AU2007240202A1 - Novel compositions and methods for cancer - Google Patents

Novel compositions and methods for cancer Download PDF

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AU2007240202A1
AU2007240202A1 AU2007240202A AU2007240202A AU2007240202A1 AU 2007240202 A1 AU2007240202 A1 AU 2007240202A1 AU 2007240202 A AU2007240202 A AU 2007240202A AU 2007240202 A AU2007240202 A AU 2007240202A AU 2007240202 A1 AU2007240202 A1 AU 2007240202A1
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David W Morris
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Sagres Discovery Inc
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Description

AUSTRALIA
F B RICE CO Patent and Trade Mark Attorneys Patents Act 1990 SAGRES DISCOVERY INC.
COMPLETE SPECIFICATION STANDARD PATENT Invention Title: Novel compositions and methods for cancer The following statement is a full description of this invention including the best method of performing it known to us:- NOVEL COMPOSITIONS AND METHODS FOR CANCER
O
Q This is a divisional of AU 2002367390, the entire contents of which are 0 incorporated herein by reference.
CI SEQUENCE LISTING CI The Sequence Listing submitted on compact disc is hereby incorporated by reference. The two, identical compact discs contain the file named A-71249. ST25. txt, created on May 29,2002, and containing 16,870. 127 bytes.
FIELD OF THE INVENTION The present invention relates to novel sequences for use in diagnosis and treatment of cancer, especially carcinomas, as well as the use of the novel compositions in screening methods.
BACKGROUND OF THE INVENTION Oncogenes are genes that can cause cancer. Carcinogenesis can occur by a wide variety of mechanisms, including infection of cells by viruses containing oncogenes.
activation of protooncogenes in the host genome, and mutations of protooncogenes and tumor suppressor genes.
There are a number of viruses known to be involved in human cancer as well as in animal cancer. Of particular interest here are viruses that do not contain oncogenes themselves; these are slow-transforming retroviruses. They induce tumors by integrating into the host genome and affecting neighbouring protooncogenes in a variety of ways, including promoter insertion, enhancer insertion, and/or truncation of a protooncogene or tumor suppressor gene. The analysis of sequences at or near the insertion sites led to the identification of a number of new protooncogenes.
S[0006] With respect to lymphoma and leukemia, murine leukemia retrovirus (MuLV), such as SL3-3 or Akv, is a potent inducer of tumors when inoculated into susceptible newborn mice, or when carried in the germline. A number of sequences have been identified as relevant in the induction of lymphoma and leukemia by analyzing the insertion sites; see Sorensen et al., J. of Virology 74:2161 (2000); Hansen et al., Genome Res. 10(2):237-43 (2000); Sorensen et al., J. Virology 70:4063 (1996); Sorensen et al., J. Virology 67:7118 (1993); Joosten et al., Virology 268:308 (2000); S and Li et al., Nature Genetics 23:348 (1999); all of which are expressly incorporated by reference herein.
C, [0007] Lymphomas are a collection of cancers involving the lymphatic system and are generally categorized as Hodgkin's disease and Non-Hodgkin lymphoma.
Hodgkin's lymphomas are of B lymphocyte origin. Non-Hodgkin lymphomas are a collection of over 30 different types of cancers including T and B lymphomas.
Leukemia is a disease of the blood forming tissues and includes B and T cell lymphocytic leukemias. It is characterized by an abnormal and persistent increase in the number of leukocytes and the amount of bone marrow, with enlargement of the spleen and lymph nodes.
[0008] Breast cancer is one of the most significant diseases that affects women. At the current rate, American women have a 1 in 8 risk of developing breast cancer by age 95 (American Cancer Society, 1992). Treatment of breast cancer at later stages is often futile and disfiguring, making early detection a high priority in medical management of the disease.
[0009] Accordingly, it is an object of the invention to provide sequences involved in cancer and in particular in oncogenesis.
SUMMARY OF THE INVENTION [0010] In accordance with the objects outlined above, the present invention provides methods for screening for compositions which modulate carcinomas, especially lymphoma and leukemia. Also provided herein are methods of inhibiting proliferation of a cell, preferably a lymphoma cell. Methods of treatment of carcinomas, including diagnosis, are also provided herein.
[0011] In one aspect, a method of screening drug candidates comprises providing a S cell that expresses a carcinoma associated (CA) gene or fragments thereof. Preferred C embodiments of CA genes are genes which are differentially expressed in cancer U cells, preferably lymphatic, breast, prostate or epithelial cells, compared to other cells.
Preferred embodiments of CA genes used in the methods herein include, but are not limited to the nucleic acids selected from Tables 1-112. The method further includes adding a drug candidate to the cell and determining the effect of the drug candidate on C the expression of the CA gene.
[0012] In one embodiment, the method of screening drug candidates includes comparing the level of expression in the absence of the drug candidate to the level of S expression in the presence of the drug candidate.
[0013] Also provided herein is a method of screening for a bioactive agent capable of binding to a CA protein (CAP), the method comprising combining the CAP and a candidate bioactive agent, and determining the binding of the candidate agent to the
CAP.
[0014] Further provided herein is a method for screening for a bioactive agent capable of modulating the activity of a CAP. In one embodiment, the method comprises combining the CAP and a candidate bioactive agent, and determining the effect of the candidate agent on the bioactivity of the CAP.
[0015] Also provided is a method of evaluating the effect of a candidate carcinoma drug comprising administering the drug to a patient and removing a cell sample from the patient. The expression profile of the cell is then determined. This method may further comprise comparing the expression profile of the patient to an expression profile of a heathy individual.
[0016] In a further aspect, a method for inhibiting the activity of an CA protein is provided. In one embodiment, the method comprises administering to a patient an inhibitor of a CA protein preferably selected from the group consisting of the sequences outlined in Tables 1-112 or their complements.
[0017] A method of neutralizing the effect of a CA protein, preferably a protein encoded by a nucleic acid selected from the group of sequences outlined in Tables 1- 112, is also provided. Preferably, the method comprises contacting an agent specific for said protein with said protein in an amount sufficient to effect neutralization.
[0018] Moreover, provided herein is a biochip comprising a nucleic acid segment which encodes a CA protein, preferably selected from the sequences outlined in S Tables 1-112.
[0019] Also provided herein is a method for diagnosing or determining the propensity to carcinomas, especially lymphoma or leukemia by sequencing at least one carcinoma or lymphoma gene of an individual. In yet another aspect of the invention, a method is provided for determining carcinoma including lymphoma and O leukemia gene copy number in an individual.
0 [0020] Novel sequences are also provided herein. Other aspects of the invention will C become apparent to the skilled artisan by the following description of the invention.
O DETAILED DESCRIPTION OF THE INVENTION [0021] The present invention is directed to a number of sequences associated with carcinomas, especially lymphoma, breast cancer or prostate cancer. The relatively tight linkage between clonally-integrated proviruses and protooncogenes forms "provirus tagging", in which slow-transforming retroviruses that act by an insertion mutation mechanism are used to isolate protooncogenes. In some models, uninfected animals have low cancer rates, and infected animals have high cancer rates. It is known that many of the retroviruses involved do not carry transduced host protooncogenes or pathogenic trans-acting viral genes, and thus the cancer incidence must therefor be a direct consequence of proviral integration effects into host protooncogenes. Since proviral integration is random, rare integrants will "activate" host protooncogenes that provide a selective growth advantage, and these rare events result in new proviruses at clonal stoichiometries in tumors.
[0022] The use of oncogenic retroviruses, whose sequences insert into the genome of the host organism resulting in carcinoma, allows the identification of host sequences involved in carcinoma. These sequences may then be used in a number of different ways, including diagnosis, prognosis, screening for modulators (including both agonists and antagonists), antibody generation (for immunotherapy and imaging), etc.
However, as will be appreciated by those in the art, oncogenes that are identified in .one type of cancer such as lymphoma or leukemia have a strong likelihood of being involved in other types of cancers as well. Thus, while the sequences outlined herein are initially identified as correlated with lymphoma, they can also be found in other types of cancers as well, outlined below.
[0023] Accordingly, the present invention provides nucleic acid and protein 0 sequences that are associated with carcinoma, herein termed "carcinoma associated" or "CA" sequences. In a preferred embodiment, the present invention provides S nucleic acid and protein sequences that are associated with carcinomas which originate in lymphatic tissue, herein termed "lymphoma associated", "leukemia associated" or "LA" sequences.
10024] Suitable cancers which can be diagnosed or screened for using the methods of the present invention include cancers classified by site or by histological type.
C Cancers classified by site include cancer of the oral cavity and pharynx (lip, tongue, salivary gland, floor of mouth, gum and other mouth, nasopharynx, tonsil, C1l oropharynx, hypopharynx, other oral/pharynx); cancers of the digestive system (esophagus; stomach; small intestine; colon and rectum; anus, anal canal, and anorectum; liver; intrahepatic bile duct; gallbladder; other biliary; pancreas; retroperitoneum; peritoneum, omentum, and mesentery; other digestive); cancers of the respiratory system (nasal cavity, middle ear, and sinuses; larynx; lung and bronchus; pleura; trachea, mediastinum, and other respiratory); cancers of the mesothelioma; bones and joints; and soft tissue, including heart; skin cancers, including melanomas and other non-epithelial skin cancers; Kaposi's sarcoma and breast cancer; cancer of the female genital system (cervix uteri; corpus uteri; uterus, nos; ovary; vagina; vulva; and other female genital); cancers of the male genital system (prostate gland; testis; penis; and other male genital); cancers of the urinary system (urinary bladder; kidney and renal pelvis; ureter; and other urinary); cancers of the eye and orbit; cancers of the brain and nervous system (brain; and other nervous system); cancers of the endocrine system (thyroid gland and other endocrine, including thymus); cancers of the lymphomas (hodgkin's disease and non-hodgkin's lymphoma), multiple myeloma, and leukemias (lymphocytic leukemia; myeloid leukemia; monocytic leukemia; and other leukemias).
[0025] Other cancers, classified by histological type, that may be associated with the sequences of the invention include, but are not limited to, Neoplasm, malignant; Carcinoma, NOS; Carcinoma, undifferentiated, NOS; Giant and spindle cell carcinoma; Small cell carcinoma, NOS; Papillary carcinoma, NOS; Squamous cell carcinoma, NOS; Lymphoepithelial carcinoma; Basal cell carcinoma, NOS; S Pilomatrix carcinoma; Transitional cell carcinoma, NOS; Papillary transitional cell O carcinoma; Adenocarcinoma, NOS; Gastrinoma, malignant; Cholangiocarcinoma; S Hepatocellular carcinoma, NOS; Combined hepatocellular carcinoma and cholangiocarcinoma; Trabecular adenocarcinoma; Adenoid cystic carcinoma; Adenocarcinoma in adenomatous polyp; Adenocarcinoma, familial polyposis coli; Solid carcinoma, NOS; Carcinoid tumor, malignant; Branchiolo-alveolar adenocarcinoma; Papillary adenocarcinoma, NOS; Chromophobe carcinoma; S Acidophil carcinoma; Oxyphilic adenocarcinoma; Basophil carcinoma; Clear cell S adenocarcinoma, NOS; Granular cell carcinoma; Follicular adenocarcinoma, NOS; S Papillary and follicular adenocarcinoma; Nonencapsulating sclerosing carcinoma; S Adrenal cortical carcinoma; Endometroid carcinoma; Skin appendage carcinoma; (7 Apocrine adenocarcinoma; Sebaceous adenocarcinoma; Ceruminous adenocarcinoma; Mucoepidermoid carcinoma; Cystadenocarcinoma, NOS; Papillary cystadenocarcinoma, NOS; Papillary serous cystadenocarcinoma; Mucinous cystadenocarcinoma, NOS; Mucinous adenocarcinoma; Signet ring cell carcinoma; Infiltrating duct carcinoma; Medullary carcinoma, NOS; Lobular carcinoma; Inflammatory carcinoma; Paget"s disease, mammary; Acinar cell carcinoma; Adenosquamous carcinoma; Adenocarcinoma w/ squamous metaplasia; Thymoma, malignant; Ovarian stromal tumor, malignant; Thecoma, malignant; Granulosa cell tumor, malignant; Androblastoma, malignant; Sertoli cell carcinoma; Leydig cell tumor, malignant; Lipid cell tumor, malignant; Paraganglioma, malignant; Extramammary paraganglioma, malignant; Pheochromocytoma; Glomangiosarcoma; Malignant melanoma, NOS; Amelanotic melanoma; Superficial spreading melanoma; Malig melanoma in giant pigmented nevus; Epithelioid cell melanoma; Blue nevus, malignant; Sarcoma, NOS; Fibrosarcoma, NOS; Fibrous histiocytoma, malignant; Myxosarcoma; Liposarcoma, NOS; Leiomyosarcoma, NOS; Rhabdomyosarcoma, NOS; Embryonal rhabdomyosarcoma; Alveolar rhabdomyosarcoma; Stromal sarcoma, NOS; Mixed tumor, malignant, NOS; Mullerian mixed tumor; Nephroblastoma; Hepatoblastoma; Carcinosarcoma, NOS; Mesenchymoma, malignant; Brenner tumor, malignant; Phyllodes tumor, malignant; Synovial sarcoma, NOS; Mesothelioma, malignant; Dysgerminoma; Embryonal carcinoma, NOS; Teratoma, malignant, NOS; Struma ovarii, malignant; Choriocarcinoma; Mesonephroma, malignant; Hemangiosarcoma; Hemangioendothelioma, malignant; Kaposi's sarcoma; Hemangiopericytoma, malignant; Lymphangiosarcoma; Osteosarcoma, NOS; Juxtacortical osteosarcoma; Chondrosarcoma, NOS; S Chondroblastoma, malignant; Mesenchymal chondrosarcoma; Giant cell tumor of C bone; Ewing's sarcoma; Odontogenic tumor, malignant; Ameloblastic odontosarcoma; Ameloblastoma, malignant; Ameloblastic fibrosarcoma; Pinealoma, malignant; Chordoma; Glioma, malignant; Ependymoma, NOS; Astrocytoma, NOS; Protoplasmic astrocytoma; Fibrillary astrocytoma; Astroblastoma; Glioblastoma, NOS; Oligodendroglioma, NOS; Oligodendroblastoma; Primitive neuroectodermal; CI Cerebellar sarcoma, NOS; Ganglioneuroblastoma; Neuroblastoma, NOS; C1 Retinoblastoma, NOS; Olfactory neurogenic tumor; Meningioma, malignant; Neurofibrosarcoma; Neurilemmoma, malignant; Granular cell tumor, malignant; Malignant lymphoma, NOS; Hodgkin's disease, NOS; Hodgkin's; paragranuloma, NOS; Malignant lymphoma, small lymphocytic; Malignant lymphoma, large cell, diffuse; Malignant lymphoma, follicular, NOS; Mycosis fungoides; Other specified non-Hodgkin's lymphomas; Malignant histiocytosis; Multiple myeloma; Mast cell sarcoma; Immunoproliferative small intestinal disease; Leukemia, NOS; Lymphoid leukemia, NOS; Plasma cell leukemia; Erythroleukemia; Lymphosarcoma cell leukemia; Myeloid leukemia, NOS; Basophilic leukemia; Eosinophilic leukemia; Monocytic leukemia, NOS; Mast cell leukemia; Megakaryoblastic leukemia; Myeloid sarcoma; and Hairy cell leukemia.
[0026] In addition, the genes may be involved in other diseases, such as but not limited to diseases associated with aging or neurodegenerative diseases.
[0027] Association in this context means that the nucleotide or protein sequences are either differentially expressed, activated, inactivated or altered in carcinomas as compared to normal tissue. As outlined below, CA sequences include those that are up-regulated expressed at a higher level), as well as those that are down-regulated expressed at a lower level), in carcinomas. CA sequences also include sequences which have been altered truncated sequences or sequences with substitutions, deletions or insertions, including point mutations) and show either the same expression profile or an altered profile. In a preferred embodiment, the CA sequences are from humans; however, as will be appreciated by those in the art, CA sequences from other organisms may be useful in animal models of disease and drug evaluation; thus, other CA sequences are provided, from vertebrates, including mammals, including rodents (rats, mice, hamsters, guinea pigs, etc.), primates, farm animals (including sheep, goats, pigs, cows, horses, etc). In some cases, prokaryotic CA sequences may be useful. CA sequences from other organisms may be obtained using the techniques outlined below.
[0028] CA sequences can include both nucleic acid and amino acid sequences. In a preferred embodiment, the CA sequences are recombinant nucleic acids. By the term "recombinant nucleic acid" herein is meant nucleic acid, originally formed in vitro, in general, by the manipulation of nucleic acid by polymerases and endonucleases, in a form not normally found in nature. Thus an isolated nucleic acid, in a linear form, or an expression vector formed in vitro by ligating DNA molecules that are not normally joined, are both considered recombinant for the purposes of this invention. It is understood that once a recombinant nucleic acid is made and reintroduced into a host cell or organism, it will replicate non-recombinantly, i.e. using the in vivo cellular 1 machinery of the host cell rather than in vitro manipulations; however, such nucleic acids, once produced recombinantly, although subsequently replicated nonrecombinantly, are still considered recombinant for the purposes of the invention.
[0029] Similarly, a "recombinant protein" is a protein made using recombinant techniques, i.e. through the expression of a recombinant nucleic acid as depicted above. A recombinant protein is distinguished from naturally occurring protein by at least one or more characteristics. For example, the protein may be isolated or purified away from some or all of the proteins and compounds with which it is normally associated in its wild type host, and thus may be substantially pure. For example, an isolated protein is unaccompanied by at least some of the material with which it is normally associated in its natural state, preferably constituting at least about more preferably at least about 5% by weight of the total protein in a given sample. A substantially pure protein comprises at least about 75% by weight of the total protein, with at least about 80% being preferred, and at least about 90% being particularly preferred. The definition includes the production of an CA protein from one organism in a different organism or host cell. Alternatively, the protein may be made at a significantly higher concentration than is normally seen, through the use of an inducible promoter or high expression promoter, such that the protein is made at increased concentration levels. Altemrnatively, the protein may be in a form not normally found in nature, as in the addition of an epitope tag or amino acid substitutions, insertions and deletions, as discussed below.
[0030] In a preferred embodiment, the CA sequences are nucleic acids. As will be appreciated by those in the art and is more fully outlined below, CA sequences are useful in a variety of applications, including diagnostic applications, which will detect 0 naturally occurring nucleic acids, as well as screening applications; for example, CN biochips comprising nucleic acid probes to the CA sequences can be generated. In the broadest sense, then, by "nucleic acid" or "oligonucleotide" or grammatical equivalents herein means at least two nucleotides covalently linked together. A nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, as outlined below (for example in antisense applications or CN when a candidate agent is a nucleic acid), nucleic acid analogs may be used that have CN alternate backbones, comprising, for example, phosphoramidate (Beaucage et al., Tetrahedron 49(10):1925 (1993) and references therein; Letsinger, J. Org. Chem.
35:3800 (1970); Sprinzl et al., Eur. J. Biochem. 81:579 (1977); Letsinger et al., Nucl.
Acids Res. 14:3487 (1986); Sawai et al, Chem. Lett. 805 (1984), Letsinger et al., J.
Am. Chem. Soc. 110:4470 (1988); and Pauwels et al., Chemica Scripta 26:141 91986)), phosphorothioate (Mag et al., Nucleic Acids Res. 19:1437 (1991); and U.S.
Patent No. 5,644,048), phosphorodithioate (Briu et al., J. Am. Chem. Soc. 111:2321 (1989), O-methylphophoroamidite linkages (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, Oxford University Press), and peptide nucleic acid backbones and linkages (see Egholm, J. Am. Chem. Soc. 114:1895 (1992); Meier et al., Chem. Int. Ed. Engl. 31:1008 (1992); Nielsen, Nature, 365:566 (1993); Carlsson et al., Nature 380:207 (1996), all of which are incorporated by reference). Other analog nucleic acids include those with positive backbones (Denpcy et al., Proc. Natl.
Acad. Sci. USA 92:6097 (1995); non-ionic backbones Patent Nos. 5,386,023, 5,637,684, 5,602,240, 5,216,141 and 4,469,863; Kiedrowshi et al., Angew. Chem.
Intl. Ed. English 30:423 (1991); Letsinger et al., J. Am. Chem. Soc. 110:4470 (1988); Letsinger et al., Nucleoside Nucleotide 13:1597 (1994); Chapters 2 and 3, ASC Symposium Series 580, "Carbohydrate Modifications in Antisense Research", Ed.
Y.S. Sanghui and P. Dan Cook; Mesmaeker et al., Bioorganic Medicinal Chem.
Lett. 4:395 (1994); Jeffs et al., J. Biomolecular NMR 34:17 (1994); Tetrahedron Lett.
37:743 (1996)) and non-ribose backbones, including those described in U.S. Patent Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7, ASC Symposium Series 580, "Carbohydrate Modifications in Antisense Research", Ed. Y.S. Sanghui and P. Dan Cook. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids (see Jenkins et al., Chem. Soc. Rev. (1995) ppl69-176). Several nucleic acid analogs are described in Rawls, C E News June S 2, 1997 page 35. All of these references are hereby expressly incorporated by O reference. These modifications of the ribose-phosphate backbone may be done for a 0 variety of reasons, for example to increase the stability and half-life of such molecules in physiological environments for use in anti-sense applications or as probes on a biochip.
[0031) As will be appreciated by those in the art, all of these nucleic acid analogs may find use in the present invention. In addition, mixtures of naturally occurring nucleic 0 acids and analogs can be made; alternatively, mixtures of different nucleic acid 0 analogs, and mixtures of naturally occurring nucleic acids and analogs may be made.
1, [0032] The nucleic acids may be single stranded or double stranded, as specified, or 0 contain portions of both double stranded or single stranded sequence. As will be C1 appreciated by those in the art, the depiction of a single strand "Watson" also defines the sequence of the other strand "Crick"; thus the sequences described herein also includes the complement of the sequence. The nucleic acid may be DNA, both genomic and cDNA, RNA or a hybrid, where the nucleic acid contains any combination of deoxyribo- and ribo-nucleotides, and any combination of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc. As used herein, the term "nucleoside" includes nucleotides and nucleoside and nucleotide analogs, and modified nucleosides such as amino modified nucleosides. In addition, "nucleoside" includes non-naturally occurring analog structures. Thus for example the individual units of a peptide nucleic acid, each containing a base, are referred to herein as a nucleoside.
[0033] An CA sequence can be initially identified by substantial nucleic acid and/or amino acid sequence homology to the CA sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.
[0034] The CA sequences of the invention were initially identified as described herein; basically, infection of mice with murine leukemia viruses (MLV) resulted in lymphoma, although many of these sequences will also be involved in other cancers as is generally outlined herein.
[0035] The CA sequences outlined herein comprise the insertion sites for the virus.
In general, the retrovirus can cause carcinomas in three basic ways: first of all, by inserting upstream of a normally silent host gene and activating it promoter 1 insertion); secondly, by truncating a host gene that leads to oncogenesis; or by S enhancing the transcription of a neighboring gene. For example, retrovirus enhancers, S including SL3-3, arc known to act on genes up to approximately 200 kilobases of the U insertion site.
[00361 In a preferred embodiment, CA sequences are those that are up-regulated in carcinomas; that is, the expression of these genes is higher in carcinoma tissue as compared to normal tissue of the same differentiation stage. "Up-regulation" as used N, herein means at least about 50%, more preferably at least about 100%, more S preferably at least about 150%, more preferably, at least about 200%, with from 300 to at least 1000% being especially preferred.
[0037] In a preferred embodiment, CA sequences are those that are down-regulated in carcinomas; that is, the expression of these genes is lower in carcinoma tissue as compared to normal 1 tissue of the same differentiation stage. "Down-regulation" as used herein means at least about 50%, more preferably at least about 100%, more preferably at least about 150%, more preferably, at least about 200%, with from 300 to at least 1000% being especially preferred.
[0038] In a preferred embodiment, CA sequences are those that are altered but show either the same [0039] expression profile or an altered profile as compared to normal lymphoid tissue of the same [0040] differentiation stage. "Altered CA sequences" as used herein refers to sequences which are truncated, contain insertions or contain point mutations.
[0041] CA proteins of the present invention may be classified as secreted proteins, transmembrane proteins or intracellular proteins.
[0042] In a preferred embodiment the CA protein is an intracellular protein.
Intracellular proteins may be found in the cytoplasm and/or in the nucleus.
Intracellular proteins are involved in all aspects of cellular function and replication (including, for example, signaling pathways); aberrant expression of such proteins results in unregulated or disregulated cellular processes. For example, many intracellular proteins have enzymatic activity such as protein kinase activity, protein phosphatase activity, protease activity, nucleotide cyclase activity, polymerase activity and the like. Intracellular proteins also serve as docking proteins that are involved in organizing complexes of proteins, or targeting proteins to various S subcellular localizations, and are involved in maintaining the structural integrity of organelles.
S [0043] An increasingly appreciated concept in characterizing intracellular proteins is the presence in the proteins of one or more motifs for which defined functions have been attributed. In addition to the highly conserved sequences found in the enzymatic domain of proteins, highly conserved sequences have been identified in proteins that are involved in protein-protein interaction. For example, Src-homology-2 (SH2) domains bind tyrosine-phosphorylated targets in a sequence dependent manner. PTB 0 domains, which are distinct from SH2 domains, also bind tyrosine phosphorylated N targets. SH3 domains bind to proline-rich targets. In addition, PH domains, 0 tetratricopeptide repeats and WD domains to name only a few, have been shown to C1 mediate protein-protein interactions. Some of these may also be involved in binding to phospholipids or other second messengers. As will be appreciated by one of ordinary skill in the art, these motifs can be identified on the basis of primary sequence; thus, an analysis of the sequence of proteins may provide insight into both the enzymatic potential of the molecule and/or molecules with which the protein may associate.
[0044] In a preferred embodiment, the CA sequences are transmembrane proteins.
Transmembrane proteins are molecules that span the phospholipid bilayer of a cell.
They may have an intracellular domain, an extracellular domain, or both. The intracellular domains of such proteins may have a number of functions including those already described for intracellular proteins. For example, the intracellular domain may have enzymatic activity and/or may serve as a binding site for additional proteins. Frequently the intracellular domain of transmembrane proteins serves both roles. For example certain receptor tyrosine kinases have both protein kinase activity and SH2 domains. In addition, autophosphorylation of tyrosines on the receptor molecule itself, creates binding sites for additional SH2 domain containing proteins.
[0045] Transmembrane proteins may contain from one to many transmembrane domains. For example, receptor tyrosine kinases, certain cytokine receptors, receptor guanylyl cyclases and receptor serine/threonine protein kinases contain a single transmembrane domain. However, various other proteins including channels and adenylyl cyclases contain numerous transmembrane domains. Many important cell surface receptors are classified as "seven transmembrane domain" proteins, as they contain 7 membrane spanning regions. Important transmembrane protein receptors include, but are not limited to insulin receptor, insulinlike growth factor receptor, 0 human growth hormone receptor, glucose transporters, transferrin receptor, epidermal growth factor receptor, low density lipoprotein receptor, epidermal growth factor receptor, leptin receptor, interleukin receptors, e.g. IL_1 receptor, II 2 receptor, etc.
[0046] Characteristics of transmembrane domains include approximately S consecutive hydrophobic amino acids that may be followed by charged amino acids.
Therefore, upon analysis of the amino acid sequence of a particular protein, the localization and number of transmembrane domains within the protein may be Spredicted.
[0047] The extracellular domains of transmembrane proteins are diverse; however, conserved motifs are found repeatedly among various extracellular domains.
Conserved structure and/or functions have been ascribed to different extracellular motifs. For example, cytokine receptors are characterized by a cluster of cysteines and a WSXWS tryptophan, S= serine, X=any amino acid (SEQ ID NO:1613) motif. Immunoglobulin-like domains are highly conserved. Mucin-like domains may be involved in cell adhesion and leucine-rich repeats participate in protein-protein interactions.
[0048] Many extracellular domains are involved in binding to other molecules. In one aspect, extracellular domains are receptors. Factors that bind the receptor domain include circulating ligands, which may be peptides, proteins, or small molecules such as adenosine and the like. For example, growth factors such as EGF, FGF and PDGF are circulating growth factors that bind to their cognate receptors to initiate a variety of cellular responses. Other factors include cytokines, mitogenic factors, neurotrophic factors and the like. Extracellular domains also bind to cell-associated molecules. In this respect, they mediate cell-cell interactions. Cell-associated ligands can be tethered to the cell for example via a glycosylphosphatidylinositol (GPI) anchor, or may themselves be transmembrane proteins. Extracellular domains also associate with the extracellular matrix and contribute to the maintenance of the cell structure.
[0049] CA proteins that are transmembrane are particularly preferred in the present invention as they are good targets for immunotherapeutics, as are described herein. In addition, as outlined below, transmembrane proteins can be also useful in imaging modalities.
[0050] It will also be appreciated by those in the art that a transmembrane protein can be made soluble by removing transmembrane sequences, for example through recombinant methods. Furthermore, transmembrane proteins that have been made soluble can be made to be secreted through recombinant means by adding an appropriate signal sequence.
100511 In a preferred embodiment, the CA proteins are secreted proteins; the secretion of which can be either constitutive or regulated. These proteins have a signal peptide or signal sequence that targets the molecule to the secretory pathway, Secreted proteins are involved in numerous physiological events; by virtue of their circulating nature, they serve to transmit signals to various other cell types. The secreted protein may function in an autocrine manner (acting on the cell that secreted the factor), a paracrine manner (acting on cells in close proximity to the cell that secreted the factor) or an endocrine manner (acting on cells at a distance). Thus secreted molecules find use in modulating or altering numerous aspects of physiology. CA proteins that are secreted proteins are particularly preferred in the present invention as they serve as good targets for diagnostic markers, for example for blood tests.
[0052] An CA sequence is initially identified by substantial nucleic acid and/or amino acid sequence homology to the CA sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.
[00531 As used herein, a nucleic acid is a "CA nucleic acid" if the overall homology of the nucleic acid sequence to one of the nucleic acids of Tables 1-112 is preferably greater than about 75%, more preferably greater than about 80%, even more preferably greater than about 85% and most preferably greater than 90%. In some embodiments the homology will be as high as about 93 to 95 or 98%. In a preferred embodiment, the sequences which are used to determine sequence identity or similarity are selected from those of the nucleic acids of Tables 1-1 12. In another embodiment, the sequences are naturally occurring allelic variants of the sequences of the nucleic acids of Tables 1-112. In another embodiment, the sequences are sequence variants as further described herein.
[00541 Homology in this context means sequence similarity or identity, with identity being preferred. A preferred comparison for homology purposes is to compare the sequence containing sequencing errors to the correct sequence. This homology will be determined using standard techniques known in the art, including, but not limited to, the local homology algorithm of Smith Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman Wunsch, J. Mol. Biol.
48:443 (1970), by the search for similarity method of Pearson Lipman, PNAS USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Drive, Madison, WI), the Best Fit sequence program described by Devereux et al., Nucl. Acid Res. 12:387-395 (1984), preferably using the default settings, or by inspection.
[0055] One example of a useful algorithm is PILEUP. PILEUP creates a multiple S sequence alignment from a group of related sequences using progressive, pairwise alignments. It can also plot a tree showing the clustering relationships used to create the alignment. PILEUP uses a simplification of the progressive alignment method of Feng Doolittle, J. Mol. Evol. 35:351-360 (1987); the method is similar to that 6 described by Higgins Sharp CABIOS 5:151-153 (1989). Useful PILEUP parameters including a default gap weight of 3.00, a default gap length weight of 0.10, and weighted end gaps.
[0056] Another example of a useful algorithm is the BLAST algorithm, described in Altschul et al., J. Mol. Biol. 215, 403-410, (1990) and Karlin et al., PNAS USA 90:5873-5787 (1993). A particularly useful BLAST program is the WU-BLAST-2 program which was obtained from Altschul et al., Methods in Enzymology, 266: 460- 480 (1996); http://blast.wustl]. WU-BLAST-2 uses several search parameters, most of which are set to the default values. The adjustable parameters are set with the following values: overlap span overlap fraction 0.125, word threshold 11.
The HSP S and HSP S2 parameters are dynamic values and are established by the program itself depending upon the composition of the particular sequence and composition of the particular database against which the sequence of interest is being searched; however, the values may be adjusted to increase sensitivity. A amino acid sequence identity value is determined by the number of matching identical residues divided by the total number of residues of the "longer" sequence in the aligned region. The "longer" sequence is the one having the most actual residues in the aligned region (gaps introduced by WU-Blast-2 to maximize the alignment score are ignored).
[00571 Thus, "percent nucleic acid sequence identity" is defined as the percentage of nucleotide residues in a candidate sequence that are identical with the nucleotide residues of the nucleic acids of Tables 1-112. A preferred method utilizes the BLASTN module of WU-BLAST-2 set to the default parameters, with overlap span and overlap fraction set to 1 and 0.125, respectively.
[0058] The alignment may include the introduction of gaps in the sequences to be aligned. In addition, for sequences which contain either more or fewer nucleotides than those of the nucleic acids of Tables 1-112, it is understood that the percentage of homology will be determined based on the number of homologous nucleosides in relation to the total number of nucleosides. Thus, for example, homology of O sequences shorter than those of the sequences identified herein and as discussed O below, will be determined using the number of nucleosides in the shorter sequence.
C1 [0059] In one embodiment, the nucleic acid homology is determined through O hybridization studies. Thus, for example, nucleic acids which hybridize under high stringency to the nucleic acids identified in the figures, or their complements, are considered CA sequences. High stringency conditions are known in the art; see for example Maniatis et al., Molecular Cloning: A Laboratory Manual, 2d Edition, 1989, and Short Protocols in Molecular Biology, ed. Ausubel, et al., both of which are hereby incorporated by reference. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen, Techniques in Biochemistry and Molecular Biology--Hybridization with Nucleic Acid Probes, "Overview of principles of hybridization and the strategy of nucleic acid assays" (1993). Generally, stringent conditions are selected to be about 5-100C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 300C for short probes 10 to nucleotides) and at least about 600C for long probes greater than nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide.
[0060] In another embodiment, less stringent hybridization conditions are used; for example, moderate or low stringency conditions may be used, as are known in the art; S see Maniatis and Ausubel, supra, and Tijssen, supra.
0 [00611 In addition, the CA nucleic acid sequences of the invention are fragments of larger genes, i.e. they are nucleic acid segments. Alternatively, the CA nucleic acid sequences can serve as indicators of oncogene position, for example, the CA sequence may be an enhancer that activates a protooncogene. "Genes" in this context includes S coding regions, non-coding regions, and mixtures of coding and non-coding regions.
