gln Ala Ala Glu Ser Tyr Tyr Arg Ala Leu Arg Val Ala Arg Asp Leu 885 890 895 Gly Gln Gln ‘Arg Asn Gln Ala Val Gly Leu Ala Asn Phe Gly Ala Leu 900 905 910 Cys Leu His Ala Gly Ala Ser Arg Leu Ala Gln His Tyr Leu Leu Glu 915 S20 925 Ala Val Arg Leu Phe Ser Arg Leu Pro Leu Gly Glu s Gly Arg Asp Y 930 935 S40 Phe Thr His Val Leu Leu Gln Leu Gly His Leu Cys Thr Arg Gln Gly 945 950 855 960 Pro Ala Gln Gln Gly Lys Gly Tyr Tyr Glu Trp Ala Leu Leu Val Ala 865 970 975

Val Glu Met Gly His Val Glu Ser Gln Leu Arg Ala Val Gln Arg Leu 280 985 950 Cys His Phe Tyr Ser Ala Val Met Pro Ser Glu Ala Gln Cys val Ile 995 1000 1005 Tyr His Glu Leu Gln Leu Ser Pro Ala Cys Lys Val Ala Asp Lys 1010 101s 1020 Val Leu Glu Gly Gln Leu Leu Glu Thr Ile Ser Gln Leu Tyr Leu 1025 1030 103s Ser Leu Gly Thr Glu Arg Ala Tyr Lys Ser Ala Leu Asp Tyr Thr 1040 1045 1050 Lys Arg Ser Leu Gly Ile Phe Ile Asp Leu Gln Lys Lys Glu Lys 1055 1060 1065 Glu Ala His Ala Trp Leu Gln Ala Gly Lys Ile Tyr Tyr Ile Leu 1070 1075 1080 - Arg Gln Ser Glu Leu Val Asp Leu Tyr Ile Gln Val Ala Gln Asn 1085 1090 1095 Val Ala Leu Tyr Thr Gly Asp Pro Asn Leu Gly Leu Glu Leu Phe 1100 1105 1110 Glu Ala Ala Gly Asp Ile Phe Phe Asp Gly Ala Trp Glu Arg Glu 1115 1120 1125 Lys Ala Val Ser Phe Tyr Arg Asp Arg Ala Leu Pro Leu Ala Val 1130 1135 1140 Thr Thr Gly Asn Arg Lys Ala Glu Leu Arg Leu Cys Asn Lys Leu 1145 1150 1155 Val Ala Leu Leu Ala Thr Leu Glu Glu Pro Gln Glu Gly Leu Glu 1160 1165 1170 Phe Ala His Met Ala Leu Ala Leu Ser Ile Thr Leu Gly Asp Arg 1175 1180 1185 Leu Asn Glu Arg val Ala Tyr His Arg Leu Ala Ala Leu Gln His 1190 1185 1200 Arg Leu Gly His Gly Glu Leu Ala Glu His Phe Tyr Leu Lys Ala

4 So : oo \

1205 1210 1215

Leu Ser Leu Cys Asn Ser Pro Leu Glu Phe Asp Glu Glu Thr Leu 1220 1225 1230

Tyr Tyr Val Lys Val Tyr Leu Val Leu Gly Asp Ile Ile phe Tyr 1235 1240 1245

Asp Leu Lys Asp Pro Phe Asp Ala Ala Gly Tyr Tyr Gln Leu Ala 1250 1255 1260

Leu Ala Ala Ala Val Asp Leu Gly Asn Lys Lys Ala Gln Leu Lys 1265 1270 1275

Ile Tyr Thr Arg Leu Ala Thr Ile Tyr His Asn Phe Leu Leu Asp 1280 1285 1290

Arg Glu Lys Ser Leu Phe Phe Tyr Gln Lys Ala Arg Thr Phe Ala 1295 1300 1305

Thr Glu Leu Asn Val Arg Arg Val Asn Leu Pro Pro Leu Pro Leu 1310 1315 1320

Cys Gly Trp Ala Pro Trp Leu Ala Pro Ser His Pro Arg 1325 1330 1335

<210> 2565

<211> S93

<212> PRT

<213> Homo sapiens

<400> 2565

Met Leu Thr Glu Leu Glu Lys Ala Leu Asn Ser Ile Ile Asp Val Tyr

1 5 10 15

His Lys Tyr Ser Leu Ile Lys Gly Asn Phe His Ala Val Tyr Arg Asp

Asp Leu Lys Lys Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg Lys 40 45

Lys Gly Ala Asp Val Trp Phe Lys Glu Leu Asp Ile Asn Thr Asp Gly 50 5S 60

Ala Val Asn Phe Gln Glu Phe Leu Ile Leu Val Ile Lys Met Gly Val

65 70 75 80

. So CY / PCT/US2003/012946 WO 2004/042346 ¢ Ala Ala His Lys Lys Ser His Glu Glu Ser His Lys Glu 85 90 <210> 2566 <211> 1186 <212> PRT <213> Homo sapiens <400> 2566 . Met Gly Val Gln Gly Leu Trp Lys Leu Leu Glu Cys Ser Gly Arg Gln 1 5 10 15 Val Ser Pro Glu Ala Leu Glu Gly Lys Ile Leu Ala Val Asp Ile Ser

Ile Trp Leu Asn Gln Ala Leu Lys Gly Val Arg Asp Arg His Gly Asn 40 45 Ser Ile Glu Asn Pro His Leu Leu Thr Leu Phe His Arg Leu Cys Lys 50 55 60 Leu Leu Phe Phe Arg Ile Arg Pro Ile Phe Val Phe Asp Gly Asp Ala 65 70 75 80 Pro Leu Leu Lys Lys Gln Thr Leu Val Lys Arg Arg Gln Arg Lys Asp 85 90 95 Leu Ala Ser Ser Asp Ser Arg Lys Thr Thr Glu Lys Leu Leu Lys Thr 100 105 110 Phe Leu Lys Arg Gln Ala Ile Lys Thr Ala Phe Arg Ser Lys Arg Asp 115 120 125 Glu Ala Leu Pro Ser Leu Thr Gln Val Arg Arg Glu Asn Asp Leu Tyr 130 135 140 Val Leu Pro Pro Leu Gln Glu Glu Glu Lys His Ser Ser Glu Glu Glu 145 150 155 160 Asp Glu Lys Glu Trp Gln Glu Arg Met Asn Gln Lys Gln Ala Leu Gln 165 170 175 Glu Glu Phe Phe His Asn Pro Gln Ala Ile Asp Ile Glu Ser Glu Asp 180 18S 190 Phe Ser Ser Leu Pro Pro Glu Val Lys His Glu Ile Leu Thr Asp Met

PCT/US2003/012946

195 200 205 Lys Glu phe Thr Lys Arg Arg Arg Thr Leu Phe Glu Ala Met Pro Glu 210 215 220 Glu Ser Asp Asp Phe Ser Gln Tyr Gln Leu Lys Gly Leu Leu Lys Lys 225 230 235 240 Asn Tyr Leu Asn Gln His Ile Glu His Val Gln Lys Glu Met Asn Gln 245 250 255 Gln His Ser Gly His Ile Arg Arg Gln Tyr Glu Asp Glu Gly Gly Phe 260 265 270 Leu Lys Glu Val Glu Ser Arg Arg Val Val Ser Glu Asp Thr Ser His 275 280 285 Tyr Ile Leu Ile Lys Gly Ile Gln Ala Lys Thr val Ala Glu Val Asp 290 295 300 Ser Glu Ser Leu Pro Ser Ser Ser Lys Met His Gly Met Ser Phe Asp 305 310 315 320 Val Lys Ser Ser Pro Cys Glu Lys Leu Lys Thr Glu Lys Glu Pro Asp 325 330 335 Ala Thr Pro Pro Ser Pro Arg Thr Leu Leu Ala Met Gln Ala Ala Leu 340 345 350 Leu Gly Ser Ser Ser Glu Glu Glu Leu Glu Ser Glu Asn Arg Arg Gln 355 360 365 Ala Arg Gly Arg Asn Ala Pro Ala Ala Val Asp Glu Gly Ser Ile Ser 370 375 380 Pro Arg Thr Leu Ser Ala Ile Lys Arg Ala Leu Asp Asp Asp Glu Asp 385 390 395 400 Val Lys Val Cys Ala Gly Asp Asp Val Gln Thr Gly Gly Pro Gly Ala 405 410 415 Glu Glu Met Arg Ile Asn Ser Ser Thr Glu Asn Ser Asp Glu Gly Leu 420 425 430 Lys Val Arg Asp Gly Lys Gly Ile Pro Phe Thr Ala Thr Leu Ala Ser 435 440 445

Ser Ser Val Asn Ser Ala Glu Glu His Val Ala Ser Thr Asn Glu Gly 450 455 460 Arg Glu Pro Thr Asp Ser Val Pro Lys Glu Gln Met Ser Leu Val His 465 470 475 480 Val Gly Thr Glu Ala Phe Pro Ile Ser Asp Glu Ser Met Ile Lys Asp 485 490 495 Arg Lys Asp Arg Leu Pro Leu Glu Ser Ala Val val Arg His Ser Asp 500 505 510 Ala Pro Gly Leu Pro Asn Gly Arg Glu Leu Thr Pro Ala Ser Pro Thr 515 520 525 Cys Thr Asn Ser Val Ser Lys Asn Glu Thr His Ala Glu Val Leu Glu 530 535 540 Gln Gln Asn Glu Leu Cys Pro Tyr Glu Ser Lys Phe Asp Ser Ser Leu 545 550 555 . 560 Leu Ser Ser Asp Asp Glu Thr Lys Cys Lys Pro Asn Ser Ala Ser Glu 565 570 575 Val Ile Gly Pro Val Ser Leu Gln Glu Thr Ser Ser Ile val Ser Val 580 585 590 Pro Ser Glu Ala Val Asp Asn Val Glu Asn Val Val Ser Phe Asn Ala 595 600 605 Lys Glu Kis Glu Asn Phe Leu Glu Thr Ile Gln Glu Gln Gln Thr Thr 610 615 620 Glu Ser Ala Gly Gln Asp Leu Ile Ser Ile Pro Lys Ala Val Glu Pro 625 630 635 640 Met Glu Ile Asp Ser Glu Glu Ser Glu Ser Asp Gly Ser Phe Ile Glu 645 650 658 Val Gln Ser Val Ile Ser Asp Glu Glu Leu Gln Ala Glu Phe Pro Glu 660 665 670 Thr Ser Lys Pro Pro Ser Glu Gln Gly Glu Glu Glu Leu Val Gly Thr 675 680 685

Arg Glu Gly Glu Ala Pro Ala Glu Ser Glu Ser Leu Leu Arg Asp Asn 690 695 700 Ser Glu Arg Asp Asp Val Asp Gly Glu Pro Gln Glu Ala Glu Lys Asp 705 710 715 720 Ala Glu Asp Ser Leu His Glu Trp Gln Asp Ile Asn Leu Glu Glu Leu 725 730 735 Glu Thr Leu Glu Ser Asn Leu Leu Ala Gln Gln Asn Ser Leu Lys Ala 740 745 750 Gln Lys Gln Gln Gln Glu Arg Ile Ala Ala Thr Val Thr Gly Gln Met 755 760 765 Phe Leu Glu Ser Gln Glu Leu Leu Arg Leu Phe Gly Ile Pro Tyr Ile 770 775 780 Gln Ala Pro Met Glu Ala Glu Ala Gln Cys Ala Ile Leu Asp Leu Thr 785 790 795 800 Asp Gln Thr Ser Gly Thr Ile Thr Asp Asp Ser Asp Ile Trp Leu Phe 805 810 815 Gly Ala Arg His Val Tyr Arg Asn Phe Phe Asn Lys Asn Lys Phe Val 820 825 830 Glu Tyr Tyr Gln Tyr Val Asp Phe His Asn Gln Leu Gly Leu Asp Arg 835 840 845 Asn Lys Leu Ile Asn Leu Ala Tyr Leu Leu Gly Ser Asp Tyr Thr Glu 850 855 860 Gly Ile Pro Thr Val Gly Cys Val Thr Ala Met Glu Ile Leu Asn Glu 865 870 875 880 Phe Pro Gly His Gly Leu Glu Pro Leu Leu Lys Phe Ser Glu Trp Trp 885 890 895 His Glu Ala Gln Lys Asn Pro Lys Ile Arg Pro Asn Pro His Asp Thr S00 905 910 Lys val Lys Lys Lys Leu Arg Thr Leu Gln Leu Thr Pro Gly Phe Pro 815 S20 925

Asn Pro Ala Val Ala Glu Ala Tyr Leu Lys Pro Val val Asp Asp Ser 930 935 940

Lys Gly Ser Phe Leu Trp Gly Lys Pro Asp Leu Asp Lys Ile Arg Glu

945 950 955 960

Phe Cys Gln Arg Tyr Phe Gly Trp Asn Arg Thr Lys Thr Asp Glu Ser

965 970 978 Leu Phe Pro Val Leu Lys Gln Leu Asp Ala Gln Gin Thr Gln Leu Arg 980 985 990 Ile Asp Ser Phe Phe Arg Leu Ala Gln Gln Glu Lys Glu Asp Ala Lys 995 1000 1005

Arg Ile Lys Ser Gln Arg Leu Asn Arg Ala Val Thr Cys Met Leu 1010 1015 1020

Arg Lys Glu Lys Glu Ala Ala Ala Ser Glu Ile Glu Ala Val Ser 1025 1030 1035

Val Ala Met Glu Lys Glu Phe Glu Leu Leu Asp Lys Ala Lys Arg 1040 1045 1050

Lys Thr Gln Lys Arg Gly Ile Thr Asn Thr Leu Glu Glu Ser Ser 1055 1060 1065

Ser Leu Lys Arg Lys Arg Leu Ser Asp Ser Lys Arg Lys Asn Thr 1070 1075 1080

Cys Gly Gly Phe Leu Gly Glu Thr Cys Leu Ser Glu Ser Ser Asp 1085 1090 1095

Gly Ser Ser Ser Glu His Ala Glu Ser Ser Ser Leu Met Asn Val 1100 1105 1110

Gln Arg Arg Thr Ala Ala Lys Glu Pro Lys Thr Ser Ala Ser Asp 1115 1120 1125

Ser Gln Asn Ser Val Lys Glu Ala Pro Val Lys Asn Gly Gly Ala 1130 1135 1140

Thr Thr Ser Ser Ser Ser Asp Ser Asp Asp Asp Gly Gly Lys Glu 1145 1150 1155

Lys Met Val Leu Val Thr Ala Arg Ser Val Phe Gly Lys Lys Arg

1160 1165 1170 Arg Lys Leu Arg Arg Ala Arg Gly Arg Lys Arg Lys Thr 1175 1180 1185 <210> 2567 <211> B84 <212> PRT <213> Homo sapiens <400> 2567 Met Pro Leu Ala Lys Asp Leu Leu His Pro Ser Pro Glu Glu Glu Lys 1 S 10 15 Arg Lys His Lys Lys Lys Arg Leu Val Gln Ser Pro Asn Ser Tyr Phe

Met Asp Val Lys Cys Pro Gly Cys Tyr Lys Ile Thr Thr Val Phe Ser 358 "40 45 His Ala Gln Thr Val Val Leu Cys Val Gly Cys Ser Thr Val Leu Cys 50 55 60 Gln Pro Thr Gly Gly Lys Ala Arg Leu Thr Glu Gly Cys Ser Phe Arg 65 70 75 80 Arg Lys Gln His <210> 2568 <211l> 691 <212> PRT <213> Homo sapiens <400> 2568 Met Asp Gly Cys Lys Lys Glu Leu Pro Arg Leu Gln Glu Pro Glu Glu 1 S 10 15 Asp Glu Asp Cys Tyr Ile Leu Asn Val Gln Ser Ser Ser Asp Asp Thr 20 25 30 Ser Gly Ser Ser Val Ala Arg Arg Ala Pro Lys Arg Gln Ala Ser Cys 40 45 Ile Leu Asn Val Gln Ser Arg Ser Gly Asp Thr Ser Gly Ser Ser Val SO 58 60

Ala Arg Arg Ala Pro Lys Arg Gln Ala Ser Ser Val val Val Ile Asp 65 70 75 80 Ser Asp Ser Asp Glu Glu Cys His Thr His Glu Glu Lys Lys Ala Lys 85 90 95 Leu Leu Glu Ile Asn Ser Asp Asp Glu Ser Pro Glu Cys Cys His val 100 105 110 Lys Pro Ala Ile Gln Glu Pro Pro Ile Val Ile Ser Asp Asp Asp Asn 115 120 125 Asp Asp Asp Asn Gly Asn Asp Leu Glu Val Pro Asp Asp Asn Ser Asp 130 135 140 Asp Ser Glu Ala Pro Asp Asp Asn Ser Asp Asp Ser Glu Ala Pro Asp 145 150 1585 160 Asp Asn Ser Asp Asp Ser Glu Ala Pro Asp Asp Asn Ser Asp Asp Ser 165 170 175 Glu Ala Pro Asp Asp Asn Ser Asp Asp Ser Asp Val Pro Asp Asp Asn 180 185 190 Ser Asp Asp Ser Ser Asp Asp Asn Ser Asp Asp Ser Ser Asp Asp Asn 195 200 205 Ser Asp Asp Ser Asp Val Pro Asp Asp Lys Ser Asp Asp Ser Asp Val 210 215 220 . Pro Asp Asp Ser Ser Asp Asp Ser Asp Val Pro Asp Asp Ser Ser Asp 225 230 235 240 Asp Ser Glu Ala Pro Asp Asp Ser Ser Asp Asp Ser Glu Ala Pro Asp 245 250 255 Asp Ser Ser Asp Asp Ser Glu Ala Pro Asp Asp Ser Ser Asp Asp Ser 260 265 270 Glu Ala Pro Asp Asp Ser Ser Asp Asp Ser Glu Ala Ser Asp Asp Ser 275 280 285 Ser Asp Asp Ser Glu Ala Ser Asp Asp Ser Ser Asp Asp Ser Glu Ala 290 295 300 Pro Asp Asp Lys Ser Asp Asp Ser Asp Val Pro Glu Asp Lys Ser Asp 974 fi.

305 310 315 320 Asp Ser Asp Val Pro Asp Asp Asn Ser Asp Asp Leu Glu Val Pro val 325 330 335 Pro Ala Glu Asp Leu Cys Asn Glu Gly Gln Ile Ala Ser Asp Glu Glu 340 345 350 Glu Leu Val Glu Ala Ala Ala Ala Val Ser Gln His Asp Ser Ser Asp 355 360 365 Asp Ala Gly Glu Gln Asp Leu Gly Glu Asn Leu Ser Lys Pro Pro Ser 370 375 380 Asp Pro Glu Ala Asn Pro Glu Val Ser Glu Arg Lys Leu Pro Thr Glu 385 390 395 400 Glu Glu Pro Ala Pro Val Val Glu Gln Ser Gly Lys Arg Lys Ser Lys 405 410 415 Thr Lys Thr Ile Val Glu Pro Pro Arg Lys Arg Gln Thr Lys Thr Lys 420 425 430 Asn Ile Val Glu Pro Pro Arg Lys Arg Gln Thr Lys Thr Lys Asn Ile 435 440 445 val Glu Pro Leu Arg Lys Arg Lys Ala Lys Thr Lys Asn Val Ser val 450 455 460 Thr Pro Gly His Lys Lys Arg Gly Pro Ser Lys Lys Lys Pro Gly Ala 465 470 475 480 Ala Lys Val Glu Lys Arg Lys Thr Arg Thr Pro Lys Cys Lys Val Pro 485 490 495 Gly Cys Phe Leu Gln Asp Leu Glu Lys Ser Lys Lys Tyr Ser Gly Lys 500 505 510 Asn Leu Lys Arg Asn Lys Asp Glu Leu Val Gln Arg Ile Tyr Asp Leu 515 520 525 Phe Asn Arg Ser Val Cys Asp Lys Lys Leu Pro Glu Lys Leu Arg Ile 530 535 540 Gly Trp Asn Asn Lys Met Val Lys Thr Ala Gly Leu Cys Ser Thr Gly 545 550 555 560

PCT/US2003/012946

Glu Met Trp Tyr Pro Lys Trp Arg Arg Phe Ala Lys Ile Gln Ile Gly 565 570 575 Leu Lys val Cys Asp Ser Ala Asp Arg Ile Arg Asp Thr Leu Ile His 580 585 580 Glu Met Cys His Ala Ala Ser Trp Leu Ile Asp Gly Ile His Asp Ser 595 600 605 His Gly Asp Ala Trp Lys Tyr Tyr Ala Arg Lys Ser Asn Arg Ile His 610 615 620 Pro Glu Leu Pro Arg Val Thr Arg Cys His Asn Tyr Lys Ile asn Tyr 625 630 635 640 Lys Val His Tyr Glu Cys Thr Gly Cys Lys Thr Arg Ile Gly Cys Tyr 645 650 655 Thr Lys Ser Leu Asp Thr Ser Arg Phe Ile Cys Ala Lys Cys Lys Gly 660 665 670 Ser Leu Val Met Val Pro Leu Thr Gln Lys Asp Gly Thr Arg Ile val 675 680 685 Pro Hig Val 690 <210> 2569 <211> 101 <212> PRT © <213> Homo sapiens <400> 2569 Met Ser Asp Gln Glu Ala Lys Pro Ser Thr Glu Asp Leu Gly Asp Lys 1 5 10 15 Lys Glu Gly Glu Tyr Ile Lys Leu Lys val Ile Gly Gln Asp Ser Ser

Glu Ile His Phe Lys val Lys Met Thr Thr His Leu Lys Lys Leu Lys 40 45 Glu Ser Tyr Cys Gln Arg Gln Gly Val Pro Met Asn Ser Leu Arg Phe 50 SS 60

T/US2003/012946

Leu Phe Glu Gly Gln Arg Ile Ala Asp Asn His Thr Pro Lys Glu Leu 65 70 75 80 Gly Met Glu Glu Glu Asp Val Ile Glu Val Tyr Gln Glu Gln Thr Gly 8S S0 95 Gly His Ser Thr val 100

<210> 2570

<211> 93

<212> PRT

<213> Homo sapiens ’ <400> 2570

Met Ser Gly Leu Arg Val Tyr Ser Thr Ser Val Thr Gly Ser Arg Glu 1 5 10 15

Ile Lys Ser Gln Gln Ser Glu Val Thr Arg Ile Leu Asp Gly Lys Arg

Ile Gln Tyr Gln Leu Val Asp Ile Ser Gln Asp Asn Ala Leu Arg Asp 40 45 Glu Met Arg Ala Leu Ala Gly Asn Pro Lys Ala Thr Pro Pro Gln Ile 50 55 . 60 Val Asn Gly Asp Gln Tyr Cys Gly Asp Tyr Glu Leu Phe Val Glu Ala 65S 70 75 80 Val Glu Gln Asn Thr Leu Gln Glu Phe Leu Lys Leu Ala 85 90

<210> 2571

<211> 666

<212> PRT

<213> Homo sapiens

<400> 2571 Met Thr Pro Pro Pro Pro Gly Arg Ala Ala Pro Ser Ala Pro Arg Ala 1 5 10 15 Arg Val Pro Gly Pro Pro Ala Arg Leu Gly Leu Pro Leu Arg Leu Arg

20 25 30 Leu Leu Leu Leu Leu Trp Ala Ala Ala Ala Ser Ala Gln Gly His Leu 35 40 45

Arg Ser Gly Pro Arg Ile Phe Ala Val Trp Lys Gly His Val Gly Gln 50 55 60 Asp Arg Val Asp Phe Gly Gln Thr Glu Pro His Thr Val Leu Phe His 65 70 75 80 Glu Pro Gly Ser Ser Ser Val Trp Val Gly Gly Arg Gly Lys Val Tyr 85 90 95 Leu Phe Asp Phe Pro Glu Gly Lys Asn Ala Ser Val Arg Thr val Asn 100 105 110 Ile Gly Ser Thr Lys Gly Ser Cys Leu Asp Lys Arg Asp Cys Glu Asn 115 120 125 Tyr Ile Thr Leu Leu Glu Arg Arg Ser Glu Gly Leu Leu Ala Cys Gly 130 135 140 Thr Asn Ala Arg His Pro Ser Cys Trp Asn Leu Val Asn Gly Thr Val 145 150 155 160 Val Pro Leu Gly Glu Met Arg Gly Tyr Ala Pro Phe Ser Pro Asp Glu ) 165 170 175 Asn Ser Leu Val Leu Phe Glu Gly Asp Glu Val Tyr Ser Thr Ile Arg 180 185 190 Lys Gln Glu Tyr Asn Gly Lys Ile Pro Arg Phe Arg Arg Ile Arg Gly 185 200 205 Glu Ser Glu Leu Tyr Thr Ser Asp Thr Val Met Gln Asn Pro Gln Phe 210 215 220 Ile Lys Ala Thr Ile Val His Gln Asp Gln Ala Tyr Asp Asp Lys Ile 225 230 235 240 Tyr Tyr Phe Phe Arg Glu Asp Asn Pro Asp Lys Asn Pro Glu Ala Pro 245 250 2558 Leu Asn Val Ser Arg Val Ala Gln Leu Cys Arg Gly Asp Gln Gly Gly 260 265 270 Glu Ser Ser Leu Ser Val Ser Lys Trp Asn Thr Phe Leu Lys Ala Met 275 280 285

PCT/US2003/012946

Leu val Cys Ser Asp Ala Ala Thr Asn Lys Asn Phe Asn Arg Leu Gln 280 295 300 Asp Val phe Leu Leu Pro Asp Pro Ser Gly Gln Trp Arg Asp Thr Arg 305 310 315 320 Val Tyr Gly Val Phe Ser Asn Pro Trp Asn Tyr Ser Ala Val Cys Val 325 330 335 Tyr Ser Leu Gly Asp Ile Asp Lys Val Phe Arg Thr Ser Ser Leu Lys 340 345 350 Gly Tyr His Ser Ser Leu Pro Asn Pro Arg Pro Gly Lys Cys Leu Pro 355 360 365 Asp Gln Gln Pro Ile Pro Thr Glu Thr Phe Gln Val Ala Asp Arg His 370 375 380 Pro Glu Val Ala Gln Arg Val Glu Pro Met Gly Pro Leu Lys Thr Pro 385 390 385 400 Leu Phe His Ser Lys Tyr His Tyr Gln Lys Val Ala Val His Arg Met 405 410 415 Gln Ala Ser His Gly Glu Thr Phe His Val Leu Tyr Leu Thr Thr Asp 420 425 430 Arg Gly Thr Ile His Lys Val val Glu Pro Gly Glu Gln Glu His Ser 435 440 445 Phe Ala Phe Asn Ile Met Glu Ile Gln Pro Phe Arg Arg Ala Ala Ala 450 455 460 Ile Gln Thr Met Ser Leu Asp Ala Glu Arg Arg Lys Leu Tyr Val Ser 465 470 475 480 Ser Gln Trp Glu Val Ser Gln Val Pro Leu Asp Leu Cys Glu val Tyr 485 490 495 Gly Gly Gly Cys His Gly Cys Leu Met Ser Arg Asp Pro Tyr Cys Gly 500 505 510 Trp Asp Gln Gly Arg Cys Ile Ser Ile Tyr Ser Ser Glu Arg Ser Val 515 520 525 Leu Gln Ser Ile Asn Pro Ala Glu Pro His Lys Glu Cys Pro Asn Pro

530 535 540 Lys Pro Asp Lys Ala Pro Leu Gln Lys Val Ser Leu Ala Pro Asn Ser 545 550 555% 560 Arg Tyr Tyr Leu Ser Cys Pro Met Glu Ser Arg His Ala Thr Tyr Ser 565 570 575 Trp Arg His Lys Glu Asn Val Glu Gln Ser Cys Glu Pro Gly His Gln 580 585 590 Ser Pro Asn Cys Ile Leu Phe Ile Glu Asn Leu Thr Ala Gln Gln Tyr 595 600 605 Gly His Tyr Phe Cys Glu Ala Gln Glu Gly Ser Tyr Phe Arg Glu Ala 610 615 620 ~ Gln His Trp Gln Leu Leu Pro Glu Asp Gly Ile Met Ala Glu His Leu 625 630 635 640 Leu Gly His Ala Cys Ala Leu Ala Ala Ser Leu Trp Leu Gly val Leu 645 650 655 Pro Thr Leu Thr Leu Gly Leu Leu Val His 660 665 <210> 2572 <211> 162 «212> PRT <213> Homo sapiens <400> 2572 Met Arg Ser Ser Pro Gly Asn Met Glu Arg Ile Val Ile Cys Leu Met 1 5 10 15 Val Ile Phe Leu Gly Thr Leu Val His Lys Ser Ser Ser Gln Gly Gln

Asp Arg His Met Ile Arg Met Arg Gln Leu Ile Asp Ile Val Asp Gln 40 45 Leu Lys Asn Tyr Val Asn Asp Leu Val Pro Glu Phe Leu Pro Ala Pro S50 55 60 Glu Asp Val Glu Thr Asn Cys Glu Trp Ser Ala Phe Ser Cys Phe Gln 65 70 75 80 980 L

CT LEE - PCT/US2003/012946

Lys Ala Gln Leu Lys Ser Ala Asn Thr Gly Asn Asn Glu Arg Ile Ile 85 90 95 Asn Val Ser Ile Lys Lys Leu Lys Arg Lys Pro Pro Ser Thr Asn Ala 100 105 110 Gly Arg Arg Gln Lys His Arg Leu Thr Cys Pro Ser Cys Asp Ser Tyr 115 120 125 Glu Lys Lys Pro Pro Lys Glu Phe Leu Glu Arg Phe Lys Ser Leu Leu 130 135 140 Gln Lys Met Ile His Gln His Leu Ser Ser Arg Thr His Gly Ser Glu 145 150 155 160 Asp Ser <210> 2573 <211> 1050 <212> PRT <213> Homo sapiens <400> 2573 Met Leu Cys Trp Gly Tyr Trp Ser Leu Gly Gln Pro Gly Ile Ser Thr 1 5 10 15 Asn Leu Gln Gly Ile Val Ala Glu Pro Gln Val Cys Gly Phe Ile Ser

Asp Arg Ser Val Lys Glu val Ala Cys Gly Gly Asn His Ser Val Phe 40 45 Leu Leu Glu Asp Gly Glu Val Tyr Thr Cys Gly Leu Asn Thr Lys Gly 50 55 60 Gln Leu Gly His Glu Arg Glu Gly Asn Lys Pro Glu Gln Ile Gly Ala 65 70 75 80 Leu Ala Asp Gln His Ile Ile His Val Ala Cys Gly Glu Ser His Ser 85 90 95 Leu Ala Leu Ser Asp Arg Gly Gln Leu Phe Ser Trp Gly Ala Gly Ser 100 105 110 Asp Gly Gln Leu Gly Leu Met Thr Thr Glu Asp Ser Val Ala Val Pro 981 WE

PCT/US2003/012946

115 120 125 Arg Leu Ile Gln Lys Leu Asn Gln Gln Thr Ile Leu Gln Val Ser Cys 130 135 140

Gly Asn Trp His Cys Leu Ala Leu Ala Ala Asp Gly Gln Phe Phe Thr

145 150 155 160 Trp Gly Lys Asn Ser His Gly Gln Leu Gly Leu Gly Lys Glu Phe Pro

165 170 175 Ser Gln Ala Ser Pro Gln Arg Val Arg Ser Leu Glu Gly Ile Pro Leu 180 185 190 Ala Gln Val Ala Ala Gly Gly Ala His Ser Phe Ala Leu Ser Leu Ser 185 200 205 Gly Ala Val Phe Gly Trp Gly Met Asn Asn Ala Gly Gln Leu Gly Leu 210 215 220 Ser Asp Glu Lys Asp Arg Glu Ser Pro Cys His Val Lys Leu Leu Arg 225 230 235 240 Thr Gln Lys val val Tyr Ile Ser Cys Gly Glu Glu His Thr Ala Val 245 250 255 Leu Thr Lys Ser Gly Gly Val Phe Thr Phe Gly Ala Gly Ser Cys Gly 260 265 270 Gln Leu Gly His Asp Ser Met Asn Asp Glu Val Asn Pro Arg Arg Val Co 275 280 285 . Leu Glu Leu Met Gly Ser Glu Val Thr Gln Ile Ala Cys Gly Arg Gln 290 295 300 His Thr Leu Ala Phe val Pro Ser Ser Gly Leu Ile Tyr Ala Phe Gly 305 310 315 320 Cys Gly Ala Arg Gly Gln Leu Gly Thr Gly His Thr Cys Asn Val Lys 328 330 335 Cys Pro Ser Pro Val Lys Gly Tyr Trp Ala Ala His Ser Gly Gln Leu 340 345 350 Ser Ala Arg Ala Asp Arg Phe Lys Tyr His Ile Val Lys Gln Ile Phe 355 360 365

03/012946

Ser Gly Gly Asp Gln Thr Phe Val Leu Cys Ser Lys Tyr Glu Asn Tyr 370 375 380 Ser Pro Ala Val Asp Phe Arg Thr Met Asn Gln Ala His Tyr Thr Ser 385 3590 395 400 Leu Ile Asn Asp Glu Thr Ile Ala Val Trp Arg Gln Lys Leu Ser Glu 405 410 415 His Asn Asn Ala Asn Thr Ile Asn Gly val val Gln Ile Leu Ser Ser 420 425 430 Ala Ala Cys Trp Asn Gly Ser Phe Leu Glu Lys Lys Ile Asp Glu His 435 440 445 Phe Lys Thr Ser Pro Lys Ile Pro Gly Ile Asp Leu Asn Ser Thr Arg 450 455 460 Val Leu Phe Glu Lys Leu Met Asn Ser Gln His Ser Met Ile Leu Glu 465 470 475 480 Gln Ile Leu Asn Ser Phe Glu Ser Cys Leu Ile Pro Gln Leu Ser Ser 485 490 495 Ser Pro Pro Asp Val Glu Ala Met Arg Ile Tyr Leu Ile Leu Pro Glu 500 505 510 Phe Pro Leu Leu Gln Asp Ser Lys Tyr Tyr Ile Thr Leu Thr Ile Pro 515 520 525 Leu Ala Met Ala Ile Leu Arg Leu Asp Thr Asn Pro Ser Lys Val Leu S30 535 540 Asp Asn Trp Trp Ser Gln Val Cys Pro Lys Tyr Phe Met Lys Leu Val 545 550 555 560 Asn Leu Tyr Lys Gly Ala Val Leu Tyr Leu Leu Arg Gly Arg Lys Thr 565 570 575 Phe Leu Ile Pro Val Leu Phe Asn Asn Tyr Ile Thr Ala Ala Leu Lys 580 585 590 Leu Leu Glu Lys Leu Tyr Lys Val Asn Leu Lys Val Lys His val Glu 595 600 605

Tyr Asp Thr Phe Tyr Ile Pro Glu Ile Ser Asn Leu Val Asp Ile Gln 610 615 620 Glu Asp Tyr Leu Met Trp Phe Leu His Gln Ala Gly Met Lys Ala Arg 625 630 635 640 Pro Ser Ile Ile Gln Asp Thr Val Thr Leu Cys Ser Tyr Pro Phe Ile 645 650 655 Phe Asp Ala Gln Ala Lys Thr Lys Met Leu Gln Thr Asp Ala Glu Leu 660 665 670 Gln Met Gln val Ala Val Asn Gly Ala Asn Leu Gln Asn Val Phe Met 675 680 685 Leu Leu Thr Leu Glu Pro Leu Leu Ala Arg Ser Pro Phe Leu Val Leu 690 695 700 His Val Arg Arg Asn Asn Leu Val Gly Asp Ala Leu Arg Glu Leu Ser 705 710 715 720 Ile His Ser Asp Ile Asp Leu Lys Lys Pro Leu Lys Val Ile Phe Asp 725 730 735 Gly Glu Glu Ala Val Asp Ala Gly Gly val Thr Lys Glu Phe Phe Leu 740 745 750 Leu Leu Leu Lys Glu Leu Leu Asn Pro Ile Tyr Gly Met Phe Thr Tyr 755 ’ 760 765 ) Tyr Gln Asp Ser Asn Leu Leu Trp Phe Ser Asp Thr Cys Phe Val Glu 770 775 780 His Asn Trp Phe His Leu Ile Gly Ile Thr Cys Gly Leu Ala Ile Tyr 785 790 795 800 Asn Ser Thr Val Val Asp Leu His Phe Pro Leu Ala Leu Tyr Lys Lys 805 810 815 Leu Leu Asn Val Lys Pro Gly Leu Glu Asp Leu Lys Glu Leu Ser Pro 820 825 830 Thr Glu Gly Arg Ser Leu Gln Glu Leu Leu Asp Tyr Pro Gly Glu Asp 835 840 845 val Glu Glu Thr Phe Cys Leu Asn Phe Thr Ile Cys Arg Glu Ser Tyr B50 855 860 Gly Val Ile Glu Gln Lys Lys Leu Ile Pro Gly Gly Asp Asn Val Thr 865 870 875 880 Val Cys Lys Asp Asn Arg Gln Glu Phe Val Asp Ala Tyr Val Asn Tyr 885 - 890 895 Val Phe Gln Ile Ser val His Glu Trp Tyr Thr Ala Phe Ser Ser Gly 900 905 910 Phe Leu Lys Val Cys Gly Gly Lys Val Leu Glu Leu Phe Gln Pro Ser 915 920 925 Glu Leu Arg Ala Met Met Val Gly Asn Ser Asn Tyr Asn Trp Glu Glu 930 935 940 Leu Glu Glu Thr Ala Ile Tyr Lys Gly Asp Tyr Ser Ala Thr His Pro 945 950 955 960 Thr val Lys Leu Phe Trp Glu Thr Phe His Glu Phe Pro Leu Glu Lys 965 S70 975 Lys Lys Lys Phe Leu Leu Phe Leu Thr Gly Ser Asp Arg Ile Pro Ile 980 985 990 . Tyr Gly Met Ala Ser Leu Gln Ile Val Ile Gln Ser Thr Ala Ser Gly 995 1000 1005 Glu Glu Tyr Leu Pro Val Ala His Thr Cys Tyr Asn Leu Leu Asp 1010 1015 1020 Leu Pro Lys Tyr Ser Ser Lys Glu Ile Leu Ser Ala Arg Leu Thr 1025 1030 1035 Gln Ala Leu Asp Asn Tyr Glu Gly Phe Ser Leu Ala 1040 1045 1050 <210> 2574 <211l> 369 <212> PRT <213> Homo sapiens <400> 2574 Met Arg Ala Cys Ile Ser Leu Val Leu Ala Val Leu Cys Gly Leu Ala 1 5 10 15

Trp Ala Glu Asp His Lys Glu Ser Glu Pro Leu Pro Gln Leu Glu Glu

Glu Thr Glu Glu Ala Leu Ala Ser Asn Leu Tyr Ser Ala Pro Thr Ser 40 45 Cys Gln Gly Arg Cys Tyr Glu Ala Phe Asp Lys His His Gln Cys His 50 S55 60 Cys Asn Ala Arg Cys Gln Glu Phe Gly Asn Cys Cys Lys Asp Phe Glu 65 70 75 80 Ser Leu Cys Ser Asp His Glu Val Ser His Ser Ser Asp Ala Ile Thr 85 90 95 Lys Glu Glu Ile Gln Ser Ile Ser Glu Lys Ile Tyr Arg Ala Asp Thr 100 105 110 Asn Lys Ala Gln Lys Glu Asp Ile Val Leu Asn Ser Gln Asn Cys Ile 115 120 125 Ser Pro Ser Glu Thr Arg Asn Gln Val Asp Arg Cys Pro Lys Pro Leu 130 135 140 Phe Thr Tyr Val Asn Glu Lys Leu Phe Ser Lys Pro Thr Tyr Ala Ala 145 150 155 } 160 a Phe Ile Asn Leu Leu Asn Asn Tyr Gln Arg Ala Thr Gly His Gly Glu 165 170 175 His Phe Ser Ala Gln Glu Leu Ala Glu Gln Asp Ala Phe Leu Arg Glu 180 185 190 Ile Met Lys Thr Ala Val Met Lys Glu Leu Tyr Ser Phe Leu His His 195 200 205 Gln Asn Arg Tyr Gly Ser Glu Gln Glu Phe Val Asp Asp Leu Lys Asn 210 215 220 Met Trp Phe Gly Leu Tyr Ser Arg Gly Asn Glu Glu Gly Asp Ser Ser 225 230 235 240 Gly Phe Glu His Val Phe Ser Gly Glu Val Lys Lys Gly Lys Val Thr 245 250 255 986

Gly Phe His Asn Trp Ile Arg Phe Tyr Leu Glu Glu Lys Glu Gly Leu 260 265 270 val Asp Tyr Tyr Ser His Ile Tyr Asp Gly Pro Trp Asp Ser Tyr Pro 275 280 285 Asp Val Leu Ala Met Gln Phe Asn Trp Asp Gly Tyr Tyr Lys Glu Val 290 295 300 Gly Ser Ala Phe Ile Gly Ser Ser Pro Glu Phe Glu Phe Ala Leu Tyr 305 310 315 320 Ser Leu Cys Phe Ile Ala Arg Pro Gly Lys val Cys Gln Leu Ser Leu 325 330 335 Gly Gly Tyr Pro Leu Ala Val Arg Thr Tyr Thr Trp Asp Lys Ser Thr 340 345 350 Tyr Gly Asn Gly Lys Lys Tyr Ile Ala Thr Ala Tyr Ile Val Ser Ser 355 360 365 Thr <210> 2575 <211> 90 <212> PRT <213> Homo sapiens . <400> 2575 Met Asp Pro Leu Arg Ala Gln Gln Leu Ala Ala Glu Leu Glu Val Glu 1 5 “10 15 Met Met Ala Asp Met Tyr Asn Arg Met Thr Ser Ala Cys His Arg Lys

) Cys Val Pro Pro His Tyr Lys Glu Ala Glu Leu Ser Lys Gly Glu Ser 40 45 val Cys Leu Asp Arg Cys Val Ser Lys Tyr Leu Asp Ile His Glu Arg 50 55 60 Met Gly Lys Lys Leu Thr Glu Leu Ser Met Gln Asp Glu Glu Leu Met 65 70 75 80 Lys Arg Val Gln Gln Ser Ser Gly Pro Ala

85 90 <210> 2576 <211> 426 <212> PRT <213> Homo sapiens <400> 2576 Met Ala Asn Asp Ser Gly Gly Pro Gly Gly Pro Ser Pro Ser Glu Arg 1 5 10 15 Asp Arg Gln Tyr Cys Glu Leu Cys Gly Lys Met Glu Asn Leu Leu Arg

Cys Ser Arg Cys Arg Ser Ser Phe Tyr Cys Cys Lys Glu His Gln Arg 40 45 Gln Asp Trp Lys Lys His Lys Leu Val Cys Gln Gly Ser Glu Gly Ala 50 55 60 . Leu Gly His Gly Val Gly Pro His Gln His Ser Gly Pro Ala Pro Pro 65 70 75 80 Ala Ala Val Pro Pro Pro Arg Ala Gly Ala Arg Glu Pro Arg Lys Ala 85 S80 95 Ala Ala Arg Arg Asp Asn Ala Ser Gly Asp Ala Ala Lys Gly Lys Val 100 105 110 Lys Ala Lys Pro Pro Ala Asp Pro Ala Ala Ala Ala Ser Pro Cys Arg 115 ©0120 125 Ala Ala Ala Gly Gly Gln Gly Ser Ala Val Ala Ala Glu Ala Glu Pro 130 : 135 140 Gly Lys Glu Glu Pro Pro Ala Arg Ser Ser Leu Phe Gln Glu Lys Ala 145 150 155 160 Asn Leu Tyr Pro Pro Ser Asn Thr Pro Gly Asp Ala Leu Ser Pro Gly 165 170 175 Gly Gly Leu Arg Pro Asn Gly Gln Thr Lys Pro Leu Pro Ala Leu Lys 180 185 1390 Leu Ala Leu Glu Tyr Ile val Pro Cys Met Asn Lys His Gly Ile Cys 195 200 205 val Val Asp Asp Phe Leu Gly Lys Glu Thr Gly Gln Gln Ile Gly Asp 210 215 220 Glu Val Arg Ala Leu His Asp Thr Gly Lys Phe Thr Asp Gly Gln Leu 225 230 235 240 Val Ser Gln Lys Ser Asp Ser Ser Lys Asp Ile Arg Gly Asp Lys Ile 245 250 255 Thr Trp Ile Glu Gly Lys Glu Pro Gly Cys Glu Thr Ile Gly Leu Leu 260 265 270 Met Ser Ser Met Asp Asp Leu Ile Arg His Cys Asn Gly Lys Leu Gly 275 280 285 Ser Tyr Lys Ile Asn Gly Arg Thr Lys Ala Met Val Ala Cys Tyr Pro 290 295 300 Gly Asn Gly Thr Gly Tyr Val Arg His Val Asp Asn Pro Asn Gly Asp 305 310 315 320 Gly Arg Cys Val Thr Cys Ile Tyr Tyr Leu Asn Lys Asp Trp Asp Ala : 325 330 335 Lys Val Ser Gly Gly Ile Leu Arg Ile Phe Pro Glu Gly Lys Ala Gln 340 345 350 Phe Ala Asp Ile Glu Pro Lys Phe Asp Arg Leu Leu Phe Phe Trp Ser 355 360 365 Asp Arg Arg Asn Pro His Glu Val Gln Pro Ala Tyr Ala Thr Arg Tyr 370 375 380 Ala Ile Thr Val Trp Tyr Phe Asp Ala Asp Glu Arg Ala Arg Ala Lys 385 390 395 400 val Lys Tyr Leu Thr Gly Glu Lys Gly Val Arg Val Glu Leu Asn Lys 405 410 415 Pro Ser Asp Ser Val Gly Lys Asp Val Phe 420 425 <210> 2577 <211> 346 «212> PRT <213> Homo sapiens

<400> 2577 Met Glu Ser Val Ser Cys Ser Ala Ala Ala Val Arg Thr Gly Asp Met i 5 10 15 Glu Ser Gln Arg Asp Leu Ser Leu Val Pro Glu Arg Leu Gln Arg Arg

Glu Gln Glu Arg Gln Leu Glu Val Glu Arg Arg Lys Gln Lys Arg Gln 40 45 Asn Gln Glu Val Glu Lys Glu Asn Ser His Phe Phe Val Ala Thr Phe S50 55 60 : Ala Arg Glu Arg Ala Ala Val Glu Glu Leu Leu Glu Arg Ala Glu Ser 65 70 75 80 val Glu Arg Leu Glu Glu Ala Ala Ser Arg Leu Gln Gly Leu Gln Lys 85 90 95 Leu Ile Asn Asp Ser Val Phe Phe Leu Ala Ala Tyr Asp Leu Arg Gln 100 105 110 Gly Gln Glu Ala Leu Ala Arg Leu Gln Ala Ala Leu Ala Glu Arg Arg 115 120 125 Arg Gly Leu Gln Pro Lys Lys Arg Phe Ala Phe Lys Thr Arg Gly Lys 130 135 140 : Asp Ala Ala Ser Ser Thr Lys Val Asp Ala Ala Pro Gly Ile Pro Pro 145 150 155 160 Ala Val Glu Ser Ile Gln Asp Ser Pro Leu Pro Lys Lys Ala Glu Gly 165 170 175 Asp Leu Gly Pro Ser Trp Val Cys Gly Phe Ser Asn Leu Glu Ser Gln 180 185 190 Val Leu Glu Lys Arg Ala Ser Glu Leu His Gln Arg Asp Val Leu Leu 185 200 205 Thr Glu Leu Ser Asn Cys Thr Val Arg Leu Tyr Gly Asn Pro Asn Thr 210 215 220 Leu Arg Leu Thr Lys Ala His Ser Cys Lys Leu Leu Cys Gly Pro Val 225 230 235 240

Al

Ser Thr Ser Val Phe Leu Glu Asp Cys Ser Asp Cys Val Leu Ala val 245 250 255 Ala Cys Gln Gln Leu Arg Ile His Ser Thr Lys Asp Thr Arg Ile Phe 260 265 270 Leu Gln Val Thr Ser Arg Ala Ile Val Glu Asp Cys Ser Gly Ile Gln 275 280 285 Phe Ala Pro Tyr Thr Trp Ser Tyr Pro Glu Ile Asp Lys Asp Phe Glu ; 290 295 300 Ser Ser Gly Leu Asp Arg Ser Lys Asn Asn Trp Asn Asp Val Asp Asp 305 310 315 320 Phe Asn Trp Leu Ala Arg Asp Met Ala Ser Pro Asn Trp Ser Ile Leu 325 330 335 Pro Glu Glu Glu Arg Asn Ile Gln Trp Asp 340 345 <210> 2578 <211> 247 <212> PRT <213> Homo sapiens <400> 2578 Met Glu Phe Pro Lys Met Leu Thr Arg Lys Ile Lys Leu Trp Asp Ile 1 5 10 15 Asn Ala His Ile Thr Cys Arg Leu Cys Ser Gly Tyr Leu Ile Asp Ala

Thr Thr Val Thr Glu Cys Leu His Thr Phe Cys Arg Ser Cys Leu Val 40 45 Lys Tyr Leu Glu Glu Asn Asn Thr Cys Pro Thr Cys Arg Ile Val Ile 50 55 60 His Gln Ser His Pro Leu Gln Tyr Ile Gly His Asp Arg Thr Met Gln ) 65 70 75 80 Asp Ile Val Tyr Lys Leu Val Pro Gly Leu Gln Glu Ala Glu Met Arg 85 90 95

\

Lys Gln Arg Glu Phe Tyr His Lys Leu Gly Met Glu Val Pro Gly Asp 100 105 110 Ile Lys Gly Glu Thr Cys Ser Ala Lys Gln His Leu Asp Ser His Arg 115 120 125 Asn Gly Glu Thr Lys Ala Asp Asp Ser Ser Asn Lys Glu Ala Ala Glu 130 135 140 Glu Lys Pro Glu Glu Asp Asn Asp Tyr His Arg Ser Asp Glu Gln Val 145 150 155 160 Ser Ile Cys Leu Glu Cys Asn Ser Ser Lys Leu Arg Gly Leu Lys Arg 165 170 175 Lys Trp lle Arg Cys Ser Ala Gln Ala Thr Val Leu His Leu Lys Lys 180 185 130 Phe Ile Ala Lys Lys Leu Asn Leu Ser Ser Phe Asn Glu Leu Asp Ile 195 200 205 Leu Cys Asn Glu Glu Ile Leu Gly Lys Asp His Thr Leu Lys Phe Val 210 215 220 Val Val Thr Arg Trp Arg Phe Lys Lys Ala Pro Leu Leu Leu His Tyr 225 230 235 240 Arg Pro Lys Met Asp Leu Leu 245 <210> 2579 <21l1l> 360 <212> PRT <213> Homo sapiens <400> 2579 Met Ala Ser Ala Thr Ala Pro Ala Ala Ala Val Pro Thr Leu Ala Ser 1 5 10 15 Pro Leu Glu Gln Leu Arg His Leu Ala Glu Glu Leu Arg Leu Leu Leu

Pro Arg Val Arg Val Gly Glu Ala Gln Glu Thr Thr Glu Glu Phe Asn 40 45 Arg Glu Met Phe Trp Arg Arg Leu Asn Glu Ala Ala Val Thr Val Ser 50 55 . - 60 992 he,

Arg Glu Ala Thr Thr Leu Thr Ile Val Phe Ser Gln Leu Pro Leu Pro 65 70 75 80 : Ser Pro Gln Glu Thr Gln Lys Phe Cys Glu Gln Val His Ala Ala Ile 85 S50 95 Lys Ala Phe Ile Ala Val Tyr Tyr Leu Leu Pro Lys Asp Gln Gly Ile 100 105 110 Thr Leu Arg Lys Leu Val Arg Gly Ala Thr Leu Asp Ile val Asp Gly 115 120 125 Met Ala Gln Leu Met Glu Val Leu Ser Val Thr Pro Thr Gln Ser Pro 130 135 140 Glu Asn Asn Asp Leu Ile Ser Tyr Asn Ser Val Trp Val Ala Cys Gln 145 150 155 160 Gln Met Pro Gln Ile Pro Arg Asp Asn Lys Ala Ala Ala Leu Leu Met 165 170 175 Leu Thr Lys Asn Val Asp Phe Val Lys Asp Ala His Glu Glu Met Glu 180 185 190 Gln Ala Val Glu Glu Cys Asp Pro Tyr Ser Gly Leu Leu Asn Asp Thr 195 200 205 Glu Glu Asn Asn Ser Asp Asn His Asn His Glu Asp Asp Val Leu Gly 210 215 220 Phe Pro Ser Asn Gln Asp Leu Tyr Trp Ser Glu Asp Asp Gln Glu Leu 225 230 235 240 Ile Ile Pro Cys Leu Ala Leu Val Arg Ala Ser Lys Ala Cys Leu Lys 245 250 255 Lys Ile Arg Met Leu Val Ala Glu Asn Gly Lys Lys Asp Gln Val Ala 260 265 270 Gln Met Ala Asp Ile Val Asp Ile Ser Asp Glu Ile Ser Pro Ser Val 275 280 285 Asp Asp Leu Ala Leu Ser Ile Tyr Pro Pro Met Cys His Leu Thr Val 290 295 300

Arg Ile Asn Ser Ala Lys Leu Val Ser Val Leu Lys Lys Ala Leu Glu 305 310 315 320 Ile Thr Lys Ala Ser His Val Thr Pro Gln Pro Glu Asp Ser Trp Iie

325 330 335 Pro Leu Leu Ile Asn Ala Ile Asp His Cys Met Asn Arg Ile Lys Glu 340 345 350 Leu Thr Gln Ser Glu Leu Glu Leu 355 360 <210> 2580 <211l> 412 <212> PRT <213> Homo sapiens <400> 2580 Met Ala Glu Asn Leu Lys Gly Cys Ser Val Cys Cys Lys Ser Ser Trp 1 5 10 15 Asn Gln Leu Gln Asp Leu Cys Arg Leu Ala Lys Leu Ser Cys Pro Ala

Leu Gly Ile Ser Lys Arg Asn Leu Tyr Asp Phe Glu Val Glu Tyr Leu 40 45 Cys Asp Tyr Lys Lys Ile Arg Glu Gln Glu Tyr Tyr Leu Val Lys Trp 50 55 60 Arg Gly Tyr Pro Asp Ser Glu Ser Thr Trp Glu Pro Arg Gln Asn Leu 65 70 75 80 Lys Cys Val Arg Ile Leu Lys Gln Phe His Lys Asp Leu Glu Arg Glu 85 90 95 Leu Leu Arg Arg His His Arg Ser Lys Thr Pro Arg His Leu Asp Pro 100 105 110 : Ser Leu Ala Asn Tyr Leu Val Gln Lys Ala Lys Gln Arg Arg Ala Leu 115 120 125 Arg Arg Trp Glu Gln Glu Leu Asn Ala Lys Arg Ser His Leu Gly Arg 130 135 140 Ile Thr Val Glu Asn Glu Val Asp Leu Asp Gly Pro Pro Arg Ala Phe

145 150 155 160 val Tyr Ile Asn Glu Tyr Arg Val Gly Glu Gly Ile Thr Leu Asn Gln

165 170 ! 17s val Ala Val Gly Cys Glu Cys Gln Asp Cys Leu Trp Ala Pro Thr Gly 180 185 190 Gly Cys Cys Pro Gly Ala Ser Leu His Lys Phe Ala Tyr Asn Asp Gln 195 200 205 Gly Gln Val Arg Leu Arg Ala Gly Leu Pro Ile Tyr Glu Cys Asn Ser 210 215 220 Arg Cys Arg Cys Gly Tyr Asp Cys Pro Asn Arg Val Val Gln Lys Gly 225 230 235 240 Ile Arg Tyr Asp Leu Cys Ile Phe Arg Thr Asp Asp Gly Arg Gly Trp 245 250 255 Gly val Arg Thr Leu Glu Lys Ile Arg Lys Asn Ser Phe Val Met Glu 260 265 270 Tyr Val Gly Glu Ile Ile Thr Ser Glu Glu Ala Glu Arg Arg Gly Gln 275 280 285 Ile Tyr Asp Arg Gln Gly Ala Thr Tyr Leu Phe Asp Leu Asp Tyr Val 290 295 300 Glu Asp Val Tyr Thr Val Asp Ala Ala Tyr Tyr Gly Asn Ile Ser His 305 310 315 320 . Phe Val Asn His Ser Cys Asp Pro Asn Leu Gln Val Tyr Asn Val Phe 325 330 335 Ile Asp Asn Leu Asp Glu Arg Leu Pro Arg Ile Ala Phe Phe Ala Thr 340 345 350 Arg Thr Ile Arg Ala Gly Glu Glu Leu Thr Phe Asp Tyr Asn Met Gln 355 360 365 Val Asp Pro Val Asp Met Glu Ser Thr Arg Met Asp Ser Asn Phe Gly 370 375 380 Leu Ala Gly Leu Pro Gly Ser Pro Lys Lys Arg Val Arg Ile Glu Cys 385 3380 395 400

Lys Cys Gly Thr Glu Ser Cys Arg Lys Tyr Leu Phe 405 410 <210> 2581 <211> 110 <212> PRT <213> Homo sapiens <400> 2581 : Met Val Tyr Glu Arg Ala Gly Glu Ala Val Pro Pro Arg Gly Leu Arg 1 5 © 10 15 Glu Lys Phe Pro Arg Ala Leu Phe Gly Trp Ala Gly Glu Arg Pro Ser

Ala Leu Cys Ala Ser Asn Pro Pro Gln Leu Ser Cys Ser Gly Arg Gly 40 45 Ala Arg Tyr Phe Arg Leu Gly Glu Val Leu Gly Thr Asp Val Gly Ser S50 3) 60 Ser Val Gly Asp Phe Ser Gly Phe Trp Pro Phe Gln Thr Leu Val Ile 65 70 75 80 Val Phe Ser Val Gln Ser Ser Phe Gly Val Trp Gly Phe Pro Ser Ser 85 90 95 Cys Ala Arg His Arg Glu Ala Trp Pro Glu Gly Pro Val Ser 100 105 110 <210> 2582 <211> 471 <212> PRT <213> Homo sapiens <400> 2582 Met Pro Asn Ser Glu Pro Ala Ser Leu Leu Glu Leu Phe Asn Ser Ile 1 5 10 15 Ala Thr Gln Gly Glu Leu Val Arg Ser Leu Lys Ala Gly Asn Ala Ser 20 25 30 Lys Asp Glu Ile Asp Ser Ala Val Lys Met Leu Val Ser Leu Lys Met 35 40 45 Ser Tyr Lys Ala Ala Ala Gly Glu Asp Tyr Lys Ala Asp Cys Pro Pro

50 55 60 Gly Asn Pro Ala Pro Thr Ser Asn His Gly Pro Asp Ala Thr Glu Ala €5 70 75 80 Glu Glu Asp Phe Val Asp Pro Trp Thr Val Gln Thr Ser Ser Ala Lys 85 90 95 Gly Ile Asp Tyr Asp Lys Leu Ile Val Arg Phe Gly Ser Ser Lys Ile 100 105 110 Asp Lys Glu Leu Ile Asn Arg Ile Glu Arg Ala Thr Gly Gln Arg Pro 115 120 125 His His Phe Leu Arg Arg Gly Ile Phe Phe Ser His Arg Asp Met Asn 130 135 140 Gln Val Leu Asp Ala Tyr Glu Asn Lys Lys Pro Phe Tyr Leu Tyr Thr 145 150 185 160 Gly Arg Gly Pro Ser Ser Glu Ala Met His Val Gly His Leu Ile Pro 165 170 175 Phe Ile Phe Thr Lys Trp Leu Gln Asp Val Phe Asn Val Pro Leu Val 180 185 190 Ile Gln Met Thr Asp Asp Glu Lys Tyr Leu Trp Lys Asp Leu Thr Leu 195 200 205 Asp Gln Ala Tyr Gly Asp Ala Val Glu Asn Ala Lys Asp Ile Ile Ala 210 215 220 Cys Gly Phe Asp Ile Asn Lys Thr Phe Ile Phe Ser Asp Leu Asp Tyr 225 230 235 240 Met Gly Met Ser Ser Gly Phe Tyr Lys Asn Val Val Lys Ile Gln Lys 245 250 255 His val Thr Phe Asn Gln Val Lys Gly Ile Phe Gly Phe Thr Asp Ser 260 265 270 Asp Cys Ile Gly Lys Ile Ser Phe Pro Ala Ile Gln Ala Ala Pro Ser 275 280 285 Phe Ser Asn Ser Phe Pro Gln Ile Phe Arg Asp Arg Thr Asp Ile Gln 250 295 300

Cys Leu Ile Pro Cys Ala Ile Asp Gln Asp Pro Tyr Phe Arg Met Thr 305 310 315 320 Arg Asp Val Ala Pro Arg Ile Gly Tyr Pro Lys Pro Ala Leu Leu His 325 330 335 Ser Thr Phe Phe Pro Ala Leu Gln Gly Ala Gln Thr Lys Met Ser Ala 340 345 350 Ser Asp Pro Asn Ser Ser Ile Phe Leu Thx Asp Thr Ala Lys Gln Ile 355 360 365 Lys Thr Lys Val Asn Lys His Ala Phe Ser Gly Gly Arg Asp Thr Ile 370 375 380 Glu Glu His Arg Gln Phe Gly Gly Asn Cys Asp Val Asp Val Ser Phe 385 3580 395 400 Met Tyr Leu Thr Phe Phe Leu Glu Asp Asp Asp Lys Leu Glu Gln Ile 405 410 © 415 Arg Lys Asp Tyr Thr Ser Gly Ala Met Leu Thr Gly Glu Leu Lys Lys 420 425 430 Ala Leu Ile Glu Val Leu Gln Pro Leu Ile Ala Glu His Gln Ala Arg . 435 440 445 . Arg Lys Glu Val Thr Asp Glu Ile Val Lys Glu Phe Met Thr Pro Arg 450 455 460 Lys Leu Ser Phe Asp Phe Gln 465 470 <210> 2583 <211> 392 <212> PRT <213> Homo sapiens <400> 2583 Met Gly Ser Leu Ser Thr Ala Asn Val Glu Phe Cys Leu Asp Val Phe 1 5 10 15 Lys Glu Leu Asn Ser Asn Asn Ile Gly Asp Asn Ile Phe Phe Ser Ser

Leu Ser Leu Leu Tyr Ala Leu Ser Met Val Leu Leu Gly Ala Arg Gly 40 45 Glu Thr Ala Glu Gln Leu Glu Lys Val Leu His Phe Ser His Thr Val S50 55 60 Asp Ser Leu Lys Pro Gly Phe Lys Asp Ser Pro Lys Cys Ser Gln Ala 65 70 75 80 Gly Arg Ile His Ser Glu Phe Gly Val Glu Phe Ser Gln Ile Asn Gln 85 So 95 Pro Asp Ser Asn Cys Thr Leu Ser Ile Ala Asn Arg Leu Tyr Gly Thr 100 105 110 Lys Thr Met Ala Phe His Gln Gln Tyr Leu Ser Cys Ser Glu lys Trp 115 120 125 Tyr Gln Ala Arg Leu Gln Thr Val Asp Phe Glu Gln Ser Thr Glu Glu 130 135 140 Thr Arg Lys Met Ile Asn Ala Trp Val Glu Asn Lys Thr Asn Gly Lys 145 150 155 160 Val Ala Asn Leu Phe Gly Lys Ser Thr Ile Asp Pro Ser Ser Val Met 165 170 175 Val Leu Val Asn Thr Ile Tyr Phe Lys Gly Gln Arg Gln Asn Lys Phe 180 185 190 Gln Val Arg Glu Thr Val Lys Ser Pro Phe Gln Leu Ser Glu Gly Lys 185 200 205 Asn Val Thr Val Glu Met Met Tyr Gln Ile Gly Thr Phe Lys Leu Ala 210 215 220 Phe Val Lys Glu Pro Gln Met Gln Val Leu Glu Leu Pro Tyr Val Asn 225 230 235 240 Asn Lys Leu Ser Met Ile Ile Leu Leu Pro Val Gly Ile Ala Asn Leu 245 250 255 Lys Gln Ile Glu Lys Gln Leu Asn Ser Gly Thr Phe His Glu Trp Thr 260 265 270 Ser Ser Ser Asn Met Met Glu Arg Glu Val Glu Val His Leu Pro Arg

275 280 285 Phe Lys Leu Glu Ile Lys Tyr Glu Leu Asn Ser Leu Leu Lys Pro Leu 290 295 . 300 Gly Val Thr Asp Leu Phe Asn Gln Val Lys Ala Asp Leu Ser Gly Met 305 310 315 320 Ser Pro Thr Lys Gly Leu Tyr Leu Ser Lys Ala Ile His Lys Ser Tyr 325 330 335 Leu Asp Val Ser Glu Glu Gly Thr Glu Ala Ala Ala Ala Thr Gly Asp 340 345 350 Ser Ile Ala Val Lys Ser Leu Pro Met Arg Ala Gln Phe Lys Ala Asn 355 360 365 His Pro Phe Leu Phe Phe Ile Arg His Thr His Thr Asn Thr Ile Leu 370 375 380 Phe Cys Gly Lys Leu Ala Ser Pro 385 390 <210> 2584 <211> 811 <212> PRT <213> Homo sapiens <400> 2584 Met Pro Leu Ser Ser Pro Asn Ala Ala Ala Thr Ala Ser Asp Met Asp 1 5 10 15 Lys Aen Ser Gly Ser Asn Ser Ser Ser Ala Ser Ser Gly Ser Ser Lys

Gly Gln Gln Pro Pro Arg Ser Ala Ser Ala Gly Pro Ala Gly Glu Ser 40 45 Lys Pro Lys Ser Asp Gly Lys Asn Ser Ser Gly Ser Lys Arg Tyr Asn 50 55 60 Arg Lys Arg Glu Leu Ser Tyr Pro Lys Asn Glu Ser Phe Asn Asn Gln 65 70 75 80 Ser Arg Arg Ser Ser Ser Gln Lys Ser Lys Thr Phe Asn Lys Met Pro 85 90 95 1000 p

Pro Gln Arg Gly Gly Gly Ser Ser Lys Leu Phe Ser Ser Ser Phe Asn 100 105 110 Gly Gly Arg Arg Asp Glu Val Ala Glu Ala Gln Arg Ala Glu Phe Ser 115 120 125 Pro Ala Gln Phe Ser Gly Pro Lys Lys Ile Asn Leu Asn His Leu Leu 130 135 140 Asn Phe Thr Phe Glu Pro Arg Gly Gln Thr Gly His Phe Glu Gly Ser 145 150 155 160 Gly His Gly Ser Trp Gly Lys Arg Asn Lys Trp Gly His Lys Pro Phe 165 170 175 Asn Lys Glu Leu Phe Leu Gln Ala Asn Cys Gln Phe Val Val Ser Glu 180 185 190 Asp Gln Asp Tyr Thr Ala His Phe Ala Asp Pro Asp Thr Leu Val Asn 195 200 : 205 Trp Asp Phe Val Glu Gln Val Arg Ile Cys Ser His Glu Val Pro Ser 210 215 220 Cys Pro Ile Cys Leu Tyr Pro Pro Thr Ala Ala Lys Ile Thr Arg Cys 225 230 235 240 Gly His Ile Phe Cys Trp Ala Cys Ile Leu His Tyr Leu Ser Leu Ser 245 250 255 Glu Lys Thr Trp Ser Lys Cys Pro Ile Cys Tyr Ser Ser Val His Lys : 260 265 270 Lys Asp Leu Lys Ser Val Val Ala Thr Glu Ser His Gln Tyr Val Val 275 280 285 Gly Asp Thr Ile Thr Met Gln Leu Met Lys Arg Glu Lys Gly Val Leu 290 295 300 val Ala Leu Pro Lys Ser Lys Trp Met Asn Val Asp His Pro Ile His 305 310 315 320 Leu Gly Asp Glu Gln His Ser Gln Tyr Ser Lys Phe Leu Leu Ala Ser 325 330 335

\ Lys Glu Gln Val Leu His Arg Val Val Leu Glu Glu Lys Val Ala Leu 340 345 350 Glu Gln Gln Leu Ala Glu Glu Lys His Thr Pro Glu Ser Cys Phe Ile 355 360 365 Glu Ala Ala Ile Gln Glu Leu Lys Thr Arg Glu Glu Ala Leu Ser Gly 370 375 380 Leu Ala Gly Ser Arg Arg Glu Val Thr Gly Val Val Ala Ala Leu Glu 385 390 395 400 Gln Leu Val Leu Met Ala Pro Leu Ala Lys Glu Ser Val Phe Gln Pro 405 410 415 Arg Lys Gly Val Leu Glu Tyr Leu Ser Ala Phe Asp Glu Glu Thr Thr 420 425 430 Glu Val Cys Ser Leu Asp Thr Pro Ser Arg Pro Leu Ala Leu Pro Leu 435 440 445 Val Glu Glu Glu Glu Ala Val Ser Glu Pro Glu Pro Glu Gly Leu Pro 450 455 460 Glu Ala Cys Asp Asp Leu Glu Leu Ala Asp Asp Asn Leu Lys Glu Gly 465 470 475 480 Thr Ile Cys Thr Glu Ser Ser Gln Gln Glu Pro Ile Thr Lys Ser Gly 485 490 495 Phe Thr Arg Leu Ser Ser Ser Pro Cys Tyr Tyr Phe Tyr Gln Ala Glu 500 50S S10 Asp Gly Gln His Met Phe Leu His Pro Val Asn Val Arg Cys Leu Val 515 520 525 Arg Glu Tyr Gly Ser Leu Glu Arg Ser Pro Glu Lys Ile Ser Ala Thr 530 535 540 Val val Glu Ile Ala Gly Tyr Ser Met Ser Glu Asp Val Arg Gln Arg 545 550 585 560 His Arg Tyr Leu Ser His Leu Pro Leu Thr Cys Glu Phe Ser Ile Cys 565 570 575 Glu Leu Ala Leu Gln Pro Pro Val Val Ser Lys Glu Thr Leu Glu Met 1002 i.

PCT/US2003/012946

580 585 590 Phe Ser Asp Asp Ile Glu Lys Arg Lys Arg Gln Arg Gln Lys Lys Ala 595 600 605 Arg Glu Glu Arg Arg Arg Glu Arg Arg Ile Glu Ile Glu Glu Asn Lys 610 615 620

Lys Gln Gly Lys Tyr Pro Glu Val His Ile Pro Leu Glu Asn Leu Gln

625 630 635 640 Gln Phe Pro Ala Phe Asn Ser Tyr Thr Cys Ser Ser Asp Ser Ala Leu

645 650 655 Gly Pro Thr Ser Thr Glu Gly His Gly Ala Leu Ser Ile Ser Pro Leu 660 665 670 Ser Arg Ser Pro Gly Ser His Ala Asp Phe Leu Leu Thr Pro Leu Ser 675 680 685 Pro Thr Ala Ser Gln Gly Ser Pro Ser Phe Cys val Gly Ser Leu Glu 690 695 700 Glu Asp Ser Pro Phe Pro Ser Phe Ala Gln Met Leu Arg Val Gly Lys 705 710 715 720 Ala Lys Ala Asp val Trp Pro Lys Thr Ala Pro Lys Lys Asp Glu Asn 725 730 735 Ser Leu Val Pro Pro Ala Pro Val Asp Ser Asp Gly Glu Ser Asp Asn 740 745 750 Ser Asp Arg Val Pro Val Pro Ser Phe Gln Asn Ser Phe Ser Gln ala 755 760 765 Ile Glu Ala Ala Phe Met Lys Leu Asp Thr Pro Ala Thr Ser Asp Pro 770 775 780 Leu Ser Glu Glu Lys Gly Gly Lys Lys Arg Lys Lys Gln Lys Gln Lys 785 790 7395 800 Leu Leu Phe Ser Thr Ser val Val His Thr Lys 805 810 <210> 2585 <211> 482 :

<212> PRT <213> Homo sapiens <400> 2585 Met Ala Glu Ala Ala Thr Pro Gly Thr Thr Ala Thr Thr Ser Gly Ala 1 S 10 15 Gly Ala Ala Ala Ala Thr Ala Ala Ala Ala Ser Pro Thr Pro Ile Pro 20 25 30 Thr Val Thr Ala Pro Ser Leu Gly Ala Gly Gly Gly Gly Gly Gly ser 40 45 Asp Gly Ser Gly Gly Gly Trp Thr Lys Gln Val Thr Cys Arg Tyr Phe 50 s5 60 Met His Gly Val Cys Lys Glu Gly Asp Asn Cys Arg Tyr Ser His Asp 65 70 75 80 Leu Ser Asp Ser Pro Tyr Ser Val val Cys Lys Tyr Phe Gln Arg Gly 85 90 85 Tyr Cys Ile Tyr Gly Asp Arg Cys Arg Tyr Glu His Ser Lys Pro Leu 100 105 110 Lys Gln Glu Glu Ala Thr Ala Thr Glu Leu Thr Thr Lys Ser Ser Leu 115 120 125 Ala Ala Ser Ser Ser Leu Ser Ser Ile val Gly Pro Leu Val Glu Met 130 135 ' 140 . Asn Thr Gly Glu Ala Glu Ser Arg Asn Ser Asn Phe Ala Thr Val Gly 145 150 155 160 Ala Gly Ser Glu Asp Trp Val Asn Ala Ile Glu Phe Val Pro Gly Gln 165 170 175 Pro Tyr Cys Gly Arg Thr Ala Pro Ser Cys Thr Glu Ala Pro Leu Gln 180 185 150 Gly Ser val Thr Lys Glu Glu Ser Glu Lys Glu Gln Thr Ala val Glu 195 200 205 Thr Lys Lys Gln Leu Cys Pro Tyr Ala Ala val Gly Glu Cys Arg Tyr 210 21s 220

T/US2003/012946

Gly Glu Asn Cys val Tyr Leu His Gly Asp Ser Cys Asp Met Cys Gly 225 230 235 240 Leu Gln Leu Leu His Pro Met Asp Ala Ala Gln Arg Ser Gln His Ile 245 250 255 Lys Ser Cys Ile Glu Ala His Glu Lys Asp Met Glu Leu Ser Phe Ala 260 265 270 Val Gln Arg Ser Lys Asp Met val Cys Gly Ile Cys Met Glu val val 275 280 285 Tyr Glu Lys Ala Asn Pro Ser Glu Arg Arg Phe Gly Ile Leu Ser Asn 290 295 300 Cys Asn His Thr Tyr Cys Leu Lys Cys Ile Arg Lys Trp Arg Ser Ala . 308 310 315 320 Lys Gln Phe Glu Ser Lys Ile Ile Lys Ser Cys Pro Glu Cys Arg Ile 325 330 335 Thr Ser Asn Phe Val Ile Pro Ser Glu Tyr Trp Val Glu Glu Lys Glu 340 345 350 Glu Lys Gln Lys Leu Ile Leu Lys Tyr Lys Glu Ala Met Ser Asn Lys 355 360 365 Ala Cys Arg Tyr Phe Asp Glu Gly Arg Gly Ser Cys Pro Phe Gly Gly 370 378 380 Asn Cys Phe Tyr Lys His Ala Tyr Pro Asp Gly Arg Arg Glu Glu Pro 385 390 385 400 Gln Arg Gln Lys Val Gly Thr Ser Ser Arg Tyr Arg Ala Gln Arg Arg 405 410 415 Asn His Phe Trp Glu Leu Ile Glu Glu Arg Glu Asn Ser Asn Pro Phe 420 425 430 Asp Asn Asp Glu Glu Glu Val Val Thr Phe Glu Leu Gly Glu Met Leu 435 440 445 Leu Met Leu Leu Ala Ala Gly Gly Asp Asp Glu Leu Thr Asp Ser Glu 450 455 460 Asp Glu Trp Asp Leu Phe His Asp Glu Leu Glu Asp Phe Tyr Asp Leu

465 470 475 480 Asp Leu <210> 2586 <211> 146 <212> PRT <213> Homo sapiens <400> 2586 Met Pro Ser Lys Gly Pro Leu Gln Ser Val Gln Val Phe Gly Arg Lys 1 5 10 15 Lys Thr Ala Thr Ala Val Ala His Cys Lys Arg Gly Asn Gly Leu Ile

Lys Val Asn Gly Arg Pro Leu Glu Met Ile Glu Pro Arg Thr Leu Gln 40 45 Tyr Lys Leu Leu Glu Pro Val Leu Leu Leu Gly Lys Glu Arg Phe Ala 50 55 60 : Gly Val Asp Ile Arg Val Arg Val Lys Gly Gly Gly His Val Ala Gln 65 70 75 80 Ile Tyr Ala Ile Arg Gln Ser Ile Ser Lys Ala Leu Val Ala Tyr Tyr 85 90 95 Gln Lys Tyr Val Asp Glu Ala Ser Lys Lys Glu Ile Lys Asp Ile Leu 100 105 110 Ile Gln Tyr Asp Arg Thr Leu Leu Val Ala Asp Pro Arg Arg Cys Glu 115 120 125 Ser Lys Lys Phe Gly Gly Pro Gly Ala Arg Ala Arg Tyr Gln Lys Ser 130 135 140 Tyr Arg 145 <210> 2587 <211l> 1674 <212> PRT <213> Homo sapiens <400> 2587 1006 Le

PCT/US2003/012946

Met Glu Asp Ala Ser Glu Ser Ser Arg Gly Val Ala Pro Leu Ile Asn 1 5 10 15 Asn Val Val Leu Pro Gly Ser Pro Leu Ser Leu Pro Val Ser Val Thr

Gly Cys Lys Ser His Arg Val Ala Asn Lys Lys Val Glu Ala Arg Ser 40 45 Glu Lys Leu Leu Pro Thr Ala Leu Pro Pro Ser Glu Pro Lys Val Asp 50 55 60 Gln Lys Leu Pro Arg Ser Ser Glu Arg Arg Gly ser Gly Gly Gly Thr 65 70 75 80 Gln Phe Pro Ala Arg Ser Arg Ala Val Ala Ala Gly Glu Ala Ala Ala 8S 90 95 Arg Gly Ala Ala Gly Pro Glu Arg Gly Ser Pro Leu Gly Arg Arg Val 100 105 110 Ser Pro Arg Cys Leu Cys Ser Gly Glu Gly Gly Gln Val Ala Val Gly 115 120 125 Val Ile Ala Gly Lys Arg Gly Arg Arg Gly Arg Asp Gly Ser Arg Arg 130 135 140 Ala Pro Gly Gly Arg Glu Met Pro Leu Leu His Arg Lys Pro Phe Val 145 150 155 160 Arg Gln Lys Pro Pro Ala Asp Leu Arg Pro Asp Glu Glu Val Phe Tyr ] 165 170 175 Cys Lys Val Thr Asn Glu Ile Phe Arg His Tyr Asp Asp Phe Phe Glu 180 185 190 Arg Thr Ile Leu Cys Asn Ser Leu Val Trp Ser Cys Ala Val Thr Gly 195 200 205 Arg Pro Gly Leu Thr Tyr Gln Glu Ala Leu Glu Ser Glu Lys Lys Ala 210 215 220 Arg Gln Asn Leu Gln Ser Phe Pro Glu Pro Leu Ile Ile Pro val Leu 225 230 235 240 Tyr Leu Thr Ser Leu Thr His Arg Ser Arg Leu His Glu Ile Cys asp

245 2590 255 Asp Ile Phe Ala Tyr Val Lys Asp Arg Tyr Phe val Glu Glu Thr val ‘260 265 270 Glu Val Ile Arg Asn Asn Gly Ala Arg Leu Gln Cys Thr Ile Leu Glu 275 280 285 Val Leu Pro Pro Ser His Gln Asn Gly Phe Ala Asn Gly His Val Asn 290 285 300 Ser Val Asp Gly Glu Thr Ile Ile Ile Ser Asp Ser Asp Asp Ser Glu 305 310 315 320 Thr Gln Ser Cys Ser Phe Gln Asn Gly Lys Lys Lys Asp Ala Ile Asp 325 330 335 Pro Leu Leu Phe Lys Tyr Lys Val Gln Pro Thr Lys Lys Glu Leu His 340 345 350 Glu Ser Ala Ile Val Lys Ala Thr Gln Ile Ser Arg Arg Lys His Leu 355 360 365 Phe Ser Arg Asp Lys Leu Lys Leu Phe Leu Lys Gln His Cys Glu Pro 370 375 380 Gln Glu Gly Val Ile Lys Ile Lys Ala Ser Ser Leu Ser Thr Tyr Lys 385 390 385 400 Ile Ala Glu Gln Asp Phe Ser Tyr Phe Phe Pro Asp Asp Pro Pro Thr 405 410 415 Phe Ile Phe Ser Pro Ala Asn Arg Arg Arg Gly Arg Pro Pro Lys Arg 420 425 430 Ile His Ile Ser Gln Glu Asp Asn Val Ala Asn Lys Gln Thr Leu Ala 435 440 445 Ser Tyr Rrg Ser Lys Ala Thr Lys Glu Arg Asp Lys Leu Leu Lys Gln 450 455 460 Glu Glu Met Lys Ser Leu Ala Phe Glu Lys Ala Lys Leu Lys Arg Glu 465 470 475 480 Lys ala Asp Ala Leu Glu Ala Lys Lys Lys Glu Lys Glu Asp Lys Glu 485 490 495

CT/US2003/012946

Lys Lys Arg Glu Glu Leu Lys Lys Ile Val Glu Glu Glu Arg Leu Lys 500 508 510 Lys Lys Glu Glu Lys Glu Arg Leu Lys Val Glu Arg Glu Lys Glu Arg 515 520 525 Glu Lys Leu Arg Glu Glu Lys Arg Lys Tyr Val Glu Tyr Leu Lys Gln 530 535 540 Trp Ser Lys Pro Arg Glu Asp Met Glu Cys Asp Asp Leu Lys Glu Leu 545 550 555 560 Pro Glu Pro Thr Pro Val Lys Thr Arg Leu Pro Pro Glu Ile Phe Gly 565 570 575 Asp Ala Leu Met Val Leu Glu Phe Leu Asn Ala Phe Gly Glu Leu Phe 580 585 530 Asp Leu Gln Asp Glu Phe Pro Asp Gly Val Thr Leu Glu Val Leu Glu 595 600 605 Glu Ala Leu Val Gly Asn Asp Ser Glu Gly Pro Leu Cys Glu Leu Leu 610 615 620 Phe Phe Phe Leu Thr Ala Ile Phe Gln Ala Ile Ala Glu Glu Glu Glu 625 630 635 640 Glu val ala Lys Glu Gln Leu Thr Asp Ala Asp Thr Lys Gly Cys Ser 645 650 655 Leu Lys Ser Leu Asp Leu Asp Ser Cys Thr Leu Ser Glu Ile Leu Arg 660 665 670 Leu His Ile Leu Ala Ser Gly Ala Asp Val Thr Ser Ala Asn Ala Lys 675 680 68S Tyr Arg Tyr Gln Lys Arg Gly Gly Phe Asp Ala Thr Asp Asp Ala Cys 630 695 700 Met Glu Leu Arg Leu Ser Asn Pro Ser Leu Val Lys Lys Leu Ser Ser 705 710 715 720 Thr Ser val Tyr Asp Leu Thr Pro Gly Glu Lys Met Lys Ile Leu His 725 730 735

Ala Leu Cys Gly Lys Leu Leu Thr Leu Val Ser Thr Arg Asp Phe Ile 740 745 750 Glu Asp Tyr Val Asp Ile Leu Arg Gln Ala Lys Gln Glu Phe Arg Glu 755 760 765 Leu Lys Ala Glu Gln His Arg Lys Glu Arg Glu Glu Ala Ala ala Arg 770 77S 780 Ile Arg Lys Arg Lys Glu Glu Lys Leu Lys Glu Gln Glu Gln Lys Met 785 790 795 800 Lys Glu Lys Gln Glu Lys Leu Lys Glu Asp Glu Gln Arg Asn Ser Thr 805 810 815 Ala Asp Ile Ser Ile Gly Glu Glu Glu Arg Glu Asp Phe Asp Thr Ser 820 825 830 Ile Glu Ser Lys Asp Thr Glu Gln Lys Glu Leu Asp Gln Asp Met Phe 835 840 845 Thr Glu Asp Glu Asp Asp Pro Gly Ser His Lys Arg Gly Arg Arg Gly 850 855 860 Lys Arg Gly Gln Asn Gly Phe Lys Glu Phe Thr Arg Gln Glu Gln Ile 865 870 875 880 Asn Cys Val Thr Arg Glu Leu Leu Thr Ala Asp Glu Glu Glu Ala Leu 885 8390 895 Lys Gln Glu His Gln Arg Lys Glu Lys Glu Leu Leu Glu Lys Ile Gln 900 905 210 Ser Ala Ile Ala Cys Thr Asn Ile Phe Pro Leu Gly Arg Asp Arg Met 915 920 925 Tyr Arg Arg Tyr Trp Ile Phe Pro Ser Ile Pro Gly Leu Phe Ile Glu S30 935 S40 Glu Asp Tyr Ser Gly Leu Thr Glu Asp Met Leu Leu Pro Arg Pro Ser 945 S50 955 960 Ser Phe Gln Asn Asn Val Gln Ser Gln Asp Pro Gln Val Ser Thr Lys 965 970 978 1010 gE i

Thr Gly Glu Pro Leu Met Ser Glu Ser Thr Ser Asn Ile Asp Gln Gly 980 985 9390 Pro Arg Asp His Ser Val Gln Leu Pro Lys Pro Val His Lys Pro Asn 995 1000 1005 Arg Trp Cys Phe Tyr Ser Ser Cys Glu Gln Leu Asp Gln Leu Ile 1010 1015 1020 Glu Ala Leu Asn Ser Arg Gly His Arg Glu Ser Ala Leu Lys Glu 1025 1030 1035 Thr Leu Leu Gln Glu Lys Ser Arg Ile Cys Ala Gln Leu Ala Arg 1040 1045 1050 Phe Ser Glu Glu Lys Phe His Phe Ser Asp Lys Pro Gln Pro Asp 1055 1060 1065 Ser Lys Pro Thr Tyr Ser Arg Gly Arg Ser Ser Asn Ala Tyr Asp 1070 1075 1080 Pro Ser Gln Met Cys Ala Glu Lys Gln Leu Glu leu Arg Leu Arg 1085 1080 1085 Asp Phe Leu Leu Asp Ile Glu Asp Arg Ile Tyr Gln Gly Thr Leu 1100 1105 1110 Gly Ala Ile Lys Val Thr Asp Arg His Ile.

Trp Arg Ser Ala Leu 1115 1120 1125 Glu Ser Gly Arg Tyr Glu Leu Leu Ser Glu Glu Asn Lys Glu Asn 1130 1135 1140 Gly Ile Ile Lys Thr val Asn Glu Asp Val Glu Glu Met Glu Ile 1145 1150 1155 Asp Glu Gln Thr Lys Val Ile Val Lys Asp Arg Leu Leu Gly Ile 1160 1165 1170 Lys Thr Glu Thr Pro Ser Thr Val Ser Thr Asn Ala Ser Thr Pro 1175 1180 1185 Gln Ser Val Ser Ser Val val His Tyr Leu Ala Met Ala Leu Phe 1190 1185 1200 Gln Ile Glu Gln Gly Ile Glu Arg Arg Phe Leu Lys Ala Pro Leu

1205 1210 1215 Asp Ala Ser Asp Ser Gly Arg Ser Tyr Lys Thr Val Leu Asp Arg 1220 1225 1230 Trp Arg Glu Ser Leu Leu Ser Ser Ala Ser Leu Ser Gln Val Phe 1235 1240 1245 Leu His Leu Ser Thr Leu Asp Arg Ser Val Ile Trp Ser Lys Ser 1250 1255 1260 Ile Leu Asn Ala Arg Cys Lys Ile Cys Arg Lys Lys Gly Asp Ala 1265 1270 127S Glu Asn Met Val Leu Cys Asp Gly Cys Asp Arg Gly His His Thr 1280 1285 1290 Tyr Cys Val Arg Pro Lys Leu Lys Thr val Pro Glu Gly Asp Trp 1295 1300 1305 Phe Cys Pro Glu Cys Arg Pro Lys Gln Arg Cys Arg Arg Leu Ser 1310 1315 1320 Phe Arg Gln Arg Pro Ser Leu Glu Ser Asp Glu Asp Val Glu Asp 1325 1330 1335 Ser Met Gly Gly Glu Asp Asp Glu Val Asp Gly Asp Glu Glu Glu : 1340 1345 1350 Gly Gln Ser Glu Glu Glu Glu Tyr Glu Val Glu Gln Asp Glu Asp 1355 1360 1365 Asp Ser Gln Glu Glu Glu Glu Val Ser Leu Pro Lys Arg Gly Arg 1370 1375 1380 Pro Gln Val Arg Leu Pro Val Lys Thr Arg Gly Lys Leu Ser Ser 1385 1390 1395 Ser Phe Ser Ser Arg Gly Gln Gln Gln Glu Pro Gly Arg Tyr Pro 1400 1405 1410 Ser Arg Ser Gln Gln Ser Thr Pro Lys Thr Thr Val Ser Ser Lys 1415 1420 1425 Thr Gly Arg Ser Leu Arg Lys Ile Asn Ser Ala Pro Pro Thr Glu 1430 1435 : 1440

PCT/US2003/012946

Thr Lys Ser Leu Arg Ile Ala Ser Arg Ser Thr Arg His Ser Hig 1445 1450 1455 Gly Pro Leu Gln Ala Asp Val Phe Val Glu Leu Leu Ser Pro Arg 1460 1465 1470 Arg Lys Arg Arg Gly Arg Lys Ser Ala Asn Asn Thr Pro Glu Asn 1475 1480 1485 . Ser Pro Asn Phe Pro Asn Phe Arg Val Ile Ala Thr Lys Ser Ser 1480 1495 1500 Glu Gln Ser Arg Ser val Asn Ile Ala Ser Lys Leu Ser Leu Gln 1505 1510 1515 Glu Ser Glu Ser Lys Arg Arg Cys Arg Lys Arg Gln Ser Pro Glu 1520 1525 1530 Pro Ser Pro Val Thr Leu Gly Arg Arg Ser Ser Gly Arg Gln Gly 1535 1540 1545 Gly Val His Glu Leu Ser Ala Phe Glu Gln Leu Val Val Glu Leu 1550 1555 1560 Val Arg His Asp Asp Ser Trp Pro Phe Leu Lys Leu Val Ser Lys 1565 1570 1578 Ile Gln Val Pro Asp Tyr Tyr Asp Ile Ile Lys Lys Pro Ile Ala 1580 1585 1590 Leu Asn Ile Ile Arg Glu Lys Val Asn Lys Cys Glu Tyr Lys Leu 1595 1600 1605 Ala Ser Glu Phe Ile Asp Asp Ile Glu Leu Met Phe Ser Asn Cys 1610 1615 1620 Phe Glu Tyr Asn Pro Arg Asn Thr Ser Glu Ala Lys Ala Gly Thr 1625 1630 1635 Arg Leu Gln Ala Phe Phe His Ile Gln Ala Gln Lys Leu Gly Leu 1640 1645 1650 His val Thr Pro Ser Asn Val Asp Gln Val Ser Thr Pro Pro Ala 1655 1660 1665

JE —

pla Lys LYS ser Arg Ile 1670 <210> 2588 <211> 103 <212> PRT <213> Homo sapiens <400> 2588 Met Ala Gln phe val AY9 Asn Leu val Glu Lys Thr pro Ala Leu val 1 5 10 15 Asn Ala Ala val ThT Tyr Ser Lys Pro arg Leu pla Thr Phe Trp TYY

TYY ala Lys val Glu Leu val Pro Pro Thr Pro Ala glu Ile PTO AXg 40 45 pla Ile gln Ser Leu Lys LYS 1le hla AsD ser Ala Gln Thr Gly Ser 50 55 60 phe Lys Gln Leu Thr val Lys Glu ala val Leu asn Gly Leu val Ala 65 70 75 80 Thr Glu val Leu Met Trp Phe TvVT yal Gly Glu 1le Ile Gly Lys Arg 85 90 95 gly lle Ile Gly TVYT asp val 100 <210> 258% <21l> 156 <212> PRT «213> Homo sapiens <400> 2589 Met Ser gly Gly Leu Leu LYS ala Leu AYS ger Asp Ser Tyr val Glu 1 5 10 15 Leu Ser Gln Tyr Arg ASP Gln His Phe Arg Gly ASP asn Glu Glu Gln 20 25 30 Glu Lys heu Leu Lys LYS ser Cys Thr Leu TYY¥ val Gly Asn Leu ser 35 40 45 phe Tyr ThT Thr Glu Glu cin Ile TY¥ Glu Leu Phe Ser Lys Ser Gly 50 S5 60 1014 b

Asp Ile Lys Lys Ile Ile Met Gly Leu Asp Lys Met Lys Lys Thr ala 65 70 75 80 Cys Gly Phe Cys Phe Val Glu Tyr Tyr Ser Arg Ala Asp Ala Glu Asn

85 90 95 Ala Met Arg Tyr Ile Asn Gly Thr Arg Leu Asp Asp Arg Ile Ile Arg 100 105 110 Thr Asp Trp Asp Ala Gly Phe Lys Glu Gly Arg Gln Tyr Gly Arg Gly 115 120 125 Arg Ser Gly Gly Gln Val Arg Asp Glu Tyr Arg Gln Asp Tyr Asp Ala 130 13S 140 Gly Arg Gly Gly Tyr Gly Lys Leu Ala Gln Asn Gln 145 150 155 <210> 2590 © <211> 436 <212> PRT <213> Homo sapiens <400> 2590 Met Asp Ser Val Ala Phe Glu Asp Val Ala Val Asn Phe Thr Gln Glu 1 5 10 15 Glu Trp Ala Leu Leu Ser Pro Ser Gln Lys Asn Leu Tyr Arg Asp Val : 30 Thr Leu Glu Thr Phe Arg Asn Leu Ala Ser Val Gly Ile Gln Trp Lys 40 45 Asp Gln Asp Ile Glu Asn Leu Tyr Gln Asn Leu Gly Ile Lys Leu Arg 50 S5 60 Ser Leu Val Glu Arg Leu Cys Gly Arg Lys Glu Gly Asn Glu His Arg €5 70 75 80 Glu Thr Phe Ser Gln Ile Pro Asp Cys His Leu Asn Lys Lys Ser Gln 85 90 95 Thr Gly Val Lys Pro Cys Lys Cys Ser Val Cys Gly Lys Val Phe Leu 100 105 110

Arg His Ser Phe Leu Asp Arg His Met Arg Ala His Ala Gly His Lys 115 120 125 Arg Ser Glu Cys Gly Gly Glu Trp Arg Glu Thr Pro Arg Lys Gln Lys 130 135 140 Gln His Gly Lys Ala Ser Ile Ser Pro Ser Ser Gly Ala Arg Arg Thr 145 150 155 160 Val Thr Pro Thr Arg Lys Arg Pro Tyr Glu Cys Lys Val Cys Gly Lys 165 170 175 Ala Phe Asn Ser Pro Asn Leu Phe Gln Ile His Gln Arg Thr His Thr 180 185 180 Gly Lys Arg Sex Tyr Lys Cys Arg Glu Ile Val Arg Ala Phe Thr Val 195 200 205 Ser Ser Phe Phe Arg Lys His Gly Lys Met His Thr Gly Glu Lys Arg 210 215 220 Tyr Glu Cys Lys Tyr Cys Gly Lys Pro Ile Asp Tyr Pro Ser Leu Phe 225 230 235 240 Gln Ile His Val Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Lys 245 250 25S Gln Cys Gly Lys Ala Phe Ile Ser Ala Gly Tyr Leu Arg Thr His Glu 260 265 270 Ile Arg Ser His Ala Leu Glu Lys Ser His Gln Cys Gln Glu Cys Gly 275 280 285 Lys Lys Leu Ser Cys Ser Ser Ser Leu His Arg His Glu Arg Thr His 290 295 300 Ser Gly Gly Lys Leu Tyr Glu Cys Gln Lys Cys Ala Lys Val Phe Arg 305 310 315 320 Cys Pro Thr Ser Leu Gln Ala His Glu Arg Ala His Thr Gly Glu Arg 325 330 335 Pro Tyr Glu Cys Asn Lys Cys Gly Lys Thr Phe Asn Tyr Pro Ser Cys 340 345 350 Phe Arg Arg His Lys Lys Thr His Ser Gly Glu Lys Pro Tyr Glu Cys

T/US2003/012946 355 360 365 Thr Arg Cys Gly Lys Ala Phe Gly Trp Cys Ser Ser Leu Arg Arg His 370 375 380 Glu Met Thr His Thr Gly Glu Lys Pro Phe Asp Cys Lys Gln Cys Gly 385 390 395 400 Lys Val Phe Thr Phe Ser Asn Tyr Leu Arg Leu His Glu Arg Thr His 405 410 415 Leu Ala Gly Arg Ser Gln Cys Phe Gly Arg Arg Gln Gly Asp His Leu 420 425 430 Ser Pro Gly val 435 <210> 25091 <211> 92 <212> PRT <213> Homo ‘sapiens <400> 2591 Met Gln Val Ser Thr Ala Ala Leu Ala Val Leu Leu Cys Thr Met Ala 1 Ss 10 15 Leu Cys Asn Gln Phe Ser Ala Ser Leu Ala Ala Asp Thr Pro Thr ala

30 . Cys Cys Phe Ser Tyr Thr Ser Arg Gln Ile Pro Gln Asn Phe Ile Ala 40 45 Asp Tyr Phe Glu Thr Ser Ser Gln Cys Ser Lys Pro Gly Val Ile Phe 50 55 60 Leu Thr Lys Arg Ser Arg Gln Val Cys Ala Asp Pro Ser Glu Glu Trp 65 70 75 80 Val Gln Lys Tyr Val Ser Asp Leu Glu Leu Ser Ala 85 90 <210> 2592 <211> 271 <212> PRT <213> Homo sapiens <400> 2592

Met Glu Ala Leu Pro Leu Leu Ala Ala Thr Thr Pro Asp His Gly Arg 1 Ss 10 15 His Arg Arg Leu Leu Leu Leu Pro Leu Leu Leu Phe Leu Leu Pro Ala

Gly Ala Val Gln Gly Trp Glu Thr Glu Glu Arg Pro Arg Thr Arg Glu 40 45 Glu Glu Cys His Phe Tyr Ala Gly Gly Gln Val Tyr Pro Gly Glu Ala 50 55 60 Ser Arg Val Ser Val Ala Asp His Ser Leu His Leu Ser Lys Ala Lys 65 70 75 80 Ile Ser Lys Pro Ala Pro Tyr Trp Glu Gly Thr Ala Val Ile Asp Gly 85 90 95 Glu Phe Lys Glu Leu Lys Leu Thr Asp Tyr Arg Gly Lys Tyr Leu Val 100 105 110 Phe Phe Phe Tyr Pro Leu Asp Phe Thr Phe Val Cys Pro Thr Glu Ile 115 120 125 Ile Ala Phe Gly Asp Arg Leu Glu Glu Phe Arg Ser Ile Asn Thr Glu 130 135 140 Val Val Ala Cys Ser Val Asp Ser Gln Phe Thr His Leu Ala Trp Ile 145 150 155 160 Asn Thr Pro Arg Arg Gln Gly Gly Leu Gly Pro Ile Arg Ile Pro Leu 165 170 175 Leu Ser Asp Leu Thr His Gln Ile Ser Lys Asp Tyr Gly Val Tyr Leu 180 185 190 Glu Asp Ser Gly His Thr Leu Arg Gly Leu Phe Ile Ile Asp Asp Lys 195% 200 205 Gly Ile Leu Arg Gln Ile Thr Leu Asn Asp Leu Pro Val Gly Arg Ser 210 215 220 val Asp Glu Thr Leu Arg Leu Val Gln Ala Phe Gin Tyr Thr Asp Lys 225 230 235 240 His Gly Glu Val Cys Pro Ala Gly Trp Lys Pro Gly Ser Glu Thr Ile

PCT/US2003/012946

245 250 255 Ile Pro Asp Pro Ala Gly Lys Leu Lys Tyr Phe Asp Lys Leu Asn 260 265 270, <210> 2593 <211> 659 <212> PRT <213> Homo sapiens <400> 2593 Met Ala Ala val Ile Leu Glu Ser Ile Phe Leu Lys Arg Ser Gln Gln 1 5 10 15 Lys Lys Lys Thr Ser Pro Leu Asn Phe Lys Lys Arg Leu Phe Leu Leu i

Thr Val His Lys Leu Ser Tyr Tyr Glu Tyr Asp Phe Glu Arg Gly Arg 40 45 Arg Gly Ser Lys Lys Gly ser Ile Asp Val Glu Lys Ile Thr Cys val SO 55 60 Glu Thr val Val Pro Glu Lys Asn Pro Pro Pro Glu Arg Gln Ile Pro 65 70 75 80 Arg Arg Gly Glu Glu Ser Ser Glu Met Glu Gln Ile Ser Ile Ile Glu 85 90 95 Arg Phe Pro Tyr Pro Phe Gln Val Val Tyr Asp Glu Gly Pro Leu Tyr 100 105 110 Val Phe Ser Pro Thr Glu Glu Leu Arg Lys Arg Trp Ile His Gln Leu 115 120 125 Lys Asn Val Ile Arg Tyr Asn Ser Asp Leu Val Gln Lys Tyr His Pro 130 135 140 Cys Phe Trp Ile Asp Gly Gln Tyr Leu Cys Cys Ser Gln Thr Ala Lys 145 150 155 160 Asn Ala Met Gly Cys Gln Ile Leu Glu Asn Arg Asn Gly Ser Leu Lys 165 170 175 Pro Gly Ser Ser His Arg Lys Thr Lys Lys Pro Leu Pro Pro Thr Pro 180 185 130

Glu Glu Asp Gln Ile Leu Lys Lys Pro Leu Pro Pro Glu Pro Ala Ala 195 200 205 Ala Pro Val Ser Thr Ser Glu Leu Lys Lys Val Val Ala Leu Tyr Asp 210 215 220 Tyr Met Pro Met Asn Ala Asn Asp Leu Gln Leu Arg Lys Gly Asp Glu 225 230 235 240 Tyr Phe Ile Leu Glu Glu Ser Asn Leu Pro Trp Trp Arg Ala Arg Asp 245 250 255 Lys Asn Gly Gln Glu Gly Tyr Ile Pro Ser Asn Tyr Val Thr Glu Ala 260 265 270 Glu Asp Ser Ile Glu Met Tyr Glu Trp Tyr Ser Lys His Met Thr Arg 275 280 285 Ser Gln Ala Glu Gln Leu Leu Lys Gln Glu Gly Lys Glu Gly Gly Phe 290 295 300 Ile Val Arg Asp Ser Ser Lys Ala Gly Lys Tyr Thr Val Ser val Phe 305 310 315 320 Ala Lys Ser Thr Gly Asp Pro Gln Gly Val Ile Arg His Tyr val Val 325 330 335 Cys Ser Thr Pro Gln Ser Gln Tyr Tyr Leu Ala Glu Lys His Leu Phe 340 345 350 Ser Thr Ile Pro Glu Leu Ile Asn Tyr His Gln His Asn Ser Ala Gly 355 360 365 Leu Ile Ser Arg Leu Lys Tyr Pro Val Ser Gln Gln Asn Lys Asn Ala 370 375 380 Pro Ser Thr Ala Gly Leu Gly Tyr Gly Ser Trp Glu Ile Asp Pro Lys 385 390 39S 400 Asp Leu Thr Phe Leu Lys Glu Leu Gly Thr Gly Gln Phe Gly Val val . 405 410 415 Lys Tyr Gly Lys Trp Arg Gly Gln Tyr Asp Val Ala Ile Lys Met Ile 420 425 430

PCT/US2003/012946

Lys Glu Gly Ser Met Ser Glu Asp Glu Phe Ile Glu Glu Ala Lys val 435 440 445 Met Met Asn Leu Ser His Glu Lys Leu Val Gln Leu Tyr Gly val Cys 450 455 460 Thr Lys Gln Arg Pro Ile Phe Ile Ile Thr Glu Tyr Met Ala Asn Gly 465 470 47S 480 Cys Leu Leu Asn Tyr Leu Arg Glu Met Arg His Arg Phe Gln Thr Gln 485 490 495 Gln Leu Leu Glu Met Cys Lys Asp Val Cys Glu Ala Met Glu Tyr Leu 500 505 510 Glu Ser Lys Gln Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Leu 515 520 525 Val Asn Asp Gln Gly Val Val Lys Val Ser Asp Phe Gly Leu Ser Arg 530 535 540 Tyr Val Leu Asp Asp Glu Tyr Thr Ser Ser val Gly Ser Lys phe Pro 545 550 555 560 Val Arg Trp Ser Pro Pro Glu Val Leu Met Tyr Ser Lys Phe Ser Ser 565 570 575 Lys Ser Asp Ile Trp Ala Phe Gly val Leu Met Trp Glu Ile Tyr Ser 580 585 590 Leu Gly Lys Met Pro Tyr Glu Arg Phe Thr Asn Ser Glu Thr Ala Glu 595 600 605 His Ile Ala Gln Gly Leu Arg Leu Tyr Arg Pro His Leu Ala Ser Glu 610 615 620 Lys Val Tyr Thr Ile Met Tyr Ser Cys Trp His Glu Lys Ala Asp Glu 625 630 635 640 Arg Pro Thr Phe Lys Ile Leu Leu Ser Asn Ile Leu Asp val Met Asp 645 650 655 Glu Glu Ser <210> 2594

US2003/012946

<211> 417 <212> PRT <213> Homo sapiens <400> 2594 Met Ser Leu Ser Asn Lys Leu Thr Leu Asp Lys Leu Asp Val Lys Gly 1 5 10 1s Lys Arg Val Val Met Arg Val Asp Phe Asn Val Pro Met Lys Asn Asn

Glin Ile Thr Asn Asn Gln Arg Ile Lys Ala Ala Val Pro Ser Ile Lys 40 45 Phe Cys Leu Asp Asn Gly Ala Lys Ser Val Val Leu Met Ser His Leu 50 55 60 Gly Arg Pro Asp Gly Val Pro Met Pro Asp Lys Tyr Ser Leu Glu Pro 65 70 75 80 Val Ala Val Glu Leu Lys Ser Leu Leu Gly Lys Asp Val Leu Phe Leu 85 So 95 Lys Asp Cys Val Gly Pro Glu Val Glu Lys Ala Cys Ala Asn Pro Ala 100 105 110 Ala Gly Ser Val Ile Leu Leu Glu Asn Leu Arg Phe His Val Glu Glu 1158 120 125 Glu Gly Lys Gly Lys Asp Ala Ser Gly Asn Lys Val Lys Ala Glu Pro 130 135 140 Ala Lys Ile Glu Ala Phe Arg Ala Ser Leu Ser Lys Leu Gly Asp Val 145 150 155 160 Tyr Val Asn Asp Ala Phe Gly Thr Ala His Arg Ala His Ser Ser Met 165 170 175 Val Gly val Asn Leu Pro Gln Lys Ala Gly Gly Phe Leu Met Lys Lys 180 185 180 Glu Leu Asn Tyr Phe Ala Lys Ala Leu Glu Ser Pro Glu Arg Pro Phe 195 200 205 Leu Ala Ile Leu Gly Gly Ala Lys Val Ala Asp Lys Ile Gln Leu Ile 210 218 220

Asn Asn Met Leu Asp Lys Val Asn Glu Met Ile Ile Gly Gly Gly Met 225 230 235 2490 Ala Phe Thr Phe Leu Lys Val Leu Asn Asn Met Glu Ile Gly Thr Ser 245 250 255 Leu Phe Asp Glu Glu Gly Ala Lys Ile Val Lys Asp Leu Met Ser Lys 260 265 270 Ala Glu Lys Asn Gly Val Lys Ile Thr Leu Pro Val Asp Phe Val Thr 275 280 285 Ala Asp Lys Phe Asp Glu Asn Ala Lys Thr Gly Gln Ala Thr Val Ala 290 295 ’ 300 Ser Gly Ile Pro Ala Gly Trp Met Gly Leu Asp Cys Gly Pro Glu Ser 305 310 315 320 Ser Lys Lys Tyr Ala Glu Ala Val Thr Arg Ala Lys Gln Ile Val Trp 325 330 335 Asn Gly Pro Val Gly val Phe Glu Trp Glu Ala Phe Ala Arg Gly Thr 340 345 350 Lys Ala Leu Met Asp Glu Val Val Lys Ala Thr Ser Arg Gly Cys Ile 355 360 365 Thr Ile Ile Gly Gly Gly Asp Thr Ala Thr Cys Cys Ala Lys Trp Asn 370 375 380 Thr Glu Asp Lys Val Ser His Val Ser Thr Gly Gly Gly Ala Ser Leu 385 390 395 400 Glu Leu Leu Glu Gly Lys Val Leu Pro Gly Val Asp Ala Leu Ser Asn 405 410 415 Ile <210> 2595 <211> 468 <212> PRT <213> Homo sapiens <400> 25895 Met Ala Pro Pro Pro Ala Arg Val His Leu Gly Ala Phe Leu Ala Val

PCT/US2003/012946

1 5 10 15 Thr Pro Asn Pro Gly Ser Ala Ala Ser Gly Thr Glu Ala Ala Ala Ala

Thr Pro Ser Lys Val Trp Gly Ser Ser Ala Gly Arg Ile Glu Pro Arg 40 45 Gly Gly Gly Arg Gly Ala Leu Pro Thr Ser Met Gly Gln His Gly Pro 50 55 60 Ser Ala Arg Ala Arg Ala Gly Arg Ala Pro Gly Pro Arg Pro Ala Arg 65 70 75 80 Glu Ala Ser Pro Arg Leu Arg Val His Lys Thr Phe Lys Phe Val Val 85 90 95 Val Gly Val Leu Leu Gln Val Val Pro Ser Ser Ala Ala Thr Ile Lys 100 105 110 Leu His Asp Gln Ser Ile Gly Thr Gln Gln Trp Glu Eis Ser Pro Leu 115 120 125 Gly Glu Leu Cys Pro Pro Gly Ser His Arg Ser Glu His Pro Gly Ala 130 135 140 Cys Asn Arg Cys Thr Glu Gly Val Gly Tyr Thr Asn Ala Ser Asn Asn 145 150 155 160 Leu Phe Ala Cys Leu Pro Cys Thr Ala Cys Lys Ser Asp Glu Glu Glu 165 170 175 Arg Ser Pro Cys Thr Thr Thr Arg Asn Thr Ala Cys Gln Cys Lys Pro 180 185 190 Gly Thr Phe Arg Asn Asp Asn Ser Ala Glu Met Cys Arg Lys Cys Ser 185 200 205 Arg Gly Cys Pro Arg Gly Met Val Lys Val Lys Asp Cys Thr Pro Trp 210 215 220 Ser Asp Ile Glu Cys Val His Lys Glu Ser Gly Asn Gly His Asn Ile 225 230 235 240 Trp Val Ile Leu Val Val Thr Leu Val Val Pro Leu Leu Leu val Ala 245 250 255

003/012946

Val Leu Ile val Cys Cys Cys Ile Gly Ser Gly Cys Gly Gly Asp Pro 260 265 270 Lys Cys Met Asp Arg Val Cys Phe Trp Arg Leu Gly Leu Leu Arg Gly 275 280 285 Pro Gly Ala Glu Asp Asn Ala His Asn Glu Ile Leu Ser Asn Ala Asp 290 295 300 Ser Leu Ser Thr Phe Val Ser Glu Gln Gln Met Glu Ser Gln Glu Pro 305 310 315 320 Ala Asp Leu Thr Gly Val Thr val Gln Ser Pro Gly Glu Ala Gln Cys 325 330 335 Leu Leu Gly Pro Ala Glu Ala Glu Gly Ser Gln Arg Arg Arg Leu Leu 340 345 350 Val Pro Ala Asn Gly Ala Asp Pro Thr Glu Thr Leu Met Leu Phe Phe 355 360 365 Asp Lys Phe Ala Asn Ile Val Pro Phe Asp Ser Trp Asp Gln Leu Met 370 375 380 Arg Gln Leu Asp Leu Thr Lys Asn Glu Ile Asp Val Val Arg ala Gly 385 350 385 400 Thr Ala Gly Pro Gly Asp Ala Leu Tyr Ala Met Leu Met Lys Trp Val 405 410 415 Asn Lys Thr Gly Arg Asn Ala Ser Ile His Thr Leu Leu Asp Ala Leu 420 425 430 Glu Arg Met Glu Glu Arg His Ala Lys Glu Lys Ile Gln Asp Leu Leu 435 440 445 Val Asp Ser Gly Lys Phe lle Tyr Leu Glu Asp Gly Thr Gly Ser Ala 450 455 460 val Ser Leu Glu 465 <210> 2596 <211> 185 <212> PRT

PCT/US2003/012946

<213> Homo sapiens <400> 2596 Met 1ys Leu Val Ser Val Ala Leu Met Tyr Leu Gly Ser Leu Ala Phe 1 S 10 15 Leu Gly Ala Asp Thr Ala Arg Leu Asp Val Ala Ser Glu Phe Arg Lys

Lys Trp Asn Lys Trp Ala Leu Ser Arg Gly Lys Arg Glu Leu Arg Met 40 45 Ser Ser Ser Tyr Pro Thr Gly Leu Ala Asp Val Lys Ala Gly Pro Ala 50 55 60 Gln Thr Leu Ile Arg Pro Gln Asp Met Lys Gly Ala Ser Arg Ser Pro 65 70 75 80 Glu Asp Ser Ser Pro Asp Ala Ala Arg Ile Arg Val Lys Arg Tyr Arg 85 SO 95 Gln Ser Met Asn Asn Phe Gln Gly Leu Arg Ser Phe Gly Cys Arg Phe 100 105 110 Gly Thr Cys Thr val Gln Lys Leu Ala His Gln Ile Tyr Gln Phe Thr 115 120 125 Asp Lys Asp Lys Asp Asn Val Ala Pro Arg Ser Lys Ile Ser Pro Gln 130 135 140 Gly Tyr Gly Arg Arg Arg Arg Arg Ser Leu Pro Glu Ala Gly Pro Gly 145 150 155 160 Arg Thr Leu Val Ser Ser Lys Pro Gln Ala His Gly Ala Pro Ala Pro 165 170 175 Pro Ser Gly Ser Ala Pro His Phe Leu 180 185 <210> 2597 <211> 851 <212> PRT <213> Homo sapiens <400> 2597 Met Ser Ser Lys Gln Glu Ile Met Ser Asp Gln Arg phe Arg Arg val 1 5 10 15

Ala Lys Asp Pro Arg Phe Trp Glu Met Pro Glu Lys Asp Arg Lys Val

Lys Ile Asp Lys Arg Phe Arg Ala Met Phe His Asp Lys Lys Phe Lys 40 45 Leu Asn Tyr Ala Val Asp Lys Arg Gly Arg Pro Ile Ser His Ser Thr 50 55 60 Thr Glu Asp Leu Lys Arg Phe Tyr Asp Leu Ser Asp Ser Asp Ser Asn 65 70 75 80 Leu Ser Gly Glu Asp Ser Lys Ala Leu Ser Gln Lys Lys Ile Lys Lys 85 90 95 Lys Lys Thr Gln Thr Lys Lys Glu Ile Asp Ser Lys Asn Leu Val Glu 100 105 110 Lys Lys Lys Glu Thr Lys Lys Ala Asn His Lys Gly Ser Glu Asn Lys 115 120 125 Thr Asp Leu Asp Asn Ser Ile Gly Iie Lys Lys Met Lys Thr Ser Cys 130 135 140 Lys Phe Lys Ile Asp Ser Asn Ile Ser Pro Lys Lys Asp Ser Lys Glu 145 150 155 160 Phe Thr Gln Lys Asn Lys Lys Glu Lys Lys Asn Ile Val Gln His Thr 165 170 175 Thr Asp Ser Ser Leu Glu Glu Lys Gln Arg Thr Leu Asp Ser Gly Thr 180 185 190 Ser Glu Ile Val Lys Ser Pro Arg Ile Glu Cys Ser Lys Thr Arg Arg 195 200 205 Glu Met Gln Ser Val Val Gln Leu Ile Met Thr Arg Asp Ser Asp Gly 210 215 220 Tyr Glu Asn Ser Thr Asp Gly Glu Met Cys Asp Lys Asp Ala Leu Glu 225 230 235 240 Glu Asp Ser Glu Ser Val Ser Glu Ile Gly Ser Asp Glu Glu Ser Glu 245 250 255

Asn Glu Ile Thr Ser Val Gly Arg Ala Ser Gly Asp Asp Asp Gly Ser 260 265 270 Glu Asp Asp Glu Glu Glu Asp Glu Asp Glu Glu Glu Asp Glu Asp Glu 275 280 285 Asp Ser Glu Asp Asp Asp Lys Ser Asp Ser Gly Pro Asp Leu Ala Arg 290 295 300 Gly Lys Gly Asn Ile Glu Thr Ser ser Glu Asp Glu Asp Asp Thr Ala 305 310 31s 320 Asp Leu Phe Pro Glu Glu Ser Gly Phe Glu His Ala Trp Arg Glu Leu 325 330 335 Asp Lys Asp Ala Pro Arg Ala Asp Glu Ile Thr Arg Arg Leu Ala Val 340 345 350 Cys Asn Met Asp Trp Asp Arg Leu Lys Ala Lys Asp Leu Leu Ala Leu 358s 360 365 Phe Asn Ser Phe Lys Pro Lys Gly Gly Val Ile Phe Ser Val Lys Ile 370 375 380 Tyr Pro Ser Glu Phe Gly Lys Glu Arg Met Lys Glu Glu Gln Val Gln 385 390 395 400 Gly Pro Val Glu Leu Leu Ser Ile Pro Glu Asp Ala Pro Glu Lys Asp 405 410 } 415 Trp Thr Ser Arg Glu Lys Leu Arg Asp Tyr Gln Phe Lys Arg Leu Lys 420 425 430 Tyr Tyr Tyr Ala val Val Asp Cys Asp Ser Pro Glu Thr Ala Ser Lys 435 440 445 Ile Tyr Glu asp Cys Asp Gly Leu Glu Phe Glu Ser Ser Cys Ser phe 450 455 460 Ile Asp Leu Arg Phe Ile Pro Asp Asp Ile Thr Phe Asp Asp Glu Pro oC 465 470 475 480 Lys Asp Val Ala Ser Glu Val Asn Leu Thr Ala Tyr Lys Pro Lys Tyr 485 4590 495 1028 o

Phe Thr Ser Ala Ala Met Gly Thr Ser Thr val Glu Ile Thr Trp Asp 500 505 510 Glu Thr Asp His Glu Arg Ile Thr Met Leu Asn Arg Lys Phe Lys Lys 51S 520 525 Glu Glu Leu Leu Asp Met Asp Phe Gln Ala Tyr Leu Ala Ser Ser Ser 530 535 540 Glu Asp Glu Glu Glu Ile Glu Glu Glu Leu Gln Gly Asp Asp Gly val 545 550 555 560 Asn Val Glu Glu Asp Gly Lys Thr Lys Lys Ser Gln Lys Asp Asp Glu 565 570 575 Glu Gln Ile Ala Lys Tyr Arg Gln Leu Leu Gln Val Ile Gln Glu Lys 580 585 590 Glu Lys Lys Gly Lys Glu Asn Asp Met Glu Met Glu Ile Lys Trp Val 595 600 605 Pro Gly Leu Lys Glu Ser Ala Glu Glu Met val Lys Asn Lys Leu Glu 610 615 620 Gly Lys Asp Lys Leu Thr Pro Trp Glu Gln Phe Leu Glu Lys Lys Lys 625 630 635 640 Glu Lys Lys Arg Leu Lys Arg Lys Gln Lys Ala Leu Ala Glu Glu Ala . 645 650 655 Ser Glu Glu Glu Leu Pro Ser Asp Val Asp Leu Asn Asp Pro Tyr Phe 660 665 670 Ala Glu Glu Val Lys Gln Ile Gly Ile Asn Lys Lys Ser val Lys Ser 675 680 685 Ala Lys Asp Gly Thr Ser Pro Glu Glu Glu Ile Glu Ile Glu Arg Gln 690 695 700 Lys Ala Glu Met Ala Leu Leu Met Met Asp Glu Asp Glu Asp Ser Lys 705 710 715 720 Lys His Phe Asn Tyr Asn Lys Ile Val Glu His Gln Asn Leu Ser Lys 725 730 735 Lys Lys Lys Lys Gln Leu Met Lys Lys Lys Glu Leu Ile Glu Asp Asp

740 745 750 Phe Glu Val Asn Val Asn Asp Ala Arg Phe Gln Ala Met Tyr Thr Ser 755 760 765 His Leu Phe Asn Leu Asp Pro Ser Asp Pro Asn Phe Lys Lys Thr Lys 770 775 780 Ala Met Glu Lys Ile Leu Glu Glu Lys Ala Arg Gln Arg Glu Arg Lys 785 790 795 800 Glu Gln Glu Leu Thr Gln Ala Ile Lys Lys Lys Glu Ser Glu Ile Glu 805 810 815 Lys Glu Ser Gln Arg Lys Ser Ile Asp Pro Ala Leu Ser Met Leu Ile 820 825 830 Lys Ser Ile Lys Thr Lys Thr Glu Gln Phe Gln Ala Arg Lys Lys Gln 835 840 845 Lys Val Lys 850 <210> 2598 <211> 244 <212> PRT <213> Homo sapiens <400> 2598 Met Val Tyr Lys Thr Leu Phe Ala Leu Cys Ile Leu Thr Ala Gly Trp 1 5 10 15 Arg Val Gln Ser Leu Pro Thr Ser Ala Pro Leu Ser Val Ser Leu Pro

Thr Asn Ile Val Pro Pro Thr Thr Ile Trp Thr Ser Ser Pro Gln Asn 40 45 Thr Asp Ala Asp Thr Ala Ser Pro Ser Asn Gly Thr His Asn Asn Ser 50 55 60 Val Leu Pro Val Thr Ala Ser Ala Pro Thr Ser Leu Leu Pro Lys Asn 65 70 75 80 Ile ser Ile Glu Ser Arg Glu Glu Glu Ile Thr Ser pro Gly Ser Asn 85 50 9s 1030 Gs EE ——

Trp Glu Gly Thr Asn Thr Asp Pro Ser Pro Ser Gly Phe Ser Ser Thr 100 10S 110 Ser Gly Gly Val His Leu Thr Thr Thr Leu Glu Glu His Ser Leu Gly 115 120 125 Thr Pro Glu Ala Gly Val Ala Ala Thr Leu Ser Gln Ser Ala Ala Glu 130 135 140 Pro Pro Thr Leu Ile Ser Pro Gln Ala Pro Ala Ser Ser Pro Ser Ser 145 150 155 160 Leu Ser Thr Ser Pro Pro Glu Val Phe Ser Ala Ser Val Thr Thr Asn 165 170 175 His Ser Ser Thr val Thr Ser Thr Gln Pro Thr Gly Ala Pro Thr Ala 180 185 190 Pro Glu Ser Pro Thr Glu Glu Ser Ser Ser Asp His Thr Pro Thr Ser 195 200 205 His Ala Thr Ala Glu Pro Val Pro Gln Glu Lys Thr Pro Pro Thr Thr 210 215 220 Val Ser Gly Lys Val Met Cys Glu Leu Ile Asp Met Glu Thr Pro Pro ’ 225 230 235 240 Pro Phe Pro Gly <210> 2599 <211> 395 <212> PRT <213> Homo sapiens <400> 25899 Met Pro Gly Arg Ser Cys Val Ala Leu Val Leu Leu Ala Ala Ala Val 1 S 10 15 Ser Cys Ala Val Ala Gln His Ala Pro Pro Trp Thr Glu Asp Cys Arg

Lys Ser Thr Tyr Pro Pro Ser Gly Pro Thr Tyr Arg Gly Ala Val Pro 40 45 Trp Tyr Thr Ile Asn Leu Asp Leu Pro Pro Tyr Lys Arg Trp His Glu

50 55 60 Leu Met Leu Asp Lys Ala Pro Met Leu Lys Val Ile Val Asn Ser Leu

65 . 70 75 80 Lys Asn Met Ile Asn Thr Phe Val Pro Ser Gly Lys val Met Gln Val 85 90 85 val Asp Glu Lys Leu Pro Gly Leu Leu Gly Asn Phe Pro Gly Pro Phe 100 105 110 Glu Glu Glu Met Lys Gly Ile Ala Ala Val Thr Asp Ile Pro Leu Gly 115 120 125 Glu Ile Ile Ser Phe Asn Ile Phe Tyr Glu Leu Phe Thr Ile Cys Thr 130 135 140 Ser Ile Val Ala Glu Asp Lys Lys Gly His Leu Ile His Gly Arg Asn 145 150 155 160 Met Asp Phe Gly Val Phe Leu Gly Trp Asn Ile Asn Asn Asp Thr Trp 165 170 175 val Ile Thr Glu Gln Leu Lys Pro Leu Thr Val Asn Leu Asp Phe Gln 180 185 190 Arg Asn Asn Lys Thr val Phe Lys Ala Ser Ser Phe Ala Gly Tyr val 195 200 205 Gly Met Leu Thr Gly Phe Lys Pro Gly Leu Phe Ser Leu Thr Leu Asn 210 215 220 Glu Arg Phe Ser Ile Asn Gly Gly Tyr Leu Gly Ile Leu Glu Trp Ile 225 230 235 240 Leu Gly Lys Lys Asp Ala Met Trp Ile Gly Phe Leu Thr Arg Thr Val 245 250 255 Leu Glu Asn Ser Thr Ser Tyr Glu Glu Ala Lys Asn Leu Leu Thr Lys 260 265 270 Thr Lys Ile Leu Ala Pro Ala Tyr Phe Ile Leu Gly Gly Asn Gln Ser 275 280 285 Gly Glu Gly Cys Val Ile Thr Arg Asp Arg Lys Glu Ser Leu Asp Val 290 295 300 1032 L

Tyr Glu Leu Asp Ala Lys Gln Gly Arg Trp Tyr Val Val Gln Thr Asn

305 310 31s 320

Tyr Asp Arg Trp Lys His Pro Phe Phe Leu Asp Asp Arg Arg Thr Pro

325 330 335

Ala Lys Met Cys Leu Asn Arg Thr Ser Gln Glu Asn Ile Ser Phe Glu 340 345 350

Thr Met Tyr Asp Val Leu Ser Thr Lys Pro val Leu Asn Lys Leu Thr

355 360 365 Val Tyr Thr Thr Leu Ile Asp Val Thr Lys Gly Gln Phe Glu Thr Tyr 370 375 380

Leu Arg Asp Cys Pro Asp Pro Cys Ile Gly Trp

385 390 395

<210> 2600

<211l> 282

<212> PRT

<213> Homo sapiens

<400> 2600

Met Ser Leu Leu Ala Thr Leu Gly Leu Glu Leu Asp Arg Ala Leu Leu

1 1) 10 15

Pro Ala Ser Gly Leu Gly Trp Leu Val Asp Tyr Gly Lys Leu Pro Pro ’ 30

Ala Pro Ala Pro Leu Ala Pro Tyr Glu Val Leu Gly Gly Ala Leu Glu :

40 45 Gly Gly Leu Pro Val Gly Gly Glu Pro Leu Ala Gly Asp Gly Phe Ser 50 55 60

Asp Trp Met Thr Glu Arg Val Asp Phe Thr Ala Leu Leu Pro Leu Glu

65 70 75 80

Pro Pro Leu Pro Pro Gly Thr Leu Pro Gln Pro Ser Pro Thr Pro Pro

85 90 95

Asp Leu Glu Ala Met Ala Ser Leu Leu Lys Lys Glu Leu Glu Gln Met

100 105 110

Glu Asp Phe Phe Leu Asp Ala Pro Pro Leu Pro Pro Pro Ser Pro Pro 115 120 } 125 Pro Leu Pro Pro Pro Pro Leu Pro Pro Ala Pro Ser Leu Pro Leu Ser 130 135 140 Leu Pro Ser Phe Asp Leu Pro Gln Pro Pro Val Leu Asp Thr Leu Asp 145 150 15S 160 Leu Leu Ala Ile Tyr Cys Arg Asn Glu Ala Gly Gln Glu Glu val Gly 165 170 175 Met Pro Pro Leu Pro Pro Pro Gln Gln Pro Pro Pro Pro Ser Pro Pro 180 185 190 Gln Pro Ser Arg Leu Ala Pro Tyr Pro His Pro Ala Thr Thr Arg Gly 195 200 205 Asp Arg Lys Gln Lys Lys Arg Asp Gln Asn Lys Ser Ala Ala Leu Arg 210 215 220 Tyr Arg Gln Arg Lys Arg Ala Glu Gly Glu Ala Leu Glu Gly Glu Cys 225 230 235 240 Gln Gly Leu Glu Ala Arg Asn Arg Glu Leu Lys Glu Arg Ala Glu Ser 245 250 255 Val Glu Arg Glu Ile Gln Tyr Val Lys Asp Leu Leu Ile Glu Val Tyr 260 265 270 Lys Ala Arg Ser Gln Arg Thr Arg Ser Cys : 27% 280 <210> 2601 <211> 23 <212> PRT <213> Homo sapiens <400> 2601 Met Glu Thr Ser Glu Gly Pro Gly Leu Glu Ser Thr Gly Ser Tyr Leu 1 5 10 15 Gly Ile Gln Gln Arg Ser Pro

<210> 2602 <211> 491

<212> PRT

<213> Homo sapiens

<400> 2602

Met Cys Asn Thr Asn Met Ser Val Pro Thr Asp Gly Ala Val Thr Thr

1 5 10 15

Ser Gln Ile Pro Ala Ser Glu Gln Glu Thr Leu val Arg Pro Lys Pro

Leu Leu Leu Lys Leu Leu Lys Ser Val Gly Ala Gln Lys Asp Thr Tyr

40 45 Thr Met Lys Glu Val Leu Phe Tyr Leu Gly Gln Tyr Ile Met Thr Lys 50 55 60

Arg Leu Tyr Asp Glu Lys Gln Gln His Ile Val Tyr Cys Ser Asn Asp

€5 70 75 80

Leu Leu Gly Asp Leu Phe Gly Val Pro Ser Phe Ser Val Lys Glu His

85 90 95

Arg Lys Ile Tyr Thr Met Ile Tyr Arg Asn Leu Val Val Val Asn Gln 100 105 110

Gln Glu Ser Ser Asp Ser Gly Thr Ser Val Ser Glu Asn Arg Cys His

115 120 125 Leu Glu Gly Gly Ser Asp Gln Lys Asp Leu Val Gln Glu Leu Gln Glu 130 135 140

Glu Lys Pro Ser Ser Ser His Leu Val Ser Arg Pro Ser Thr Ser Ser

145 150 185 160

Arg Arg Arg Ala Ile Ser Glu Thr Glu Glu Asn Ser Asp Glu Leu Ser

165 170 175

Gly Glu Arg Gln Arg Lys Arg His Lys Ser Asp Ser Ile Ser Leu Ser 180 185 190

Phe Asp Glu Ser Leu Ala Leu Cys Val Ile Arg Glu Ile Cys Cys Glu

195 200 205 Arg Ser Ser Ser Ser Glu Ser Thr Gly Thr Pro Ser Asn Pro Asp Leu 210 215 220

Asp Ala Gly Val Ser Glu His Ser Gly Asp Trp Leu Asp Gln Asp Ser 225 230 235 240 Val Ser Asp Gln Phe Ser Val Glu Phe Glu Val Glu Ser Leu Asp Ser 245 250 255 Glu Asp Tyr Ser Leu Ser Glu Glu Gly Gln Glu Leu Ser Asp Glu Asp 260 265 270 Asp Glu Val Tyr Gln Val Thr Val Tyr Gln Ala Gly Glu Ser Asp Thr 275 280 285 Asp Ser Phe Glu Glu Asp Pro Glu Ile Ser Leu Ala Asp Tyr Trp Lys 250 295 300 Cys Thr Ser Cys Asn Glu Met Asn Pro Pro Leu Pro Ser His Cys Asn 305 310 315s 320 Arg Cys Trp Ala Leu Arg Glu Asn Trp Leu Pro Glu Asp Lys Gly Lys 325 330 335 Asp Lys Gly Glu Ile Ser Glu Lys Ala Lys Leu Glu Asn Ser Thr Gln 340 345 350 Ala Glu Glu Gly Phe Asp Val Pro Asp Cys Lys Lys Thr Ile Val Asn 355 360 365 Asp Ser Arg Glu Ser Cys Val Glu Glu Asn Asp Asp Lys Ile Thr Gln 370 3758 380 Ala Ser Gln Ser Gln Glu Ser Glu Asp Tyr Ser Gln Pro Ser Thr Ser 385% 390 395 400 Ser Ser Ile Ile Tyr Ser Ser Gln Glu Asp Val Lys Glu Phe Glu Arg 405 410 415 Glu Glu Thr Gln Asp Lys Glu Glu Ser Val Glu Ser Ser Leu Pro Leu 420 425 430 Asn Ala Ile Glu Pro Cys Val Ile Cys Gln Gly Arg Pro Lys Asn Gly 435 440 445 Cys Ile Val His Gly Lys Thr Gly His Leu Met Ala Cys Phe Thr Cys 450 455 460 Ala Lys Lys Leu Lys Lys Arg Asn Lys Pro Cys Pro Val Cys Arg Gln 1036 Y

465 470 475 480 Pro Ile Gln Met Ile Val Leu Thr Tyr Phe Pro 485 490 <210> 2603 <211> 950 <212> PRT <213> Homo sapiens <400> 2603 Met Gly Val Pro Ala Phe Phe Arg Trp Leu Ser Arg Lys Tyr Pro Ser 1 5 10 15 Ile Ile Val Asn Cys Val Glu Glu Lys Pro Lys Glu Cys Asn Gly Val

Lys Ile Pro Val Asp Ala Ser Lys Pro Asn Pro Asn Asp Val Glu Phe 40 45 Asp Asn Leu Tyr Leu Asp Met Asn Gly Ile Ile His Pro Cys Thr His 50 SS 60 Pro Glu Asp Lys Pro Ala Pro Lys Asn Glu Asp Glu Met Met val Ala 65 70 75 80 Ile Phe Glu Tyr Ile Asp Arg Leu Phe Ser Ile Val Arg Pro Arg Arg 85 90 95 Leu Leu Tyr Met Ala Ile Asp Gly Val Ala Pro Arg Ala Lys Met Asn 100 105 110 Gln Gln Arg Ser Arg Arg Phe Arg Ala Ser Lys Glu Gly Met Glu Ala 115 120 125 Ala Val Glu Lys Gln Arg Val Arg Glu Glu Ile Leu Ala Lys Gly Gly 130 135 140 Phe Leu Pro Pro Glu Glu Ile Lys Glu Arg Phe Asp Ser Asn Cys Ile 145 150 155 160 Thr Pro Gly Thr Glu Phe Met Asp Asn Leu Ala Lys Cys Leu Arg Tyr 165 170 175 Tyr Ile Ala Asp Arg Leu Asn Asn Asp Pro Gly Trp Lys Asn Leu Thr 180 185 190

T/US2003/012946

Val Ile Leu Ser Asp Ala Ser Ala Pro Gly Glu Gly Glu His Lys Ile 185 200 205 Met Asp Tyr Ile Arg Arg Gln Arg Ala Gln Pro Asn His Asp Pro Asn 210 21s 220 Thr His His Cys Leu Cys Gly Ala Asp Ala Asp Leu Ile Met Leu Gly 225 230 235 240 Leu Ala Thr His Glu Pro Asn Phe Thr Ile Ile Arg Glu Glu Phe Lys 245 250 255 Pro Asn Lys Pro Lys Pro Cys Gly Leu Cys Asn Gln Phe Gly His Glu 260 265 270 Val Lys Asp Cys Glu Gly Leu Pro Arg Glu Lys Lys Gly Lys His Asp 275 280 285 Glu Leu Ala Asp Ser Leu Pro Cys Ala Glu Gly Glu Phe Ile Phe Leu 290 . 295 300 Arg Leu Asn Val Leu Arg Glu Tyr Leu Glu Arg Glu Leu Thr Met Ala 305 310 315 320 Ser Leu Pro Phe Thr Phe Asp Val Glu Arg Ser Ile Asp Asp Trp Val 325 330 335 Phe Met Cys Phe Phe Val Gly Asn Asp Phe Leu Pro His Leu Pro Ser 340 345 350 Leu Glu Ile Arg Glu Asn Ala Ile Asp Arg Leu Val Asn Ile Tyr Lys ) 355 360 365 Asn Val Val His Lys Thr Gly Gly Tyr Leu Thr Glu Ser Gly Tyr val 370 375 380 Asn Leu Gln Arg Val Gln Met Ile Met Leu Ala Val Gly Glu Val Glu 385 390 395 400 Asp Ser Ile Phe Lys Lys Arg Lys Asp Asp Glu Asp Ser Phe Arg Arg 405 410 415 Arg Gln Lys Glu Lys Arg Lys Arg Met Lys Arg Asp Gln Pro Ala Phe 420 425 430 1038 L

Thr Pro Ser Gly Ile Leu Thr Pro His Ala Leu Gly Ser Arg Asn Ser 435 440 445 Pro Gly Ser Gln Val Ala Ser Asn Pro Arg Gln Ala Ala Tyr Glu Met 450 455 460 Arg Met Gln Asn Asn Ser Ser Pro Ser Ile Ser Pro Asn Thr Ser Phe 465 470 475 480 Thr Ser Asp Gly Ser Pro Ser Pro Leu Gly Gly Ile Lys Arg Lys Ala 485 490 495 Glu Asp Ser Asp Ser Glu Pro Glu Pro Glu Asp Asn Val Arg Leu Trp 500 505 510 Glu Ala Gly Trp Lys Gln Arg Tyr Tyr Lys Asn Lys Phe Asp Val Asp 515 520 525 Ala Ala Asp Glu Lys Phe Arg Arg Lys Val Val Gln Ser Tyr Val Glu 530 538 540 Gly Leu Cys Trp Val Leu Arg Tyr Tyr Tyr Gln Gly Cys Ala Ser Trp 545 550 555 560 Lys Trp Tyr Tyr Pro Phe His Tyr Ala Pro Phe Ala Ser Asp Phe Glu 565 570 575 Gly Ile Ala Asp Met Pro Ser Asp Phe Glu Lys Gly Thr Lys Pro Phe 580 585 590 Lys Pro Leu Glu Gln Leu Met Gly Val Phe Pro Ala Ala Ser Gly Asn 595 600 605 Phe Leu Pro Pro Ser Trp Arg Lys Leu Met Ser Asp Pro Asp Ser Ser 610 615 620 Ile Ile Asp Phe Tyr Pro Glu Asp Phe Ala Ile Asp Leu Asn Gly Lys 625 630 635 640 Lys Tyr Ala Trp Gln Gly Val Ala Leu Leu Pro Phe Val Asp Glu Arg 645 650 655 Arg Leu Arg Ala Ala Leu Glu Glu Val Tyr Pro Asp Leu Thr Pro Glu 660 665 670 Glu Thr Arg Arg Asn Ser Leu Gly Gly Asp Val Leu Phe Val Gly Lys