S Accordingly, as will be appreciated by those in the art, using the sequences provided herein, additional sequences of the CA genes can be obtained, using techniques well known in the art for cloning either longer sequences or the full length sequences; see Maniatis et al., and Ausubel, et al., supra, hereby expressly incorporated by reference.
Il n general, this is done using PCR, for example, kinetic PCR.
[0062] Once the CA nucleic acid is identified, it can be cloned and, if necessary, its constituent parts recombined to form the entire CA nucleic acid. Once isolated from its natural source, contained within a plasmid or other vector or excised therefrom as a linear nucleic acid segment, the recombinant CA nucleic acid can be further used as a probe to identify and isolate other CA nucleic acids, for example additional coding regions. It can also be used as a "precursor" nucleic acid to make modified or variant CA nucleic acids and proteins.
10063] The CA nucleic acids of the present invention are used in several ways. In a first embodiment, nucleic acid probes to the CA nucleic acids are made and attached to biochips to be used in screening and diagnostic methods, as outlined below, or for administration, for example for gene therapy and/or antisense applications.
Alternatively, the CA nucleic acids that include coding regions of CA proteins can be put into expression vectors for the expression of CA proteins, again either for screening purposes or for administration to a patient.
10064] In a preferred embodiment, nucleic acid probes to CA nucleic acids (both the nucleic acid sequences outlined in the figures and/or the complements thereof) are made. The nucleic acid probes attached to the biochip are designed to be substantially complementary to the CA nucleic acids, i.e. the target sequence (either the target sequence of the sample or to other probe sequences, for example in sandwich assays), such that hybridization of the target sequence and the probes of the present invention occurs. As outlined below, this complementarity need not be perfect; there may be any number of base pair mismatches which will interfere with hybridization between O the target sequence and the single stranded nucleic acids of the present invention.
S However, if the number of mutations is so great that no hybridization can occur under even the least stringent of hybridization conditions, the sequence is not a complementary target sequence. Thus, by "substantially complementary" herein is meant that the probes are sufficiently complementary to the target sequences to S hybridize under normal reaction conditions, particularly high stringency conditions, as outlined herein.
[00651 A nucleic acid probe is generally single stranded but can be partially single 1 and partially double stranded. The strandedness of the probe is dictated by the O structure, composition, and properties of the target sequence. In general, the nucleic acid probes range from about 8 to about 100 bases long, with from about 10 to about bases being preferred, and from about 30 to about 50 bases being particularly preferred. That is, generally whole genes are not used. In some embodiments, much longer nucleic acids can be used, up to hundreds of bases.
[00661 In a preferred embodiment, more than one probe per sequence is used, with either overlapping probes or probes to different sections of the target being used.
That is, two, three, four or more probes, with three being preferred, are used to build in a redundancy for a particular target. The probes can be overlapping have some sequence in common), or separate.
[0067] As will be appreciated by those in the art, nucleic acids can be attached or immobilized to a solid support in a wide variety of ways. By "immobilized" and grammatical equivalents herein is meant the association or binding between the nucleic acid probe and the solid support is sufficient to be stable under the conditions of binding, washing, analysis, and removal as outlined below. The binding can be covalent or non-covalent. By "non-covalent binding" and grammatical equivalents herein is meant one or more of either electrostatic, hydrophilic, and hydrophobic interactions. Included in non-covalent binding is the covalent attachment of a molecule, such as, streptavidin to the support and the non-covalent binding of the biotinylated probe to the streptavidin. By "covalent binding" and grammatical equivalents herein is meant that the two moieties, the solid support and the probe, are attached by at least one bond, including sigma bonds, pi bonds and coordination bonds. Covalent bonds can be formed directly between the probe and the solid support or can be formed by a cross linker or by inclusion of a specific reactive group on either the solid support or the probe or both molecules. Immobilization may also involve a combination of covalent and non-covalent interactions.
N [0068] In general, the probes are attached to the biochip in a wide variety of ways, as will be appreciated by those in the art. As described herein, the nucleic acids can either be synthesized first, with subsequent attachment to the biochip, or can be O directly synthesized on the biochip.
[00691 The biochip comprises a suitable solid substrate. By "substrate" or "solid support" or other grammatical equivalents herein is meant any material that can be modified to contain discrete individual sites appropriate for the attachment or association of the nucleic acid probes and is amenable to at least one detection method. As will be appreciated by those in the art, the number of possible substrates are very large, and include, but are not limited to, glass and modified or C\1 functionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, TeflonTM, etc.), polysaccharides, nylon or nitrocellulose, resins, silica or silica_based materials including silicon and modified silicon, carbon, metals, inorganic glasses, etc. In general, the substrates allow optical detection and do not appreciably fluoresce.
[0070] In a preferred embodiment, the surface of the biochip and the probe may be derivatized with chemical functional groups for subsequent attachment of the two.
Thus, for example, the biochip is derivatized with a chemical functional group including, but not limited to, amino groups, carboxy groups, oxo groups and thiol groups, with amino groups being particularly preferred. Using these functional groups, the probes can be attached using functional groups on the probes. For example, nucleic acids containing amino groups can be attached to surfaces comprising amino groups, for example using linkers as are known in the art; for example, homo-or hetero-bifunctional linkers as are well known (see 1994 Pierce Chemical Company catalog, technical section on cross_linkers, pages 155 200, incorporated herein by reference). In addition, in some cases, additional linkers, such as alkyl groups (including substituted and heteroalkyl groups) may be used.
[0071] In this embodiment, the oligonucleotides are synthesized as is known in the art, and then attached to the surface of the solid support. As will be appreciated by those skilled in the art, either the 5' or 3' terminus may be attached to the solid support, or attachment may be via an internal nucleoside.
[0072] In an additional embodiment, the immobilization to the solid support may be O very strong, yet non-covalent. For example, biotinylated oligonucleotides can be S made, which bind to surfaces covalently coated with streptavidin, resulting in attachment.
[0073] Alternatively, the oligonucleotides may be synthesized on the surface, as is known in the art. For example, photoactivation techniques utilizing photopolymerization compounds and techniques are used. In a preferred embodiment, the nucleic acids can be synthesized in situ, using well known photolithographic techniques, such as those described in WO 95/25116; WO i 95/35505; U.S. Patent Nos. 5,700,637 and 5,445,934; and references cited within, all O of which are expressly incorporated by reference; these methods of attachment form CI the basis of the Affymetrix GeneChip technology.
[0074] In addition to the solid-phase technology represented by biochip arrays, gene expression can also be quantified using liquid-phase arrays. One such system is kinetic polymerase chain reaction (PCR). Kinetic PCR allows for the simultaneous amplification and quantification of specific nucleic acid sequences. The specificity is derived from synthetic oligonucleotide primers designed to preferentially adhere to single-stranded nucleic acid sequences bracketing the target site. This pair of oligonucleotide primers form specific, non-covalently bound complexes on each strand of the target sequence. These complexes facilitate in vitro transcription of double-stranded DNA in opposite orientations. Temperature cycling of the reaction mixture creates a continuous cycle of primer binding, transcription, and re-melting of the nucleic acid to individual strands. The result is an exponential increase of the target dsDNA product. This product can be quantified in real time either through the use of an intercalating dye or a sequence specific probe. SYBR® Greene I, is an example of an intercalating dye, that preferentially binds to dsDNA resulting in a concomitant increase in the fluorescent signal. Sequence specific probes, such as used with TaqMan® technology, consist of a fluorochrome and a quenching molecule covalently bound to opposite ends of an oligonucleotide. The probe is designed to selectively bind the target DNA sequence between the two primers. When the DNA strands are synthesized during the PCR reaction, the fluorochrome is cleaved from the probe by the exonuclease activity of the polymerase resulting in signal dequenching.
The probe signaling method can be more specific than the intercalating dye method, but in each case, signal strength is proportional to the dsDNA product produced.
Each type of quantification method can be used in multi-well liquid phase arrays with each well representing primers and/or probes specific to nucleic acid sequences of C interest. When used with messenger RNA preparations of tissues or cell lines, and an array of probe/primer reactions can simultaneously quantify the expression of multiple gene products of interest. See Germer, et al., Genome Res. 10:258-266 (2000); Heid, C. et al., Genome Res. 6, 986-994 (1996).
[0075] In a preferred embodiment, CA nucleic acids encoding CA proteins are used to make a variety of expression vectors to express CA proteins which can then be C used in screening assays, as described below. The expression vectors may be either self-replicating extrachromosomal vectors or vectors which integrate into a host genome. Generally, these expression vectors include transcriptional and translational regulatory nucleic acid operably linked to the nucleic acid encoding the CA protein.
The term "control sequences" refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism. The control sequences that are suitable for prokaryotes, for example, include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
10076] [0077] Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, "operably linked" means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice. The transcriptional and translational regulatory nucleic acid will generally be appropriate to the host cell used to express the CA protein; for example, transcriptional and translational regulatory nucleic acid sequences from Bacillus are preferably used to express the CA protein in Bacillus.
Numerous types of appropriate expression vectors, and suitable regulatory sequences are known in the art for a variety of host cells.
[0078] In general, the transcriptional and translational regulatory sequences may include, but are not limited to, promoter sequences, ribosomal binding sites, transcriptional start and stop sequences, translational start and stop sequences, and enhancer or activator sequences. In a preferred embodiment, the regulatory sequences include a promoter and transcriptional start and stop sequences.
[0079] Promoter sequences encode either constitutive or inducible promoters. The promoters may be either naturally occurring promoters or hybrid promoters. Hybrid S promoters, which combine elements of more than one promoter, are also known in the art, and are useful in the present invention.
S [0080] In addition, the expression vector may comprise additional elements. For example, the expression vector may have two replication systems, thus allowing it to be maintained in two organisms, for example in mammalian or insect cells for expression and in a procaryotic host for cloning and amplification. Furthermore, for integrating expression vectors, the expression vector contains at least one sequence homologous to the host cell genome, and preferably two homologous sequences which flank the expression construct. The integrating vector may be directed to a specific locus in the host cell by selecting the appropriate homologous sequence for inclusion in the vector. Constructs for integrating vectors are well known in the art.
[00811 In addition, in a preferred embodiment, the expression vector contains a selectable marker gene to allow the selection of transformed host cells. Selection genes are well known in the art and will vary with the host cell used.
[0082] The CA proteins of the present invention are produced by culturing a host cell transformed with an expression vector containing nucleic acid encoding an CA protein, under the appropriate conditions to induce or cause expression of the CA protein. The conditions appropriate for CA protein expression will vary with the choice of the expression vector and the host cell, and will be easily ascertained by one skilled in the art through routine experimentation. For example, the use of constitutive promoters in the expression vector will require optimizing the growth and proliferation of the host cell, while the use of an inducible promoter requires the appropriate growth conditions for induction. In addition, in some 'embodiments, the timing of the harvest is important. For example, the baculoviral systems used in insect cell expression are lytic viruses, and thus harvest time selection can be crucial S for product yield.
S [0083] Appropriate host cells include yeast, bacteria, archaebacteria, fungi, and insect, plant and animal cells, including mammalian cells. Of particular interest are Drosophila melanogaster cells, Saccharomyces cerevisiae and other yeasts, E. coli, S Bacillus subtilis, Sf9 cells, C129 cells, 293 cells, Neurospora, BHK, CHO, COS, HeLa cells, THP 1 cell line (a macrophage cell line) and human cells and cell lines.
C[ (0084] In a preferred embodiment, the CA proteins are expressed in mammalian cells.
C Mammalian expression systems are also known in the art, and include retroviral systems. A preferred expression vector system is a retroviral vector system such as is generally described in PCT/US97/01019 and PCT/US97/01048, both of which are hereby expressly incorporated by reference. Of particular use as mammalian promoters are the promoters from mammalian viral genes, since the viral genes are often highly expressed and have a broad host range. Examples include the early promoter, mouse mammary tumor virus LTR promoter, adenovirus major late promoter, herpes simplex virus promoter, and the CMV promoter. Typically, transcription termination and polyadenylation sequences recognized by mammalian cells are regulatory regions located 3' to the translation stop codon and thus, together with the promoter elements, flank the coding sequence. Examples of transcription terminator and polyadenlytion signals include those derived form (0085] The methods of introducing exogenous nucleic acid into mammalian hosts, as well as other hosts, is well known in the art, and will vary with the host cell used.
Techniques include dextran-mediated transfection, calcium phosphate precipitation, polybrene mediated transfection, protoplast fusion, electroporation, viral infection, encapsulation of the polynucleotide(s) in liposomes, and direct microinjection of the DNA into nuclei.
[0086] In a preferred embodiment, CA proteins are expressed in bacterial systems.
Bacterial expression systems are well known in the art. Promoters from bacteriophage may also be used and are known in the art. In addition, synthetic promoters and hybrid promoters are also useful; for example, the tac promoter is a hybrid of the trp and lac promoter sequences. Furthermore, a bacterial promoter can include naturally occurring promoters of non-bacterial origin that have the ability to bind bacterial RNA polymerase and initiate transcription. In addition to a functioning promoter sequence, an efficient ribosome binding site is desirable. The expression vector may also include a signal peptide sequence that provides for secretion of the CA protein in bacteria. The protein is either secreted into the growth media (gram- S positive bacteria) or into the periplasmic space, located between the inner and outer membrane of the cell (gram-negative bacteria). The bacterial expression vector may also include a selectable marker gene to allow for the selection of bacterial strains that have been transformed. Suitable selection genes include genes which render the bacteria resistant to drugs such as ampicillin, chloramphenicol, erythromycin, O kanamycin, neomycin and tetracycline. Selectable markers also include biosynthetic O genes, such as those in the histidine, tryptophan and leucine biosynthetic pathways.
Ci These components are assembled into expression vectors. Expression vectors for 0 bacteria are well known in the art, and include vectors for Bacillus subtilis, E. coli, C Streptococcus cremoris, and Streptococcus lividans, among others. The bacterial expression vectors are transformed into bacterial host cells using techniques well known in the art, such as calcium chloride treatment, electroporation, and others.
[0087] In one embodiment, CA proteins are produced in insect cells. Expression vectors for the transformation of insect cells, and in particular, baculovirus-based expression vectors, are well known in the art.
[0088] In a preferred embodiment, CA protein is produced in yeast cells. Yeast expression systems are well known in the art, and include expression vectors for Saccharomyces cerevisiae, Candida albicans and C. maltosa, Hansenula polymorpha, Kluyveromyces fragilis and K. lactis, Pichia guillerimondii and P. pastoris, Schizosaccharomyces pombe, and Yarrowia lipolytica.
[0089] The CA protein may also be made as a fusion protein, using techniques well known in the art. Thus, for example, for the creation of monoclonal antibodies. If the desired epitope is small, the CA protein may be fused to a carrier protein to form an immunogen. Alternatively, the CA protein may be made as a fusion protein to increase expression, or for other reasons. For example, when the CA protein is an CA peptide, the nucleic acid encoding the peptide may be linked to other nucleic acid for expression purposes.
[0090] In one embodiment, the CA nucleic acids, proteins and antibodies of the invention are labeled. By "labeled" herein is meant that a compound has at least one element, isotope or chemical compound attached to enable the detection of the compound. In general, labels fall into three classes: a) isotopic labels, which may be radioactive or heavy isotopes; b) immune labels, which may be antibodies or antigens; and c) colored or fluorescent dyes. The labels may be incorporated into the CA 0 nucleic acids, proteins and antibodies at any position. For example, the label should C be capable of producing, either directly or indirectly, a detectable signal. The 0 detectable moiety may be a radioisotope, such as 3 H, 14C, 32 P, 5"S, or 1251, a fluorescent or chemiluminescent compound, such as fluorescein isothiocyanate, S rhodamine, or luciferin, or an enzyme, such as alkaline phosphatase, betagalactosidase or horseradish peroxidase. Any method known in the art for C conjugating the antibody to the label may be employed, including those methods C" described by Hunter et al., Nature, 144:945 (1962); David et al., Biochemistry, S13:1014 (1974); Pain et al., J. Immunol. Meth., 40:219 (1981); and Nygren, J.
Histochem. and Cytochem., 30:407 (1982).
[0091] Accordingly, the present invention also provides CA protein sequences. An CA protein of the present invention may be identified in several ways. "Protein" in this sense includes proteins, polypeptides, and peptides. As will be appreciated by those in the art, the nucleic acid sequences of the invention can be used to generate protein sequences. There are a variety of ways to do this, including cloning the entire gene and verifying its frame and amino acid sequence, or by comparing it to known sequences to search for homology to provide a frame, assuming the CA protein has homology to some protein in the database being used. Generally, the nucleic acid sequences are input into a program that will search all three frames for homology.
This is done in a preferred embodiment using the following NCBI Advanced BLAST parameters. The program is blastx or blastn. The database is nr. The input data is as "Sequence in FASTA format". The organism list is "none". The "expect" is 10; the filter is default. The "descriptions" is 500, the "alignments" is 500, and the "alignment view" is pairwise. The "query Genetic Codes" is standard The matrix is BLOSUM62; gap existence cost is 11, per residue gap cost is 1; and the lambda ratio is .85 default. This results in the generation of a putative protein sequence.
[0092] Also included within one embodiment of CA proteins are amino acid variants of the naturally occurring sequences, as determined herein. Preferably, the variants are preferably greater than about 75% homologous to the wild-type sequence, more preferably greater than about 80%, even more preferably greater than about 85% and most preferably greater than 90%. In some embodiments the homology will be as high as about 93 to 95 or 98%. As for nucleic acids, homology in this context means sequence similarity or identity, with identity being preferred. This homology will be determined using standard techniques known in the art as are outlined above for the nucleic acid homologies.
O [0093] CA proteins of the present invention may be shorter or longer than the wild type amino acid sequences. Thus, in a preferred embodiment, included within the definition of CA proteins are portions or fragments of the wild type sequences herein.
In addition, as outlined above, the CA nucleic acids of the invention may be used to obtain additional coding regions, and thus additional protein sequence, using techniques known in the art.
[0094] In a preferred embodiment, the CA proteins are derivative or variant CA ri proteins as compared to the wild-type sequence. That is, as outlined more fully below, the derivative CA peptide will contain at least one amino acid substitution, C, deletion or insertion, with amino acid substitutions being particularly preferred. The amino acid substitution, insertion or deletion may occur at any residue within the CA peptide.
[0095] Also included in an embodiment of CA proteins of the present invention are amino acid sequence variants. These variants fall into one or more of three classes: substitutional, insertional or deletional variants. These variants ordinarily are prepared by site specific mutagenesis of nucleotides in the DNA encoding the CA protein, using cassette or PCR mutagenesis or other techniques well known in the art, to produce DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture as outlined above. However, variant CA protein fragments having up to about 100-150 residues may be prepared by in vitro synthesisusing established techniques. Amino acid sequence variants are characterized by the predetermined nature of the variation, a feature that sets them apart from naturally occurring allelic or interspecies variation of the CA protein amino acid sequence. The variants typically exhibit the same qualitative biological activity as the naturally occurring analogue, although variants can also be selected which have modified characteristics as will be more fully outlined below.
[0096] While the site or region for introducing an amino acid sequence variation is predetermined, the mutation per se need not be predetermined. For example, in order to optimize the performance of a mutation at a given site, random mutagenesis may be conducted at the target codon or region and the expressed CA variants screened for the optimal combination of desired activity. Techniques for making substitution mutations at predetermined sites in DNA having a known sequence are well known, for example, Ml 3 primer mutagenesis and LAR mutagenesis. Screening of the mutants is done using assays of CA protein activities.
[0097] Amino acid substitutions are typically of single residues; insertions usually will be on the order of from about 1 to 20 amino acids, although considerably larger insertions may be tolerated. Deletions range from about 1 to about 20 residues, although in some cases deletions may be much larger.
[0098] Substitutions, deletions, insertions or any combination thereof may be used to arrive at a final derivative. Generally these changes are done on a few amino acids to minimize the alteration of the molecule. However, larger changes may be tolerated in certain circumstances. When small alterations in the characteristics of the CA protein are desired, substitutions are generally made in accordance with the following chart: Chart I Original Residue Ala Arg Asn Asp Cys Gin Glu Gly His lie Leu Lys Met Phe Ser Thr Trp Tyr Val Exemplary Substitutions Ser Lys Gin, His Glu Ser Asn Asp Pro Asn, Gin Leu, Val lie, Val Arg, Gin, Glu Leu, Ile Met, Leu, Tyr Thr Ser Tyr Trp, Phe lie, Leu [0099] Substantial changes in function or immunological identity are made by selecting substitutions that are less conservative than those shown in Chart I. For example, substitutions may be made which more significantly affect: the structure of the polypeptide backbone in the area of the alteration, for example the alpha-helical or beta-sheet structure; the charge or hydrophobicity of the molecule at the target site; or the bulk of the side chain. The substitutions which in general are expected to produce the greatest changes in the polypeptide's properties are those in which a O hydrophilic residue, e.g. seryl or threonyl is substituted for (or by) a hydrophobic O residue, e.g. leucyl, isoleucyl, phenylalanyl, valyl or alanyl; a cysteine or proline is CN substituted for (or by) any other residue; a residue having an electropositive side 0 chain, e.g. lysyl, arginyl, or histidyl, is substituted for (or by) an electronegative C residue, e.g. glutamyl or aspartyl; or a residue having a bulky side chain, e.g.
phenylalanine, is substituted for (or by) one not having a side chain, e.g. glycine.
[0100] The variants typically exhibit the same qualitative biological activity and will elicit the same immune response as the naturally-occurring analogue, although variants also are selected to modify the characteristics of the CA proteins as needed.
Alternatively, the variant may be designed such that the biological activity of the CA protein is altered. .For example, glycosylation sites may be altered or removed, dominant negative mutations created, etc.
10101] Covalent modifications of CA polypeptides are included within the scope of this invention, for example for use in screening. One type of covalent modification includes reacting targeted amino acid residues of an CA polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N-or Cterminal residues of an CA polypeptide. Derivatization with bifunctional agents is useful, for instance, for crosslinking CA polypeptides to a water-insoluble support matrix or surface for use in the method for purifying anti-CA antibodies or screening assays, as is more fully described below. Commonly used crosslinking agents include, 1,1 -bis(diazoacetyl)-2-phenylethane, glutaraldehyde, Nhydroxysuccinimide esters, for example, esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'dithiobis(succinimidylpropionate), bifunctional maleimides such as bis-N-maleimido- 1,8-octane and agents such as methyl-3-[(p-azidophenyl)dithio]propioimidate.
[0102] Other modifications include deamidation of glutaminyl and asparaginyl residues to the corresponding glutamyl and aspartyl residues, respectively, hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl, S threonyl or tyrosyl residues, methylation of the a-amino groups of lysine, arginine, and histidine side chains Creighton, Proteins: Structure and Molecular 0 Properties, W.H. Freeman Co., San Francisco, pp. 79-86 (1983)], acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group.
C [0103] Another type of covalent modification of the CA polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of the polypeptide. "Altering the native glycosylation pattern" is intended for purposes herein to mean deleting one or more carbohydrate moieties found in native sequence O CA polypeptide, and/or adding one or more glycosylation sites that are not present in the native sequence CA polypeptide.
[0104] Addition of glycosylation sites to CA polypeptides may be accomplished by altering the amino acid sequence thereof. The alteration may be made, for example, by the addition of, or substitution by, one or more serine or threonine residues to the native sequence CA polypeptide (for O-linked glycosylation sites). The CA amino acid sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA encoding the CA polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.
[0105] Another means of increasing the number of carbohydrate moieties on the CA polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide.
Such methods are described in the art, in WO 87/05330 published 11 September 1987, and in Aplin and Wriston, LA Crit. Rev. Biochem., pp. 259-306 (1981).
[0106] Removal of carbohydrate moieties present on the CA polypeptide may be accomplished chemically or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation. Chemical deglycosylation techniques are known in the art and described, for instance, by Hakimuddin, et al., Arch. Biochem. Biophys., 259:52 (1987) and by Edge et al., Anal.
Biochem., 118:131 (1981). Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo-and exo-glycosidases as described by Thotakura et al., Meth. Enzymol., 138:350 (1987).
[0107] Another type of covalent modification of CA comprises linking the CA 0 polypeptide to one of a variety of nonproteinaceous polymers, polyethylene 0 glycol, polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U.S.
Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337.
O [0108] CA polypeptides of the present invention may also be modified in a way to form chimeric molecules comprising an CA polypeptide fused to another, C heterologous polypeptide or amino acid sequence. In one embodiment, such a C chimeric molecule comprises a fusion of an CA polypeptide with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind. The epitope tag is generally placed at the amino-or carboxyl-terminus of the CA polypeptide, although internal fusions may also be tolerated in some instances. The presence of such epitope-tagged forms of an CA polypeptide can be detected using an antibody against the tag polypeptide. Also, provision of the epitope tag enables the CA polypeptide to be readily purified by affinity purification using an anti-tag antibody or another type of affinity matrix that binds to the epitope tag. In an alternative embodiment, the chimeric molecule may comprise a fusion of an CA polypeptide with an immunoglobulin or a particular region of an immunoglobulin.
For a bivalent form of the chimeric molecule, such a fusion could be to the Fc region of an IgG molecule.
[0109] Various tag polypeptides and their respective antibodies are well known in the art. Examples include poly-histidine (poly-his) or poly-histidine-glycine (poly-hisgly) tags; the flu HA tag polypeptide and its antibody 12CA5 [Field et al., Mol. Cell.
Biol., 8:2159-2165 (1988)]; the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and 9E10 antibodies thereto [Evan et al., Molecular and Cellular Biology, 5:3610-3616 (1985)]; and the Herpes Simplex virus glycoprotein D (gD) tag and its antibody [Paborsky et al., Protein Engineering, 3(6):547-553 (1990)]. Other tag polypeptides include the Flag-peptide [Hopp et al., BioTechnology, 6:1204-1210 (1988)]; the KT3 epitope peptide [Martin et al., Science, 255:192-194 (1992)]; tubulin epitope peptide [Skinner et al., J. Biol. Chem., 266:15163-15166 (1991)]; and the T7 gene 10 protein peptide tag [Lutz-Freyermuth et al., Proc. Natl. Acad. Sci. USA, 87:6393-6397 (1990)].
[0110] Also included with the definition of CA protein in one embodiment are other CA proteins of the CA family, and CA proteins from other organisms, which are cloned and expressed as outlined below. Thus, probe or degenerate polymerase chain reaction (PCR) primer sequences may be used to find other related CA proteins from humans or other organisms. As will be appreciated by those in the art, particularly Suseful probe and/or PCR primer sequences include the unique areas of the CA nucleic acid sequence. As is generally known in the art, preferred PCR primers are from about 15 to about 35 nucleotides in length, with from about 20 to about 30 being preferred, and may contain inosine as needed. The conditions for the PCR reaction are well known in the art.
[0111] In addition, as is outlined herein, CA proteins can be made that are longer than those encoded by the nucleic acids of the figures, for example, by the elucidation of additional sequences, the addition of epitope or purification tags, the addition of other fusion sequences, etc.
10112] CA proteins may also be identified as being encoded by CA nucleic acids.
Thus, CA proteins are encoded by nucleic acids that will hybridize to the sequences of the sequence listings, or their complements, as outlined herein.
[0113] In a preferred embodiment, the invention provides CA antibodies. In a preferred embodiment, when the CA protein is to be used to generate antibodies, for example for immunotherapy, the CA protein should share at least one epitope or determinant with the full length protein. By "epitope" or "determinant" herein is meant a portion of a protein which will generate and/or bind an antibody or T-cell receptor in the context of MHC. Thus, in most instances, antibodies made to a smaller CA protein will be able to bind to the full length protein. In a preferred embodiment, the epitope is unique; that is, antibodies generated to a unique epitope show little or no cross-reactivity.
[0114] In one embodiment, the term "antibody" includes antibody fragments, as are known in the art, including Fab, Fab 2 single chain antibodies (Fv for example), chimeric antibodies, etc., either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA technologies.
[01151 Methods of preparing polyclonal antibodies are known to the skilled artisan.
Polyclonal antibodies can be raised in a mammal, for example, by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. The immunizing agent may include a protein encoded by a nucleic acid of the figures or fragment thereof or a fusion S protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Examples of adjuvants which may be employed include Freund's complete adjuvant and MPL- TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).
The immunization protocol may be selected by one skilled in the art without undue Sexperimentation.
10116] The antibodies may, alternatively, be monoclonal antibodies. Monoclonal antibodies may be prepared using hybridoma methods, such as those described by N Kohler and Milstein, Nature, 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes may be immunized in vitro. The immunizing agent will typically include a polypeptide encoded by a nucleic acid of Tables 1-112, or fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes ("PBLs") are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell [Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103]. Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin.
Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth ofHGPRT-deficient cells.
[0117] In one embodiment, the antibodies are bispecific antibodies. Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for a protein encoded by a nucleic acid of Tables 1-112, or a fragment thereof, the other one is for any other antigen, and preferably for a cellsurface protein or receptor or receptor subunit, preferably one that is tumor specific.
S[0118] In a preferred embodiment, the antibodies to CA are capable of reducing or eliminating the biological function of CA, as is described below. That is, the addition of anti-CA antibodies (either polyclonal or preferably monoclonal) to CA (or cells C containing CA) may reduce or eliminate the CA activity. Generally, at least a C1 decrease in activity is preferred, with at least about 50% being particularly preferred and about a 95-100% decrease being especially preferred.
[0119] In a preferred embodiment the antibodies to the CA proteins are humanized antibodies. Humanized forms of non human murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab') 2 or other antigen binding subsequences of antibodies) which contain minimal sequence derived from non_human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues form a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non_human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non_human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non_human immunoglobulin and all or substantially all of the framework residues (FR) regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region typically that of a human immunoglobulin [Jones et al., Nature, 321:522_525 (1986); Riechmann et al., Nature, 332:323329 (1988); and Presta, Curr. Op. Struct. Biol., 2:593_596 (1992)].
[0120] Methods for humanizing nonhuman antibodies are well known in the art.
Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is nonhuman. These non_human amino acid residues are S often referred to as import residues, which are typically taken from an import variable C domain. Humanization can be essentially performed following the method of Winter and co_workers [Jones et al., Nature, 321:522_525 (1986); Riechmann et al., Nature, 332:323_327 (1988); Verhoeyen et al., Science, 239:1534_1536 (1988)], by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.
[0121] Human antibodies can also be produced using various techniques known in the art, including phage display libraries [Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)]. The techniques of Cole et al. and Boemer et al. are also available for the preparation of human monoclonal antibodies [Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p.
77 (1985) and Boemer et al., J. Immunol., 147(1):86_95 (1991)]. Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks et al., Bio/Technology 779_783 (1992); Lonberg et al., Nature 368 856_859 (1994); Morrison, Nature 368, 81213 (1994); Fishwild et al., Nature Biotechnology 14, 845_51 (1996); Neuberger, Nature Biotechnology 14, 826 (1996); Lonberg and Huszar, Intern. Rev.
Immunol. 13 65_93 (1995).
[0122] By immunotherapy is meant treatment of a carcinoma with an antibody raised against an CA protein. As used herein, immunotherapy can be passive or active.
Passive immunotherapy as defined herein is the passive transfer of antibody to a recipient (patient). Active immunization is the induction of antibody and/or T-cell responses in a recipient (patient). Induction of an immune response is the result of providing the recipient with an antigen to which antibodies are raised. As appreciated by one of ordinary skill in the art, the antigen may be provided by injecting a polypeptide against which antibodies are desired to be raised into a recipient, or contacting the recipient with a nucleic acid capable of expressing the antigen and O under conditions for expression of the antigen.
[0123] In a preferred embodiment, oncogenes which encode secreted growth factors C1 may be inhibited by raising antibodies against CA proteins that are secreted proteins C as described above. Without being bound by theory, antibodies used for treatment, bind and prevent the secreted protein from binding to its receptor, thereby inactivating the secreted CA protein.
[0124] In another preferred embodiment, the CA protein to which antibodies are raised is a transmembrane protein. Without being bound by theory, antibodies used for treatment, bind the extracellular domain of the CA protein and prevent it from binding to other proteins, such as circulating ligands or cell-associated molecules.
The antibody may cause down-regulation of the transmembrane CA protein. As will be appreciated by one of ordinary skill in the art, the antibody may be a competitive, non-competitive or uncompetitive inhibitor of protein binding to the extracellular domain of the CA protein. The antibody is also an antagonist of the CA protein.
Further, the antibody prevents activation of the transmembrane CA protein. In one aspect, when the antibody prevents the binding of other molecules to the CA protein, the antibody prevents growth of the cell. The antibody may also sensitize the cell to cytotoxic agents, including, but not limited to TNF.-, TNF-, IL-1, INF. and IL-2, or chemotherapeutic agents including 5FU, vinblastine, actinomycin D, cisplatin, methotrexate, and the like. In some instances the antibody belongs to a sub-type that activates serum complement when complexed with the transmembrane protein thereby mediating cytotoxicity. Thus, carcinomas may be treated by administering to a patient antibodies directed against the transmembrane CA protein.
[0125] In another preferred embodiment, the antibody is conjugated to a therapeutic moiety. In one aspect the therapeutic moiety is a small molecule that modulates the activity of the CA protein. In another aspect the therapeutic moiety modulates the activity of molecules associated with or in close proximity to the CA protein. The S therapeutic moiety may inhibit enzymatic activity such as protease or protein kinase activity associated with carcinoma.
O [0126] In a preferred embodiment, the therapeutic moiety may also be a cytotoxic agent. In this method, targeting the cytotoxic agent to tumor tissue or cells, results in a reduction in the number of afflicted cells, thereby reducing symptoms associated with carcinomas, including lymphoma. Cytotoxic agents are numerous and varied and include, but are not limited to, cytotoxic drugs or toxins or active fragments of such toxins. Suitable toxins and their corresponding fragments include diphtheria A 0 chain, exotoxin A chain, ricin A chain, abrin A chain, curcin, crotin, phenomycin, 71 enomycin and the like. Cytotoxic agents also include radiochemicals made by 0 conjugating radioisotopes to antibodies raised against CA proteins, or binding of a CN radionuclide to a chelating agent that has been covalently attached to the antibody.
Targeting the therapeutic moiety to transmembrane CA proteins not only serves to increase the local concentration of therapeutic moiety in the carcinoma of interest, i.e., lymphoma, but also serves to reduce deleterious side effects that may be associated with the therapeutic moiety.
[0127] In another preferred embodiment, the CA protein against which the antibodies are raised is an intracellular protein. In this case, the antibody may be conjugated to a protein which facilitates entry into the cell. In one case, the antibody enters the cell by endocytosis. In another embodiment, a nucleic acid encoding the antibody is administered to the individual or cell. Moreover, wherein the CA protein can be targeted within a cell, the nucleus, an antibody thereto contains a signal for that target localization, a nuclear localization signal.
[0128] The CA antibodies of the invention specifically bind to CA proteins. By "specifically bind" herein is meant that the antibodies bind to the protein with a binding constant in the range of at least 10 4 10- 6 with a preferred range being 7 10 9
M
1 [0129] In a preferred embodiment, the CA protein is purified or isolated after expression. CA proteins may be isolated or purified in a variety of ways known to those skilled in the art depending on what other components are present in the sample.
Standard purification methods include electrophoretic, molecular, immunological and chromatographic techniques, including ion exchange, hydrophobic, affinity, and reverse-phase HPLC chromatography, and chromatofocusing. For example, the CA protein may be purified using a standard anti-CA antibody column. Ultrafiltration S and diafiltration techniques, in conjunction with protein concentration, are also useful.
0 For general guidance in suitable purification techniques, see Scopes, Protein Purification, Springer-Verlag, NY (1982). The degree of purification necessary will S vary depending on the use of the CA protein. In some instances no purification will be necessary.
[0130] Once expressed and purified if necessary, the CA proteins and nucleic acids S are useful in a number of applications.
[0131] In one aspect, the expression levels of genes are determined for different cellular states in the carcinoma phenotype; that is, the expression levels of genes in normal tissue and in carcinoma tissue (and in some cases, for varying severities of lymphoma that relate to prognosis, as outlined below) are evaluated to provide expression profiles. An expression profile of a particular cell state or point of development is essentially a "fingerprint" of the state; while two states may have any particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is unique to the state of the cell. By comparing expression profiles of cells in different states, information regarding which genes are important (including both up- and downregulation of genes) in each of these states is obtained. Then, diagnosis may be done or confirmed: does tissue from a particular patient have the gene expression profile of normal or carcinoma tissue.
[0132] "Differential expression," or grammatical equivalents as used herein, refers to both qualitative as well as quantitative differences in the genes temporal and/or cellular expression patterns within and among the cells. Thus, a differentially expressed gene can qualitatively have its expression altered, including an activation or inactivation, in, for example, normal versus carcinoma tissue. That is, genes may be turned on or turned off in a particular state, relative to another state. As is apparent to the skilled artisan, any comparison of two or more states can be made. Such a qualitatively regulated gene will exhibit an expression pattern within a state or cell type which is detectable by standard techniques in one such state or cell type, but is not detectable in both. Alternatively, the determination is quantitative in that expression is increased or decreased; that is, the expression of the gene is either upregulated, resulting in an increased amount of transcript, or downregulated, resulting in a decreased amount of transcript. The degree to which expression differs need only be large enough to quantify via standard characterization techniques as outlined below, such as by use of Affymetrix GeneChip® expression arrays, Lockhart, Nature Biotechnology, 14:1675-1680 (1996), hereby expressly incorporated by reference. Other techniques include, but are not limited to, quantitative reverse transcriptase PCR, Northern analysis and RNase protection. As outlined above, preferably the change in expression upregulation or downregulation) is at least about 50%, more preferably at least about 100%, more preferably at least about 150%, more preferably, at least about 200%, with from 300 to at least 1000% being especially preferred.
1 [0133] As will be appreciated by those in the art, this may be done by evaluation at either the gene transcript, or the protein level; that is, the amount of gene expression may be monitored using nucleic acid probes to the DNA or RNA equivalent of the gene transcript, and the quantification of gene expression levels, or, alternatively, the final gene product itself (protein) can be monitored, for example through the use of antibodies to the CA protein and standard immunoassays (ELISAs, etc.) or other techniques, including mass spectroscopy assays, 2D gel electrophoresis assays, etc.
Thus, the proteins corresponding to CA genes, i.e. those identified as being important in a particular carcinoma phenotype, lymphoma, can be evaluated in a diagnostic test specific for that carcinoma.
[0134] In a preferred embodiment, gene expression monitoring is done and a number of genes, i.e. an expression profile, is monitored simultaneously, although multiple protein expression monitoring can be done as well. Similarly, these assays may be done on an individual basis as well.
[0135] In this embodiment, the CA nucleic acid probes may be attached to biochips as outlined herein for the detection and quantification of CA sequences in a particular cell. The assays are done as is known in the art. As will be appreciated by those in the art, any number of different CA sequences may be used as probes, with single sequence assays being used in some cases, and a plurality of the sequences described herein being used in other embodiments. In addition, while solid-phase assays are described, any number of solution based assays may be done as well.
[0136] In a preferred embodiment, both solid and solution based assays may be used S to detect CA sequences that are up-regulated or down-regulated in carcinomas as Scompared to normal tissue. In instances where the CA sequence has been altered but 0 shows the same expression profile or an altered expression profile, the protein will be detected as outlined herein.
[0137] In a preferred embodiment nucleic acids encoding the CA protein are detected.
Although DNA or RNA encoding the CA protein may be detected, of particular interest are methods wherein the mRNA encoding a CA protein is detected. The presence of mRNA in a sample is an indication that the CA gene has been transcribed to form the mRNA, and suggests that the protein is expressed. Probes to detect the S mRNA can be any nucleotide/deoxynucleotide probe that is complementary to and base pairs with the mRNA and includes but is not limited to oligonucleotides, cDNA or RNA. Probes also should contain a detectable label, as defined herein. In one method the mRNA is detected after immobilizing the nucleic acid to be examined on a solid support such as nylon membranes and hybridizing the probe with the sample.
Following washing to remove the non-specifically bound probe, the label is detected.
In another method detection of the mRNA is performed in situ. In this method permeabilized cells or tissue samples are contacted with a detectably labeled nucleic acid probe for sufficient time to allow the probe to hybridize with the target mRNA.
Following washing to remove the non-specifically bound probe, the label is detected.
For example a digoxygenin labeled riboprobe (RNA probe) that is complementary to the mRNA encoding a CA protein is detected by binding the digoxygenin with an anti-digoxygenin secondary antibody and developed with nitro blue tetrazolium and 5_bromo_4_chloro_3_indoyl phosphate.
(0138] In a preferred embodiment, any of the three classes of proteins as described herein (secreted, transmembrane or intracellular proteins) are used in diagnostic assays. The CA proteins, antibodies, nucleic acids, modified proteins and cells containing CA sequences are used in diagnostic assays. This can be done on an individual gene or corresponding polypeptide level, or as sets of assays.
[0139] As described and defined herein, CA proteins find use as markers of carcinomas, including lymphomas such as, but not limited to, Hodgkin's and non- Hodgkin lymphoma. Detection of these proteins in putative carcinoma tissue or patients allows for a determination or diagnosis of the type of carcinoma. Numerous S methods known to those of ordinary skill in the art find use in detecting carcinomas.
In one embodiment, antibodies are used to detect CA proteins. A preferred method separates proteins from a sample or patient by electrophoresis on a gel (typically a d denaturing and reducing protein gel, but may be any other type of gel including
C
isoelectric focusing gels and the like). Following separation of proteins, the CA protein is detected by immunoblotting with antibodies raised against the CA protein.
Methods of immunoblottingare well known to those of ordinary skill in the art.
[0140] In another preferred method, antibodies to the CA protein find use in in situ imaging techniques. In this method cells are contacted with from one to many antibodies to the CA protein(s). Following washing to remove non-specific antibody S binding, the presence of the antibody or antibodies is detected. In one embodiment C~ the antibody is detected by incubating with a secondary antibody that contains a detectable label. In another method the primary antibody to the CA protein(s) contains a detectable label. In another preferred embodiment each one of multiple primary antibodies contains a distinct and detectable label. This method finds particular use in simultaneous screening for a plurality of CA proteins. As will be appreciated by one of ordinary skill in the art, numerous other histological imaging techniques are useful in the invention.
[0141] In a preferred embodiment the label is detected in a fluorometer which has the ability to detect and distinguish emissions of different wavelengths. In addition, a fluorescence activated cell sorter (FACS) can be used in the method.
[01421 In another preferred embodiment, antibodies find use in diagnosing carcinomas from blood samples. As previously described, certain CA proteins are secreted/circulating molecules. Blood samples, therefore, are useful as samples to be probed or tested for the presence of secreted CA proteins. Antibodies can be used to detect the CA proteins by any of the previously described immunoassay techniques including ELISA, immunoblotting (Western blotting), immunoprecipitation, BIACORE technology and the like, as will be appreciated by one of ordinary skill in the art.
[0143] In a preferred embodiment, in situ hybridization of labeled CA nucleic acid probes to tissue arrays is done. For example, arrays of tissue samples, including CA tissue and/or normal tissue, are made. In situ hybridization as is known in the art can S then be done.
S [01441 It is understood that when comparing the expression fingerprints between an
U
individual and a standard, the skilled artisan can make a diagnosis as well as a prognosis. It is further understood that the genes which indicate the diagnosis may differ from those which indicate the prognosis.
[0145] In a preferred embodiment, the CA proteins, antibodies, nucleic acids, modified proteins and cells containing CA sequences are used in prognosis assays.
As above, gene expression profiles can be generated that correlate to carcinoma, S especially lymphoma, severity, in terms of long term prognosis. Again, this may be done on either a protein or gene level, with the use of genes being preferred. As S above, the CA probes are attached to biochips for the detection and quantification of CA sequences in a tissue or patient. The assays proceed as outlined for diagnosis.
[0146] In a preferred embodiment, any of the CA sequences as described herein are used in drug screening assays. The CA proteins, antibodies, nucleic acids, modified proteins and cells containing CA sequences are used in drug screening assays or by evaluating the effect of drug candidates on a "gene expression profile" or expression profile ofpolypeptides. In one embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent, Zlokamrnik, et al., Science 279, 84-8 (1998), Heid, et al., Genome Res., 6:986-994 (1996).
10147] In a preferred embodiment, the CA proteins, antibodies, nucleic acids, modified proteins and cells containing the native or modified CA proteins are used in screening assays. That is, the present invention provides novel methods for screening for compositions which modulate the carcinoma phenotype. As above, this can be done by screening for modulators of gene expression or for modulators of protein activity. Similarly, this may be done on an individual gene or protein level or by evaluating the effect of drug candidates on a "gene expression profile". In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent, see Zlokarnik, supra.
S [0148] Having identified the CA genes herein, a variety of assays to evaluate the effects of agents on gene expression may be executed. In a preferred embodiment, N assays may be run on an individual gene or protein level. That is, having identified a particular gene as aberrantly regulated in carcinoma, candidate bioactive agents may
C
be screened to modulate the genes response. "Modulation" thus includes both an increase and a decrease in gene expression or activity. The preferred amount of modulation will depend on the original change of the gene expression in normal versus tumor tissue, with changes of at least 10%, preferably 50%, more preferably 100-300%, and in some embodiments 300-1000% or greater. Thus, if a gene exhibits S a 4 fold increase in tumor compared to normal tissue, a decrease of about four fold is desired; a 10 fold decrease in tumor compared to normal tissue gives a 10 fold increase in expression for a candidate agent is desired, etc. Alternatively, where the CA sequence has been altered but shows the same expression profile or an altered expression profile, the protein will be detected as outlined herein.
[0149] As will be appreciated by those in the art, this may be done by evaluation at either the gene or the protein level; that is, the amount of gene expression may be monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, the level of the gene product itself can be monitored, for example through the use of antibodies to the CA protein and standard immunoassays.
Alternatively, binding and bioactivity assays with the protein may be done as outlined below.
[0150] In a preferred embodiment, gene expression monitoring is done and a number of genes, i.e. an expression profile, is monitored simultaneously, although multiple protein expression monitoring can be done as well.
[0151] In this embodiment, the CA nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of CA sequences in a particular cell. The assays are further described below.
[0152] Generally, in a preferred embodiment, a candidate bioactive agent is added to the cells prior to analysis. Moreover, screens are provided to identify a candidate bioactive agent which modulates a particular type of carcinoma, modulates CA proteins, binds to a CA protein, or interferes between the binding of a CA protein and an antibody.
[0153] The term "candidate bioactive agent" or "drug candidate" or grammatical equivalents as used herein describes any molecule, protein, oligopeptide, small organic or inorganic molecule, polysaccharide, polynuclcotide, etc., to be tested for S bioactive agents.that are capable of directly or indirectly altering either the carcinoma phenotype, binding to and/or modulating the bioactivity of an CA protein, or the expression of a CA sequence, including both nucleic acid sequences and protein sequences. In a particularly preferred embodiment, the candidate agent suppresses a CA phenotype, for example to a normal tissue fingerprint. Similarly, the candidate S agent preferably suppresses a severe CA phenotype. Generally a plurality of assay mixtures are run in parallel with different agent concentrations to obtain a differential response to the various concentrations. Typically, one of these concentrations serves as a negative control, at zero concentration or below the level of detection.
[0154] In one aspect, a candidate agent will neutralize the effect of an CA protein.
By "neutralize" is meant that activity of a protein is either inhibited or counter acted against so as to have substantially no effect on a cell.
[0155] Candidate agents encompass numerous chemical classes, though typically they are organic or inorganic molecules, preferably small organic compounds having a molecular weight of more than 100 and less than about 2,500 daltons. Preferred small molecules are less than 2000, or less than 1500 or less than 1000 or less than 500 D.
Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Candidate agents are also found among biomolecules including peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Particularly preferred are peptides.
[0156] Candidate agents are obtained from a wide variety of sources including libraries of synthetic or natural compounds. For example, numerous means are available for random and directed synthesis of a wide variety of organic compounds and biomolecules, including expression of randomized oligonuclcotides.
Alternatively, libraries of natural compounds in the form of bacterial, fungal, plant and animal extracts are available or readily produced. Additionally, natural or synthetically produced libraries and compounds are readily modified through S conventional chemical, physical and biochemical means. Known pharmacological
C
agents may be subjected to directed or random chemical modifications, such as S acylation, alkylation, esterification, amidification to produce structural analogs.
[0157] In a preferred embodiment, the candidate bioactive agents are proteins. By "protein" herein is meant at least two covalently attached amino acids, which includes N proteins, polypeptides, oligopeptides and peptides. The protein may be made up of 0 naturally occurring amino acids and peptide bonds, or synthetic peptidomimetic structures. Thus "amino acid", or "peptide residue", as used herein means both i naturally occurring and synthetic amino acids. For example, homo-phenylalanine, 0 citrulline and noreleucine are considered amino acids for the purposes of the C1 invention. "Amino acid" also includes imino acid residues such as proline and hydroxyproline. The side chains may be in either the or the configuration. In the preferred embodiment, the amino acids are in the or L-configuration. If nonnaturally occurring side chains are used, non-amino acid substituents may be used, for example to prevent or retard in vivo degradations.
[0158] In a preferred embodiment, the candidate bioactive agents are naturally occurring proteins or fragments of naturally occurring proteins. Thus, for example, cellular extracts containing proteins, or random or directed digests ofproteinaceous cellular extracts, may be used. In this way libraries of procaryotic and eucaryotic proteins may be made for screening in the methods of the invention. Particularly preferred in this embodiment are libraries of bacterial, fungal, viral, and mammalian proteins, with the latter being preferred, and human proteins being especially preferred.
[0159] In a preferred embodiment, the candidate bioactive agents are peptides of from about 5 to about 30 amino acids, with from about 5 to about 20 amino acids being preferred, and from about 7 to about 15 being particularly preferred. The peptides may be digests of naturally occurring proteins as is outlined above, random peptides, or "biased" random peptides. By "randomized" or grammatical equivalents herein is meant that each nucleic acid and peptide consists of essentially random nucleotides and amino acids, respectively. Since generally these random peptides (or nucleic acids, discussed below) are chemically synthesized, they may incorporate any nucleotide or amino acid at any position. The synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of all or most of S the possible combinations over the length of the sequence, thus forming a library of Cr randomized candidate bioactive proteinaceous agents.
U [01601 In one embodiment, the library is fully randomized, with no sequence preferences or constants at any position. In a preferred embodiment, the library is biased. That is, some positions within the sequence are either held constant, or are selected from a limited number of possibilities. For example, in a preferred embodiment, the nucleotides or amino acid residues are randomized within a defined class, for example, of hydrophobic amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines or histidines for phosphorylation sites, etc., or to purines, etc.
10161] In a preferred embodiment, the candidate bioactive agents are nucleic acids, as defined above.
[0162] As described above generally for proteins, nucleic acid candidate bioactive agents may be naturally occurring nucleic acids, random nucleic acids, or "biased" random nucleic acids. For example, digests ofprocaryotic or eucaryotic genomes may be used as is outlined above for proteins.
[01631 In a preferred embodiment, the candidate bioactive agents are organic chemical moieties, a wide variety of which are available in the literature.
[0164] In assays for altering the expression profile of one or more CA genes, after the candidate agent has been added and the cells allowed to incubate for some period of time, the sample containing the target sequences to be analyzed is added to the biochip. If required, the target sequence is prepared using known techniques. For example, the sample may be treated to lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR occurring as needed, as will be appreciated by those in the art. For example, an in vitro transcription with labels covalently attached to the nucleosides is done. Generally, the nucleic acids are labeled with a label as defined herein, with biotin-FITC or PE, cy3 and cy5 being particularly preferred.
10165] In a preferred embodiment, the target sequence is labeled with, for example, a fluorescent, chemiluminescent, chemical, or radioactive signal, to provide a means of S detecting the target sequence's specific binding to a probe. The label also can be an enzyme, such as, alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that can be detected.
d Alternatively, the label can be a labeled compound or small molecule, such as an enzyme inhibitor, that binds but is not catalyzed or altered by the enzyme. The label also can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin. For the example of biotin, the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence.
As known in the art, unbound labeled streptavidin is removed prior to analysis.
S [0166] As will be appreciated by those in the art, these assays can be direct F hybridization assays or can comprise "sandwich assays", which include the use of multiple probes, as is generally outlined in U.S. Patent Nos. 5,681,702, 5,597,909, 5,545,730, 5,594,117, 5,591,584, 5,571,670, 5,580,731, 5,571,670, 5,591,584, 5,624,802, 5,635,352, 5,594,118, 5,359,100, 5,124,246 and 5,681,697, all of which are hereby incorporated by reference. In this embodiment, in general, the target nucleic acid is prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex.
[0167] A variety of hybridization conditions may be used in the present invention, including high, moderate and low stringency conditions as outlined above. The assays are generally run under stringency conditions which allows formation of the label probe hybridization complex only in the presence of target. Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic salt concentration pH, organic solvent concentration, etc.
[0168] These parameters may also be used to control non-specific binding, as is generally outlined in U.S. Patent No. 5,681,697. Thus it may be desirable to perform certain steps at higher stringency conditions to reduce non-specific binding.
[0169] The reactions outlined herein may be accomplished in a variety of ways, as will be appreciated by those in the art. Components of the reaction may be added simultaneously, or sequentially, in any order, with preferred embodiments outlined below. In addition, the reaction may include a variety of other reagents may be included in the assays. These include reagents like salts, buffers, neutral proteins, e.g.
albumin, detergents, etc which may be used to facilitate optimal hybridization and detection, and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inkibitors, nuclease inhibitors, anti-microbial agents, etc., may be used, depending on the sample preparation methods and purity of the target. In addition, either solid phase or solution based kinetic PCR) assays may be used.
[0170] Once the assay is run, the data is analyzed to determine the expression levels, and changes in expression levels as between states, of individual genes, forming a gene expression profile.
[0171] In a preferred embodiment, as for the diagnosis and prognosis applications, having identified the differentially expressed gene(s) or mutated gene(s) important in any one state, screens can be run to alter the expression of the genes individually.
That is, screening for modulation of regulation of expression of a single gene can be done. Thus, for example, particularly in the case of target genes whose presence or absence is unique between two states, screening is done for modulators of the target gene expression.
[0172] In addition, screens can be done for novel genes that are induced in response to a candidate agent. After identifying a candidate agent based upon its ability to suppress a CA expression pattern leading to a normal expression pattern, or modulate a single CA gene expression profile so as to mimic the expression of the gene from normal tissue, a screen as described above can be performed to identify genes that are specifically modulated in response to the agent. Comparing expression profiles between normal tissue and agent treated CA tissue reveals genes that are not expressed in normal tissue or CA tissue, but are expressed in agent treated tissue.
These agent specific sequences can be identified and used by any of the methods described herein for CA genes or proteins. In particular these sequences and the proteins they encode find use in marking or identifying agent treated cells. In addition, antibodies can be raised against the agent induced proteins and used to target novel therapeutics to the treated CA tissue sample.
[0173] Thus, in one embodiment, a candidate agent is administered to a population of CA cells, that thus has an associated CA expression profile. By "administration" or "contacting" herein is meant that the candidate agent is added to the cells in such a manner as to allow the agent to act upon the cell, whether by uptake and intracellular O action, or by action at the cell surface. In some embodiments, nucleic acid encoding a proteinaceous candidate agent a peptide) ma' be put into a viral construct such as a retroviral construct and added to the cell, such that expression of the peptide agent is accomplished; see PCT US97/01019, hereby expressly incorporated by reference.
C [0174] Once the candidate agent has been administered to the cells, the cells can be C washed if desired and are allowed to incubate under preferably physiological conditions for some period of time. The cells are then harvested and a new gene expression profile is generated, as outlined herein.
O [01751 Thus, for example, CA tissue may be screened for agents that reduce or suppress the CA phenotype. A change in at least one gene of the expression profile indicates that the agent has an effect on CA activity. By defining such a signature for the CA phenotype, screens for new drugs that alter the phenotype can be devised.
With this approach, the drug target need not be known and need not be represented in the original expression screening platform, nor does the level of transcript for the target protein need to change.
[0176] In a preferred embodiment, as outlined above, screens may be done on individual genes and gene products (proteins). That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of either the expression of the gene or the gene product itself can be done.
The gene products of differentially expressed genes are sometimes referred to herein as "CA proteins" or an "CAP". The CAP may be a fragment, or alternatively, be the full length protein to the fragment encoded by the nucleic acids of Tables 1-112.
Preferably, the CAP is a fragment. In another embodiment, the sequences are sequence variants as further described herein.
[0177] Preferably, the CAP is a fragment of approximately 14 to 24 amino acids long.
More preferably the fragment is a soluble fragment. Preferably, the fragment includes a non-transmembrane region. In a preferred embodiment, the fragment has an Nterminal Cys to aid in solubility. In one embodiment, the c-terminus of the fragment is kept as a free acid and the n-terminus is a free amine to aid in coupling, to cysteine.
[0178] In one embodiment the CA proteins are conjugated to an immunogenic agent as discussed herein. In one embodiment the CA protein is conjugated to BSA.
'[0179] In a preferred embodiment, screening is done to alter the biological function of U the expression product of the CA gene. Again, having identified the importance of a Sgene in a particular state, screening for agents that bind and/or modulate the biological activity of the gene product can be run as is more fully outlined below.
[0180] In a preferred embodiment, screens are designed to first find candidate agents that can bind to CA proteins, and then these agents may be used in assays that evaluate the ability of the candidate agent to modulate the CAP activity and the Scarcinoma phenotype. Thus, as will be appreciated by those in the art, there are a number of different assays which may be run; binding assays and activity assays.
10181] In a preferred embodiment, binding assays are done. In general, purified or isolated gene product is used; that is, the gene products of one or more CA nucleic acids are made. In general, this is done as is known in the art. For example, antibodies are generated to the protein gene products, and standard immunoassays are run to determine the amount of protein present. Alternatively, cells comprising the CA proteins can be used in the assays.
[0182] Thus, in a preferred embodiment, the methods comprise combining a CA protein and a candidate bioactive agent, and determining the binding of the candidate agent to the CA protein. Preferred embodiments utilize the human or mouse CA protein, although other mammalian proteins may also be used, for example for the development of animal models of human disease. In some embodiments, as outlined herein, variant or derivative CA proteins may be used.
[0183] Generally, in a preferred embodiment of the methods herein, the CA protein or the candidate agent is non-diffusably bound to an insoluble support having isolated sample receiving areas i microtiter plate, an array, etc.). The insoluble supports may be made of any composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening. The surface of such supports may be solid or porous and of any convenient shape. Examples of suitable insoluble supports include microtiter plates, arrays, membranes and beads. These are typically made of glass, plastic polystyrene), polysaccharides, nylon or nitrocellulose, TeflonM, etc. Microtiter plates and arrays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples. The particular manner of binding of the composition is not crucial so long as it is compatible with the reagents and overall methods of the invention, maintains the activity of the composition and is nondiffusable. Preferred methods of binding include the use of antibodies (which do not sterically block either the ligand binding site or activation sequence when the protein is bound to the support), direct binding to "sticky" or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding of the protein or agent, excess unbound C material is removed by washing. The sample receiving areas may then be blocked 0 through incubation with bovine serum albumin (BSA), casein or other innocuous protein or other moiety.
[0184] In a preferred embodiment, the CA protein is bound to the support, and a candidate bioactive agent is added to the assay. Alternatively, the candidate agent is bound to the support and the CA protein is added. Novel binding agents include specific antibodies, non_natural binding agents identified in screens of chemical libraries, peptide analogs, etc. Of particular interest are screening assays for agents that have a low toxicity for human cells. A wide variety of assays may be used for this purpose, including labeled in vitro protein_protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.) and the like.
[0185] The determination of the binding of the candidate bioactive agent to the CA protein may be done in a number of ways. In a preferred embodiment, the candidate bioactive agent is labeled, and binding determined directly. For example, this may be done by attaching all or a portion of the CA protein to a solid support, adding a labeled candidate agent (for example a fluorescent label), washing off excess reagent, and determining whether the label is present on the solid support. Various blocking and washing steps may be utilized as is known in the art.
[0186] By "labeled" herein is meant that the compound is either directly or indirectly labeled with a label which provides a detectable signal, e.g. radioisotope, fluorescers, enzyme, antibodies, particles such as magnetic particles, chemiluminescers, or specific binding molecules, etc. Specific binding molecules include pairs, such as biotin and streptavidin, digoxin and antidigoxin etc. For the specific binding members, the complementary member would normally be labeled with a molecule which provides for detection, in accordance with known procedures, as outlined above. The label can directly or indirectly provide a detectable signal.
S [0187] In some embodiments, only one of the components is labeled. For example, Sthe proteins (or proteinaceous candidate agents) may be labeled at tyrosine positions S using 1251, or with fluorophores. Alternatively, more than one component may be labeled with different labels; using 1251 for the proteins, for example, and a fluorophor Sfor the candidate agents.
[0188] In a preferred embodiment, the binding of the candidate bioactive agent is determined through the use of competitive binding assays. In this embodiment, the competitor is a binding moiety known to bind to the target molecule CA protein), such as an antibody, peptide, binding partner, ligand, etc. Under certain circumstances, there may be competitive binding as between the bioactive agent and the binding moiety, with the binding moiety displacing the bioactive agent.
[0189] In one embodiment, the candidate bioactive agent is labeled. Either the candidate bioactive agent, or the competitor, or both, is added first to the protein for a time sufficient to allow binding, if present. Incubations may be performed at any temperature which facilitates optimal activity, typically between 4 and 40 CC.
Incubation periods are selected for optimum activity, but may also be optimized to facilitate rapid high through put screening. Typically between 0.1 and 1 hour will be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding.
[0190] In a preferred embodiment, the competitor is added first, followed by the candidate bioactive agent. Displacement of the competitor is an indication that the candidate bioactive agent is binding to the CA protein and thus is capable of binding to, and potentially modulating, the activity of the CA protein. In this embodiment, either component can be labeled. Thus, for example, if the competitor is labeled, the presence of label in the wash solution indicates displacement by the agent.
Alternatively, if the candidate bioactive agent is labeled, the presence of the label on the support indicates displacement.
[0191] In an alternative embodiment, the candidate bioactive agent is added first, with incubation and washing, followed by the competitor. The absence of binding by the competitor may indicate that the bioactive agent is bound to the CA protein with a higher affinity. Thus, if the candidate bioactive agent is labeled, the presence of the C label on the support, coupled with a lack of competitor binding, may indicate that the candidate agent is capable of binding to the CA protein.
S [0192] In a preferred embodiment, the methods comprise differential screening to identity bioactive agents that are capable of modulating the activity of the CA proteins. In this embodiment, the methods comprise combining a CA protein and a competitor in a first sample. A second sample comprises a candidate bioactive agent, a CA protein and a competitor. The binding of the competitor is determined for both N"1 samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the CA protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the CA protein.
[0193J Alternatively, a preferred embodiment utilizes differential screening to identify drug candidates that bind to the native CA protein, but cannot bind to modified CA proteins. The structure of the CA protein may be modeled, and used in rational drug design to synthesize agents that interact with that site. Drug candidates that affect CA bioactivity are also identified by screening drugs for the ability to either enhance or reduce the activity of the protein.
[0194] Positive controls and negative controls may be used in the assays. Preferably all control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples is for a time sufficient for the binding of the agent to the protein. Following incubation, all samples are washed free of nonspecifically bound material and the amount of bound, generally labeled agent determined. For example, where a radiolabel is employed, the samples may be counted in a scintillation counter to determine the amount of bound compound.
[0195] A variety of other reagents may be included in the screening assays. These include reagents like salts, neutral proteins, e.g. albumin, detergents, etc which may be used to facilitate optimal proteinprotein binding and/or reduce non_specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti_microbial agents, etc., may be used. The mixture of components may be added in any order that provides for the requisite binding.
U
[0196] Screening for agents that modulate the activity of CA proteins may also be done. In a preferred embodiment, methods for screening for a bioactive agent capable of modulating the activity of CA proteins comprise the steps of adding a candidate bioactive agent to a sample of CA proteins, as above, and determining an alteration in r the biological activity of CA proteins. "Modulating the activity of an CA protein" includes an increase in activity, a decrease in activity, or a change in the type or kind of activity present. Thus, in this embodiment, the candidate agent should both bind to CA proteins (although this may not be necessary), and alter its biological or biochemical activity as defined herein. The methods include both in vitro screening methods, as are generally outlined above, and in vivo screening of cells for alterations in the presence, distribution, activity or amount of CA proteins.
[0197] Thus, in this embodiment, the methods comprise combining a CA sample and a candidate bioactive agent, and evaluating the effect on CA activity. By "CA activity" or grammatical equivalents herein is meant one of the CA protein's biological activities, including, but not limited to, its role in tumorigenesis, including cell division, preferably in lymphatic tissue, cell proliferation, tumor growth and transformation of cells. In one embodiment, CA activity includes activation of or by a protein encoded by a nucleic acid of Tables 1-112. An inhibitor of CA activity is the inhibition of any one or more CA activities.
[0198] In a preferred embodiment, the activity of the CA protein is increased; in another preferred embodiment, the activity of the CA protein is decreased. Thus, bioactive agents that are antagonists are preferred in some embodiments, and bioactive agents that are agonists may be preferred in other embodiments.
[0199] In a preferred embodiment, the invention provides methods for screening fbr bioactive agents capable of modulating the activity of a CA protein. The methods comprise adding a candidate bioactive agent, as defined above, to a cell comprising CA proteins. Preferred cell types include almost any cell. The cells contain a recombinant nucleic acid that encodes a CA protein. In a preferred embodiment, a library of candidate agents are tested on a plurality of cells.
S [0200] In one aspect, the assays are evaluated in the presence or absence or previous S or subsequent exposure of physiological signals, for example hormones, antibodies, Speptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells cellcell contacts). In another example, the determinations are determined at different stages of the cell cycle process.
1 0201] In this way, bioactive agents are identified. Compounds with pharmacological activity are able to enhance or interfere with the activity of the CA protein.
S [0202] In one embodiment, a method of inhibiting carcinoma cancer cell division, is S provided. The method comprises administration of a carcinoma cancer inhibitor.
S [0203] In a preferred embodiment, a method of inhibiting lymphoma carcinoma cell division is provided comprising administration of a lymphoma carcinoma inhibitor.
[0204] In another embodiment, a method of inhibiting tumor growth is provided. The method comprises administration of a carcinoma cancer inhibitor. In a particularly preferred embodiment, a method of inhibiting tumor growth in lymphatic tissue is provided comprising administration of a lymphoma inhibitor.
[02051 In a further embodiment, methods of treating cells or individuals with cancer are provided. The method comprises administration of a carcinoma cancer inhibitor.
Preferably, the carcinoma is a lymphoma carcinoma.
[0206] In one embodiment, a carcinoma cancer inhibitor is an antibody as discussed above. In another embodiment, the carcinoma cancer inhibitor is an antisense molecule. Antisense molecules as used herein include antisense or sense oligonucleotides comprising a singe-stranded nucleic acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA (antisense) sequences for carcinoma cancer molecules. Antisense or sense oligonucleotides, according to the present invention, comprise a fragment generally at least about 14 nucleotides, preferably from about 14 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, for example, Stein and Cohen, Cancer Res. 48:2659, (1988) and van der Krol et al., BioTechniques 6:958, (1988).
[0207] Antisense molecules may be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand binding molecule, as described in WO 91/04753. Suitable ligand binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule Sdoes not substantially interfere with the ability of the ligand binding molecule to bind Sto its corresponding molecule or receptor, or block entry of the sense or antisense Soligonucleotide or its conjugated version into the cell. Alternatively, a sense or an antisense oligonucleotide may be introduced into a cell containing the target nucleic acid sequence by formation of an oligonucleotide-lipid complex, as described in WO 90/10448. It is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to C methods of treatment.
[0208] The compounds having the desired pharmacological activity may be administered in a physiologically acceptable carrier to a host, as previously described.
The agents may be administered in a variety of ways, orally, parenterally e.g., subcutaneously, intraperitoneally, intravascularly, etc. Depending upon the manner of introduction, the compounds may be formulated in a variety of ways. The concentration of therapeutically active compound in the formulation may vary from about 0.1_100% wgt/vol. The agents may be administered alone or in combination with other treatments, radiation.
[0209] The pharmaceutical compositions can be prepared in various forms, such as granules, tablets, pills, suppositories, capsules, suspensions, salves, lotions and the like. Pharmaceutical grade organic or inorganic carriers and/or diluents suitable for oral and topical use can be used to make up compositions containing the therapeutically_active compounds. Diluents known to the art include aqueous media, vegetable and animal oils and fats. Stabilizing agents, wetting and emulsifying agents, salts for varying the osmotic pressure or buffers for securing an adequate pH value, and skin penetration enhancers can be used as auxiliary agents.