675 680 685 His His Pro Leu His Asp Phe Ile Leu Glu Leu Tyr Gln Thr Gly Ser 690 695 700 Thr Glu Pro Val Glu Val Pro Pro Glu Leu Cys His Gly Ile Gln Gly 705 710 715 720 Lys Phe Ser Leu Asp Glu Glu Ala Ile Leu Pro Asp Gln Ile Val Cys 725 730 7358 Ser Pro Val Pro Met Leu Arg Asp Leu Thr Gln Asn Thr Val Val Ser 740 745 750 Ile Asn Phe Lys Asp Pro Gln Phe Ala Glu Asp Tyr Ile Phe Lys Ala 755 760 765 Val Met Leu Pro Gly Ala Arg Lys Pro Ala Ala Val Leu Lys Pro Ser 770 775 780 Asp Trp Glu Lys Ser Ser Asn Gly Arg Gln Trp Lys Pro Gln Leu Gly 785 790 795 800 Phe Asn Arg Asp Arg Arg Pro Val His Leu Asp Gln Ala Ala Phe Arg 805 810 815 Thr Leu Gly His Val Met Pro Arg Gly Ser Gly Thr Gly Ile Tyr Ser 820 825 830 Asn Ala Ala Pro Pro Pro Val Thr Tyr Gln Gly Asn Leu Tyr Arg Pro 835 840 845 Leu Leu Arg Gly Gln Ala Gln Ile Pro Lys Leu Met Ser Asn Met Arg 850 855 860 Pro Gln Asp Ser Trp Arg Gly Pro Pro Pro Leu Phe Gln Gln Gln Arg B65 870 B75 880 Phe Asp Arg Gly Val Gly Ala Glu Pro Leu Leu Pro Trp Asn Arg Met . B85 850 895 Leu Gln Thr Gln Asn Ala Ala Phe Gln Pro Asn Gln Tyr Gln Met Leu 900 90S 910 Ala Gly Pro Gly Gly Tyr Pro Pro Arg Arg Asp Asp Arg Gly Gly Arg 915 $20 925 1040

PCT/US2003/012946

Gln Gly Tyr Pro Arg Glu Gly Arg Lys Tyr Pro Leu Pro Pro Pro Ser 830 935 940 Gly Arg Tyr Asn Trp Asn 945 950 <210> 2604 <211> 313 <212> PRT ’ <213> Homo sapiens <400> 2604 Met Ser Gln Ser Arg His Arg Ala Glu Ala Pro Pro Leu Glu Arg Glu 1 5 10 15 "Asp Ser Gly Thr Phe Ser Leu Gly Lys Met Ile Thr Ala Lys Pro Gly

Lys Thr Pro Ile Gln Val Leu His Glu Tyr Gly Met Lys Thr Lys Asn 40 45 Ile Pro Val Tyr Glu Cys Glu Arg Ser Asp Val Gln Ile His Val Pro 50 S55 60 Thr Phe Thr Phe Arg Val Thr val Gly Asp Ile Thr Cys Thr Gly Glu 65 70 75 80 Gly Thr Ser Lys Lys Leu Ala Lys His Arg Ala Ala Glu Ala Ala Ile 85 90 85 Asn Ile Leu Lys Ala Asn Ala Ser Ile Cys Phe Ala Val Pro Asp Pro 100 105 110 Leu Met Pro Asp Pro Ser Lys Gln Pro Lys Asn Gln Leu Asn Pro Ile 115 120 125 Gly Ser Leu Gln Glu Leu Ala Ile His His Gly Trp Arg Leu Pro Glu 130 135 140 Tyr Thr Leu Ser Gln Glu Gly Gly Pro Ala His Lys Arg Glu Tyr Thr - 145 150 155 160 Thr Ile Cys Arg Leu Glu Ser Phe Met Glu Thr Gly Lys Gly Ala Ser 165 170 175

Lys Lys Gln Ala Lys Arg Asn Ala Ala Glu Lys Phe Leu Ala Lys Phe 180 185 180 Ser Asn Ile Ser Pro Glu Asn His Ile Ser Leu Thr Asn Val Val Gly 195 200 205 His Ser Leu Gly Cys Thr Trp His Ser Leu Arg Asn Ser Pro Gly Glu 210 2158 220 Lys Ile Asn Leu Leu Lys Arg Ser Leu Leu Ser Ile Pro Asn Thr Asp 225 230 235 240 Tyr Ile Gln Leu Leu Ser Glu Ile Ala Lys Glu Gln Gly Phe Asn Ile 245 250 255 Thr Tyr Leu Asp Ile Asp Glu Leu Ser Ala Asn Gly Gln Tyr Gln Cys 260 265 270 Leu Ala Glu Leu Ser Thr Ser Pro Ile Thr Val Cys His Gly Ser Gly 275 280 285 Ile Ser Cys Gly Asn Ala Gln Ser Asp Ala Ala His Asn Ala Leu Gln . 290 295 300 Tyr Leu Lys Ile Ile Ala Glu Arg Lys 305 310 <210> 2605 <211> 188 <212> PRT <213> Homo sapiens <400> 2605 Met Ser Asn Val Arg Val Ser Asn Gly Ser Pro Ser Leu Glu Arg Met 1 5 10 15 Asp Ala Arg Gln Ala Glu His Pro Lys Pro Ser Ala Cys Arg Asn Leu

Phe Gly Pro Val Asp His Glu Glu Leu Thr Arg Asp Leu Glu Lys His 40 45 Cys Arg Asp Met Glu Glu Ala Ser Gln Arg Lys Trp Asn Phe Asp Phe 50 SS 60 Gln Asn His Lys Pro Leu Glu Gly Lys Tyr Glu Trp Gln Glu Val Glu 65 70 : 75 80

03/012946 Lys Gly Ser Leu Pro Glu Phe Tyr Tyr Arg Pro Pro Arg Pro Pro Lys 85 90 95 Gly Ala Cys Lys Val Pro Ala Gln Glu Ser Gln Asp Val Ser Gly Ser 100 105 110 Arg Pro Ala Ala Pro Leu Ile Gly Ala Pro Ala Asn Ser Glu Asp Thr 115 120 125 His Leu Val Asp Pro Lys Thr Asp Pro Ser Asp Ser Gln Thr Gly Leu 130 135 140 Ala Glu Gln Cys Ala Gly Ile Arg Lys Arg Pro Ala Thr Asp Asp Ser 145 150 155 160 Ser Thr Gln Asn Lys Arg Ala Asn Arg Thr Glu Glu Asn Val Ser Asp 165 170 175 Gly Ser Pro Asn Ala Gly Ser Val Glu Gln Thr Pro Lys Lys Pro Gly 180 185 190 Leu Arg Arg Arg Gln Thr 195 <210> 2606 <211> 727 <212> PRT <213> Homo sapiens <400> 2606 Met Arg Pro Leu Leu Leu Leu Ala Leu Leu Gly Trp Leu Leu Leu Ala 1 5 10 15 Glu Ala Lys Gly Asp Ala Lys Pro Glu Asp Asn Leu Leu Val Leu Thr Val Ala Thr Lys Glu Thr Glu Gly Phe Arg Arg Phe Lys Arg Ser Ala

40 . 45 Gln Phe Phe Asn Tyr Lys Ile Gln Ala Leu Gly Leu Gly Glu Asp Trp oC 50 55 60 Asn Val Glu Lys Gly Thr Ser ala Gly Gly Gly Gln Lys Val Arg Leu 65 70 75 80

Leu Lys Lys Ala Leu Glu Lys His Ala Asp Lys Glu Asp Leu Val Ile 85 90 95 Leu Phe Thr Asp Ser Tyr Asp Val Leu Phe Ala Ser Gly Pro Arg Glu 100 105 110 Leu Leu Lys Lys Phe Arg Gln Ala Arg Ser Gln Val Val Phe Ser Ala 115 120 125 Glu Glu Leu Ile Tyr Pro Asp Arg Arg Leu Glu Thr Lys Tyr Pro Val 130 135 140 Val Ser Asp Gly Lys Arg Phe Leu Gly Ser Gly Gly Phe Ile Gly Tyr 145 150 155 160 Ala Pro Asn Leu Ser Lys Leu Val Ala Glu Trp Glu Gly Gln Asp Ser 165 170 175 Asp Ser Asp Gln Leu Phe Tyr Thr Lys Ile Phe Leu Asp Pro Glu Lys 180 185 190 Arg Glu Gln Ile Asn Ile Thr Leu Asp His Arg Cys Arg Ile Phe Gln 195 200 205 Asn Leu Asp Gly Ala Leu Asp Glu Val Val Leu Lys Phe Glu Met Gly 210 215 220 His Val Arg Ala Arg Asn Leu Ala Tyr Asp Thr Leu Pro Val Leu Ile 225 230 235 240 His Gly Asn Gly Pro Thr Lys Leu Gln Leu Asn Tyr Leu Gly Asn Tyr 245 250 255 Ile Pro Arg Phe Trp Thr Phe Glu Thr Gly Cys Thr val Cys Asp Glu 260 265 270 Gly Leu Arg Ser Leu Lys Gly Ile Gly Asp Glu Ala Leu Pro Thr val 275 280 285 Leu Val Gly Val Phe Ile Glu Gln Pro Thr Pro Phe Val Ser Leu Phe 290 295 300 Phe Gln Arg Leu Leu Arg Leu His Tyr Pro Gln Lys His Met Arg Leu 308 310 315 320 Phe Ile His Asn His Glu Gln His His Lys Ala Gln Val Glu Glu Phe 1044

325 330 335 Leu Ala Gln His Gly Ser Glu Tyr Gln Ser Val Lys Leu Val Gly Pro 340 345 350 Glu Val Arg Met Ala Asn Ala Asp Ala Arg Asn- Met Gly Ala Asp Leu 355 360 365 Cys Arg Gln Asp Arg Ser Cys Thr Tyr Tyr Phe Ser Val Asp Ala Asp 370 375 380 Val Ala Leu Thr Glu Pro Asn Ser Leu Arg Leu Leu Ile Gln Gln Asn 385 390 395 400 Lys Asn Val Ile Ala Pro Leu Met Thr Arg His Gly Arg Leu Trp Ser 405 410 415 Asn Phe Trp Gly Ala Leu Ser Ala Asp Gly Tyr Tyr Ala Arg Ser Glu 420 425 430 Asp Tyr Val Asp Ile Val Gln Gly Arg Arg Val Gly Val Trp Asn Val 435 440 445 Pro Tyr Ile Ser Asn Ile Tyr Leu Ile Lys Gly Ser Ala Leu Arg Gly 450 45S 460 Glu Leu Gln Ser Ser Asp Leu Phe His His Ser Lys Leu Asp Pro Asp 465 470 475 480 Met Ala Phe Cys Ala Asn Ile Arg Gln Gln Asp Val Phe Met Phe Leu 485 490 495 Thr Asn Arg His Thr Leu Gly His Leu Leu Ser Leu Asp Ser Tyr Arg 500 505 510 Thr Thr His Leu His Asn Asp Leu Trp Glu Val Phe Ser Asn Pro Glu 515 520 525 Asp Trp Lys Glu Lys Tyr Ile His Gln Asn Tyr Thr Lys Ala Leu Ala 530 535 540 ) Gly Lys Leu Val Glu Thr Pro Cys Pro Asp Val Tyr Trp Phe Pro Ile 545 550 585 560 Phe Thr Glu Val Ala Cys Asp Glu Leu Val Glu Glu Met Glu His Phe 565 570 S75

Gly Gln Trp Ser Leu Gly Asn Asn Lys Asp Asn Arg Ile Gln Gly Gly 580 585 580 Tyr Glu Asn Val Pro Thr Ile Asp Ile His Met Asn Gln Ile Gly Phe 585 600 605 Glu Arg Glu Trp His Lys Phe Leu Leu Glu Tyr Ile Ala Pro Met Thr 610 615 620 Glu Lys Leu Tyr Pro Gly Tyr Tyr Thr Arg Ala Gln Phe Asp Leu Ala 625 630 635 640 Phe Val Val Arg Tyr Lys Pro Asp Glu Gln Pro Ser Leu Met Pro His 645 650 655 His Asp Ala Ser Thr Phe Thr Ile Asn Ile Ala Leu Asn Arg Val Gly ) 660 665 670 Val Asp Tyr Glu Gly Gly Gly Cys Arg Phe Leu Arg Tyr Asn Cys Ser 675 680 685 Ile Arg Ala Pro Arg Lys Gly Trp Thr Leu Met His Pro Gly Arg Leu 690 695 700 Thr His Tyr His Glu Gly Leu Pro Thr Thr Arg Gly Thr Arg Tyr Ile 705 710 715 720 Ala Val Ser Phe Val Asp Pro 725 <210> 2607 <211> 537 <212> PRT <213> Homo sapiens <400> 2607 Met Ala Trp Arg Gly Ala Gly Pro Ser Val Pro Gly Ala Pro Gly Gly 1 5 10 15 Val Gly Leu Ser Leu Gly Leu Leu Leu Gln Leu Leu Leu Leu Leu Gly © 30 Pro Ala Arg Gly Phe Gly Asp Glu Glu Glu Arg Arg Cys Asp Pro Ile 40 45 1046 oo oo

Arg Ile Ser Met Cys Gln Asn Leu Gly Tyr Asn Val Thr Lys Met Pro 50 55 60 Asn Leu Val Gly His Glu Leu Gln Thr Asp Ala Glu Leu Gln Leu Thr 65 70 75 80 Thr Phe Thr Pro Leu Ile Gln Tyr Gly Cys Ser Ser Gln Leu Gln Phe 85 90 9S Phe Leu Cys Ser Val Tyr Val Pro Met Cys Thr Glu Lys Ile Asn Ile 100 105 110 Pro Ile Gly Pro Cys Gly Gly Met Cys Leu Ser Val Lys Arg Arg Cys 115 120 125 Glu Pro Val Leu Lys Glu Phe Gly Phe Ala Trp Pro Glu Ser Leu Asn 130 135 140 Cys Ser Lys Phe Pro Pro Gln Asn Asp His Asn His Met Cys Met Glu 145 150 155 160 Gly Pro Gly Asp Glu Glu Val Pro Leu Pro His Lys Thr Pro Ile Gln 165 170 175 Pro Gly Glu Glu Cys His Ser Val Gly Thr Asn Ser Asp Gln Tyr Ile 180 185 1390 Trp Val Lys Arg Ser Leu Asn Cys Val Leu Lys Cys Gly Tyr Asp Ala 1985 200 205 Gly Leu Tyr Ser Arg Ser Ala Lys Glu Phe Thr Asp Ile Trp Met Ala 210 215 220 Val Trp Ala Ser Leu Cys Phe Ile ser Thr Ala Phe Thr Val Leu Thr 225 230 235 240 phe Leu Ile Asp Ser Ser Arg Phe Ser Tyr Pro Glu Arg Pro Ile Ile 245 250 255 Phe Leu Ser Met Cys Tyr Asn Ile Tyr Ser Ile Ala Tyr Ile Val Arg . 260 265 270 Leu Thr val Gly Arg Glu Arg Ile Ser Cys Asp Phe Glu Glu Ala Ala 275 280 285 Glu Pro Val Leu Ile Gln Glu Gly Leu Lys Asn Thr Gly Cys Ala Ile

290 295 300 Ile Phe Leu Leu Met Tyr Phe Phe Gly Met Ala Ser Ser Ile Trp Trp- 305 310 315 320 Val Ile Leu Thr Leu Thr Trp Phe Leu Ala Ala Gly Leu Lys Trp Gly 325 330 335 His Glu Ala Ile Glu Met His Ser Ser Tyr Phe His Ile Ala Ala Trp 340 : 345 350 Ala Ile Pro Ala Val Lys Thr Ile Val Ile Leu Ile Met Arg Leu Val 355 360 365 Asp Ala Asp Glu Leu Thr Gly Leu Cys Tyr Val Gly Asn Gln Asn Leu 370 375 380 Asp Ala Leu Thr Gly Phe Val Val Ala Pro Leu Phe Thr Tyr Leu val 385 390 395 400 Ile Gly Thr Leu Phe Ile Ala Ala Gly Leu Val Ala Leu Phe Lys Ile 405 410 415 Arg Ser Asn Leu Gln Lys Asp Gly Thr Lys Thr Asp Lys Leu Glu Arg 420 425 430 Leu Met Val Lys Ile Gly Val Phe Ser Val Leu Tyr Thr val Pro Ala 435 440 445 Thr Cys Val Ile Ala Cys Tyr Phe Tyr Glu Ile Ser Asn Trp Ala Leu 450 455 460 Phe Arg Tyr Ser Ala Asp Asp Ser Asn Met Ala Val Glu Met Leu Lys 465 470 475 480 Ile Phe Met Ser Leu Leu Val Gly Ile Thr Ser Gly Met Trp Ile Trp 485 450 495 Ser Ala Lys Thr Leu His Thr Trp Gln Lys Cys Ser Asn Arg Leu Val 500 505 510 Asn Ser Gly Lys Val Lys Arg Glu Lys Arg Gly Asn Gly Trp Val Lys 515 520 525 Pro Gly Lys Gly Ser Glu Thr Val val 530 5385 1048 hn

<210> 2608 <211> 362 <212> PRT <213> Homo sapiens <400> 2608 Met Leu Val Met Ala Pro Arg Thr Val Leu Leu Leu Leu Ser Ala Ala 1 S 10 15 Leu Ala Leu Thr Glu Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe

Tyr Thr Ser Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ser 40 © 45 Val Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ala 50 55 60 Ala Ser Pro Arg Glu Glu Pro Arg Ala Pro Trp Ile Glu Gln Glu Gly 65 70 75 80 Pro Glu Tyr Trp Asp Arg Asn Thr Gln Ile Tyr Lys Ala Gln Ala Gln 85 S0 95 Thr Asp Arg Glu Ser Leu Arg Asn Leu Arg Gly Tyr Tyr Asn Gln Ser 100 105 110 Glu Ala Gly Ser His Thr Leu Gln Ser Met Tyr Gly Cys Asp Val Gly 115 120 125 Pro Asp Gly Arg Leu Leu Arg Gly His Asp Gln Tyr Ala Tyr Asp Gly 130 ’ 135 140 Lys Asp Tyr Ile Ala Leu Asn Glu Asp Leu Arg Ser Trp Thr Ala Ala 145 150 155 160 Asp Thr Ala Ala Gln Ile Thr Gln Arg Lys Trp Glu Ala Ala Arg Glu 165 170 175 Ala Glu Gln Arg Arg Ala Tyr Leu Glu Gly Glu Cys Val Glu Trp Leu 180 185 190 Arg Arg Tyr Leu Glu Asn Gly Lys Asp Lys Leu Glu Arg Ala Asp Pro 195 200 205 1049

Pro Lys Thr His Val Thr His His Pro Ile Ser Asp His Glu Ala Thr 210 215 220 Leu Arg Cys Trp Ala Leu Gly Phe Tyr Pro Ala Glu Ile Thr Leu Thr 225 230 235 240 Trp Gln Arg Asp Gly Glu Asp Gln Thr Gln Asp Thr Glu Leu Val Glu 24S 250 255 Thr Arg Pro Ala Gly Asp Arg Thr Phe Gln Lys Trp Ala Ala Val Val 260 265 270 Val Pro Ser Gly Glu Glu Gln Arg Tyr Thr Cys His Val Gln His Glu 275 280 285 Gly Leu Pro Lys Pro Leu Thr Leu Arg Trp Glu Pro Ser Ser Gln Ser 290 295 300 Thr Val Pro Ile Val Gly Ile Val Ala Gly Leu Ala Val Leu Ala val 305 310 315 320 Val val Ile Gly Ala Val val Ala Ala Val Met Cys Arg Arg Lys Ser 325 330 335 Ser Gly Gly Lys Gly Gly Ser Tyr Ser Gln Ala Ala Cys Ser Asp Ser 340 345 350 Ala Gln Gly Ser Asp Val Ser Leu Thr Ala 355 360 <210> 2609 <211> 350 <212> PRT <213> Homo sapiens <400> 2609 Met Glu Thr Asn Ser Ser Leu Pro Thr Asn Ile Ser Gly Gly Thr Pro 1 Ss 10 15 Ala val Ser Ala Gly Tyr Leu Phe Leu Asp Ile Ile Thr Tyr Leu Val

Phe Ala Val Thr Phe Val Leu Gly Val Leu Gly Asn Gly Leu Val Ile 40 45 Trp Val Ala Gly Phe Arg Met Thr His Thr Val Thr Thr Ile Ser Tyr 50 55 . 60

Leu Asn Leu Ala Val Ala Asp Phe Cys Phe Thr Ser Thr Leu Pro Phe 65 70 75 80 Phe Met Val Arg Lys Ala Met Gly Gly His Trp Pro Phe Gly Trp Phe

85 S0 95 Leu Cys Lys Phe Val Phe Thr Ile Val Asp Ile Asn Leu Phe Gly Ser 100 105 110 Val Phe Leu Ile Ala Leu Ile Ala Leu Asp Arg Cys Val Cys Val Leu 115 120 12% His Pro Val Trp Thr Gln Asn His Arg Thr Val Ser Leu Ala Lys Lys 130 135 140 Val Ile Ile Gly Pro Trp Val Met Ala Leu Leu Leu Thr Leu Pro Val 145 150 155 160 Ile Ile Arg Val Thr Thr Val Pro Gly Lys Thr Gly Thr val Ala Cys 165 170 175 Thr Phe Asn Phe Ser Pro Trp Thr Asn Asp Pro Lys Glu Arg Ile Asn 180 185 180 Val Ala val Ala Met Leu Thr Val Arg Gly Ile Ile Arg Phe Ile Ile 195 200 205 Gly Phe Ser Ala Pro Met Ser Ile Val Ala Val Ser Tyr Gly Leu Ile 210 215 220 Ala Thr Lys Ile His Lys Gln Gly Leu Ile Lys Ser Ser Arg Pro Leu 225 230 235 240 Arg Val Leu Ser Phe Val Ala Ala Ala Phe Phe Leu Cys Trp Ser Pro 245 250 255 Tyr Gln Val val Ala Leu Ile Ala Thr Val Arg Ile Arg Glu Leu Leu 260 265 270 Gln Gly Met Tyr Lys Glu Ile Gly Ile Ala val Asp Val Thr Ser Ala 275 280 285 Leu Ala Phe Phe Asn Ser Cys Leu Asn Pro Met Leu Tyr Val Phe Met 290 295 300

Gly Gln Asp Phe Arg Glu Arg Leu Ile His Ala Leu Pro Ala Ser Leu 305 310 315 320 Glu Arg Ala Leu Thr Glu Asp Ser Thr Gln Thr Ser Asp Thr Ala Thr 325 330 335 Asn Ser Thr Leu Pro Ser Ala Glu val Glu Leu Gln Ala Lys 340 345 350

4 . <210> 2610 <211> 638 <212> PRT <213> Homo sapiens <400> 2610 , Met Ser Ala Ser Ser Ser Gly Gly Ser Pro Arg Phe Pro Ser Cys Gly 1 5 10 15 Lys Asn Gly Val Thr Ser Leu Thr Gln Lys Lys Val Leu Arg Ala Pro Cys Gly Ala Pro Ser Val Thr Val Thr Lys Ser His Lys Arg Gly Met 40 45 Lys Gly Asp Thr Val Asn Val Arg Arg Ser Val Arg Val Lys Thr Lys 50 55 €0 Asn Pro Pro His Cys Leu Glu Ile Thr Pro Pro Ser Ser Glu Lys Leu 65 70 75 80 Val Ser Val Met Arg Leu Ser Asp Leu Ser Thr Glu Asp Asp Asp Ser 85: 90 95 Gly His Cys Lys Met Asn Arg Tyr Asp Lys Lys Ile Asp Ser Leu Met 100 105 110 Asn Ala Val Gly Cys Leu Lys Ser Glu Val Lys Met Gln Lys Gly Glu 115 120 125 Arg Gln Met Ala Lys Arg Phe Leu Glu Glu Arg Lys Glu Glu Leu Glu 130 135 140 Glu Val Ala His Glu Leu Ala Glu Thr Glu His Glu Asn Thr val Leu 145 150 155 160 Arg His Asn Ile Glu Arg Met Lys Glu Glu Lys Asp Phe Thr Ile Leu

165 170 175 Gln Lys Lys His Leu Gln Gln Glu Lys Glu Cys Leu Met Ser Lys Leu 180 185 190 Val Glu Ala Glu Met Asp Gly Ala Ala Ala Ala Lys Gln Val Met Ala 195 200 205 Leu Lys Asp Thr Ile Gly Lys Leu Lys Thr Glu Lys Gln Met Thr Cys 210 215 220 Thr Asp Ile Asn Thr Leu Thr Arg Gln Lys Glu Leu Leu Leu Gln Lys 225 230 235 240 Leu Ser Thr Phe Glu Glu Thr Asn Arg Thr Leu Arg Asp Leu Leu Arg 245 250 255 Glu Gln His Cys Lys Glu Asp Ser Glu Arg Leu Met Glu Gln Gln Gly 260 265 270 Ala Leu Leu Lys Arg Leu Ala Glu Ala Asp Ser Glu Lys Ala Arg Leu 275 280 285 Leu Leu Leu Leu Gln Asp Lys Asp Lys Glu Val Glu Glu Leu Leu Gln 2380 295 300 Glu Ile Gln Cys Glu Lys Ala Gln Ala Lys Thr Ala Ser Glu Leu Ser 305 310 315 320 Lys Ser Met Glu Ser Met Arg Gly His Leu Gln Ala Gln Leu Arg Ser 325 330 335 Lys Glu Ala Glu Asn Ser Arg Leu Cys Met Gln Ile Lys Asn Leu Glu 340 345 350 Arg Ser Gly Asn Gln His Lys Ala Glu Val Glu Ala Ile Met Glu Gln 355 360 365 Leu Lys Glu Leu Lys Gln Lys Gly Asp Arg Asp Lys Glu Ser Leu Lys 370 378 380 Lys Ala Ile Arg Ala Gln Lys Glu Arg Ala Glu Lys Ser Glu Glu Tyr 385 390 395 400 Ala Glu Gln Leu His Val Gln Leu Ala Asp Lys Asp Leu Tyr Val Ala 405 410 415

Glu Ala Leu Ser Thr Leu Glu Ser Trp Arg Ser Arg Tyr Asn Gln Val 420 425 430 Val Lys Glu Lys Gly Asp Leu Glu Leu Glu Ile Ile Val Leu Asn Asp 435 440 445 Arg Val Thr Asp Leu Val Asn Gln Gln Gln Thr Leu Glu Glu Lys Met 450 455 460 Arg Glu Asp Arg Asp Ser Leu Val Glu Arg Leu His Arg Gln Thr Ala 465 470 475 480 Glu Tyr Ser Ala Phe Lys Leu Glu Asn Glu Arg Leu Lys Ala Ser Phe 485 490 49S Ala Pro Met Glu Asp Lys Leu Asn Gln Ala His Leu Glu Val Gln Gln 500 505 510 Leu Lys Ala Ser Val Lys Asn Tyr Glu Gly Met Ile Asp Asn Tyr Lys 515 520 525 Ser Gln Val Met Lys Thr Arg Leu Glu Ala Asp Glu Val Ala Ala Gln 530 535 540 “Leu Glu Arg Cys Asp Lys Glu Asn Lys Ile Leu Lys Asp Glu Met Asn 545 550 555 560 Lys Glu Ile Glu Ala Ala Arg Arg Gln Phe Gln Ser Gln Leu Ala Asp 565 570 575 Leu Gln Gln Leu Pro Asp lle Leu Lys Ile Thr Glu Ala Lys Leu Ala 580 585 590 Glu Cys Gln Asp Gln Leu Gln Gly Tyr Glu Arg Lys Asn Ile Asp Leu 595 600 605 Thr Ala Ile Ile Ser Asp Leu Arg Ser Arg Val Arg Asp Trp Gln Lys 610 615 620 Gly Ser His Glu Leu Thr Arg Ala Gly Ala Arg Ile Pro Arg 625 630 635 <210> 2611 <211> 197 <212> PRT } 1054

<213> Homo sapiens <400> 2611 Met Thr Leu Leu Pro Gly Leu Leu Phe Leu Thr Trp Leu His Thr Cys 1 5 10 15 Leu Ala His His Asp Pro Ser Leu Arg Gly His Pro His Ser His Gly

Thr Pro His Cys Tyr Ser Ala Glu Glu Leu Pro Leu Gly Gln Ala Pro 40 45 Pro His Leu Leu Ala Arg Gly Ala Lys Trp Gly Gln Ala Leu Pro Val 50 55 60 Ala Leu Val Ser Ser Leu Glu Ala Ala Ser His Arg Gly Arg His Glu 65 70 75 80 ’ Arg Pro Ser Ala Thr Thr Gln Cys Pro Val Leu Arg Pro Glu Glu Val 85 S0 95 Leu Glu Ala Asp Thr His Gln Arg Ser Ile Ser Pro Trp Arg Tyr Arg 100 105 110 val Asp Thr Asp Glu Asp Arg Tyr Pro Gln Lys Leu Ala Phe Ala Glu 115 120 125 Cys Leu Cys Arg Gly Cys Ile Asp Ala Arg Thr Gly Arg Glu Thr Ala 130 135 140 . Ala Leu Asn Ser Val Arg Leu Leu Gln Ser Leu Leu Val Leu Arg Arg 145 150 155 160 Arg Pro Cys Ser Arg Asp Gly Ser Gly Leu Pro Thr Pro Gly Ala Phe 165 170 175 Ala Phe His Thr Glu Phe Ile His Val Pro Val Gly Cys Thr Cys Val 180 185 190 Leu Pro Arg Ser Val LL J. 195 <210> 2612 <211l> 570 <212> PRT <213> Homo sapiens

<400> 2612 Met Asn Val val Phe Ala Val Lys Gln Tyr Ile Ser Lys Met Ile Glu 1 5 10 15 Asp Ser Gly Pro Gly Met Lys Val Leu Leu Met Asp Lys Glu Thr Thr

Gly Ile Val Ser Met Val Tyr Thr Gln Ser Glu Ile Leu Gln Lys Glu 40 45 Val Tyr Leu Phe Glu Arg Ile Asp Ser Gln Asn Arg Glu Ile Met Lys 50 55 60 His Leu Lys Ala Ile Cys Phe Leu Arg Pro Thr Lys Glu Asn Val Asp 65 70 75 80 Tyr Ile Ile Gln Glu Leu Arg Arg Pro Lys Tyr Thr Ile Tyr Phe Ile 85 90 95 Tyr Phe Ser Asn Val Ile Ser Lys Ser Asp Val Lys Ser Leu Ala Glu 100 105 110 Ala Asp Glu Gln Glu Val val Ala Glu Val Gln Glu Phe Tyr Gly Asp 115 120 125 Tyr Ile Ala Val Asn Pro His Leu Phe Ser Leu Asn Ile Leu Gly Cys 130 135 140 Cys Gln Gly Arg Asn Trp Asp Pro Ala Gln Leu Ser Arg Thr Thr Gln 145 150 155 160 Gly Leu Thr Ala Leu Leu Leu Ser Leu Lys Lys Cys Pro Met Ile Arg 165 170 1758 Tyr Gln Leu Ser Ser Glu Ala Ala Lys Arg Leu Ala Glu Cys Val Lys 180 185 190 Gln Val Ile Thr Lys Glu Tyr Glu Leu Phe Glu Phe Arg Arg Thr Glu 195 200 205 Val Pro Pro Leu Leu Leu Ile Leu Asp Arg Cys Asp Asp Ala Ile Thr 210 215 220 Pro Leu Leu Asn Gln Trp Thr Tyr Gln Ala Met Val His Glu Leu Leu 225 230 235 240 1056 LL So

Gly Ile Asn Asn Asn Arg Ile Asp Leu Ser Arg Val Pro Gly Ile Ser 245 250 255 Lys Asp Leu Arg Glu Val Val Leu Ser Ala Glu Asn Asp Glu Phe Tyr 260 265 270 Ala Asn Asn Met Tyr Leu Asn Phe Ala Glu Ile Gly Ser Asn Ile Lys 275 280 285 Asn Leu Met Glu Asp Phe Gln Lys Lys Lys Pro Lys Glu Gln Gln Lys 2%0 295 300 Leu Glu Ser Ile Ala Asp Met Lys Ala Phe Val Glu Asn Tyr Pro Gln 305 310 315 320 Phe Lys Lys Met Ser Gly Thr Val Ser Lys His val Thr val val Gly 325 330 335 Glu Leu Ser Arg Leu Val Ser Glu Arg Asn Leu Leu Glu Val Ser Glu 340 345 350 val Glu Gln Glu Leu Ala Cys Gln Asn Asp His Ser Ser Ala Leu Gln 355 360 365 asn Ile Lys Arg Leu Leu Gln Asn Pro Lys Val Thr Glu Phe Asp Ala 370 375 380 Ala Arg Leu Val Met Leu Tyr Ala Leu His Tyr Glu Arg His Ser Ser 385 330 385 400 Asn Ser Leu Pro Gly Leu Met Met Asp Leu Arg Asn Lys Gly val Ser 405 410 415 Glu Lys Tyr Arg Lys Leu Val Ser Ala Val Val Glu Tyr Gly Gly Lys 420 425 430 Arg Val Arg Gly Ser Asp Leu Phe Ser Pro Lys Asp Ala Val Ala Ile 435 440 445 Thr Lys Gln Phe Leu Lys Gly Leu Lys Gly val Glu Asn Val Tyr Thr 450 455 460 Gln His Gln Pro Phe Leu His Glu Thr Leu Asp His Leu Ile Lys Gly 465 470 475 480

Arg Leu Lys Glu Asn Leu Tyr Pro Tyr Leu Gly Pro Ser Thr Leu Arg 485 490 495 Asp Arg Pro Gln Asp Ile Ile Val Phe val Ile Gly Gly Ala Thr Tyr 500 505 510 Glu Glu Ala Leu Thr Val Tyr Asn Leu Asn Arg Thr Thr Pro Gly Val 515 520 525 Arg Ile val Leu Gly Gly Thr Thr val His Asn Thr Lys Ser Phe Leu 530 535 540 Glu Glu Val Leu Ala Ser Gly Leu His Ser Arg Ser Lys Glu Ser Ser 545 550 555 560 Gln val Thr Ser Arg Ser Ala Ser Arg Arg 565 570 <210> 2613 <211s> 474 <212> PRT <213> Homo sapiens <400> 2613 Met Thr Ile Leu Thr Tyr Pro Phe Lys Asn Leu Pro Thr Ala Ser Lys 1 5 10 15 Trp Ala Leu Arg Phe Ser Ile Arg Pro Leu Ser Cys Ser Ser Gln Leu

Arg Ala Ala Pro Ala Val Gln Thr Lys Thr Lys Lys Thr Leu Ala Lys 40 45 Pro Asn Ile Arg Asn Val Val Val Val Asp Gly Val Arg Thr Pro Phe 50 55 60 Leu Leu Ser Gly Thr Ser Tyr Lys Asp Leu Met Pro His Asp Leu Ala 65 70 75 80 Arg Ala Ala Leu Thr Gly Leu Leu His Arg Thr Ser Val Pro Lys Glu 85 90 95 Val val Asp Tyr Ile Ile Phe Gly Thr Val Ile Gln Glu Val Lys Thr 100 105 110 Ser Asn Val Ala Arg Glu Ala Ala Leu Gly Ala Gly Phe Ser Asp Lys 115 120 125 1058 3 oo

Thr Pro Ala His Thr Val Thr Met Ala Cys Ile Ser Ala Asn Gln Ala 130 135 140 Met Thr Thr Gly Val Gly Leu Ile Ala Ser Gly Gln Cys Asp Val Ile 145 150 155 160 val Ala Gly Gly Val Glu Leu Met Ser Asp Val Pro Ile Arg His Ser 165 170 175 Arg Lys Met Arg Lys Leu Met Leu Asp Leu Asn Lys Ala Lys Ser Met 180 185 180 Gly Gln Arg Leu Ser Leu Ile Ser Lys Phe Arg Phe Asn Phe Leu Ala 185 200 205 Pro Glu Leu Pro Ala Val Ser Glu Phe Ser Thr Ser Glu Thr Met Gly 210 215 220 His Ser Ala Asp Arg Leu Ala Ala Ala Phe Ala Val Ser Arg Leu Glu 225 230 235 240 Gln Asp Glu Tyr Ala Leu Arg Ser His Ser Leu Ala Lys Lys Ala Gln 245 250 255 Asp Glu Gly Leu Leu Ser Asp Val Val Pro Phe Lys Val Pro Gly Lys 260 265 270 Asp Thr Val Thr Lys Asp Asn Gly Ile Arg Pro Ser Ser Leu Glu Gln 275 280 285 Met Ala Lys Leu Lys Pro Ala Phe Ile Lys Pro Tyr Gly Thr Val Thr 290 295 300 Ala Ala Asn Ser Ser Phe Leu Thr Asp Gly Ala Ser Ala Met Leu Ile 305 310 315 320 Met Ala Glu Glu Lys Ala Leu Ala Met Gly Tyr Lys Pro Lys Ala Tyr 325 330 335 Leu Arg Asp Phe Met Tyr Val Ser Gln Asp Pro Lys Asp Gln Leu Leu 340 345 350 Leu Gly Pro Thr Tyr Ala Thr Pro Lys Val Leu Glu Lys Ala Gly Leu 355 360 365

Thr Met Asn Asp Ile Asp Ala Phe Glu Phe His Glu Ala Phe Ser Gly 370 375 380 Gln Ile Leu Ala Asn Phe Lys Ala Met Asp Ser Asp Trp Phe Ala Glu 385 390 385 400 Asn Tyr Met Gly Arg Lys Thr Lys Val Gly Leu Pro Pro Leu Glu Lys 405 . 410 415 Phe Asn Asn Trp Gly Gly Ser Leu Ser Leu Gly His Pro Phe Gly Ala 420 425 430 Thr Gly Cys Arg Leu Val Met Ala Ala Ala Asn Arg Leu Arg Lys Glu 435 440 445 Gly Gly Gln Tyr Gly Leu Val Ala Ala Cys Ala Ala Gly Gly Gln Gly 450 455 460 His Ala Met Ile val Glu Ala Tyr Pro Lys 465 470 <210> 2614 <211> 793 <212> PRT <213> Homo sapiens <400> 2614 Met Glu Ser Arg Ala Glu Gly Gly Ser Pro Ala Val Phe Asp Trp Phe 1 5 10 15 Phe Glu Ala Ala Cys Pro Ala Ser Leu Gln Glu Asp Pro Pro Ile Leu

Arg Gln Phe Pro Pro Asp Phe Arg Asp Gln Glu Ala Met Gln Met val 40 45 Pro Lys Phe Cys Phe Pro Phe Asp val Glu Arg Glu Pro Pro Ser Pro 50 55 60 Ala val Gln His Phe Thr Phe Ala Leu Thr Asp Leu Ala Gly Asn Arg 65 70 75 80 Arg Phe Gly Phe Cys Arg Leu Arg Ala Gly Thr Gln Ser Cys Leu Cys 85 90 95 Ile Leu Ser His Leu Pro Trp Phe Glu Val Phe Tyr Lys Leu Leu Asn :

100 105 110 Thr Val Gly Asp Leu Leu Ala Gln Asp Gln Val Thr Glu Ala Glu Glu 115 120 125 Leu Leu Gln Asn Leu Phe Gln Gln Ser Leu Ser Gly Pro Gln Ala Ser 130 135 140 Val Gly Leu Glu Leu Gly Ser Gly Val Thr Val Ser Ser Gly Gln Gly 145 150 155 160 Ile Pro Pro Pro Thr Arg Gly Asn Ser Lys Pro Leu Ser Cys Phe Val 165 170 178 Ala Pro Asp Ser Gly Arg Leu Pro Ser Ile Pro Glu Asn Arg Asn Leu 180 185 1390 Thr Glu Leu Val Val Ala Val Thr Asp Glu Asn Ile Val Gly Leu Phe 195 200 205 Ala Ala Leu Leu Ala Glu Arg Arg Val Leu Leu Thr Ala Ser Lys Leu 210 215 220 Ser Thr Leu Thr Ser Cys val His Ala Ser Cys Ala Leu Leu Tyr Pro 225 230 235 240 Met Arg Trp Glu His Val Leu Ile Pro Thr Leu Pro Pro His Leu Leu 245 250 255 Asp Tyr Cys Cys Ala Pro Met Pro Tyr Leu Ile Gly Val His Ala Ser 260 265 270 Leu Ala Glu Arg Val Arg Glu Lys Ala Leu Glu Asp Val Val val Leu 275 280 285 Asn Val Asp Ala Asn Thr Leu Glu Thr Thr Phe Asn Asp Val Gln Ala 290 295 300 Leu Pro Pro Asp Val Val Ser Leu Leu Arg Leu Arg Leu Arg Lys Val 305 310 315 320 Ala Leu Ala Pro Gly Glu Gly Val Ser Arg Leu Phe Leu Lys Ala Gln 325 330 335 Ala Leu Leu Phe Gly Gly Tyr Arg Asp Ala Leu Val Cys Ser Pro Gly 340 345 350

Gln Pro Val Thr Phe Ser Glu Glu Val Phe Leu Ala Gln Lys Pro Gly 355 360 365 Ala Pro Leu Gln Ala Phe His Arg Arg Ala Val His Leu Gln Leu Phe 370 37S 380 Lys Gln Phe Ile Glu Ala Arg Leu Glu Lys Leu Asn Lys Gly Glu Gly 385 390 395 400 Phe Ser Asp Gln Phe Glu Gln Glu Ile Thr Gly Cys Gly Ala Ser Pro 405 410 415 Gly Ala Leu Arg Ser Tyr Gln Leu Trp Ala Asp Asn Leu Lys Lys Gly 420 425 430 Gly Gly Ala Leu Leu His Ser Val Lys Ala Lys Thr Gln Pro Ala val 435 440 445 Lys Asn Met Tyr Arg Ser Ala Lys Ser Gly Leu Lys Gly Val Gln Ser 450 455 460 Leu Leu Met Tyr Lys Asp Gly Asp Ser Val Leu Gln Arg Gly Gly Ser 465 470 475 480 Leu Arg Ala Pro Ala Leu Pro Ser Arg Ser Asp Arg Leu Gln Gln Arg 485 490 495 Leu Pro Ile Thr Gln His Phe Gly Lys Asn Arg Pro Leu Arg Pro Ser 500 505 510 Arg Arg Arg Gln Leu Glu Glu Gly Thr Ser Glu Pro Pro Gly Ala Gly S15 520 525 Thr Pro Pro Leu Ser Pro Glu Asp Glu Gly Cys Pro Trp Ala Glu Glu 530 535 540 Ala Leu Asp Ser Ser Phe Leu Gly Ser Gly Glu Glu Leu Asp Leu Leu 545 550 555 560 Ser Glu Ile Leu Asp Ser Leu Ser Met Gly Ala Lys Ser Ala Gly Ser 565 570 575 Leu Arg Pro Ser Gln Ser Leu Asp Cys Cys His Arg Gly Asp Leu Asp 580 585 5580

Ser Cys Phe Ser Leu Pro Asn Ile Leu Arg Trp Gln Pro Asp Asp Lys 585 600 605 Lys Leu Pro Glu Pro Glu Pro Gln Pro Leu Ser Leu Pro Ser Leu Gln 610 615 620 Asn Ala Ser Ser Leu Asp Ala Thr Ser Ser Ser Lys Asp Ser Arg Ser 625 630 635 640 Gln Leu Ile Pro Ser Glu Ser Asp Gln Glu Val Thr Ser Pro Ser Gln 645 650 655 Ser Ser Thr Ala Ser Ala Asp Pro Ser Ile Trp Gly Asp Pro Lys Pro 660 665 670 Ser Pro Leu Thr Glu Pro Leu Ile Leu His Leu Thr Pro Ser His Lys 67S 680 685 Ala Ala Glu Asp Phe Thr Ala Gln Glu Asn Pro Thr Pro Trp Leu Ser 690 695 700 Thr Ala Pro Thr Glu Pro Ser Pro Pro Glu Ser Pro Gln Ile Leu Ala 705 710 715 720 Pro Thr Lys Pro Asn Phe Asp Ile Ala Trp Thr Ser Gln Pro Leu Asp 725 730 735 Pro Ser Ser Asp Pro Ser Ser Leu Glu Asp Pro Arg Ala Arg Pro Pro 740 745 750 Lys Ala Leu Leu Ala Glu Arg Ala His Leu Gln Pro Arg Glu Glu Pro 755 760 765 Gly Ala Leu Asn Ser Pro Ala Thr Pro Thr Ser Asn Cys Gln Lys Ser 770 775 780 Gin Pro Ser Lys Pro Ala Gln Ser Arg 785 790 <210> 2615 <211> 83 <212> PRT <213> Homo sapiens <400> 2615 Met Ser Phe Phe Gln Leu Leu Met Lys Arg Lys Glu Leu Ile Pro Leu

1 5 10 15 Val val Phe Met Thr Val Ala Ala Gly Gly Ala Ser Ser Phe Ala Val

Tyr Ser Leu Trp Lys Thr Asp Val Ile Leu Asp Arg Lys Lys Asn Pro 40 45 Glu Pro Trp Glu Thr Val Asp Pro Thr Val Pro Gln Lys Leu Ile Thr 50 55 60 Ile Asn Gln Gln Trp Lys Pro Ile Glu Glu Leu Gln Asn Val Gln Arg 65 70 75 80 Val Thr Lys <210> 2616 <211> 2413 <212> PRT <213> Homo sapiens <400> 2616 Met Gly Ile Ser Thr Val Ile Leu Glu Met Cys Leu Leu Trp Gly Gln 1 5 10 15 Val Leu Ser Thr Gly Gly Trp Ile Pro Arg Thr Thr Asp Tyr Ala Ser 20 25 30 Leu Ile Pro Ser Glu Val Pro Leu Asp Gln Thr Val Ala Glu Gly Ser 35 40 45 Pro Phe Pro Ser Glu Ser Thr Leu Glu Ser Thr Ala Ala Glu Gly Ser 50 55 60 Pro Ile Ser Leu Glu Ser Thr Leu Glu Ser Thr Val Ala Glu Gly Ser 65 70 75 80 Leu Ile Pro Ser Glu Ser Thr Leu Glu Ser Thr val Ala Glu Gly Ser 85 90 9s Asp Ser Gly Leu Ala Leu Arg Leu Val Asn Gly Asp Gly Arg Cys Gln 100 105 110 Gly Arg Val Glu Ile Leu Tyr Arg Gly Ser Trp Gly Thr Val Cys Asp 115 120 125

Asp Ser Trp Asp Thr Asn Asp Ala Asn Val val Cys Arg Gln Leu Gly 130 135 140 Cys Gly Trp Ala Met Ser Ala Pro Gly Asn Ala Trp Phe Gly Gln Gly 145 150 155 160 Ser Gly Pro Ile Ala Leu Asp Asp Val Arg Cys Ser Gly His Glu Ser 165 170 175 Tyr Leu Trp Ser Cys Pro His Asn Gly Trp Leu Ser His Asn Cys Gly 180 185 190 His Gly Glu Asp Ala Gly Val Ile Cys Ser Ala Ala Gln Pro Gln Ser 195 200 205 Thr Leu Arg Pro Glu Ser Trp Pro Val Arg lle Ser Pro Pro Val Pro 210 215 220 Thr Glu Gly Ser Glu Ser Ser Leu Ala Leu Arg Leu Val Asn Gly Gly 225 230 235 240 Asp Arg Cys Arg Gly Arg Val Glu Val Leu Tyr Arg Gly Ser Trp Gly 245 250 255 Thr Val Cys Asp Asp Tyr Trp Asp Thr Asn Asp Ala Asn Val Val Cys 260 265 270 Arg Gln Leu Gly Cys Gly Trp Ala Met Ser Ala Pro Gly Asn Ala Gln 275 280 285 Phe Gly Gln Gly Ser Gly Pro Ile Val Leu Asp Asp Val Arg Cys Ser 290 295 300 Gly His Glu Ser Tyr Leu Trp Ser Cys Pro His Asn Gly Trp Leu Thr 305 310 315 320 His Asn Cys Gly His Ser Glu Asp Ala Gly val Ile Cys Ser Ala Pro 325 330 335 Gln Ser Arg Pro Thr Pro Ser Pro Asp Thr Trp Pro Thr Ser His Ala 340 345 350 Ser Thr Ala Gly Pro Glu Ser Ser Leu Ala Leu Arg Leu Val Asn Gly 355 360 365

Gly Asp Arg Cys Gln Gly Arg val Glu Val Leu Tyr Arg Gly Ser Trp 370 375 380 Gly Thr Val Cys Asp Asp Ser Trp Asp Thr Ser Asp Ala Asn Val Val 385 390 395 400 Cys Arg Gln Leu Gly Cys Gly Trp Ala Thr Ser Ala Pro Gly Asn Ala 405 410 415 Arg Phe Gly Gln Gly Ser Gly Pro Ile Val Leu Asp Asp Val Arg Cys 420 425 430 Ser Gly Tyr Glu Ser Tyr Leu Trp Ser Cys Pro His Asn Gly Trp Leu 435 440 445 Ser His Asn Cys Gln His Ser Glu Asp Ala Gly Val Ile Cys Ser Ala 450 455 460 Ala His Ser Trp Ser Thr Pro Ser Pro Asp Thr Leu Pro Thr Ile Thr 465 470 475 480 Leu Pro Ala Ser Thr val Gly Ser Glu Ser Ser Leu Ala Leu Arg Leu 485 490 4935 val Asn Gly Gly Asp Arg Cys Gln Gly Arg Val Glu Val Leu Tyr Arg 500 505 510 Gly Ser Trp Gly Thr Val Cys Asp Asp Ser Trp Asp Thr Asn Asp Ala 515 520 525 Asn Val Val Cys Arg Gln Leu Gly Cys Gly Trp Ala Met Leu Ala Pro 530 535 540 Gly Asn Ala Arg Phe Gly Gln Gly Ser Gly Pro Ile Val Leu Asp Asp 545 550 555 560 val Arg Cys Ser Gly Asn Glu Ser Tyr Leu Trp Ser Cys Pro His Asn 565 570 575 Gly Trp Leu Ser His Asn Cys Gly His Ser Glu Asp Ala Gly Val Ile 580 585 590 Cys Ser Gly Pro Glu Ser Ser Leu Ala Leu Arg Leu Val Asn Gly Gly 595 600 605 Asp Arg Cys Gln Gly Arg Val Glu Val Leu Tyr Arg Gly Ser Trp Gly

610 615 620 Thr Val Cys Asp Asp Ser Trp Asp Thr Asn Asp Ala Asn Val Val Cys 625 630 635 640 Arg Gln Leu Gly Cys Gly Trp Ala Met Ser Ala Pro Gly Asn Ala Arg 645 650 655 Phe Gly Gln Gly Ser Gly Pro Ile Val Leu Asp Asp Val Arg Cys Ser 660 665 670 Gly His Glu Ser Tyr Leu Trp Ser Cys Pro Asn Asn Gly Trp Leu Ser 675 680 685 His Asn Cys Gly His His Glu Asp Ala Gly Val Ile Cys Ser Ala Ala 690 695 700 Gln Ser Arg Ser Thr Pro Arg Pro Asp Thr Leu Ser Thr Ile Thr Leu 705 710 715 720 Pro Pro Ser Thr Val Gly Ser Glu Ser Ser Leu Thr Leu Arg Leu Val 725 730 7358 Asn Gly Ser Asp Arg Cys Gln Gly Arg Val Glu Val Leu Tyr Arg Gly 740 745 750 Ser Trp Gly Thr Val Cys Asp Asp Ser Trp Asp Thr Asn Asp Ala Asn : 755 760 765 Val Val Cys Arg Gln Leu Gly Cys Gly Trp Ala Met Ser Ala Pro Gly 770 775 780 Asn Ala Arg Phe Gly Gln Gly Ser Gly Pro Ile Val Leu Asp Asp Val 785 790 7985 800 Arg Cys Ser Gly His Glu Ser Tyr Leu Trp Ser Cys Pro His Asn Gly 80S 810 815 Trp Leu Ser His Asn Cys Gly His His Glu Asp Ala Gly val Ile Cys 820 825 830 Ser Val Ser Gln Ser Arg Pro Thr Pro Ser Pro Asp Thr Trp Pro Thr 835 840 845 Ser His Ala Ser Thr Ala Gly Ser Glu Ser Ser Leu Ala Leu Arg Leu 850 855 860

Val Asn Gly Gly Asp Arg Cys Gln Gly Arg Val Glu Val Leu Tyr Arg 865 870 875 880 Gly Ser Trp Gly Thr Val Cys Asp Asp Ser Trp Asp Thr Ser Asp Ala

885 890 895 Asn Val Val Cys Arg Gln Leu Gly Cys Gly Trp Ala Thr Ser Ala Pro S00 905 910 Gly Asn Ala Arg Phe Gly Gln Gly Ser Gly Pro Ile Val Leu Asp Asp 915 S20 925

Val Arg Cys Ser Gly Tyr Glu Ser Tyr Leu Trp Ser Cys Pro His Asn 930 935 940

Gly Trp Leu Ser His Asn Cys Gln His Ser Glu Asp Ala Gly val Ile

945 950 955 960

Cys Ser Ala Ala His Ser Trp Ser Thr Pro Ser Pro Asp Thr Leu Pro

965 S70 975 Thr Ile Thr Leu Pro Ala Ser Thr val Gly Ser Glu Ser Ser Leu Ala $80 985 990 Leu Arg Leu Val Asn Gly Gly Asp Arg Cys Gln Gly Arg Val Glu Val 995 1000 1005

Leu Tyr Gln Gly Ser Trp Gly Thr Val Cys Asp Asp Ser Trp Asp 1010 1015 1020

Thr Asn Asp Ala Asn Val Val Cys Arg Gln Pro Gly Cys Gly Trp 1025 1030 1035

Ala Met Ser Ala Pro Gly Asn Ala Arg Phe Gly Gln Gly Ser Gly 1040 1045 1050

Pro Ile Val Leu Asp Asp Val Arg Cys Ser Gly His Glu Ser Tyr 1055 1060 1065

Pro Trp Ser Cys Pro His Asn Gly Trp Leu Ser His Asn Cys Gly 1070 1075 1080

His Ser Glu Asp Ala Gly Val Ile Cys Ser Ala Ser Gln Ser Arg 1085 1090 109s

1068 . a

Pro Thr Pro Ser Pro Asp Thr Trp Pro Thr Ser His Ala Ser Thr 1100 1105 1110

Ala Gly Ser Glu Ser Ser Leu Ala Leu Arg Leu Val Asn Gly Gly 1115 1120 1125

Asp Arg Cys Gln Gly Arg Val Glu Val Leu Tyr Arg Gly Ser Trp 1130 1135 1140

Gly Thr Val Cys Asp Asp Tyr Trp Asp Thr Asn Asp Ala Asn Val 1145 1150 1155

Val Cys Arg Gln Leu Gly Cys Gly Trp Ala Met Ser Ala Pro Gly 1160 1165 1170

Asn Ala Arg Phe Gly Gln Gly Ser Gly Pro Ile val Leu Asp Asp 1175 1180 1i85

Val Arg Cys Ser Gly His Glu Ser Tyr Leu Trp Ser Cys Pro His 1190 1185 1200

Asn Gly Trp Leu Ser His Asn Cys Gly His His Glu Asp Ala Gly 1205 1210 1215

Val Ile Cys Ser Ala Ser Gln Ser Gln Pro Thr Pro Ser Pro Asp 1220 1225 1230

Thr Trp Pro Thr Ser His Ala Ser Thr Ala Gly Ser Glu Ser Ser 1235 1240 1245

Leu Ala Leu Arg Leu Val Asn Gly Gly Asp Arg Cys Gln Gly Arg 1250 1255 1260

Val Glu Val Leu Tyr Arg Gly Ser Trp Gly Thr val Cys Asp Asp 1265 1270 1275 Tyr Trp Asp Thr Asn Asp Ala Asn Val Val Cys Arg Gln Leu Gly

1280 1285 1280

Cys Gly Trp Ala Thr Ser Ala Pro Gly Asn Ala Arg Phe Gly Gln 1295 1300 1305

Gly Ser Gly Pro Ile Val Leu Asp Asp Val Arg Cys Ser Gly His 1310 1315 1320

Glu Ser Tyr Leu Trp Ser Cys Pro His Asn Gly Trp Leu Ser His 1325 1330 1335 Asn Cys Gly His His Glu Asp Ala Gly Val Ile Cys Ser Ala Ser 1340 1345 1350 Gln Ser Gln Pro Thr Pro Ser Pro Asp Thr Trp Pro Thr Ser His 1355 1360 1365 nla Ser Thr Ala Gly Ser Glu Ser Ser Leu Ala Leu Arg Leu Val 1370 1375 1380 : Asn Gly Gly Asp Arg Cys Gln Gly Arg Val Glu Val Leu Tyr Arg 1385 1390 1395 Gly Ser Trp Gly Thr Val Cys Asp Asp Tyr Trp Asp Thr Asn Asp 1400 1405 1410 Ala Asn Val Val Cys Arg Gln Leu Gly Cys Gly Trp Ala Thr Ser 1415 1420 1425 Ala Pro Gly Asn Ala Arg Phe Gly Gln Gly Ser Gly Pro Ile Val 1430 1435 1440 Leu Asp Asp Val Arg Cys Ser Gly His Glu Ser Tyr Leu Trp Ser 1445 1450 1455 Cys Pro His Asn Gly Trp Leu Ser His Asn Cys Gly His His Glu 1460 1465 1470 Asp Ala Gly Val Ile Cys Ser Ala Ser Gln Ser Gln Pro Thr Pro 1475 1480 1485 Ser Pro Asp Thr Trp Pro Thr Ser Arg Ala Ser Thr Ala Gly Ser 1490 1498 1500 . Glu Ser Thr Leu Ala Leu Arg Leu Val Asn Gly Gly Asp Arg Cys 1505 1510 1515 Arg Gly Arg val Glu Val Leu Tyr Gln Gly Ser Trp Gly Thr Val . 1520 1525 1530 Cys Asp Asp Tyr Trp Asp Thr Asn Asp Ala Asn Val Val Cys Arg 1535 1540 1545 Gln Leu Gly Cys Gly Trp Ala Met Ser Ala Pro Gly Asn Ala Gla 1070

]

i... LL

1550 1555 1560 Phe Gly Gln Gly Ser Gly Pro Ile Val Leu Asp Asp Val Arg Cys 1565 1570 1575 Ser Gly His Glu Ser Tyr Leu Trp Ser Cys Pro His Asn Gly Trp 1580 1585 1590 Leu Ser His Asn Cys Gly His His Glu Asp Ala Gly val Ile Cys 1595 1600 1605 Ser Ala Ala Gln Ser Gln Ser Thr Pro Arg Pro Asp Thr Trp Leu 1610 1615 1620 Thr Thr Asn Leu Pro Ala Leu Thr Val Gly Ser Glu Ser Ser Leu 1625 1630 1635 Ala Leu Arg Leu Val Asn Gly Gly Asp Arg Cys Arg Gly Arg Val 1640 1645 1650 Glu Val Leu Tyr Arg Gly Ser Trp Gly Thr Val Cys Asp Asp Ser 1655 1660 1665 Trp Asp Thr Asn Asp Ala Asn Val Val Cys Arg Gln Leu Gly Cys 1670 1675 1680 Gly Trp Ala Met Ser Ala Pro Gly Asn Ala Arg Phe Gly Gln Gly 1685 1690 1695 Ser Gly Pro Ile Val Leu Asp Asp Val Arg Cys Ser Gly Asn Glu 1700 1705 1710 Ser Tyr Leu Trp Ser Cys Pro His Lys Gly Trp Leu Thr His Asn 1715 1720 1725 Cys Gly His His Glu Asp Ala Gly Val Ile Cys Ser Ala Thr Gln 1730 1735 1740 Ile Asn Sex Thr Thr Thr Asp Trp Trp His Pro Thr Thr Thr Thr 1745 1750 1755 Thr Ala Arg Pro Ser Ser Asn Cys Gly Gly Phe Leu Phe Tyr Ala 1760 1765 1770 Ser Gly Thr Phe Ser Ser Pro Ser Tyr Pro Ala Tyr Tyr Pro Asn 1775 1780 1785

Asn Ala Lys Cys Val Trp Glu Ile Glu Val Asn Ser Gly Tyr Arg 1790 1795 1800 Ile Asn Leu Gly Phe Ser Asn Leu Lys Leu Glu Ala His His Asn 1805 1810 1815 Cys Ser Phe Asp Tyr Val Glu Ile Phe Asp Gly Ser Leu Asn Ser 1820 1825 1830 Ser Leu Leu Leu Gly Lys Ile Cys Asn Asp Thr Arg Gln Ile Phe 1835 1840 1845 Thr Ser Ser Tyr Asn Arg Met Thr Ile His Phe Arg Ser Asp Ile 1850 1855 1860 Ser Phe Gln Asn Thr Gly Phe Leu Ala Trp Tyr Asn Ser Phe Pro 1865 1870 1875 Ser Asp Ala Thr Leu Arg Leu Val Asn Leu Asn Ser Ser Tyr Gly 1880 1885 1850 Leu Cys Ala Gly Arg val Glu Ile Tyr His Gly Gly Thr Trp Gly 1895 1900 1905 Thr Val Cys Asp Asp Ser Trp Thr Ile Gln Glu Ala Glu val val 1810 1815 1520 Cys Arg Gln Leu Gly Cys Gly Arg Ala Val Ser Ala Leu Gly Asn 1925 1930 193% Ala Tyr Phe Gly Ser Gly Ser Gly Pro Ile Thr Leu Asp Asp Val 1940 1945 . 1950 Glu Cys Ser Gly Thr Glu Ser Thr Leu Trp Gln Cys Arg Asn Arg 1955 1960 1965 Gly Trp Phe Ser His Asn Cys Asn His Arg Glu Asp Ala Gly Val 1970 1975 1580 Ile Cys Ser Gly Asn His Leu Ser Thr Pro Ala Pro Phe Leu Asn 1985 1990 1995 Ile Thr Arg Pro Asn Thr Asp Tyr Ser Cys Gly Gly Phe Leu Ser 2000 2005 2010 1072

"Vi. oo

Gln Pro Ser Gly Asp Phe Ser Ser Pro Phe Tyr Pro Gly Asn Tyr 2015 2020 2025 Pro Asn Asn Ala Lys Cys Val Trp Asp Ile Glu Val Gln Asn Asn 2030 2035 2040 Tyr Arg Val Thr val Ile Phe Arg Asp Val Gln Leu Glu Gly Gly 2045 2050 2055 Cys Asn Tyr Asp Tyr Ile Glu Val Phe Asp Gly Pro Tyr Arg Ser 2060 2065 2070 Ser Pro Leu Ile Ala Arg Val Cys Asp Gly Ala Arg Gly Ser Phe 2075 2080 2085 Thr Ser Ser Ser Asn Phe Met Ser Ile Arg Phe Ile Ser Asp His 2090 2095 2100 Ser Ile Thr Arg Arg Gly Phe Arg Ala Glu Tyr Tyr Ser Ser Pro 2105 2110 2115 Ser Asn Asp Ser Thr Asn Leu Leu Cys Leu Pro Asn His Met Gln 2120 2125 2130 Ala Ser Val Ser Arg Ser Tyr Leu Gln Ser Leu Gly Phe Ser Ala 2135 2140 2145 Ser Asp Leu Val Ile Ser Thr Trp Asn Gly Tyr Tyr Glu Cys Arg 2150 2155 . 2160 Pro Gln Ile Thr Pro Asn Leu Val Ile Phe Thr Ile Pro Tyr Ser 2165 2170 2175 Gly Cys Gly Thr Phe Lys Gln Ala Asp Asn Asp Thr Ile Asp Tyr 2180 2185 2190 Ser Asn Phe Leu Thr Ala Ala Val Ser Gly Gly Ile Ile Lys Arg 2195 2200 2205 Arg Thr Asp Leu Arg Ile His Val Ser Cys Arg Met Leu Gln Asn i 2210 2215 2220 Thr Trp Val Asp Thr Met Tyr Ile Ala Asn Asp Thr Ile His Val 2225 2230 2235

Ala Asn Asn Thr Ile Gln Val Glu Glu Val Gln Tyr Gly Asn Phe 2240 2245 2250 Asp Val Asn Ile Ser Phe Tyr Thr Ser Ser Ser Phe Leu Tyr Pro 2255 2260 2265 Val Thr Ser Arg Pro Tyr Tyr Val Asp Leu Asn Gln Asp Leu Tyr 2270 2275 2280 Val Gln Ala Glu Ile Leu His Ser Asp Ala Val Leu Thr Leu Phe 2285 2290 2295 Val Asp Thr Cys Val Ala Ser Pro Tyr Ser Asn Asp Phe Thr Ser 2300 2305 2310 Leu Thr Tyr Asp Leu Ile Arg Ser Gly Cys Val Arg Asp Asp Thr 2315 2320 2325 Tyr Gly Pro Tyr Ser Ser Pro Ser Leu Arg Ile Ala Arg Phe Arg 2330 2335 2340 Phe Arg Ala Phe His Phe Leu Asn Arg Phe Pro Ser Val Tyr Leu ’ 2345 2350 2355 Arg Cys Lys Met Val Val Cys Arg Ala Tyr Asp Pro Ser Ser Arg 2360 2365 2370 Cys Tyr Arg Gly Cys Val Leu Arg Ser Lys Arg Asp Val Gly Ser 2375 2380 2385 Tyr Gln Glu Lys Val Asp Val Val Leu Gly Pro Ile Gln Leu Gln 2390 2395 2400 Thr Pro Pro Arg Arg Glu Glu Glu Pro Arg 2405 2410 <210> 2617 <211l> 143 <212> PRT <213> Homo sapiens <400> 2617 oo Met Gly Lys Cys Arg Gly Leu Arg Thr Ala Arg Lys Leu Arg Ser His 1 5 10 15 Arg Arg Asp Gln Lys Trp His Asp Lys Gln Tyr Lys Lys Ala His Leu

Gly Thr Ala Leu Lys Ala Asn Pro Phe Gly Gly Ala Ser His Ala Lys 35 40 45 Gly Ile val Leu Glu Lys Val Gly Val Glu Ala Lys Gln Pro Asn Ser S50 55 60 Ala Ile Arg Lys Cys Val Arg Val Gln Leu Ile Lys Asn Gly Lys Lys 65 70 75 80 Ile Thr Ala Phe Val Pro Asn Asp Gly Cys Leu Asn Phe Ile Glu Glu 85 90 95 Asn Asp Glu Val Leu Val Ala Gly Phe Gly Arg Lys Gly His Ala Val 100 105 110 Gly Asp Ile Pro Gly Val Arg Phe Lys Val Val Lys Val Ala Asn Val 115 120 125 Ser Leu Leu Ala Leu Tyr Lys Gly Lys Lys Glu Arg Pro Arg Ser 130 135 140 <210> 2618 <211> 272 <212> PRT <213> Homo sapiens <400> 2618 Met Glu Glu Glu Ala Ile Ala Ser Leu Pro Gly Glu Glu Thr Glu Asp 1 S 10 15 Met Asp Phe Leu Ser Gly Leu Glu Leu Ala Asp Leu Leu Asp Pro Arg

Gln Pro Asp Trp His Leu Asp Pro Gly Leu Ser Ser Pro Gly Pro Leu 40 45 Ser Ser Ser Gly Gly Gly Ser Asp Ser Gly Gly Leu Trp Arg Gly Asp 50 55 60 Asp Asp Asp Glu Ala Ala Ala Ala Glu Met Gln Arg Phe Ser Asp Leu 65 70 75 80 Leu Gln Arg Leu Leu Asn Gly Ile Gly Gly Cys Ser Ser Ser Ser Asp 85 90 95

Ser Gly Ser Ala Glu Lys Arg Arg Arg Lys Ser Pro Gly Gly Gly Gly 100 105 110 Gly Gly Gly Ser Gly Asn Asp Asn Asn Gln Ala Ala Thr Lys Ser Pro 115 120 125 Arg Lys Ala Ala Ala Ala Ala Ala Arg Leu Asn Arg Leu Lys Lys Lys 130 135 140 Glu Tyr Val Met Gly Leu Glu Ser Arg Val Arg Gly Leu Ala Ala Glu 145 150 155 160 Asn Gln Glu Leu Arg Ala Glu Asn Arg Glu Leu Gly Lys Arg Val Gln 165 170 175 Ala Leu Gln Glu Glu Ser Arg Tyr Leu Arg Ala Val Leu Ala Asn Glu 180 185 190 Thr Gly Leu Ala Arg Leu Leu Ser Arg Leu Ser Gly Val Gly Leu Arg : 195 200 205 Leu Thr Thr Ser Leu Phe Arg Asp Ser Pro Ala Gly Asp His Asp Tyr 210 215 220 Ala Leu Pro Val Gly Lys Gln Lys Gln Asp Leu Leu Glu Glu Asp Asp 225 230 235 240 Ser Ala Gly Gly Val Cys Leu His Val Asp Lys Asp Lys Val Ser Val 245 250 255 Glu Phe Cys Ser Ala Cys Ala Arg Lys Ala Ser Ser Ser Leu Lys Met 260 265 270 <210> 2619 <211> 694 <212> PRT <213> Homo sapiens <400> 26189 Met Lys His Leu Lys Arg Trp Trp Ser Ala Gly Gly Gly Leu Leu His 1 5 10 15 Leu Thr Leu Leu Leu Ser Leu Ala Gly Leu Arg Val Asp Leu Asp Leu

Tyr Leu Leu Leu Pro Pro Pro Thr Leu Leu Gln Asp Glu Leu Leu Phe 40 45 1076 i Co

Leu Gly Gly Pro Ala Ser Ser Ala Tyr Ala Leu Ser Pro Phe Ser Ala 50 585 60 Ser Gly Gly Trp Gly Arg Ala Gly His Leu His Pro Lys Gly Arg Glu 65 70 75 80 Leu Asp Pro Ala Ala Pro Pro Glu Gly Gln Leu Leu Arg Glu Val Arg 85 SO 9s Ala Leu Gly val Pro Phe Val Pro Arg Thr Ser val Asp Ala Trp Leu 100 105 110 Val His Ser val Ala Ala Gly Ser Ala Asp Glu Ala His Gly Leu Leu 115 120 125 Gly Ala Ala Ala Ala Ser Ser Thr Gly Gly Ala Gly Ala Ser Val Asp 130 135 140 Gly Gly Ser Gln Ala Val Gln Gly Gly Gly Gly Asp Pro Arg Ala Ala 145 150 155 160 Arg Ser Gly Pro Leu Asp Ala Gly Glu Glu Glu Lys Ala Pro Ala Glu 165 170 175 Pro Thr Ala Gln Val Pro Asp Ala Gly Gly Cys Ala Ser Glu Glu Asn 180 185 150 Gly Val Leu Arg Glu Lys His Glu Ala Val Asp His Ser Ser Gln His 195 200 205 Glu Glu Asn Glu Glu Arg Val Ser Ala Gln Lys Glu Asn Ser Leu Gln 210 215 220 Gln Asn Asp Asp Asp Glu Asn Lys Ile Ala Glu Lys Pro Asp Trp Glu 225 230 235 240 Ala Glu Lys Thr Thr Glu Ser Arg Asn Glu Arg His Leu Asn Gly Thr 245 250 255 Asp Thr Ser Phe Ser Leu Glu Asp Leu Phe Gln Leu Leu Ser Ser Gln 260 265 270 Pro Glu Asn Ser Leu Glu Gly Ile Ser Leu Gly Asp Ile Pro Leu Pro 275 280 285

Gly Ser Ile Ser Asp Gly Met Asn Ser Ser Ala His Tyr His Val Asn 290 295 300 Phe Ser Gln Ala Ile Ser Gln Asp Val Asn Leu His Glu Ala Ile Leu 305 310 315 320 Leu Cys Pro Asn Asn Thr Phe Arg Arg Asp Pro Thr Ala Arg Thr Ser 325 330 335 Gln Ser Gln Glu Pro Phe Leu Gln Leu Asn Ser His Thr Thr Asn Pro 340 345 350 Glu Gln Thr Leu Pro Gly Thr Asn Leu Thr Gly Phe Leu Ser Pro Val 355 360 365 Asp Asn His Met Arg Asn Leu Thr Ser Gln Asp Leu Leu Tyr Asp Leu 370 375 380 Asp Ile Asn Ile Phe Asp Glu Ile Asn Leu Met Ser Leu Ala Thr Glu

385. 390 385 400 Asp Asn Phe Asp Pro Ile Asp Val Ser Gln Leu Phe Asp Glu Pro Asp 405 410 415 Ser Asp Ser Gly Leu Ser Leu Asp Ser Ser His Asn Asn Thr Ser Val 420 425 430 Ile Lys Ser Asn Ser Ser His Ser Val Cys Asp Glu Gly Ala Ile Gly 435 440 445 Tyr Cys Thr Asp His Glu Ser Ser Ser His His Asp Leu Glu Gly Ala 450 455 460 Val Gly Gly Tyr Tyr Pro Glu Pro Ser Lys Leu Cys His Leu Asp Gln 465 470 475 480 Ser Asp Ser Asp Phe His Gly Asp Leu Thr Phe Gln His Val Phe His 485 490 495 Asn His Thr Tyr His Leu Gln Pro Thr Ala Pro Glu Ser Thr Ser Glu 500 505 510 Pro Phe Pro Trp Pro Gly Lys Ser Gln Lys Ile Arg Ser Arg Tyr Leu 515 520 525

Glu Asp Thr Asp Arg Asn Leu Ser Arg Asp Glu Gln Arg Ala Lys Ala 530 535 540 Leu His Ile Pro Phe Ser Val Asp Glu Ile val Gly Met Pro Val Asp 545 550 555 560 Ser Phe Asn Ser Met Leu Ser Arg Tyr Tyr Leu Thr Asp Leu Gln Val 565 570 575 Ser Leu Ile Arg Asp Ile Arg Arg Arg Gly Lys Asn Lys Val Ala Ala . 580 585 590 Gln Asn Cys Arg Lys Arg Lys Leu Asp Ile Ile Leu Asn Leu Glu Asp 595 600 605 Asp Val Cys Asn Leu Gln Ala Lys Lys Glu Thr Leu Lys Arg Glu Gln 610 615 620 Ala Gln Cys Asn Lys Ala Ile Asn Ile Met Lys Gln Lys Leu His Asp 625 630 635 640 Leu Tyr His Asp Ile Phe Ser Arg Leu Arg Asp Asp Gln Gly Arg Pro ‘ 645 650 655 Val Asn Pro Asn His Tyr Ala Leu Gln Cys Thr His Asp Gly Ser Ile 660 665 670 Leu Ile Val Pro Lys Glu Leu Val Ala Ser Gly His Lys Lys Glu Thr 675 680 685 Gln Lys Gly Lys Arg Lys 690 <210> 2620 <211> 3°91 <212> PRT <213> Homo sapiens <400> 2620 Met Lys Cys Leu Val Thr Gly Gly Asn Val Lys Val Leu Gly Lys Ala 1 5 10 15 val His Ser Leu Ser Arg Ile Gly Asp Glu Leu Tyr Leu Glu Pro Leu : 20 25 30 Glu Asp Gly Leu Ser Leu Arg Thr val Asn Ser Ser Arg Ser Ala Tyr 40 45

Ala Cys Phe Leu Phe Ala Pro Leu Phe Phe Gln Gln Tyr Gln Ala Ala 50 55 60 Thr Pro Gly Gln Asp Leu Leu Arg Cys Lys Ile Leu Met Lys Ser Phe 65 70 75 80 Leu Ser Val Phe Arg Ser Leu Ala Met Leu Glu Lys Thr val Glu Lys 85 90 95 Cys Cys Ile Ser Leu Asn Gly Arg Ser Ser Arg Leu val val Gln Leu 100 105 110 His Cys Lys Phe Gly Val Arg Lys Thr His Asn Leu Ser Phe Gln Asp 115 120 125 Cys Glu Ser Leu Gln Ala Val Phe Asp Pro Ala Ser Cys Pro His Met 130 135 140 Leu Arg Ala Pro Ala Arg Val Leu Gly Glu Ala Val Leu Pro Phe Ser 145 150 155 160 Pro Ala Leu Ala Glu val Thr Leu Gly Ile Gly Arg Gly Arg Arg Val 165 170 175 Ile Leu Arg Ser Tyr His Glu Glu Glu Ala Asp Ser Thr Ala Lys Ala 180 185 190 Met Val Thr Glu Met Cys Leu Gly Glu Glu Asp Phe Gln Gln Leu Gln 185 200 205 Ala Gln Glu Gly val Ala Ile Thr Phe Cys Leu Lys Glu Phe Arg Gly 210 215 220 Leu Leu Ser Phe Ala Glu Ser Ala Asn Leu Asn Leu Ser Ile His Phe 225 230 235 240 Asp Ala Pro Gly Arg Pro Ala Ile Phe Thr Ile Lys Asp Ser Leu Leu 245 250 255 Asp Gly His Phe val Leu Ala Thr Leu Ser Asp Thr Asp Ser His Ser 260 265 270 Gln Asp Leu Gly Ser Pro Glu Arg His Gln Pro Val Pro Gln Leu Gln 275 280 285

Ala His Ser Thr Pro His Pro Asp Asp Phe Ala Asn Asp Asp Ile Asp 250 295 300

Ser Tyr Met Ile Ala Met Glu Thr Thr Ile Gly Asn Glu Gly Ser Arg

305 310 315 320

Val Leu Pro Ser Ile Ser Leu Ser Pro Gly Pro Gln Pro Pro Lys Ser

325 330 335 Pro Gly Pro His Ser Glu Glu Glu Asp Glu Ala Glu Pro Ser Thr Val 340 345 350 Pro Gly Thr Pro Pro Pro Lys Lys Phe Arg Ser Leu Phe Phe Gly Ser 355 360 365

Ile Leu Ala Pro Val Arg Ser Pro Gln Gly Pro Ser Pro Val Leu Ala 370 375 380

Glu Asp Ser Glu Gly Glu Gly

385 390

<210> 2621

<211> 1429

<212> PRT

<213> Homo sapiens

<400> 2621

Met Ala Gly Gly Ala Trp Gly Arg Leu Ala Cys Tyr Leu Glu Phe Leu

1 5 10 15

Lys Lys Glu Glu Leu Lys Glu Phe Gln Leu Leu Leu Ala Asn Lys Ala

His Ser Arg Ser Ser Ser Gly Glu Thr Pro Ala Gln Pro Glu Lys Thr 40 45

Ser Gly Met Glu Val Ala Ser Tyr Leu Val Ala Gln Tyr Gly Glu Gln 50 55 60

Arg Ala Trp Asp Leu Ala Leu His Thr Trp Glu Gln Met Gly Leu Arg

65 70 75 80

Ser Leu Cys Ala Gln Ala Gln Glu Gly Ala Gly His Ser Pro Ser Phe

85 90 SS Pro Tyr Ser Pro Ser Glu Pro His Leu Gly Ser Pro Ser Gln Pro Thr

100 105 110 Ser Thr Ala Val Leu Met Pro Trp Ile His Glu Leu Pro Ala Gly Cys 115 120 125 Thr Gln Gly Ser Glu Arg Arg Val Leu Arg Gln Leu Pro Asp Thr Ser 130 135 140 Gly Arg Arg Trp Arg Glu Ile Ser Ala Ser Leu Leu Tyr Gln Ala Leu 145 150 155 160 Pro Ser Ser Pro Asp His Glu Ser Pro Ser Gln Glu Ser Pro Asn Ala 165 170 175 Pro Thr Ser Thr Ala Val Leu Gly Ser Trp Gly Ser Pro Pro Gln Pro 180 185 190 Ser Leu Ala Pro Arg Glu Gln Glu Ala Pro Gly Thr Gln Trp Pro Leu 195 200 205 Asp Glu Thr Ser Gly Ile Tyr Tyr Thr Glu Ile Arg Glu Arg Glu Arg 210 215 220 Glu Lys Ser Glu Lys Gly Arg Pro Pro Trp Ala Ala Val Val Gly Thr 225 230 235 240 Pro Pro Gln Ala His Thr Ser Leu Gln Pro His His His Pro Trp Glu 245 250 255 Pro Ser Val Arg Glu Ser Leu Cys Ser Thr Trp Pro Trp Lys Asn Glu 260 265 270 Asp Phe Asn Gln Lys Phe Thr Gln Leu Leu Leu Leu Gln Arg Pro His 275 280 285 + Pro Arg Ser Gln Asp Pro Leu Val Lys Arg Ser Trp Pro Asp Tyr Val 290 295 300 i Glu Glu Asn Arg Gly His Leu Ile Glu Ile Arg Asp Leu Phe Gly Pro 305 310 31s 320 Gly Leu Asp Thr Gln Glu Pro Arg Ile Val Ile Leu Gln Gly Ala Ala 328 330 335 Gly Ile Gly Lys Ser Thr Leu Ala Arg Gln Val Lys Glu Ala Trp Gly 340 345 350

Arg Gly Gln Leu Tyr Gly Asp Arg Phe Gln His Val Phe Tyr Phe Ser 385 360 365 Cys Arg Glu Leu Ala Gln Ser Lys Val Val Ser Leu Ala Glu Leu Ile 370 375 380 Gly Lys Asp Gly Thr Ala Thr Pro Ala Pro Ile Arg Gln Ile Leu Ser 38S 390 395 400 Arg Pro Glu Arg Leu Leu Phe Ile Leu Asp Gly Val Asp Glu Pro Gly 405 410 415 Trp Val Leu Gln Glu Pro Ser Ser Glu Leu Cys Leu His Trp Ser Gln 420 425 430 Pro Gln Pro Ala Asp Ala Leu Leu Gly Ser Leu Leu Gly Lys Thr Ile 435 440 445 Leu Pro Glu Ala Ser Phe Leu Ile Thr Ala Arg Thr Thr Ala Leu Gln 450 455 460 Asn Leu Ile Pro Ser Leu Glu Gln Ala Arg Trp Val Glu Val Leu Gly 465 470 475 480 Phe Ser Glu Ser Ser Arg Lys Glu Tyr Phe Tyr Arg Tyr Phe Thr Asp 485 430 495 Glu Arg Gln ala Ile Arg Ala Phe Arg Leu Val Lys Ser Asn Lys Glu 500 505 510 Leu Trp Ala Leu Cys Leu Val Pro Trp Val Ser Trp Leu Ala Cys Thr 515 520 525 Cys Leu Met Gln Gln Met Lys Arg Lys Glu Lys Leu Thr Leu Thr Ser . 530 535 540 Lys Thr Thr Thr Thr Leu Cys Leu His Tyr Leu Ala Gln Ala Leu Gln 545 850 555 560 Ala Gln Pro Leu Gly Pro Gln Leu Arg Asp Leu Cys Ser Leu Ala Ala 565 570 575 Glu Gly Ile Trp Gln Lys Lys Thr Leu Phe Ser Pro Asp Asp Leu Arg 580 585 580

Lys His Gly Leu Asp Gly Ala Ile Ile Ser Thr Phe Leu Lys Met Gly 595 600 605 Ile Leu Gln Glu His Pro Ile Pro Leu Ser Tyr Ser Phe Ile His Leu 610 615 620 Cys Phe Gln Glu Phe Phe Ala Ala Met Ser Tyr Val Leu Glu Asp Glu 625 630 . 635 640 Lys Gly Arg Gly Lys His Ser Asn Cys Ile Ile Asp Leu Glu Lys Thr 645 650 655 Leu Glu Ala Tyr Gly Ile His Gly Leu Phe Gly Ala Ser Thr Thr Arg 660 665 670 Phe Leu Leu Gly Leu Leu Ser Asp Glu Gly Glu Arg Glu Met Glu Asn 675 680 685 Ile Phe His Cys Arg Leu Ser Gln Gly Arg Asn Leu Met Gln Trp Val 690 695 700 Pro Ser Leu Gln Leu Leu Leu Gln Pro His Ser Leu Glu Ser Leu His 705 710 718 720 Cys Leu Tyr Glu Thr Arg Asn Lys Thr Phe Leu Thr Gln Val Met Ala 725 730 735 His Phe Glu Glu Met Gly Met Cys Val Glu Thr Asp Met Glu Leu Leu 740 745 750 Val Cys Thr Phe Cys Ile Lys Phe Ser Arg His Val Lys Lys Leu Gln 755 760 765 Leu Ile Glu Gly Arg Gln His Arg Ser Thr Trp Ser Pro Thr Met Val 770 775 780 Val Leu Phe Arg Trp Val Pro Val Thr Asp Ala Tyr Trp Gln Ile Leu 785 790 795 800 Phe Ser Val Leu Lys Val Thr Arg Asn Leu Lys Glu Leu Asp Leu Ser 805 B10 815 Gly Asn Ser Leu Ser His Ser Ala Val Lys Ser Leu Cys Lys Thr Leu 820 825 830

03/012946

Arg Arg Pro Arg Cys Leu Leu Glu Thr Leu Arg Leu Ala Gly Cys Gly 835 840 845 Leu Thr Ala Glu Asp Cys Lys Asp Leu Ala Phe Gly Leu Arg Ala Asn 850 B55 860 Gln Thr Leu Thr Glu Leu Asp Leu Ser Phe Asn Val Leu Thr Asp Ala 865 870 875 880 Gly Ala Lys His Leu Cys Gln Arg Leu Arg Gln Pro Ser Cys Lys Leu 885 8390 895 Gln Arg Leu Gln Leu Val Ser Cys Gly Leu Thr Ser Asp Cys Cys Gln 900 905 910 Asp Leu Ala Ser Val Leu Ser Ala Ser Pro Ser Leu Lys Glu Leu Asp 915 920 925 Leu Gln Gln Asn Asn Leu Asp Asp Val Gly Val Arg Leu Leu Cys Glu $30 935 940 Gly Leu Arg His Pro Ala Cys Lys Leu Ile Arg Leu Gly Leu Asp Gln 945 950 955 960 Thr Thr Leu Ser Asp Glu Met Arg Gln Glu Leu Arg Ala Leu Glu Gln 965 970 975 Glu Lys Pro Gln Leu Leu Ile Phe Ser Arg Arg Lys Pro Ser Val Met 980 985 930 Thr Pro Thr Glu Gly Leu Asp Thr Gly Glu Met Ser Asn Ser Thr Ser 995 1000 1005 Ser Leu Lys Arg Gln Arg Leu Gly Ser Glu Arg Ala Ala Ser His 1010 1015 1020 Val Ala Gln Ala Asn Leu Lys Leu Leu Asp Val Ser Lys Ile Phe 1025 1030 1035 Pro Ile Ala Glu Ile Ala Glu Glu Ser Ser Pro Glu Val Val Pro 1040 1045 1050 ) Val Glu Leu Leu Cys Val Pro Ser Pro Ala Ser Gln Gly Asp Leu 1055 1060 1065 His Thr Lys Pro Leu Gly Thr Asp Asp Asp Phe Trp Gly Pro Thr

1070 1075 1080

Gly Pro Val Ala Thr Glu Val val Asp Lys Glu Lys Asn Leu Tyr 1085 1090 1095

Arg Val His Phe Pro Val Ala Gly Ser Tyr Arg Trp Pro Asn Thr 1100 1105 1110

Gly Leu Cys Phe Val Met Arg Glu Ala Val Thr val Glu Ile Glu 1115 1120 1125

Phe Cys Val Trp Asp Gln Phe Leu Gly Glu Ile Asn Pro Gln His 1130 1135 1140

Ser Trp Met Val Ala Gly Pro Leu Leu Asp Ile Lys Ala Glu Pro 1145 1150 1155

Gly Ala Val Glu Ala Val His Leu Pro His Phe val Ala Leu Gln 1160 1165 -1170

Gly Gly His Val Asp Thr Ser Leu Phe Gln Met Ala His Phe Lys 1175 1180 1185

Glu Glu Gly Met Leu Leu Glu Lys Pro Ala Arg Val Glu Leu His 1190 118S 1200

His Ile Val Leu Glu Asn Pro Ser Phe Ser Pro Leu Gly val Leu 1205 1210 1215

Leu Lys Met Ile His Asn Ala Leu Arg Phe Ile Pro Val Thr Ser 1220 1225 1230

Val Val Leu Leu Tyr His Arg Val His Pro Glu Glu Val Thr Phe 1235 1240 1245

His Leu Tyr Leu Ile Pro Ser Asp Cys Ser Ile Arg Lys Glu Leu 1250 1255 1260

Glu Leu Cys Tyr Arg Ser Pro Gly Glu Asp Gln Leu Phe Ser Glu 1265 1270 1275

Phe Tyr Val Gly His Leu Gly Ser Gly Ile Arg Leu Gln Val Lys 1280 1285 1250

Asp Lys Lys Asp Glu Thr Leu Val Trp Glu Ala Leu Val Lys Pro 1295 1300 1305

PCT/US2003/012946

Gly Asp Leu Met Pro Ala Thr Thr Leu Ile Pro Pro Ala Arg Ile 1310 1315 1320 Ala Val Pro Ser Pro Leu Asp Ala Pro Gln Leu Leu His Phe Val 1325 1330 1335 Asp Gln Tyr Arg Glu Gln Leu Ile Ala Arg Val Thr Ser val Glu 1340 1345 1350 Val Val Leu Asp Lys Leu His Gly Gln Val Leu Ser Gln Glu Gln 1355 1360 1365 Tyr Glu Arg Val Leu Ala Glu Asn Thr Arg Pro Ser Gln Met Arg 1370 1375 1380 Lys Leu Phe Ser Leu Ser Gln Ser Trp Asp Arg Lys Cys Lys Asp 1385 13590 1385 Gly Leu Tyr Gln Ala Leu Lys Glu Thr His Pro His Leu Ile Met 1400 1405 141310 Glu Leu Trp Glu Lys Gly Ser Lys Lys Gly Leu Leu Pro Leu Ser ] 1415 1420 1425 Ser <210> 2622 <211l> 179 <212> PRT <213> Homo sapiens <400> 2622 Met Ala Ala Leu Gln Lys Ser val Ser Ser Phe Leu Met Gly Thr Leu 1 5 10 15 Ala Thr Ser Cys Leu Leu Leu Leu Ala Leu Leu Val Gln Gly Gly Ala

Ala Ala Pro Ile Ser Ser His Cys Arg Leu Asp Lys Ser Asn Phe Gln 40 45 Gln Pro Tyr Ile Thr Asn Arg Thr Phe Met Leu Ala Lys Glu Ala Ser 50 55 60

Leu Ala Asp Asn Asn Thr Asp Val Arg Leu Ile Gly Giu Lys Leu Phe 65 70 75 B80 His Gly Val Ser Met Ser Glu Arg Cys Tyr Leu Met Lys Gln Val Leu

85 80 95 Asn Phe Thr Leu Glu Glu Val Leu Phe Pro Gln Ser Asp Arg Phe Gln 100 105 110 Pro Tyr Met Gln Glu Val Val Pro Phe Leu Ala Arg Leu Ser Asn Arg 115 120 125 Leu Ser Thr Cys His Ile Glu Gly Asp Asp Leu His Ile Gln Arg Asn 130 135 140 Val Gln Lys Leu Lys Asp Thr Val Lys Lys Leu Gly Glu Ser Gly Glu 145 150 155 160 Ile Lys Ala Ile Gly Glu Leu Asp Leu Leu Phe Met Ser Leu Arg Asn 165 170 175 Ala Cys Ile <210> 2623 <211l> 261 <212> PRT <213> Homo sapiens <400> 2623 Met Ser Arg Arg Tyr Asp Ser Arg Thr Thr Ile Phe Ser Pro Glu Gly 1 S 10 15 Arg Leu Tyr Gln Val Glu Tyr Ala Met Glu Ala Ile Gly His Ala Gly

Thr Cys Leu Gly Ile Leu Ala Asn Asp Gly Val Leu Leu Ala Ala Glu 40 45 Arg Arg Asn Ile His Lys Leu Leu Asp Glu Val Phe Phe Ser Glu Lys 50 55 60 Ile Tyr Lys Leu Asn Glu Asp Met Ala Cys Ser Val Ala Gly Ile Thr 65 70 75 80 Ser Asp Ala Asn Val Leu Thr Asn Glu Leu Arg Leu Ile Ala Gln Arg 85 90 95

Tyr Leu Leu Gln Tyr Gln Glu Pro Ile Pro Cys Glu Gln Leu val Thr 100 105 110 Ala Leu Cys Asp Ile Lys Gln Ala Tyr Thr Gln Phe Gly Gly Lys Arg 115 120 125 Pro Phe Gly Val Ser Leu Leu Tyr Ile Gly Trp Asp Lys His Tyr Gly 130 135 140 Phe Gln Leu Tyr Gln Ser Asp Pro Ser Gly Asn Tyr Gly Gly Trp Lys 145 150 155 160 Ala Thr Cys Ile Gly Asn Asn Ser Ala Ala Ala Val Ser Met Leu Lys 165 170 175 Gln Asp Tyr Lys Glu Gly Glu Met Thr Leu Lys Ser Ala Leu Ala Leu 180 185 190 Ala Ile Lys Val Leu Asn Lys Thr Met Asp Val Ser Lys Leu Ser Ala 195 200 205 Glu Lys Val Glu Ile Ala Thr Leu Thr Arg Glu Asn Gly Lys Thr Val 210 215 220 Ile Arg Val Leu Lys Gln Lys Glu Val Glu Gln Leu Ile Lys Lys His 225 230 235 240 Glu Glu Glu Glu Ala Lys Ala Glu Arg Glu Lys Lys Glu Lys Glu Gln 245 250 255 Lys Glu Lys Asp Lys 260 <210> 2624 <211l> 377 <212> PRT <213> Homo sapiens : <400> 2624 Met Lys Phe Pro Gly Pro Leu Glu Asn Gln Arg Leu Ser Phe Leu Leu 1 5 10 15 Glu Lys Ala Ile Thr Arg Glu Ala Gln Met Trp Lys Val Asn Val Arg

Lys Met Pro Ser Asn Gln Asn Val Ser Pro Ser Gln Arg Asp Glu val 40 45 Ile Gln Trp Leu Ala Lys Leu Lys Tyr Gln Phe Asn Leu Tyr Pro Glu SO 55 60 Thr Phe Ala Leu Ala Ser Ser Leu Leu Asp Arg Phe Leu Ala Thr val 65 70 - 75 80 Lys Ala His Pro Lys Tyr Leu Ser Cys Ile Ala Ile Ser Cys Phe Phe 85 90 S85 Leu Ala Ala Lys Thr val Glu Glu Asp Glu Arg Ile Pro Val Leu Lys 100 105 110 Val Leu Ala Arg Asp Ser Phe Cys Gly Cys Ser Ser Ser Glu Ile Leu 115 120 125 Arg Met Glu Arg Ile Ile Leu Asp Lys Leu Asn Trp Asp Leu His Thr 130 135 140 Ala Thr Pro Leu Asp Phe Leu His Ile Phe His Ala Ile Ala Val ser 145 150 155 160 Thr Arg Pro Gln Leu Leu Phe Ser Leu Pro Lys Leu Ser Pro Ser Gln 165 170 175 His Leu Ala Val Leu Thr Lys Gln Leu Leu His Cys Met Ala Cys Asn 180 185 190 Gln Leu Leu Gln Phe Arg Gly Ser Met Leu Ala Leu Ala Met Val Ser 195 200 205 Leu Glu Met Glu Lys Leu Ile Pro Asp Trp Leu Ser Leu Thr Ile Glu 210 215 220 Leu Leu Gln Lys Ala Gln Met Asp Ser Ser Gln Leu Ile His Cys Arg 225 230 235 240 Glu Leu Val Ala His His Leu Ser Thr Leu Gln Ser Ser Leu Pro Leu 245 250 255 Asn Ser Val Tyr Val Tyr Arg Pro Leu Lys His Thr Leu Val Thr Cys 260 265 270 Asp Lys Gly Val Phe Arg Leu His Pro Ser Ser val Pro Gly Pro Asp

275 280 285 Phe Ser Lys Asp Asn Ser Lys Pro Glu Val Pro Val Arg Gly Thr ala 290 295 300 Ala Phe Tyr His His Leu Pro Ala Ala Ser Gly Cys Lys Gln Thr Ser 305 310 315 320 Thr Lys Arg Lys Val Glu Glu Met Glu Val Asp Asp Phe Tyr Asp Gly 325 330 335 Ile Lys Arg Leu Tyr Asn Glu Asp Asn Val Ser Glu Asn Val Gly Ser 340 345 350 Val Cys Gly Thr Asp Leu Ser Arg Gln Glu Gly His Ala Ser Pro Cys 355 360 365 Pro Pro Leu Gln Pro Val Ser Val Met 370 } 375 <210> 2625 <211> 575 <212> PRT <213> Homo sapiens <400> 2625 Met Leu Gly Val Leu Val Leu Gly Ala Leu Ala Leu Ala Gly Leu Gly 1 5 10 15 Phe Pro Ala Pro Ala Glu Pro Gln Pro Gly Gly Ser Gln Cys Val Glu

His Asp Cys Phe Ala Leu Tyr Pro Gly Pro Ala Thr Phe Leu Asn Ala 40 45 Ser Gln Ile Cys Asp Gly Leu Arg Gly His Leu Met Thr val Arg Ser 50 58 60 Ser Val Ala Ala Asp Val Ile Ser Leu Leu Leu Asn Gly Asp Gly Gly 65 70 75 80 Val Gly Arg Arg Arg Leu Trp Ile Gly Leu Gln Leu Pro Pro Gly Cys 85 90 95 Gly Asp Pro Lys Arg Leu Gly Pro Leu Arg Gly Phe Gln Trp Val Thr 100 105 110

Gly Asp Asn Asn Thr Ser Tyr Ser Arg Trp Ala Arg Leu Asp Leu Asn 115 120 125 Gly Ala Pro Leu Cys Gly Pro Leu Cys Val Ala Val Ser Ala Ala Glu 130 135 140 Ala Thr Val Pro Ser Glu Pro Ile Trp Glu Glu Gln Gln Cys Glu Val 145 150 155% 160 Lys Ala Asp Gly Phe Leu Cys Glu Phe His Phe Pro Ala Thr Cys Arg 165 170 175 Pro Leu Ala Val Glu Pro Gly Ala Ala Ala Ala Ala Val Ser Ile Thr 180 185 150 Tyr Gly Thr Pro Phe Ala Ala Arg Gly Ala Asp Phe Gln Ala Leu Pro 195 200 205 Val Gly Ser Ser Ala Ala Val Ala Pro Leu Gly Leu Gln Leu Met Cys 210 215 220 Thr Ala Pro Pro Gly Ala Val Gln Gly His Trp Ala Arg Glu Ala Pro 225 230 238 240 Gly Ala Trp Asp Cys Ser Val Glu Asn Gly Gly Cys Glu His Ala Cys 245 250 255 Asn Ala Ile Pro Gly Ala Pro Arg Cys Gln Cys Pro Ala Gly Ala Ala 260 265 270 Leu Gln Ala Asp Gly Arg Ser Cys Thr Ala Ser Ala Thr Gln Ser Cys 275 280 285 Asn Asp Leu Cys Glu His Phe Cys Val Pro Asn Pro Asp Gln Pro Gly 290 295 300 Ser Tyr Ser Cys Met Cys Glu Thr Gly Tyr Arg Leu Ala Ala Asp Gln 305 310 315 320 His Arg Cys Glu Asp Val Asp Asp Cys Ile Leu Glu Pro Ser Pro Cys 325 330 335 Pro Gln Arg Cys Val Asn Thr Gln Gly Gly Phe Glu Cys His Cys Tyr 340 345 350

Pro Asn Tyr Asp Leu Val Asp Gly Glu Cys Val Glu Pro Val Asp Pro 355 360 365 Cys Phe Arg Ala Asn Cys Glu Tyr Gln Cys Gln Pro Leu Asn Gln Thr 370 375 380 Ser Tyr Leu Cys Val Cys Ala Glu Gly Phe Ala Pro Ile Pro His Glu 385 390 385 400 Pro His Arg Cys Gln Met Phe Cys Asn Gln Thr Ala Cys Pro Ala Asp 405 410 415 Cys Asp Pro Asn Thr Gln Ala Ser Cys Glu Cys Pro Glu Gly Tyr Ile 420 425 430 Leu Asp Asp Gly Phe Ile Cys Thr Asp Ile Asp Glu Cys Glu Asn Gly 435 440 445 Gly Phe Cys Ser Gly Val Cys His Asn Leu Pro Gly Thr Phe Glu Cys 450 455 ’ 460 Ile Cys Gly Pro Asp Ser Ala Leu Ala Arg His Ile Gly Thr Asp Cys 465 470 475 480 Asp Ser Gly Lys Val Asp Gly Gly Asp Ser Gly Ser Gly Glu Pro Pro 485 490 495 Pro Ser Pro Thr Pro Gly Ser Thr Leu Thr Pro Pro Ala Val Gly Leu 500 505 510 Val His Ser Gly Leu Leu Ile Gly Ile Ser Ile Ala Ser Leu Cys Leu 515 520 525 val val Ala Leu Leu Ala Leu Leu Cys His Leu Arg Lys Lys Gln Gly 530 535 540 Ala Ala Arg Ala Lys Met Glu Tyr Lys Cys Ala Ala Pro Ser Lys Glu 545 550 555 560 val val Leu Gln His Val Arg Thr Glu Arg Thr Pro Gln Arg Leu 565 570 575 <210> 2626 <211> 332 <212> PRT <213> Homo sapiens

<400> 2626 Met Ala Ala Val Phe Leu Val Thr Leu Tyr Glu Tyr Ser Pro Leu Phe 1 5 10 15 Tyr Ile Ala Val Val Phe Thr Cys Phe Ile val Thr Thr Gly Leu Val ) 20 25 30 Leu Gly Trp Phe Gly Trp Asp Val Pro Val Ile Leu Arg Asn Ser Glu 40 45 Glu Thr Gln Phe Ser Thr Arg Val Phe Lys Lys Gln Met Arg Gln Val 50 S5 60 Lys Asn Pro Phe Gly Leu Glu Ile Thr Asn Pro Ser Ser Ala Ser Ile 65 70 75 80 Thr Thr Gly Ile Thr Leu Thr Thr Asp Cys Leu Glu Asp Ser Leu Leu . 85 S0 95 Thr Cys Tyr Trp Gly Cys Ser Val Gln Lys Leu Tyr Glu Ala Leu Gln 100 105 110 Lys His val Tyr Cys Phe Arg Ile Ser Thr Pro Gln Ala Leu Glu Asp 115 120 125 Ala Leu Tyr Ser Glu Tyr Leu Tyr Gln Glu Gln Tyr Phe Ile Lys Lys 130 135 140 Asp Ser Lys Glu Glu Ile Tyr Cys Gln Leu Pro Arg Asp Thr Lys Ile 145 150 155 160 Glu Asp Phe Gly Thr Val Pro Arg Ser Arg Tyr Pro Leu val Ala Leu 165 170 175 Leu Thr Leu Ala Asp Glu Asp Asp Arg Glu Ile Tyr Asp Ile Ile Ser 180 185 150 Met Val Ser Val Ile His Ile Pro Asp Arg Thr Tyr Lys Leu Ser Cys 195 200 205 Arg Ile Leu Tyr Gln Tyr Leu Leu Leu Ala Gln Gly Gln Phe His Asp 210 2158 220 Leu Lys Gln Leu Phe Met Ser Ala Asn Asn Asn Phe Thr Pro Ser Asn 225 230 235 240

Asn Ser Ser Ser Glu Glu Lys Asn Thr Asp Arg Ser Leu Leu Glu Lys 245 250 255 Val Gly Leu Ser Glu Ser Glu Val Glu Pro Ser Glu Glu Asn Ser Lys 260 265 270 Asp Cys Val val Cys Gln Asn Gly Thr val Asn Trp Val Leu Leu Pro 275 280 285

Cys Arg His Thr Cys Leu Cys Asp Gly Cys Val Lys Tyr Phe Gln Gln

290 295 300 Cys Pro Met Cys Arg Gln Phe Val Gln Glu Ser Phe Ala Leu Cys Ser 305 310 315 320 Gln Lys Glu Gln Asp Lys Asp Lys Pro Lys Thr Leu

325 330 <210> 2627 <211> SO <212> DNA <213> Homo sapiens <400> 2627 agagcacttg cagagcctgg gacaacctcc ttattgaagg gaagagggac 50 <210> 2628 <211> SO <212> DNA <213> Homo sapiens <400> 2628 taaggagtgt tggagatatg tgatttggct agtgctattt aaagacaccc 50 <210> 2629 <211> SO <212> DNA <213> Homo sapiens <400> 2629 gccaagacaa taagctaggc tactgggtcc agctactact ttggtgggat 50 <210> 2630 <21l1> 50 <212> DNA <213> Homo sapiens <400> 2630 gtaaaggcta tacttgtctt gttcaccttyg ggatgacgcec gcatgatatg SO

<210> 2631 <211> 50 <212> DNA <213> Homo sapiens <400> 2631 tgtcagagat tgcctgtggc tctaatatge acctcaagat tttaaggaga 50 <210> 2632 <211> 50 <212> DNA <213> Homo sapiens <400> 2632 ctttgcctaa accctatgge ctcctgtgca tctgtactca ccctgtacca 50 <210> 2633 <211> 50 <212> DNA <213> Homo sapiens <400> 2633 accttgggtt gagtaatgct cgtctgtgtg ttttagtttc atcacctgtt 50 <210> 2634 <211> 70 <212> DNA <213> Homo sapiens <400> 2634 atttatatta gtttagccaa aggataagtg tcctatgggg atggtccact gtcactgttt 60 ctctgetgtt 70 <210> 2635 <211> 50 <212> DNA <213> Homo sapiens<400> 2635 cccatgtaag cacccctteca tttggcattc cccacttgag aattaccctt 50 <210> 2636 <211l> 50 <212> DNA <213> Homo sapiens <400> 2636 tggaccgtaa tgaatgaatg tacacgccat aaacgccctt tgttcaagea se 50 : ’ <210> 2637 <211> 50 <212> DNA <213> Homo sapiens

<400> 2637 tttcaagaca gaaagtgacg cagagaacct ccccggccca gtctcgacgce 50 <210> 2638 <211> 50 <212> DNA <213> Homo sapiens <400> 2638 tgcactaaac agttgcccca aaagacatat cttgttttaa ggcccagacc SO <210> 2639 <211> 50 <212> DNA <213> Homo sapiens <400> 2639 gggtaggcag cttgcaccca gttctccttt atctcaactt attttcctgg 50 <210> 2640 <211> 50 <212> DNA <213> Homo sapiens <400> 2640 ttaatgccag tecctcatgta acctcaggta tcttcagett gtggagaata 50 <210> 2641 <211> 50 <212> DNA <213> Homo sapiens <400> 2641 tgattttgca acttaggatg tttttgagtc ccatggttca ttttgattgt 50 <210> 2642 <211> 50 <212> DNA <213> Homo sapiens <400> 2642 tttgagcgat ctctcacatg atggggttct ttagtacatg gtaacagcca 50 <210> 2643 <211s> 50 <212> DNA <213> Homo sapiens <400> 2643 tgtttcgtaa attaaatagg tctggcccag aagacccact caattgcctt 50 <210> 2644 <211> 50 <212> DNA

<213> Homo sapiens <400> 2644 accttgtaag tgcctaagaa atgagactac aagctccatt tcagcaggac 50 <210> 2645 <211> 50 <212> DNA <213> Homo sapiens <400> 2645 acagggcctc agcaagggag ccatacattt ttgtaacatt ttgatatgtt S0 <210> 2646 <21l1l> 50 <212> DNA <213> Homo sapiens <400> 2646 acaaccaacc agtttcetttt ctagccaatc atctctgaag agttgectgtt 50 <210> 2647 <211> 50 <212> DNA <213> Homo sapiens <400> 2647 cacacctgca cactcacggc tgaaatctcc ctaacccagg gggaccttag 50 <210> 2648 <211> 50 <212> DNA ’ <213> Homo sapiens <400> 2648 catcctcagg tggtcaggcg tagatcacca gaataaaccc agcttccctc 50 <210> 26495 <211> SO <212> DNA <213> Homo sapiens <400> 2649 gggagtgttg tgactgaaat gcttgaaacc aaagcttcag ataaacttgce 50 <210> 2650 <211> 50 <212> DNA <213> Homo sapiens <400> 2650 Ctctcctcag actgctcaag agaagcacat gaaaaccatt acctgacttt 50 <210> 2651

<211> 50 <212> DNA <213> Homo sapiens <400> 2651 atccagccec acccaatgge cttttgtget tgtttcctat aacttcagta 50 <210> 2652 <211l> 50 <212> DNA <213> Homo sapiens <400> 2652 tttacaagaa ttgtccatgt gcttccctag gctgagctgg cattggtctg 50 <210> 2653 <211> 50 <212> DNA <213> Homo sapiens <400> 2653 catggagact tgaggagggc ttgaggttgg tgaggttagg tgcgtgtttc 50 <210> 2654 <211> 50 <212> DNA <213> Homo sapiens <400> 2654 tgtctgtttt aatcatgtat ctggaatagg gtcgggaagg gtttgtgcta 50 <210> 2655 <211> 50 <212> DNA <213> Homo sapiens <400> 2655 acaagtttac atgataaaaa gaaatgtgat ttgtcttccc ttectttgeac 50 <210> 2656 <211> 50 <212> DNA <213> Homo sapiens <400> 2656 aaaaatacac atcacaccca tttaaaagtg atcttgagaa ccttttcaaa S0 <210> 2657 <211> 50 <212> DNA <213> Homo sapiens <400> 2657 tgtgtgttga tcccaagaca atgaaagttt gcactgtatg ctggacggca 50

<210> 2658 <211> 50 <212> DNA <213> Homo sapiens <400> 2658 acctagcgga caatgatgga gagatctatg atgatattgc tgatggctge 50 <210> 2659 <211> 50 <212> DNA <213> Homo sapiens <400> 2659 gcaatccaca atctgacatt ctcaggaagc ccccaagttg atatttctat 50 <210> 2660 <211> 50 <212> DNA <213> Homo sapiens <400> 2660 gcctccaacc atgttcccett cttettagca ccacaaataa tcaaaaccca 50 <210> 2661 <211> 50 <212> DNA <213> Homo sapiens <400> 2661 ‘ ggcagagaag gaggagtatg agcatcagaa gagggagctg gagcaaatct 50 <210> 2662 <211> 50 ) <212> DNA <213> Homo sapiens <400> 2662 tggaaatgtc atctaaccat taagtcatgt gtgaacacat aaggacgtgt 50 <210> 2663 <211> 50 <212> DNA <213> Homo sapiens <400> 2663 tgccattaag caggaatgtc atgttccagt tcattacaaa agaaaacaat : 50 <210> 2664 <211> 50 . <212> DNA <213> Homo sapiens <400> 2664 :

cctctcagga cgtgccgggt ttatcattge tttgttattt gtaaggactg 50 <210> 2665 <211l> 50 <212> DNA <213> Homo sapiens <400> 2665 cgaagaagag ccacagtgag ggagatccca tccecttgtc tgaactggag 50 <210> 2666 <211l> 50 <212> DNA <213> Homo sapiens <400> 2666 ttgatgatgt aacttgacct tccagagtta tggaaatttt gtccccatgt 50 <210> 2667 <211> 50 <212> DNA <213> Homo sapiens <400> 2667 ctggacaact ttgagtactg acatcattga taaataaact ggcttgtggt 50 <210> 2668 <211l> 50 <212> DNA <213> Homo sapiens <400> 2668 aggtttcatc aggtggttaa agtcgtcaaa gttgtaagtg actaaccaag 50 <210> 2669 <211> 50 <212> DNA <213> Homo sapiens <400> 2669 acctgttatc ctttgtagag cacacagagt taaaagttga atatagcaat S50 <210> 2670 <211> 50 <212> DNA <213> Homo sapiens

’ <400> 2670 gggcggcccg gagccagcca ggcagtttta ttgaaatctt tttaaataat 50 <210> 2671 <211> 50 <212> DNA <213> Homo sapiens

<400> 2671 tccctaatag aaagccacct attctttgtt ggatttctte aagtttttet 50 <210> 2672

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2672 tgccttttga gcaaataggg aatctaaggg aggaaattat caactgtgca 50 <210> 2673

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2673 .gagcacccag agggattttt cagtgggaag cattacactt tgctaaatca 50 <210> 2674

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2674 acagctcaag taccctaatt tagttctttt ggactaatac aattcaggaa 50 <210> 2675

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2675 ttecctgectg gattatttaa aaagccatgt gtggaaaccc actatttaat S50 <210> 2676

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2676 gcagaaaagg ggaactcatt tagctcacga gtggtcgagt gaagattgaa 50 <210> 2677

<211> 50

<212> DNA . .

<213> Homo sapiens :

<400> 2677 acagcaaagc cccaactaat ctttagaagc atattggaac tgataactec 50 <210> 2678

<211> 50 . .

<212> DNA <213> Homo sapiens <400> 2678 atcctgagct gcacttacct gtgagagtct tcaaactttt aaaccttgcec 50 <210> 2679 <211> 50 <212> DNA <213> Homo sapiens <400> 2679 acagggcctc agcaagggag ccatacattt ttgtaacatt ttgatatgtt 50 <210> 2680 <211> 50 <212> DNA <213> Homo sapiens <400> 2680 acgacccatt ttgcaagact taaagccgga agaacacatt ttcagattgt 50 <210> 2681 <211> 50 <212> DNA <213> Homo sapiens <400> 2681 aactgaacac aattttggga caacgtttaa acattacttt tcatacttga 50 <210> 2682 <211> 50 <212> DNA <213> Homo sapiens <400> 2682 cacgcttagg gcagggatct gggaaattec agtgatctce tttagcagag 50 <210> 2683 <211> 50 . <212> DNA <213> Homo sapiens <400> 2683 agcatgtgtc tgccatttca tttgtacgct tgttcaaaac caagtttgtt 50 / <210> 2684 <211> 50 <212> DNA <213> Homo sapiens <400> 2684 cttgtatctc taaatatggt gtgatatgaa ccagtccatt cacattggaa 50

CT

<210> 2685 <211> 50 <212> DNA <213> Homo sapiens <400> 2685 cagaggtggg agtaactgct ggtagtgcct tctttggttg tgttgctcag 50 <210> 2686 <211> 50 <212> DNA <213> Homo sapiens <400> 2686 tccagggacc aacattaaca caaccaatca acacatcatg ttacagaact 50 <210> 2687 <211> 50 <212> DNA <213> Homo sapiens <400> 2687 tgtgggttga gaccagcact ctgtgaaacc ttgaaatgag aagtaaaggc 50 1 <210> 2688 <211> 50 <212> DNA <213> Homo sapiens <400> 2688 ctttgecctaa accctatggc ctectgtgca tctgtactca ccctgtacca 50 <210> 2689 <211> 50 <212> DNA <213> Homo sapiens <400> 2689 aaatacaaac attctaatta aaggctttgc aacacatgcc ttgtetgttt 50 <210> 2690 <21ll> 50 <212> DNA <213> Homo sapiens <400> 2690 tgggcatggt tgaatctgaa accctccttc tgtggcaact tgtactgaaa 50 <210> 2691 <21ll1l> 50 <212> DNA <213> Homo sapiens <400> 26891 ctcatctaaa gacaccttcc tttccactgg ctgtcaagcce acagggcacc 50

<210> 2692 <211> 50 <212> DNA <213> Homo sapiens <400> 2692 gagttaccac accccatgag ggaagctcta aatagccaac acccatctgt 50 <210> 2693 <211> 50 <212> DNA <213> Homo sapiens <400> 2693 cccacactgc tttgctgtgt atacgcttgt tgccctgaaa taaatatgca 50 <210> 2694 <211> 50 <212> DNA } <213> Homo sapiens <400> 2694 cctgaaacag ctgccaccat cactcgcaag agaatcccct ccatctttgg 50 <210> 2695 <211> 50 <212> DNA <213> Homo sapiens <400> 2695 ggaagaaccg tccagagctg agtgacgctg ggatccggga tcaaagttgg 50 <210> 2696 <211l> 50 <212> DNA <213> Homo sapiens <400> 2696 atttccagtg agcttatcat gctgtcttta catggggttt tcaattttge So <210> 2697 <211l> 50 <212> DNA <213> Homo sapiens <400> 2697 oo tgcaagacat agaatagtgt tggaaaatgt gcaatatgtg atgtggcaaa 50° <210> 2698 <211> 50 <212> DNA <213> Homo sapiens

<400> 2698 agtactcatg acttgagaga cgtggacgga gccagcttct accttgcttg 50 <210> 2699 <211> 50 <212> DNA

<213> Homo sapiens

<400> 2699 ccttccaaag cggtcacctg atagggaagt cttacggcta ggaagttaca 50 <210> 2700

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2700 tgttataaaa gaggattttc ccaccttgac accaggcaat gtagttagca 50 <210> 2701

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2701 aataagggtg ttgccctttg ttcecctcaca taatcgtgaa aggctgcttt 50 <210> 2702

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2702 cggattccaa attacttaaa gcctttatgg gaacacggta gattgtaggt 50 <210> 2703

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2703 acacttgatc tcttccttat ttctctcaga aaacctgtag gattgtgect 50 <210> 2704

<211> 50

<212> DNA

<213> Homo sapiens .

<400> 2704 , cccgaggagg aagacgaatc gttaaacatc tgaaagggtc aggtgagtat 50 <210> 2705

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2705 gctagcacga ctctgecttg ttoctttgga gacaattgtt atcatcaata 50 <210> 2706

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2706 ccctcaaatc tcccaatcta ctccagggaa aagacacttc aagtgagaga S0 <210> 2707

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2707 ggaccaaagg ctgattcttg gagatttaac tccccacagg caatgggttt SO <210> 2708 © <211> 50

<212> DNA

<213> Homo sapiens

<400> 2708 gcctecececgtg catctgtact caccctgtac gacaaacaca ttacattatt 50 <210> 2709

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2709 cagactattc cccacctgct tcccagecttc acaataaacg gctgcegtcte 50 <210> 2710

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2710 aactcttggc ctcagaggaa ggaaaagcaa ctcaacactc atggtcaagt 50

<210> 2711

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2711 tgggaaagtg tgagttaata ttggacacat tttatcctga tccacagtgg 50

<210> 2712

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2712 ttaaaaggag cacattaaaa ttctcagagg acttggcaag ggccgcacag 50

<210> 2713

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2713 gcacacgcca tctgtgtaac ttcaggatct gttctgttte accatgtaac 50

<210> 2714

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2714 ttggagcgtt tttgtgtttg agatattagc tcaggtcaat tccaaagagt 50 <210> 2715 <211> 50

<212> DNA

<213> Homo sapiens

<400> 2715 aggaaaccaa gccctcacag gaaagaaagc ctgattcaag aaaacaaagt 50

<210> 2716

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2716 accttgtaag tgcctaagaa atgagactac aagctccatt tcagcaggac 50 <210> 2717 <211> 50

<212> DNA

<213> Homo sapiens

<400> 2717 gcctcagtac agagggggct ctggaagtgt ttgttgactg aataaacgga 50

<210> 2718

<211l> 50

<212> DNA

<213> Homo sapiens

<400> 2718 ggttaacgcet tctgtgagga ccttetgget cttgagatac cctaaatatt 50

<210> 2719 <211> 50 <212> DNA <213> Homo sapiens <400> 2719 aggcaaaagt catttcttcc ctatattttg tcatgcttat ctcecectgtcte 50 <210> 2720 . <211l> 50 <212> DNA <213> Homo sapiens <400> 2720 gagaaagctc ccagtctgtc tttcccaaca tcccttcagt ttcaataagce S50 <210> 2721 <211> 50 <212> DNA <213> Homo sapiens <400> 2721 ggaggttagg aagccctttt aaagtacaaa ccccocggcat ggggaatttt 50 ’ <210> 2722 <211> 50 <212> DNA <213> Homo sapiens <400> 2722 gaaaggataa tttcgaaccc ttgcatagtt tcggtatggg ccgtgccaac 50 <210> 2723 <211> 50 <212> DNA <213> Homo sapiens <400> 2723 cagacctgtg ggctgattcc agactgagag ttgaagtttt gtgtgcatca 50 <210> 2724 <211> 50 <212> DNA <213> Homo sapiens <400> 2724 aaatctcatt tgcaagttct cccattaagc aagggagtag tttactagga 50 <210> 2725 <211> 50 <212> DNA <213> Homo sapiens <400> 2725 caaacaccgg cagttgaaag gaaaaggacg gggaatgtga tggaaaagag 50 <210> 2726 <211l> 50 <212> DNA <213> Homo sapiens <400> 2726 tggataaatc tgagcaactt tcttctttgt gctccaggaa cctacgcact 50 <210> 2727 h <211> 50 <212> DNA <213> Homo sapiens <400> 2727 gacattcatc tgtttccact gagtctgagt cttcaagttt tcactccagc 50 <210> 2728 <211> 50 <212> DNA <213> Homo sapiens <400> 2728 cagtggttcc tgagagaatc ttagttcaaa ggactgcccc cgcecaaccec 50

<210> 2728 <211> 51 <212> DNA <213> Homo sapiens <400> 2729 taggctatag agatgtgagg gattattatt agtcacacct ctagtcatgc c 51 <210> 2730 <211> 50 <212> DNA <213> Homo sapiens . <400> 2730 actctttgtc tttttaagac ccctaatagce cctttgtaac ttgatggectt 50 <210> 2731 <211> 50 <212> DNA <213> Homo sapiens <400> 2731 acctccaaga acatctgcet ttgttgaacg tgtttattac ctgtccactc 50 <210> 2732 <211> 50 <212> DNA <213> Homo sapiens -

<400> 2732 ttgtgctcect gatacgacgt tgccacagtt aatccgttct gatctctgct 50 <210> 2733 <211> 50 <212> DNA <213> Homo sapiens <400> 2733 acccttggtc actggtgttt caaacattct ggcaagtcac atcaatcaag 50 <210> 2734 <211l> 50 <212> DNA <213> Homo sapiens <400> 2734 tgtttcgtaa attaaatagg tctggcccag aagacccact caattgectt 50 <210> 2735 <211l> 50 <212> DNA <213> Homo sapiens <400> 2735 ttgtaaggtt ccggggaact gactcaacat ggttctccaa ctcgaggttg 50 <210> 2736 <211> 50 <212> DNA <213> Homo sapiens <400> 2736 tggtccactg tcactgtttc tctgctgttg caaatacatg gataacacat 50 <210> 2737 <211> 50 <212> DNA <213> Homo sapiens <400> 2737 ggaacttctg cttccactta cgatgaagga acttgtactc aatccatcca 50 <210> 2738 <211> 50 <212> DNA <213> Homo sapiens <400> 2738 tgctcaggge acatgcacac agacatttat ctctgcactc acattttgtg 50 <210> 2739 <211> 50

<212> DNA <213> Homo sapiens <400> 2739 tgtcctctga acctgagtga agaaatatac tctgtccttt gtacctgcgt 50 <210> 2740 <211> 50 <212> DNA <213> Homo sapiens . <400> 2740 tgcactctac cagatttgaa catctagtga ggttcacatt catactaagt 50 <210> 2741 <211l> 50 <212> DNA <213> Homo sapiens <400> 2741 gggtgtgatg aatagcgaat catctcaaat ccttgagcac tcagtctagt 50 <210> 2742 <211> 50 <212> DNA <213> Homo sapiens <400> 2742 tgctgaaagt ggtcccaaag gggtactagt ttttaagcectc ccaactccecce 50 <210> 2743 <211> 50 <212> DNA <213> Homo sapiens <400> 2743 tgtttcgtaa attaaatagg tctggcccag aagacccact caattgectt 50 <210> 2744 <211> 50 <212> DNA <213> Homo sapiens <400> 2744 agaatggcag acctgtttge tgaagtgttc ataagataac aataggcttg 50 <210> 2745 <211> 50 <212> DNA <213> Homo sapiens <400> 2745 ggcccagtgc taatgtaacc aatgatgcca tgtcgatatt ggaaaccata 50

<210> 2746 <211> 50 <212> DNA <213> Homo sapiens <400> 2746 tcttgtccta gtcattgtgg caaccccatc tgacaccttg tgtagtacct 50 <210> 2747 <211> 50 <212> DNA <213> Homo sapiens <400> 2747 aagagtaaga ggcaacagat agagtgtcct tggtaataag aagtcagaga 50 <210> 2748 <211> SO <212> DNA <213> Homo sapiens <400> 2748 tttccaatge tccttgctcc attttaaact tgctgtcctt tataagagaa 50 <210> 2748S <211> 50 <212> DNA <213> Homo sapiens <400> 2749 acattcatct gtttccactg aggtctgagt cttcaagttt tcaccccagce 50 <210> 2750 <211l> 50 <212> DNA } <213> Homo sapiens <400> 2750 tgtgtgcgac agggaggaag tttcaataaa gcaacaacaa gcttcaagga 50 <210> 2751 <211> 50 <212> DNA <213> Homo sapiens <400> 2751 ctccaccacc tgaccagagt gttctcttca gaggactggce tcctttccca 50 <210> 2752 <211> 50 <212> DNA <213> Homo sapiens <400> 2752 cceccaaccac aggcatcagg caaccatttg aaataaaact ccttcagect 50

<210> 2753 <211> 50 <212> DNA <213> Homo sapiens <400> 2753 cgctcaaagg tcactgagac ttttgcctca cctaaagaga ccaaggctca 10) <210> 2754 <21l1> 50 <212> DNA <213> Homo sapiens <400> 2754 ccctttgtga gaagaagcag gtttcctttc ctatggattg atgtgaccct SO <«210> 2755 <211> 50 <212> DNA <213> Homo sapiens <400> 2755 agaaggaccc ctggttgaga accacggttg tatagaaagg aattgaagca 50 <210> 2756 <211l> 50 <212> DNA <213> Homo sapiens <400> 2756 aggtgccagc aactgaataa atacctctcc cagtgtaaat ctggagccaa 50 <210> 2757 <21l1> 50 <212> DNA <213> Homo sapiens <400> 2757 gaaggaagaa gtggggtgga agaagtgggg tgggacgaca gtgaaatcta 50 <210> 2758 <211l> 50 <212> DNA <213> Homo sapiens <400> 2758 tgaaatatgg gaaagttgct gctattgatt cagggtctgt cttggaggca 50 <210> 2759 <211> 50 <212> DNA <213> Homo sapiens

<400> 2759 tgattacaaa aggcgtattc tttcatggtt tctgcaatga gaggaagtgt 50 <210> 2760 <211> 50 <212> DNA <213> Homo sapiens <400> 2760 aggagctatg attagacttc tgttagactt cctcactcta tcacccacat 50 <210> 2761 <211> 50 ‘ <212> DNA <213> Homo sapiens <400> 2761 agttgttagt tgccctgcta cctagtttgt tagtgcattt gagcacacat 50 <210> 2762 <211l> 50 <212> DNA <213> Homo sapiens <400> 2762 aagtggaagt gggtgaattc tactttttat gttggagtgg accaatgtct 50 <210> 2763 <211> 50 <212> DNA <213> Homo sapiens

<400> 2763 catttgtacc ctaggcccac gaacccacga gaatgtcctc tgacttccag S50

<210> 2764

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2764 gcactgaata tcgaacaagc actcaaattg aagtatcagt catgttttgt 50 <210> 2765

<211> 50 <212> DNA

<213> Homo sapiens }

<400> 2765S tctacctgca gtctccattg tttccagagt gaacttgtaa ttatcttgtt 50

<210> 2766

<211> 50

<212> DNA

<213> Homo sapiens <400> 2766 ggccagectg gacccaatca tgaggaagat gcagactctt atgagaacat 50 <210> 2767 <211l> 50 <212> DNA <213> Homo sapiens <400> 2767 tgggattcat tggcccatag gtacattgga aaatgtatat ctctccagct 50 <210> 2768 <211> 50 <212> DNA <213> Homo sapiens <400> 2768 accgtgtaaa gtggggatgg ggtaaaagtg gttaacgtac tgttggatca 50 <210> 2769 <211l> 50 <212> DNA <213> Homo sapiens <400> 2769 tggcaaattc tgcgagtgtg ataatttcaa ctgtgataga tccaatggct 50 <210> 2770 <211> 50 <212> DNA <213> Homo sapiens <400> 2770 cctagggtga aacacgtgac agaagaataa agactattga atagtcctct 50 <210> 2771 <211> 50 <212> DNA <213> Homo sapiens <400> 2771 tgagcetttc acacctgtge tggcgetgga aaattatttg tgctcagctg SO <210> 2772 <211> 50 <212> DNA <213> Homo sapiens <400> 2772 tgctattgce ttcctatttt gcataataaa tgcttcagtg aaaatgcagce 50 «210> 2773

<211> 50 <212> DNA

<213> Homo sapiens

<400> 2773 gtgtaacaca gtgccttcaa taaatggtat agcaaatgtt ttgacatgaa 50 <210> 2774

<211> 50

<212> DNA

<213> Homo sapiens <400> 2774 tgccaagcac agtgcctgca tgtatttatc caataaatgt gaaattctgt 50 <210> 2775 }

<211l> 50

<212> DNA

<213> Homo sapiens

<400> 2775 acattgtaat agaaacagat ttcccaaatt ccagecctggc atgaggtaat 50 <210> 2776

<211> 50

<212> DNA .