[0210] Without being bound by theory, it appears that the various CA sequences are important in carcinomas. Accordingly, disorders based on mutant or variant CA genes may be determined. In one embodiment, the invention provides methods for identifying cells containing variant CA genes comprising determining all or part of the sequence of at least one endogenous CA genes in a cell. As will be appreciated by those in the art, this may be done using any number of sequencing techniques. In a preferred embodiment, the invention provides methods of identifying the CA genotype of an individual comprising determining all or part of the sequence of at least one CA gene of the individual. This is generally done in at least one tissue of the individual, and may include the evaluation of a number of tissues or different
C
samples of the same tissue. The method may include comparing the sequence of the S sequenced CA gene to a known CA gene, a wild-type gene. As will be appreciated by those in the art, alterations in the sequence of some oncogenes can be an indication of either the presence of the disease, or propensity to develop the disease, or prognosis evaluations.
1 [0211] The sequence of all or part of the CA gene can then be compared to the sequence of a known CA gene to determine if any differences exist. This can be done using any number of known homology programs, such as Bestfit, etc. In a preferred embodiment, the presence of a difference in the sequence between the CA gene of the patient and the known CA gene is indicative of a disease state or a propensity for a disease state, as outlined herein.
[0212] In a preferred embodiment, the CA genes are used as probes to determine the number of copies of the CA gene in the genome. For example, some cancers exhibit chromosomal deletions or insertions, resulting in an alteration in the copy number of a gene.
[0213] In another preferred embodiment CA genes are used as probes to determine the chromosomal location of the CA genes. Information such as chromosomal location finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as translocations, and the like are identified in CA gene loci.
[0214] Thus, in one embodiment, methods of modulating CA in cells or organisms are provided. In one embodiment, the methods comprise administering to a cell an anti-CA antibody that reduces or eliminates the biological activity of an endogenous CA protein. Alternatively, the methods comprise administering to a cell or organism a recombinant nucleic acid encoding a CA protein. As will be appreciated by those in the art, this may be accomplished in any number of ways. In a preferred embodiment, for example when the CA sequence is down-regulated in carcinoma, the activity of the CA gene is increased by increasing the amount of CA in the cell, for example by overexpressing the endogenous CA or by administering a gene encoding the CA sequence, using known gene-therapy techniques, for example. In a preferred embodiment, the gene therapy techniques include the incorporation of the exogenous O gene using enhanced homologous recombination (EHR), for example as described in PCT/US93/03868, hereby incorporated by reference in its entirety. Alternatively, for example when the CA sequence is up-regulated in carcinoma, the activity of the endogenous CA gene is decreased, for example by the administration of a CA antisense nucleic acid.
[0215] In one embodiment, the CA proteins of the present invention may be used to generate polyclonal and monoclonal antibodies to CA proteins, which are useful as described herein. Similarly, the CA proteins can be coupled, using standard technology, to affinity chromatography columns. These columns may then be used to purify CA antibodies. In a preferred embodiment, the antibodies are generated to epitopes unique to a CA protein; that is, the antibodies show little or no crossreactivity to other proteins. These antibodies find use in a number of applications.
For example, the CA antibodies may be coupled to standard affinity chromatography columns and used to purify CA proteins. The antibodies may also be used as blocking polypeptides, as outlined above, since they will specifically bind to the CA protein.
[0216] In one embodiment, a therapeutically effective dose of a CA or modulator thereof is administered to a patient. By "therapeutically effective dose" herein is meant a dose that produces the effects for which it is administered. The exact dose will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques. As is known in the art, adjustments for CA degradation, systemic versus localized delivery, and rate of new protease synthesis, as well as the age, body weight, general health, sex, diet, time of administration, drug interaction and the severity of the condition may be necessary, and will be ascertainable with routine experimentation by those skilled in the art.
10217] A "patient" for the purposes of the present invention includes both humans and other animals, particularly mammals, and organisms. Thus the methods are applicable to both human therapy and veterinary applications. In the preferred embodiment the patient is a mammal, and in the most preferred embodiment the patient is human.
[0218] The administration of the CA proteins and modulators of the present invention can be done in a variety of ways as discussed above, including, but not limited to, orally, subcutaneously, intravenously, intranasally, transdermally, intraperitoneally, Sintramuscularly, intrapulmonary, vaginally, rectally, or intraocularly. In some instances, for example, in the treatment of wounds and inflammation, the CA proteins and modulators may be directly applied as a solution or spray.
S [0219J The pharmaceutical compositions of the present invention comprise a CA protein in a form suitable for administration to a patient. In the preferred 0 embodiment, the pharmaceutical compositions are in a water soluble form, such as being present as pharmaceutically acceptable salts, which is meant to include both g acid and base addition salts. "Pharmaceutically acceptable acid addition salt" refers to those salts that retain the biological effectiveness of the free bases and that are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p_toluenesulfonic acid, salicylic acid and the like.
"Pharmaceutically acceptable base addition salts" include those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Particularly preferred are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.
[0220] The pharmaceutical compositions may also include one or more of the following: carrier proteins such as serum albumin; buffers; fillers such as microcrystalline cellulose, lactose, corn and other starches; binding agents; sweeteners and other flavoring agents; coloring agents; and polyethylene glycol.
Additives are well known in the art, and are used in a variety of formulations.
[0221] In a preferred embodiment, CA proteins and modulators are administered as therapeutic agents, and can be formulated as outlined above. Similarly, CA genes (including both the full-length sequence, partial sequences, or regulatory sequences of the CA coding regions) can be administered in gene therapy applications, as is known in the art. These CA genes can include antisense applications, either as gene therapy for incorporation into the genome) or as antisense compositions, as will be appreciated by those in the art.
[0222] In a preferred embodiment, CA genes are administered as DNA vaccines, either single genes or combinations of CA genes. Naked DNA vaccines are generally known in the art. Brower, Nature Biotechnology, 16:1304-1305 (1998).
[0223] In one embodiment, CA genes of the present invention are used as DNA vaccines. Methods for the use of genes as DNA vaccines are well known to one of ordinary skill in the art, and include placing a CA gene or portion of a CA gene under the control of a promoter for expression in a patient with carcinoma. The CA gene used for DNA vaccines can encode full-length CA proteins, but more preferably encodes portions of the CA proteins including peptides derived from the CA protein.
In a preferred embodiment a patient is immunized with a DNA vaccine comprising a plurality ofnucleotide sequences derived from a CA gene. Similarly, it is possible to immunize a patient with a plurality of CA genes or portions thereof as defined herein.
Without being bound by theory, expression of the polypeptide encoded by the DNA vaccine, cytotoxic T-cells, helper T-cells and antibodies are induced which recognize and destroy or eliminate cells expressing CA proteins.
[02241 In a preferred embodiment, the DNA vaccines include a gene encoding an adjuvant molecule with the DNA vaccine. Such adjuvant molecules include cytokines that increase the immunogenic response to the CA polypeptide encoded by the DNA vaccine. Additional or alternative adjuvants are known to those of ordinary skill in the art and find use in the invention.
[0225] In another preferred embodiment CA genes find use in generating animal models of carcinomas, particularly lymphoma carcinomas. As is appreciated by one of ordinary skill in the art, when the CA gene identified is repressed or diminished in CA tissue, gene therapy technology wherein antisense RNA directed to the CA gene will also diminish or repress expression of the gene. An animal generated as such serves as an animal model of CA that finds use in screening bioactive drug candidates. Similarly, gene knockout technology, for example as a result of S homologous recombination with an appropriate gene targeting vector, will result in the absence of the CA protein. When desired, tissue-specific expression or knockout of the CA protein may be necessary.
[0226] It is also possible that the CA protein is overexpressed in carcinoma. As such, S transgenic animals can be generated that overexpress the CA protein. Depending on the desired expression level, promoters of various strengths can be employed to 0 express the transgene. Also, the number of copies of the integrated transgene can be N determined and compared for a determination of the expression level of the transgene.
S Animals generated by such methods find use as animal models of CA and are CN additionally useful in screening for bioactive molecules to treat carcinoma.
102271 The CA nucleic acid sequences of the invention are depicted in Tables 1-112.
The sequences in Tables 1 (SEQ ID NOS:1-460) and 2 (SEQ ID NOS:461-952) depict mouse tags, i.e. the genomic insertion sites. SEQ ID NOS:953-1612 include genomic sequence, mRNA and coding sequences for both mouse and human. N/A indicates a gene that has been identified, but for which there has not been a name ascribed. The different sequences of Tables 3-112 are assigned the following SEQ ID Nos: Table 3 (mouse gene: Fscnl; human gene SNL) Mouse genomic sequence (SEQ ID NO:953) Mouse mRNA sequence (SEQ ID NO:954) Mouse coding sequence (SEQ ID NO:955) Human genomic sequence (SEQ ID NO:956) Human mRNA sequence (SEQ ID NO:957) Human coding sequence (SEQ ID NO:958) Table 4 (mouse gene Map3k6; human gene MAP3K6) Mouse genomic sequence (SEQ ID NO:959) Mouse mRNA sequence (SEQ ID NO:960) Mouse coding sequence (SEQ ID NO:961) Human genomic sequence (SEQ ID NO:962) Human mRNA sequence (SEQ ID NO:963) O Human coding sequence (SEQ ID NO:964) Table 5 (mouse gene Fosb; human gene FOSB) Mouse genomic sequence (SEQ ID NO:965) S Mouse mRNA sequence (SEQ ID NO:966) Mouse coding sequence (SEQ ID NO:967) Human genomic sequence (SEQ ID NO:968) Human mRNA sequence (SEQ ID NO:969) Human coding sequence (SEQ ID NO:970) STable 6 (mouse gene cmkbr7; human gene: CCR7) Mouse genomic sequence (SEQ ID NO:971) Mouse mRNA sequence (SEQ ID NO:972) Mouse coding sequence (SEQ ID NO:973) Human genomic sequence (SEQ ID NO:974) Human mRNA sequence (SEQ ID NO:975) Human coding sequence (SEQ ID NO:976) Table 7 (mouse gene: Ccndl; human gene: CCND1) Mouse genomic sequence (SEQ ID NO:977) Mouse mRNA sequence (SEQ ID NO:978) Mouse coding sequence (SEQ ID NO:979) Human genomic sequence (SEQ ID NO:980) Human mRNA sequence (SEQ ID NO:981) Human coding sequence (SEQ ID NO:982) Table 8 (mouse gene: Ccnd3; human gene: CCND3) Mouse genomic sequence (SEQ ID NO:983) Mouse mRNA sequence (SEQ ID NO:984) Mouse coding sequence (SEQ ID NO:985) Human genomic sequence (SEQ ID NO:986) Human mRNA sequence (SEQ ID NO:987) Human coding sequence (SEQ ID NO:988) S Table 9 (mouse gene: Wnt3; human gene: WNT3) S Mouse genomic sequence (SEQ ID NO:989) Mouse mRNA sequence (SEQ ID NO:990) Mouse coding sequence (SEQ ID NO:991) Human genomic sequence (SEQ ID NO:992) Human mRNA sequence (SEQ ID NO:993) Human coding sequence (SEQ ID NO:994) S Table 10 (mouse gene: Batf; human gene: BATF) S Mouse genomic sequence (SEQ ID NO:995) S Mouse mRNA sequence (SEQ ID NO:996) Mouse coding sequence (SEQ ID NO:997) Human genomic sequence (SEQ ID NO:998) Human mRNA sequence (SEQ ID NO:999) Human coding sequence (SEQ ID NO:1000) Table 11 (mouse gene: Irf4; human gene: IRF4) Mouse genomic sequence (SEQ ID NO:1001) Mouse mRNA sequence (SEQ ID NO:1002) Mouse coding sequence (SEQ ID NO:1003) Human genomic sequence (SEQ ID NO:1004) Human mRNA sequence (SEQ ID NO:1005) Human coding sequence (SEQ ID NO:1006) Table 12 (mouse gene: Notchl; human gene: NOTCH1) Mouse genomic sequence (SEQ ID NO:1007) Mouse mRNA sequence (SEQ ID NO:1008) Mouse coding sequence (SEQ ID NO:1009) Human genomic sequence (SEQ ID NO:1010) Human mRNA sequence (SEQ ID NO:1011) Human coding sequence (SEQ ID NO:1012) Table 13 (mouse gene: Myc; human gene MYC) Mouse genomic sequence (SEQ ID NO:1013) S Mouse mRNA sequence (SEQ ID NO: 1014) Mouse coding sequence (SEQ ID NO: 1015) 0 Human genomic sequence (SEQ ID NO:1016) Human mRNA sequence (SEQ ID NO:1017) Human coding sequence (SEQ ID NO:1018) C, Table 14 (mouse gene Bach2; human gene BACH2) N Mouse genomic sequence (SEQ ID NO:1019) Mouse mRNA sequence (SEQ ID NO:1020) Mouse coding sequence (SEQ ID NO:1021) OHuman genomic sequence (SEQ ID NO:1022) Human mRNA sequence (SEQ ID NO:1023) Human coding sequence (SEQ ID NO:1024) Table 15 (mouse gene Wnt human gene WNT 1) Mouse genomic sequence (SEQ ID NO:1025) Mouse mRNA sequence (SEQ ID NO:1026) Mouse coding sequence (SEQ ID NO:1027) Human genomic sequence (SEQ ID NO:1028) Human mRNA sequence (SEQ ID NO:1029) Human coding sequence (SEQ ID NO:1030) Table 16 (mouse gene Rasgrpl; human gene: RASGRP1) Mouse genomic sequence (SEQ ID NO:1031) Mouse mRNA sequence (SEQ ID NO:1032) Mouse coding sequence (SEQ ID NO:1033) Human genomic sequence (SEQ ID NO:1034) Human mRNA sequence (SEQ ID NO:1035) Human coding sequence (SEQ ID NO:1036) Table 17 (mouse gene: Nmycl; human gene: MYCN) Mouse genomic sequence (SEQ ID NO:1037) Mouse mRNA sequence (SEQ ID NO:1038) Mouse coding sequence (SEQ ID NO:1039) Human genomic sequence (SEQ ID NO: 1040) S Human mRNA sequence (SEQ ID NO: 1041) D Human coding sequence (SEQ ID NO:1042) Table 18 (mouse gene: Myb; human gene: MYB) Mouse genomic sequence (SEQ ID NO:1,043) SMouse mRNA sequence (SEQ ID NO:1044) Mouse coding sequence (SEQ ID NO:1045) Human genomic sequence (SEQ ID NO: 1046) Human mRNA sequence (SEQ ID NO:1047) Human coding sequence (SEQ ID NO:1048) Table 19 (mouse gene: Sox4; human gene: SOX4) Mouse genomic sequence (SEQ ID NO:1049) Mouse mRNA sequence (SEQ ID NO:1050) Mouse coding sequence (SEQ ID NO:1051) Human genomic sequence (SEQ ID NO:1052) Human mRNA sequence (SEQ ID NO:1053) Human coding sequence (SEQ ID NO: 1054) Table 20 (mouse gene: Tcofl; human gene: TCOF1) Mouse genomic sequence (SEQ ID NO: 1055) Mouse mRNA sequence (SEQ ID NO:1056) Mouse coding sequence (SEQ ID NO:1057) Human genomic sequence (SEQ ID NO:1058) Human mRNA sequence (SEQ ID NO: 1059) Human coding sequence (SEQ ID NO:1060) Table 21 (mouse gene: Pimi; human gene: PIM1) Mouse genomic sequence (SEQ ID NO:1061) Mouse mRNA sequence (SEQ ID NO:1062) Mouse coding sequence (SEQ ID NO:1063) Human genomic sequence (SEQ ID NO:1064) Human mRNA sequence (SEQ ID NO:1065) S Human coding sequence (SEQ ID NO:1066) Table 22 (mouse gene: Wnt3a; human gene: WNT3A) Mouse genomic sequence (SEQ ID NO:1067) Mouse mRNA sequence (SEQ ID NO:1068) Mouse coding sequence (SEQ ID NO:1069) C Human genomic sequence (SEQ ID NO:1070) C Human mRNA sequence (SEQ IDNO:1071) Human coding sequence (SEQ ID NO:1072) Table 23 (mouse gene: Ly6e; human gene LY6E) Mouse genomic sequence (SEQ ID NO:1073) Mouse mRNA sequence (SEQ ID NO:1074) Mouse coding sequence (SEQ ID NO:1075) Human genomic sequence (SEQ ID NO:1076) Human mRNA sequence (SEQ ID NO:1077) Human coding sequence (SEQ ID NO:1078) Table 24 (mouse gene: Rasa2; human gene RASA2) Mouse genomic sequence (SEQ ID NO: 1079) Mouse mRNA sequence (SEQ ID NO:1080) Mouse coding sequence (SEQ ID NO:1081) Human genomic sequence (SEQ ID NO:1082) Human mRNA sequence (SEQ ID NO:1083) Human coding sequence (SEQ ID NO:1084) Table 25 (mouse gene: Gatal; human gene GATA1) Mouse genomic sequence (SEQ ID NO:1085) Mouse mRNA sequence (SEQ ID NO:1086) Mouse coding sequence (SEQ ID NO:1087) Human genomic sequence (SEQ ID NO:1088) Human mRNA sequence (SEQ ID NO:1089) Human coding sequence (SEQ ID NO:1090) Table 26 (mouse gene: Fkbp5; human gene Mouse genomic sequence (SEQ ID NO: 1091) SMouse mRNA sequence (SEQ ID NO:1092) Mouse coding sequence (SEQ ID NO:1093) Human genomic sequence (SEQ ID NO: 1094) Human mRNA sequence (SEQ ID NO:1095) Human coding sequence (SEQ ID NO:1096) N Table 27 (mouse gene: Rel; human gene REL) Mouse genomic sequence (SEQ ID NO: 1097) S Mouse mRNA sequence (SEQ ID NO: 1098) Mouse coding sequence (SEQ ID NO:1099) Human genomic sequence (SEQ ID NO:1100) Human mRNA sequence (SEQ ID NO: 1101) Human coding sequence (SEQ ID NO: 1102) Table 28 (mouse gene: Icsbp; human gene ICSBP1) Mouse genomic sequence (SEQ ID NO:1103) Mouse mRNA sequence (SEQ ID NO:1104) Mouse coding sequence (SEQ ID NO:1105) Human genomic sequence (SEQ ID NO:1106) Human mRNA sequence (SEQ ID NO:1107) Human coding sequence (SEQ ID NO:1108) Table 29 (mouse gene: Bmil; human gene BMI1) Mouse genomic sequence (SEQ ID NO:1109) Mouse mRNA sequence (SEQ ID NO:1110) Mouse coding sequence (SEQ ID NO: 1111) Human genomic sequence (SEQ ID NO:1112) Human mRNA sequence (SEQ ID NO: 1113) Human coding sequence (SEQ ID NO: 1114) Table 30 (mouse gene: Runxl; human gene RUNX1) Mouse genomic sequence (SEQ ID NO: 1115) Mouse mRNA sequence (SEQ ID NO:1116) Mouse coding sequence (SEQ ID NO:1117) Human genomic sequence (SEQ ID NO:1 118) Human mRNA sequence (SEQ ID NO: 1119) Human coding sequence (SEQ ID NO: 1120) Table 31 (mouse gene: I12ra; human gene IL2RA) Mouse genomic sequence (SEQ ID NO:1121) Mouse mRNA sequence (SEQ ID NO:1122) Mouse coding sequence (SEQ ID NO:1123) Human genomic sequence (SEQ ID NO:1124) Human mRNA sequence (SEQ ID NO:1125) Human coding sequence (SEQ ID NO:1126) Table 32 (mouse gene: Nfkbl; human gene NFKB 1) Mouse genomic sequence (SEQ ID NO:1127) Mouse mRNA sequence (SEQ ID NO:1128) Mouse coding sequence (SEQ ID NO:1129) Human genomic sequence (SEQ ID NO: 1130) Human mRNA sequence (SEQ ID NO:1131) Human coding sequence (SEQ ID NO:1132) Table 33 (mouse gene: Fyn; human gene FYN) Mouse genomic sequence (SEQ ID NO: 1133) Mouse mRNA sequence (SEQ ID NO:1134) Mouse coding sequence (SEQ ID NO: 1135) Human genomic sequence (SEQ ID NO:1136) Human mRNA sequence (SEQ ID NO:1137) Human coding sequence (SEQ ID NO:1138) Table 34 (mouse gene: Nfkbill; human gene NFKBIL1) Mouse genomic sequence (SEQ ID NO:1139) Mouse mRNA sequence (SEQ ID NO:1140) Mouse coding sequence (SEQ ID NO:1141)
O
Human genomic sequence (SEQ ID NO: 1142) Human mRNA sequence (SEQ ID NO:1143) Human coding sequence (SEQ ID NO:1144) Table 35 (mouse gene: Flt3; human gene FLT3) Mouse genomic sequence (SEQ ID NO:1145) S Mouse mRNA sequence (SEQ ID NO: 1146) Mouse coding sequence (SEQ ID NO: 1147) C- Human genomic sequence (SEQ ID NO: 1148) 0 Human mRNA sequence (SEQ ID NO: 1149) C Human coding sequence (SEQ ID NO: 1150) Table 36 (mouse gene: Dntt; human gene DNTT) Mouse genomic sequence (SEQ ID NO:1151) Mouse mRNA sequence (SEQ ID NO:1152) Mouse coding sequence (SEQ ID NO:1153) Human genomic sequence (SEQ ID NO: 1154) Human mRNA sequence (SEQ ID NO: 1155) Human coding sequence (SEQ ID NO:1156) Table 37 (mouse gene: Znfnlal; human gene ZNFN1A1) Mouse genomic sequence (SEQ ID NO:1157) Mouse mRNA sequence (SEQ ID NO:1158) Mouse coding sequence (SEQ ID NO:1159) Human genomic sequence (SEQ ID NO:1160) Human mRNA sequence (SEQ ID NO:1161) Human coding sequence (SEQ ID NO:1162) Table 38 (mouse gene: Tbx21; human gene TBX21) Mouse genomic sequence (SEQ ID NO:1163) Mouse mRNA sequence (SEQ ID NO:1164) Mouse coding sequence (SEQ ID NO:1165) Human genomic sequence (SEQ ID NO:1166) Human mRNA sequence (SEQ ID NO:1167) S Human coding sequence (SEQ ID NO: 1168) Table 39 (mouse gene: Stat5b; human gene Mouse genomic sequence (SEQ ID NO: 1169) S Mouse mRNA sequence (SEQ ID NO: 1170) Mouse coding sequence (SEQ ID NO:1171) C1 Human genomic sequence (SEQ ID NO: 1172) S Human mRNA sequence (SEQ ID NO:1173) Human coding sequence (SEQ ID NO: 1174) S Table 40 (mouse gene: Sema4d; human gene SEMA4D) Mouse genomic sequence (SEQ ID NO: 1175) Mouse mRNA sequence (SEQ ID NO:1176) Mouse coding sequence (SEQ ID NO 1177) Human genomic sequence (SEQ ID NO 1178) Human mRNA sequence (SEQ ID NO:1179) Human coding sequence (SEQ ID NO:1180) Table 41 (mouse gene: Mdm2; human gene MDM2) Mouse genomic sequence (SEQ ID NO:1181) Mouse mRNA sequence (SEQ ID NO:1182) Mouse coding sequence (SEQ ID NO:1183) Human genomic sequence (SEQ ID NO:1184) Human mRNA sequence (SEQ ID NO:1185) Human coding sequence (SEQ ID NO:1186) Table 42 (mouse gene: Prlr; human gene PRLR) Mouse genomic sequence (SEQ ID NO:1187) Mouse mRNA sequence (SEQ ID NO:1188) Mouse coding sequence (SEQ ID NO:1189) Human genomic sequence (SEQ ID NO: 1190) Human mRNA sequence (SEQ ID NO:1191) Human coding sequence (SEQ ID NO: 1192) S Table 43 (mouse gene: Topl; human gene TOP1) Mouse genomic sequence (SEQ ID NO:1193) J Mouse mRNA sequence (SEQ ID NO:1194) Mouse coding sequence (SEQ ID NO: 1195) Human genomic sequence (SEQ ID NO: 1196) Human mRNA sequence (SEQ ID NO:1197) O Human coding sequence (SEQ ID NO: 1198) Table 44 (mouse gene: DusplO; human gene DUSPI0) Mouse genomic sequence (SEQ ID NO: 1199) Mouse mRNA sequence (SEQ ID NO: 1200) Mouse coding sequence (SEQ ID NO:1201) Human genomic sequence (SEQ ID NO:1202) Human mRNA sequence (SEQ ID NO:1203) Human coding sequence (SEQ ID NO:1204) Table 45 (mouse gene: Fil; human gene FLII) ,Mouse genomic sequence (SEQ ID NO:1205) Mouse mRNA sequence (SEQ ID NO:1206) Mouse coding sequence (SEQ ID NO:1207) Human genomic sequence (SEQ ID NO:1208) Human mRNA sequence (SEQ ID NO: 1209) Human coding sequence (SEQ ID NO:1210) Table 46 (mouse gene: Tk2; human gene TK2) Mouse genomic sequence (SEQ ID NO:1211) Mouse mRNA sequence (SEQ ID NO:1212) Mouse coding sequence (SEQ ID NO:1213) Human genomic sequence (SEQ ID NO:1214) Human mRNA sequence (SEQ ID NO:1215) Human coding sequence (SEQ ID NO:1216) Table 47 (mouse gene: Nuprl) Mouse genomic sequence (SEQ ID NO:1217) Mouse mRNA sequence (SEQ ID NO:1218) S Mouse coding sequence (SEQ ID NO:1219) O Human genomic sequence (SEQ ID NO:1220) Human mRNA sequence (SEQ ID NO:1221) Human coding sequence (SEQ ID NO: 1222) C Table 48 (mouse gene: Zfhxlb; human gene ZFHX1B) Mouse genomic sequence (SEQ ID NO: 1223) Mouse mRNA sequence (SEQ ID NO: 1224) S Mouse coding sequence (SEQ ID NO:1225) Human genomic sequence (SEQ ID NO:1226) Human mRNA sequence (SEQ ID NO:1227) Human coding sequence (SEQ ID NO:1228) Table 49 (mouse gene: Vdacl; human gene VDAC1) Mouse genomic sequence (SEQ ID NO: 1229) Mouse mRNA sequence (SEQ ID NO:1230) Mouse coding sequence (SEQ ID NO:1231) Human genomic sequence (SEQ ID NO:1232) Human mlRA sequence (SEQ ID NO:1233) Human coding sequence (SEQ ID NO:1234) Table 50 (mouse gene: Nfatcl; human gene NFATCI) Mouse genomic sequence (SEQ ID NO: 1235) Mouse mRNA sequence (SEQ ID NO:1236) Mouse coding sequence (SEQ ID NO:1237) Human genomic sequence (SEQ ID NO:1238) Human mRNA sequence (SEQ ID NO: 1239) Human coding sequence (SEQ ID NO:1240) Table 51 (mouse gene: Syk; human gene SYK) Mouse genomic sequence (SEQ ID NO:1241) Mouse mRNA sequence (SEQ ID NO:1242) Mouse coding sequence (SEQ ID NO:1243) Human genomic sequence (SEQ ID NO:1244) Human mRNA sequence (SEQ ID NO:1245) Human coding sequence (SEQ ID NO:1246) S Table 52 (mouse gene: Gnbl; human gene GNB1) Mouse genomic sequence (SEQ ID NO:1247) Mouse mRNA sequence (SEQ D NO:1248) Mouse codimRNA sequence (SEQ ID NO:1248) 0 Mouse coding sequence (SEQ ID NO: 1249) N, Human genomic sequence (SEQ ID NO:1250) O Human mRNA sequence (SEQ ID NO:1251) Human coding sequence (SEQ ID NO: 1252).
Table 53 (mouse gene: Ccnd2; human gene CCND2) Mouse genomic sequence (SEQ ID NO:1253) Mouse mRNA sequence (SEQ ID NO:1254) Mouse coding sequence (SEQ ID NO:1255) Human genomic sequence (SEQ ID NO:1256) Human mRNA sequence (SEQ ID NO:1257) Human coding sequence (SEQ ID NO: 1258) Table 54 (mouse gene Tnfrsf6; human gene TNFRSF6) Mouse genomic sequence (SEQ ID NO:1259) Mouse mRNA sequence (SEQ ID NO:1260) Mouse coding sequence (SEQ ID NO:1261) Human genomic sequence (SEQ ID NO:1262) Human mRNA sequence (SEQ ID NO:1263) Human coding sequence (SEQ ID NO:1264) Table 55 (mouse gene Irf2; human gene IRF2) Mouse genomic sequence (SEQ ID NO:1265) Mouse mRNA sequence (SEQ ID NO:1266) Mouse coding sequence (SEQ ID NO:1267) Human genomic sequence (SEQ ID NO:1268) Human mRNA sequence (SEQ ID NO:1269) O Human coding sequence (SEQ ID NO:1270) U) Table 56 (mouse gene Morf; human gene: MORF) Mouse genomic sequence (SEQ ID NO:1271) Mouse mRNA sequence (SEQ ID NO:1272) Mouse coding sequence (SEQ ID NO:1273) g Human genomic sequence (SEQ ID NO: 1274) N Human mRNA sequence (SEQ ID NO:1275) Human coding sequence (SEQ ID NO: 1276) Table 57 (mouse gene: Runx3; human gene: RUNX3) Mouse genomic sequence (SEQ ID NO:1277) Mouse mRNA sequence (SEQ ID NO:1'278) Mouse coding sequence (SEQ ID NO:1279) Human genomic sequence (SEQ ID NO:1280) Human mRNA sequence (SEQ ID NO:1281) Human coding sequence (SEQ ID NO:1282) Table 58 (mouse gene: Bell Ib; human gene: BCLI IB) Mouse genomic sequence (SEQ ID NO:1283) Mouse mRNA sequence (SEQ ID NO:1284) Mouse coding sequence (SEQ ID NO:1285) Human genomic sequence (SEQ ID NO:1286) Human mRNA sequence (SEQ ID NO:1287) Human coding sequence (SEQ ID NO:1288) Table 59 (mouse gene: Arhgefl; human gene: ARHGEF1) Mouse genomic sequence (SEQ ID NO:1289) Mouse mRNA sequence (SEQ ID NO: 1290) Mouse coding sequence (SEQ ID NO:1291) Human genomic sequence (SEQ ID NO:1292) Human mRNA sequence (SEQ ID NO: 1293) Human coding sequence (SEQ ID NO:1294) Table 60 (mouse gene: Ptprk; human gene: PTPRK) Mouse genomic sequence (SEQ ID NO:1295) U Mouse mRNA sequence (SEQ ID NO: 1296) Mouse coding sequence (SEQ ID NO:1297) Human genomic sequence (SEQ ID NO:1298) Human mRNA sequence (SEQ ID NO:1299) Human coding sequence (SEQ ID NO: 1300) Table 61 (mouse gene: Mcmd5; human gene: Mouse genomic sequence (SEQ ID NO:1301) Mouse mRNA sequence (SEQ ID NO:1302) Mouse coding sequence (SEQ ID NO:1303) Human genomic sequence (SEQ ID NO:1304) Human mRNA sequence (SEQ ID NO:1305) Human coding sequence (SEQ ID NO:1306) Table 62 (mouse gene: Matn4; human gene: MATN4) Mouse genomic sequence (SEQ ID NO:1307) Mouse mRNA sequence (SEQ ID NO:1308) Mouse coding sequence (SEQ ID NO:1309) Human genomic sequence (SEQ ID NO:1310) Human mRNA sequence (SEQ ID NO:1311) Human coding sequence (SEQ ID NO:1312) Table 63 (mouse gene: Tnfsfl 1; human gene TNFSFI1) Mouse genomic sequence (SEQ ID NO:1313) Mouse mRNA sequence (SEQ ID NO:1314) Mouse coding sequence (SEQ ID NO:1315) Human genomic sequence (SEQ ID NO:1316) Human mRNA sequence (SEQ ID NO:1317) Human coding sequence (SEQ ID NO:1318) Table 64 (mouse gene: Itk; human gene ITK) Mouse genomic sequence (SEQ ID NO: 1319) S Mouse mRNA sequence (SEQ ID NO:1320) S Mouse coding sequence (SEQ ID NO:1321) Human genomic sequence (SEQ ID NO: 1322) Human mRNA sequence (SEQ ID NO:1323) Human coding sequence (SEQ ID NO:1324) C Table 65 (mouse gene: Fish; human gene: N/A) C Mouse genomic sequence (SEQ ID NO:1325) S Mouse mRNA sequence (SEQ ID NO:1326) Mouse coding sequence (SEQ ID NO:1327) Human genomic sequence (SEQ ID NO: 1328) Human mRNA sequence (SEQ ID NO:1329) Human coding sequence (SEQ ID NO:1330) Table 66 (mouse gene: Egr2; human gene EGR2) Mouse genomic sequence (SEQ ID NO:1331) Mouse mRNA sequence (SEQ ID NO:1332) Mouse coding sequence (SEQ ID NO:1333) Human genomic sequence (SEQ ID NO:1334) Human mRNA sequence (SEQ ID NO:1335) Human coding sequence (SEQ ID NO:1336) Table 67 (mouse gene: Sosl; human gene SOS1) Mouse genomic sequence (SEQ ID NO: 1337) Mouse mRNA sequence (SEQ ID NO:1338) Mouse coding sequence (SEQ ID NO:1339) Human genomic sequence (SEQ ID NO:1340) Human mRNA sequence (SEQ ID NO:1341) Human coding sequence (SEQ ID NO:1342) Table 68 (mouse gene: Pou2afl; human gene POU2AF1) Mouse genomic sequence (SEQ ID NO:1343) Mouse mRNA sequence (SEQ ID NO:1344) Mouse coding sequence (SEQ ID NO:1345)
O
Human genomic sequence (SEQ ID NO:1346) Human mRNA sequence (SEQ ID NO:1347) S Human coding sequence (SEQ ID NO:1348) Table 69 (mouse gene: Mef2c; human gene MEF2C) Mouse genomic sequence (SEQ ID NO:1349) Mouse mRNA sequence (SEQ ID NO:1350) Mouse coding sequence (SEQ ID NO:1351) Human genomic sequence (SEQ ID NO:1352) Human mRNA sequence (SEQ ID NO:1353) S Human coding sequence (SEQ ID NO: 1354) Table 70 (mouse gene: Map3k8; human gene MAP3K8) Mouse genomic sequence (SEQ ID NO:1355) Mouse mRNA sequence (SEQ ID NO:1356) Mouse coding sequence (SEQ ID NO:1357) Human genomic sequence (SEQ ID NO:1358) Human mRNA sequence (SEQ ID NO:1359) Human coding sequence (SEQ ID NO: 1360) Table 71 (mouse gene: Fgfr3; human gene FGFR3) Mouse genomic sequence (SEQ ID NO:1361) Mouse mRNA sequence (SEQ ID NO: 1362) Mouse coding sequence (SEQ ID NO:1363) Human genomic sequence (SEQ ID NO:1364) Human mRNA sequence (SEQ ID NO:1365) Human coding sequence (SEQ ID NO:1366) Table 72 (mouse gene: Cbx8; human gene CBX8) Mouse genomic sequence (SEQ ID NO:1367) Mouse mRNA sequence (SEQ ID NO:1368) Mouse coding sequence (SEQ ID NO:1369) Human genomic sequence (SEQ ID NO:1370) Human mRNA sequence (SEQ ID NO:1371) S Human coding sequence (SEQ ID NO:1372) Table 73 (mouse gene: Lmo2; human gene LMO2) Mouse genomic sequence (SEQ ID NO: 1373) S Mouse mRNA sequence (SEQ ID NO:1374) Mouse coding sequence (SEQ ID NO:1375) C1 Human genomic sequence (SEQ ID NO:1376) C Human mRNA sequence (SEQ ID NO: 1377) Human coding sequence (SEQ ID NO: 1378) Table 74 (mouse gene: Itprl; human gene ITPRI) Mouse genomic sequence (SEQ ID NO:1379) Mouse mRNA sequence (SEQ ID NO: 1380) Mouse coding sequence (SEQ ID NO:1381) Human genomic sequence (SEQ ID NO:1382) Human mRNA sequence (SEQ ID NO:1383) Human coding sequence (SEQ ID NO: 1384) Table 75 (mouse gene: Sell; human gene SELL) Mouse genomic sequence (SEQ ID NO:1385) Mouse mRNA sequence (SEQ ID NO:1386) Mouse coding sequence (SEQ ID NO:1387) Human genomic sequence (SEQ ID NO:1388) Human mRNA sequence (SEQ ID NO: 1389) Human coding sequence (SEQ ID NO:1390) Table 76 (mouse gene: Dpt; human gene DPT) Mouse genomic sequence (SEQ ID NO:1391) Mouse mRNA sequence (SEQ ID NO:1392) Mouse coding sequence (SEQ ID NO:1393) Human genomic sequence (SEQ ID NO:1394) Human mRNA sequence (SEQ ID NO:1395) Human coding sequence (SEQ ID NO:1396) S Table 77 (mouse gene: Pap; human gene PAP) Mouse genomic sequence (SEQ ID NO:1397) Mouse mRNA sequence (SEQ ID NO:1398) Mouse coding sequence (SEQ ID NO:1399) Human genomic sequence (SEQ ID NO: 1400) Human mRNA sequence (SEQ ID NO:1401) Human coding sequence (SEQ ID NO:1402) Ci Table 78 (mouse gene: Blm; human gene BLM) 0 Mouse genomic sequence (SEQ ID NO:1403) C Mouse mRNA sequence (SEQ ID NO: 1404) Mouse coding sequence (SEQ ID NO:1405) Human genomic sequence (SEQ ID NO:1406) Human mRNA sequence (SEQ ID NO: 1407) Human coding sequence (SEQ ID NO:1408) Table 79 (mouse gene: Blrl; human gene BLRI) Mouse genomic sequence (SEQ ID NO: 1409) Mouse mRNA sequence (SEQ ID NO:1410) Mouse coding sequence (SEQ ID NO:1411) Human genomic sequence (SEQ ID NO:1412) Human mRNA sequence (SEQ ID NO:1413) Human coding sequence (SEQ ID NO:1414) Table 80 (mouse gene: Ptp4a2; human gene PTP4A2) Mouse genomic sequence (SEQ ID NO:1415) Mouse mRNA sequence (SEQ ID NO:1416) Mouse coding sequence (SEQ ID NO:1417) Human genomic sequence (SEQ ID NO:1418) Human mRNA sequence (SEQ ID NO:1419) Human coding sequence (SEQ ID NO:1420) Table 81 (mouse gene: Mcm3ap; human gene MCM3AP) Mouse genomic sequence (SEQ ID NO:1421) Mouse mRNA sequence (SEQ ID NO:1422) Mouse coding sequence (SEQ ID NO:1423) Human genomic sequence (SEQ ID NO:1424) Human mRNA sequence (SEQ ID NO:1425) Human coding sequence (SEQ ID NO: 1426) Table 82 (mouse gene: Jak2; human gene JAK2) Mouse genomic sequence (SEQ ID NO:1427) Mouse mRNA sequence (SEQ ID NO:1428) Mouse coding sequence (SEQ ID NO:1429) Human genomic sequence (SEQ ID NO:1430) Human mRNA sequence (SEQ ID NO:1431) Human coding sequence (SEQ ID NO: 1432) Table 83 (mouse gene: Fusl; human gene FUS 1) Mouse genomic sequence (SEQ ID NO:1433) Mouse mRNA sequence (SEQ ID NO: 1434) Mouse coding sequence (SEQ ID NO:1435) Human genomic sequence (SEQ ID NO:1436) Human mRNA sequence (SEQ ID NO: 1437) Human coding sequence (SEQ ID NO:1438) Table 84 (mouse gene: Rassfl; human gene RASSF1) Mouse genomic sequence (SEQ ID NO:1439) Mouse mRNA sequence (SEQ ID NO:1440) Mouse coding sequence (SEQ ID NO:1441) Human genomic sequence (SEQ ID NO:1442) Human mRNA sequence (SEQ ID NO:1443) Human coding sequence (SEQ ID NO:1444) Table 85 (mouse gene: Pik3rl; human gene PIK3RI) Mouse genomic sequence (SEQ ID NO:1445) Mouse mRNA sequence (SEQ ID NO:1446) Mouse coding sequence (SEQ ID NO:1447) Human genomic sequence (SEQ ID NO: 1448) Human mRNA sequence (SEQ ID NO: 1449) Human coding sequence (SEQ ID NO: 1450) Table 86 (mouse gene: Braf; human gene BRAF) Mouse genomic sequence (SEQ ID NO:1451) Mouse mRNA sequence (SEQ ID NO:1452) Mouse coding sequence (SEQ ID NO:1453) Human genomic sequence (SEQ ID NO:1454) Human mRNA sequence (SEQ ID NO:1455) Human coding sequence (SEQ ID NO:1456) Table 87 (mouse gene: Tle3; human gene: TLE3) Mouse genomic sequence (SEQ ID NO:1457) Mouse mRNA sequence (SEQ ID NO:1458) Mouse coding sequence (SEQ ID NO:1459) Human genomic sequence (SEQ ID NO:1460) Human mRNA sequence (SEQ ID NO: 1461) Human coding sequence (SEQ ID NO:1462) Table 88 (mouse gene: Nek2; human gene NEK2) Mouse genomic sequence (SEQ ID NO:1463) Mouse mRNA sequence (SEQ ID NO:1464) Mouse coding sequence (SEQ ID NO:1465) Human genomic sequence (SEQ ID NO:1466) Human mRNA sequence (SEQ ID NO: 1467) Human coding sequence (SEQ ID NO:1468) Table 89 (mouse gene: Nr3cl; human gene NR3C1) Mouse genomic sequence (SEQ ID NO: 1469) Mouse mRNA sequence (SEQ ID NO:1470) Mouse coding sequence (SEQ ID NO:1471) Human genomic sequence (SEQ ID NO:1472) Human mRNA sequence (SEQ ID NO: 1473) Human coding sequence (SEQ ID NO:1474) O Table 90 (mouse gene: Dadl; human gene DAD1) Mouse genomic sequence (SEQ ID NO: 1475) 0 Mouse mRNA sequence (SEQ ID NO:1476) Mouse coding sequence (SEQ ID NO:1477) Human genomic sequence (SEQ ID NO:1478) C Human mRNA sequence (SEQ ID NO: 1479) Human coding sequence (SEQ ID NO: 1480) Table 91 (mouse gene: Lck; human gene LCK) Mouse genomic sequence (SEQ ID NO:1481) Mouse mRNA sequence (SEQ ID NO:1482) Mouse coding sequence (SEQ ID NO:1483) Human genomic sequence (SEQ ID NO:1484) Human mRNA sequence (SEQ ID NO:1485) Human coding sequence (SEQ ID NO:1486) Table 92 (mouse gene: Git2; human gene GIT2) Mouse genomic sequence (SEQ ID NO: 1487) Mouse mRNA sequence (SEQ ID NO:1488) Mouse coding sequence (SEQ ID NO:1489) Human genomic sequence (SEQ ID NO:1490) Human mRNA sequence (SEQ ID NO:1491) Human coding sequence (SEQ ID NO:1492).
Table 93 (mouse gene: Anp32; human gene N/A) Mouse genomic sequence (SEQ ID NO:1493) Mouse mRNA sequence (SEQ ID NO:1494) Mouse coding sequence (SEQ ID NO:1495) Human genomic sequence (SEQ ID NO:1496) Human mRNA sequence (SEQ ID NO:1497) Human coding sequence (SEQ ID NO:1498).
Table 94 (mouse gene: Map2k5; human gene Mouse genomic sequence (SEQ ID NO:1499) Mouse mRNA sequence (SEQ ID NO: 1500) Mouse coding sequence (SEQ ID NO:1501) Human genomic sequence (SEQ ID NO: 1502) Human mRNA sequence (SEQ ID NO:1503) Human coding sequence (SEQ ID NO:552 1504).
S Table 95 (mouse gene: Cd28; human gene CD28) Mouse genomic sequence (SEQ ID NO: 1505) S Mouse mRNA sequence (SEQ ID NO:1506) Mouse coding sequence (SEQ ID NO:1507) Human genomic sequence (SEQ ID NO:1508) Human mRNA sequence (SEQ ID NO: 1509) Human coding sequence (SEQ ID NO:1510).
Table 96 (mouse gene: Sept9; human gene Msf) Mouse genomic sequence (SEQ ID NO:1511) Mouse mRNA sequence (SEQ ID NO:1512) Mouse coding sequence (SEQ ID NO:1513) Human genomic sequence (SEQ ID NO:1514) Human mRNA sequence (SEQ ID NO:1515) Human coding sequence (SEQ ID NO:1516).
Table 97 (mouse gene: FzdlO; human gene Mouse genomic sequence (SEQ ID NO:1517) Mouse mRNA sequence (SEQ ID NO:1518) Mouse coding sequence (SEQ ID NO:1519) Human genomic sequence (SEQ ID NO:1520) Human mRNA sequence (SEQ ID NO:1521) Human coding sequence (SEQ ID NO:1522).
Table 98 (mouse gene: Calm2; human gene CALM2) Mouse genomic sequence (SEQ ID NO:1523) S Mouse mRNA sequence (SEQ ID NO: 1524) SMouse coding sequence (SEQ ID NO: 1525) Human genomic sequence (SEQ ID NO: 1526) Human mRNA sequence (SEQ ID NO:1527) Human coding sequence (SEQ ID NO:1528).
C Table 99 (mouse gene: Ncf4; human gene NCF4) SMouse genomic sequence (SEQ ID NO: 1529) Mouse mRNA sequence (SEQ ID NO: 1530) S Mouse coding sequence (SEQ ID NO: 1531) Human genomic sequence (SEQ ID NO:1532) Human mRNA sequence (SEQ ID NO:1533) Human coding sequence (SEQ ID NO: 1534).
Table 100 (mouse gene: Rac2; human gene RAC2) Mouse genomic sequence (SEQ ID NO:1535) Mouse mRNA sequence (SEQ ID NO:1536) Mouse coding sequence (SEQ ID NO:1537) Human genomic sequence (SEQ ID NO:1538) Human mRNA sequence (SEQ ID NO:1539) Human coding sequence (SEQ ID NO: 1540).
Table 101 (mouse gene: Mbnl; human gene MBNL) Mouse genomic sequence (SEQ ID NO: 1541) Mouse mRNA sequence (SEQ ID NO:1542) Mouse coding sequence (SEQ ID NO:1543) Human genomic sequence (SEQ ID NO:1544) Human mRNA sequence (SEQ ID NO:1545) Human coding sequence (SEQ ID NO:1546).
Table 102 (mouse gene: mCG10516; human gene N/A) Mouse genomic sequence (SEQ ID NO: 1547) Mouse mRNA sequence (SEQ ID NO:1548) Mouse coding sequence (SEQ ID NO:1549) Human genomic sequence (SEQ D O Human genomiRNA sequence (SEQ ID NO:1550) Human mRNA sequence (SEQ ID NO:1551) Human coding sequence (SEQ ID NO:1552) Table 103 (mouse gene: Rorc; human gene RORC) Mouse genomic sequence (SEQ ID NO:1553) SMouse mRNA sequence (SEQ ID NO:1554) Mouse coding sequence (SEQ ID NO:1555) S Human genomic sequence (SEQ ID NO:1556) Human mRNA sequence (SEQ ID NO: 1557) Human coding sequence (SEQ ID NO:1558) Table 104 (mouse gene mCG15938; human gene BATI) Mouse genomic sequence (SEQ ID NO:1559) Mouse mRNA sequence (SEQ ID NO:1560) Mouse coding sequence (SEQ ID NO:1561) Human genomic sequence (SEQ ID NO:1562) Human mRNA sequence (SEQ ID NO:1563) Human coding sequence (SEQ ID NO:1564) Table 105 (mouse gene: Iqgapl; human gene IQGAP1) Mouse genomic sequence (SEQ ID NO:1565) Mouse mRNA sequence (SEQ ID NO: 1566) Mouse coding sequence (SEQ ID NO:1567) Human genomic sequence (SEQ ID NO:1568) Human mRNA sequence (SEQ ID NO:1569) Human coding sequence (SEQ ID NO: 1570) Table 106 (mouse gene Zpf29; human gene: hCG27579) Mouse genomic sequence (SEQ ID NO:1571) Mouse mRNA sequence (SEQ ID NO:1572) Mouse coding sequence (SEQ ID NO:1573) Human genomic sequence (SEQ ID NO:1574) Human mRNA sequence (SEQ ID NO: 1575) S Human coding sequence (SEQ ID NO:1576) Table 107 (mouse gene: Kcnj9; human gene: KCNJ9) Mouse genomic sequence (SEQ ID NO: 1577) Mouse mRNA sequence (SEQ ID NO: 1578) Mouse coding sequence (SEQ ID NO:1579) Human genomic sequence (SEQ ID NO:1580) C Human mRNA sequence (SEQ ID NO: 1581) Human coding sequence (SEQ ID NO:1582) S Table 108 (mouse gene: Ppp3cc; human gene: PPP3CC) Mouse genomic sequence (SEQ ID NO:1583) Mouse mRNA sequence (SEQ ID NO:1584) Mouse coding sequence (SEQ ID NO:1585) Human genomic sequence (SEQ ID NO: 1586) Human mRNA sequence (SEQ ID NO: 1587) Human coding sequence (SEQ ID NO: 1588) Table 109 (mouse gene: mCG9110; human gene: hCG27579) Mouse genomic sequence (SEQ ID NO:1589) Mouse mRNA sequence (SEQ ID NO:1590) Mouse coding sequence (SEQ ID NO:1591) Human genomic sequence (SEQ ID NO:1592) Human mRNA sequence (SEQ ID NO:1593) Human coding sequence (SEQ ID NO: 1594) Table 110 (mouse gene: mCG2257; human gene: PRDM11) Mouse genomic sequence (SEQ ID NO:1595) Mouse mRNA sequence (SEQ ID NO:1596) Mouse coding sequence (SEQ ID NO:1597) Human genomic sequence (SEQ ID NO: 1598) Human mRNA sequence (SEQ ID NO:1599) Human coding sequence (SEQ ID NO:1600) Table 111 (mouse gene: mCG17918; human gene: hCG23764) S Mouse genomic sequence (SEQ ID NO:1601) SMouse mRNA sequence (SEQ ID NO:1602) Mouse coding sequence (SEQ ID NO:1603) Human genomic sequence (SEQ ID NO:1604) Human mRNA sequence (SEQ ID NO:1605) Human coding sequence (SEQ ID NO:1606) Table 112 (mouse gene: Lfng; human gene: LFNG) Mouse genomic sequence (SEQ ID NO:1607) Mouse mRNA sequence (SEQ ID NO:1608) Mouse coding sequence (SEQ ID NO:1609) Human genomic sequence (SEQ ID NO:1610) Human mRNA sequence (SEQ ID NO: 1611) Human coding sequence (SEQ ID NO:1612).
Table 1 SEQ SEQUENCE~te "SEQUENCE") CLONE CLASS GENE ID j1C jr T NO:{C T {C "CLONE "CLAS "GENE" 2} SIFICA \L 2)
TION"
MUTATION \L 2) GATCAAAGCAATCTCTATGTCT-fTCTCTG
CTGTCCTCCTCAGACATCTCCAGAGAGC
TGGGATATYHCT17CCCAMrGAGA-rI
ATGAAGFFGTTTCTAGAGTGCATGAGGC
AGGT7GAAGGATAAGTACACAGGTCCC AAGGAACCAAGCGT=fCACTGACGGTG ATGAGTCTTGTTCGTGAGA'G1TGTGA TTCTCAGCCTrCTCTrCCCCTGTGTGTG CTCTTCAT1TICTGGTrCTGTCTGCCTrAO PM000619 CACCTCCTGGGGAAGTGCTGTGCmT- p000632 A Spr GATIC'IrrGGAGCCCAGTI'Gl'rAATCATA
AGAGCTGATATTTTGAAAGAGTGTGTCA
ACCTAGATGCACAGGGAAGCCAAAGCA
2 EM000620 TTCAGCC p000633 D
ATATGACCACAAGGAAATAJ\GATAAAG
TGTTCATACTGAA1TrATAATGAAAAGT
GATC
3 1rM000621 p000634 C
GAACAGGCATGGCTTTACTTGTACAATG
AGGAAACCAAGGCAGAGATTGCAAAGC
GGGTCCTACACO MTGCTCCATGCCCTG C1TCTCTGACCACAGTGTACTGAGAATA
TGCTGAGCCCTAGTTCCTGGGGAGGAGG
CAGAAGAGAGCAGCATCCTIGCCCACTFIG
AAGGCGTGCACACATAGTTCCTGTCTGA
4 11000622 TC p000638 ID GATCAGGAGACCACACCCAGCTAGCCTl
CTCTGACTGGGTATCCTTGGTCAGCCAG
C='~CTrCACCTCATGTTCTCA1TrTGCA AACTCACATGAACACTAMflGACCTACA CACTTCATAAAGCTG1TAGAGAC
GAGATAATACAGGAGGAACGCTACAAT
IM000623 ATTAAATGATATGTATT7ATAT pOOO 6 3 9 D
AGTGTTTAGGTCAGCTGGTGCAGGAGAA
GCTTCITGAGGAAGACGACCATCTGGCA
AGGCCTGATGGTAGAAAATAATGGAC'fl
CTCTCCAACTGAGTAGGAA=~GATGAT
16 IM000624 IC p000640 ID F SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ED {TC {TC (TC
NO:
"CLONE "CLAS "GENE" 21 STFICA \L 2)
TION"
-MUTATION \L 2) ATCAGTAAG'rTAATCCTAAGAA~rACTA TGCA1TPTCCCCTCTIT1TIAACAACAT TCCTCCTfrAGC1TATATGAGGCTCTAGTG
CCCGGAGACMTAATACTGCCCTAACAT
GATGGTGGCTC1TGTCCCTCT7CTCAG
CCACTGAAATCTGACAGTGGGGAAGA
ATAATAAGAATAAGAAACTFAGATGGT
T1TAAATATAGATATAAAAACAGTrCTT CGACTATTCTCAATAAAGAAATrCAGTC 7 AAAAGAATTTCAGTCCTAACACAATGAT EM000625 c p000641 D
GATCATCAGAGTCCTGCATCTTATGTGT
GCAGTGTrCAGCAATACAGGCTTACC
TTCAACCTCTAACAGGCAACCAGATGCT
ACAATAGC'ITATA1TG1TIAGAAATCA
CTTGGACTACTCTAAACAACAACTTGAG
TGAAGGCTCTTGTATCTGATACTGGAG
TGTrAGTCTATGACACTTGTGGGGAG
ACATGTCTGCACAAGTAGCATATGTGTG
TACATGTATATrGTATACATATATAGTIT
TGCTCTATGTATGTATGTGTATATGTATG
8 TATGTATATGTATATGTATGTATATATAT 1M000626 AG pOOO 642
D
AAGGGACCTGATAATCGTGITGGCAACT
GGGCTACAATTAGTrATCAATrGC'FrGC
'TFGCCACCTGCCCTGCTCCATAGAGAAT
CATAGTCTGGGGAGTGTGGAGGAATAG
CGGAGTCATCTAAACACATCACTGCTGC
CCCCACCATTTGCCTGCCAGCAGGCCCC
9 1M000627 TGCCTTTCATI=GCATITCTCCCTCTTA CAAGCAAATGGCGCTCACTGATC p000643 D GTTrGGGGATTGTACAGAATGCACAGCG
TAGTATTCAGGAAAAAGGAAACTGGGA
AATAATGTATAAATTAAAATCAGCTI
TAATITAGCTTAACACACACATACGAAGG
1M000628 CAAAAATGTAACGTTAC1TGATC p000644 lK yc GATCTCATrACAGATGGTrGTGAGCTAC M000629 CATGTGG pO000647 R SEQ SEQUENCE{tc "SEQUENCE") CLONE CLASS GENE ID {TC {TC {TC