<213> Homo sapiens

<400> 2776 tcactatctt tctgataaca gaattgccaa ggcagcggga tctcgtatct 50 <210> 2777

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2777 tctcaaagga gtaactgcag cttggtttga aatttgtact gtttctatca 50 <210> 2778

<211s> 50

<212> DNA

<213> Homo sapiens

<400> 2778 gacaggatcc cccagagacc ccatttgect ctcaacactce agaccttcaa 50 <210> 2779

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2779 agtgccttcc ctgectgtgg gggtcatgct geccactttta atgggtcctc 50

1117 . _ I _ _

oo Co

<210> 2780

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2780 attccattct attgtttaca caacgattac tcgaagatga ctgcaaaggt 50 <210> 2781

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2781 actgagagtg gtgtctggat atattccttt tgtcttcatc actttctgaa 50 <210> 2782

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2782 gaagctgcta ggggaaggac tggcctggct ccagaatgtt gttgectttt 50 <210> 2783

<211> 50

<212> DNA

'<213> Homo sapiens

<400> 2783 agccctgcaa aaattcagag tccttgcaaa attgtctaaa atgtcagtgt 50 <210> 2784

<211l> 50

<212> DNA

<213> Homo sapiens

<400> 2784 gggcagagaa ggtggagagt aaagacccaa cattactaac aatgatacag S50 <210> 2785

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2785 aatatatgca attctccectec ccccagcect tccctgaccce ctaagttatt 50 . <210> 2786 . <211> 50

<212> DNA

<213> Homo sapiens

<400> 2786 agggagactc tcagccttca gcttcctaaa ttetgtgtct gtgactttcg 50 <210> 2787 <211l> 50 <212> DNA <213> Homo sapiens <400> 2787 atgctggtgt catgtgacat ttgttgagtc tcgggcatgt tcacggtggg 50 <210> 2788 <211> 51 <212> DNA <213> Homo sapiens <400> 2788 caccgcctcect gectccgect cttceccactgg agagcccgag gtcaaaaggt c 51 <210> 2788 <211> 50 <212> DNA <213> Homo sapiens <400> 2789 atttggacag atgcagaagg aactgttagt gagtcaagac aaacacatct 50 <210> 2790 <211> 50 <212> DNA <213> Homo sapiens <400> 2780 acattttcct ccgcataagc ctgcgtcaga ttaaaacact gaactgacaa So <210> 2791 <211> 50 <212> DNA

<213> Homo sapiens <400> 2791 tccagccage cagctcattt cactttacac cctcatggac tgggattata ’ 50 <210> 2792 <211> 50 <212> DNA <213> Homo sapiens <400> 2792 ctggtetgtg tcgttggett tatgacagga agtgcctgtg ggttatctta 50 <210> 27893 <211> 50 <212> DNA <213> Homo sapiens

<400> 2783 accaaaaagg gctacattac caccactgta tcataaaagc cagccacctt 50

<210> 2794

<211> 50

<212> DNA

<213> Homo sapiens

<400> 2794 gattcttgtc tggctaataa atcatcacca actgecttct cctacaggga 50 <210> 27895

<211l> SO

<212> DNA

<213> Homo sapiens

<400> 2795 ccccagacga aaataccaaa tgcatggaga gctcccgtga gtggttaata 50 <210> 2796

<211> 1549

<212> DNA

<213> Homo sapiens

<400> 2796 cttcagccgt gtatgcaaat ggataaccgg ttgcctccca aaaaagttcce aggtttcotgt 60 tcctttcget atggattgtc tttccttgtg cactgttgta atgttataat aacagcacag 120 cgtgcgtgec tgaacctcac aatggtagtc atggtgaata gcacagatcc acatggtttg 180 cccaacacct ccacaaagaa gctcctggat aatataaaga accctatgta taattggagce 240 ccagatatcc agggaatcat cttgagttcc acctcctatg gtgtcatcat catccaagtt 300 cctgttggat acttctctgg aatatattct acaaagaaaa tgattggcett tgcattatge 360 ctcagctctg tgttaagcct gctcatccca ccagcagctg gaattggagt agcttgggte 420 gttgtatgtc gagcagttca gggagcagcc caggggatag ttgcaacagc ccagtttgaa 480 atatatgtca aatgggctcc tcccctggaa cgaggccgac ttacttctat gagtacatca 540 gggtttttge tgggaccctt tattgtccta cttgtgactg gagttatctg tgaatctctg 600 ggctggecca tggtcttcta tatttttggt gettgtggct gtgeccgtatg tcttctectgg 660 ttecgttctgt tttatgatga ccccaaagac cacccatgta taagcatcag tgaaaaggaa 720 tacatcacat cctcecctggt ccagcaggtc agttcaagta gacaatctct gectatcaag 780 gctatactta agtcgcttce agtctggget atttccattg gtagttttac gtttttctgg 840 tcacataaca tcatgacact atacactcca atgtttatca actecatget tcatgttaat 900 ataaaagaga atgggttctt gtecttcecctt ccctatttgt ttgecctggat ctgtggtaac 960

1120 a ctagcaggtc agttatcaga cttcttectg accaggaata ttctcagegt aattgctgte 1020 cggaaactct tcacagcagc aggatttctc cttcctgcaa tctttggtgt ctgectgect 1080 tacctgagtt ccaccttcta cagcattgtc attttcctaa tacttgetgg tgcaacaggce 1140 agcttttget tgggtggagt gtttataaat ggcttggata ttgctcccag atattttgga 1200 tttattaaag catgttcaac tttaactgga atgataggag gactaattgc ttccactttg 1260 actggattga tccttaagca ggatccggaa .tccgeoctggt ttaaaacctt catcctgatg 1320 gcagccatta atgtgactgg cctaattttc taccttatag ttgctacagc agaaattcag 1380 gactgggcta aagaaaaaca acacacacgt ctctgaagtg tgaaacagag cacttgcaga 1440 gcctgggaca acctccttat tgaagggaag agggaccagc acatgaggct gaggctgagg 1500 ggcagtcacc agcaccagga agaaggtggt aggaggagtc ctaggggct 1549 <210> 2797 <21l> 626 <212> DNA

~ <213> Homo sapiens <400> 2797 tttttttttc catttctatg agtttaatac agtaccaggg ttcagacatt tccatgaaat 60 attaactcta aacaaacata acagcattct agcagtagtc ttcagctaac atgctaatgg 120 gattaagttg ctagaaccct ctgttagtat gtggacacaa gacagattgg catacctggt 180 ttaggcatca ctccaaacaa agtttgtaat ccaggattac tagattccta aaccctattt 240 atgcaaggac aggggtgtct ttaaatagca ctagccaaat cacatatcte caacactcct 300 taattttcca gtgcaaaata acttctttta tttattaggc taattaggga accttctaga 360 actctctaga gataaagatc attaaggcct tatagtagtc cttcaaacac taccaaccac 420 ttcctaaaag atgtgtgtec agttaaagta ttttaaattt tagctacaac cttatagagg 480 attaagaata cacacacacg cacacacaca cacacctgtc tatactagaa tatttaaaag 540 taagttatag acaatataat agctagataa aacaaaagaa taaggtatat gggttttata 600 aagacacaca gtataatgat ggtgtc 626 <210> 27958 <211> 5601 <212> DNA <213> Homo sapiens <400> 2798 atggaccccg ttggcctcca getcggcaac aagaacctgt ggagctgtct tgtgaggctg 60 ctcaccaaag acccagaatg gctgaacgcc aagatgaagt tcttcctcec caacacggac 120 ctggattcca ggaacgagac cttggaccct gaacagagag tcatcctgca actcaacaag 180 :

ctgcatgtcc agggttcgga cacctggcag tctttcattc attgcgtgtg catgcagetg 240 gaggtgccte tggacctgga ggtgcttctg ctaagtactt ttggctatga tgatgggttce 300 accagccagc tgggagctga ggggaaaagc caacctgaat ctcagctcca ccatggcctg 360 aagcgcccac atcagagctg tgggtcctca ccccgeccgga agcagtgcaa gaagcagcag 420 ctagagttgg ccaagaagta cctgcagctc ctgcggacct ctgcccagca gcgctacagg 480 agccaaatcc ctgggtcagg gcagccccac gcctteccacc aggtctatgt ccctccaatce 540 ctgcgeecggg ccacagcatce cttagacact ccggaggggg ccattatggg ggacgtcaag 600 gtggaagatg gtgctgacgt gagcatctcg gacctcttca acaccagggt taacaagggce 660 ccgagggtga ccgtgctttt ggggaaggct ggcatgggca agaccacgct ggcccacegg 720 ctctgccaga agtgggcaga gggccatctg aactgtttcce aggccectgtt cctttttgaa 780 ttccgcecage tcaacttgat cacgaggttc ctgacaccgt ccgagctecet ttttgatctg 840 tacctgagcc ctgaatcgga ccacgacact gtcttccagt acctggagaa gaacgctgac 900 caagtcctge tgatctttga tgggctagat gaggccctcc agcctatggg tcctgatggce 960 ccaggcccag tcctcaccct tttctcccat ctctgcaatg ggaccctect gecctggctge 1020 cgggtgatgg ctacctececg tccagggaag ctgectgect gectgcocctge agaggcagcec 1080 atggtccaca tgttgggctt tgatgggcca cgggtggaag aatatgtgaa tcacttcttc 1140 agcgcccagce catcgcggga gggggccectg gtggagttac agacaaatgg acgtctccga 1200 agcctgtgtg cggtgecccge actgtgccaa gtcgeectgte tctgeccteca ccatctgett 1260 cctgaccacg ccccaggceca gtetgtggec ctcectgecca acatgactcea gctctatatg 1320 cagatggtgc tcgccctcag cccccetggg cacttgecca cctegtecct actggacctg 1380 ggggaggtgg ccctgagggg cctggagaca gggaaggtta tcttctatgec aaaagatatt 1440 gctccaccct tgatagecttt tggggecact cacagectgce tgacttcctt ctgegtctgce 1500 acaggccctg ggcaccagca gacaggctat gctttcacce acctcagcct gcaggagttt 1560 cttgetgeec tgcacctgat ggccagccce aaggtgaaca aagacacact tacccagtat 1620 gttaccctec attccegotg ggtacagcgg accaaagceta gactgggect ctcagaccac 1680 ctceccacct tocctggeggg cctggeatce tgcacctgec gecccttect tagccacctg 1740 gcgcagggca atgaggactg tgtgggtgcc aagcaggctg ctgtagtgea ggtgttgaag 1800 aagttggcca cccgcaagcet cacagggceca aaggttgtag agctgtgtcea ctgtgtggat 1860 gagacacagg agcctgagct ggccagtctc accgcacaaa gectccccta tcaactgcecc 1920 ttccacaatt tcccactgac ctgcaccgac ctggccaccce tgaccaacat cctagagcac 1980 agggaggccc ccatccacct ggattttgat ggctgtccce tggagcccca ctgccctgag 2040 gctctggtag gctgtgggca gatagagaat ctcagcttta agagcaggaa gtgtggggat 2100 gcctttgcag aagccctctc caggagcttg ccgacaatgg ggaggctgca gatgcetgggg 2160 ttagcaggaa gtaaaatcac tgcccgaggc atcagccacc tggtgaaagc tttgectcete 2220 tgtccacage tgaaagaagt cagttttcgg gacaaccagc tcagtgacca ggtggtgcetg 2280 aacattgtgg aggrecroes tcacctacca cggctccgga agcttgacct gagcagcaac 2340 agcatctgcg tgtcaaccet actctgcttg gcaagggtgg cagtcacgtg tcctacegte 2400 aggatgcttc aggccaggga gcggaccatc atcttcecttc tttccecgec cacagagaca 2460 actgcagagc tacaaagagc tccagacctg caggaaagtg acggccagag gaaaggggcet 2520 cagagcagaa gcttgacgct caggctgcag aagtgtcagc tccaggtcca cgatgcggag 2580 gccctcatag ccctgctcca ggaaggccct cacctggagg aagtggacct ctcagggaac 2640 cagctggaag atgaaggctg tcggctgatg gcagaggctg catcccaget gcacategcec 2700 aggaagctgg acctcagcga caacgggctt tctgtggeccg gggtgcattg tgtgcectgagg 2760 gcecgtgagtg cgtgctggac cctggcagag ctgcacatca gecctgcagca caaaactgtg 2820 atcttcatgt ttgcccagga gccagaggag cagaaggggc cccaggagag ggctgcattt 2880 cttgacagcc tcatgctcca gatgcecctct gagctgecctc tgagctcccg aaggatgagg 2940 ctgacacatt gtggcctcca agaaaagcac ctagagcagce tctgcaagge tctgggagga 3000 agctgccacc tecggtcacct ccacctcgac ttctcaggca atgetctggg ggatgaaggt 3060 gcagccegge tggctcaget gectcccaggg ctgggagcte tgcagtcecctt gaacctcagt 3120 gagaacggtt tgtccctgga tgcegtgttg ggcttggttc ggtgcttctc cactctgcag 3180 tggctcttcc gcttggacat cagctttgaa agccaacaca tcctcctgag aggggacaag 3240 acaagcaggg atatgtgggce cactggatct ttgccagact tcccagctge agccaagttce 3300 ttagggttcc gtcagcgctg catccccagg agectcectgec tcagtgagtg tectctggag 3360 cccccaagec tcacccgect ctgtgccact ctgaaggact gcocccgggacc cctggaactg 3420

. caattgtcct gtgagttcct gagtgaccag agcctggaga ctctactgga ctgcttacct 3480 caactcecctc agctgagect gctgcagetg agccagacgg gactgtccce gaaaagecce 3540 ttecctgetgg ccaacacctt aagecctgtgt ccacgggtta aaaaggtgga tctcaggtee 3600 3 ctgcaccatg caactttgca cttcagatcc aacgaggagg aggaaggcgt gtgctgtgge 3660 aggttcacag gctgcagcct cagccaggag cacgtagagt cactctgctg gttgctgage 3720 aagtgtaaag acctcagcca ggtggatctc tcagcaaacc tgctgggcga cagcggactc 3780 agatgccttc tggaatgtct gececgecaggtg cccatctccg gtttgcecttga tctgagtcac 3840 aacagcattt ctcaggaaag tgccctgtac ctgctggaga cactgcecetc ctgeccacgt 3900 gtccgggagg cctcagtgaa cctgggetct gagcagagct tccggattca cttcetccaga 3960 gaggaccagg ctgggaagac actcaggcta agtgagtgca gcttccggcc agagcacgtg 4020 tccaggetgg ccaceggcett gagcaagtcc ctgcagctga cggagctcac gctgacccag 4080 tgctgcctgg gocagaagca getggecate ctectgagcet tggtggggeg acccgcaggg 4140 ctgttcagcc tcagggtgca ggagccgtgg gcggacagag ccagggattct ctccctgtta 4200 gaagtctgcg cccaggcctc aggcagtgtc actgaaatca gcatctccga gacccagcag 4260 cagctctgtg tccagctgga atttcctege caggaagaga atccagaagce tgtggcactc 4320 aggttggctc actgtgacct tggagcccac cacagccttc ttgtcgggea gcetgatggag 4380 acatgtgcca ggctgcagca gctcagcttg tctcaggtta acctctgtga ggacgatgat 4440 gccagttccec tgctgctgea gagcctcctg ctgtccctet ctgagctgaa gacatttcgg 4500 ctgacctcca gctgtgtgag caccgagggc ctcgececcacce tggcatetgg tctgggecac 4560 tgccaccact tggaggagcet ggacttgtct aacaatcaat ttgatgagga gggcaccaag 4620 gcgctgatga gggcccttga ggggaaatgg atgctaaaga ggctggacct cagtcacctt 4680 ctgctgaaca gctccacctt ggccttgett actcacagac taagccagat gacctgcctg 4740 cagagcctca gactgaacag gaacagtatc ggtgatgtcg gttgctgeca cctttectgag 4800 gctctcaggg ctgccaccag cctagaggag ctggacttga gccacaacca gattggagac 4860 gctggtgtce agcacttage taccatcctg cctgggctge cagagctcag gaagatagac 4920 ctctcaggga atagcatcag ctcagccggg ggagtgcagt tggcagagtce tctegttett 4980 tgcaggcgcc tggaggagtt gatgcttggce tgcaatgccc tgggggatcc cacagccectg 5040 gggctggctc aggagctgec ccagcacctg agggtcctac acctaccatt cagccatctg 5100 ggcccaggtg gggccctgag cctggeccag gccectggatg gatcccccca tttggaagag 5160 atcagcttgg cggaaaacaa cctggcotgga ggggtcctge gtttcotgtat ggagctcccg 5220 ctgctcagac agatagacct ggtttcctgt aagattgaca accagactgc caagctcctc 5280 acctccagct tcacgagctg ccetgecectg gaagtaatct tgctgtcecctg gaatctcctce 5340 ggggatgagg cagctgccga gctggeccag gtgctgecga agatgggccg gctgaagaga 5400 gtggacctgg agaagaatca gatcacagct ttgggggcct ggctcctggce tgaaggactg 5460 gcccaggggt ctagcatcca agtcatcege ctctggaata accccattce ctgcgacatg 5520 gcccagcace tgaagagcca ggagceccagg ctggactttg ccttetttga caaccagccc 5580 caggcccctt ggggtacttg a 5601

<210> 2799 <211> 5133 <212> DNA <213> Homo sapiens <400> 2799 cctectttcac cctgtctagg ttgccagcaa atcccacggg cctcctgacg ctgecectgg 60 ggccacaggt ccectcgagtg ctggaaggat gaaggattcc tgcatcactg tgatggccat 120 ggcgctgctg tctgggttct ttttcttege gecggectceg agctacaacc tggacgtgeg 180 gggcgecgegg agcttcteec caccgecgogc cgggaggcac tttggatacc gegtcectgcea 240 ggtcggaaac ggggtcatcg tgggagctcc aggggagggg aacagcacag gaagcectcta 300 tcagtgccag tcgggcacag gacactgcct gccagtcacce ctgagaggtt ccaactatac 360 ctccaagtac ttgggaatga ccttggcaac agaccccaca gatggaagca ttttggectg 420 tgaccctggg ctgtctcgaa cgtgtgacca gaacacctat ctgagtggece tgtgttacct 480 cttccgeccag aatctgcagg gtcccatget gcaggggcegce cctggttttce aggaatgtat 540 caagggcaac gtagacctgg tatttctgtt tgatggtteg atgagcttgc agccagatga 600 atttcagaaa attctggact tcatgaagga tgtgatgaag aaactcagca acacttcgta 660 ccagtttgct gctgttcagt tttccacaag ctacaaaaca gaatttgatt tctcagatta 720 tgttaaatgg aaggaccctg atgctctgct gaagcatgta aagcacatgt tgctgttgac 780 caataccttt ggtgccatca attatgtcge gacagaggtg ttccgggagg agctgggggce 840 ccggccagat gccaccaaag tgcttatcat catcacggat ggggaggcca ctgacagtgg 900 caacatcgat gcggeccaaag acatcatccg ctacatcatc gggattggaa agcattttca 960 gaccaaggag agtcaggaga ccctccacaa atttgcatca aaacccgcga gcgagtttgt 1020 gaaaattctg gacacatttg agaagctgaa agatctattc actgagctgc agaagaagat 1080 ctatgtcatt gagggcacaa gcaaacagga cctgacttcc ttcaacatgg agctgtcctce 1140 cagcggcatc agtgctgacc tcagcagggg ccatgcagtc gtgggggcag taggagccaa 1200 ggactgggct gggggcttte ttgacctgaa ggcagacctg caggatgaca catttattgg 1260 gaatgaacca ttgacaccag aagtgagagc aggctatttg ggttacaccg tgacctggct 1320 gcectecegg caaaagactt cgttgctgge ctecgggagec cctcgatacc agcacatggg 1380 ccgagtgetg ctgttccaag agccacaggg cggaggacac tggagccagg tccagacaat 1440 ccatgggacc cagattggct cttatttcgg tggggagctg tgtggegtcg acgtggacca 1500 agatggggag acagagctgc tgctgattgg tgccccactg ttctatgggg agcagagagg 1560 aggccgggtg tttatctacce agagaagaca gttggggttt gaagaagtcet cagagctgca 1620 gggggacccc ggctacccac tcgggceggtt tggagaagcc atcactgctc tgacagacat 1680 caacggcgat gggctggtag acgtggctgt gggggeccct ctggaggage agggggcetgt 1740 gtacatcttc aatgggaggc acggggggct tagtccccag ccaagtcagc ggatagaagg 1800 gacccaagtg ctctcaggaa ttcagtggtt tggacgctcc atccatgggg tgaaggacct 1860 tgaaggggat ggcttggcag atgtggctgt gggggcetgag agccagatga tcgtgctgag 1920 ctcccggeece gtggtggata tggtcaccct gatgtecttce tctccagetg agatcccagt 1980 gcatgaagtg gagtgctcct attcaaccag taacaagatg aaagaaggag ttaatatcac 2040 aatctgtttc cagatcaagt ctctctacce ccagttccaa ggcecgectgg ttgccaatct 2100 cacttacact ctgcagctgg atggccaccg gaccagaaga cgggggttgt tcccaggagg 2160 gagacatgaa ctcagaagga atatagctgt caccaccagc atgtcatgca ctgacttctc 2220 atttcatttc ccggtatgtg ttcaagacct catctccccc atcaatgttt ccctgaattt 2280 ctctctttgg gaggaggaag ggacaccgag ggaccaaagg gcgcagggea aggacatacc 2340 gcccatcctg agaccctcce tgcactcgga aacctgggag atcccttttg agaagaactg 2400 tggggaggac aagaagtgtg aggcaaactt gagagtgtcc ttctetectg caagatccag 2460 agccctgegt ctaactgctt ttgecagecct ctctgtggag ctgagcctga gtaacttgga 2520 agaagatgct tactgggtcc agctggacct gcacttccce ccgggactct ccttccgcaa 2580 ggtggagatg ctgaagcccc atagccagat acctgtgagc tgcgaggagce ttcctgaaga 2640 gtccaggctt ctgtccaggg cattatcettg caatgtgagc tctceccatct tcaaagcagg 2700 ccactcggtt gctctgcaga tgatgtttaa tacactggta aacagctcct ggggggactc 2760 ggttgaattg cacgccaatg tgacctgtaa caatgaggac tcagacctcc tggaggacaa 2820 ctcagccact accatcatcc ccatcctgta ccccatcaac atcctcatcc aggaccaaga 2880 agactccaca ctctatgtca gtttcacccc caaaggcccec aagatccacc aagtcaagcea 2940 catgtaccag gtgaggatcc agccttecat ccacgaccac aacataccca ccctggaggce 3000 tgtggttggg gtgccacagc ctceccagcga ggggcccatce acacaccagt ggagcgtgca 3060 gatggagcct cecegtgcect goccactatga ggatctggag aggctcecgg atgcagctga 3120 gccttgtete cccggagece tgttecgctg cectgttgte ttcaggcagg agatcctegt 3180 ccaagtgatc gggactctgg agctggtggg agagatcgag goctcttcca tgttcagect 3240 ctgcagctcc ctctccatct ccttcaacag cagcaagcat ttccacctct atggcagcaa 3300 cgcctecectg gecccaggttg tcatgaaggt tgacgtggtg tatgagaagce agatgctcta 3360 cctctacgtg ctgagcggeca tcggggggct getgctgetg ctgetcattt tcatagtget 3420 gtacaaggtt ggtttcttca aacggaacct gaaggagaag atggaggctg gcagaggtgt 3480 1126 - oo oo cccgaatgga atccctgcag aagactctga gcagctggca tctgggcaag aggctgggga 3540 tcecggetge ctgaagcccce tccatgagaa ggactctgag agtggtggtg gcaaggactg 3600 agtccaggece tgtgaggtgc agagtgccca gaactggact caggatgccc agggccactce 3660 tgcctetgee tgecattectge cgtgtgecct cgggecgagtc actgectcetc cctggecctce 3720 agtttcccta tctcgaacat ggaactcatt cctgaatgtc tectttgcag gctcataggg 3780 aagacctgct gagggaccag ccaagagggc tgcaaaagtg agggcttgtc attaccagac 3840 ggttcaccag cctctcttgg ttecttcecctt ggaagagaat gtctgatcta aatgtggaga 3500 aactgtagtc tcaggaccta gggatgttct ggccctcacc cctgecctgg gatgtccaca 3960 gatgccteca cecccccagaa cctgtecttg cacactccce tgcactggag tccagtctcet 4020 tctgctggca gaaagcaaat gtgacctgtg tcactacgtg actgtggcac acgccttgtt 4080 cttggccaaa gaccaaattc cttggcatgc cttccagcac cctgcaaaat gagaccctcg 4140 tggccttece cagectcette tagagcecgtg atgecctcect gttgaagcte tggtgacacc 4200 agcctttctc ccaggccagg ctccttcctg tcttecctgca ttcacccaga cagctcecctce 4260 tgcctgaacc ttccatetcg cccaccccte ctteccttgac cagcagatcec cagctcacgt 4320 cacacacttg gttgggtcct cacatctttc acacttccac caccctgcac tactccectca 4380 aagcacacgt catgtttctt catccggcag cctggatgtt ttttcectgt ttaatgattg 4440 acgtacttag cagctatctc tcagtgaact gtgagggtaa aggctatact tgtcttgtte 4500 accttgggat gacgccgcat gatatgtcag ggcgtgggac atctagtagg tgcttgacat 4560 aatttcactg aattaatgac agagccagtg ggaagataca gaaaaagagg gccggggctg 4620 ggcgeggtgg ttcacgectg taatcccage actttgggag gccaaggagg gtggatcacce 4680 tgaggtcagg agttagaggc cagcctggcg aaaccccatc tctactaaaa atacaaaate 4740 caggcgtggt ggcacacacc tgtagtccca gctactcagg aggttgaggt aggagaattg 4800 cttgaacctg ggaggtggag gttgcagtga gccaagattg cgccattgca ctccagectg 4860 ggcaacacag cgagactccg tctcaaggaa aaaataaaaa taaaaagcgg gcacgggccce 4920 ggacatcccc acccttggag gctgtcttet caggctetge cctgccctag ctccacaccc 4980 tctcccagga cccatcacgc ctgtgcagtg gcccccacag aaagactgag ctcaaggtgg 5040 gaaccacgtc tgctaacttg gagccccagt gccaagcaca gtgcctgcat gtatttatcc 5100 aataaatgtg aaattctgtc caaaaaaaaa aaa 5133 <210> 2800 <21l1l> 2376 <212> DNA

<213> Homo sapiens <400> 2800 cgcgecggece ctgtccteccg gecccgagatg aatcctgcegg cagaagccga gttcaacate 60 ctcctggcca ccgactccta caaggttact cactataaac aatatccacc caacacaagc 120 aaagtttatt cctactttga atgccgtgaa aagaagacag aaaactccaa attaaggaag 180 gtgaaatatg aggaaacagt attttatggg ttgcagtaca ttcttaataa gtacttaaaa 240 : ggtaaagtag taaccaaaga gaaaatccag gaagccaaag atgtctacaa agaacatttce 300 caagatgatg tctttaatga aaagggatgg aactacattc ttgagaagta tgatgggcat 360 cttccaatag aaataaaagc tgttcctgag ggctttgtca ttcccagagg aaatgttctc 420 ttcacggtgg aaaacacaga tccagagtgt tactggctta caaattggat tgagactatt 480 cttgttcagt cctggtatcc aatcacagtg gccacaaatt ctagagagca gaagaaaata 540 ttggccaaat atttgttaga aacttctggt aacttagatg gtctggaata caagttacat 600 gattttggct acagaggagt ctcttcccaa gagactgctg gcataggagce atctgctcac 660 ttggttaact tcaaaggaac agatacagta gcaggacttg ctctaattaa aaaatattat 720 ggaacgaaag atcctgttcc aggctattct gttccagcag cagaacacag taccataaca 780 gcttggggga aagaccatga aaaagatgct tttgaacata ttgtaacaca gttttcatca 840 gtgcctgtat ctgtggtcag cgatagctat gacatttata atgegtgtga gaaaatatgg 900 ggtgaagatc taagacattt aatagtatcg agaagtacac aggcaccact aataatcaga 960 cctgattctg gaaaccectct tgacactgtg ttaaaggttt tggagatttt aggtaagaag 1020 tttcctgtta ctgagaactc aaagggttac aagttgctgc caccttatct tagagttatt 1080 caaggggatg gagtagatat taatacctta caagagattg tagaaggcat gaaacaaaaa 1140 atgtggagta ttgaaaatat tgcctteggt tctggtggag gtttgctaca gaagttgaca 1200 agagatctct tgaattgttc cttcaagtgt agctatgttg taactaatgg ccttgggatt 1260 aacgtcttca aggacccagt tgctgatccc aacaaaaggt ccaaaaaggg ccgattatct 1320 ttacatagga cgccagcagg gaattttgtt acactggagg aaggaaaagg agaccttgag 1380 gaatatggtc aggatcttct ccatactgtc ttcaagaatg gcaaggtgac aaaaagctat 1440 tcatttgatg aaataagaaa aaatgcacag ctgaatattg aactggaagc agcacatcat 1500 taggctttat gactgggtgt gtgttgtgtg tatgtaatac ataatgttta ttgtacagat 1560 gtgtggggtt tgtgttttat gatacattac agccaaatta tttgttggtt tatggacata 1620 ctgccetttc attttttttc ttttccagtg tttaggtgat ctcaaattag gaaatgcatt 1680 taaccatgta aaagatgagt gctaaagtaa gctttttagg gccctttgec aataggtagt 1740 cattcaatct ggtattgatc ttttcacaaa taacagaact gagaaacttt tatatataac 1800 tgatgatcac ataaaacaga tttgcataaa attaccatga ttgctttatg tttatattta 1860 acttgtattt ttgtacaaac aagattgtgt aagatatatt tgaagtttca gtgatttaac 1920 agtctttcca acttttcatg atttttatga gcacagactt tcaagaaaat acttgaaaat 1980 aaattacatt gccttttgtc cattaatcag caaataaaac atggccttaa caaagttgtt 2040 tgtgttattg tacaatttga aaattatgtc gggacatacc ctatagaatt actaacctta 2100 ctgccecttg tagaatatgt attaatcatt ctacattaaa gaaaataatg gttcttactg 2160 gaatgtctag gcactgtaca gttattatat atcttggttg ttgtattgta ccagtgaaat 2220 gccaaatttg aaaggcctgt actgcaattt tatatgtcag agattgcctg tggctctaat 2280 atgcacctca agattttaag gagataatgt ttttagagag aatttctgct tccactatag 2340 aatatataca taaatgtaaa atacttacaa aagtgg 2376 <210> 2801 <211> 1158 <212> DNA <213> Homo sapiens <400> 2801 gcctgctget ctggcccctg gtcctgteoct cttctccage atggtgtgtc tgaagctcec 60 tggaggctee agcottggcag cgttgacagt gacactgatg gtgctgaget cccgactggce 120 tttcgetggg gacacccgac cacgtttett ggagctgegt aagtctgagt gtcatttctt 180 caatgggacg gagcgggtgc ggtacctgga cagatacttc cataaccagg aggagttcct 240 gegettegac agcgacgtgg gggagtaccg ggeggtgacg gagetgggge ggcctgtege 300 cgagtcectgg aacagccaga aggacctcct ggagcagaag cggggecggg tggacaatta 360 ctgcagacac aactacgggg ttggtgagag cttcacagtg cagcggcegag tccatcctca 420 ggtgactgtg tatcctgcaa agacccagcc cctgcagcac cacaacctecec tggtctgcecte 480 tgtgagtggt ttctatccag gcagcattga agtcaggtgg ttccggaacg gccaggaaga 540 gaaggctggg gtggtgtcca cgggcctgat ccagaatgga gactggacct tccagacccet 600 ggtgatgcta gaaacagttc ctcggagtgg agaggtttac acttgccaag tggagcaccec 660 aagcgtaacg agcgctctca cagtggaatg gagagcacgg tctgaatctg cacagagcaa 720 gatgctgagt ggagtcgggg gctttgtgct gggectgetc ttocttgggg ccgggetgtt 780 catctacttc aggaatcaga aaggacactc tggacttcag ccaacaggat tcctgagctg 840 aagtgcagat gacaatttaa ggaagaatct tctgccccag ctttgcagga tgaaaagctt 900 tccecgectgg ctgttattct tccacgagag agggctttct caggacctag ttgctactgg 960 ttcagcaact gcagaaaatg tcctcccttg tggettocte agttcctgec cttggectga 1020 agtcccagca ttgatggcag cgcctcatct tcaacttttg tgctccectt tgcctaaace 1080 ctatggcctc ctgtgcatct gtactcaccc tgtaccacaa acacattaca ttattaaatg 1140

. tttctcaaag atggagtt 1158 <210> 2802 <21l1l> 3597 <212> DNA <213> Homo sapiens <400> 2802 ggcgaatgga gcaggggcgce gcagataatt aaagatttac acacagctgg aagaaatcat 60 agagaagccg ggcgtggtgg ctcatgeccta taatcccage acttttggag gctgaggcegg 120 gcagatcact tgagatcagg agttcgagac cagcctggtg ccttagcatc tcccaatggg 180 gtggctttge tctgggctce tgttccetgt gagctgectg gtcctgetge aggtggcaag 240 ctctgggaac atgaaggtct tgcaggagcc cacctgegtc tccgactaca tgagcatcte 300 tacttgcgag tggaagatga atggtcccac caattgcage accgagctcc gecctgttgta 360 ccagctggtt tttctgctct ccgaagccca cacgtgtatc cctgagaaca acggaggede 420 ggggtgcgtg tgccacctge tcatggatga cgtggtcagt gcggataact atacactgga 480 cctgtggget gggcagcagc tgctgtggaa gggctccttc aagcccagceg agcatgtgaa 540 acccagggcc ccaggaaacc tgacagttca caccaatgtc tccgacactc tgctgctgac 600 ctggagcaac ccgtatcccc ctgacaatta cctgtataat catctcacct atgcagtcaa 660 catttggagt gaaaacgacc cggcagattt cagaatctat aacgtgacct acctagaacc 720 ctcectccge atcgcagcca gcaccctgaa gtctgggatt tcctacaggg cacgggtgag 780 ggcectggget cagtgctata acaccacctg gagtgagtgg agccccagca ccaagtggcea 840 caactcctac agggagccct tcgagcagca cctoctgctg ggegtcageg tttoctgeat 900 tgtcatcctg gecegtctgec tgttgtgcta tgtcagcatc accaagatta agaaagaatg 960 gtgggatcag attcccaacc cagcccgcag ccgectcgtg gctataataa tccaggatgce 1020 tcaggggtca cagtgggaga agcggtcccg aggccaggaa ccagcecaagt geccacactg 1080 gaagaattgt cttaccaagc tcttgccctg ttttctggag cacaacatga aaagggatga 1140 agatcctcac aaggctgeca aagagatgec tttccagggc tctggaaaat cagcatggtg 1200 cccagtggag atcagcaaga cagtcctctg gccagagagc atcagcgtgg tgcgatgtgt 1260 ggagttgttt gaggcccegg tggagtgtga ggaggaggag dgaggtagagg aagaaaaagg 1320 gagcttctgt gcatcgectg agagcagcag ggatgacttc caggagggaa gggagggcat 1380 tgtggcececgg ctaacagaga gcectgttcct ggacctgcte ggagaggaga atgggggctt 1440 ttgccagcag gacatggggg agtcatgcct tcttccacct tcgggaagta cgagtgctca 1500 catgccctgg gatgagttcce caagtgcagg gcccaaggag gcacctcect ggggcaagga 1560 gcagcetecte cacctggage caagtcctcc tgccagcccg acccagagtc cagacaacct 1620 gacttgcaca gagacgcccc tcgtcatcge aggcaaccct gcttaccgca gcttcagcaa 1680 ctccectgage cagtcacegt gtcccagaga gctgggtcca gacccactgc tggccagaca 1740 cctggaggaa gtagaacccg agatgccctg tgtcccccag ctotctgage caaccactgt 1800 gccccaacct gagccagaaa cctgggagca gatcctccgce cgaaatgtcc tccagcatgg 1860 ggcagctgca gcccccgtct cggcccccac cagtggctat caggagtttg tacatgceggt 1920 ggagcagggt ggcacccagg ccagtgcggt ggtgggettg ggtcccccag gagaggetgg 1980 ttacaaggcc ttctcaagcc tgecttgccag cagtgetgtg tccccagaga aatgtgggtt 2040 tggggctage agtggggaag aggggtataa gectttccaa gacctcattc ctggctgeec 2100 tggggaccct gccccagtce ctgtcccectt gttcaccttt ggactggaca gggagccacce 2160 tcgcagtccg cagagctcac atctcccaag cagctcccca gagcacctgg gtctggagec 2220 gggggaaaag gtagaggaca tgccaaagcc cccacttccc caggagcagg ccacagaccec 2280 ccttgtggac agcctgggca gtggcattgt ctactcagcc cttacctgcc acctgtgegg 2340 ccacctgaaa cagtgtcatg gccaggagga tggtggccag acccctgtca tggccagtcc 2400 ttgctgtgge tgctgctgtg gagacaggtc ctcgeccect acaacccecc tgagggcccce 2460 agacccctet ccaggtgggg ttccactgga ggecagtctg tgtccggect cectggcacc 2520 ctcgggcatc tcagagaaga gtaaatcctce atcatccttc catcctgeccce ctggcaatge 2580 tcagagctca agccagaccc ccaaaatcgt gaactttgtc tcegtgggac ccacatacat 2640 gagggtctcet taggtgcatg tectcttgtt gectgagtctg cagatgagga ctagggctta 2700 tccatgcctg ggaaatgcca cctecctggaa ggcagccagg ctggcagatt tccaaaagac 2760 ttgaagaacc atggtatgaa ggtgattggc cccactgacg ttggcctaac actgggctge 2820 agagactgga ccccgcecag cattgggctg ggctcgccac atcccatgag agtagagggce 2880 actgggtcge cgtgccccac ggcaggcccec tgcaggaaaa ctgaggccct tgggcaccte 2940 gacttgtgaa cgagttgttg gctgctcect ccacagettc tgcagcagac tgtecctgtt © 3000 BN gtaactgcce aaggcatgtt ttgeccacca gatcatggec cacgtggagg cccacctgece 3060 tctgtctcac tgaactagaa gccgagccta gaaactaaca cagccatcaa gggaatgact 3120 tgggeggect tgggaaatcg atgagaaatt gaacttcagg gagggtggtc attgcctaga 3180 ggtgctcatt catttaacag agcttcctta ggttgatgct ggaggcagaa tceceggetgt 3240 caaggggtgt tcagttaagg ggagcaacag aggacatgaa aaattgctat gactaaagca 3300 gggacaattt gctgccaaac acccatgccc agctgtatgg ctgggggctc ctcgtatgca 3360 tggaaccccc agaataaata tgetcagcca ccctgtgggce cgggcaatcc agacagcagg 3420 cataaggcac cagttaccct gcatgttggc ccagacctca ggtgctaggg aaggcgggaa 3480 ccttgggttg agtaatgctce gtctgtgtgt tttagtttca tcacctgtta tctgtgtttg 3540 ctgaggagag tggaacagaa ggggtggagt tttgtataaa taaagtttct ttgtctce 3597 <210> 2803 <21l1l> 696 <212> DNA <213> Homo sapiens <400> 2803 ttecceceee ccccoeeecce cececcgeecga gcacaggaca cagctgggtt ctgaagctte 60 tgagttctge agcctcacct ctgagaaaac ctcttttcca ccaataccat gaagctetge 120 gtgactgtcc tgtctctect catgctagta getgecttct getctccage getctcagea 180 ccaatgggct cagaccctec caccgcctge tgcttttctt acaccgcgag gaagcttcct 240 cgcaactttg tggtagatta ctatgagacc agcagcctct gcetcccagec agcetgtggta 300 ttccaaacca aaagaagcaa gcaagtctgt gctgatccca gtgaatcctg ggtccaggag 360 tacgtgtatg acctggaact gaactgagct gctcagagac aggaagtctt cagggaaggt 420 cacctgagece cggatgcttc tccatgagac acatctectc catactcagg actcctctcece 480 gcagttcctg tceccttctet taatttaatc ttttttatgt gccgtgttat tgtattaggt 540 gtcatttcca ttatttatat tagtttagcc aaaggataag tgtcctatgg ggatggtcca 600 ctgtcactgt ttctctgctg ttgcaaatac atggataaca catttgattc tgtgtgtttt 660 ccataataaa actttaaaat aaaatgcaga cagtta 696

<210> 2804

<211l> 1451

<212> DNA

<213> Homo sapiens

<400> 2804 gaagagcaag cgccatgttg aagccatcat taccattcac atcectctta ttectgcage 60 tgcccctget gggagtgggg ctgaacacga caattctgac gcccaatggg aatgaagaca 120 }

ccacagctga tttcttcctg accactatge ccactgactc cctcagtgtt tccactctge 180 cccteccaga ggttcagtgt tttgtgttca atgtcgagta catgaattgc acttggaaca 240 gcagctctga gccccagcct accaacctca ctctgcatta ttggtacaag aactcggata 300 atgataaagt ccagaagtgc agccactatc tattctctga agaaatcact tctggctgtc 360 agttgcaaaa aaaggagatc cacctctacc aaacatttgt tgttcagctc caggacccac 420 gggaacccag gagacaggcec acacagatgc taaaactgca gaatctggtg atcccctggg 480 ctccagagaa cctaacactt cacaaactga gtgaatccca gctagaactg aactggaaca 540 acagattctt gaaccactgt ttggagcact tggtgcagta ccggactgac tgggaccaca 600 gctggactga acaatcagtg gattatagac ataagttctc cttgecctagt gtggatggge 660 agaaacgcta cacgtttcgt gttcggagcc gctttaaccc actctgtgga agtgctcage 720 attggagtga atggagccac ccaatccact gggggagcaa tacttcaaaa gagaatcctt 780 tceotgtttge attggaagcc gtggttatct ctgttggctc catgggattg attatcagcee 840

: ttctctgtgt gtatttctgg ctggaacgga cgatgccecccg aattcccacc ctgaagaacce 900 tagaggatct tgttactgaa taccacggga acttttecgge ctggagtggt gtgtctaagg 960 gactggctga gagtctgcag ccagactaca gtgaacgact ctgcctcgtc agtgagattc 1020 ccccaaaagg aggggccctt ggggaggggc ctggggcctc cccatgcaac cagcatagcec 1080 cctactgggec ccccccatgt tacaccctaa agcctgaaac ctgaacccca atectctgac 1140 agaagaaccc cagggtcctg tagccctaag tggtactaac tttccttcat tcaacccacc 1200 tgcgtctcat actcacctca ccccactgtg gctgatttgg aattttgtgc ccccatgtaa 1260 gcaccccttc atttggcatt ccccacttga gaattaccct tttgeccccga acatgttttt 1320 cttctcccte agtetggecce tteccttttcg caggattctt cctecctcece tcttteccte 1380 ccttecctett tccatctacce ctcecgattgt tcctgaaccg atgagaaata aagtttctgt 1440 tgataatcat c 1451 <210> 2805 <211> 1439 <212> DNA <213> Homo sapiens <400> 2805 taattctctc acattcccat ggaaggtaaa gccatcgcga cgtctctegg tggtgatcgt 60 gtattgatat tcccgtgttc tcctcgetct tcocttcegttt ttacatcccg gctctctage 120 ctgcctctaa agcgtgegtce tatcggtggt gctgtctctt gttccggegt caatggcttg 180 actcggtgga attccattgt ttcgactcge cgactcgttc ctgttcgttc aattaactcg 240 gaatcggact cggactccga cttccctcac gagaatcagc agggaaatcc aggtttgggg 300 aaatttaagg aataccaaga atgggactca tggacggcca agttctccgg tggagcaaac 360 attccgtttc tcatgctcca attgcctcag atcatcctca atacccagaa tcttttggeg 420

!

ggaaacaata ccgctctttce ggctgtccca tggctgggaa tgttgactgg tttgttagga 480 aacctttcgt tgctttctta ttttgctaag aagagagaaa aagaagcagc tgtggtgcaa 540 acactgggag tggtctctac tcacattgtg cttgcacagc tcacaatggce tgaagcaatg 600 cctattcagt attttgttgc tacttcagct gttgtcacca tcggtctcat tgtgaactgt 660 ttgtactatt tcggtaagct tagcaaaact gtgtggcaac tgtgggaaga cgttatcact 720 attggtggac tctcegttct tcctcaaatc atgtggtcaa catttgtccc tcttgtacca 780 aacagtatct tgectgggac aactgctttt ggtattgctg tggcagctat aatcatggct 840 cgaactggga aactttcaga gaaaggtgtt aggtttgtag ggtctttatc tggatggaca 900 gcaactctta tgttcatgtg gatgccagtt tcccaaatgt ggacaaattt tctaaacccg 960 gacaacataa aaggcttatc gtcaatcaca atgttgectct cgatgatggg aaacgggctt 1020 atgatcccte gagcactatt tatccgtgat ttgatgtggce tcactggttc gctatgggca 1080 actctctttt atggatatgg aaatattctt tgcttatacc tggtaaattg caccagccag 1140 tcattctteg tggcagctac aattggtttg atctcatgga taggactggc tttgtggaga 1200 gatgcagtgg cttatggtca caactcgeeg tttagatctt tgaaagaact tgtttttgga 1260 ccgtaatgaa tgaatgtaca cgccataaac gcecctttgtt caagcaagtc catagagatt 1320 acatgtattt tcattctttt ttcctaaggg ttataagaca actactctgt aatttcatgt 1380 atttttttac ttgaatcata tagtaaaata atgtctgata tcaaaaaaaa aaaaaaaaa 1439 <210> 2806 } <211> 954

<212> DNA

<213> Homo sapiens

<400> 2806 ggcacgaggc ggttgcacac ttttttaaaa aaagtaaatg gatttgccac aattaaatgt 60 cataacattt atgacagaat ataaaatatt aacatatttt aagccaagtt ttaggtgtat 120 tttttgaatc ttggttataa acccaatttt aaagggcgat gtatccagcg ttgtgaaggc 180 aacagagtgt acccatattt atatttttat aaaataccta taagactgtg aatctecttgt 240 gctaatggct gagttaattg aaggatcgtt ttgccccttt ttagcctcec agagcttcga 300 ggactcaatt cgaacccgaa atcctgcegt gggggagggg ttgegtcgag acctgggccec 360 ggggaggttc tcctgegtca ctttctgtec tgaaaggegce ccttectggt ttctgtggcet 420 ccaattttct atgcagcccc acaccccttg ttgttttgat cctgagaaat aaaagggagg 480 ctgaattatt caaattaaaa tgaggtttcc ccttcatgga agtgctgetg acccttcgtg 540 cagaaatggg gagcacttga ggacacaggt gggtggaggc cctttgtgeg tggctggtcg 600 tattcgggca gccctocegte getttttata aaactttgtg tgagaagaat atattgataa 660 tgtcagtgaa acaagcagac attgaaatgg aggcacagat tactccacaa ggagttcttce 720 tgtatatttt ttctagatgc aaataccttt ttaattatgt taattaatgt taagactttc 780 taggcttata tcgaagctgt gtgtgggtca cggggtgatc actgctaact ggataaagtt 840 tgtgcagcac attcctgagt gtacgatatt gacctgtagc ccagcgtgaa aaatttataa 900 ataaattttt cattgatctt tttatattaa aaaaaaaaaa aaaaaaaaaa gttg 954 <210> 2807 <211> 458 <212> DNA <213> Homo sapiens <400> 2807 atggaggctg aagctgctgt tcggaggccc tctattggtg cctcetctcecct gccgtcatca 60 ctatggcagg aaaacagaga tggtttagta atgaattatc attcccaaac ccgtgtccac 120 ctggaacatc aggatgggac catgtttgaa aatcgggtct ttccaaatgt aattaagtaa i80 ggcgaggcca tactgcattt acaatgggcc caatccagtg tccctatgag agacggaaga 240 ggagacacag acacaaagca ggaggccaca taaagacaga ggcagagact gaagtgatgce 300 tgccccaage ccaggggatg cctggagtcc ccaggagctg ggagaggcag gaagggaccec 360 tccectagag tcectcttggag ggaactgata caattgcaga gtgcactaaa cagttgcccce 420 aaaagacata tcttgtttta aggcccagac ctgaaattt 459 <210> 2808 <211> 553 <212> DNA <213> Homo sapiens <400> 2808 acaacatggt ctccacatgg ctggctggct ggctgteccct gtgtgtgtgt gacacacggt 60 gtgagtgcag ggctgtgcgt gtgtgggagg gtgtctatgt ggcactgact gtcttagctc 120 agagctggtg gatcctctecc atggacaatg acactttaag gattgtcttg gtttgttttt 180 cctatttgtg gggtattttc cccctcagge tecetgggtct getgctgect caaggtgtcec 240 tgaccttgag gctgatgagg ggacccctgc ctgtttcccce catactgagt tctagggagg 300 tgctcaccce agactcttag gaagggtcta gagaaatgag aggagcccaa gccaggggcec 360 } agctccgaga aagggtaacc tccacgcttc tctctcccaa attggaaatg aagacaggtt 420 ttcaaaggca caggctcccc ctgccagett ctaggatctt ccttggtgtg caatgggcca 480 gttaggggta ggcagcttgc acccagttct cctttatctc aacttattgt cctggggaga 540 ggtgctagag gga 553

<210> 2809 <211> 4628 <212> DNA <213> Homo sapiens <400> 2808 gagcagaccc cgaaagcccc atcctggacc tggaccttca cctgcccttg ctgtgettca 60 ggcctgagaa ggtgctacag atcctgacat gcatcctgac ggaacagegg atcgtcttct 120 tctectcgga ctgggctctg ctgacgetgg tcactgagtg cttcatggee tacctgtatc 180 cgctgcagtg gcagcaccce ttecgtgccca tcctgtecgga ccagatgctg gatttegtcea 240 tggccecccac gtccttcetg atgggctgecc atctcgacca cttcgaagaa gtcagcaagg 300 aagccgacgg tttagttctg ataaatattg atcatgggag catcacctac tccaagtcca 360 cggacgataa cgtggacatt cctgatgtcc ccctectggce agcccagacg tttattcaga 420 gggtgcagag cctccagectc caccatgage tgcacgcecgc ccacctceccte tccagcacag 480 acctgaagga gggccgagec caccggcggt cctggcagca gaaactcaac tgccagatac 540 agcagaccac cctgcagctg ctcgtgagca tcttcaggga tgtaaagaat catttaaact 600 atgaacacag agtctttaat agtgaagaat ttctcaaaac cagggctcca ggggaccatc 660 agttttataa gcaggtctta gacacctaca tgttccattc ttttcttaaa gcccggctca 720 ataggaggat ggacgccttt gctcagatgg acctcgacac ccagtcggag gaggacagaa 780 taaatggaat gcttctaagt ccaaggagac cgaccgttga gaaaagagcc tcccggaagt 840 ‘cctegeacct gcatgtcace cacaggcgca tggtggtcag catgcccaac ctgcaggaca 900 ttgccatgce tgagctggca cccaggaact cctcgctccg gctgacggac accgcaggct 960 gtaggggcag cagcgcagtt ctgaatgtca cgccgaagtc cccgtataca ttcaagattce 1020 ccgaaatcca ctttcecgetg gagagcaagt gcgtgcaggc ataccatgec cactttgtcet 1080 ccatgctgag cgaggccatg tgctttctgg cccccgataa ctctctgectc ctggeccget 1140 atttgtacct ccgagggctc gtttatctga tgcagggaca gctgctgaac gcecctcttgg 1200 acttccagaa tctgtataaa acagacatac ggatctttcc cactgatttg gtgaagagga 1260 cggtggaatc catgtctgcc cctgagtggg agggggctga gcaggcgeccg gagctgatga 1320 ggctcatcag cgagatcctg gacaageccgc acgaggcctc gaagctggac gaccacgtga 1380 agaagttcaa gctgcccaag aagcacatgc agctgggcga cttcatgaag cgggtccagg 1440 agtcagggat cgtgaaggac gccagcatca tacaccggct gttcgaggcecc ttgactgtag 1500 gacaggagaa acaaatcgac ccagaaacat tcaaagattt ctacaactgc tggaaggaga 1560 cggaagcaga agcccaggag gtcagtctge cgtggetggt gatggaacac ctggataaaa 1620 acgagtgtgt gtgtaagttg tccagctccg tcaagacaaa cctaggcgtt ggcaagatceg 1680 ccatgaccca gaagcgectg ttectcocctaa ccgaaggaag geccaggctac ttggagattt 1740 ccaccttcag aaatatagag gaggtcagga gaaccactac tacatttcta cttcggagaa 1800 tacccacttt aaaaatcaga gtggcgtcca agaaagaagt cttcgaagcc aacctgaaaa 1860 ccgagtgtga cctttggcac ctgatggtga aggagatgtg ggctgggaag aagctggcecg 1920 atgaccacaa ggaccctcac tacgtccagc aggcgctgac caacgtcttg ctgatggacg 1980 ccgtegtggg cacactgcag tcaccaggcg ccatctacge tgcctccaag ttatcctact 2040 ttgataagat gagtaacgaa atgcccatga cgcttcecgga gacaaccctg gaaacactga 2100 agcataaaat caacccctcg gcggggdagg cgttcccaca agcggtggac gtgctgcetct 2160 acactccagg gcatcttgac ccagccgaaa aagttgaaga tgotcaccee aagttatggt 2220 gtgctctgag cgaaggcaag gtgaccgtgt tcaatgcttc ttcatggacc atccaccagce 2280 actcctttaa agtgggcact gcaaaagtga actgcatggt gatggccgac cagaaccagg 2340 tgtgggttgg ctcggaagac tccgtcatct acatcatcaa cgtccacagc atgtcctgcea 2400 acaagcagct cacagcccac tgctccagtg tcacggattt gattgtgcag gacggacagg 2460 aggcacccag caacgtgtac tcgtgcagca tggacggcat ggtgctggtg tggaatgtga 2520 gcacactgca ggtgaccagc cgcttccage tgccgegagg tggectgacg tccatcagac 2580 tgcacggegg ccgectgtgg tgectgcacag gtaacagcat catggtcatg aaaatgaatg 2640 gatccctcca tcaagaattg aagattgagg agaacttcaa agacaccagt acctccttcee 2700 tggccttcca gctecttect gaggaggagce agctgtggge ggcectgtgca ggacgcagceg 2760 aggtttacat ctggagcctg aaggacctgg cccagcccce gcagagggtg cccctcgagg 2820 actgctctga gatcaactgc -atgatccggg tgaagaagca ggtctgggtg ggcagccgag 2880 ggctggggca gggaacaccc aaggggaaaa tctacgtgat tgacgecgag aggaagaccg 2940 tggagaagga gectggtggeg cacatggaca ccgtgaggac gctgtgecteg gcoctgaggaca 3000 gatacgtget gagtgggtcg ggcagggagg aggggaaagt cgccatttgg aaaggcgaat 3060 aaacgtggct gagtctgcca agtggaactg tgccctatgt gtggggactg gctgccccct 3120 agagcctgcc aggagcagaa gcctggaggg gtggcagggc agagcagccc aggctcagca 3180 tggagcccac ttaccgtgtg gccagccgeg agacccatgg ccacgcacct tctctcagge 3240 : cttcgggccc cctggttaaa ctgcaccaag ggtgttteoct gttggggtgt gtctcaggcea 3300 ggcagctgeg tettgttggt gataacctct getgggaggt tactttgttg cctagaaagt 3360 tctggaatcc acaaccaggg gctggcactg gagccagcag cttggccgag tcacaggtga 3420 ccegtggecec tcacgtctet ggttttacct ttccttactt cattcattca ctcacccagt 3480 ccttacgaat caccgaggaa cactgggctg agcacatgac agggagcctg gagccccgdg 3540 gcctccageg aggcctgaga agggtggttc gggtaaccac tgtgggctct ctcccatcac 3600 agaaggtgga cagggcctac ccaggtggag gggaccacce tgcgatcagg tgtttgegac 3660 aggggttggg ccagctgagg caagctgtct ttttteccctt ttctttttaa tagatgcaac 3720 atttttataa taatcctaga gacctttttt ctaccaaaga tcacagacca gaaaaagttc 3780 catctaaaat atcatgccca ggaaagcaca tgggatcaaa agtaaaatag catcatgtgt 3840 gatctcgtct tccagegtgce cgctcagtte cccgaatccg tgtgcacacg tgtgatctcg 3300 tcttcagtgt gccgctcagt tccctgaatc cgtgtgcaca ctgcgtatgt gtacgegcag 3960 catgctatac tgaactcaac aagatcttgg ctgtacataa atatttgtaa aagagaccct 4020 ttgcaccttt ttactgtcat gttgagactt cattacttaa atgttctacg gaaggttctg 4080 gtgtggttgt tggagccgga gggagcgtgt cagcacgtgc tgagggcatg gggectgecce 4140 cctgggcacce catccacaag ctgggccacyg gagctccage ttctcaggac aaagccccgg 4200 ggctggcgeca tcctgagggt ctctgggggt gtttgccagg ctcecctgggat gggecgettt 4260 cagaagccct gcagtgcctc cagatggaaa ggegggcccg goctccggtt gggtctgeat 43240 tttggagagt ccacaccacg gaccaggttt tcccccaagg cttggctttg tgtagctact 4380 aacttcttgg ggcattctga gagtgtgggc agagagaatt atgtggcctc atcctcecce 4440 aaggctgtgc ttgcagcccg ggcaccttcce cactttctag ctctggagag gttggatttt 4500 gcttttgtaa acacatgaat ccttatgata aaagtctgtc agtcaaaaat acatttataa 4560 attatttaat gccagtcctc atgtaacctc aggtatcttc agcttgtgga gaataaatct 4620 ggtttaat 4628 <210> 2810

<211> 1245

<212> DNA

<213> Homo sapiens

<400> 2810 ggcacgaggc aggegctgac gaggagcccg gcetgagggag gatgegccge tgacgcectge 60 gggagccgcg cgcctggggdc gggaggatgc tccagagggg cctctggecg tggegcacge 120 ggctgetgee gacccetgge acctggecgec cagcgegece gtggccgetg ccgecteege i80 cccaggtttt gegtgtgaag ctgtgtggaa atgtgaaata ctaccagtca caccattata 240 gtaccgtggt gccacctgat gaaataacag ttatttatag acatggcctt cccttggtaa 300 cacttacctt gccatctaga aaagaacgtt gtcaattcgt agtcaaacca atgttgtcaa 360 cagttggttc attccttcag gacctacaaa atgaagataa gggtatcaaa actgcagcca 420 tcttcacagc agatggcaac atgatttcag cttctacctt gatggatatt ttgctaatga 480 atgattttaa acttgtcatt aataaaatag catatgatgt gcagtgtcca aagagagaaa 540 aaccaagtaa tgagcacact gctgagatgg aacacatgaa atccttggtt cacagactat 600 ttacaatctt gcatttagaa gagtctcaga aaaagagaga gcaccattta ctggagaaaa 660 ttgaccacct gaaggaacag ctgcagcceccc ttgaacaggt gaaagctgga atagaagctc 720 attcggaage caaaaccagt ggactcctgt gggctggatt ggcactgetg tccattcagg 780 gtggggcact ggcctggcte acgtggtggg tgtactcctg ggatatcatg gagccagtta 840 catacttcat cacatttgca aattctatgg tcttttttgc atactttata gtcactcgac 900 aggattatac ttactcagct gttaagagta ggcaatttct tcagttcttc cacaagaaat 960 caaagcaaca gcactttgat gtgcagcaat acaacaagtt aaaagaagac cttgctaagg 1020 ctaaagaatc cctgaaacag gcgcgtcatt ctctctgttt gcaaatgcaa gtagaagaac 1080 tcaatgaaaa gaattaatct tacagtttta aatgtcgtca gattttccat tatgtattga 1140 ttttgcaact taggatgttt ttgagtccca tggttcattt tgattgttta atctttgtta 1200 ttaaattctt gtaaaacaga aaaaaaaaaa aaaaaaaaaa aaaaa 1245 <210> 2811

<211> 3780

<212> DNA

<213> Homo sapiens

<400> 2811 tactggacaa acatttcctc caaggacaca gctctctgcc tccatgtcac cacctttgaa 60 ggactgactg attccctcgg ctggtgccag tgcctgetce tgccatgggg cccgcgggga 120 gectgetggg cagcggacag atgcagatca ccctgtgggg aagtctggca gctgtcegcca 180 ttttcttegt catcacctte ctcatcttcc cgtgctctag ttgtgacagg gaaaagaagc 240 cgcgacagca tagtggggac catgagaacc tgatgaacgt gccttcagac aaggagatgt 300 tcagcecgttc agttactagc ctggcaacag atgctcctge cagcagtgag cagaatgggg 360 cactcaccaa tggggacatt ctttcagagg acagtactct gacctgcatg cagcattacg 420 aggaagtcca gacatcggcc tcggatctgce tggattccca ggacagcaca gggaaaccaa 480 aatgtcatca gagtcgggag ctgcccagaa tccctoccga gagcegcagtg gataccatgc 540 tcacggcgag aagtgtggac ggggaccagg ggctggggat ggaagggccce tatgaagtgc 600 tcaaggacag ctcctcccaa gaaaacatgg tggaggactg cttgtatgaa actgtgaagg 660 agatcaagga ggtggctgca gctgcacacc tggagaaagg ccacagtggc aaggcaaaat 720 ctacttctge ctcgaaagag ctcccaggge cccagactga aggcaaaget gagtttgctg 780 aatatgcctc ggtggacaga aacaaaaaat gtcgtcaaag tgttaatgta gagagtatcce 840 ttggaaattc atgtgatcca gaagaggagg ccccaccacc tgtccctgtt aagecttctgg 900 acgagaatga aaaccttcag gagaaggaag ggggagaggc ggaagagagt gccacagaca 960 cgaccagtga aactaacaag agatttagct cattgtcata caagtctcgg gaagaagacc 1020 ccactctcac agaagaagag atctcagcta tgtactcatc agtaaataaa cctggacagt 1080 tagtgaataa atcggggcag tcgcttacag ttccggagtc cacctacacce tccattcaag 1140 gggacccaca gaggtcaccc tcctcctgta atgatctcta tgctactgtt aaagacttceg 1200 aaaaaactcc aaacagcaca cttccaccag cagggaggcc cagcgaggag ccagagcctg 1260 attatgaagc gatacagact ctcaacagag aggaagaaaa ggccaccctg gggaccaatg 1320 gccaccacgg tctcecgtcoccca aaggagaacg actacgagag cataagtgac ttgcagcaag 1380 gcagagatat taccaggctc tagcaaccca gaagacaacc ctgggtagcc tgtgatcagt 1440 gtctggagac gtttcttctg tggaagagaa gaagtgacac aaacctatac ttcatatgct 1500 gctttagtca cctgaagatg gttggagagg ccctgtcgac tgttctccca gttgttcagt 1560 ttctgagaca gagaggtacg gactaggctg cacctgagtg tgcccctgec tgccagatgg 1620 acaggtacac ccaagcacat ctccctgctg caccctcacc acccacaaaa gatcccagcet 1680 gtcagtggtc tcatctcatt agtgaggaaa gccaagctgt atggaaaagc tgcactcacc 1740 aaggaccaca atgccccecgg cctaaagtac tgccattcag aaaagcaggt ttttecttect 1800 ctctttcectt ttctctgtct gctactgact ttaaggcttt ttccccettg aaatgtccag 1860 attcctgtgg ttcatcccaa ggaaattttc acacaaagct tggecctttgce cctcaatata 1920 ggtgttttag gatggtgaca aaccatggct gctgctttct gcccagctcg ccagtectec 1980 ccaaagagtt gcgcatcagce acctggggat ctggaccctg cgggtgaagg gatggggagg 2040 gacgtccctg gagtctctte tgtcectttgtt ccttcecttatt ttggcattcg atatcagcag 2100 cctctecceca aagtacttga agtcagtttt agatgcttta ttttattttt ctagtcaaaa 2160 acgtgtttcc cccagtgttt gaaaactcgt ccgaatcttt tcagtatttt ccatgagtat 2220 tgtggtactt ctagacttgt ttaagcccag aactcattcc ttcaaaacag agagccttaa 2280 tctttatgtt gggacacaga ccacatattt ggacggcagc catgcatcca tcgctgaagg 2340. gctgtggaca tgaatgtgta tttcccatgg tctccgcectge ccacaccaac agtgtggcat 2400 ctcataagtt aactgctacc ctaaggtaat ctaagattaa aatgtaaaca tttatttttg 2460 ttatgtaagt ttataagatg ttttatgttc aatgcctaat ttctcaaaag tgccagaaaa 2520 aaatgtatat tagctatttt gattttatgt acaatgattt atactctcct tttgaaaaga 2580 taccataaag cacataagct agatcactac aaggagctgt tatctttttt ctaatcaagt 2640 gtttaaaaca ctgatggttt ttaaagactc acctttttaa atggtacttg gagctcctga 2700 ttcaaattac ctagaccccc tagagaaata aatggaatat acataaataa tcattttcag 2760 tggtttatgg tgggcaatat tgcaatattt gaaatggtaa aaatggaaag aagaacaaaa 2820 tatgatgaga ggtggctgtg aattataaac ctcataaaag tgtcataatt ccattaaggt 2880 ttaattatat tttttcagaa aacagtgatg aattctgtag tccagtgctt gccaatgcaa 2940 attgcctatt ggaatcttet tcctatattt tacaaacatc agtggctgaa atagctcaga 3000 gtaagagctc agcctggttt gaatttaatc atctctttag atcttataag geccagcatta 3060 ggaaacttgt tcacttttca ttttcaaagg agcctagttg aagtgctatt atgagtgtgg 3120 gctatggaaa gacagctttt cctacactga taaagaaaaa aaatgaggaa attatttcat 3180 ccccttgtga catctgtgac tttttggatt taataatcectt getgtttttc ctctttatga 3240 caaagaatat aattgggagg atgaagtgtc ttaaaaattg tagagaccag ctcactggaa 3300 tgtttttcca tccctgtatt catggcttga ctttgtgact gctctacact gecatgtctga 3360 cattgcagag tgagctatgt tgaggtaaac tggttggttg tcattatttt gcaatcagcec 3420 tggtctctcc catgaagatg tcgtgtgcat aagcacaatc atcactgatt agaagatcac 3480 agcagaatac ccttggatta gagagaagtt cgtaccttgc atttctctga attctagtct 3540 ctcataagca ctgctttget ggatgatttt cactgctttg tgttaatgac tttgagcgat 3600 ctctcacatg atggggttct ttagtacatg gtaacagcca tgtcatctta cacacctage 3660 attgtgaatg ctgtagtgac atcctttata ggcaccttac agctcaaaac ttttgtttca 3720 tttcatgcet tacttatcaa aaaggcagga aagtaggtat gatctctaaa gtaaaaaaaa 3780 <210> 2812 <211> 2176 <212> DNA <213> Homo sapiens <400> 2812 aaaaatgcaa tgattattga tatctaggtg acctgaaaaa aaatagtgaa tgtgctttgt 60 aaactgtaaa gcacttgtat tctactgtga taagcgttgt ggatacaaag aaaggagcaa 120 gcataaaaaa gtgctctttc aaaaggatat agtactatgc .agacacaagg aattgtttga 180 taaatgaata aattatatgt atatttgagg ccaatttgtg tttgctgctc tggtaatttt 240 gagtaaaaat gcagtattcc aggtatcaga aacgaaaaca catggaaact gcttttaaac 300 tttaaaatat actgaaaaca taagggacta agcttgttgt ggtcacctat aatgtgccag 360 ataccatgct gggtgctaga gctaccaaag ggggaaaagt attctcatag aacaaaaaat 420 ttcagaaagg tgcatattaa agtgctttgt aaactaaagc atgatacaaa tgtcaatggg 480 ctacatattt atgaatgaat gaatggatga atgaatatta agtgcctctt acataccage 540 tattttgggt actgtaaaat acaagattaa ttctcctatg taataagagg aaagtttatt 600 ctctatacta ttcagatgta aggaatgata tattgcttaa ttttaaacaa tcaagacttt 660 actggtgagg ttaagttaaa ttattactga tacatttttc caggtaacca ggaaagagct 720

~ agtatgagga aatgaagtaa tagatgtgag atccagaccg aaagtcactt aattcagctt 780 gcgaatgtgce tttctaaatt ataaagcact tgtaaatgaa aaatttgatg ctttctgtat B40 gaataaaact ttctgtaagc taggtattgt ctctacaaaa ttctcattgt atagttaaac 900 cacagtgaga agggttctat aagtagttat acaaaccaag ggtttaaata cctgttaaat 960 agatcaattt tgattgccta ctatgtgaac tcactgttaa aggcactgaa aatttatcat 1020 atttcattta gccacagcca aaaataaggc aatacctatg ttagcatttt gtgaactcta 1080 aggcaccata taaatgtaac tgttgatttt ctcacttggt gctgggtact aggtttataa 1140 aattgtatga tagttattat attgtgcaaa taaagtagga aaatttgaat aacaatgatt 1200 atcttttgaa tacgcatacg caagggattg gttgtctgaa gaatgccact atagtagtta 1260 tctattgtgt gccaatctca ttgctaggca ttggggatgc aaagataaac catctrtatt 1320 gtgtcttggg tagcagaaga aaatatgtgt aaaatcaatt tataatttgt aaactgccac 1380 ccatatataa gctatatctg ctgaatgatc attgattact cttatcctta gagataacaa 1440 ctgggggcac aaacatttat tatcattatt gaacctacaa cagagatcta tgtgtagatt 1500 tacgaagcct acagttctat acagatagga atgaactatt ggcttactga atggtgatta 1560 ctttctgtgg ggctcggaac tacatgccct aggatataaa aatgatgtta tcattataga 1620 gtgctcacag aaggaaatga agtaatatag gtgtgagatc cagaccaaaa gtcatttaac 1680 aagtttattc agtgatgaaa acatgggaca aatggactaa tataaggcag tgtactaagc 1740 tgagtagaga gataaagtcc tgtccagaag atacatgctt cctggcctga ttgaggagat 1800 ggaaaatttt tgcaaaaaac aaggtgttgt ggtcttccat ccagtttctt aagtgctgat 1860 gataaaagtg aattagaccc accttgacct ggcctacaga agtaaaggag taaaaataaa 1920 tgectcagge gtgetttttg attcatttga taaacaaagc atcttttatg tggaatatac 1980 cattctgggt cctgaggata agagagatga gggcattaga tcactgacag ctgaagatag 2040 aagaacatct ttggtttgat tgtttaaata atatttcaat gcctattctce tgcaaggtac 2100 tatgtttcgt aaattaaata ggtctggccc agaagaccca ctcaattgec tttgagatta 2160 aaaaaaaaaa aaaaaa 2176

<210> 2813 <211> 580 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (1)... (1) <223> n is a, ¢, g, tor u } <400> 2813 nccttttgee catgttgtcet ggaatgccct tcttctcocct cttgtttaca tcaagcatca 60 gactgaatat ccctcttgtg cggccttcta aaacctcceg tccaaagcga aatatattgce 120 cctetattta tacttttaca gecatttggca cacaagtaca gagtagtagc tttttatcac 180 attctctgat aattatatag atatggtatt tcttagctet ctctccaact ggctaataag 240 ttgctttttg tctgagtgece taattttgtg ttttgtgtct gagtgectca gttcctcaaa 300 aaaaggtttt ttgattagtt cattattcat ttgaacatgg aaattatgct cactagtggc 360 aaatgccact aaccgtattc cagaagctag gtgtcatgtt tgcaataaga tatattatcc 420 cttctacaag tcacctttta tttcaggcat ttgtaaatgc ccattaataa agtatggttc 480 ataaatttta ccttgtaagt gcctaagaaa tgagactaca agctccattt cagcaggaca 540 caataaatat tattttataa tgccgaaaaa aaaaaaaaaa 580 <210> 2814 <211l> 5426 <212> DNA <213> Homo sapiens <400> 2814 ggggaggaag aaaggcgaag gcaaggcgaa ggggtggaga gtgatatgaa gagcgagaga 60 aaagagagga cagcggacga gcagatccgg tatctggaat cccggegect agaacgtgtt 120 tttcgggaga gcaaaggcetg tgtctacgge aggctgggga tatagcectct ccttecgatg 180 aaaagagaaa ggaagaatgg actacagcca ccaaacgtcc ctagtcccat gtggacaaga 240 taaatacatt tccaaaaatg aacttctctt gcatctgaag acctacaact tgtactatga 300 aggccagaat ttacagctcc ggcaccggga ggaagaagac gagttcattg tggaggggct 360 cctgaacatc tectggggee tgecgccggece cattcgectg cagatgcagg atgacaacga 420 acgcattcga ccccctccat cctcoctecte ctggcactct ggctgtaacc tgggggctca 480 gggaaccact ctgaagcccc tgactgtgcc caaagttcag atctcagagg tggatgcccce 540 gccggagggt gaccagatgc caagctccac agactccagg ggcctgaage ccctgcagga 600 ggacaccceca cagctgatge gcacacgcag tgatgttggg gtgcgtcgec gtggcaatgt 660 :

gaggacgcct agtgaccagc ggcgaatcag acgccaccge ttctccatca acggccattt 720 ctacaaccat aagacatccg tgttcacacc agcctatgge tctgtcacca acgtccgcat 780 caacagcacc atgaccaccc cacaggtcct gaagectgetg ctcaacaaat ttaagattga 840 gaattcagca gaggagtttg ccttgtacgt ggtccatacg agtggtgaga aacagaagct S00 gaaggccacc gattacccge tgattgcccg aatcctccag ggcccatgtg agcagatctce 960 caaagtgttc ctaatggaga aggaccaggt ggaggaagtc acctacgacg tggcccagta 1020 tataaagttc gagatgccgg tacttaaaag cttcattcag aagctccagg aggaagaaga 1080 tcgggaagta aagaagctga tgcgcaagta caccgtgetce cggctaatga ttcgacagag 1140 gctggaggag atagccgaga ccccagcaac aatctgagcc atgagaacga ggggatctgg 1200 gcaccccagg aaccgccatt gcccataaga cccccaggaa gctaggcact ttctttccat 1260 ggaaacattt agacacaaac ctccccagct ccggccaagc catcatttgc tacctggagc 1320 tggatgtaga agtcagcaga cagctcccta tccctggacce cctgcectee ttttttetge 1380 tcacaaggac ttttgatttt agttataagg aggacccaaa atgtgtgtgt gtacatgtgt 1440 gtgcacacat ggtacgtgtc catgtgecta cctgatactt tcacatgtaa ttaaattcca 1500 ggcaaccagc acaagagccg tgagcttggc acatgtgetg ctecgtgagca ggaaaatcag 1560 aggagccact gatctgagtg gtatttaggt tgaaggaaag atttctectc tcaagtgcca 1620 gggagcagcc acacgtctgt ctgtgtttag agagggaaga gggttctcca ggttcaccat 1680 ttgggttgtt tatatgttgg tagaaattct ccctgtatge ctagaaggat cagtgaatgt 1740 aagagccttg gaaattaaca aaataacagc cacataacct tgeggcaagt ctgatggaaa 1800 gaaaaagata aaccatccgt ggggtagatg caataagccc acgtattttt acactggaaa 1860 cgttgattgt tttaaatgac aaagacatat gtgatgttct atgtggaaac ctgtgaagag 1920 tggattctge ctcecatctet gectccatgg ctacctttag gagacagaga agatccectgtg 1980 tgtttctetg tacccagetg acagcctgte tctatggege ttccttgagt ggaaggaaat 2040 gtctcaagaa acaaagatct cgctggtgceg tacacagtgce tgaccagcta gtgtggccag 2100 ggcetggtgg cctggtggec aggaagtttc aggttgaagg gaaatgtcga ggctacctgce 2160 agatatgaca ggtgccttga acgcagccca tcttcatgtc atcaaaggtce ttcctgeact 2220 tgaagctggg gcgatgtttg cagtcaagac cattctttcc aacctcetggg ttcttgcaag 2280 ttgccctcac cttgtgtgtg gagatgcatt ccaagaatga agectcatct tgctactgag 2340 tgtggggttc agggaagctc tttaggccac ctggtgaagg tgcatgggga ggatggagct 2400 tectectcage tcctctgage agecacctat gtgatcttta aatccaacce caatgggaga 2460 aaagggcaag aacagtctgt gccctgggac tcctatcagg aagcttgaca ggcagctggg 2520 catcagtgca gctgatatcg tttgaggagg gagacagatg cttggacctg ggtgcctgge 2580 tatggagatt gaccaagcaa gatcaggagc tcctgatagc aggcgtcttt gagcctaget 2640 ggggtagagg cactgcccat ctcttctcca ccttctctec acagaatgtt tgcagagctg 2700 ggcagttgag gaaaggacag cccctggttg gtgcctccaa aggaaggtgg acttttttgg 2760 tggagacgtt tctgccctgg gcaccctect gcecccccgatt catacctatg gecttcecttgag 2820 aaggctcaca gctgtggtct taacgtagac tgcagaaaga tggcatgcgg cccctggcat 2880 ttcgeccaagg gttttatagc aagtctccectt cctccatagg gacagcagca ccagccctgt 2940 ggggcatgga gtggaagccc agaagggctt ctgcaagctg cacagaactg gggtaagaag 3000 acaaagagta gccaccggga gaggcttcct ttgttacagc tgggaaagaa cagttctgtg 3060 aatgcaaaca cctecctgagt tttgcaattg agaaaatgat ttggagaact tctcecttctgg 3120 taatttttat tttgaatgtt cagggcctta gttggcccca gtaattctcc ttggaggact 3180 tgggagaaga atttccacaa agcaaactac taaccactag ctcttactgg acagcgattt 3240 ctggcttata agagttctct ttgatttgca ctagcactac gatagtgtta gatggggaaa 3300 tactgcaaca tgtccagttg gccagatcac tttccaaggg agcgatacta aggcagactce 3360 agctttttaa agatgggagg tcaggaggtg gaagtgagag gagatcccat ctcacacaac 3420 acacttccac gtaatgcaga ccacactttt ccattttgtc ctgccctett gagaggtcat 3480 ttctcacgtc ctaagaacct gatcagaaat tttggaaggg ttctttgaaa tagcagcagt 3540 tgaaacagag acactttgcc acagtgtgga gcagattttc tcactggtat cacatggtct 3600 tgcagtttty aactcttcga ccgatttgtg ggagtttatg taattgcgtg caatgaacct 3660 gaaattgtgt aaaggacaaa agaccagttt atagggttgg gttttttttc caacttgtga 3720 aaagcagttt agctgcatct gtctccccac cacccccacc ccgggagggg cttatgttac 3780 aaggtgatca agtgaaggaa aaacctgagc ctatctgget gggatggtgg aattaagcac 3840 aaggtcacat tctctgtgat cacatgagag ggaaggtgat gacttaaatg gcaggaggtg 3900 gggattatct tggggagagg ctgaaaagca caaaagatag tcttccetgt acgtattggt 3960 gaagaacgtg cacaaggctg gatggacttc aacttggagt tgagttgagg caagaggatt 4020 tctggatatt agtcacccat ctgcaagaaa aatgctgagg cctcgggtca agattttgat. 4080 . ctgagacatg ctgatgcttc aaggagaaat attttcacaa tcctctettc cctcaccaga 4140 agagaacagt actctctcct agaaacctct aggtaaacac attttatcct aatatcggta 4200 gcatataatg ccccccccaa aatatctgtt ttccatgcaa aaaagtctca acaagaagtc 4260 tgtggagttg agtggttact tcaaagtgtc aggagagtga agaaattggc cacagaagag 4320 .

caagaagctc tcttaagaaa agggaattct ctttaaagaa accaccacca acaacaaaac 4380 aaccaaaaaC catgttttat gtcaaagctc tgtagcacag agaatgtggt gtcacagata 4440 catcgccgag agaggtttct ttctttcettt tttttttttt tgagacagag tctggttctg 4500 tttcccagge tggagtgcag tggtgggatce tcagctcact gcaacatccg cctctggggt 4560 tcaagtgatt ctcctgtctc agcctcccaa gtagctggaa ttacagggac ccgcecaccac 4620 gcccggcetaa tttttttgtg tggttttagt agaggtgggg tttcaccatc ttggccaggce 4680 tggtcttgaa ctcctgacct cgtgatccac ccgcctaggce ctcccaaagt gttgggatta 4740 caggecgtgag ccactgtgcc cagccaaaag agaaatttct acatgaacaa ggcaatttcea 4800 gtgtcttaca gcggccaaac catgacgtga agaatgagat aggagacagg agatcaccat 4860 aagcgtccet gatatagcag cacacatttt cacgtttcca cttaaatcgt tttgcacaaa 4920 gtcttgette gectcagatga gatgagatat gatttcctag agatgtaaaa ataagaatga 4980 atgtggcgcce cccttettec agatgtaata gaaagctctg ccctatcaca aggggggtgt 5040 tgaagcgcec cttgtgtttt aactgtattt aactgagcac aagatgcaca agctgtggtg 5100 ggaaaccctc agtttacctt tggagtcttce cctgcagatc gcagacctgt ttccaggcetg 5160 atgtttctgg tgtgtaattg ctagcgtttc tgaagggttt tcccaattgt tttagccttg 5220 tgaagtattc ttaattataa cttgcctttc agcgatggta catgacttga ttcaacgttt 5280 ggttctgaac ttacacactg atgcgtttac tcatctaaca taatctgaca gggcctcagce 5340 aagggagcca tacatttttg taacattttg atatgtttta atgcatctga cttagatctt 5400 actgaaataa agcacttttc aaagag 5426

<210> 2815

<211> 6050

<212> DNA

<213> Homo sapiens

<400> 2815 ggcttcccca cgggaggacg cgaggccccg geccagccat ggecccectdgg cgcaaagctg 60 acaaggagcg gcacggcgtg gccatataca acttccaagg cagcggagcc ccccagcectcect 120 ccctgcagat cggcgatgtg gtgcgaatac aggagacgtg tggagactgg tataggggat 180 acctcataaa gcacaaaatg ttacagggca tttttcctaa gtcatttatc cacatcaagg. 240 aagtgacagt tgagaaaaga agaaatactg agaacatcat tcctgcagaa attcctctgyg 300 cacaagaagt gacaacgaca ctttgggaat ggggaagcat ctggaaacaa ctctatgtgg 360 ccagcaaaaa ggagcgtttt ctccaggtgc agtccatgat gtacgatctg atggagtgga 420 ggtcccaget tctctcagga accttaccca aggatgagct gaaggaactg aagcagaaag 480 tcacgtccaa aattgactat ggcaacaaaa tccttgagct tgatttgatt gtcagagatg 540 aagacggaaa tatcttggac cctgataata ccagtgtcat cagcttgttc catgcacatg 600 aggaagcaac tgataaaatc acagagcgta tcaaagaaga aatgtcaaaa gaccagccag 660 attatgcaat gtattcccgg atctcctcat cccccaccca tagectctat gtgtttgtga 720 gaaactttgt gtgcagaatt ggggaagatg ctgagctctt catgtctctc tacgacccca 780 acaagcaaac ggtcataagt gagaactacc tagtgcgatg gggcagccgg ggcttcccta 840 aggagattga gatgctcaac aatctgaagg tggtcttcac ggatcttgga aacaaagacc 900 tcaacaggga taaaatttac ttgatttgtc aaatagtccg ggtcggcaag atggatctta 960 aggatactgg tgcaaagaag tgcacgcagg gactgaggag gccctttggg gtggcagtta 1020 tggatataac agacatcatc aaggggaaag cagagagtga tgaagaaaag cagcacttca 1080 ttccttttca cccggttaca gectgagaatg acttcctaca cagectgcetg ggcaaagtcea 1140 tagcctccaa gggggacagt ggagggcaag gcctctgggt gaccatgaag atgctggtgg 1200 gtgacatcat tcagattcgc aaggactatc cacacctggt ggacaggacce accgtggtgg 1260 ccaggaagct gggattccca gagatcatca tgccagggga tgtcaggaac gacatctaca 1320 ttactctctt acaaggtgac tttgacaagt acaacaagac cacacagagg aatgtggaag 1380 tcatcatgtg tgtgtgcgcg gaggatggca aaacgctgcc taatgcaatt tgcgtgggag 1440 caggggacaa gcccatgaat gagtatcgct ccgttgtgta ctatcaagtc aaacagccac 1500 gctggatgga aacagtcaag gtggctgtcc ctattgaaga catgcagagg atccatctgce 1560 gattcatgtt tcgacatcgg tcatctctgg aatctaaaga taaaggagaa aagaactttg 1620 ccatgtccta tgtgaagctg atgaaagaag atgggactac tctacacgat ggattccatg 1680 acttagttgt cctcaagggg gacagcaaga agatggagga tgccagcegeca tacctgacce 1740 ttccttctta tcgacaccat gtggaaaaca agggggccac gctgagcagg agctccagcea 1800 gtgttggggg gctttctgtc agctcccggg atgtgttctc catttccacc ctggtgtgcet 1860 ccacaaagct cactcagaat gtgggcttge tgggtttgct gaagtggegt atgaagcctc 1920 aactgctaca ggagaattta gaaaagttga agattgtgga tggagaggaa gtggtgaagt 1980 ttctccagga tactctggat gccctcttca acatcatgat ggagcattct caaagtgatg 2040 aatatgacat cctecgtettt gatgccttga tttacataat aggactcatt gcagaccgga 2100 aatttcagca tttcaacacc gttctggagg cttacatcca acagcatttc agtgcgacct 2160 tggcttacaa gaaattgatg acagtgctga agacttactt ggatacctcc agcagagggg 2220 agcaatgtga gccaatccta agaacgctga aggctttgga atatgtgttc aagttcattg 2280 ttcggtcgag gacattattt tcacagcttt atgaaggcaa agaacagatg gagtttgaag 2340 aatccatgag acggctcttt gaatccatca acaatctgat gaaaagtcaa tacaaaacta 2400 ccatcectttt gcaggtggcg gectttgaaat acatcccatc tgtcctgcat gatgtagaaa 2460 tggtctttga tgcgaagtta ctcagccaac tcctgtatga gttctacacc tgcatcectce 2520 ctgtgaaact ccagaagcag aaagtacagt ctatgaatga gatagtccag agcaacctct 2580 ttaaaaagca agaatgeccgg gacattctgce ttcectgtcat caccaaagag ctgaaggagce 2640 tgctggagca gaaggatgac atgcaacacc aggtcctgga gaggaagtac tgcgttgaat 2700 tgctcaacag catcttggaa gtccttagcet accaggatgc ggecttcacc taccaccata 2760 tccaagagat catggtccag ctgctgcgga cagtgaaccg gacagtcatc accatgggcce 2820 gggatcacat tctgattagt cactttgtgg catgtatgac agccatctta aaccagatgg 2880 gtgaccagca ctactccttc tacattgaga ccttccagac cagctctgaa cttgtggact 2940 tcttgatgga gaccttcatc atgttcaagg acctcattgg aaagaacgtg taccctggag 3000 actggatggc catgagcatg gttcaaaaca gggtcttect gagagctatc aacaagtttg 3060 cagaaaccat gaaccagaag ttcctagaac acacgaactt tgagttccag ctgtggaaca 3120 actattttca tctggcagtg gcttttatca cccaggattc tctgcagctg gagcagttcect 3180 cacacgccaa atacaacaaa atcctgaata agtatgggga catgagacgg ctaattggct 3240 tctccatcecg tgatatgtgg tacaagcttg gtcagaacaa aatctgcttc atcccaggca 3300 tggtaggacc tatattagag atgacactta tccctgagge tgagctccgg aaagecacca 3360 taccaatctt cttcgacatg atgctgtgtg aatatcaaag aagtggggat ttcaaaaagt 3420 ttgaaaacga aatcatcctg aagctggacc acgaggtaga agggggcecga ggcgacgage 3480 agtacatgca gctgctggag tcaatcctga tggaatgtgc tgcagagcac ccaaccattg 3540 ccaagtcggt ggagaacttc gtgaacctgg tcaaaggcct cctggagaag ctgctggatt 3600 accggggtgt gatgacagat gagagcaaag acaaccgcat gagetgcact gtgaacctgc 3660 tgaatttcta caaagataac aacagggagg agatgtacat aaggtacctg tacaaactcc 3720 gcgatcttca cctggactgt gacaattaca cagaggctgc ctacacgctc cttctccaca 3780 cctggettct caagtggtcg gatgagcagt gtgcatcaca ggtcatgcag acaggccagc 3840 agcaccccca gacacaccgg cagctcaagg agacgctcta cgagaccatce ataggctact 3900. ttgacaaagg aaagatgtgg gaagaggcca taagtctgtg caaggagctg gcggaacagt 33860 acgagatgga gatctttgac tatgagctgc tcagccagaa cctgatccag caggcaaaat 4020 tctatgaaag catcatgaaa atcctcaggc ccaaaccaga ctactttgct gttggatact 4080 acggccaggg attcccctcc ttcctgcgga acaaagtgtt catctaccege gggaaggaat 4140 atgagcgaag agaagatttc cagatgcagc tgatgaccca gttccccaat gcagagaaga 4200 tgaacaccac ctctgcececced ggagatgatg tgaagaatgc cccaggccag tatatccagt 4260 gcttcactgt ccagcctgtc ttggatgaac atcccaggtt caagaataag ccagtgcctg 4320 accagattat aaacttctac aaatccaact acgtgcaaag gttccactac tcccggececg 4380 tgcgcagggg gaccgtagac ccagagaatg agtttgcttc catgtggatt gagagaacct 4440 ccttcgtgac tgcatacaag ctgccgggga tcctgcegetg gtttgaggtg gtgcacatgt 4500 cgcagaccac aattagtcct ctggagaatg ccatagaaac catgtccacg gccaatgaga 4560 agatcctgat gatgataaac cagtaccaga gtgatgagac cctccccatc aacccactct 4620 ccatgctcct gaacgggatt gtggaccctg ctgtcatggg aggcttcgcc aagtatgaga 4680 aggccttctt cactgaagag tatgtcaggg accaccctga ggaccaggac aagctgacce 4740 acctcaagga cctgattgca tggcagatcc ccttcttggg agctgggatt aagatccatg 4800 agaaaagggt gtcagataac ttgcgaccct tccatgaccg gatggaggaa tgtttcaaga 4860 acctgaaaat gaaggtggag aaggagtacg gtgtccgaga gatgcctgac tttgacgaca 4920 ggagagtggg ccgccccagg tctatgctge gectcatacag acagatgtcc atcatctetce 4980 tggcttccat gaattctgac tgcagcaccc ccagcaagcc tacctcagag agctttgacce 5040 tggaattagc atcacccaag acgccgagag tggagcagga ggaaccgatc tecccgggga 5100 gcaccctgcc tgaggtcaag ctgcggaggt ccaagaagag gacaaagaga agcagcegtag 5160 tttttgcgga tgagaaagca gctgcagagt cggacctgaa gecggctttec aggaagcatg 5220 agttcatgag tgacaccaac ctctecggagc atgeggccat cccectcaag gegtctgtec 5280 tctctcaaat gagctttgcc agccagtcca tgectaccat ceccageccetg geogctctcag 5340 tggcaggcat ccctgggttg gatgaggcca acacatctcc ccgectcage cagaccttec 5400 tccaactctc agatggtgac aagaagacac tcacacggaa gaaggtcaat cagttcttca 5460 agacaatgct ggccagcaaa tcggctgaag aaggcaaaca gatcccagac tcgctgtcca 5520 cggacctgtg agctgctgcect gactagggct gcatgggaga gccagggagg ggagtttcetg 5580 gaagaggaaa gccatgcgtg gaacatcgaa gcctcagaga gtgggagact gtccccatca 5640 gttgtcctta cttagaggag acagagaggc caatcaggtc ccagagctgg agtgctaaca 5700 agcccagcat cccctgggge tgtgatcatg gtggatgagg aagcctcaac gtagattcct 5760 gaactcaagg taccagcaag aatgccttcet cccagtgtge tctccccaac atcctaggcea 5820 cagctttcat aacccagttt cttaggtgta agaaactgct tttatctcat ttattaagtc 5880 tcagaactta acagaaaagg aagcctttta aatattcttt ttaattttat tttagattaa 5940 cagttttgta ctttacattt ttttatacaa ccaaccagtt tcttttctag ccaatcatct 6000 ctgaagagtt gctgtttctt actgacaata aaaaatgttc tcttggtteg 6050 <210> 2816 <211> 1030 <212> DNA <213> Homo sapiens <400> 2816 agatgtaaac caatttcagg ccacaactcc cttttctggt acagacagac catgatgcgg 60 ggactggagt tgctcattta ctttaacaac aacgttccga tagatgattc agggatgccc 120 gaggatcgat tctcagctaa gatgcctaat gcatcattct ccactctgaa gatccagccce 180 tcagaaccca gggactcagc tgtgtacttc tgtgccagca gtttctcgac ctgttecgget 240 aactatggct acaccttegg tteggggacc aggttaaccg ttgtagagga cctgaacaag 300 gtgttceccac ccgaggtcgce tgtgtttgag ccatcagaag cagagatctc ccacacccaa 360 aaggccacac tggtgtgcct ggccacaggc ttcttececg accacgtgga gctgagetgg 420 tgggtgaatg ggaaggaggt gcacagtggg gtcagcacag acccgcagcec cctcaaggag 480 cagcccgccc tcaatgactc cagatactge ctgagcagcece gcctgagggt ctcggccacc 540 ttctggcaga acccccgcaa ccacttecege tgtcaagtcc agttctacgg gctctcggag 600 aatgacgagt ggacccagga tagggccaaa cccgtcaccece agatcgtcag cgccgaggcc 660 tggggtagag cagactgtgg ctttacctcg gtgtcctacc agcaaggggt cctgtctgcece 720 accatcctct atgagatcct gctagggaag gccaccctgt atgctgtgct ggtcagegec 780 cttgtgttga tggccatggt caagagaaag gatttctgaa ggcagccctg gaagtggagt 840 taggagcttc taacccgtca tggtttcaat acacattctt cttttgccag cgcttctgaa 900 gagctgcetct cacctctetg catcccaata gatatccccce tatgtgcatg cacacctgca 960 cactcacggc tgaaatctcc ctaacccagg gggaccttag catgcctaag tgactaaacc 1020 aataaaaatg 1030 <210> 2817

<211> 2454

<212> DNA

<213> Homo sapiens

<400> 2817 ggaataggtt agtttcagac aagcctgctt gcecggagctce agcagacacce aggcctteceg 60 ggcaggcctg geccaccgtg ggcctcagag ctgetgeotgg ggeattcaga accggctcete 120 cattggcatt gggaccagag accccgcaag tggectgttt gcctggacat ccacctgtac 180 gtcecccaggt ttecgggagge ccaggggega tgccagacce cgeggegceac ctgceccttet 240 tctacggcag catctcgegt geccgaggecg aggagcacct gaagctggeg ggcatggcgg 300 acgggctctt cctgectgege cagtgectge getcgetggg cggctatgtg ctgtegeteg 360 tgcacgatgt gcgcttccac cactttecca tecgagcgeca gctcaacgge acctacgcca 420 ttgccggegg caaagcgcac tgtggaccgg cagagctctg cgagttctac tcgecgegacce 480 ccgacgggcet gccctgcaac ctgcgcaagc cgtgcaaceg goccgtcggge ctcgagccge 540 agccgggggt cttcgactge ctgcgagacg ccatggtgcg tgactacgtg cgccagacgt 600 ggaagctgga gggcgaggcc ctggagcagg ccatcatcag ccaggccceg caggtggaga 660 agctcattge tacgacggcc cacgagcgga tgccctggta ccacagcagc ctgacgegtg 720 aggaggccga gcgcaaactt tactctgggg cgcagaccga cggcaagttc ctgctgaggce 780 cgcggaagga gcagggcaca tacgccctgt ccctcatcta tgggaagacg gtgtaccact 840 acctcatcag ccaagacaag gcgggcaagt actgcattcc cgagggcacc aagtttgaca 900 cgctctggca gctggtggag tatctgaage tgaaggcgga cgggctcatce tactgcctga 960 aggaggcctg ccccaacagc agtgccagca acgcctcagg ggctgctgct cccacactcec 1020 cagcccaccc atccacgttg actcatcctc agagacgaat cgacaccctc aactcagatg 1080 gatacacccc tgagccagca cgcataacgt ccccagacaa accgeggccg atgeccatgg 1140 acacgagcgt gtatgagagc ccctacagcg acccagagga gctcaaggac aagaagctct 1200 tcctgaageg cgataacctc ctcatagctg acattgaact tggctgcgge aactttggcet 1260 cagtgcgcca gggcgtgtac cgcatgcgca agaagcagat cgacgtggecc atcaaggtge 1320 tgaagcaggg cacggagaag gcagacacgg aagagatgat gcgcgaggcg cagatcatge 1380 accagctgga caacccctac atcgtgegge tcattggecgt ctgccaggec gaggccctea 1440 tgetggtcat ggagatggct gggggegggc cgctgcacaa gttecctggtc ggcaagaggg 1500 aggagatccc tgtgagcaat gtggccgage tgctgcacca ggtgtccatg gggatgaagt 1560 acctggagga gaagaacttt gtgcaccgtg acctggcggce ccgcaacgtce ctgctggtta 1620 accggcacta cgccaagatc agcgactttg geoctctcocaa agcactgggt geccgacgaca 1680 gctactacac tgcccgctca gcagggaagt ggccgctcaa gtggtacgca cccgaatgcea 1740 tcaacttccg caagttctcc agccgcageg atgtcetggag ctatggggtc accatgtggg 1800 aggccttgte ctacggccag aagccctaca agaagatgaa agggccggag gtcatggect 1860 tcatcgagca gggcaagcgg atggagtgcc caccagagtg tccacccgaa ctgtacgcac 1820 tcatgagtga ctgctggatc tacaagtggg aggatcgccc cgactteoctg accgtggage 1880 agcgcatgcg agcctgttac tacagecctgg ccagcaaggt ggaagggecc ccaggcagca 2040 cacagaaggc tgaggctgcc tgtgcctgag ctccegctgce ccaggggage cctccacgec 2100 ggctcttccc caccctcage cccaccecag gtcctgcagt ctggctgage cctgettggt 2160 tgtctccaca cacagctggg ctgtggtagg gggtgtctca ggccacaccg gccttgcatt 2220 gcectgectgg cccectgtee tcteotggetg gggagcaggg aggtccggga gggtgegget 2280 gtgcagcctg tcecctgggectg gtggcectceceg gagggccctg agctgaggge attgcttaca 2340 cggatgcctt cccctgggec ctgacattgg agcctgggeca tcectcaggtg gtcaggegta 2400 gatcaccaga ataaacccag cttccctctt gaaaaaaaaa aaaaaaaaaa aacc 2454 <210> 2818 <211> 2761 <212> DNA <213> Homo sapiens <400> 2818 agaggacgcc cggtgaaggg gctccagcect ggcagtttct gegtgttage atttctagaa 60 tagagtgggt gggaactgac ccaagtaaag tcccagagac tcgaacactg acgcacagga 120 aagcctcaag:-tgggaggaga aatgcaaatc ccctactgat gatggcgtca gecggctttcet 180 cctagggact gtgaggggcg cttctgactt tggacttgag cactgcctgg gacctgtget 240 gagagagcgc tagcatgtct cagtggaatc aagtccaaca gttagaaatc aagtttttgg 300 agcaggtgga tcaattctat gatgacaact ttcccatgga aattcggcat ctgttggccce 360 aatggattga aaatcaagac tgggaggcag cttctaacaa tgaaaccatg gcaacgattc 420 ttcttcaaaa cttgttaata caactggatg aacagttagg tcgtgtttcc aaagagaaaa 480 acctactctt gatacacaat ctaaaaagaa ttaggaaggt ccttcaggga aaatttcatg 540 gaaatccaat gcatgtagct gtggttattt caaactgttt aagggaagag aggagaatat 600 tggctgcagc caacatgcct gtccaggggce ctctagagaa atccttacaa agttcttcag 660 tttcagaaag acagaggaat gtggagcaca aagtggctgc cattaaaaac agtgtgcaga 720 tgacagaaca agataccaaa tacttagaag atctgcaaga cgaatttgac tacaggtata 780 aaacaattca gacaatggat cagagtgaca agaatagtgc catggtgaat caggaagttt 840 tgacactgca ggaaatgctt aacagcctcg atttcaagag aaaggaggct ctcagtaaaa 800 tgacccaaat catccatgag acagacctgt taatgaacac catgctcata gaagagctgc 960 aagactggaa gcggcggcag caaatcgcct gcatcggggg tccactceccac aatgggctceg 1020 accagcttca gaactgcttt acactattgg cagaaagtct tttccaactg agaaggcaat 1080 tggagaaact agaggagcaa tctaccaaaa tgacatatga aggtgatccc attccaatgce 1140 aaagaactca catgctagaa agagtcacct tcttgatcta caaccttttc aagaactcat 1200 ttgtggttga gcgacagcca tgtatgccaa cccaccctca gaggccgttg gtacttaaaa 1260 ccctaattca gttcactgta aaactaaggc tactaataaa attgccagaa ctaaactatce 1320 aggtaaaggt taaggcatca attgacaaga atgtttcaac tctaagcaac cgaagatttg 1380 tactttgtgg aactaatgtc aaagccatgt ctattgaaga atcttccaat gggagtctct 1440 cagtagaatt tcgacatttg caaccaaagg aaatgaagtc cagtgctgga ggtaaaggaa 1500 atgagggctg tcacatggtg actgaagaac ttcattccat aacgtttgaa acacagatct 1560 gcetctatgg cctgaccata gatttggaga ccagctcatt gocctgtggtg atgatttcca 1620 atgtcagtca gttacctaat gcttgggcat ccatcatttg gtacaacgtg tcaaccaacg 1680 attcccagaa cttggttttc tttaataatc ctccacctge cacattgagt caactactgg 1740 aggtgatgag ctggcagttt tcatcgtacg ttggtcgtgg tcttaactca gatcaactcc 1800 atatgctggc agagaagctt acagtccaat ctagctacag tgatggtcac ctcacctggg 1860 ccaagttctg caaggaacat ttacctggta aatcatttac cttttggaca tggcttgaag 1920 caatattgga tctaattaag aaacacattc ttcccctttg gattgatggg tatgtcatgg 1980 gectttgttag caaagagaag gaacggctgt tgctaaagga taaaatgcct ggcacctttt 2040 tattaagatt cagtgaaagc catctcggag gaataacttt cacctgggtg gaccattctg 2100 aaagtgggga agtgagattc cactctgtag aaccctacaa taaaggccgg ttgtctgctc 2160 tgccattcge tgacatcctg cgagactaca aagttattat ggctgaaaac attcctgaaa 2220 accctctgaa gtacctatat cctgacatte ccaaagacaa agccttcggt aaacactaca 2280 gctctcagcc ttgcgaagtt tcaagaccaa cagaaagggg tgacaaaggt tatgttcectt 2340 ctgtttttat ccccatctca acaatccgaa gtgattcaac agagccacat tctccatcag 2400 accttcttcc catgtctcca agtgtgtatg cggtgttgag agaaaacctg agtcccacaa 2460 caattgaaac tgcaatgaag tctccttatt ctgctgaatg acaggataaa ctctgacgca 2520 ccaagaaagg aagcaaatga aaaagtttaa agactgttct ttgcccaata accacatttt 2580 atttcttcag ctttgtaaat accaggttct aggaaatgtt tgacatctga agctctctte 2640 acactcccgt ggcactcctc aattgggagt gttgtgactg aaatgcttga aaccaaagct 2700 tcagataaac ttgcaagata agacaacttt aagaaaccag tgttaataac aatattaaca 2760 g a. 2761 <210> 281% <211> 1190 <212> DNA <213> Homo sapiens <400> 2819 .

cagatccatc aggtccgagc tgtgttgact accacttttc ccttegtetce aattatgtct 60 tggaaaaagg ctttgcggat ccccggaggc cttcgggcag caactgtgac cttgatgetg 120 tcgatgctga gcaccccagt ggctgaggge agagactcte ccgaggattt cgtgtaccag 180 tttaagggca tgtgctactt caccaacggg acagagcgcg tgcgtcttgt gagcagaagce 240 atctataacc gagaagagat cgtgcgcttc gacagcgacg tgggggagtt ccgggeggtg 300 acgctgctgg ggctgectge cgecgagtac tggaacagcc agaaggacat cctggagagg 360 aaacgggcgg cggtggacag ggtgtgcaga cacaactacc agttggagct ccgcacgacce 420 ttgcagecgge gagtggagcc cacagtgacc atctccccat ccaggacaga ggecctcaac 480 caccacaacc tgectggtctg ctcggtgaca gatttctatc cagcccagat caaagtccgg 540 tggtttcgga atgaccagga ggagacagct ggcgttgtgt ccacccccct tattaggaat 600 ggtgactgga ccttccagat cctggtgatg ctggaaatga ctccccageg tggagacgtce 660 tacacctgcc acgtggagca ccccagecctc cagagccecca tcaccgtgga gtggcgggct 720 caatctgaat ctgcccagag caagatgctg agtggcattg gaggcttcecgt gctgaggetg 780 atcttecctecg ggectgggect tatcatccat cacaggagtc agaaagggct cctgcactga 840 ctecctgagac tattttaact gggattggtt atcacttttc tgtaacgcct gettgtcect 900 gcccagaatt cccagctgtc tgtgtcagce tgtcccectg agatcagagt cctacagtgg 960 ctgtcacgca gccaccaggt catctccttt catccccacec ttgaggcgga tggctgtgac 1020 cctacttcet gcactgacec acagcctetg cctgtgcacg gccagctgca tctactcagg 1080 ccccaagggg tttcectgttte tattctctee tcagactgect caagagaagce acatgaaaac 1140 cattacctga ctttagagct tttttacata attaaacatg atcctgagtt 1190 <210> 2820 <211> 3003 <212> DNA <213> Homo sapiens <400> 2820 . tcggggagag aagctggact gcagctggtt tcaggaactt ctcttgacga gaagagagac 60 caaggaggec aagcaggggce tgggccagag gtgccaacat ggggaaactg aggctcecgget 120 cggaaaggtg aagtaacttg tccaagatca caaagctggt gaacatcaag ttggtgctat 180 ggcaaggctg ggaaactgca gcctgacttg ggectgccctg atcatcctge tgctccoceccgg 240 aagtctggag gagtgcgggc acatcagtgt ctcagccceccc atcgtccacce tgggggatcece 300 catcacagcc tcctgcatca tcaagcagaa ctgcagccat ctggacccgg agecacagat 360 tctgtggaga ctgggagcag agcttcagecc cgggggcagg cagcagcgte tgtctgatgg 420

1154 So gacccaggaa tctatcatca ccctgcccca cctcaaccac actcaggcct ttctctectg 480 ctgcctgaac tggggcaaca gcctgcagat cctggaccag gttgagctgec gcgcaggcta 540 ccctccagece ataccccaca acctcectectg cctcatgaac ctcacaacca gcagcctcat 600 ctgccagtgg gagccaggac ctgagaccca cctacccacc agcttcactc tgaagagttt 660 caagagccgg ggcaactgtc agacccaagg ggactccatc ctggactgcg tgcccaagga 720 cgggcagagc cactgctgca tcccacgcaa acacctgetg ttgtaccaga atatgggcat 780 ctgggtgcag gcagagaatg cgctggggac cagcatgtcc ccacaactgt gtecttgatec 840 catggatgtt gtgaaactgg agccccccat gctgcggacc atggacccca gccctgaage 900 ggcccectece caggcaggcet gectacaget gtgctgggag ccatggcagc caggectgca 960 cataaatcag aagtgtgagc tgcgccacaa gccgcagcegt ggagaagcca gctgggcact 1020 ggtgggccce ctcccecttgg aggcccttca gtatgagetc tgecgggctec tcccagccac 1080 ggcctacace ctgcagatac gctgcatccg ctggeccccetg cctggeccact ggagcgactg 1140 gagccccagc ctggagctga gaactaccga acgggccccec actgtcagac tggacacatg 1200 gtggcggcag aggcagctgg accccaggac agtgcagctg ttctggaagc cagtgeccct 1260 ggaggaagac agcggacgga tccaaggtta tgtggtttct tggagaccct caggccaggce 1320 tggggeccatc ctgccectcect gcaacaccac agagctcagce tgcaccttec acctgectte 1380 agaagcccag gaggtggccce ttgtggecta taactcagcce gggacctcte gtcccactece 1440 ggtggtcttc tcagaaagca gaggcccagc tctgaccaga ctccatgcca tggcccgaga 1500 ccctcacagec ctctgggtag gctgggagec ccccaatcca tggectcagg getatgtgat 1560 tgagtggggc ctgggcccee ccagcgcgag caatagcaac aagacctgga ggatggaaca 1620 gaatgggaga gccacggggt ttctgctgaa ggagaacatc aggccctttc agctctatga 1680 gatcatcgtg actcccttgt accaggacac catgggaccc tcccagcatg tctatgecta 1740 ctctcaagaa atggctcecct cccatgccecc agagctgcat ctaaagcaca ttggcaagac 1800 ctgggcacag ctggagtggg tgcctgagcc ccctgagetg gggaagagcece cccttaccca 1860 ctacaccatc ttctggacca acgctcagaa ccagtcctte tccgccatee tgaatgecte 1920 ctcecegtgge tttgtcecctee atggectgga geccgcecagt ctgtatcaca tccacctcat 1980 ggctgecage caggctgggg ccaccaacag tacagtcctc accctgatga ccttgaccce 2040 agaggggtcg gagctacaca tcatcctggg cctgttecgge ctcctgctgt tgctcacctg 2100 cctetgtgga actgcctgge tctgttgcag ccccaacagg aagaatcccee tctggccaag 2160 tgtcccagac ccagctcaca gcagectggg ctectgggtg cccacaatca tggaggagga 2220 tgccttccag ctgccecggee ttggcacgcec acccatcacc aagctcacag tgctggagga 2280 ggatgaaaag aagccggtgc cctgggagtc ccataacagc tcagagacct gtggecteec 2340 cactctggtc cagacctatg tgctccaggg ggacccaaga gcagtttcca cccagccecceca 2400 atcccagtct ggcaccagcg atcaggtect ttatgggcag ctgctgggca gccccacaag 2460 cccagggeca gggcactatc tccgctgtga ctccactcag ccectettgg cgggcctcac 2520 cceccagecee aagtcectatg agaacctcetg gttceccaggece agcccecttgyg ggacectggt 2580 daccccagec ccaagccagg aggacgactg tgtctttggg ccactgetca acttcceect 2640 cctgcagggg atccgggtcc atgggatgga ggcgcectgggg agcttctagg gcttectgag 2700 gttcccttet tgggcctgee tcttaaagge ctgagctagc tggagaagag aggagggtec 2760 ataagcccat gactaaaaac taccccagcc caggctctca ccatctccag tcaccagcat 2820 ctcecctetec tcccaatcte cataggetgg goctcccagg cgatctgeat actttaagga 2880 ccagatcatg ctccatccag ccccacccaa tggcettttg tgecttgttte ctataacttc 2940 AQLATLgEAS actagttttt ggtttgcagt ttttgttgtt gtttatagac actcttgggt 3000 gta 3003 <210> 2821 <211l> 718 <212> DNA <213> Homo sapiens <400> 2821 ttaagcaaag gaaaccaaag gaatcgttte aaatggactc atggcttaga aatcetttatt 60 cttagggcag tcagtagtat tctaaagcett tctgacaaga taaaggaagt caccaaaatt 120 tcttttttta aattgtatct aatcctcaac aacaaaccaa aacagaacaa ttaaacagcc 180 aaataaaacc tcagggacaa catttttggt gtatttgagc cctecccagca agtttcacct 240 tgggtttgta ttttaaatgt tttacaagaa ttgtccatgt gcttcectag gctgagetgg 300 cattggtctg ctgacctgtt tttgtgtttt tctttttttt atacacaaca tttatttcaa 360 actattggga gggatgagag tggcttaaaa acttccatcc ctacttttca agagtgcagt 420 tgattctgaa tctgaaagce cgcctctgtc ctaaaataca aacCaagcaca gacattaaac 480 ctggatacta tatgataaag agggatgtaa ctattgaatt ggatacaagg atcagaatgg 540 aaagaaactc acgatgaaat tgaacctggt ttttgratat ttatcaaact tgtgctgaga 600 atagtgtctg attatacgac ttttaagcaa agttgggtgt aattaggtga aaacagccca 660 ggtcctccecg ggagcacaga ggggctaggg gcotggteett ctegtttget ctagtett 718 <210> 2822 <211> 2776

<212> DNA

<213> Homo sapiens

<400> 2822 cagggcagac tggtagcaaa gcccccacge ccagccagga gcaccgeccge ggactccage 60 acaccgaggg acatgctggg cctgcgecec ccactgctcg ccetggtggg geotgetctec 120 ctcgggtgeg tectctctca ggagtgcacg aagttcaagg tcagcagctg ccgggaatgc 180 atcgagtcgg ggecceggetg cacctggtgc cagaagctga acttcacagg gccgggggat 240 cctgactcca ttcgectgecga cacccggeea cagctgctca tgaggggcetg tgcggctgac 300 gacatcatgg accccacaag cctcgctgaa acccaggaag accacaatgg gggccagaag 360 cagctgtcec cacaaaaagt gacgctttac ctgcgaccag gccaggcage agcgttcaac 420 gtgaccttcc ggcgggccaa gggctacccc atcgacctgt actatctgat ggacctctcce 480 tactccatge ttgatgacct caggaatgtc aagaagctag gtggcgacct gctccgggcce 540 ctcaacgaga tcaccgagtc cggccgcatt ggcttegggt ccttegtgga caagaccgtg 600 ctgccgttcg tgaacacgca ccctgataag ctgcgaaacc catgccccaa caaggagaaa 660 gagtgccagc ccccgtttge cttcaggeac gtgctgaagc tgaccaacaa ctccaaccag 720 tttcagaccg aggtcgggaa gcagctgatt tceggaaacc tggatgcacc cgagggtggg 780 ctggacgcca tgatgcaggt cgccgectge ccggaggaaa tcggectggeg caacgtcacg 840 cggctgetgg tgtttgccac tgatgacgge ttecattteg cgggcgacgg aaagctggge S00 gccatcctga ccecccaacga cggecgetgt cacctggagg acaacttgta caagaggagc 960 aacgaattcg actacccatc ggtgggccag ctggcgcaca agctggctga aaacaacatc 1020 cagcccatct tcgeggtgac cagtaggatg gtgaagacct acgagaaact caccgagatc 1080 atccccaagt cagccgtggg ggagctgtct gaggactcca gcaatgtggt ccatctcatt 1140 aagaatgctt acaataaact ctcctecagg gtcttcctgg atcacaacge cetccccgac 1200 accctgaaag tcacctacga ctccttctge agcaatggag tgacgcacag gaaccagecc 1260 agaggtgact gtgatggcgt gcagatcaat gtcccgatca ccttccaggt gaaggtcacg 1320 gccacagagt gcatccagga gcagtcogttt gtcatccggg cgctgggett cacggacata 1380 gtgaccgtge aggttcttce ccagtgtgag tgcecggtgec gggaccagag cagagaccgc 1440 agcctctgce atggcaaggg cttettggag tgcggcatet gcaggtgtga cactggctac 1500 attgggaaaa actgtgagtg ccagacacag ggccggagca gccaggagct ggaaggaagc 1560 tgccggaagg acaacaactc catcatctgc tcagggctgg gggactgtgt ctgcgggcag 1620 tgcctgtgee acaccagcga cgtccecegge aagctgatat acgggcagta ctgcgagtgt 1680 gacaccatca actgtgagcg Ctacaacggc caggtctgceg gcggccecggg gagggggcte 1740 tgcttctgeg ggaagtgceccg ctgccacceg ggctttgagg gctcagegtg ccagtgcgag 1800 aggaccactg agggctgcct gaacccgegg cgtgttgagt gtagtggtcg tggccggtge 1860 cgctgcaacg tatgcgagtg ccattcaggc taccagctgc ctctgtgeca ggagtgcccee 1920 ggctgccect caccctgtgg caagtacatc tcctgegecg agtgcctgaa gttcgaaaag 1980 ggcccctttg ggaagaactg cagcgeggeg tgtccgggec tgcagcotgte gaacaaccce 2040 gtgaagggca ggacctgcaa ggagagggac tcagagggct gctgggtggce ctacacgctg 2100 gagcagcagg acgggatgga ccgctacctc atctatgtgg atgagagccg agagtgtgtg 2160 gcaggeccca acatcgeege catcegtcggg ggcaccgtgg caggcategt gotgategge 2220 attctcctge tggtcatctg gaaggctctg atccacctga gcgaccteccg ggagtacagg 2280 cgctttgaga aggagaagct caagtcccag tggaacaatg ataatcccct tttcaagagce 2340 gccaccacga cggtcatgaa ccccaagttt getgagagtt aggagcactt ggtgaagaca 2400 aggccgtcag gacccaccat gtctgcccca tcacgeggec gagacatgge ttggccacag 2460 ctcttgagga tgtcaccaat taaccagaaa tccagttatt ttcegeecte aaaatgacag 2520 ccatggccgg ceggtgettc tgggggecteg teggggggac agctccacte tgactggcac 2580 agtctttgca tggagacttg aggagggctt gaggttggtg aggttaggtg cgtgtttcct 2640 gtgcaagtca ggacatcagt ctgattaaayg gtggtgccaa tttatttaca tttaaacttg 2700 tcagggtata aaatgacatc ccattaatta tattgttaat caatcacgtg tatagaaaaa 2760 aaaataaaac ttcaat 2776 <210> 2823 <211> 4428 <212> DNA <213> Homo sapiens <400> 2823 aggtcacaga gcagtgataa ctacctgcca gtgtctctta ggagtgaggt acctggagtt 60 cggggacccc aacctgtgac aatgacagca gacaaattgg ttttotttgt gaatggcaga 120 aaggtggtgg agaaaaatgc agatccagag acaacccttt tggcctacct gagaagaaag 180 ttggggetga gtggaaccaa gectcggetgt ggagaggggg gctgcgggge ttgcacagtg 240 atgctctcca agtatgatcg tctgcagaac aagatcgtece acttttctge caatgcctgce 300 ctggccceca tctgetectt gecaccatgtt gcagtgacaa ctgtggaagg aataggaagc 360 accaagacga ggctgcatcce tgtgcaggag agaattgcca aaagccacgg ctcccagtgce 420 gggttctgca cccectggeat cgtcatgagt atgtacacac tgctccggaa tcagcecgag 480 cccaccatgg aggagattga gaatgccttc caaggaaatc tgtgcecgetg cacaggctac 540 agacccatce tccagggctt ccggaccttt gccagggatg gtggatgctg tggaggagat 600 gggaataatc caaattgctg catgaaccag aagaaagacc actcagtcag ccactcgeea 660 tctttattca aaccagagga gttcacgcce ctggatccaa cccaggagec catttttece 720 ccagagttgc tgaggctgaa agacactcct cggaagcagc tgcgatttga aagggagcgt 780 gtgacgtgga tacaggcctce aaccctcaag gagctgcectgg acctcaagge tcagcacccet 840 gacgccaagc tggtcgtggg gaacacggag attggcattg agatgaagtt caagaatatg 900 ctgttteccta tgattgtctg cccagectgg atccctgage tgaattcggt agaacatgga 960 cccgacggta tcteoctttgg agetgettge ccectgagea ttgtggaaaa aaccctggtg 1020 gatgctgttg ctaagcttce tgcccaaaag acagaggtgt tcagaggggt cctggagcag 1080 ctgcgetggt ttgctgggaa gcaagtcaag tetgtggegt ccgttggagg gaacatcatc 1140 : actgccagce ccatctcega cetcaaccoe gtgttcatgg ccagtggggc caagctgaca 1200 ctagtgtcca gaggcaccag gagaactgte cagatggacc acaccttctt cectggctac 1260 agaaagaccc tgctgagccc ggaggagata ctgctctcca tagagatcee ctacagcagg 1320 gagggggagt atttctcagce attcaagcag gectcccgga gagaagatga cattgccaag 1380 gtaaccagtg gcatgagagt tttattcaag ccaggaacca cagaggtaca ggagctggcc 1440 ctttgctatg gtggaatggc caacagaacc atctcagecc tcaagaccac tcagaggcag 1500 ctttccaagc tctggaagga ggagctgetg caggacgtgt gtgcaggact ggcagaggag 1560 ctgcatctgc ctcccgatge ccctggtgge atggtggact tcecggtgcac cctcaccectce 1620 agcttcttet tcaagttcta cctgacagtc cttcagaagc tgggccaaga gaacctggaa 1680 gacaagtgtg gtaaactgga ccccactttc gecagtgcaa ctttactgtt tcagaaagac 1740 cccccageccg atgtccaget cttccaagag gtgcccaagg gtcagtctga ggaggacatg 1800 gtgggccggce ccctgeccca cctggcagcg gacatgcadgg cctctggtga ggccgtgtac 1860 tgtgacgaca ttcctcgcta cgagaatgag ctgtctctcce ggctggtcac cagcacccgg 1820 gcccacgcea agatcaagtce catagataca tcagaagcta agaaggttec agggtttgtt 1980 tgtttcattt ccgctgatga tgttcectggg agtaacataa ctggaatttg taatgatgag 2040 acagtctttg cgaaggataa ggttacttgt gttgggcata tcattggtge tgtggttget 2100 gacaccccgg aacacacaca gagagctgcc caaggggtga aaatcaccta tgaagaacta 2160 ccagccatta tcacaattga ggatgctata aagaacaact ccttttatgg acctgagctg 2220 aagatcgaga aaggggacct aaagaagggg ttttccgaag cagataatgt tgtgtcaggg 2280 gagatataca tcggtggcca agagcacttce tacctggaga ctcactgcac cattgctgtt 2340

Ccaaaaggcg aggcagggga gatggagctc tttgtgtcta cacagaacac catgaagacc 2400 cagagctttg ttgcaaaaat gttgggggtt ccagcaaacc ggattgtggt tcgagtgaag 2460 agaatgggag gaggctttgg aggcaaggag acccggagca ctgtggtgtce cacggcagtg 2520 gccctggetg catataagac cggecgcect gtgcgatgea tgctggacceg tgatgaggac 2580 atgctgataa ctggtggcag acatcccttce ctggccagat acaaggttgg cttcatgaag 2640 actgggacag ttgtggctct tgaggtggac cacttcagca atgtggggaa cacccaggat 2700 ctctctcaga gtattatgga acgagcttta ttccacatgg acaactgcta taaaatcccec 2760 aacatccggg gcactgggeg geotgtgcaaa accaacctte cctccaacac ggcctteegg 2820 ggctttgggg ggccccaggg gatgctcatt goccgagtgcet ggatgagtga agttgcagtg 2880 acctgtggga tgcctgcaga ggaggtgcgg agaaaaaacce tgtacaaaga aggggacctg 2940 acacacttca accagaagct tgagggtttc accttgecca gatgctggga agaatgccta 3000 gcaagctctc agtatcatge tcggaagagt gaggttgaca agttcaacaa ggagaattgt 3060 tggaaaaaga gaggattgtg cataattccc accaagtttg gaataagctt cacagttcct 3120 tttctgaate aggcaggagce cctacttcat gtgtacacag atggctctgt gctgctgacce 3180 cacgggggga ctgagatggg ccaaggcctt cataccaaaa tggtccaggt ggccagtaga 3240 gctctgaaaa tcecccacctc taagatttat atcagcgaga caagcactaa cactgtgccce 3300 aacacctctc ccacggctge ctctgtcage getgacctcea atggacaggc cgtctatgcg 3360

( gettgtcaga ccatcttgaa aaggctggaa ccctacaaga agaagaatcc cagtggctce 3420 tgggaagact gggtcacagc tgcctacatg gacacagtga gcttgtctge cactgggttt 3480 tatagaacac ccaatctggg Ctacagcttt gagactaact cagggaaccyg cttccactac 3540 ttcagctatg gggtggcttg ctctgaagta gaaatcgact gcctaacagg agatcataag 3600 aaccteccgca cagatattgt catggatgtt ggctccagte taaaccctgce cattgatatt 3660 ggacaggtgg aaggggcatt tgtccaggge cttggcctct tcacectaga ggagctacac 3720 tattcccccg aggggagect gcacaccegt ggccctagca cctacaagat cccggcattt 3780 ggcagcatce ccattgagtt cagggtgtcc ctgctccgeg actgccccaa caagaaggcec 3840 atctatgcat cgaaggctgt tggagagccg cccctettee tggectgette tatcttettt 3900 gccatcaaag atgccatceg tgcagetcga goctcagcaca caggtaataa cgtgaaggaa 3960 ctcttccgee tagacagcec tgecaccccg gagaagatcece gcaatgcctg cgtggacaag 4020 ttcaccacce tgtgtgtcac tggtgtccca gaaaactgca aaccctggte tgtgagggtc 4080 taaagagaga gtcctcagca gagtcttctt gtgectgectt tgggcttceca tggagcagga 4140 ggaacatacc acagaacatg gatctattaa agtcacagaa tgacagacct gtgatttgte 4200 aagatgggat ttggaagaca agtgaatgca atggaagatt ttgatcaaaa atgtaatttg 4260 taaacacaat gataagcaaa ttcaaaactg ttatgcctaa atggtgaata tgcaattagg 4320 atcattttct gtctgtttta atcatgtatc tggaataggg tcgggaaggg tttgtgctat 4380 tccccactta ctggacagce tgtataacct caaaaaaaaa aaaaaaaa 4428 <210> 2824 . <211> 1702 <212> DNA <213> Homo sapiens <400> 2824 aaattttcca gccgatcact ggagctgact tccgcaatcc cgatggaata aatctagcac 60 ccctgatggt gtgecccacac tttgctgecg aaacgaagec agacaacaga tttccatcag 120 caggatgtgg gggctcaagg ttctgctget acctgtggtg agctttgctc tgtaccctga 180 ggagatactg gacacccact gggagctatg gaagaagacc cacaggaagc aatataacaa 240 caaggtggat gaaatctctc ggecgtttaat ttgggaaaaa aacctgaagt atatttccat 300 ccataacctt gaggcttctc ttggtgtcca tacatatgaa ctggctatga accacctggg 360 ggacatgacc agtgaagagg tggttcagaa gatgactgga ctcaaagtac ccctgtctca 420 ttcececgecagt aatgacaccc tttatatcee agaatgggaa ggtagagccc cagactctgt 480 cgactatcga aagaaaggat atgttactcc tgtcaaaaat cagggtcagt gtggttcctg 540 ttgggectttt agectctgtgg gtgocectgga gggccaactc aagaagaaaa ctggcaaact 600 cttaaatctg agtccccaga acctagtgga ttgtgtgtect gagaatgatg gctgtggagg 660 gggctacatg accaatgcct tccaatatgt gcagaagaac cggggtattg actctgaaga 720 tgcctaccca tatgtgggac aggaagagag ttgtatgtac aacccaacag gcaaggcagce 780 taaatgcaga gggtacagag agatccccga ggggaatgag aaagccctga agagggcagt 840 ggcccgagtg ggacctgtct ctgtggccat tgatgcaagc ctgacctect tccagtttta 900 cagcaaaggt gtgtattatg atgaaagctg caatagcgat aatctgaacc atgcggtttt 960 ggcagtggga tatggaatcc agaagggaaa caagcactgg ataattaaaa acagctgggg 1020 agaaaactgg ggaaacaaag gatatatcct catggctcga aataagaaca acgcctgtgg 1080 cattgccaac ctggccagct tccocccaagat gtgactccag ccagccaaat ccatcctgcet 1140 cttccatttc ttccacgatg gtgcagtgta acgatgcact ttggaaggga gttggtgtgce 1200 tatttttgaa gcagatgtgg tgatactgag attgtctgtt cagtttcccce atttgtttgt 1260 gcttcaaatg atccttcecta ctttgcttect ctccacccat gacctttttc actgtggcca 1320 tcaggacttt ccctgacagc tgtgtactct taggctaaga gatgtgacta cagcctgccec 1380 ctgactgtgt tgtcccaggg ctgatgctgt acaggtacag gectggagatt ttcacatagg 1440 ttagattctc attcacggga ctagttagct ttaagcaccce tagaggacta gggtaatctg 1500 acttctcact tcctaagttc ccttctatat cctcaaggta gaaatgtcta tgttttctac 1560 tccaattcat aaatctattc ataagtcttt ggtacaagtt tacatgataa aaagaaatgt 1620 gatttgtctt cccttctttg cacttttgaa ataaagtatt tatctcctgt ctacagttta 1680 ataaatagca tctagtacac at \ 1702 <210> 2825 <211> 2771 <212> DNA <213> Homo sapiens <400> 2825 cgaggcggat cgggtgttgc atccatggag cgagctgaga gctcgagtac agaacctget 60 aaggccatca aacctattga tcggaagtca gtccatcaga tttgctctgg gcaggtggta 120 ctgagtctaa gcactgecggt aaaggagtta gtagaaaaca gtctggatgce tggtgccact 180 aatattgatc taaagcttaa ggactatgga gtggatctta ttgaagtttc agacaatgga 240 tgtggggtag aagaagaaaa cttcgaaggc ttaactctga aacatcacac atctaagatt 300 caagagtttg ccgacctaac tcaggttgaa acttttggct ttcgggggga agctctgage 360 tcactttgtg cactgagcga tgtcaccatt tctacctgec acgcatcgge gaaggttgga 420 actcgactga tgtttgatca caatgggaaa attatccaga aaacccecta cceecegecce 480 agagggacca cagtcagcegt gcagcagtta ttttccacac tacctgtgeg ccataaggaa 540 tttcaaagga atattaagaa ggagtatgcc aaaatggtec aggtcttaca tgcatactgt 600 atcatttcag caggcatccg tgtaagttgc accaatcagc ttggacaagg aaaacgacag 660 cctgtggtat gcacaggtgg aagccccagc ataaaggaaa atatcggctc tgtgtttggg 720 cagaagcagt tgcaaagcct cattcctttt gttcagctge cccctagtga ctcegtgtgt 780 gaagagtacg gtttgagctg ttcggatgct ctgcataatc ttttttacat ctcaggtttce 840 atttcacaat gcacgcatgg agttggaagg agttcaacag acagacagtt tttctttatc 900 aaccggeggce cttgtgaccc agcaaaggtc tgcagactcg tgaatgaggt ctaccacatg 960 tataategac accagtatcc atttgttgtt cttaacattt ctgttgattc agaatgcgtt 1020 gatatcaatg ttactccaga taaaaggcaa attttgctac aagaggaaaa gcttttgttg 1080 gcagttttaa agacctcttt gataggaatg tttgatagtg atgtcaacaa gctaaatgtc 1140 agtcagcagc cactgctgga tgttgaaggt aacttaataa aaatgcatgc agcggatttg 1200 gaaaagccca tggtagaaaa gcaggatcaa tcecccttcat taaggactgg agaagaaaaa 1260

1162 , So aaagacgtgt ccatttccag actgcgagag geccttttcte ttcgtcacac aacagagaac 1320 aagcctcaca gcccaaagac tccagaacca agaaggagcc ctctaggaca gaaaaggggt 1380 atgctgtctt ctagcacttec aggtgccatc tctgacaaag gecgtectgag acctcagaaa 1440 gaggcagtga gttccagtca cggacccagt gaccctacgg acagagcgga ggtggagaag 1500 gactcgggge acggcagcac ttccgtggat tctgaggggt tcagcatccc agacacggge 1560 agtcactgca gcagcgagta tgcggecage tccccagngy acaggggctc gcaggaacat 1620 gtggactctc aggagaaagc gcctgaaact gacgactctt tttcagatgt ggactgccat 1680 tcaaaccagg aagataccgg atgtaaattt cgagttttgc ctcagccaac taatctcgca 1740 accccaaaca caaagcgttt taaaaaagaa gaaattcttt ccagttctga catttgtcaa 1800 aagttagtaa atactcagga catgtcagcc tctcaggttg atgtagctgt gaaaattaat 1860 aagaaagttg tgcccctgga cttttcetatg agttctttag ctaaacgaat aaagcagtta 1820 catcatgaag cacagcaaag tgaaggggaa cagaattaca ggaagtttag ggcaaagatt 1980 tgtcctggag aaaatcaagce agccgaagat gaactaagaa aagagataag taaaacgatg 2040 tttgcagaaa tggaaatcat tggtcagttt aacctgggat ttataataac caaactgaat 2100 gaggatatct tcatagtgga ccagcatgcc acggacgaga agtataactt cgagatgctg 2160 cagcagcaca ccgtgctcca ggggcagagg ctcatagcac ctcagactct caacttaact 2220 gctgttaatg aagctgttct gatagaaaat ctggaaatat ttagaaagaa tggctttgat 2280 tttgttatcg atgaaaatgc tccagtcact gaaagggcta aactgatttce cttgccaact 2340 agtaaaaact ggaccttcgg accccaggac gtcgatgaac tgatcttcat gctgagcgac 2400 agccctgggg tcatgtgccg gecttecccga gtcaagcaga tgtttgecte cagagcctgc 2460 cggaagtcgg tgatgattgg gactgctctt aacacaagcg agatgaagaa actgatcacc 2520 cacatggggg agatggacca cccctggaac tgtccccatg gaaggccaac catgagacac 2580 atcgccaacc tgggtgtcat ttctcagaac tgaccgtagt cactgtatgg aataattggt 2640 tttatcgcag atttttatgt tttgaaagac agagtcttca ctaacctttt ttgttttaaa 2700 atgaaacctg ctacttaaaa aaaatacaca tcacacccat ttaaaagtga tcttgagaac 2760 cttttcaaac ¢ 2771 <210> 2826 <211> 3682 <212> DNA <213> Homo sapiens <400> 2826 gcgagcgcag cggagectgg agagaaggcg ctgggctgeg agggegcgag ggcgcgaggg 60 cagggggcaa ccggacceccg cccgcaccea tggegeeegt cgeegtetgg geccgegetgg 120 ccgtcggact ggagctctgg gctgcggege acgccttgec ¢gcccaggtyg gcatttacac 180 cctacgccce ggagcccggg agcacatgcc ggctcagaga atactatgac cagacagctce 240 agatgtgctg cagcaaatgce tcgecgggee aacatgcaaa agtcttctgt accaagacct 300 cggacaccgt gtgtgactcc tgtgaggaca gcacatacac ccagctctgg aactgggttc 360 ccgagtgcett gagctgtgge tcccgetgta gctctgacca ggtggaaact caagcctgca 420 ctcgggaaca gaaccgcatc tgcacctgea ggcccggetg gtactgegeg ctgagcaage 480 aggaggggtg ccggetgtge gegecgetge gcaagtgcecg ccegggcette ggcgtggcca 540 gaccaggaac tgaaacatca gacgtggtgt gcaagccctg tgccecgggg acgttctceca 600 acacgacttc atccacggat atttgcaggc cccaccagat ctgtaacgtg gtggccatcc 660 ctgggaatgc aagcatggat gcagtctgca cgtccacgtc ccccaccegg agtatggecce 720 caggggcagt acacttacce cagccagtgt ccacacgatc ccaacacacg cagccaacte 780 cagaacccag cactgctcca agcacctect tectgcteec aatgggccecc agcccecccag 840 ctgaagggag cactggcgac ttecgctctte cagttggact gattgtgggt gtgacagcct 900 tgggtctact aataatagga gtggtgaact gtgtcatcat gacccaggtg aaaaagaagc 260 ccttgtgect gcagagagaa gccaaggtgc ctcacttgcee tgccgataag goceccggggta 1020 cacagggccc cgagcagcag cacctgctga tcacagcgec gagectccage agcagctccce 1080 tggagagctce ggecagtgeg ttggacagaa gggcgeccac tcggaaccag ccacaggcac 1140 caggcgtgga ggccagtggg gccggggagg cccgggcceag caccgggagce tcagattcett 1200 cccectggtgg ccatgggace caggtcaatg tcacctgcat cdtgaacgtc tgtagcagcet 1260 ctgaccacag ctcacagtgce tecteccaag ccagetccac aatgggagac acagattcca 1320 gcccctegga gtecccecgaag gacgagcagg tccccttete caaggaggaa tgtgeccttte 1380 ggtcacagct ggagacgcca gagaccctgc tggggagcac cgaagagaag cccctgecceece 1440 ttggagtgce tgatgetggg atgaagccca gttaaccagg ccggtgtggg ctgtgtegta 1500 gccaaggtgg getgagecet ggcaggatga ccetgecgaag gggeccetggt ccttccagge 1560 ccccaccact aggactctga ggctctttet gggccaagtt cctctagtge cctecacage 1620 cgcagectece ctectgacctg caggecaaga gcagaggcag cgagttgtgg aaagcctctg 1680 ctgccatgge gtgtecctet cggaaggctg gctgggcatg gacgttecggg gcatgetggg 1740 gcaagtccect gactctctgt gacctgecece gcccagetge acctgccage ctggettctg 1800 gagcccttgg gttttttgtt tgtttgtttg tttgtttgtt tgtttctcecee cctgggetct 1860 1164 B gccccagecte tggcttccag aaaaccccag catccttttce tgcagagggg ctttctggag 1920 aggagggatg ctgcctgagt cacccatgaa gacaggacag tgcttcagecec tgaggctgag 1980 actgcgggat ggtcctgggg ctctgtgcag ggaggaggtg gcagccctgt agggaacggg 2040 gtccttcaag ttagctcagg aggcttggaa agcatcacct caggccaggt gcagtggcetc 2100 acgcctatga tcccagcact ttgggagget gaggcgggtg gatcacctga ggttaggagt 2160 tcgagaccag cctggccaac atggtaaaac cccatctcta ctaaaaatac agaaattagc 2220 €gggcgtggt ggcgggcacce tatagtccca gctactcaga agcctgaggc tgggaaatcg 2280 tttgaacceg ggaagcggag gttgcaggga gccgagatca cgccactgcea ctccagcctg 2340 ggcgacagag Cgagagtctg tctcaaaaga aaaaaaaaag caccgcctce asatgccaac 2400 ttgtcctttt gtaccatggt gtgaaagtca gatgcccaga gggeccaggce aggccaccat 2460 attcagtgct gtggectggg caagataacg cacttctaac tagaaatctg ccaatttttt 2520 aaaaaagtaa gtaccactca ggccaacaag ccaacgacaa agccaaactc tgccagccac 2580 atccaacccc ccacctgeca tttgcacect ccgecttcac tccggtgtge ctgcagcecc 2640 gcgectectt ccttgctgte ctaggccaca ccatctcectt tcagggaatt tcaggaacta 2700 gagatgactg agtcctcgta geccatctctc tactcctacc tcagectaga cectcctect 2760 cccccagagg ggtgggttee tcttcocccac tcecccacctt caattcetgg gecccaaacg 2820 ggctgeeoctg ccactttggt acatggeccag tgtgatccca agtgccagte ttgtgtctge 2880 gtctgtgttg cgtgtegtgg gtgtgtgtag ccaaggtcgg taagttgaat ggcctgcctt 25840 gaagccactg aagctgggat tcctcccecat tagagtcagce cttecccecte ccagggccag 3000 ggccctgcag aggggaaacc agtgtagect tgeccggatt ctgggaggaa gcaggttgag 3060 gggctcctgg aaaggctcag tctcaggage atggggataa aggagaaggc atgaaattgt 3120 ctagcagagc aggggcaggdg tgataaattg ttgataaatt ccactggact tgagcttgge 3180 agctgaacta ttggagggtg ggagagccca gccattacca tggagacaag aagggtttte 3240 caccctggaa tcaagatgtc agactggetg getgcagtga cgtgcacctg tactcaggag 3300 gctgagggga ggatcactgg agcccaggag tttgaggetg cagcgagcta tgatecgecgcece 3360 actacactcc agcctgagca acagagtgag accctgtcte ttaaagaaaa aaaaagtcag 3420 actgctggga ctggccaggt ttctgcccac attggaccca catgaggaca tgatggagcg 3480 cacctgccee ctggtggaca gtcctgggag aacctcaggce ttccttggca tcacagggca 3540 gagccgggaa gcgatgaatt tggagactct gtggggcctt ggttcccttg tgtgtgtgtg 3600 ttgatcccaa gacantgasa gtttgcactg tatgctggac ggcattcctg cttatcaata 3660 aacctgtttg ttttaaaaaa aa 3682

<210> 2827 <211> 2400 <212> DNA <213> Homo sapiens <400> 2827 taggatggaa aggcagatgt aaagtccctc atggcgaaat ataacacggg gggcaacccg 60 acagaggatg tctcagtcaa tagccgaccc ttcagagtca cagggccaaa ctcatcttca 120 ggaatacaag caagaaagaa cttattcaac aaccaaggaa atgccagccc tcctgcagga 180 cccagcaatg tacctaagtt tgggtcccca aagccacctg tggcagtcaa accttcttcet 240 gaggaaaagc ctgacaagga acccaagccce ccgtttctaa agcccactgg agcaggccaa 300 agattcggaa caccagccag cttgaccacce agagaccccg aggcgaaagt gggatttctg 360 aaacctgtag gccccaagcec catcaacttg cccaaagaag attccaaacc tacatttccec 420 tggcctectg gaaacaagcc atctcttcac agtgtaaacc aagaccatga cttaaagcca 480 ctaggccecga aatctgggcc tactcctcca acctcagaaa atgaacagaa gcaagcgttt 540 cccaaattga ctggggttaa agggaaattt atgtcagcat cacaagatct tgaacccaag 600 ccccteotteoe ccaaacccgc ctttggcocag aageccgccce taagtaccga gaactcccat 660 gaagacgaaa gccccatgaa gaatgtgtct tcatcaaaag ggtccccage tcccctggga 720 gtcaggtcea aaagcggccc tttaaaacca gcaagggaag actcagaaaa taaagaccat 780 gcaggggaga tttcaagttt gccctttcct ggagtggttt tgaaacctgc tgcgagcagg 840 ggaggcctag gtctctccaa aaatggtgaa gaaaaaaagg aagataggaa gatagatgct 900 gctaagaaca ccttccagag caaaataaat caggaagagt tggcctcagg gactcctcect 960 gccaggttcec ctaaggcccc ttctaagetg acagtggggg ggccatgggg ccaaagtcag 1020 gaaaaggaaa agggagacaa gaattcagec accccgaaac agaagccatt gcecteecttg 1080 tttaccttgg gtccacctcc accaaaaccC aacagaccac caaatgttga cctgacgaaa 1140 ttccacaaaa cctcttctgg aaacagtact agcaaaggcc agacgtctta ctcaacaact 1200 tccctgecac cacctccacc atcccatceg gecagccaac caccattgcece agcatctcac 1260 ccatcacaac caccagtccc aagcctacct cccagaaaca ttaaacctcc gtttgaccta 1320 aaaagccctg tcaatgaaga caatcaagat ggtgtcacgc actctgatgg tgctggaaat 1380 ctagatgagyg aacaagacag tgaaggagaa acatatgaag acatagaagc atccaaagaa 1440 agagagaaga aaagggaaaa ggaagasaag aagaggttag agctggagaa aaaggaacag 1500 aaagagaaag aaaagaaaga acaagaaata aagaagaaat ttaaactaac aggccctatt 1560 caagtcatcc atcttgcaaa agcttgttgt gatgtcaaag gaggaaagaa tgaactgagc 1620 ttcaagcaag gagagcaaat tgaaatcatc cgcatcacag acaacccaga aggaaaatgg 1680 ttgggcagaa cagcaagggg ttcatatggc tatattaaaa caactgctgt agagattgac 1740 tatgattctt tgaaactgaa aaaagactct cttggtgccce cttcaagacc tattgaagat 1800 gaccaagaag tatatgatga tgttgcagag caggatgata ttagcagcca cagtcagagt 1860 ggaagtggag ggatattccc tccaccacca gatgatgaca tttatgatgg gattgaagag 1920 gaagatgctg atgatggttt ccctgctcct cctaaacaat tggacatggg agatgaagtt 1980 tacgatgatg tggatacctc tgatttcecet gtttcatcag cagagatgag tcaaggaact 2040 aattttggaa aagctaagac agaagaaaag gaccttaaga agctaaaaaa gcaggaaaaa 2100 gaagaaaaag acttcaggaa aaaatttaaa tatgatggtg aaattagagt cctatattca 2160 actaaagtta caacttccat aacttctaaa aagtggggaa ccagagatct acaggtaaaa 2220 cctggtgaat ctctagaagt tatacaaacc acagatgaca caaaagttct ctgcagaaat 2280 gaagaaggga aatatggtta tgtccttcgg agttacctag cggacaatga tggagagatc 2340 tatgatgata ttgctgatgg ctgcatctat gacaatgact agcactcaac tttggtcatt 2400 <210> 2828 <211> 2015 <212> DNA <213> Homo sapiens <400> 2828 cggaggcacg gaagatgagg aagatgatca ggaggatgat gaaggtgaag agggagatga 60 agacgatgac gacgatggct ctgaggggac ctcaggggct gcecgagetgg gggggegete 120 aagctgcgag gatcecggget gecccgcgaga cgaggagcgg gcgeccaggat ggggtcgatg 180

.aagtccaagt tcctccaggt cggaggcaat acattctcaa aaactgaaac cagcgccagc 240 ccacactgtc ctgtgtacgt gccggatccc acatccacca tcaagcecggg gcecctaatagce 300 cacaacagca acacaccagg aatcagggag gcaggctctg aggacatcat cgtggttgec 360 ctgtatgatt acgaggccat tcaccacgaa gacctcagct tccagaaggg ggaccagatg 420 gtggtcecctag aggaatccgg ggagtggtgg aaggctcgat ccctggccac ccggaaggag 480 ggctacatcc caagcaacta tgtcgccege gttgactcte tggagacaga ggagtggttt 540 ttcaagggca tcagccggaa ggacgcagag cgccaactgce tggctcccgg caacatgctg 600 ggctecttca tgatceggga tagcgagacc actaaaggaa gctactettt gtccgtgcga 660 gactacgacc ctcggcaggg agataccgtg aaacattaca agatccggac cctggacaac 720 gggggcttct acatatccce cegaagcacce ttceagcactce tgcaggagct ggtggaccac 780 tacaagaagg ggaacgacgg gctctgccag aaactgtegg tgccctgeat gtcttccaag 840

CCccagaagc cttgggagaa agatgcctgg gagatccctc gggaatccect caagctggag 900 aagaaacttg gagctgggca gtttggggaa gtctggatgg ccacctacaa Caagcacace 960 aaggtggcag tgaagacgat gaagccaggg agcatgtcgg tggaggectt Cctggcagag 1020 gccaacgtga tgaaaactct gcagcatgac aagctggtca aacttcatgc ggtggtcace 1080 aaggagccca tctacatcat cacggagttc atggccaaag gaagcttgct ggactttctg 1140 aaaagtgatg agggcagcaa gcagccattg ccaaaactca ttgacttcte agcccagatt 1200 gcagaaggca tggccttcat cgagcagagg aactacatcece accgagacct ccgagctgcec 1260 aacatcttgg tctctgcatc cctggtgtgt aagattgetg actttggcet ggeccgggte 1320 attgaggaca acgagtacac ggctcgggaa ggggccaagt tccccatcaa gtggacagcet 1380 cctgaagcca tcaactttgg ctocttcace atcaagtcag acgtctggtc ctttggtatce 1440 ctgctgatgyg agatcgtcac ctacggccgg atcccttacce cagggatgtc aaaccctgaa 1500 gtgatccgag ctctggageg tggataccgg atgcctecgece cagagaactg cccagaggag 1560 ctctacaaca tcatgatgeg ctgctggaaa aaccgtccgg aggagcggec gaccttcgaa 1620 tacatccaga gtgtgctgga tgacttctac acggccacag agagccagta ccaacagcag 1680

~ Cccatgatagg gaggaccagg gcagggcagg gggtgcccag gtggtggctce gaaggtggcet 1740 ccagcaccat ccgccaggge ccacaccccce ttectactece cagacaccca ccctcgctte 1800 agccacagtt tcctcatctg tccagtgggt aggttggact ggaaaatctc tttttgacte 1860 ttgcaatcca caatctgaca ttctcaggaa gcccccaagt tgatatttoet atttcectgga 1820 atggttggat tttagttaca gctgtgattt ggaagggaaa ctttcaaaat agtgaaatga 1980 atatttaaat aaaagatata aatgcaagtc ttacg 2015 <210> 2829 <211> 1501 <212> DNA <213> Homo sapiens <400> 2829 agcgagtect tettttectg actgcagote ttttcatttt gccatccttt tccagctcca 60 tgatggttct gcaggtttet gcggcecece ggacagtgge tetgacggeg ttactgatgg 120 tgctgctcac atctgtggtc cagggcaggg ccactccaga gaattacctt ttccagggac 180 ggcaggaatg ctacgegttt aatgggacac agcgcttceet ggagagatac atctacaace 240 gggaggagtt cgecgegette gacagcgacg tgggggagtt ccgggeggtg acggagctgg 300 ggcggectge tgcggagtac tggaacagec agaaggacat cctggaggag aagcgggcag 360 tgccggacag gatgtgcaga cacaactacg agctgggegg geccatgacc ctgcagegec 420 gagtccagcc tagggtgaat gtttccccct ccaagaaggg gcccttgcag caccacaacc 480 tgcttgtctg ccacgtgacg gatttctacc caggcagcat tcaagtccga tggttcectga 540 atggacagga ggaaacagct ggggtcgtgt ccaccaacct gatccgtaat ggagactgga 600 ccttccagat cctggtgatg ctggaaatga ccccccagca gggagatgtc tacacctgcee 660 aagtggagca caccagcctg gatagtcctg tcaccgtgga gtggaaggca cagtctgatt 720 ctgcceggag taagacattg acgggagetg ggggcttcgt gctggggcetc atcatctgtg 780 gagtgggcat cttcatgcac aggaggagca agaaagttca acgaggatct gcataaacag 840 ggttcctgag ctcactgaaa agactattgt gecttaggaa aagcatttgce tgtgtttcegt 900 tagcatctgg ctccaggaca gaccttcaac ttccaaattg gatactgctg ccaagaagtt 960 gctctgaagt cagtttctat cattctgctc tttgattcaa agcactgttt ctctcactgg 1020 gcctccaace atgttccctt cttcttagca ccacaaataa tcaaaaccca acatgactgt 1080 ttgttttcet ttaaaaatat gcaccaaatc atctctcatc acttttctcet gagggtttta 1140 gtagacagta ggagttaata aagaagttca ttttggttta aacataggaa agaagagaac 1200 catgaaaatg gggatatgtt aactattgta taatggggcc tgttacacat gacactcttc 1260 tgaattgact gtatttcagt gagctgcccc caaatcaagt ttagtgccct catccattta 1320 tgtctcagac cactattctt aactattcaa tggtgagcag actgcaaatc tgcctgatag 1380 gacccatatt cccacagcac taattcaaca tataccttac tgagagcatg ttttatcatt 1440 accattaaga agttaaatga acatcagaat ttaaaatcat aaatataatc taatacactt 1500 t 1501 <210> 2830 <211> 1832 <212> DNA <213> Homo sapiens <400> 2830 atgcaggccc cacgggagct cgcggtgggce atcgacctgg gcaccaccta ctegtgegtg 60 ggcgtgtttc agcagggecg cgtggagatc ctggccaacg accagggcaa ccgcaccacg 120 cccagctacyg tggeccttcac cgacaccgag cggctggteg gggacgcgge caagagecag 180 gecggecctga acccccacaa caccgtgttc gatgccaage ggctgatcgg gegcaagtte 240 .. gcggacacca cggtgcagtc ggacatgaag cactggccct tecgggtggt gagcgagggce 300 ggcaagccca aggtgccggt atcgtaccgc ggggaggaca agacgttcta ccccgaggag 360 atctcgtcca tggtgctgag caagatgaag gagacggccg aggcgtacct gggccagccec 420 gtgaagcacg cagtgatcac cgtgecegee tatttcaatg actcgcagcg ccaggccacc 480 aaggacgcgg gggccatcge ggggctcaac gtgttgcgga tcatcaatga gecccacggea 540 gctgccatcg cctatgggcet ggaccggcegg ggcgcgggag agcgcaacgt gectcattttt 600 gacctgggtg ggggcacctt cgatgtgtcg gttctctcecca ttgacgctgg tgtctttgag 660 gtgaaagcca ctgctggaga tacccacctg ggaggagagg acttcgacaa ccggcetcgtg 720 aaccacttca tggaagaatt ccggcggaag catgggaagg acctgagegg gaacaagegt 780 gccctcggea ggctgcgcac agcctgtgag cgcgccaagce gcaccctgte ctccagcacce 840 caggccacce tggagataga ctccctgttc gagggcegtgg acttctacac gtccatcact 900 cgtgcecget ttgaggaact gtgctcagac ctcettccegea geaccctgga geecggtggag 960 aaggccctge gggatgccaa gctggacaag gcccagattc atgacgtegt cctggtgggag 1020 ggctccacte gcatccccaa ggtgcagaag ttgctgcagg acttcttcaa cggcaaggag 1080 ctgaacaaga gcatcaaccc tgatgaggct gtggcctatg gggctgcectgt gcaggcggcec 1140 gtgttgatgg gggacaaatg tgagaaagtg caggatctcc tgctgctgga tgtggctceccc 1200 ctgtctctgg ggctggagac agcaggtggg gtgatgacca cgctgatcca gaggaacgcec 1260 actatcccca ccaagcagac ccagactttc accacctact cggacaacca gectggggtce 1320 ttcatccagg tgtatgaggg tgagagggcc atgaccaagg acaacaacct getggggegt 1380 tttgaactca gtggcatcec tcctgeccca cgtggagtcc cccagataga ggtgaccttt 1440 gacattgatg ctaatggcat cctgagcgtg acagccactg acaggagcac aggtaaggct 1500 aacaagatca ccatcaccaa tgacaagggc cggctgagca aggaggaggt ggagaggatg 1560 gttcatgaag ccgagcagta caaggctgag gatgaggccc agagggacag agtggctgce 1620 aaaaactcgc tggaggccca tgtcttccat gtgaaaggtt ctttgcaaga ggaaagcctt 1680 agggacaaga ttcccgaaga ggacaggcgc aaaatgcaag acaagtgtcg ggaagtcctt 1740 gcctggetgg agcacaacca gctggcagag aaggaggagt atgagcatca gaagagggag 1800 ctggagcaaa tctgtcgeec catcttetee aggctctatg gggggectgg tgtccectggg 1860 ggcagcagtt gtggcactca agceccgccag ggggacceca gcaccggcece catcattgag 1920 gaggttgatt ga 1932

<210>. 2831 . .. . . - PE .