NO:
"CLONE 'CLAS "GENE" 21 SIFICA \L 2)
TION"
MUTATION kL 2)
GATCTCAGGAGGCACCGAGAGACTCAG
CATGGACTCAAATGAGTACCCTGGCAGC
CCGCAACACCAGCTGTGTAACACTACCG
TGAGGGATGTCT[CCCTGCCI'GCCTCCA
GCCCCTTCTCAGGCCCTGAGTCCAGTGT
GCAAAGCTCATCATGGTTAGTCCCCYTFC
12 IM000630 ACCT p000649 K Of]
AGAGCACCCGACTGCTCTTCCGAAGGTC
CAGAGTTCAAATCCCAGCAACCACATGG
TGGCTCACAACCATCCGTAACAAGATC
13 IM000631 pOOO 6 5O R
GATCAAATCCTGTCAGGGAGAGGGGCTC
CTCCCAG'fAGTGCCATCCCATAATAATA
AGAAGGACTCCTGGGCCTCAGTGAAGTC
AGGCTGACCACFACTGCAGGTTAGTCAT
GACCAGTAGCCAGAATGGAACGAAGGG
TGACCCAGTGTGAGGACACAGCCCCAG
GCAACTGCTTCTGCTTrGAGCCAAGTTG
T-TACCCCAAAGCTCGTCATTCCGCTTGG
TTrCTCATGTGTGTGAGCTGCACATATG 14 [IM000632 GAGGTCCCCCTTI'GTITCCCTT p000651 D
GTGAGGAAGGTCCCTCTGCATTCTAACC
TrCCTCAACTCCACCAGCCTCGGCGTl7 AAGGGAGAAATAITACCG~rCCCFFTGG GCCAAGTflGGAGCCAGTFGAAGTAGTCG GAAATGTACAGTCACAGGAAAT-rGCTGG
TACCAAGGCTGGAGGAACAAAGAGAAG
ACTTGTCACAAGAGGCCAGAGAGGAAG
TCACCCAGTACAAACTGAAGCGCGCGCG
CACACACACACACACACACACACACAC
1M000633 GCACACACACACACACACGATC p000652 D
TGGCCGCCTAGACAAGCTGACCATCACC
TCCCAGAACCTGCAACTGGAGjAGCC'ITC
GCATGAAGCTTCCGAAATGTGCGTGCTC
CACCTGTCCCTCACCTCACAGACATCAT
16 11M000634 rrTcCCAMI~AGCCCCTCCCGATC p000654 A i
GATCCCCTGGAAMTACAGTCGGTTCCA
17 1M000635 ACAATCATGTAGATG I pO00656 IC F SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID {TC ITC {TC
NO:
"CLONE "CLAS 'GENE" 2) STFICA \L 2)
TION"
MUTATION T12) GATCGGCTATAGCATGTCAATGTrfA CCCAGAAGAATAGCACAGATATATMrC ACATCAATGCTrATI'GCAGTATTATTCA
CAGTGGCTATGTAATGGAACCAACCTAC
ATGGCCAGCAACTGAATAGATTAAGAA
AATATATATACACAATGGTGCTT=C
GGCTATAAAGAAGAATGAAGTTATGTTG
M~GTTAGAAGATGGATGAAAGTGGAGA
TGATAATATCAAGTGCACAGTCAACCTC
TCTCTCTCACCTCCCCCGCCCCGCTCTI
CTCTCTCATATACA1TfGAGAGTAGCAG
TAAACTGTCTGAGAACAAAGGOGATTA
ATGGGAGGGGAGAAGATTAAGGAGCGG
18 1M000636 AAGGGTAGTAGGTAGTAT p000659 A Cr2
GATCGGCTTCTATGGACTGAGTGTGTAA
19 IN4000637 GAAAACATT pOOO 66 I D TrAGGAGGGTAGAGAACA1TCAGGAAT CAAGAACAAGCATIrAACACCCACTGA GCTATCCTGTGGATGGTGGTGG1T7r rG=1GT'rGG=rTGTIAGGAAGTCAG
GGATGGGGTGGGAATCTCACTCTGTGGC
TAGACTTGCAACAATCCCAAATTCTOG
AATGATAAGCAAGAGAGCTGTCTAGTCC
CAGTCrCAGATACATGCTGTTAATM~CT
ACTACTGCTATAACACATAGGCTCAAAT
GCGGTGGCTTACCTAACACACCCTGTGC
AGTTCTGAAAGTCGTAACTCTGGCACGA
1N4000638 TC p000662 D
ATGCTAAGCTGTGACTCCTCTCGATACG
21 1NM000639 AGACCCTGGCTGCCCTCCMICCCGATC p,000663 D
GATCGTCTGGAAGAGCAGTCAGTATTCT
TAACTGCTGAGCCATC1TGCAGCCCCC AGTCTTrGGGTTrG TTG1T TGGTrGGTTGG'ITGGTTrGGTTTAGTG GTTGGTTCAAGACAGGG1TTrCTCTGTG
TTGCCCTGGATGTCCTGGAACTCTCTTTG
TAGACCAGGGTGGCCM~AACTCACAGA
AATGCGCCTGCTAGGATTrAAAGCTGTGT CCCACCACTATATATATATGfGTG 122 1 M000640 I ,000665 IR I- SEQ SEQIJENCE~tc "SEQUENCE") CLONE CLASS GENE ID ITC ITC {TC
NO:
"CLONE "CLAS "GENE" 21 SIFICA \L 21
TION"
MUTATION \L 2} GTCACAGTG2FAGAGCCACAGACGGGG
GAACCTACTGGCTIGTICCTGGGTTCCTGT
AAACTAGGGGACAAAGCTGCCACAGCC
23 1M000641 AGACTTAGCTGCGATC p 000666
D
GATCGCTGCTTCTGTAAATCCGCAACGA
CAAT7GTTATCTrCTCCTTCTIrTC1T= ATTTGT1TYCTAT1TA1TrCAGAT
GAACTCTCATGTAGCCCAGGCTGGTCTC
AAAC'rCCCTCTGTAGCTGACGGCAACCT
TGAAC
24 1M000642 p000668 R ITCCTACACCATAGCAMrAGTTGTAGG 1M000643 CAGAAGCGATC 00O0669 D GATCGGCTCAAGGGCTCTAATTrAGTCT AGGAAGTCM1'AGGAAACATGAAAATCT
CCGAGATAAGACCCGGGGTAAAAAGCT
TGAGCCACGGAG'ITAGACATGCCCAGG
GTGGAG]CATGTTCAGAGGT-rCAAGACC CGAATCAGCTACGTAAATAAAGCAlTITG AGGCCTACCTrGGGCTACAAGAGAGTIATrc TlTAAATAAATAAGATGA7TAAAAAAA ACTGITICCCCTTrAGATGGATTAAAAA
AACAAGACAAAACAAAACAAAACAAAA
26 1M000644 ACCCGTcITrGc11ci'rAA p000672 D CTGTCCGTGTGGGAAACGn7rAGCAAGT CCGAGCGTG'rrTCGATC 27 1M000645 p000673 K Nrnyc ATGCGTTCGTATGACAGTrrCTCCAAATG
ACTGTCCCAAAGTCCCAGATJ'CCTGGAA
ACAGTAAAGAGTGGCTCAAACTGTrAGTC
ACTAGTCTATTATCTTAATCATAGTAAC
CAMTGGGTTTGAC1TGAAAACCTGTGA CAGGGAGATAAAT7I1TCTGCCACTGTAGG TGAAGC1TGGAAGGGCTAACCCAATGA 128 IM000646 ATATGGTCAGTCGATC W,000676 C SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: (TC (TC {TC "CLONE "CLAS "GENE" 2) SIFIC \L 2)
TION"
MUTATION \L 2)
AGATGAAGCTATCCCCAGTCCCTAAGCT
GAG'TTCTGCCTGAGACTA'TI7GAAACAG GGTACCCCTGGGTCCCAGn7CAGTrGAC
AGGTAGTGGACGCATGAGAACGGCATA
CCTGGTGGCCGTGCCCGAGAGTGCTGTC
CCTGACCTGCCACTGTGTrCTCCAGAGC
AGCMTCCAATCTGCCTGCTCCTGTCTCC
CCTGCCTGTrGGCACCAGGCAGCCAGAA -FrCCATTTGn1TrGCTrCGCGATAGG CTC'FrGCCATGTAGTCCTTCCTGGCCTAG AACTTGATATGTAGACU7CCCCCCT7GG
ATC
29 IM000647 p 000678 C
CCGTGTCCGTGGGCATGTGCGTGTACAG
ACAGACATACATGCGCCGCATGAGTGT
GAACACCAGAGGTCAACCTCAGGTGTCC
TMGATGTrATCTACCTTGTrrGAA
GCAAGGTCTAGGATTGACCAATGAGCCC
CAAGTAGGGATC
IM000648 p000679 D
GATCCATAGGCAGAGAAGGCAGTATA
GGACATTGGTCATTGTACCTCATTTGTG
AGGGGTCACCTTGGAAATGTGCTGAGAC
31 1M000649 TAGGTI'CTAGGAGAAGCTCGCCA p000682 D
CTGGCACTGTGTGGCAGAAACAGTGAAC
AGTGTAGCGGTGCAGAATGTGTGTGCTG
TGGG1TIAGCACCAGGGCTGCATGAGA
CTGCAGACATGC'TATGACGCAGGAAGG
CTrCAGGACACAGCACACATGTGTGCTAA CATACATG I ITIACCTCAGACTCAGCTC CCATrGAC=IIAATrAATITIGGCCA 7rCCACAACAGAACC'ITCTGCTCCCT TTrTCAATCTrATGTATATATCTFCCTAC AITAGTrACAGGACTGTGACCTACAGT 32 [M000650 TTAAAACTCGGGGATC p000684 D SEQ SEQUENCE~tc "SEQUJENCE") CLONE CLASS GENE NOD (TC [TC {TC "CLONE "CLAS "GENE" 2) SIFICA \L2} lION" MUTATION \L 2) GATCCCTCCCCTCCCT7C1TI117CCCGCC
AAGCGTCGGCGAAGCCCTGCCCTTCAGG
AGGCAGGAGGGGAGCTAGTGAGGCGA
GTrcGGACCCAGCAGCl'GAGAGCAGCGC
AGCCCAGGGGTCCTCGGCCGCGCAGACC
CCCGGAATAA
33 1M000651 p000685 K Mc
CTACCACAGCCGCAGTGCTCTGGAGGGA
CTCTAGTAGCCAGGGGTGGCAGC'ITGGT
TGGGCCACJCATCTCACTATGTAGCCTA
G'GTCCTGGAA'ITGCTATGTAAATGT
GGCTACCCTCAAACTCATAGAGAGCCTC
CCACCTCTCCTGAGATTATAGGCACATG
34 IM000652 CTACCATGCCCTAAGTGGATC p000686 D
GGAGCAGGCCG'ITCTGAATCAACTFTGGC
AGAGTGAAGGAGGCACTCTCCACACAA
ACAGGAAAAGGGCAGTGGTGAC7ITCTA GGCAGGGAACTGGTTACATTT1TAT 'FUGAAGGTrGAAGAGTCc3TGACAT7CTGG
GAAATAGGCAAGATGGCCG'TTCCCCTC
AGCTACAACCAGCCATGCAGACCTCCTT
GCAGGGACCTGGCTATCTACACTGGAAC
CAGAAAGGCACGCCCTGCTTTAGCCTCA
GGCAGAACGATAATAACAGCGTGCTAG
CTCAGTAGTCTGTGTGCTGGAAGGGIFJT
ATGAGGAGGAAGTCCGCAATTACATATIT
TCTGGGCAAACATTrAACCAAGAT'rGAAA
CCTAGATIMGAAGAGAAGTAGCAGGT
GGATC
IM000653 IIp000687 D SEQ SEQIJENCE{tc "SEQUENCE") CLONE CLASS GENE NO: {TC {TC {TC "CLONE "CLAS "GENE"M 2} SIFICA \L 2)
TION"
MUATION \L 2) AGATGAACTrATAAATGCATCTGCAGTC
CTCAAATAAAGATGAATAGTAACCCAG
AGGCGTGGTAGTGCGCTCTTCAAACCCA
GTGCTCAGAAGGTGCAAACAAAAGGAC
CGGGAGTCCAAGGCTAGCCTTGACrAGA
AGGGGCCATGTCTCAAAGAACAACAAC
CAAGAGCrG=~ATGGAM3TCAGTCTGT
GTTCCCAGGGGGACAGCATCAGTCTAAG
rrGGCGGnGTTGTTGGCTGAGCATGCA
CAAATCCCTAACAGCACATAAAGCAAGT
TGTGTCACACACTCACAGTGCCCAGAyI- CACTGGATC Mm.1313 36 1M000654 pOOO688 B 36 GTCCATrGTGTACTGAGAGAGGAGTrAG GTAGAAAGCCITrCCTCAGATGTGCCCT
CAAAGAAGCTGCTACAAGTGCCCTCATC
CCACGT-rGCCAAGGATC 37 LM000655 p000689 D
AGCTGTAGGGAAGCCCAAAGCACAGAC
GACTGCTGCTGCTGCTGCGG'ITCCCA~r CTGGGTTGACCrITAGAAACGGGGTrCA
TCTCCTCCAGCAGCTCCGGGAAGGAGG
TGAAGGGGACTAACCATGATGAGO-ITG
CACACTGGACTCAGGGCCTGAGALGGG
GCTGGAGGGAGGCAGGGAAGACATCCC
TCACGGTAGTGTrACACAGCTGGGYIr CGGGCTGCCAGGGTACTCA1TITGAGTCC
ATGCTGAGTCTCTCGGTGCCTCCTGAGA
.38 1M000656 TC Ip000694 IK Oft] SEQ SEQUENCEftc "SEQUENCE") CLONE CLASS GENE 1{FC TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 2}
TION"
MUTATION \L 2)
GATCGCCCCAGTACCTCAAA'ITGTGTG
AGTGTGTGTGTGTGTGTGTATGCATATA
TGCATrACAAGCATATACATGCATGCATA TATATAATACACATAGACATrATATACAC ACATATAGACGCATACATGCA'GTATr
GCATGCATCTATGTATGTACATATCCAG
AACCAAATATACCAAACACGCAGACAC
AGCACACATAGGACAATAGTAATIGTGA
ATC'rAACTGGTGGGGYJ'TATGGGTCAAG
AGCCAGGGTAGAGGAAACTGGCTAAGG
CTCTAACCATCCTAGAGCAGGCACATrCT
ACCAGGAAAAGAAACAAGGAAAAGAGC
39 IM000657 AGAG~rGAGGGTTACTTAACATG p000695 D ACAGAATCTGTGGGTCAFlATTACG1TI' ATAGGAACAGGATITTTCTITTCCThETCTGA CTCTAC=~CTAGAAAGGCCGACThITA AATCCrCATGCTCVrGTCTAYFGACAGG 1IMOO0658 AAAAGATGGGcvr1cCACAcTrGATC p,000700 D
GATCAGGCTGGCCYI'GAACTCACAGAGA
CCCACCTGCCTCTGCCTCCTGCATGCTG
GGATITAAAGGTGTGTGCCACCACTGCCC
AGCTCACAAAGTAGTAGTAGGACTAGTA
CTAGTACTIAATAATAACAAACA'I1IACAA CAATCTrAAMTAThI=GTITCTACCTIT
AAAATCTCCCAACTGTCTIT=ATATTGC
CTCAAGTCTTCCCTCAGTCCCTGGCCTTC
ATAGCTTGACThTrGCTAGAGG'JTATC AGTGGCl'CATCTCTCTCCTGAGATrGAG
UI'GGCTAGACCACTATTCAGAGGGAGA
ATGTAATGTCTCAGACATCATAGCCA&I'
CCTCAGTrCTCCI ITTIGCTGACTGACCAC J-17GCCAAACTAGTTTTCCTAAGCCATA CCT7TTC TrAAAAAATAGTCM~C'Fr ATAGTGGGTGCTGGGTrTGAAC'n'CTGTr
CCTC'GCCTCACCTTGCACTGGTAGTA
141 1M000659 I AGTGA=AC p000702 1C SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ED {TC {TC {TC 0O: "CLONE "CLAS, "GENE" 2} SIFICA \L 2)
TION"
MUTATION \L 2)
GATCAAGAACGAAACCCCTGAAAACAT
AAAACAGTAAGATAACAATAGGGTGCC
TGATI=GTCGAAACCTTCTrGTCACCTG
TCACTGAGATTGTCAACTCCTI=CACCA
CCCTACATACGTrAGT7AGCTCAGTTrA
CGAGAG'FITGCAAAGGCCCCCACCAGTA
CCCTGCAAC1TfACCCACCCCTGCATGG
GACTGTGAGAAAATGGGACTGGAGAGT
AACCCTCTTCAGGCTCACAATCTGAGCT
AGTCAGAGCATCTCACGGGTCCCGGGAC
TCAGTGTGCTTTCCTCTrCGGTA-TTG
ACTTTAAACAATGTGTACCGATATGGGT
GAATAATACAACATCCATGGAGAAAjTA 42 1M000660 AGCCAAATCAAGACACT7CTTCAGAGG p000703 D
GATCAAAAACATCAACGTAAGGAGCCC
TAATGACGCTGTGACGGMTAGAAT
GGTCTACCCAAACGTAGCCAAGTCTAAC
TATGTrATGGAGGTGGTAAAAGCAGTTA
ACCTAAACATCTGGGACACTCACAGAAT
GATAGGTAGOTAGGTAGATAGATAGAT
GATAGATAGATAGATAGATAGACAGA
CAGACAGACAGATGT-rGAATAAAAAGT GACGTrACAGTGATG1TAGCTCAAGGC AGGGC1TICAGGCCATITCCCCTGGTCT 43 IM000661 CACCC pOOO 7
O
4
D
CTACTAAGTCCAGAGCAGAGAAGGAGG
CGCCGCCTGTGTGCACAGCGGAGTCrGG
GAGAGACCACCGGCCCAAACCAGTAAA
44 11M000662 CACAGGGCACCCACCGTGCTCCGATC Ip000706 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: {TC {TC ITC "CLONE "CLAS "GENE" 2) SIFICA L 2}
TION"
MUTATION \L 2}
ACAGTAATCTGATTATCTTGCAGTAGAT
AAMhGTCTACCTGTPAATGACTCTGC'IT crrGAACTACGTCCCAGTAGATGCCATG
CYICAGCCTGGTAAGTGACACTAATAC
TACCTCCAAACTGTCACTTGGA7FGTCA
GGGTTTTGGTGTGGTGATGATACAGGAG
AAATGTAAAACACGGAGTTGATGATAG
AAAGGAG'rCACIrAATACA'T1TrG1CTAGG
AAAAGTCAAGTGACACACAGCAGAATC
TACCTGAAGGAGCTCCGCCAATAGGGCT
GGAAGATAACTCTCGCACTAACCTGCT-T
TATTAGGAACTGTAGGAAAGGCAGGTCT
GCAGCACAGTFGAAGMIAGGTJGC'GA
GAAAGTITfCTGGTCATA1YIATTCACCA
GTGATGATC
IIM000663 p000708 D 46 IM000664 GTIAGCAAGTCCGAGCGTGTTCGATC p000709 K iy
AGGCAAACCCATGTGAGGCM~CTCACA
TCMTCCT'rGGATGCCTGCACACACCTG ACTTGACAGAMTCAAATCAGAC1TATC AACTCACCTCT7CAGTCCTGGGCCTC1-TC CTGTATCAATCTrAGATIAGAAAAIIG GT-rCCACTGTGTACCAGCC'FrGAACCAG
GAATGCAGAGCCAACCACCCCTGGGGT
GTCCCAGGCAGCTGGGCTGGATGCTACC
TGTCATGCTCITGATC
147 1M000665 1 p000710 IC I- SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID{TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2) ATGTATGAGTGTGGGGCTGGGT17TGAAC
CTGTGTCACCTTAGGACTCTCTGAACCT
CGGTCCTATTAGACGGAGGGGCTATT
CGGAGTCCTCATCTAATGGAGACACT
GTGGGTATCAGAGGGCAACACTGTGGTA
TrGGGGGTGGGGGGTrGCTGCTrAGAGC
TCAGAGAAGAGGAGTTGGCTTGCTCTA
CAGAACATGCAGGCTGAGGTGTGGGTG
CAGGGT1TCCCTOAGGCCCCGGCTCTGA CCCTCTCCCCACTCGAM1CCTGCGCAGG TGAGCGACAAACGTTCCAACAGCTTrCCG
CCAGGCCATCCTTCAGGGAAACCGCAGG
CTGAGCAGCAAGGCCCTGCTGGAGGAG
AGGGGCTGAGCCTCTCTCAGCGGCTCA
TCCGCCACGTGGCCTACGAGACTCTGCC
CCGGGAGATTGACCGCAAGTGGTACTAT
GACAGCTACACCTGCTGCCTCCGCCGG
TTCATGATC
48 1M000666 p000711 C GATCATnTCTCTCGAGATGGATrAAA
GCTATGCTGCAGAAGGACCCGTGTGTGT
CCTGTGTGTGTGTGTCCTCGCCOGGCGAG
ACTCCTTATCACACATGACAGCITCAAA
GCCCCCAGATTCAATAGGTrCCAGGAGT TCACA1TAACACTCATGGGGTCAAAGT
GCAGGCAGATGGTGGAGCCTGTGGAAG
GTCATCAGACAAACAACCTGGTGGTrGC
AGCAGAAATCACCAGGCAAGTAG
49 11M000667 p000712 R
GATCTGGCTAGCAGGGAGCCATACAG
IM000668 CCAGACATCTATCATCCrrA p,000713 D SEQ SEQUENCE{tc "SEQUENCE"} CLONE CLASS GENE
ID
NO: {TC {TC (TC "CLONE "CLAS "GENE" 2) SIFICA \L 2}
TION"
MUTATION \L 21 GATCATGTACClCACCTGTCAG'lFTGA
CAGGTGGGAGGTGATATCTC'TVFCATT
CATGTA'ITCTITGAA.AGT'17GT-rCATGCA TATAATACATrCTGGTTCAJLrrCACCACT
CCACCCTTTGTATCCCCTGCGTACCGA
GCCCCCATTCTCACCAAGTC'IT'ACTGTI
TfATCTCAGTTIGGGGC'TAGFT-TGT TGTC'1T17FG'rGTIT=GAAACAGG GTCCCGrrATGCAGCCCTGGCCCTGAAC TrGCTAAATAAACCAGGTGGCrGAA
TTCAGAGTTCTGCACACCTCTGTTACCC
AAGTGCTCAGATTAAAGGCGTATACTAC
51 1M000669 CAC p0007 14 C GATCAAITCAATCTA1TlGCAATAXCC'[G
GTTTII'-TITCCGCAACTCCAAGATGGG
GGGGGUGGGGCCCAGTCAGGAGAGGTT
TCAACACAAACGCACTAGTAT~rACACA CAGAATCTCCTCCACTGTTCTTCT-rCTrT GC'TrAAAAGTCT1T7GTTCCGGAATCTAT
AGATAGGGAGACAGATGGCTAGCTCCC
CAAGGCTGAGAGCAGAGGAGAGTA'IAA
ACAGGGAAGTCAAGGGGTCTGGGAG(G
52 IIM000670 CAAGGTAAGGAAGCCACAG pO 0 0 7 ]S D CAATGCCnrCCCCGCGAGATGGAGTGGC
TG'FATCCCTAAGTGCTCTCCAAGTAT
ACGTGGCAGTGAGTGCCGAGCATm' AATAAAATTCCAGACATCGTrTCCTG 53 1M00067 1 CATAGACCTCATCTGCGGFUGATC pOO0716 K Myc 'rAGTA'T7CAGGAAAAAGGAAACTGGGA AATTAATGTATAAA'TAAAATCAGC~rF
TAATTAGCTTAACACACACATACGAAGG
54 IM000672 CAAAAATGTAACG1TACTTTGATC p000718 IK Myc GATCAGAAAAACAGCCCATrATTCAAGA 1M000673 TTCAGGT p0007 19 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE {I TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MTATION \L 2)
TAACTFCAAMTAATAATTATCACATGCT
AGGAACTAAAGAGGTGCACAAAACAAA
CCAACAGTGGTTCCTATCCTGTCTAACA
GAAGAAACTACAATTGTGGTGGGATG
CCACATAAATGACAGCAACGGGACCTA
CAGAAAATTAAGTCACAGAGAGAATGG
ACCA1TCTGCAGAGACCTGGAAAACAG
ACAAGGGAAGAAACATGGTGTGTCTAA
GTGATGGGGCAGGTGGTGCAAACGCTA
GAGGCAAGCAGAGGGGATATGAAACTG
TGCTGGACAGCTGGACAGAAGGGAGGC
rGGAAGGGAAGAGAGGACCCTCTGFTrr
GACTCAATGGCTAGATGCCATGTGCCAA
ATAAGAAAGCACTrGGGGGGTTCTGTGG
GAAATCGGAACAGAGGGACTGGAATCA
AACCTCAACGTTrCCTTGCATACTCCAGA TAAGAACCAGGCTT7GAGCCAGGGCCTG GGAAGAGGGCTGGCCTACATATCTCA1T
TAGAGATGAGCAAACAGGACTGGGAG
CTCTAGGTCTrCAGTGACACGCTI-GCTTr 56 IIN4000674 GGCCCGCAGGAGACCCTGGc1TTrGATC O02D
GATCATGTCATGGGTCAACAGAAATAAT
TCTGAAAGGCTAAGTCAMTCT-rCTACC
CCCAAGAAAAATCAAGAACACCCCACA
TACAAACCTrCCGTAGTAAACTGAGAA
TGGAGCCATGGCCAGAGCCCCTCTGCTC
TCCCATCCCCCAACCAAGAACCAAAC
57 I1M000675 p000721 D
ATATAACTTCTITTAAAAAAGAAT
TAT-rTAT=1ATGTATATAAGTTCCTTAT AGCTGTATrCAGAGACGCCAGAAGAGA 158 1EM000676 iGCATCTGATC pOOO 722
IR
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID J T T NO:{T C {C "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
IMUTATION \L 2)
GATGATAGCACAGTGGGGTGCCATCTGT
CACCCCTAGACAAACATCn7TAACCNGC ATCTC'TCCTGAAGCCCACnrGGACCAC
CCM~GGAAAACCATCACCAAGGCCAGT
AAGGTACCCGTGGTGACTCACCTCAGCC
TAGCCCACCATAGACGGTTrAGCAGAGCA
GGTGTGTGTAAGTCAGAGCCAGACAATC
AGAACACTrCTCCCTGCTCCAAAGTAGCA ATGTAAAAAA'IFFGAACCCAAAGTrG 59 1IM000677 p000724 D
GATCAAAGTAACGITACAITPGCC'TT
CGTATGTGTGTGCTAAGCTrAATrAAAAG CTGA1TIAATTTATACATTAA'flTCCCA
GTITCCII=CCTGAATACTACGCTGTG
CATTCTGTACAATCCCCAAACGTATACA
TACACACUrTATATATACACGATAATCT
AGCYI'AIAACCAACCAGAAACATGAGT
C1TTGCTCTGTGCA'ITGG17TCTAGAM~ AT7ATATAATGCATA'ITCCCTCGGGAY1r 1M\000678 GCTTATCC p000727 K IMyc GATCATTrGATGCT'rCAGATAAATATGTr Mm. 1278 61 [M000679 AAATOGTGAC p000728 B 181
GATCAAGATAATCCCCCACAGGCATGCC
CAGAGGCCCA'TrTCCTAGGTGAGACTAT AGTCTGTCAAGTrGACAATGCTAACCAT
TGCAGTGAGGGAGAGAAAGAAGGCCAG
GATGGTGGCTCTCTGTrACTCTGCTrACC
CACGGGGTGCAAGGACAGTGGGGGATG
GGCCTGAGCTTCCTCATGAACACACACA
TGAGAGCAGTCAGCACATGGCCTC'ICC
TCTAAGCT-rCACAGTGGCAGCCGCACCT CTGCTG1TAAGACCTAACATGTGGCCGG
GCAGTGGTGGCACACGCCTTAATCCCA
GCACTCGGGAGGCAGAGGCAGGTGGAT
TTCTGAGT-FCGAGG*2CAGCCTGGTCTCC
AGAGTGAGT-FCCAGGACAGCCAGGGCT
ACACAGAGAAACCCTGTCTTGAAAAACG
AAAACCAAAACCAACCAACCAACCAAC
CAAACAAACCATCTAACATGTACATCcTr
ATCCATGTGCACGAATCATAC
62 1M0006H0 p 000729 IR F SEQ SEQUENCE{tc "SEQUENCE") CLONE CLASS GENE ID T T T NO:{T {C {C "CLONE "CLAS "GENE" 2) SWFICA \L 2)
TION"
MUTATION \L 2)
AGACCAGTGCCGGAGCCGTCCTGGCTG
AGGCAGCCCAAGTCCTTGAAGAGCTTGA
AGAGGTCGCTGCGGAACTTGACGCCGAT
GAAGGCATACAAGAAAGGGTrGACGCA
GCAGCGGACGGAGGCCAGGCTGTAGGT
GACGTCATAGGCAATG~rGAGCTGG CTGGMTCGCAGCTGCTATTGGTGATGfl GAAG77GGCCACCGTCTGAGCCAGGACC
ACCCCATTGTAGGGCAGCTGGAAGACTA
63 rmo00681 TGAAGACTACCACCACGGCAATGATC p 00 07 30 A Cmkbr7 CCCTCTCAAGCCTrCCTUGTTACTFAGCC
WTATAGGTCTGTCATATACCATCAT
CTT7AAMIACAGCTAATATCCAMTAT ATATGATTATGTACCATATTGCyJMG
GGGTCTGGATTGCCCTACTCAGGATGAC
CTITTCTAGTrGATC 64 EM000682 p000731 D GATCATGATG7GTrGAAGCACAGAA
ACTATAAGACAGTGCCCJ&AGAGCCTCTC
TGGAGATAGCC
J1M000683 pOOO 7 32 D GATCGTG1-rAGACACAAGTAJAGAATG AATGAGTCTTCCTGATI-=~AAATrAAC
T'TCTCCCCATATTGGGTGTCACAC=II
TAAATCAGAAAGGAGAATCTGGACGGT
TCCAGGCCTGCAGCGCCATGCrrGCAAA AGGTTrACAGAATCGCTCTGc3ACACT 66 IIM000684 pOOO73 4
D
CTACCACAGCATCTI=GAGTGTATATA
GTCAOTGTMCACATGF1ATCTATGAAC ATATGCAAATGAGGT-1GAGAATTAAG TGCTGATAGACTCATGGO'rrAGGGOTn
TGATTGCCTGCTAATGATC
167 1LM000685 Ip000735 ID F SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: (TC fTC {TC "CLONE "CLAS 'GENE" 2} SIFICA \L 2)
TION"
MUTATION JL2)
GATCACGAAACGGTGACTAAACAAG
ACTGAACCACAGGCAGATACCAAACCC
AAAGCTCTATGTCTAGTGTCTAGAATAC
ATAGG'l'GGG'FAGCCATGCCCCTGTIGA
GCCTGCCACGTGCAGCAGACATAAGACA
ATACTATAGACAACCACTCTAGTCAG
AATTGCAATGATGTCTrGGCAAACTAC
TCTAGTCTCCTTTGGCCAGGAGCTGCTA
AGTGT1-'CAGGCTIGAGG'I'ACA~rACC TAGGTIAGGTGGGACTrGTGTGCCCC'TGTG CTCCTGGGTGCICCTrCATGTCTGCTATGC rrGCCCn7~ 68 1M000686 p000736 D V
GATCATGTCAACTATACCTGGACACGGA
CCITCATCCTTGCTGGTrCACTACCTCT GGCACCCTGCAACATCrGCAGTfTG
GAACCCTGTGCATCTATCTCCTCACACT
GGCAGGGAACTTGTTCATCATTGTCTlG GTCCAGGCAGATrCAGGGCTGTCCACTC CCATGTACTrCT-FrATCAG'GFCTCcTCC
TCTGGAACTCTGGTATGTCAGCACCA
CAGTGCCCACCTI'GCTGCATACC'ITGCT
CCATGGGCCTTCACCCATCCCCTCGTCT
GCATGCTTTrGTCCAGCTGTATGTCTTCCA
CTCCTTGGGCATGACCGAGTGCTACCTG
CTAGGTGTCATGGCTCTGGACCGCTACC
FI'GCTATCTGTCGTCCACTGCACTACCAT
GCACTCATGAGCAGACAGGTACAGAAA
GAGTrAGTTGGGG1TACATGGTTGGCTG
GTITFCAGCTGCCTGGTGCCTGCAGGT
CTCACTFGCCTCFJTACCTrATTGM1GAA 169 1M000687 JAGAAGTGGCCCAYrACfT p000737 C 1
I
SEQ
ID
NO:
MIUTATION
1 IMI000688 SEQUENCE(te "SEQUENCE"}l
CTGTCAATTCATCCAGCTCTAGGCCGGT
GTCTGGCTCGATGCTAGGT7ACA GTGCCGATGCATAGGATTrTACAGTCAG
AGTGGCCTAAGCAACAGCTAATATTGT
MCTTGCTG77CTGGGAACTAGATGTTC
AAGGTCAAGGCGTCAGTAGCTTGTTAT
GAGACCTCTCTGCTGTCGGGCTGTGTT
TCAAGTTrrCCCCCCTCGTGCATGTG TGTTCCTA1TrCCTCTGCATGkAAGACC
AGTAGAGCCAAGTGGTGGCACACACC-
TGATC
GATCATGAGAGGCGAGACCCAGACA
TCTCTAACTC7CTTGCCACTCAGGAG
CCACCTGTGGCCCCAGCTGGCCACCAGC
CGTTCCTCCCTCAGAGGCCTICCATm.CCA CAAAAGGCCIT[CCTGGTrGnrCAGGACA GAGCCTGGnrCCCTGATACCCCTT~CTCJ.
CAGTGGCCACTGAAGUTACAGGGATGCA
GCCAGCCGTGGTTGCCATGTCTGTATAT
GAT-rTCcAG G M GTCCGCATGAGTCCCAGGGACCAC TCAGAGTGGCTGGCAGGCAHrGTGGAGT
TGFTGCAGCGGGACGTCTGTG.IM
GGGATGATC
GATCACCTGGGAAGGGGGAAGGACA
AGTCGAGCTCCCAGCCCACA'I-TCTCCT
AGGGTAGCAGCTCCCTCACP~'AGTGT
'CLONE
(TC
"CLONE I"CLAS \L 2) SIFICA \L 2}
TION"
\L 2)
CLASS
TC
GENE
ITC
"GENE"
p000738 ID I-- 71 ITMOO0689 p000739 ID I-- 72 JIMOO0 690 000740 ID I- 73 73 I 4000691
D
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: {TC {TC {TC "CLONE "CLAS "GENE" \L 2} SILICA \L 21
TION
MUTATION \L 2}
GATCAGTI'CTTA'ITAAACAATACAGACT
TAGGCAAAATGAGTCAGAAATAAGGAT
ATCGCATATCCCGAGACCAMTGAACTC
TAAGAAGTATI1'fCTATTATrAAAGTAG 17CACCAGGCAGTGGTGGCACACACCYI'
TAATCCCAGCACTCGGGAGGCAGAGGC
AGGTFGGATTTCTCAGTFI7GAGGCCAGCC TGGjTCTAGAGAGTGAGTTCCAGGACAGC
CAGGGCTACAGAGAGAAACCCTGTCTGG
74 ACAAACCAAAAAAAAAAAAAAAAAAAA LM000692 AG p000744 R
GATCATCACAGATGACATAGAACCAAA
CTGTAACI]CTAGACTACATGTAGCAG
ACATIT
1IM000693 p000745 D
GATCATACATGAATACAAGCAGGCTI'CT
GGTATACTCTITAAGTTGAATrCTGTTnC T]GTAGTCGTAGTCTrGTCTI-frCCAGTIhr 'rAAATTCTAGAACAGGTATACTGTAGAG CACCCGCCTCCCCTTrGCTCFGGAGGTAG GGTAGAGTGGGAGITrAAGGTCAGT1 CC AA65702 76 IPM000694 p000746 B 18 ATICTCYI7GTAAAACTCACT1CTG1TC ACCCATI=GTCTGTGTCCTI'ACTAAAT7r
AT'ITCTATATAGGAATICTTTGTATCTTCT
GATATAAGCTAGCGCATGGGTACCACCA
GCACCCAAGTCATCTGCTGAGGTGCTTC
TAACC'ITGC'ITGATTCAGTGTCTrCAACA
GAAGGTGGAGTAAACAGGTCATVITTA
77 P400O0695 CCCITAGAGAGI1TCAGATC p000748 D
GATCTCCGGGTGCCAGACYI'GCCCAGCA
AGCACTrCl-ACCTGCTGAGCCATCCTGA GGGCCTFGGAMIA AA AA AAAA AAATATT 78 IM000696 GACATATTGYFC Ip0007 4 9 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID {TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 21
TION"
MUTATION \L 2)
GATCTCCTAAAACTCCCTGTGTCAGGAA
ACMTCTGTGC1TIGTAITGCGTTCCTG TGTrCGTGGAAGGCCCCCACGCCTrCAT CCTTGCTAATTC1T=~GGATAGCTTGT-r GCTrAACTAGATTGGCCCMTTT'TGGCT AGTA=r~CTGCTGTACCTATGAGTGGT
GTGGGAGAACTGTGCAGACITCCAGGA
AGCGCAGCCATGAAGCTACATGTGCCTA
rGTGTAGACACATCATGGATI=CTTACT AG1TrACTAGTGGGTGATAATCTGTCCT
TITTGAGCTCTCCAGAACGTTCTAGAAGG
TAAGGAc3AGAAATCACTTAAGAGAG 79 1M000697 pOOO 7 52 D
ATCTGATAGTAAGTAAAAGGACAOCTA
AAGATGAAGGGAAAGCAGGAGAOTCCT
GGAAGAAGAAACTAGTGTTTCTAAGAGT
TCATCAT-rGATAAAATGCAAAAGAAGTC AMCATACATG1TAGGAAACTGAAT CCTCTrG1TITGGGGATGTTTG1TrGA GGCAAAGGCTCTCTrACAGAGCCCTGGC TG11TCTGGAGTrrCTGTATATCAGGCTCTG
GCCTCAAACTCAAGAGATC
1M000698 p000753 D
ACATCAAGAGGAAGTTGGAAATGTATC
1TrrAGCTATCT-rATATCCTGGTAGCI~rA AGAM~CC1TrTGTGTGACTlTATAGT'rCT
CAAAATAT=~AAGGGTCAGGGGAGGA
AGCACTFTCAAGAAATGAGATGGGAGA
GGGAATGTCMTGTGrrGGCCTGGAGAT 81 I1M000699 c p000755 D AGCTATACCTGAAAT1TrGGCCAAGAACA GAAGCTCAGGAAATAGTGTGATT'rAAAA ACCAAAACCAAITrACAAAAGGAAGAC 82 IM000700 TGTGGTGTAGATC pOOO 7 5 6
D
CCACAACTGAAAGCAACACACACAGTA
ITI=CTGTGGG3T=AGGATGTATCCAC ACTCCCGAACTTCCTrCCCTGAAGCAC CCCTCAGTTTACTCTGAAGCATGG'T7G
AGTCCCAAGGCCAGTGTCAACTTTCTGC
CAAGTCTCAATGGCAAAAGTCTOTI=A
83 IM000701 ATCTGCTCAGGCTAATGTAGATC p000757 D
SEQ
ID
NO:
SEQUENCEftc "SEQUJENCE") ICLONE IULASS jF(2 1 fTC "CLONEI" 'CLAS
GENE
(TC
"GENE'
\L 2) \L 21
SIFTCA
TION"
\L 2)
MTATION
34 LM000702 CTTCCAGTCThITIAGCTA'T[FA'IGATA TGAA'FFCCCTCCrrA'IGTATCATCCA GATTCTACCTAA4TACTTCCATAAGT ATCAAGGACCACTCAAAyT-CATAT-r
GGACTFAGAAGCTCCACTTTAAA~-A
GA1TCTATAGAAAGAGCCTGATGGG GGCATGAAATGGG3TCCATC-FCCACCATC
ACGCACACATGAACAAAGAAAAGGAGG
AAATGGTGIT7AAGAAAACTrACATCA1'A CTAFT-lAAAAATAAGGAGGAAG
GAGG
AGGGAGAGAAGAGAGAAGCI'CATG
CTTAGGCAAGAGTGCTAAGAAAA1IAC
AGTTAACAGATC
GATCTCCTAAAACTCCCTGTGTCAGGAA
ACMTCTGTGCTr[GTATTGCGTTICCTG
'FTCGTGGAAGGCCCCCACGCCTTCAT
CCTTGCTAATC~rrTGGATAGC7GT GCTTrAACTAGAl'FGGCCCTITCTFGGCT AGTATTF7CTGCTGTACCTATGAGTGGT ~3TGGGAGAACTGTGCAGACTrCCAGGA
&GCGCAGCCATGAAGCTACAITG'I'GCCFA
I'GT
p000758 I IM000 703 D000759 D
I--
86 JIM000704
GATCTGAGTGCTGGGAACCAAACCTGGG
TCCTCTGCAACAG'ITI'GTGCTC-AGCTG
CCGAGCTTT
GTAGGGCGATGGGCACAGGC'ITCGGGA
CAGTCCGCGCGACGCTCAGGCGGACAA
CGGGAGGCGGGCGGGGAAGGCAGGGGC
TGCAGTGTCAAGTCCCTGACCCGGGAGG
CTCGGjAAACTTCACTGCCTCTGCGCA[FC CGGCATGGCCCCTCCCAC7CGGACfl-CG
TCAAAAAACCGCCACCGTGGAGTGTCCC
AGTATGTGCGGTrGTGGGACACTATCG CACTGlITGCCCTGGCTCTTCTCCTJAGACC CCCMhGTGAGCCAAGAGAACGCTG
GGCAGATC
p000760 IR I-- IM000705 D 00076 I IB Mm.2739 3
U
SEQ SEQUENCE{tc "SEQUENCE") CLONE ICLASS GENE ID T T T NO:{T C C "CLONE "CLAS 'GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2) GATCTCGTTACGGATGG7GTGAGCCAC 88 IN4000706 CATGTGG1TGCTGGGATAA pOO0762 R CTGGGTGACCTrAGAAACGGGAGTTCA
TCTCCTCCAGCAGCTCCGGGAAGGAGG
TGAAGGGGACTAACCATGATAGCMG~
CACACTGGACTCAGGGCCTGAGAAGGG
GCTGGAGGGAGGCAGGGAAGACATCCC
TCACGGTAGTGTTACACACTGGTGflG
CGGGCTGCCAGGGTACTCAMTGAGTGC
ATGCTGAGTCTCTCGGTGJCCCCTGAGA
TC
89 1M4000707 p000763 K Gfil
GATCTCAGGAGGCACCGAGAGACTCAG
CATGGACTCAAATGAGTACCCTGGCAGC
CCGCAACACCAGTGCGTAACACTACCG
TGGGTTTCCTCTCTC
GCCCC7TCTCAGGGCCCTGAGTCCAGTGT
GCAAAGCTCATCATGGTAGTCCCC'C
ACCTTCCT-TCCCGGAGCTGCJTGGAGGAG
ATGAACTCCCGTrCTAA0GTCACCCA
GAGTGGGAACCGCAGCAGCAGCAGCAG
1M000708 TCGTCTGTGCMhGGGCUFCCCTA pOOO764 K Gfil
GGAAGAAGTGTGTGCAGGCCATGGTCA
AGTCCTGCATGGCTCCCATCTGGGTCCA
GCAGCACCCAGCCTCCAGTGCTnGCTCC
TGATGTCCCAGTGAACTCAGGTCCTGAG
CAGCAAATCCCAGGGGCCAGTCCTAGG
GAGAAAAAGAACACACTGCCATTCAG
TGCCTCAACAGAAGCA4CCAGGCGTC AGTCATGTCCT'rG1TACCCACATCACA CCTAGACTCCCTGGGTATCATGCTCTGT Mm. 1535 91 1rM000709 GTGAGATC p000765 B 12
GATMTAGGATATATCATMAGGAGA
CAATGTF1rrMAJ&TATGGCATAGC
CACAGAGATAAAAATAAGAAAATAGAT
ACATCGAATTCAGTAAATGAGGAAGT
92 1M00071 10 TCTTArACGACpOOO766 A MtpnJ SEQ SEQIJENCE~tc "SEQUENCE") CLONE CLASS GENE
ID
NO: {TC {TC {TC "CLONE "CLAS "GENE" 21 SIFICA \L 2)
TION"
MUTATION \L 2}
GAGGTAAGTCTGTTCAGTGTAGCTATCC
TAGCAGCTAACAGTCCTCAAAACT=T
TAGAGATC
93 1M000711 p000767 D CTACAGATGCATrATrAATATTACWFI AAAAAAACCCAGTATACTGCT-rGAAAAC
AGTGAATGCAATGGG'ITCTCATTCACCT
TCCTGCTCTCAATCAATCTCCATCTCTAA
AGCAAGAAGTGGGGGCCCTrCTGGCTGA
GCGAGGGGTGAAGGGAGGGGAAGAGAT
94 1LM000712 cI p000768 D GATCTGGAGAAGATGITCAAGThrlI'AAAA 1M000713 TGAGGCAG p000769 D GAG TGAAGCAAGAAM~GGAGCCCAGC
TGCCGCAGCCTI=CCMTCAGCAAAG
CTCGGGAGTGATAGATATGCATGAACCA
AAGCAAAGCCTTGAGAGTGCCACTTGGC
CCTGCCTCCTGAGGGTCTCAGGGCATCA
GCTGGAGACCACCCTGTGACCCACACAT
CACCGACTATGAAAACAGGTCATCAGAG
96 1M000714 'IAATAAAGATC p000770 D
CAATGAACAGGACACATGC'ITCACACGA
CAGTCCAAAAATGCAAAGTGTGGAAGA
ATCCACAGCCATAGCCrrCATrACTAG 97 1M000715 ATC p000771 D
ATGCCTT-CCTGGTAGAAGAGGGCCATGC
TGTGGCGGGGAGGGGCCACTCAATTTT
CCTGCTCCCT1CCCTGTCCCATATTCTC AGG0AGCTI7CTAGAAGCGTAOCCTIGCATrc TrCATGCCCTGACTITGGCACCAAATGC'ITr GCTrTGTATCAACACCGCTITCTC7TrCTG
CTCTTCCAGCTCGCAGCCATTCAAATA
ATACCACCCGGTACCCGTGGAATCAGGA
GCAGAGATTCCAAATTGAGTCCTAAAAT
98 CAAATCCAAATGGGCCCGTCAGCTAGAT IM000716 c p000773 D
SEQ
ID
NO:
SEQUENCE{tc
"SEQUENCE")
CLONE
[TC
"CLONE
CLASS
{TC
"CLAS
SIFICA
TION"
GENE
ITC
"GENE"
\L 21
MUTATIOIS
99 0TO0717 100 IM000718 AGGCGAGCGAnTACTAAGGAC'1GAA GACTCCTAAGAC1TGTCTCCTGCTCCCTG GCCAGCGGTGGAGCTCAGCAGATnG
CAAGCTCAGCTCAGGTCTCAGTGATGCA
AAGCACCCTCGrACTCCATGTGTGTT ACCTCGTGGTCTCA1
TCAAACACCCGCACACAGACCTCCCA
CCGTATCCAGAGCATTGnCGATGCT
TCTGGAAACTATGCAAGCCC'J.A
ATATCCAATCAGATC
GTGTGTGTGTGTGTGTGTGTGTGTGTGT
GTGTGTnACAAGGTCTCATACAGAATCC
AGGCTGTCTCAACTACTGGAGTCAAG
CCATCTTCTCACCTGGCTnAGCTGGGGT
CACAGACTTGTGCCATCATGCCCAATGG
AATGCTGTCCTTGGAAAGCCTGCTA
CTGTCATATACTGTCATAGGAGTTAGCG
ACTGCTGGCrrATTCCTTCGCTP..GCTTG
GAGATC
F
CCCCCTTCCTGTCACCTCCTGACCCCTTG
CGCAAAGGAGGCTCGTGGCCCGCTGTCC
CACTGGGGGATGGGGCTOGG3OnGAGA
AGGCAGTGAGCGCJ&TACGCCAGG
AAGTGAAGTTrGTGGTnGGGGGCTGA GCTCCGAAGGAGAflAAAAAAAAAAAA AAAAAGTCAGAGAGACAGATC p ClTrfGTATAAGCAGCAAC&AAAGCCA
GAGGCAGTCCACAGATC
p 4 ATACAACAGGAGCAAAGC1'GGAGGGGA
ACAGATATAGAGGACAGTTCAGGGCAT
CTGCAGAGGTGCTGTGGAATGGGGAGG
GGACAGTGGATAGGGGACflACCCTG
AGCATCTCGGTAATAGCATGGGTCACA
CTGCGGAAGCGCTCCTGTCCTGCAGTGT
CCCAGATC IpO \L2} p000774 ID 000776R 101 JIM000719 000777 ID 000778 JD 12 IiM000720 103 Rah37 1 M000721 00780 070A Rb SEQ SEQUENCE~tc "SEQUJENCE"} CLONE CLASS GENE ID IC J T NO:{T {C {T "CLONE "CLAS "GENE" 2) S1FICA \L 21
TION
MUTATION \L 2}
GATCTATGTCATCMCCAGGACTCAGAG
'fl7AAGAGAGTTACCAAGTGAGAGCTCTC ATCACCTTCTGAAGCAGTGAGAArrGG AACCCAGAAAGATGCACATfGCACGGGC
ACACACACACCCACGGGCACACACCCA
CCCACCCATGCAGAGAGAGAGAGAGAG
AGAGAGAGAGAGAGAACTCACACTGGT
104 ILM000722 ACTGCAGTAAACGGGAGCTTGThr p000781 D GATCTTCMTCTCTGCTCAATTAGTrCAC YTCTGCTrrCATCTCc'I=TC'TIGATA
AACCATGAGITUCATTAGGGCTATTACA
105 IM000723 ATCACATGCAG'ITITICC17ATAGTA p000782 D
GAATTAGGCCTAGAAACAJTAGAATCCA
106 1M000724 GACCACGGAGCTCCCCAGATO pOOO 783
D
GAT~~rCTI7GYCTAGAACGACCCTGAAGGC
AGCAGAACAGAGCAGGACTGAAGGGCA
CCAAGGGGA'TrTCAACTC1TFCAGAAAAA ATAAGTGACTCACCTTCTCACAAAc3AGC
AAGAATCACAGAGGTCAGATTGTCTCCT
CCTGCCCATCAGGGACAGAGTCCCCCAT
C]TrGCCITGCTCCATCTGGCAGGTAAG
AGAT'GGGAAGTICTICCITT-]CCCTCGGTCT
GCAGCATCCCTGGCATCCCTGGGGAGTG
107 [IM000725 TTGGCACAGAACCCCCCTCCCAA p000784 C
GATCTGTGTGGGCAAAGCCCATGTGCTG
CAGTGTGTCTGGGTAGAA-ATGAGTTGTG
TGGTGCTCAAATGTAAATGAAGTCCCTG
108 1M000726 TGTT p000785I D
GATCTCATTACAGATGGATGTGAGCCAC
CATGTGGTI7GCIGGjGAAITGAACTCAGG ACCT1ITGGAAGAGCAG'I'CAGTGCCC'FFA
ACTGCTGAGCCATCTCTCCAGCCCCCCA
CCrTnTI=AAAAGATI-ATTATAG TTI1GCTITTIAACAGTACTGGAACAT CrCAGTAATTIGCTAAGTTGTCCTI-GCTCC
AGGTGAGCAGTCATATITCTCCAAFFC
TGGTITrCCTACTTGTGTCAGAGACCAA
AATAGCTTGTTTAATCAGTTAGAGCTCT
109 1M000727 TTAGTTACCGATATCTGTGTAGTAA P000787 R
U
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE
ID
NO: {TC (TC {TC "CLONE "CLAS "GENE" \L 2) SIFICA \L2)
TION"
MUTATION \L 2)
TAAGAACATAAAAGCAAAATTTGGAGG
CTCAAGATrCAGTITTAGTTGCTAGAGGG
CTCACATAGCATGCCCTCCCCACCCGGG
ATCA1TCTCAM~ATCGAGGCATAAG
GCCAGGTGTGGTGGGATATGTGCTGGGA
TGCATAAGATC
110 1M000728 pOOO 7 88 D
GAAAGGCACACTGGTGAAGGCTGAGGA
CCACCAAAGCTGCATrCTGCTAGGCTA
GGTAGAACAAGAATGGTGCTCCACTAA
GAACTCAAAAAGCCACAGCCCACCCCTG
AGGCCCTCCATCTGACACATGCCGGTCA
CCTGTCCTCCCACAGCCCAGCACAGAGA
AGCCACCATCCCTCCC M CCCACCTCCT
GCAGCTGACAGTGTGCATCTFCCGCAC
ATTCCTCTCrCCTCAATCAGGTCAGAAT 11 1M000729 GTA'TTCCAAAGATC pOO0789 D
CACTGAAAATGGCTAGAATTCTGGTGAT
GGGTGAGCCGATC
112 1M000730 pOOO 7 93 D
GATCGGAGTCCCGMTCAGAGGCCCC
ACTTCTATGGCTCCTGCCTTCC77GGCTA CATCCA1TCCTGCTGAGCTCCTG3AAAC CTGTGTATCAAGTCTTJCCAGT7AGTGC GTrCTGAGTGGCTCTAGAAACCGCT'rCC CATrACAGCGAAAGACCCGTATAAACCA
TGTTCTCITCCTCTGTGACAAGAGACAA
CAGAGACCGCACAAAGGACTGTCTGGCC
TGGGGGGGGGTCCCTGGTTCACAGCTTC
113 1M000731 AGTCCTGA p000794 D
GATCGCTCAATATAACAGCAACATGCCA
AGTGCCACT-rGTAAAATrGTTGTTGAG CAGTCTCA~rATCAACTGAAGCACAATG TCAGGCTAGCAAGAGGCAGGn7CAG~rG TTrGATTAGCGATAGCACACACAAGCCAG CACATGCTI=CrGTGAGITCTAT 1114 1M000732I p000795 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: {TC {TC {TC "CLONE "CLAS "GENE" \L 21 SIFICA \L2}
TION"
MUTATION \L 2}
GATCGCTGAGMTITACAGAGCAGGG
ACGGCTCAGCTCGGATGCCAAAGCTACC
AAGAGCTGCAAACGCAAJACTrAGCAGA 115 1IM000733 AGCACACGTACTCCC p000796 A Cited2
GATCGCACAGGTAAAATGGGGACTCACF
TAGCTAAAACAACAACAACAAACAGC
CTGATGAGTCGAAAGTCTCY-ITAGGI-IG
CCCTCTGTTCTCCAGCCCCACATCCTGA
AGGCTGTLGCATrCCTCCCACAGCAGTCT
CAAAATAACCATAGTGCTCAAGTCCCCT
G3TATCAAATGGTGGTATCTGCATCCACC CTACAGGTGTCTGArFTCMhC'M-rc TI-rGTAAGTGTGTCTGGOTGTMnTGCCTG
AGCGTATGTATGCGCCTAGTACCTGCAG
116 IM000734 AGGCCAGAATAAGGTGTCAG p000797 D F
GATCGTGAGAGGCGAGAAACCCAGACA
TCTCTAACCCTT"CTUrGCCAACTCAG
GAG
CCACCTGTGGCCCCAGCTGGCCACCAGC
CGTFCCTCCCTCAGAGGCCTCCAMTCCA
CAAAAGGCC'rrCCTGG'rG'n-CAGGACA GAGCCTFGGT-rTCCCTGATACCCCTTCTCT
CAGTGGCCACTGAAGTTACAGGGATGCA
GCCAGCCGTGGTTGCCATrGTCTGTATAT
GCTAATCTCCGAATTCCACTTCCTGTUTA
117 LM000735 GA1TCTCGG p000798 D ACTGTCCGTGTFGCiGAAACG'I-rFAGCAAG TCCGAGCGTGYJ7CGATC 1118 1M000736 pOOO799 K Nnzyc SEQ SEQUENCEltc "SEQUENCE") CLONE CLASS GENE 0O: {TC (TC (TC "CLONE "CLAS "GENE" 2) SIFICA \L 21
TION"
MUTATION T2) AMrCr11TGAGTACTFCATATA~GAGC TTCGCATCTACACCACTCT1TGCTCGCCAC TCCTCr1TCTrCCATTACTACTGT
CCACTCTCCAAACTTCATAATCTCTTAA
TTACTATTGTTA1TTrACACACACACACA
CACACACACACACACACACACACACAC
GTATATGTAACCTACTGAATClACTA
ATAGCMACTATCTCCAAGTACAGG
CACTTGATAAATCT-cTGTCAATCTCCCA' GAACAGAA0CCTTAAGAGTCAMAA 4
&GT
TCT=ATCTCAGGCTGTnCTG1TCTATG 119 IM000737 CCTIIGCT=~AATCCATCACCGATC O01D
GAATGTCTAGATGGAGACTGGACAGAG
TUGOATrCCTAGACACCTAACAGAAGCG
AAAGCAGGGGATGGATAAGGTGGGTGC
CTCGTCCTACAGCAGGTTCTGAGTGTCC
GCAGAGACTCCCATGGCT.GGCACCATG
GTrGAAGC1TCCATCGATC 120 1M000738 p 0 00803 C CTA1TICGTTCTCTCCGATC 121 EM000739 p000804 D
GATCCTCATGTCAAGGCAGGGGCAGACC
AGGGTCAAGGGAAAAACACCI'GCT-1.CC TGGGT7GTAAATGCCAGAAAGGGAAGG
CACGGGGTGGGTAGGGTGCJAGAACATG
122 IM000740 GCCCAGACCCCTGTCTCITCTCT pO 008 06 D GCACCTGAC1TCCTCATATAAGACACA
ACATCTTGAGTGCTGCGCAGGTGTACCA
GG3ATACAGGTGAATCCAATCTGGTGGAG A1TGCCCCTGCTGCCCTGATAGCTGA
AGCTGCGTGCCTGGTGAGGTGGCATGGC
CTGCTGTGCGTGGATGGGAACTGAGAGT
ATAAAAGAGCGAGAGGCCCGGGpT'AGA GGAGGATrATTATrCGAGAGAGGATTGT
TATATTGGGAGATATGAACAAGGGAG
ATATAAACAGGGGAGATATA&ACAAGG
GAGATATATGGAGAAAGAAGJAACAGG
123 M0004 1 ACTGAATAAATGTGTGCAGJ&AGGATC pOO08O8
R
SEQ SEQUENCEftc "SEQUENCE") CLONE CLASS GENE ID llTC (TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 2}
TION"
MUTATION \L 2}
GATCCTTCTCCTGTCTTCTC'ITCTGGAAG
GCTGGGCTACATGCCAACATGTCAGAGT
TTrACCTGGGTrCCTTGCAGAGG1TfGA AcrCAGGTCCTTGTACTTrACACAGGAGC 'rAC1TrGCGTAT7GAGTCAATA=F~GTG
TGTGMTGTGTAGGTGTGITCATGTCTGT
124 1M000742 ATACTTG p000809 D GATCGTGCATrGCATGGGTGTG'ITIGGG 125 1MO0743 GAGAGG'ITCTGTCCTI'GCTAAG O01D
AGCTCAGCTFGTCAGGCCTGATTGTGAA
CACTTCACCAACCGAGCCATCTCGTCAG
CACAGCCCTGTYITMrATTCCCA1TFCYC[ T-CTGTATrCTG1TGAATTTCrCACAT
ACTCTCCTFITCTCTITCTGCCTI'CTTCTGG
'IMCTGCATCATI1rCTATA'I7GACATTrA AACAACCCCCAAAATJ1CAAGATACATCA ACAAAAA'ITrAVrCAACTAGTC1TTG1'TA C'ITCCATATCAATAATGAAAGAAAAl7A AAACC'IMCAAA1TCAACAAATCCCTAC
ACTACATATAATCACTITCCTCTATGCTA
AATCCAAC'ITGAA-ATTATATCC'FCAATA
CCC'fGCTGGTAT1TIACTGTCTACATCA 126 IM000744 CrGCCTAGTc'rrcG3ATC p,000812D
CTGGTATATGAACGAAGTTGGTCTGTAA
AGGCCGTCTAGAACAAGGGTrCIrcAAcc
CGAGGGTCGCACCGGGGTCACCTAAGA
CTACTrGGGAAAGCACAAATFA=~ACATT ACGACTCATAACAGTAGCAAAA1TACAG TTATGAACTAGCAACAAAAAATAGrn1 ATGG1TGGGGATrACCACAACATGAGGA ACTGTA1TCAAGGGTCGCAGCAITAGGA AGGTI7GAGAACCACCGATC 127 1M000745 pOOO 8 1 5
R
TrCTAACCTGCTAGGGI-rCTCACGTGG GTrCfTCIGAGGGCTCTCTGGCTTCCC
TACTGAGCTGTAGCTGCCAAAG'ITGAAG
GGGTGGGTCTCCGTTGCGTCTCCCCAGTC
TTrACAGCTCCTGAAACACACTAAGGTA T'17A1TICAAATCCCTGTIFGTGI'GCGAT 128 1M000746 c p000819 ID I- SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: {TC {TC {TC "CLONE "CLAS "GENE" 2) SIFICA \L 2}
TION"
MUTATION 2) AGGGCCCTrCCACCTCTrCTAGAATTrCG
GTAAGCTAAAAGTACATGTATCCGATTA
ATCTGAAATAATIGTAGACAG'ITTGG
TGACGGGTGc3AGGGTGTGTGGTrGCGCG 129 1IM000747 ATC p,000820 C GATCGGCGAGACCACGATrCGGATGCA ACAGCAAAAGGCITrATTGGATACACGG
GTACCCGGGCGACTCAGTCTATCGGAGG
ACTGGCGCGCCGAGTGTGGGGTTCGGAC
130 1M000748 CAp000823 R
TGGGTGTGGAGATGAACGTGGGAACCG
TGGAAATGACCCTAGAATGGGGCTCAA
ATGTGAAAGGCATGCCAGAGGTrGCTCT GTrGTT=AAGTCCCTGCCGAACATTAG AATITrAGCCTCAGTMIAAAAGCTGT7A CrGCCTAGTTGGGTGCTrCTrCTrAAAA AGCAACCAA AA AAA AAA AAGCCGFIT
CACTCTGAAATGTATTAGAAAITITGCAT
TAGCCCAATGGCTAATAAGCGATC
131 IM000749 p000824 D GTrATAAGGA'rrGCATACAAATGGCATC
AGGACTGGATGTGGTGGCACATGTCITG
TATCACAGCACTrGGTGAAGAGAGc3CAG
GGGAATCTCTTTGAGTTACAGGCTAGCC
AGCATGACACGGTGAGACTCTGTCT-'AA
ACAAACAAACAAACAAAAAAACAAACA
132 IM000750 AAGGTAGCATAAGAGCGATC p000825 D ACCTGAATCTTrGAATAATGGGCTGTTr 133 1M000751 TCGGATC 00O0827 D
AACTAATACCITTCCTTCCGCTGCGATGT
TTrCATGAGACTCTGGGTrAGTGCATGGT* CAGGGGCCCAGGCAAACAGTGGCAGT7 134 14000752 ICTGCCCAGGATC Jp 000831 ID I-- SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE {D TC I TC (TC
NO:
"CLONE 'CLAS "GENE" 2} SLFICA \L 2)
TION"
MUTATION \L 2) GTTrAAAGAGCCGGTrCGACCCGCTTrC CG'I1TCGCTCCGGGTCAGCTAGTACTGT
GAACCGCTCGGTCGGOTCCGGCGCTGCT
GCGCACClrACTCGCCGGGACCCTGAAGC CCCCCAACTACATATAGGGGFCTrCCCG
GAAAGTACGCAGGAAGTCGCGTTCGGC
CCCCTCCCCCCAGCACCACACCCAOTCC
135 IIM000753 CTTCCACCCCCCGGGATC p000832 D
GATCCCAGTAGAGACAGAAACAGTGCC
TGGYI'AAGAAMTCCAGGCAGOATGGT
ACAGGATTGCAATCTCAGCATGGGAGAC
AGAGGCAGGATMCCAGGCCAGCCTGG
GCTACAGTATAAATGGGACCCTGTCTCA
AGTAAYIX3AAAAAAAAACAGAGAAAGA
ATTTGGAGACTGTGACTATAGCYFGGTG
ATGGAG'rCCGITU-IGCCTAGCAGAGTGAA
GCAGCTGTGCTCC'IGTGTTCACACCACA
136 WM000754 AAATAA p000833 D V GATCCAGTGAATrCTGGGCA'GTGAGTG TGTGACACAACTTGCTCTATGTGCTG1T AGGGA'TrTGTGCATGCTCAGCCAACAAC AACCGCCAACTTAGACTGATGC rGTCCC Mm. 1313 137 1MN000755 CCTGAGAACACAGACTGACAA p000834 B 36
GATCCI'CCCTACCGGTCCTCGGGCAGAC
CTCCAGCCCTTCGCCAGACACTGTTGGA
AAGCAGGCACGCCTTCCACAGTATGGTC
TGAGG'TAACCCATGACAGCACTCTGGG
TFGCCTGGTGGTG'TTCCTGGTGGGGACGT
CAGTAGC'rGTAGCTCTGTCATJTGGTCCT[
GCAGCGTCTCATI'CCAACTATVFCITCCCAIP.
9138 11M000756 ITCACTCCTCT 0835 ID SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE IDIT T IT NO:{T{C
C
"CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L2) ATATGTG'IMTGTGCGTGTGTGTAGATciT
GCATGCATGGCATGTATGTACCCATATA
AATATGTGTATGTGTGTGAAGTGCTGAT
GTATTTCACACAGCATrTGGATrrAAT
GGAGAAGGTAGCTCAGATGTCAAGTGT
GCCCTCCTGTCAGGAGAGGAAGCCTGAT
GTGCCTGCTGTCATAACTCTGGTT=GAT
AAATACAGCACGAGTGA'TI=GGCTGT
TGGGTMTGCCGTGTATGGATC
139 1M000757 p000837 D GTITrGC1TGCAACA1TGTCATAGCTrAGT
GAACAGTATAGCATTGTTCTGGCTCAAG
AAGCCCTGGTrCrrCAAAGCTCCTACFT AGATGAAATTATMrGATCACAAACAAA AArrTTTTGCAITrTrAGATAATGAAG
GATC
140 1M000758 p000838 C
GATCCTAGGCCAGTCAGGGCTACCAATA
AGAACCTGCCACACACACAAAGGA
GCAAAFTITGCAAAAACTCTAGTCTCA
TGGTGTGACGGTCTI'AAACATCTrFGAG
GGGCTCGAACTGGTGAGGTGOGTCGGA
GGTAAAAGGGC'TT7GATGCACAACCTGA GTrCAACCCCGTGTIArAAGAC-TrTCTG
CAATGATTCTGGTCTGCAGTCCTAGCGC
AGCACAGTCAAGGAGAGATTGAGGCT
GAAACGGAAGAATGGAAGMrGCATAA
CAGCTCAGTGGCAGAAATAACAGGAGA
GACCTGACCTrAAAAACAGGGTGTAAG
GTGAGAAATGATGACAAATGACATCCA
CTTCAACTGTGCTACGAACAGCTACCTG
TGCACACCCCAAACACACACACACAC
141 ITMOO0759 ACA p000839 D
GTAAGAGGGAATGTACTCTCTGCCATCG
GGACACCCAGTOGAACTGCTCACCTGGA
GTCTTGCCTCCACGAAGACTAGGATC
142 1M000760 p000840 D SEQ SEQUENCEftc "SEQUENCE") CLONE CLASS GENE NOD {TC (TC {TC "CLONE "CLAS "GENE' 2) SIFICA \L2)
TION"
MUTATION U, 21
GGGAM~CAGGGCATAGAGCTTAGTTCC
AGACAAAACCAAAGTTAGCAGTCGCCTC
TCTC'ITAAAGACGTTCTCTCTAGCCGCA
GATGACCTCAGAAGGGGCTFCTGGGAGC
CGACTCCCACCCTrCC]TCTCTG'flAGA
GAATCTGGTTGGGCTGTGAGGAGCGACC
CACGAGACGGGCTCCCTGTAGTGAcrITA 143 1rM000761 GGCCAGTGGGAACCAACGAGGATC p000842 D
ACACACACTAACACACACTCACTCACAC
ATACTCACACACACTCACACACACTGUC
ACACACAGACACACACACACACACACA
144 1M000762 CACACACTTTCCACCAGGATC p000843 R 0ATCCCTGC3ATATGGCAGTCTCTACATG
GTCCATCCTAGTCTCAGCTCCAAACTT
TGTCTCTGTAACTCCYITCCATGGGTG MT TGTTCCCACT-rCTAAGGAGGGGCATAGT GTCCACACTTCAGTCTTCATrrFFCITGA GTIT7CATGTG'TTAGCAAAI1TGTATC1TA
TATC'ITGGGTATCCTAGGTIMGGGCTA
ATATCCACYI'ATCAGTGAGTACATATTG
TGTGAGTLCCTGTTCAAATmCATITC TATrCACCA'ITGTGTGTATATGTGTGTGT
GTGTGTGTATGTATATGACGTG'I'GTATG
TTrGTGTGTrGTIATIATATAACGTGTrG'L'AT'GTI
TGGGGGTCAAAGGCATGCTCATGCCACA
GTGAATGAGTAGACATCAGAGGACAAC
1T~CAGGACTCAGTTCTC7FGTTCTACCC TGTGGTTrCCAGGACACTAACCCAGGTCA
TCAGGCATGGTGACAAAGG=IIGACTC
AAGGAGCCAFFITACATGccFrCATAAGA 145 1IMOO0763 AGGGCC p000844 R GCACI'AGGAAGGAAA'ITIGACCCGTGTTrG 1TGG'ITrGTG'ITCTGGITTG~rCGGTGGT GCTn=GTITr=GThrGTTTG1T=r 146 LM000764 ITTGTATCAGGATC p000845 R SEQ SEQUENCE(tc "SEQUENCE") CLONE CLASS GENE, ED (TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L2)
TION"
MUTATION \L 2) GATCCTGGITrTCTCTTGACACAGAAC AC1TCTCCTGATTGACTCTGGTCCAGAC ATTTC1TTCAAAGGCAGAGGACTCTGGC
TAGCTGTGGATGACT~TTCAGATGAAG
TCATrGGTTGCGATTGGAAACGTAATC
AGAGCAGG
147 IiMOO0765 p000847 D GATCGCATTAGGGTITTr=ATGGT1TrC TCATCTrCTC1TCAAA1TAGCATAGAAG CCTCTrCCTAAAGAATGGATACTTAAIT C'ITAACTTGAAAATATC1TICTCTGTGT
GTI=CCTCTCCATTGACTGTTCGCTCTA
TCTATCTATCTATCTATCCATCTATCTAC
TGAAATAAAAATAAGGGAACGCCTrCT TCTCTCATTCTTGTTrGTTGTrfGMTGT TTTGT1TIGAGACAGGGTrTTTCTG
TGTAGCCCTGGCTGTCCTGGAACTCACT
TTrGTAGACCAGGCTGGTCTTGAACTCAG
AATCTGCCTGCCTCTGCCTCCCAAGTG
CTGGGATrAAAGGCGTGCACCACCACCA CCTGGCTrCTCTrCATTC~TAAAACGA
=GAAACCIT=~AGTGAGGTCAAC
ATTGTGTACTCCAGTCCCACTCATCTrCC TGTCCCTfCCCTCTrAGGCCTGCCTGTCT GGTACCTCACTCATG'ITTGTGTAT7CTCT OTGCTGAGCCTCTrCTGTG=-TCCCAGC ACATGGCTGCTGGCTCCAG'IMCAT-rCC 1148 1 M000766 AGTCCCTTGTGATGTGAGCCTAGTrCAG O05IR SEQ SEQUENCE~tc "SEQUJENCE") CLONE CLASS GENE NO: {TC ITC (TC "CLONE "CLAS "GENE" 2) SIFICA \L 2}
TION"
IMUTATION \L 2)
CTCTCATGGCATGGGTCTCAAGGTCCTG
CCAT1TCTGCTCCATC1IACCCCAGCAC ATCCTGTAGACAGGACAAATrGTAGGCC GGAGG=T-GTGGCTGGGTrAGAGACCC AGT-rCTCCACTGGAAGCCCTGCCCGGT
TACAGGAGGTGACCAGTTTCTGGCTCCA
TGTCCCCCATTGCTAGGAGTCTTAGCTG
GGGTCATTCTCACAGATfCCTGGGAGAT TACTCTATITATCTCCTTG1TCAAAGTG
TTCCATCAGATATTAATTITCTCAAGAT
TCAATATrCTCAAATATTA'ITCTCAAGCT ATGGACCC'FFCAAATTrACAGATAGAT17 TATGAAITGAAAAGT'rGTGTGG3TFGAAT
ATGTAGTTGAGGGTGACITGAACTTCT
GG'I ITIICCTGTGTCTACCTI'CCAAGTGC'I'
GGGGTITACAGGTATGAGCCATCACGCCA
GT7TCTGTAGCACTGAGGCTCAAACACA
GGGCTTCTGTCTGCTAGGCAAGCACITCC
ACCTACCAAGCCAAATCCCCGGGC'=A
CTGCAI'CT'ITGTGTGTATATGTATGGTAT
GTGCGTGjTGTATGI'AAGGATATATGTAC
CTGTGT
149 M000767 p000854 R
GATCAACACCTGAAAAGTGGCGCCGCCT
ATACACATCCG'AATI'GAGAAGTATGTG
GAAGATrCCATCCGTGAAAT'rCAATTrAT
CATGCAAGCCAAGTGGAAGCGCTTCCCT
GGGGAAGGAACCCAGCAGCCGCATCAA
AACGACCCCACCTGTCTAY1TCATGTC AAAAciAG'rGAGAAGTCTGGGTGATGAA
ATAGAGAGCATACATCAGCTTAATGAAA
ATTTCCAGGGGTCCCTGGCTGTAATGGG
150 ILMOO0768 AGTCCCAT p000858 D
GATCACCACCAGGGTGTTGAGAAAAAA
AAAAAGCAAGTI7AGTAGATGTTAG 151 IM000769 p000860 D GATCTGACAAAACCTACCTGTT=hGAA CACATGTrGGGACAGCAGTCTGAGAGAA TCTATGAATfAAAAITCCYF-FCTGAG'ICTG 152 1M000770 IGCACA'TTGGTACAC Ip000861 ID F SEQ SEQUENCEftc "SEQUENCE") CLONE ICLASS GENE IDIT T T NO:{C {T C "CLONE "CLAS "GENE"M 2) SIFICA \L 2)
TION"
MUTATION \L 2) GATCAl7ATACCCCAAATGGTACTGTAT CTATATATACCTCAAACATGTCATGrrA
AAGAAAATACTCTGTTGAACTAA'ITCAC
153 1M000771 ITGTIT p000863 D
GATCACAGGACTGAATCACATI-TATGCC
154 IM000772 AT p000864 D GATCAT'TrACT'rGTTTrGGTGTrrC ATGM~GTGGCTCCTTrATGTAGTCTAGAT
ATTAACTTGAAGTCTGAAGTGGAACTAC
155 IM000773 CAAAGATTTTCTrCCATCCTCATCT pOOOS 6 5 D
GATCAACCGCAGATGAGGTCTATGGAGG
AAAAACGATGTCTGGAATnITTAA~AA T-rGCTCAGC 156 1M000774 p000866 K yc
GATCATCATGTCAAACCTGACACGTGAC
GAGACAAATCTGTGTGCACAGAGGTGTG
ACATCCTAAAJAGTACTAACAATACCGC'
GGGCAGGGACACACGCGGCAAlIJCCAG
TCCTGGTATCCATGGCTCAAGCTCTGCA
CGGAGAGCCCGGCACACGGCAGGAG
AGAGCCACAGGCTAAGGAGAGCAATGC
157 IM000775 TAACTAACATGGCACCCGTGTTAG p 0 0 0 8 67 D
GATCTGGCTCCAAGGGCCTGTACTCAT
GTCTACAATGCTCCTACACAGATATAT
158 IM000776 p000868 D SEQ SEQUENCE{tc "SEQUENCE") CLONE CLASS GENE ID {TC {TC ITC
NO:
"CLONE 'CLAS "GENE 21 SIFICA TL 2}
TION"
MUTATION kL 2)
GATCAGCCTTCCTCCAAAGGTACCTGCA
TAGAAGAGACCTCTGCTCTCACCTACTC
TCCTCTACAGITCAGCCCATATGGC17C
ACCTGCATCCCCTAGAGACACACACACA
GACACACACACACACACACAGAAACAC
GCACACAGCACACACAACAGACACAAC
ACGCACACTCACAACACAAACAGACAC
AACACACACTCACAACACACTCACACAC
ACACACAACACACACACACAACACACA
CTCACAAACACACTAGTACACAAAGACT
CCAACACACACATrCCCATGCACTACTC CCTCAGTATCCGCCGCA'nGTGTTCAC
ACTCATCCACACTCTCACACATGTAGCA
CACACACATCAT'rCCTACACAGGCATGG
ACACACACATGCTCCTATACAGGCATGC
CCAGTACTCTCACATGCATGMIGCACG
TCCCAAACAGG'FrCCCACAAGGG1TrG
GCAAAGTACATGCATCCTCACACGCTAA
159 TGCAAGCCGTCACACCCCATACCACAAG 1rM000777 CATGCAC p 000870