<211> 2035 ’

<212> DNA

<213> Homo sapiens

<400> 2831 cgagcccecge cgaaccgagg ccacccggag ccgtgeccag tcecacgcegg ccgtgececgyg 60 cggccttaag aaccaggcaa cctctgectt cttccctett ccacteggag tcgegcetceg 120 :

cgcgececteca ctgcagcccce tgegtegeeg ggaccctege gcgegaccag ccgaatcget 180 cctgcagcag agccaacatg cccatcactce ggatgcgcat gagaccctgg ctagagatgc 240 agattaattc caaccaaatc ccggggctca tctggattaa taaagaggag atgatcttec 300 agatcccatg gaagcatgct gccaagcatg getgggacat caacaaggat gcctgtttgt 360 tceggagetg ggccattcac acaggccgat acaaagcagg ggaaaaggag ccagatccca 420 agacgtggaa ggccaacttt cgctgtgcca tgaactccct geccagatatce gaggaggtga 480 aagaccagag caggaacaag ggcagctcag ctgtgcgagt gtaccggatg cttccacctc 540 tcaccaagaa €cagagaaaa gaaagaaagt cgaagtccag ccgagatgct aagagcaagg 600 . Ccaagaggaa gtcatgtggg gattccagece ctgatacctt ctctgatgga ctcagcaget 660 ccactctgee tgatgaccac agcagctaca cagttccagg ctacatgcag gacttggagg 720 tggagcaggc cctgactcca gcactgtcgce catgtgctgt cagcagcact ctccccgact 780 ggcacatccc agtggaagtt gtgccggaca gcaccagtga tctgtacaac ttccaggtgt 840 cacccatgee ctccacctet gaagctacaa cagatgagga tgaggaaggg aaattacctg 900 aggacatcat gaagctcttg gagcagtcgg agtggcagec aacaaacgtg gatgggaagg 960 ggtacctact caatgaacct ggagtecage ccacctctgt ctatggagac tttagctgta 1020 aggaggagcc agaaattgac agcccagggg gggatattgg gctgagtcta cagecgtgtct 1080 tcacagatct gaagaacatg gatgccacct ggctggacag cctgctgacc ccagtceccggt 1140 tgcectecat ccaggccatt ccctgtgecac cgtagcaggg cccctgggec cctcttatte 1200 ctctaggcaa gcaggacctg gcatcatggt ggatatggtg cagagaagct ggacttctgt 1260 gggccectca acagccaagt gtgaccccac tgecaagtgg ggatgggcct ccctecttgg 1320 gtcattgacc tctcagggcc tggcaggcca gtgtctgggt ttttettgtg gtgtaaagct 1380 ggccctgect cctgggaaga tgaggttctg agaccagtgt atcaggtcag ggacttggac 1440 aggagtcagt gtctggettt ttectctgag cccagetgec tggagagggt ctecgctgtea 1500 ctggctgget cctaggggaa cagaccagtg accccagaaa agcataacac caatcccagg 1560 gctggctctg cactaagcga aaattgcact aaatgaatct cgttccaaag aactacccct 1620 tttcagctga gccctgggga ctgttccaaa gccagtgaat gtgaaggaaa ctcccctcecet 1680 tcggggcaat gctecectcag cctcagagga goctctaccct gctcecectget ttggctgagg 1740 ST ggcttgggaa aaaaacttgg cactttttcg tgtggatctt gccacatttc tgatcagagg 1800 tgtacactaa catttcccce gagctettgg cctttgeatt tatttataca gtgeccttgcet 1860 cggggcccac caccccctca agccccagca gccctcaaca ggcccaggga gggaagtgtg 1820 agcgcettgg tatgacttaa aattggaaat gtcatctaac cattaagtca tgtgtgaaca 1980 cataaggacg tgtgtaaata tgtacatttg tctttttata aaaagtaaaa ttgtt 2035 <210> 2832 <211> 4068 <212> DNA <213> Homo sapiens ) <400> 2832 gaattcctce tctcttcace ccgttagctg ttttcaatgt aatgctgecg tecttetctt 60 gcactgecett ctgegctaac acctccattc ctgtttataa ccgtgtattt attacttaat 120 gtatataatg taatgttttg taagttatta atttatatat ctaacattgc ctgccaatgg 180 tggtgttaaa tttgtgtaga aaactctgcc taagagttac gactttttct tgtaatgttt 240 tgtattgtgt attatataac ccaaacgtca cttagtagag acatatggcc cccttggcag 300 agaggacagg ggtgggcttt tgttcaaagg gtctgccctt tecctgecctg agttgctact 360 tctgcacaac ccctttatga accagttttc acccgaattt tgactgtttc atttagaaga 420 aaagcaaaat gagaaaaagc tttcctcatt tctccttgag atggcaaagc actcagaaat 480 gacatcacat accctaaaga accctgggat gactaaggca gagagagtct gagaaaactc 540 tttggtgctt ctgcctttag ttttaggaca catttatgca gatgagctta taagagaccg 600 ttccctecge cttecttecte agaggaagtt tcttggtaga tcaccgacac ctcatccagg 660 cggggggttg gggggaaact tggcaccagc catcccaggce agagcaccac tgtgatttgt 720 tctcctggtyg gagagagetg gaaggaagga gccagcgtge aaataatgaa ggagcacggg 780 ggcaccttca gtagcaccgg aatcagcggt ggtageggtg actctgectat ggacagcectg 840 cagccgctec agectaacta catgcctgtg tgtttgtttg cagaagaatc ttatcaaaaa 900 ttagcaatgg aaacgctgga ggaattagac tggtgtttag accagctaga gaccatacag 960 acctaccggt ctgtcagtga gatggcttct aacaagttca aaagaatgct gaaccgggag 1020 ctgacacacc tctcagagat gagccgatca gggaaccagg tgtctgaata catttcaaat 1080 actttcttag acaagcagaa tgatgtggag atcccatctc ctacccagaa agacagggag 1140 aaaaagaaaa agcagcagct catgacccag ataagtggag tgaagaaatt aatgcatagt 1200 tcaagcctaa acaatacaag catctcacgc tttggagtca acactgaaaa tgaagatcac 1260 ctggccaagg agctggaaga cctgaacaaa tggggtctta acatctttaa tgtggctgga 1320 tattctcaca atagacccct aacatgcatc atgtatgcta tattccagga aagagacctc 1380 ctaaagacat tcagaatctc atctgacaca tttataacct acatgatgac tttagaagac 1440 cattaccatt ctgacgtggc atatcacaaC agcctgcacg ctgctgatgt agcccagtceg 1500 acccatgttc tcctttctac accagcatta gacgctgtct tcacagattt ggagatccetg 1560 gctgecattt ttgcagetgce catccatgac gttgatcatc ctggagtctc caatcagttt 1620 ctcatcaaca caaattcaga acttgctttg atgtataatg atgaatctgt gttggaaaat 1680 catcaccttg ctgtgggttt caaactgctg caagaagaac actgtgacat cttcatgaat 1740 ctcaccaaga agcagcgtca gacactcagg aagatggtta ttgacatggt gttagcaact 1800 gatatgtcta aacatatgag cctgctggca gacctgaaga caatggtaga aacgaagaaa 1860 gttacaagtt caggcgttct tctcctagac aactataccg atcgcattca ggtccttege 1920 aacatggtac actgtgcaga cctgagcaac cccaccaagt ccttggaatt gtatcggcaa 1980 tggacagacc gcatcatgga ggaatttttc cagcagggag acaaagagcg ggagagggga 2040 atggaaatta gcccaatgtg tgataaacac acagcttctg tggaaaaatc ccaggttggt 2100 ttcatcgact acattgtcca tccattgtgg gagacatggg cagatttggt acagcctgat 2160 gctcaggaca ttctcgatac cttagaagat aacaggaact ggtatcagag catgatacct 2220 caaagtccct caccaccact ggacgagcag aacagggact gccagggtct gatggagaag 2280 tttcagtttg aactgactct cgatgaggaa gattctgaag gacctgagaa ggagggagag 2340 ggacacagct atttcagcag cacaaagacg ctttgtgtga ttgatccaga aaacagagat 2400 tccctgggag agactgacat agacattgca acagaagaca agtccccegt ggatacataa 2460 tcccectcte cctgtggaga tgaacattct atccttgatg agcatgccag ctatgtggta 2520 gggccagccc accatggggg ccaagacctg cacaggacaa gggccacctg gcctttcagt 2580 tacttgagtt tggagtcaga aagcaagacc aggaagcaaa tagcagctca ggaaatccca 2640 cggttgactt gccttgatgg caagcttggt ggagagggct gaagctgttg ctgggggccg 2700 attctgatca agacacatgg cttgaaaatg gaagacacaa aactgagaga tcattctgca 2760 ctaagtttcg ggaacttatc cccgacagtg actgaactca ctgactaata acttcattta 2820 tgaatcttct cacttgtccc tttgtctgec aacctgtgtg ccttttttgt aaaacatttt 2880 catgtcttta aaatgcctgt tgaatacctg gagtttagta tcaacttcta cacagataag 2940 ctttcaaagt tgacaaactt ttttgactct ttctggaaaa gggaaagaaa atagtcttecc 3000 ttctttcttg ggcaatatce ttcactttac tacagttact tttgcaaaca gacagaaagg 3060 atacacttct aaccacattt tacttccttc ccetgttgtc cagtccaact ccacagtcac 3120 . oo. tcttaaaact tctctctgtt tgcctgectc caacagtact tttaactttt tgctgtaaac 3180 agaataaaat tgaacaaatt agggggtaga aaggagcagt ggtgtcgttc accgtgagag 3240 tctgcataga actcagcagt gtgccctget gtgtcttgga ccctgeccec cacaggagtt 3300 gctacagtcc ctggcectge ttcccatcct cctctcttca ccecgttage tgttttcaat 3360 gtaatgctgec cgtccttcete ttgcactgece ttctgcgeta acacctccat tcctgtttat 3420 aaccgtgtat ttattactta atgtatataa tgtaatgttt tgtaagttat taatttatat 3480 atctaacatt gcctgccaat ggtggtgtta aatttgtgta gaaaactctg cctaagagtt 3540 acgacttttt cttgtaatgt tttgtattgt gtattatata accCaaacgt cacttagtag 3600 agacatatgg cccccttgge agagaggaca ggggtggget tttgttcaaa gggtctgecc 3660 tttccctgee tgagttgecta cttectgcaca acccctttat gaaccagttt tggaaacaat 3720 attctcacat tagatactaa atggtttata ctgagtcttt tacttttgta tagcttgata 3780 ggggcagggg caatgggatg tagtttttac ccaggttcta tccaaatcta tgtgggcatg 3840 agttgggtta taactggatc ctactatcat tgtggctttg gttcaaaagg aaacactaca 3900 tttgctcaca gatgattctt ctgattcttc tgaatgctcc cgaactactg actttgaaga 3960 ggtagcctcc tgcctgccat taagcaggaa tgtcatgttc cagttcatta caaaagaaaa 4020 caataaaaca atgtgaattt ttataataaa aaaaaaaaaa aggaattc 4068 -«210> 2833 : <21l> 664 <212> DNA <213> Homo sapiens <400> 2833 ggattgttgg tctgegtgga acttctcagg tggacaccag agcatggaac acatccacga 60 cagcgatgge agttccagca gcagccacca gagectcaag agcacagceca aatgggegge 120 atccctggag aatctgctgg aagacccaga aggcgtgaaa agatttaggg aatttttaaa 180 aaaggaattc agtgaagaaa atgttttgtt ttggctagca tgtgaagatt ttaagaaaat 240 gcaagataag acgcagatgc aggaaaaggc aaaggagatc tacatgacct ttctgtccag 300 caaggcctca tcacaggtca acgtggaggg gcagtctcgg ctcaacgaga agatcctgga 360 agaaccgcac cctctgatgt tccagaaact ccaggaccag atctttaatc tcatgaagta 420 cgacagctac agccgctttc ttaagtctga cttgttttta aaacacaagc gaaccgagga 480 agaggaagaa gatttgcctg atgctcaaac tgcagctaaa agagcttcca gaatttataa 540 cacatgagcc cccaaaaagc cgggactggc agctttaaga agcaaaggaa tttcctctca 600 ggacgtgccg ggtttatcat tgctttgtta tttgtaagga ctgaaatgta caaaaccctt 660 ) caat 664 <210> 2834 «211> 615 <212> DNA <213> Homo sapiens :

<400> 2834 gctcagagag aagtgacttt gagctcacag tgtcaccgcc tgctgatggg agagctgaat 60 tcaaaaccag ggtgtctccc tgagcagagg gacctgcaca cagagactcc ctectgggcet 120 cctggcacca tggccccact gaagatgctg geccectggtca cecetectect gggggettet 180 ctgcagcaca tccacgcagce tcgagggacc aatgtgggec gggagtgectg cctggagtac 240 ttcaagggag ccattcccct tagaaagctg aagacgtggt accagacatc tgaggactgce 300 tccagggatg ccatcgtttt tgtaactgtg cagggcaggg ccatctgttc ggaccccaac 360 aacaagagag tgaagaatgc agttaaatac ctgcaaagcc ttgagaggtc ttgaagectce 420 ctcaccccag actcctgact gtctceccggg actacctggg acctccaccg ttggtgttca 480 ccgeccccecac cctgagegec tgggtccagg ggaggccttc cagggacgaa gaagagccac 540 agtgagggag atcccatccc cttgtctgaa ctggagccat gggcacaaag ggcccagatt 600 aaagtcttta tcctce 615 <210> 2835

<211> 885 <212> DNA

<213> Homo sapiens

<400> 2835 agcctacgca cgaaagtgac tagggaggdaa ggatattata aagtgatgca aacagaaatt 60 ccaccagcct ccatgtatca tcatgtgtca taactcagtc aagctcagtg agcattctca 120 gcacattgcc tcaacagctt caaggtgagc cagctcaaga ctttgctctc caccaggcag 180 aagatgacag actgtgaatt tggatatatt tacaggctgg ctcaggacta tctgcagtge 240 gtcctacaga taccacaacce tggatcaggt ccaagcaaaa cgtccagagt gctacaaaat 300 gttgcgttct cagtccaaaa agaagtggaa aagaatctga agtcatgctt ggacaatgtt 360 aatgttgtgt ccgtagacac tgccagaaca ctattcaacc aagtgatgga aaaggagttt 420 gaagacggca tcattaactg gggaagaatt gtaaccatat ttgcatttga aggtattctc 480 atcaagaaac ttctacgaca gcaaattgcc ccggatgtgg atacctataa ggagatttca 540 tattttgttg cggagttcat aatgaataac acaggagaat ggataaggca aaacggaggc 600 tgggaaaatg gctttgtaaa gaagtttgaa cctaaatctg gctggatgac ttttctagaa 660 gttacaggaa agatctgtga aatgctatct ctcetgaage aatactgttg accagaaagg 720 acactccata ttgtgaaacc ggcctaattt ttctgactga tatggaaacg attgccaaca 780 catacttcta cttttaaata aacaactttg atgatgtaac ttgaccttcc agagttatgg 840 aaattttgtc cccatgtaat gaataaattg tatgtatttt tctct 885

PCT/US2003/012946

<210> 2836 <211> 1875 <212> DNA <213> Homo sapiens <400> 2836 aaagcatcca gttectttge ggtectette ttcagcacat gccaaagctg ttcetcacgg 60 cctgtgagac aagagcatct tggatgtagg acaatggaag agttagatgc Cttattggag 120 gaactggaac gctccaccct tcaggacagt gatgaatatt ccaacccagc tectettecc 180 ctggatcagc attccagaaa ggagactaac cttgatgaga cttcggagat cctttcetatt 240 caggataaca caagtcectt gccggcgcag ctegtgtata ctaccaatat ccaggagctc 300 aatgtctaca gtgaagccca agagccaaag gaatcaccac caccttctaa aacgtcagca 360 gctgctcagt tggatgaget catggctcac ctgactgaga tgcaggccaa ggttgcagtg 420 agagcagatg ctggcaagaa gcacttacca gacaagcagg atcacaaggc ctcectggac 480 tcaatgcttg g9ggtctgga gcaggaattg caggaccttg gcattgccac agtgcccaag 540 ggccattgtg catcctgeca gaaaccgatt gctgggaagg tgatccatgc tctagggcaa 600 tcatggcatc ctgagcattt tgtctgtact cattgcaaag aagagattgg ctccagtccece 660 ttctttgagce ggagtggctt ggcctactge cccaacgact accaccaact tttttctcca 720 cgctgtgett actgegetge tcccatectg gataaagtgc tgacagcaat gaaccagacc 780 tggcacccag agcacttctt ctgctctcac tgcggagagy tgtttggtge agaaggcttt 840 catgagaagg acaagaagcc atattgccga aaggatttct tagccatgtt ctcacccaag 900 tgtggtggct gcaatcgecce agtgttggaa aactacctte cagccatgga cactgtctgg 960 cacccagagt gectttgtttg tggggactgce ttcaccagtt tttctactgg ctecttettt 1020 gaactggatg gacgtccatt ctgtgagctc cattaccatc acegccgggg aacgctetge 1080 catgggtgtg ggcagcccat cactggcegt tgtatcagtg ccatggggta caagttccat 1140 cctgagcact ttgtgtgtgce tttctgectg acacagttgt cgaagggcat tttcagggag 1200 cagaatgaca agacctattg tcaaccttgce ttcaataagc tcttcccact gtaatgccaa 1260 ctgatccata gcctcttcag attccttata aaatttaaac Caagagagga gaggaaaggg 1320 taaattttct gttactgacc ttctgcttaa tagtcttata gaaaaaggaa aggtgatgag 1380 Caaataaagg aacttctaga ctttacatga ctaggctgat aatcttattt tttaggcttc 1440 - tatacagtta attctataaa ttctctttet cectctette tccaatcaag cacttggagt 1500 tagatctagg tccttctatc tecgtcectet acagatgtat tttccacttg cataattcat 1560 gccaacactg gttttcttag gtttcteceat tttcacctct agtgatggcc ctactcatat 1620 cttctetaat ttggtectga tacttgttte ttttcacgtt ttcccatttg ccctgtgget 1680 cactgtctta caatcactgc tgtggaatca tgataccact tttagctctt tgcatcttcc 1740 ttcagtgtat ttttgttttt caagaggaag tagattttaa ctggacaact ttgagtactg 1800 acatcattga taaataaact ggcttgtggt ttcaataaaa aaaaaaaaaa aaaaaaaaaa 1860 aaaaaaaaaa aaaaa 1875 <210> 2837 <211> 2366 <212> DNA <213> Homo sapiens <400> 2837 gaccacgegt atcgatgtcg acccacagga ttgtcacaga gggcagggtg gtgactgagg 60 accagctect catgcttgag gectgtggtga tgcacctcgg gatccgctct gccegcetgtg 120 tcctgggcat ggagggtcag caggruates tgcacctgcc cctatcccag aaggggccct 180 tctggacatg ggagcctagt gecccctcgaa ctctgcetceca ggtcctacag gatccagecc 240 tgaaagacct cgtcctcacc tgecccaccce tgcecctggea ttccetgate ctgecggeccc 300 agtatgagat ccaagccatc atgcacatgc gcaggaccat tgtcaagatc ccttctacce 360 tggaggtcga cgtggaggac gtcaccgect cctcecggcea cgtccacttt atcaaaccgce 420 tgctgctgag cgaggtcctg gectgggaag gcecetttece cctgteccatg gagatcctgg 480 aggttcctga gggcecgeccce atcttectca geccgtgggt gggctcocttg caaaaaggec 540 agaggctttg cgtctatggc ctagcctcac caccctggceg ggtcctggec tcaagcaagg 600 gccgcaaggt gcccaggcac ttectggtgt cagggggcta ccaaggcaag ctgcggegge 660 ggccaaggga gttccccacg gectatgacc tcctaggtge tttccageca ggecggecac 720 tccgggtggt ggccacaaag gactgtgagg gcgagaggga ggagaatccce gagttcacgt 780 ccctggetgt gggtgaccgg ctggaggtge tggggcctag ccaggcccat ggggcccagg 840 gcagtgacgt ggatgtcttg gtttgtcagc ggctgagtga ccaggctggg gaagatgagg S00 aggaagagtg caaagaggag gcagagaccc agagcgggtc ctgctgccct tccacttece 560 tggcagtttc gtggaggaga tgagtgacag ccggegctac agccectggecag atctgactge 1020 ccagttttca atgecttgtg aggtcaaggt ggtggccaag gacaccagcc accccaatga 1080 ccctcagaac ctccttectg ggectgcegge tggaggagaa gatcacagag ccattcttgg 1140 tggtgagcct ggactctgag ctgggatgtg ctttgagatc cctcccecgga ggctggacct 1200 gactgtcgtg gaggccaagg ggcagccaga cttgeccagag gggtctctec ccatagccac 1260 agtggaggaa gctggaacag acacctttta ttattgtctt cggaagttac cagcctgtga 1320 gatccaagcc cccccaccca ggcccectaa aaatcagggc ctcagcaagce agaggagaca 1380 cagcagtgag ggaggcgtca agtcttctca agtcttagga ttgcagcaac acgttcggct 1440 gcccaaaccc aaggcgaaga ccttgccaga gttcatcaag gatggctcca gtacgtacag 1500 caagattcct gecccacagga agggccacag gcccgctaag ccccaaagge aggatctaga 1560 tgatgatgaa catgattatg aagaaatact tgagcaattt cagaaaacca tctaagtget 1620 ggaggaacca cgcttcctaa ctgetgctte tcagggaatc cgacaccagec caaccatttt 1680 aagcctctaa aagacctcgg gcaagtctca cagaaactga gctgcagacg gggagtaget 1740 ttgtggaaac tgatttgatg gacactgcac cagcttecett caggttctag attcttgceta 1800 cttagggcgg gctggtttgg acctaacatc tcgcacgtga ctccetceage ctcagagcct 1860 tgggatgcag agcagctggce agggttcctc tcaatcctge aaccccaget gtcccaccegg 15820 tggatgcaga ggggaatccg aggccatcaa ccttggtgac agcagcgcag tgccaatget 1980 gatcacactg catgggagat tttgttaacg tctgccaccc ccactcteac ccccaagcete 2040 taagccceeg ggaggcctgg actgtcttec tcatctctgt -agcaccaage ctgatagatc 2100 tgtatatggt aaacaggggt ttaaccacat gtggttaaca tggattaatg tgggaatttg 2160 gcttcaagaa cacaacctta ggaccttggg ccccaaaage tggtggtgaa atgagaggag 2220 Ccaatttaag aagaccctta tggagacctg aggctgcaga aactggtagg tttcatcagg 2280 tggttaaagt cgtcaaagtt gtaagtgact aaccaagatt atttcatttt aaaaccacag 2340 aataaaaatg acacctgagc ttctec 2366 <210> 2838 ’ <211> 6383 <212> DNA <213> Homo sapiens <400> 2838 cgcggecget atatataatg cagcatcaca ccatgtaggg catttactct tattttatac 60 attcagatat gtttgaaaca ttcttaaggc tacaaaacag aacatagaaa aataaacagg 120 aatatattca acacttacaa aaagtgatat gataaagaat ataaagtact agttteccttt 180 taacacttca aaagatatgt atatatactt ttttttacaa gtaacatcac aaatgctcac 240 atcttcacat gctcttaaag tattatttgt actcagtgta aggctattat cgtttttcat 300 acataaaatt ttctagctct gtaacacaat gcaattttta atccattcaa gtaagttcaa 360 Cccccaaagtt gccgcettece agcattaaga catgcaccca ceccctettet aagattttct 420 aaacttgtat ttcggggaga aagacctctt ttaaaaaata atccaattag tgggagagta 480 aatggctgac attagtagca aaaccttagt tatctgaaaa taacatattg gaaatgagac 540 attattagga ttttaaacaa acaatagcat ttagacataa agtaggaagc aaaatacagt 600 aaacagaaat agtgtagcca aatatcattc tcttcagcta ccttaagtaa aagacaaaac 660 atttacctca tctaaaaatg aaggtaaaac gaaagaggca aaaataaata ttgctagttt 720 ctaggatggc tgaatgtttt ctaaaccaga aatggttaga aaggaacttt attgcaccaa 780 gtcaatcata agcaagtttg cagttcacag gcattttaat tcaaccttga gtcacaaagg 840 agaacaacac gctgcgagaa tacagtctac agtctgcatt aaataagaat atatcagcat 900 tgtggtctgg gaaaacctat gcecttgccagg acaaggcagg gtgctgagcect taggtcatge 960 catgaaaatg aatttgtggg ttatcagtaa acagtatgag gactacacag atgccagcat 1020 cctgctgcca aggagacatg gggcaagagt tgaagatttg agaggaaatg aagagacata 1080 cacaacacca aaggaaaagg gggctggaat caagttcagc caaagcacct aacacaaaaa 1140 acaggtgagc tttggtcagt ctgttcttca aaatatgtat gatcatatgg taatgaagtt 1200 tcataatttc caactcaaaa atacaaatga tcctcagttc tatacttttg cctctattct 1260 cttataaaga aatatgtcaa cataacagta tgacataaca gttaaaataa ggacaaaagc 1320 ttgcttatct tagtttgacc tcagcataag gcaaaatccc ctggagaata catttaaaaa 1380 caaacttaaa aggaaaaaaa gcgaaaccaa cttcatgcaa agattccttt taaaactatc 1440 aaaagtcagt tcttttattc cagaggtcac tgagaaaagt accatctgct aaaattctct 1500 ttcaagcact tcttccatca tatcctagag gtgagatatg ggaaacagaa agcaaatcag 1560 tgttcctcag gagctatatc tgttactcaa ttgagggtaa gacaaagtga caatgaagat 1620 atgagtagta tttccttcca atttttaaag attttcagaa gectgagatca aaccccacte 1680 aataaaatgc aggagactag aagcaacaac ttattttgga ctcctgagat caaacacatt 1740 gaactttcaa atctgggtgt ttctatcaaa atgtgatttt cattaaaatc agtaagctag 1800 tectacataa aaaagcatga gctgaaagtg gaggaccctce tatcttctca ttecttaact 1860 gagccaccga tgttaagaaa aaaatggctt aagcggtacc ttcaacaact attctagtta 1920 agaaggtgac aacaaattga ggccgcgaat tceggcgaaaa ctctttectt tggttgtget 1980 aagaggtgat gcccaaggtg caccaccttt caagaactgg atcatgaaca actttatcct 2040 cctggaagaa cagctcatca agaaatccca acaaaagaga agaacttctc cctcgaactt 2100 taaagtcecge ttectttgtgt taaccaaagc cagcctggca tactttgaag atcgtcatgg 2160 . gaagaagcgc acgctgaagg ggtccattga gctctcecga atcaaatgtg ttgagattgt 2220 gaaaagtgac atcagcatcc catgccacta taaatacccg tttcaggtgg tgcatgacaa 2280 ctacctccta tatgtgtttg ctccagatcg tgagagccgg cagcgctggg tgetggccct 2340 taaagaagaa acgaggaata ataacagttt ggtgcctaaa tatcatccta atttctggat 2400 ggatgggaag tggaggtgct gttctcaget ggagaagctt gcaacaggct gtgcccaata 2460 tgatccaacc aagaatgctt caaagaagcc tcttcctecet actcctgaag acaacaggcg 2520 accactttgg gaacctgaag aaactgtggt cattgcctta tatgactace aaaccaatga 2580 tcctcaggaa ctcgecactge ggcgcaacga agagtactgce ctgctggaca gttctgagat 2640 tcactggtgg agagtccagg acaggaatgg gcatgaagga tatgtaccaa gcagttatct 2700 ggtggaaaaa tctccaaata atctggaaac ctatgagtgg tacaataaga gtatcagccg 2760 agacaaagct gaaaaacttc ttttggacac aggcaaagaa ggagccttca tggtaaggga 2820 ttccaggact gcaggaacat acaccgtgtc tgttttcacc aaggctgttg taagtgagaa 2880 caatccctgt ataaagcatt atcacatcaa ggaaacaaat gacaatccta agcgatacta 2940 tgtggctgaa aagtatgtgt tcgattccat ccectcttete atcaactatc accaacataa 3000 tggaggagge ctggtgactc gactccggta tccagtttgt tttgggaggce agaaagcccce 3060 agttacagca gggctgagat acgggaaatg ggtgatcgac ccectcagage tcacttttgt 3120 gcaagagatt ggcagtgggc aatttgggtt ggtgcatctg ggctactgge tcaacaagga 3180 caaggtggct atcaaaacca ttcgggaagg ggctatgtca gaagaggact tcatagagga 3240 ggctgaagta atgatgaaac tctctcatcc Caaactggtg cagctgtatg gggtgtgcect 3300 ggagcaggcce cccatctgec tggtgtttga gttcatggag cacggctgce tgtcagatta 3360 tctacgcacc cagcggggac tttttgetge agagaccctg ctgggcatgt gtctggatgt 3420 gtgtgagggc atggcctacc tggaagaggc atgtgtcatc cacagagact tggctgccag 3480 aaattgtttg gtgggagaaa accaagtcat caaggtgtct gactttggga tgacaaggtt 3540 cgttctggat gatcagtaca ccagttccac aggcaccaaa ttcccggtga agtgggcatc 3600 cccagaggtt ttctetttca gtcgctatag cagcaagtcc gatgtgtggt catttggtgt 3660 gctgatgtgg gaagttttca gtgaaggcaa aatcccgtat gaaaaccgaa gcaactcaga 3720 ggtggtggaa gacatcagta ccggatttcg gttgtacaag ccecggctgg cctccacaca 3780 cgtctaccag attatgaatc actgctggaa agagagacca gaagatcggc cagccttcte 3840 cagactgctg cgtcaactgg Ctgaaattgc agaatcagga ctttagtaga gactgagtac 3900 Caggccacgg gctcagatcc tgaatggagg aaggatatgt cctcattceca tagagcatta 3960 gaagctgcca ccagcccagg accctccaga ggcagectgg cctgtacteca gtccctgagt 4020 caccatggaa gcagcatcct gaccacagct ggcagtcaag ccacagctgg agggtcagcc 4080 accaagctgg gagctgagcce agaacaggag tgatgtctct gcccttectce tagecctecttg 4140 tcacatgtgg tgcacaaacc tcaacctgac agctttcaga cagecattett gcacttctta 4200

PCT/US2003/012946 gcaacagaga gagacatgac gtaagaccca gattgctatt tttattgtta tttttcaaca 4260 gtgaatctaa agtttatggt tccagggact ttttatttga cccaacaaca cagtatccca 4320 ggatatggag gcaaggggaa caagagcatg agtgtttttc caagaaactg gtgagttaag 4380 taagattaga gtgagtgtgc tctgttgetg tgatgectgtc agccacaget tcctgoegta 4440 gagaatgata gagcagctgce tcacacagga ggccggatat ctgataagca gctttatgag 4500 gttttacaga gtatgctgct acctctctcec ttgaagggag catggcagac ccattggatg 4560 gattggggtg aacagttcag gtcccatgcet tggagcattg ggtatctgat gtctgcacca 4620 gaacaagaga acctctgacg gtggagaacc atgtggtgta agaagagatc ttaggtctct 4680 tctttatacc aagctcatgt tttataccaa gctcatcttt tataccaagce tgtgcaggtg 4740 actatgccte ctcttctgeca cagaatgett €caccagcat cctgagaaga aatgattact 4800 tctgtaaaac atcctttttt ccagcctetg ggaatcagec ccccecetcte tgcactatce 4860 gatcctcatc aacagaggge agcattgtgt tggtcagtgt tceccttggeg agcaattgaa 4320 acttgtttag gccctagggt tgagcaattt taaggttgag actccaagtc tcctaaaatt 4980 ctaggagaga aataaagagt ctgtttttgc tcaaaccatc aggatggaaa cagtcaggca 5040 ctgactgggg tgcttccaag aggcatgaga gtgcctactce tggcttgagec acttctatat 5100 gcaaggtgaa tatgtactga gctaggagac ttccctgcaa aatctctgtt caccctgggt 5160 tcacatcecce atgaggtaat attattatte ccattrttaca aataatgtaa ctgaggcttt 5220 aaaaagccaa gacatctgcc caaagtgatg gaactagaaa gtctagaget ggtattctag 5280 Cccaaatctg tctgaccgeca atacacagat tatttattee tattagacac tggcttctac 5340 tgaaaatgaa acttattgca gagggaataa atacaaagat ggaaagccag taaagaagtc 5400 agtatagaac cactagcgat agtgttgctc tggcacagac cactgtggtt gatgcatggc 5460 cctccaactt ggaataggat tttcctttte ctattctgta tcecttacctt ggtcatgtta 5520 atgactttgg agttattcag ttectgacee tttaattctce acaaccaacc agtcatgttg 5580 cttgaagcca ttatagacga gcttcaaagc aactttaaaa gattgttatg tagaagtatg 5640 agttcttcct ttaattatca ttccaacttt cagctgtagt cttcttgaac acttatgagg 5700 agggaggaca ttccctgata taagagagga tggtgttgca attggctctt tctaaatcat 5760 gtgacgtttt gactggcttg agattcagat gcataatttt taattattgt gaagtggaga 5820 gcctcaagat aaaactctgt cattacgaag atgattttac tcagcttatc caaaattatce 5880 tctgtttact ttttagaatt ttgtacatta tcttttggga tccttaatta gagatgattt 5940 ctggaacatt cagtctagaa agaaaacatt ggaattgact gatctctgtg gtttggttta 6000 gaaaattccc ctgtgcatgg tattaccttt ttcaagctca gattcatcta atcctcaact 6060 gtacatgtgt acattcttca cctcctggtg cecctatcccg caaaatggge ttocectgecetg 6120 ggrttttcte ttectcacatt ttttaaatgg tccecetgtgt ttgtagagaa ctceccttata 6180 cagagttttg gttctagttt tatttcgtag attttgcatt ttgtaccttt tgagactatg 6240 tatttatatt tggatcagat gcatatttat taatgtacag tcactgctag tgttcaaaat 6300 aaaaatgtta caaatacctg ttatcctttg tagagcacac agagttaaaa gttgaatata 6360 gcaatattaa agctgcattt taa 6383 <210> 2839 <211> 1531 <212> DNA - <213> Homo sapiens <400> 2839 agtcacagag ggaacacaga gcctagttgt aaacggacag agacgagagg ggcaagggag 60 gacagtggat gacagggaag acgagtgggg gcagagctge tcaggaccat ggctgaggcec 120 atcacctatg cagatctgag gtttgtgaag gctcececctga agaagagcat ctccagecegg 180 ttaggacagg acccaggggc tgatgatgat ggggaaatca cctacgagaa tgttcaagtg 240 cccgeagtee taggggtgece ctcaagcettg gcttcttctg tactagggga caaagcagcg 300 gtcaagtcgg agcagccaac tgcgtectgg agagecgtga cgtcaccagec tgtcgggegg 360 attctccect geccgcacaac ctgcctgega tacctecctge tecggectgcet cctcacctge 420 ctgctgttag gagtgaccgc catctgecctg ggagtgeget atctgcaggt gtctcagcag 480 ctccagcaga cgaacagggt tctggaagtc actaacagca gcctgaggca gcagectccege 540 ctcaagataa cgcagctggg acagagtgca gaggatctge aggggtccag gagagagctg 600 gcgcagagtc aggaagcact acaggtggaa cagagggctc atcaggcggc cgaagggcag 660 ctacaggcct gccaggcaga cagacagaag acgaaggaga ccttgcaaag tgaggagcaa 720 Cagaggaggg ccttggagca gaagctgagc aacatggaga acagactgaa gcccttctte 780 acatgcgget cagcagacac ctgctgtecyg tcgggatgga taatgcatca gaaaagctge 840 ttttacatet cacttacttce aaaaaattgg caggagagcc aaaaacaatg tgaaactctg 500 tcttecaage tggccacatt cagtgaaatt tatccacaat cacactctta ctacttctta 960 aattcactgt tgccaaatgg tggttcaggg aattcatatt ggactggcct cagctctaac 1020 aaggattgga agttgactga tgatacacaa cgcactagga cttatgctca aagctcaaaa 1080 tgtaacaagg tacataaaac ttggtcatgg tggacactgg agtcagagtc atgtagaagt 1140 tctettecect acatctgtga gatgacaget ttcaggtttc cagattagga cagtectttg 1200 cactgagttg acactcatgc caacaagaac ctgtgccect ccttcctaac ctgaggcetg 1260 gggttcctca gaccatctcc ttcattctgg gcagtgccag ccaccggctg acccacacct 1320 gacacttcca gccagtctgc tgcectgectec ctctteoctga aactggactg ttcoctgggaa 1380 aagggtgaag ccacctctag aagggacttt ggcctccccc caagaacttc ccatggtaga 1440 atggggtggg ggaggagggc gcacgggctg agcggatagg ggcggeccgg agccagecag 1500 gcagttttat tgaaatcttt ttaaataatt g 1531 <210> 2840 <211> 4446 <212> DNA <213> Homo sapiens <400> 2840 tgeettgacce aggacttggg actttgegaa aggatcgegg ggcccggaga ggtgttggag 60 agcacaatgg ctgaacaagt ccttecctcag gectttgtatt tgagcaatat gcggaaagcet 120 . gtgaagatac gggagagaac tccagaagac atttttaaac ctactaatgg gatcattcat 180 cattttaaaa ccatgcaccg atacacactg gaaatgttca gaacttgcca gttttgtect 240 cagtttcggg agatcatcca caaagccctce atcgacagaa acatccaggc caccctggaa 300 agccagaaga aactcaactg gtgtcgagaa gtccggaagc ttgtggcgct gaaaacgaac 360 ggtgacggca attgcctcat gcatgccact tctcagtaca tgtggggegt tcaggacaca 420 gacttggtac tgaggaaggc gctgttcagc acgctcaagg aaacagacac acgcaacttt 480 aaattccgct ggcaactgga gtctctcaaa tctcaggaat ttgttgaaac ggggctttgc 540 tatgatactc ggaactggaa tgatgaatgg gacaatctta tcaaaatggc ttccacagac 600 acacccatgg cccgaagtgg acttcagtac aactcactgg aagaaataca catatttgtc 660 ctttgcaaca tcctcagaag gccaatcatt gtcatttcag acaaaatgct aagaagtttg 720 gaatcaggtt ccaatttcgc ccctttgaaa gtgggtggaa tttacttgec tctccactgg 780 cctgecccagg aatgctacag ataccccatt gttctecggcect atgacagcca tcattttgta 840 ccettggtga ccctgaagga cagtgggccect gaaatccgag ctgttccact tgttaacaga 900 gaccggggaa gatttgaaga cttaaaagtt cactttttga cagatcctga aaatgagatg 960 aaggagaagc tcttaaaaga gtacttaatg gtgatagaaa tccccgtcca aggctgggac 1020 catggcacaa ctcatctcat caatgccgca aagttggatg aagctaactt accaaaagaa 1080 atcaatctgg tagatgatta ctttgaactt gttcagcatg agtacaagaa atggcaggaa 1140 aacagcgagc aggggaggag agaggggcac gcccagaatc ccatggaacc ttccgtgcecc 1200 cagctttctce tcatggatgt aaaatgtgaa acgcccaact gccccttett catgtctgtg 1260 aacacccagc ctttatgcca tgagtgctca gagaggcggc aaaagaatca aaacaaactc 1320 ccaaagctga actccaagcc gggccctgag gggctccctg gecatggcget cggggectcet 1380 cggggagaag cctatgagcc cttggcgtgg aaccctgagg agtccactgg ggggcctcecat 1440 tcggccccac cgacagcacc cagcecctttt ctgttcagtg agaccactgce catgaagtge 1500

. aggagccccg gcotgeccctt cacactgaat gtgcagcaca acggattttg tgaacgttgce 1560 cacaacgccce ggcaacttca cgccagccac gccccagacc acacaaggca cttggatccece 1620 gggaagtgcc aagcctgcet ccaggatgtt accaggacat ttaatgggat ctgcagtact 1680 tgcttcaaaa ggactacagc agaggcctcc tccagcctca gcaccagect ccctecttec 1740 tgtcaccagc gttccaagte agatcccteg cggctcecgtec ggagcccetce cccgcattcet 1800 tgccacagag ctggaaacga cgcccctgct ggctgectgt ctcaagectge acggactcct 1860 ggggacagga cggggacgag caagtgcaga aaagccggct gegtgtattt tgggactcca 1920 gaaaacaagg gcttttgcac actgtgtttc atcgagtaca gagaaaacaa acattttgct 1980 gctgectcag ggaaagtcag tcccacageg tccaggttcec agaacaccat tccgtgectg 2040 gggagggaat gcggcaccct tggaagcacc atgtttgaag gatactgcca gaagtgttte 2100 attgaagctc agaatcagag atttcatgag gccaaaagga cagaagagca actgagatcg 2160 agccagcgca gagatgtgec tcgaaccaca caaagcacct caaggcccaa gtgcgeccgg 2220 gccteoctgea agaacatcct ggectgecge agcgaggage tctgcatgga gtgtcageat 2280 cccaaccaga ggatgggccc tggggcccac cggggtgagc ctgecccccga agaccccocce 2340 aagcagegtt gecgggccec cgectgtgat cattttggea atgccaagtg caacggctac 2400 tgcaacgaat gctttcagtt caagcagatg tatggctaac cggaaacagg tgggtcacct 2460 cctgcaagaa gtggggcctc gagctgtcag tcatcatggt gctatcctct gaacccectca 2520 gctgccactg caacagtggg cttaagggtg tctgagcagg agaggaaaga taagctcttc 2580 gtggtgccca cgatgctcag gtttggtaac ccgggagtgt tcccaggtgg ccttagaaag 2640 caaagcttgt aactggcaag ggatgatgtc agattcagcc caaggttcct cctctcctac 2700 caagcaggag gccaggaact tctttggact tggaaggtgt gcggggactg gccgaggcecc 2760 ctgcaccctg cgcatcagga ctgcttcatc gtcttggetg agaaagggaa aagacacaca 2820 agtcgecgtgg gttggagaag ccagagccat tccacctcec ctececccagce atctctcaga 2880 gatgtgaage cagatcctca tggcagcgag gccctctgca agaagctcaa ggaagctcag 23840 ggaaaatgga cgtattcaga gagtgtttgt agttcatggt ttttccctac ctgecccggtt 3000 cctttcectga ggacccggea gaaatgcaga accatccatg gactgtgatt ctgaggcetge 3060 tgagactgaa catgttcaca ttgacagaaa aacaagctgc tctttataat atgcaccttt 3120 taaaaaatta gaatatttta ctgggaagac gtgtaactct ttgggttatt actgtcttta 3180 cttctaaaga agttagcttg aactgaggag taaaagtgtg tacatatata atataccctt 3240 acattatgta tgagggattt ttttaaatta tattgaaatg ctgccctaga agtacaatag 3300 gaaggctaaa taataataac ctgttttctg gttgttgttg gggcatgagc ttgtgtatac 3360 actgcttgca taaactcaac cagctgcctt tttaaaggga gctctagtec tttttgtgta 3420 attcacttta tttattttat tacaaacttc aagattattt aagtgaagat atttcttcag 3480 ctctggggaa aatgccacag tgttctcctg agagaacatc cttgetttga gtcaggetgt 3540 gggcaagttc ctgaccacag ggagtaaatt ggcctctttg atacactttt gcttgectcec 3600 ccaggaaaga aggaattgca tccaaggtat acatacatat tcatcgatgt ttcegtgcette 3660 tccttatgaa actccagcta tgtaataaaa aactatactc tgtgttctgt taatgcctct 3720 gagtgtccta cctecttgga gatgagatag ggaaggagca gggatgagac tggcaatggt 3780 cacagggaaa gatgtggcct tttgtgatgg ttttattttc tgttaacact gtgtcctggg 3840 ggggctggga agtcccoctge atcccatggt accctggtat tgggacagca aaagccagta 3500 accatgagta tgaggaaatc tctttctgtt gctggcttac agtttctctg tgtgctttgt 3960 ggttgctgtc atatttgctc tagaagaaaa aaaaaaaagg aggggaaatg cattttccce 4020 agagataaag gctgccattt tgggggtctg tacttatggc ctgaaaatat ttgtgatcca 4080 taactctaca cagcctttac tcatactatt aggcacactt tccccttaga gccccctaag 4140 tttttcccag acgaatcttt ataatttctt tccaaagata ccaaataaac ttcagtgttt 4200 tcatctaatt ctcttaaagt tgatatctta atattttgtg ttgatcatta tttccattct 4260 taatgtgaaa aaaagtaatt atttatactt attataaaaa gtatttgaaa tttgcacatt 4320 taattgtccc taatagaaag ccacctattc tttgttggat ttcttcaagt ttttctaaat 4380 aaatgtaact tttcacaaga gtcaacatta aaaaataaat tatttaagaa caaaaaaaaa 4440 aaaaaa 4446 <210> 2841 ) <211> 1714 <212> DNA <213> Homo sapiens <400> 2841 . . . Sn ggggcatttt gtgcctgect agctatccag acagagcagc taccctcage tctagctgat 60 actacagaca gtacaacaga tcaagaagta tggcagtgac aactcgtttg acacggttgc 120 acgaaaagat cctgcaaaat cattttggag ggaagcggct tagccttctc tataagggta 180 gtgtccatgg attccgtaat ggagttttgc ttgacagatg ttgtaatcaa gggcctactc 240 taacagtgat ttatagtgaa gatcatatta ttggagcata tgcggaagag agttaccagg 300 aaggaaagta tgcttccatc atcctttttg cacttcaaga tactaaaatt tcagaatgga 360 aactaggact atgtacacca gaaacactgt tttgttgtga tgttacaaaa tataactcce 420 caactaattt ccagatagat ggaagaaata gaaaagtgat tatggactta aagacaatgg 480 aaaatcttgg acttgctcaa aattgtacta tctctattca ggattatgaa gtttttcgat 540 gcgaagattc actggatgaa agaaagataa aaggggtcat tgagctcagg aagagcttac 600 tgtctgcctt gagaacttat gaaccatatg gatccctggt tcaacaaata cgaattctge 660 tgctgggtcc aattggagct gggaagtcca gctttttcaa ctcagtgagg tetgttttec 720 aagggcatgt aacgcatcag getttggtgg gcactaatac aactgggata tctgagaagt 780 ataggacata ctctattaga gacgggaaag atggcaaata cctgccgttt attctgtgtg 840 actcactggg gctgagtgag aaagaaggcg gcctgtgcag ggatgacata ttctatatct 900 tgaacggtaa cattcgtgat agataccagt ttaatcccat ggaatcaatc aaattaaatc 960 atcatgacta cattgattcc ccatcgctga aggacagaat tcattgtgtg gcatttgtat 1020 ttgatgccag ctctattcaa tacttctect ctcagatgat agtaaagatc aaaagaattc 1080 gaagggagtt ggtaaacgct ggtgtggtac atgtggcttt gctcactcat gtggatagca 1140 tggatttgat tacaaaaggt gaccttatag aaatagagag atgtgagcct gtgaggtcca 1200 agctagagga agtccaaaga aaacttggat ttgctctttc tgacatcteg gtggttagea 1260 attattcctc tgagtgggag ctggaccctg taaaggatgt tctaattctt tctgetctga 1320 gacgaatgct atgggctgca gatgacttct tagaggattt gccttttgag caaataggga 1380 atctaaggga ggaaattatc aactgtgcac aaggaaaaaa atagatatgt gaaaggttca 1440 cgtaaatttc ctcacatcac agaagattaa aattcagaaa ggagaaaaca cagaccaaag 1500 agaagtatct aagaccaaag ggatgtgttt tattaatgtc taggatgaag aaatgcatag 1560 aacattgtag tacttgtaaa taactagaaa taacatgatt tagtcataat tgtgaaaaat 1620 agtaataatt tttcttggat ttatgttctg tatctgtgaa aaaataaatt tcttataaaa 1680 ctcggaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1714 <210> 2842 <211> 2665 <212> DNA <213> Homo sapiens <400> 2842 ggctctggge atcaccagcg gccccaggga aaaagaaaga aatgggaaac agcatgaaat 60 Ccaccectge gocctgececgag aggcccctgc ccaacccgga gggactggat agcgacttec 120 ttgcegtget aagtgactac ccgtctectg acatcagccc cccgatattc cgeccgagggg 180 agaaactgcg tgtgatttct gatgaagggg getggtggaa agctatttct cttagcactg 240 gtcgagagag ttacatccct ggaatatgtg tggccagagt ttaccatgge tggectgtttg 300 agggcctggg cagagacaag gccgaggagce tgctgcagct gccagacaca aaggtcggcet 360 ccttcatgat cagagagagt gagaccaaga aagggtttta ctcactgtcg gtgagacaca 420 ggcaggtaaa gcattaccge attttccgtc tgccgaacaa ctggtactac atttccccga 480 ggctcacctt ccagtgcctg gaggacctgg tgaaccacta ttctgaggtg gcoctgatggec 540 tgtgctgtgt gctcaccacg ccctgectga cacaaagcac ggctgcccca gcagtgaggg 600 cctccagetc acctgtcacc ttgegtcaga agactgtgga ctggaggaga gtgtccagac 660 tgcaggagga ccccgaggga acagagaacc cgcttggggt agacgagtcce cttttcagcect 720 atggccttcg agagagcatt gcctcttacc tgtcectgac cagtgaggac aacacctcct 780 ttgatcgaaa gaagaaaagc atctccctga tgtatggtgg cagcaagaga aagagctcat 840 tcttctcatc accaccttac tttgaggact agccaagaac agacacaatg gttcatgccec 900 aaaaggaaca gaagttccaa ctattgcctg ggatcttgeg aaaagcgagg ttcecectgate 960 cctgggagece tcacgtattt tagaagccaa gagaagccac atggagactc aaattcgcat 1020 cttctctatc cacatcatga ccaaaggaac ccctccctgg tgtctgatca gggctgtgge 1080 atcacaaaac attggatcat gacatgtcgg gcgatgcttg gaaaagccca gcatgtatgt 1140 atgcacacat tgtgtgtgtg ggaaggacaa agccactctc acaagaaagg gcaccaggac 1200 tgctctccaa ggaactggac ctgtccagac agttacactc caaggtcatt ggagagaact 1260

. tctgtatggg caagcctgag agggagagga aacaaaagct gtgtcctggce agaaggtctg 1320 ggtttgcaga tgggtgecct gaatggaact actttaacta atccataggg acttctggta 1380 tgctttccte tctttttaaa ggaacttcgt gacactaaac attagcccaa aggacttctt 1440 agccttcaat tgggagatac ctttggtctg ctcctgcacc aaagccatat gggtggaagt 1500 cagttggcct ccctggttct gcagagggce agaagaatga gagagaggaa gactgctgge 1560 agggaaatcg aggaggcgag actagaactg caccagcttc cctgatgtct gcagccatgg 1620 ctttgcagcg caaacagaac ttctctggga tgctgggatt cttgcctgta tgaatgcatc 1680 aagtattcat ttattgcccg aataggcatt gcattaagtc ctctgttagg tgtcaggcaa 1740 gccaaaaaaa aaaaaaagat gctaagtcct aacccccaac agaagtgttc acagtgtaga 1800 cgggaaaaaa tgtataaaca aatgtgtaaa aagagaaatc agctcatggc ttaggatgga 1860 attagagaca ggtgagggac actcaggagc tcatttteca gectgctcttc agagtggaag 1920 ggctggctgg atcgggtagg taagaatagce tggatttttt agaaaagaaa tggatacagt 13980 ctaaagaatt aactcacceg gtactttatt Ctaagaaggg tctggcatcce atatgaggaa 2040 aaatgctcag ctccaggaaa gatggggagt ccaagtggat taatgatgtce atgcataatt 2100 ttaagagaca agggagaaaa cacaatgtat agccagagaa ggagaagcete ccatccaaat 2160 cctactagga agagagtggg ctgcagatga atctgtgact catgtttcece tgtttcaaag 2220 ggatcctggg gaaggagggg aacatgcttg cagtatctct ccctgtctgt ctgctcacat 2280 aagcattcecg tccatctaag Cctcatcgtgc tactggtatg tgtatgtgeca gttacacagt 2340 ttecetgtate ataaatccta gtgtgtttat acaaggagac atctgtggtt tcceccaaccg 2400 ttccaaaagg ctatttcaaa ggaaccagcc cacgtatgag aaatgaatgt aacactgtgg 2460 acattgactt cccgcataag gcagggtgac cccctgaact ccagatgttt gcacagtatc 2520 ttatgtgttg ttttecegttg tgacgaatgt gattggaaca tttggggagc acccagaggg 2580 atttttcagt gggaagcatt acactttgct aaatcatgta tttattcctg attaaaacaa 2640 acctaataaa tatttaacce ttggce 2665 <210> 2843 <211> 1061 <212> DNA <213> Homo sapiens <400> 2843 ctctgttttc tcaaagctga agtcggctag gtttgcaaag ctgtgggcetg agcactcagg 60 caatcacact ctcagaaact gecggcggcte tggactgcag cctcccaagg ctccatgeca 120 gacaaagcat gcgtgtcaca cttgctacaa tagcctggat ggtttetttt gtctccaatt 180 attcacacac agcaaatatt ttgccagata tcgaaaatga agatttcatc aaagactgcg 240 ttcgaatcca taacaagttec cgatcagagg tgaaaccaac agccagtgat atgctataca 300 tgacttggga cccagcacta gcccaaattg caaaagcatg ggccagcaat tgccagtttt 360 cacataatac acggctgaag ccaccccaca agctgcaccc aaacttcact tcactgggag 420 agaacatctg gactgggtct gtgcccattt tttctgtgte ttcecgecate acaaactggt 480 atgacgaaat ccaggactat gacttcaaga ctcggatatg Caaaaaagtc tgtggccact 540 acactcaggt tgtttgggca gatagttaca aagttggctg cgcagttcaa ttttgcccta 600 aagtttctgg ctttgacgct ctttccaatg gagcacattt tatatgcaac tacggaccag 660 gagggaatta cccaacttgg ccatataaga gaggagecac ctgcagtgee tgccccaata 720 atgacaagtg tttggacaat ctctgtgtta accgacagcg agaccaagtg aaacgttact 780 actctgttgt atatccaggc tggcccatat atccacgtaa cagatacact tctetettte 840 tcattgttaa ttcagtaatt ctaatactgt ctgttataat taccattttg gtacagctca 900 ) 1188 y oo agtaccctaa tttagttctt ttggactaat acaattcagg aaagaaaaaa cccaaaaacc 960 aacctcattc acatatggct tttttttaac caataacaat taggtgtact tctattttaa 1020 aacatttcag aaaaaaatat atgttatagc aatactctta c 1061 <210> 2844 <211> 2088 <212> DNA <213> Homo sapiens <400> 2844 gaattcggca cgagcgcgcg gcgaatctca acgectgcgec gtctgeggge gcttecggge 60 caccagtttc tctgctttce accctggege cccccagecc tggctcccca gctgecgctge 120 ccecgggegte cacgccctge gggcttagcg ggttcagtgg gctcaatctg cgcagcgeca 180 cctecatgtt gaccaagect ctacagggge ctcccgcegec ccecgggace cccacgecge 240 cgccaggagg caaggatcgg gaagcgttcg aggccgagta tcgactcggce cccctectgg 300 gtaagggggg ctttggcacc gtcttcgcag gacaccgect cacagatcga ctccaggtgg 360 ccatcaaagt gattccccgg aatcgtgtge tgggctggtce cceccttgtca gactcagtca 420 catgcccact cgaagtcgca ctgctatgga aagtgggtgc aggtggtggg caccctggeg 480 tgatccgect gettgactgg tttgagacac aggaaggctt catgctggtc ctcgagegge 540 ctttgccege ccaggatcte tttgactata tcacagagaa gggcccactg ggtgaaggcc 600 caagccgctg cttctttgge caagtagtgg cagccatcca gcactgccat tcccgtggag 660 ttgtccatcg tgacatcaag gatgagaaca tcctgataga cctacgccgt ggctgtgceca 720 aactcattga ttttggttct ggtgccctge ttcatgatga accctacact gactttgatg 780 ggacaagggt gtacagcccc ccagagtgga tctctcgaca ccagtaccat gcactcccgg 840 ccactgtctg gtcactggge atcctectet atgacatggt gtgtggggac attccctttg 900 agagggacca ggagattctg gaagctgage tccacttccc agcccatgte tccccagact 960 gectgtgecct aatcecgcegg tgcctggece ccaaaccttc ttcccgacce tcactggaag 1020 agatcctgct ggacccctgg atgcaaacac cagccgagga tgttaccecct caacccctece 1080 aaaggaggcc ctgccccttt ggectggtec ttgctaccct aagectggec tggectggece 1140 tggcccccaa tggtcagaag agccatccca tggccatgtc acagggatag atggacattt 1200 . gttgacttgg ttttacaggt cattaccagt cattaaagtc cagtattact aaggtaaggg 1260 attgaggatc aggggttaga agacataaac caagtttgcc cagttccctt cccaatccta 1320 caaaggagcc ttcctcccag aacctgtggt cecctgatttt ggagggggaa cttcttgett 1380 ctcattttge taaggaagtt tattttggtg aagttgttcc cattttgage cccgggacte 1440 ttattttgat gatgtgtcac cccacattgg cacctcctac taccaccaca Caaacttagt 1500 tcatatgctt ttacttggge aagggtgett tecttcecaat accccagtag cttttatttt 1560 agtaaaggga ccctttccce tagcctaggg tcccatattg ggtcaagctg Cttacctgee 1620 tcagcccagg attttttatt ttgggggagg taatgccectg ttgttaccec aaggcttctt 1680 ttteettttt tttttteetg ggtgagggga ccctactttg ttatcccaag tgctcttatt 1740 ctggtgagaa gaaccttaat tccataattt gggaaggaat ggaagatgga caccaccgga 1800 caccaccaga caataggatg ggatggatgg ttttttgggg gatgggctag gggaaataag 1860 gcttgetgtt tgttttectg gggcgetece tccaattttg cagatttttg caacctectce 1920 : ctgagccggg attgtccaat tactaaaatg taaataatca cgtattgtgg ggaggggagt 13980 tccaagtgtg ccctectttt ttttectgec tggattattt aaaaagccat gtgtggaaac 2040 ccactattta ataaaagtaa tagaatcaga aaaaaaaaaa aaaaaaaa 2088 <210> 2845 <211> 1666 <212> DNA <213> Homo sapiens <400> 2845 atttgcttte tectttttecct ttettecgga tgagaggcta agccataata gaaagaatgg 60 agaattattg attgaccgtce tttattctgt gggectctgat tcteccaatgg gaataccaag 120 ggatggtttt ccatactgga Re oanaser aaagacactc aaggacagac atttttggca 180 gagcatagat gaaaatggca agttcecctgg ctttecttet gctcaacttt catgtctcec 240 tcetettggt ccagetgete actccttget cagctcagtt ttetgtgett ggaccctctg 300 ggcccatcct ggccatggtg ggtgaagacg ctgatctgce ctgtcacctg ttceccgacca 360 tgagtgcaga gaccatggag ctgaagtggg taagttccag cctaaggcag gtggtgaacyg 420 tgtatgcaga tggaaaggaa gtggaagaca ggcagagtgc accgtatcga gggagaactt 480 cgattctgcg ggatggcatc actgcaggga aggctgctct ccgaatacac aacgtcacag 540 cctctgacag tggaaagtac ttgtgttatt tccaagatgg tgacttctat gaaaaagccce 600 tggtggagct gaaggttgca gcactgggtt ctaatcttca cgtcgaagtg aagggttatg 660 aggatggagg gatccatctg gagtgcaggt ccaccggetg gtacccccaa ccccaaatac 720 agtggagcaa cgccaagaga gagaacatcc cagctgtgga agcacctgtg gttgcagatg 780 gagtgggcct atatgaagta gcagcatctg tgatcatgag aggcggctec ggggagggtyg 840 tatcctgcat catcagaaat tceceteecteg gectggaaaa gacagccage atttccatcg 900 cagacccctt cttcaggagc gecccageccct ggatcgcage cctggcaggg accctgccta 260 1190 ! So tcttgectget gettctegec ggagccagtt acttcttgtg gagacaacag aaggaaataa 1020 ctgctctgte cagtgagata gaaagtgagc aagagatgaa agaaatggga tatgctgcaa 1080 cagagcggga aataagccta agagagagcc tccaggagga actcaagagg aaaaaatcca 1140 gtacttgact cgtggagagg agtcttcgtec cgataccaat aagtcagcct gatgctctaa 1200 tggaaaaatg gccctctteca agecctggtga ggaaatgctt cagatgagge tccaccttgt 1260 taaataaatt ggatgtatgg aaaaatagac tgcagaaaag gggaactcat ttagctcacg 1320 agtggtcgag tgaagattga aaattaacct ctgagggcca gcacagcagc tcatgcctgt 1380 : aatcctagca ctttggaagg ctgaggaggg cggatcacaa ggtcaggaga tcaagaccat 1440 cctggctaac acggtgaaac cccgtctcta ctaaaaatac aaaaaataaa aaattagcecg 1500 ggcatggtga cgggcacctg tagtcccagc tactcgggag gctgaggcag gagaatggca 1560 tgaacccgga aggcagagct tgcagtgage cgagatcacg ccactgcact ccagcctggg 1620 agacagagcg agactctgtc tcaagaaaaa aaaaaaaaaa aaaaaa 1666 <210> 2846 <211> 850 <212> DNA <213> Homo sapiens <400> 2846 gaattccggc aaaatgcatg acagtaacaa tgtggagaaa gacattacac catctgaatt 60 gcctgcaaac ccaggttgte tgcattcaaa agagcattct attaaagcta ccttaatttg 120 gcgcettattt ttcttaatca tgtttctgac aatcatagtg tgtggaatgg ttgectgcecttt 180 aagcgcaata agagctaact gccatcaaga gccatcagta tgtcttcaag ctgcatgecc 240 agaaagctgg attggttttc aaagaaagtg tttctatttt tctgatgaca ccaagaactg 300 gacatcaagt cagaggtttt gtgactcaca agatgctgat cttgctcagg ttgaaagctt 360 ccaggaactg aatttcctgt tgagatataa aggcccatct gatcactgga ttgggctgag 420 cagagaacaa ggccaaccat ggaaatggat aaatggtact gaatggacaa gacagtttcc 480 tatcctggga gcaggagagt gtgcctattt gaatgacaaa ggtgccagta gtgccaggca 540 ctacacagag aggaagtgga tttgttccaa atcagatata catgtctaga tgttacagca 600 aagccccaac taatctttag aagcatattg gaactgataa ctccatttta aaatgagcaa 660 agaatttatt tcttatacca acaggtatat gaaaatatgc tcaatatcac taataactgg 720 gaaaatacaa atcaaaatca tagtaaaata ttacctgttt tcatggtgct aatattacct 780 gttctcccac tgcetaatgac atacccgaga atgagtaatt tataaataaa agagatttaa 840 ttgaaaaaaa 850

<210> 2847 <211l> 761

<212> DNA

<213> Homo sapiens

<400> 2847 atccccaccc aaagcctgat ggacccegge tggccatgct gtceccctecc tgtggegttt 60 cttagcagat ggctgcagag cttcgttgat ggtcttttcet gtactggagg cctcctgagg 120 cagcgaacgt gcaaatttgc aggtgctgca tcccaagcecc ctcatgctcc tgecttcctg 180 agggccagag gggagcccca ggacccatta agccaccecce gtgttectge cgtcagtgee 240 aactgccgca tgtggaagca tctacccegtt cactccagtc ccaccccacg cctgactccee 300 ctctggaaac tgcaggccag atggttgctg ccacaacttg tgtaccttca gggatgggge 360 tcttactcce tcetgaggec agctgctcta atatcgatgg tectgettge cagagagttce 420 ctctacccag caaaaatgag tgtctcagaa gtgtgctcct ctggcctcag ttcectectett 480 ttggaacaac ataaaacaaa tttaattttc tacgcctcectg gggatatctg ctcagccaat 540 ggaaaatctg ggttcaacca gccecctgeca tttcttaaga ctttctgetc cactcacagg 600 atcctgagct gcacttacct gtgagagtct tcaaactttt aaaccttgcc agtcaggact 660 tttgctattg caaatagaaa acccaactca acctgcttaa gcagaaaata aatttattga 720 ttcaagtttg gagaaaaaaa aaaaaaaaaa aaaaaaaaaa a 761 <210> 2848

<211l> 5426

<212> DNA

<213> Homo sapiens

<400> 2848 ggggaggaag aaaggcgaag gcaaggcgaa ggggtggaga gtgatatgaa gagcgagaga 60 aaagagagga cagcggacga gcagatcecgg tatctggaat cccggecgect agaacgtgtt 120 tttcgggaga gcaaaggctg tgtctacggc aggctgggga tatagcctct ccttccgatg 180 aaaagagaaa ggaagaatgg actacagcca ccaaacgtcce ctagtcccat gtggacaaga 240 taaatacatt tccaaaaatg aacttctctt gcatctgaag acctacaact tgtactatga 300 aggccagaat ttacagctcc ggcaccggga ggaagaagac gagttcattg tggagggget 360 cctgaacatce tcctggggce tgcgeccggec cattcgcecctg cagatgcagg atgacaacga 420 acgcattcga ccccctccat cctectcecte ctggcactct ggectgtaacc tgggggcetca 480 gggaaccact ctgaagccce tgactgtgec caaagttcag atctcagagg tggatgccce 540 gccggagggt gaccagatgc caagctccac agactccagg ggectgaage cectgcagga 600

1192 ggacacccca cagctgatgc gcacacgcag tgatgttggg gtgcgtcgcc gtggcaatgt 660 gaggacgcct agtgaccagc ggcgaatcag acgccaccgc ttctcecatca acggccattt 720 ctacaaccat aagacatccg tgttcacacc agcctatggc tctgtcacca acgtccgcat 780 caacagcacc atgaccaccc cacaggtcct gaagctgctg ctcaacaaat ttaagattga 840 gaattcagca gaggagtttg ccttgtacgt ggtccatacg agtggtgaga aacagaagct 900 gaaggccacc gattacccge tgattgcccg aatcctccag ggcccatgtg agcagatctc 960 caaagtgttc ctaatggaga aggaccaggt ggaggaagtc acctacgacg tggcccagta 1020 tataaagttc gagatgccgg tacttaaaag cttcattcag aagctccagg aggaagaaga 1080 tcgggaagta aagaagctga tgcgcaagta caccgtgctc cggctaatga ttcgacagag 1140 gctggaggag atagccgaga ccccagcaac aatctgagec atgagaacga ggggatctgg 1200 gcaccccagg aaccgccatt gcccataaga cccccaggaa gctaggcact ttctttccat 1260 ggaaacattt agacacaaac ctccccagct ccggccaagc catcatttgce tacctggagce 1320 tggatgtaga agtcagcaga cagctcccta tccctggacc cctgccctcec ttttttetge 1380 tcacaaggac ttttgatttt agttataagg aggacccaaa atgtgtgtgt gtacatgtgt 1440 gtgcacacat ggtacgtgtc catgtgccta cctgatactt tcacatgtaa ttaaattcca 1500 ggcaaccagc acaagagccdg tgagcttgge acatgtgctg ctcgtgagca ggaaaatcag 1560 aggagccact gatctgagtg gtatttaggt tgaaggaaag atttctcctc tcaagtgceca 1620 gggagcagce acacgtctgt ctgtgtttag agagggaaga gggttctcca ggttcaccat 1680 ttgggttgtt tatatgttgg tagaaattct cecctgtatgc ctagaaggat cagtgaatgt 1740 aagagccttg gaaattaaca aaataacagc cacataacct tgcggcaagt ctgatggaaa 1800 gaaaaagata aaccatccgt ggggtagatg caataagccce acgtattttt acactggaaa 1860 cgttgattgt tttaaatgac aaagacatat gtgatgttct atgtggaaac ctgtgaagag 1920 tggattctgc ctccatctct goccteccatgg ctacctttag gagacagaga agatcctgtg 1980 tgtttctectyg tacccagctg acagectgtce tctatggege ttecttgagt ggaaggaaat 2040 gtctcaagaa acaaagatct cgctggtgcg tacacagtgc tgaccagcta gtgtggccag 2100 ggcctggtgg cctggtggece aggaagtttc aggttgaagg gaaatgtcga ggctacctgce 2160 agatatgaca ggtgccttga acgcagccca tcttcatgtc atcaaaggtc ttcctgcact 2220 tgaagctggg gcgatgtttyg cagtcaagac cattctttcc aacctctggg ttcttgcaag 2280 ttgccctcac cttgtgtgtg gagatgcatt ccaagaatga agcctcatct tgctactgag 2340 tgtggggttc agggaagcte tttaggccac ctggtgaagg tgcatgggga ggatggagct 2400 tctcoctcage tcctectgage agccacctat gtgatcttta aatccaaccc caatgggaga 2460 aaagggcaag aacagtctgt gcecctgggac tcctatcagg aagcttgaca ggcagctggg 2520 catcagtgca gctgatatcg tttgaggagg gagacagatg cttggacctg ggtgcectgge 2580 tatggagatt gaccaagcaa gatcaggagc tcctgatagc aggegteottt gagcctaget 2640 ggggtagagg cactgcccat ctcttcteca cettectetce acagaatgtt tgcagagctg 2700 ggcagttgag gaaaggacag cccctggttg gtgectccaa aggaaggtgg acttttttgg 2760 tggagacgtt tctgccctgg gcaccctecct gecccecgatt catacctatg gcttcttgag 2820 aaggctcaca getgtggtct taacgtagac tgcagaaaga tggcatgegg cccoctggeat 2880 ttcgccaagg gttttatage aagtctcecett cctccatagg gacagcagca ccagccctgt 2940 ggggcatgga gtggaagccc agaagggctt ctgcaagetg cacagaactg gggtaagaag 3000 acaaagagta gccaccggga gaggcttcct ttgttacage tgggaaagaa cagttctgtg 3060 aatgcaaaca cctcctgagt tttgcaattg agaaaatgat ttggagaact tctcttctgg 3120 taatttttat tttgaatgtt cagggcctta gttggcccca gtaattctcc ttggaggact 3180 tgggagaaga atttccacaa agcaaactac taaccactag ctcttactgg acagcgattt 3240 ctggcttata agagttctct ttgatttgea ctagcactac gatagtgtta gatggggaaa 3300 tactgcaaca tgtccagttg gccagatcac tttccaaggg agcgatacta aggcagactc 3360 agctttttaa agatgggagg tcaggaggtg gaagtgagag gagatcccat ctcacacaac 3420 acacttccac gtaatgcaga ccacactttt ccattttgtc ctgccctett gagaggtcat 3480 ttctcacgtc ctaagaacct gatcagaaat tttggaaggg ttctttgaaa tagcagcagt 3540 tgaaacagag acactttgcc acagtgtgga gecagattttc tcactggtat cacatggtct 3600 tgcagttttg aactettcga cegatttgtg ggagtttatg taattgcgtg caatgaacct 3660 gaaattgtgt aaaggacaaa agaccagttt atagggttgg gttttttttc caacttgtga 3720 aaagcagttt agctgcatct gtctcececcac cacccccacce ccgggagggg cttatgttac 3780 aaggtgatca agtgaaggaa aaacctgage ctatctggcet gggatggtgg aattaagcac 3840 aaggtcacat tctctgtgat cacatgagag ggaaggtgat gacttaaatg gcagggggtg 3900 gggattatct tggggagagg ctgaaaagca caaaagatag tctteccctgt acgtattggt 3360 gaagaacgtg cacaaggctg gatggactte aacttggagt tgagttgagg caagaggatt 4020 tctggatatt agtcacccat ctgcaagaaa aatgctgagg cctcgggtca agattttgat 4080 ctgagacatg ctgatgcttc aaggagaaat attttcacaa tcctctctte cctcaccaga 4140 agagaacagt actctctcet agaaacctct aggtaaacac attttatect aatatcggta 4200 gcatataatg ccccccccaa aatatctgtt ttccatgcaa aaaagtctca acaagaagtce 4260

PCT/US2003/012946 tgtggagttg agtggttact tcaaagtgtc aggagagtga agaaattggc cacagaagag 4320 Caagaagctc tcttaagaaa agggaattct ctttaaagaa accaccacca acaacaaaac 4380 aaccaaaaac catgttttat gtcaaagctc tgtagcacag agaatgtggt gtcacagata 4440 catcgccgag agaggtttct ttcotttottt tttttttttt tgagacagag tctggttctg 4500 ttteccagge tggagtgecag tggtgggatc tcagctcact gcaacatccg cctctggggt 4560 tcaagtgatt ctcctgtete agectceccaa gtagctggaa ttacagggac ccgccaccac 4620 gccecggectaa tttttttgtg tggttttagt agaggtgggg tttcaccatc ttggccaggce 4680 tggtcttgaa ctcctgacct cgtgatccac ccgcctagge ctcccaaagt gttgggatta 4740 caggcgtgag ccactgtgec cagccaaaag agaaatttct acatgaacaa ggcaatttca 4800 gtgtcttaca gcggccaaac catgacgtga agaatgagat aggagacagg agatcaccat 4860 aagcgtecct gatatagcag cacacatttt cacgtttcca cttaaatecgt tttgcacaaa 4920 gtcttgeotte gectcagatga gatgagatat gatttcctag agatgtaaaa ataagaatga 4980 atgtggcgec cccttcettee agatgtaata gaaagctctg ccctatcaca aggggggtgt 5040 tgaagcgccece cttgtgtttt aactgtattt aactgagcac aagatgcaca agctgtggtg 5100 ggaaaccctc agtttacctt tggagtcttc cctgcagatce gcagacctgt ttccaggetg 5160 atgtttctgg tgtgtaattg ctagcgtttc tgaagggttt tcccaattgt tttagecttg 5220 tgaagtattc ttaattataa cttgcctttc agcgatggta catgacttga ttcaacgttt 5280 ggttctgaac ttacacactg atgcgtttac tcatctaaca taatctgaca gggecctcage 5340 aagggagcca tacatttttg taacattttg atatgtttta atgcatctga cttagatctt 5400 actgaaataa agcacttttc aaagag 5426 <210> 2849 <211> 2206 <212> DNA <213> Homo sapiens <400> 2849 ¢gcggggceca gggeggegge ccccagggag ttggcaggat ggcagagggc aaggcaggcg 60 gcgcggcecgg cctettegec aagcaggtge agaagaagtt tagcagggcc caggagaagg 120 tgctgcagaa attggggaaa gctgtagaaa ccaaagatga acgatttgaa caaagcgcta 180 acaacttcta ccaacaacag gcagaaggcc acaagctgta caaggacctg aagaacttce 240 I ttagtgcagt caaagtgatg catgaaagtt caaaaagagt gtcagaaacc ctgcaggaga 300 tctacagcag cgagtgggat ggtcatgagg agctgaagge catcgtatgg aataatgatc 360 tcctttggga agactacgag gagaaactgg ctgaccaggce tgtaaggace atggaaatct 420 atgttgccca gttcagtgaa attaaggaga gaattgccaa gcggggtcgg aaactcgtgg 480 actatgacag tgcccgacac cacctggagg cagtgcagaa tgccaagaag aaagatgagg 540 ccaagactgc caaggcagag gaagagttca acaaagccca gactgtgttt gaagatctga 600 accaagaact actagaggag ctgcctattc tttataatag tcgtattggc tgctatgtga 660 ccatcttcca aaacatttcc aacttgaggg atgtcttcta cagggaaatg agcaagctga 720 accacaatct ctacgaggtg atgagcaaac tggagaagca acattccaat aaagtctttg 780 tggtgaaggg actgtcaagc agcagcaggc gctctttagt catttctccc ccagttcgaa 840 cagctacagt ctccagtect cttacctcac ctactagtce ctctacactt tcecttgaaga S00 gtgagagtga atctgtctca gcaactgaag atctggcacc tgatgcagec caaggggaag 960 acaattctga gatcaaggag ctcttagaag aggaggaaat agagaaggaa ggatctgaag 1020 caagctcctc tgaggaagat gagcctctac cagectgcaa tggccccgec caggcccage 1080 cctctcctac cactgaaagg gccaagtccc aggaggaagt tctccccagc tccacaactc 1140 catcaccagg cggagccctg agcccttecag ggcagcectte atcatctgcc acagaagtag 1200 tccteccgaac ccgcaccgeca agtgaaggat ctgaacaacc aaagaagaga gcctctatcece 1260 agaggacctc agcaccccct agtaggccte ctccacccag agccactgca agccccagge 1320 cctectcagg gaacatacct tccagcccta cagectctgg agggggttca cccaccagcce 1380 ctagggcctc cttggggact gggactgcaa gtcctaggac ctccctagag gtctctcecta 1440 atccagaacc accagagaag ccagtaagaa ctcctgaggc caaagaaaat gaaaacatce 1500 acaatcagaa ccctgaagaa ctttgtactt cccccacctt aatgacatet caggttgcett 1560 cagagcctgg agaggcaaag aagatggaag acaaggaaaa ggataataag cttatctcag 1620 ctgactcctc ggagggccaa gaccagcttc aagtctccat ggtaccagaa aacaacaacc 1680 tcacagcacc tgaacctcaa gaagaggtat ccacaagtga aaatccacaa ctctgaagag 1740 aaactaccaa gactcctcct gccccaaacc tcgccagaga agctcttcaa ccagaggdta 1800 taggtcagag ggatataaga gccagcatcc atccectgggt tctcagtagg aatgctggtg 1860 ctgtctaaag acctggcatt aatggaggcg gaggagcagce cttacgggag ggatggaggg 1920 aggcaggctyg gggagaagag aacattagac tcagggaata tttaattctg gttttagcat 1980 tattagaata agactttata cattaactaa agtggagctt taatcactat aaaaagcaaa 2040 agtatctata gacacagaca cttgcctata cagagacata accacacaca ctcagaggat 2100 agtgaacaaa tctgtctttg acttacgacc cattttgcaa gacttaaagc cggaagaaca 2160 cattttcaga ttgttaaata aagtctgatt ctgactaaaa aaaaaa 2206

<210> 2850 <211> 1712 <212> DNA <213> Homo sapiens <400> 2850 cagttagctt caaacaaaaa cgaaagttag accaagggaa cgtattagat atggaagtaa 60 agaaaaagaa acatgataaa caagaacaga aaggaagtgt gggagctaca ttcaaattag 120 gtgactcttt gtcaaaccca aacgaaagag ccattgttaa agaaaagatg gtatcaaata 180 ctaagtctgt agacacgaaa gcgagttcat ctaaatttag tagaattcta actcctaagg 240 agtatttaca aaggcagaag cataaagaag ctccgagtaa taaagcatcg aagaaaatct 300 gtgtgaaaaa cgtgccatgt gattctgaac atatgagacc aagtaaactt gccgtgcagg 360 ttgaaagttg tgggaaatca aatgagaaac acagcagcgg cgtgcagacc tctaaagaat 420 cattaaatgg cttgacaagc catggtaaaa acctcaaaat ccaccattct caggagtcta 480 aaacatacaa cattctaagg aatgttaaag aaaaagttgg tgggaagcag cctgataaaa 540 tatggattga taagactaaa ttagacaaat taaccaatat aagcaacgaa gctcaattca 600 gccaaatgcc tccccaagta aaggatcaaa agaaattata tctgaataga gttgggttta 660 aatgcactga acgtgaaagc atttctctca ccaaattaga aagttcaccc aggaagcttce 720 ataaagataa gagacaggaa aataaacata agaccttttt accggtgaaa ggtaacacag 780 aaaaatcaaa catgctggag tttaaattat gtccagatat cttactaaag aatacaaact 840 ctgtggaaga acggaaggat gtaaagcctc atcctaggaa ggagcaagcc cctctgcaag 800 tttcaggaat aaaaagtaca aaagaagact ggttaaaatt tgttgctaca aagaaaagga 960 cacagaaaga cagccaagag agagataatg ttaattcaag actctcgaag agaagcttca 1020 gtgcagatgg atttgagatg ctacaaaacc cagtaaaaga ttcaaaagaa atgtttcaaa 1080 cctacaaaca gatgtacctg gagaagagaa gcagaagcct tggtagcagt cctgtaaaat 1140 aattacaaga tgtggttttg taattgccac tgggaaattt ctttcctttt ctgttcaaaa 1200 tatttcgetg aaactaatga gaaatgccat gataaagatt tctcagagtt tggttceccac 1260 tttcattgta tttcattgaa agtgcttaat taaaatggct tgagaacttt gggtagccat 1320 gtgtaagaaa tggatggtat tcaccgggga aacaaggtat ttgaatttct aEtELaLiga 1380 accagattta ccattatttt aaaaggaatg cttatacaaa tcaatttgaa attctaccca 1440 . tcttgaggga ggaccgttcc tcagttaagg acttgtttat ttaaatggga ctgtaaatat 1500 gttttggttt ctaagctata ttagcaaaat ttatttttca aaaacgccca ctgtgatgtg 1560 aatgtcaaaa tatattctta agtgttttat aactaattgt aaactttttt tcagaagtct 1620 tattttatac ttgtgaaact gaacacaatt ttgggacaac gtttaaacat tacttttcat 1680 acttgaaata aacatttatt ttttaaaaaa ct 1712 <210> 2851 <211l> 1726 <212> DNA <213> Homo sapiens <400> 2851 tttttccagt gaaacaaaac gtaagaatct gagtttgttt ttcaaagatc actaaatttt 60 agttatgatt atatcacatt ttccaaaatg tgtggcagtt tttgcectec ttgctetgag 120 tgttggtgca ctggacactt ttattgctge agtatatgag catgcggtga tattaccaaa 180 cagaacagaa acacctgttt caaaagaaga agctttgctc ctgatgaaca agaacataga 240 tgttttggag aaagcagtta agctggcagc gaagcagggt gcacatatca ttgtgaccce 300 agaagatgga atctatggtt ggatcttcac cagggagagc atttacccct atctagagga 360 tataccagac cctggagtga actggattcc atgtagagac ccctggagat tcggcaacac 420 accagtgcaa caaagactca gctgcctgge caaggacaac tctatctatg tcgtggctaa 480 tattggggac aagaagccat gcaatgctag tgactctcag tgtccceetg atggeegtta 540 Ccaatacaac actgatgtgg tgtttgattc tcagggaaaa ctgttggcac gctaccataa 600 gtacaatctt tttgeacctg aaattcagtt tgatttcccce aaggattcag aacttgtgac 660 ttttgacact ccctttggga agtttggcat ttttacttgc tttgacattt tttctcatga 720 cccagctgeg gtggtggtgg atgaagtttc aattgacagc attctctacc ccacagcatg 780 gtacaacacg ctgccectee tcteggetgt teccttcecat tcagcatggg ccaaggccat 840 gggagtcaat ctacttgctg caaataccca caacaccagc atgcacatga cagggagtgg 900 aatctacgcc ccagaagcag tcaaggtgta ccactatgac atggaaacag agagtggtca 960 gctgttgcta tcagaactga agtctecggec cecgeccgtgag cccacctace ctgcagctgt 1020 tgactggcat gcgtatgcca gcagtgtcaa gccattttee tctgaacagt cagattttet 1080 ggggatgatt tattttgatg agtttacctt caccaagctt aagagaaata caggaaatta 1140 cacagcttgc cagaaagatc tgtgttgtca cttaacttac aagatgtctg agaagcgaac 1200 agacgagatc tatgccctag gtgecttttga tggactgeac acagtagaag gccaatatta 1260 cttacagata tgtgcattac tgaagtgtca aaccactgac ctggaaacgt gtggagaacc 1320 tgtggggtca gcttttacca agtttgaaga cttctcccte agtggcacat ttggaacgcg 1380 ttatgttttc ccacagatca ttctaagtgg gagtcagctt gcccctgaaa gacattatga 1440 gatttcaaga gatggacgct tgaggagccg aagtggagcce ccttegectyg tcttagttat 1500 ggccctgtat ggaagagtgt ttgagaagga Ccccteccacge ttagggceagg gatctgggaa 1560 1198 BN attccagtga tctcectttag Cagagccctt ttaggattag cctggctaag aaaggaagaa 1620 aaaaaagaga tcegttagtg tctgtttaga aaagatgtta taaacttaca gaaacaaata 1680 taataaactg aagcagattt gaaaagcaaa aaaaaaaaaa aaaaaa 1726 <210> 2852 <211> 7603 <212> DNA <213> Homo sapiens <400> 2852 ttttettget tttetteect tttttttett tttgcaaaca aaacaaaaaa cagcatagaa 60 gaaagagcaa aataaagaag aagaagagga ggaagagagg gaaagagagg aagggaaaaa 120 aaacaccaac ccgggcagag gaggaggtgc ggcggcggcg geggeggcegg cagcggegge 180 agceggegegg cggeggetcg gaccccctec cccggcotcec ceccatcagtg cagetctecg 240 ggcgatgcca gaatagatgc cggggcaatg tcccgecgea aacagggcaa cccgeageac 300 ttgtcccaga gggagctcat caccccagag gctgaccatg tggaggccge catcctcgaa 360 gaagacgagg gtctggagat agaggagcca agtggcctgg ggctgatggt gggtggccece 420 gaccctgacc tgctcacctg tggccagtgt caaatgaact tccccttggg ggacatccetg 480 gtttttatag agcacaaaag gaagcagtgt ggcggcagct tgggtgectg ctatgacaag 540 gccctggaca aggacagccc geccaccctce tcacgcteeg agctcaggaa agtgtccgag 600 ccggtggaga tcgggatcca agtcaccccec gacgaagatg accacctget ctcacccacg 660 aaaggcatct gtcccaagca ggagaacatt gcaggtaaag atgagccttc cagctacatt 720 tgcacaacat gcaagcagcc cttcaacagc gecgtggttcce tgctgcageca cgecgcagaac 780 acgcacggct tccgcatcta cctggagccc gggccggcca gcagctcget cacgcegegg 840 ctcaccatcc cgcegeeget cgggecggag gocgtggege agtcccegct catgaattte 900 ctgggcgaca gcaacccctt caacctgetg cgcatgacgg gecccatcct gcgggaccac 960 ccgggctteg gcgagggecg cctgecggge acgccgecte tcttcagtee cecegecgege 1020 caccacctgg acccgecaccg cctcagtgee gaggagatgg ggctcgtcgce ccagcacccc 1080 agtgectteg accgagtcat gecgcctgaac cccatggcca tcgactcgee cgccatggac 1140 ttectecgegge ggctccgega getggecggge aacagctcca cgccgeegee cgtgtccecg 1200 ggccgeggea accctatgca ccggctcctg aacceccttec agcecagece caagtcecccg 1260 ttcctgageca cgeccgecget gecgeccatg ccecctggeg gcacgecgec cccgecagecg 1320 ccagccaaga dgcaagtcgtg cgagttctge ggcaagacct tcaagttcca gagcaatctc 1380 atcgtgcacc ggcgcagtca cacgggcgag aagccctaca agtgccagct gtgcgaccac 1440 gecgtgetege aggccagcaa gctcaagege cacatgaaga cgcacatgca caaggccggce 1500 tcgectggecg goccgctcecga cgacgggetce tcggecgeca gcteccecga gecccggcace 1560 agcgagctgg cgggcgaggg cctcaaggcg goccgacggtg acttccgcca ccacgagage 1620 gacccgtege tgggccacga gecggaggag gaggacgagg aggaggagga ggaggaggag 1680 gagctgctac tggagaacga gagceggcecc gagtcgagct tcagcatgga ctcggagetg 1740 agccgcaacc gegagaacgg cggtggtggg gtgceccgggg tceccgggcgce ggggggcggc 1800 gcggeccaagg cgctggectga cgagaaggcg ctggtgetgg gcaaggtcat ggagaacgtg 1860 ggcctaggeg cactgecgca gtacggcgag ctcctggceg acaagcagaa gcgeggcegec 1920 ttcctgaagc gtgcggecggg cggeggggac gcgggcgacg acgacgacgc gggcggctge 1980 ggggacgegg gegcgggegg cgcggtcaac gggcgegggg gceggcttege gecaggeacce 2040 gagcccttco ccgggetctt cccgegcaag cccgegecge tgeccagcce cgggctcaac 2100 agcgccgeca agegcatcaa ggtggagaag gacctggage tgccgcccge cgegcotcatce 2160 ccgtccgaga acgtgtactc gcagtggctg gtgggctacg cggcgtcgeg gcacttcatg 2220 aaggaccccet tcctgggett cacggacgca cgacagtcge ccttecgecac gtcgtccgag 2280 cactcgteceg agaacggcag cctgegettc tecacgccge ccggggacct gctggacggc 2340 ggcctctegg gecgcagegg cacggccage ggaggcageca ccccgcacct gggeggeccg 2400 ggccccggge ggcccagetc caaggagggce cgccgcagceg acacgtgcega gtactgegge 2460 aaggtgttca agaactgcag caacttgacg gtgcaccggc ggagccacac cggcgagegg 2520 ccttacaagt gcgagctgtg caactacgeg tgcgcgcaga gcagcaagct cacgegecac 2580 atgaagacge acgggcagat cggcaaggag gtgtaccget gcgacatctg ccagatgecc 2640 ttcagcgtct acagcaccct ggagaaacac atgaaaaagt ggcacggcga gcacttgctg 2700 actaacgacg tcaaaatcga gcaggccgag aggagctaag cgegcgggcc ccggegeccec 2760 gcacctgtac agtggaaccg ttgccaaccg agagaatgct gacctgactt gcctccgtgt 2820 caccgccace ccgcaccecg cgtgtccccg gggeccaggg gaggcggeac tccaacctaa 2880 cctgtgtctg cgaagtccta tggaaacccg agggttgatt aaggcagtac aaattgtgga 2940 gecttttaac tgtgcaataa tttctgtatt tattgggttt tgtaattttt ttggcatgtg 3000 caggtacttt ttattattat tttttctgtt tgaattcctt taagagattt tgttgggtat 3060 ccatcccttc tttgtitttt ttttaacccg gtagtagect gagcaatgac tcgcaagcaa 3120 tgttagaggg gaagcatatc ttttaaatta taatttgggg ggaggggtgg tgctgctrtt 3180 ttgaaattta agctaagcat gtgtaatttc ttgtgaagaa gccaacactc aaatgacttt 3240 1200 x Co taaagttgtt tactttttca ttccttectt ttttttgtce tgaaataaaa agtggcatgc 3300 agtttttttt ttaattattt tttaattttt tttttggttt ttgtttttgg ggtggggggt 3360 gtggatgtac agcggataac aatctttcaa gtcgtagcac tttgtttcag aactggaatg 3420 gagatgtagc actcatgtcg tcccgagtca agecggccttt tctgtgttga tttecggettt 3480 catattacat aagggaaacc ttgagtggtg gtgctggggg aggcacccca cagactcage 3540 gccgccagag atagggtttt tggagggctc ctctgggaaa tggcccgaca gcattcectgag 3600 gttgtgcatg accagcagat actatcctgt tggtgtgccec tggggtgcca tggctgctat 3660 tcgctgtaga ttaggctaca taaaatgggce tgagggtacc tttttgggga gatggggtgg 3720 cctgcagtga cacagaaagg aagaaactag cggtgttctt ttaggcgttt tctggcttga 3780 cggcttctct ctttttttaa atcaccccca ccacataaat ctcaaatcct atgttgetac 3840 aaggggtcat ccatcatttc ccaagcagac gaatgcccta attaattgaa gttagtgtte 3900 tctcatttaa tgcacactga tgatattgta gggatgggtg gggtggggat cttgcaaatt 3960 tctattctct tttactgaaa aagcagggga tgagttecat cagaaggtgc ccagcgctac 4020 ttcccaggtt tttatttttt ttttcctatc tcattaggtt ggaaggtact aaatattgaa 4080 ctgttaagat tagacatttg aattctgttg acccgcactt taaagctttt gtttgcattt 4140 aaattaaatg gcttctaaac aagaaattgc agcatattct tctctttggc ccagaggtgg 4200 gttaaactgt aagggacagc tgagattgag tgtcagtatt gctaagcgtg gcattcacaa 4260 tactggcact ataaagaaca aaataaaata ataatttata ggacagtttt tctactgcca 4320 ttcaatttga tgtgagtgee ttgaaaactg atcttcctat ttgagtctct tgagacaaat 4380 gcaaaacttt ttttttgaaa tgaaaagact ttttaaaaaa gtaaaacaag aaaagtacat 4440 tctttagaaa ctaacaaagc cacatttact ttaagtaaaa aaaaaaaaaa ttctggttga 4500 agatagagga tatgaaatgc cataagaccc aatcaaatga agaaataaac ccagcacaac 4560 cttggacatc cattagctga attatcctca gecceccttttg tttttgggac aacgctgcett 4620 agatatggag tggaggtgat ttactgctga attaaaactc aagtgacaca agttacaagt 4680 tgatatcgtt gaatgaaaag caaaacaaaa acaattcagg aacaacggct aattttttet 4740 aaagttaaat ttagtgcact ctgtcttaaa aatacgttta cagtattggg tacatacaag 4800 ggtaaaaaaa aaattgtgtg tatgtgtgtt ggagcgatct ttttttttca aagtttgcett 4860 aataggttat acaaaaatgc cacagtggcc gcgtgtatat tgttttcttt tggtgacggg 4920 gttttagtat atattatata tattaaaatt tcttgattac tgtaaaagtg gaccagtatt 4980 tgtaataatc gagaatgcct gggcatttta caaaacaaga aaaaaaatac ccttttcttt 5040 tccttgaaaa tgttgcagta aaatttaaat ggtgggtcta taaatttgtt cttgttacag 5100 taactgtaaa gtcggagttt tagtaaattt ttttctgcct tgggtgttga atttttattt 5160 caaaaaaaat gtatagaaac ttgtatttgg ggattcaaag gggattgcta caccatgtag 5220 aaaaagtatg tagaaaaaaa gtgcttaata ttgttattgc tttgcagaaa aaaaaaaaat 5280 cacatttctg acctgtactt atttttctct tccoccgectcc ctctggaatg gatatattgg 5340 ttggttcata tgatgtaggc acttgctgta tttttactgg agctcgtaat tttttaactg S400 taagcttgte cttttaaagg gatttaatgt acctttttgt tagtgaattt ggaaataaaa 5460 agaaaaaaaa aacaaaaaca aacaggctgc cataatatat ttttttaatt tggcaggata 5520 aaatattgca aaaaaaacac atttgtatgt taagtcctat tgtacaggag aaaaagggtt 5580 gtttgacaac ctttgagaaa aagaaacaaa aggaagtagt taaatgcttt ggttcacaaa 5640 } tcatttagtt gtatatattt tttgtcggaa ttggcctaca cagagaaccg ttcgtgttgg 5700 ‘gcttectetet gaacgcoccecg aaccttgcat caaggctect tggtgtggcc acagcagace 5760 } agatgggaaa ttatttgtgt tgagtggaaa aaaatcagtt tttgtaaaga tgtcagtaac 5820 attccacatc gtcctccectt tctctaagag gecatctcta agatgtcaga tgtagaggag 5880 agagagcgag agaacatctt ccttctctac catcactcet gtggcggtca ccaccaccac 5940 ctctcecegec cttaccagca gaaagcaatg caaactgagc tgctttagte cttgagaaat 6000 } tgtgaaacaa acacaaatat cataaaagga gctggtgatt cagctgggtc caggtgaagt 6060 gacctgctgt tgagaccggt acaaattgga tttcaggaag gagactccat cacagcecagg 6120 . acctttcgtg ccatggagag tgttggectc ttgtcetttcet tccctgettt gectgetttge 6180 tctctgaaac ctacattccg tcagtttccg aatgcgaggg cctgggatga atttggtgcc 6240 tttecatatc tcgttetcte teecttceccect gegtttecte tccatcctte atcctccatt 6300 ggtcettttt ttttctttca ttttttattt aatttctttt cttectgtcet gttectccce €360 taatcctcta ttttattttt attttttgta aagccaagta gctttaagat aaagtggtgg 6420 tcttttggat gagggaataa tgcattttta aataaaatac caatatcagg aagccatttt 6480 ttatttcagg aaatgtaaga aaccattatt tcaggttatg aaagtataac caagcatcct 6540 : tttgggcaat tccttaccaa atgcagaagc ttttctgttce gatgcactct ttcctecttg 6600 ccacttacct ttgcaaagtt aaaaaaaagg ggggagggaa tgggagagaa agctgagatt 6660 oo .. tcagtttcct actgcagttt cctacctgca gatccagggdg ctgctgttge ctttggatge 6720 cccactgagg tcctagagtg cctccagggt ggtcttcectg tagtcataac agctagccag 6780 tgctcaccag cttaccagat tgccaggact aagccatccc aaagcacaag cattgtgtgt 6840 ctctgtgact gcagagaaga gagaattttg cttctgtttt gtgtttaaaa aaccaacacg 6500 : 1202 Y Co gaagcagatg atcccgagag agaggcctct agcatgggtg acccagecga cctcaggecg 6960 gtttccgecac tgccacaact ttgttcaaag ttgcccccaa ttggaacctg ccacttggca 7020 ttagagggtc tttcatgggg agagaaggag actgaattac tctaagcaaa atgtgaaaag 7080 taaggaaatc agcctttcat ceccggtccta agtaaccgtc agccgaaggt ctcgtggaac 7140 acaggcaaac ccgtgatttt ggtgectcett gtaactcagc cctgcaaage aaagtcccat 7200 tgatttaagt tgtttgcatt tgtactggca aggcaaaata tttttattac cttttctatt 7260 acttattgta tgagcttttg ttgtttactt ggaggttttg tcttttacta caagtttgga 7320 actatttatt attgcttggt atttgtgcte tgtttaagaa acaggcactt ttttttatta 7380 tggataaaat gttgagatga caggaggtca tttcaatatg gcttagtaaa atatttattg 7440 ttcctttatt ctctgtacaa gattttgggc ctettttttt ccttaatgtc acaatgttga 7500 gttcagcatg tgtctgccat ttcatttgta cgcttgttca aaaccaagtt tgttctggtt 7560 tcaagttata aaaataaatt ggacatttaa cttgatctcc aaa 7603 <210> - 2853 <211l> 3869 <212> DNA <213> Homo sapiens <400> 2853 gagecggtgg cgcaggtgtc ggggtcctceg agcgcccagc ctgggagcat gattgtggac 60 aagctgetgg acgacagceeg cggcggagag gggctgcggg acgcggeggg cggctgegge 120 ctcatgacca gcccgctcaa cctgagctac ttctacggcg cgtcgccgec cgccgcoegec 180 ccgggegect gocgacgccag ctgeteggtc ttgggcccct cggegeccgg ctegececcgge 240 teccgactect cecgacttcte ctotgecteg tcggtgteoct cctgeggege cgtggagtec 300 cggtcgagag gcggcegeceg cgecgagegce cagccagttg agccccatat gggggttgge 360 aggcagcaga gaggcccctt tcaaggtgtt cgggtaaaga actcagtgaa ggaactcetg 420 ttgcacatcc gaagtcataa acagaaggct tctggccaag ctgtggatga ttttaagaca 480 caaggtgtga acatagaaca gttcagagaa ttgaagaaca cagtatcata cagtgggaaa 540 aggaaagggc ccgattcgtt gtctgatgga cctgcttgca aaaggccage tctgttgeat 600 tcccaatttt tgacaccacc tcaaacacca acgcccogggg agagcatgga agatgttcat 660 Ctcaatgaac ccaaacagga gagcagtgct gatctgcttc agaacattat caacattaag 720 aatgaatgca gccccgttte cctgaacaca gttcaagtta gectggcetgaa ccccgtggtg 780 gtccctcaga gctcccecge agagcagtgt caggacttcoc atggagggea ggtettttet 840 ccacctcaga aatgccaacc attccaagtc aggggctccc aacaaatgat agaccaggcet 900 tccctgtace agtattctce acagaaccag catgtagagc agcagccaca ctacacccac 960 aaaccaactc tggaatacag tccttttccc atacctcccc agtcccecge ttatgaacca 1020 aacctctttg atggtccaga atcacagttt tgcccaaacc aaagcttagt ttcecttett 1080 ggtgatcaaa gggaatctga gaatattgct aatcccatge agacttccte cagtgttcag 1140 cagcaaaatg atgctcactt gcacagcttc agcatgatgc ccagcagcgc ctgtgaggcec 1200 atggtggggc acgagatggc ctctgactct tcaaacactt cactgccatt ctcaaacatg 1260 ggaaatccaa tgaacaccac acagttaggg aaatcacttt ttcagtggca ggtggagcag 1320 gaagaaagca aattggcaaa tatttcccaa gaccagtttc tttcaaagga tgcagatagt 1380 gacacgttcc ttcatattgc tgttgcccaa gggagaaggg cactttccta tgttcttgea 1440 agaaagatga atgcacttca catgctggat attaaagagc acaatggaca gagtgccttt 1500 caggtggcag tggctgccaa tcagcatctc attgtgcagg atctggtgaa catcggggea 1560 caggtgaaca ccacagactg ctggggaaga acacctctge atgtgtgtge tgagaagggce 1620 cactcccagg tgcttcaggc gattcagaag ggagcagtgg gaagtaatca gtttgtggat 1680 cttgaggcaa ctaactatga tggcctgact ccccttcact gtgcagtcat agcccacaat 1740 gctgtggtece atgaactcca gagaaatcaa cagcctcatt cacctgaagt tcaggagcett 1800 ttactgaaga ataagagtct ggttgatacc attaagtgcc taattcaaat gggagcagcg 1860 gtggaagcga aggatcgcaa aagtggccgc acagccctge atttggcagc tgaagaagea 1920 aatctggaac tcattcgcct ctttttggag ctgcccagtt gectgtcttt tgtgaatgea 1380 aaggcttaca atggcaacac tgccctccat gttgctgcca gcttgcagta tcggttgaca 2040 caattagatg ctgtccgect gttgatgagg aagggagcag acccaagtac tcggaacttg 2100 gagaacgaac agccagtgca tttggttccc gatggccctg tgggagaaca gatccgacgt 2160 A, gaaagtccat tcagcagaga gctccaccgt attagctcca ttagcttgga 2220 gcctggectag caacactcac tgtcagttag gcagtcctga tgtatctgta catagaccat 2280 ttgccttata ttggcaaatg taagttgttt ctatgaaaca aacatattta gttcactatt 2340 atatagtggg ttatattaaa agaaaagaag aaaaatatct aatttctctt ggcagatttg 2400 catatttcat acccaggtat ctgggatcta gacatctgaa tttgatctca atggtaacat 2460 tgccttcaat taacagtage ttttgagtag gaaaggactt tgatttgtgg cacaaaacat 2520 tattaatata gctattgaca gtttcaaagc aggtaaattg taaatgtttc tttaagaaaa 2580 agcatgtgaa aggaaaaagg taaatacagc attgaggctt catttggcct tagtccctgg 2640 gagttactgg cgttggacag gcttcagtca ttggactaga tgaaaggtgt ccatggttag 2700 aatttgatct ttgcaaactg tatataattg ttatttttgt ccttaaaaat attgtacata 2760

1204 cttggttgtt aacatggtca tatttgaaat gtataagtcc ataaaataga aaagaacaag 2820 tgaattgttg ctatttaaaa aaattttaca attcttacta aggagttttt attgtgtaat 2880 cactaagtct ttgtagataa agcagatggg gagttacgga gttgttcctt tactggctga 2940 aagatatatt cgaattgtaa agatgctttt tctcatgcat tgaaattata cattatttgt 3000 agggaattgc atgctttttt ttttttttet cccgagacag ggtcttgctc tggcgcccag 3060 gctggagtac agtggcatga tcttggctca cttcagectt gacttgggct caagtgatcce 3120 tcctacctga gecttctgag taactgggac tacaggtgtg cactcoctege ctggctaatt 3180 ttttattttt tgtacaggca ggatcttgcc accttgccca ggctggtctt gaactcctga 3240 gctcatgcca tctgectgee ttagtctccc aaaatgctgg gattacagga gtgagccacc 3300 atgccegget ggcagttgca tggaagagaa cacctcttta tggcttaccc tctagaattt 3360 ctaatttatg tgttctgttg aaatttttgt ttttttacct ttattgaaac aacaaaaagt 3420 cagtattgaa acatatcttc ctgttttctg ttgtcaaatg atgataatgt gccatgatgt 3480 tttatatata tcattcagaa aaagttttat tttttaataa cattctatta acattatttt 3540 gcttgceget ggcatgcctg aggaatgtat ttggctttga ttacacacta agtttttgta 3600 ataaatttga ctcattaaaa accttttttt tttaaaaaaa aaaaaaagaa aatctcatta 3660 gtgaacttat ctttgcagct gagtacttaa attcttttta aaaagatacc ctttggattg 3720 atcacattgt ttgacccagt atgtcttgta gacacgttag ttataatcac cttgtatctc 3780 taaatatggt gtgatatgaa ccagtccatt cacattggaa aaactgatgg ttttaaataa 3840 actaattcac taataaaaaa aaaaaaaaa 3869 <210> 2854 <211> - 34898 <212> DNA <213> Homo sapiens <400> 2854 cgggagtagc gcagtcgecca aagccgccge tgccaaagct gecgccacta gecgggeatg 60 gccatggegt ccccggecat cgggcagege ccgtacccge tactcttgga ccccgagcecg 120 ccgegetatc tacagagect gagcggcccc gagctaccgce cgecgccccce cgaccggtcece 180 tcgegectet gtgtcecegge geccctcotec actgcgeccecg gggcgcgega ggggcgcage 240 gcceggaggg ctgccegggg gaacctggag cccccgecce gggectcccg acccgcetcge 300 ccgetecegge ctggtetgca gcagagactg cggcggeggce ctggagegcecc ccgaccccege 360 gacgtgcgga gcatcttcga gecagccgcag gatcccagag tcecggcgga gcgaggcgag 420 gggcactgct tcgecgagtt ggtgctgecg ggcggccecg gcetggtgtga cctgtgegga 480 cgagaggtgc tgcggcagge gcetgegetge actaactgta aattcacctg tcacccagaa 540 tgccgcagec tgatccagtt ggactgcagt cagcaggagg gtttatcccg ggacagaccc 600 tctccagaaa gcaccctcac cgtgaccttc agccagaatg tctgtaaacc tgtggaggag 660 acacagcgcc cgcccacact gcaggagatc aagcagaaga tcgacagcta caacacgcga 720 gagaagaact gcctgggcat gaaactgagt gaagacggca cctacacggg tttcatcaaa 780 gtgcatctga aactccggcg gcctgtgacg gtgecctgcectyg ggatccggee ccagtccatce 840 tatgatgcca tcaaggaggt gaacctggcg gctaccacgg acaagceggac atccttctac 900 ctgcecectag atgccatcaa gcagctgcac atcagcagca ccaccacegt cagtgaggtc 960 atccaggggc tgctcaagaa gttcatggtt gtggacaatc cccagaagtt tgcacttttt 1020 aagcggatac acaaggacgg acaagtgctc ttccagaaac tctccattgc tgaccgeccece 1080 ctctacctgc gectgettge tgggectgac acggaggtce tcagcetttgt gctaaaggag 1140 aatgaaactg gagaggtaga gtgggatgcc ttctccatcc ctgaacttca gaacttcectc 1200 teccteocotggt gecattcagat ttatttgtat tattaattat tattttgcaa cagacacttt 1260 ttctcaggac atctctggca ggtgcatttg tgcctgccca gcagttccag ctgtggcaaa 1320 agtctcttcc atggacaagt gtttgcacga gggttcagct gtgecccgececc ccaggctgtg 1380 ccccaccaca gattctgecca aggatcagaa ctcatgtgaa acaaacagct gacgtcctcet 1440 ctcgatctgc aagcctttca ccaaccaaat agttgcctct ctcgtcacca aactggaacc 1500 tcacaccagc cggcaaagga aggaagaaag gttttagagc tgtgtgttet ttctetggea 1560 ttgattccte tttgagttct cttacttgec acgtacagga ccattattta tgagtgaaaa 1620 gttgtagcac attccttttg caggtctgag ctaagccecct gaaagcaggg taatgctcat 1680 aaaaggactg ttcccgegge cccaaggtgc ctgttgttca cacttaaggg aagtttataa 1740 agctactggc cccagatgct cagggtaagg agcaccaaag ctgaggctgg ctcagagatc 1800 tccagagaag ctgcagcctg ccctggccct ggctctggec ctggeccaca ttgcacatgg 1860 aaacccaaag gcatatatct gcgtatgtgt ggtacttagt cacatctttg tcaacaaact 1920 gttegttttt aagttacaaa tttgaattta atgttgtcat categtcatg tgtttcccca 1980 aagggaagcc agtcattgac catttaaaaa gtctcctgct aagtatggaa atcagacagt 2040 aagagaaagc Caaaaagcaa tgcagagaaa ggtgtccaag ctgtcttcag ccttccccag 2100 ctaaagagca gaggagggcc tgggctactt gggttcccca teggectcca gcactgcctce 2160 cctcctececca ctgcgactct gggatctcca ggtgctgece aaggagttge cttgattaca 2220 gagaggggag cctccaattc ggccaacttg gagtcettte tgttttgaag catgggecag 2280

1206 . oo acccggcact gcgetcggag agccggtggg cctggectcece ccgtcgacct cagtgecttt 2340 ttgttttcag agagaaatag gagtagggcg agtttgectg aagctetget getggettcet 2400 cctgccagga agtgaacaat ggcggeggtg tgggagacaa ggccaggaga gcccgcegttce 2460 agtatgggtt gagggtcaca gacctccctc ccatctgggt geoctgagttt tgactccaat 2520 cagtgatacc agaccacatt gacagggagg atcaaattcc tgacttacat ttgcactggc 2580 ttettgttta ggctgaatcc taaaataaat tagtcaaaaa attccaacaa gtagccagga 2640 ctgcagagac actccagtgc agagggagaa ggacttgtaa ttttcaaagc agggctggtt 2700 ttccaaccca gectctgaga aaccatttct ttgctatcct ctgecttcec aagtcectcet 2760 tgggtcggtt caagcccaag cttgttcgtg tagcttcaga agttccectet ctgacccagg 2820 ctgagtccat actgcccctg atcccagaag gaatgctgac ccctegtegt atgaactgtg 2880 catagtctcc agagcttcaa aggcaacaca agctcgcaac tctaagattt ttttaaacca 23940 caaaaaccct ggttagccat ctcatgctca gecttatcac ttcecctcect ttagaaactc 3000 tctcectget gtatattaaa gggagcaggt ggagagtcat tttcecttcegt cctgcatgtce 3060 tctaacatta atagaaggca tggctcctgc tgcaaccgct gtgaatgetg ctgagaacct 3120 ccctctatgg ggatggctat tttatttttg agaaggaaaa aaaaagtcat gtatatatac 3180 acataaaggc atatagctat atataaagag ataagggtgt ttatgaaatg agaaaattat 3240 tggacaattc agactttact aaagcacagt tagacccaag gcctatgctg aggtctaaac 3300 ctctgaaaaa agtatagtat cgagtacccg ttccctecca gaggtgggag taactgctag 3360 tagtgcctte tttggttgtg ttgctcagtg tgtaagtgtt tgtttccagg atattttctt 3420 tttaaatgtc tttcttatat gggttttaaa aaaaagtaat aaaagcctgt tgcaaaaatg 3480 aaaaaaaaaa aaaaaaaa 3498 <210> 2855 <211> 1505

<212> DNA <213> Homo sapiens <400> 2855 gctggtecgga ggctegcagt gectgteggeg agaagcagtce gggtttggag cgcttgggte 60 gcgttggtge gcggtggaac gecgcccaggg accccagttc ccgegagcag ctcecgegecg 120 cgcctgagag actaagctga aactgctgcet cagctcccaa gatggtgcca cccaaattgce 180 atgtgctttt ctgcctectge ggotgectgg ctgtggttta tccttttgac tggcaataca 240 taaatcctgt tgcccatatg aaatcatcag catgggtcaa caaaatacaa gtactgatgg 300 ctgetgcaag ctttggceccaa actaaaatcc cccggggaaa tgggccttat tccgttggtt 360 gtacagactt aatgtttgat cacactaata agggcacctt cttgcgttta tattatcecat 420 cccaagataa tgatcgcctt gacacccttt ggatcccaaa taaagaatat ttttggggte 480 ttagcaaatt tcttggaaca cactggctta tgggcaacat tttgaggtta ctetttggtt 540 caatgacaac tcctgcaaac tggaattccc ctctgaggec tggtgaaaaa tatccacttg 600 ttgtttttte tcatggtctt ggggcattca ggacacttta ttctgctatt ggcattgace 660 tggcatctca tgggtttata gttgctgctg tagaacacag agatagatct gcatctgcaa 720 cttactattt caaggaccaa tctgctgcag aaatagggga caagtcttgg ctctacctta 780 gaaccctgaa acaagaggag gagacacata tacgaaatga gcaggtacgg caaagagcaa 840 aagaatgttc ccaagctctc agtctgattc ttgacattga tcatggaaag ccagtgaaga 900 atgcattaga tttaaagttt gatatggaac aactgaagga ctctattgat agggaaaaaa 960 tagcagtaat tggacattct tttggtggag caacggttat tcagactctt agtgaagatc 1020 agagattcag atgtggtatt gccctggatg catggatgtt tccactgggt gatgaagtat 1080 attccagaat tcctcageccc ctctttttta tcaactctga atatttecaa tatcctgcecta 1140 atatcataaa aatgaaaaaa tgctactcac ctgataaaga aagaaagatg attacaatca 1200 ggggttcagt ccaccagaat tttgctgact tcacttttgc aactggcaaa ataattggac 1260 acatgctcaa attaaaggga gacatagatt caaatgtagc tattgatctt agcaacaaag 1320 cttcattagc attcttacaa aagcatttag gacttcataa agattttgat cagtgggact 1380 gcttgattga aggagatgat gagaatctta ttccagggac caacattaac acaaccaatc 1440 aacacatcat gttacagaac tcttcaggaa tagagaaata caattaggat taaaataggt 1500 tee 1505 <210> 2856 <211l> 5220 <212> DNA <213> Homo sapiens ] <400> 2856 cagtcgctcc gagcggeccge gagcagagec gcoccagecct gtcagectgcg ccgggacgat 60 aaggagtcag gccagggegg gatgacactc attgattcta aagcatcttt aatctgccag 120 gcggaggggg ctttgetggt ctttettgga ctattccaga gaggacaact gtcatetggg 180 aagtaacaac gcaggatgcc ccctggggtg gactgcccca tggaattctg gaccaaggag 240 gagaatcaga gcgttgtggt tgacttcctg ctgeccacag gggtctacct gaacttcect 300 gtgtcccgea atgccaacct cagcaccatc aagcagctge tgtggcaccg cgcccagtat 360 gagccgctcet tccacatget cagtggccce gaggectatg tgttcacctg catcaaccag 420 acagcggagce agcaagagct ggaggacgag caacggcgtc tgtgtgacgt gcageccctte 480 ctgeceecgtee tgegeetggt ggeccegtgag ggcgaccdceg tgaagaagct catcaactca 540 cagatcagcc tcctcatcgg caaaggecte cacgagtttg actccttgtg cgacccagaa 600 gtgaacgact ttcgcgccaa gatgtgccaa ttctgcecgagg aggcggcecgc ccgcecggceag 660 cagctgggct gggaggcctg gctgcagtac agtttcccecc tgcagctgga gecctceggcet 720 caaacctggg ggcctggtac cctgeggcte ccgaaccggg cccttctggt caacgttaag 780 tttgagggca gcgaggagag cttcaccttc caggtgtcca ccaaggacgt gccgctggeg 840 ctgatggect gtgccctgeg gaagaaggec acagtgttcc ggcagcecget ggtggagcag 900 ccggaagact acacgctgca ggtgaacggce aggcatgagt acctgtatgg caactacccg 960 ctctgccagt tccagtacat ctgcagctge ctgcacagtg ggttgaccec tcacctgace 1020 atggtccatt cctcctccat cctcgccatg cgggatgagc agagcaacce tgccccccag 1080 gtccagaaac cgcgtgccaa accacctccc attcctgcga agaagecttce ctctgtgtec 1140 ctgtggtcec tggagcagec gttocgcatc gagctcatcc agggcagcaa agtgaacgece 1200 gacgagcgga tgaagctggt ggtgcaggcce gggcttttcc acggcaacga gatgctgtge 1260 aagacggtgt ccagctcgga ggtgagcgtg tgctcggage ccgtgtggaa gcagcggetg 1320 gagttcgaca tcaacatctg cgacctgcce cgcatggccc gtctctgett tgecgctgtac 1380 gcecgtgatcg agaaagccaa gaaggctcgce tccaccaaga agaagtccaa gaaggcggac 1440 tgccccattg cctgggecaa cctcatgetg tttgactaca aggaccagct taagaccggg 1500 gaacgctgce tctacatgtg gcoccctccgte ccagatgaga agggcgagcet gctgaaccce 1560 acgggcactg tgcgcagtaa ccccaacacg gatagcgccg ctgccctgct catctgectg 1620 cccgaggtgg ccccgcacce cgtgtactac cccgecctgg agaagatctt ggagetgggg 1680 . cgacacagcg agtgtgtgca tgtcaccgag gaggagcagce tgcagctgcg ggaaatcectg 1740 gagcggcggg ggtctgggga getgtatgag cacgagaagg acctggtgtg gaagctgegg 1800 catgaagtcc aggagcactt cccggaggeg ctagcccgge tgctgetggt caccaagtgg 1860 aacaagcatg aggatgtggc ccagatgctc tacctgctgt gctectggcec ggagctgccec 1820 gtcctgagcg ccctggaget gotagacttc agcttecccg attgccacgt aggctccttc 1980 gccatcaagt cgectgcggaa actgacggac gatgagctgt tccagtacct gctgcagetg 2040 gtgcaggtge tcaagtacga gtcctacctg gactgcgage tgaccaaatt cctgctggac 2100 cgggcecctgg ccaaccgcaa gatcggccac ttecttttet ggcacctcecg ctecgagatg 2160 cacgtgeccgt cggtggccct gegettcgge ctcatcetgg aggcctactg caggggcagce 2220 acccaccaca tgaaggtgct gatgaagcag ggggaagcac tgagcaaact gaaggccctg 2280 N 1209 aatgacttcg tcaagctgag ctctcagaag acccccaagce cccagaccaa ggdagctgatg 2340 cacttgtgca tgcggcagga ggcctaccta gaggccctet cccacctgeca gtececacte 2400 gaccccagca ccctgetggce tgaagtctgce gtggagcagt gcaccttcat ggactccaag 2460 atgaagcccc tgtggatcat gtacagcaac gaggaggcag gcagcggcgg cagcgtggge 2520 atcatcttta agaacgggga tgaccteegg caggacatgc tgaccctgca gatgatccag 2580 Cctcatggacg tcctgtggaa gcaggagggg ctggacctga ggatgaccce ctatggctgce 2640 ctcecccaccg gggaccgcac aggectcatt gaggtggtac tccgttcaga caccatcgee 2700 aacatccaac tcaacaagag caacatggca gccacagceg ccttcaacaa ggatgeccetg 2760 ctcaactggc tgaagtccaa gaacccgggg gaggccctgg atcgagccat tgaggagttc 2820 accctctect gtgctggeta ttgtgtggce acatatgtge tgggcattgg cgatecggcac 2880 agcgacaaca tcatgatccecg agagagtggg cagctgttcc acattgattt tggccacttt 2940 ctggggaatt tcaagaccaa gtttggaatc aaccgcgagce gtgtcccatt catcctcacce 3000 tatgactttg tccatgtgat tcagcaggag aagactaata atagtgagaa atttgaacgg 3060 ttcecgggget actgtgaaag ggcctacacc atcctgecgge gecacggget tctettecte 3120 cacctctttg ccectgatgeg ggcggcaggce ctgcctgage tcagetgcte caaagacatc 3180 cagtatctca aggactcect ggcactgggg aaaacagagg aggaggcact gaagcacttce 3240 cgagtgaagt ttaacgaagc cctcegtgag agctggaaaa ccaaagtgaa ctggctggcec 3300 cacaacgtgt ccaaagacaa caggcagtag tggctcctcc cagccctggg cccaagagga 3360 ggcggctgeg ggtcegtgggg accaagcaca ttggtcctaa aggggctgaa gagcctgaac 3420 tgcacctaac gggaaagaac cgacatggct gecttttgtt tacactggtt atttatttat 3480 gacttgaaat agtttaagga gctaaacagc cataaacgga aacgcctect tcattcagceg 3540 gcggtgetgg gecccocgag gctgcacctg gctctegget gaggattgtc accccaagtce 3600 ttccagetgg tggatctggg cccagcaaag actgttctcce tceccgaggga accttettee 3660

~ caggcctece gecagactge ctgggtecctyg gcgectggeg gtcacctggt gcctactgte 3720 cgacaggatg cctegatcct cgtgcgacce accctgtgta tcctcectag actgagttct 3780 ggcagctcece cgaggcagec ggggtacect Ctagattcag ggatgcttge tctccacttt 3840 tcaagtgggt cttgggtacg agaattcect catctttetce tactgtaaag tgattttgtt 3900 tgcaggtaag aaaataatag atgactcacc acacctctac ggctggggag atcaggccca 3960 gccccataaa ggagaatcta cgctggtcct caggacgtgt taaagagatc tgggectcat 4020 gtagctcacc ccggtcacgc atgaaggcaa aagcaggtca gaagcgaata ctctgccatt 4080 1210 Co atctcaaaaa tctttttttt trtttttttg agatggggtc ttcctetgtt geccaggetg 4140 gagtgcagtg gtgcaatctt ggctcactgt aacctccgcc tcccaggtte aagtgattcet 4200 tcttgccteca gectectgag tagctgggat tacaggtgty caccacccgt acccagctaa 4260 tttttgtatt ttagtagaga cgggggtttc accatgttgg ctgggectggt ctegaactce 4320 tgacctcagg tgatccaccc gecctgagect cccaaagtge tgggattaca ggcatgagcc 4380 accacgcccg gecccactctg ccattgtcta agccacctct gaaagcaggt tttaacaaaa 4440 ggatgaggcc agaactcttc cagaaccatc acctttggga acctgcetgtg agagtgctga 4500 ggtaccagaa gtgtgagaac gagggggcgt gctgggatct ttctctctga ctatacttag 4560 tttgasatgg tgcaggetta gtcttaagee tccaaaggcc tggatttgag cagctttaga 4620 aatgcaggtt ctagggcttc tcccagcctt cagaagccaa ctaactctgc agatggggct 4680 aggactgtgg gcecttttagca gcccacaggt gatcctaaca tatcaggcca tggactcagg 4740 acctgccegg tgatgctgtt gatttetcaa aggtotteca aaactcaaca gagccagaag 4800 tagccgeceg ctcagcgget caggtgccag ctectgttetg attcaccagg ggtcegtcag 4860 tagtcattgc cacccgcggg gcacctccct ggccacacgc ctgttcccag caagtgctga 4920 aactcactag accgtctgecc tgtttecgaaa tggggaaagc cgtgcgtgcg cgttatttat 4980 ttaagtgcgc ctgtgtgcge gggtgtggga gcacactttg caaagccaca gecgtttctgg 5040 ttttgggtgt acagtcttgt gtgcctggcg agaagaatat tttctatttt tttaagtcat 5100 ttcatgtttc tgtctgggga aggcaagtta gttaagtatc actgatgtgg gttgagacca 5160 gcactctgtg aaaccttgaa atgagaagta aaggcagatyg aaaagaaaaa aaaaaaaaaa 5220 <210> 2857 <211> 1158 <212> DNA <213> Homo sapiens <400> 2857 gecctgetget ctggccectg gtectgtect cttectceccage atggtgtgte tgaagetcec 60 tggaggctcc agcttggcag cgttgacagt gacactgatg gtgctgagct cccgactgge 120 tttcgectggg gacacccgac cacgtttcectt ggagctgegt aagtcectgagt gtcatttctt 180 caatgggacg gagcgggtgc ggtacctgga cagatacttc cataaccagg aggagttcct 240 gegecttecgac agcgacgtgg gggagtaccg ggcggtgacg gagetgggge ggcctgtege 300 cgagtcctgg aacagccaga aggacctcct ggagcagaag cggggccgdg tggacaatta 360 ctgcagacac aactacgggg ttggtgagag cttcacagtg cagcggcgag tccatcctca 420 ggtgactgtg tatcctgcaa agacccagcc cctgcagcac cacaacctcc tggtctgcte 480

E.

tgtgagtggt ttctatccag gcagcattga agtcaggtgg ttecggaacg gccaggaaga 540 gaaggctggg gtggtgtcca cgggectgat ccagaatgga gactggacct tccagaccect 600 ggtgatgcta gaaacagttc ctcggagtgg agaggtttac acttgccaag tggagcacec 660 aagcgtaacyg agcgcetcetca cagtggaatg gagagcacgg tctgaatctg cacagagcaa 720 gatgctgagt ggagtcgggg gctttgtgcet gggcctgctce ttecttgggg ccgggctgtt 780 catctacttce aggaatcaga aaggacactc tggacttecag ctcaacaggat tcctgagcetg 840 aagtgcagat gacaatttaa ggaagaatct tctgcceccag ctttgcagga tgaaaagctt 900 tcecegeectgg ctgttattet tccacgagag agggctttcet caggacctag ttgctactgg 960 ttcagcaact gcagaaaatg teccteecttg tggcttecte agttcctgcc cttggectga 1020 agtcccageca ttgatggcag cgecctcatet tcaacttttg tgctccectt tgcctaaace 1080 ctatggcctc ctgtgcatct gtactcacce tgtaccacaa acacattaca ttattaaatg 1140 tttctcaaag atggagtt 1158 <210> 2858 <21l1l> 6807 <212> DNA <213> Homo sapiens <400> 2858 tctagagtaa gaaactagct gagcaacgtg gtgtcacact atacacccat taagacaaca 60 ggcacatgtg tcatgtccat tttgtggaaa agatatgtaa aataatttta agtaaaaaag 120 ataaatataa aaaagtgaat gcatacaaaa caatttcaca aaattgaatg ttactcaaaa 180 atcacagctc attttaagct gcacaaaata gtcatttttt tctttataat tgctcaaatt 240 cataatcaaa cagaagaaag ttcctgtett ggaagtagtg ctatgccceca attcttccag 300 agccagtact ttaaacaatt ccatttcatt attttcctgt agactaattc ttaggacatc 360 agcatatctc tcttcaagca ttaaaaaaat ctctttagag tcagtggatc aatagacagt 420 tcectgtttte cacacaactg aaagggtgga gcccccaaac cacaagggga agaaggaagt 480 taaaagatgt taaatactgg ggccagectcea cectggtcag cctagcacte tgacctagca 540 gtcaacatga aggctctcat tgttctgggg cttgtectec tttetgttac ggtecaggge 600 aaggtctttg aaaggtgtga gttggccaga actctgaaaa gattgggaat ggatggctac 660 aggggaatca gcctagcaaa ctgtaagtct actctccata attccagaga attagctacg 720 tatggaacag acactaggag agaaggaaga agaagaaggg gctttgagtg aatagatgtt 780 ttatttettt gtgggtttgt atacttacaa tggctaaaaa catcagtttg gttctttata 840 accagagata cccgataaag gaatacgggce atggcagggg aaaattccat tctaagtaaa $00 acaggacctg ttgtactgtt ctagtgctag gaagtttgct gggtgcctga gattcaatgg 960 cacatgtaag ctgactgaaa gatacatttg aggacctggc agagctctct caagtccttg 1020 gtatgtgact ccagttattt cccattttga acttgggetc tgagagccta gagtgatgca 1080 gtatttttct tgtcttcaag tcccectgeceg tgatgtggga tttttatttt tatttttatt 1140 ttattttatt ttatttttaa agacagtctc actgtgtggc ccaggctgga gtgcagtggc 1200 atgatctcag ctcactgcaa cctctgecctt ctgggctcaa gtgattctcg tgcttcagec 1260 ttctgagtag ctgtgactac aggtgtgtac caccacaccc agctaatttt ttgtattttc 1320 agtagagatg gggtttcacc atgttggcca agctggtctt gaactcctgg cctcaaatga 1380 tetgeccace tcagectecce aaagtggtag gattacaggt gtgaaccact gcacccagcce 1440 gacatgggat ttttaacagt gatgttttta aagaatatat tgaattccet acacaagagc 1500 agtaggaacc tagttccctt cagtcactct ttgtatagga tcccagaaac tcagcatgaa 1560 atgttttatt atttttatct actctacttg attaactatc tttcattttc tcccacacaa 1620 ttcaagatgt gccatgagga aaagttattt tatagtttag tacatagttg tcgatgtaat 1680 aatctctgta gttttcagat tgaattcaga catttcccct caatagctat ttttgaatga 1740 atgagtgaag ggatgaaatc acggaatagt cttgttttca agattctaac ttgatatcca 1800 aattcacctt tagatattat aagaaaattt ctatcagaaa atccttatgt ttttetgatt 1860 aaaaaaagca tttttccatc agcctatgta tctgctatga atttacaaaa tctactcaac 1920 agctctgttg atttttctgt tcttggctga atgttgcctg agggatggga gcacgggaag 1980 ggtaaaagca atggaagaaa catgtatttt aatattttaa aagtatgtta tattgttegt 2040 tggtgttaca agatgatttg cattacaaaa ggattctctt acaagtccct tatcttaaca 2100 ctaaagtgct aagatatttt ataagtaaat ctttatactt ataaaacaaa tcagtaaaat 2160 agaagtagct aagtagaact gattttgcta tagagtataa gtcacttagt gttgctgttt 2220 attactaaaa ataagttctt ttcagggatg tgtttggcca aatgggagag tggttacaac 2280 acacgagcta caaactacaa tgctggagac agaagcactg attatgggat atttcagatc 2340 aatagccget actggtgtaa tgatggcaaa accccaggag cagttaatgc ctgtcattta 2400 tecctgcagtg gtaagacaag ctaatatttg accaatctgg ttatacttac aagaattgag 2460 actcaataca aatgaaaaag ccttgaaagg ttcatgaggg acctagaaaa actacatctc 2520 aacttccaga aagtcattat tattttcctc ataattccct gagtaagaaa tttaaagaag 2580 tggtatcata aaaggttgat gttttttaat atacagaagt ttctggaatg acctattaat 2640 ttactgtcaa tggccttact gatgctttgt ccagaacaat gccattgctc ctgcttactt 2700 tggggaggtt ttgggataat ttagttgtat ggtecttttt caattgtttt actttttttt 2760 ttatgaaatg ttctaaatgt atagaaaatt agagacatta gtataataaa cagccatatg 2820 cccattatge actttaaaag ttgttaacat tttgccatag ttgcttectte tatgeccectttt 2880 tttttttttt tttttttttt tgctgagagt tttttgtttg gttttgtttt gttttatttt 2940 gagacagggt ctcctgtccc caggctgtag tcagtggcac catcacagct cactgcagct 3000 caagtgatca tcccaccaca gcctcccaag tagctgggac tacaggtgtg caccaccatg 3060 cctggcaaat TAL EEIRaLh tttagtacag gcaaattctg tgttgcccag gctggtcttg 3120 aactcctgag ttcaagcaat cttcccacct cagectcctt aagctgcetgyg aattacaggc 3180 gttagcactg tacctggcta ctgctgagag acttttaagt gaattaggaa catgatgata 3240 ttccatttct aaattcttta gtttacatct tcaaaaaata cagttcctgt agaattatta 3300 ttgtaaataa caaattaact taaggattta tttatttgga gtgaaacaaa tattttactg 3360 aactcataaa aatagaaata ccatgtggaa tcctcagtgt caaaaatatt gcagaaatct 3420 - tgcaaagttg atattattaa attgttaaat attaaaattc ccaataaaga acattaatct 3480 tatttctaaa atccagttaa ttaaaaaaat ttatattata taataatatt tggtcattaa 3540 ataaaaatta gaaaatacaa ataagaaaaa taacacccat aatcttacta cccagaggtt 3600 tataaccatg ggtaaattct ggtatatatt cttccagaat gtatatcaat catgtgtatg 3660 aatgttaaat tatatcatac acatataaac ccacatacaa acatgtaaat actgtgtgct 3720 tttgcaaaaa ttaaattgta ttatacacac ggctttacaa tttgcttcett atcacacaaa 3780 attatttgca tgtcagcaaa tacaaatcgg tttttaatga tcttttgcete cattttccag 3840 atgagaaaaa aatacaaatc tgtatcatca ttttaaaaga atgactagaa ttttaatata 3900 tgaatattct ataatttact gatccaattg ttactattga gcacttaggt tgtttccecatt 3960 tttccctcat aaattgctat gaatagcttt ttgtatacat ctttgggtge atttcttatt 4020 tcttttggat aaattttcaa taatagaact gctgagtaaa atatcactag gtgttttrte 4080 acagtgtcta gtgcaaagaa gacctttaat cattttgtta atacttccag agcttccaat 4140 gactttggta aatgaagaaa aaaatgcttc atttcatgct gaatgggaga gaatgaagag 4200 agttttcccecc aacaattaca catatatgga ctcatagaaa ataatatctt accattcttt 4260 ccacagccta acagaaaaaa gctggctaaa cctaaattta aaataaaata tctattaaag 4320 tttttattcc ttaccacctg tctttcagct ttgetgcaag ataacatcgc tgatgetgta 4380 gcttgtgcaa agagggttgt ccgtgatcca caaggcatta gagcatggta tgttttaagt 4440 gttaaaaggg aaaactatct tactctactg ttgatatata caatgagagc agacttttaa 4500 agaccaaagt atgctaatga cacctcaaaa ttgcagcttt tggcttatge taaatgatgt 4560 attacctaca tccttgaaga aacaatctac tttaactgat ccagaatctt actcttttac 4620 tcctcaattt attttagggg atttctagag ttttaagatg cttcacactc tatcagttec 4680 ttgtcatatc ttgaaattct ttttagaata agtaagtgtg ggccgggcac agtgctcacg 4740 cctgtaatcc cagcactttg ggagaccgag gcagatggat cacctgaggt caggagttcg 4800 agaccagcct gcctaacatg gcaaaacccc atctccacta aaaatacaaa aaattagcetg 4860 ggtgtggtgc aggtgcctgt aatcccagcc actcgggagg ctgaggcagg agacttgett 4920 gaacccggga ggtggaggtt gcagaggatt gcgccattgt acttcagect gggcgacaga 4580 gtgagactct gtctcaaata aatagcataa aaaataaacg tggaattcac tttgcagttg 5040 ctgctgtaca acgcacatta ctcaatcttt atgttcggca ttctatgctc tactgagaaa 5100 tttgggtagg agtgaagtat tttgtataca tatcttcatt taataaatag caatagctgg 5160 gtctatctta ctattttatc tattgataaa atattttgtt tccccaagga gtgcgaagta 5220 tgtatattac aatgaagata tgttttaacc tttcaccatt tgcttcatct ttttctacag 5280 ggtggcatgg agaaatcgtt gtcaaaacag agatgtccgt cagtatgttc aaggttgtgg 5340 agtgtaactc cagaattttc cttcttcagc tcattttgtce tctctcacat taagggagta 5400 ggaattaagt gaaaggtcac actaccatta tttcccoccttc aaacaaataa tatttttaca 5460 gaagcaggag caaaatatgg cctttcttct aagagatata atgttcacta atgtggttat 5520 tttatattaa gcctacaaca tttttcagtt tgcaaataga actaatactg gtgaaaattt 5580 acctaaaacc ttggttatca aatacatctc cagtacattc cgttcttttt ttttrtttee 5640 tttttttttg agacagtctc gctctgtege ccaggctgga gtgcagtggc gcaatctegg 5700 ctcactgcaa cctccaccte ccgggttcac gecattctec tgcctcagece tecccgagtag 5760 ctgggattac gggecgccecgce caccacgcecec ggctaatttt ttgtattttt agtagagaca 5820 gggtttcacc gtgttagcca ggatggtctc gatctcctga ccttgtgatc cacccaccte 5880 ggcctcccaa agtgectggga ttacaggegt gagccactgc gcccggccac attcagttcet 5940 tatcaaagaa ataacccaga cttaatcttg aatgatacga ttatgcccaa tattaagtaa 6000 aaaatataag aaaaggttat cttaaataga tcttaggcaa aataccagct gatgaaggca 6060 tctgatgect tcatctgttc agtcatctcc aaaaacagta aaaataacca ctttttgttg €120 ggcaatatga aatttttaaa ggagtagaat accaaatgat agaaacagac tgcctgaatt 6180 gagaattttg attttttaaa gtgtgtttct ttctaaattg ctgttcctta atttgattaa 6240 tttaattcat gtattatgat taaatctgag gcagatgagc ttacaagtat tgaaataatt 6300 actaattaat cacaaatgtg aagttatgca tgatgtaaaa aatacaaaca ttctaattaa 6360 aggctttgca acacatgecct tgtctgtttt tatttagact cctatagtgt ctctgaagaa 6420 aagaatacag atatttgaaa aaatatgatt tggtgctctt aatatctctt atatcgtcac 6480 ttacctcact taaatagtca gatattgctg gagaaaaatt cacaagcatg ctgacaggte 6540 tcactttaaa ttcataacca taaatctcaa atgagccctce aagtctgccect gaccatttta 6600 gttacttctc tacaatcctt ccatttttat gtccctagte tccaaaatga ctgttactat 6660 tttacttttc ctcttctcte ttcaaagcct caagacacac attcagccte ctcctetgece 6720 cccttatcet ccaccctceet ctgectctcag cagataaact ggectcatat tacacttceta 6780 aaacaaaagc aacttcatac caagctt 6807 <210> 2858 <211> 1497 <212> DNA <213> Homo sapiens <400> 2859 accgctggec ccagggaaag ccgagcggec accgagecgg cagagaccca ccgageggeg 60 gcggagggag cagcgcecggg gcgcacgagg gcaccatggce ccagacgecce gecttegaca 120 agcccaaagt agaactgcat gtccacctag acggatccat caagcctgaa accatcttat 180 actatggcag gaggagaggg atcgccctcc cagctaacac agcagagggg ctgctgaacg 240 tcattggcat ggacaagccg ctcaccecttc cagacttect ggccaaattt gactactaca 300 tgcctgctat cgecgggetgce cgggaggcta tcaaaaggat cgectatgag tttgtagaga 360 tgaaggccaa agagggcgtg gtgtatgtgg aggtgcggta cagtccgcac ctgctggcca 420 actccaaagt ggagccaatc ccctggaacc aggctgaagg ggacctcacc ccagacgagg 480 tggtggcecet agtgggeccag ggectgcagg agggggagcg agacttcggg gtcaaggecce 540 ggtccatcct gtgctgcatg cgccaccagc ccaactggtce ccccaaggtg gtggagetgt 600 gtaagaacta ccagcagcag accgtggtag ccattgacct ggctggagat gagaccatcc 660 caggaagcag cctcttgeet ggacatgtcc aggcctacca ggaggctgtg aagagcggca 720 ttcaccgtac tgtccacgecc ggggaggtgg gctcggeccga agtagtaaaa gaggctgtgg 780 acatactcaa gacagagcgg ctgggacacg gctaccacac cctggaagac caggcccttt 840 ataacaggct gcggcaggaa aacatgcact tcgagatctg cccetggtee agctacctca 900 ctggtgcctg gaagecggac acggagcatg cagtcatteg gctcaaaaat gaccaggcta 560 actactcgct caacacagat gacccgctca tcttcaagte caccctggac actgattacc 1020 agatgaccaa acgggacatg ggctttactg aagaggagtt taaaaggctg aacatcaatg 1080 cggccaaatc tagtttcctc ccagaagatg aaaagaggga gcttctcgac ctgctctata 1140 aagcctatgg gatgccacct tcagcctctg cagggcagaa cctctgaaga cgecactcct 1200

1216 y tcaagccttc accctgtgga gtcaccccaa ctectgtgggg ctgagcaaca tttttacatt 1260 tattccttcc aagaagacca tgatctcaat agtcagttac tgatgctcct gaacectatg 1320 tgtccatttec tgcacacacg tatacctegg catggccgcg tcacttctct gattatgtgce 1380 cctggcaggg accagcgecc ttgcacatgg gcatggttga atctgaaacc ctccttctgt 1440 ggcaacttgt actgaaaatc tggtgctcaa taaagaagcc catggctggt ggcatgc 1497 <210> 2860 <211> 3151 <212> DNA R <213> Homo sapiens <400> 2860 cccggccaga caccetcacce tgeggtgece agctgcccag gctgaggcaa gagaaggcca 60 gaaaccatgc ccatggggtc tectgcaaccg ctggccacct tgtacctget ggggatgctg 120 gtcgcttect gecteggacg gctcagectgg tatgacccag atttccagge aaggctcacce 180 cgttccaact cgaagtgcca gggccagetg gaggtctacce tcaaggacgg atggcacatg 240 gtttgcagec agagctgggg cecggagctee aagcagtggg aggacceccag tcaagcgtca 300 aaagtctgcc agcggctgaa ctgtggggtg cccttaagec ttggeccctt ccttgtcace 360 tacacacctc agagctcaat catctgctac ggacaactgg gctecttcte caactgcagce 420 cacagcagaa atgacatgtg tcactctcectg ggcctgacct gcttagaacc ccagaagaca 480 acacctccaa cgacaaggcc ccocgcoccace acaactccag ageccacagc tccteccagg 540 ctgcagetgg tggcacagtce tggcggccag cactgtgceg gegtggtgga gttctacage 600 ggcagcctgg ggggtaccat cagctatgag gcccaggaca agacccagga cctggagaac 660 ttcctctgeca acaacctcca gtgtggetcee ttcttgaagc atctgccaga gactgaggca 720 ggcagagecc aagacccagg ggagccacgg gaacaccagc ccttgccaat ccaatggaag 780 atccagaact caagctgtac ctccctggag cattgcttca ggaaaatcaa gccccagaaa 840 agtggccgag ttcttgcect cctttgctca ggtttccage ccaaggtgca gagccgtctg 900 gtggggggca gcagcatctg tgaaggcacce gtggaggtgc gccagggggc tcagtgggea 960 gecetgtgtg acagctctte agccaggage tcgetgeggt gggaggaggt gtgccgggag 1020 cagcagtgtg gcagcgtcaa ctcctatcga gtgctggacg ctggtgaccc aacatccegg 1080 gggctcttct gtccccatca gaagctgtec cagtgccacg aactttggga gagaaattcce 1140 tactgcaaga aggtgtttgt cacatgccag gatccaaacc ccgcaggect ggccgcaggce 1200 acggtggcaa gcatcatcct ggecetggtg ctcctggtgg tgetgetggt cgtgtgegge 1260 ccccttgect acaagaagct agtgaagaaa ttccgccaga agaagcageg ccagtggatt 1320

CE EEE ggcccaacgg gaatgaacca aaacatgtcet ttccatcgca accacacgge aaccgtccga 1380 tcccatgctg agaaccccac agcctceccac gtggataacg aatacagcca acctcccagg 1440 aactcccgee tgtcagctta tccagetctg gaaggggttc tgcatcgcte Ctccatgcag 1500 cctgacaact cctccgacag tgactatgat ctgcatgggg ctcagaggct gtaaagaact 1560 gggatccatg agcaaaaagc cgagagccag acctgtttgt cctgagaaaa ctgtcegcete 1620 ttcacttgaa atcatgtcce tatttctacc ccggccagaa catggacaga ggccagaagc 1680 cttcecggaca ggecgetgctg ccccgagtgg caggccagcet cacactctgc tgcacaacag 1740 ctcggeegee cetccacttg tggaagctgt ggtgggcaga gccccaaaac aagcagcctt 1800 ccaactagag actcgggggt gtctgaaggg ggcccecttt ccctgeececge tggggagegg 1860 cgtctcagtg aaatcggctt tetoctcaga ctctgtecet ggtaaggagt gacaaggaag 1920 ctcacagctg ggcgagtgca ttttgaatag ttttttgtaa gtagtgcttt tcctecettee 1980 tgacaaatcg agcgetttgg cotottetgt gcagcatcca cecectgegga tcceteotggg 2040 gaggacagga aggggactcc cggagacctc tgcagcegtg gtggtcagag getgctcatce 2100 tgagcacaaa gacagctctg cacattcacc gcagctgeca gccaggggte tgggtgggea 2160 ccaccctgac ccacagegtc accccactce ctctgtctta tgactcccet ceoccaaccce 2220 ctcatctaaa gacaccttce tttccactgg ctgtcaagcc cacagggcac cagtgccacc 2280 cagggccetg cacaaagggg cgcectagtaa accttaacca acttggtttt ttgcttcace 2340 cagcaattaa aagtcccaag ctgaggtagt ttcagtccat cacagttcat cttctaacce 2400 aagagtcaga gatggggctg gtcatgttce tttggtttga ataactcect tgacgaaaac 2460 agactcctct agtacttgga gatcttggac gtacacctaa tcccatgggg ccteggette 2520 cttaactgca agtgagaaga ggaggtctac ccaggagcct cgggtctgat caagggagag 2580 gccaggcgca gctcactgeg gectctaaga aggtgaagca acatgggaac acatcctaag 2640 acacatecta agacaggtcc tttctecacg ccatttgatg ctgtatctce tgggagcaca 2700 ggcatcaatg gtccaagceg cataataagt ctggaagagc aaaagggagt tactaggata 2760 tggggtgggc tgctcccaga atctgetcag ctttctgecece ccaccaacac cctccaacca 2820 ggccttgect tctgagagec ccegtggeca agcccaggtc acagatcttc ccecgaccat 2880 gctgggaatc cagaaacagg gaccccattt gtctteeccat atctggtgga ggtgaggggg 2540 ctcctcaaaa gggaactgag aggctgctcet tagggagggc aaaggttcgg gggcagccag 3000 tgtctcccat cagtgecttt tttaataaaa gcotctttcat ctatagtttg gccaccatac 3060 agtggcctca aagcaaccat ggcctactta aaaaccaaac Caaaaataaa gagtttagtt 3120 gaggagaaaa aaaaaaaaaa aaaaaaaaaa a 3151 <210> 2861 <211> 1653 <212> DNA <213> Homo sapiens <400> 2861 agcgatttca tcttcaggec tggactacac cactcaccet cccagtgtge ttgagaaaca 60 aactgcaccc actgaactcec gcagctagea tccaaatcag cccttgagat ttgaggectt 120 ggagactcag gagttttgag agcaaaatga caacacccag aaattcagta aatgggactt 180 tcceggcaga gccaatgaaa ggcocctattg ctatgcaatce tggtccaaaa ccactcttca 240 ggaggatgtc ttcactggtg ggccccacgc aaagcttctt catgagggaa tctaagactt 300 tgggggctgt ccagattatg aatgggctct tccacattge cctggggggt cttctgatga 360 tcccagcagg gatctatgea cccatctgtg tgactgtgtg gtaccctcte tggggaggca 420 ttatgtatat tatttccgga tcactcctgg cagcaacgga gaaaaactcc aggaagtgtt 480 tggtcaaagg aaaaatgata atgaattcat tgagcctctt tgctgccatt tctggaatga 540 ttctttcaat catggacata cttaatatta aaatttccca ttttttaaaa atggagagtc 600 tgaattttat tagagctcac acaccatata ttaacatata caactgtgaa ccagctaatc 660 cctctgagaa aaactcccca tctacccaat actgttacag catacaatct ctgttcttgg 720 gcattttgtc agtgatgctg atctttgect tcttccagga acttgtaata gctggcatcg 780 ttgagaatga atggaaaaga acgtgctcca gacccaaatc taacatagtt ctcctgtcag 840 cagaagaaaa aaaagaacag actattgaaa taaaagaaga agtggttggg ctaactgaaa 900 catcttccca accaaagaat gaagaagaca ttgaaattat tccaatccaa gaagaggaag 960 dagaagaaac agagacgaac tttccagaac ctccccaaga tcaggaatcc tcaccaatag 1020 aaaatgacag ctctccttaa gtgatttctt ctgttttctg tttcecttttt taaacattag 1080 tgttcatagc ttccaagaga catgctgact ttcatttett gaggtactct gcacatacgc 1140 accacatctc tatctggcct ttgcatggag tgaccatagc tccttetcte ttacattgaa 1200 tgtagagaat gtagccattg tagcagcttg tgttgtcacg cttecttcttt tgagcaactt 1260 tcttacactg aagaaaggca gaatgagtgc ttcagaatgt gatttectac taacctgttc 1320 cttggatagg ctttttagta tagtattttt ttttgtcatt ttctccatca acaaccaggag 1380 agactgcacc tgatggaaaa gatatatgac tgcttcatga cattcctaaa ctatecttttt 1440 tttattccac atctacgttt ttggtggagt ccecttttgea tcattgtttt aaggatgata 1500 aaaaaaaaat aacaactagg gacaatacag aacccattcce atttatcttt ctacagggct 1560 gacattgtgg cacattctta gagttaccac accccatgag ggaagctcta aatagccaac 1620 acccatctgt tttttgtaaa aacagcatag ctt 1653 <210> 2862

<211> 2325

<212> DNA

<213> Homo sapiens

<400> 2862 ttttttaaag taagatgttt aagaaattaa acagtcttag ggagagttta tgactgtatt 60 Caaaaagttt tttaaattag cttgttatcc cttcatgtga taactaatct caaatacttt 120 ttcgatacct cagagcatta ttttcataat gagctgtgtt cacaatcttt ttaggttaac 180 tcgttttete tttgtcatta aggagaaaca ctttgatatt ctgatagagt ggccttcatt 240 ttagtatttt tcaagaccac ttttcaacta ctcactttag gataagtttt aggtaaaatg 300 tgcatcatta tcctgaatta tttcagttaa gcatgttagt tggtggcata agagaaaact 360 caatcagata gtgctgagac aggactgtgg agacacctta gaaggacaga ttctgttccg 420 aatcaccgat gcggcgtcag caggactggce ctagcggagg ctctgggagg gtggctgcca 480 ggcccggect gggetttggg tctecccgga ctacccagag ctgggatgecg tggcttctge 540 tgccgggecg actggetget cagccccage ccttgttaat ggacttggag gaatgattcc 600 atgccaaage tttgcaaggc tcgcagtgac caggcgcceg acatgggagt gcatcecgcecce 660 caaccctttt cccectegte tectgtgaga attcceccgte ggatacgagc agcgtggccg 720 ttggctgect cgcacaggac ttccttcecg actccatcac tttctectgg aaatacaaga 780 acaactctga catcagcagc acccgggget tcccatcagt cctgagaggg ggcaagtacg 840 cagccacctc acaggtgetg ctgccttcca aggacgtcat gcagggcaca gacgaacacg S00 tggtgtgcaa agtccagcac cccaacggca acaaagaaaa gaacgtgeccect cttccagtga 960 ttgccgaget gectcoccaaa gtgagegtet tcgteccace cecgecgacgge ttcttceggea 1020 accccegeaa gtccaagcte atctgccagg ccacgggttt cagtccccegg cagattcagg 1080 tgtcectgget gcgegagggg aagcaggtgg ggtctggcgt caccacggac caggtgcagg 1140 ctgaggcaaa ggagtctggg cccacgacct acaaggtgac cagcacactg accatcaaag 1200 agagcgactg gctcagecag agcatgttca cctgcegggt ggatcacagg ggcctgacct 1260 tccagcagaa tgcgtectce atgtgtgtcc ccgatcaaga cacagccatc cgggtctteg 1320 Ccatcccece atcetttgee agcatcttcc tcaccaagtc caccaagttg acctgectad 1380 tcacagacct gaccacctat gacagcgtga ccatctcctg gacccgcecag aatggccaag 1440 ctgtgaaaac ccacaccaac atctccgaga gccaccccaa tgccacttte agcgecegtgg 1500 gtgaggccag catctgcgag gatgactgga attccgggga gaggttcacg tgcaccgtga 1560 c€ccacacaga cctgcccteg ccactgaagc agaccatctc Ccggeccaaa ggggtggeee 1620 tgcacaggcc cgatgtctac ttgectgccac cagcccggga gcagctgaac ttgcgggagt 1680 cggccaccat cacgtgectyg gtgacggget tctctecege ggacgtette gtgcagtgga 1740 tgcagagggg gcagcecttg tcececeggaga agtatgtgac cagcgcecca atgectgagce 1800 cccaggeeccce aggeccggtac ttcgeccaca gecatectgac cgtgtccgaa gaggaatgga 1860 acacggggga gacctacacc tgegtggtgg cccatgaggc cctgcccaac agggtcaccg 1920 agaggaccgt ggacaagtcc accgaggagg aggtgagege cgacgaggag ggctttgaga 1980 acctgtgggc caccgectec accttcatcg tcctcttect cctgagecte ttctacagta 2040 ccaccgtcac cttgttcaag gtgaaatgat Cccaacagaa gaacatcgga gaccagagag 2100 aggaactcaa agggcgcage tccgggtetg gggtectgec tgecgtggecet gttggcacgt 2160 gtttctctec cccgeeegge ctecagttgt gtgetctcac acaggcttcc ttctcgacceg 2220 gcaggggctg getggettge aggcacgagg tgggctctac cccacactge tttgetgtgt 2280 atacgcttgt tgccctgaaa taaatatgca cattttatec atgaa 2325 «210> 2863 <211> 430 <212> DNA <213> Homo sapiens <400> 2863 gacagccacg aagatcctac caaaatgaag cgcttectct tcctectact caccatcage 60 ctcctggtta tggtacagat acaaactgga ctctcaggac aaaacgacac cagccaaacce 120 agcagcccct cagcatccag cagcatgagc ggaggcattt tccttttett cgtggccaat 180 gecataatcc acctettctg cttecagttga ggtgacacgt ctcagcctta gcecetgtgee 240 ccctgaaaca gctgccacca tcactcgcaa gagaatccce tccatctttg ggaggggttg 300 atgccagaca tcaccaggtt gtagaagttg acaggcagtg ccatgggggc aacagccaaa 360 ataggggggt aatgatgtag gggccaagca gtgcccagcet gggggagaat aaagttaccc 420 ttgtactgca 430

<210> 2864

<211> 1824

<212> DNA

<213> Homo sapiens

<400> 2864 cagctctctg tcagaatggce caccatggta ccatccgtgt tgtggcccag ggcctgectgg 60 actctgctgg tctgctgtct gctgacceca ggtgtccagg ggcaggagtt ccttttgegg 120 gtggagccecce agaaccctgt gctctetget ggagggtecc tgtttgtgaa ctgcagtact 180 gattgteccca gctctgagaa aatcgccttg gagacgtcecece tatcaaagga. gctggtggee 240 agtggcatgg gctgggcagce Cttcaatctc agcaacgtga ctggcaacag tcggatceete 300 tgctcagtgt actgcaatgg ctcccagata acaggctcet ctaacatcac cgtgtacggg 360 ctccecggage gtgtggaget ggcacccctg cctecttgge agccggtggg ccagaactte 20 accctgeget geccaagtgga gggtgggtcg ccceggaccea gcctcacggt ggtgctgctt 480 cgctgggagg aggagctgag ccggcagece gcagtggagg agccagcgga ggtcactgee 540 actgtgctgg ccagcagaga cgaccacgga gccecctttet catgccgcac agaactggac 600 atgcagececec aggggctggg actgttcgtg aacacctcag cccceegeca gctccgaacce 660 tttgtectge ccgtgacece cccgegeecte gtggeececece ggttcttgga ggtggaaacg 720 tcgtggeegg tggactgcac cctagacggg ctttttccag cctcagagge ccaggtctac 780 ctggcgectgg gggaccagat gctgaatgeg acagtcatga accacgggga cacgctaacg 840 gccacagcca cagccacggce gcgegecggat caggagggtg cccgggagat cgtctgcaac S00 gtgaccctag 999gcgagag acgggaggcc cgggagaact tgacggtctt tagcttccta 960 ggacccattg tgaacctcag €gagcccace gcccatgagg ggtccacagt gaccgtgagt 1020 tgcatggctg gggctcgagt ccaggtcacg ctggacggag tteeggceege ggcccecgggyg 1080 cagccagctc aacttcaget aaatgctacc gagagtgacg acggacgcag cttcttctge 1140 agtgccactc tcgaggtgga cggcgagttce ttgcacagga acagtagcgt ccagctgcega 1200 gtcctgtatg gtcccaaaat tgaccgagec acatgcccec agcacttgaa atggaaagat 1260 faaaacgagac acgtcctgca gtgccaagece aggggcaacc cgtaccccga getgeoggtgt 1320 ttgaaggaag gctccagecg ggaggtgecg gtggggatce cgttecttegt caacgtaaca 1380 cataatggta cttatcagtg ccaagcgtcce agctcacgag gcaaatacac cctggtegtg 1440 gtgatggaca ttgaggctgg gagctcccac tttgtcceceg tcttegtgge ggtgttactg 1500 accctgggeg tggtgactat cgtactggcce ttaatgtacg tcttecaggga gcaccaacgg 1560 agcggcagtt accatgttag ‘ggaggagagc acctatctge cectcacgtce tatgcagecceg 1620 acagaagcaa tgggggaaga accgtccaga gctgagtgac gectgggatce gggatcaaag 1680 ttggecggggyg cttggectgtg ccctcagatt ccgcaccaat aaagccttca aactccctaa 1740 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1800 aaaaaaaaaa aaaaaaaaaa aaaa 1824 <210> 2865

<21l1l> 4882

<212> DNA

<213> Homo sapiens

<400> 2B65 agaggaggaa attgttcctc gtctgataag acaacagtgg agaaaggacg catgctgttt 60 cttagggaca cggctgactt ccagatatga ccatgtattt gtggcttaaa ctcttggcat 120 ttggctttge ctttectggac acagaagtat ttgtgacagg gcaaagccca acaccttcec 180 ccactggatt gactacagca aagatgccca gtgttccact ttcaagtgac cccttaccta 240 ctcacaccac tgcattctca cccgcaagca cctttgaaag agaaaatgac ttctcagaga 300 ccacaacttc tcttagtcca gacaatactt ccacccaagt atccccggac tctttggata 360 atgctagtgce ttttaatacc acaggtgttt catcagtaca gacgcctcac cttecccacge 420 acgcagactc gcagacgccc tctgctggaa ctgacacgca gacattcagce ggctccgecg 480 ccaatgcaaa actcaaccct accccaggceca gcaatgctat ctcagatgcc taccttaatg 540 cctctgaaac aaccactctg agecccttectg gaagcgetgt catttcaacc acaacaatag 600 ctactactcc atctaagcca acatgtgatg aaaaatatgc aaacatcact gtggattact 660 tatataacaa ggaaactaaa ttatttacag caaagctaaa tgttaatgag aatgtggaat 720 gtggaaacaa tacttgcaca aacaatgagg tgcataacct tacagaatgt aaaaatgcgt 780 ctgtttccat atctcataat tcatgtactg ctcctgataa gacattaata ttagatgtgce 840 caccaggggt tgaaaagttt cagttacatg attgtacaca agttgaaaaa gcagatacta S00 ctatttgttt aaaatggaaa aatattgaaa cctttacttg tgatacacag aatattacct 960 acagatttca gtgtggtaat atgatatttg ataataaaga aattaaatta gaaaaccttg 1020 aacccgaaca tgagtataag tgtgactcag aaatactcta taataaccac aagtttacta 1080 acgcaagtaa aattattaaa acagattttg ggagtccagg agagcctcag attatttttt 1140 gtagaagtga agctgcacat caaggagtaa ttacctggaa tccccctcaa agatcattte 1200 ataattttac cctctgttat ataaaagaga cagaaaaaga ttgcctcaat ctggataaaa 1260 acctgatcaa atatgatttg caaaatttaa aaccttatac gaaatatgtt ttatcattac 1320 atgcctacat cattgcaaaa gtgcaacgta atggaagtgc tgcaatgtgt catttcacaa 1380 ctaaaagtgc tcctccaage caggtctgga acatgactgt ctccatgaca tcagataata 1440 gtatgcatgt caagtgtagg cctcccaggg accgtaatgg cccccatgaa cgttaccatt 1500 tggaagttga agctggaaat actctggtta gaaatgagtc gcataagaat tgcgatttcc 1560 gtgtaaaaga tcttcaatat tcaacagact acacttttaa ggcctatttt cacaatggag 1620 actatcctgg agaacccttt attttacatc attcaacatc ttataattct aaggcactga 1680 tagcatttct ggcatttctg attattgtga catcaatagc cctgcttgtt gttctctaca 1740 aaatctatga tctacataag aaaagatcct gcaatttaga tgaacagcag gagcttgttg 1800 aaagggatga tgaaaaacaa ctgatgaatg tggagccaat ccatgcagat attttgttgg 1860 aaacttataa gaggaagatt gctgatgaag gaagactttt tctggctgaa tttcagagea 1920 tcecgegggt gttcagcaag tttectataa aggaagctcg aaagcccttt aaccagaata 1980 aaaaccgtta tgttgacatt ctteccttatg attataaccg tgttgaacte tctgagataa 2040 acggagatgc agggtcaaac tacataaatg ccagctatat tgatggttte aaagaaccca 2100 ggaaatacat tgctgcacaa ggtcccaggg atgaaactgt tgatgatttc tggaggatga 2160 tttgggaaca gaaagccaca gttattgtca tggtcactcg atgtgaagaa ggaaacagga 2220 acaagtgtgc agaatactgg ccgtcaatgg aagagggcac tcgggetttt ggagatgttg 2280 ttgtaaagat caaccagcac aaaagatgtc cagattacat cattcagaaa ttgaacattg 2340 taaataaaaa agaaaaagca actggaagag aggtgactca cattcagttc accagctgge 2400 cagaccacgg ggtgcctgag gatcctcact tgctcctcaa actgagaagg agagtgaatg 2460 ccttcagcaa tttcttcagt ggtcccattg tggtgcactg cagtgctggt gttgggcgca 2520 caggaaccta tatcggaatt gatgccatge tagaaggect ggaagccgag aacaaagtgg 2580 atgtttatgg ttatgttgtc aagctaaggc gacagagatg cctgatggtt caagtagagg 2640 cccagtacat cttgatccat caggetttgg tggaatacaa tcagtttgga gaaacagaag 2700 tgaatttgtc tgaattacat ccatatctac ataacatgaa gaaaagggat ccacccagtg 2760 agccgtctecc actagaggct gaattccaga gacttcctte atataggagc tggaggacac 2820 agcacattgg aaatcaagaa gaaaataaaa gtaaaaacag gaattctaat gtcatcccat 2880 atgactataa cagagtgcca cttaaacatg agctggaaat gagtaaagag agtgagcatg 2940 attcagatga atcctctgat gatgacagtg attcagagga accaagcaaa tacatcaatg 3000 catcttttat aatgagctac tggaaacctg aagtgatgat tgctgctcag ggaccactga 3060 aggagaccat tggtgacttt tggcagatga tcttccaaag aaaagtcaaa gttattgtta 3120 tgctgacaga actgaaacat ggagaccagg aaatctgtge tcagtactgg ggagaaggaa 3180 agcaaacata tggagatatt gaagttgacc tgaaagacac agacaaatct tcaacttata 3240 cccttegtgt ctttgaactg agacattcca agaggaaaga ctctcgaact gtgtaccagt 3300 accaatatac aaactggagt gtggagcagc ttectgcaga acccaaggaa ttaatctcta 3360 tgattcaggt cgtcaaacaa aaacttcecce agaagaattc ctctgaaggg aacaagcatc 3420 acaagagtac acctctactc attcactgca gggatggatc tcagcaaacg ggaatatttt 3480 gtgctttgtt aaatctctta gaaagtgegg aaacagaaga ggtagtggat atttttcaag 3540 1224 A tggtaaaagc tctacgcaaa gctaggccag gcatggtttc cacattcgag caatatcaat 3600 tcctatatga cgtcattgcc agcacctacc ctgctcagaa tggacaagta aagaaaaaca 3660 accatcaaga agataaaatt gaatttgata atgaagtgga caaagtaaag caggatgcta 3720 attgtgttaa tccacttggt gccccagaaa agctccctga agcaaaggaa caggctgaag 3780 gttctgaacc cacgagtggc actgaggggc cagaacattc tgtcaatggt cctgcaagtc 3840 cagctttaaa tcaaggttca taggaaaaga cataaatgag gaaactccaa acctcctgtt 3900 agctgttatt tctatttttg tagaagtagg aagtgaaaat aggtatacag tggattaatt 3960 aaatgcagcg aaccaatatt tgtagaaggg ttatatttta ctactgtgga aaaatattta 4020 agatagtttt gccagaacag tttgtacaga cgtatgctta ttttaaaatt ttatctctta 4080 ttcagtaaaa aacaacttct ttgtaatcgt tatgtgtgta tatgtatgtg tgtatgggtg 4140 tgtgtttgtg tgagagacag agaaagagag agaattcttt caagtgaatc taaaagcttt 4200 tgcttttcet ttgtttttat gaagaaaaaa tacattttat attagaagtg ttaacttagc 4260 ttgaaggatc tgtttttaaa aatcataaac tgtgtgcaga ctcaataaaa tcatgtacat 4320 ttctgaaatg acctcaagat gtcctecttg ttctactcat atatatctat cttatatact 4380 tactatttta cttctagaga tagtacataa aggtggtatg tgtgtgtatg ctactacaaa 4440 aaagttgtta actaaattaa cattgggaaa tcttatattc catatattag catttagtce 4500 aatgtctttt taagcttatt taattaaaaa atttccagtg agcttatcat gctgtcttta 4560 catggggttt tcaattttgc atgctcgatt attccctgta caatatttaa aatttattge 4620 ttgatacttt tgacaacaaa ttaggttttg tacaattgaa cttaaataaa tgtcattaaa 4680 ataaataaat gcaatatgta ttaatattca ttgtataaaa atagaagaat acaaacatat 4740 ttgttaaata tttacatatg aaatttaata tagctatttt tatggaattt ttcattgata 4800 tgaaaaatat gatattgcat atgcatagtt cccatgttaa atcccattca taactttcat 4860 taaagcattt actttgaatt tc 4882 <210> 2866 <211l> 1702 <212> DNA <213> Homo sapiens <400> 2866 agactcaaca agagctccag caaagacttt cactgtagct tgacttgacc tgagattaac 60 tagggaatct tgagaataaa gatgagctct gaaaattgtt tcgtagcaga gaacagctct 120 ttgcatccgg agagtggaca agaaaatgat gccaccagtc cccatttcte aacacgtcat 180 gaagggtcct tccaagttcc tgtcctgtgt gctgtaatga atgtggtctt catcaccatt 240

EE es Sa ttaatcatag ctctcattgce cttatcagtg ggccaataca attgtccagg ccaatacaca 300 ttctcaatgc catcagacag ccatgtttct tcatgctctg aggactgggt tggctaccag 360 aggaaatgct actttatttc tactgtgaag aggagctgga cttcagccca aaatgcttgt 420 tctgaacatg gtgctactct tgctgtcatt gattctgaaa aggacatgaa ctttctaaaa 480 cgatacgcag gtagagagga acactgggtt ggactgaaaa aggaacctgg tcacccatgg 540 aagtggtcaa atggcaaaga atttaacaac tggttcaacg ttacagggtc tgacaagtgt 600 gtttttctga aaaacacaga ggtcagcagc atggaatgtg agaagaattt atactggata 660 tgtaacaaac cttacaaata ataaggaaac atgttcactt attgactatt atagaatgga 720 actcaaggaa atctgtgtca gtggatgctg ctctgtggte cgaagtctte catagagact 780 ttgtgaaaaa aaattttata gtgtcttggg aattttcttc caaacagaac tatggaaaaa 840 aaggaagaaa ttccaggaaa atctgcactg tgggctttta ttgeccatgag ctagaagcat 900 cacaggttga ccaataacca tgcccaagaa tgagaagaat gactatgcaa cctttggatg 960 cactttatat tattttgaat ccagaaataa tgaaataact aggcgtggac ttactattta 1020 ttgctgaatg actaccaaca gtgagagccc ttcatgcatt tgcactactg gaaggagtta 1080 gatgttggta ctagatactg aatgtaaaca aaggaattat ggctggtaac ataggttttt 1140 agtctaattg aatcccttaa actcagggag catttataaa tggacaaatg cttatgaaac 1200 taagatttgt aatatttctc tctttttaga gaaatttgec aatttacttt gttattttte 1260 cccaaaaaga atgggatgat cgtgtattta tttttttact tcctcagetg tagacaggtce 1320 cttttcgatg gtacatattt ctttgecttt ataatctttt atacagtgtc ttacagagaa 1380 aagacataag caaagactat gaggaatatt tgcaagacat agaatagtgt tggaaaatgt 14490 gcaatatgtg atgtggcaaa tctctattag gaaatattct gtaatcttca gacctagaat 1500 aatactagtc ttataatagg tttgtgactt tcctaaatca attctattac gtgcaatact 1560 tcaatacttc atttaaaata tttttatgtg caataaaatg tatttgtttg tattttgtgt 1620 tcagtacaat tataagctgt ttttatatat gtgaaataaa agtagaataa acacaaaaaa 1680 aaaaaaaaaa aaaaaaaaaa aa 1702 <210> 2867 <211> 563 <212> DNA <213> Homo sapiens <400> 28867 tgaagagtgg aagagacatt ccagaggagg attgcctteg tcagggtaac ggggtgggct 60 gctcaggtgc cctaccctte acccccttct gtatcagatt ggacctccca ctcccatctce 120 actctgecgtg tacaatcttc catatccgca agttcactgg cactcttctg gcacctggge 180 aagatcccag aacagaggat ggagtgactg gcctcacaga gcttagtgcc cgactcaggg 240 gaaatgggac tggtgcatgg gaaatggtca gcctaggata ggacacgaga gtctgaaatt 300 caaagcaacc agcttgaagt ggtttgagaa gctggaagca aacatgggct agagagatag 360 ggcagaagtc aagacgagga tctggactga tgtggagaca agtagccacg gaagcatgaa 420 ctgtatcctg cacaaagtcc ctcttcceccg cctectaatt cattatgecc aaaagtgcett 480 acgtgaaatt ccagcccaga gtactcatga cttgagagac gtggacggag ccagcttcta 540 ccttgettgg acgtctectee cect 563 <210> 2868 <211> 822 <212> DNA <213> Homo sapiens <400> 2868 gatcctcttt cectecttece caccctcatt ataggctgeg aagcctcectc tcetgcacctg 60 ataacaaaac gtcatatgag aagcatggta gatccttagc atcaaaggtt gaggactctt 120 attctgatta taagtagtgg ctcttgacta caatcaagtc tcaaataata gtgtaagaga 180 ataaagcaga ataataagac taagttaaca gtttaggctt ctttggaatc atgcgggcct 240 agatgaaaat cccaacactg tcctttacta gctaagtgac cttgagcaac tgattacacc 300 ctttgatgcc tcagttttct cctctgtgtt gtggggtaat agtaatatct acttcecctggg 360 gttgttcgtg aagattaatt aacaattata cttgtcaaag ctttagcaca gtgccctgta 420 tgttatttce ttggccaaac tttcttactc tgccatttgt tcaatgtcct aatgagcatg 480 aacactacat taggtatcat gcagaacact ctaaagataa gtattatgat ctctatttca 540 cagataagga aatttaaact gggagaggct aaagggctga cttgcccaag gtcacttgaa 600 actaatatgc cagcagagac agaattagga gccaagtata tttaagagcc aagtgtattg 660 aacctaaaat ctgggctcct aaataccaag cttcactgge tctctggtcc cagtgagagt 720 tggtgctaaa aagtattccg gaatgaaaag ttctcttcca gagaccctgg ccttcecaaag 780 cggtcacctg atagggaagt cttacggcta ggaagttaca aa 822 <210> 2868 <211> 1182 <212> DNA <213> Homo sapiens <400> 2869 gaattccgct agactaagtt ggtcatgatg cagaagctac tcaaatgcag tcggcttgtce 60 ctggctcttg ccctcatect ggttctggaa tectcagttc aaggttatcce tacgcagaga 120 gccaggtacc aatgggtgcg ctgcaatcca gacagtaatt ctgcaaactyg ccttgaagaa 180 aaaggaccaa tgttcgaact acttccaggt gaatccaaca agatcccccg tcetgaggact 240 gaccttttte caaagacgag aatccaggac ttgaatcgta tcttcccact ttctgaggac 300 tactctggat caggcttcgg ctccggctcec ggectectggat caggatctgg gagtggectte 360 ctaacggaaa tggaacagga ttaccaacta gtagacgaaa gtgatgcttt ccatgacaac 420 cttaggtctc ttgacaggaa tctgccctca gacagccagg acttgggtca acatggatta 480 gaagaggatt ttatgttata aaagaggatt ttcccacctt gacaccaggc aatgtagtta 540 gcatatttta tgtaccatgg ttatatgatt aatcttggga caaagaattt tatagaaatt 600 tttaaacatc tgaaaaagaa gcttaagttt tatcatcctt ttttttctca tgaattctta 660 aaggattatg ctttaatgct gttatctatc ttattgttct tgaaaatacc tgcatttttt | 720 ggtatcatgt tcaaccaaca tcattatgaa attaattaga ttcccatggc cataaaatgg 780 ctttaaagaa tatatatata tttttaaagt agcttgagaa gcaaattggc aggtaatatt 840 tcatacctaa attaagactc tgacttggat tgtgaattat aatgatatgc cccttttctt 900 ataaaaacaa aaaaaaaata atgaaacaca gtgaatttgt agagtggggg tatttgacat 960 attttacagg gtggagtgta ctatatacta ttacctttga atgtgtttgc agagctagtg 1020 gatgtgtttg tctacaagta tgattgctgt tacataacac cccaaattaa ctcccaaatt 1080 aaaacacagt tgtgctgtca atacctcata ctgctttacc tttttttcct ggatatctgt 1140 gtattttcaa atgttactat atattaaagc agaaatataa cc 1182 <210> 2870 <211> 537 : <212> DNA <213> Homo sapiens <400> 2870 tttttttttt tttttttttt tctttaaaca cacttcattt ttttttaaag agttattaca 60 tccacacacg gttcaaaaat caaattatga aaggtatata gttaagacta gctgttcaaa 120 acaaaagcag cctttcacga ttatgtgagg gaacaaaggg caacaccctt attagtgcca 180 gtttaaaacc ttecttcaca ccctggactce tgccctatgt gegtectggt tgattttaac 240 ctacatccta acatttaggc cagtttecctt tcatccttbct tacaaatata aaatctctta 300 cccttctcta atattatttg gcattccaaa ataaggaaght gtcatggtta aaaccaaatc 360 aaaggcaatt ctgactgtgc acagctcagc ctccacccaa cctcagaacc actggatcag 420 accaggtttt agtttttttg tacatttact tgataactaa gacacaattt gecctacagtg 480

1228 aaatgcttag ttctgacacg tatcgctcaa tccactgtca agaattcata acaaagt 537 <210> 2871 <211> 503 <212> DNA <213> Homo sapiens <400> 2871 ttttttttta gtataagcat atcccatgca atttttggaa catatactga aaaattatac 60 tgaaagtcaa atcaaactga tctggcaacc ctatctagtt acctacaatc taccgtgttc 120 ccataaaggc tttaagtaat ttggaatccg ttaacacatt tagcttattc tttccccatt 180 ggttcececctgg gecttagagea gacagcaage ctttcectttca cttggccaag aaggcacctce 240 cttttcccat ctaacaggtt gggatcacag ctagttggtg gcaaagcagt ccacatgcat 300 gttgtttatc tttttaagga tatggtcata gtttccaccc cteccttacct ctectgacte 360 accatctcta agcecttccca cacaggceccct gcectgcagecg ccggagaact gaccgtgcett 420 gtgggtccac tcecteetee cacatcttec ttaagectca atccatceca gttcatccat 480 gcccttteca aagtectgtg att 503 <210> 2872 <211> 448 <212> DNA <213> Homo sapiens <400> 2872 tttttttttc caataaaacc actgcagatc taaaatactc tcttggttta aaccacacaa 60 aaagcaattt aataggcaca atcctacagg ttttctgaga gaaataagga agagatcaag 120 tgtaagctac gtaaaattca cgttttgcac cttataaagc aaacttcaat gttgttaaat 180 aaccagtaga aaatatctac aaaaatcaaa ctaaacacct gttcttataa gcagcagtcc 240 tctattttect ctctaaacca tatattccca actcagaccce tctetgtgac ccactgttcee 300 caaagcatag agtctgaaga agaaatataa aacatttcgg acattcgttc acaaaaccaa 360 attagacctt tccacaaagt acaggagata aaacagaaac acttccattt tatctaattt 420 atggcaaata gttcaaggaa tgcctatt 448 <210> 2873 <211> 449 <212> DNA <213> Homo sapiens <400> 2873 tttttecttgg tcatctacct ttaatgtttg gtcttaagtc ttataaacac atatcattta 60 atataaaaaa aaaaggatac tcacctgacc ctttcagatg tttaacgatt cgtcttcctc 120 ctcggggatg ctttttetga aggatgctgg cctggggaaa acagaaccgg aagggtaaca 180 cctgccatac ctaataaaac caatgagaaa tacgaggccce cgagatggag tttetgggag 240 attcctgaag agcacgcectgt ggcgattgag atgatgacgc gtggagctgc cececteect 300 gtctcccaca tcagggacct gtccctectac aggaggaatt ctactcctga ggccacecgte 360 ccctgtcact caggtggect gcatgcacag cacttctgge tctgaaagcg tcaccteatg 420 getgtttctg ccttettget ggtgaattt 449 <210> 2874 <211> 3362 <212> DNA <213> Homo sapiens <400> 2874 agactccctg tctttgeggt ttgggagatg atgagaaacc acagaattgc tagtagttta 60 tgtggagatc aggtcttctc caagaaaaaa aaaaagaaaa aaaaaaacaa catggctgca 120 aaggagaaac tggaggcagt gttaaatgtg gccctgaggg tgccaagceat catgctgttg 180 gatgtcctgt acagatggga tgtcagctcc tttttccage agatccaaag aagtagcctt 240 agtaataacc ctctttteca gtataagtat ttggctctta atatgcatta tgtaggttat 300 atcttaagtg tggtgctgcet aacattgccc aggcagcatce tggttcaget ttatctatat 360 tttttgactg ctectgectect ctatgctgga catcaaattt ccagggacta tgttcggagt 420 gaactggagt ttgcctatga gggaccaatg tatttagaac ctctctctat gaatcggttt 480 accacagcct taataggtca gttggtggtg tgtactttat gctectgtgt catgaaaaca 540 aagcagattt ggctgtttte agctcacatg cttcectetge tagcacgact ctgccttgtt 600 cctttggaga caattgttat catcaataaa tttgctatga tttttactgg attggaagtt 660 ctctattttc ttgggtctaa tcttttggta ccttataacc ttgctaaatc tgcatacaga 720 gaattggttc aggtagtgga ggtatatggc cttetegect tgggaatgtc cctgtggaat 780 caactggtag tccetgttcet tttcatggtt ttctggceteg tcttatttge tcttcagatt 840 tactcctatt tcagtactcg agatcagcct gcatcacgtg agaggcttct tttoettttt 860 ctgacaagta ttgcggaatg ctgcagcact ccttactcte ttttgggttt ggtcttcacg 960 gtttettttg ttgecettggg tgttcetcaca ctctgcaagt tttacttgca gggttatcga 1020 gctttcatga atgatcctge catgaatcgg ggcatgacag aaggagtaac gctgttaatc 1080 ctggcagtge agactggget gatagaactg caggttgttce atecgggcatt cttgctcagt 1140 attatccttt tcattgtcgt agcttetatc ctacagtcta tgttagaaat tgcagatcct 1200 attgttttgg cactgggagc atctagagac aagagcttgt ggaaacactt ccgtgctgta 1260 agcctttgtt tatttttatt ggtattccct gcttatatgg cttatatgat ttgccagttt 1320 ttccacatgg atttttggct tcttatcatt atttccagca gecattcttac ctctctteag 1380 gttctgggaa cactttttat ttatgtctta tttatggttg aggaattcag aaaagagcca 1440 gtggaaaaca tggatgatgt catctactat gtgaatggca cttaccgcet gctggagttt 1500 cttgtggcec tctgtgtggt ggcctatgge gtctcagaga ccatctttgg agaatggaca 1560 gtgatgggcet caatgatcat cttcattcat tcctactata acgtgtgget tcgggceceag 1620 ctggggtgga agagctttct tctcegecagg gatgetgtga ataagattaa atcgttacce 1680 attgctacga dagagcagct tgagaaacac aatgatattt gtgccatctg ttatcaggac 1740 atgaaatctg ctgtgatcac geccttgcagt cattttttce atgcaggctg tcttaagaaa 1800 tggctgtatg tccaggagac ctgccctetg tgccactgee atctgaaaaa ctectcccag 1860 cttccaggat taggaactga geccagttcta cagcctcatg ctggagctga gcaaaacgtc 1920 atgtttcagg aaggtactga acccccagge caggagcata ctccagggac caggatacag 1980 gaaggttcca gggacaataa tgagtacatt gccagacgac cagataacca ggaaggggct 2040 tttgacccca aagaatatce tcacagtgeg aaagatgaag cacatcctgt tgaatcagcc 2100 tagaggagaa gcagcaggaa tgatgctttg atactctgga ggagaagtta actcaagatg 2160 gaattcatgt tctgatttga ggaatgaaaa tgagatgatc aggcaggaaa ctgacattcc 2220 aaggatctaa tccaggaagt actctcagtg gggaccacct gctttcatce cctgacattg 2280 tgggagaaat tttgcaatgt atgctaatca aaatgtattt atatgttctec tgctgatgtt 2340 ttatagaggt ttgtgaagaa aattcaacct cagcaacttc agaaactgcec cctgatacgt 2400 gtgagagaga aataaaatca gattttgagt gttgaaggga ctgaggaagt gaggataaag 2460 agcatgagga cagcatggaa 4gaaggaggc agaagtggaa ctgaacttte actctccatg 2520 ggacagatca atctcattat caagtctgaa tagcaaccag ccctctectce caccececgttt 2580 ctcctcagtt aattggaget cagtcaggtg attattgagt cttgtacagc actgaaatga 2640 aatcaaagat gaagaagcat tgattgtatt cgaagattga agcacgctca tactttgtat 2700 gtgctttagg gaaggggtgg gtgggcactt gggccttgcg ggtgcattca tgtaatctga 2760 gactcttgaa ctttatgacg gagtcttcaa tattttgatg tatatgaaac ttttgttaaa 2820 tatgttgtat acttcgctgg ctgtgtgaag taaactaaaa ctctgatgaa cactttggag 2880 tctgctttag tgaaggagac caaagtggga agggctttag ggcactgata gaggccctgg 2540 gtgtactttt caatcctgtg taatgtttaa ttcttgeaac tgaatcaaaa cagtgttaaa 3000 ttatggcaat atttgcactt tgggaatgag tacataactyg tatgatcaca ctctgcaaat 3060 gccactttta aagctgttaa tagactttgec accttttett tgacaaggat gtgtcatatt 3120 taaattttta cattcatcat ggctacaggt d4gaactgggg aggggggaat gtaatttttt 3180 atgggaattt tgatatgaaa agaaactagt catttattta tacaatagge ttggctcaaa 3240 aagtgttttt cagacctcgg tattcctaat gtgggatgtg actttatttt atttttagta 3300 gcaaatttgg atgtagactg acagacatag ctgaatgtct taataaattt aaatttgaag 3360 at 3362 <210> 2875 <211> 591 <212> DNA <213> Homo sapiens <400> 2875 ttttetgttt catcattaca aatagactca tagctcttta atttttecat ttaacacttt 60 aattttccat aggcctagat tttcaagaag tccaatatct ctcacttgaa gtgtetttte 120 cctggagtag attgggagat ttgagggata tctgtccaaa gatgagacag tctgtttcta 180 gtttcccatc cagcctgatg gggcgtctac agttgttacc acaaggtgtc gctgttgaac 240 agattctggt gcagtctagt gcatagctgt ccacttctag agtgatcact tgctgggcca 300 agttecctcte cttaagtggt gtctcacatt aaggttccca aattacagac tcattaattc 360 accctaataa gctcatccag gcagtttagg tcttcagggg cttccagect ccaacacaca 420 ttgggccaaa accagectgt accaccagct €caagccctg tgttgaatcet aggtcattgg 480 tccagatgec cettcattet gggcctgtgg tgtcctttce agacagcaga cctcagttaa 540 gggcatccca gtccatcaga gaagttccag gatcacagac Cctcaaaaqgg g 591 <210> 2876

<211> 1437

<212> DNA

<213> Homo sapiens

<400> 2876 gctteetcag acatgecget gctgetactg ctgccectge tgtgggcagg ggccetgget 60 atggatccaa atttctggcet gcaagtgcag gagtcagtga cggtacagga gggtttgtge 120 gtcectegtge cctgcacttt cttecatcee ataccctact acgacaagaa ctcececcagtt 180 catggttact ggttceggga aggagccatt atatccgggg actctccagt ggccacaaac 240 aagctagatc aagaagtaca ggaggagact cagggcagat tccgectect tggggatcece 300 agtaggaaca actgctcect gagcatcgta gacgccagga ggagggataa tggttcatac 360 ttetttegga tggagagagg aagtaccaaa tacagttaca aatctccecea gctctetgtg 420 catgtgacag acttgaccca caggcccaaa atcctcatec ctggeactet agaacccggce 480 cactccaaaa accttacctg ctctgtgtce tgggecctgtyg agcagggaac acccecegatce 540 ttctcetggt tgtcagectge ceccacctec ctgggcccca ggactactca ctecteggtg 600 ctcataatca ccccacggce ccaggaccac ggcaccaacc tgacctgtca ggtgaagttce 660 gctggagetyg gtgtgactac ggagagaacc, atccagctca acgtcaccta tgttccacag 720 aacccaacaa ctggtatctt tccaggagat ggctcaggga aacaagagac cagagcagga 780 ctggttcatg gggccattgg aggagctggt gttacagccc tgctegetct ttgtctctgc 840 Ctcatcttct tcatagtgaa gacccacagg aggaaagcag ccaggacagc agtgggcagce 900 aatgacaccc accctaccac agggtcagec tcccecgaaac accagaagaa ctccaagtta 960 catggcccca ctgaaacctc aagctgttca ggtgccgecce ctactgtgga gatggatgag 1020 gagctgecatt atgcttcect caactttcat gggatgaatce cttccaagga cacctccacc 1080 gaatactcag aggtcaggac ccagtgagga accctcaaga gcatcaggct cagctagaag 1140 atccacatcc tctacaggtc ggggaccaaa ggctgattct tggagattta actccccaca 1200 ggcaatgggt ttatagacat tatgtgagtt tcectgetata ttaacatcat cttgagactt 1260 tgcaagcaga gagtcgtgga atcaaatctg tgctctttca tttgctaagt gtatgatgtc 1320 acacaagctc cttaaccttc catgtctcca ttttcttete tgtgaagtag gtataagaag 1380 tcctatctca tagggatgcet gtgagcatta aataaaggta cacatggaaa acaccag 1437 <210> 2877 <211> 1182 <212> DNA <213> Homo sapiens <400> 2877 tagttctcce tgagtgagac ttgcctgett ctctggecece tggtcctgte ctgttctcca 60 gcatggtgtg tctgaagcte cctggaggct cctgcatgac agcgctgaca gtgacactga 120 tggtgctgag ctccccactg getttggetg gggacacceg accacgttte ttgtggcagce 180 ttaagtttga atgtcatttc ttcaatggga cggagcgggt gcggttgctyg gaaagatgca 240 tctataacca agaggagtcc gtgcgetteg acagcgacgt gggggagtac cgggcggtga 300 c€ggagctggg gcggcctgat gccgagtact ggaacagcca gaaggacctc ctggagcaga 360 ggcgggccge ggtggacacc tactgcagac acaactacgg ggttggtgag agcttcacag 420 tgcagcggcg agttgagect aaggtgactg tgtatcctte aaagacccag cccctgcagce 480 accacaacct cctggtctge tctgtgagtg gtttctatcc aggcagcatt gaagtcaggt 540 ggttccggaa cggccaggaa gagaaggctg gggtggtgtc cacaggcctg atccagaatg 600 gagattggac cttccagacc ctggtgatge tggaaacagt tccteggagt ggagaggttt 660 acacctgcca agtggagcac ccaagtgtga €gagccctcet cacagtggaa tggagagcac 720 ggtctgaatc tgcacagagc aagatgctga gtggagtcgg gggettegtyg ctgggectge 780 tctteocttgg ggcecgggetg ttcatctact tcaggaatca gaazggacac tctggactte 840 agccaacagg attcctgage tgaaatgcag atgaccacat tcaaggaaga accttctgtc 500 c¢cagctttgc agaatgaaaa gctttectge ttggcagtta ttcttccaca agagagqgct 960 ttctcaggac ctggttgcta ctggttegge aactgcagaa aatgtcctecc cttgtggett 1020 cctcagectee tgeccttgge ctgaagtcce agcattgatg acagecgccte atcttcaact 1080 tttgtgctee cctttgecta aaccgtatgg cctececgtge atctgtactce accctgtacg 1140 acaaacacat tacattatta aatgtttctc aaagatggag tt 1182 <210> 2878 <211> 2412 <212> DNA <213> Homo sapiens <400> 2878 agtcccatgg ggaatgtcaa caggcagggg cagcactgca gagatttcat catggtctce 60 caggcectca ggctectetg ccttetgett gggcttcagg getgectgge tgcagtcette 120 gtaacccagg aggaagccca cggcgtcectg caccggcgecc ggcgegccaa cgcgttectg 180 gaggagctge ggcegggete cctggagagag gagtgcaagg aggagcagtg ctcettegag 240 gaggccceggg agatcttcaa ggacgcggag aggacgaagc tgttctggat ttcttacagt 300 gatggggacc agtgtgcctc aagtccatge cagaatgggg gctcctgcaa ggaccagcetce 360 cagtcctata tctgcttctg cectcectgce ttcgagggec ggaactgtga gacgcacaag 420 gatgaccagc tgatctgtgt gaacgagaac ggcggctgtg agcagtactg cagtgaccac 480 acgggcacca agcgctcctg tcggtgccac gaggggtact ctctgctgge agacggggtg 540 tecctgecacac ccacagttga atatccatgt ggaaaaatac ctattctaga aaaaagaaat 600 gccagcaaac cccaaggecg aattgtgggg ggcaaggtgt gecccaaagg ggagtgtcca 660 tggcaggtce tgttgttggt gaatggagct cagttgtgtg gggggaccct gatcaacace 720 atctgggtgg tctecgegge ccactgtttce gacaaaatca agaactggag gaacctgatc 780 gcggtgctgg gcgagcacga cctcagegag cacgacgggg atgagcagag ccggcgggatg 840 gcgcaggtca tcatccccag cacgtacgtc ccgggcacca ccaaccacga catcgcgctg 900 ttcecgectge accagccegt ggtcctcact gaccatgtgg tgeccctctg cctgcocccgaa 960 ¢ggacgttct ctgagaggac gctggectte gtgegettet cattggtcag cggctgggge 1020 cagctgctgg accgtggcege cacggccctg gagctcatgg tgetcaacgt gccceggetg 1080 atgacccagg actgcctgca gcagtcacgg aaggtgggag actccccaaa tatcacggag 1140 tacatgttect gtgecggcta ctcggatgge agcaaggact cctgcaaggg ggacagtgga 1200 ggcccacatg ccacccacta ccggggcacg tggtacctga cgggcatcgt cagctgggge 1260 cagggctgcg caaccgtggg ccactttggg gtgtacacca gggtctcecca gtacatcgag 1320 tggctgcaaa agctcatgcg ctcagagcca cgcccaggag tcctcecctgeg ageccccattt 1380 ccctagecceca gcagccctgg cctgtggaga gaaagccaag gctgegtega actgtectgg 1440 caccaaatcc catatattct tctgcagtta atggggtaga ggagggcatg ggagggaggg 1500 agaggtgggg agggagacag agacagaaac agagagagac agagacagag agagactgag 1560 ggagagactc tgaggacatg gagagagact caaagagact ccaagattca aagagactaa 1620 tagagacaca gagatggaat agaaaagatg agaggcagag gcagacaggc gctggacaga 1680 ggggcagggg agtgccaagg ttgtcctgga ggcagacagc ccagctgagc ctccttacct 1740 cccttcagec aagccccacce tgcacgtgat ctgectggecce tcaggectget gctctgectt 1800 cattgctgga gacagtagag gcatgaacac acatggatgc acacacacac acgccaatgce 1860 acacacacag agatatgcac acacacggat gcacacacag atggtcacac agagatacgc 1920 aaacacaccg atgcacacgc acatagagat atgcacacac agatgcacac acagatatac 1980 acatggatgc acgcacatgc caatgcacgc acacatcagt gcacacggat gcacagagat 2040 atgcacacac cgatgtgcgc acacacagat atgcacacac atggatgagc acacacacac 2100 caagtgcgca cacacaccga tgtacacaca cagatgcaca cacagatgca cacacaccda 2160 tgctgactcc atgtgtgctg tcctcectgaag geoggttgttt agctctcact tttetggttc 2220 ttatccatta tcatcttcac ttcagacaat tcagaagcat caccatgcat ggtggcgaat 2280 gcccccaaac tcteccccaa atgtatttcect cccttcegetg ggtgccggge tgcacagact 2340 attccecace tgcttcccag cttcacaata aacggctgeg tctcecctecge acacctgtgg 2400 tgcctgccac cc 2412 <210> 2878 <21l> 1257 <212> DNA <213> Homo sapiens <400> 2879 aagtctcaga ggctggagag cagagcacca agatcgttct ggcaggaaca gccagtggga 60 ggttccagct gagcgctcce cagaggtgag ctgatcceca gecacagceac acaggaccag 120 gctgegagaa cagcatcatc agcatcatge tattacaatc ccaaaccatg ggggtttctce 180 acagctttac accaaagggc atcactatcc ctcaaagaga gaaacctgga cacatgtacc 240 aaaacgaaga ttacctgcag aacgggctge caacagaaac caccgttctt gggactgtcc 300 agatcctgtg ttgeetgttg atttcaagtc tgggggccat cttggttttt gctcectace 360 cctcccactt caatccagca atttccacea ctttgatgte tgggtaccca tttttaggag 420 ctctgtgttt tggcattact ggatccctet caattatcte tggaaaacaa tcaactaagce 480 cctttgacct gagcagcttg acctcaaatg cagtgagttc tgttactgca ggagcaggcc 540 tcttectect tgctgacagc atggtagccc tgaggactgc ctctecaacat tgtggctcag 600 aaatggatta tctatcctca ttgecttatt cggagtacta ttatccaata tatgaaatca 660 aagattgtct cctgaccagt gtcagtttaa caggtgtcct agtggtgatg ctcatcttcea 720 ctgtgctgga gctcttatta gctgcataca gttctgtett ttggtggaaa cagctctact | 780 ccaacaaccce tgggagttca ttttectecga cccagtcaca agatcatatc caacaggtca 840 aaaagagttc ttcacggtct tggatataag taactcttgg cctcagagga aggaaaagca S00 actcaacact catggtcaag tgtgattaga ctttectgaa atctcetgeea ttttagatac 960 tgtgaaacaa actaaaaaaa aaaaagcttt tgttttgtat ttgtttacta tgagtcgtta 1020 tttaatttct cttgaaaata atttcctcaa agcccaagtc aataaatgtt atcagccagt 1080 cttccaaaat ggtcataaac tttataaact getttgggta aactgagcag aaggtgatac 1140 acagaaggga aaatgtgcac tcatgctagt gtgaatttgg taagtcgegt gactctgcag 1200 gectgtttetg tattatttte acactcatat tgcttaaata ttacatatta gggattg 1257 <210> 2880 <211> 2216 <212> DNA <213> Homo sapiens ) <400> 2880 ggaagctcag cagtgtcecac tgtcgecatt cecttggecat agaaaacaat gtatttgaat 60 tttgatgtaa gcatagcaaa ttgaagatga agatgacacg ttgatttctt gtttgaaatt 120 aaccaagtec cgagaaaaga aagtgaatag tgttagcacg aggaggaagg aagaaatgga 180 gattagattg gatactcttt ctgcatcact gggtagatcc agcactttaa atgactgcaa 240 cttggaagat aaattagctt ggtatgaagg tgaagcttac atgtggcatc actggaagcc 300 ttttcectgaa aaccctetet ggacatgtct tgatttccaa atagcacaag ttggaccctg 360 ggactactgc tcctecttgta ttcgccacac acgtctcaag tcttecctget cagatatgga 420 tctectacat tcatggcgaa gcagcagttt tgggaatttc gategtttte ggaataattc 480 tttatcaaaa ccagatgatt caactgagge acatgaagga gatcccacaa atggaagtgg 540 agaacaaagt aaaacttcaa ataatggagg cggtttgggt aaaaaaatga gagctatttce 600 atggacaatg aagaaaaaag tgggtaaaaa gtacatcaaa gccctttctg aggaaaagga 660 tgaggaagat ggagagaatg cccacccata tagaaacagt gaccctgtga ttgggaccca 720 ctacagagaag gtgtccctca aagccagtga ctccatggat agtctctaca gtggacagag 780 Ctcatcaagt ggcataacaa gctgttcaga tggtacaagt aaccgggaca gctttcgact 840 ggatgacgat ggcccctatt caggaccatt ctgtggcegt gecagagtge atacggattt S00 cacgccaagt ccctatgaca ctgactccct caaaatcaag aaaggagaca tcatagacat 960 tatttgcaaa acaccaatgg ggatgtggac aggaatgttg aacaataaag tgggaaactt 1020 caaattcatt tatgtggatg tcatctcaga agaggaagca gcccccaaga aaataaaggce 1080 aaaccgaagg agtaacagca aaaaatccaa gactctgcag gagttcctag agaggattca 1140 tctgcaggaa tacacctcaa cacttttgct caatggttat gagactctag aagatttaaa 1200 agatataaaa gagagtcacc tcattgaatt aaatattgaa aacccagatg acagaagaag 1260 gttactatca gctgctgaaa acttccttga agaagaaatt attcaagagc aagaaaatga 1320 acctgagcce ctatccttga getcagacat ctccttaaat aagtcacagt tagatgactg 1380 cccaagggac tctggttgct atatctcatc aggaaattca gataatggca aagaggatct 1440 ggagtctgaa aatctgtctg acatggtaca taagattatt atcacagagc caagtgactg 1500 aacacgcatt cccaactata tatctacaga tgcattccat tttaactett cttgagctaa 1560 aacgtcaaat aggagaggaa gataagataa atatttgtaa ataaaaccta aagtttaaat 1620 gttttaatct gaataattgt acataaaatt ttgtatctct aacattccaa attactgtca 1680 ataaaatata tatttattat tttaaatgct atgtgttaat atttcacttg cttgtattag 1740 aaaggcaaaa tgtaagactt tggtatgtgt gacatatgct ttatttggct ttattttaca 1800 agtacagtat ctgcaaaaaa caaagtaacc ttttttcata cctgccagtt ttgaatttat 1860 atatgttatt gaacaaatag taatagagga ttecgectgttg aaacaagttg tccaagcaat 1920 gttatattca tttttatact tattgggaaa gtgtgagtta atattggaca cattttatcc 1980 tgatccacag tggagtttta gtaattatat tttgttgatt tcttcatttt gttttctggt 2040 ataaaagtag agataatgtg tagtcacttc tgatttagtg aaaccaattg taataattgt 2100 ggaaatgttt tgtctttaag tgtaaatatt ttaaaatttg acatacccta atgttaataa 2160 taaaaagaac tatttgcata aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 2216 <210> 2881 <211> 1847 <212> DNA <213> Homo sapiens <400> 2881 ctcctgcect ccactgactc cagagaggga gatccccagt acttgactcec atcacgcaga 60 tgggagcagg caccagctat ggagagggat acagctgcgt ctccacatga cccatcctge 120 atgacaccaa agccaccgcec agacagtgcce tcggattcta tgcaaaacct gggaagcgga 180 gacctacccec agccccggga ggaagctagce tcttcagggg accgtctgag gactggagtt 240 tgatccatga acctggcttc gaggccttge ttttctectet tcttcattca tattcattec 300 caacacctta gaaggtgttg cttaatttat ttctagaaaa gcagcccaga gtcagtcatt 360 gaagccttcc ccaccecctg gccaaaaaaa aaaaaaaaaa aaaactggac acattttgga 420 tctgttggga gcttggagtc cagtggttgg catagttgtc acattgggag cagagaagaa 480 gcaaccaggg gccctgatca ggggactgag ccgtagagtc ccaggatggc acccaatgge 540 acagcctctt ccttttgeet ggactctacc gcatgcaaga tcaccatcac cgtggtcectt 600 gcggtcctca tectecatcac cgttgcectgge aatgtggtcecg tetgtctgge cgtgggettg 660 aaccgecggce tecgcaacct gaccaattgt ttcatcecgtgt ccttggctat cactgacctg 720 ctcetcggee teectggtgect gcecccttcectet gecatctacce agectgtcctg caagtggage 780 tttggcaagg tcttctgcaa tatctacacc agcctggatg tgatgctctg cacagcctcce 840 attcttaacc tcttcatgat cagoctcgac cggtactgcg ctgtcatgga cccactgegg 900 taccctgtge tggtcaccce agttcgggtc gecatctcte tggtcttaat ttgggtcatc 960 tccattacec tgtcctttct gtctatccac ctggggtgga acagcaggaa cgagaccage 1020 aagggcaatc ataccacctc taagtgcaaa gtccaggtca atgaagtgta cgggctggtg 1080 gatgggctgg tcaccttcta cctececgecta ctgatcatgt gcatcaccta ctaccgcatce 1140 ttcaaggtcg cccgggatca ggccaagagg atcaatcaca ttagctcecctg gaaggcagcc 1200 accatcaggg agcacaaagc cacagtgaca ctggccgccg tcatggggge cttcatcatce 1260 tgctggtttc cctacttcac cgecgtttgtg taccgtgggc tgagagggga tgatgccatc 1320 aatgaggtgt tagaagccat cgttctgtgg ctgggctatg ccaactcagc cctgaacccee 1380 atcctgtatg ctgcgctgaa cagagacttc cgcaccgggt accaacagct cttetgetge 1440 aggctggcca accgcaactc ccacaaaact tctctgaggt ccaacgcctc tcagctgtcc 1500 aggacccaaa gccgagaacc caggcaacag gaagagaaac ccctgaagct ccaggtgtgg 1560 agtgggacag aagtcacggc cccccaggga gccacagaca ggtaatagcec ctagecattg 1620 gtgcacagga tgggggcaat gggaggggat gctactgatg ggaatgatta agggagctgc 1680 tgtttaggtg gtgctggttt atgttctagg aactcttcat gagcactttg taaacaccct 1740 cttgcttaat cctcccaacg gecccccaaag gtagaactta gotcectttt aaaaggagcea 1800 cattaaaatt ctcagaggac ttggcaaggg ccgcacagct ggggcat 1847

<210> 2882

<211> 1841

<212> DNA

<213> Homo sapiens

<400> 2882 catcaggcac gaggcaggaa gtgcacaggc gtccggegtg ctectceccte cctgcagecc 60 cgggcagcat ctcccagagg ctccgeggec caggcectcecctg gtgtgtctge agtgcaggtg 120 gctcctggaa gaccctcagce ctgcectgectg aggccatgtc ggactacgag aacgatgacg 180 agtgctggag cgtcctggag ggcttcecggg tgacgctcac ctcecggtcatc gacccctcac 240 gcatcacacc ttacctgcgg cagtgcaagg tcctgaaccce cgatgatgag gagcaggtgce 300 tcagcgacce caacctggtc atccgcaaac ggaaagtggg tgtgctcctg gacatcetge 360 agcggaccgg ccacaagggdc tacgtggcct tcctcgagag cctggagctc tactacccge 420 agctgtacaa gaaggtcaca ggcaaggagc cggcccgcgt cttctccatg atcatcgacg 480 cgtccgggga gtcaggectg actcagectge tgatgactga ggtcatgaag ctgcagaaga 540 aggtgcagga cctgaccgcg ctgctgagct ccaaagatga cttcatcaag gagctgeggg 600 tgaaggacag cctgctgcgce aagcaccagg agcgtgtgca gaggctcaag gaggagtgeg 660 aggccggcag ccgcgagctc aagcgctgca aggaggagaa ctacgacctg gccatgcgec 720 tggcgcacca gagtgaggag aagggcgccg cgctcatgeg gaaccgtgac ctgcagctgg 780 agattgacca gctcaagcac agcctcatga aggccgagga cgactgcaag gtggagcgea 840 agcacacgct gaagctcagg cacgccatgg agcagcggcc cagccaggag ctgctgtggg 900 agctgcagca ggagaaggcc ctgctccagg ccecgggtgca ggagcectggag gectecgtec 960 aggaggggaa gctggacagg agcagcccct acatccaggt actggaggag gactggeggce 1020 aggcgctgcg ggaccaccag gagcaggcca acaccatctt ctccecctgege aaggacctcec 1080 gccagggega ggcccgacge ctccggtgeca tggaggagaa ggagatgttc gagetgeagt 1140 gcctggcact acgtaaggac tccaagatgt acaaggaccg catcgaggcc atectgetge 1200 agatggagga ggtcgccatt gagcgggacc aggccatagc cacgcgggag gagctgcacg 1260 cacagcacgc ccyggggcctg caggagaagg acgcgctgeg caagcaggtg cgggagetgg 1320 gcgagaaggc ggatgagctg cagctgcagg tgttccagtg tgaggcgcag ctactggecg 1380 tggagggcag gctcaggcegg cagcagctgg agacgctcecgt cctgagetec gacctggaag 1440 atggctcacc caggaggtcec caggagctct cactccecccca ggacctggag gacacccagce 1500 tctcagacaa aggctgcctt gocggegggg ggagcccgaa acagceccttt gcagctctge 1560 accaggagca ggttttgcgg aacccccatg acgcaggcecc agccggactg ccgggcattg 1620 gggccgtttg ttaagcggea ctcattttge ggaggccatg cgggtgctca ccacccccat 1680 gcacacgcca tctgtgtaac ttcaggatct gttetgtttc accatgtaac acacaataca 1740 tgcatgcatt gtattagtgt tagaaaacac agctgcgtaa ataaacagca cgggtgacce 1800 gcaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 1841 <210> 2883 «21> 2243 <212> DNA <213> Homo sapiens <220> <221> wmisc_feature <222> (39)..(39) <223> nis a, ¢, g, t or u <400> 2883 cctcagcctg caaaggatgt atgtatgcct atttctttng ccatagcatt tgtaaggaga 60 ctgggacata taggtgagca atggaacata tacaaagtaa taatgtctct aagataaata 120 tttacaattc acaaatgtac aaagaatttt atagatgcat ccataattca cattttgtgt 180 cattatcacc attttctcct aaattacata aaacttattt tatttattga catgtgcttc 240 atatttatca tttatcactg cctgctaatt ttcatcagga gcatcaatgg ctattcaata 300 tcctatttat gtaccatagt ttataaatgt attgacattt aagtgataat ttattatggt 360 ttttgctatt ataacttatt gaattgatga aatgacatac ttttattaac tgatttttct 420 aatattaatt tctagttcca tgaggcttce acttggatgg taaaaagggt agacagcatt 480 ctacttatat gcataaatta atctaggagt gaattttatt tatctgggaa taatttttag 540 atatggcaac tctcattcat ttgacaagaa aaatctaaag ctcataaacc ctgaatccta 600 tatgcttact ctcacaaaaa tctctaaatg tecctgetggg atttatccac agtttagatt 660 agacctggaa tacatatggt catgcaacaa tgatcttaga acaggacttt aacttggctt 720 taggaactga ggctgagagt aatagaattg attttttgtg tgtgtgtgaa gctcctatta 780 taataatgag aatactttga ttcactcagt taaagttttec ccctgattta ttgtgtacat 840 acaatgaagg atcaagaaag agaaattttt aaatggaagc attagccaga caagtttgac S00 Ctcacagttt tactagggga tatatcacct agttttggat ctatttctaa catcttaaca 960 ttgtgaaaag agtcttggga aactggttaa atcccaaaga atgctgcaat aggaggttgg 1020 Ccccttatgag ttatttaata tcttgagetg cttcggaaaa tgttgectgag caggcattga 1080 agagtatcga taaaatttat tgagaatttg tttattatga ttaacagagg taaaagccag 1140 tatattactg attaatatag gtaaaagcca gttaagaaat tgggaatgct ttctcettctg 1200 ctttcttcta cgatgcacaa ggcgtttcac atttatgeccc ctatgaaaat tactaggetg 1260 tcctagtcat tagatctttc agcagtttgt agttttagag cttctaagtt gacttctgtce 1320 ttttctattc atacaattac acattctgtg atgatatttt tggctcttga tttacattgg 1380 gtactttcac aacccactgc tcatgaaatt tgcttttgta ctactggttg tttttgcata 1440 ggcccctecca ggeccacgacce aggtgtttgg attttataaa cgggccgttt gcattgtgaa 1500 ctgagctaca acaggcaggc aggggcagca agatggtgtt gcagacccag gtcttcattt 1560 ctctgttget ctggatctct ggtgaggaat taaaaagtgc cacagtcttt tcagagtaat 1620 atctgtgtag aaataaaaaa aattaagata tagttggaaa taatgactat ttccaatatg 1680 gatccaatta tctgctgact tataatacta ctagaaagca aatttaaatg acatatttca 1740 attatatctg agacagcgtg tataagttta tgtataatca ttgtccatta ctgactacag 1800 gtgcctacgg ggacatcgtg atgacccagt ctccagactce cctggetgtg tctectgggceg 1860 agagggccac catcaactgc aagtccagcc agagtgtttt atacagctcc aacaataaga 1920 actacttagc ttggtaccag cagaaaccag gacagcctcc taagttgctc atttactggg 1980 catctacccg ggaatccggg gtccctgacc gattcagtgg cagecgggtct gggacagatt 2040 tcactctcac catcagcagce ctgcaggctg aagatgtggc agtttattac tgtcagcaat 2100 atgatactat tcccactttc ggcggaggga ccaaggtgga gatcaaacgt aagtgcactt 2160 tcctaatact ttttcttata aggttttaaa tttggagcgt ttttgtgttt gagatattag 2220 ctcaggtcaa ttccaaagag tac 2243 <210> 2884 <211> 374 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (91) .. (91) <223> n is a, c, g, t or u <220> <221> misc_feature <222> (151) .. (151) <223> nis a, ¢c, g, t or u <220> <221> misc_feature <222> (155)... (155) <223> mn is a, ¢, g, tor u <220> <221> misc_feature

<222> (312) ..(312)

<223> nis a, ¢, g, t or u

<220>

<221> misc_feature

<222> (319)..(319)

<223> n is a, ¢, g, t or u

<400> 2884 caaaaagttt gtactaaaca atcacctggg aagggtggcc gacttcccaa tgcagattec 60 tgggccecat ccccaaattg ggttattagg ntctectcca gatagctcag cattccaget 120 ttggctgaca agcctcactce agctgactct ntttnagttg cactattaaa cgtcttecat 180 gcaggcttta tagggaagga caaggcaaag aacaaagcag tcaacaataa ggaaaccaag 240 ccctcacagg aaagaaagec tgattcaaga aaacaaagtt tgaaacaagg catatttata 300 tttaaaaatg gnattaagnt tcttaaagtyg gcttccataa tecttcectt aattattatg 360 ttaccattta tgat 374 <210> 2885S

<211> 580

<212> DNA

<213> Homo sapiens

<220>

<221> misc_feature

<222> (1) ..(1)

<223> nis a, ¢, g, t or u

<400> 2885 nccttttgee catgttgtet ggaatgccct tcttctecct cttgtttaca tcaagcatca 60 gactgaatat ccctettgtg cggectteta aaacctcccg tccaaagcga aatatattgc 120 cctctattta tacttttaca gcatttggca cacaagtaca gagtagtagc tttttatcac 180 attctctgat aattatatag atatggtatt tcttagctct ctctccaact ggctaataag 240 ttgetttttg tctgagtgec taattttgtg ttrtgtgtet gagtgcctca gttcctcaaa 300 daaaggtttt ttgattagtt cattattcat ttgaacatgg aaattatget cactagtggc 360 aaatgccact aaccgtattc cagaagctag gtgtcatgtt tgcaataaga tatattatcc 420 cttctacaag tcacctttta tttcaggcat ttgtaaatgc ccattaataa agtatggttc 480 ataaatttta ccttgtaagt gcctaagaaa tgagactaca agctccattt cagcaggaca 540 caataaatat tattttataa tgccgaaaaa aaaaaaaaaa 580 <210> 2886 <211> 836 <212> DNA <213> Homo sapiens

<400> 2886 gatctcttgg gatcctgaaa gggggcagga aaggctgggg tcccagtcca ccctaatggt 60 atctgagtgt cctagggett cagtttteccc acctgtccaa tgggaccctt tctgtectca 120 ccctacaagg ggcacaaagg gatgacacca aacctggcag gaacttttca cgcaatcaag 180 ggaaggaaag gcattcctgg cagagggaac agcatgccaa gcgtgagaag gctcagagta 240 aggaggttaa gagcccaagt attggagcct acagttttge ccctteccatg cagtgtgaca 300 gtgggcaagt tcctttcect ctctgggtct cagttctgtce ccctgcaaaa tggtcagage 360 ttacceccttg gctgtgcagg gtcaactttc tgactggtga gagggattct catgcaggtt 420 aagcttctgcec tgctectect cacctgcaaa gcttttctge cacttttgce tccttggaaa 480 actcttatcc atctctcaaa actccagcta ccacatcctt gcagccttce ctcatatacce 540 cccactacta ctgtagccct gtcctteeocet ccagccccac tetggceectg gggetgggga 600 agtgtctgtg tccagctgte tececctgace tcagggttece ttgggggctg ggetgaggec 660 tcagtacaga gggggctctg gaagtgtttg ttgactgaat aaacggaatt cagtgcgaaa 720 acaaaaaaat aggaaataaa agatctcgga aaatagcatt ttgttaaaac cttggggggt 780 aaaaccccgg ggagttttaa cggaaaaatt ccagggaaca caacttgggg gccaaa 836 <210> 2887

<211> 742

<212> DNA

<213> Homo sapiens

<400> 2887 ttttgtttag ctaaagtcat ggggacaact cttcaattta gaacttaagt tgaattataa 60 aaatgatgga tataagtggt agctgtatct agtgaagtgt ctgtcagtaa gtgaaacatt 120 ttttggtggt ggcttatcca caaacagttt agttgtagaa taaaacttat gagtgacatc 180 tggaaagtaa ccatgctaag atggcaagca cactggaaac aattaggcca cttggcttte 240 ttttgctgta ttgttttata agcctacttt acctcccagt cttggaaaca agttttagtt 300 ttttattggt ttggagacta gagccaatag tataatgttc tcaaaggaaa cagacttgag 360 ttgttggatt agaggaacta acccaactta tatgattttg tttttggttt ttgtcgtgta 420 gttatggcac tgtcttattt ggaacatttg caactaggga taatacaaca tttttaactc 480 tcatttgaca acctactact aatcacagac cacaagggta atgaccaaat ttatgtggtt 540 tttgcactcc atagttgtct tagcccaatc tttetatact cttacgatta ctggggttaa 600 cgcttetgtg aggaccttet ggctcttgag ataccctaaa tatttacaga tacttagata 660 tcttgaagat agaataggat atcgagattg taccaaatag gaatatcagg agtatggtac 720 aaatgagcag atacctgttg aa 742 <210> 2888 <211> 440 <212> DNA <213> Homo sapiens <400> 2888 ttttttgggt tttaaggagt ttattgctaa tetgtaaaac agaaagagac aggagataag 60 catgacaaaa tatagggaag aaatgacttt tgcctaaact tccaaattgt gtacaattga 120 agcctctget ttatagctct tagcacacct ctcaaataag aaggcagtac tgggaaggct 180 ctgaacctgt ggcagaacca ctgatagctg tggagctatt ccaaggagtc tgggaatcag 240 ggggattatc aagatcattg ttagaataaa ttaatcttac tgtatatata gcagaagttt 300 tcaagcatat gtaaatgcta ctaataacca aataattaca ccttgttttt ctttaaactg 360 taactctcaa gtatgtctct acataatttt ttgatggtag tgtctgcatg ctcaaaaagce 420 ttgaaaacac tactggagaa 440 <210> 2889 <211> 524 <212> DNA <213> Homo sapiens <400> 2889 tgcttattga aactgaaggg atgttgggaa agacagactg ggagctttct ctaaatttta 60 atacagcatc agtgcttcct ataatgtcca ggttaggaga gaagcaaatg gagctttact 120 aaggaagaga aagtgatcaa taccagtgag aaaggtgaaa aaaaaaaaaa acaaacaaaa 180 acgaaaaaaa aacctaagca aattcagtga gaaaagaaaa agcagaactt agagtcctta 240 cccttcaatt taaggaagga gagttattgc ctagcagaat cttgaaataa aatttcctta 300 gaaagcccca gaaagttttg tgtgtattgc aagtccaaag gataaggaga acttctatat 360 gctttettet tatttccact gggcaaagta ctgctccatc aagactcagc ccgccatgag 420 gctttecaat caactctcaa ccaccacaac agttagggct ttttectcta tgttgcaaag 480 cactttctgc ataactcaga atgcaaaatg tactcattca tttg 524 <210> 2890 <211> 575% <212> DNA <213> Homo sapiens <400> 2890 tttetttttt ttttttittt tttttttttt tttttttttt tttttttttt tttttttttt 60 ttttttggac ccaaaaaaaa aaaactttta aggaaggggg acccagttaa aaccccttcc 120 aaatgcggcce caaccctgece ccacggaaac cggccatggc aacccctaaa taaaaagggg 180 tttttgagge ggceggeecc ctacccaaagg atgcccccaa tttttttttg ccagggggga 240 atgtccttgg acacggggcec ccaaaattec ccatgcecggg ggtttgtact ttaaaagggc 300 ttcctaacct cetecegggtg ttcctaaggg ccatgctgga gctaaaactt gtaaaaaaag 360 gcccaggcectt cccccaggtc cgagtaaatt ttcacagggg gggggaacca ccecectggece 420 ttggggattt tcecgttgact Ccaaaacagt ttggccacgg ccagaaccac atgggggtaa 480 tgctcacact ttttaaggga atccacgctt tggggectcc tgtggggcet tgcctggagg 540 aagatggect cacaccaaag gataccggag ttggg 575 <210> 2891 <211> 467 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (428) ..(428) <223> nis a, c, g, t or u <400> 2891 tgatgccaag ccecccaggag ggctttattt tttcttttcea acatcctgga acgcggcttt 60 cctggccatt tttgeccgga tcceccaagac cccggegttg gcacggccca taccgaaact 120 atgcaagggt tcgaaattat ccttteccte acggacaact cgagctttct ccttattata 180 ctaccttcce taccggecatg accggaccgg tcacctgggg ggccacgcac atttctacag 240 gaaaactggc tcccttettg ggggccgagg gcttcctgtg gaaaaggatg agtttggage 300 ggtactccct cageccggtgce acgttgatct ggagggactc cgcggacttg ctcctgcetee 360 tgggatccac aaaaatgcgc taaggtccgg cccaccttet tgggaatgcc geeccaccctg 420 agctcctnca ggatgaatcce gcggccgact cgcaccttct tgggtac 467 <210> 2892 <211> 473 <212> DNA <213> Homo sapiens <400> 2892 ttcatttaat ggcacatgat gatgcacaca aaacttcaac tctcagtctg gaatcagccc 60 acaggtctge agctataaaa atcatctcga aaacatgaga tttcagagat ccagttctca 120 gtgttacctt gaagatgaca atttatgaag aaacaggtga ttttaatceg aaattgecag 180 gaaacaaatt actcctcaaa agcccttgga aagtaataag atagctaggc agaaaaaaaa 240 agattctgca aaactaaact taatgtgtat tcatctagac ctgaattaaa aataaaatte 300 cactataaaa agaatttttc aaaatgttag gcccaagaat atggccatat tgttceccatct 360 tgaagaaccc agttgattca gtttcattac tggectccecc actcttctaa gtaagtccect 420 cactataaac atttacgaat tccatctcag cattagtact aaacaatatt cat 473 <210> 2893 <211> 546 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (280) .. (280) <223> nis a, c, g, t oru <220> <221> misc_feature <222> (537)... (537) <223> nis a, ¢, g, £t or u <400> 2893 cggtagtcaa ctcagttact tttaatatta aatgtctttt tatcctagta aactactcce 60 ttgcttaatg ggagaacttg caaatgagat ttaaaacatt gtaattttta taaggtaaca 120 gaagctagat ccctttcact gttcatctca agctattgat cttgtcagtg ttgtacagat 180 ctagaatggg ttgtcaggga taaggtcact gatctgatgg tgattgttga catctgctga 240 ctccacacaa caaccctagg ggaccggtgce tttgagcatn cttattttca gatggtttge 300 ccacttcatg cagttaacag ctgttggtgt tgggcttcaa atccaggtct ttcggacatc 360 aaatcccagc ctcttaacaa ctcaccaagce agtgattact actcceccaac ataggggcag 420 tatgtacaag tcatgttgaa ctaatacagt ttctttettt gataggaata ctaattttgt 480 tgaacaagaa aatatgtact ggataagagt aaggcatttg acaaggcgtc ctgtganatc 540 tgtgaa 546 <210> 2894 <211> 1993 <212> DNA <213> Homo sapiens <400> 28954 actcatttat accaggaaac agacaagaga acaagaggct gccgaagaca aaacttctcect 60 gcaagcacct gtgcacagca atgtgcgtgg gcatctgtga gaagaagaga atctgtgaag 120 tttgagcaag cggccttece aagatgtacce gaatatctca actgatgtca acaccagtag 180 caagttcttc caggttggaa agagaatatg ctggagagct gtctcccacg tgcattttcc 240 caagtttcac ctgtgattcec ctggatggtt accattcttt tgaatgcggc tccatagatc 300 ccctgacagg ctcccactat acctgtcgcc gaagtcccag actcectcacc aatggctact 360 atatttggac tgaagacagc ttcctgtgcocg acaaagatgg caacataact ctgaacccat 420 cccagaccag cgttatgtat aaggagaact tagttagtac ctccaaatct tggctgcatg 480 gaagtatctt tggtgacatc aactcttctc caagtgaaga caactggttg aaggggacca 540 ggaggttgga cacagaccat tgcaatggaa atgcagatga tttagactgt tcttctctga 600 ctgatgactg ggagtcaggg aagatgaatg cagagtctgt gatcacctcecc tcttccagee 660 acatcatatc tcagcctcct ggaggaaact cccatagctt gtctcttcag tcccagttga 720 cagcttectga acgtttccaa gagaatagtt cggatcattc agaaaccagg ttgttgcaag 780 aggtcttctt tcaggcaatc ctgettgctg tgtgcecttaat cacttctgca tgtgcaagat 840 ggtttatggg agaaatatta gccagtgtct tcacatgctc attgatgata actgtagctt 900 atgtgaaatc attgtttctc agccttgcca gectatttcaa aaccactgec tgtgcteggt 960 ttgtcaaaat ttgacaacca tttaggaatg ccttcgatga atgtcctcca tctgaatatc 1020 tggaaattgt ccaacttgca gtctacttgg aatcaagtgt tttattggaa gggagtaagc 1080 gagtaatgga gaaaaagcca ttttagtttg actatgtgat tttaaaatga tctcagtttt 1140 tccatcaaaa ttataatatg ctcatgaaaa taatattaat ttgccttccc tttgcaaaca 1200 ccggcagttg aaaggaaaag gacggggaat gtgatggaaa agagaccgcc tggaataaat 1260 gtccccctat gattctttaa ggcagtggtt ctcgagcecttg aattttcatt aggaaattcet 1320 gtgaggagct tgtaaccaga tttctgggtc tgccacatgce acctatctet tgctgaattg 1380 ctttaataga ataatgagag caagtttgtc taactaatac caacctgaca acttgaataa 1440 caataaatgc aatttgtaca taaaatataa tgctgcaaaa gtttgtcatt cacctcagtg 1500 gagtgacttg atattaggtg gtaaccgtag atgatggtta atatgaaaat ggacaggaaa 1560 gaagcatttt ctgaaagtta tattcttttg aaccacgttc taaaccaagt ttttaatctt 1620 cttggggctc gtaattacct ttcactttaa tgtcacttaa agatataaca cagaaaaatg 1680 ccttgagggc aaaatatagg caaaacacca atgcgctttc aaatgcatga aaatggtgca 1740 gttgtaccct tgagccecttga ctcaagggcet gtagatgttc cctttccacc ccccacactt 1800 ggtgecgtgtt cacaaagcaa atatggcctg taattcaaat ttgttctatg tgatactctce 1860 tgagtaaaaa ctcatacatg cagaaaattg tctttgctcg aaatgataat gccaaaatat 1920 aactttatat ataatttgca tttagtacat ttttggttaa aaaataaact aataaataag 1580 tgaagtcatc agc 1993 <210> 28895

<211> 521 <212> DNA <213> Homo sapiens <400> 2895 tgatgtttac ttaagcttta tttatatata tagtgcgtag gttcctggag cacaaagaag 60 aaagttgctc agatttatcc agacctcaca taagtttata gatttcaagt agccactgta 120 ttttattaca gaaaatacat tcttcaagag gaaaatgtta aggccatagc agctttcacc 180 ttagctatct aagcttgtat taggtcatca ttaaatagta tctgtatcat tcttatgtgt 240 tccgtaagtt atgccacaaa taccagacca agtacactca gtctagaaac aaaaaagtgg 300 gaaataaagg ttaaaacatt ctaataggtg taatgggctg atagatgact ttatattaca 360 aagctactta agacaattct acttttctag aatacaacgc attaatataa acatttgaaa 420 ttcagaagat ttggcctgtg gatgctttgt ttctcaatge aattcttgtt aatatgttag 480 taagtaataa tttattaata ccaataataa aaaattaaca t 521 <210> 28896 <211>. 1679 <212> DNA <213> Homo sapiens <400> 2896 gtttgttggc tgcggcagca ggtagcaaag tgacgccgag ggcctgagtg ctccagtage 60 caccgcatct ggagaaccag cggttaccat ggaggggatc agtatataca cttcagataa 120 ctacaccgag gaaatgggcet caggggacta tgactccatg aaggaaccct gtttcececgtga 180 agaaaatgct aatttcaata aaatcttcct gcccaccatc tactccatca tcttcettaac 240 tggcattgtg ggcaatggat tggtcatcct ggtcatgggt taccagaaga aactgagaag 300 catgacggac aagtacaggc tgcacctgtec agtggccgac ctecctctttg tcatcacgcet 360 tccettctgg gcagttgatg ccgtggcaaa ctggtacttt gggaacttcc tatgcaaggce 420 agtccatgtc atctacacag tcaacctcta cagcagtgtc ctcatcctgg ccttcatcag 480 tctggaccge tacctggcca tcgtccacgc caccaacagt cagaggccaa ggaagctgtt 540 ggctgaaaag gtggtctatg ttggcgtctg gatccctgec ctectgctga ctattececcga 600 cttcatcttt gccaacgtca gtgaggcaga tgacagatat atctgtgacc gcttctaccec 660 caatgacttg tgggtggttg tgttccagtt tcagcacatc atggttggcc ttatcctgece 720 tggtattgtc atcctgtect gectattgcat tatcatctcc aagctgtcac actccaaggg 780 ccaccagaag cgcaaggccC tcaagaccac agtcatcctc atcectggett tcttegectg 840 ttggctgcct tactacattg ggatcagcat cgactccttc atcctecctgg aaatcatcaa S00 gcaagggtgt gagtttgaga acactgtgca caagtggatt tccatcaccg aggccctagce 960 tttcttccac tgttgtctga accccatcct ctatgcttte cttggagcecca aatttaaaac 1020 ctctgeccag cacgcactca cctectgtgag cagagggtcc agcctcaaga teoctcetccaa 1080 aggaaagcga ggtggacatt catctgtttc cactgagtct gagtcttcaa gttttcactce 1140 cagctaacac agatgtaaaa gacttttttt tatacgataa ataacttttt tttaagttac 1200 acatttttca gatataaaag actgaccaat attgtacagt ttttattgct tgttggattt 1260 ttgtettgtg tttectttagt ttttgtgaag tttaattgac ttatttatat aaattttttt 1320 tgtttcatat tgatgtgtgt ctaggcagga cctgtggcca agttcttagt tgctgtatgt 1380 ctcgtggtag gactgtagaa aagggaactg aacattccag agcecgtgtagt gaatcacgta 1440 aagctagaaa tgatccccag ctgtttatgce atagataatc tctecattec cgtggaacgt 1500 ttttcoctgtt cttaagacgt gattttgectg tagaagatgg cacttataac caaagcccaa 1560 agtggtatag aaatgctggt ttttcagttt tcaggagtgg gttgatttca gcacctacag 1620 tgtacagtct tgtattaagt tgttaataaa agtacatgtt aaacttactt agtgttatg 1679 <210> 2897 <211> 450 <212> DNA <213> Homo sapiens <400> 2897 ttttggcggyg gcagaggttg gegggggeag tectttgaac taagattcte tcaggaacca 60 ctgcaggaaa tgaagtgatt cagaactcac caattatgaa ctaaccttca atgccagagg 120 ctttaacagt ttctaataaa aattcagttc agatctcaag ttcagataag tctgaaaaaa 180 cacttcaagg tcatctgaac gaacatattc taccagtact ttatataatt gtatttacct 240 gttcctaaaa ctttccgtga aagaaatgtt gaattttctt cagaaatagt tttgagcaaa 300 atgtcaaaac aattctccca tgctcagtgt acttttgact atactctgaa aatatttctt 360 cttgttttcec tgcacttacc tgttagtgtg ctcacactcc tgtattatgg aacatgttca 420 gtaactcata cacatgtaac acagaagtct 450 <210> 2898 <21ll> 260 <212> DNA <213> Homo sapiens <400> 2898 ggcatgacta gaggtgtgac taataataat ccctcacatc tctatagcct aatacagttt 60 tccaagggtt ttctcatcca tgatctcatt tgatccttgc agcagtccta tgaggaaggce 120 agcacataca tcattagctc ccttttgcca aagaggaaac aaaaaacagg tgaaagggac 180 ttgtctaagg gcacccagcCt ctaagggaca gagcaaagta acaggtcatt tcttttttec 240 atttattttt agagacagag 260 <210> 2899 . <211> 452 <212> DNA <213> Homo sapiens <400> 2899 tttttttttt tttttttttt tttttttttt tttttttttt tttggaaatt ggaaagggca 60 aattaattaa gttttttaaa gccatcaagt tacaaagggc tattaggggt cttaaaaaga 120 caaagagtat ccaataaaac aaaaagcaat tccagatggt tttaggtgga acaattttgg 180 gccagttata tctataggcc attcecctaatt tacttagcaa actttatccc ggggattggce 240 aaattaaaaa aaaggaagaa ccaacctata ttttcttttc ggttttttgg aaacagagcc 300 tccactetgt catccagget ggagtacagg ggggggatct cagctcaaca taccctcaac 360 ctttggggtt caaggaatct cgggcctaac cctcccaagc agttgggact acaggcatgce 420 accaccgggce teggceccaatt ttttgcattt tt 452 <210> 29500 <211> 511 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (500)... (500) <223> n is a, c, g, £t or u <400> 2900 ttttttttag tgttttaggt tttaatgtca agattaagca tcaaacaatt gtaaaataaa 60 gatgttttaa cagagtggac aggtaataaa cacgttcaac aaaggcagat gttcttggag 120 gttaaatccc actaatcaac acgattaact ttaagggtcc tgagactttc aatagcatgt 180 acctcatgga ctaaaaaaga ggaagagttt atgcttcaca attaatctcc agaacttgac 240 acatgtaatt cttatcacca aggctttaga ttgaaaagta atagaaaaca acagtaactg 300 ttctggtaca gtctagcatt tccaatgtgc ttctttttat tttaatgaaa aaaaaagata 360 cattatatca aacaaaactg ttgatggatc cacatctttg caggctcttt gcggaatggc 420 tcaccaaata cacatttcca tctttagatc attatactgc ttaaacagca agatatgcta 480 aagagatatg aatatgattn tgacctacca t 511 <210> 28901 «211> 541

<212> DNA

<213> Homo sapiens

<400> 2901 ttttttttet tttetttcet gacgtataca gatcatcctg gacagtttat ttctctaatt 60 ctgttaatca aagcagagat cagaacggat taactgtggc aacgtcgtat caggagcaca 120 aagagaagcc tgcctctttc agtttggtcet tttctccagc aaaacagaaa tgcaatttag 180 tcaaacacat acagaggccc cactgtactg cctcactgat ggagggaaat acttgggtge 240 aatcacacac agtgttagtg attggcaact gtccagtgct atttcgctaa aactggtaaa 300 aacagtttec ttgggcaagce agctgattgg ctacttcata ctgtgctgag ttgggctcag 360 cttgtectgtc tctgggaggc cctaaggggc tcctettttt cagctaggga taaggggaga 420 ctgtcaacca gtatcttagc gtgaactgte aatcgctgag ccecctgccaa ggactctctg 480 gaagtccctec aggtatgctg aaaatacctt atactgaaaa ggtagctctc gctgcateca 540 c 541 <210> 2902

<21l> 646

<212> DNA

<213> Homo sapiens

<400> 2902 gaattaaaaa taatactttt attgctggtt atgctttctt aaaagtaaaa attattettg 60 attgatgtga cttgccagaa tgtttgaaac accagtgacc aagggtcact atatctgcce 120 ccaaacaatt ccaccatgtt tacttatata gcactcacca aaccagaaga gaggctggga 180 tattctcagg ccactgcact gaacatcaat atgaaagaac catgaatgat gcgacaactg 240 agttgatttt ctacctcctc tgcccaccat gactttgcac cccaaattct ttcagtgtct 300 tttcaaggta caaccctect tctgggcaca ggttggctgg gtcacctcaa ggtatgttce 360 ttcattctge agtgatttcc tgectctget caattaagga agttgagaat acagataact 420 caggatcatg tttaattatg taaaaaagct ctaaagtcag gtaatggttt tcatgtgctt 480 ctcttgagca gtctgaggag agaatagaaa cagaaacccce ttggggcctg agtagacgca 540 gctggccatg cacaggcaga ggctettggt cagtgcagga agcagagtca cagccatcgce 600 cttggggtgg ggatgaaatg agatgacctg ttggctgtat gacagc 646 <210> 2803

<211> 557

<212> DNA

<213> Homo sapiens

<400> 2903 atctcaaagg caattgagtg ggtcttctgg gccagaccta tttaatttac gaaacatagt 60 accttgcaga gaataggcat tgaaatatta tttaaacaat caaaccaaag atgttcttet 120 atcttcagct gtcagtgatc taatgccecte atctctetta tcctcaggac ccagaatggt 180 atattccaca taaaagatgc ttrgtttatc aaatgaatca aaaagcacgc ctgaggcatt 240 tatttttact cctttactte tgtaggccag gtcaaggtgg gtctaattca cttttatcat 300 cagcacttaa gaaactggat ggaagaccac aacaccttgt tttttgcaaa aattttccat 360 ctcctcaate aggccaggaa gcatgtatct tctggacagg actttatcte tctactecage 420 ttagtacact geccttatatt agtccatttg tcccatgttt tcatcactga ataaacttgt 480 taaatgactt ttggtctgga tctcacacct atattacttc atttccttct gtgagcactc 540 tataatgata acatcat 557 <210> 2904 i <211l> 488 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (239)... (239) <223> nis a, ¢, g, t or u <400> 2904 gcggceccgegy aaactttgea ggcccgegge atcgagcacg gcgggcectag ggcgggtgtg 60 tgcgegtggg tcgegaggtg acaggagccg gecctegtce ttaatggage ggccagagct 120 9ggtgggggc ggccecgggag ctcggggttc ccggcactac ctgaatgcag cccgaagcca 180 agttgtgcac gecgtttgtcc tataaaagcg aagtgagtgg attcccattt tggaatccnc 240 ggtgtctecca acctcecgagtt ggagaaccat gttgagtcag ttcceccggaa ccttacaaat 300 ggactccact teccececgtte ccattectace gtttttttta aaaaatgatt tttttgagtg 360 gcggttcecag gattagtcaa atagcttetc ccgagaatgce tctttaaaag attgtcagac 420 acctttgggt taagtctcag tttttgcatg ggccecgaatt geagtcetat gaatttctga 480 tttattca 488 <210> 2905 : <211> 696

<212> DNA

<213> Homo sapiens

<400> 2905 ttcecececcece ceececececce cceccgecega gcacaggaca cagctgggtt ctgaagcttc 60 tgagttctge agecctcacct Ctgagaaaac ctcttttceca ccaataccat gaagctctgce 120 gtgactgtcc tgtctctect catgctagta gotgcocttct gctctcecage gctctcagea 180 ccaatgggct cagaccctec caccgcctge tgcttttett acaccgcgag gaagcttect 240 cgcaactttg tggtagatta ctatgagacc agcagcctct gctceccagece agctgtggta 300 ttccaaacca aaagaagcaa gcaagtctgt gctgatccca gtgaatcctg ggtccaggag 360 tacgtgtatg acctggaact gaactgagct gctcagagac aggaagtctt cagggaaggt 420 cacctgagcec cggatgcttc tccatgagac acatctcetc catactcagg actcctctec 480 gcagttccetg tecccttctet taatttaate ttttttatgt gccgtgttat tgtattaggt 540 gtcatttcca ttatttatat tagtttagcc aaaggataag tgtcctatgg ggatggtcea 600 ctgtcactgt ttctctgctg ttgcaaatac atggataaca catttgattc tgtgtgtttt 660 ccataataaa actttaaaat aaaatgcaga cagtta 696 <210> 2906 <211> 347 <212> DNA <213> Homo sapiens <400> 2906 tttttaagtc acccagtttg tggtacttta ttacagcagc tcaaggagaa ttacaaagtg 60 gatggattga gtacaagttc cttcatcgta agtggaagca gaagttccta actcttttag 120 tatttgtcat ctgaactact tttctatctt ttacctectce caatagataa gttattagaa 180 ggcaaatatt gcttecttgat tttttgtttt ccgtctatct aagcttgaat tttatgtgca 240 cgtaaggtag atgtgaaatt catgggcatc aaatatgggt gggtaaaata taattttgtt 300 ttctataatt aaaattattc tatatctaga tccttgttge attgggg 347 <210> 2507 <211> 549 <212> DNA <213> Homo sapiens <400> 2507 ttttttgttt tcccttgact ttatttatct tcataagtca caaaatgtga gtgcagagat 60 aaatgtctgt gtgcatgtgc cctgagcaca cagggtggca taactcggca cactcataat 120 gacacagcecg ttcacccage cacagatagt gacagggcac acatggcgac acccacatgt 180 acggagataa atctccccca ccatgacatg ggtagacaga aaacacgccg cagtatactc 240 tagtatgttt acacaaacag ggagacaggc ccgtgcaatg catgtcacca acacccacac 300 tcagagtgac atctgctgga ggtgctcaga cacagccacc caccgtgaca tgccgagact 360 cacatatgtc acatgacaca ggcatgcatg ccacattcac tgtgactctc agtcctattc 420 attcatcacc tttctgggag atacactgaa atgtccacce tttgcaaaat gcacacacac 480

. 0 gcgcacgcac acacgcacac acacgaacac acgcgcacac acgcacacac acgcacgcag 540 gtgtacaca 549 <210> 2808 <211> 400 <212> DNA <213> Homo sapiens <400> 2908 ctttctttte tettctttet tcacgcaggt acaaaggaca gagtatattt cttcactcag 60 gttcagagga cagaataatg aatcttcttt ctttccttct ttettecctte ctteettett 120 tecectteette cttcocectttt cetatggaca gctgagaatc attttcotaac tttatcaaat 180 atgctcecte ctcttaagat agectgcecct ggectgcettce tatgtctctt gcagtctgac 240 caggcactgt agggaagagg cccaaatgca cccacctgge ccagatatcc agaggccaag 300 gccacggtcc tgcaccacag cgtgagagtt cttctttgca gtgectacaa acctatgett 360 gcecccaaac tcgctcaggg gtaacggggt tggggaaaga 400 <210> 2909 <211> 547 <212> DNA <213> Homo sapiens <400> 2909 tttttttett tettggtttt gaacctttaa taaaagtaaa aaatgaatgc aaaaagaaca 60 caatgttgaa aacttagtat gaatgtgaac ctcactagat gttcaaatct ggtagagtgc 120 aaattttgtt catactattt tacattttta caaactcaaa tcactttggt tcatatattt 180 tctataaact attggcaaaa aaatcctcaa atttacattc ttttggctac attatttcta 240 acagatatag atttacttcc ggtttcggag agaaagactt attgtgtgtg cgtgatcaag 300 tctgttttaa agattcactc gctgcectttca tctaataact tetggttttt cataaaatgce 360 tgacatcttc attggaaatt tttttcatgt aactgttttc attttcagaa aatatataag 420 ggggtcattc caaagttcag aatgatccta tttttttaaa aaacaaaatt cctgtaaaac 480 aaattaactc caggaactta aaatttactc caagacattt ccctcaaaac aaagcaaaaa 540 acceccag 547 <210> 2910 <211> 549 <212> DNA <213> Homo sapiens <400> 2810 attttggaaa atgttaaaat ttattaataa tagttaacat cacatagtta attaaactag 60 ttatgtattg tacataatga caacatcttc actagactga gtgctcaagg atttgagatg 120 attcgctatt catcacaccce ctgaagattga gatccactgt atttacacaa agcaaagcca 180 tgtcagcaag ggactgtcaa cctgattetg agaacataaa cattcaaaat ttattttcca 240 gtgttccttt ttggaaacca acaacacatc tttaatacct acacacacac acatctctac 300 ctttaaaaaa aaaaaaaaag tgtaacttca cagatagtac ctaatcttca agcttaaaat 360 ttaagttaaa attaatctct attttgtggg caccctttag tgaactaaaa tctacatgaa 420 accttttgge ttttgtgtag caggaaatac ccacgttttg ggtcaattag tgcagatggg 480 agcagcagag gagctacacc agacagcaaa gcaagactag agcaaacgag aaggaccagc 540 ccctagecce 549 <210> 2911 <211> 408 <212> DNA <213> Homo sapiens ’ <400> 2911 tttttgcaat gtagttttgt tggaggccat tttttattge agacttgaag agctattacg 60 ttcgeggegt ggegeceggt ggtceccaag gggagggaag gg9ggaggcgg ggcgaggaca 120 gtgaccggag tctcctcage ggtggetttt ctgcttggca gectcagegg ctggcgccaa 180 aaccggactc cgcccacttc ctcgcecectg cggtgcgagg gtgtggaatc ctccagacgc 240 tgggggaggg ggagttggga gcttaaaaac tagtacccct ttgggaccac tttcagcagce 300 gaactctcct gtacaccagg ggtcagttcc acagacgcgg gccaggggtg ggtcattgeg 360 gcgtgaacaa taatttgact agaagttgat tcgggtgttt ccggaagg 408 <210> 2912 <211l> 525 <212> DNA <213> Homo sapiens <400> 2912 taatctcaaa ggcaattgag tgggtcttcet gggccagacc tatttaattt acgaaacata 60 gtaccttgca gagaataggc attgaaatat tatttaaaca atcaaaccaa agatgttctt 120 ctatcttcag ctgtcagtga tctaatgccc tcatctctet tatcctcagg acccagaatg 180 gtatattcca cataaaagat getttgttta tcaaatgaat caaaaagcac gcctgaggca 240 tttattttta ctcetttact tectgtaggece aggtcaaggt gggtctaatt cacttttatc 300 atcagcactt aagaaactgg atggaagacc acaacacctt gttttttgca aaaattttece 360 atctcctcaa tcaggccagg aagcatgtat cttctggaca ggactttatc tctctactca 420 gcttagtaca ctgccttata ttagtccatt tgtcccatgt tttcatcact gaataaactt 480 gttaaatgac ttttggtctg gatctcacac ctatattact tcatt 525 <210> 2913 <211> 1085 <212> DNA . <213> Homo sapiens <400> 2913 ttatggatcc agaatgtata ttcattcagc atattaaaga tatgtgcttt gacattcatt 60 tgaattggag attcaagcct attgttatct tatgaacact tcagcaaaca ggtctgccat 120 tcttaaaaat ataatgcttt gttggacaaa agggacaagc cacgtcccct ggtcctctee 180 tctattegee tgtgaactee atccacacgt aaaggacctce tgggtctgac tgtccectece 240 acaggcatgg tgctgggaaa aggaaacagg catatctggce ttttcagatt ttaaaccgga 300 aactctcaca gtcacaaatc caccatgaga cttgggagat tggatgagct gtctcccaaa 360 ccctaacacc ttccaccttc tcaaaatgaa ggctgccctt tcactgggag gttctgaatg 420 cgggattggt gctgactcag gectgggcaca aaggagaaca ggaggacatg gaaaatccga 480 caattcgaag tacaaatatt tcaaacacat gtgaaaacca tttggaaaga agaaaagagg 540 tatctggaat gatttcatga cagaaatgaa aaaagataaa tttagttcta atcttcecctgg 600 caacaaagcc ccagaggaga aggtttcatt gtctgaagat aaaaacacac ccgtttgect 660 ggatatgaac acagtattcc tgcaccaaat tctagaaaga atatactttc ttctaacaaa 720 gccaagagtt tttcttgtac tcattacagg gggcttttaa tcctaacata ttttttaact 780 ccttatgaaa atgcataaaa gttaaaaaga tatttcacga tagaatcaag cctatgaaat 840 cgtcaaatct attaactcct taacgaaccg aattaaggac caaaaacaaa ccttgttttt S00 tcacaaaggt tggatgttgt aaacgtccga aagtgtectt ttatacgaaa gacagtaatc 960 tggggaaata tttactggaa tgacacaggt ctttggggga aggaactatt taccggataa 1020 atgggaaaag aaatgttagc gagactatgg tataacacgg gctaggagat aacaaataaa 1080 tatta 1085S <210> 2914 «211> 2610 <212> DNA <213> Homo sapiens <400> 2914 ccgetggttc cgtaacaaca teccgttgge ttcoccctcagg cggecgggacc agtgcagecg 60 ccgectecca ggategtecg ccggtcaggg ccocttgecct ccecggecaca ggccaccatg 120 gccaccaacc cacagecgca gecgectect ccggecgecge cgectecccc gocgcagecg 180 cagccgcagc caccgccgec geccogecggge cccggggcetg geccccggege gggeggggcg 240 ggcggegegyg gtgcgggege cggggaccceg cagectcgtgg ccatgatcgt gaaccaccte 300 aagagccagg ggctcttcga ccagttccge agagactgcc tggccgacgt ggacaccaag 360 cctgegtatc agaatctgag acagcgtgtt gacaactttg ttgcaaatca cttggcaact 420 cacacatgga gtccgcatct caataagaac cagctaagaa acaacattag acaacaagtc 480 ctcaaatcag gaatgttgga gtctggtatt gaccgaatta tttctcaggt tgtggaccca 540 aagatcaacc acacattcag acctcaggta gagaaagctg tgcatgagtt tttggccacg 600 ctaaatcaca aagaggaagg aagtggcaac acagctcccg atgatgagaa accagacact 660 tcccttatta cacaaggtgt tectactcct gggceccagtg ctaatgtagc caatgatgcece 720 atgtcgatat tggaaaccat aacttctctt aaccaagaag ccagtgctgc tagggcttca 780 acagaaacat caaatgccaa gaccagtgag agagcgtcaa aaaaacttcc atctcagceca B40 accactgata ctagtactga caaagaaaga acttcagagg acatggctga taaagaaaaa S00 tctacagctg actctggagg tgaaggactg gaaacagccc caaagtctga agagttcagce 960 gacctcceet gtccagtcga agaaattaaa aattacacaa aagagcataa taatttaatt 1020 ctgctaaata aggatgttca acaggaaagc agtgagcaaa aaaataaatc aacagacaaa 1080 ggtgaaaaga agccagacag caatgagaaa ggdagaaagaa agaaagaaaa gaaggaaaag 1140 actgaaaaga aatttgatca ctcaaaaaag agtdaagata cacagaaagt taaagatgaa 1200 aaacaagcaa aggaaaaaga agtagagagt ttaaaacttc cttcagaaaa gaacagtaat 1260 aaagctaaaa ctgttgaagg gacaaaagaa gatttctctt tgatagattc tgatgtggat 1320 ggacttacag acatcacagt tagctctgtt cataccagtg acctttcatc ttttgaagaa 1380 gatactgagg aggaagttgt aacgtctgat agcatggaag aaggagagat tacgtcagat 1440 gatgaagaga agaacaaaca gaataaaaca aaaactcaaa ctagtgattc tagtgaagga 1500 aaaacaaaaa gtgtacggca tgcgtatgtc cacaaaccat atctttactc aaaatactat 1560 agtgattctg atgatgagct tactgtagaa caacgacgac agtccattgg tattttgtgg 1620 ttttaggcca aagaaaaaga agagaggctt ttaagaaggc aaatcaatag agaaaaactt 1680 gaagaaaaaC gaaaacagaa agcagaaaag acaaagtctt caaaaaccaa gggtcaaggc 1740 aggagtagtg tggacttaga agaatcatca acaaagagtt tggaacctaa agccgccaga 1800 attaaagaag tccttaaaga acggaaagtt ttagaaaaaa aagtagcctt aagcaaaaag 1860 agaaaaaaag attcaaggaa tgttgaagag aactccaaaa agaaacagca atatgaagaa 1920 gattccaaag aaacccttaa aacaagtgag cattgtgaaa aggaaaaaat ttcttcttca 1980

CEES mm———

aaggagctga agcatgttca tgcaaaaagt gaaccaagta aacctgcccg gagactttca 2040 gagtctttge atgtagttga Cgaaaacaaa aatgaatcca aattagaaag agaacataaa 2100 agacggacat ctacccctgt tatcatggag ggggtacagg aagagactga Cacaagagat 2160 gtaaaaaggc aagtagaacg ctcagaaatt tgcaccgaag agceccagaa acagaaaagc 2220 acacttaaaa acgaaaagca tctaaagaaa gatgattctg aaacaccaca tttgaaaagc 2280 ctacttaaga aagaggtgaa atcctccaag gagaagcctg aaagagagaa aactccatcg 2340 gaagacaaat tgtctgtgaa acataaatat aaaggtgatt gtatgcataa aacaggtgat 2400 gagactgagc ttcactctte tgagaaaggt ttaaaagtag aggaaaatat tcaaaagcaa 2460 agtcaacaaa caaagcttte ttcagatgat daaaccgaac gaaaaagtaa acataggaat 2520 gaaaggaaat tatcagtatt aggcaaagat ggaaagccag tttctgaata tattataaaa 2580 acagatgaga atgttcgtaa agaaaaaaaa 2610 <210> 2915 <211> 279 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (B6)..(118) <223> n is a, c, g, t or u <400> 2915 gcaggtacta gcttcaactc tctaaataaa tttcaaggcet ttgtgaaaat aacctctett 60 ctcattcaag ggtatgttta ctggtnnnnn LNOONNNNNN OMONMNNNNNN NNNNNANRAac 120 tgtaaaagga tagtgtttge atctagagga ctagagacat gcctgcacat ccctcacctt 180 caaaggtgaa Ctctacacag gattcttgte ctagtcattg tggcaacccc atctgacacc 240 ttgtgtagta cctecggecge gaccacgcta atcactagt 279 <210> 2916 <211> 1082 <212> DNA <213> Homo sapiens <400> 2916 gatcccagac cteggcttge agtagtgtta gactgaagat aaagtaagtg ctgtttgggce 60 taacaggatc tcectettgea gtctgcagcece caggacgctg attccagcag cgccttaceyg 120 €gcagcccga agattcacta tggtgaaaat cgccttcaat acccctaccg ccgtgcaaaa 180 ggaggaggcg cggcaagacg tggaggcecct cctgageccege acggtcagaa ctcagatact 240 gaccggcaag gagctccgag ttgccaccca ggaaaaagag ggctectctg ggagatgtat 300 gcttactctc ttaggecttt cattcatctt ggcaggactt attgttggtg gagcctgcat 360 ttacaagtac ttcatgccca agagcaccat ttaccgtgga gagatgtgcet tttttgattce 420 tgaggatcct gcaaattcce ttcgtggagg agagcctaac ttcctgectg tgactgagga 480 ggctgacatt cgtgaggatg acaacattgc aatcattgat gtgcetgtcc ccagtttcte 540 tgatagtgac cctgcagcaa ttattcatga ctttgaaaag ggaatgactg cttacctgga 600 cttgttgctg gggaactgct atctgatgce cctcaatact tctattgtta tgcctccaaa 660 aaatctggta gagctctttg gcaaactggc gagtggcaga tatctgcctce aaacttatgt 720 ggttcgagaa gacctagttg ctgtggagga aattcgtgat gttagtaacc ttggcatctt 780 tatttaccaa ctttgcaata acagaaagtc cttcecgectt cgtcgcagag acctcttget B40 gggtttcaac aaacgtgcca ttgataaatg ctggaagatt agacacttcc ccaacgaatt 900 ’ tattgttgag accaagatct gtcaagagta agaggcaaca gatagagtgt ccttggtaat S60 aagaagtcag agatttacaa tatgacttta acattaaggt ttatgggata ctcaagatat 1020 ttactcatgc atttactcta ttgcttatgc cgtaaaaaaa aaaaaaaaaa aaaaaaaaaa 1080 aa 1082 <210> 2917 <211> €10 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (7)..(8) <223> nis a, ¢, g, t or u <220> <221> misc_feature <222> (605)... (605) <223> nis a, ¢, g, t or u <220> <221> misc_feature <222> (608).. (608) <223> nis a, ¢, g, t or u <400> 2917 aattctnnaa ctcaaataaa agcagggaaa tatgtcagct aattaaaaaa aaacggcaac 60 ttgaacaata cttgtctctc agtaaatagt aaagaccatc acaaaataaa aggtattctt 120 atttgttatt atttaataga agacacattc tctggtccat ttatatcctg tatacaaatt 180 aacttatttt gattgtatcc atgcaatcta agacaataaa aatagaagaa aaaacagcca 240 cataaacagc aaagtgttat tactgattta attgaattga tttgacattt tcagtccact 300 gatatatttc ctgagataaa agttgeoctt agtattcatg aatctgtagt tcattcttag 360 taattttaac atgaaaaatt gatgtgttta aattttcact ttaatattca tgttttctat 420 aaaatattgt aaaattctaa gatattatgg ttatacatat ttattactat tattacatat 480 taatgtgaat tttgagaaac tttcctttgc atgattttct caaattacaa aatatattat 540 tctcttataa aggacagcaa gtttaaaatg gagcaaggag cattggaaat atatttaaag 600 ggaangangg 610 <210> 2918 <211> 1679 <212> DNA <213> Homo sapiens <400> 2918 gtttgttgge tgcggcagca ggtagcaaag tgacgccgag ggcctgagtg ctccagtagce 60

/

caccgcatct ggagaaccag cggttaccat ggaggggatc agtatataca cttcagataa 120 ctacaccgag gaaatgggct caggggacta tgactccatg aaggaaccct gtttccgtga 180 agaaaatgct aatttcaata aaatcttcct gcccaccatc tactccatca tcttcttaac 240 tggcattgtg ggcaatggat tggtcatcct ggtcatgggt taccagaaga aactgagaag 300 catgacggac aagtacaggc tgcacctgtc agtggccgac ctcctctttg tcatcacget 360 tecccttctgg gcagttgatg ccgtggcaaa ctggtacttt gggaacttcc tatgcaaggc 420 agtccatgtc atctacacag tcaacctcta cagcagtgte ctcatcctgg ccttcatcag 480 tctggaccge tacctggcca tcgtccacgc caccaacagt cagaggccaa ggaagctgtt 540 ggctgaaaag gtggtctatg ttggcgtctg gatccctgec ctcctgctga ctattcccga 600 cttcatcttt gccaacgtca gtgaggcaga tgacagatat atctgtgace gcttctacce 660 caatgacttg tgggtggttg tgttccagtt tcagcacatc atggttggcc ttatcctgec 720 tggtattgtc atcctgtect gectattgcat tatcatctec aagctgtcac actccaaggg 780 ccaccagaag cgcaaggccc tcaagaccac agtcatcctce atcctggcett tcttegectg 840 ttggctgcct tactacattg ggatcagcat cgactcctte atectcctgg aaatcatcaa 900 gcaagggtgt gagtttgaga acactgtgca caagtggatt teccatcacceg aggccctage 960 ’ tttcttccac tgttgtctga accccatcct ctatgctttc cttggagcca aatttaaaac 1020 ctctgcccag cacgcactca cctctgtgag cagagggtcc agcctcaaga tcctctccaa 1080 aggaaagcga ggtggacatt catctgtttc cactgagtct gagtcttcaa gttttcacte 1140 cagctaacac agatgtaaaa gacttttttt tatacgataa ataacttttt tttaagttac 1200 acatttttca gatataaaag actgaccaat attgtacagt ttttattgct tgttggattt 1260 .

ttgtcttgtg tttctttagt ttttgtgaag tttaattgac ttatttatat aaattttttt 1320 tgtttcatat tgatgtgtgt ctaggcagga cctgtggceca agttcttagt tgctgtatgt 1380 ctcgtggtag gactgtagaa aagggaactg aacattccag agcgtgtagt gaatcacgta 1440 aagctagaaa tgatccccag ctgtttatgc atagataatc tctccattce cgtggaacgt 1500 ttttcctgtt cttaagacgt gattttgctg tagaagatgg cacttataac caaagcccaa 1560 agtggtatag aaatgctagt ttttcagttt tcaggagtgg gttgatttca gcacctacag 1620 tgtacagtct tgtattaagt tgttaataaa agtacatgtt aaacttactt agtgttatg 1678 <210> 2919 <211l> 2232 <212> DNA <213> Homo sapiens <400> 2919 cttccecette tctgeccctge tccaggcacc aggctcettte cccttcagtg tctcagagga 60 ggggacggca gcaccatgga cccccgettg tccactgtcc gccagacctg ctgectgette 120 aatgtccgca tcgcaaccac cgeccctggeoce atctaccatg tgatcatgag cgtcttgttg 180 ttcatcgagec actcagtaga ggtggcccat ggcaaggegt cctgcaagct ctcccagatg 240 ggctacctca ggatcgctga cctgatctee agcttcoctge tcatcaccat gctcttcatce 300 atcagcctga gectactgat cggcgtagtc aagaaccggg agaagtacct gctgcccttce 360 ctgtccctge aaatcatgga ctatctectg tgcoctgetca ceetgeotggg ctcectacatt 420 gagctgcecg cctacctceaa gttggectce cggagcecgtg ctagectecte caagttccce 480 ctgatgacgc tgcagctgct ggacttcetge ctgagcatcc tgaccctetg cagctcctac 540 atggaagtgc ccacctatcet caacttcaag tccatgaacce acatgaatta cctccccage 600 caggaggata tgcctcataa ccagttcatc aagatgatga tcatcttttce catcgectte 660 atcactgtcc ttatcttcaa ggtctacatg ttcaagtgceg tgtggcggtg ctacagattg 720 atcaagtgca tgaactcggt ggaggagaag agaaactcca agatgctcca gaaggtggtce 780 ctgcecgtect acgaggaage cctgtetttg ccatcgaaga ccccagaggg gggcccagca 840 ccacccccat actcagaggt gtgaccctcg ccaggcccca gccccagtge tgggaggggt 900 ggagctgcct cataatctge ttttttgeott tggtggeccce tgtggcctgg gtgggcccte S60 ccgcecectec ctggcaggac aatctgettg tgtcteccte gctggectge tcctectgea 1020

' gggcctgtga getgetcaca actgggtcaa cgctttaggce tgagtcactc ctcgggtctc 1080 tccataattc agcccaacaa tgettggttt atttcaatca gectctgacac ttgtttagac 1140 gattggccat tctaaagttg gtgagtttgt caagcaacta tcgacttgat cagttcagcce 1200 aagcaactga caaatcaaaa acccacttgt cagttcagta aaataatttg gtcaaacaac 1260 agtctattgc attgatttat aaatagttgt cagttcacat agcaatttaa tcaagtaatc 1320 attaattagt taccccctat atataaatat atgtaatcaa tttcttcaaa tagcttgett 1380 acatgataat caattagcca accatgagtc atttagaata gtgataaata gaatacacag 1440 aatagtgatg aaattcaatt taaaaaatca cgttagcctc caaaccattt aattcaaatg 1500 aacccatcaa ctggatgcca actctggcga atgtaggacc tctgagtggc tgtataattg 1560 ttaattcaaa tgaaattcat ttaaacagtt gacaaactgt cattcaacaa ttagctccag 1620 gaaataacag ttatttcatc ataaaacagt cccttcaaac acacaattgt tctgctgaag 1680 agttgtcatc aacaatccaa tgctcaccta ttcagttgct ctgtggtcag tgtggctgea 1740 tagcagtgga ttccatgaaa ggagtcattt tagtgatgag ctgccagtcc attcccaggc 1800 caggctgtcg ctggccatcc attcagtcga ttcagtcata ggcgaatctg ttctgcccega 1860 ggcttgtggt caagcaaaaa ttcagccctg aaatcaggca catctgttceg ttggactaaa 1920 cccacaggtt agttcagtca aagcaggcaa ccceccttgtg ggcactgacc ctgccactgg 1980 ggtcatggeg gttgtggcag ctggggaggt ttggccccaa cagccctcect gtgecctgett 2040 : ccctgtgtgt cggggtcctce cagggagctg acccagaggt ggaggccacg gaggcagggt 2100 ctctggggac tgtcgggggg tacagaggga gaaggctctg caagagctcc ctggcaatac 2160 ccecettgtgt aattgetttg tgtgcgacag ggaggaagtt tcaataaagc aacaacaagce 2220 ttcaaggaat tc 2232 <210> 2920 <211> 1620 <212> DNA <213> Homo sapiens <400> 2920 caaaggactt cctagtgggt gtgaaaggca gcggtggcca cagaggcggc ggagagatgg 60 ccttcagecgg ttcccagget cecctacctga gtccagetgt ccccttttet gggactatte 120 aaggaggtct ccaggacgga cttcagatca ctgtcaatgg gaccgttctc agctccagtg 180 gaaccaggtt tgctgtgaac tttcagactdg gcttcagtgg aaatgacatt gecttccact 240 tcaacccteg gtttgaagat ggagggtacg tggtgtgcaa cacgaggcag aacggaagct 300 gggggcecega ggagaggagd acacacatgc ctttccagaa ggggatgcce tttgacctcet 360 gcttectggt gcagagctca gatttcaagg tgatggtgaa cgggatcctc ttegtgcagt 420 acttccaccg cgtgcccttc caccgtgtgg acaccatctt cgtcaatggc tctgtgcagce 480 tgtcctacat cagcttccag ccteccecggeg tgtggcctge caacccgget cccattaccce 540 agacagtcat ccacacagtg cagagcgccce ctggacagat gttctctact ccegecatce 600 cacctatgat gtacccccac cccgectate cgatgecttt catcaccace attctgggag 660 ggctgtaccc atccaagtec atcctectgt caggcactgt cctgeccagt gectcagaggt 720 tccacatcaa cctgtgctet gggaaccaca tcgccttcca cctgaaccte cgttttgatg 780 agaatgctgt ggtccgcaac acccagatcg acaactcctg ggggtctgag gagcgaagtce 840 tgcceccgaaa aatgccette gtecgtggec agagcttctc agtgtggatc ttgtgtggag 900 ctcactgcect caaggtggcce gtggatggtc agcacctgtt tgaatactac catcgcectga 260 ggaacctgcc caccatcaat agactggaag tggggggcga catccagetg acccatgtge 1020 agacataggc ggcttcctgg ccctggggec gggggctggg gtgtggggca gtetgggtcec 1080 tctcatcatc cccacttecce aggcccagec tttecaacce tgcctgggat ctgggcttta 1140 atgcagaggc catgtccttg tctggtcectg cttctggcta cagccaccct ggaacggaga 1200 aggcagctga cggggattgc cttcctcage cgcagcagca cctggggcte cagectgctgg 1260 aatcctacca tcccaggagg caggcacage cagggagagg ggaggagtgg gcagtgaaga 1320 tgaagcccca tgctcagtcc cctecccatecc cccacgcage tccaccccag tcoccaagceca 1380 ccagetgtct getcctggtg ggaggtggee tecctcagece ctectctetg acctttaacce 1440 tcactctcac cttgcaccgt gcaccaacce ttcacccectce ctggaaagca ggcctgatgg 1500 cttcccactg gecctccacca cctgaccaga gtgttctett cagaggactg gotcctttec 1560 cagtgtcctt aaaataaaga aatgaaaatg cttgttggca aaaaaaaaaa aaaaaaaaaa 1620 <210> 2921 <211> 916 <212> DNA <213> Homo sapiens <400> 28921 acttctcgct cgacacagcc agagctggag gtgggtgccc ggcacggagg ggocctgegga 60 ccaatggctc tgccctgcac cttagggctc gggatgctge tggccetgec aggggccttg 120 ggctegggtg gcagcgcgga ggacagegtg ggetccaget ctgtcacegt tgtectgetg 180 ctgctgetge tcoctactget ggccactgge ctagcactgg cctggcegceeg cctcagecgt 240 gactcagggg gctactacca cccggcccgc ctaggtgecg cgectgtgggg cegcacgcgg 300 cgcctgetet gggccagcce cccaggtege tggetgcagg cccgagctga gotggggtece 360 acagacaatg accttgagcg acaggaggat gagcaggaca cagactatga ccacgtcgceg 420 gatggtggcc tgcaggctga ccctggggaa ggcgagcagc aatgtggaga ggcgtccage 480 Ccagagcagg tccccgtgcg ggctgaggaa gccagagaca gtgacacgga gggcgacctg 540 gtcctcgget ccccaggacc agegagegca gggggcagtg ctgaggccct getgagtgac 600 ctgcacgecct ttgetggcag cgcagcctgg gatgacageg ccagggcagce tgggggcecag 660 ggcctccatg tcaccgcact gtagaggccg gtcttggtgt cccatccctg tcacagcege 720 tcactccceg tgectcetget tcccaagatg ccatggetgg actggacccc cagcccacat 780 gaccatgcct cagactgtca cccctaccag ttcecaagtc catgtgtacc ccgcectcacca 840 cgggaacggc cccccccaac cacaggcatc aggcaaccat ttgaaataaa actccttcag 900 cctgtgaaaa aaaaaa 916 <210> 2922 <211> 1272 <212> DNA <213> Homo sapiens <400> 2922 gaattcggcc aaagaggcct atgcttctcet gaagacttgec agcaaggctt gctgaggctce 60 acagaagata gccccagtgt tttggagtgg ttttgaatgt gattctgaga tcagactgac 120 tgagctggaa tcctggettt atatcttacc agctacacaa ccttggagtce ttagaaattt 180 tttcttttca ataagcagtc atccttactt tccctcaaga tgacaaacag ttcgttecttc 240 tgcccagttt ataaagatct ggagccattce acgtattttt tttatttagt tttccttgtt 300 ggaattattg gaagttgttt tgcaacctgg gcttttatac agaagaatac gaatcacagg 360 tgtgtgagca tctacttaat taatttgctt acagccgatt tecctgcttac tctggcatta 420 ccagtgaaaa ttgttgttga cttgggtgtg gcaccttgga agctgaagat attccactgce 480 caagtaacag cctgcctcat ctatatcaat atgtatttat caattatctt cttagcattt 540 gtcagcattg accgctgtct tcagctgaca cacagctgcea agatctaccg aatacaagaa 600 cccggatttg ccaaaatgat atcaaccgtt gtgtggctaa tggtccttct tataatggtg 660 ccaaatatga tgattcccat caaagacatc aaggaaaagt caaatgtggg ttgtatggag 720 tttaaaaagg aatttggaag aaattggcat ttgctgacaa atttcatatg tgtagcaata 780 tttttaaatt tctcagccat cattttaata tccaattgcc ttgtaattcg acagctctac 840 agaaacaaag ataatgaaaa ttacccaaat gtgaaaaagg ctctcatcaa catactttta 900 gtgaccacgg gctacatcat atgectttgtt ccttaccaca ttgtccgaat ccecgtatace 960 ctcagccaga cagaagtcat aactgattgc tcaaccagga tttcactctt caaagccaaa 1020 gaggctacac tgctectgge tgtgtegaac ctgtgetttg atcctatect gtactatcac 1080 ctctcaaaag cattccgetc aaaggtcact gagacttttg cctcacctaa agagaccaag 1140 gctcagaaag aaaaattaag atgtgaaaat aatgcataaa agacaggatt ttttgtgeta 1200 ccaattctgg ccttactgga ccataaagtt aattatagct ttgaaagata aaaaaaaaaa 1260 aaaagcggce gc 1272 <210> 2923 <211> 413 <212> DNA <213> Homo sapiens <400> 2923 tttttttttr tttttgtaga gggtcacatc aatccatagg aaaggaaacc tgcttcttct 60 cacaaaggga taacttttgt tttcctcatg agtcaacttg aaggataact ttaaaaaatt 120 ggtccatgca gcagagtgag actccgtctc aaaaaaaaaa aaaaaaaaaa aaaaaggtcce 180 atgcagaaga ctatcttrtt ccaatttgta taagggaact atgtaagttc actgtagctc 240 tgggtatcct caacccacag atctggcagg cagcttgcag cccatcttca gaggagggcec 300 aagtgtccat tcagactcgg gtatttccac actagctgtc tttgagttcc atcaagtaga 360 tagagaactt ctgatccaag ggattttata gagattacaa ccccctcgtg ccg 413 <210> 2924 <21l1l> 474 <212> DNA <213> Homo sapiens <400> 2924 ttetttettt tgcttcaatt cectttcectata caaccgtggt tctcaaccag gggtccttet 60 ggtccccagg ggatgctagg tggtgtcectgg gggcatttgt gactgttatg actcagggat 120 gctcctggeg tggagtgggt ggaggccagg gatgctgatc agaaccttge agtggccagg 180 acaaccccac cccagagaac gacccagecce tgaatgccaa gggggagaga ctctgectta 240 attatttgga aaaatattgt atctgctccc tgttgacacc agacactaga aaaaattccce 300 gatggggtgyg atggcagaaa ccaagggggg ccccagctcecce tgcegattctce ctcectctcete 360 ccteccccact cagggtgtgg attacaatgt gtgcagcctc ctggaacctc aggaggacag 420 aggatcatga gacacagagt ttcttgggga tctgtggaat cccctaaccc ccgg 474 <210> 2925 <21l> 199 «212> PRT <213> Homo sapiens ’ <400> 2925 Met Ser Ser Glu Asn Cys Phe Val Ala Glu Asn Ser Ser Leu His Pro 1 5 10 is

Glu Ser Gly Gln Glu Asn Asp Ala Thr Ser Pro His Phe Ser Thr Arg

His Glu Gly Ser Phe Gln Val Pro Val Leu Cys Ala Val Met Asn Val 40 45 Val Phe Ile Thr Ile Leu Ile Ile Ala Leu Ile Ala Leu Ser Vail Gly S50 55 60 Gln Tyr Asn Cys Pro Gly Gln Tyr Thr Phe Ser Met Pro Ser Asp Ser 65 70 75 80 His Val Ser Ser Cys Ser Glu Asp Trp Val Gly Tyr Gln Arg Lys Cys 85 80 95 Tyr Phe Ile Ser Thr Val Lys Arg Ser Trp Thr Ser Ala Gln Asn Ala 100 105 110 Cys Ser Glu His Gly Ala Thr Leu Ala Val Ile Asp Ser Glu Lys Asp 115 120 125 Met Asn Phe Leu Lys Arg Tyr Ala Gly Arg Glu Glu His Trp Val Gly 130 135 140 Leu Lys Lys Glu Pro Gly His Pro Trp Lys Trp Ser Asn Gly Lys Glu 145 150 155 160 Phe Asn Asn Trp Phe Asn Val Thr Gly Ser Asp Lys Cys Val Phe Leu 165 170 175 Lys Asn Thr Glu Val Ser Ser Met Glu Cys Glu Lys Asn Leu Tyr Trp 180 185 190 Ile Cys Asn Lys Pro Tyr Lys 185 <210> 2926 <211> 326 <212> PRT <213> Homo sapiens <400> 292s Met Asp Tyr Ser His Gln Thr Ser Leu Val Pro Cys Gly Gln Asp Lys 1 5 10 15 Tyr Ile Ser Lys Asn Glu Leu Leu Leu His Leu Lys Thr Tyr Asn Leu 20 25 . 30

Tyr Tyr Glu Gly Gln Asn Leu Gln Leu Arg His Arg Glu Glu Glu Asp 40 45 Glu Phe Ile Val Glu Gly Leu Leu Asn Ile Ser Trp Gly Leu Arg Arg S50 55 60 Pro Ile Arg Leu Gln Met Gln Asp Asp Asn Glu Arg Ile Arg Pro Pro 65 70 75 80 Pro Ser Ser Ser Ser Trp His Ser Gly Cys Asn Leu Gly Ala Gln Gly 85 90 95 Thr Thr Leu Lys Pro Leu Thr Val Pro Lys Val Gln Ile Ser Glu Val 100 105 110 Asp Ala Pro Pro Glu Gly Asp Gln Met Pro Ser Ser Thr Asp Ser Arg 115 120 125 Gly Leu Lys Pro Leu Gln Glu Asp Thr Pro Gln Leu Met Arg Thr Arg 130 : 135 140 Ser Asp Val Gly Val Arg Arg Arg Gly Asn Val Arg Thr Pro Ser Asp 145 150 155% : 160 Gln Arg Arg Ile Arg Arg His Arg Phe Ser Ile Asn Gly His Phe Tyr 165 170 175% Asn His Lys Thr Ser val Phe Thr Pro Ala Tyr Gly Ser Val Thr Asn 180 185 180 Val Arg Ile Asn Ser Thr Met Thr Thr Pro Gln Val Leu Lys Leu Leu 195 200 205 Leu Asn Lys Phe Lys Ile Glu Asn Ser Ala Glu Glu Phe Ala Leu Tyr 210 . 215 220 Val val His Thr Ser Gly Glu Lys Gln Lys Leu Lys Ala Thr Asp Tyr 225 230 235 240 Pro Leu Ile Ala Arg Ile Leu Gln Gly Pro Cys Glu Gln Ile Ser Lys 245 250 255 Val Phe Leu Met Glu Lys Asp Gln Val Glu Glu Val Thr Tyr Asp Val 260 265 270

Ala Gln Tyr Ile Lys Phe Glu Met Pro Val Leu Lys Ser Phe Ile Gln 275 280 285 Lys Leu Gln Glu Glu Glu Asp Arg Glu Val Lys Lys Leu Met Arg Lys 290 285 300 Tyr Thr Val Leu Arg Leu Met Ile Arg Gln Arg Leu Glu Glu Ile Ala 305 310 315 320 Glu Thr Pro Ala Thr Ile 325 <210> 2927 <211> 364 <212> PRT <213> Homo sapiens <400> 2927 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala 1 5 10 15 Met Asp Pro Asn Phe Trp Leu Gln Val Gln Glu Ser Val Thr Val Gln

Glu Gly Leu Cys Val Leu Val Pro Cys Thr Phe Phe His Pro Ile Pro 40 45 Tyr Tyr Asp Lys Asn Ser Pro Val His Gly Tyr Trp Phe Arg Glu Gly 50 55 60 Ala Ile Ile Ser Gly Asp Ser Pro Val Ala Thr Asn Lys Leu Asp Gln 65 70 75 80 Glu Val Gln Glu Glu Thr Gln Gly Arg Phe Arg Leu Leu Gly Asp Pro 85 90 95 Ser Arg Asn Asn Cys Ser Leu Ser Ile Val Asp Ala Arg Arg Arg Asp 100 105 110 Asn Gly Ser Tyr Phe Phe Arg Met Glu Arg Gly Ser Thr Lys Tyr Ser 115 120 125 Tyr Lys Ser Pro Gln Leu Ser Val His Val Thr Asp Leu Thr His Arg 130 135 140 Pro Lys Ile Leu Ile Pro Gly Thr Leu Glu Pro Gly His Ser Lys Asn

145 150 155 160 Leu Thr Cys Ser Val Ser Trp Ala Cys Glu Gln Gly Thr Pro Pro Ile 165 170 175 Phe Ser Trp Leu Ser Ala Ala Pro Thr Ser Leu Gly Pro Arg Thr Thr 180 185 190 His Ser Ser Val Leu Ile Ile Thr Pro Arg Pro Gln Asp His Gly Thr 195 200 205 Asn Leu Thr Cys Gln Val Lys Phe Ala Gly Ala Gly Val Thr Thr Glu 210 215 220 Arg Thr Ile Gln Leu Asn Val Thr Tyr Val Pro Gln Asn Pro Thr Thr 225 230 235 240 Gly Ile Phe Pro Gly Asp Gly Ser Gly Lys Gln Glu Thr Arg Ala Gly 245 250 255 Leu Val His Gly Ala Ile Gly Gly Ala Gly Val Thr Ala Leu Leu Ala 260 265 270 Leu Cys Leu Cys Leu Ile Phe Phe Ile Val Lys Thr His Arg Arg Lys 27S 280 285 Ala Ala Arg Thr Ala Val Gly Ser Asn Asp Thr His Pro Thr Thr Gly 290 295 300 Ser Ala Ser Pro Lys His Gln Lys Asn Ser Lys Leu His Gly Pro Thr 305 310 315 320 Glu Thr Ser Ser Cys Ser Gly Ala Ala Pro Thr val Glu Met Asp Glu 325 330 335 Glu Leu His Tyr Ala Ser Leu Asn Phe His Gly Met Asn Pro Ser Lys 340 345 350 Asp Thr Ser Thr Glu Tyr Ser Glu Val Arg Thr Gln 355 360 <210> 2928 <211> 326 <212> PRT <213> Homo sapiens <400> 2928 .

Met Asp Tyr Ser His Gln Thr Ser Leu val Pro Cys Gly Gln Asp Lys 1 5 10 15 Tyr Ile Ser Lys Asn Glu Leu Leu Leu His Leu Lys Thr Tyr Asn Ley

Tyr Tyr Glu Gly Gln Asn Leu Gln Leu Arg His Arg Glu Glu Glu Asp 40 45 Glu Phe Ile Val Glu Gly Leu Leu Asn Ile Ser Trp Gly Leu Arg Arg SO SS 60 Pro Ile Arg Leu Gln Met Gln Asp Asp Asn Glu Arg Ile Arg Pro Pro 65 70 75 80 Pro Ser Ser Ser Ser Trp His Ser Gly Cys Asn Leu Gly Ala Gln Gly 85 90 95 Thr Thr Leu Lys Pro Leu Thr Val Pro Lys val Gln Ile Ser Glu val 100 105 110 Asp Ala Pro Pro Glu Gly Asp Gln Met Pro Ser Ser Thr Asp Ser Arg 115 120 125 Gly Leu Lys Pro Leu Gin Glu Asp Thr Pro Gln Leu Met Arg Thr Arg 130 135 140 ’ Ser Asp Val Gly val Arg Arg Arg Gly Asn Val Arg Thr Pro Ser Asp 145 150 155 160 Gln Arg Arg 1le Arg Arg His Arg Phe Ser Ile Asn Gly His Phe Tyr 165 170 175 Asn His Lys Thr Ser val Phe Thr Pro Ala Tyr Gly Ser Val Thr Asn 180 185 190 Val Arg Ile Asn Ser Thr Met Thr Thr Pro Gln Val Leu Lys Leu Len 195 200 205 Leu Asn Lys Phe Lys Ile Glu Asn Ser Ala Glu Glu Phe Ala Leu Tyr 210 215 220 Val val His Thr Ser Gly Glu Lys Gln Lys Leu Lys Ala Thr Asp Tyr 225% 230 235 240

Pro Leu Ile Ala Arg Ile Leu Gln Gly Pro Cys Glu Gln Ile Ser Lys 245 250 255 Val Phe Leu Met Glu Lys Asp Gln Val Glu Glu Val Thr Tyr Asp Val 260 265 270 Ala Gln Tyr Ile Lys Phe Glu Met Pro Val Leu Lys Ser Phe Ile Gln 275 280 285 Lys Leu Gln Glu Glu Glu Asp Arg Glu Val Lys Lys Leu Met Arg Lys 290 295 300 Tyr Thr Val Leu Arg Leu Met Ile Arg Gln Arg Leu Glu Glu Ile Ala 305 310 315% 320 Glu Thr Pro Ala Thr Ile 325 <210> 2929 <211> 1842 <212> PRT <213> Homo sapiens <400> 2929 Leu Pro His Gly Arg Thr Arg Gly Pro Gly Pro Ala Met Ala Pro Trp 1 5 10 15 Arg Lys Ala Asp Lys Glu Arg His Gly Val Ala Ile Tyr Asn Phe Gln 2S 30 Gly Ser Gly Ala Pro Gln Leu Ser Leu Gln Ile Gly Asp Val Val Arg 40 45 Ile Gln Glu Thr Cys Gly Asp Trp Tyr Arg Gly Tyr Leu Ile Lys His 50 55 60 Lys Met Leu Gln Gly Ile Phe Pro Lys Ser Phe Ile His Ile Lys Glu 65 70 75 80 val Thr Val Glu Lys Arg Arg Asn Thr Glu Asn Ile Ile Pro Ala Glu 85 90 95 Ile Pro Leu Ala Gln Glu Val Thr Thr Thr Leu Trp Glu Trp Gly Ser 100 105 110 Ile Trp Lys Gln Leu Tyr Val Ala Ser Lys Lys Glu Arg Phe Leu Gln 115 120 125

Val Gln Ser Met Met Tyr Asp Leu Met Glu Trp Arg Ser Gln Leu Leu 130 135 140 Ser Gly Thr Leu Pro Lys Asp Glu Leu Lys Glu Leu Lys Gln Lys Val 145 150 155 160 Thr Ser Lys Ile Asp Tyr Gly Asn Lys Ile Leu Glu Leu Asp Leu Ile 165 170 175 Val Arg Asp Glu Asp Gly Asn Ile Leu Asp Pro Asp Asn Thr Ser Val 180 185 150 Ile Ser Leu Phe His Ala His Glu Glu Ala Thr Asp Lys Ile Thr Glu 195 200 205 Arg Ile Lys Glu Glu Met Ser Lys Asp Gln Pro Asp Tyr Ala Met Tyr 210 215 220 Ser Arg Ile Ser Ser Ser Pro Thr His Ser Leu Tyr Val Phe Val Arg 225 230 235 240 Asn Phe Val Cys Arg Ile Gly Glu Asp Ala Glu Leu Phe Met Ser Leu 245 250 255 Tyr Asp Pro Asn Lys Gln Thr Val Ile Ser Glu Asn Tyr Leu Val Arg 260 265 270 Trp Gly Ser Arg Gly Phe Pro Lys Glu Ile Glu Met Leu Asn Asn Leu 275 280 285 Lys Val Val Phe Thr Asp Leu Gly Asn Lys Asp Leu Asn Arg Asp Lys 290 2385 300 Ile Tyr Leu Ile Cys Gln Ile Val Arg Val Gly Lys Met Asp Leu Lys 308 310 315 320 Asp Thr Gly Ala Lys Lys Cys Thr Gln Gly Leu Arg Arg Pro Phe Gly 325 330 335 Val ala Val Met Asp Ile Thr Asp Ile Ile Lys Gly Lys Ala Glu Ser 340 345 350 Asp Glu Glu Lys Gln His Phe Ile Pro Phe His Pro Val Thr Ala Glu 355 360 365

Asn Asp Phe Leu His Ser Leu Leu Gly Lys val Ile Ala Ser Lys Gly 370 375 380 Asp Ser Gly Gly Gln Gly Leu Trp Val Thr Met Lys Met Leu Val Gly 385 390 395 400 Asp Ile Ile Gln Ile Arg Lys Asp Tyr Pro His Leu Val Asp Arg Thr 405 410 415 Thr Val val Ala Arg Lys Leu Gly Phe Pro Glu Ile Ile Met Pro Gly 420 425 430 Asp Val Arg Asn Asp Ile Tyr Ile Thr Leu Leu Gln Gly Asp Phe Asp 435 440 445 Lys Tyr Asn Lys Thr Thr Gln Arg Asn Val Glu Val Ile Met Cys Val 450 455 460 Cys Ala Glu Asp Gly Lys Thr Leu Pro Asn Ala Ile Cys Val Gly Ala 465 470 475 480 Gly Asp Lys Pro Met Asn Glu Tyr Arg Ser Val Val Tyr Tyr Gln Val 485 490 495 Lys Gln Pro Arg Trp Met Glu Thr Val Lys Val Ala Val Pro Ile Glu 500 505 510 Asp Met Gln Arg Ile His Leu Arg Phe Met Phe Arg His Arg Ser Ser 515 520 525 Leu Glu Ser Lys Asp Lys Gly Glu Lys Asn Phe Ala Met Ser Tyr Val 530 535 540 Lys Leu Met Lys Glu Asp Gly Thr Thr Leu His Asp Gly Phe His Asp 545 550 555 560 Leu Val Val Leu Lys Gly Asp Ser Lys Lys Met Glu Asp Ala Ser Ala 565 570 575 Tyr Leu Thr Leu Pro Ser Tyr Arg His His Val Glu Asn Lys Gly Ala hy 580 585 590 Thr Leu Ser Arg Ser Ser Ser Ser Val Gly Gly Leu Ser Val Ser Ser 595 600 605

Arg Asp Val Phe Ser Ile Ser Thr Leu Val Cys Ser Thr Lys Leu Thr 610 615 620 Gln Asn Val Gly Leu Leu Gly Leu Leu Lys Trp Arg Met Lys Pro Gln 625 630 635 640 Leu Leu Gln Glu Asn Leu Glu Lys Leu Lys Ile Val Asp Gly Glu Glu 645 650 655 Val Val Lys Phe Leu Gln Asp Thr Leu Asp Ala Leu Phe Asn Ile Met 660 665 670 Met Glu His Ser Gln Ser Asp Glu Tyr Asp Ile Leu Val Phe Asp Ala 675 680 685 Leu Ile Tyr Ile Ile Gly Leu Ile Ala Asp Arg Lys Phe Gln His Phe 690 695 700 Asn Thr Val Leu Glu Ala Tyr Ile Gln Gln His Phe Ser Ala Thr Leu 705 710 715 720 Ala Tyr Lys Lys Leu Met Thr Val Leu Lys Thr Tyr Leu Asp Thr Ser 725 730 735 Ser Arg Gly Glu Gln Cys Glu Pro Ile Leu Arg Thr Leu Lys Ala Leu 740 745 750 Glu Tyr val Phe Lys Phe Ile Val Arg Ser Arg Thr Leu Phe Ser Gln 755 760 765 Leu Tyr Glu Gly Lys Glu Gln Met Glu Phe Glu Glu Ser Met Arg Arg 770 775 780 Leu Phe Glu Ser Ile Asn Asn Leu Met Lys Ser Gln Tyr Lys Thr Thr 785 790 795 800 Ile Leu Leu Gln Val Ala Ala Leu Lys Tyr Ile Pro Ser Val Leu His 805 810 815 Asp Val Glu Met Val Phe Asp Ala Lys Leu Leu Ser Gln Leu Leu Tyr 820 825 830 Glu Phe Tyr Thr Cys Ile Pro Pro Val Lys Leu Gln Lys Gln Lys Val 835 840 845 Gln Ser Met Asn Glu Ile Val Gln Ser Asn Leu Phe Lys Lys Gln Glu

850 855 860 Cys Arg Asp Ile Leu Leu Pro Val Ile Thr Lys Glu Leu Lys Glu Leu 865 870 875 880 Leu Glu Gln Lys Asp Asp Met Gln His Gln Val Leu Glu Arg Lys Tyr 885 830 895 Cys Val Glu Leu Leu Asn Ser Ile Leu Glu Val Leu Ser Tyr Gln Asp 800 S05 910 Ala Ala Phe Thr Tyr His His Ile Gln Glu Ile Met Val Gln Leu Leu 915 920 S525 Arg Thr Val Asn Arg Thr Val Ile Thr Met Gly Arg Asp His Ile Leu 930 935 940 ’ Ile Ser His Phe val Ala Cys Met Thr Ala Ile Leu Asn Gln Met Gly 945 950 955 960 Asp Gln His Tyr Ser Phe Tyr Ile Glu Thr Phe Gln Thr Ser Ser Glu 965 970 975 Leu Val Asp Phe Leu Met Glu Thr Phe Ile Met Phe Lys Asp Leu Ile 980 985 930 Gly Lys Asn Val Tyr Pro Gly Asp Trp Met Ala Met Ser Met Val Gln 995 1000 1005 Asn Arg Val Phe Leu Arg Ala Ile Asn Lys Phe Ala Glu Thr Met 1010 1015 1020 Asn Gln Lys Phe Leu Glu His Thr Asn Phe Glu Phe Gln Leu Trp 1025 1030 1035 Asn Asn Tyr Phe His Leu Ala Val Ala Phe Ile Thr Gln Asp Ser 1040 1045 1050 Leu Gln Leu Glu Gln Phe Ser His Ala Lys Tyr Asn Lys Ile Leu 1055 1060 1065 Asn Lys Tyr Gly Asp Met Arg Arg Leu Ile Gly Phe Ser Ile Arg 1070 1075 1080 Asp Met Trp Tyr Lys Leu Gly Gln Asn Lys Ile Cys Phe Ile Pro 1085 1090 1085

Gly Met Val Gly Pro Ile Leu Glu Met Thr Leu Ile Pro Glu Ala 1100 1105 1110

Glu Leu Arg Lys Ala Thr Ile Pro Ile Phe Phe Asp Met Met Leu 1115 1120 1125

Cys Glu.

Tyr Gln Arg Ser Gly Asp Phe Lys Lys Phe Glu Asn Glu 1130 1135 1140

Ile Ile Leu Lys Leu Asp His Glu Val Glu Gly Gly Arg Gly Asp 1145 1150 1155

Glu Gln Tyr Met Gln Leu Leu Glu Ser Ile Leu Met Glu Cys Ala 1160 1165 1170

Ala Glu His Pro Thr Ile Ala Lys Ser Val Glu Asn Phe Val Asn 1175 1180 1185

Leu Val Lys Gly Leu Leu Glu Lys Leu Leu Asp Tyr Arg Gly val 1150 1185 1200

Met Thr Asp Glu Ser Lys Asp Asn Arg Met Ser Cys Thr Val Asn 1205 1210 1215

Leu Leu Asn Phe Tyr Lys Asp Asn Asn Arg Glu Glu Met Tyr Ile 1220 1225 1230

Arg Tyr Leu Tyr Lys Leu Arg Asp Leu His Leu Asp Cys Asp Asn 1235 1240 1245

Tyr Thr Glu Ala Ala Tyr Thr Leu Leu Leu His Thr Trp Leu Leu 1250 1255 1260

Lys Trp Ser Asp Glu Gln Cys Ala Ser Gln Val Met Gln Thr Gly 1265 1270 1275

Gln Gln His Pro Gln Thr His Arg Gln Leu Lys Glu Thr Leu Tyr 1280 1285 1290

Glu Thr Ile Ile Gly Tyr Phe Asp Lys Gly Lys Met Trp Glu Glu 1295 1300 1305

Ala Ile Ser Leu Cys Lys Glu Leu Ala Glu Gln Tyr Glu Met Glu 1310 131s 1320

Ile Phe Asp Tyr Glu Leu Leu Ser Gln Asn Leu Ile Gln Gln Ala 1325 1330 1335 Lys Phe Tyr Glu Ser Ile Met Lys Ile Leu Arg Pro Lys Pro Asp 1340 1345 1350 Tyr Phe Bala val Gly Tyr Tyr Gly Gln Gly Phe Pro Ser Phe Leu 1355 1360 1365 Arg Asn Lys Val Phe Ile Tyr Arg Gly Lys Glu Tyr Glu Arg Arg 1370 1375 1380 Glu Asp Phe Gln Met Gln Leu Met Thr Gln Phe Pro Asn Ala Glu 1385 13580 1395 Lys Met Asn Thr Thr Ser Ala Pro Gly Asp Asp Val Lys Asn Ala 1400 1405 1410 Pro Gly Gln Tyr Ile Gln Cys Phe Thr Val Gln Pro Val Leu Asp 1415 1420 1425 Glu His Pro Arg Phe Lys Asn Lys Pro Val Pro Asp Gln Ile Ile 1430 1435 1440 Asn Phe Tyr Lys Ser Asn Tyr Val Gln Arg Phe His Tyr Ser Arg 1445 1450 1455 Pro Val Arg Arg Gly Thr Val Asp Pro Glu Asn Glu Phe Ala Ser 1460 1465 1470 Met Trp Ile Glu Arg Thr Ser Phe Val Thr Ala Tyr Lys Leu Pro 1475 1480 1485 Gly Ile Leu Arg Trp Phe Glu Val Val His Met Ser Gln Thr Thr 1490 1495 1500 Ile Ser Pro Leu Glu Asn Ala Ile Glu Thr Met Ser Thr Ala Asn 1505 1510 ’ 1515 Glu Lys Ile Leu Met Met Ile Asn Gln Tyr Gln Ser Asp Glu Thr 1520 1525 1530 Leu Pro Ile Asn Pro Leu Ser Met Leu Leu Asn Gly Ile Val Asp 1535 1540 1545

Pro Ala Val Met Gly Gly Phe Ala Lys Tyr Glu Lys Ala Phe Phe 1550 1555 1560 Thr Glu Glu Tyr Val Arg Asp His Pro Glu Asp Gln Asp Lys Leu 1565 1570 1575 Thr His Leu Lys Asp Leu Ile Ala Trp Gln Ile Pro Phe Leu Gly 1580 1585 1550 Ala Gly Ile Lys Ile His Glu Lys Arg Val Ser asp Asn Leu Arg 1585 1600 1605 Pro Phe His Asp Arg Met Glu Glu Cys Phe Lys Asn Leu Lys Met 1610 1615 1620 Lys Val Glu Lys Glu Tyr Gly val Arg Glu Met Pro Asp Phe Asp 1625 1630 1635 Asp Arg Arg Val Gly Arg Pro Arg Ser Met Leu Arg Ser Tyr Arg i 1640 1645 1650 Gln Met Ser Ile Ile Ser Leu Ala Ser Met Asn Ser Asp Cys Ser 1655 1660 1665 Thr Pro Ser Lys Pro Thr Ser Glu Ser Phe Asp Leu Glu Leu Ala 1670 1675 1680 Ser Pro Lys Thr Pro Arg Val Glu Gln Glu Glu Pro Ile Ser Pro 1685 1650 16895 Gly Ser Thr Leu Pro Glu Val Lys Leu Arg Arg Ser Lys Lys Arg 1700 1705 1710 Thr Lys Arg Ser Ser Val Val Phe Ala Asp Glu Lys Ala Ala Ala 1715 1720 1725 Glu Ser Asp Leu Lys Arg Leu Ser Arg Lys His Glu Phe Met Ser 1730 1735 1740 Asp Thr Asn Leu Ser Glu His Ala Ala Ile Pro Leu Lys Ala Ser 1745 1750 1755 Val Leu Ser Gln Met Ser Phe Ala Ser Gln Ser Met Pro Thr Ile 1760 1765 1770 Pro Ala Leu Ala Leu Ser Val Ala Gly Ile Pro Gly Leu Asp Glu

1775 1780 1785

Ala Asn Thr Ser Pro Arg Leu Ser Gln Thr Phe Leu Gln Leu Ser 1790 1795 1800

Asp Gly Asp Lys Lys Thr Leu Thr Arg Lys Lys Val Asn Gln Phe 1805 1810 1815

Phe Lys Thr Met Leu Ala Ser Lys Ser Ala Glu Glu Gly Lys Gln 1820 1825 1830

Ile Pro Asp Ser Leu Ser Thr Asp Leu 1835 1840

<210> 2330

<211> 386

<212> PRT

<213> Homo sapiens

<400> 2930

Met Glu Glu Leu Asp Ala Leu Leu Glu Glu Leu Glu Arg Ser Thr Leu

1 5 10 15

Gln Asp Ser Asp Glu Tyr Ser Asn Pro Ala Pro Leu Pro Leu Asp Gln

His Ser Arg Lys Glu Thr Asn Leu Asp Glu Thr Ser Glu Ile Leu Ser 40 45

Ile Gln Asp Asn Thr Ser Pro Leu Pro Ala Glan Leu Val Tyr Thr Thr 50 55 60

Asn Ile Gln Glu Leu Asn Val Tyr Ser Glu Ala Gln Glu Pro Lys Glu

65 70 75 80

Ser Pro Pro Pro Ser Lys Thr Ser Ala Ala Ala Gln Leu Asp Glu Leu

85 S50 95 Met Ala His Leu Thr Glu Met Gln Ala Lys Val Ala Val Arg Ala Asp 100 105 110 Ala Gly Lys Lys His Leu Pro Asp Lys Gln Asp His Lys Ala Ser Leu 115 120 125

Asp Ser Met Leu Gly Gly Leu Glu Gln Glu Leu Gln Asp Leu Gly Ile

130 135 140

Ala Thr Val Pro Lys Gly His Cys Ala Ser Cys Gln Lys Pro Ile Ala 145 150 1558 160 Gly Lys Val Ile His Ala Leu Gly Gln Ser Trp His Pro Glu His Phe 165 170 175 Val Cys Thr His Cys Lys Glu Glu Ile Gly Ser Ser Pro Phe Phe Glu 180 185 190 Arg Ser Gly Leu Ala Tyr Cys Pro Asn Asp Tyr His Gln Leu Phe Ser 195 200 205 Pro Arg Cys Ala Tyr Cys Ala Ala Pro Ile Leu Asp Lys Val Leu Thr 210 215 220 Ala Met Asn Gln Thr Trp His Pro Glu His Phe Phe Cys Ser His Cys 225 230 235 240 Gly Glu val Phe Gly Ala Glu Gly Phe His Glu Lys Asp Lys Lys Pro 245 250 255 Tyr Cys Arg Lys Asp Phe Leu Ala Met Phe Ser Pro Lys Cys Gly Gly 260 265 270 Cys Asn Arg Pro Val Leu Glu Asn Tyr Leu Ser Ala Met Asp Thr Val 275 280 285 Trp His Pro Glu Cys Phe Val Cys Gly Asp Cys Phe Thr Ser Phe Ser 290 295 300 Thr Gly Ser Phe Phe Glu Leu Asp Gly Arg Pro Phe Cys Glu Leu His 305 310 315 320 Tyr His His Arg Arg Gly Thr Leu Cys His Gly Cys Gly Gln Pro Ile 325 330 335 Thr Gly Arg Cys Ile Ser Ala Met Gly Tyr Lys Phe His Pro Glu His 340 345 350 Phe Val Cys Ala Phe Cys Leu Thr Gln Leu Ser Lys Gly Ile Phe Arg 35% 360 365 Glu Gln Asn Asp Lys Thr Tyr Cys Gln Pro Cys Phe Asn Lys Leu Phe 370 378 380

Pro Leu

<210> 2931 <211l> 368 <212> PRT <213> Homo sapiens <400> 2931 Met Val Leu Glu Val Ser Asp His Gln Val Leu Asn Asp Ala Glu Val 1 5 10 15 Ala Ala Leu Leu Glu Asn Phe Ser Ser Ser Tyr Asp Tyr Gly Glu Asn

Glu Ser Asp Ser Cys Cys Thr Ser Pro Pro Cys Pro Gln Asp Phe Ser 40 45 Leu Asn Phe Asp Arg Ala Phe Leu Pro Ala Leu Tyr Ser Leu Leu Phe 50 85 60 Leu Leu Gly Leu Leu Gly Asn Gly Ala Val Ala Ala Val Leu Leu Ser 65 70 75 80 Arg Arg Thr Ala Leu Ser Ser Thr Asp Thr Phe Leu Leu His Leu Ala 85 S0 95 Val Ala Asp Thr Leu Leu Val Leu Thr Leu Pro Leu Trp Ala Val Asp 100 105 110 Ala Ala Val Gln Trp Val Phe Gly Ser Gly Leu Cys Lys Val Ala Gly 115 120 125 Ala Leu Phe Asn Ile Asn Phe Tyr Ala Gly Ala Leu Leu Leu Ala Cys 130 135 140 Ile Ser Phe Asp Arg Tyr Leu Asn Ile Val His Ala Thr Gln Leu Tyr 145 150 155 160 Arg Arg Gly Pro Pro Ala Arg Val Thr Leu Thr Cys Leu Ala Val Trp 165 170 175 Gly Leu Cys Leu Leu Phe Ala Leu Pro Asp Phe Ile Phe Leu Ser Ala 180 185 190 His His Asp Glu Arg Leu Asn Ala Thr His Cys Gln Tyr Asn Phe Pro 195 200 205

Gln Val Gly Arg Thr Ala Leu Arg Val Leu Gln Leu Val Ala Gly Phe 210 215 220 Leu Leu Pro Leu Leu Val Met Ala Tyr Cys Tyr Ala His Ile Leu Ala 225 230 235 240 val Leu Leu Val Ser Arg Gly Gln Arg Arg Leu Arg Ala Met Arg Leu 245 250 255 val Val Val Val Val Val Ala Phe Ala Leu Cys Trp Thr Pro Tyr His 260 265 270 Leu Val Val Leu Val Asp Ile Leu Met Asp Leu Gly Ala Leu Ala Arg 275 280 285 Asn Cys Gly Arg Glu Ser Arg Val Asp Val Ala Lys Ser Val Thr Ser 290 295 300 Gly Leu Gly Tyr Met His Cys Cys Leu Asn Pro Leu Leu Tyr Ala Phe 308 310 315 320 Val Gly Val Lys Phe Arg Glu Arg Met Trp Met Leu Leu Leu Arg Leu 325 330 335 Gly Cys Pro Asn Gln Arg Gly Leu Gln Arg Gln Pro Ser Ser Ser Arg 340 345 350 Arg Asp Ser Ser Trp Ser Glu Thr Ser Glu Ala Ser Tyr Ser Gly Leu 355 360 365 <210> 2932 <211> 359 <212> PRT <213> Homo sapiens <400> 2932 Met Ala Glu Ala Ile Thr Tyr Ala Asp Leu Arg Phe Val Lys Ala Pro 1 5 10 15 Leu Lys Lys Ser Ile Ser Ser Arg Leu Gly Gln Asp Pro Gly Ala Asp

Asp Asp Gly Glu Ile Thr Tyr Glu Asn Val Gln Val Pro Ala Val Leu 40 45

Gly val Pro Ser Ser Leu Ala Ser Ser Val Leu Gly Asp Lys Ala Ala 50 55 60 Val Lys Ser Glu Gln Pro Thr Ala Ser Trp Arg Ala Val Thr Ser Pro 65 70 75 80 Ala Val Gly Arg Ile Leu Pro Cys Arg Thr Thr Cys Leu Arg Tyr Leu 85 90 95 Leu Leu Gly Leu Leu Leu Thr Cys Leu Leu Leu Gly Val Thr Ala Ile 100 105 110 Cys Leu Gly val Arg Tyr Leu Gln Val Ser Gln Gln Leu Gln Gln Thr 118 120 125 Asn Arg Val Leu Glu Val Thr Asn Ser Ser Leu Arg Gln Gln Leu Arg 130 135 140 Leu Lys Ile Thr Gln Leu Gly Gln Ser Ala Glu Asp Leu Gln Gly Ser 145 150 155 160 Arg Arg Glu Leu Ala Gln Ser Gln Glu Ala Leu Gln Val Glu Gln Arg } 165 170 175 Ala His Gln Ala Ala Glu Gly Gln Leu Gln Ala Cys Gln Ala Asp Arg 180 185 180 Gln Lys Thr Lys Glu Thr Leu Gln Ser Glu Glu Gln Gln Arg Arg Ala 195 200 205 Leu Glu Gln Lys Leu Ser Asn Met Glu Asn Arg Leu Lys Pro Phe Phe 210 215 220 Thr Cys Gly Ser Ala Asp Thr Cys Cys Pro Ser Gly Trp Ile Met His 225 230 235 240 Gln Lys Ser Cys Phe Tyr Ile Ser Leu Thr Ser Lys Asn Trp Gln Glu 245 250 255 Ser Gln Lys Gln Cys Glu Thr Leu Ser Ser Lys Leu Ala Thr Phe Ser 260 265 270 Glu Ile Tyr Pro Gln Ser His Ser Tyr Tyr Phe Leu Asn Ser Leu Leu 275 280 285 Pro Asn Gly Gly Ser Gly Asn Ser Tyr Trp Thr Gly Leu Ser Ser Asn

290 295 300 Lys Asp Trp Lys Leu Thr Asp Asp Thr Gln Arg Thr Arg Thr Tyr Ala 305 310 315 320 Gln Ser Ser Lys Cys Asn Lys Val His Lys Thr Trp Ser Trp Trp Thr 325 330 335 Leu Glu Ser Glu Ser Cys Arg Ser Ser Leu Pro Tyr Ile Cys Glu Met 340 345 350 Thr Ala Phe Arg Phe Pro Asp 355 <210> 2933 <211> 266 <212> PRT <213> Homo sapiens <400> 2933 Met Arg Val Thr Leu Ala Thr Ile Ala Trp Met Val Ser Phe Val Ser 1 5 10 15 Asn Tyr Ser His Thr Ala Asn Ile Leu Pro Asp Ile Glu Asn Glu Asp

Phe Ile Lys Asp Cys Val Arg Ile His Asn Lys Phe Arg Ser Glu Val 40 45 Lys Pro Thr Ala Ser Asp Met Leu Tyr Met Thr Trp Asp Pro Ala Leu 50 55 60 Ala Gln Ile Ala Lys Ala Trp Ala Ser Asn Cys Gln Phe Ser His Asn 65 70 75 80 Thr Arg Leu Lys Pro Pro His Lys Leu His Pro Asn Phe Thr Ser Leu 85 90 95 Gly Glu Asn Ile Trp Thr Gly Ser Val Pro Ile Phe Ser Val Ser Ser 100 105 110 Ala Ile Thr Asn Trp Tyr Asp Glu Ile Gln Asp Tyr Asp Phe Lys Thr 115 120 125 Arg Ile Cys Lys Lys Val Cys Gly His Tyr Thr Gln Val Val Trp Ala 130 135 140

Asp Ser Tyr Lys Val Gly Cys Ala Val Gln Phe Cys Pro Lys Val Ser 145 150 155 160 Gly Phe Asp Ala Leu Ser Asn Gly Ala His Phe Ile Cys Asn Tyr Gly

165 170 175 Pro Gly Gly Asn Tyr Pro Thr Trp Pro Tyr Lys Arg Gly Ala Thr Cys 180 185 190 Ser Ala Cys Pro Asn Asn Asp Lys Cys Leu Asp Asn Leu Cys Val Asn 185 200 : 205 Arg Gln Arg Asp Gln Val Lys Arg Tyr Tyr Ser Val Val Tyr Pro Gly :

210 215% 220 Trp Pro Ile Tyr Pro Arg Asn Arg Tyr Thr Ser Leu Phe Leu Ile Val 225 230 235 240 Asn Ser Val Ile Leu Ile Leu Ser Val Ile Ile Thr Ile Leu Val Gln

245 250 2585 Leu Lys Tyr Pro Asn Leu Val Leu Leu Asp 260 265 <210> 2934 <211> 1429 <212> PRT <213> Homo sapiens <400> 2934 Met Ala Gly Gly Ala Trp Gly Arg Leu Ala Cys Tyr Leu Glu Phe Leu 1 5 10 15 Lys Lys Glu Glu Leu Lys Glu Phe Gln Leu Leu Leu Ala Asn Lys Ala

His Ser Arg Ser Ser Ser Gly Glu Thr Pro Ala Gln Pro Glu Lys Thr 40 45 Ser Gly Met Glu Val Ala Ser Tyr Leu Val Ala Gln Tyr Gly Glu Gln 50 55 60 Arg Ala Trp Asp Leu Ala Leu His Thr Trp Glu Gln Met Gly Leu Arg 65 70 75 80 Ser Leu Cys Ala Gln Ala Gln Glu Gly Ala Gly His Ser Pro Ser Phe

85 90 95 Pro Tyr Ser Pro Ser Glu Pro His Leu Gly Ser Pro Ser Gln Pro Thr ’ 100 105 110 Ser Thr Ala val Leu Met Pro Trp Ile His Glu Leu Pro Ala Gly Cys 115 120 125 Thr Gln Gly Ser Glu Arg Arg Val Leu Arg Gln Leu Pro ASp Thr Ser 130 135 140 Gly Arg Arg Trp Arg Glu Ile Ser Ala Ser Leu Leu Tyr Gln Ala Leu 145 150 155 160 Pro Ser Ser Pro Asp His Glu Ser Pro Ser Gln Glu Ser Pro Asn Ala 165 170 175 Pro Thr Ser Thr Ala Val Leu Gly Ser Trp Gly Ser Pro Pro Gln Pro 180 185 150 Ser Leu Ala Pro Arg Glu Gln Glu Ala Pro Gly Thr Gln Trp Pro Leu 185 200 205 Asp Glu Thr Ser Gly Ile Tyr Tyr Thr Glu Ile Arg Glu Arg Glu Arg 210 215 220 Glu Lys Ser Glu Lys Gly Arg Pro Pro Trp Ala Ala Val val Gly Thr 225 230 235 240 Pro Pro Gln Ala His Thr Ser Leu Gln Pro His His His Pro Trp Glu 245 250 255 Pro Ser Val Arg Glu Ser Leu Cys Ser Thr Trp Pro Trp Lys Asn Glu 260 265 270 Asp Phe Asn Gln Lys Phe Thr Gln Leu Leu Leu Leu Gln Arg Pro His 275 280 285 Pro Arg Ser Gln Asp Pro Leu Val Lys Arg Ser Trp Pro Asp Tyr val 290 295 300 Glu Glu Asn Arg Gly His Leu Ile Glu Ile Arg Asp Leu Phe Gly Pro 305 310 315 320 Gly Leu Asp Thr Gln Glu Pro Arg Ile Val Ile Leu Gln Gly Ala Ala 325 330 335

Gly Ile Gly Lys Ser Thr Leu Ala Arg Gln Val Lys Glu Ala Trp Gly 340 345 350 Arg Gly Gln Leu Tyr Gly Asp Arg Phe Gln His Val Phe Tyr Phe Ser 355 360 365 Cys Arg Glu Leu Ala Gln Ser Lys Val Val Ser Leu Ala Glu Leu Ile 370 375 380 Gly Lys Asp Gly Thr Ala Thr Pro Ala Pro Ile Arg Gln Ile Leu Ser 385 380 395 400 Arg Pro Glu Arg Leu Leu Phe Ile Leu Asp Gly Val Asp Glu Pro Gly 405 410 415 Trp Val Leu Gln Glu Pro Ser Ser Glu Leu Cys Leu His Trp Ser Gln 420 425 430 Pro Gln Pro Ala Asp Ala Leu Leu Gly Ser Leu Leu Gly Lys Thr Ile 435 440 445 Leu Pro Glu Ala Ser Phe Leu Ile Thr Ala Arg Thr Thr Ala Leu Gln 450 455 460 Asn Leu Ile Pro Ser Leu Glu Gln Ala Arg Trp Val Glu Val Leu Gly 465 470 475 480 Phe Ser Glu Ser Ser Arg Lys Glu Tyr Phe Tyr Arg Tyr Phe Thr Asp 485 490 495 Glu Arg Gln Ala Ile Arg Ala Phe Arg Leu Val Lys Ser Asn Lys Glu 500 505 510 Leu Trp Ala Leu Cys Leu Val Pro Trp Val Ser Trp Leu Ala Cys Thr 515 520 525 Cys Leu Met Gln Gln Met Lys Arg Lys Glu Lys Leu Thr Leu Thr Ser 530 535 540 Lys Thr Thr Thr Thr Leu Cys Leu His Tyr Leu Ala Gln Ala Leu Gln 545 550 555 560 Ala Gln Pro Leu Gly Pro Gln Leu Arg Asp Leu Cys Ser Leu Ala Ala : 565 570 575

Glu Gly Ile Trp Gln Lys Lys Thr Leu Phe Ser Pro Asp Asp Leu Arg 580 585 590 Lys His Gly Leu Asp Gly Ala Ile Ile Ser Thr Phe Leu Lys Met Gly 598 600 605 Ile Leu Gln Glu His Pro Ile Pro Leu Ser Tyr Ser Phe Ile His Leu 610 615 620 Cys Phe Gln Glu Phe Phe Ala Ala Met Ser Tyr Val Leu Glu Asp Glu 625 630 635 640 Lys Gly Arg Gly Lys His Ser Asn Cys Ile Ile Asp Leu Glu Lys Thr 645 650 655 Leu Glu Ala Tyr Gly Ile His Gly Leu Phe Gly Ala Ser Thr Thr Arg 660 . 665 670 Phe Leu Leu Gly Leu Leu Ser Asp Glu Gly Glu Arg Glu Met Glu Asn 675 680 685 Ile Phe His Cys Arg Leu Ser Gln Gly Arg Asn Leu Met Gln Trp Val 6390 695 700 Pro Ser Leu Gln Leu Leu Leu Gln Pro His Ser Leu Glu Ser Leu His 708 710 715 720 Cys Leu Tyr Glu Thr Arg Asn Lys Thr Phe Leu Thr Gln Val Met Ala 725 730 735 His Phe Glu Glu Met Gly Met Cys Val Glu Thr Asp Met Glu Leu Leu 740 745 750 Val Cys Thr Phe Cys Ile Lys Phe Ser Arg His Val Lys Lys Leu Gln 755 760 765 Leu Ile Glu Gly Arg Gln His Arg Ser Thr Trp Ser Pro Thr Met Val 770 775 780 Val Leu Phe Arg Trp Val Pro Val Thr Asp Ala Tyr Trp Gln Ile Leu = 785 780 795 800 Phe Ser Val Leu Lys Val Thr Arg Asn Leu Lys Glu Leu Asp Leu Ser 805 810 815

Gly Asn Ser Leu Ser His Ser Ala Val Lys Ser Leu Cys Lys Thr Leu 820 825 830 Arg Arg Pro Arg Cys Leu Leu Glu Thr Leu Arg Leu Ala Gly Cys Gly 835 840 845 Leu Thr Ala Glu Asp Cys Lys Asp Leu Ala Phe Gly Leu Arg Ala Asn 850 855 860 Gln Thr Leu Thr Glu Leu Asp Leu Ser Phe Asn Val Leu Thr Asp Ala 865 870 875 880 Gly Ala Lys His Leu Cys Gln Arg Leu Arg Gln Pro Ser Cys Lys Leu 885 890 895 Gln Arg Leu Gln Leu Val Ser Cys Gly Leu Thr Ser Asp Cys Cys Gln 900 905 910 Asp Leu Ala Ser Val Leu Ser Ala Ser Pro Ser Leu Lys Glu Leu Asp 915 920 925 Leu Gln Gln Asn Asn Leu Asp Asp Val Gly Val Arg Leu Leu Cys Glu 930 935 940 Gly Leu Arg His Pro Ala Cys Lys Leu Ile Arg Leu Gly Leu Asp Gln 945 950 955 960 Thr Thr Leu Ser Asp Glu Met Arg Gln Glu Leu Arg Ala Leu Glu Gln 965 970 875 Glu Lys Pro Gln Leu Leu Ile Phe Ser Arg Arg Lys Pro Ser Val Met 980 985 $90 Thr Pro Thr Glu Gly Leu Asp Thr Gly Glu Met Ser Asn Ser Thr Ser 9385 1000 1005 Ser Leu Lys Arg Gln Arg Leu Gly Ser Glu Arg Ala Ala Ser His 1010 1015 1020 val Ala Gln Ala Asn Leu Lys Leu Leu Asp Val Ser Lys Ile Phe 1025 1030 1035 Pro Ile Ala Glu Ile Ala Glu Glu Ser Ser Pro Glu Val Val Pro 1040 1045 1050 val Glu Leu Leu Cys Val Pro Ser Pro Ala Ser Gln Gly Asp Leu

1055 1060 1065

His Thr Lys Pro Leu Gly Thr Asp Asp Asp Phe Trp Gly Pro Thr 1070 107s 1080

Gly Pro Val Ala Thr Glu Val Val Asp Lys Glu Lys Asn Leu Tyr 1085 1090 1095

Arg Val His Phe Pro Val Rla Gly Ser Tyr Arg Trp Pro Asn Thr 1100 1105 1110

Gly Leu Cys Phe Val Met Arg Glu Ala Val Thr Val Glu Ile Glu 1115 1120 1125

Phe Cys Val Trp Asp Gln Phe Leu Gly Glu Ile Asn Pro Gln His 1130 1135 1140

Ser Trp Met Val Ala Gly Pro Leu Leu Asp Ile Lys Ala Glu Pro 1145 1150 1155

Gly Ala Val Glu Ala Val His Leu Pro His Phe Val Ala Leu Gln 1160 1165 1170

Gly Gly His Val Asp Thr Ser Leu Phe Gln Met Ala His Phe Lys 1175 1180 1185

Glu Glu Gly Met Leu Leu Glu Lys Pro Ala Arg Val Glu Leu His 11S0 11958 1200

His Ile Val Leu Glu Asn Pro Ser Phe Ser Pro Leu Gly val Leu 1205 1210 1215

Leu Lys Met Ile His Asn Ala Leu Arg Phe Ile Pro Val Thr Ser 1220 1225 1230

Val Val Leu Leu Tyr His Arg Val His Pro Glu Glu Val Thr Phe 1235 1240 1245

His Leu Tyr Leu Ile Pro Ser Asp Cys Ser Ile Arg Lys Glu Leu 1250 1255 1260

Glu Leu Cys Tyr Arg Ser Pro Gly Glu Asp Gln Leu Phe Ser Glu 1265 1270 1275

Phe Tyr Val Gly His Leu Gly Ser Gly Ile Arg Leu Gln Val Lys 1280 1285 1290

Asp Lys Lys Asp Glu Thr Leu Val Trp Glu Ala Leu Val Lys Pro 12395 1300 1305

Gly Asp Leu Met Pro Ala Thr Thr Leu Ile Pro Pro Ala Arg Ile 1310 1315 1320

Ala Val Pro Ser Pro Leu Asp Ala Pro Gln Leu Leu His Phe Val 1325 1330 1335

Asp Gln Tyr Arg Glu Gln Leu Ile Ala Arg Val Thr Ser Val Glu 1340 1345 1350 val Val Leu Asp Lys Leu His Gly Gln Val Leu Ser Gln Glu Gln 1355 1360 1365

Tyr Glu Arg Val Leu Ala Glu Asn Thr Arg Pro Ser Gln Met Arg 1370 1375 1380

Lys Leu Phe Ser Leu Ser Gln Ser Trp Asp Arg Lys Cys Lys Asp 1385 1390 1395

Gly Leu Tyr Gln Ala Leu Lys Glu Thr His Pro His Leu Ile Met 1400 1405 1410

Glu Leu Trp Glu Lys Gly Ser Lys Lys Gly Leu Leu Pro Leu Ser 1415 1420 1425

Ser

<210> 2935

<211> 352

<212> PRT

<213> Homo sapiens

<400> 28535

Met Glu Gly Ile Ser Ile Tyr Thr Ser Asp Asn Tyr Thr Glu Glu Met

1 5 10 15

Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys Phe Arg Glu Glu

Asn Ala Asn Phe Asn Lys Ile Phe Leu Pro Thr Ile Tyr Ser Ile Ile 40 45

Phe Leu Thr Gly Ile Val Gly Asn Gly Leu Val Ile Leu Val Met Gly 50 55 60 Tyr Gln Lys Lys Leu Arg Ser Met Thr Asp Lys Tyr Arg Leu His Leu 65 70 75 80 Ser Val Ala Asp Leu Leu Phe Val Ile Thr Leu Pro Phe Trp Ala Val 85 90 95 Asp Ala Val Ala Asn Trp Tyr Phe Gly Asn Phe Leu Cys Lys Ala Val 100 105 110 His Val Ile Tyr Thr Val Asn Leu Tyr Ser Ser Val Leu Ile Leu Ala 115 120 125 Phe Ile Ser Leu Asp Arg Tyr Leu Ala Ile Val His Ala Thr Asn Ser 130 135 140 Gln Arg Pro Arg Lys Leu Leu Ala Glu Lys val Val Tyr Val Gly val 145 150 155 160 Trp Ile Pro Ala Leu Leu Leu Thr Ile Pro Asp Phe Ile Phe Ala Asn 165 170 175 Val Ser Glu Ala Asp Asp Arg Tyr Ile Cys Asp Arg Phe Tyr Pro Asn 180 185 190 Asp Leu Trp Val Val Val Phe Gln Phe Gln His Ile Met Val Gly Leu 195 200 205 Ile Leu Pro Gly Ile Val Ile Leu Ser Cys Tyr Cys Ile Ile Ile Ser 210 21s 220 Lys Leu Ser His Ser Lys Gly His Gln Lys Arg Lys Ala Leu Lys Thr 225 230 235 240 Thr val Ile Leu Ile Leu Ala Phe Phe Ala Cys Trp Leu Pro Tyr Tyr 245 250 255 Ile Gly Ile Ser Ile Asp Ser Phe Ile Leu Leu Glu Ile Ile Lys Gln 260 265 270 Gly Cys Glu Phe Glu Asn Thr Val His Lys Trp Ile Ser Ile Thr Glu 275 280 285 Ala Leu Ala Phe Phe His Cys Cys Leu Asn Pro Ile Leu Tyr Ala Phe :

250 295 300 Leu Gly Ala Lys Phe Lys Thr Ser Ala Gln His Ala Leu Thr Ser Val 305 310 315 320 Ser Arg Gly Ser Ser Leu Lys Ile Leu Ser Lys Gly Lys Arg Gly Gly 325 330 335 His Ser Ser Val Ser Thr Glu Ser Glu Ser Ser Ser Phe His Ser Ser 340 345 350 <210> 2936 <211l> 248 <212> PRT <213> Homo sapiens <400> 2936 Met Leu Ser Thr Val Gly Ser Phe Leu Gln Asp Leu Gln Asn Glu Asp 1 5 10 15 Lys Gly Ile Lys Thr Ala Ala Ile Phe Thr Ala Asp Gly Asn Met Ile

Ser Ala Ser Thr Leu Met Asp Ile Leu Leu Met Asn Asp Phe Lys Leu 40 45 val Ile Asn Lys Ile Ala Tyr Asp Val Gln Cys Pro Lys Arg Glu Lys 50 55 60 Pro Ser Asn Glu His Thr Ala Glu Met Glu His Met Lys Ser Leu Val 65 70 75 80 His Arg Leu Phe Thr Ile Leu His Leu Glu Glu Ser Gln Lys Lys Arg 85 20 95 Glu His His Leu Leu Glu Lys Ile Asp His Leu Lys Glu Gln Leu Gln 100 105 110 Pro Leu Glu Gln Val Lys Ala Gly Ile Glu Ala His Ser Glu Ala Lys 115 120 125 Thr Ser Gly Leu Leu Trp Ala Gly Leu Ala Leu Leu Ser lle Gln Gly 130 135 140 Gly Ala Leu Ala Trp Leu Thr Trp Trp Val Tyr Ser Trp Asp Ile Met 145 150 155 160

Glu Pro Val Thr Tyr Phe Ile Thr Phe Ala Asn Ser Met Val Phe Phe 165 170 175 Ala Tyr Phe Ile Val Thr Arg Gln Asp Tyr Thr Tyr Ser Ala Val Lys 180 185 130 Ser Arg Gln Phe Leu Gln Phe Phe His Lys Lys Ser Lys Gln Gln His 1395 200 205 Phe Asp Val Gln Gln Tyr Asn Lys Leu Lys Glu Asp Leu Ala Lys Ala 210 215 220 Lys Glu Ser Leu Lys Gln Ala Arg His Ser Leu Cys Leu Gln Met Gln 225 230 235 240 Val Glu Glu Leu Asn Glu Lys Asn 24S <210> 2937 <21ls> 790 <212> PRT <213> Homo sapiens <400> 2937 ) Met Ala Glu Gln Val Leu Pro Gln Ala Leu Tyr Leu Ser Asn Met Arg 1 5 10 15 Lys Ala Val Lys Ile Arg Glu Arg Thr Pro Glu Asp Ile Phe Lys Pro

Thr Asn Gly Ile Ile His His Phe Lys Thr Met His Arg Tyr Thr Leu 40 45 Glu Met Phe Arg Thr Cys Gln Phe Cys Pro Gln Phe Arg Glu Ile Tle 50 55 60 His Lys Ala Leu Ile Asp Arg Asn Ile Gln Ala Thr Leu Glu Ser Gln 65S 70 75 80 Lys Lys Leu Asn Trp Cys Arg Glu Val Arg Lys Leu Val Ala Leu Lys 85 90 95 Thr Asn Gly Asp Gly Asn Cys Leu Met His Ala Thr Ser Gln Tyr Met 100 105 110 Trp Gly Val Gln Asp Thr Asp Leu Val Leu Arg Lys Ala Leu Phe Ser

11S 120 125 Thr Leu Lys Glu Thr Asp Thr Arg Asn Phe Lys Phe Arg Trp Gln Leu 130 135 140 Glu Ser Leu Lys Ser Gln Glu Phe Val Glu Thr Gly Leu Cys Tyr Asp 1458 150 155 160 Thr Arg Asn Trp Asn Asp Glu Trp Asp Asn Leu Ile Lys Met Ala Ser 165 170 175 Thr Asp Thr Pro Met Ala Arg Ser Gly Leu Gln Tyr Asn Ser Leu Glu 180 185 190 Glu Ile His Ile Phe Val Leu Cys Asn Ile Leu Arg Arg Pro Ile Ile 195 200 205 val Ile Ser Asp Lys Met Leu Arg Ser Leu Glu Ser Gly Ser Asn Phe 210 215 220 Ala Pro Leu Lys Val Gly Gly Ile Tyr Leu Pro Leu His Trp Pro Ala 225 230 235 240 Gln Glu Cys Tyr Arg Tyr Pro Ile Val Leu Gly Tyr Asp Ser His His 245 250 255 Phe Val Pro Leu Val Thr Leu Lys Asp Ser Gly Pro Glu Ile Arg Ala 260 265 270 Val Pro Leu Val Asn Arg Asp Arg Gly Arg Phe Glu Asp Leu Lys Val 275 280 285 His Phe Leu Thr Asp Pro Glu Asn Glu Met Lys Glu Lys Leu Leu Lys 290 295 300 Glu Tyr Leu Met Val Ile Glu Ile Pro Val Gln Gly Trp Asp His Gly 305 310 315 320 Thr Thr His Leu Ile Asn Ala Ala Lys Leu Asp Glu Ala Asn Leu Pro 325 330 335 Lys Glu Ile Asn Leu Val Asp Asp Tyr Phe Glu Leu Val Gln His Glu 340 345 350 Tyr Lys Lys Trp Gln Glu Asn Ser Glu Gln Gly Arg Arg Glu Gly His 355 360 365

Ala Gln Asn Pro Met Glu Pro Ser Val Pro Gln Leu Ser Leu Met Asp 370 375 380 val Lys Cys Glu Thr Pro Asn Cys Pro Phe Phe Met Ser Val Asn Thr 385 350 395 400 Gln Pro Leu Cys His Glu Cys Ser Glu Arg Arg Gln Lys Asn Gln Asn 405 410 415 Lys Leu Pro Lys Leu Asn Ser Lys Pro Gly Pro Glu Gly Leu Pro Gly 420 425 430 Met Ala Leu Gly Ala Ser Arg Gly Glu Ala Tyr Glu Pro Leu Ala Trp 435 440 445 Asn Pro Glu Glu Ser Thr Gly Gly Pro His Ser Ala Pro Pro Thr Ala 450 455 460 Pro Ser Pro Phe Leu Phe Ser Glu Thr Thr Ala Met Lys Cys Arg Ser 465 470 : 475 480 Pro Gly Cys Pro Phe Thr Leu Asn Val Gln His Asn Gly Phe Cys Glu 485 490 495 Arg Cys His Asn Ala Arg Gln Leu His Ala Ser His Ala Pro Asp His 500 505 S10 Thr Arg His Leu Asp Pro Gly Lys Cys Gln Ala Cys Leu Gln Asp Val 515 520 525 Thr Arg Thr Phe Asn Gly Ile Cys Ser Thr Cys Phe Lys Arg Thr Thr 530 535 540 Ala Glu Ala Ser Ser Ser Leu Ser Thr Ser Leu Pro Pro Ser Cys His 545 550 555 560 Gln Arg Ser Lys Ser Asp Pro Ser Arg Leu Val Arg Ser Pro Ser Pro 565 570 575 His Ser Cys His Arg Ala Gly Asn Asp Ala Pro Ala Gly Cys Leu Ser 580 585 590 Gln Ala Ala Arg Thr Pro Gly Asp Arg Thr Gly Thr Ser Lys Cys Arg 595 600 605

Lys Ala Gly Cys Val Tyr Phe Gly Thr Pro Glu Asn Lys Gly Phe Cys 610 615 620 Thr Leu Cys Phe Ile Glu Tyr Arg Glu Asn Lys His Phe Ala Ala Ala 625 630 635 640 Ser Gly Lys Val Ser Pro Thr Ala Ser Arg Phe Gln Asn Thr Ile Pro 645 650 655 Cys Leu Gly Arg Glu Cys Gly Thr Leu Gly Ser Thr Met Phe Glu Gly 660 665 670 Tyr Cys Gln Lys Cys Phe Ile Glu Ala Gln Asn Gln Arg Phe His Glu 675 680 685 Ala Lys Arg Thr Glu Glu Gln Leu Arg Ser Ser Gln Arg Arg Asp Val 690 695 700 Pro Arg Thr Thr Gln Ser Thr Ser Arg Pro Lys Cys Ala Arg Ala Ser 705 710 715 720 Cys Lys Asn Ile Leu Ala Cys Arg Ser Glu Glu Leu Cys Met Glu Cys 725 730 735 Gln His Pro Asn Gln Arg Met Gly Pro Gly Ala His Arg Gly Glu Pro 740 745 750 Ala Pro Glu Asp Pro Pro Lys Gln Arg Cys Arg Ala Pro Ala Cys Asp 755 760 765 His Phe Gly Asn Ala Lys Cys Asn Gly Tyr Cys Asn Glu Cys Phe Gln 770 775 780 Phe Lys Gln Met Tyr Gly 785 790 <210> 2938 <21l1l> 206 <212> PRT <213> Homo sapiens <400> 2938 Met Ala Leu Pro Cys Thr Leu Gly Leu Gly Met Leu Leu Ala Leu Pro 1 S 10 15 Gly Ala Leu Gly Ser Gly Gly Ser Ala Glu Asp Ser Val Gly Ser Ser

Ser Val Thr Val val Leu Leu Leu Leu Leu Leu Leu Leu Leu Ala Thr 40 45 Gly Leu Ala Leu Ala Trp Arg Arg Leu Ser Arg Asp Ser Gly Gly Tyr 50 55 60 Tyr His Pro Ala Arg Leu Gly Ala Ala Leu Trp Gly Arg Thr Arg Arg 65 70 75 80 Leu Leu Trp Ala Ser Pro Pro Gly Arg Trp Leu Gln Ala Arg Ala Glu 85 90 85 Leu Gly Ser Thr Asp Asn Asp Leu Glu Arg Gln Glu Asp Glu Gln Asp 100 105 110 Thr Asp Tyr Asp His Val Ala Asp Gly Gly Leu Gln Ala Asp Pro Gly 115 120 125 : Glu Gly Glu Gln Gln Cys Gly Glu Ala Ser Ser Pro Glu Gln Val Pro . 130 135 140 Val Arg Ala Glu Glu Ala Arg Asp Ser Asp Thr Glu Gly Asp Leu val 145 150 155 160 Leu Gly Ser Pro Gly Pro Ala Ser Ala Gly Gly Ser Ala Glu Ala Leu 165 170 175 Leu Ser Asp Leu His Ala Phe Ala Gly Ser Ala Ala Trp Asp Asp Ser 180 185 120 Ala Arg Ala Ala Gly Gly Gln Gly Leu His Val Thr Ala Leu 195 200 205 <210> 2939 <211> 718 <212> PRT <213> Homo sapiens <400> 2939 Met Ile Val Asp Lys Leu Leu Asp Asp Ser Arg Gly Gly Glu Gly Leu 1 S 10 15 Arg Asp Ala Ala Gly Gly Cys Gly Leu Met Thr Ser Pro Leu Asn Leu 20 25 30

Ser Tyr Phe Tyr Gly Ala Ser Pro Pro Ala Ala Ala Pro Gly Ala Cys 40 45 Asp Ala Ser Cys Ser Val Leu Gly Pro Ser Ala Pro Gly Ser Pro Gly 50 55 60 Ser Asp Ser Ser Asp Phe Ser Ser Ala Ser Ser Val Ser Ser Cys Gly 65 70 75 80 Ala Val Glu Ser Arg Ser Arg Gly Gly Ala Arg Ala Glu Arg Gln Pro 8S 90 95 Val Glu Pro His Met Gly Val Gly Arg Gln Gln Arg Gly Pro Phe Gln 100 105 110 Gly Val Arg Val Lys Asn Ser Val Lys Glu Leu Leu Leu His Ile Arg 115 120 125 Ser His Lys Gln Lys Ala Ser Gly Gln Ala Val Asp Asp Phe Lys Thr 130 135 140 Gln Gly Val Asn Ile Glu Gln Phe Arg Glu Leu Lys Asn Thr Val Ser 145 150 155 160 Tyr Ser Gly Lys Arg Lys Gly Pro Asp Ser Leu Ser Asp Gly Pro ala 165 170 175 Cys Lys Arg Pro Ala Leu Leu His Ser Gln Phe Leu Thr Pro Pro Gln 180 185 150 Thr Pro Thr Pro Gly Glu Ser Met Glu Asp Val His Leu Asn Glu Pro 195 200 205 Lys Gln Glu Ser Ser Ala Asp Leu Leu Gln Asn Ile Ile Asn Ile Lys 210 215 220 Asn Glu Cys Ser Pro Val Ser Leu Asn Thr Val Gln val Ser Trp Leu 225 230 235 240 Asn Pro Val Val Val Pro Gln Ser Ser Pro Ala Glu Gln Cys Gln Asp’ 245 250 255 Phe His Gly Gly Gln Val Phe Ser Pro Pro Gln Lys Cys Gln Pro Phe 260 265 270

Gln Val Arg Gly Ser Gln Gln Met Ile Asp Gln Ala Ser Leu Tyr Gln 275 280 285 Tyr Ser Pro Gln Asn Gln His Val Glu Gln Gln Pro His Tyr Thr His 290 285 : 300 Lys Pro Thr Leu Glu Tyr Ser Pro Phe Pro Ile Pro Pro Gln Ser Pro 305 310 315 320 Ala Tyr Glu Pro Asn Leu Phe Asp Gly Pro Glu Ser Gln Phe Cys Pro 325 330 335 . Asn Gln Ser Leu Val Ser Leu Leu Gly Asp Gln Arg Glu Ser Glu Asn 340 345 350 Ile Ala Asn Pro Met Gln Thr Ser Ser Ser Val Gln Gln Gln Asn Asp 355 360 365 Ala His Leu His Ser Phe Ser Met Met Pro Ser Ser Ala Cys Glu Ala 370 375 380 Met Val Gly His Glu Met Ala Ser Asp Ser Ser Asn Thr Ser Leu Pro 385 390 395 400 Phe Ser Asn Met Gly Asn Pro Met Asn Thr Thr Gln Leu Gly Lys Ser 405 410 415 Leu Phe Gln Trp Gln Val Glu Gln Glu Glu Ser Lys Leu Ala Asn Ile 420 425 430 Ser Gln Asp Gln Phe Leu Ser Lys Asp Ala Asp Gly, Asp Thr Phe Leu 435 440 445 His Ile Ala Val Ala Gln Gly Arg Arg Ala Leu Ser Tyr Val Leu Ala 450 455 460 Arg Lys Met Asn Ala Leu His Met Leu Asp Ile Lys Glu His Asn Gly 465 470 475 480 Gln Ser Ala Phe Gln Val Ala Val Ala Ala Asn Gln His Leu Ile Val 485 490 495 Gln Asp Leu Val Asn Ile Gly Ala Gln Val Asn Thr Thr Asp Cys Trp 1500 505 510 Gly Arg Thr Pro Leu His Val Cys Ala Glu Lys Gly His Ser Gln Val

515 520 525 Leu Gln Ala Ile Gln Lys Gly Ala val Gly Ser Asn Gln Phe Val Asp 530 535 540 Leu Glu Ala Thr Asn Tyr Asp Gly Leu Thr Pro Leu His Cys Ala Val 545 550 555 560 Ile Ala His Asn Ala Val Val His Glu Leu Gln Arg Asn Gln Gln Pro 565 570 575 His Ser Pro Glu Val Gln Glu Leu Leu Leu Lys Asn Lys Ser Leu Val 580 585 590 Asp Thr Ile Lys Cys Leu Ile Gln Met Gly Ala Ala Val Glu Ala Lys 595 600 605 Asp Arg Lys Ser Gly Arg Thr Ala Leu His Leu Ala Ala Glu Glu Ala 610 615 620 Asn Leu Glu Leu Ile Arg Leu Phe Leu Glu Leu Pro Ser Cys Leu Ser 625 630 635 640 Phe Val Asn Ala Lys Ala Tyr Asn Gly Asn Thr Ala Leu His Val Ala 645 650 655 Ala Ser Leu Gln Tyr Arg Leu Thr Gln Leu Asp Ala Val Arg Leu Leu 660 665 670 Met Arg Lys Gly Ala Asp Pro Ser Thr Arg Asn Leu Glu Asn Glu Gln 675 680 685 Pro Val His Leu Val Pro Asp Gly Pro Val Gly Glu Gln Ile Arg Arg €90 695 700 Ile Leu Lys Gly Lys Ser Ile Gln Gln Arg Ala Pro Pro Tyr 705 710 715 <210> 2940 <211> 247 <212> PRT <213> Homo sapiens <400> 2940 Met Gln Pro Ile Leu Leu Leu Leu Ala Phe Leu Leu Leu Pro Arg Ala 1 S 10 15

Asp Ala Gly Glu Ile Ile Gly Gly His Glu Ala Lys Pro His Ser Arg

Pro Tyr Met Ala Tyr Leu Met Ile Trp Asp Gln Lys Ser Leu Lys Arg 40 45 Cys Gly Gly Phe Leu Ile Gln Asp Asp Phe Val Leu Thr Ala Ala His 50 55 60 Cys Trp Gly Ser Ser Ile Asn Val Thr Leu Gly Ala His Asn Ile Lys 65 70 75 80 Glu Gln Glu Pro Thr Gln Gln Phe Ile Pro Val Lys Arg Pro Ile Pro 85 90 95 His Pro Ala Tyr Asn Pro Lys Asn Phe Ser Asn Asp Ile Met Leu Leu 100 105 110 Gln Leu Glu Arg Lys Bla Lys Arg Thr Arg Ala Val Gln Pro Leu Arg 115 120 125 Leu Pro Ser Asn Lys Ala Gln Val Lys Pro Gly Gln Thr Cys Ser Val 130 135 140 Ala Gly Trp Gly Gln Thr Ala Pro Leu Gly Lys His Ser His Thr Leu 145 150 155 160 Gln Glu Val Lys Met Thr Val Gln Glu Asp Arg Lys Cys Glu Ser Asp 165 170 175 Leu Arg His Tyr Tyr Asp Ser Thr Ile Glu Leu Cys Val Gly Asp Pro 180 185 190 Glu Ile Lys Lys Thr Ser Phe Lys Gly Asp Ser Gly Gly Pro Leu Val 195 200 205 Cys Asn Lys Val Ala Gln Gly Ile Val Ser Tyr Gly Arg Asn Asn Gly 210 215 220 Met Pro Pro Arg Ala Cys Thr Lys Val Ser Ser Phe Val His Trp Ile 228 230 235 240 Lys Lys Thr Met Lys Arg Tyr 245

<210> 2941 <211> 191 <212> PRT <213> Homo sapiens <400> 2941 Met His Asp Ser Asn Asn Val Glu Lys Asp lle Thr Pro Ser Glu Leu 1 S 10 15 Pro Ala Asn Pro Gly Cys Leu His Ser Lys Glu His Ser Ile Lys Ala

Thr Leu Ile Trp Arg Leu Phe Phe Leu Ile Met Phe Leu Thr Ile Ile 40 45 val Cys Gly Met Val Ala Ala Leu Ser Ala Ile Arg Ala Asn Cys His 50 55 60 Gln Glu Pro Ser Val Cys Leu Gln Ala Ala Cys Pro Glu Ser Trp Ile 65 70 75 80 Gly Phe Gln Arg Lys Cys Phe Tyr Phe Ser Asp Asp Thr Lys Asn Trp 85 90 95 Thr Ser Ser Gln Arg Phe Cys Asp Ser Gln Asp Ala Asp Leu Ala Gln 100 105 110 ’ Val Glu Ser Phe Gln Glu Leu Asn Phe Leu Leu Arg Tyr Lys Gly Pro 115 120 125 Ser Asp His Trp Ile Gly Leu Ser Arg Glu Gln Gly Gln Pro Trp Lys 130 135 140 Trp Ile Asn Gly Thr Glu Trp Thr Arg Gln Phe Pro Ile Leu Gly Ala 145 150 155 160 Gly Glu Cys Ala Tyr Leu Asn Asp Lys Gly Ala Ser Ser Ala Arg His 165 170 175 Tyr Thr Glu Arg Lys Trp Ile Cys Ser Lys Ser Asp Ile His Val 180 185 190 <210> 2942 <211> 441 <212> PRT <213> Home sapiens <400> 2942

PCT/US2003/012946

Met Glu Ile Arg Leu Asp Thr Leu Ser Ala Ser Leu Gly Arg ser Ser 1 5 10 15 Thr Leu Asn Asp Cys Asn Leu Glu Asp Lys Leu Ala Trp Tyr Glu Gly

Glu Ala Tyr Met Trp His His Trp Lys Pro Phe Pro Glu Asn Pro Leu 40 45 Trp Thr Cys Leu Asp Phe Gln Ile ala Gln val Gly Pro Trp Asp Tyr 50 55 60 Cys Ser Ser Cys Ile Arg His Thr Arg Leu Lys Ser Ser Cys Ser Asp 65 70 75 80 Met Asp Leu Leu His Ser Trp Arg Ser Ser Ser Phe Gly Asn Phe Asp 85 50 95 Arg Phe Arg Asn Asn Ser Leu Ser Lys Pro Asp Asp Ser Thr Glu Ala : 100 105 110 His Glu Gly Asp Pro Thr Asn Gly ser Gly Glu Gln Ser Lys Thr Ser 115 120 125 Asn Asn Gly Gly Gly Leu Gly Lys Lys Met Arg Ala Ile Ser Trp Thr 130 135 140 Met Lys Lys Lys val Gly Lys Lys Tyr Ile Lys Ala Leu Ser Glu Glu 145 150 } 155 160 Lys Asp Glu Glu Asp Gly Glu Asn Ala His Pro Tyr Arg Asn Ser Asp 165 170 175 Pro val Ile Gly Thr His Thr Glu Lys val ser Ley Lys Ala Ser Asp 180 . 185 190 Ser Met Asp Ser Leu Tyr Ser Gly Gln Ser Ser Ser Ser Gly Ile Thr 195 200 205 Ser Cys Ser Asp Gly Thr Ser Asn Arg Asp Ser Phe Arg Leu Asp Asp 210 215 220 Asp Gly Pro Tyr Ser Gly Pro Phe Cys Gly Arg ala Arg Val His Thr 225 230 235 240

Asp Phe Thr Pro Ser Pro Tyr Asp Thr Asp Ser Leu Lys Ile Lys Lys 245 250 255 Gly Asp Ile Ile Asp Ile Ile Cys Lys Thr Pro Met Gly Met Trp Thr 260 265 270 Gly Met Leu Asn Asn Lys Val Gly Asn Phe Lys Phe Ile Tyr Val Asp 275 280 285 val Ile Ser Glu Glu Glu Ala Ala Pro Lys Lys Ile Lys Ala Asn Arg 290 295 300 Arg Ser Asn Ser Lys Lys Ser Lys Thr Leu Gln Glu Phe Leu Glu Arg 305 310 315 320 Ile His Leu Gln Glu Tyr Thr Ser Thr Leu Leu Leu Asn Gly Tyr Glu 325 330 335 Thr Leu Glu Asp Leu Lys Asp Ile Lys Glu Ser His Leu Ile Glu Leu 340 345 350 Asn Ile Glu Asn Pro Asp Asp Arg Arg Arg Leu Leu Ser BRla Ala Glu 355 360 365 Asn Phe Leu Glu Glu Glu Ile Ile Gln Glu Gln Glu Asn Glu Pro Glu 370 375 380 Pro Leu Ser Leu Ser Ser Asp Ile Ser Leu Asn Lys Ser Gln Leu Asp 385 350 395 400 Asp Cys Pro Arg Asp Ser Gly Cys Tyr Ile Ser Ser Gly Asn Ser Asp 405 410 415 Asn Gly Lys Glu Asp Leu Glu Ser Glu Asn Leu Ser Asp Met Val His 420 425 430 Lys Ile Ile Ile Thr Glu Pro Ser Asp 435 440 <210> 2943 <21l> 564 <212> PRT <213> Homo sapiens <400> 2943 Met Lys Glu His Gly Gly Thr Phe Ser Ser Thr Gly Ile Ser Gly Gly 1 5 10 15

Ser Gly Asp Ser Ala Met Asp Ser Leu Gln Pro Leu Gln Pro Asn Tyr

Met Pro Val Cys Leu Phe Ala Glu Glu Ser Tyr Gln Lys Leu Ala Met 40 45 Glu Thr Leu Glu Glu Leu Asp Trp Cys Leu Asp Gln Leu Glu Thr Ile 50 55 60 Gln Thr Tyr Arg Ser Val Ser Glu Met Ala Ser Asn Lys Phe Lys Arg 65 70 75 80 Met Leu Asn Arg Glu Leu Thr His Leu Ser Glu Met Ser Arg Ser Gly 85 90 95 Asn Gln Val Ser Glu Tyr Ile Ser Asn Thr Phe Leu Asp Lys Gln Asn i00 105 110 Asp Val Glu Ile Pro Ser Pro Thr Gln Lys Asp Arg Glu Lys Lys Lys 115 120 125 Lys Gln Gln Leu Met Thr Gln Ile Ser Gly Val Lys Lys Leu Met His 130 135 140 Ser Ser Ser Leu Asn Asn Thr Ser Ile Ser Arg Phe Gly Val Asn Thr 145 150 155 160 Glu Asn Glu Asp His Leu Ala Lys Glu Leu Glu Asp Leu Asn Lys Trp 165 170 175 Gly Leu Asn Ile Phe Asn Val Ala Gly Tyr Ser His Asn Arg Pro Leu 180 185 1350 Thr Cys Ile Met Tyr Ala Ile Phe Gln Glu Arg Asp Leu Leu Lys Thr 185 200 205 Phe Arg Ile Ser Ser Asp Thr Phe Ile Thr Tyr Met Met Thr Leu Glu 210 215 220 Asp His Tyr His Ser Asp Val Ala Tyr His Asn Ser Leu His Ala Ala 225 230 235 240 Asp Val Ala Gln Ser Thr His Val Leu Leu Ser Thr Pro Ala Leu Asp 245 250 255

Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile Phe Ala Ala Ala 260 265 270 Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln Phe Leu Ile Asn 275 280 285 Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Glu Ser Val Leu Glu 290 295 300 Asn His His Leu Ala Val Gly Phe Lys Leu Leu Gln Glu Glu His Cys 305 310 315 320 Asp Ile Phe Met Asn Leu Thr Lys Lys Gln Arg Gln Thr Leu Arg Lys 325 330 335 Met Val Ile Asp Met Val Leu Ala Thr Asp Met Ser Lys His Met Ser 340 345 350 Leu Leu Ala Asp Leu Lys Thr Met Val Glu Thr Lys Lys Val Thr Ser 355 360 365 Ser Gly Val Leu Leu Leu Asp Asn Tyr Thr Asp Arg Ile Gln Val Leu 370 375 380 Arg Asn Met Val His Cys Ala Asp Leu Ser Asn Pro Thr Lys Ser Leu 385 390 395 400 Glu Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu Glu Phe Phe Gln 405 410 415 Gln Gly Asp Lys Glu Arg Glu Arg Gly Met Glu Ile Ser Pro Met Cys 420 425 430 Asp Lys His Thr Ala Ser Val Glu Lys Ser Gln Val Gly Phe Ile Asp 435 440 445 Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp Leu Val Gln Pro 450 455 460 Asp Ala Gln Asp Ile Leu Asp Thr Leu Glu Asp Asn Arg Asn Trp Tyr 465 470 475 480 Gln Ser Met Ile Pro Gln Ser Pro Ser Pro Pro Leu Asp Glu Gln Asn 485 490 495

Arg Asp Cys Gln Gly Leu Met Glu Lys Phe Gln Phe Glu Leu Thr Leu 500 50% 510 Asp Glu Glu Asp Ser Glu Gly Pro Glu Lys Glu Gly Glu Gly His Ser 515 520 525

Tyr Phe Ser Ser Thr Lys Thr Leu Cys Val Ile Asp Pro Glu Asn Arg

530 535 540 Asp Ser Leu Gly Glu Thr Asp Ile Asp Ile Ala Thr Glu Asp Lys Ser 545 550 555 S60 Pro Val Asp Thr <210> 2944 <211> 91 . <212> PRT <213> Homo sapiens <400> 2944 Met Lys Val Ser Ala Ala Ala Leu Ala Val Ile Leu Ile Ala Thr Ala 1 5 10 15 Leu Cys Ala Pro Ala Ser Ala Ser Pro Tyr Ser Ser Asp Thr Thr Pro

Cys Cys Phe Ala Tyr Ile Ala Arg Pro Leu Pro Arg Ala His Ile Lys 40 45

Glu Tyr Phe Tyr Thr Ser Gly Lys Cys Ser Asn Pro Ala Val Val Phe

50 55 60 Val Thr Arg Lys Asn Arg Gln Val Cys Ala Asn Pro Glu Lys Lys Trp 65 70 75 80 Val Arg Glu Tyr Ile Asn Ser Leu Glu Met Ser

CH) 90 <210> 2945 <211> 461 <212> PRT <213> Homo sapiens <400> 2945 Met Ala Pro Val Ala Val Trp Ala Ala Leu Ala Val Gly Leu Glu Leu 1 5 10 15

Trp Ala Ala Ala His Ala Leu Pro Ala Gln Val Ala Phe Thr Pro Tyr

Ala Pro Glu Pro Gly Ser Thr Cys Arg Leu Arg Glu Tyr Tyr Asp Gln 40 45 Thr Ala Gln Met Cys Cys Ser Lys Cys Ser Pro Gly Gln His Ala Lys 50 55 60 Val Phe Cys Thr Lys Thr Ser Asp Thr Val Cys Asp Ser Cys Glu Asp 65 70 75 80 Ser Thr Tyr Thr Gln Leu Trp Asn Trp Val Pro Glu Cys Leu Ser Cys 85 90 95 Gly Ser Arg Cys Ser Ser Asp Gln Val Glu Thr Gln Ala Cys Thr Arg 100 105 110 Glu Gln Asn Arg Ile Cys Thr Cys Arg Pro Gly Trp Tyr Cys Ala Leu 115 120 125 Ser Lys Gln Glu Gly Cys Arg Leu Cys Ala Pro Leu Arg Lys Cys Arg 130 135 140 Pro Gly Phe Gly Val Ala Arg Pro Gly Thr Glu Thr Ser Asp Val Val 145 150 155 160 Cys Lys Pro Cys Ala Pro Gly Thr Phe Ser Asn Thr Thr Ser Ser Thr 165 170 175 Asp Ile Cys Arg Pro His Gln Ile Cys Asn Val Val Ala Ile Pro Gly 180 185 150 Asn Ala Ser Met Asp Ala Val Cys Thr Ser Thr Ser Pro Thr Arg Ser 195 200 205 Met Ala Pro Gly Ala Val His Leu Pro Gln Pro Val Ser Thr Arg Ser } 210 215 220 Gln His Thr Gln Pro Thr Pro Glu Pro Ser Thr Ala Pro Ser Thr Ser Co : 225 230 235 240 Phe Leu Leu Pro Met Gly Pro Ser Pro Pro Ala Glu Gly Ser Thr Gly 245 250 255

Asp Phe Ala Leu Pro Val Gly Leu Ile val Gly Val Thr Ala Leu Gly 260 265 270 Leu Leu Ile Ile Gly Val Val Asn Cys Val Ile Met Thr Gln Val Lys 275 280 285 Lys Lys Pro Leu Cys Leu Gln Arg Glu Ala Lys Val Pro His Leu Pro 290 295 300 Ala Asp Lys Ala Arg Gly Thr Gln Gly Pro Glu Gln Gln His Leu Leu 305 310 315 320 Ile Thr Ala Pro Ser Ser Ser Ser Ser Ser Leu Glu Ser Ser Ala Ser 325 330 335 Ala Leu Asp Arg Arg Ala Pro Thr Arg Asn Gln Pro Gln Ala Pro Gly 340 345 350 Val Glu Ala Ser Gly Ala Gly Glu Ala Arg Ala Ser Thr Gly Ser Ser 355 360 365 Asp Ser Ser Pro Gly Gly His Gly Thr Gln Val Asn val Thr Cys Ile 370 375 380 Val Asn Val Cys Ser Ser Ser Asp His Ser Ser Gln Cys Ser Ser Gln 385 390 395 400 Ala Ser Ser Thr Met Gly Asp Thr Asp Ser Ser Pro Ser Glu Ser Pro 405 410 415 Lys Asp Glu Gln Val Pro Phe Ser Lys Glu Glu Cys Ala Phe Arg Ser 420 425 430 Gln Leu Glu Thr Pro Glu Thr Leu Leu Gly Ser Thr Glu Glu Lys Pro 435 440 445 Leu Pro Leu Gly Val Pro Asp Ala Gly Met Lys Pro Ser 450 455 460 <210> 2946 <211> 823 oo <212> PRT <213> Homo sapiens <400> 2946 Met Ser Arg Arg Lys Gln Gly Asn Pro Gln His Leu Ser Gln Arg Glu 1 5 10 15 .

aaa CO Leu Ile Thr Pro Glu Ala Asp His Val Glu Ala Ala Ile Leu Glu Glu Asp Glu Gly Leu Glu Ile Glu Glu Pro Ser Gly Leu Gly Leu Met Val 40 45 Gly Gly Pro Asp Pro Asp Leu Leu Thr Cys Gly Gln Cys Gln Met Asn 50 55 60 Phe Pro Leu Gly Asp Ile Leu Val Phe Ile Glu His Lys Arg Lys Gln 65 70 75 80 Cys Gly Gly Ser Leu Gly Ala Cys Tyr Asp Lys Ala Leu Asp Lys Asp 85 90 95 Ser Pro Pro Pro Ser Ser Arg Ser Glu Leu Arg Lys Val Ser Glu Pro 100 105 110 Val Glu Ile Gly Ile Gln Val Thr Pro Asp Glu Asp Asp His Leu Leu 115 120 125 Ser Pro Thr Lys Gly Ile Cys Pro Lys Gln Glu Asn Ile Ala Gly Lys 130 135 140 Asp Glu Pro Ser Ser Tyr Ile Cys Thr Thr Cys Lys Gln Pro Phe Asn 145 150 155 160 Ser Ala Trp Phe Leu Leu Gln His Ala Gln Asn Thr His Gly Phe Arg 165 170 175 Ile Tyr Leu Glu Pro Gly Pro Ala Ser Ser Ser Leu Thr Pro Arg Leu 180 185 190 Thr Ile Pro Pro Pro Leu Gly Pro Glu Ala Val Ala Gln Ser Pro Leu 195 200 205 Met Asn Phe Leu Gly Asp Ser Asn Pro Phe Asn Leu Leu Arg Met Thr 210 215 220 Gly Pro Ile Leu Arg Asp His Pro Gly Phe Gly Glu Gly Arg Leu Pro 225 230 235 240 Gly Thr Pro Pro Leu Phe Ser Pro Pro Pro Arg His His Leu Asp Pro 245 250 255 1311 hn.

i PéTIU S2003/012946

His Arg Leu Ser Ala Glu Glu Met Gly Leu Val Ala Gln His Pro Ser 260 265 270 Ala Phe Asp Arg Val Met Arg Leu Asn Pro Met ala Ile Asp Ser Pro 275 280 285 Ala Met Asp Phe Ser Arg Arg Leu Arg Glu Leu Ala Gly Asn Ser Ser 290 295 300 Thr Pro Pro Pro Val Ser Pro Gly Arg Gly Asn Pro Met His Arg Leu 305 310 315 320 Leu Asn Pro Phe Gln Pro Ser Pro Lys Ser Pro Phe Leu Ser Thr Pro 325 330 335 Pro Leu Pro Pro Met Pro Pro Gly Gly Thr Pro Pro Pro Gln Pro Pro 340 345 350 Ala Lys Ser Lys Ser Cys Glu Phe Cys Gly Lys Thr Phe Lys Phe Gln 355 360 365 Ser Asn Leu Ile Val His Arg Arg Ser His Thr Gly Glu Lys Pro Tyr 370 375 380 Lys Cys Gln Leu Cys Asp His Ala Cys Ser Gln Ala Ser Lys Leu Lys 385 390 385 400 Arg His Met Lys Thr His Met His Lys Ala Gly Ser Leu Ala Gly Arg 405 410 415 Ser Asp Asp Gly Leu Ser Ala Ala Ser Ser Pro Glu Pro Gly Thr Ser 420 425 430 Glu Leu Ala Gly Glu Gly Leu Lys Ala Ala Asp Gly Asp Phe Arg His 435 440 445 His Glu Ser Asp Pro Ser Leu Gly His Glu Pro Glu Glu Glu Asp Glu 450 455 460 Glu Glu Glu Glu Glu Glu Glu Glu Leu Leu Leu Glu Asn Glu Ser Arg 465 470 475 480 Pro Glu Ser Ser Phe Ser Met Asp Ser Glu Leu Ser Arg Asn Arg Glu 485 490 495 1312 dM

Asn Gly Gly Gly Gly Val Pro Gly Val Pro Gly Ala Gly Gly Gly Ala 500 505 510 Ala Lys Ala Leu Ala Asp Glu Lys Ala Leu Val Leu Gly Lys Val Met 515 520 525 Glu Asn Val Gly Leu Gly Ala Leu Pro Gln Tyr Gly Glu Leu Leu Ala 530 535 540 Asp Lys Gln Lys Arg Gly Ala Phe Leu Lys Arg Ala Ala Gly Gly Gly 545 550 555 560 Asp Ala Gly Asp Asp Asp Asp Ala Gly Gly Cys Gly Asp Ala Gly Ala 565 570 575 Gly Gly Ala Val Asn Gly Arg Gly Gly Gly Phe Ala Pro Gly Thr Glu 580 585 590 Pro Phe Pro Gly Leu Phe Pro Arg Lys Pro Ala Pro Leu Pro Ser Pro 595 600 605 Gly Leu Asn Ser Ala Ala Lys Arg Ile Lys Val Glu Lys Asp Leu Glu 610 615 620 Leu Pro Pro Ala Ala Leu Ile Pro Ser Glu Asn Val Tyr Ser Gln Trp 625 630 635 640 Leu Val Gly Tyr Ala Ala Ser Arg His Phe Met Lys Asp Pro Phe Leu 645 650 655 Gly Phe Thr Asp Ala Arg Gin Ser Pro Phe Ala Thr Ser Ser Glu His 660 665 670 Ser Ser Glu Asn Gly Ser Leu Arg Phe Ser Thr Pro Pro Gly Asp Leu 675 680 685 Leu Asp Gly Gly Leu Ser Gly Arg Ser Gly Thr Ala Ser Gly Gly Ser 690 695 700 Thr Pro His Leu Gly Gly Pro Gly Pro Gly Arg Pro Ser Ser Lys Glu 705 710 715 720 Gly Arg Arg Ser Asp Thr Cys Glu Tyr Cys Gly Lys Val Phe Lys Asn 725 730 735 Cys Ser Asn Leu Thr Val Eis Arg Arg Ser His Thr Gly Glu Arg Pro

740 745 750 Tyr Lys Cys Glu Leu Cys Asn Tyr Ala Cys Ala Gln Ser Ser Lys Leu 755 760 765 Thr Arg His Met Lys Thr His Gly Gln Ile Gly Lys Glu Val Tyr Arg 770 775 780 Cys Asp lle Cys Gln Met Pro Phe Ser Val Tyr Ser Thr Leu Glu Lys 785 ) 790 795 800 His Met Lys Lys Trp His Gly Glu His Leu Leu Thr Asn Asp Val Lys 805 810 B15 Ile Glu Gln Ala Glu Arg Ser 820 <210> 2947 <211> 441 <212> PRT <213> Homo sapiens <400> 2947 Met Val Pro Pro Lys Leu His Val Leu Phe Cys Leu Cys Gly Cys Leu 1 5 10 15 Ala Val Val Tyr Pro Phe Asp Trp Gln Tyr Ile Asn Pro Val Ala His Met Lys Ser Ser Ala Trp Val Asn Lys Ile Gln Val Leu Met Ala Ala 40 45 Ala Ser Phe Gly Gln Thr Lys Ile Pro Arg Gly Asn Gly Pro Tyr Ser

50 . 55 60 val Gly Cys Thr Asp Leu Met Phe Asp His Thr Asn Lys Gly Thr Phe 65 70 75 80 Leu Arg Leu Tyr Tyr Pro Ser Gln Asp Asn Asp Arg Leu Asp Thr Leu 85 90 95 Trp Ile Pro Asn Lys Glu Tyr Phe Trp Gly Leu Ser Lys Phe Leu Gly 100 105 110 Thr His Trp Leu Met Gly Asn Ile Leu Arg Leu Leu Phe Gly Ser Met 115 120 125

Thr Thr Pro Ala Asn Trp Asn Ser Pro Leu Arg Pro Gly Glu Lys Tyr 130 135 140 Pro Leu Val Val Phe Ser His Gly Leu Gly Ala Phe Arg Thr Leu Tyr 145 150 155 160 Ser Ala Ile Gly Ile Asp Leu Ala Ser His Gly Phe Ile Val Ala Ala 165 170 175 Val Glu His Arg Asp Arg Ser Ala Ser Ala Thr Tyr Tyr Phe Lys Asp 180 185 150 Gln Ser Ala Ala Glu Ile Gly Asp Lys Ser Trp Leu Tyr Leu Arg Thr 185 200 205 Leu Lys Gln Glu Glu Glu Thr His Ile Arg Asn Glu Gln Val Arg Gln 210 215 220 Arg Ala Lys Glu Cys Ser Gln Ala Leu Ser Leu Ile Leu Asp Ile Asp 225 230 235 240 His Gly Lys Pro Val Lys Asn Ala Leu Asp Leu Lys Phe Asp Met Glu 245 250 255 Gln Leu Lys Asp Ser Ile Asp Arg Glu Lys Ile Ala Val Ile Gly His 260 265 270 Ser Phe Gly Gly Ala Thr Val Ile Gln Thr Leu Ser Glu Asp Gln Arg 275 280 285 Phe Arg Cys Gly Ile Ala Leu Asp Ala Trp Met Phe Pro Leu Gly Asp 290 285 300 Glu Val Tyr Ser Arg Ile Pro Gln Pro Leu Phe Phe Ile Asn Ser Glu 305 310 315 320 Tyr Phe Gln Tyr Pro Ala Asn Ile Ile Lys Met Lys Lys Cys Tyr Ser 325 330 } 335 . Pro Asp Lys Glu Arg Lys Met Ile Thr Ile Arg Gly Ser Val His Gln 340 345 350 Asn Phe Ala Asp Phe Thr Phe Ala Thr Gly Lys Ile Ile Gly His Met 355 360 365

PCT/US2003/012946

Leu Lys Leu Lys Gly Asp Ile Asp Ser Asn Val Ala Ile Asp Leu Ser 370 375 380 Asn Lys Ala Ser Leu Ala Phe Leu Gln Lys His Leu Gly Leu His Lys 385 390 395 400 Asp Phe Asp Gln Trp Asp Cys Leu Ile Glu Gly Asp Asp Glu Asn Leu 405 410 415 Ile Pro Gly Thr Asn Ile Asn Thr Thr Asn Gln His Ile Met Leu Gln 420 425 430 ) Asn Ser Ser Gly Ile Glu Lys Tyr Asn 435 440 <210> 2948 <211> 1044 <212> PRT <213> Homo sapiens <400> 2948 ’ Met Pro Pro Gly val Asp Cys Pro Met Glu Phe Trp Thr Lys Glu Glu 1 5 10 15 Asn Gln Ser val val val Asp Phe Leu Leu Pro Thr Gly val Tyr Leu

Asn Phe Pro Val Ser Arg Asn Ala Asn Leu Ser Thr Ile Lys Gln Leu 40 45 leu Trp His Arg Ala Gln Tyr Glu Pro Leu Phe His Met Leu Ser Gly 50 55 60 Pro Glu Ala Tyr val Phe Thr Cys Ile Asn Gln Thr Ala Glu Gln Gln 65 70 75 80 Glu Leu Glu Asp Glu Gln Arg Arg Leu Cys Asp Val Gln Pro Phe Leu 85 90 95 Pro Val Leu Arg Leu val Ala Arg Glu Gly Asp Arg val Lys Lys Leu 100 105 110 Ile Asn Ser Gln Ile Ser Leu Leu Ile Gly Lys Gly Leu His Glu Phe 118 120 125 Asp Ser Leu Cys Asp Pro Glu Val Asn Asp Phe Arg Ala Lys Met Cys 130 135 140

Gln Phe Cys Glu Glu Ala Ala Ala Arg Arg Gln Gln Leu Gly Trp Glu 145 150 155 160 Ala Trp Leu Gln Tyr Ser Phe Pro Leu Gln Leu Glu Pro Ser Ala Gln 165 170 175 Thr Trp Gly Pro Gly Thr Leu Arg Leu Pro Asn Arg Ala Leu Leu Val 180 185 190 Asn Val Lys Phe Glu Gly Ser Glu Glu Ser Phe Thr Phe Gln Val Ser 195 200 205 Thr Lys Asp Val Pro Leu Ala Leu Met Ala Cys Ala Leu Arg Lys Lys 210 215 220 Ala Thr Val Phe Arg Gln Pro Leu Val Glu Gln Pro Glu Asp Tyr Thr 225 230 235 240 Leu Gln Val Asn Gly Arg His Glu Tyr Leu Tyr Gly Asn Tyr Pro Leu 245 250 255 Cys Gln Phe Gln Tyr Ile Cys Ser Cys Leu His Ser Gly Leu Thr Pro 260 265 270 His Leu Thr Met Val His Ser Ser Ser Ile Leu Ala Met Arg Asp Glu 275 280 285 Gln Ser Asn Pro Ala Pro Gln Val Gln Lys Pro Arg Ala Lys Pro Pro 290 295 300 Pro Ile Pro Ala Lys Lys Pro Ser Ser Val Ser Leu Trp Ser Leu Glu 305 310 315 320 Gln Pro Phe Arg Ile Glu Leu Ile Gln Gly Ser Lys Val Asn Ala Asp 325 330 335 Glu Arg Met Lys Leu Val Val Gln Ala Gly Leu Phe His Gly Asn Glu 340 345 350 Met Leu Cys Lys Thr Val Ser Ser Ser Glu Val Ser Val Cys Ser Glu 355 360 365 Pro Val Trp Lys Gln Arg Leu Glu Phe Asp Ile Asn Ile Cys Asp Leu 370 378 380

Pro Arg Met Ala Arg Leu Cys Phe Ala Leu Tyr Ala Val Ile Glu Lys 385 390 385 400 Ala Lys Lys Ala Arg Ser Thr Lys Lys Lys Ser Lys Lys Ala Asp Cys 405 410 415 Pro Ile Ala Trp Ala Asn Leu Met Leu Phe Asp Tyr Lys Asp Gln Leu 420 425 430 Lys Thr Gly Glu Arg Cys Leu Tyr Met Trp Pro Ser Val Pro Asp Glu 435 440 445 Lys Gly Glu Leu Leu Asn Pro Thr Gly Thr Val Arg Ser Asn Pro Asn 450 455 460 Thr Asp Ser Ala Ala Ala Leu Leu Ile Cys Leu Pro Glu Val Ala Pro 465 470 47s 480 His Pro Val Tyr Tyr Pro Ala Leu Glu Lys Ile Leu Glu Leu Gly Arg 485 490 495 His Ser Glu Cys Val His Val Thr Glu Glu Glu Gln Leu Gln Leu Arg 500 505 510 Glu Ile Leu Glu Arg Arg Gly Ser Gly Glu Leu Tyr Glu His Glu Lys 515 520 525 Asp Leu Val Trp Lys Leu Arg His Glu Val Gln Glu His Phe Pro Glu 530 535 540 Ala Leu Ala Arg Leu Leu Leu Val Thr Lys Trp Asn Lys His Glu Asp 545 550 555 560 Val Ala Gln Met Leu Tyr Leu Leu Cys Ser Trp Pro Glu Leu Pro Val 565 570 575 Leu Ser Ala Leu Glu Leu Leu Asp Phe Ser Phe Pro Asp Cys His val 580 585 590 Gly Ser Phe Ala Ile Lys Ser Leu Arg Lys Leu Thr Asp Asp Glu Leu 595 600 605 Phe Gln Tyr Leu Leu Gln Leu Val Gln Val Leu Lys Tyr Glu Ser Tyr 610 615 620

Leu Asp Cys Glu Leu Thr Lys Phe Leu Leu Asp Arg Ala Leu Ala Asn 625 630 635 640 Arg Lys Ile Gly His Phe Leu Phe Trp His Leu Arg Ser Glu Met His 645 650 655 Val Pro Ser Val Ala Leu Arg Phe Gly Leu Ile Leu Glu Ala Tyr Cys 660 665 670 i Arg Gly Ser Thr His His Met Lys Val Leu Met Lys Gln Gly Glu Ala 675 680 685 Leu Ser Lys Leu Lys Ala Leu Asn Asp Phe Val Lys Leu Ser Ser Gln 690 695 700 Lys Thr Pro Lys Pro Gln Thr Lys Glu Leu Met His Leu Cys Met Arg 705 710 715 720 Gln Glu Ala Tyr Leu Glu Ala Leu Ser His Leu Gln Ser Pro Leu Asp 725 730 735 Pro Ser Thr Leu Leu Ala Glu Val Cys Val Glu Gln Cys Thr Phe Met 740 745 750 Asp Ser Lys Met Lys Pro Leu Trp Ile Met Tyr Ser Asn Glu Glu Ala 755 760 765 Gly Ser Gly Gly Ser Val Gly Ile Ile Phe Lys Asn Gly Asp Asp Leu 770 775 780 Arg Gln Asp Met Leu Thr Leu Gln Met Ile Gln Leu Met Asp Val Leu 785 790 795 800 Trp Lys Gln Glu Gly Leu Asp Leu Arg Met Thr Pro Tyr Gly Cys Leu 805 810 815 Pro Thr Gly Asp Arg Thr Gly Leu Ile Glu Val Val Leu Arg Ser Asp 820 825 830 Thr Ile Ala Asn Ile Gln Leu Asn Lys Ser Asn Met Ala Ala Thr Ala 835 840 845 Ala Phe Asn Lys Asp Ala Leu Leu Asn Trp Leu Lys Ser Lys Asn Pro 850 855 860 Gly Glu Ala Leu Asp Arg Ala Ile Glu Glu Phe Thr Leu Ser Cys Ala

865 870 875 880 Gly Tyr Cys Val Ala Thr Tyr Val Leu Gly Ile Gly Asp Arg His Ser 885 8390 895 Asp Asn Ile Met Ile Arg Glu Ser Gly Gln Leu Phe His Ile Asp Phe S00 905 S10 Gly His Phe Leu Gly Asn Phe Lys Thr Lys Phe Gly Ile Asn Arg Glu 915 820 825 Arg Val Pro Phe Ile Leu Thr Tyr Asp Phe Val His Val Ile Gln Gln 930 935 840 Gly Lys Thr Asn Asn Ser Glu Lys Phe Glu Arg Phe Arg Gly Tyr Cys 945 950 955 960 Glu Arg Ala Tyr Thr Ile Leu Arg Arg His Gly Leu Leu Phe Leu His 965 $70 975 Leu Phe Ala Leu Met Arg Ala Ala Gly Leu Pro Glu Leu Ser Cys Ser 980 $85 990 Lys Asp Ile Gln Tyr Leu Lys Asp Ser Leu Ala Leu Gly Lys Thr Glu 385 1000 1005 Glu Glu Ala Leu Lys His Phe Arg Val Lys Phe Asn Glu Ala Leu 1010 1015 1620 Arg Glu Ser Trp Lys Thr Lys Val Asn Trp Leu Ala His Asn Val 1025 1030 1035 Ser Lys Asp Asn Arg Gln ©1040 «210> 2949 <211> 167 <212> PRT <213> Homo sapiens <400> 2949 Met Glu His Ile His Asp Ser Asp Gly Ser Ser Ser Ser Ser His Gln 1 S 10 15 Ser Leu Lys Ser Thr Ala Lys Trp Ala Ala Ser Leu Glu Asn Leu Leu

Glu Asp Pro Glu Gly Val Lys Arg Phe Arg Glu Phe Leu Lys Lys Glu 35 40 45

Phe Ser Glu Glu Asn Val Leu Phe Trp Leu Ala Cys Glu Asp Phe Lys

50 55 60 )

Lys Met Gln Asp Lys Thr Gln Met Gln Glu Lys Ala Lys Glu Ile Tyr

€5 70 75 80

Met Thr Phe Leu Ser Ser Lys Ala Ser Sex Gln Val Asn Val Glu Gly

85 90 95 Gln Ser Arg Leu Asn Glu Lys Ile Leu Glu Glu Pro His Pro Leu Met 100 105 110

Phe Gln Lys Leu Gln Asp Gln Ile Phe Asn Leu Met Lys Tyr Asp Ser 115 120 125

Tyr Ser Arg Phe Leu Lys Ser Asp Leu Phe Leu Lys His Lys Arg Thr

130 135 140

Glu Glu Glu Glu Glu Asp Leu Pro Asp Ala Gln Thr Ala Ala Lys Arg

145 150 155 160

Ala Ser Arg Ile Tyr Asn Thr

165

<210> 2950

<211l> 263

<212> PRT

<213> Homo sapiens

<400> 2950

Met Val Lys Ile Ala Phe Asn Thr Pro Thr Ala Val Gln Lys Glu Glu

1 5 10 15

Ala Arg Gln Asp Val Glu Ala Leu Leu Ser Arg Thr val Arg Thr Gln

Tle Leu Thr Gly Lys Glu Leu Arg Val Ala Thr Gln Glu Lys Glu Gly 40 45

Ser Ser Gly Arg Cys Met Leu Thr Leu Leu Gly Leu Ser Phe Ile Leu

50 55 60 Ala Gly Leu Ile Val Gly Gly Ala Cys Ile Tyr Lys Tyr Phe Met Pro

65 70 75 80 Lys Ser Thr Ile Tyr Arg Gly Glu Met Cys Phe Phe Asp Ser Glu Asp 85 90 9s Pro Ala Asn Ser Leu Arg Gly Gly Glu Pro Asn Phe Leu Pro val Thr 100 105 110 Glu Glu Ala Asp Ile Arg Glu Asp Asp Asn Ile Ala Ile Ile Asp Val 115 120 125 Pro Val Pro Ser Phe Ser Asp Ser Asp Pro Ala Ala Ile Ile His Asp 130 135 140 Phe Glu Lys Gly Met Thr Ala Tyr Leu Asp Leu Leu Leu Gly Asn Cys 145 150 155 160 Tyr Leu Met Pro Leu Asn Thr Ser Ile Val Met Pro Pro Lys Asn Leu 165 170 175 Val Glu Leu Phe Gly Lys Leu Ala Ser Gly Arg Tyr Leu Pro Gln Thr 180 185 190 Tyr Val val Arg Glu Asp Leu Val Ala Val Glu Glu Ile Arg Asp Val 195 200 205 Ser Asn Leu Gly Ile Phe Ile Tyr Gln Leu Cys Asn Asn Arg Lys Ser . 210 215 220 Phe Arg Leu Arg Arg Arg Asp Leu Leu Leu Gly Phe Asn Lys Arg Ala 225 230 235 240 Ile Asp Lys Cys Trp Lys Ile Arg His Phe Pro Asn Glu Phe Ile Val 245 250 255 Glu Thr Lys Ile Cys Gln Glu 260 <210> 2951 <211l> 201 <212> PRT <213> Homo sapiens <400> 2951 Met Asp Pro Gly Trp Pro Cys Cys Pro Leu Pro Val Ala Phe Leu Ser 1 5 10 15

Arg Trp Leu Gln Ser Phe Val Asp Gly Leu Phe Cys Thr Gly Gly Leu

Leu Arg Gln Arg Thr Cys Lys Phe Ala Gly Ala Ala Ser Gln Ala Pro 40 45 His Ala Pro Ala Phe Leu Arg Ala Arg Gly Glu Pro Gln Asp Pro Leu 50 55 60 Ser His Pro Arg Val Pro Ala Val Ser Ala Asn Cys Arg Met Trp Lys 65 70 75 80 His Leu Pro Val His Ser Ser Pro Thr Pro Arg Leu Thr Pro Leu Trp 85 90 95 Lys Leu Gln Ala Arg Trp Leu Leu Pro Gln Leu Val Tyr Leu Gln Gly 100 105 110 Trp Gly Ser Tyr Ser Leu Leu Arg Pro Ala Ala Leu Ile Ser Met Val 115 120 125 : Leu Leu Ala Arg Glu Phe Leu Tyr Pro Ala Lys Met Ser Val Ser Glu 130 135 140 Val Cys Ser Ser Gly Leu Ser Ser Pro Leu Leu Glu Gln His Lys Thr 145 150 155 160 Asn Leu Ile Phe Tyr Ala Ser Gly Asp Ile Cys Ser Ala Asn Gly Lys 165 170 175 Ser Gly Phe Asn Gln Pro Leu Pro Phe Leu Lys Thr Phe Cys Ser Thr 180 185 150 His Arg Ile Leu Ser Cys Thr Tyr Leu 195 200 <210> 2952 <211> 492 <212> PRT <213> Homo sapiens <400> 2952 Met Ser Asp Tyr Glu Asn Asp Asp Glu Cys Trp Ser Val Leu Glu Gly 1 5 10 15 Phe Arg Val Thr Leu Thr Ser Val Ile Asp Pro Ser Arg Ile Thr Pro

Tyr Leu Arg Gln Cys Lys Val Leu Asn Pro Asp Asp Glu Glu Gln Val 40 45 Leu Ser Asp Pro Asn Leu Val Ile Arg Lys Arg Lys Val Gly Val Leu 50 55 60 Leu Asp Ile Leu Gln Arg Thr Gly His Lys Gly Tyr Val Ala Phe Leu 65 70 75 BO Glu Ser Leu Glu Leu Tyr Tyr Pro Gln Leu Tyr Lys Lys Val Thr Gly 85 90 95 Lys Glu Pro Ala Arg Val Phe Ser Met Ile Ile Asp Ala Ser Gly Glu 100 105 110 Ser Gly Leu Thr Gln Leu Leu Met Thr Glu Val Met Lys Leu Gln Lys 115 120 125 Lys Val Gln Asp Leu Thr Ala Leu Leu Ser Ser Lys Asp Asp Phe Ile 130 135 140 Lys Glu Leu Arg Val Lys Asp Ser Leu Leu Arg Lys His Gln Glu Arg 145 150 155 160 Val Gln Arg Leu Lys Glu Glu Cys Glu Ala Gly Ser Arg Glu Leu Lys CC 165 : 170 175 Arg Cys Lys Glu Glu Asn Tyr Asp Leu Ala Met Arg Leu Ala His Gln 180 185 130 Ser Glu Glu Lys Gly Ala Ala Leu Met Arg Asn Arg Asp Leu Gln Leu 195 200 205 Glu Ile Asp Gln Leu Lys His Ser Leu Met Lys Ala Glu Asp Asp Cys 210 215 220 Lys Val Glu Arg Lys His Thr Leu Lys Leu Arg His Ala Met Glu Gln 225 230 235 240 Arg Pro Ser Gln Glu Leu Leu Trp Glu Leu Gln Gln Glu Lys Ala Leu 245 250 255 Leu Gln Ala Arg Val Gln Glu Leu Glu Ala Ser Val Gln Glu Gly Lys 260 265 270

PCT/US2003/012946

Leu Asp Arg Ser Ser Pro Tyr Ile Gln Val Leu Glu Glu Asp Trp Arg 275 ’ 280 285 Gln Ala Leu Arg Asp His Gln Glu Gln Ala Asn Thr Ile Phe Ser Leu 290 295 300 Arg Lys Asp Leu Arg Gln Gly Glu Ala Arg Arg Leu Arg Cys Met Glu 305 310 315 320 Glu Lys Glu Met Phe Glu Leu Gln Cys Leu Ala Leu Arg Lys Asp Ser 325 330 335 Lys Met Tyr Lys Asp Arg Ile Glu Ala Ile Leu Leu Gln Met Glu Glu 340 345 350 Val Ala Ile Glu Arg Asp Gln Ala Ile Ala Thr Arg Glu Glu Leu His 355 360 365 Ala Gln His Ala Arg Gly Leu Gln Glu Lys Asp Ala Leu Arg Lys Gln 370 375 380 Val Arg Glu Leu Gly Glu Lys Ala Asp Glu Leu Gln Leu Gln Val Phe 385 390 395 400 Gln Cys Glu Ala Gln Leu Leu Ala val Glu Gly Arg Leu Arg Arg Gln 405 410 415 Gln Leu Glu Thr Leu Val Leu Ser Ser Asp Leu Glu Asp Gly Ser Pro 420 425 430 Arg Arg Ser Gln Glu Leu Ser Leu Pro Gln Asp Leu Glu Asp Thr Gln 435 440 445 Leu Ser Asp Lys Gly Cys Leu Ala Gly Gly Gly Ser Pro Lys Gln Pro 450 455 460 Phe Ala Ala Leu His Gln Glu Gln Val Leu Arg Asn Pro His Asp Ala 465 470 475 480 Gly Pro Ala Gly Leu Pro Gly Ile Gly Ala val Cys 485 490 <210> 2953 <21l1l> 92 <212> PRT

<213> Homo sapiens <400> 2953 Met Lys Leu Cys Val Thr Val Leu Ser Leu Leu Met Leu Val Ala Ala 1 5 10 15 Phe Cys Ser Pro Ala Leu Ser Ala Pro Met Gly Ser Asp Pro Pro Thr

Ala Cys Cys Phe Ser Tyr Thr Ala Arg Lys Leu Pro Arg Asn Phe Val 40 45 Val Asp Tyr Tyr Glu Thr Ser Ser Leu Cys Ser Gln Pro Ala Val Val 50 55 60 Phe Gln Thr Lys Arg Ser Lys Gln Val Cys Ala Asp Pro Ser Glu Ser 6S : 70 75 80 Trp Val Gln Glu Tyr Val Tyr Asp Leu Glu Leu Asn 8S 90 <210> 2954 <21l1l> 266 <212> PRT <213> Homo sapiens <400> 2954 i Met Val Cys Leu Lys Leu Pro Gly Gly Ser Cys Met Thr Ala Leu Thr 1 5 10 15 Val Thr Leu Met Val Leu Ser Ser Pro Leu Ala Leu Ala Gly Asp Thr 20 25 30 Arg Pro Arg Phe Leu Trp Gln Leu Lys Phe Glu Cys His Phe Phe Asn 35 40 45 Gly Thr Glu Arg Val Arg Leu Leu Glu Arg Cys Ile Tyr Asn Gln Glu S50 55 60 Glu Ser Val Arg Phe Asp Ser Asp Val Gly Glu Tyr Arg Ala Val Thr 65 70 75 80 Glu Leu Gly Arg Pro Asp Ala Glu Tyr Trp Asn Ser Gln Lys Asp Leu 85 80 95 Leu Glu Gln Arg Arg Ala Ala Val Asp Thr Tyr Cys Arg His Asn Tyr 100 105 110

Gly Val Gly Glu Ser Phe Thr Val Gln Arg Arg Val Glu Pro Lys Val 115 120 125 Thr Val Tyr Pro Ser Lys Thr Gln Pro Leu Gln His His Asn Leu Leu 130 135 140 Val Cys Ser val Ser Gly Phe Tyr Pro Gly Ser Ile Glu Val Arg Trp 145 150 155 160 Phe Arg Asn Gly Gln Glu Glu Lys Ala Gly Val val Ser Thr Gly Leu 165 170 175 Ile Gln Asn Gly Asp Trp Thr Phe Gln Thr Leu Val Met Leu Glu Thr 180 185 190 Val Pro Arg Ser Gly Glu Val Tyr Thr Cys Gln Val Glu His Pro Ser 1395 200 205 Val Thr Ser Pro Leu Thr val Glu Trp Arg Ala Arg Ser Glu Ser Ala 210 215 220 Gln Ser Lys Met Leu Ser Gly Val Gly Gly Phe Val Leu Gly Leu Leu 225 230 235 240 Phe Leu Gly Ala Gly Leu Phe Ile Tyr Phe Arg Asn Gln Lys Gly His 245 250 255 Ser Gly Leu Gln Pro Thr Gly Phe Leu Ser 260 265 <210> 2955 <211> 359 <212> PRT <213> Homo sapiens <400> 2955 Met Ala Glu Ala Ile Thr Tyr Ala Asp Leu Arg Phe Val Lys Ala Pro 1 5 10 15 Leu Lys Lys Ser Ile Ser Ser Arg Leu Gly Gln Asp Pro Gly Ala Asp

Asp Asp Gly Glu Ile Thr Tyr Glu Asn Val Gln Val Pro Ala Val Leu 40 45

Gly Val Pro Ser Ser Leu Ala Ser Ser Val Leu Gly Asp Lys Ala Ala So 55 60 val Lys Ser Glu Gln Pro Thr Ala Ser Trp Arg Ala Val Thr Ser Pro 65 70 75 80 Ala Val Gly Arg Ile Leu Pro Cys Arg Thr Thr Cys Leu Arg Tyr Leu 85 90 95 Leu Leu Gly Leu Leu Leu Thr Cys Leu Leu Leu Gly Val Thr Ala Ile 100 105 110 Cys Leu Gly Val Arg Tyr Leu Gln Val Ser Gln Gln Leu Gln Gln Thr 115 120 125 Asn Arg Val Leu Glu Val Thr Asn Ser Ser Leu Arg Gln Gln Leu Arg 130 135 140 Leu Lys Ile Thr Gln Leu Gly Gln Ser Ala Glu Asp Leu Gln Gly Ser 145 150 155 160 Arg Arg Glu Leu Ala Gln Ser Gln Glu Ala Leu Gln Val Glu Gln Arg 165 170 175 Ala His Gln Ala Ala Glu Gly Gln Leu Gln Ala Cys Gln Ala Asp Arg 180 185 190 Gln Lys Thr Lys Glu Thr Leu Gln Ser Glu Glu Gln Gln Arg Arg Ala 195 200 205 Leu Glu Gln Lys Leu Ser Asn Met Glu Asn Arg Leu Lys Pro Phe Phe 210 215 220 Thr Cys Gly Ser Ala Asp Thr Cys Cys Pro Ser Gly Trp Ile Met His 225 230 235 240 Gln Lys Ser Cys Phe Tyr Ile Ser Leu Thr Ser Lys Asn Trp Gln Glu 245 250 255 Ser Gln Lys Gln Cys Glu Thr Leu Ser Ser Lys Leu Ala Thr Phe Ser 260 265 270 Glu Ile Tyr Pro Gln Ser His Ser Tyr Tyr Phe Leu Asn Ser Leu Leu 275 280 285 Pro Asn Gly Gly Ser Gly Asn Ser Tyr Trp Thr Gly Leu Ser Ser Asn

290 295 300 Lys Asp Trp Lys Leu Thr Asp Asp Thr Gln Arg Thr Arg Thr Tyr Ala 305 310 315 320 Gln Ser Ser Lys Cys Asn Lys Val His Lys Thr Trp Ser Trp Trp Thr 325 330 335 Leu Glu Ser Glu Ser Cys Arg Ser Ser Leu Pro Tyr Ile Cys Glu Met 340 345 350 Thr Ala Phe Arg Phe Pro Asp 355 <210> 2956 «211> 643 <212> PRT <213> Homo sapiens <400> 2956 Met Gln Ala Pro Arg Glu Leu Ala Val Gly Ile Asp Leu Gly Thr Thr 1 5) 10 15 Tyr Ser Cys Val Gly Val Phe Gln Gln Gly Arg Val Glu Ile Leu Ala

Asn Asp Gln Gly Asn Arg Thr Thr Pro Ser Tyr Val Ala Phe Thr Asp 40 45 Thr Glu Arg Leu Val Gly Asp Ala Ala Lys Ser Gln Ala Ala Leu Asn 50 55 60 Pro His Asn Thr Val Phe Asp Ala Lys Arg Leu Ile Gly Arg Lys Phe 65 70 75 80 Ala Asp Thr Thr val Gln Ser Asp Met Lys His Trp Pro Phe Arg Val 85 90 95 val Ser Glu Gly Gly Lys Pro Lys Val Pro Val Ser Tyr Arg Gly Glu 100 105 110 Asp Lys Thr Phe Tyr Pro Glu Glu Ile Ser Ser Met Val Leu Ser Lys 115 120 125 Met Lys Glu Thr Ala Glu Ala Tyr Leu Gly Gln Pro Val Lys His Ala 130 135 140

PCT/US2003/012946

Val Ile Thr val Pro Ala Tyr Phe Asn Asp Ser Gln Arg Gln Ala Thr

145 150 155 160 Lys Asp Ala Gly Ala Ile Ala Gly Leu Asn Val Leu Arg Ile Ile Asn

165 170 175 Glu Pro Thr Ala Ala Ala Ile Ala Tyr Gly Leu Asp Arg Arg Gly Ala 180 185 190 Gly Glu Arg Asn Val Leu Ile Phe Asp Leu Gly Gly Gly Thr Phe Asp 195 200 205 Val Ser Val Leu Ser Ile Asp Ala Gly Val Phe Glu Val Lys Ala Thr 210 215 220 Ala Gly Asp Thr His Leu Gly Gly Glu Asp Phe Asp Asn Arg Leu Val 225 230 235 240 Asn His Phe Met Glu Glu Phe Arg Arg Lys His Gly Lys Asp Leu Ser 245 250 255 Gly Asn Lys Arg Ala Leu Gly Arg Leu Arg Thr Ala Cys Glu Arg Ala 260 265 270 Lys Arg Thr Leu Ser Ser Ser Thr Gln Ala Thr Leu Glu Ile Asp Ser 275 280 2885 Leu Phe Glu Gly Val Asp Phe Tyr Thr Ser Ile Thr Arg Ala Arg Phe 290 295 300 Glu Glu Leu Cys Ser Asp Leu Phe Arg Ser Thr Leu Glu Pro Val Glu 305 310 315 320 Lys Ala Leu Arg Asp Ala Lys Leu Asp Lys Ala Gln Ile His Asp val 325 330 335 Val Leu Val Gly Gly Ser Thr Arg Ile Pro Lys Val Gln Lys Leu Leu 340 345 350 Gln Asp Phe Phe Asn Gly Lys Glu Leu Asn Lys Ser Ile Asn Pro Asp 355 360 365 Glu Ala val Ala Tyr Gly Ala Ala Val Gln Ala Ala Val Leu Met Gly 370 375 380

Asp Lys Cys Glu Lys Val Gln Asp Leu Leu Leu Leu Asp Val Ala Pro 385 390 395 400 Leu Ser Leu Gly Leu Glu Thr Ala Gly Gly val Met Thr Thr Leu Ile 405 410 415 Gln Arg Asn Ala Thr Ile Pro Thr Lys Gln Thr Gln Thr Phe Thr Thr 420 425 430 Tyr Ser Asp Asn Gln Pro Gly Val Phe Ile Gln Val Tyr Glu Gly Glu 435 440 445 Arg Ala Met Thr Lys Asp Asn Asn Leu Leu Gly Arg Phe Glu Leu Ser 450 455 460 Gly Ile Pro Pro Ala Pro Arg Gly val Pro Gln Ile Glu Val Thr Phe 465 470 475 480 Asp Ile Asp Ala Asn Gly Ile Leu Ser Val Thr Ala Thr Asp Arg Ser 485 490 495 Thr Gly Lys Ala Asn Lys Ile Thr Ile Thr Asn Asp Lys Gly Arg Leu 500 505 510 Ser Lys Glu Glu Val Glu Arg Met Val His Glu Ala Glu Gln Tyr Lys 515 520 525 Ala Glu Asp Glu Ala Gln Arg Asp Arg Val Ala Ala Lys Asn Ser Leu 530 535 540 Glu Ala His Val Phe His Val Lys Gly Ser Leu Gln Glu Glu Ser Leu 545 550 555 560 Arg Asp Lys Ile Pro Glu Glu Asp Arg Arg Lys Met Gln Asp Lys Cys 565 S70 575 Arg Glu Val Leu Ala Trp Leu Glu His Asn Gln Leu Ala Glu Lys Glu 580 585 590 Glu Tyr Glu His Gln Lys Arg Glu Leu Glu Gln Ile Cys Arg Pro Ile 595 600 605 Phe Ser Arg Leu Tyr Gly Gly Pro Gly val Pro Gly Gly Ser Ser Cys 610 615 620 Gly Thr Gln Ala Arg Gln Gly Asp Pro Ser Thr Gly Pro Ile Ile Glu

625 630 635 640 Glu Val Asp <210> 2957 <211l> 565 <212> PRT } <213> Homo sapiens <400> 2957 Met Ala Glu Gly Lys Ala Gly Gly Ala Ala Gly Leu Phe Ala Lys Gln 1 5 16 15 Val Gln Lys Lys Phe Ser Arg Ala Gln Glu Lys Val Leu Gln Lys Leu

Gly Lys Ala Val Glu Thr Lys Asp Glu Arg Phe Glu Gln Ser Ala Asn 40 45 Asn Phe Tyr Gln Gln Gln Ala Glu Gly His Lys Leu Tyr Lys Asp Leu 50 55 60 Lys Asn Phe Leu Ser Ala Val Lys Val Met His Glu Ser Ser Lys Arg 65 70 75 80 Val Ser Glu Thr Leu Gln Glu Ile Tyr Ser Ser Glu Trp Asp Gly His 85 90 95 Glu Glu Leu Lys Ala Ile Val Trp Asn Asn Asp Leu Leu Trp Glu Asp 100 : 105 110 Tyr Glu Glu Lys Leu Ala Asp Gln Ala Val Arg Thr Met Glu Ile Tyr 115 120 125 Val Ala Gln Phe Ser Glu Ile Lys Glu Arg Ile Ala Lys Arg Gly Arg 130 135 140 Lys Leu Val Asp Tyr Asp Ser Ala Arg His His Leu Glu Ala Val Gln 145 150 155 160 Asn Ala Lys Lys Lys Asp Glu Ala Lys Thr Ala Lys Ala Glu Glu Glu 165 170 175 Phe Asn Lys Ala Gln Thr Val Phe Glu Asp Leu Asn Gln Glu Leu Leu 180 185 190

Glu Glu Leu Pro Ile Leu Tyr Asn Ser Arg Ile Gly Cys Tyr Val Thr 185 200 205 Ile Phe Gln Asn Ile Ser Asn Leu Arg Asp Val Phe Tyr Arg Glu Met 210 215 220 Ser Lys Leu Asn His Asn Leu Tyr Glu Val Met Ser Lys Leu Glu Lys 225 230 235 240 Gln His Ser Asn Lys Val Phe Val Val Lys Gly Leu Ser Ser Ser Ser 245 250 255 Arg Arg Ser Leu Val Ile Ser Pro Pro Val Arg Thr Ala Thr Val Ser 260 265 270 Ser Pro Leu Thr Ser Pro Thr Ser Pro Ser Thr Leu Ser Leu Lys Ser 275 280 285 Glu Ser Glu Ser Val Ser Ala Thr Glu Asp Leu Ala Pro Asp Ala Ala 2590 2385 300 Gln Gly Glu Asp Asn Ser Glu Ile Lys Glu Leu Leu Glu Glu Glu Glu 305 310 315 320 Ile Glu Lys Glu Gly Ser Glu Ala Ser Ser Ser Glu Glu Asp Glu Pro 325 330 335 Leu Pro Ala Cys Asn Gly Pro Ala Gln Ala Gln Pro Ser Pro Thr Thr 340 345 350 Glu Arg Ala Lys Ser Gln Glu Glu Val Leu Pro Ser Ser Thr Thr Pro 355 360 365 Ser Pro Gly Gly Ala Leu Ser Pro Ser Gly Gln Pro Ser Ser Ser Ala 370 375 380 Thr Glu Val Val Leu Arg Thr Arg Thr Ala Ser Glu Gly Ser Glu Gln 385 390 395 400 Pro Lys Lys Arg Ala Ser Ile Gln Arg Thr Ser Ala Pro Pro Ser Arg 405 410 415 Pro Pro Pro Pro Arg Ala Thr Ala Ser Pro Arg Pro Ser Ser Gly Asn 420 425 430

Ile Pro Ser Ser Pro Thr Ala Ser Gly Gly Gly Ser Pro Thr Ser Pro 435 440 445 Arg Ala Ser Leu Gly Thr Gly Thr Ala Ser Pro Arg Thr Ser Leu Glu 450 455 460 Val Ser Pro Asn Pro Glu Pro Pro Glu Lys Pro Val Arg Thr Pro Glu 465 470 475 480 Ala Lys Glu Asn Glu Asn Ile His Asn Gln Asn Pro Glu Glu Leu Cys 485 4350 495 Thr Ser Pro Thr Leu Met Thr Ser Gln Val Ala Ser Glu Pro Gly Glu 500 505 510 Ala Lys Lys Met Glu Asp Lys Glu Lys Asp Asn Lys Leu Ile Ser Ala 515 520 525 Asp Ser Ser Glu Gly Gln Asp Gln Leu Gln Val Ser Met Val Pro Glu 530 535 540 Asn Asn Asn Leu Thr Ala Pro Glu Pro Gln Glu Glu Val Ser Thr Ser 545 550 585 560 Glu Asn Pro Gln Leu 565 <210> 2958 <211> 349 <212> PRT ’ <213> Homo sapiens <400> 2958 Met Glu Thr Pro Pro Val Asn Thr Ile Gly Glu Lys asp Thr Ser Gln 1 5 10 15 Pro Gin Gln Glu Trp Glu Lys Asn Leu Arg Glu Asn Leu Asp Ser Val

Ile Gln Ile Arg Gln Gln Pro Arg Asp Pro Pro Thr Glu Thr Leu Glu 40 45 Leu Glu Val Ser Pro Asp Pro Ala Ser Gln Ile Leu Glu His Thr Gln 50 55 60 Gly Ala Glu Lys Leu Val Ala Glu Leu Glu Gly Asp Ser His Lys Ser 65 70 75 80

His Gly Ser Thr Ser Gln Met Pro Glu Ala Leu Gln Ala Ser Asp Leu 85 20 95 Trp Tyr Cys Pro Asp Gly Ser Phe Val Lys Lys Ile Val Ile Arg Gly 100 105 110 His Gly Leu Asp Lys Pro Lys Leu Gly Ser Cys Cys Arg Val Leu Ala 115 120 125 Leu Gly Phe Pro Phe Gly Ser Gly Pro Pro Glu Gly Trp Thr Glu Leu 130 135 140 Thr Met Gly Val Gly Pro Trp Arg Glu Glu Thr Trp Gly Glu Leu Ile 145 150 155 160 Glu Lys Cys Leu Glu Ser Met Cys Gln Gly Glu Glu Ala Glu Leu Gln 165 170 175 Leu Pro Gly His Ser Gly Pro Pro Val Arg Leu Thr Leu Ala Ser Phe 180 185 190 Thr Gln Gly Arg Asp Ser Trp Glu Leu Glu Thr Ser Glu Lys Glu Ala 195 200 205 Leu Ala Arg Glu Glu Arg Ala Arg Gly Thr Glu Leu Phe Arg Ala Gly 210 215 220 Asn Pro Glu Gly Ala Ala Arg Cys Tyr Gly Arg Ala Leu Arg Leu Leu 225 230 235 240 Leu Thr Leu Pro Pro Pro Gly Pro Pro Glu Arg Thr val Leu His Ala 245 250 255 Asn Leu Ala Ala Cys Gln Leu Leu Leu Gly Gln Pro Gln Leu Ala Ala 260 265 270 Gln Ser Cys Asp Arg Val Leu Glu Arg Glu Pro Gly His Leu Lys Ala 275 280 285 Leu Tyr Arg Arg Gly Val Ala Gln Ala Ala Leu Gly Asn Leu Glu Lys 290 285 300 Ala Thr Ala Asp Leu Lys Lys Val Leu Ala Ile Asp Pro Lys Asn Arg 305 310 315 320

Ala Ala Gln Glu Glu Leu Gly Lys Val Val Ile Gln Gly Lys Asn Gln 325 330 33% Asp Ala Gly Leu Ala Gln Gly Leu Arg Lys Met Phe Gly 340 345 <«210> 2959 <211> 620 <212> PRT <213> Homo sapiens <400> 2959 Met Asn Asn Phe Ile Leu Leu Glu Glu Gln Leu Ile Lys Lys Ser Gln 1 5 10 15 Gln Lys Arg Arg Thr Ser Pro Ser Asn Phe Lys Val Arg Phe Phe val

Leu Thr Lys Ala Ser Leu Ala Tyr Phe Glu Asp Arg His Gly Lys Lys 40 45 Arg Thr Leu Lys Gly Ser Ile Glu Leu Ser Arg Ile Lys Cys Val Glu 50 S55 60 Ile Val Lys Ser Asp Ile Ser Ile Pro Cys His Tyr Lys Tyr Pro Phe 65 70 75 BO Gln Val Val His Asp Asn Tyr Leu Leu Tyr Val Phe Ala Pro Asp Arg 85 90 95 Glu Ser Arg Gln Arg Trp Val Leu Ala Leu Lys Glu Glu Thr Arg Asn 100 10% 110 Asn Asn Ser Leu Val Pro Lys Tyr His Pro Asn Phe Trp Met Asp Gly 115 120 125 Lys Trp Arg Cys Cys Ser Gln Leu Glu Lys Leu Ala Thr Gly Cys Ala 130 135 140 Gln Tyr Asp Pro Thr Lys Asn Ala Ser Lys Lys Pro Leu Pro Pro Thr 145 150 155 160 Pro Glu Asp Asn Arg Arg Pro Leu Trp Glu Pro Glu Glu Thr val Val 165 170 175 Ile Ala Leu Tyr Asp Tyr Gln Thr Asn Asp Pro Gln Glu Leu Ala Leu

180 185 190 Arg Arg Asn Glu Glu Tyr Cys Leu Leu Asp Ser Ser Glu Ile His Trp 198 200 205 Trp Arg Val Gln Asp Arg Asn Gly His Glu Gly Tyr Val Pro Ser Ser 210 215 220 Tyr Leu Val Glu Lys Ser Pro Asn Asn Leu Glu Thr Tyr Glu Trp Tyr 225 230 235 240 Asn Lys Ser Ile Ser Arg Asp Lys Ala Glu Lys Leu Leu Leu Asp Thr 245 250 255 Gly Lys Glu Gly Ala Phe Met Val Arg Asp Ser Arg Thr Ala Gly Thr 260 265 270 Tyr Thr val Ser val Phe Thr Lys Ala Val Val Ser Glu Asn Asn Pro 275 280 285 Cys Ile Lys His Tyr His Ile Lys Glu Thr Asn Asp Asn Pro Lys Arg 250 295 300 Tyr Tyr Val Ala Glu Lys Tyr Val Phe Asp Ser Ile Pro Leu Leu Ile 305 310 315 320 Asn Tyr His Gln His Asn Gly Gly Gly Leu Val Thr Arg Leu Arg Tyr 325 330 335 Pro Val Cys Phe Gly Arg Gln Lys Ala Pro Val Thr Ala Gly Leu Arg 340 345 350 Tyr Gly Lys Trp Val Ile Asp Pro Ser Glu Leu Thr Phe Val Gln Glu 355 360 36S Ile Gly Ser Gly Gln Phe Gly Leu Val His Leu Gly Tyr Trp Leu Asn 370 375 380 Lys Asp Lys Val Ala Ile Lys Thr Ile Arg Glu Gly Ala Met Ser Glu 385 390 3385 400 Glu Asp Phe Ile Glu Glu Ala Glu Val Met Met Lys Leu Ser His Pro 405 410 415 Lys Leu Val Gln Leu Tyr Gly Val Cys Leu Glu Gln Ala Pro Ile Cys 420 425 430

Leu Val Phe Glu Phe Met Glu His Gly Cys Leu Ser Asp Tyr Leu Arg 435 440 445 Thr Gln Arg Gly Leu Phe Ala Ala Glu Thr Leu Leu Gly Met Cys Leu 450 455 460 Asp Val Cys Glu Gly Met Ala Tyr Leu Glu Glu Ala Cys Val Ile His 465 470 475 480 Arg Asp Leu Ala Ala Arg Asn Cys Leu Val Gly Glu Asn Gln Val Ile 485 490 495 Lys Val Ser Asp Phe Gly Met Thr Arg Phe Val Leu Asp Asp Gln Tyr 500 505 510 Thr Ser Ser Thr Gly Thr Lys Phe Pro Val Lys Trp Ala Ser Pro Glu 515 520 525 Val Phe Ser Phe Ser Arg Tyr Ser Ser Lys Ser Asp Val Trp Ser Phe 530 535 540 Gly Val Leu Met Trp Glu Val Phe Ser Glu Gly Lys Ile Pro Tyr Glu 545 550 555 560 Asn Arg Ser Asn Ser Glu Val Val Glu Asp Ile Ser Thr Gly Phe Arg 565 570 575 Leu Tyr Lys Pro Arg Leu Ala Ser Thr His Val Tyr Gln Ile Met Asn 580 585 590 His Cys Trp Lys Glu Arg Pro Glu Asp Arg Pro Ala Phe Ser Arg Leu 595 600 605 Leu Arg Gln Leu Ala Glu Ile Ala Glu Ser Gly Leu 610 615 620 <210> 23960 <21l> 262 <212> PRT a. <213> Homo sapiens <400> 2960 Met Asp Pro Arg Leu Ser Thr Val Arg Gln Thr Cys Cys Cys Phe Asn 1 S 10 15

Val Arg Ile Ala Thr Thr Ala Leu Ala Ile Tyr His Val Ile Met Ser

Val Leu Leu Phe Ile Glu His Ser Val Glu Val Ala His Gly Lys Ala 40 45 Ser Cys Lys Leu Ser Gln Met Gly Tyr Leu Arg Ile Ala Asp Leu Ile SO 55 60 Ser Ser Phe Leu Leu Ile Thr Met Leu Phe Ile Ile Ser Leu Ser Leu 65 70 75 80 Leu Ile Gly Val Val Lys Asn Arg Glu Lys Tyr Leu Leu Pro Phe Leu 85 90 95 Ser Leu Gln Ile Met Asp Tyr Leu Leu Cys Leu Leu Thr Leu Leu Gly 100 105 110 Ser Tyr Ile Glu Leu Pro Ala Tyr Leu Lys Leu Ala Ser Arg Ser Arg 115 120 125 / Ala Ser Ser Ser Lys Phe Pro Leu Met Thr Leu Gln Leu Leu Asp Phe 130 135 140 Cys Leu Ser Ile Leu Thr Leu Cys Ser Ser Tyr Met Glu Val Pro Thr 145 150 155 160 Tyr Leu Asn Phe Lys Ser Met Asn His Met Asn Tyr Leu Pro Ser Gln 165 170 175 Glu Asp Met Pro His Asn Gln Phe Ile Lys Met Met Ile Ile Phe Ser 180 185 190 Ile Ala Phe Ile Thr Val Leu Ile Phe Lys Val Tyr Met Phe Lys Cys 195 200 205 Val Trp Arg Cys Tyr Arg Leu Ile Lys Cys Met Asn Ser Val Glu Glu 210 215 220 Lys Arg Asn Ser Lys Met Leu Gln Lys Val Val Leu Pro Ser Tyr Glu 225 230 235 240 Glu Ala Leu Ser Leu Pro Ser Lys Thr Pro Glu Gly Gly Pro Ala Pro 245 250 255 Pro Pro Tyr Ser Glu Val

PCT/US2003/012946

<210> 2961 <211> 467 <212> PRT <213> Homo sapiens <400> 2961 Met Gln Met Asp Asn Arg Leu Pro Pro Lys Lys Val Pro Gly Phe cys 1 5 10 15 Ser Phe Arg Tyr Gly Leu Ser Phe Leu Val His Cys Cys Asn Val Ile

Ile Thr Ala Gln Arg Ala Cys Leu Asn Leu Thr Met Val Val Met val 40 45 Asn Ser Thr Asp Pro His Gly Leu Pro Asn Thr Ser Thr Lys Lys Leu 50 55 60 Leu Asp Asn Ile Lys Asn Pro Met Tyr Asn Trp Ser Pro Asp Ile Gln 65 70 75 80 Gly Ile Ile Leu Ser Ser Thr Ser Tyr Gly Val Ile Ile Ile Gln val 85 S0 95 Pro Val Gly Tyr Phe Ser Gly Ile Tyr Ser Thr Lys Lys Met Ile Gly 100 105 110 Phe Ala Leu Cys Leu Ser Ser Val Leu Ser Leu Leu Ile Pro Pro Ala 115 120 125 Ala Gly Ile Gly val ala Trp Val Val Val Cys Arg Ala Val Gln Gly 130 135 140 Ala Ala Gln Gly Ile Val Ala Thr Ala Gln Phe Glu Ile Tyr Val Lys 145 150 155 160 Trp Ala Pro Pro Leu Glu Arg Gly Arg Leu Thr Ser Met Ser Thr Ser 165 170 175 Gly Phe Leu Leu Gly Pro Phe Ile Val Leu Leu Val Thr Gly val Ile 180 185 190 Cys Glu Ser Leu Gly Trp Pro Met Val Phe Tyr Ile Phe Gly Ala Cys 195 200 205

PCT/US2003/012946

Gly Cys Ala val Cys Leu Leu Trp Phe Val Leu Phe Tyr Asp Asp Pro 210 215 220 Lys Asp His Pro Cys Ile Ser Ile Ser Glu Lys Glu Tyr Ile Thr Ser 225 230 235 240 Ser Leu Val Gln Gln val Ser Ser Ser Arg Gln Ser Leu Pro Ile Lys 245 250 255 Ala Ile Leu Lys Ser Leu Pro Val Trp Ala Ile Ser Ile Gly Ser phe 260 265 270 Thr Phe Phe Trp Ser His Asn Ile Met Thr Leu Tyr Thr Pro Met Phe 275 280 285 Ile Asn Ser Met Leu His Val Asn Ile Lys Glu Asn Gly Phe Leu Ser 290 295 300 i Ser Leu Pro Tyr Leu Phe Ala Trp Ile Cys Gly Asn Leu Ala Gly Gln 305 310 315 320 Leu Ser Asp Phe Phe Leu Thr Arg Asn Ile Leu Ser Val Ile Ala Val 325 330 335 Arg Lys Leu Phe Thr Ala Ala Gly Phe Leu Leu Pro Ala Ile Phe Gly 340 345 350 Val Cys Leu Pro Tyr Leu Ser Ser Thr Phe Tyr Ser Ile Val Ile Phe 355 360 365 Leu Ile Leu Ala Gly Ala Thr Gly Ser Phe Cys Leu Gly Gly val phe 370 375 380 Ile Asn Gly Leu Asp Ile Ala Pro Arg Tyr Phe Gly Phe Ile Lys Ala 385 390 395 400 Cys Ser Thr Leu Thr Gly Met Ile Gly Gly Leu Ile Ala Ser Thr Leu 405 410 415 Thr Gly Leu Ile Leu Lys Gln Asp Pro Glu Ser Ala Trp Phe Lys Thr 420 425 430 Phe Ile Leu Met Ala Ala Ile Asn Val Thr Gly Leu Ile Phe Tyr Leu 435 440 445

PCT/US2003/012946

Ile val Ala Thr Ala Glu Ile Gln Asp Trp Ala Lys Glu Lys Gln His 450 455 460 Thr Arg Leu 465 <210> 2962 <211> 444 <212> PRT <213> Homo sapiens <400> 2962 Met Val Ser Gln Ala Leu Arg Leu Leu Cys Leu Leu Leu Gly Leu Gln 1 5 10 15 Gly Cys Leu Ala Ala val Phe Val THr Gln Glu Glu Ala His Gly val

Leu His Arg Arg Arg Arg Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro "35 40 45 Gly Ser Leu Glu Axg Glu Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu 50 55 60 Ala Arg Glu Ile Phe Lys Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile 65 70 75 80 Ser Tyr Ser Asp Gly Asp Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly 85 So 85 Gly Ser Cys Lys Asp Gln Leu Gln Ser Tyr Ile Cys phe Cys Leu Pro \ 100 105 110 Ala Phe Glu Gly Arg Asn Cys Glu Thr His Lys Asp Asp Gln Leu Ile 115 120 125 Cys Val Asn Glu Asn Gly Gly Cys Glu Gln Tyr Cys Ser Asp His Thr 130 135 140 Gly Thr Lys Arg Ser Cys Arg Cys His Glu Gly Tyr Ser Leu Leu Ala 145 150 155 160 Asp Gly val Ser Cys Thr Pro Thr val Glu Tyr Pro Cys Gly Lys Ile 165 170 175 Pro Ile Leu Glu Lys Arg Asn Ala Ser Lys Pro Gln Gly Arg Ile val 180 185 1380

Gly Gly Lys Val Cys Pro Lys Gly Glu Cys Pro Trp Gln Val Leu Leu 195 200 205 Leu Val Asn Gly Ala Gln Leu Cys Gly Gly Thr Leu Ile Asn Thr Ile 210 215 220 © Trp Val Val Ser Ala Ala His Cys Phe Asp Lys Ile Lys Asn Trp Arg 225 230 235 240 Asn Leu Ile Ala Val Leu Gly Glu His Asp Leu Ser Glu His Asp Gly 245 250 255 Asp Glu Gln Ser Arg Arg Val Ala Gln Val Ile Ile Pro Ser Thr Tyr 260 265 270 val Pro Gly Thr Thr Asn His Asp Ile Ala Leu Leu Arg Leu His Gln 275 280 285 Pro Val Val Leu Thr Asp His Val Val Pro Leu Cys Leu Pro Glu Arg 290 295 300 Thr Phe Ser Glu Arg Thr Leu Ala Phe Val Arg Phe Ser Leu Val Ser 305 310 315 320 Gly Trp Gly Gln Leu Leu Asp Arg Gly Ala Thr Ala Leu Glu Leu Met 325 330 335 val Leu Asn Val Pro Arg Leu Met Thr Gln Asp Cys Leu Gln Gln Ser 340 345 350 Arg Lys Val Gly Asp Ser Pro Asn Ile Thr Glu Tyr Met Phe Cys Ala 355 360 365 Gly Tyr Ser Asp Gly Ser Lys Asp Ser Cys Lys Gly Asp Ser Gly Gly 370 375 380 Pro His Ala Thr His Tyr Arg Gly Thr Trp Tyr Leu Thr Gly Ile val 385 390 395 400 Ser Trp Gly Gln Gly Cys Ala Thr Val Gly His Phe Gly Val Tyr Thr 405 410 415 Arg Val Ser Gln Tyr Ile Glu Trp Leu Gln Lys Leu Met Arg Ser Glu 420 425 430

PCT/US2003/012946

Pro arg Pro Gly Val Leu Leu Arg Ala Pro phe Pro 435 440 <210> 2963 <21ls> 272 <212> PRT <213> Homo sapiens <400> 2963 Arg Cys Lys Pro Ile Ser Gly His Asn Ser Leu Phe Trp Tyr Arg Gln 1 5 10 15 Thr Met Met Arg Gly Leu Glu Leu Leu Ile Tyr phe Asn Asn Asn va)

Pro Ile Asp Asp Ser Gly Met Pro Glu Asp Arg Phe Ser Ala Lys Met 40 45 Pro Asn Ala Ser Phe Ser Thr Leu Lys Ile Gln Pro Ser Glu Pro Arg 50 55 60 Asp Ser Ala val Tyr Phe Cys Ala Ser Ser Phe Ser Thr Cys Ser Ala 65 70 75 80 Asn Tyr Gly Tyr Thr Phe Gly Ser Gly Thr Arg Leu Thr Val val Glu 85 90 85 Asp Leu Asn Lys val Phe Pro Pro Glu Val Ala val Phe Glu Pro Ser 100 105 110 Glu Ala Glu Ile Ser His Thr Gln Lys Ala Thr Leu Val Cys Leu Ala 115 120 125 Thr Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly 130 135 140 Lys Glu val His ser Gly Val Ser Thr Asp Pro Gln Pro Leu Lys Glu 145 150 155 160 Gln Pro Ala Leu Asn Asp Ser Arg Tyr Cys Leu Ser Ser Arg Leu Arg 165 170 175 Val Ser Ala Thr Phe Trp Gln Asn Pro Arg Asn His phe Arg Cys Gln 180 185 130 Val Gln Phe Tyr Gly Leu Ser Glu Asn Asp Glu Trp Thr Gin Asp Arg

185 200 205 Ala Lys Pro Val Thr Gln Ile Val Ser Ala Glu Ala Trp Gly Arg Ala 210 215 220 Asp Cys Gly Phe Thr Ser Val Ser Tyr Gln Gln Gly Val Leu Ser Ala 225 230 235 240 Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val 245 250 255 Leu Val Ser Ala Leu Val Leu Met Ala Met Val Lys Arg Lys Asp Phe 260 265 270 <210> 2964 <211l> 276 <212> PRT <213> Homo sapiens <400> 2964 Met Tyr Arg Ile Ser Gln Leu Met Ser Thr Pro Val Ala Ser Ser Ser 1 5 10 15 Arg Leu Glu Arg Glu Tyr Ala Gly Glu Leu Ser Pro Thr Cys Ile Phe

Pro Ser Phe Thr Cys Asp Ser Leu Asp Gly Tyr His Ser Phe Glu Cys 40 45 Gly Ser Ile Asp Pro Leu Thr Gly Ser His Tyr Thr Cys Arg Arg Ser 50 55 60 Pro Arg Leu Leu Thr Asn Gly Tyr Tyr Ile Trp Thr Glu Asp Ser Phe 65 70 75 80 Leu Cys Asp Lys Asp Gly Asn Ile Thr Leu Asn Pro Ser Gln Thr Ser 85 90 S95 val Met Tyr Lys Glu Asn Leu Val Ser Thr Ser Lys Ser Trp Leu His 100 : 105 110 Gly Ser Ile Phe Gly Asp Ile Asn Ser Ser Pro Ser Glu Asp Asn Trp 115 120 125 Leu Lys Gly Thr Arg Arg Leu Asp Thr Asp His Cys Asn Gly Asn Ala 130 135 140

Asp Asp Leu Asp Cys Ser Ser Leu Thr Asp Asp Trp Glu Ser Gly Lys 145 150 155 160 Met Asn Ala Glu Ser val Ile Thr Ser Ser Ser Ser His Ile Ile Ser

165 170 175 Gln Pro Pro Gly Gly Asn Ser His Ser Leu Ser Leu Gln Ser Gln Leu 180 185 1580 Thr Ala Ser Glu Arg Phe Gln Glu Asn Ser Ser Asp His Ser Glu Thr 195 200 205 Arg Leu Leu Gln Glu Val Phe Phe Gln Ala Ile Leu Leu Ala Val Cys 210 215 220 Leu Ile Thr Ser Ala Cys Ala Arg Trp Phe Met Gly Glu Ile Leu Ala 225 230 235 240 Ser Val Phe Thr Cys Ser Leu Met Ile Thr val Ala Tyr Val Lys Ser 245 250 255 Leu Phe Leu Ser Leu Ala Ser Tyr Phe Lys Thr Thr Ala Cys Ala Arg 260 265 270 Phe Val Lys Ile 275 <210> 2965 <211> 133 <212> PRT <213> Homo sapiens <400> 2965 Met Val Leu Gln Thr Gln Val Phe Ile Ser Leu Leu Leu Trp Ile Ser 1 5 10 15 Gly Ala Tyr Gly Asp Ile val Met Thr Gln Ser Pro Asp Ser Leu Ala val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser 40 45 Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln 50 55 60 Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg

PCT/US2003/012946

65 70 75 80 Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp BS 20 95 Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp val Ala val Tyr 100 105 110 Tyr Cys Gln Gln Tyr Asp Thr Ile Pro Thr Phe Gly Gly Gly Thr Lys 115 120 125 Val Glu Ile Lys Arg 130 <210> 2966 <211ls> 369 <212> PRT <213> Homo sapiens <400> 2966 Met Leu Lys Pro Ser Leu Pro Phe Thr Ser Leu Leu Phe Leu Gln Leu 1 5 10 15 Pro Leu Leu Gly Val Gly Leu Asn Thr Thr Ile Leu Thr Pro Asn Gly ’ 30 Asn Glu Asp Thr Thr Ala Asp Phe Phe Leu Thr Thr Met Pro Thr Asp 40 45 Ser Leu Ser Val Ser Thr Leu Pro Leu Pro Glu val Gln Cys Phe Val 50 55 60 Phe Asn Val Glu Tyr Met Asn Cys Thr Trp Asn Ser Ser Ser Glu Pro } 65 70 75 80 Gln Pro Thr Asn Leu Thr Leu His Tyr Trp Tyr Lys Asn Ser Asp Asn BS 90 95 Asp Lys Val Gln Lys Cys Ser His Tyr Leu Phe Ser Glu Glu Ile Thr 100 105 110 Ser Gly Cys Gln Leu Gln Lys Lys Glu Ile His Leu Tyr Gln Thr Phe 115 120 125 Val Val Gln Leu Gln Asp Pro Arg Glu Pro Arg Arg Gln Ala Thr Gln 130 135 140

Met Leu Lys Leu Gln Asn Leu val Ile Pro Trp Ala Pro Glu Asp Leu 145 150 155 le60 Thr Leu His Lys Leu Ser Glu Ser Gln Leu Glu Leu Asn Trp Asn Asn 165 170 175 Arg Phe Leu Asn His Cys Leu Glu His Leu Val Gln Tyr Arg Thr Asp 180 185 190 Trp Asp His Ser Trp Thr Glu Gln Ser val Asp Tyr Arg His Lys Phe 195 200 205 Ser Leu Pro Ser val Asp Gly Gln Lys Arg Tyr Thr Phe Arg Val Arg 210 215 220 Ser Arg Phe Asn Pro Leu Cys Gly Ser Ala Gln His Trp Ser Glu Trp 225 230 235 240 Ser His Pro Ile His Trp Gly Ser Asn Thr Ser Lys Glu Asn Pro phe 245 250 255 Leu Phe Ala Leu Glu Ala val val Ile Ser Val Gly Ser Met Gly Leu 260 265 270 Ile Ile Ser Leu Leu Cys Val Tyr Phe Trp Leu Glu Arg Thr Met Pro 275 280 285 Arg Ile Pro Thr Leu Lys Asn Leu Glu Asp Leu Val Thr Glu Tyr His 290 295 300 Gly Asn Phe Ser ala Trp Ser Gly Val Ser Lys Gly Leu Ala Glu Ser 305 310 315 320 Leu Gln Pro Asp Tyr Ser Glu Arg Leu Cys Leu Val Ser Glu Ile Pro 325 330 335 Pro Lys Gly Gly Ala Leu Gly Glu Gly Pro Gly Ala Ser Pro Cys Asn 340 © 345 350 Gln His Ser Pro Tyr Trp Ala Pro Pro cys Tyr Thr Leu Lys Pro Glu 355 360 365 Thr

<210> 2967 <211> 323 <212> PRT <213> Homo sapiens <400> 2967 Met Ala Phe Ser Gly Ser Gln Ala Pro Tyr Leu Ser Pro Ala val Pro 1 5 10 15 Phe Ser Gly Thr Ile Gln Gly Gly Leu Gln Asp Gly Leu Gln Ile Thr

Val Asn Gly Thr Val Leu Ser Ser Ser Gly Thr Arg Phe Ala Val Asn 40 45 : Phe Gln Thr Gly Phe Ser Gly Asn Asp Ile Ala Phe His Phe Asn Pro 50 55 60 Arg Phe Glu Asp Gly Gly Tyr Val Val Cys Asn Thr Arg Gln Asn Gly 65 70 75 80 Ser Trp Gly Pro Glu Glu Arg Arg Thr His Met Pro Phe Gln Lys Gly 85 90 8s Met Pro Phe Asp Leu Cys Phe Leu Val Gln Ser Ser Asp Phe Lys Val 100 105 110 Met Val Asn Gly Ile Leu Phe Val Gln Tyr Phe His Arg Val Pro Phe 115 120 125 His Arg val Asp Thr Ile Phe Val Asn Gly Ser Val Gln Leu Ser Tyr 130 135 140 Ile Ser Phe Gln Pro Pro Gly Val Trp Pro Ala Asn Pro Ala Pro Ile 145 - 150 155 160 Thr Gln Thr Val Ile His Thr val Gln Ser Ala Pro Gly Gln Met Phe 165 170 175 Ser Thr Pro Ala Ile Pro Pro Met Met Tyr Pro His Pro Ala Tyr Pro 180 185 190 Met Pro Phe Ile Thr Thr Ile Leu Gly Gly Leu Tyr Pro Ser Lys Ser 195 200 205 Ile Leu Leu Ser Gly Thr val Leu Pro Ser Ala Gln Arg Phe His Ile 210 215 220

PCT/US2003/012946

Asn Leu Cys Ser Gly Asn His Ile Ala Phe His Leu Asn Ley Arg Phe 225 230 235 240 Asp Glu Asn Ala Val val Arg Asn Thr Gln Ile Asp Asn Ser Trp Gly 245 250 255 Ser Glu Glu Arg Ser Leu Pro Arg Lys Met Pro Phe Val Arg Gly Gln 260 265 270 Ser Phe Ser Val Trp Ile Leu Cys Gly Ala His Cys Leu Lys val Ala 275 280 285 ’ Val Asp Gly Gln His Leu Phe Glu Tyr Tyr His Arg Leu Arg Asn Leu } 2380 295 300 Pro Thr Ile Asn Arg Leu Glu Val Gly Gly Asp Ile Gln Leu Thr His 305 310 31s 320 Val Gln Thr <210> 2968 <21l1l> 1866 <212> PRT <213> Homo sapiens <400> 2968 Met Asp Pro Val Gly Leu Gln Leu Gly Asn Lys Asn Leu Trp Ser Cys 1 5 10 15 Leu Val Arg Leu Leu Thr Lys Asp Pro Glu Trp Leu Asn Ala Lys Met

Lys Phe Phe Leu Pro Asn Thr Asp Leu Asp Ser Arg Asn Glu Thr Leu 40 45 Asp Pro Glu Gln Arg Val Ile Leu Gln Leu Asn Lys Leu His val Gln 50 55 60 Gly Ser Asp Thr Trp Gln Ser Phe Ile His Cys Val Cys Met Gln Leu 65 70 75 80 Glu Val Pro Leu Asp Leu Glu Val Leu Leu Leu Ser Thr Phe Gly Tyr 85 90 95

Asp Asp Gly Phe Thr Ser Gln Leu Gly Ala Glu Gly Lys Ser Gln Pro 100 105 110 } Glu Ser Gln Leu His His Gly Leu Lys Arg Pro His Gln Ser Cys Gly 115 120 125 Ser Ser Pro Arg Arg Lys Gln Cys Lys Lys Gln Gln Leu Glu Leu Ala 130 135 140 Lys Lys Tyr Leu Gln Leu Leu Arg Thr Ser Ala Gln Gln Arg Tyr Arg 145 150 155 160 Ser Gln Ile Pro Gly Ser Gly Gln Pro His Ala Phe His Gln Val Tyr 165 170 175 Val Pro Pro Ile Leu Arg Arg Ala Thr Ala Ser Leu Asp Thr Pro Glu 180 185 190 Gly Ala Ile Met Gly Asp Val Lys Val Glu Asp Gly Ala Asp Val Ser 195 200 205 Ile Ser Asp Leu Phe Asn Thr Arg Val Asn Lys Gly Pro Arg Val Thr 210 215 220 Val Leu Leu Gly Lys Ala Gly Met Gly Lys Thr Thr Leu 2la His Arg 225 230 235 240 Leu Cys Gln Lys Trp Ala Glu Gly His Leu Asn Cys Phe Gln Ala Leu 245 250 255 Phe Leu Phe Glu Phe Arg Gln Leu Asn Leu Ile Thr Arg Phe Leu Thr 260 265 270 Pro Ser Glu Leu Leu Phe Asp Leu Tyr Leu Ser Pro Glu Ser Asp His 275 280 285 Asp Thr Val Phe Gln Tyr Leu Glu Lys Asn Ala Asp Gln Val Leu Leu 290 2895 300 Ile Phe Asp Gly Leu Asp Glu Ala Leu Gln Pro Met Gly Pro Asp Gly 305 310 315 320 Pro Gly Pro Val Leu Thr Leu Phe Ser His Leu Cys Asn Gly Thr Leu 325 330 335 Leu Pro Gly Cys Arg Val Met Ala Thr Ser Arg Pro Gly Lys Leu Pro

340 345 350 Ala Cys Leu Pro Ala Glu Ala Ala Met Val His Met Leu Gly Phe Asp 355 360 365 Gly Pro Arg Val Glu Glu Tyr Val Asn His Phe Phe Ser Ala Gln Pro 370 375 380 Ser Arg Glu Gly Ala Leu Val Glu Leu Gln Thr Asn Gly Arg Leu Arg 385 390 385 400 Ser Leu Cys Ala Val Pro Ala Leu Cys Gln Val Ala Cys Leu Cys Leu 405 410 415 His His Leu Leu Pro Asp His Ala Pro Gly Gln Ser Val Ala Leu Leu 420 425 430 Pro Asn Met Thr Gln Leu Tyr Met Gln Met Val Leu Ala Leu Ser Pro 435 440 445 Pro Gly His Leu Pro Thr Ser Ser Leu Leu Asp Leu Gly Glu Val Ala 450 455 460 Leu Arg Gly Leu Glu Thr Gly Lys Val Ile Phe Tyr Ala Lys Asp Ile 465 470 475 480 Ala Pro Pro Leu Ile Ala Phe Gly Ala Thr His Ser Leu Leu Thr Ser 485 490 495 Phe Cys Val Cys Thr Gly Pro Gly His Gln Gln Thr Gly Tyr Ala Phe 500 505 510 Thr His Leu Ser Leu Gln Glu Phe Leu Ala Ala Leu His Leu Met Ala 515 520 525 Ser Pro Lys Val Asn Lys Asp Thr Leu Thr Gln Tyr Val Thr Leu His 530 535 540 Ser Arg Trp Val Gln Arg Thr Lys Ala Arg Leu Gly Leu Ser Asp His 545 550 555 560 Leu Pro Thr Phe Leu Ala Gly Leu Ala Ser Cys Thr Cys Arg Pro Phe 565 570 575 Leu Ser His Leu Ala Gln Gly Asn Glu Asp Cys Val Gly Ala Lys Gln 580 585 590

Ala Ala Val val Gln Val Leu Lys Lys Leu Ala Thr Arg Lys Leu Thr 58S 600 605 Gly Pro Lys Val Val Glu Leu Cys His Cys Val Asp Glu Thr Gln Glu 610 615 620 Pro Glu Leu Ala Ser Leu Thr Ala Gln Ser Leu Pro Tyr Gln Leu Pro 625 630 635 640 Phe His Asn Phe Pro Leu Thr Cys Thr Asp Leu Ala Thr Leu Thr Asn 645 650 655 Ile Leu Glu His Arg Glu Ala Pro Ile His Leu Asp Phe Asp Gly Cys 660 665 670 Pro Leu Glu Pro His Cys Pro Glu Ala Leu Val Gly Cys Gly Gln Ile 675 - 680 685 Glu Asn Leu Ser Phe Lys Ser Arg Lys Cys Gly Asp Ala Phe Ala Glu 690 695 700 Ala Leu Ser Arg Ser Leu Pro Thr Met Gly Arg Leu Gln Met Leu Gly 705 710 715 720 Leu Ala Gly Ser Lys Ile Thr Ala Arg Gly Ile Ser His Leu Val Lys 725 730 735 Ala Leu Pro Leu Cys Pro Gln Leu Lys Glu Val Ser Phe Arg Asp Asn 740 745 750 Gln Leu Ser Asp Gln Val Val Leu Asn Ile Val Glu Val Leu Pro His 755 760 765 Leu Pro Arg Leu Arg Lys Leu Asp Leu Ser Ser Asn Ser Ile Cys Val 770 775 780 Ser Thr Leu Leu Cys Leu Ala Arg Val Ala Val Thr Cys Pro Thr Val 785 790 795 800 Arg Met Leu Gln Ala Arg Glu Arg Thr Ile Ile Phe Leu Leu Ser Pro 805 810 815 Pro Thr Glu Thr Thr Ala Glu Leu Gln Arg Ala Pro Asp Leu Gln Glu 820 825 830

: PCT/US2003/012946

Ser Asp Gly Gln Arg Lys Gly Ala Gln Ser Arg Ser Leu Thr Leu Arg 835 840 845 Leu Gln Lys Cys Gln Leu Gln Val His Asp Ala Glu Ala Leu Ile Ala 850 855 860 Leu Leu Gln Glu Gly Pro His Leu Glu Glu Val Asp Leu Ser Gly Asn 865 870 875 880 Gln Leu Glu Asp Glu Gly Cys Arg Leu Met Ala Glu Ala ala Ser Gln 885 890 895 Leu His Ile Ala Arg Lys Leu Asp Leu Ser Asp Asn Gly Leu Ser val 900 905 910 Ala Gly Val His Cys Val Leu Arg Ala Val Ser Ala Cys Trp Thr Leu 918 $20 825 Ala Glu Leu His Ile Ser Leu Gln His Lys Thr Val Ile Phe Met Phe 930 935 940 Ala Gln Glu Pro Glu Glu Gln Lys Gly Pro Gln Glu Arg Ala Ala Phe 945 950 955 960 Leu Asp Ser Leu Met Leu Gln Met Pro Ser Glu Leu Pro Leu Ser Ser 965 970 975 Arg Arg Met Arg Leu Thr His Cys Gly Leu Gln Glu Lys His Leu Glu 980 985 990 Gln Leu Cys Lys Ala Leu Gly Gly Ser Cys His Leu Gly His Leu His 995 1000 1005 Leu Asp Phe Ser Gly Asn Ala Leu Gly Asp Glu Gly ala Ala Arg 1010 1015 1020 Leu Ala Gln Leu Leu Pro Gly Leu Gly Ala Leu Gln Ser Leu Asn 1025 1030 1035 Leu ser Glu Asn Gly Leu Ser Leu Asp Ala Val Leu Gly Leu Val 1040 1045 1050 Arg Cys Phe Ser Thr Leu Gln Trp Leu Phe Arg Leu Asp Ile Ser 1055 1060 1065

Phe Glu Ser Gln His Ile Leu Leu Arg Gly Asp Lys Thr Ser Arg 1070 1075 1080 Asp Met Trp Ala Thr Gly Ser Leu Pro Asp Phe Pro Ala Ala Ala 1085 1090 1095 Lys Phe Leu Gly Phe Arg Gln Arg Cys Ile Pro Arg Ser Leu Cys 1100 1105 1110 Leu Ser Glu Cys Pro Leu Glu Pro Pro Ser Leu Thr Arg Leu Cys 1115 1120 1125 Ala Thr Leu Lys Asp Cys Pro Gly Pro Leu Glu Leu Gln Leu Ser 1130 1135 1140 Cys Glu Phe Leu Ser Asp Gln Ser Leu Glu Thr Leu Leu Asp Cys 1145 1150 1155 Leu Pro Gln Leu Pro Gln Leu Ser Leu Leu Gln Leu Ser Gln Thr 1160 1165 1170 Gly Leu Ser Pro Lys Ser Pro Phe Leu Leu Ala Asn Thr Leu Ser 1175S 1180 1185 Leu Cys Pro Arg Val Lys Lys Val Asp Leu Arg Ser Leu His His 1190 1185 1200 Ala Thr Leu His Phe Arg Ser Asn Glu Glu Glu Glu Gly Val Cys 1205 1210 1215 Cys Gly Arg Phe Thr Gly Cys Ser Leu Ser Gln Glu His Val Glu 1220 1225 1230 Ser Leu Cys Trp Leu Leu Ser Lys Cys Lys Asp Leu Ser Gln Val 1235 1240 1245 Asp Leu Ser Ala Asn Leu Leu Gly Asp Ser Gly Leu Arg Cys Leu 1250 1255 1260 Leu Glu Cys Leu Pro Gln Val Pro Ile Ser Gly Leu Leu Asp Leu 1265 1270 ’ 1275 Ser His Asn Ser Ile Ser Gln Glu Ser Ala Leu Tyr Leu Leu Glu 1280 1285 1290 Thr Leu Pro Ser Cys Pro Arg Val Arg Glu Ala Ser Val Asn Leu

1295 1300 1305 Gly Ser Glu Gln Ser Phe Arg Ile His Phe Ser Arg Glu Asp Gln 1310 1315 1320 Ala Gly Lys Thr Leu Arg Leu Ser Glu Cys Ser Phe Arg Pro Glu 1325 1330 1338 His Val Ser Arg Leu Ala Thr Gly Leu Ser Lys Ser Leu Gln Leu 1340 1345 1350 Thr Glu Leu Thr Leu Thr Gln Cys Cys Leu Gly Gln Lys Gln Leu 1355 1360 1365 Ala Ile Leu Leu Ser Leu Val Gly Arg Pro Ala Gly Leu Phe Ser 1370 1375 1380 Leu Arg Val Gln Glu Pro Trp Ala Asp Arg Ala Arg Val Leu Ser 1385 1390 1395 Leu Leu Glu Val Cys Ala Gln Ala Ser Gly Ser Val Thr Glu Ile 1400 1405 1410 Ser Ile Ser Glu Thr Gln Gln Gln Leu Cys Val Gln Leu Glu Phe 1415 1420 1425 Pro Arg Gln Glu Glu Asn Pro Glu Ala Val Ala Leu Arg Leu Ala 1430 1435 1440 His Cys Asp Leu Gly Ala His His Ser Leu Leu Val Gly Gln Leu 1445 1450 1455 Met Glu Thr Cys Ala Arg Leu Gln Gln Leu Ser Leu Ser Gln Val 1460 1465 1470 Asn Leu Cys Glu Asp Asp Asp Ala Ser Ser Leu Leu Leu Gln Ser 1475 1480 1485 Leu Leu Leu Ser Leu Ser Glu Leu Lys Thr Phe Arg Leu Thr Ser 1490 1495 1500 Ser Cys Val Ser Thr Glu Gly Leu Ala His Leu Ala Ser Gly Leu 1505 1510 1515 Gly His Cys His His Leu Glu Glu Leu Asp Leu Ser Asn Asn Gln 1520 1525 1530

Phe Asp Glu Glu Gly Thr Lys Ala Leu Met Arg Ala Leu Glu Gly 1535 1540 1545

: Lys Trp Met Leu Lys Arg Leu Asp Leu Ser His Leu Leu Leu Asn 1550 1555 1560

Ser Ser Thr Leu Ala Leu Leu Thr His Arg Leu Ser Gln Met Thr 1565 1570 1575

Cys Leu Gln Ser Leu Arg Leu Asn Arg Asn Ser Ile Gly Asp Val 1580 1585 1590

Gly Cys Cys His Leu Ser Glu Ala Leu Arg Ala Ala Thr Ser Leu 1595 1600 1605

Glu Glu Leu Asp Leu Ser His Asn Gln Ile Gly Asp Ala Gly Val 1610 1615 1620

Gln His Leu Ala Thr Ile Leu Pro Gly Leu Pro Glu Leu Arg Lys 1625 1630 1635

Ile Asp Leu Ser Gly Asn Ser Ile Ser Ser Ala Gly Gly Val Gln 1640 1645 1650

Leu Ala Glu Ser Leu Val Leu Cys Arg Arg Leu Glu Glu Leu Met 1655 1660 1665

Leu Gly Cys Asn Ala Leu Gly Asp Pro Thr Ala Leu Gly Leu Ala 1670 1675 1680

Gln Glu Leu Pro Gln His Leu Arg Val Leu His Leu Pro Phe Ser 1685 1690 1685

His Leu Gly Pro Gly Gly Ala Leu Ser Leu Ala Gln Ala Leu Asp 1700 1705 1710

Gly Ser Pro His Leu Glu Glu Ile Ser Leu Ala Glu Asn Asn Leu 171S 1720 1725

Ala Gly Gly val Leu Arg Phe Cys Met Glu Leu Pro Leu Leu Arg 1730 1735 1740

Gln Ile Asp Leu Val Ser Cys Lys Ile Asp Asn Gln Thr Ala Lys 1745 1750 1755

Leu Leu Thr Ser Ser Phe Thr Ser Cys Pro Ala Leu Glu Val Tle 1760 1765 1770 Leu Leu Ser Trp Asn Leu Leu Gly Asp Glu Ala Ala Ala Glu Leu 1775 1780 1785 Ala Gln Val Leu Pro Lys Met Gly Arg Leu Lys Arg Val Asp Leu 1780 1795 1800 Glu Lys Asn Gln Ile Thr Ala Leu Gly Ala Trp Leu Leu Ala Glu 1805 1810 1815 Gly Leu Ala Gln Gly Ser Ser Ile Gln Val Ile Arg Leu Trp Asn 1820 1828S 1830 Asn Pro Ile Pro Cys Asp Met Ala Gln His Leu Lys Ser Gln Glu 1835 1840 1845 Pro Arg Leu Asp Phe Ala Phe Phe Asp Asn Gln Pro Gln Ala Pro 1850 1855 1860 Trp Gly Thr 1865 <210> 2969 <211> 547 <212> PRT <213> Homo sapiens <400> 2969 Met Ala Thr Met Val Pro Ser Val Leu Trp Pro Arg Ala Cys Trp Thr 1 LD) 10 15 Leu Leu Val Cys Cys Leu Leu Thr Pro Gly Val Gln Gly Gln Glu Phe

Leu Leu Arg Val Glu Pro Gln Asn Pro Val Leu Ser Ala Gly Gly Ser 40 45 Leu Phe Val Asn Cys Ser Thr Asp Cys Pro Ser Ser Glu Lys Ile Ala 50 55 60 Leu Glu Thr Ser Leu Ser Lys Glu Leu Val Ala Ser Gly Met Gly Trp 65 70 75 80 Ala Ala Phe Asn Leu Ser Asn Val Thr Gly Asn Ser Arg Ile Leu Cys

PCT/US2003/012946

85 20 95 Ser Val Tyr Cys Asn Gly Ser Gln Ile Thr Gly Ser Ser Asn Ile Thr 100 105 110 Val Tyr Gly Leu Pro Glu Arg Val Glu Leu Ala Pro Leu Pro Pro Trp 118 120 125 Gln Pro Val Gly Gln Asn Phe Thr Leu Arg Cys Gln Val Glu Gly Gly 130 135 140 Ser Pro Arg Thr Ser Leu Thr Val Val Leu Leu Arg Trp Glu Glu Glu 145 150 155 160 Leu Ser Arg Gln Pro Ala val Glu Glu Pro Ala Glu Val Thr Ala Thr 165 170 175 Val Leu Ala Ser Arg Asp Asp His Gly Ala Pro Phe Ser Cys Arg Thr 180 185 190 Glu Leu Asp Met Gln Pro Gln Gly Leu Gly Leu Phe Val Asn Thr Ser 195 200 205 Ala Pro Arg Gln Leu Arg Thr Phe Val Leu Pro val Thr Pro Pro Arg 210 215 220 Leu Val Ala Pro Arg Phe Leu Glu Val Glu Thr Ser Trp Pro val Asp 225 230 235 240 Cys Thr Leu Asp Gly Leu Phe Pro Ala Ser Glu Ala Gln Val Tyr Leu 245 250 255 Ala Leu Gly Asp Gln Met Leu Asn Ala Thr Val Met Asn His Gly Asp 260 265 270 Thr Leu Thr Ala Thr Ala Thr Ala Thr Ala Arg Ala Asp Gln Glu Gly 275 280 285 Ala Arg Glu Ile Val Cys Asn Val Thr Leu Gly Gly Glu Arg Arg Glu 290 295 300 Ala Arg Glu Asn Leu Thr Val Phe Ser Phe Leu Gly Pro Ile Val Asn 305 310 315 320 Leu Ser Glu Pro Thr Ala His Glu Gly Ser Thr Val Thr val Ser Cys 325 330 335

Met Ala Gly Ala Arg Val Gln Val Thr Leu Asp Gly Val Pro Ala Ala 340 345 350 Ala Pro Gly Gln Pro Ala Gln Leu Gln Leu Asn Ala Thr Glu Ser Asp 355 360 365 Asp Gly Arg Ser Phe Phe Cys Ser Ala Thr Leu Glu Val Asp Gly Glu 370 375 380 Phe Leu His Arg Asn Ser Ser Val Gln Leu Arg Val Leu Tyr Gly Pro 385 390 395 400 Lys Ile Asp Arg Ala Thr Cys Pro Gln His Leu Lys Trp Lys Asp Lys 405 410 415 Thr Arg His Val Leu Gln Cys Gln Ala Arg Gly Asn Pro Tyr Pro Glu 420 425 430 Leu Arg Cys Leu Lys Glu Gly Ser Ser Arg Glu Val Pro Val Gly Ile

435. 440 445 Pro Phe Phe Val Asn Val Thr His Asn Gly Thr Tyr Gln Cys Gln Ala 450 455 460 ’ Ser Ser Ser Arg Gly Lys Tyr Thr Leu Val Val Val Met Asp Ile Glu 465 470 475 480 Ala Gly Ser Ser His Phe Val Pro Val Phe Val Ala Val Leu Leu Thr 485 490 495 Leu Gly Val Val Thr Ile val Leu Ala Leu Met Tyr Val Phe Arg Glu 500 505 510 His Gln Arg Ser Gly Ser Tyr His Val Arg Glu Glu Ser Thr Tyr Leu 515 520 525 Pro Leu Thr Ser Met Gln Pro Thr Glu Ala Met Gly Glu Glu Pro Ser 530 535 540 Arg Ala Glu 545 <210> 2970 <211> 260 <212> PRT

$2003/012946

<213> Homo sapiens <400> 2970 Met Arg Pro Glu Asp Arg Met Phe His Ile Arg Ala Val Ile Leu Arg 1 5 10 15 Ala Leu Ser Leu Ala Phe Leu Leu Ser Leu Arg Gly Ala Gly Ala Ile

Lys Ala Asp His Val Ser Thr Tyr Ala Ala Phe Val Gln Thr His Arg 40 45 Pro Thr Gly Glu Phe Met Phe Glu Phe Asp Glu Asp Glu Met Phe Tyr 50 55 60 Val Asp Leu Asp Lys Lys Glu Thr Val Trp His Leu Glu Glu Phe Gly 65 70 75 80 Gln Ala Phe Ser Phe Glu Ala Gln Gly Gly Leu Ala Asn Ile Ala Ile 85 S0 95 Leu Asn Asn Asn Leu Asn Thr Leu Ile Gln Arg Ser Asn His Thr Gln 100 105 110 Ala Thr Asn Asp Pro Pro Glu Val Thr val Phe Pro Lys Glu Pro val 115 120 125 Glu Leu Gly Gln Pro Asn Thr Leu Ile Cys His Ile Asp Lys Phe Phe 130 135 140 Pro Pro Val Leu Asn Val Thr Trp Leu Cys Asn Gly Glu Leu Val Thr 145 150 155 160 Glu Gly Val Ala Glu Ser Leu Phe Leu Pro Arg Thr Asp Tyr Ser Phe 165 170 175 His Lys Phe His Tyr Leu Thr Phe Val Pro Ser Ala Glu Asp Phe Tyr 180 185 190 Asp Cys Arg Val Glu His Trp Gly Leu Asp Gln Pro Leu Leu Lys His 195 200 205 Trp Glu Ala Gln Glu Pro Ile Gln Met Pro Glu Thr Thr Glu Thr val 210 215 220 Leu Cys Ala Leu Gly Leu Val Leu Gly Leu val Gly Ile Ile Val Gly

225 230 235 240 Thr Val Leu Ile Ile Lys Ser Leu Arg Ser Gly His Asp Pro Arg Ala

245 250 255 Gln Gly Thr Leu 260

<210> 2971 <211> 495 <212> PRT <213> Homo sapiens <400> 2971

Met Pro Met Gly Ser Leu Gln Pro Leu ala Thr Leu Tyr Leu Leu Gly 1 5 10 15

Met Leu Val Ala Ser Cys Leu Gly Arg Leu Ser Trp Tyr Asp Pro Asp

Phe Gln Ala Arg Leu Thr Arg Ser Asn Ser Lys Cys Gln Gly Gln Leu 40 45 Glu val Tyr Leu Lys Asp Gly Trp His Met Val Cys Ser Gln Ser Trp 50 55 60

Gly Arg Ser Ser Lys Gln Trp Glu Asp Pro Ser Gln Ala Ser Lys Val

65 70 75 80

Cys Gln Arg Leu Asn Cys Gly val Pro Leu Ser Leu Gly Pro Phe Leu

85 90 95 val Thr Tyr Thr Pro Gln Ser Ser fle Ile Cys Tyr Gly Gln Leu Gly 100 105 110 Ser Phe Ser Asn Cys Ser His Ser Arg Asn Asp Met Cys His Ser Leu 115 120 125 Gly Leu Thr Cys Leu Glu Pro Gln Lys Thr Thr Pro Pro Thr Thr Arg 130 135 140

Pro Pro Pro Thr Thr Thr Pro Glu Pro Thr Ala Pro Pro Arg Leu Gln

145 150 155 160

Leu Val Ala Gln Ser Gly Gly Gln His Cys Ala Gly Val Val Glu Phe

165 170 175

PCT/US2003/012946

Tyr Ser Gly Ser Leu Gly Gly Thr Ile Ser Tyr Glu Ala Gln Asp Lys 180 185 190 Thr Gln Asp Leu Glu Asn Phe Leu Cys Asn Asn Leu Gln Cys Gly Ser 195 200 205 Phe Leu Lys His Leu Pro Glu Thr Glu Ala Gly Arg Ala Gln Asp Pro 210 215 220 Gly Glu Pro Arg Glu His Gln Pro Leu Pro Ile Gln Trp Lys Ile Gln 225 230 235 240 Asn Ser Ser Cys Thr Ser Leu Glu His Cys Phe Arg Lys Ile Lys Pro 245 250 255 Gln Lys Ser Gly Arg Val Leu Ala Leu Leu Cys Ser Gly Phe Gln Pro 260 265 270 Lys Val Gln Ser Arg Leu Val Gly Gly Ser Ser Ile Cys Glu Gly Thr : 275 280 285 Val Glu val Arg Gln Gly Ala Gln Trp Ala Ala Leu Cys Asp Ser Ser 290 295 300 Ser Ala Arg Ser Ser Leu Arg Trp Glu Glu Val Cys Arg Glu Gln Gln 305 310 315 320 Cys Gly Ser Val Asn Ser Tyr Arg val Leu Asp Ala Gly Asp Pro Thr 325 330 335 Ser Arg Gly Leu Phe Cys Pro His Gln Lys Leu Ser Gln Cys His Glu 340 345 350 Leu Trp Glu Arg Asn Ser Tyr Cys Lys Lys Val Phe Val Thr Cys Gln 355 360 365 Asp Pro Asn Pro Ala Gly Leu Ala Ala Gly Thr Val Ala Ser Ile Ile 370 375 380 Leu Ala Leu Val Leu Leu Val Val Leu Leu Val Val Cys Gly Pro Leu: 385 390 395 400 Ala Tyr Lys Lys Leu Val Lys Lys Phe Arg Gln Lys Lys Gln Arg Gln 405 410 415

Trp Ile Gly Pro Thr Gly Met Asn Gln Asn Met Ser Phe His Arg Asn 420 425 430 His Thr Ala Thr val Arg Ser His Ala Glu Asn Pro Thr Ala Ser His 435 440 445 Val Asp Asn Glu Tyr Ser Gln Pro Pro Arg Asn Ser Arg Leu Ser Ala 450 455 460 Tyr Pro Ala Leu Glu Gly Val Leu His Arg Ser Ser Met Gln Pro Asp 465 470 475 480 Asn Ser Ser Asp Ser Asp Tyr Asp Leu Kis Gly Ala Gln Arg Leu 485 490 495

<210> 2972

<21l> 130

<212> PRT

<213> Homo sapiens

<400> 2972

Lys Val Phe Glu Arg Cys Glu Leu Ala Arg Thr Leu Lys Arg Leu Gly 1 5 10 15

Met Asp Gly Tyr Arg Gly Ile Ser Leu Ala Asn Trp Met Cys Leu Ala

Lys Trp Glu Ser Gly Tyr Asn Thr Arg Ala Thr Asn Tyr Asn Ala Gly is 40 45 Asp Arg Ser Thr Asp Tyr Gly lle Phe Gln Ile Asn Ser Arg Tyr Trp 50 55 60 Cys Asn Asp Gly Lys Thr Pro Gly Ala Val Asn Ala Cys His Leu Ser 65 70 75 80 Cys Ser Ala Leu Leu Gln Asp Asn Ile Ala Asp Ala Val Ala Cys Ala 85 920 95 Lys Arg Val val Arg Asp Pro Gln Gly Ile Arg Ala Trp Val Ala Trp 100 10S 110 Arg Asn Arg Cys Gln Asn Arg Asp Val Arg Gln Tyr Val Gln Gly Cys 115 120 125 Gly val 130

<210> 2973 <211> 491 <212> PRT <213> Homo sapiens <400> 2973 Met Asn Pro Ala Ala Glu Ala Glu Phe Asn Ile Leu Leu Ala Thr Asp 1 5 10 15 Ser Tyr Lys Val Thr His Tyr Lys Gln Tyr Pro Pro Asn Thr Ser Lys

Val Tyr Ser Tyr Phe Glu Cys Arg Glu Lys Lys Thr Glu Asn Ser Lys 40 45 Leu Arg Lys Val Lys Tyr Glu Glu Thr Val Phe Tyr Gly Leu Gln Tyr 50 S55 60 Ile Leu Asn Lys Tyr Leu Lys Gly Lys Val Val Thr Lys Glu Lys Ile 65 70 75 80 Gln Glu Ala Lys Asp Val Tyr Lys Glu His Phe Gln Asp Asp Val Phe 85 90 95 Asn Glu Lys Gly Trp Asn Tyr Ile Leu Glu Lys Tyr Asp Gly His Leu 100 105 110 Pro Ile Glu Ile Lys Ala Val Pro Glu Gly Phe Val Ile Pro Arg Gly 115 120 125 Asn Val Leu Phe Thr val Glu Asn Thr Asp Pro Glu Cys Tyr Trp Leu 130 135 140 Thr Asn Trp Ile Glu Thr Ile Leu Val Gln Ser Trp Tyr Pro Ile Thr 145 150 155 160 Val Ala Thr Asn Ser Arg Glu Gln Lys Lys Ile Leu Ala Lys Tyr Leu 165 170 175 Leu Glu Thr Ser Gly Asn Leu Asp Gly Leu Glu Tyr Lys Leu His Asp 180 185 190 Phe Gly Tyr Arg Gly Val Ser Ser Gln Glu Thr Ala Gly Ile Gly Ala 195 200 205

Ser Ala His Leu Val Asn Phe Lys Gly Thr Asp Thr Val Ala Gly Leu 210 215 220 Ala Leu Ile Lys Lys Tyr Tyr Gly Thr Lys Asp Pro Val Pro Gly Tyr 225 230 235 240 Ser Val Pro Ala Ala Glu His Ser Thr Ile Thr Ala Trp Gly Lys Asp 245 250 255 His Glu Lys Asp Ala Phe Glu His Ile Val Thr Gln Phe Ser Ser Val 260 265 270 Pro Val Ser val val Ser Asp Ser Tyr Asp Ile Tyr Asn Ala Cys Glu 275 280 285 Lys Ile Trp Gly Glu Asp Leu Arg His Leu Ile Val Ser Arg Ser Thr 290 295 300 Gln Ala Pro Leu Ile Ile Arg Pro Asp Ser Gly Asn Pro Leu Asp Thr 305 310 315 320 val Leu Lys Val Leu Glu Ile Leu Gly Lys Lys Phe Pro Val Thr Glu 325 330 335 Asn Ser Lys Gly Tyr Lys Leu Leu Pro Pro Tyr Leu Arg Val Ile Gln 340 345 350 Gly Asp Gly Val Asp Ile Asn Thr Leu Gln Glu Ile Val Glu Gly Met 355 360 36S Lys Gln Lys Met Trp Ser Ile Glu Asn Ile Ala Phe Gly Ser Gly Gly 370 375 380 Gly Leu Leu Gln Lys Leu Thr Arg Asp Leu Leu Asn Cys Ser Phe Lys 385 390 395 400 Cys Ser Tyr Val Val Thr Asn Gly Leu Gly Ile Asn Val Phe Lys Asp 405 410 415 Pro Val Ala Asp Pro Asn Lys Arg Ser Lys Lys Gly Arg Leu Ser Leu 420 425 430 His Arg Thr Pro Ala Gly Asn Phe Val Thr Leu Glu Glu Gly Lys Gly 435 440 445 Asp Leu Glu Glu Tyr Gly Gln Asp Leu Leu His Thr val Phe Lys Asn

450 455 460 i Gly Lys Val Thr Lys Ser Tyr Ser Phe Asp Glu Ile Arg Lys Asn Ala 465 470 475 480 Gln Leu Asn Ile Glu Leu Glu Ala Ala His His 485 490 <210> 2974 <211> 862 <212> PRT . <213> Homo sapiens <400> 2974 Met Glu Arg Ala Glu Ser Ser Ser Thr Glu Pro Ala Lys Ala Ile Lys 1 5 10 15 Pro Ile Asp Arg Lys Ser Val His Gln Ile Cys Ser Gly Gln val val

Leu Ser Leu Ser Thr Ala Val Lys Glu Leu Val Glu Asn Ser Leu Asp ) 35 40 45 Ala Gly Ala Thr Asn Ile Asp Leu Lys Leu Lys Asp Tyr Gly Val Asp 50 55 60 Leu Ile Glu Val Ser Asp Asn Gly Cys Gly Val Glu Glu Glu Asn Phe 65 70 75 80 Glu Gly Leu Thr Leu Lys His His Thr Ser Lys Ile Gln Glu Phe Ala 85 90 85 Asp Leu Thr Gln Val Glu Thr Phe Gly Phe Arg Gly Glu Ala Leu Ser 100 105 110 Ser Leu Cys Ala Leu Ser Asp Val Thr Ile Ser Thr Cys His Ala Ser 115 120 125 Ala Lys Val Gly Thr Arg Leu Met Phe Asp His Asn Gly Lys Ile Ile 130 135 140 Gln Lys Thr Pro Tyr Pro Arg Pro Arg Gly Thr Thr Val Ser Val Gln 145 150 155 160 Gln Leu Phe Ser Thr Leu Pro Val Arg His Lys Glu Phe Gln Arg Asn 165 170 175

CEE ——————...

Ile Lys Lys Glu Tyr Ala Lys Met Val Gln Val Leu His Ala Tyr Cys 180 185 190 Ile Ile ser Ala Gly Ile Arg Val Ser Cys Thr Asn Gln Leu Gly Gln 18s 200 205 Gly Lys Arg Gln Pro Val val Cys Thr Gly Gly Ser Pro Ser Ile Lys 210 21s 220 Glu Asn Ile Gly Ser val Phe Gly Gln Lys Gln Leu Gln Ser Leu Ile 225 230 235 240 Pro Phe Val Gln Leu Pro Pro Ser Asp Ser Val Cys Glu Glu Tyr Gly 245 250 255 Leu Ser Cys Ser Asp Ala Leu His Asn Leu Phe Tyr Ile Ser Gly Phe 260 265 270 Ile Ser Gln Cys Thr His Gly Val Gly Arg Ser Ser Thr Asp Arg Gln : 275 280 285 Phe Phe Phe Ile Asn Arg Arg Pro Cys Asp Pro Ala Lys Val Cys Arg 2390 295 300 Leu Val Asn Glu Val Tyr His Met Tyr Asn Arg His Gln Tyr Pro Phe 305 310 315 320 Val val Leu Asn Ile Ser val Asp Ser Glu Cys Val Asp Ile Asn Val 325 330 335 Thr Pro Asp Lys Arg Gln Ile Leu Leu Gln Glu Glu Lys Leu Leu Leu 340 345 350 Ala Val Leu Lys Thr Ser Leu Ile Gly Met Phe Asp Ser Asp val Asn ) 355 360 365 Lys Leu Asn Val Ser Gln Gln Pro Leu Leu Asp Val Glu Gly Asn Leu 370 375 380 Ile Lys Met His Ala Ala Asp Leu Glu Lys Pro Met Val Glu Lys Gln 385 390 395 400 Asp Gln Ser Pro Ser Leu Arg Thr Gly Glu Glu Lys Lys Asp val Ser 405 410 415

Ile Ser Arg Leu Arg Glu Ala Phe Ser Leu Arg His Thr Thr Glu Asn 420 425 430 Lys Pro His Ser Pro Lys Thr Pro Glu Pro Arg Arg Ser Pro Leu Gly 435 440 445 Gln Lys Arg Gly Met Leu Ser Ser Ser Thr Ser Gly Ala Ile Ser Asp 450 455 460 Lys Gly Val Leu Arg Pro Gln Lys Glu Ala Val Ser Ser Ser His Gly 465 470 475 480 Pro Ser Asp Pro Thr Asp Arg Ala Glu Val Glu Lys Asp Ser Gly His 485 490 495 Gly Ser Thr Ser Val Asp Ser Glu Gly Phe Ser Ile Pro Asp Thr Gly 500 505 510 Ser His Cys Ser Ser Glu Tyr Ala Ala Ser Ser Pro Gly Asp Arg Gly 515 520 825 Ser Gln Glu His Val Asp Ser Gln Glu Lys Ala Pro Glu Thr Asp Asp 530 535 540 Ser Phe Ser Asp Val Asp Cys His Ser Asn Gln Glu Asp Thr Gly Cys 545 550 555 560 Lys Phe Arg Val Leu Pro Gln Pro Thr Asn Leu Ala Thr Pro Asn Thr 565 570 575 Lys Arg Phe Lys Lys Glu Glu Ile Leu Ser Ser Ser Asp Ile Cys Gln 580 585 590 Lys Leu Val Asn Thr Gln Asp Met Ser Ala Ser Gln Val Asp Val Ala 595 600 605 Val Lys Ile Asn Lys Lys Val Val Pro Leu Asp Phe Ser Met Ser Ser 610 615 620 Leu Ala Lys Arg Ile Lys Gln Leu His His Glu Ala Gln Gln Ser Glu 625 630 635 640 Gly Glu Gln Asn Tyr Arg Lys Phe Arg Ala Lys Ile Cys Pro Gly Glu 645 650 655 Asn Gln Ala Ala Glu Asp Glu Leu Arg Lys Glu Ile Ser Lys Thr Met

PCT/US2003/012946

660 665 670 Phe Ala Glu Met Glu Ile Ile Gly Gln Phe Asn Leu Gly phe Ile Ile . 675 680 685 Thr Lys Leu Asn Glu Asp Ile Phe Ile Val Asp Gln His Ala Thr Asp 690 695 700 Glu Lys Tyr Asn Phe Glu Met Leu Gln Gln His Thr Val Leu Gln Gly 705 710 715 720 Gln Arg Leu Ile Ala Pro Gln Thr Leu Asn Leu Thr Ala Val Asn Glu 725 730 735 Ala Val Leu Ile Glu Asn Leu Glu Ile Phe Arg Lys Asn Gly Phe Asp 740 745 750 Phe Val Ile Asp Glu Asn Ala Pro Val Thr Glu Arg Ala Lys Leu Ile 755 760 765 Ser Leu Pro Thr Ser Lys Asn Trp Thr Phe Gly Pro Gln Asp Val Asp 770 775 780 Glu Leu Ile Phe Met Leu Ser Asp Ser Pro Gly Val Met Cys Arg Pro 785 790 795 800 Ser Arg Val Lys Gln Met Phe Ala Ser Arg Ala Cys Arg Lys Ser Val 805 810 B15 Met Ile Gly Thr Ala Leu Asn Thr Ser Glu Met Lys Lys Leu Ile Thr 820 825 830 His Met Gly Glu Met Asp His Pro Trp Asn Cys Pro His Gly Arg Pro 835 840 845 Thr Met Arg His Ile Ala Asn Leu Gly val Ile Ser Gln Asn 850 855 860 <210> 2975 <211> 1256 <212> PRT . <213> Homo sapiens <400> 2975 Met Tyr Leu Trp Leu Lys Leu Leu Ala Phe Gly Phe Ala Phe Leu Asp 1 5 10 15

Thr Glu Val Phe Val Thr Gly Gln Ser Pro Thr Pro Ser Pro Thr Gly

Leu Thr Thr Ala Lys Met Pro Ser val Pro Leu Ser Ser Asp Pro Leu 40 45 Pro Thr His Thr Thr Ala Phe Ser Pro Ala Ser Thr Phe Glu Arg Glu S50 : S55 60 Asn Asp Phe Ser Glu Thr Thr Thr Ser Leu Ser Pro Asp Asn Thr Ser 65 70 78 80 Thr Gln Val Ser Pro Asp Ser Leu Asp Asn Ala Ser Ala Phe Asn Thr 85 90 95 Thr Gly Val Ser Ser Val Gln Thr Pro His Leu Pro Thr His Ala Asp 100 105 110 Ser Gln Thr Pro Ser Ala Gly Thr Asp Thr Gln Thr Phe Ser Gly Ser 115 120 125 Ala Ala Asn Ala Lys Leu Asn Pro Thr Pro Gly Ser Asn Ala Ile Ser 130 135 140 Asp Ala Tyr Leu Asn Ala Ser Glu Thr Thr Thr Leu Ser Pro Ser Gly 145 150 155 160 Ser Ala Val Ile Ser Thr Thr Thr Ile Ala Thr Thr Pro Ser Lys Pro 165 170 175 Thr Cys Asp Glu Lys Tyr Ala Asn Ile Thr val Asp Tyr Leu Tyr Asn 180 185 180 Lys Glu Thr Lys Leu Phe Thr Ala Lys Leu Asn Val Asn Glu Asn val 195 200 205 Glu Cys Gly Asn Asn Thr Cys Thr Asn Asn Glu Val His Asn Leu Thr 210 215 220 Glu Cys Lys Asn Ala Ser Val Ser Ile Ser His Asn Ser Cys Thr Ala 225 230 235 240 Pro Asp Lys Thr Leu Ile Leu Asp Val Pro Pro Gly Val Glu Lys Phe 245 250 255

Gln Leu His Asp Cys Thr Gln Val Glu Lys Ala Asp Thr Thr Ile Cys 260 265 270 Leu Lys Trp Lys Asn Ile Glu Thr Phe Thr Cys Asp Thr Gln Asn Ile 275 280 285 Thr Tyr Arg Phe Gln Cys Gly Asn Met Ile Phe Asp Asn Lys Glu Ile 290 295 300 Lys Leu Glu Asn Leu Glu Pro Glu His Glu Tyr Lys Cys Asp Ser Glu 305 310 315 320 Ile Leu Tyr Asn Asn His Lys Phe Thr Asn Ala Ser Lys Ile Ile Lys 325 330 335 Thr Asp Phe Gly Ser Pro Gly Glu Pro Gln Ile Ile Phe Cys Arg Ser 340 345 350 Glu Ala Ala His Gln Gly Val Ile Thr Trp Asn Pro Pro Gln Arg Ser 355 360 365 Phe His Asn Phe Thr Leu Cys Tyr Ile Lys Glu Thr Glu Lys Asp Cys 370 375 380 Leu Asn Leu Asp Lys Asn Leu Ile Lys Tyr Asp Leu Gln Asn Leu Lys 385 390 395 400 Pro Tyr Thr Lys Tyr Val Leu Ser Leu His Ala Tyr Ile Ile Ala Lys 405 410 415 Val Gln Arg Asn Gly Ser Ala Ala Met Cys His Phe Thr Thr Lys Ser 420 425 430 Ala Pro Pro Ser Gln Val Trp Asn Met Thr Val Ser Met Thr Ser Asp 435 440 445 Asn Sex Met His Val Lys Cys Arg Pro Pro Arg Asp Arg Asn Gly Pro 450 455 460 His Glu Arg Tyr His Leu Glu Val Glu Ala Gly Asn Thr Leu Val Arg 465 470 475 480 Asn Glu Ser His Lys Asn Cys Asp Phe Arg Val Lys Asp Leu Gln Tyrx 485 490 495 Ser Thr Asp Tyr Thr Phe Lys Ala Tyr Phe His Asn Gly Asp Tyr Pro

500 505 510 Gly Glu Pro Phe Ile Leu His His Ser Thr Ser Tyr Asn Ser Lys Ala 515 520 525 Leu Ile Ala Phe Leu Ala Phe Leu Ile Ile Val Thr Ser Ile Ala Leu 530 535 540 Leu Val val Leu Tyr Lys Ile Tyr Asp Leu His Lys Lys Arg Ser Cys S45 550 585 560 Asn Leu Asp Glu Gln Gln Glu Leu Val Glu Arg Asp Asp Glu Lys Gln 565 570 575 Leu Met Asn Val Glu Pro Ile His Ala Asp Ile Leu Leu Glu Thr Tyr 580 585 590 Lys Arg Lys Ile Ala Asp Glu Gly Arg Leu Phe Leu Ala Glu Phe Gln 595 600 605 Ser Ile Pro Arg Val Phe Ser Lys Phe Pro Ile Lys Glu Ala Arg Lys 610 615 620 Pro Phe Asn Gln Asn Lys Asn Arg Tyr Val Asp Ile Leu Pro Tyr Asp 625 630 635 640 Tyr Asn Arg Val Glu Leu Ser Glu Ile Asn Gly Asp Ala Gly Ser Asn 645 650 655 Tyr Ile Asn Ala Ser Tyr Ile Asp Gly Phe Lys Glu Pro Arg Lys Tyr . 660 665 670 Ile Ala Ala Gln Gly Pro Arg Asp Glu Thr Val Asp Asp Phe Trp Arg 675 680 685 Met Ile Trp Glu Gln Lys Ala Thr Val Ile Val Met Val Thr Arg Cys 690 695 700 Glu Glu Gly Asn Arg Asn Lys Cys Ala Glu Tyr Trp Pro Ser Met Glu 705 710 715 720 Glu Gly Thr Arg Ala Phe Gly Asp Val Val val Lys Ile Asn Gln His 725 730 735 Lys Arg Cys Pro Asp Tyr Ile Ile Gln Lys Leu Asn Ile Val Asn Lys 740 745 750

Lys Glu Lys Ala Thr Gly Arg Glu Val Thr His Ile Gln Phe Thr Ser 755 760 765 Trp Pro Asp His Gly Val Pro Glu Asp Pro His Leu Leu Leu Lys Leu 770 775 780 Arg Arg Arg Val Asn Ala Phe Ser Asn Phe Phe Ser Gly Pro Ile Val 785 790 795 800 Val His Cys Ser Ala Gly Val Gly Arg Thr Gly Thr Tyr Ile Gly Ile 805 810 815 Asp Ala Met Leu Glu Gly Leu Glu Ala Glu Asn Lys Val Asp Val Tyr 820 825 830 Gly Tyr Val Val Lys Leu Arg Arg Gln Arg Cys Leu Met Val Gln Val 835 840 845 Glu Ala Gln Tyr Ile Leu Ile His Gln Ala Leu Val Glu Tyr Asn Gln 850 855 860 Phe Gly Glu Thr Glu Val Asn Leu Ser Glu Leu His Pro Tyr Leu His 865 870 875 880 Asn Met Lys Lys Arg Asp Pro Pro Ser Glu Pro Ser Pro Leu Glu Ala 885 850 895 Glu Phe Gln Arg Leu Pro Ser Tyr Arg Ser Trp Arg Thr Gln His Ile 500 905 910 Gly Asn Gln Glu Glu Asn Lys Ser Lys Asn Arg Asn Ser Asn Val Ile 915 920 825 Pro Tyr Asp Tyr Asn Arg Val Pro Leu Lys His Glu Leu Glu Met Ser 930 935 S40 Lys Glu Ser Glu His Asp Ser Asp Glu Ser Ser Asp Asp Asp Ser Asp 945 950 955 960 Ser Glu Glu Pro Ser Lys Tyr Ile Asn Ala Ser Phe Ile Met Ser Tyr S65 S70 975 Trp Lys Pro Glu Val Met Ile Ala Ala Gln Gly Pro Leu Lys Glu Thr 980 985 930

Ile Gly Asp Phe Trp Gln Met Ile Phe Gln Arg Lys Val Lys val Ile

995 1000 1005

Val Met Leu Thr Glu Leu Lys His Gly Asp Gln Glu Ile Cys Ala 1010 1015 1020

Gln Tyr Trp Gly Glu Gly Lys Gln Thr Tyr Gly Asp Ile Glu Val 1025 1030 1035

Asp Leu Lys Asp Thr Asp Lys Ser Ser Thr Tyr Thr Leu Arg Val 1040 1045 1050

Phe Glu Leu Arg His Ser Lys Arg Lys Asp Ser Arg Thr Val Tyr 1055 1060 1065

Gln Tyr Gln Tyr Thr Asn Trp Ser Val Glu Gln Leu Pro Ala Glu 1070 1075 1080

Pro Lys Glu Leu Ile Ser Met Ile Gln val Val Lys Gln Lys Leu 1085 1050 1095

Pro Gln Lys Asn Ser Ser Glu Gly Asn Lys His His Lys Ser Thr 1100 1105 1110

Pro Leu Leu Ile His Cys Arg Asp Gly Ser Gln Gln Thr Gly 1le 1115 1120 1125

Phe Cys Ala Leu Leu Asn Leu Leu Glu Ser Ala Glu Thr Glu Glu 1130 1135 1140 ’

Val Val Asp Ile Phe Gln Val Val Lys Ala Leu Arg Lys Ala Arg 1145 1150 1155

Pro Gly Met Val Ser Thr Phe Glu Gln Tyr Gln Phe Leu Tyr Asp 1160 1165 1170

Val Ile Ala Ser Thr Tyr Pro Ala Gln Asn Gly Gln Val Lys Lys 1175 1180 1185

Asn Asn His Gln Glu Asp Lys Ile Glu Phe Asp Asn Glu Val Asp : 1190 1195 1200

Lys val Lys Gln Asp Ala Asn Cys Val Asn Pro Leu Gly Ala Pro

1205 1210 1215

Glu Lys Leu Pro Glu Ala Lys Glu Gln Ala Glu Gly Ser Glu Pro 1220 1225 1230 Thr Ser Gly Thr Glu Gly Pro Glu His Ser Val Asn Gly Pro ala 1235 1240 1245 Ser Pro Ala Leu Asn Gln Gly Ser 1250 1255 <210> 297¢ <211> 319 <212> PRT <213> Homo sapiens <400> 2976 Met Lys Met Ala Ser Ser Leu Ala Phe Leu Leu Leu Asn Phe His Val 1 5 10 15 Ser Leu Leu Leu Val Gln Leu Leu Thr Pro Cys Ser Ala Gln Phe Ser

Val Leu Gly Pro Ser Gly Pro Ile Leu Ala Met Val Gly Glu Asp ala 40 45 Asp Leu Pro Cys His Leu Phe Pro Thr Met Ser Ala Glu Thr Met Glu 50 S5 60 Leu Lys Trp Val Ser Ser Ser Leu Arg Gln Val Val Asn Val Tyr Ala 65 70 75 80 Asp Gly Lys Glu val Glu Asp Arg Gln Ser Ala Pro Tyr Arg Gly Arg 85 So 95 Thr Ser Ile Leu Arg Asp Gly Ile Thr Ala Gly Lys Ala Ala Leu Arg 100 105 110 Ile His Asn val Thr Ala Ser Asp Ser Gly Lys Tyr Leu Cys Tyr Phe 115 120 125 Gln Asp Gly Asp Phe Tyr Glu Lys Ala Leu Val Glu Leu Lys Val Ala 130 135 140 Ala Leu Gly Ser Asn Leu His Val Glu Val Lys Gly Tyr Glu Asp Gly 145 150 155 160 Gly Ile His Leu Glu Cys Arg Ser Thr Gly Trp Tyr Pro Gln Pro Gln 165 170 175

US2003/012946

Ile Gln Trp Ser Asn Ala Lys Gly Glu Asn Ile Pro Ala Val Glu Ala 180 185 150 Pro Val val Ala Asp Gly val Gly Leu Tyr Glu Val Ala Ala Ser val 185 200 205 Ile Met Arg Gly Gly Ser Gly Glu Gly Val Ser Cys Ile Ile Arg Asn 210 215 220 Ser Leu Leu Gly Leu Glu Lys Thr Ala Ser Ile Ser Ile Ala Asp Pro . 225 230 235 240 Phe Phe Arg Ser Ala Gln Pro Trp Ile Ala Ala Leu Ala Gly Thr Leu 245 250 255 Pro Ile Leu Leu Leu Leu Leu Ala Gly Ala Ser Tyr Phe Leu Trp Arg 260 265 270 Gln Gln Lys Glu Ile Thr Ala Leu Ser Ser Glu Ile Glu Ser Glu Gln : 275 280 285 Glu Met Lys Glu Met Gly Tyr Ala Ala Thr Glu Arg Glu Ile Ser Leu 290 295 300 Arg Glu Ser Leu Gln Glu Glu Leu Lys Arg Lys Lys Ser Ser Thr 305 310 315 <210> 2977 <211> 240 «212> PRT <213> Homo sapiens <400> 2977 Met Leu Leu Gln Ser Gln Thr Met Gly Val Ser His Ser Phe Thr Pro 1 5 10 15 Lys Gly Ile Thr Ile Pro Gln Arg Glu Lys Pro Gly His Met Tyr Gln

Asn Glu Asp Tyr Leu Gln Asn Gly Leu Pro Thr Glu Thr Thr val Leu 40 45 Gly Thr Val Gln Ile Leu Cys Cys Leu Leu Ile Ser Ser Leu Gly Ala 50 55 60

Ile Leu Val Phe Ala Pro Tyr Pro Ser His Phe Asn Pro Ala Ile Ser 65 70 75 80 Thr Thr Leu Met Ser Gly Tyr Pro Phe Leu Gly Ala Leu Cys Phe Gly 85 90 95 Ile Thr Gly Ser Leu Ser Ile Ile Ser Gly Lys Gln Ser Thr Lys Pro 100 105 110 Phe Asp Leu Ser Ser Leu Thr Ser Asn Ala Val Ser Ser Val Thr Ala 115 120 125 Gly Ala Gly Leu Phe Leu Leu Ala Asp Ser Met Val Ala Leu Arg Thr 130 135 140 Ala Ser Gln His Cys Gly Ser Glu Met Asp Tyr Leu Ser Ser Leu Pro 145 ' 150 185 160 Tyr Ser Glu Tyr Tyr Tyr Pro Ile Tyr Glu Ile Lys Asp Cys Leu Leu 165 170 175 Thr Ser Val Ser Leu Thr Gly Val Leu Val Val Met Leu Ile Phe Thr 180 185 190 Val Leu Glu Leu Leu Leu Ala Ala Tyr Ser Ser Val Phe Trp Trp Lys 195 200 205 Gln Leu Tyr Ser Asn Asn Pro Gly Ser Ser Phe Ser Ser Thr Gln Ser 210 215 220 Gln Asp His Ile Gln Gln Val Lys Lys Ser Ser Ser Arg Ser Trp Ile 225 230 235 240 <210> 2978 <21l1l> 266 <212> PRT <213> Homo sapiens <400> 2978 Met Val Cys Leu Lys Leu Pro Gly Gly Ser Ser Leu Ala Ala Leu Thr 1 S 10 15 Val Thr Leu Met Val Leu Ser Ser Arg Leu Ala Phe Ala Gly Asp Thr

Arg Pro Arg Phe Leu Glu Leu Arg Lys Ser Glu Cys His Phe Phe Asn 40 45

T

Gly Thr Glu Arg Val Arg Tyr Leu Asp Arg Tyr Phe His Asn Gln Glu SO 55 60 Glu Phe Leu Arg Phe Asp Ser Asp Val Gly Glu Tyr Arg Ala Val Thr 65 70" 75 80 Glu Leu Gly Arg Pro Val Ala Glu Ser Trp Asn Ser Gln Lys Asp Leu 85 90 95 Leu Glu Gln Lys Arg Gly Arg Val Asp Asn Tyr Cys Arg His Asn Tyr 100 105 110 Gly val Gly Glu Ser Phe Thr Val Gln Arg Arg Val His Pro Gln Val 11s 120 125 Thr Val Tyr Pro Ala Lys Thr Gln Pro Leu Gln His His Asn Leu Leu 130 135 140 Val Cys Ser Val Ser Gly Phe Tyr Pro Gly Ser Ile Glu Val Arg Trp 145 150 155 160 Phe Arg Asn Gly Gln Glu Glu Lys Ala Gly Val val Ser Thr Gly Leu . 168 170 175 Ile Gln Asn Gly Asp Trp Thr Phe Gln Thr Leu Val Met Leu Glu Thr 180 185 190 Val Pro Arg Ser Gly Glu Val Tyr Thr Cys Gln Val Glu His Pro Ser 195 200 205 Val Thr Ser Ala Leu Thr Val Glu Trp Arg Ala Arg Ser Glu Ser Ala 210 215 220 Gln Ser Lys Met Leu Ser Gly Val Gly Gly Phe Val Leu Gly Leu Leu 225 230 235 240 Phe Leu Gly Ala Gly Leu Phe Ile Tyr Phe Arg Asn Gln Lys Gly His 245 250 255 Ser Gly Leu Gln Pro Thr Gly Phe Leu Ser 260 265 <210> 2979 <211> 325 <212> PRT

PCT/US2003/012946

<213> Homo sapiens <400> 2979 Met Pro Ile Thr Arg Met Arg Met Arg Pro Trp Leu Glu Met Gln Ile 1 5 10 15 Asn Ser Asn Gln Ile Pro Gly Leu Ile Trp Ile Asn Lys Glu Glu Met

Ile Phe Gln Ile Pro Trp Lys His Ala Ala Lys His Gly Trp Asp 1le 40 45 Asn Lys Asp Ala Cys Leu Phe Arg Ser Trp Ala Ile His Thr Gly Arg 50 55 60 Tyr Lys Ala Gly Glu Lys Glu Pro Asp Pro Lys Thr Trp Lys Ala Asn 65 70 75 80 Phe Arg Cys Ala Met Asn Ser Leu Pro Asp Ile Glu Glu Val Lys Asp 8S 80 95 Gln Ser Arg Asn Lys Gly Ser Ser Ala Val Arg Val Tyr Arg Met Leu 100 105 110 Pro Pro Leu Thr Lys Asn Gln Arg Lys Glu Arg Lys Ser Lys Ser Ser 115 120 . 125 Arg Asp Ala Lys Ser Lys Ala Lys Arg Lys Ser Cys Gly Asp Ser Ser 130 135 140 Pro Asp Thr Phe Ser Asp Gly Leu Ser Ser Ser Thr Leu Pro Asp Asp 145 150 155 160 His Ser Ser Tyr Thr Val Pro Gly Tyr Met Gln Asp Leu Glu Val Glu 165 170 175 Gln Ala Leu Thr Pro Ala Leu Ser Pro Cys Ala Val Ser Ser Thr Leu 180 185 180 Pro Asp Trp His Ile Pro val Glu Val val Pro Asp Ser Thr Ser Asp 185 200 205 Leu Tyr Asn Phe Gln Val Ser Pro Met Pro Ser Thr Ser Glu Ala Thr 210 215 220 Thr Asp Glu Asp Glu Glu Gly Lys Leu Pro Glu Asp Ile Met Lys Leu

225 230 235 240 Leu Glu Gln Ser Glu Trp Gln Pro Thr Asn Val Asp Gly Lys Gly Tyr 245 250 255 Leu Leu Asn Glu Pro Gly Val Gln Pro Thr Ser Val Tyr Gly Asp Phe 260 265 270 Ser Cys Lys Glu Glu Pro Glu Ile Asp Ser Pro Gly Gly Asp Ile Gly 275 280 285 Leu Ser Leu Gln Arg Val Phe Thr Asp Leu Lys Asn Met Asp Ala Thr 290 295 300 Trp Leu Asp Ser Leu Leu Thr Pro Val Arg Leu Pro Ser Ile Gln Ala 305 310 315 320 Ile Pro Cys Ala Pro 325 <210> 2980 <211> 132 <212> PRT <213> Homo sapiens <400> 2980 Met Glu Phe Asp Leu Asn Gly Asn Gly Asp Ile Gly Glu Lys Arg Val 1 5 10 15 Ile Cys Gly Gly Arg Val Val Cys Arg Pro Lys Lys Thr Glu Val Ser

Pro Thr Cys Ser Ile Pro His Asp Leu Gly Gly Gly Pro Pro Thr Thr 40 45 val Gly Gly Arg Arg Met Gly Met Arg Lys Trp Glu Arg Arg Glu Arg 50 55 60 Val Ser Pro Pro Ser Pro His Pro His Pro Leu Pro Pro Asp Ile Met 65 70 75 80 Ser Leu Lys Arg Met Leu Glu Lys Leu Gly Val Pro Lys Thr His Leu 85 90 95 Glu Leu Lys Lys Leu Ile Gly Glu Val Ser Ser Gly Ser Gly Glu Thr 100 105 110

Phe Ser Tyr Pro Asp Phe Leu Arg Met Met Leu Gly Lys Arg Ser Ala 115 120 125 Ile Leu Lys Met 130 <210> 2981 <211> 319 <212> PRT <213> Homo sapiens <400> 2981 Met Thr Asn Ser Ser Phe Phe Cys Pro Val Tyr Lys Asp Leu Glu Pro ’ 1 5 10 15 Phe Thr Tyr Phe Phe Tyr Leu Val Phe Leu Val Gly Ile Ile Gly Ser

Cys Phe Ala Thr Trp Ala Phe Ile Gln Lys Asn Thr Asn His Arg Cys 40 45 Val Ser Ile Tyr Leu Ile Asn Leu Leu Thr Ala Asp Phe Leu Leu Thr 50 55 60 Leu Ala Leu Pro Val Lys Ile Val val Asp Leu Gly Val Ala Pro Trp 65 70 75 80 Lys Leu Lys Ile Phe His Cys Gln Val Thr Ala Cys Leu Ile Tyr Ile 85 90 95 Asn Met Tyr Leu Ser Ile Ile Phe Leu Ala Phe Val Ser Ile Asp Arg 100 105 110 Cys Leu Gln Leu Thr His Ser Cys Lys Ile Tyr Arg Ile Gln Glu Pro 115 120 125 Gly Phe Ala Lys Met Ile Ser Thr Val Val Trp Leu Met Val Leu Leu 130 135 140 Ile Met Val Pro Asn Met Met Ile Pro Ile Lys Asp Ile Lys Glu Lys 145 150 158 160 Ser Asn Val Gly Cys Met Glu Phe Lys Lys Glu Phe Gly Arg Asn Trp 165 170 175 His Leu Leu Thr Asn Phe Ile Cys Val Ala Ile Phe Leu Asn Phe Ser

03/012946

180 185 190 Ala Ile Ile Leu Ile Ser Asn Cys Leu Val Ile Arg Gln Leu Tyr Arg 195 200 205 Asn Lys Asp Asn Glu Asn Tyr Pro Asn Val Lys Lys Ala Leu Ile Asn 210 215 220 Ile Leu Leu Val Thr Thr Gly Tyr Ile Ile Cys Phe Val Pro Tyr His 225 230 235 240 Ile Val Arg Ile Pro Tyr Thr Leu Ser Gln Thr Glu Val Ile Thr Asp ’ 245 250 255 Cys Ser Thr Arg Ile Ser Leu Phe Lys Ala Lys Glu Ala Thr Leu Leu 260 265 270 Leu Ala Val Ser Asn Leu Cys Phe Asp Pro Ile Leu Tyr Tyr His Leu 275 280 285 Ser Lys Ala Phe Arg Ser Lys Val Thr Glu Thr Phe Ala Ser Pro Lys 290 295 300

Glu Thr Lys Ala Gln Lys Glu Lys Leu Arg Cys Glu Asn Asn Ala

3058 310 315

<210> 2982

<211> 334 "<212> PRT

<213> Homo sapiens

<400> 29B2

Met Leu Thr Lys Pro Leu Gln Gly Pro Pro Ala Pro Pro Gly Thr Pro 1 5 10 15

Thr Pro Pro Pro Gly Gly Lys Asp Arg Glu Ala Phe Glu Ala Glu TYY

Arg Leu Gly Pro Leu Leu Gly Lys Gly Gly Phe Gly Thr Val Phe Ala 40 45 Gly His Arg Leu Thr Asp Arg Leu Gln Val Ala Ile Lys Val Ile Pro SO 55 60 Arg Asn Arg Val Leu Gly Trp Ser Pro Leu Ser Asp Ser Val Thr Cys 65 70 75 80

Pro Leu Glu Val Ala Leu Leu Trp Lys Val Gly Ala Gly Gly Gly His 85 90 985 Pro Gly val Ile Arg Leu Leu Asp Trp Phe Glu Thr Glm Glu Gly Phe 100 105 110 Met Leu Val Leu Glu Arg Pro Leu Pro Ala Gln Asp Leu Phe Asp Tyr 115 120 125 Ile Thr Glu Lys Gly Pro Leu Gly Glu Gly Pro Ser Arg Cys Phe Phe 130 135 140 Gly Gln Val Val ala Ala Ile Gln His Cys His Ser Arg Gly Val val ” 145 150 155 160 His Arg Asp Ile Lys Asp Glu Asn Ile Leu Ile Asp Leu Arg Arg Gly 165 170 175 Cys Ala Lys Leu Ile Asp Phe Gly Ser Gly Ala Leu Leu His Asp Glu 180 185 150 Pro Tyr Thr Asp Phe Asp Gly Thr Arg Val Tyr Ser Pro Pro Glu Trp 195 200 205 Ile Ser Arg His Gln Tyr His Ala Leu Pro Ala Thr Val Trp Ser Leu 210 215 220 Gly Ile Leu Leu Tyr Asp Met Val Cys Gly Asp lle Pro Phe Glu Arg 225 230 ‘ 235 240 Asp Gln Glu Ile Leu Glu Ala Glu Leu His Phe Pro Ala His Val Ser 245 250 255 Pro Asp Cys Cys Ala Leu Ile Arg Arg Cys Leu Ala Pro Lys Pro Ser 260 265 270 Ser Arg Pro Ser Leu Glu Glu Ile Leu Leu Asp Pro Trp Met Gln Thr 275 280 285 Pro Ala Glu Asp Val Thr Pro Gln Pro Leu Gln Arg Arg Pro Cys Pro 290 295 300 Phe Gly Leu Val Leu Ala Thr Leu Ser Leu Ala Trp Pro Gly Leu Ala 305 310 318 320

Pro Asn Gly Gln Lys Ser His Pro Met Ala Met Ser Gln Gly 325 330

<210> 2983 <21ll> 158 <212> PRT <213> Homo sapiens <400> 2983 Met Met Gln Lys Leu Leu Lys Cys Ser Arg Leu Val Leu Ala Leu Ala 1 5 10 15 Leu Ile Leu Val Leu Glu Ser Ser Val Gln Gly Tyr Pro Thr Gln Arg

Ala Arg Tyr Gln Trp Val Arg Cys Asn Pro Asp Ser Asn Ser Ala Asn

40 45 Cys Leu Glu Glu Lys Gly Pro Met Phe Glu Leu Leu Pro Gly Glu Ser 50 5S 60 Asn Lys Ile Pro Arg Leu Arg Thr Asp Leu Phe Pro Lys Thr Arg Ile 65 70 75 80 Gln Asp Leu Asn Arg Ile Phe Pro Leu Ser Glu Asp Tyr Ser Gly Ser 85 S80 95

Gly Phe Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Phe

100 105 110 Leu Thr Glu Met Glu Gln Asp Tyr Gln Leu Val Asp Glu Ser Asp Ala

115 120 125 Phe His Asp Asn Leu Arg Ser Leu Asp Arg Asn Leu Pro Ser Asp Ser 130 135 140 Gln Asp Leu Gly Gln His Gly Leu Glu Glu Asp Phe Met Leu 145 150 155 <210> 2984 <211> 1019 <212> PRT <213> Homo sapiens <400> 2984 Ala Asp Pro Glu Ser Pro Ile Leu Asp Leu Asp Leu His Leu Pro Leu 1 S 10 15

Leu Cys Phe Arg Pro Glu Lys Val Leu Gln Ile Leu Thr Cys Ile Leu

Thr Glu Gln Arg Ile Val Phe Phe Ser Ser Asp Trp Ala Leu Leu Thr 40 45 Leu Val Thr Glu Cys Phe Met Ala Tyr Leu Tyr Pro Leu Gln Trp Gln SO 55 60 His Pro Phe Val Pro Ile Leu Ser Asp Gln Met Leu Asp Phe Val Met 65 70 75 80 Ala Pro Thr Ser Phe Leu Met Gly Cys His Leu Asp His Phe Glu Glu 85 90 95 Val Ser Lys Glu Ala Asp Gly Leu Val Leu Ile Asn Ile Asp His Gly 100 105 110 Ser Ile Thr Tyr Ser Lys Ser Thr Asp Asp Asn Val Asp Ile Pro Asp 115 120 125 Val Pro Leu Leu Ala Ala Gln Thr Phe Ile Gln Arg Val Gln Ser Leu 130 135 140 Gln Leu His His Glu Leu His Ala Ala His Leu Leu Ser Ser Thr Asp 145 150 155 160 Leu Lys Glu Gly Arg Ala His Arg Arg Ser Trp Gln Gln Lys Leu Asn 165 170 175 Cys Gln Ile Gln Gln Thr Thr Leu Gln Leu Leu Val Ser Ile Phe Arg 180 185 190 Asp Val Lys Asn His Leu Asn Tyr Glu His Arg Val Phe Asn Ser Glu 185 200 205 Glu Phe Leu Lys Thr Arg Ala Pro Gly Asp His Gln Phe Tyr Lys Gln 210 215 220 Val Leu Asp Thr Tyr Met Phe His Ser Phe Leu Lys Ala Arg Leu Asn 225 230 235 240 Arg Arg Met Asp Ala Phe Ala Gln Met Asp Leu Asp Thr Gln Ser Glu 245 250 255

Glu Asp Arg Ile Asn Gly Met Leu Leu Ser Pro Arg Arg Pro Thr Val 260 265 270 Glu Lys Arg Ala Ser Arg Lys Ser Ser His Leu His Val Thr His Arg 275 280 28S Arg Met Val val Ser Met Pro Asn Leu Gln Asp Ile Ala Met Pro Glu 290 28S 300 Leu Ala Pro Arg Asn Ser Ser Leu Arg Leu Thr Asp Thr Ala Gly Cys 305 310 315 320 Arg Gly Ser Ser Ala Val Leu Asn Val Thr Pro Lys Ser Pro Tyr Thr 325 330 335 Phe Lys Ile Pro Glu Ile His Phe Pro Leu Glu Ser Lys Cys Val Gln 340 345 350 Ala Tyr His Ala His Phe Val Ser Met Leu Ser Glu Ala Met Cys Phe 355 360 365 Leu Ala Pro Asp Asn Ser Leu Leu Leu Ala Arg Tyr Leu Tyr Leu Arg 370 375 380 Gly Leu Val Tyr Leu Met Gln Gly Gln Leu Leu Asn Ala Leu Leu Asp 385 390 395 400 Phe Gln Asn Leu Tyr Lys Thr Asp Ile Arg Ile Phe Pro Thr Asp Leu 405 410 415 Val Lys Arg Thr Val Glu Ser Met Ser Ala Pro Glu Trp Glu Gly Ala 420 425 430 Glu Gln Ala Pro Glu Leu Met Arg Leu Ile Ser Glu Ile Leu Asp Lys 435 440 445 Pro His Glu Ala Ser Lys Leu Asp Asp His Val Lys Lys Phe Lys Leu 450 455 460 Pro Lys Lys His Met Gln Leu Gly Asp Phe Met Lys Arg Val Gln Glu 465 470 475 480 Ser Gly Ile Val Lys Asp Ala Ser Ile Ile His Arg Leu Phe Glu Ala 485 490 495 Leu Thr val Gly Gln Glu Lys Gln Ile Asp Pro Glu Thr Phe Lys Asp

S2003/012946

500 505 510 Phe Tyr Asn Cys Trp Lys Glu Thr Glu Ala Glu Ala Gln Glu Val ger 515 520 525 Leu Pro Trp Leu Val Met Glu His Leu Asp Lys Asn Glu Cys val cys 530 53s 540 Lys Leu Ser Ser Ser Val Lys Thr Asn Leu Gly val Gly Lys Ile Ala 545 550 555 560 Met Thr Gln Lys Arg Leu Phe Leu Leu Thr Glu Gly Arg Pro Gly Tyr 565 570 575 Leu Glu Ile Ser Thr Phe Arg Asn Ile Glu Glu Val Arg Arg Thr Thr 580 585 590 Thr Thr Phe Leu Leu Arg Arg Ile Pro Thr Leu Lys Ile Arg Val Ala 595 600 605 Ser Lys Lys Glu Val Phe Glu Ala Asn Leu Lys Thr Glu Cys Asp Leu 610 615 620 Trp His Leu Met Val Lys Glu Met Trp ala Gly Lys Lys Leu Ala Asp 625 630 635 640 Asp His Lys Asp Pro His Tyr Val Gln Gln Ala Leu Thr Asn Val Leu 645 650 655 Leu Met Asp Ala Val Val Gly Thr Leu Gln Ser Pro Gly Ala Ile Tyr 660 665 670 Ala Ala Ser Lys Leu Ser Tyr Phe Asp Lys Met Ser Asn Glu Met Pro 675 680 685 Met Thr Leu Pro Glu Thr Thr Leu Glu Thr Leu Lys His Lys Ile Asn 690 695 700 Pro Ser Ala Gly Glu Ala Phe Pro Gln Ala Val Asp Val Leu Leu Tyr 705 710 715 720 Thr Pro Gly His Leu Asp Pro Ala Glu Lys val Glu Asp Ala His Pro 725 730 735 Lys Leu Trp Cys Ala Leu Ser Glu Gly Lys Val Thr Val Phe Asn Ala 740 745 750

Ser Ser Trp Thr Ile His Gln His Ser Phe Lys Val Gly Thr Ala Lys 755 760 765 Val Asn Cys Met Val Met Ala Asp Gln Asn Gln Val Trp Val Gly Ser 770 775 780 Glu Asp Ser Val Ile Tyr Ile Ile Asn Val His Ser Met Ser Cys Asn 785 790 795 800 Lys Gln Leu Thr Ala His Cys Ser Ser Val Thr Asp Leu Ile Val Gln 805 810 815 Asp Gly Gln Glu Ala Pro Ser Asn Val Tyr Ser Cys Ser Met Asp Gly 820 825 830 Met Val Leu Val Trp Asn Val Ser Thr Leu Gln Val Thr Ser Arg Phe 835 840 845 Gln Leu Pro Arg Gly Gly Leu Thr Ser Ile Arg Leu His Gly Gly Arg 850 855 860 Leu Trp Cys Cys Thr Gly Asn Ser Ile Met Val Met Lys Met Asn Gly 865 870 875 880 Ser Leu His Gln Glu Leu Lys Ile Glu Glu Asn Phe Lys Asp Thr Ser 885 890 895 Thr Ser Phe Leu Ala Phe Gln Leu Leu Pro Glu Glu Glu Gln Leu Trp 900 905 : 910 Ala Ala Cys Ala Gly Arg Ser Glu Val Tyr Ile Trp Ser Leu Lys Asp 915 920 925 Leu Ala Gln Pro Pro Gln Arg Val Pro Leu Glu Asp Cys Ser Glu Ile 830 935 940 Asn Cys Met lle Arg Val Lys Lys Gln Val Trp Val Gly Ser Arg Gly 945 950 855 960 Leu Gly Gln Gly Thr Pro Lys Gly Lys Ile Tyr Val Ile Asp Ala Glu 965 970 975 Arg Lys Thr val Glu Lys Glu Leu Val Ala His Met Asp Thr val Arg 980 985 990

Thr Leu Cys Ser Ala Glu Asp Arg Tyr Val Leu Ser Gly Ser Gly Arg 995 1000 1005 Glu Glu Gly Lys Val Ala Ile Trp Lys Gly Glu 1010 1015 <210> 2985 <211> 783 <212> PRT <213> Homo sapiens <400> 2985 Met Ala Lys Tyr Asn Thr Gly Gly Asn Pro Thr Glu Asp Val Ser Val 1 5 10 15 Asn Ser Arg Pro Phe Arg Val Thr Gly Pro Asn Ser Ser Ser Gly Ile

Gln Ala Arg Lys Asn Leu Phe Asn Asn Gln Gly Asn Ala Ser Pro Pro 40 45 Ala Gly Pro Ser Asn Val Pro Lys Phe Gly Ser Pro Lys Pro Pro Val 50 55 60 Ala Val Lys Pro Ser Ser Glu Glu Lys Pro Asp Lys Glu Pro Lys Pro 65 70 75 80 Pro Phe Leu Lys Pro Thr Gly Ala Gly Gln Arg Phe Gly Thr Pro Ala 85 90 95 Ser Leu Thr Thr Arg Asp Pro Glu Ala Lys Val Gly.

Phe Leu Lys Pro 100 105 110 Val Gly Pro Lys Pro Ile Asn Leu Pro Lys Glu Asp Ser Lys Pro Thr 115 120 125 Phe Pro Trp Pro Pro Gly Asn Lys Pro Ser Leu His Ser Val Asn Gln 130 135 140 Asp His Asp Leu Lys Pro Leu Gly Pro Lys Ser Gly Pro Thr Pro Pro 145 150 155 160 Thr Ser Glu Asn Glu Gln Lys Gln Ala Phe Pro Lys Leu Thr Gly Val 165 170 175 Lys Gly Lys Phe Met Ser Ala Ser Gln Asp Leu Glu Pro Lys Pro Leu

180 . 185 190 Phe Pro Lys Pro Ala Phe Gly Gln Lys Pro Pro Leu Ser Thr Glu Asn 195 200 205 Ser His Glu Asp Glu Ser Pro Met Lys Asn Val Ser Ser Ser Lys Gly 210 215 220 Ser Pro Ala Pro Leu Gly Val Arg Ser Lys Ser Gly Pro Leu Lys Pro 225 230 235 240 Ala Arg Glu Asp Ser Glu Asn Lys Asp His Ala Gly Glu Ile Ser Ser 245 250 255 Leu Pro Phe Pro Gly Val Val Leu Lys Pro Ala Ala Ser Arg Gly Gly 260 265 270 Leu Gly Leu Ser Lys Asn Gly Glu Glu Lys Lys Glu Asp Arg Lys Ile 275 280 285 Asp Ala Ala Lys Asn Thr Phe Gln Ser Lys Ile Asn Gln Glu Glu Leu 290 295 300 Ala Ser Gly Thr Pro Pro Ala Arg Phe Pro Lys Ala Pro Ser Lys Leu 305 310 315 320 Thr Val Gly Gly Pro Trp Gly Gln Ser Gln Glu Lys Glu Lys Gly Asp 325 330 335 Lys Asn Ser Ala Thr Pro Lys Gln Lys Pro Leu Pro Pro Leu Phe Thr 340 345 350 Leu Gly Pro Pro Pro Pro Lys Pro Asn Arg Pro Pro Asn Val Asp Leu 355 360 365 Thr Lys Phe His Lys Thr Ser Ser Gly Asn Ser Thr Ser Lys Gly Gln 370 375 380 Thr Ser Tyr Ser Thr Thr Ser Leu Pro Pro Pro Pro Pro Ser His Pro 385 350 385 400 Ala Ser Gln Pro Pro Leu Pro Ala Ser His Pro Ser Gln Pro Pro Val 405 410 415 Pro Ser Leu Pro Pro Arg Asn Ile Lys Pro Pro Phe Asp Leu Lys Ser 420 425 430

2 46

Pro Val Asn Glu Asp Asn Gln Asp Gly Val Thr His Ser Asp Gly Ala 435 440 445 Gly Asn Leu Asp Glu Glu Gln Asp Ser Glu Gly Glu Thr Tyr Glu Asp 450 455 460 Ile Glu Ala Ser Lys Glu Arg Glu Lys Lys Arg Glu Lys Glu Glu Lys 465 470 475 480 Lys Arg Leu Glu Leu Glu Lys Lys Glu Gln Lys Glu Lys Glu Lys Lys 485 4950 495 Glu Gln Glu Ile Lys Lys Lys Phe Lys Leu Thr Gly Pro Ile Gln val 500 505 510 Ile His Leu Ala Lys Ala Cys Cys Asp Val Lys Gly Gly Lys Asn Glu 515 520 525 Leu Ser Phe Lys Gln Gly Glu Gln Ile Glu Ile Ile Arg Ile Thr Asp 530 535 540 Asn Pro Glu Gly Lys Trp Leu Gly Arg Thr Ala Arg Gly Ser Tyr Gly 545 550 555 560 Tyr Ile Lys Thr Thr Ala val Glu Ile Asp Tyr Asp Ser Leu Lys Leu 565 570 575 Lys Lys Asp Ser Leu Gly Ala Pro Ser Arg Pro Ile Glu Asp Asp Gln 580 585 590 Glu val Tyr Asp Asp Val Ala Glu Gln Asp Asp Ile Ser Ser His Ser 595 600 605 Gln Ser Gly Ser Gly Gly Ile Phe Pro Pro Pro Pro Asp Asp Asp Ile 610 615 620 Tyr Asp Gly Ile Glu Glu Glu Asp Ala Asp Asp Gly Phe Pro Ala Pro 625 630 635 640 Pro Lys Gln Leu Asp Met Gly Asp Glu Val Tyr Asp Asp Val Asp Thr 645 650 655 Ser Asp Phe Pro Val Ser Ser Ala Glu Met Ser Gln Gly Thr Asn Phe 660 665 670

Gly Lys Ala Lys Thr Glu Glu Lys Asp Leu Lys Lys Leu Lys Lys Gln 675 680 685 Glu Lys Glu Glu Lys Asp Phe Arg Lys Lys Phe Lys Tyr Asp Gly Glu 680 695 700 Ile Arg Val Leu Tyr Ser Thr Lys Val Thr Thr Ser Ile Thr Ser Lys 705 710 715 720 Lys Trp Gly Thr Arg Asp Leu Gln Val Lys Pro Gly Glu Ser Leu Glu 725 730 735 Val Ile Gln Thr Thr Asp Asp Thr Lys Val Leu Cys Arg Asn Glu Glu 740 745 750 Gly Lys Tyr Gly Tyr Val Leu Arg Ser Tyr Leu Ala Asp Asn Asp Gly 758 760 765 Glu Ile Tyr Asp Asp Ile Ala Asp Gly Cys Ile Tyr Asp Asn Asp 770 775 780 <210> 2986 <211> 266 <212> PRT <213> Homo sapiens <400> 2986 Met Val Cys Leu Lys Leu Pro Gly Gly Ser Ser Leu Ala Ala Leu Thr 1 5 10 15 Val Thr Leu Met Val Leu Ser Ser Arg Leu Ala Phe Ala Gly Asp Thr

Arg Pro Arg Phe Leu Glu Leu Arg Lys Ser Glu Cys His Phe Phe Asn 40 45 Gly Thr Glu Arg Val Arg Tyr Leu Asp Arg Tyr Phe His Asn Gln Glu 50 85 60 Glu Phe Leu Arg Phe Asp Ser Asp Val Gly Glu Tyr Arg Ala Val Thr 65 70 75 80 Glu Leu Gly Arg Pro Val Ala Glu Ser Trp Asn Ser Gln Lys Asp Leu 85 S80 95 Leu Glu Gln Lys Arg Gly Arg Val Asp Asn Tyr Cys Arg His Asn Tyr aaa

100 105 110 Gly Val Gly Glu Ser Phe Thr Val Gln Arg Arg val His Pro Gln Val 115 120 125 Thr Val Tyr Pro Ala Lys Thr Gln Pro Leu Gln His His Asn Leu Leu 130 135 140 Val Cys Ser Val Ser Gly Phe Tyr Pro Gly Ser Ile Glu Val Arg Trp 145 150 155 160 Phe Arg Asn Gly Gln Glu Glu Lys Ala Gly Val val Ser Thr Gly Leu 165 170 175 Ile Gln Asn Gly Asp Trp Thr Phe Gln Thr Leu Val Met Leu Glu Thr 180 185 190 Val Pro Arg Ser Gly Glu Val Tyr Thr Cys Gln Val Glu His Pro Ser 1385 200 205 Val Thr Ser Ala Leu Thr Val Glu Trp Arg Ala Arg Ser Glu Ser Ala 210 215 220 Gln Ser Lys Met Leu Ser Gly Val Gly Gly Phe Val Leu Gly Leu Leu 225 230 235 240 Phe Leu Gly Ala Gly Leu Phe Ile Tyr Phe Arg Asn Gln Lys Gly His 245 250 255 Ser Gly Leu Gln Pro Thr Gly Phe Leu Ser 260 265 <210> 2987 <211> 363 <212> PRT <213> Homo sapiens <400> 2987 Met Glu Val Lys Lys Lys Lys His Asp Lys Gln Glu Gln Lys Gly Ser 1 S 10 15 Val Gly Ala Thr Phe Lys Leu Gly Asp Ser Leu Ser Asn Pro Asn Glu

Arg Ala Ile Val Lys Glu Lys Met Val Ser Asn Thr Lys Ser Val Asp 40 45

PCT/US2003/012946

Thr Lys Ala Ser Ser Ser Lys Phe Ser Arg Ile Leu Thr Pro Lys Glu S50 55 60 Tyr Leu Gln Arg Gln Lys His Lys Glu Ala Pro Ser Asn Lys Ala Ser 65 70 75 80 Lys Lys Ile Cys Val Lys Asn Val Pro Cys Asp Ser Glu His Met Arg 85 90 95 Pro Ser Lys Leu Ala Val Gln Val Glu Ser Cys Gly Lys Ser Asn Glu 100 105 110 Lys His Ser Ser Gly Val Gln Thr Ser Lys Glu Ser Leu Asn Gly Leu 115 120 125 Thr Ser His Gly Lys Asn Leu Lys Ile His His Ser Gln Glu Ser Lys : 130 135 140 Thr Tyr Asn Ile Leu Arg Asn Val Lys Glu Lys val Gly Gly Lys Gln 145 150 155 160 Pro Asp Lys Ile Trp Ile Asp Lys Thr Lys Leu Asp Lys Leu Thr Asn 165 170 175 ' Ile Ser Asn Glu Ala Gln Phe Ser Gln Met Pro Pro Gln Val Lys Asp 180 185 190 Gln Lys Lys Leu Tyr Leu Asn Arg Val Gly Phe Lys Cys Thr Glu Arg 195 200 205 Glu Ser Ile Ser Leu Thr Lys Leu Glu Ser Ser Pro Arg Lys Leu His 210 215 220 Lys Asp Lys Arg Gln Glu Asn Lys His Lys Thr Phe Leu Pro Val Lys 225 230 235 240 Gly Asn Thr Glu Lys Ser Asn Met Leu Glu Phe Lys Leu Cys Pro Asp 245 250 255 Ile Leu Leu Lys Asn Thr Asn Ser Val Glu Glu Arg Lys Asp Val Lys 260 265 270 Pro His Pro Arg Lys Glu Gln Ala Pro Leu Gln Val Ser Gly Ile Lys 275 280 285

PCT/US2003/012946

Ser Thr Lys Glu Asp Trp Leu Lys Phe Val Ala Thr Lys Lys Arg Thr 290 295 300 Gln Lys Asp Ser Gln Glu Arg Asp Asn Val Asn Ser Arg Leu Ser Lys 305 310 315 320 Arg Ser Phe Ser Ala Asp Gly Phe Glu Met Leu Gln Asn Pro val Lys 325 330 33s Asp Ser Lys Glu Met Phe Gln Thr Tyr Lys Gln Met Tyr Leu Glu Lys 340 345 350 Arg Ser Arg Ser Leu Gly Ser Ser Pro val Lys 355 360 <210> 2988 <211> 836 <212> PRT <213> Homo sapiens <400> 2988 Met Ala Arg Leu Gly Asn Cys Ser Leu Thr Trp Ala Ala Leu Ile Ile 1 5 10 15 Leu Leu Leu Pro Gly Ser Leu Glu Glu Cys Gly His Ile Ser val Ser

Ala Pro Ile Val His Leu Gly Asp Pro Ile Thr ala Ser Cys Ile Ile 40 45 Lys Gln Asn Cys Ser His Leu Asp Pro Glu Pro Gln Ile Leu Trp Arg 50 55 60 Leu Gly Ala Glu Leu Gln Pro Gly Gly Arg Gln Gln Arg Leu Ser Asp 65 70 75 80 Gly Thr Gln Glu Ser Ile Ile Thr Leu Pro His Leu Asn His Thr Gln 85 So 95 Ala Phe Leu Ser Cys Cys Leu Asn Trp Gly Asn Ser Leu Gln Ile Leu 100 105 110 Asp Gln Val Glu Leu Arg Ala Gly Tyr Pro Pro Ala Ile Pro His Asn 115 120 125 Leu Ser Cys Leu Met Asn Leu Thr Thr Ser Ser Leu Ile Cys Gln Trp 130 135 140

Glu Pro Gly Pro Glu Thr His Leu Pro Thr Ser Phe Thr Leu Lys Ser 145 150 155 160 Phe Lys Ser Arg Gly Asn Cys Gln Thr Gln Gly Asp Ser Ile Leu Asp

165 170 175 Cys Val Pro Lys Asp Gly Gln Ser His Cys Cys Ile Pro Arg Lys His 180 185 190 Leu Leu Leu Tyr Gln Asn Met Gly Ile Trp Val Gln Ala Glu Asn Ala 195 200 205 Leu Gly Thr Ser Met Ser Pro Gln Leu Cys Leu Asp Pro Met Asp Val

210 215 220 Val Lys Leu Glu Pro Pro Met Leu Arg Thr Met Asp Pro Ser Pro Glu 225 230 ’ 235 240 Ala Ala Pro Pro Gin Ala Gly Cys Leu Gln Leu Cys Trp Glu Pro Trp

245 250 255 Gln Pro Gly Leu His Ile Asn Gln Lys Cys Glu Leu Arg His Lys Pro 260 265 270 Gln Arg Gly Glu Ala Ser Trp Ala Leu Val Gly Pro Leu Pro Leu Glu 275 280 285 Ala Leu Gln Tyr Glu Leu Cys Gly Leu Leu Pro Ala Thr Ala Tyr Thr 290 295 300 Leu Gln Ile Arg Cys Ile Arg Trp Pro Leu Pro Gly His Trp Ser Asp 305 310 315 320 Trp Ser Pro Ser Leu Glu Leu Arg Thr Thr Glu Arg Ala Pro Thr Val 325 330 335 Arg Leu Asp Thr Trp Trp Arg Gln Arg Gln Leu Asp Pro Arg Thr Val 340 345 350 Gln Leu Phe Trp Lys Pro Val Pro Leu Glu Glu Asp Ser Gly Arg Ile 355 360 365 Gln Gly Tyr Val Val Ser Trp Arg Pro Ser Gly Gln Ala Gly Ala Ile 370 37S 380

Leu Pro Leu Cys Asn Thr Thr Glu Leu Ser Cys Thr Phe His Leu Pro 385 390 395 400 Ser Glu Ala Gln Glu Val Ala Leu Val Ala Tyr Asn Ser Ala Gly Thr 405 410 415 Ser Arg Pro Thr Pro Val Val Phe Ser Glu Ser Arg Gly Pro Ala Leu 420 425 430 Thr Arg Leu His Ala Met Ala Arg Asp Pro His Ser Leu Trp Val Gly 435 440 445 Trp Glu Pro Pro Asn Pro Trp Pro Gln Gly Tyr Val Ile Glu Trp Gly 450 455 460 Leu Gly Pro Pro Ser Ala Ser Asn Ser Asn Lys Thr Trp Arg Met Glu 465 470 475 480 Gln Asn Gly Arg Ala Thr Gly Phe Leu Leu Lys Glu Asn Ile Arg Pro 485 430 495 Phe Gln Leu Tyr Glu Ile Ile Val Thr Pro Leu Tyr Gln Asp Thr Met 500 505 510 Gly Pro Ser Gln His Val Tyr Ala Tyr Ser Gln Glu Met Ala Pro Ser 515 520 525 His Ala Pro Glu Leu His Leu Lys His Ile Gly Lys Thr Trp Ala Gln 530 535 540 Leu Glu Trp Val Pro Glu Pro Pro Glu Leu Gly Lys Ser Pro Leu Thr 545 550 555 560 His Tyr Thr Ile Phe Trp Thr Asn Ala Gln Asn Gln Ser Phe Ser Ala 565 570 575 Ile Leu Asn Ala Ser Ser Arg Gly Phe Val Leu His Gly Leu Glu Pro 580 585 590 Ala Ser Leu Tyr His Ile His Leu Met Ala Ala Ser Gln Ala Gly Ala 585 600 605 Thr Asn Ser Thr Val Leu Thr Leu Met Thr Leu Thr Pro Glu Gly Ser 610 615 620

Glu Leu His Ile Tle Leu Gly Leu Phe Gly Leu Leu Leu Leu Leu Thr 625 630 635 640 Cys Leu Cys Gly Thr Ala Trp Leu Cys Cys Ser Pro Asn Arg Lys Asn 645 650 655 Pro Leu Trp Pro Ser Val Pro Asp Pro Ala His Ser Ser Leu Gly Ser 660 665 670 Trp Val Pro Thr Ile Met Glu Glu Asp Ala Phe Gln Leu Pro Gly Leu 675 680 685 Gly Thr Pro Pro Ile Thr Lys Leu Thr Val Leu Glu Glu Asp Glu Lys 690 695 700 Lys Pro Val Pro Trp Glu Ser His Asn Ser Ser Glu Thr Cys Gly Leu 705 710 715 720 Pro Thr Leu Val Gln Thr Tyr Val Leu Gln Gly Asp Pro Arg Ala Val 725 730 735 Ser Thr Gln Pro Gln Ser Gln Ser Gly Thr Ser Asp Gln Val Leu Tyr 740 745 750 Gly Gln Leu Leu Gly Ser Pro Thr Ser Pro Gly Pro Gly His Tyr Leu 755 760 765 Arg Cys Asp Ser Thr Gln Pro Leu Leu Ala Gly Leu Thr Pro Ser Pro 770 775 780 Lys Ser Tyr Glu Asn Leu Trp Phe Gln Ala Ser Pro Leu Gly Thr Leu 785 790 795 800 Val Thr Pro Ala Pro Ser Gln Glu Asp Asp Cys Val Phe Gly Pro Leu 80S 810 815 Leu Asn Phe Pro Leu Leu Gln Gly Ile Arg Val His Gly Met Glu Ala 820 825 830 Leu Gly Ser Phe 835 <210> 2989 <21l1> 276 <212> PRT <213> Homo sapiens

<400> 2989 Met Gly Asn Ser Met Lys Ser Thr Pro Ala Pro Ala Glu Arg Pro Leu 1 5 10 15 Pro Asn Pro Glu Gly Leu Asp Ser Asp Phe Leu Ala Val Leu Ser Asp

Tyr Pro Ser Pro Asp Ile Ser Pro Pro Ile Phe Arg Arg Gly Glu Lys 40 45 Leu Arg Val Ile Ser Asp Glu Gly Gly Trp Trp Lys Ala Ile Ser Leu 50 55 60 Ser Thr Gly Arg Glu Ser Tyr Ile Pro Gly Ile Cys Val Ala Arg Val €5 70 75 80 Tyr His Gly Trp Leu Phe Glu Gly Leu Gly Arg Asp Lys Ala Glu Glu 85 90 95 Leu Leu Gln Leu Pro Asp Thr Lys Val Gly Ser Phe Met Ile Arg Glu 100 105 110 Ser Glu Thr Lys Lys Gly Phe Tyr Ser Leu Ser Val Arg His Arg Gln 115 120 125 Val Lys His Tyr Arg Ile Phe Arg Leu Pro Asn Asn Trp Tyr Tyr Ile 130 135 140 Ser Pro Arg Leu Thr Phe Gln Cys Leu Glu Asp Leu Val Asn His Tyr 145 150 155 160 Ser Glu val Ala Asp Gly Leu Cys Cys Val Leu Thr Thr Pro Cys Leu 165 170 175 Thr Gln Ser Thr Ala Ala Pro Ala Val Arg Ala Ser Ser Ser Pro Val 180 185 190 Thr Leu Arg Gln Lys Thr Val Asp Trp Arg Arg Val Ser Arg Leu Gln 185 200 205 Glu Asp Pro Glu Gly Thr Glu Asn Pro Leu Gly Val Asp Glu Ser Leu 210 215 220 Phe Ser Tyr Gly Leu Arg Glu Ser Ile Ala Ser Tyr Leu Ser Leu Thr 225 230 235 240

Ser Glu Asp Asn Thr Ser Phe Asp Arg Lys Lys Lys Ser Ile Ser Leu 245 250 255 Met Tyr Gly Gly Ser Lys Arg Lys Ser Ser Phe Phe Ser Ser Pro Pro 260 265 270 Tyr Phe Glu Asp 275 <210> 2890 <211l> 359% <212> PRT <213> Homo sapiens <400> 29380 Met Ala Pro Asn Gly Thr Ala Ser Ser Phe Cys Leu Asp Ser Thr Ala 1 5 10 15 Cys Lys Ile Thr Ile Thr Val Val Leu Ala Val Leu Ile Leu Ile Thr

Val Ala Gly Asn Val Val Val Cys Leu Ala Val Gly Leu Asn Arg Arg 40 45 Leu Arg Asn Leu Thr Asn Cys Phe Ile Val Ser Leu Ala Ile Thr Asp S50 S5 60 Leu Leu Leu Gly Leu Leu Val Leu Pro Phe Ser Ala Ile Tyr Gln Leu 65 70 75 80 Ser Cys Lys Trp Ser Phe Gly Lys Val Phe Cys Asn Ile Tyr Thr Ser 85 90 98 Leu Asp Val Met Leu Cys Thr Ala Ser Ile Leu Asn Leu Phe Met Ile 100 105 110 Ser Leu Asp Arg Tyr Cys Ala Val Met Asp Pro Leu Arg Tyr Pro Val 115 120 125 Leu val Thr Pro Val Arg Val Ala Ile Ser Leu Val Leu Ile Trp Val 130 135 140 Ile Ser Ile Thr Leu Ser Phe Leu Ser Ile His Leu Gly Trp Asn Ser 145 150 155 160 Arg Asn Glu Thr Ser Lys Gly Asn His Thr Thr Ser Lys Cys Lys Val

T/US2003/012946

165 170 175 Gln Val Asn Glu Val Tyr Gly Leu val Asp Gly Leu Val Thr phe Tyr 180 185 130 Leu Pro Leu Leu Ile Met Cys Ile Thr Tyr Tyr Arg Ile Phe Lys val 195 200 205 Ala Arg Asp Gln Ala Lys Arg Ile Asn His Ile Ser Ser Trp Lys Ala 210 215 220 Ala Thr Ile Arg Glu His Lys Ala Thr val Thr Leu Ala Ala Val Met 225 230 235 240 Gly Ala Phe Ile Ile Cys Trp Phe Pro Tyr Phe Thr Ala Phe val Tyr 245 250 255 Arg Gly Leu Arg Gly Asp Asp Ala Ile Asn Glu Val Leu Glu Ala Ile 260 265 270 Val Leu Trp Leu Gly Tyr Ala Asn Ser Ala Leu Asn Pro Ile Leu Tyr 275 280 285 Ala Ala Leu Asn Arg Asp Phe Arg Thr Gly Tyr Gln Gln Leu Phe Cys 230 285 300 Cys Arg Leu Ala Asn Arg Asn Ser His Lys Thr Ser Leu Arg Ser Asn 305 310 315 320 Ala Ser Gln Leu Ser Arg Thr Gln Ser Arg Glu Pro Arg Gln Gln Glu 325 330 335 Glu Lys Pro Leu Lys Leu Gln Val Trp Ser Gly Thr Glu Val Thr Ala 340 345 350 Pro Gln Gly Ala Thr Asp Arg 358 <210> 2991 <211> 505 <212> PRT <213> Homo sapiens <400> 2991 Met Gly Ser Met Lys Ser Lys Phe Leu Gln Val Gly Gly Asn Thr Phe 1 5 10 15

Ser Lys Thr Glu Thr Ser Ala Ser Pro His Cys Pro Val Tyr Val Pro

Asp Pro Thr Ser Thr Ile Lys Pro Gly Pro Asn Ser His Asn Ser Asn 40 45 Thr Pro Gly Ile Arg Glu Ala Gly Ser Glu Asp Ile Ile Val Val Ala 50 55 60 Leu Tyr Asp Tyr Glu Ala Ile His His Glu Asp Leu Ser Phe Gln Lys 65 70 75 80 Gly Asp Gln Met Val Val Leu Glu Glu Ser Gly Glu Trp Trp Lys Ala 85 30 95 Arg Ser Leu Ala Thr Arg Lys Glu Gly Tyr Ile Pro Ser Asn Tyr Val 100 105 110 Ala Arg Val Asp Ser Leu Glu Thr Glu Glu Trp Phe Phe Lys Gly Ile 115 120 125 Ser Arg Lys Asp Ala Glu Arg Gln Leu Leu Ala Pro Gly Asn Met Leu 130 135 140 Gly Ser Phe Met Ile Arg Asp Ser Glu Thr Thr Lys Gly Ser Tyr Ser 145 150 155 160 Leu Ser Val Arg Asp Tyr Asp Pro Arg Gln Gly Asp Thr Val Lys His 165 170 175 Tyr Lys Ile Arg Thr Leu Asp Asn Gly Gly Phe Tyr Ile Ser Pro Arg 180 185 190 Ser Thr Phe Ser Thr Leu Gln Glu Leu Val Asp His Tyr Lys Lys Gly 185 200 205 Asn Asp Gly Leu Cys Gln Lys Leu Ser Val Pro Cys Met Ser Ser Lys 210 215 220 Pro Gln Lys Pro Trp Glu Lys Asp Ala Trp Glu Ile Pro Arg Glu Ser 225 230 235 240 Leu Lys Leu Glu Lys Lys Leu Gly Ala Gly Gln Phe Gly Glu val Trp 245 250 255

Met Ala Thr Tyr Asn Lys His Thr Lys Val Ala Val Lys Thr Met Lys 260 265 270 Pro Gly Ser Met Ser Val Glu Ala Phe Leu Ala Glu Ala Asn Val Met 275 280 285 Lys Thr Leu Gln His Asp Lys Leu Val Lys Leu His Ala Val Val Thr 290 295 300 Lys Glu Pro Ile Tyr Ile Ile Thr Glu Phe Met Ala Lys Gly Ser Leu 305 310 315 320 Leu Asp Phe Leu Lys Ser Asp Glu Gly Ser Lys Gln Pro Leu Pro Lys 325 330 335 Leu Ile Asp Phe Ser Ala Gln Ile Ala Glu Gly Met Ala Phe Ile Glu 340 345 350 Gln Arg Asn Tyr Ile His Arg Asp Leu Arg Ala Ala Asn Ile Leu Val 355 360 365 Ser Ala Ser Leu Val Cys Lys Ile Ala Asp Phe Gly Leu Ala Arg Val 370 375 380 Ile Glu Asp Asn Glu Tyr Thr Ala Arg Glu Gly Ala Lys Phe Pro Ile 385 380 395 400 Lys Trp Thr Ala Pro Glu Ala Ile Asn Phe Gly Ser Phe Thr Ile Lys 405 410 415 Ser Asp Val Trp Ser Phe Gly Ile Leu Leu Met Glu Ile Val Thr Tyr 420 425 430 Gly Arg Ile Pro Tyr Pro Gly Met Ser Asm Pro Glu Val Ile Arg Ala 435 440 445 Leu Glu Arg Gly Tyr Arg Met Pro Arg Pro Glu Asn Cys Pro Glu Glu 450 455 460 Leu Tyr Asn Ile Met Met Arg Cys Trp Lys Asn Arg Pro Glu Glu Arg 465 470 475 480 Pro Thr Phe Glu Tyr Ile Gln Ser Val Leu Asp Asp Phe Tyr Thr ala 485 490 495 Thr Glu Ser Gln Tyr Gln Gln Gln Pro

1S2003/012946

500 508 <210> 2992 <211> 1333 <212> PRT <213> Homo sapiens <400> 2992 Met Thr Ala Asp Lys Leu Val Phe Phe Val Asn Gly Arg Lys Val Val 1 S 10 15 Glu Lys Asn Ala Asp Pro Glu Thr Thr Leu Leu Ala Tyr Leu Arg Arg lys Leu Gly Leu Ser Gly Thr Lys Leu Gly Cys Gly Glu Gly Gly Cys 40 45 Gly Ala Cys Thr Val Met Leu Ser Lys Tyr Asp Arg Leu Gln Asn Lys 50 55 60 Ile val His Phe Ser Ala Asn Ala Cys Leu Ala Pro Ile Cys Ser Leu 65 70 75 80 His His Val Ala Val Thr Thr val Glu Gly Ile Gly Ser Thr Lys Thr 85 90 S95 Arg Leu His Pro Val Gln Glu Arg Ile Ala Lys Ser His Gly Ser Gln 100 105 110 Cys Gly Phe Cys Thr Pro Gly Ile Val Met Ser Met Tyr Thr Leu Leu 115 120 125 Arg Asn Gln Pro Glu Pro Thr Met Glu Glu Ile Glu Asn Ala Phe Gln 130 135 140 Gly Asn Leu Cys Arg Cys Thr Gly Tyr Arg Pro Ile Leu Gln Gly Phe 145 150 155 160 Arg Thr Phe Ala Arg Asp Gly Gly Cys Cys Gly Gly Asp Gly Asn Asn 165 170 175 Pro Asn Cys Cys Met Asn Gln Lys Lys Asp His Ser Val Ser His Ser 180 185 190 Pro Ser Leu Phe Lys Pro Glu Glu Phe Thr Pro Leu Asp Pro Thr Gln 195 200 205

Glu Pro Ile Phe Pro Pro Glu Leu Leu Arg Leu Lys Asp Thr Pro Arg 210 215 220 Lys Gln Leu Arg Phe Glu Arg Glu Arg val Thr Trp Ile Gln Ala Ser 225 230 235 240 Thr Leu Lys Glu Leu Leu Asp Leu Lys Ala Gln His Pro Asp Ala Lys 245 250 255 Leu Val Val Gly Asn Thr Glu Ile Gly Ile Glu Met Lys Phe Lys Asn 260 265 270 Met Leu Phe Pro Met Ile Val Cys Pro Ala Trp Ile Pro Glu Leu Asn 275 280 285 Ser Val Glu His Gly Pro Asp Gly Ile Ser Phe Gly Ala Ala Cys Pro 250 295 300 Leu Ser Ile Val Glu Lys Thr Leu Val Asp Ala Val Ala Lys Leu Pro 305 310 315 320 Ala Gln Lys Thr Glu Val Phe Arg Gly Val Leu Glu Gln Leu Arg Trp 325 330 335 Phe Ala Gly Lys Gln Val Lys Ser Val Ala Ser Val Gly Gly Asn Ile 340 345 350 Ile Thr Ala Ser Pro Ile Ser Asp Leu Asn Pro Val Phe Met Ala Ser 355 360 365 Gly Ala Lys Leu Thr Leu Val Ser Arg Gly Thr Arg Arg Thr Val Gln 370 375 380 Met Asp His Thr Phe Phe Pro Gly Tyr Arg Lys Thr Leu Leu Ser Pro 385 390 395 400 Glu Glu Ile Leu Leu Ser Ile Glu Ile Pro Tyr Ser Arg Glu Gly Glu 405 410 415 Tyr Phe Ser Ala Phe Lys Gln Ala Ser Arg Arg Glu Asp Asp Ile Ala : . 420 425 430 Lys Val Thr Ser Gly Met Arg Val Leu Phe Lys Pro Gly Thr Thr Glu 435 440 445

Val Gln Glu Leu Ala Leu Cys Tyr Gly Gly Met Ala Asn Arg Thr Ile 450 455 460 Ser Ala Leu Lys Thr Thr Gln Arg Gln Leu Ser Lys Leu Trp Lys Glu 465 470 475 480 Glu Leu Leu Gln Asp Val Cys Ala Gly Leu Ala Glu Glu Leu His Leu 485 490 495 Pro Pro Asp Ala Pro Gly Gly Met Val Asp Phe Arg Cys Thr Leu Thr S00 505 510 Leu Ser Phe Phe Phe Lys Phe Tyr Leu Thr Val Leu Gln Lys Leu Gly 515 520 525 Gln Glu Asn Leu Glu Asp Lys Cys Gly Lys Leu Asp Pro Thr Phe Ala 530 535 540 Ser Ala Thr Leu Leu Phe Gln Lys Asp Pro Pro Ala Asp Val Gln Leu 545 550 555 560 Phe Gln Glu Val Pro Lys Gly Gln Ser Glu Glu Asp Met Val Gly Arg 565 570 575 Pro Leu Pro His Leu Ala Ala Asp Met Gln Ala Ser Gly Glu Ala Val 580 585 590 Tyr Cys Asp Asp Ile Pro Arg Tyr Glu Asn Glu Leu Ser Leu Arg Leu 595 600 605 Val Thr Ser Thr Arg Ala His Ala Lys Ile Lys Ser Ile Asp Thr Ser 610 615 620 Glu Ala Lys Lys Val Pro Gly Phe Val Cys Phe Ile Ser Ala Asp Asp 625 630 635 640 Val Pro Gly Ser Asn Ile Thr Gly Ile Cys Asn Asp Glu Thr Val Phe 645 650 655 Ala Lys Asp Lys Val Thr Cys Val Gly His Ile Ile Gly Ala Val Val 660 665 670 Ala Asp Thr Pro Glu His Thr Gln Arg Ala Ala Gln Gly Val Lys Ile 675 680 ’ 685 Thr Tyr Glu Glu Leu Pro Ala Ile Ile Thr Ile Glu Asp Ala Ile Lys

690 695 700 Asn Asn Ser Phe Tyr Gly Pro Glu Leu Lys Ile Glu Lys Gly Asp Leu 705 710 715 720 Lys Lys Gly Phe Ser Glu Ala Asp Asm Val Val Ser Gly Glu Ile Tyr 725 730 735 Ile Gly Gly Gln Glu His Phe Tyr Leu Glu Thr His Cys Thr Ile Ala 740 745 750 Val Pro Lys Gly Glu Ala Gly Glu Met Glu Leu Phe Val Ser Thr Gln 755 760 765 Asn Thr Met Lys Thr Gln Ser Phe Val Ala Lys Met Leu Gly Val Pro 770 775 780 Ala Asn Arg Ile Val val Arg Val Lys Arg Met Gly Gly Gly Phe Gly 785 790 795 B0O Gly Lys Glu Thr Arg Ser Thr Val Val Ser Thr Ala Val Ala Leu Ala 805 810 815 Ala Tyr Lys Thr Gly Arg Pro Val Arg Cys Met Leu Asp Arg Asp Glu 820 825 830 Asp Met Leu Ile Thr Gly Gly Arg His Pro Phe Leu Ala Arg Tyr Lys 835 840 845 Val Gly Phe Met Lys Thr Gly Thr val Val Ala Leu Glu Val Asp His 850 855 860 Phe Ser Asn Val Gly Asn Thr Gln Asp Leu Ser Gln Ser Ile Met Glu 865 870 875 880 Arg Ala Leu Phe His Met Asp Asn Cys Tyr Lys Ile Pro Asn Ile Arg 885 890 895 Gly Thr Gly Arg Leu Cys Lys Thr Asn Leu Pro Ser Asn Thx Ala Phe S00 905 910 Arg Gly Phe Gly Gly Pro Gln Gly Met Leu Ile Ala Glu Cys Trp Met 915 S20 925 Ser Glu Val Ala Val Thr Cys Gly Met Pro Ala Glu Glu Val Arg Arg 930 935 940

PCT/US2003/012946

Lys Asn Leu Tyr Lys Glu Gly Asp Leu.Thr His Phe Asn Gln Lys Leu 945 950 855 960 Glu Gly Phe Thr Leu Pro Arg Cys Trp Glu Glu Cys Leu Ala Ser Ser 865 970 975 Gln Tyr His Ala Arg Lys Ser Glu Val Asp Lys Phe Asn Lys Glu Asn 980 985 990 Cys Trp Lys Lys Arg Gly Leu Cys Ile Ile Pro Thr Lys Phe Gly Ile 995 1000 1005 Ser Phe Thr val Pro Phe Leu Asn Gln Ala Gly Ala Leu Leu His 1010 1015 1020 val Tyr Thr Asp Gly Ser Val Leu Leu Thr His Gly Gly Thr Glu 1025 1030 1035 Met Gly Gln Gly Leu His Thr Lys Met Val Gln Val Ala Ser Arg 1040 1045 1050 Ala Leu Lys Ile Pro Thr Ser Lys Ile Tyr Ile Ser Glu Thr Ser 1055 1060 1065 Thr Asn Thr Val Pro Asn Thr Ser Pro Thr Ala Ala Ser Val Ser 1070 1075 1080 : Ala Asp Leu Asn Gly Gln Ala val Tyr Ala Ala Cys Gln Thr Ile : 1085 1090 1095 : Leu Lys Arg Leu Glu Pro Tyr Lys Lys Lys Asn Pro Ser Gly Ser 1100 1105 1110 Trp Glu Asp Trp Val Thr Ala Ala Tyr Met Asp Thr Val Ser Leu 1115 1120 1125 Ser Ala Thr Gly Phe Tyr Arg Thr Pro Asn Leu Gly Tyr Ser Phe 1130 1135 1140 Glu Thr Asn Ser Gly Asn Arg Phe His Tyr Phe Ser Tyr Gly Val 1145 1150 1155 Ala Cys Ser Glu Val Glu Ile Asp Cys Leu Thr Gly Asp His Lys 1160 1165 1170

Asn Leu Arg Thr Asp Ile Val Met Asp Val Gly Ser Ser Leu Asn 1175 1180 1185 Pro Ala Ile Asp Ile Gly Gln Val Glu Gly Ala Phe Val Gln Gly 1150 1185 1200 Leu Gly Leu Phe Thr Leu Glu Glu Leu His Tyr Ser Pro Glu Gly 1205 1210 1215 Ser Leu His Thr Arg Gly Pro Ser Thr Tyr Lys Ile Pro Ala Phe 1220 1225 1230 Gly Ser Ile Pro Ile Glu Phe Arg Val Ser Leu Leu Arg Asp Cys 1235 1240 1245 Pro Asn Lys Lys Ala Ile Tyr Ala Ser Lys Ala Val Gly Glu Pro 1250 1255 1260 Pro Leu Phe Leu Ala Ala Ser Ile Phe Phe Ala Ile Lys Asp Ala 1265 1270 1275 Ile Arg Ala Ala Arg Ala Gln His Thr Gly Asn Asn Val Lys Glu 1280 1285 1290 Leu Phe Arg Leu Asp Ser Pro Ala Thr Pro Glu Lys Ile Arg Asn 1295 1300 1305 Ala Cys Val Asp Lys Phe Thr Thr Leu Cys Val Thr Gly Val Pro 1310 1315 1320 Glu Asn Cys Lys Pro Trp Ser Val Arg Val 1325 21330 <210> 2883 <211> 415 <212> PRT <213> Homo sapiens <400> 2993 Met Glu Gly Lys Ala Ile Ala Thr Ser Leu Gly Gly Asp Arg Val Leu 1 5 10 15 Ile Phe Pro Cys Ser Pro Arg Ser Ser Phe Val Phe Thr Ser Arg Leu

Ser Ser Leu Pro Leu Lys Arg Ala Ser Ile Gly Gly Ala Val Ser Cys

40 45 Ser Gly Val Asn Gly Leu Thr Arg Trp Asn Ser Ile Val Ser Thr Arg 50 55 60 Arg Leu Val Pro Val Arg Ser Ile Asn Ser Glu Ser Asp Ser Asp Ser 65 70 75 80 Asp Phe Pro His Glu Asn Gln Gln Gly Asn Pro Gly Leu Gly Lys Phe 85 90 95 Lys Glu Tyr Gln Glu Trp Asp Ser Trp Thr Ala Lys Phe Ser Gly Gly 100 105 110 nla Asn Ile Pro Phe Leu Met Leu Gln Leu Pro Gln Ile Ile Leu Asn 1158 120 125 Thr Gln Asn Leu Leu Ala Gly Asn Asn Thr Ala Leu Ser Ala Val Pro 130 135 140 Trp Leu Gly Met Leu Thr Gly Leu Leu Gly Asn Leu Ser Leu Leu Ser 145 150 155 160 Tyr Phe Ala Lys Lys Arg Glu Lys Glu Ala Ala Val Val Gln Thr Leu 165 170 175 Gly Val val Ser Thr His Ile Val Leu Ala Gln Leu Thr Met Ala Glu 180 185 150 Ala Met Pro Ile Gln Tyr Phe Val Ala Thr Ser Ala Val val Thr Ile 195 200 205 Gly Leu Ile Val Asn Cys Leu Tyr Tyr Phe Gly Lys Leu Ser Lys Thr . 210 215 220 val Trp Gln Leu Trp Glu Asp Val Ile Thr Ile Gly Gly Leu Ser Val 225 230 235 240 Leu Pro Gln Ile Met Trp Ser Thr Phe Val Pro Leu Val Pro Asn Ser 245 250 255 Ile Leu Pro Gly Thr Thr Ala Phe Gly Ile Ala Val Ala Ala Ile Ile 260 265 270 Met Ala Arg Thr Gly Lys Leu Ser Glu Lys Gly Val Arg Phe Val Gly 275 280 285

Ser Leu Ser Gly Trp Thr Ala Thr Leu Met Phe Met Trp Met Pro val 290 295 300 Ser Gln Met Trp Thr Asn Phe Leu Asn Pro Asp Asn Ile Lys Gly Leu 305 310 315 320 Ser Ser Ile Thr Met Leu Leu Ser Met Met Gly Asn Gly Leu Met Ile 325 330 335 Pro Arg Ala Leu Phe Ile Arg Asp Leu Met Trp Leu Thr Gly Ser Leu 340 345 350 Trp Ala Thr Leu Phe Tyr Gly Tyr Gly Asn Ile Leu Cys Leu Tyr Leu 358 360 365 Val Asn Cys Thr Ser Gln Ser Phe Phe Val Ala Ala Thr Ile Gly Leu 370 375 380 Ile Ser Trp Ile Gly Leu Ala Leu Trp Arg Asp Ala val Ala Tyr Gly 385 380 3985 400 His Asn Ser Pro Phe Arg Ser Leu Lys Glu Leu Val Phe Gly Pro 405 410 415 <210> 23994 <211l> 363 <212> PRT <213> Homo sapiens <400> 2994 Met Ala Gln Thr Pro Ala Phe Asp Lys Pro Lys Val Glu Leu His Val 1 5 10 15 His Leu Asp Gly Ser Ile Lys Pro Glu Thr Ile Leu Tyr Tyr Gly Arg

Arg Arg Gly Ile Ala Leu Pro Ala Asn Thr Ala Glu Gly Leu Leu Asn 40 45 Val Ile Gly Met Asp Lys Pro Leu Thr Leu Pro Asp Phe Leu Ala Lys 50 55 60 Phe Asp Tyr Tyr Met Pro Ala Ile Ala Gly Cys Arg Glu Ala Ile Lys 65 70 75 80

Arg Ile Ala Tyr Glu Phe Val Glu Met Lys Ala Lys Glu Gly val val 85 90 95 Tyr Val Glu val Arg Tyr Ser Pro His Leu Leu Ala Asn Ser Lys Val 100 105 110 Glu Pro Ile Pro Trp Asn Gln Ala Glu Gly Asp Leu Thr Pro Asp Glu 115 120 125 Val val Ala Leu Val Gly Gln Gly Leu Gln Glu Gly Glu Arg Asp Phe 130 135 140 Gly val Lys Ala Arg Ser Ile Leu Cys Cys Met Arg His Gln Pro Asn 145 150 155 160 Trp Ser Pro Lys Val Val Glu Leu Cys Lys Asn Tyr Gln Gln Gln Thr 165 170 175 val val Ala Ile Asp Leu Ala Gly Asp Glu Thr Ile Pro Gly Ser Ser 180 185 190 Leu Leu Pro Gly His Val Gln Ala Tyr Gln Glu Ala Val Lys Ser Gly 195 200 205 Ile His Arg Thr Val His Ala Gly Glu Val Gly Ser Ala Glu Val Val 210 215 220 Lys Glu Ala Val Asp Ile Leu Lys Thr Glu Arg Leu Gly His Gly Tyr 225 230 235 240 His Thr Leu Glu Asp Gln Ala Leu Tyr Asn Arg Leu Arg Gln Glu Asn 245 250 255 Met His Phe Glu Ile Cys Pro Trp Ser Ser Tyr Leu Thr Gly Ala Trp 260 265 270 Lys Pro Asp Thr Glu His Ala Val Ile Arg Leu Lys Asn Asp Gln Ala 275 280 285 Asn Tyr Ser Leu Asn Thr Asp Asp Pro Leu Ile Phe Lys Ser Thr Leu 290 295 300 Asp Thr Asp Tyr Gln Met Thr Lys Arg Asp Met Gly Phe Thr Glu Glu 305 310 31s 320 Glu Phe Lys Arg Leu Asn Ile Asn Ala Ala Lys Ser Ser Phe Leu Pro

325 330 335 Glu Asp Glu Lys Arg Glu Leu Leu Asp Leu Leu Tyr Lys Ala Tyr Gly 340 345 350 Met Pro Pro Ser Ala Ser Ala Gly Gln Asn Leu 355 360 <210> 2995 <211> 691 <212> PRT <213> Homo sapiens <400> 2995 Met Met Arg Asn His Arg Ile Ala Ser Ser Leu Cys Gly Asp Gln val 1 5 10 15 Phe Ser Lys Lys Lys Lys Lys Lys Lys Lys Asn Asn Met Ala Ala Lys

Glu Lys Leu Glu Ala Val Leu Asn Val Ala Leu Arg Val Pro Ser Ile 40 45 Met Leu Leu Asp Val Leu Tyr Arg Trp Asp Val Ser Ser Phe Phe Gln 50 55 60 Gln Ile Gln Arg Ser Ser Leu Ser Asn Asn Pro Leu Phe Gln Tyr Lys 65 70 75 BO Tyr Leu Ala Leu Asn Met His Tyr Val Gly Tyr Ile Leu Ser val Val 85 50 9s Leu Leu Thr Leu Pro Arg Gln His Leu Val Gln Leu Tyr Leu Tyr Phe 100 105 110 Leu Thr Ala Leu Leu Leu Tyr Ala Gly His Gln Ile Ser Arg Asp Tyr 115 . 120 125 Val Arg Ser Glu Leu Glu Phe Ala Tyr Glu Gly Pro Met Tyr Leu Glu 130 135 140 Pro Leu Ser Met Asn Arg Phe Thr Thr Ala Leu Ile Gly Gln Leu Val 145 150 155 160 Val Cys Thr Leu Cys Ser Cys Val Met Lys Thr Lys Gln Ile Trp Leu 165 170 175

Phe Ser Ala His Met Leu Pro Leu Leu Ala Arg Leu Cys Leu Val Pro 180 185 190 Leu Glu Thr Ile val Ile Ile Asn Lys Phe Ala Met Ile Phe Thr Gly 195 200 205 Leu Glu Val Leu Tyr Phe Leu Gly Ser Asn Leu Leu Val Pro Tyr Asn 210 215 220 Leu Ala Lys Ser Ala Tyr Arg Glu Leu Val Gln Val Val Glu Val Tyr 225 230 235 240 Gly Leu Leu Ala Leu Gly Met Ser Leu Trp Asn Gln Leu Val Val Pro 245 250 258 Val Leu Phe Met Val Phe Trp Leu Val Leu Phe Ala Leu Gln Ile Tyr 260 265 270 Ser Tyr Phe Ser Thr Arg Asp Gln Pro Ala Ser Arg Glu Arg Leu Leu 275 280 285 Phe Leu Phe Leu Thr Ser Ile Ala Glu Cys Cys Ser Thr Pro Tyr Ser 290 295, 300 Leu Leu Gly Leu Val Phe Thr Val Ser Phe Val Ala Leu Gly val Leu 305 310 315 320 Thr Leu Cys Lys Phe Tyr Leu Gln Gly Tyr Arg Ala Phe Met Asn Asp 325 330 335 Pro Ala Met Asn Arg Gly Met Thr Glu Gly Val Thr Leu Leu Ile Leu 340 345 350 Ala val Gln Thr Gly Leu Ile Glu Leu Gln Val Val His Arg Ala Phe 355 360 365 Leu Leu Ser Ile Ile Leu Phe Ile Val Val Ala Ser Ile Leu Gln Ser 370 375 380 Met Leu Glu Ile Ala Asp Pro Ile Val Leu Ala Leu Gly Ala Ser Arg 385 390 395 400 Asp Lys Ser Leu Trp Lys His Phe Arg Ala Val Ser Leu Cys Leu Phe 405 410 415

Leu Leu Val Phe Pro Ala Tyr Met Ala Tyr Met Ile Cys Gln Phe Phe 420 425 430 His Met Asp Phe Trp Leu Leu Ile Ile Ile Ser Ser Ser Ile Leu Thr 435 440 445 Ser Leu Gln Val Leu Gly Thr Leu Phe Ile Tyr Val Leu Phe Met val 450 455 460 Glu Glu Phe Arg Lys Glu Pro val Glu Asn Met Asp Asp Val Ile Tyr 465 470 475 480 Tyr Val Asn Gly Thr Tyr Arg Leu Leu Glu Phe Leu Val Ala Leu Cys 485 490 495 Val Val Ala Tyr Gly Val Ser Glu Thr Ile Phe Gly Glu Trp Thr Val 500 505 510 Met Gly Ser Met Ile Ile Phe Ile His Ser Tyr Tyr Asn Val Trp Leu 515 520 525 Arg Ala Gln Leu Gly Trp Lys Ser Phe Leu Leu Arg Arg Asp Ala val S30 535 540 Asn Lys Ile Lys Ser Leu Pro Ile Ala Thr Lys Glu Gln Leu Glu Lys 545 550 555 560 His Asn Asp Ile Cys Ala Ile Cys Tyr Gln Asp Met Lys Ser Ala Val 565 570 575 Ile Thr Pro Cys Ser His Phe Phe His Ala Gly Cys Leu Lys Lys Trp 580 585 550 Leu Tyr Val Gln Glu Thr Cys Pro Leu Cys His Cys His Leu Lys Asn 595 600 605 Ser Ser Gln Leu Pro Gly Leu Gly Thr Glu Pro Val Leu Gln Pro His 610 615 620 Ala Gly Ala Glu Gln Asn Val Met Phe Gln Glu Gly Thr Glu Pro Pro 625 630 635 640 Gly Gln Glu His Thr Pro Gly Thr Arg Ile Gln Glu Gly Ser Arg Asp 645 650 655 Asn Asn Glu Tyr Ile Ala Arg Arg Pro Asp Asn Gln Glu Gly Ala Phe

1 46

660 665 670 Asp Pro Lys Glu Tyr Pro His Ser Ala Lys Asp Glu Ala His Pro Val 675 680 685 Glu Ser Ala 690

<210> 299¢

<211> 390

<212> PRT

<213> Homo sapiens

<400> 2996

Met Ala Ser Pro Ala Ile Gly Gln Arg Pro Tyr Pro Leu Leu Leu Asp 1 5 10 15

Pro Glu Pro Pro Arg Tyr Leu Gln Ser Leu Ser Gly Pro Glu Leu Pro

Pro Pro Pro Pro Asp Arg Ser Ser Arg Leu Cys Val Pro Ala Pro Leu 40 45 Ser Thr Ala Pro Gly Ala Arg Glu Gly Arg Ser Ala Arg Arg Ala Ala 50 SS 60 Arg Gly Asn Leu Glu Pro Pro Pro Arg Ala Ser Arg Pro Ala Arg Pro 65 70 75 80 Leu Arg Pro Gly Leu Gln Gln Arg Leu Arg Arg Arg Pro Gly Ala Pro 85 90 95 Arg Pro Arg Asp Val Arg Ser Ile Phe Glu Gln Pro Gln Asp Pro Arg 100 105 110 Val Pro Ala Glu Arg Gly Glu Gly His Cys Phe Ala Glu Leu Val Leu 115 120 125 Pro Gly Gly Pro Gly Trp Cys Asp Leu Cys Gly Arg Glu Val Leu Arg 130 135 140 Gln Ala Leu Arg Cys Thr Asn Cys Lys Phe Thr Cys His Pro Glu Cys 145 150 155 160 Arg Ser Leu Ile Gln Leu Asp Cys Ser Gln Gln Glu Gly Leu Ser Arg 165 170 175

Asp Arg Pro Ser Pro Glu Ser Thr Leu Thr Val Thr Phe Ser Gln Asn 180 185 190 Val Cys Lys Pro Val Glu Glu Thr Gln Arg Pro Pro Thr Leu Gln Glu . 195 200 205 Ile Lys Gln Lys Ile Asp Ser Tyr Asn Thr Arg Glu Lys Asn Cys Leu 210 215 220 Gly Met Lys Leu Ser Glu Asp Gly Thr Tyr Thr Gly Phe Ile Lys Val 225 230 235 240 His Leu Lys Leu Arg Arg Pro Val Thr Val Pro Ala Gly Ile Arg Pro 245 250 255 Gln Ser Ile Tyr Asp Ala Ile Lys Glu Val Asn Leu Ala Ala Thr Thr 260 265 270 Asp Lys Arg Thr Ser Phe Tyr Leu Pro Leu Asp Ala Ile Lys Gln Leu 275 280 285 His Ile Ser Ser Thr Thr Thr val Ser Glu Val Ile Gln Gly Leu Leu 290 295 300 Lys Lys Phe Met Val Val Asp Asn Pro Gln Lys Phe Ala Leu Phe Lys 305 310 315 320 Arg Ile His Lys Asp Gly Gln Val Leu Phe Gln Lys Leu Ser Ile Ala 325 ‘ 330 335 Asp Arg Pro Leu Tyr Leu Arg Leu Leu Ala Gly Pro Asp Thr Glu val 340 345 350 Leu Ser Phe Val Leu Lys Glu Asn Glu Thr Gly Glu Val Glu Trp Asp 355 360 365 Ala Phe Ser Ile Pro Glu Leu Gln Asn Phe Leu Ser Ser Trp Cys Ile 370 375 380 Gln Ile Tyr Leu Tyr Tyr 385 390 <210> 2997 <211> 287 <212> PRT <213> Homo sapiens o

<400> 2997 Met Thr Thr Pro Arg Asn Ser Val Asn Gly Thr Phe Pro Ala Glu Pro 1 5 10 15 Met Lys Gly Pro Ile Ala Met Gln Ser Gly Pro Lys Pro Leu Phe Arg

Arg Met Ser Ser Leu Val Gly Pro Thr Gln Ser Phe Phe Met Arg Glu 40 45 Ser Lys Thr Leu Gly Ala Val Gln Ile Met Asn Gly Leu Phe His Ile So 55 60 Ala Leu Gly Gly Leu Leu Met Ile Pro Ala Gly Ile Tyr Ala Pro Ile 65 70 75 80 Cys Val Thr Val Trp Tyr Pro Leu Trp Gly Gly Ile Met Tyr Ile Ile 85 90 95 Ser Gly Ser Leu Leu Ala Ala Thr Glu Lys Asn Ser Arg Lys Cys Leu 100 105 110 Val Lys Gly Lys Met Ile Met Asn Ser Leu Ser Leu Phe Ala Ala Ile 115 120 125 Ser Gly Met Ile Leu Ser Ile Met Asp Ile Leu Asn Ile Lys Ile Ser 130 135 140 His Phe Leu Lys Met Glu Ser Leu Asn Phe Ile Arg Ala His Thr Pro 145 150 155 160 Tyr Ile Asn Ile Tyr Asn Cys Glu Pro Ala Asn Pro Ser Glu Lys Asn 165 170 175 Ser Pro Ser Thr Gln Tyr Cys Tyr Ser Ile Gln Ser Leu Phe Leu Gly 180 18S 150 Ile Leu Ser Val Met Leu Ile Phe Ala Phe Phe Gln Glu Leu val Ile 195 200 205 Ala Gly Ile Val Glu Asn Glu Trp Lys Arg Thr Cys Ser Arg Pro Lys 210 215 220 Ser Asn Ile Val Leu Leu Ser Ala Glu Glu Lys Lys Glu Gln Thr Ile 225 230 235 240

Glu Ile Lys Glu Glu Val val Gly Leu Thr Glu Thr Ser Ser Gln Pro 245 250 255 Lys Asn Glu Glu Asp Ile Glu Ile Ile Pro Ile Gln Glu Glu Glu Glu 260 265 270 Glu Glu Thr Glu Thr Asn Phe Pro Glu Pro Pro Gln Asp Gln Glu Ser 275 280 285 Ser Pro Ile Glu Asn Asp Ser Ser Pro 290 295 <210> 2998 <211> 261 <212> PRT <213> Homo sapiens <400> 2998 Met Ser Trp Lys Lys Ala Leu Arg Ile Pro Gly Gly Leu Arg Ala Ala 1 5 10 15 Thr Val Thr Leu Met Leu Ser Met Leu Ser Thr Pro Val Ala Glu Gly

Arg Asp Ser Pro Glu Asp Phe Val Tyr Gln Phe Lys Gly Met Cys Tyr 40 45 Phe Thr Asn Gly Thr Glu Arg Val Arg Leu Val Ser Arg Ser Ile Tyr 50 55 60 ) Asn Arg Glu Glu Ile Val Arg Phe Asp Ser Asp Val Gly Glu Phe Arg 65 70 75 80 ala val Thr Leu Leu Gly Leu Pro Ala Ala Glu Tyr Trp Asn Ser Gln 85 S80 95 Lys Asp Ile Leu Glu Arg Lys Arg Ala Ala Val Asp Arg val Cys Arg 100 105 110 His Asn Tyr Gln Leu Glu Leu Arg Thr Thr Leu Gln Arg Arg val Glu 115 120 125 Pro Thr Val Thr Ile Ser Pro Ser Arg Thr Glu Ala Leu Asn His His 130 135 140

PCT/US2003/012946

Asn Leu Leu Val Cys Ser Val Thr Asp Phe Tyr Pro Ala Gln Ile Lys 145 150 155 160 Val Arg Trp Phe Arg Asn Asp Gln Glu Glu Thr Ala Gly val val Ser 165 170 175 Thr Pro Leu Ile Arg Asn Gly Asp Trp Thr Phe Gln Ile Leu Val Met 180 185 150 Leu Glu Met Thr Pro Gln Arg Gly Asp Val Tyr Thr Cys His Val Glu 185 200 205 His Pro Ser Leu Gln Ser Pro Ile Thr Val Glu Trp Arg Ala Gln Ser 210 215 220 Glu Ser Ala Gln Ser Lys Met Leu Ser Gly Ile Gly Gly Phe Val Leu 225 230 235 240 Gly Leu Ile Phe Leu Gly Leu Gly Leu Ile Ile His His Arg Ser Gln 245 250 255 Lys Gly Leu Leu His 260 <210> 2999 <211> 258 . <212> PRT <213> Homo sapiens <400> 2999 Met Met Val Leu Gln Val Ser Ala Ala Pro Arg Thr Val Ala Leu Thr 1 5 10 15 Ala Leu Leu Met Val Leu Leu Thr Ser Val val Gln Gly Arg Ala Thr

Pro Glu Asn Tyr Leu Phe Gln Gly Arg Gln Glu Cys Tyr Ala Phe Asn 40 45 Gly Thr Gln Arg Phe Leu Glu Arg Tyr Ile Tyr Asn Arg Glu Glu Phe 50 $5 60 Ala Arg Phe Asp Ser Asp Val Gly Glu Phe Arg Ala Val Thr Glu Leu 65 70 75 80 Gly Arg Pro Ala Ala Glu Tyr Trp Asn Ser Gln Lys Asp Ile Leu Glu 85 90 85

Glu Lys Arg Ala val Pro Asp Arg Met Cys Arg His Asn Tyr Glu Leu

100 105 110 Gly Gly Pro Met Thr Leu Gln Arg Arg Val Gln Pro Arg Val Asn Val

115 120 125 Ser Pro Ser Lys Lys Gly Pro Leu Gln His His Asn Leu Leu Val Cys : 130 135 140 His Val Thr Asp Phe Tyr Pro Gly Ser Ile Gln Val Arg Trp Phe Leu 145 150 155 160 Asn Gly Gln Glu Glu Thr Ala Gly Val Val Ser Thr Asn Leu Ile Arg 165 170 175

Asn Gly Asp Trp Thr Phe Gln Ile Leu Val Met Leu Glu Met Thr Pro

180 185 190 Gln Gln Gly Asp Val Tyr Thr Cys Gln Val Glu His Thr Ser Leu Asp

195 200 205 Ser Pro Val Thr Val Glu Trp Lys Ala Gln Ser Asp Ser Ala Arg Ser 210 215 220 Lys Thr Leu Thr Gly Ala Gly Gly Phe Val Leu Gly Leu Ile Ile Cys 225 230 235 240 Gly val Gly Ile Phe Met His Arg Arg Ser Lys Lys Val Gln Arg Gly 245 250 255

Ser Ala <210> 3000 <21l1l> 17S <212> PRT <213> Homo sapiens <400> 3000 Met Thr Asp Cys Glu Phe Gly Tyr Ile Tyr Arg Leu Ala Gin Asp Tyr 1 5 10 15 Leu Gln Cys Val Leu Gln Ile Pro Gln Pro Gly Ser Gly Pro Ser Lys

Thr Ser Arg val Leu Gln Asn Val Ala Phe Ser Val Gln Lys Glu val 35 40 45 Glu Lys Asn Leu Lys Ser Cys Leu Asp Asn Val Asn Val val Ser Val 50 55 60 Asp Thr Ala Arg Thr Leu Phe Asn Gln Val Met Glu Lys Glu Phe Glu 65 70 75 80 Asp Gly Ile Ile Asn Trp Gly Arg Ile Val Thr Ile Phe Ala Phe Glu 85 90 95 Gly Ile Leu Ile Lys Lys Leu Leu Arg Gln Gln Ile Ala Pro Asp Val 100 105 110 Asp Thr Tyr Lys Glu Ile Ser Tyr Phe Val Ala Glu Phe Ile Met Asn 115 120 125 Asn Thr Gly Glu Trp Ile Arg Gln Asn Gly Gly Trp Glu Asn Gly Phe 130 135 140 Val Lys Lys Phe Glu Pro Lys Ser Gly Trp Met Thr Phe Leu Glu Val 145 150 155 160 Thr Gly Lys Ile Cys Glu Met Leu Ser Leu Leu Lys Gln Tyr Cys 165 170 175

<210> 3001

<211l> 825

<212> PRT .

<213> Homo sapiens

<400> 3001

Met Gly Trp Leu Cys Ser Gly Leu Leu Phe Pro Val Ser Cys Leu Val 1 S 10 15

Leu Leu Gln Val Ala Ser Ser Gly Asn Met Lys Val Leu Gln Glu Pro

Thr Cys Val Ser Asp Tyr Met Ser Ile Ser Thr Cys Glu Trp Lys Met 40 45 Asn Gly Pro Thr Asn Cys Ser Thr Glu Leu Arg Leu Leu Tyr Gln Leu 50 55 60 Val phe Leu Leu Ser Glu Ala His Thr Cys Ile Pro Glu Asn Asn Gly 65 70 75 80

Gly Ala Gly Cys Val Cys His Leu Leu Met Asp Asp Val Val Ser Ala 85 90 95 Asp Asn Tyr Thr Leu Asp Leu Trp Ala Gly Gln Gln Leu Leu Trp Lys 100 105 110 Gly Ser Phe Lys Pro Ser Glu His Val Lys Pro Arg Ala Pro Gly Asn 115 120 125 Leu Thr Val His Thr Asn Val Ser Asp Thr Leu Leu Leu Thr Trp Ser 130 135 140 Asn Pro Tyr Pro Pro Asp Asn Tyr Leu Tyr Asn His Leu Thr Tyr Ala 145 150 155 160 Val Asn Ile Trp Ser Glu Asn Asp Pro Ala Asp Phe Arg Ile Tyr Asn 165 170 175 Val Thr Tyr Leu Glu Pro Ser Leu Arg Ile Ala Ala Ser Thr Leu Lys 180 185 190 Ser Gly Ile Ser Tyr Arg Ala Arg Val Arg Ala Trp Ala Gln Cys Tyr 195 200 205 Asn Thr Thr Trp Ser Glu Trp Ser Pro Ser Thr Lys Trp His Asn Ser 210 215 220 Tyr Arg Glu Pro Phe Glu Gln His Leu Leu Leu Gly Val Ser val Ser 225 230 235 240 Cys Ile Val Ile Leu Ala val Cys Leu Leu Cys Tyr Val Ser Tle Thr 245 250 255 Lys Ile Lys Lys Glu Trp Trp Asp Gln Ile Pro Asn Pro Ala Arg Ser 260 265 270 Arg Leu Val Ala Ile Ile Ile Gln Asp Ala Gln Gly Ser Gln Trp Glu 275 280 285 Lys Arg Ser Arg Gly Gln Glu Pro Ala Lys Cys Pro His Trp Lys Asn 290 295 300 Cys Leu Thr Lys Leu Leu Pro Cys Phe Leu Glu His Asn Met Lys Arg 305 310 3158 320

Asp Glu Asp Pro His Lys Ala Ala Lys Glu Met Pro Phe Gln Gly Ser 325 330 335 Gly Lys Ser Ala Trp Cys Pro Val Glu Ile Ser Lys Thr Val Leu Trp 340 345 350 Pro Glu Ser Ile Ser Val Val Arg Cys Val Glu Leu Phe Glu Ala Pro 355 360 365 Val Glu Cys Glu Glu Glu Glu Glu Val Glu Glu Glu Lys Gly Ser Phe 370 375 380 Cys Ala Ser Pro Glu Ser Ser Arg Asp Asp Phe Gln Glu Gly Arg Glu 385 390 395 400 Gly Ile Val Ala Arg Leu Thr Glu Ser Leu Phe Leu Asp Leu Leu Gly 405 410 415 Glu Glu Asn Gly Gly Phe Cys Gln Gln Asp Met Gly Glu Ser Cys Leu 420 425 430 Leu Pro Pro Ser Gly Ser Thr Ser Ala His Met Pro Trp Asp Glu Phe 435 440 445 Pro Ser Ala Gly Pro Lys Glu Ala Pro Pro Trp Gly Lys Glu Gln Pro 450 455 460 Leu His Leu Glu Pro Ser Pro Pro Ala Ser Pro Thr Gln Ser Pro Asp 465 470 475 480 Asn Leu Thr Cys Thr Glu Thr Pro Leu Val Ile Ala Gly Asn Pro Ala 485 490 495 Tyr Arg Ser Phe Ser Asn Ser Leu Ser Gln Ser Pro Cys Pro Arg Glu 500 505 510 Leu Gly Pro Asp Pro Leu Leu Ala Arg His Leu Glu Glu Val Glu Pro 515 520 525 Glu Met Pro Cys Val Pro Gln Leu Ser Glu Pro Thr Thr Val Pro Gln 530 535 540 Pro Glu Pro Glu Thr Trp Glu Gln Ile Leu Arg Arg Asn Val Leu Gln 545 550 555 560

His Gly Ala Ala Ala Ala Pro Val Ser Ala Pro Thr Ser Gly Tyr Gln 565 570 575 Glu Phe Val His Ala Val Glu Gln Gly Gly Thr Gln Ala Ser Ala Val 580 585 590 Val Gly Leu Gly Pro Pro Gly Glu Ala Gly Tyr Lys Ala Phe Ser Ser 585 600 605 Leu Leu Ala Ser Ser Ala Val Ser Pro Glu Lys Cys Gly Phe Gly Ala 610 615 620 Ser Ser Gly Glu Glu Gly Tyr Lys Pro Phe Gln Asp Leu Ile Pro Gly 625 630 635 640 Cys Pro Gly Asp Pro Ala Pro Val Pro Val Pro Leu Phe Thr Phe Gly 645 650 655 Leu Asp Arg Glu Pro Pro Arg Ser Pro Gln Ser Ser His Leu Pro Ser 660 665 670 Ser Ser Pro Glu His Leu Gly Leu Glu Pro Gly Glu Lys Val Glu Asp 675 680 685 Met Pro Lys Pro Pro Leu Pro Gln Glu Gln Ala Thr Asp Pro Leu Val 690 695 700 Asp Ser Leu Gly Ser Gly Ile val Tyr Ser Ala Leu Thr Cys His Leu 705 710 715 720 Cys Gly His Leu Lys Gln Cys His Gly Gln Glu Asp Gly Gly Gln Thr 725 730 735 Pro Val Met Ala Ser Pro Cys Cys Gly Cys Cys Cys Gly Asp Arg Ser 740 745 750 Ser Pro Pro Thr Thr Pro Leu Arg Ala Pro Asp Pro Ser Pro Gly Gly 755 760 765 Val Pro Leu Glu Ala Ser Leu Cys Pro Ala Ser Leu Ala Pro Ser Gly 770 775 780 Ile Ser Glu Lys Ser Lys Ser Ser Ser Ser Phe His Pro Ala Pro Gly 785 790 795 800 Asn Ala Gln Ser Ser Ser Gln Thr Pro Lys Ile Val Asn Phe Val Ser

I 946

805 810 81S Val Gly Pro Thr Tyr Met Arg Val Ser 820 825 <210> 3002 <211l> 285 <212> PRT <213> Homo sapiens <400> 3002 Met Asp Asp Ser Thr Glu Arg Glu Gln Ser Arg Leu Thr Ser Cys Leu 1 5 10 15 Lys Lys Arg Glu Glu Met Lys Leu Lys Glu Cys Val Ser Ile Leu Pro

Arg Lys Glu Ser Pro Ser val Arg Ser Ser Lys Asp Gly Lys Leu Leu 40 45 Ala Ala Thr Leu Leu Leu Ala Leu Leu Ser Cys Cys Leu Thr val val 50 55 60 . Ser Phe Tyr Gln Val Ala Ala Leu Gln Gly Asp Leu Ala Ser Leu Arg 65 70 75 80 Ala Glu Leu Gln Gly His His Ala Glu Lys Leu Pro Ala Gly Ala Gly 85 S0 95 Ala Pro Lys Ala Gly Leu Glu Glu Ala Pro Ala Val Thr Ala Gly Leu 100 105 110 Lys Ile Phe Glu Pro Pro Ala Pro Gly Glu Gly Asn Ser Ser Gln Asn 115 120 125 Ser Arg Asn Lys Arg Ala Val Gln Gly Pro Glu Glu Thr Val Thr Gln 130 135 140 Asp Cys Leu Gln Leu Ile Ala Asp Ser Glu Thr Pro Thr Ile Gln Lys 145 150 155 160 Gly Ser Tyr Thr Phe Val Pro Trp Leu Leu Ser Phe Lys Arg Gly Ser 165 170 175 Ala Leu Glu Glu Lys Glu Asn Lys Ile Leu Val Lys Glu Thr Gly Tyr 180 185 190

PCT/US2003/012946

Phe Phe Ile Tyr Gly Gln Val Leu Tyr Thr Asp Lys Thr Tyr Ala Met 195 200 205 Gly His Leu Ile Gln Arg Lys Lys Val His Val Phe Gly Asp Glu Leu 210 215 220 Ser Leu Val Thr Leu Phe Arg Cys Ile Gln Asn Met Pro Glu Thr Leu 225 230 235 240 Pro Asn Asn Ser Cys Tyr Ser Ala Gly Ile Ala Lys Leu Glu Glu Gly 245 250 255 : Asp Glu Leu Gln Leu Ala Ile Pro Arg Glu Asn Ala Gln Ile Ser Leu 260 265 270 Asp Gly Asp Val Thr Phe Phe Gly Ala Leu Lys Leu Leu 2758 280 285 i <210> 3003 <211> 444 <212> PRT <213> Homo sapiens <400> 3003 Met Ala Val Thr Thr Arg Leu Thr Arg Leu His Glu Lys Ile Leu Gln 1 5 10 15 Asn His Phe Gly Gly Lys Arg Leu Ser Leu Leu Tyr Lys Gly Ser Val

His Gly Phe Arg Asn Gly Val Leu Leu Asp Arg Cys Cys Asn Gln Gly 40 45 Pro Thr Leu Thr Val Ile Tyr Ser Glu Asp His Ile Ile Gly Ala Tyr 50 55 60 Ala Glu Glu Ser Tyr Gln Glu Gly Lys Tyr Ala Ser Ile Ile Leu Phe 65 70 75 80 Ala Leu Gln Asp Thr Lys Ile Ser Glu Trp Lys Leu Gly Leu Cys Thr 85 90 95 Pro Glu Thr Leu Phe Cys Cys Asp Val Thr Lys Tyr Asn Ser Pro Thr 100 105 110 Asn Phe Gln Ile Asp Gly Arg Asn Arg Lys Val Ile Met Asp Leu Lys

PCT/US2003/012946 115 120 125 Thr Met Glu Asn Leu Gly Leu Ala Gln Asn Cys Thr Ile Ser Ile Gln 130 135 140 Asp Tyr Glu Val Phe Arg Cys Glu Asp Ser Leu Asp Glu Arg Lys Ile 145 150 155 160 Lys Gly val Ile Glu Leu Arg Lys Ser Leu Leu Ser Ala Leu Arg Thr 165 170 175 Tyr Glu Pro Tyr Gly Ser Leu Val Gln Gln Ile Arg Ile Leu Leu Leu 180 185 130 Gly Pro Ile Gly Ala Gly Lys Ser Ser Phe Phe Asn Ser Val Arg Ser 195 200 205 Val Phe Gln Gly His Val Thr His Gln Ala Leu Val Gly Thr Asn Thr 210 215 220 Thr Gly Ile Ser Glu Lys Tyr Arg Thr Tyr Ser Ile Arg Asp Gly Lys 225 230 235 240 Asp Gly Lys Tyr Leu Pro Phe Ile Leu Cys Asp Ser Leu Gly Leu Ser 245 250 255 Glu Lys Glu Gly Gly Leu Cys Arg Asp Asp Ile Phe Tyr Ile Leu Asn 260 265 270 Gly Asn Ile Arg Asp Arg Tyr Gln Phe Asn Pro Met Glu Ser Ile Lys 275 280 285 Leu Asn His His Asp Tyr Ile Asp Ser Pro Ser Leu Lys Asp Arg Ile 290 295 300 His Cys val Ala Phe Val Phe Asp Ala ser Ser Ile Gln Tyr Phe Ser 305 310 315 320 Ser Gln Met Ile Val Lys Ile Lys Arg Ile Arg Arg Glu Leu Val Asn 325 330 335 Ala Gly Val Val His Val Ala Leu Leu Thr His Val Asp Ser Met Asp 340 345 350 Leu Ile Thr Lys Gly Asp Leu Ile Glu Ile Glu Arg Cys Glu Pro val 355 360 365 1429 bd . . id -

Arg Ser Lys Leu Glu Glu Val Gln Arg Lys Leu Gly Phe Ala Leu Ser 370 375 380 Asp Ile Ser Val Val Ser Asn Tyr Ser Ser Glu Trp Glu Leu Asp Pro 385 390 395 400 Val Lys Asp Val Leu Ile Leu Ser Ala Leu Arg Arg Met Leu Trp Ala 405 410 415 Ala Asp Asp Phe Leu Glu Asp Leu Pro Phe Glu Gln Ile Gly Asn Leu 420 425 430 Arg Glu Glu Ile Ile Asn Cys Ala Gln Gly Lys Lys 435 440 <210> 3004 <211> 432 <212> PRT <213> Homo sapiens <400> 3004 Met Gly Pro Ala Gly Ser Leu Leu Gly Ser Gly Gln Met Gln Ile Thr 1 5 10 15 Leu Trp Gly Ser Leu Ala Ala Val Ala Ile Phe Phe Val Ile Thr Phe

Leu Ile Phe Pro Cys Ser Ser Cys Asp Arg Glu Lys Lys Pro Arg Gln 40 45 His Ser Gly Asp His Glu Asn Leu Met Asn Val Pro Ser Asp Lys Glu 50 55 60 Met Phe Ser Arg Ser Val Thr Ser Leu Ala Thr Asp Ala Pro Ala Ser 65 70 75 80 Ser Glu Gln Asn Gly Ala Leu Thr Asn Gly Asp Ile Leu Ser Glu Asp 85 90 95 Ser Thr Leu Thr Cys Met Gln His Tyr Glu Glu Val Gln Thr Ser Ala 100 105 110 Ser Asp Leu Leu Asp Ser Gln Asp Ser Thr Gly Lys Pro Lys Cys His 115 120 125

Gln Ser Arg Glu Leu Pro Arg Ile Pro Pro Glu Ser Ala Val Asp Thr 130 135 140 Met Leu Thr Ala Arg Ser Val Asp Gly Asp Gln Gly Leu Gly Met Glu 145 150 155 160 Gly Pro Tyr Glu Val Leu Lys Asp Ser Ser Ser Gln Glu Asn Met Val 165 170 175 Glu Asp Cys Leu Tyr Glu Thr val Lys Glu Ile Lys Glu Val Ala Ala 180 185 150 Ala Ala His Leu Glu Lys Gly His Ser Gly Lys Ala Lys Ser Thr Ser 195 200 205 Ala Ser Lys Glu Leu Pro Gly Pro Gln Thr Glu Gly Lys Ala Glu Phe 210 215 220 Ala Glu Tyr Ala Ser Val Asp Arg Asn Lys Lys Cys Arg Gln Ser val 225 230 235 240 Asn Val Glu Ser Ile Leu Gly Asn Ser Cys Asp Pro Glu Glu Glu Ala 24s 250 255 Pro Pro Pro Val Pro Val Lys Leu Leu Asp Glu Asn Glu Asn Leu Gln 260 265 270 Glu Lys Glu Gly Gly Glu Ala Glu Glu Ser Ala Thr Asp Thr Thr Ser 275 280 285 Glu Thr Asn Lys Arg Phe Ser Ser Leu Ser Tyr Lys Ser Arg Glu Glu 290 295 300 Asp Pro Thr Leu Thr Glu Glu Glu Ile Ser Ala Met Tyr Ser Ser Val 305 310 31S 320 Asn Lys Pro Gly Gln Leu Val Asn Lys Ser Gly Gln Ser Leu Thr val 325 330 335 Pro Glu Ser Thr Tyr Thr Ser Ile Gln Gly Asp Pro Gln Arg Ser Pro 340 34S 350 Ser Ser Cys Asn Asp Leu Tyr Ala Thr val Lys Asp Phe Glu Lys Thr 355 360 365 Pro Asn Ser Thr Leu Pro Pro Ala Gly Arg Pro Ser Glu Glu Pro Glu

370 375 380 Pro Asp Tyr Glu Ala Ile Gln Thr Leu Asn Arg Glu Glu Glu Lys Ala 385 390 395 400 Thr Leu Gly Thr Asn Gly His His Gly Leu val Pro Lys Glu Asn Asp 405 410 415 Tyr Glu Ser Ile Ser Asp Leu Gln Gln Gly Arg Asp Ile Thr Arg Leu 420 425 430 <210> 3005 <211> 501 <212> PRT <213> Homo sapiens . <400> 3005 Met Ile Ile Ser His Phe Pro Lys Cys Val Ala Val Phe Ala Leu Leu 1 S 10 15 Ala Leu Ser Val Gly Ala Leu Asp Thr Phe Ile Ala Ala val Tyr Glu

His Ala Val Ile Leu Pro Asn Arg Thr Glu Thr Pro Val Ser Lys Glu 40 45 Glu Ala Leu Leu Leu Met Asn Lys Asn Ile Asp Val Leu Glu Lys Ala So 55 60 Val Lys Leu Ala Ala Lys Gln Gly Ala His Ile Ile val Thr Pro Glu 65 70 75 80 Asp Gly Ile Tyr Gly Trp Ile Phe Thr Arg Glu Ser Ile Tyr Pro Tyr 85 90 95 Leu Glu Asp Ile Pro Asp Pro Gly Val Asn Trp Ile Pro Cys Arg Asp 100 105 110 Pro Trp Arg Phe Gly Asn Thr Pro Val Gln Gln Arg Leu Ser Cys Leu 115 120 125 Ala Lys Asp Asn Ser Ile Tyr Val val Ala Asn Ile Gly Asp Lys Lys : 130 135 140 Pro Cys Asn Ala Ser Asp Ser Gln Cys Pro Pro Asp Gly Arg Tyr Gln 145 150 155 160

Tyr Asn Thr Asp Val Val Phe Asp Ser Gln Gly Lys Leu Leu Ala Arg 165 170 175 Tyr His Lys Tyr Asn Leu Phe Ala Pro Glu Ile Gln Phe Asp Phe Pro 180 185 150 Lys Asp Ser Glu Leu Val Thr Phe Asp Thr Pro Phe Gly Lys Phe Gly 185 200 205 Ile Phe Thr Cys Phe Asp Ile Phe Ser His Asp Pro Ala Ala Val val 210 215 220 Val Asp Glu Val Ser Ile Asp Ser Ile Leu Tyr Pro Thr ala Trp Tyr 225 230 235 240 Asn Thr Leu Pro Leu Leu Ser Ala Val Pro Phe His Ser Ala Trp Ala 245 250 255 Lys Ala Met Gly Val Asn Leu Leu Ala Ala Asn Thr His Asn Thr Ser 260 265 270 Met His Met Thr Gly Ser Gly Ile Tyr Ala Pro Glu Ala Val Lys Val 275 280 285 Tyr His Tyr Asp Met Glu Thr Glu Ser Gly Gln Leu Leu Leu Ser Glu 290 295 300 Leu Lys Ser Arg Pro Arg Arg Glu Pro Thr Tyr Pro Ala Ala Val Asp 305 310 315 320 Trp His Ala Tyr Ala Ser Ser Val Lys Pro Phe Ser Ser Glu Gln Ser 325 330 335 Asp Phe Leu Gly Met Ile Tyr Phe Asp Glu Phe Thr Phe Thr Lys Leu 340 345 350 Lys Arg Asn Thr Gly Asn Tyr Thr Ala Cys Gln Lys Asp Leu Cys Cys 355 360 365 His Leu Thr Tyr Lys Met Ser Glu Lys Arg Thr Asp Glu Ile Tyr Ala 370 375 380 Leu Gly Ala Phe Asp Gly Leu His Thr val Glu Gly Gln Tyr Tyr Leu 385 350 395 400

Gln Ile Cys Ala Leu Leu Lys Cys Gln Thr Thr Asp Leu Glu Thr Cys 405 410 415 Gly Glu Pro val Gly Ser Ala Phe Thr Lys Phe Glu Asp Phe Ser Leu 420 425 430 Ser Gly Thr Phe Gly Thr Arg Tyr Val Phe Pro Gln Ile Ile Leu Ser 435 440 445 Gly Ser Gln Leu Ala Pro Glu Arg His Tyr Glu Ile Ser Arg Asp Gly 450 455 460 Arg Leu Arg Ser Arg Ser Gly Ala Pro Leu Pro Val Leu Val Met Ala 465 470 475 480 Leu Tyr Gly Arg Val Phe Glu Lys Asp Pro Pro Arg Leu Gly Gln Gly ’ 485 490 435 Ser Gly Lys Phe Gln 500 <210> 3006 <211> 329 <212> PRT <213> Homo sapiens <400> 3006 Met Trp Gly Leu Lys Val Leu Leu Leu Pro Val Val Ser Phe Ala Leu 1 5 10 15 Tyr Pro Glu Glu Ile Leu Asp Thr His Trp Glu Leu Trp Lys Lys Thr

His Arg Lys Gln Tyr Asn Asn Lys Val Asp Glu Ile Ser Arg Arg Leu 40 45 Ile Trp Glu Lys Asn Leu Lys Tyr Ile Ser Ile His Asn Leu Glu Ala 50 55 60 Ser Leu Gly Val His Thr Tyr Glu Leu Ala Met Asn His Leu Gly Asp 65 70 75 80 Met Thr Ser Glu Glu val Val Gln Lys Met Thr Gly Leu Lys Val Pro 85 80 95 Leu Ser His Ser Arg Ser Asn Asp Thr Leu Tyr Ile Pro Glu Trp Glu 100 105 110

Gly Arg Ala Pro Asp Ser Val Asp Tyr Arg Lys Lys Gly Tyr Val Thr 115 120 125 Pro Val Lys Asn Gln Gly Gln Cys Gly Ser Cys Trp Ala Phe Ser Ser 130 135 140 Val Gly Ala Leu Glu Gly Gln Leu Lys Lys Lys Thr Gly Lys Leu Leu 145 150 155 160 Asn Leu Ser Pro Gln Asn Leu Val Asp Cys Val Ser Glu Asn Asp Gly 165 170 17% Cys Gly Gly Gly Tyr Met Thr Asn Ala Phe Gln Tyr Val Gln Lys Asn 180 185 190 Arg Gly Ile Asp Ser Glu Asp Ala Tyr Pro Tyr Val Gly Gln Glu Glu 185 200 205 Ser Cys Met Tyr Asn Pro Thr Gly Lys Ala Ala Lys Cys Arg-Gly Tyr 210 215 220 Arg Glu Ile Pro Glu Gly Asn Glu Lys Ala Leu Lys Arg Ala Val Ala 225 230 235 240 Arg Val Gly Pro Val Ser Val Ala Ile Asp Ala Ser Leu Thr Ser Phe 245 250 255 Gln Phe Tyr Ser Lys Gly Val Tyr Tyr Asp Glu Ser Cys Asn Ser Asp 260 265 270 Asn Leu Asn His Ala Val Leu Ala Val Gly Tyr Gly Ile Gln Lys Gly 275 280 285 , Asn Lys His Trp Ile Ile Lys Asn Ser Trp Gly Glu Asn Trp Gly Asn 290 295 300 Lys Gly Tyr Ile Leu Met Ala Arg Asn Lys Asn Asn Ala Cys Gly Ile 305 310 315 320 Ala Asn Leu Ala Ser Phe Pro Lys Met 325 <210> 3007 <211> 1170 <212> PRT

<213> Homo sapiens <400> 3007 Met Lys Asp Ser Cys Ile Thr Val Met Ala Met Ala Leu Leu ser gly 1 5 10 15 Phe Phe Phe Phe ala Pro ala Ser Ser Tyr Asn Leu Asp Val Arg Gly

Ala Arg Ser Phe Ser Pro Pro Arg ala Gly Arg His Phe Gly Tyr Arg 40 45 Val Leu Gln val Gly Asn Gly val Ile val Gly Ala Pro Gly Glu Gly So S5 60 Asn Ser Thr Gly Ser Leu Tyr Gln Cys Gln Ser Gly Thr Gly His Cys 65 70 75 80 Leu Pro Val Thr Leu Arg Gly Ser Asn Tyr Thr Ser Lys Tyr Leu Gly BS 90 95 Met Thr Leu Ala Thr Asp Pro Thr Asp Gly Ser Ile Leu ala Cys Asp 100 105 110 Pro Gly Leu Ser Arg Thr Cys Asp Gln Asn Thr Tyr Leu Ser Gly Leu 115 120 125 Cys Tyr Leu Phe Arg Gln Asn Leu Gln Gly Pro Met Leu Gln Gly Arg 130 135 140 Pro Gly Phe Gln Glu Cys Ile Lys Gly Asn val Asp Leu Val Phe Leu 145 150 155% 160 Phe Asp Gly Ser Met Ser Leu Gln Pro Asp Glu Phe Gln Lys Ile Leu 165 170 175 Asp Phe Met Lys Asp Val Met Lys Lys Leu Ser Asn Thr Ser Tyr Gln 180 185 190 Phe Ala Ala val Gln Phe Ser Thr Ser Tyr Lys Thr Glu Phe Asp Phe } 195 : 200 205 Ser Asp Tyr val Lys Trp Lys Asp Pro Asp Ala Leu Leu Lys His val 210 215 220 Lys His Met Leu Leu Leu Thr Asn Thr phe Gly Ala Ile Asn Tyr Val

S2003/012946

225 230 235 240 Ala Thr Glu val Phe Arg Glu Glu Leu Gly Ala Arg Pro Asp Ala Thr 245 250 255 Lys Val Leu Ile Ile Ile Thr Asp Gly Glu Ala Thr Asp Ser Gly Asn 260 265 270 Ile Asp Ala Ala Lys Asp Ile Ile Arg Tyr Ile Ile Gly Ile Gly Lys 275 280 285 His Phe Gln Thr Lys Glu Ser Gln Glu Thr Leu His Lys Phe Ala Ser 290 295 300 Lys Pro Ala Ser Glu Phe Val Lys Ile Leu Asp Thr Phe Glu Lys Leu 305 310 315 320 Lys Asp Leu Phe Thr Glu Leu Gln Lys Lys Ile Tyr Val Ile Glu Gly 325 330 335 } Thr Ser Lys Gln Asp Leu Thr Ser Phe Asn Met Glu Leu Ser Ser Ser 340 345 350 Gly Ile Ser Ala Asp Leu Ser Arg Gly His Ala Val val Gly Ala val 3585 360 365 Gly Ala Lys Asp Trp Ala Gly Gly Phe Leu Asp Leu Lys Ala Asp Leu 370 375 380 Gln Asp Asp Thr Phe Ile Gly Asn Glu Pro Leu Thr Pro Glu Val Arg 385 390 395 400 Ala Gly Tyr Leu Gly Tyr Thr Val Thr Trp Leu Pro Ser Arg Gln Lys 405 410 415 Thr Ser Leu Leu Ala Ser Gly Ala Pro Arg Tyr Gln His Met Gly Arg 420 42s 430 Val Leu Leu Phe Gln Glu Pro Gln Gly Gly Gly His Trp Ser Gln Val . 435 440 445 Gln Thr Ile His Gly Thr Gln Ile Gly Ser Tyr Phe Gly Gly Glu Leu 450 455 460 Cys Gly Val Asp Val Asp Gln Asp Gly Glu Thr Glu Leu Leu Leu Ile 465 470 475 480

Gly Ala Pro Leu Phe Tyr Gly Glu Gln Arg Gly Gly Arg Val Phe Ile 485 4950 495 Tyr Gln Arg Arg Gln Leu Gly Phe Glu Glu Val Ser Glu Leu Gln Gly 500 505 510 Asp Pro Gly Tyr Pro Leu Gly Arg Phe Gly Glu Ala Ile Thr Ala Leu 515 520 525 Thr Asp Tle Asn Gly Asp Gly Leu Val Asp Val Ala Val Gly Ala Pro $30 535 540 Leu Glu Glu Gln Gly Ala Val Tyr Ile Phe Asn Gly Arg His Gly Gly 545 550 S55 560 Leu Ser Pro Gln Pro Ser Gln Arg Ile Glu Gly Thr Gln Val Leu Ser 565 ’ 570 575 Gly Ile Gln Trp Phe Gly Arg Ser Ile His Gly val Lys Asp Leu Glu 580 585 590 Gly Asp Gly Leu Ala Asp Val Ala Val Gly Ala Glu Ser Gln Met Ile 585 600 605 Val Leu Ser Ser Arg Pro Val Val Asp Met Val Thr Leu Met Ser Phe 610 615 620 Ser Pro Ala Glu Ile Pro Val His Glu Val Glu Cys Ser Tyr Ser Thr 625 630 635 640 Ser Asn Lys Met Lys Glu Gly Val Asn Ile Thr Ile Cys Phe Gln Ile 645 650 655 Lys Ser Leu Tyr Pro Gln Phe Gln Gly Arg Leu Val Ala Asn Leu Thr 660 665 670 Tyr Thr Leu Gln Leu Asp Gly His Arg Thr Arg Arg Arg Gly Leu Phe 675 680 685 Pro Gly Gly Arg His Glu Leu Arg Arg Asn Ile Ala Val Thr Thr Ser 690 695 700 Met Ser Cys Thr Asp Phe Ser Phe His Phe Pro Val Cys Val Gln Asp 708 710 715 720 1438

RR.

03/012946 Leu Ile Ser Pro Ile Asn Val Ser Leu Asn Phe Ser Leu Trp Glu Glu 725 730 735 Glu Gly Thr Pro Arg Asp Gln Arg Ala Gln Gly Lys Asp Ile Pro Pro 740 745 750 Ile Leu Arg Pro Ser Leu His Ser Glu Thr Trp Glu Ile Pro Phe Glu 755 760 765 Lys Asn Cys Gly Glu Asp Lys Lys Cys Glu Ala Asn Leu Arg Val Ser 770 775 780 Phe Ser Pro Ala Arg Ser Arg Ala Leu Arg Leu Thr Ala Phe Ala Ser 785 790 785 800 Leu Ser Val Glu Leu Ser Leu Ser Asn Leu Glu Glu Asp Bla Tyr Trp 805 810 81s Val Gln Leu Asp Leu His Phe Pro Pro Gly Leu Ser Phe Arg Lys Val 820 825 830 Glu Met Leu Lys Pro His Ser Gln Ile Pro Val Ser Cys Glu Glu Leu 835 840 845 Pro Glu Glu Ser Arg Leu Leu Ser Arg Ala Leu Ser Cys Asn Val Ser 850 855 860 Ser Pro Ile Phe Lys Ala Gly His Ser val Ala Leu Gln Met Met Phe

865. 870 875 880 Asn Thr Leu Val Asn Ser Ser Trp Gly Asp Ser Val Glu Leu His Ala 885 890 89s Asn Val Thr Cys Asn Asn Glu Asp Ser Asp Leu Leu Glu Asp Asn Ser 900 905 810 Ala Thr Thr Ile Ile Pro Ile Leu Tyr Pro Ile Asn Ile Leu Ile Gln 915 820 825 Asp Gln Glu Asp Ser Thr Leu Tyr Val Ser Phe Thr Pro Lys Gly Pro or 930 935 940 Lys Ile His Gln Val Lys His Met Tyr Gln Val Arg Ile Gln Pro Ser 945 950 955 860

Ile His Asp His Asn Ile Pro Thr Leu Glu Ala Val Val Gly val Pro 965 S70 975 Gln Pro Pro Ser Glu Gly Pro Ile Thr His Gln Trp Ser Val Gln Met 980 985 990 Glu Pro Pro Val Pro Cys His Tyr Glu Asp Leu Glu Arg Leu Pro Asp 995 1000 1005 Ala Ala Glu Pro Cys Leu Pro Gly Ala Leu Phe Arg Cys Pro Val 1010 1015 1020 Val Phe Arg Gln Glu Ile Leu Val Gln Val Ile Gly Thr Leu Glu 1025 1030 1035 Leu Val Gly Glu Ile Glu Ala Ser Ser Met Phe Ser Leu Cys Ser 1040 1045 1050 Ser Leu Ser Ile Ser Phe Asn Ser Ser Lys His Phe His Leu Tyr 1055 1060 1065 Gly Ser Asn Ala Ser Leu Ala Gln Val Val Met Lys Val Asp Val 1070 1075 1080 Val Tyr Glu Lys Gln Met Leu Tyr Leu Tyr Val Leu Ser Gly Ile 1085 1090 1085 Gly Gly Leu Leu Leu Leu Leu Leu Ile Phe Ile Val Leu Tyr Lys 1100 1105 1110 Val Gly Phe Phe Lys Arg Asn Leu Lys Glu Lys Met Glu Ala Gly 1115 1120 1125 Arg Gly Val Pro Asn Gly Ile Pro Ala Glu Asp Ser Glu Gln Leu 1130 1135 1140 Ala Ser Gly Gln Glu ala Gly Asp Pro Gly Cys Leu Lys Pro Leu 1145 1150 1155 His Glu Lys Asp Ser Glu Ser Gly Gly Gly Lys Asp 1160 1165 1170 ) <210> 3008 <211l> 502 <212> PRT <213> Homo sapiens 1440

<400> 3008 Met Ala Thr Asn Pro Gln Pro Gln Pro Pro Pro Pro Ala Pro Pro Pro 1 5 10 15 Pro Pro Pro Gln Pro Gln Pro Gln Pro Pro Pro Pro Pro Pro Gly Pro

Gly Ala Gly Pro Gly Ala Gly Gly Ala Gly Gly Ala Gly Ala Gly Ala 40 45 Gly Asp Pro Gln Leu Val Ala Met Ile Val Asn His Leu Lys Ser Gln 50 55 60 Gly Leu Phe Asp Gln Phe Arg Arg Asp Cys Leu Ala Asp Val Asp Thr 65 70 75 80 Lys Pro Ala Tyr Gln Asn Leu Arg Gln Arg Val Asp Asn Phe Val Ala 85 90 95 Asn His Leu Ala Thr His Thr Trp Ser Pro His Leu Asn Lys Asn Gln 100 105 110 Leu Arg Asn Asn Ile Arg Gln Gln Val Leu Lys Ser Gly Met Leu Glu 115 120 125 Ser Gly Ile Asp Arg Ile Ile Ser Gln Val Val Asp Pro Lys Ile Asn 13¢ 135 140 His Thr Phe Arg Pro Gln Val Glu Lys Ala Val His Glu Phe Leu Ala 145 150 155 160 Thr Leu Asn His Lys Glu Glu Gly Ser Gly Asn Thr Ala Pro Asp Asp 165 170 175 Glu Lys Pro Asp Thr Ser Leu Ile Thr Gln Gly Val Pro Thr Pro Gly 180 185 190 Pro Ser Ala Asn Val Ala Asn Asp Ala Met Ser Ile Leu Glu Thr Ile 195 200 205 Thr Ser Leu Asn Gln Glu Ala Ser Ala Ala Arg Ala Ser Thr Glu Thr 210 215 220 Ser Asn Ala Lys Thr Ser Glu Arg Ala Ser Lys Lys Leu Pro Ser Gln 225 230 235 240

Pro Thr Thr Asp Thr Ser Thr Asp Lys Glu Arg Thr Ser Glu Asp Met 245 250 255 Ala Asp Lys Glu Lys Ser Thr Ala Asp Ser Gly Gly Glu Gly Leu Glu 260 265 270 Thr Ala Pro Lys Ser Glu Glu Phe Ser Asp Leu Pro Cys Pro Val Glu 275 280 285 Glu Ile Lys Asn Tyr Thr Lys Glu His Asn Asn Leu Ile Leu Leu Asn 290 295 300 Lys Asp Val Gln Gln Glu Ser Ser Glu Gln Lys Asn Lys Ser Thr Asp 305 310 315 320 Lys Gly Glu Lys Lys Pro Asp Ser Asn Glu Lys Gly Glu Arg Lys Lys 325 330 335 Glu Lys Lys Glu Lys Thr Glu Lys Lys Phe Asp His Ser Lys Lys Ser 340 345 350 Glu Asp Thr Gln Lys Val Lys Asp Glu Lys Gln Ala Lys Glu Lys Glu 355 360 365 Val Glu Ser Leu Lys Leu Pro Ser Glu Lys Asn Ser Asn Lys Ala Lys 370 375 380 Thr Val Glu Gly Thr Lys Glu Asp Phe Ser Leu Ile Asp Ser Asp Val 385 390 385 400 Asp Gly Leu Thr Asp Ile Thr Val Ser Ser Val His Thr Ser Asp Leu 405 410 415 Ser Ser Phe Glu Glu Asp Thr Glu Glu Glu Val Val Thr Ser Asp Ser 420 425 430 Met Glu Glu Gly Glu Ile Thr Ser Asp Asp Glu Glu Lys Asn Lys Gln 435 440 445 Asn Lys Thr Lys Thr Gln Thr Ser Asp Ser Ser Glu Gly Lys Thr Lys or 450 455 : 460 Ser val Arg His Ala Tyr Val His Lys Pro Tyr Leu Tyr Ser Lys Tyr 465 470 475 480

Tyr Ser Asp Ser Asp Asp Glu Leu Thr val Glu Gln Arg Arg Gln Ser 485 490 495 Ile Gly Ile Leu Trp Phe 500 <210> 3009 <211l> 61 <212> PRT <213> Homo sapiens <400> 3009 Met Lys Arg Phe Leu Phe Leu Leu Leu Thr Ile Ser Leu Leu Val Met 1 5 10 15 Val Gln Ile Gln Thr Gly Leu Ser Gly Gln Asn Asp Thr Ser Gln Thr

Ser Ser Pro Ser Ala Ser Ser Ser Met Ser Gly Gly Ile Phe Leu Phe 40 45 Phe Val Ala Asn Ala Ile Ile His Leu Phe Cys Phe Ser 50 55 60 <210> 3010 <21l1l> 352 <212> PRT <213> Homo sapiens <400> 3010 Met Glu Gly Ile Ser Ile Tyr Thr Ser Asp Asn Tyr Thr Glu Glu Met 1 5 10 15 Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys Phe Arg Glu Glu 20 25 30 Asn Ala Asn Phe Asn Lys Ile Phe Leu Pro Thr Ile Tyr Ser Ile Ile 35 40 45 Phe Leu Thr Gly Ile Val Gly Asn Gly Leu Val Ile Leu Val Met Gly 50 55 60 Tyr Gln Lys Lys Leu Arg Ser Met Thr Asp Lys Tyr Arg Leu His Leu 65 70 75 80 Ser Val Ala Asp Leu Leu Phe Val Ile Thr Leu Pro Phe Trp Ala Val 85 90 95

Asp Ala Val Ala Asn Trp Tyr Phe Gly Asn Phe Leu Cys Lys Ala Val 100 105 110 His Val Ile Tyr Thr Val Asn Leu Tyr Ser Ser Val Leu Ile Leu Ala 115 120 © 125 Phe Ile Ser Leu Asp Arg Tyr Leu Ala Ile Val His Ala Thr Asn Ser 130 135 140 Gln Arg Pro Arg Lys Leu Leu Ala Glu Lys Val val Tyr Val Gly Val 145 150 155 160 Trp Ile Pro Ala Leu Leu Leu Thr Ile Pro Asp Phe Ile Phe Ala Asn 165 170 178 Val Ser Glu Ala Asp Asp Arg Tyr Ile Cys Asp Arg Phe Tyr Pro Asn 180 185 190 Asp Leu Trp Val Val Val Phe Gln Phe Gln His Ile Met Val Gly Leu 195 200 205 Ile Leu Pro Gly Ile Val Ile Leu Ser Cys Tyr Cys Ile Ile Ile Ser 210 215 220 Lys Leu Ser His Ser Lys Gly His Gln Lys Arg Lys Ala Leu Lys Thr 225 230 235 240 Thr Val Ile Leu Ile Leu Ala Phe Phe Ala Cys Trp Leu Pro Tyr Tyr } 245 250 255 Ile Gly Ile Ser Ile Asp Ser Phe Ile Leu Leu Glu Ile Ile Lys Gln 260 265 . 270 Gly Cys Glu Phe Glu Asn Thr Val His Lys Trp Ile Ser Ile Thr Glu 275 280 285 Ala Leu Ala Phe Phe His Cys Cys Leu Asn Pro Ile Leu Tyr Ala Phe 2590 285 300 Leu Gly Ala Lys Phe Lys Thr Ser Ala Gln His Ala Leu Thr Ser val 305 310 315 320 Ser Arg Gly Ser Ser Leu Lys Ile Leu Ser Lys Gly Lys Arg Gly Gly 325 330 335

His Ser Ser Val Ser Thr Glu Ser Glu Ser Ser Ser Phe His Ser Ser 340 345 350

<210> 3011

<211> 94

<212> PRT

<213> Homo sapiens

<400> 3011

Met Ala Pro leu Lys Met Leu Ala Leu Val Thr Leu Leu Leu Gly Ala

1 5 10 15

Ser Leu Gln His Ile His Ala Ala Arg Gly Thr Asn Val Gly Arg Glu } 30

Cys Cys Leu Glu Tyr Phe Lys Gly Ala Ile Pro Leu Arg Lys Leu Lys

40 45 Thr Trp Tyr Gln Thr Ser Glu Asp Cys Ser Arg Asp Ala Ile Val Phe 50 55 €0

Val Thr val Gln Gly Arg Ala Ile Cys Ser Asp Pro Asn Asn Lys Arg

65 70 75 80

Val Lys Asn Ala Val Lys Tyr Leu Gln Ser Leu Glu Arg Ser

85 90

<210> 3012

<211> 748

<212> PRT

<213> Homo sapiens

<400> 3012

Met Ser Gln Trp Asn Gln Val Gln Gln Leu Glu Ile Lys Phe Leu Glu

1 5 10 15

Gln val Asp Gln Phe Tyr Asp Asp Asn Phe Pro Met Glu Ile Arg His 20 25 30

Leu Leu Ala Gln Trp Ile Glu Asn Gln Asp Trp Glu Ala Ala Ser Asn

35 40 45 Asn Glu Thr Met Ala Thr Ile Leu Leu Gln Asn Leu Leu Ile Gln Leu 50 SS 60 Asp Glu Gln Leu Gly Arg Val Ser Lys Glu Lys Asn Leu Leu Leu Ile 65 70 75 80

His Asn Leu Lys Arg Ile Arg Lys Val Leu Gln Gly Lys Phe His Gly 85 90 95 Asn Pro Met His val Ala Val Val Ile Ser Asn Cys Leu Arg Glu Glu 100 105 110 Arg Arg Ile Leu Ala Ala Ala Asn Met Pro Val Gln Gly Pro Leu Glu : 115 120 125 Lys Ser Leu Gln Ser Ser Ser Val Ser Glu Arg Gln Arg Asn val Glu 130 135 140 His Lys Val Ala Ala Ile Lys Asn Ser Val Gln Met Thr Glu Gln Asp 145 150 155 160 Thr Lys Tyr Leu Glu Asp Leu Gln Asp Glu Phe Asp Tyr Arg Tyr Lys 165 170 175 Thr Ile Gln Thr Met Asp Gln Ser Asp Lys Asn Ser Ala Met Val Asn : 180 185 180 Gln Glu Val Leu Thr Leu Gln Glu Met Leu Asn Ser Leu Asp Phe Lys 195 200 205 Arg Lys Glu Ala Leu Ser Lys Met Thr Gln Ile Ile His Glu Thr Asp 210 215 220 Leu Leu Met Asn Thr Met Leu Ile Glu Glu Leu Gln Asp Trp Lys Arg 225 230 235 240 Arg Gln Gln Ile Ala Cys Ile Gly Gly Pro Leu His Asn Gly Leu Asp 245 250 255 Gln Leu Gln Asn Cys Phe Thr Leu Leu Ala Glu Ser Leu Phe Gln Leu 260 265 270 Arg Arg Gln Leu Glu Lys Leu Glu Glu Gln Ser Thr Lys Met Thr Tyr 275 280 - ’ 285 Glu Gly Asp Pro Ile Pro Met Gln Arg Thr His Met Leu Glu Arg val 250 295 300 Thr Phe Leu Ile Tyr Asn Leu Phe Lys Asn Ser Phe Val Val Glu Arg 305 310 315 320

Gln Pro Cys Met Pro Thr His Pro Glan Arg Pro Leu Val Leu Lys Thr 325 330 335 Leu Ile Gln Phe Thr Val Lys Leu Arg Leu Leu Ile Lys Leu Pro Glu 340 345 350 Leu Asn Tyr Gln Val Lys val Lys Ala Ser Ile Asp Lys Asn Val Ser 355 360 365 Thr Leu Ser Asn Arg Arg Phe Val Leu Cys Gly Thr Asn Val Lys Ala 370 375 380 Met Ser Ile Glu Glu Ser Ser Asn Gly Ser Leu Ser Val Glu Phe Arg 385 390 395 400 His Leu Gln Pro Lys Glu Met Lys Ser Ser Ala Gly Gly Lys Gly Asn 405 410 415 Glu Gly Cys His Met Val Thr Glu Glu Leu His Ser Ile Thr Phe Glu 420 425 430 Thr Gln Ile Cys Leu Tyr Gly Leu Thr Ile Asp Leu Glu Thr Ser Ser 435 440 445 Leu Pro Val Val Met Ile Ser Asn Val Ser Gln Leu Pro Asn Ala Trp 450 455 460 Ala Ser Ile Ile Trp Tyr Asn Val Ser Thr Asn Asp Ser Gln Asn Leu 465 470 475 480 val Phe Phe Asn Asn Pro Pro Pro Ala Thr Leu Ser Gln Leu Leu Glu 485 490 495 Val Met Ser Trp Gln Phe Ser Ser Tyr Val Gly Arg Gly Leu Asn Ser 500 505 510 Asp Gln Leu His Met Leu Ala Glu Lys Leu Thr Val Gln Ser Ser Tyr S15 520 525 Ser Asp Gly His Leu Thr Trp Ala Lys Phe Cys Lys Glu His Leu Pro 530 535 540 Gly Lys Ser Phe Thr Phe Trp Thr Trp Leu Glu Ala Ile Leu Asp Leu 545 550 555 560 Ile Lys Lys His Ile Leu Pro Leu Trp Ile Asp Gly Tyr Val Met Gly

565 570 575 Phe val Ser Lys Glu Lys Glu Arg Leu Leu Leu Lys Asp Lys Met Pro 580 585 590 Gly Thr Phe Leu Leu Arg Phe Ser Glu Ser His Leu Gly Gly Ile Thr 595 600 605 Phe Thr Trp Val Asp His Ser Glu Ser Gly Glu Val Arg Phe His Ser 610 615 620 val Glu Pro Tyr Asn Lys Gly Arg Leu Ser Ala Leu Pro Phe Ala Asp 625 630 635 640 Ile Leu Arg Asp Tyr Lys Val Ile Met Ala Glu Asn Ile Pro Glu Asn 645 650 655 Pro Leu Lys Tyr Leu Tyr Pro Asp Ile Pro Lys Asp Lys Ala Phe Gly 660 665 670 Lys His Tyr Ser Ser Gln Pro Cys Glu Val Ser Arg Pro Thr Glu Arg 675 680 685 Gly Asp Lys Gly Tyr Val Pro Ser Val Phe Ile Pro Ile Ser Thr Ile 690 695 700 Arg Ser Asp Ser Thr Glu Pro His Ser Pro Ser Asp Leu Leu Pro Met 705 710 715 720 Ser Pro Ser Val Tyr Ala Val Leu Arg Glu Asn Leu Ser Pro Thr Thr 725 730 735 Ile Glu Thr Ala Met Lys Ser Pro Tyr Ser Ala Glu 740 745 <210> 3013 <211> 92 <212> PRT <213> Homo sapiens <400> 3013 Met Lys Leu Cys Val Thr Val Leu Ser Leu Leu Met Leu val Ala Ala 1 5 10 15 Phe Cys Ser Pro Ala Leu Ser Ala Pro Met Gly Ser Asp Pro Pro Thr

Ala Cys Cys Phe Ser Tyr Thr Ala Arg Lys Leu Pro Arg Asn Phe Val 35 40 45

Val Asp Tyr Tyr Glu Thr Ser Ser Leu Cys Ser Gln Pro Ala Val Val

50 55 60

Phe Gln Thr Lys Arg Ser Lys Gln Val Cys Ala Asp Pro Ser Glu Ser

65 70 75 80

Trp Val Gln Glu Tyr Val Tyr Asp Leu Glu Leu Asn

85 90

<210> 3014

<211> 444

<212> PRT

<213> Homo sapiens

<400> 3014

Met Val Ser Gln Ala Leu Arg Leu Leu Cys Leu Leu Leu Gly Leu Gln

1 5 10 15

Gly Cys Leu Ala Ala Val Phe Val Thr Gln Glu Glu Ala His Gly Val

Leu His Arg Arg Arg Arg Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro 40 45

Gly Ser Leu Glu Arg Glu Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu

50 55 . 60 :

Ala Arg Glu Ile Phe Lys Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile

€5 70 75 80

Ser Tyr Ser Asp Gly Asp Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly

85 90 95 Gly Ser Cys Lys Asp Gln Leu Gln Ser Tyr Ile Cys Phe Cys Leu Pro 100 105 110

Ala Phe Glu Gly Arg Asn Cys Glu Thr His Lys Asp Asp Gln Leu Ile 115 120 125

Cys Val Asn Glu Asn Gly Gly Cys Glu Gln Tyr Cys Ser Asp His Thr

130 135 140 Gly Thr Lys Arg Ser Cys Arg Cys His Glu Gly Tyr Ser Leu Leu Ala

145 150 155 160 Asp Gly val Ser Cys Thr Pro Thr Val Glu Tyr Pro Cys Gly Lys Ile 165 170 175 Pro Ile Leu Glu Lys Arg Asn Ala Ser Lys Pro Gln Gly Arg Ile Val 180 185 190 Gly Gly Lys Val Cys Pro Lys Gly Glu Cys Pro Trp Gln Val Leu Leu 185 200 205 Leu Val Asn Gly Ala Gln Leu Cys Gly Gly Thr Leu Ile Asn Thr Ile 210 215 220 Trp Val Val Ser Ala Ala His Cys Phe Asp Lys Ile Lys Asn Trp Arg 225 230 235 240 Asn Leu Ile Ala Val Leu Gly Glu His Asp Leu Ser Glu His Asp Gly 245 250 255 Asp Glu Gln Ser Arg Arg Val Ala Gln Val Ile Ile Pro Ser Thr Tyr 260 265 270 Val Pro Gly Thr Thr Asn His Asp Ile Ala Leu Leu Arg Leu His Gln 275 280 285 Pro Val Val Leu Thr Asp His Val Val Pro Leu Cys Leu Pro Glu Arg 290 295 300 Thr Phe Ser Glu Arg Thr Leu Ala Phe Val Arg Phe Ser Leu Val Ser 305 310 315 320 Gly Trp Gly Gln Leu Leu Asp Arg Gly Ala Thr Ala Leu Glu Leu Met 325 330 335 Val Leu Asn Val Pro Arg Leu Met Thr Gln Asp Cys Leu Gln Gln Ser R 340 345 350 Arg Lys Val Gly Asp Ser Pro Asn Ile Thr Glu Tyr Met Phe Cys Ala 355 360 365 Gly Tyr Ser Asp Gly Ser Lys Asp Ser Cys Lys Gly Asp Ser Gly Gly 370 375 380 Pro His Ala Thr His Tyr Arg Gly Thr Trp Tyr Leu Thr Gly Ile Val 385 390 395 400.

Ser Trp Gly Gln Gly Cys Ala Thr Val Gly His Phe Gly Val Tyr Thr 405 410 415 Arg Val Ser Gln Tyr Ile Glu Trp Leu Gln Lys Leu Met Arg Ser Glu 420 425 430 Pro Arg Pro Gly Val Leu Leu Arg Ala Pro Phe Pro 435 440 <210> 3015 <211l> 769 <212> PRT <213> Homo sapiens <400> 3015 Met Leu Gly Leu Arg Pro Pro Leu Leu Ala Leu Val Gly Leu Leu Ser 1 5 10 15 Leu Gly Cys Val Leu Ser Gln Glu Cys Thr Lys Phe Lys Val Ser Ser

Cys Arg Glu Cys Ile Glu Ser Gly Pro Gly Cys Thr Trp Cys Gln Lys 40 45 Leu Asn Phe Thr Gly Pro Gly Asp Pro Asp Ser Ile Arg Cys Asp Thr 50 55 60 Arg Pro Gln Leu Leu Met Arg Gly Cys Ala Ala Asp Asp Ile Met Asp 65 70 75 80 Pro Thr Ser Leu Ala Glu Thr Gln Glu Asp His Asn Gly Gly Gln Lys 85 90 95 Gln Leu Ser Pro Gln Lys Val Thr Leu Tyr Leu Arg Pro Gly Gln Ala 100 105 110 Ala Ala Phe Asn Val Thr Phe Arg Arg Ala Lys Gly Tyr Pro Ile Asp 115 120 125 Leu Tyr Tyr Leu Met Asp Leu Ser Tyr Ser Met Leu Asp Asp Leu Arg - 130 135 140 Asn Val Lys Lys Leu Gly Gly Asp Leu Leu Arg Ala Leu Asn Glu Ile 145 150 155 160

Thr Glu Ser Gly Arg Ile Gly Phe Gly Ser Phe Val Asp Lys Thr Val 165 170 175 Leu Pro Phe Val Asn Thr His Pro Asp Lys Leu Arg Asn Pro Cys Pro 180 185 190 Asn Lys Glu Lys Glu Cys Gln Pro Pro Phe Ala Phe Arg His Val Leu 195 200 205 Lys Leu Thr Asn Asn Ser Asn Gln Phe Gln Thr Glu Val Gly Lys Gln 210 215 220 Leu Ile Ser Gly Asn Leu Asp Ala Pro Glu Gly Gly Leu Asp Ala Met 225 230 235 240 Met Gln Val Ala Ala Cys Pro Glu Glu Ile Gly Trp Arg Asn Val Thr 245 250 255 Arg Leu Leu Val Phe Ala Thr Asp Asp Gly Phe His Phe Ala Gly Asp 260 265 270 Gly Lys Leu Gly Ala Ile Leu Thr Pro Asn Asp Gly Arg Cys His Leu 275 280 285 Glu Asp Asn Leu Tyr Lys Arg Ser Asn Glu Phe Asp Tyr Pro Ser Val 290 295 300 Gly Gln Leu Ala His Lys Leu Ala Glu Asn Asn Ile Gln Pro Ile Phe 305 310 315 320 Ala val Thr Ser Arg Met Val Lys Thr Tyr Glu Lys Leu Thr Glu Ile 325 330 + 335 Ile Pro Lys Ser Ala Val Gly Glu Leu Ser Glu Asp Ser Ser Asn Val 340 345 350 Val His Leu Ile Lys Asn Ala Tyr Asn Lys Leu Ser Ser Arg Val Phe 355 360 365 Leu Asp His Asn Ala Leu Pro Asp Thr Leu Lys Val Thr Tyr Asp Ser 370 375 380 Phe Cys Ser Asn Gly Val Thr His Arg Asn Gln Pro Arg Gly Asp Cys 385 390 395 400 Asp Gly Val Gln Ile Asn Val Pro Ile Thr Phe Gln Val Lys Val Thr

405 410 415 Ala Thr Glu Cys Ile Gln Glu Gln Ser Phe Val Ile Arg Ala Leu Gly 420 425 430 Phe Thr Asp Ile Val Thr val Gln Val Leu Pro Gln Cys Glu Cys Arg 435 440 445 Cys Arg Asp Gln Ser Arg Asp Arg Ser Leu Cys His Gly Lys Gly Phe 450 455 460 Leu Glu Cys Gly Ile Cys Arg Cys Asp Thr Gly Tyr Ile Gly Lys Asn 465 470 475 480 Cys Glu Cys Gln Thr Gln Gly Arg Ser Ser Gln Glu Leu Glu Gly Ser 485 430 495 Cys Arg Lys Asp Asn Asn Ser Ile Ile Cys Ser Gly Leu Gly Asp Cys 500 505 510 Val Cys Gly Gln Cys Leu Cys His Thr Ser Asp Val Pro Gly Lys Leu 515 520 525 Ile Tyr Gly Gln Tyr Cys Glu Cys Asp Thr Ile Asn Cys Glu Arg Tyr 530 535 540 Asn Gly Gln Val Cys Gly Gly Pro Gly Arg Gly Leu Cys Phe Cys Gly 545 550 555 S60 Lys Cys Arg Cys His Pro Gly Phe Glu Gly Ser Ala Cys Gln Cys Glu 565 570 575 Arg Thr Thr Glu Gly Cys Leu Asn Pro Arg Arg Val Glu Cys Ser Gly 580 585 + 580 Arg Gly Arg Cys Arg Cys Asn Val Cys Glu Cys His Ser Gly Tyr Gln 595 600 605 Leu Pro Leu Cys Gln Glu Cys Pro Gly Cys Pro Ser Pro Cys Gly Lys 610 615 620 Tyr Ile Ser Cys Ala Glu Cys Leu Lys Phe Glu Lys Gly Pro Phe Gly ’ 625 630 635 640 Lys Asn Cys Ser Ala Ala Cys Pro Gly Leu Gln Leu Ser Asn Asn Pro 645 €50 655

IEEE RRR.

Val Lys Gly Arg Thr Cys Lys Glu Arg Asp Ser Glu Gly Cys Trp Val 660 665 670 Ala Tyr Thr Leu Glu Gln Gln Asp Gly Met Asp Arg Tyr Leu Ile Tyr 675 680 685 Val Asp Glu Ser Arg Glu Cys Val Ala Gly Pro Asn Ile Ala Ala Ile 6390 695 700 Val Gly Gly Thr val ala Gly Ile val Leu Ile Gly Ile Leu Leu Leu 705 710 718 720 Val Ile Trp Lys Ala Leu Ile His Leu Ser Asp Leu Arg Glu Tyr Arg 725 730 735 Arg Phe Glu Lys Glu Lys Leu Lys Ser Gln Trp Asn Asn Asp Asn Pro 740 745 750 Leu Phe Lys Ser Ala Thr Thr Thr Val Met Asn Pro Lys Phe Ala Glu 758 760 765 Ser <210> 3016 <211l> 50 <212> DNA <213> Homo sapiens <400> 3016 gggaggaaca ctgcactctt aagctteege cgtctcaacc cctcacagga 50 <210> 3017 <211> 50 <212> DNA <213> Homo sapiens <400> 3017 aggagtcttt tacccggtgt getttgeege agtcatccaa aataaattca 50 <210> 3018 <211l> 590 <212> DNA <213> Homo sapiens <400> 3018 cacctgattc cccectettge Ccacaggact ctgctgttgt tttcattctg 50

<210> 3019 <21ll> 50 <212> DNA <213> Homo sapiens <400> 3019 attatatttg tccctatcag aatcctcgaa tccctagcag ccagtcecctg SO <210> 3020 <211> 50 <212> DNA <213> Homo sapiens <400> 3020 gtcccttagg ggagggagag ttgtcctctt tgcccacagt ctaccctcag 50 <210> 3021 <211> 50 <212> DNA <213> Homo sapiens <400> 3021 cttgggccag actgtcaggg ttcaaggagg gcatcaggag cagacggaga 50 <210> 3022 <211> 50 <212> DNA <213> Homo sapiens <400> 3022 ctcttcaagg ggtctacatg gcaactgtga ggaggggaga ttcagtgtgg 50 <210> 3023 <211> 50 <212> DNA <213> Homo sapiens <400> 3023 taagcataaa acctgacacg ttaaaatccc tgccectttgg tgagceccact 50 <210> 3024 <211> 50 <212> DNA <213> Homo sapiens <400> 3024 tgctggtatt ctcactgcca catttttgga aacctgtatt acaccttaaa 50 <210> 3025 <211> 50 <212> DNA <213> Homo sapiens <400> 3025 cagtcactgg gtctatatta aacagcaacc agagcaacaa atggcaaaca 50

<210> 3026 <211> 50 <212> DNA <213> Homo sapiens <400> 3026 tctagcccag cattgatcta gaagcagagg aatcccagceg ccttttaaaa 50 <210> 3027 <211> 50 <212> DNA <213> Homo sapiens <400> 3027 tgggcaagac atgattaatg aatcagaatc ctgtttcatt ggtgacttgg 50 <210> 3028 <211l> 50 <212> DNA <213> Homo sapiens <400> 3028 tgcagattcc tagtagcatg ccttacctac agcactatgt gecatttgctg 50 . <210> 3029 <211> 50 <212> DNA <213> Homo sapiens <400> 30289 ggtctgagag tctgtgaaga tggcccagtce ttctatccece cacctaaaaa 50 <210> 3030 <211l> 50 <212> DNA <213> Homo sapiens <400> 3030 cttgaccaaa cccacagcct gtctcttctce ttgtttagtt acttacggca 50 <210> 3031 <21l> 50 <212> DNA <213> Homo sapiens <400> 3031 ccactgtcac tgtttctctg ctgttgcaaa tacatggata acacatttga : : 50 <210> 3032 <211> 50 <212> DNA <213> Homo sapiens

<400> 3032 tgcagccact attgttagtc tcttgattca taatgactta agcacacttg 50 <210> 3033 <21l> 50 <212> DNA <213> Homo sapiens <400> 3033 cctgatggag agaagaaggc atatgttcga ctggctcctg attacgatge 50 <210> 3034 <211> 50 <212> DNA <213> Homo sapiens <400> 3034 gccgaattgt ctttggtgcect tttcacttgt gttttaaaat aaggattttt 50 <210> 3035 <211> 50 <212> DNA <213> Homo sapiens <400> 3035 ctggaggacc tgttgatgct agttcagagt atcaccaaga gctggagagg 50 <210> 3036 <21l> 50 <212> DNA <213> Homo sapiens <400> 3036 accatccaat cggacaagct ttcagaacct tattgaagga tttgaagcac 50 <210> 3037 <211l> 50 <212> DNA <213> Homo sapiens <400> 3037 agaaatgttc agtaatgaaa aaatatatcc aatcagagcc atcccgaaaa 50 <210> 3038 <211> 50 <212> DNA <213> Homo sapiens <400> 3038 agcggactca ggctccagcect gtggctacaa catagggttt ttatacaaga 50 <210> 3038 <211> 50 <212> DNA

<213> Homo sapiens <400> 3039 accagactga caaatgtgta tcggatgectt ttgttcaggg ctgtgatcgg 50 <210> 3040 <211> 50 <212> DNA <213> Homo sapiens <400> 3040 ccactgtcac tgtttctctg ctgttgcaaa tacatggata acacatttga 50 <210> 3041 <211> 50 <212> DNA <213> Homo sapiens <400> 3041 aagtgaacaa aataagcaac taaatgagac ctaataattg gccttcgatt 50 <210> 3042 <211> 50 <212> DNA <213> Homo sapiens <400> 3042 tctgttgata gctggagaac tttagtttca agtactacat tgtgaaagca 50 <210> 3043 <211> 50 <212> DNA <213> Homo sapiens <400> 3043 gacctcatct ccaagatgga gaagatctga cctccacgga gccgctgtcec 50 <210> 3044 <211> S50 <212> DNA <213> Homo sapiens <400> 3044 ctgaccgcca ctctcacatt tgggcectctte gectggcecttg gtggagetgg 50 <210> 3045 <211> 50 <212> DNA oC <213> Homo sapiens <400> 3045 atacagccce ggcagaaaac gcctaaagtc agatgagaga ccagtacata 50 <210> 3046

<211> 50 <212> DNA <213> Homo sapiens <400> 3046 aacagaagtc aagagaacat agaccaactt gctgcatgag taaggtggct 50 <210> 3047 <211l> 50 <212> DNA <213> Homo sapiens <400> 3047 agaggactat agtggaagtg aaagcattct gtgtttactc tttgcattaa 50 <210> 3048 <211> 50 <212> DNA <213> Homo sapiens <400> 3048 caggtcaacc cccaccggac ctacaacccg cagtcccaca tcatctcagg 50 <210> 3049 <211l> 50 <212> DNA <213> Homo sapiens <400> 3048 ccttccagaa gctacgaaaa agggagctgt ttaaatttaa taaatctctg 50 <210> 3050 <211> 50 <212> DNA <213> Homo sapiens <400> 3050 ccaatggata tttctgtatt actagggagg catttacagt cctctaatgt 50 <210> 3051 <211> 50 <212> DNA <213> Homo sapiens <400> 3051 atctgacatt attgtaacta ccgtgtgatc agtaagattc ctgtaagaaa 50 <210> 3052 or <211> 50 <212> DNA <213> Homo sapiens <400> 3052 tccaatgcag tcccattcett tatggcoctat agtctcacte ccaactacee 50

<210> 3053 <211> 50 <212> DNA <213> BHBomo sapiens <400> 3053 tcctaggtag ggtttaatcc ccagtaaaat tgccatattg cacatgtctt 50 <210> 3054 <211> 50 <212> DNA <213> Homo sapiens <400> 3054 gggcattcca ccgaaattct tggggaaatt tagtagcectt cattttagca 50 <210> 3055 <211> 50 <212> DNA <213> Homo sapiens <400> 3055 aaagggtttt atccactgtc atttcaattg gataacattt tgtcaagttt 50 <210> 3056 <211> 50 <212> DNA <213> Homo sapiens <400> 3056 aattcctgaa ccgttggatc accttctgtc agtccatcat ctccaccctg 50 <210> 3057 <211> 50 ’ <212> DNA <213> Homo sapiens <400> 3057 ggcaggaggt tctcactgtt gtgaaggttg tagacgttgt gtaatgtgtt 50 <210> 3058 <211l> 50 <212> DNA <213> Homo sapiens <400> 3058 gtgggtaagg ggctcaagct gtgatgctgc tggttttatc tctagtgaaa 50 <210> 3059 <211> 50 <212> DNA <213> Homo sapiens <400> 3059 agacaaagag agcataaata tagctctact catgggtacc ataccagtgt 50 <210> 3060 <211> 50 <212> DNA <213> Homo sapiens <400> 3060 cttcaggcce aagttcaacg ggttaaagag gtccgctcecc aaattattct 50 <210> 3061 <211> SO . <212> DNA <213> Homo sapiens <400> 3061 aacaagccat gtttgcccta gtccaggatt gecctcacttg agacttgcta 50 <210> 3062 <21l> 50 <212> DNA <213> Homo sapiens <400> 3062 tctteetggg aatgtgatgt gtttttcact ggttctaatt ctgtcettect 50 <210> 3063 <211> 50 <212> DNA <213> Homo sapiens <400> 3063 tgatctgact ggaaaacaat cctgtatccc ctcccaaaga atcatgggcet 50 <210> 3064 <211> 50 <212> DNA <213> Homo sapiens <400> 3064 aacaagccat gtttgcccta gtccaggatt gecctcacttg agacttgcta 50 <210> 3065 <211> 50 <212> DNA <213> Homo sapiens <400> 3065 acagcatgag aaactgttag tacgcatacc tcagttcaaa cctttaggga 50 <210> 3066 <21l> 50 <212> DNA <213> Homo sapiens

<400> 3066 tctctgactt cttattacca aggacactct atctgttgec tcttactctt 50 <210> 3067 <211> 50 <212> DNA <213> Homo sapiens <400> 3067 gagagctttc tcccecgectt cagtttectga tggatctage catgttgaaa S0 <210> 3068 <211> 50 <212> DNA <213> Homo sapiens <400> 3068 ggaggaatgg ctgtgceccgt cccctccact taagcgacct gagtctccag 50 <210> 3069 <211s> 50 <212> DNA <213> Homo sapiens <400> 3069 ggaaatgttg ctgtggggga ttcattgtaa ctctccttgt gaactgctca 50 <210> 3070 <211> 50 <212> DNA <213> Homo sapiens <400> 3070 aggtgggctg gacttctacc tgccctcaag ggtgtgtata ttgtataggg 50 <210> 3071 <211> 50 <212> DNA <213> Homo sapiens <400> 3071 cagacgctcc agtgctgecg aggttagtgt gtttattaga cctgaaatga 50 <210> 3072 <211l> 50 <212> DNA <213> Homo sapiens - <400> 3072 ccttgggetg agtttgetgg tcctgaagat tacagttttg gttagagaga 50 <210> 3073 <211> SO

<212> DNA <213> Homo sapiens <400> 3073 tctcggttta cctttttget gttgtggttce tttgttettg ctggtttgct S50 <210> 3074 <211l> 50 <212> DNA <213> Homo sapiens <400> 3074 tgtgctaagc ctgatgaaat gtgctccttc aatctccatg aaaccatcgt 50 <210> 3075 <211> 50 <212> DNA <213> Homo sapiens <400> 3075 ttcctgtcecte catgttgtgg tcaagattgce catttgecttc ctgagtttca 50 <210> 3076 <211> 50 <212> DNA <213> Homo sapiens <400> 3076 ataacagact ccagctcctg gtccaccegg catgtcagtc agcactctgg 50 <210> 3077 <211> 50 <212> DNA <213> Homo sapiens <400> 3077 gggagccatc cctctctacc aaggtggcaa tgatggaggg aacttgcatg 50 <210> 3078 <211> 50 <212> DNA <213> Homo sapiens <400> 3078 ttgacctcece atttttacta tttgccaata cctttttcta ggaatgtgcet 50 <210> 3079 <211l> 50 <212> DNA <213> Homo sapiens <400> 3079 ggaggcagcc agggcttacce tgtacactga cttgagacca gttgaataaa 50

<210> 3080 <211> 50 <212> DNA <213> Homo sapiens <400> 3080 tagttagagt ccaagacatg gttccteecce ctttgtctgt acatcctgge 50 <210> 3081 <211> 50 <212> DNA <213> Homo sapiens <400> 3081 tttgcatcce gagttttgta ttccaagaaa atcaaagggg gccaatttgt 50 <210> 3082 <211l> 63 <212> DNA . <213> Homo sapiens <400> 3082 ggccagtgaa ttgtaatacg actcactata gggaggcggt tttttttttt tttttttttt 60 ttt 63 <210> 3083 <211l> 463 <212> DNA <213> Homo sapiens <400> 3083 ttggcttgac tcaggattta aaaactggaa cggtgaaggt gacagcagtc ggttggacga 60 gcatcccecca aagttcacaa tgtggccgag gactttgatt gcacattgtt gttttttaat 120 agtcattcca aatatgagat gcattgttac aggaagtccc ttgccatcct aaaagcaccce 180 cacttctctc taaggagaat ggcccagtcc tcteccaagt ccacacaggg gagggatage 240 attgctttecg tgtaaattat gtaatgcaaa atttttttaa tcttcgectt aatctttttt 300 attttgtttt attttgaatg atgagccttc gtgccccececc ttcccecttt tttcccccaa 360 cttgagatgt atgaaggctt ttggtctccc tgggagtggg tggaggcagce cgggcttacce 420 tgtacactga cttgagacca gttgaataaa agtgcacacc tta 463 <210> 3084 <211> 491 ) <212> DNA <213> Homo sapiens <400> 3084 gaagagtacc agaaaagtct gctagagcag taccatctgg gtctggatca aaaacgcaga 60 aaatatgtgg ttggagagct catttggaat tttgccgatt tcatgactga acagtcaccg 120 .

acgagagtgc tggggaataa aaaggggatc ttcactcggc agagacaacc aaaaagtgca 180 gcgttecttt tgcgagagag atactggaag attgccaatg aaaccaggta tccccactca 240 gtagccaagt cacaatgttt ggaaaacagc ccgtttactt gagcaagact gataccacct 300 gcgtgtccct tcctccccga gtcagggcga cttccacagc agcagaacaa gtgcctectg 360 gactgttcac ggcagaccag aacgtttctg gcctgggttt tgtggtcatc tattctagca 420 gggaacacta aaggtggaaa taaaagattt tctattatgg aaataaagag ttggcatgaa 480 agtcgctact g 491 <210> 3085 <211> 20 <212> DNA <213> Homo sapiens <400> 3085 cacaatgtgg ccgaggactt 20 <210> 3086 <211> 20 <212> DNA <213> Homo sapiens <400> 3086 tgtggccgag gactttgatt - 20 <210> 3087 <211> 20 <212> DNA <213> Homo sapiens <400> 3087 : tggcttttag gatggcaagg 20 <210> 3088 <211l> 20 <212> DNA <213> Homo sapiens <400> 3088 ggagggcttag tttgcttect 20 <210> 3089 <211> 20 <212> DNA <213> Homo sapiens <400> 3089 aagtgcagcg ttcecttttge 20

<210> 3050 <21l1l> 20 } <212> DNA <213> Homo sapiens <400> 3090 agcgttcctt ttgcgagaga 20 <210> 3091 <211s> 20 <212> DNA } <213> Homo sapiens <400> 30891 cgggctgttt tccaaacatt 20 <210> 3092 <211> 20 <212> DNA <213> Homo sapiens <400> 3092 gaagggacac gcaggtggta 20 <210> 3093 <211> 20 <212> DNA <213> Homo sapiens <400> 3083 taccacctgc gtgtcccttce 20 <210> 3094 <211> 21 <212> DNA <213> Homo sapiens <400> 3094 gaggcacttg ttctgctgct g 21 <210> 3095 <211> 20 <212> DNA <213> Homo sapiens <400> 3095 tgtggccgag gactttgatt 20 <210> 3096 <211> 327 <212> DNA <213> Homo sapiens <400> 3096 ggggactctg gaggccctct tgtgtgtaac aaggtggccc agggcattgt ctcctatgga €0 .

cgaaacaatg gcatgcctcc acgagcctgc accaaagtct caagctttgt acactggata 120 aagaaaacca tgaaacgcta ctaactacag gaagcaaact aagcccccge tgtaatgaaa 180 caccttctect ggagccaagt ccagatttac actgggagag gtgccagcaa ctgaataaat 240 acctctccca gtgtaaatct ggagccaagt ccagatttac actgggagag gtgccagcaa 300 ctgaataaat acctcttagc tgagtgg 327 <210> 3097 <211> 20 <212> DNA <213> Homo sapiens <400> 3097 acgagcctgc accaaagtct 20 <210> 30898 <211> 20 <212> DNA <213> Homo sapiens <400> 3098 aaacaatggc atgcctccac 20 <210> 3098 <211> 20 <212> DNA <213> Homo sapiens <400> 3099 tcattacagc gggggcttag 20 <210> 3100 <21l1l> 20 <212> DNA <213> Homo sapiens <400> 3100 gggggcttag tttgcttcct 20 <210> 3101 <21l1ls> 5252 <212> DNA <213> Homo sapiens <400> 3101 ctctctccca gaacgtgtcect ctgctgcaag gcaccgggec ctttcgctct gcagaactge 60 acttgcaaga ccattatcaa ctcctaatcc cagctcagaa agggagcectc tgcgactcat 120 tcatcgcect ccaggactga ctgcattgca cagatgatgg atatttacgt atgtttgaaa 180 cgaccatcct ggatggtgga caataaaaga atgaggactg cttcaaattt ccagtggctg 240 ttatcaacat ttattcttct atatctaatg aatcaagtaa atagccagaa aaagggggct 300 cctcatgatt tgaagtgtgt aactaacaat ttgcaagtgt ggaactgttc ttggaaagca 360 ccctectggaa caggccgtgg tactgattat gaagtttgca ttgaaaacag gtccegttcet 420 tgttatcagt tggagaaaac cagtattaaa attccagctc tttcacatgg tgattatgaa 480 ataacaataa attctctaca tgattttgga agttctacaa gtaaattcac actaaatgaa 540 caaaacgttt ccttaattcc agatactcca gagatcttga atttgtctge tgatttctca 600 acctctacat tatacctaaa gtggaacgac aggggttcag tttttccaca ccgctcaaat 660 gttatctggg aaattaaagt tctacgtaaa gagagtatgg agctcgtaaa attagtgacc 720 cacaacacaa ctctgaatgg caaagataca cttcatcact ggagttgggce ctcagatatg 780 cccttggaat gtgccattca ttttgtggaa attagatgect acattgacaa tcttcattett B40 tctggtctcg aagagtggag tgactggagc cctgtgaaga acatttcttg gatacctgat S00 tctcagacta aggtttttcc tcaagataaa gtgatacttg taggctcaga cataacattt 960 tgttgtgtga gtcaagaaaa agtgttatca gcactgattg gccatacaaa ctgecceecttg 1020 atccatcttg atggggaaaa tgttgcaatc aagattcgta atatttctgt ttctgcaagt 1080 agtggaacaa atgtagtttt tacaaccgaa gataacatat ttggaaccgt tatttttget 1140 ggatatccac cagatactcc tcaacaactg aattgtgaga cacatgattt aaaagaaatt 1200 atatgtagtt ggaatccagg aagggtgaca gcgttggtgg gcccacgtgce tacaagctac 1260 actttagttg aaagtttttc aggaaaatat gttagactta aaagagctga agcacctaca 1320 aacgaaagct atcaattatt atttcaaatg cttccaaatc aagaaatata taattttact 1380 ttgaatgctc acaatccgct gggtcgatca caatcaacaa ttttagttaa tataactgaa 1440 aaagtttatc cccatactcc tacttcattc aaagtgaagg atattaattc aacagctgtt 1500 aaactttctt ggcatttacc aggcaacttt gcaaagatta attttttatg tgaaattgaa 1560 attaagaaat ctaattcagt acaagagcag cggaatgtca caatcaaagg agtagaaaat 1620 tcaagttatc ttgttgctct ggacaagtta aatccataca ctctatatac ttttcggatt 1680 cgttgttcta ctgaaacttt ctggaaatgg agcaaatgga gcaataaaaa acaacattta 1740 acaacagaag ccagtccttc aaaggggcct gatacttgga gagagtggag ttctgatgga 1800 aaaaatttaa taatctattg gaagccttta cccattaatg aagctaatgg aaaaatactt -1860 c- tcctacaatg tatcgtgttc atcagatgag gaaacacagt ccctttctga aatccctgat 1820 cctcagcaca aagcagagat acgacttgat aagaatgact acatcatcag cgtagtggcet 1980 aaaaattctg tgggctcatc accaccttcc aaaatagcga gtatggaaat tccaaatgat 2040 .

gatctcaaaa tagaacaagt tgttgggatg ggaaagggga ttctcctcac ctggcattac 2100 gaccccaaca tgacttgcga ctacgtcatt aagtggtgta actcgtctcg gtcggaacca 2160 tgccttatgg actggagaaa agttccctca aacagcactg aaactgtaat agaatctgat 2220 gagtttcgac caggtataag atataatttt ttcctgtatg gatgcagaaa tcaaggatat 2280 caattattac gctccatgat tggatatata gaagaattgg ctcccattgt tgcaccaaat 2340 tttactgttg aggatacttc tgcagattcg atattagtaa aatgggaaga cattcctgtg 2400 gaagaactta gaggcttttt aagaggatat ttgttttact ttggaaaagg agaaagagac 2460 acatctaaga tgagggtttt agaatcaggt cgttctgaca taaaagttaa gaatattact 2520 gacatatccc agaagacact gagaattgct gatcttcaag gtaaaacaag ttaccacctg 2580 gtcttgcgag cctatacaga tggtggagtg ggcccggaga agagtatgta tgtggtgaca 2640 aaggaaaatt ctgtgggatt aattattgcc attctcatcc cagtggcagt ggctgtcatt 2700 gttggagtgg tgacaagtat cctttgctat cggaaacgag aatggattaa agaaaccttc 2760 taccctgata ttccaaatcc agaaaactgt aaagcattac agtttcaaaa gagtgtctgt 2820 gagggaagca gtgctcttaa aacattggaa atgaatcctt gtaccccaaa taatgttgag 2880 gttctggaaa ctcgatcagc atttcctaaa atagaagata cagaaataat ttccccagta 2940 gctgagegtc ctgaagatcg ctectgatgca gagecctgaaa accatgtggt tgtgtectat 3000 tgtccaccca tcattgagga agaaatacca aacccagccg cagatgaagc tggagggact 3060 gcacaggtta tttacattga tgttcagtcg atgtatcagc ctcaagcaaa accagaagaa 3120 gaacaagaaa atgaccctgt aggaggggca ggctataagc cacagatgca cctccccatt 3180 aattctactg tggaagatat agctgcagaa gaggacttag ataaaactgc gggttacaga 3240 cctcaggcca atgtaaatac atggaattta gtgtctccag actctcctag atccatagac 3300 agcaacagtg agattgtctc atttggaagt ccatgctcca ttaattcccg acaatttttg 3360 attcctccta aagatgaaga ctctcctaaa tctaatggag gagggtggtc ctttacaaac 3420 ttttttcaga acaaaccaaa cgattaacag tgtcaccgtg tcacttcagt cagccatctc 3480 aataagctct tactgctagt gttgctacat cagcactggg cattcttgga gggatcctgt 3540 gaagtattgt taggaggtga acttcactac atgttaagtt acactgaaag ttcatgtgct 3600 tttaatgtag tctaaaagcc aaagtatagt gactcagaat cctcaatcca caaaactcaa 3660 gattgggagc tctttgtgat caagccaaag aattctcatg tactctacct tcaagaagca 3720 tttcaaggct aatacctact tgtacgtaca tgtaaaacaa atcccgecege aactgtttte 3780 tgttctgttg tttgtggttt tctcatatgt atacttggtg gaattgtaag tggatttgca 3840 ggccagggag aaaatgtcca agtaacaggt gaagtttatt tgectgacgt ttactccttt 3900 ctagatgaaa accaagcaca gattttaaaa cttctaagat tattctecte tatccacagce 3960 attcacaaaa attaatataa tttttaatgt agtgacagcg atttagtgtt ttgtttgata 4020 aagtatgctt atttctgtgec ctactgtata atggttatca aacagttgtc tcaggggtac 4080 aaactttgaa aacaagtgtg acactgacca gcccaaatca taatcatgtt ttcttgetgt 4140 gataggtttt gcttgecttt tcattatttt ttagetttta tgcttgettc cattatttca 4200 gttggttgcec ctaatattta aaatttacac ttctaagact agagacccac attttttaaa 4260 aatcatttta ttttgtgata cagtgacagc tttatatgag caaattcaat attattcata 4320 agcatgtaat tccagtgact tactatgtga gatgactact aagcaatatc tagcagcgtt 4380 agttccatat agttctgatt ggatttcgtt cctcctgagg agaccatgcc gttgagcecttg 4440 gctacccagg cagtggtgat ctttgacacc ttctggtgga tgttcctcce actcatgagt 4500 cttttcatca tgccacatta tctgatccag tecctcacatt tttaaatata aaactaaaga 4560 gagaatgctt cttacaggaa cagttaccca agggctgttt cttagtaact gtcataaact 4620 gatctggatc catgggcata cctgtgttcg aggtgcagca attgcttggt gagcectgtgca 4680 gaattgattg ccttcagcac agcatecctet gecccaccctt gtttctcata agecgatgtcet 4740 ggagtgattg tggttcttgg aaaagcagaa ggaaaaacta aaaagtgtat cttgtatttt 4800 ccctgececte aggttgecta tgtattttac cttttcatat ttaaggcaaa agtacttgaa 4860 aattttaagt gtccgaataa gatatgtcett ttttgtttgt tttttttggt tggttgtttg 4920 ttttttatca tctgagattc tgtaatgtat ttgcaaataa tggatcaatt aatttttttt 4980 gaagctcata ttgtatcttt ttaaaaacca tgttgtggaa aaaagccaga gtgacaagtg 5040 acaaaatcta tttaggaact ctgtgtatga atcctgattt taactgctag gattcagcta 5100 aatttctgag ctttatgatc tgtggaaatt tggaatgaaa tcgaattcat tttgtacata 5160 catagtatat taaaactata taatagttca tagaaatgtt cagtaatgaa aaaatatatc 5220 caatcagagc catcccgaaa aaaaaaaaaa aa 5252 <210> 3102 <211> 5252 <212> DNA <213> Homo sapiens <220> <221> mwmisc_feature <222> (3967) .. (3988) <223> nis a, c, g, t oru <400> 3102 ctctectecca gaacgtgtet ctgetgcaag gcaccgggec ctttcgectct gcagaactgce _60 acttgcaaga ccattatcaa ctcctaatcc cagctcagaa agggagcectc tgcgactcat 120 tcatecgceoet ccaggactga ctgcattgca cagatgatgg atatttacgt atgtttgaaa 180 cgaccatcct ggatggtgga caataaaaga atgaggactg cttcaaattt ccagtggcetg 240 ttatcaacat ttattcttct atatctaatg aatcaagtaa atagccagaa aaagggggct 300 cctcatgatt tgaagtgtgt aactaacaat ttgcaagtgt ggaactgttc ttggaaagca 360 ccctectggaa caggcecgtgg tactgattat gaagtttgea ttgaaaacag gtcccgttcet 420 tgttatcagt tggagaaaac cagtattaaa attccagctc tttcacatgg tgattatgaa 480 ataacaataa attctctaca tgattttgga agttctacaa gtaaattcac actaaatgaa 540 caaaacgttt ccttaattcc agatactcca gagatcttga atttgtctgce tgatttctca 600 acctctacat tatacctaaa gtggaacgac aggggttcag tttttccaca ccgctcaaat 660 gttatctggg aaattaaagt tctacgtaaa gagagtatgg agctcgtaaa attagtgacce 720 cacaacacaa ctctgaatgg caaagataca cttcatcact ggagttgggc ctcagatatg 780 cccttggaat gtgccattca ttttgtggaa attagatget acattgacaa tcttcatttt 840 tctggtctecg aagagtggag tgactggagc cctgtgaaga acatttcttg gatacctgat S00 tctcagacta aggtttttcc tcaagataaa gtgatacttg taggctcaga cataacattt 960 tgttgtgtga gtcaagaaaa agtgttatca gcactgattg gccatacaaa ctgccccttg 1020 atccatcttg atggggaaaa tgttgcaatc aagattcgta atatttetgt ttctgcaagt 1080 agtggaacaa atgtagtttt tacaaccgaa gataacatat ttggaaccgt tatttttgct 1140 ggatatccac cagatactcc tcaacaactg aattgtgaga cacatgattt aaaagaaatt 1200 atatgtagtt ggaatccagg aagggtgaca gcgttggtgg gcccacgtgce tacaagctac 1260 actttagttg aaagtttttc aggaaaatat gttagactta aaagagctga agcacctaca 1320 aacgaaagct atcaattatt atttcaaatg cttccaaatc aagaaatata taattttact 1380 ttgaatgctc acaatcegct gggtcgatca caatcaacaa ttttagttaa tataactgaa 1440 aaagtttatc cccatactcc tacttcattc aaagtgaagg atattaattc aacagctgtt 1500 aaactttctt ggcatttacc aggcaacttt gcaaagatta attttttatg tgaaattgaa 1560 attaagaaat ctaattcagt acaagagcag cggaatgtca caatcaaagg agtagaaaat 1620 tcaagttatc ttgttgctct ggacaagtta aatccataca ctctatatac ttttcggatt 16890 cgttgttcta ctgaaacttt ctggaaatgg agcaaatgga gcaataaaaa acaacattta 1740 acaacagaag ccagtccttc aaaggggcct gatacttgga gagagtggag ttctgatgga 1800 aaaaatttaa taatctattg gaagccttta cccattaatg aagctaatgg aaaaatactt 1860 tcctacaatg tatcgtgttc atcagatgag gaaacacagt ccctttctga aatccctgat 1820 cctcagcaca aagcagagat acgacttgat aagaatgact acatcatcag cgtagtgget 1980 aaaaattctg tgggctcatc accaccttcc aaaatagcga gtatggaaat tccaaatgat 2040 gatctcaaaa tagaacaagt tgttgggatg ggaaagggga ttctcctcac ctggcattac 2100 gaccccaaca tgacttgcga ctacgtcatt aagtggtgta actecgtcteg gtcggaacca 2160 tgccttatgg actggagaaa agttccctca aacagcactg aaactgtaat agaatctgat 2220 gagtttcgac caggtataag atataatttt ttcctgtatg gatgcagaaa tcaaggatat 2280 caattattac gctccatgat tggatatata gaagaattgg ctcccattgt tgcaccaaat 2340 tttactgttg aggatacttc tgcagattcg atattagtaa aatgggaaga cattcctgtg 2400 gaagaactta gaggcttttt aagaggatat ttgttttact ttggaaaagg agaaagagac 2460 acatctaaga tgagggtttt agaatcaggt cgttctgaca taaaagttaa gaatattact 2520 gacatatccc agaagacact gagaattgcet gatcttcaag gtaaaacaag ttaccacctg 2580 gtcttgegag cctatacaga tggtggagtg ggcccggaga agagtatgta tgtggtgaca 2640 aaggaaaatt ctgtgggatt aattattgcc attctcatcc cagtggcagt ggctgtcatt 2700 gttggagtgg tgacaagtat cctttgctat cggaaacgag aatggattaa agaaaccttc 2760 taccctgata ttccaaatcc agaaaactgt aaagcattac agtttcaaaa gagtgtctgt 2820 gagggaagca gtgctcttaa aacattggaa atgaatcctt gtaccccaaa taatgttgag 2880 gttctggaaa ctcgatcagc atttcctaaa atagaagata cagaaataat ttccccagta 2940 gctgagegtc ctgaagatcg ctctgatgca gagcctgaaa accatgtggt tgtgtcctat 3000 tgtccaccca tcattgagga agaaatacca aacccagccg cagatgaagc tggagggact 3060 gcacaggtta tttacattga tgttcagtcg atgtatcagc ctcaagcaaa accagaagaa 3120 gaacaagaaa atgaccctgt aggaggggca ggctataagc cacagatgca cctccccatt 3180 aattctactg tggaagatat agctgcagaa gaggacttag ataaaactgc gggttacaga 3240 cctcaggcca atgtaaatac atggaattta gtgtctccag actctcctag atccatagac 3300 agcaacagtg agattgtctc atttggaagt ccatgctcca ttaattcccg acaatttttg 3360 attcctcecta aagatgaaga ctctcctaaa tctaatggag gagggtggtc ctttacaaac 3420 ttttttcaga acaaaccaaa cgattaacag tgtcaccgtg tcacttcagt cagccatctce 3480 aataagctct tactgctagt gttgctacat cagcactggg cattcttgga gggatcctgt 3540 gaagtattgt taggaggtga acttcactac atgttaagtt acactgaaag ttcatgtgct 3600 tttaatgtag tctaaaagcc aaagtatagt gactcagaat cctcaatcca caaaactcaa 3660 gattgggagc tctttgtgat caagccaaag aattctcatg tactctacct tcaagaagca 3720 tttcaaggct aatacctact tgtacgtaca tgtaaaacaa atcccgccgce aactgttttce 3780 tgttctgttg tttgtggttt tctcatatgt atacttggtg gaattgtaag tggatttgca 3840 ggccagggag aaaatgtcca agtaacaggt gaagtttatt tgcctgacgt ttactccttt 3900 ctagatgaaa accaagcaca gattttaaaa cttctaagat tattctcctc tatccacage 3960 attcacnnnn nnnnnnnnnn nnnnnnnngt agtgacagcg atttagtgtt ttgtttgata 4020 aagtatgctt atttctgtgc ctactgtata atggttatca aacagttgtc tcaggggtac 4080 aaactttgaa aacaagtgtg acactgacca gcccaaatca taatcatgtt ttcttgctgt 4140 gataggtttt gcttgccttt tcattatttt ttagectttta tgcttgettce cattatttca 4200 gttggttgec ctaatattta aaatttacac ttctaagact agagacccac attttttaaa 4260 aatcatttta ttttgtgata cagtgacagc tttatatgag caaattcaat attattcata 4320 agcatgtaat tccagtgact tactatgtga gatgactact aagcaatatc tagcagcgtt 4380 agttccatat agttctgatt ggatttcgtt cctcctgagg agaccatgcc gttgagcttg 4440 gctacccagg cagtggtgat ctttgacacc ttctggtgga tgttcctccc actcatgagt 4500 cttttcatca tgccacatta tctgatccag tcctcacatt tttaaatata aaactaaaga 4560 gagaatgctt cttacaggaa cagttaccca agggctgttt cttagtaact gtcataaact 4620 gatctggatc catgggcata cctgtgttecg aggtgcagca attgecttggt gagctgtgcea 4680 gaattgattg ccttcagcac agcatcctect gocccaccctt gtttctcata agcgatgtcet 4740 ggagtgattg tggttcttgg aaaagcagaa ggaaaaacta aaaagtgtat cttgtatttt 4800 ccctgecectec aggttgecta tgtattttac cttttcatat ttaaggcaaa agtacttgaa 4860 aattttaagt gtccgaataa gatatgtctt ttttgtttgt tttttttggt tggttgtttg 4920 tcttttatca tctgagattc tgtaatgtat ttgcaaataa tggatcaatt aatttttttt 4980 gaagctcata ttgtatcttt ttaaaaacca tgttgtggaa aaaagccaga gtgacaagtg 5040 acaaaatcta tttaggaact ctgtgtatga atcctgattt taactgctag gattcagcta 5100 aatttctgag ctttatgatc tgtggaaatt tggaatgaaa tcgaattcat tttgtacata 5160 catagtatat taaaactata taatagttca tagaaatgtt cagtaatgaa aaaatatatc 5220 caatcagagc catcccgaaa aaaaaaaaaa aa 5252 <210> 3103 <211> 841 <212> DNA <213> Homo sapiens <400> 3103 tttttttttt ttttcttaaa tagcatttat tttctctcaa aaagcectatt atgtactaac 60 aagtgttcct ctaaattaga aaggcatcac tactaaaatt ttatacatat tttttatata 120 agagaaggaa tattgggtta caatctgaat ttctctttat gatttctctt aaagtataga 180 acagctatta aaatgactaa tattgctaaa atgaaggcta ctaaatttcc ccaagaattt 240 cggtggaatg cccaaaaatg gtgttaagat atgcagaagg gcccatttca agcaaagcaa 300 tctctccace ccttcataaa agatttaagc taaaaaaaaa aaaaaaagaa gaaaatccaa 360 cagctgaaga cattgggcta tttataaatc ttctcecagt cccccagaca gcctcacatg 420 ggggctgtaa acagctaact aaaatatctt tgagactctt atgtccacac ccactgacac 4B0O aaggagagct gtaaccacag tgaaactaga ctttgctttc ctttagcaag tatgtgccta 540 tgatagtaaa ctggagtaaa tgtaacagta ataaaacaaa ttttttttaa aaataaaaat 600 tatacctttt tctccaacaa acggtaaaga ccacgtgaag acatccataa aattaggcaa 660 ccagtaaaga tgtggagaac cagtaaactg tcgaaattca tcacattatt ttcatacttt -720 aatacagcag ctttaattat tggagaacat caaagtaatt aggtgccgaa aaacattgtt 780 attaatgaag ggaacccctg acgtttgacc ttttetgtac catctatagc cctggacttg 840 a 841 <210> 3104 <211l> 841 <212> DNA <213> Homo sapiens <220> <221> misc_feature : <222> (94) ..(121) <223> nis a, ¢c, g, toru <220> <221> misc_feature

<222> (569)... (604)

<223> n is a, ¢c, g, tor u

<400> 3104 tttttttttt ttttcttaaa tagcatttat tttctctcaa aaagcctatt atgtactaac 60 aagtgttcct ctaaattaga aaggcatcac tacnnnnnnn NOnNNnNNNn NOnnnnonnn 120 ngagaaggaa tattgggtta caatctgaat ttctctttat gatttctctt aaagtataga 180 acagctatta aaatgactaa tattgctaaa atgaaggcta ctaaatttcc ccaagaattt 240 cggtggaatg cccaaaaatg gtgttaagat atgcagaagg gcccatttca agcaaagcaa 300 tctctccace ccttcataaa agatttaagc taaaaaaaaa aaaaaaagaa gaaaatccaa 360 cagctgaaga cattgggcta tttataaatc ttctcccagt cccccagaca gcctcacatg 420 ggggctgtaa acagctaact aaaatatctt tgagactctt atgtccacac ccactgacac 480 aaggagagct gtaaccacag tgaaactaga ctttgctttc ctttagcaag tatgtgccta 540 tgatagtaaa ctggagtaaa tgtaacagnn nnnnnnnnnn nnnnnnnnnn nnnnonnonnnn 600 nnnncctttt tctccaacaa acggtaaaga ccacgtgaag acatccataa aattaggcaa 660 ccagtaaaga tgtggagaac cagtaaactg tcgaaattca tcacattatt ttcatacttt 720 aatacagcag ctttaattat tggagaacat caaagtaatt aggtgccgaa aaacattgtt 780 attaatgaag ggaacccctg acgtttgacc ttttctgtac catctatagc cctggacttg 840 a 841 <210> 3105 <211> 63 <212> DNA : <213> Homo sapiens <400> 3105 ggccagtgaa ttgtaatacg actcactata gggaggcggt tttttttettt ttttteeeet 60 ttt €3 <210> 3106 <211]> 609 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (303) ..(304) <223> nis a, c, g, t or u <400> 3106 acatcagtgg ctacatgtga gctcagacct gggtctgctg ctgtctgtct tcccaatatc 60 catgaccttg actgatgcag gtgtctaggg atacaggtca cacagccgtc catcccegtce 120 ctgctggage ccagagcacg gaagcctggce cctccgagga gacagaaggg agtgtcggac 180 accatgacga gagcttggca gaataaataa cttctttaaa caattttacg gcatgaagaa 240 atctggacca gtttattaaa tgggatttct gccacaaacc ttggaagaat cacatcatct 300 tanncccaag tgaaaactgt gttgcgtaac aaagaacatg actgcgctcc acacatacat 360 cattgcecgg cgaggcggga cacaagtcaa cgacggaaca cttgagacag gcctacaact 420 gtgcacgggt cagaagcaag tttaagccat acttgctgca gtgagactac atttctgtcet 480 atagaagata cctgacttga tctgtttttc agctccagtt cccagatgtg cgtgttgtgg 540 tccccaagta tcaccttcca atttctggga gcagtgctcet ggeccggatcc ttgccgegcg 600 gataaaaac . 60%

<210> 3107 <211> 50 <212> DNA <213> Homo sapiens <400> 3107 gaaattggaa ggtgatactt ggggaccaca acacgcacat ctgggaactg 50 <210> 3108 <211> 738 <212> DNA <213> Homo sapiens <400> 3108 aaagcagaat tgagagtttg ttcttacaca caagtttaat gccaccttec tctgtectgec 60 atggaccaac aagcaatata tgctgagtta aacttaccca cagactcagg cccagaaagt 120 tcttcacctt catctctteec tcgggatgtc tgtcagggtt caccttggca tcaatttgce 180 ctgaaactta gctgtgctgg gattattete cttgtettgg ttgttactgg gttgagtgtt 240 tcagtgacat ccttaataca gaaatcatca atagaaaaat gcagtgtgga cattcaacag 300 agcaggaata aaacaacaga gagaccgggt ctcttaaact gcccaatata ttggcagcaa 360 ctccgagaga aatgcttgtt attttctcac actgtcaacc cttggaataa cagtctagcet 420 gattgttcca ccaaagaatc cagcctgctg cttattcgag ataaggatga attgatacac 480 acacagaacc tgatacgtga caaagcaatt ctgttttgga ttggattaaa tttttcatta 540 tcagaaaaga actggaagtg gataaacggc tcttttttaa attctaatga cttagaaatt 600 agaggtgatg ctaaagaaaa cagctgtatt tccatctcac agacatctgt gtattctgag 660 tactgtagta cagaaatcag atggatctgc caaaaagaac taacacctgt gagaaataaa 720 gtgtatcctg actcttga 738 <210> 3109 <211> 3809 <212> DNA <213> Homo sapiens <400> 3109 gccgetgtta tgeogtattec cgtagaccca agcaccagceC gecgcttcac acctccctcec 60 ccggecttee cctgecggegg cggcggcggce aagatgggcg agaacagcgg cgcgctgagce 120 gcgecaggcgg ccgtggggec cggagggcgce gcccggeecg aggtgcgetce gatggtggac 180 gtgctggcgg accacgcagg cgagctcgtg cgcaccgaca gccccaactt cctctgctec 240 gtgctgecct cgcactggcg ctgcaacaag acgctgecccg tcgecttcaa ggtggtggca 300 ttgggggacg tgccggatgg tacggtggtg actgtgatgg caggcaatga cgagaactac 360 tccgetgage tgegecaatge ctcggecgte atgaagaacce aggtggccag gttcaacgac 420 cttcgetteg tgggccgeag tgggcgaggg aagagtttca ccctgaccat cactgtgttce 480 accaacccca cccaagtggc gacctaccac cgagccatca aggtgaccgt ggacggaccc 540 cgggagccca gacggcaccg gcagaagctg gaggaccaga ccaagccgtt ccctgaccegc 600 tttggggacc tggaacggct gogcatgcgg gtgacaccga gcacacccag cccccgaggce 660 tcactcagca ccacaagcca cttcagcagc cagccccaga ccccaatcca aggcacctceg 720 gaactgaacc cattctccga ccceccgecag tttgaccgcet ccttcoccccac getgcecaacce 780 ctcacggaga gecgettccc agaccccagg atgcattatc ccggggecat gtcagetgec 840 ttccoctaca gcocgeccacgcee ctcgggcacg agcatcagca gcecctcagegt ggcgggcatg 900 ccggcecacca geocgctteca ccatacctac ctcccgecac cctacccggg ggccccgcag 960 aaccagagcg ggcccttcca ggecaaccceg tccccctacce acctctacta cgggacatce 1020 tctggctect accagttectce catggtggcc ggcagcagca gtgggggcga ccgctcacct 1080 acccgcatge tggcctcttg caccagcage getgcctctg tcgecgecgg caacctcatg 1140 aaccccagec tgggcggeca gagtgatggc gtggaggccg acggcagcca cagcaactca 1200 cccacggccece tgagcacgcc aggccgcatg gatgaggcecg tgtggceggcec ctactgaccg 1260 ccctggtgga ctcctccege tggaggeggg gaccctaaca accttcaaga ccagtgatgg 1320 gccggetecg aggctccggg cgggaatggg acctgcogetc cagggtggtce tcggteccag 1380 ggtggtccca gctggtggga gectctgget gcatctgtge agccacatcce ttgtacagag 1440 gcataggtta ccacccccac cceggeccgg gatactgecc ccggeccaga tcctggecgt 1500 ctcatcccat acttctgtgg ggaatcagcc tcctgccacce cccccggaag gacctcactg 1560 tctccagcta tgcccagtge tgcatgggac ccatgtctcc tgggacagag gccatctctce 1620 ttccagagag aggcagcatt ggcccacagg ataagcctca ggccctggga aacctecccga 1680 cccctgecace ttcgttggag ccectgcate cectgggtcc agccccctct gcatttacac 1740 agatttgagt cagaactgga aagtgtcccc cacccccacc accctcgage ggggttcccce 1800 tcattgtaca gatggggcag gacccagcac gctgctggca gagatggttt gagaacacat 1860 ccaagccagt cccecccagce cagettccce tccgttecta actgttgget ttcccccage 1520 cgcacggtcc caggcccaga gaagatgagt ctatggcatc aggttcttaa accaggaaag 1980 cacctacaga ccggctcctc catgcacttt accagctcaa cgcatccact ctctgttctce 2040 ttggcagggc gggggagggg ggataggagg tcccctttec cctaggtggt ctcataatte 2100 catttgtgga gagaacagga gggccagata gataggtcct agcagaaggc attgaggtga 2160 gggatcattt tgggtcagac atcaatgtcc ctgtcccccece tgggtccagc caagctgtgce 2220 cccatccece aagectcctg ggaggatcca gcocaaatctt gegactcectg gcacacacct 2280 gtctgtaacc tgttttgtgc tctgaaagca aatagtcctg agcaaaaaaa aaaaaaaaaa 2340 acaaaaaaac aaaaaaaaaa caaaacagtt tttaaaactg attttagaaa aagaagctta 2400 atctaacgtt ttcaaacaca aggtctctta caggtatagt tcecgtgatta tgatagctct 2460 gtgattataa gcaacatccc cgeccccctct ccecceccgeg gacccccage tgcectectga 2520 gggtgtgggg ttattagggt ctcaatactt tctcaagggg ctacactccc catcaggcag 2580 catcccacca gecctgcacca caggctcccec tgggaggacg agggaaacgc tgatgagacg 2640 ctgggcatct ctcctctgtg getctaggac atctgtccag gaggctgggc ggaggtgggce 2700 aggatgtgag aggtggggag tactggctgt gcgtggcagg acagaagcac tgtaaagggc 2760 tctcecagege agctcagetg cactgcgttc cgaggtgaag tcttgeecect gaattttgca 2820 aaatgggaaa gtgggcgctt gccaagggcce aggctgcatg gattctcaca tcagagttct 2880 ctggccctag aaaggcttag aaaaggcgta agggaactca taaaggctag cagcatgcgg 2940 tattttaact ttctgccteg gecctectgtgg atgcagaaat ctgecctaca aaatgctctt 3000 cattggttgt ctctgtgaga gcactgtcec cacccaacct gtcacaacgg ccagaaccat 3060 acaccagaga cacactggca ggttaggcag tccttetggt gatecctatte cattecetcec 3120 tgctgeggtt tctcttggec tgtcctcact ggaaaaacag tctccatcte ctcaaaatag 3180 ttgctgactc cctgcaccca aggggcctct ccatgccttc ttaggaagca gctatgaatce 3240 cattgtcctt gtagtttctt ccctcctgtt ctctggttat agetggtcecee aggtcagcegt 3300 gggaggcacc tttgggttcc cagtgcccag cactttgtag tctcatccca gattactaac 3360 ccttcctgat cctggagagg cagggatagt aaataaattg ctcttectac ceccatccece 3420 atcccctgac aaaaagtgac ggcagccgta ctgagtctgt aaggcccaaa gtgggtacag 3480 acagcctggg ctggtaaaag taggtcctta tttacaaggc tgcgttaaag ttgtactagg 3540 caaacacact gatgtaggaa gcacgaggaa aggaagacgt tttgatatag tgttactgtg 3600 agcctgtcag tagtgggtac caatcttttg tgacatattg tcatgctgag gtgtgacacc 3660 tgctgcactc atctgatgta aaaccatccc agagctggeg agaggatgga gctgggtgga 3720 aactgctttg cactatcgtt tgcttggtgt ttgtttttaa cgcacaactt gcttgtacag 3780 taaactgtct tctgtactat ttaactgta 3809 <210> 3110

<211l> 1161

<212> DNA

<213> Homo sapiens . Co. . : }

<400> 3110 caaagagcta catgccacat gctgttctcc agecctgctgt gtgtatttgt ggecttcage 60 tactctggat caagtgtggc ccagaaggtt actcaagccc agtcatcagt atccatgcca 120 gtgaggaaag cagtcaccct gaactgcctg tatgaaacaa gttggtggtce atattatatt 180 ttttggtaca agcaacttcc cagcaaagag atgattttcc ttattcgcca gggttctgat 240 gaacagaatg caaaaagtgg tcgctattct gtcaacttca agaaagcagc gaaatccgtce 300 gccttaacca tttcagectt acagctagaa gattcagcaa agtacttttg tgctcttggg 360 acgggggtga ggggactcca ggacaccgat aaactcatct ttggaaaagg aacccgtgtg 420 actgtggaac caagaagtca gcctcatacc aaaccatcecg tttttgtcat gaaaaatgga 480 acaaatgtcg cttgtctggt gaaggaattc taccccaagg atataagaat aaatctegtg 540 tcatccaaga agataacaga gtttgatcct getattgtca tctctcccag tgggaagtac 600 aatgctgtca agcttggtaa atatgaagat tcaaattcag tgacatgttc agttcaacac 660 gacaataaaa ctgtgcactc cactgacttt gaagtgaaga cagattctac agatcacgta 720 aaaccaaagg aaactgaaaa cacaaagcaa ccttcaaaga gctgccataa acccaaagcec 780 atagttcata ccgagaaggt gaacatgatg tccctcacag tgettgggct acgaatgctg 840 tttgcaaaga ctgttgccgt caattttctc ttgactgcca agttattttt cttgtaaggce 900 tgactggcat gaggaagcta cactcctgaa gaaaccaaag gcttacaaaa atgcatctec 860 ttggcttctg acttctttgt gattcaagtt gacctgtcat agccttgtta aaatggctge 1020 tagccaaacc actttttctt caaagacaac aaacccagcet catcctccag cttgatggga 1080 agacaaaagt cctggggaag gggggtttat gtcctaactg ctttgtatgc tgttttataa 1140 agggatagaa ggatataaaa a 1161 <210> 3111 <21l> 611 <212> DNA <213> Homo sapiens «220> <221> misc_feature <222> (543) ..(543) <223> n is a, ¢, g, tor u <400> 3111 ttttttatgg gttteccttaa atgtttttat ggttaaaatc tgtacaaaca gatatattta 60 tataagttac atattttaag aaaaatcagt catttttcat atataattgc aaagaattaa 120 gatcatttaa ctttagcact ataagcaagc attaaattaa atgcactcag atttttggca 180 cattatatgg cattccttat accacatatt tataagatct aaaggattat aaacatatta 240 cacataataa ttaagtccaa tataaattgt gttcaggtta taaaatgccc tatttaagtt 300 gtgctcttgg tgagggtgaa cagaaaagaa aaggcttctt ctttagcect taagcectatg 360 acacaatttc catgctggta attcctttca tcttctgaag aatctctatt ttattataac 420 attattggct ttcagcttgg aatttctcta cgcagattgt ctattgacag tgccaaggaa 480 acatctcact gtccacagaa tagcagcctc cacccagttg aaagctgcac attgtttceca 540 ctntaccatt ggtacttccc tctgatggca tccagcacac gaccattagc ctgagtgatg 600 cccaactgag c 611 <210> 3112 <211> 572 <212> DNA <213> Homo sapiens <400> 3112 ttttggggac ttecttagctt gctcetctect gagtcccact ggccacccca gcacacagca 60 gaggcctage aagtctcaag tgaggcaatc ctggactagg gcaaacatgg cttgttccaa 120 aagccggggg ttaaggaatc aaagtcaggt gaaactatca ctttcacaaa agettttcett 180 gactcctggg cctagtatct tttgeccetg gcagaatgta acagcaaaat gtctcocttcet 240 gaaacggaag gcacagccct ctttcagaag caaaacacct taacactcgg cttctatttg 300 cttaagaatt tacaaataga aatgagaatc aaaggtttta actcatctga tagcactggg 360 cacccaatgt tcacagcctg cttctttgaa ttgttagtgt ctccccaata aataaataca 420 gaaccttgga tacccttcga attttaaaat accttaaagt cttccattaa tcttattttt 480 taaaaatgct aggtttgttt cagttacctg cagcaatcaa aaagctttgg caccttcttt 540 Agigaatiy TRUABIATHG gatgcatcaa gg 572

<210> 3113 <211> 1026 <212> DNA <213> Homo sapiens <400> 3113 cagcatgttg agccgggcag tgtgecggcac cagcaggcag ctgectecgg ttttggggta 60 tctgggctcc aggcagaage acagectcce cgacctgccc tacgactacg gegecctgga 120 acctcacatc aacgcgcaga tcatgcagct gcaccacagc aagcaccacg cggcctacgt 180 gaacaacctg aacgtcaccg aggagaagta ccaggaggcg ttggccaagg gagatgttac 240 agcccagata gctcttcage ctgcactgaa gttcaatggt ggtggtcata tcaatcatag 300 cattttctgg acaaacctca gccctaacgg tggtggagaa cccaaagggg agttgctgga 360 agccatcaaa ctggactttg gttcctttga caagtttaag gagaagctga cggctgcatce 420 tgttggtgtc caaggctcag gttggggttg gcttggtttc aataaggaac ggggacactt 480 acaaattgct gcttgtccaa atcaggatcc actgcaagga acaacaggcc ttattccact 540 gctggggatt gatgtgtggg agcacgcetta ctaccttcag tataaaaatg tcaggcctga 600 ttatctaaaa gctatttgga atgtaatcaa ctgggagaat gtaactgaaa gatacatggc 660 ttgcaaaaag taaaccacga tcgttatgct gagtatgtta agctctttat gactgttttt 720 gtagtggtat agagtactgc agaatacagt aagctgctct attgtagcat ttcttgatgt 780 tgcttagtca cttatttcat aaacaactta atgttctgaa taatttctta ctaaacattt 840 tgttattggg caagtgattg aaaatagtaa atgctttgtg tgattgaatc tgattggaca 900 ttttcttcag agagctaaat tacaattgtc atttataaaa ccatcaaaaa tattccatcc 960 atatactttg gggacttgta gggatgcctt tctagtccta ttctattgca gttatagaaa 1020 atctag 1026 <210> 3114 <21l1> 1271 <212> DNA <213> Homo sapiens <400> 3114 ctgtattgtg gttcectggaa cactttagag gcttgtgatt ctactgcecttc ttattcacac 60 tataatacat gtctcaccaa tagatgattc aagaacatca tttaaataca caatttttca 120 ttctctattt ttgctaaatt tcttcatact caactttcag attctttaat ctccagctca 180 gcttcaacaa ttcaacgctg ttctttctga aaaagtacac atcgtgectt ctctacttcg 240 ctcttggaac ataatttctc atggcagett ttactaaact gagtattgag ccagcattta 300 ctccaggacc caacatagaa ctccagaaag actctgactg ctgttcttge caagaaaaat 360 gggttgggta ccggtgcaac tgttacttca tttccagtga acagaaaact tggaacgaaa 420 gtcggcatcet ctgtgecttct cagaaatcca gectgcttca gcecttcaaaac acagatgaac 480 tggattttat gagctccagt caacaatttt actggattgg actctcttac agtgaggagc 540 acaccgcctg gttgtgggag aatggctctg cactctccca gtatctattt ccatcatttg 600 aaacttttaa tacaaagaac tgcatagcgt ataatccaaa tggaaatgct ttagatgaat 660 cctgtgaaga taaaaatcgt tatatctgta agcaacagct catttaaatg tttcttgggg 720 cagagaaggt ggagagtaaa gacccaacat tactaacaat gatacagttg catgttatat 780 tattactaat tgtctacttc tggagtctat aaaatgtttt taaacagtgt catatacaat 840 tgtcatgtat gtgaaacaat gtgttttaaa attgatgaaa ttcgttcacc tacatttgag 900 -

A aattataaaa ttaacataaa gaattttgta ttttcattta atgtatataa tgttaaattc 960 aatgtagttt tattacacat ttatgtaatt ttatttacat tcttgctaat tctcagcaga 1020 aatttaaata agatttaatt cacatcaaat aaaatttaga aaataaaatt taactcacac 1080 tgcccaggcet ggagcatagt ggcaagatca tagctcattg caagctcaag tgatcctcct 1140 gactcagecct cccaagtagc taggactgca ggcaccatgt cactatgccc gactaatttt 1200 taatttttaa ttttttgtca agacaaggtc ttgctatgtt gcccaggctg gtcttgaact 1260 cctggcctca a 1271 <210> 3115 <211l> 358 <212> DNA <213> Homo sapiens <400> 3115 gggtttatce caggatattc attgatagaa aattaaagga gtaatttata aaatcactac 60 atgaacaagt aaaaacacac acagcaaaat ttacatcaaa attattacgt ggtacagaat 120 ccaaaagtca taaaaagcaa aagctatctt tttttcactc tggcacccat ctgttcttcce 180 ’ ctggagtcaa acactattac caatttttag gtatacttcc aaagatactt actgcattta 240 caagcacaga cttatattga ttctaaaaga ataagagaca ttttcagcat gttgctttgt 300 tcaacaccac agtatatctt aaagatggtc ccccatcaat acatatagag atctetct 358 <210> 3116 : <211> 4045 <212> DNA <213> Homo sapiens <400> 3116 gcagccagag ctcagcaggg ccctggagag atggccacgg tcccagcace ggggaggact 60 ggagagcgcg cgctgccace gecccatgtce tcagccaggg cttccttect cggetccacce 120 ctgtggatgt aatggcggcce cctgetctgt cctggegtct geccctectce atcctcctee 180 tgccecetgge tacctcttgg gecatctgcag cggtgaatgg cacttcccag ttcacatgct 240 tctacaactc gagagccaac atctcctgtg tctggageca agatggggct ctgcaggaca 300 cttcectgeca agtccatgec tggceccggaca gacggcggtg gaaccaaacc tgtgagctgce 360 tcccegtgag tcaagcatcc tgggcctgca acctgatcct cggagecccea gattctcaga 420 aactgaccac agttgacatc gtcaccctga gggtgctgtg ccgtgagagd gtgcgatgga 480 gggtgatggc catccaggac ttcaagccct ttgagaacct tcgectgatg gcccccatct 540 ccctccaagt tgtccacgtg gagacccaca gatgcaacat aagctgggaa atctcccaag 600

La cctcccacta ctttgaaaga cacctggagt tcgaggcececg gacgctgtec ccaggccaca 660 cctgggagga ggcccccctg ctgactctca agcagaagca ggaatggate tgcctggaga 720 cgctcaccce agacacccag tatgagtttc aggtgegggt caagcctctg caaggcgagt 780 tcacgacctg gagcccctgg agccagccec tggccttcag gacaaagect gcagcccttg 840 ggaaggacac cattccgtgg ctcggccacc tectegtggg cctcageggg gettttgget 900 tcatcatctt agtgtacttg ctgatcaact gcaggaacac cgggccatgg ctgaagaagg 960 tcctgaagtg taacacccca gacccctcga agttctttte ccagctgage tcagagcatg 1020 gaggagacgt ccagaagtgg ctctcttcege ccttcceccte atcgtectte ageecctggeg 1080 gcctggcace tgagatctcg ccactagaag tgctggagag ggacaaggtg acgcagctge 1140 tcctgecageca ggacaaggtg cctgageccg catccttaag cagcaaccac tcgetgacca 1200 gctgettcac caaccagggt tacttcottct tccacctece ggatgeccttg gagatagagg 1260 cctgeccaggt gtactttact tacgacccct actcagagga agaccctgat gagggtgtgg 1320 ccggggcace cacagggtct tccccccaac cecctgcagcee tctgtcaggg gaggacgacyg 1380 cctactgcac cttecccctce agggatgacc tgectgetcett cteccccagt ctccteggtg 1440 gcceccagece cccaagcact geccoctgggg gcagtgggge cggtgaagag aggatgccec 1500 cttctttgca agaaagagtc cccagagact gggaccccca gecccctgggg ccteccacce 1560 caggagtccc agacctggtg gattttcagc caccccoectga getggtgetg cgagaggcetg 1620 gggaggaggt ccctgacgct ggccccaggg agggagtcag tttcocccectgg tccaggecte 1680 ctgggcaggg ggagttcagg gcccttaatg ctcgeoctgcecce cctgaacact gatgcectact 1740 tgtcccteca-agaactccag ggtcaggacce caactcactt ggtgtagaca gatggccagg 1800 gtgggaggca ggcagctgec tgctcectgege cgagcctcag aaggaccctg ttgagggtec 1860 tcagtccact gctgaggaca ctcagtgtce agttgcagcet ggacttctce acccggatag 1920 cccccaccca gtcctgcaca cttggtecat ccatttccaa acctecactg ctgetcoccgg 1980 gtcctgectge ccgagccagg aactgtgtgt gttgcagggg ggcagtaact ccccaactec 2040 ctcgttaatc acaggatccc acgaatttag gctcagaagc atcgctcecectce tccagecectg 2100 cagctattca ccaatatcag tcctcgeggc tctccagggce teccctgecct gacctettec 2160 ctgggttttc tgcceccagee tectcecttec ctececctece cgtccacagg gcagcctgag 2220 cgtgetttcc aaaacccaaa tatggccacg ctccccctecg gttcaaaacc ttgcacaggt 2280 cccactgcce tcagccccac ttctcagect ggtacttgta cctceggtgt cgtgtgggga 2340 catcecccttec tgcaatcctc cctaccgtcec tcctgageca ctcagagctc cctcacacce 2400 cctctgttge acatgctatt ccctggggct gctgtgeget ccccetcate taggtgacaa 2460

\ \

acttcecctga ctcttcaagt geccggttttg cttectectgg agggaagcac tgcctcectt 2520 aatctgeccag aaacttctag cgtcagtget ggagggagaa gctgtcaggg acccagggeg 2580 cctggagaaa gaggccctgt tactattcet ttgggatctce tgaggcctca gagtgettgg 2640 ctgctgtatc tttaatgetg gggecccaagt aagggcacag atccccccac aaagtggatg 2700 cctgetgeat cttcccacag tggcttcaca gacccacaag agaagctgat ggggagtaaa 2760 ccctggagtc cgaggcccag gcagcagccce cgcectagtgg tgggccctga tgctgccagg 2820 cctgggacct cccactgccec cctccactgg aggggtctec tcetgcagectc agggactgge 2880 acactggcct ccagaagdgc agctccacag ggcagggcct cattattttt cactgceccca 2940 gacacagtgc ccaacacccc gtcgtatacc ctggatgaac gaattaatta cctggcacca 3000 cctegtetgg getecectgeg cctgacatte acacagagag gcagagtcecc gtgceccatta 3060 ggtctggecat geccectecct gcaaggggcet caacccccta cccegacccce tccacgtatce 3120 ttteectagge agatcacgtt gcaatggctce aaacaacatt ccaccccagce aggacagtga 3180 ccccagtece agctaactct gacctgggag ccctcaggca cctgcactta caggcecttge 3240 tcacagctga ttgggcacct gaccacacgc ccccacagge tctgaccagce agcectatgag 3300 ggggtttggce accaagctet gtccaatcag gtaggctggg cctgaactag ccaatcagat 3360 caactctgtc ttgggcgttt gaactcaggg agggadggccce ttgggagcag gtgcttgtgg 3420 acaaggctcc acaagcgttg ageccttggaa aggtagacaa gcgttgagcc actaagcaga 3480 ggaccttggg ttcccaatac aaaaatacct actgctgaga gggctgctga ccatttggtce 3540 aggattcctg ttgcctttat atccaaaata aactccectt tettgaggtt gtctgagtcet 3600 tgggtctatg ccttgaaaaa agctgaatta ttggacagtc tcacctcctg ccatagggtc 3660 ctgaatgttt cagaccacaa ggggctccac acctttgetg tgtgttetgg ggcaacctac 3720 taatcctctce tgcaagtcgg tctcocttatec cccccaaatg gaaattgtat ttgecttetce 3780

' cactttggga ggctcccact tettgggagg gttacatttt ttaagtctta atcatttgtg 3840 acatatgtat ctatacatcc gtatctttta atgatccgtg tgtaccatct ttgtgattat 3500 ttcecttaata ttttttettt aagtcagttc attttegttg aaatacattt atttaaagaa 35860 aaatctttgt tactctgtaa atgaaaaaac ccattttcgc tataaataaa aggtaactgt 4020 acaaaataag tacaatgcaa caaaa -— 4045 <210> 3117 <21l1> 573 <212> DNA <213> Homo sapiens

1484 J

<220> <221> misc_feature <222> (521) .. (521) <223> nis a, ¢, g, t or u <400> 3117 gattgtataa ataatttatt tctgttcaca gcatcatata tgcattataa aaggctatgg 60 aaacaaaaga gaaggatgat gagacagaga attacagcag tagaaaggaa aacagaaacc 120 agggcacaca gttccaacac cagaacagag aatttgggaa gataattgct ctgaaacaga 180 actggcctce ctgtgtctat tagaaaacat ttccaaagct cacggaggga ggccaacttce 240 ccctatggga aacecattca ctcgccaaag ggcagaaggc atcataaatc acccattgat 300

. acattggtgg ggggctcctg tcccectggt gaccactcca aggtgatttg atctgtgett 360 cctctgttgg gtcagagacg aaacgggcta ttattaggtc aaacattaca gaaatcaact 420 gagactctta actagtagtt gatacaccac agggctttac tttactgcac aattactaac 480 agttgattgc acccttaagt attgattatg caaaaaacaa natcatctcg catcagtttt 540 aaagcatgac agggtttgaa cagtgatctt gaa 573 :