R
GATCAGATGTGGAAATTAGAGAGAAGT
T1TAACGCTCATGCACATrTCTGAAA
ACTCMIIGCGAGGTATACTGGTAGATAA
ATGAACATI'GGTCAGACTCCTCTAGMh
AAACCACTCTCTTCCCCGCTATGGGGOG
AGGCGAGAGGCAMrCTAAAGCTTATAT GTAG17GCAAAGTGTGTGTGGTGTGTGT
GCATGTATGTGCATGTGGTGTGTGTGTG
TGTGCATGTGGTGTGTGTGCATGTATGT
GCATGTGGTATGTGTGTGAGTGGTGTGT
GTGCATGTGTGTGCATGTrA'TGTGCACCG
TGTTGTGTGTGTATGTGTGCATGTGGTGT
160 IM000778 GTGTGCATGTATGTGCATGTGGTGT p000871 R GTAACATCTACTAACTGCTrFThIT 161 EN4000779 TCTCAACACCCTGGTGGTGATG 00O0872 ID
SEQ
11D
NO:
SEQUENCE~tc
"SEQUENCE")
CLONE
(TC
"CLONE
2}
CLASS
(TC
"CLAS
SIFICA
TION"
\L 21
GENE
{TC
''GENE''l \L 2)
MUTATION
162 PJM000780 163 JEM000781I 164 IMOo 0782
GATCATAAGGACTGTAGCAGGCWAG
GCGCGTGCCCA4rAAAGATGGCMC CTCTCCCACCCCAGC M JGATGCTCTGAT
TATCCTAA
GATCAGGCTGGCCm'J&CTCAGGGAGA
G
C rCMCMCTTC T~f-[JJ 0 GAGACAGGrFCTCTGTATAGCCCTGG
CTGTCCTGGAAITCACGTAGGCCAGGA
TGGCTCAGTCTGC7C'ATAGACCA
GGACCACCAGCCCAGAGATAACACCAC
TCACAGTGGGTGGTCCTCCCCACATTG
ATC
GATCACACACTCATGTGGCTGTCAA
CTGTGATTGCTGATACAGGGCTGT
ACAAGTCAGCTATAGCTCCGCAT-GCAG
CTGCAAC p
GATCACMTAGAGAAATCCCCACAG
CTGGATCGTGGAGGTATCCCCAAC
TGAAGCTCGTCTCTGTGATAAT-rCCAT CCTGTGTcAA4GnGACGAACCAGCC
AGTACACAAGTCGACACAAAACTAGCC
AGTACACAAGTCAACACACAACGCGCA
CAAGCTGAGGCAAGAGACCAAGCA
TCTACCAGGCCTCAGT-GCTATGTCCAC
TTCTGCAGCCACTCCAAAACACCTGTCA
GAAAT-rCGGTTrTGATAGAGAACTCACCG
AGGGAMCCCTACACAGGTCAACCA
GrGCACAATACAACCTA
PC
GATCACrTGATAAAGATGCTCTGAGCAG
AGGCTCACAGGJ&ACCCAGCCCTGTGTGC
TCCCCAGGAGcGAGA'n-CAGCAGTCAC
AGTGCAGTGTTCACGTGACCGTGCGCAG
GCCATGAGCACTAC
P
p000874 ID Ip 00 0875 IB NIM.8363 000876 JR 165 JIN4000783 '000877 'D I- I 116 ILM000784 ~00878 _JA ICctS 167 B A1615991I 167 4000785 SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID f T T NO:{T {T C "CLONE "CLAS "GENE" 2) SIFICA \L 2}
TION"
MUTATION \L 2)
CTCCTITTTCAGCAAGCTCCTCACATCAC
AGGCCTTCTC11TGGGATGGCAGCCGCCT
TCTATCTGGAAAGTATGTGACAGCTCAC
ACAATCCTGTAAGTCTrCCATGTAATCA
CATI'CGACTGCCTCTCTCTGAACGTGCTC
CATGCCAGGGCCATG'IGGAGGGAGCAG
CAAGACYFGAGCTCAGCTAGTCTATGAA
GATGGTGGCAGAACAGGCTCTGCTGCCT
TGATC MMU767 168 1M000786 p 00088 1 B 154
GATCAAGAGTTCAAAGTCATCTTCAGCT
ACAAATGAAGTTGGAGACCAATCCAGA
CCCTCTCTCAGAAAAAAAGGAAAAAGG
AGAAAGCAAAAGGAAAGGAGGGGGAG
ACCGAGAAAGAGAAGAGGGAAGGAAA
GGGAAGTCAACAGAACTCAAGGTCAGC
169 CTGGGAGGGTGAATGAGGCArrGTFGTC Mm. 1388 11N1000787 T p000882 B 09 GATCACCTCCACMrATGGTGGACAGAG
GATGGCAGTAGTAACTGCCCCAAGGAA
ACAGAAACAACAACAACAACAACAACA
ACACCTCCAAAAAGACCAAAGCAGTAA
GCTGTAGAACAAATGCAAAGAGCCAAA
170 IM0007 88 c p000883 R
GTTCCACCTATAAGG'FIGCAGACCCCYP
TAGCTCC1TGGGTAC2ITTCTCTAGCTCCT
CCATTGGGGGCCCTGTGATC
171 1M4000789 pOOO 8 8 4 R SEQ SEQUENCEftc
"SEQUENCE")
NO:
MUTATION
GATCACATGGACCGATrGCCGCGGGACA
TCGCACAGGAGCGTATGCACCACGATAT
CGTGCGGCTI=GGATGAGTACAACCTG
GTGCGCAGCCCACAGCTGCATGGCACTG
CCCTGGGTGGCACACCCACTCTGTCTCC
CACACTCTGCTCGCCCAATGGCTACCTG
GGCAATCTCAAGTCTGCCACACAG3GGCA
AGAAGGCCCGCAAGCCCAGCACCAAAG
GGTG~GGTACAGACA
GGACCTCAAGGCACGGAGGAAG&GTC
TCAGGATGGCAGGGCTGCTGTGAC
AGCTCGAGCATGTGTCGCCTGTGGACT
CCCTCGAGTCACCCCATGGCTACVI7GTC AGATGTGGNCTCGCCACCCCrCrCCCC TCTTCA1-rCCAG GACTCCAGA CrCTA ~3ATATAATrATG-fTAGAGGGAACT !rT=AAATrGAAGTTCA1TrfATTGTAT 3AAA1TA1TTTGATAA 172 jJM000790 pO00885 IK [Votchl 173 JIM00 0791 pOO0886
GATCAGCATGGTTACAGAGTAAGT'AC
AGGACAGCCAGGGCTCCGTGGAGAGAC
CCTTGTCAGAACACACAA
A
4 ATrAGAAAGAGACCCTCTCTCTGAT-J-
GACCAATCACCCGTGTCAATCTTGCCA
CAACCGAATCACCACCA&AflGCCAGAC AAGCGGCTATGCTGGGMT'1ltJGAGGflG
GACTCCTCAGGTAGCCCGTGTCTAGGCA
GAATGATGCCAGCAGCTACAC I II I AG AAAGTAGCAG~rCGC ACCTAGGAATGCAGC IRp 087 174 175 ~IM000792 W1000793 GATCAGTCATGTCCM~AGACGmrACUr TCATCCCAACTrroGA~cA-p.CAAGC pOO0888 p000888 SEQ SEQUENCE~tc "SEQUENCE"} CLONE CLASS GENE
EID
NO: {TC ITC {TC "CLONE "CLAS "GENE" 2) SIFICA \L 2} TI ON" MUTATION \L 2) TrACAAAGGCAGAAATATCAGAAAGAG CCTGAAGTAGCAGCTGTrAACCTGTACC AGGAACTGGCCGAAGTACACACGCGTr AACTCAGCCCTAA~rATTCTCGGGAGAT ACAGTrGATTATCATACACATGTCAAAA
TGGAAAATAAATGGGTAACTAAAAATT
GAGGAAAATAAGATTAACACJ-TAAACA
176 1M000794 ACCTAGTTCATTATGCCACG*JTGATC pOOO 8 9O D F 177 1IMOO0795 GATCAGAGTGGGACAGATTAAATGT-rA p000891 D
AAACAAATACAAAGTGATAATGTGTGA
CATCTGAAc'I~i'CAATGAGATAGGTAA TrATCTCTGGGCAATIGG3TAAATGTGCT
GGCCAGGAAACGTCACAGCCAGAGTTCA
ATCTCCAGGAACTrAGGTGGGGAAGGA GATAACTGAC'rrCCAAATGCTCACCCCC AAATATACAATTrAAAATAAAAATCTTCC 178 1M000796 FI1ATGAGTAGCAACTGATC p,000892 D 179 JIM000797 TAcccci'GGTCGTCCAACACTCCGATC p000893 D GATCATGACATAGACTrGAGTCAC1-TCT
CTGCAGTGTCAATAAAAGCCCCTAAG
GGACAGTGTGGACThrAGAGATAAC 180 IM000798 p000894 D AATGCCAGCCATAGTGGCACACAC=hr AATCCCAACACTCAGGAGAAGTTAAGTr
TCTCTTAGCTCAAGGCCAAGTAGCT-FGG
GCTACTCCGTGAATTCCAGCCCAACTAC
ATAGTAAAACTAGCCT'TAAAAAAAAAG
OCACAGGGAGAGGGAGATAACAAAAAT
GCCCAACTCCTAGCTACAGTAACTGTAG
181 GAATI'AAGATAGAATCTGTAG'TFGTFT IIM000799 ATCATrATCGTGATGATC p000895 A l GArCAITGGCTTGAT-rGTAACATrTATCAA AGCTI7CCTTGGCACACTGCAGGGCTGTC TTCGGGAAACTGCGTA17GTGCTCTTCA
GGTACAAAGCATAGAGCCC'IACATGAG
AAACGCTGGGGTrAACTTrC3-rCTAG'rC cc'[CTGCCCCACT'rGTGGCGC1TCCCACT 182 IM000800 CATGACTTCTrCAGTGTGTATTrCACTT p000896 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID T T T NO:{T C {C "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION TL2}
GATCATGCTGAACTCUGAAAGTATTCT
AGCAAAATGTGGCTrAAAAGAAAGAAC AACATrAACTAGGTATGCMIGAuA.AA 1TACCTGTGGTAAAAMTCCACAAGCAT 183 GAGAAGTrTG'ITTCTTITGTrGAACC'ICA EM000801 GAG p000897 D GATCATATATCAATITATTI=AACTn 184 GTTrGTI17G7TGTfITGTTrGTGTfCG 1M000802 AGACAGGGTTCTCTGTGTAGCCCTGG p000898 R AT7GTGTATCCAGAGTGTGACAAGGTAT 185 EM000803 ATATGGTrGTGTGATC p000899 D GATCTCTGTCTGGAAGAGTGCTrGCTG GTTCCGACTAC1Tlrl-rli-TI III ITII r Tr-GCTTGGGTrCANATTGGCTTCA GG'rrCTGGGCCCTrrCGTGGGTTGTGCT 186 IIM000804 GCANAGCCCCA1NACAATGTCTrGGQ p000900 R
CAGGAAACCAGGGGAAATGGGACACAG
TGACATCTGAGTCC1TAGAAGAGGTCCC
ACAAAGGTCTATATGACCTAGCAACGTC
ACTW'TGAGWrA1TfCTCAGACACAGTO
GATGMTGTCACAGCACACTGTAGGACA
TCCCAGAACAGCACCATGGGAGACCAT
GGT'rGGTGCAACAGAGAACATGCACACT GAGACAGTACAAGAGTrCCCAAGCAAG
CAGACACAAACAATGGACTCAATACAC
187 JIM000805 ATACAGTGGCAGATC pOOO9O 2 C
GATCTGCTCACCAAAAATCTTGTCCTAG
188 GGAAGTTGAGT'TGAACTGCGTGCTrAC JIM000806 TGGCAAACACGCGGTGCCCPAAFFI'AA p000903 D ACAGTrCCCCCTGGAAATGGTCCCTGTA 189 1 M000807 CCAGAGGAGCAGATC p000904 D SEQ SEQUENCE{tc "SEQUENCE") CLONE CLASS GENE ID (TC (TC (TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 21
TION"
MUTATION \L 2)
GTGGGGCCCAGACTCCAATCCCGAAATA
lCATTAGCTGCTGCGCACT7CTCCGAGG AAGTh[rACACCAGTACCC'I'AAGTYFCAAG
TCTCAGAAGCCTCCAAATCCTCGTTGGA
CCCCrATAMICAC~rrGGTCATCCGACTG
TAACTCACTCACCGACAAGACAAAGAAT
ATCTTAGGCTCCGTCGTAAAAGAACGAG
CCCGGTTCACCGCAGCTCC1TPATAGTC TCC M GTGCGAGATC Mn.2 179 190 1M000808 p000905 B 18 GATCTGAAGATrAThIGACAACAGCTAA AAAAAAAAAAACCAAAAAAA4~ACCCC[TT ATTACTAACCAAGGGAAAATrGCAAAAA TAAT'rAAAAGTTCCTCAATTAAGTAA
ATATCCAAAAAGATTGGTTOTATAACAA
AGTTGAAGAGTCAAACAGTATFI'GAATA
191 IM000809 A p000906 D AGCTCA1TGCCGrrAA3TrCCTCAGCCT AATGAGAATCTAAGCC'T7GA'rTl'GTATG TACCATAGCATCTAc3ATC 192 1M000810 p000907 C CCT'rGAACCTAGT-rCAGGGAATAGGCCA
CC'IGGG'IGGGACTAGTGCTGGTTGGGGA
,rGAAAAGACAG'FrGGCTCAGGTGAACCC
TGCTCGCACCCTGGTCATCGTCTGAGAC
TGCYITGATTGCTGACCCCAGTGCTCCA
GCAAGAAC'FrGCG'rTC'rrGITCTCTCCAC
TCAAGCCGGAAGAAATCTGAGGAGAG
GTGTGAATCCTGAGCCAGGA[FGTCCAAA
ACAACGGAGTTGAGCCAGAAGGACGTC
TAGTTGGGCAGAGTTAGCTCAGTCCCCT
GACCCCCAGTCCGTGCAAGCTCOAGGGT
GTTATATAGTGATACAGATC
193 1M00081 1 p000909 D GATCTCTrCTflATCTCTACCTI1TGGGGC ACAATC3TATCTGGGGACACCACAGAGC
CCAAGAAT-TGTCCTGTATCAGAAATFUG
GACC=TCTGTGGCTATCTGTAAACCCC
ACTGAC'ITAAAG=IAAGTAGAAAAGG
ATATGCCT-flrGTAGCATGGTAAGGTCT 194 10008 12 Y-rATGGCACAGGAGGATIGTrCATCCATGTF pOOO 9
I
2
R
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ED {TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2) CTTCCTFCCITTrGAAACAGGGTl-rC
TCTGTGTAGCCCTGGCTGTCCTGGACCT
CAATCTGTAGACCAGGCTGGCCTCGAAC
195 EM000813 TCAGAGATC pOOO 9
I
3 R
GATCTGGTCCACMTACACAGCTGACCA
196 IM000814 TOAGACCATGTNCACATAG p000914 D
ACATGACATATCACCCTCAITCAGAGTT
CAGAGTCTTCAGAAAACTGGGCGCCTGA
AAAACCTGACC1TrAAATI=CGTCCAT AGTrCTrCTG'IrGAATGAATATT-CAT 197 EM000815 AAAAGC1TCATAAATGCCAAGATC p000915 D 198 1M000816 GATCTrCACAGCGCACCCAGGGATC p000916 D CTITrCTTGGTATTTAGGGAGTCAGGA AAAGAAAAACCA'TGGG1T]TACATTA G='~CAGGTAGGGTrGTGGCT=rGAG
CAACAATAACGTATGACM~GTGGTCGG
199 1M000817 TTGTAGATC pOO 0 9 17 D GATCTTC1TATATCTGGTTCCTGGGCGC 200 1M000818 UTCCGGTAT p000919 D
GATCTCTGACAGGGMICAAAGAACTGT
TACTGATGTTAGATTGCCTCTGAAGAC
ATCACATATACTGTGCTACTCTGC =TGT
CAGAGTCCCGGGCCCTGGGCACCCCAGA
CGGCAGCAGAGGAAGAGCGGGGTATCA
CTICTATACITCGGTAAAGTCATTGGG
201 ILM000819 ATATGTGCCCT p000920 C T CTCCTCTATCATTATC1TCTrCCT 202 1 M000820 TCUCCATCTGTTTGTTT 00pO0921 D SEQ SEQ1JENCE~te "SEQUJENCE") CLONE CLASS GENE NO: {TC {TC (TC "CLONE "CLAS "GENE" 2} SIFICA \L2}
TION"
IMUTATION \L 2} GATCTGCTCACCAAAAATCTrGTCCTAG GGAAGTTGAGTTTGAACTGCGTGCI1AC TGGCAAACACGCGGTGCCCAAA'I1TAAG
GAGTGCCAACGACTTCGCGGGCCAGCA
AGGTGAAACCGGAGCOCGCACGAGTGA
GCAGTGGCCAGGAGGCCTGGCCAAGAG
GCCAGGGTCCCTGAGCATGACCGAGAG
CTGjGCGTGCTCTCTGTAACCCCCAATCA GTrCACCTAATCTrCGGGTCGAAAC'GA
GCCCTGCAGGAGGCGGGGCTGAGACTG
CATCCCAGCTCCTGGCCCGCTCCAGGGG
CGACCC
203 IMOO0821 p000922 D 204 IM000822 CCAGGCATCTCCAT-ICTT'AATCCAGATC p000923 D CATAGACTCIT-FCAY1T'AGAATAAAGTG
TTCCACCTAACATCCTGTAGGAAGTGAT
GAAACTAAAAAGAAAAAI'AAACGCATT
ITCTC1TCTCTCGTrACITICCATTCA CTAAACAAAATFGACTMfIr=rTCCAT
GAGAGTTCACACTGGGTCTGCCTCAGTA
AGAGTCACACTG17CAGCCCACACACGC TGTGATATGTTA'T7ACTCATTCTCTTCT
CAGGAACCACTCTCACATGTGAACCCTG
205 1M000823 AATACCAGCTCCCTCCCTC1TCAGATC p000925 D
ATAGGTTCTGTCTCAAAACAAACAAAAA
ACCAAAACATGTCCACAGGGTCCAACA
GACACAGTCTCCGCCACTCACAACTAAT
GGGTACACAAATACACACCTCAGCCTrA
CATGGTTACAGAGAGAAGCAGGACCAC
AAGGTAGGCAGGC2ACCTAACAC'ITIGCIT- CTrGGAAGTTGGAGCACACACACACACA CAGAAACACACACACACIrUCTCACACT
CACACACACATTCTCTCTCTCTCACACA
CACACACATGCACACATGGTCTflGTACA
AGGTCCTCCTGGGATGGGCACACACAGG
GGTAAGAGGACTCCAGATC
206 1IM000824 p000926 D I- GATCGAACACNCTNGGAC'TrGNTAAACG 207 1 N000825 NTrCCCACACNGACAGA p000928 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ED (TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L2)
TION"
MUTATION \L 2)
GATCGTCTGGCCCGACCGCGCCTCAGTA
GATTTFGGGTCCTGGTCTGAGCAGCCGGG
CTGGTGCGGGTGTCGTCACTAGGATAAT
GAATACAGCTCCACTACCTATACTACCC
AAGACGACCCCTCACACGCTCTGCGAGG
AAACCGGTFC I IGGAC 208 1M000826 p000930 D
GATCGACCGCAGATGAGGTCTATGGAGG
AAAAACGATGTCTGGAA1TrATTAAAA
TITGCTCAGC
209 1M000827 p 0 0 0 9 3 3 K Myc
AGTAGACTGAGAMTGTGAGCGCTAAGA
TAAAGATGAGCAAAGG1TGGCAGCTCT
TAGGTATCTGAGGGCCACCGTCCTCTAC
AAAGCAACGAGAGGCACGGCGGATTAG
GATAGACTGGTTGCATCCAAACACTACC
TTGCTGCCTCAAAGGC'ITATrGGACACC
ACAGAAAGACCTCTGGTGGAGGCAGAA
210 OEMOO0828 GTCACAGGACTCCTCGTCAGAGACGATG 00O0934 D
GATCGGCCTTCCTGCAAAGCTACCTGCA
TAGAAGAGACCTCTGCTCTCACCTACTC
TCCTCTACAGTTCAGCCCATATGGCTTC
ACGTGCATCCCCTACACACACACACACA
GACACACACACACACACACAAACACAC
ACACAACACACACAACACACACAACAC
ACACTCACAACACAAACACACACAACA
CACACTCACAACACACTCACACACACAC
ACACAACACACACACACACAACACACA
CTCACAAACACACTAGTACACAAAGACT
CCAACACACACATTCCCATGCACTACTC
CCTCAGTATCCGCCGCATrTGTGCTCAC ACTCATCCACACTCTCACACTrGTAGCA
CACACACATCATTCCTACACAGGCATGG
ACACACATGCTCCTATACAGGCATGCCC
AGTACTCTCACAT6CATGTrGCACGT7 CCCAAACAGGT-rCCCACAAGGGTTTGGC
AAAGTACATGCATCCTCACACGCAAATG
CAAGCCGTCACACCGCATACCACAAGCA
.211 1M0 00829 TGCWk p000937 R SEQ SEQIJENCE~tc "SEQUENCE") CLONE CLASS GENE ED ITC ITC ITC
NO:
"CLONE "CLAS "GENE" 21 SIFICA \L 21
TION"
MUTATION \L 2)
ACACCACATGCACATACATGCACACACA
CCACATGCACACATACACACACAACACA
TGCACATACATGCATFACACATGCACACA
CACCACTCACACACATACCACATGCACA
TACATGCACACACACCACATGCACACAC
ACACACACCACATGCACATACATGCACA
CACACCACACACACTTIGCAACTACATA
TAAGCT1TACJAAATGCC'ICTICGCCTCCC CCCATAGCGGGGAAGAGAGTGGTlTAA ACTAGAGGAGTCTGACCAATGTTCA'fl'
ATCTACCAGTATACCTCGCAAAGAG'IT
TCAGAAATGTGCATGAGCTGTTAAAAAC 14s. 17043 212 IM000830 ICTTA'fCCTCAT p000938 B 4
GCTGGACCCCGGTGACAGACTGTGCAGA
213 1M000831 TGGATC p 000939 K Pimi 214 [M000832 TTAGCAAGTCCGAGCGTGTTCGATC p000941 K Nrnzyc 215 1M000833 ACTGCACACATTrGCCGGTTGTCGATC p000943 K Notch] CAAGTGTAGACATrGCAGGAAAAAAA'r
ATGGTGACAGTGAACAAAGCCCGTGAA
GGTGACAAAAGCCAGTTAAAGTAGGAC
AAGGCAGAGCGAGGCGGATGACCGGGA
CCAGGCCCAAGAAAATAAACGAAGGCC
AGGAIC AW32 14 216 1M000834 p000944 B 168
GTCGGAGGAGCTGGCTGGACCGGTACAT
GCCCTGGCCATCCAGGCGAAGACCCCCG
CCCAGTGGAGAGAAAACCCACAGTTGG
ACA77AGTCCCCCCTGCCTAGGTGGGAG CAAGAAAACTCGAGGGACC'TCl-AATAA
ATACCTGGATTGGGAGAACGATC
217 1M000835 p0009 46
IR
GATCGCGGGGCTATCTATAGAGTCCCCG
CIGATGTrCTGAGAAATGAGCCCTAGAAAT
GACTAGAAAGAAAATCGAAGTATTCT'G
GCTCCTGGAGAC~rCCGCAGCGA0AAGT CACAGA'I7CAGGACACAGATT'GACAGG
AGCTGCGGGCGCTGGTAG
1218 11M000836 I p 000950 ID I-- SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: {TC {TC {TC "CLONE "CLAS "GENE" 2} SIFICA \L 2}
TION"
MUTATION \L 2) GATCCCAGGAITrGGGAGGCAGAGGCA 219 1M4000837 GTTGGCCCCA p000953 R
CAGGCTGGCCTCAAACCTGCAGAGATGC
TCCTGTCTCTGAGTGTAGAM~AATA
AGGGGTTCACGATC
220 1M000838 p000954 K Lck GTTGCTGGGCCCTAAGCGCCCACA77C
ACAGCTCCGATGCTCATCAGCATGACTC
TCCTGAGCACAT'rATCTGGTGGTGGCTG
ACACTCTCTTCAGTACCCCCCCCCCTCCC
AAAAAAGAAAAAAGAAAAAAAGGACTG
GrrGCTAAAAGAAGTAAAAGTCAAGTC
ATCAAAAACAATGTAATATCCTGTGTGA
AAGTCACGAAGCCTTGCGGMhGAGTCC
CTCGATC
221 1M000839 p000955 D
GATCGGCCGGCTGTCCAGCGACCGGAG
AAAGGAGAGCACTCGAATCGCAGAAGC
TATCAGGTGAGTCCGACCTCrCTCTGJ&A TGAACG;rIGGGGAGCCTGCCAACGGT GACCAAAMIAGCCAGTrFAAAAGTACAG
GCTGCCCAGCTGTAACGTACATCAAAC
222 IL000840 AATGTGCGATTTTAT=IrAGTGTG&A pOOO956 D
ATAGTAACACTTGGGAGGAGCCATCCC
AGTGAGGCTCGTATAGCATAGCCCTGTC
CAATAGAGCCTCTG1TGCACTCTGTGTA CACTrAGCTCC17GCTFAGGGATIr=
TACATOGGGACACAGCACCCCAAM'
CACATrGGACAGACTCCAGGACACCCCT
CGGTGTCCTGTGACGCATACAACAGCCC
CCCACGGGGCTGCACCGAAAACGCCAC
AGTACTGAGGCTGCACCTCACTCATCA
CACACACGTCTATGGCTCAACGTCCTGG
AGAAAAGGCTGCGACAGA7TCCCACATC
TGGGAATGCAGTGAAAAAGCACTCACA
CTGGGGGTGGGGTGGGGCTGGGGGGGC
ACCCTGTCT-rCCCGTCnrCCCATGACCCT C'CCC1TCCAGGAGACCATAGCCAGAG CTGACAGGAGATrCAGTCGCAGCTGCAC 223 E1M000841 ACGCTGCTGCCI'TGCCGATC pO00957 ID F SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: (TC {TC {TC "CLONE "CLAS "GENE" 2) SIFICA \L 2) lION" MUTATION \L 2)
GATC(IGGCAGGACACACATI'GGGGAGG
CCCATCAAGCCCGAGCCTGcciTG'rGAG CCCCCGGAT7GGCAGGGCAGAGAGGAA AGCTGCTGC0TGCT=ATAGACT'rGGG
GAAGTCACAGGCTCCGCTTGCTTGGGGG
AGGCAGGAAACCCCCTCCACCTAGGCGT
CTGCCAGAGCACCCGCAGGCTTMCTr
GTCTCTGTCCCCCTCCCCAGCACCTCTTC
CCCTGAACAGCTTCCCTCTCCTGGCCCT
GCTGTCCC1TrAAAGGAACTTGAATCAG AGUrGAGAATGATGGTGACTCAGGGTGG
AAGGGGTGGTCACTTG
224 1M000842 p000959 D
CCAGGGCTACACAGAGAAACCCTGTCTC
GAACAAACAAACAAACAAACAAACAAA
CAAACAAAGT FAAAAATAAAAT'rGATAT 225 1M000843 ACGATC p000960 R
GATCCAGGACATGGCAGAATATGGTCAT
CTC'LTF'GCT-rGCATGTCACACGAATGG ccTrCTGGCTCCACCCCTGAffGCTTGCTC CCCITGGAAGCCTCTTrGAGCCTAGCTAA C1T1CCTGTTCACCTIlTGTAYrATGTGC TCCCACCATGGCCCACCAGGCTCTGC1T
GCAGCACTGCAGCCTGCAGCTCCAGCGG
CCTMTACATGGCTCCTGTAAACAAGTCC
CAGAGGCCTCAGTGTCATCATTTCAGCA
ACCGCCTCACTFCIGGTGCCGCCTTCCT
TTFAJTACMr~CATA1TCTGTGACCGAAA
TACCCCCAAAGAAGCTACTCAAGGAAA
GCAG'rATGTGTGGGCTCACCA7TFAGAGG
TCAGTCCCCTGCAGCAGTGGAAGCATGT
GCTGGTGACGC
1226 1 M000844 1 p000976 ID F
U
SEQ SEQIJENCE~te "SEQUENCE") CLONE CLASS GENE NO: (TC {TC {TC "CLONE 'CLAS "GENE" "TL2) SIFICA \L 2)
TION"
MUTATION \L 2) GATCGCTAC~fT]CAGAGACGCCTiCA TAAGGGGAGAATGGAfiAGATGCTGGT TGACTrGAAAGATITrCTCTCTGATrGTr TrACAGGAAGTGCATCTGTACACATGA
GAGACTCCGGGTGGAGAGGCATTGTGG
CGGYFGAGATGCACCTGGGAGTGCCAAC
TGCCCGGGCTTGTACCACAGCTCTGCAT
AGCAGGCTGGAGCAAGCAGCCAGCp
CCAT'TGTGCCCTAGCCTCATCTCCTCCAG
AAGAGGTTATCTGGGCTCTGTGTAACCT
CTGCTCIIIGGCTATGGTATTCCTTCT-G
GTGCTFMTCTGTGGTCAACCTCCAGGTAC
AC1TAGGGCCTATCCTAGACAGACTGGG AAGAAAGAATGACATTCCCATrGACCTC TGTFIIATITCCTGGAAATCCAGACCTr GTrCCAGTTAGTGGAGCATGGGGT7AGA CCAACCACACTGCTAAGAG=r~GGCCT 227 1M00845 GTAGACATATCTGG0
C
TAGCAAGGTAAGTACTrGTCTCAAITC
CAGGTAGTATAGAAGAAACATATATG-
ACAGM'TAACACCAGAACAATCACACA
GTGTTGTA1TJAGCTAAAATATGACTCT GTGG1TrCAAATGGCATAGT-rGTGGAC AACTTrAATTAAGCACGCTCI-ATAAGAC
GTGATAGAGTATGTGCCATCCAGATACT
AAGAACTGTGTCCAAAGAGCTTrGGGAC ACACACTAAGGGGCCTGCCTCTrCATA ACGGGGATGAAAATGACTGAGGCTrCA 228 DM000846 CA1TIGCACAGTACGATC p000988 D AAGCCATCTGGGTCTCAAGyrGCrM.A&A CT'fAATAACTCCCTCCCTGTG=ffGTCCT
TTATCTAATGGTAAAATATGACCTAATG
AAATAGGTrCCTAAGGC1TTGATATAG GCATGATGITrGAAGGATGGAGGACAGA
GTGGATGGAAAATCAGAGMCCGACA
GAAAACCACAAGCAGCTAACAAAAGTC
CACAACCAAAGCCTGTGCCTGAAATGTC
ACCTACAATGCAGTGGACTAITCATATG
229 M000847 CCAGCCTGGTCCTCATGCGATC pOOO 99 1 D SEQ SEQUENCE~te "SEQUENCE") CLONE CLASS GENE NO:{C {T {C "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2} ACCAAc3AACAGAcICCCCAAACTAATAG GATGG'TGi-rGCACGTGTACATGTGTA
TGCATGCGTGCATATACGTGTGTGTGTO
TGTGTGTGTGTGTACACCCACACGTGTG
CATGTGTGTTGTGTGTTITIAAGCAAAC
CTCAGTFGTGTCATACATACTCTCCTATAC
TrCCCCTCCC'1I-'G'IrcCATATGAGGGTGC CTTCTrATCTCACAGGG1TG'TFTG3T-r 1TICTATAACAGAATGCCGCTGATGCT CTTICTATATGAACCCTACAT1TAAT ACT-rATCCATAAGCAAAGGAACAGTATC TrATCTTGCGGATC 230 1M000848 p000992 R
CTGGGGGCTCTGCTACGCGTCAAACGCC
TGGAGAACCCCTCGCCCCAGGCGCCGGC
ACGCCGCCTCCTGCCTCCCTGAGCGCTG
CTGCATCCTGCACGCCCTGGAACCCAGG
AGCGCCCCAGCGACCCTGACTCCCfGCC
AGCACGTCCAAGGCTGCTTACCCCAGCA
ACCTCCCATCCCCTGAGCCCTCAGTAAA
TGCCATCTGTAGCAGCTGTTTGTCTGAG
CGCCCTGTACTAGGGGGCCGGTGGGCTG
GGTGACAATGATAATGGAATAGTGGCTG
TCCTACTGAGGACAGCACAGTACTGYI1'
GGGACCTGTACTGGTAAGGAATACATGC
CTGCTTCCTCTGGACT1TGCGGGTCTCAC CGGGTGCCTGGGCTACCCT-rCTAGGCTT CACTGAGGCGGGTTCccTrGGGAGGCTCT
GAGGTI'ACMTCAGCGTCTGCCAGGGGT
CCACAGCAC7ITAGCCAAGGGGCTrATGGA 17CACTCGTGGTCTGCCAGGACCAGGCT
TGTTGTGAGGGCCCCAGGTGGATC
231 1M000849 W0O09 93 A Saas SEQ SEQUENCE~te "SEQUENCE") CLONE CLASS GENE ID {TC {TC (TC
NO:
"CLONE "CLAS "GENE" 2} SIFICA \L 2)
TION"
MUTATION \L 2) GTGTTrCTTTCT1Tl=IT~CTITI=C TT=Cl I I C'ITlI rITI AAATCT AAGTAAGGTGCAACAATGTAATrCGAA GGGGCAGTGTC1TrCCTTrCCTGTAGTCTC TGCTrAAT-TCCTGAAGMTGCCAAACCA
GGAGTTAGGAAAAGTTGGAAACCTGCA
GAGAGAGCGTqTGAGAGGTIlTGAGATGT
TATAGGAGAGGG'TI'GGCAATGTGTGGA
GTACAGGTAACTTGCGGTKArG1TJTCT
TGGCCCTCTATCTTCATCCT=GTGM~G
232 1M000850 CTA=TACCT-rGCTGTCGGATC pO000994 R GATCCTTGAGTCTGTACrrAGCCTGAGA
GCGCTATAACACTATATACAAAGTACG
ACTAGAAACTCCACACACATGTTGAC
TGACTrAATGTGTAGCCCTGCAATGGTr GACAGTrGGGGGTCAGGGGGCTC'ITGCA
CTGAGGGTAGTGTATAGCCTAAAGAGAT
AATCAAGATGATAAGTACATCCACACTA
GGACAGGAGCTTTAACAAGAGCTTAG
TGAAGGGAACTCTGGGAGCCTCAAGG
233 1M000851 AAGGCATAT pOOO 9 9 5
D
AGCAACACCTCATGTGGGAATTCATACA
rGTAGGTAATCAGTCTACTAGCTGAAC TATATCTCCAACCCAGGAGGTCAGG1T
GTFGTIGMAACAATCTAGTI=GAA
ACAGTCATATCCTAGGCTGGCCTCAAGT
TATGTAGTCAAAGATGGCCTrAAAAGAT GACTCTTGGTTrATLCCAAGTGCTGGG
ATTATAGATATGCACACCACCACACCTC
ATGTCTGCGGGGCTGGACTGCAAATCCA
GAGCTrCATGCATGTGAGGCAAGCACTG TACCAACTCGACTTGGATACTCGAT-rG AAAGTCA'TI1ATAACAGGATC 1234 FN000852 I p000996 F SEQ SEQUENCE~te "SEQUENCE") CLONE CLASS GENE ID TIT
IT
NO:{C C C "CLONE "CLAS "GENE" "1 2) SIFICA \L 2)
TION"
MUTATION \L 2)
CTACTI'ATCTATCATCTATATGTCTATCA
TCTATCTATCTATCTATCTATCTATCTAT
CTATCTFATCTATCATCTATCATCTATCAT
CTATCATCAATCATCTATCTAGCATCTAT
C17CCAGAGCTCATG17GTGGCTTGGGC
'FTCTCATTCACCATCATCGAAGGTAGIT
GCATFI-rGTATFGGMTCTrAGAAGCA
GGAGGCACATGAAACAACTTGCTAACCC
MFCCTGGTCTTrTG1TGTTGT(GTGGT
GGTGGTGGTGATGGTGGTGCTGGTGGTG
GTGGTGATGTGCACAGGAGACCTGTCC
GGTATGGAGATATGGAGAGCGTCTACGT
235 1M00O0853 CCTCATGGGATC p000997 R
GTGGGAGGCGGAGGGTGGAGATGAITT
GAGAAGCAGTT1GTCGATTCCTCCTTCTT
CCAAACATCAAAGGCAGCGGTGGATGA
CAAACTGAAGGACAGAGGG1TTGATGA
TGCAAGAGGAGCCAGCAGCAACCAAGG
CCAGCCTCTFGCGGGTGTGGGCAGGGCC
TC'TrACAATGAGTTCACACACACACA
CACACACACAGAGAGAGAGAGAGAGAG
AGAGAGAGAGAGAGAGAGAGAGAGAG
AGAGAGACTGCTCMICAGAACAGCCCF
AGGAGGTTAGCTTCAGACTAAGACAGG
AGACAGAGAGTCCTTGA'F1GCCAAGG
TTGCACAGCTGGGGAGAAACCCAGCTAT
GGC'TTCACCTTGGCCCTrGTfrAGGACTC CTrCCTAGTCCGGTrGCAGTCTCCTGGA'r 236- 1M000854 c p000998 R GTATrAGAGGCCAGGCCAFYCAGAAGAT
GTGGCAAGA'ITGTCATGTGGAAAATATT
TGAAACCAT7CTAACCTAGTCATrCCAT
CATCAATAATAATAATAATAATAATACT
ACTAAAATGAAAAAACCTAGATAYT=G
AGACTGTACTGCTGTATITTAAGAAT
CACGGAAAT17AGCACTGAAATFTAGTG CTAGrI=AAGAATAC1TTrGTACCGTTAC TrGGACCCACAA FrGCTTAGAGCAAGGG 237 1M000855 ATC 1POOO 99 9 C SEQ SEQUENCE~tc "SEQUENCE")
ID
NO:
IMUTATION
GATCCTGAGACAGTACAGGAACTAAGA
AGCCCTGGGCAAMTGCAGTGTGCACAC
CCAGCCTGAA'1GCCTGGTrGTCACCA
GCCTACCAATAGAGCATI'GTAGTGGCAG
GGATGTCTGCTGGTGTCTCGCAGACAAC
YTMGAGGTCCTGCTrCTCCAGAAGTGT GCAGCTGGCAAITAGCAGCCTGGTCT17
TCCTGTCGCCAAGACCAGTGCTTCCACC
AACCTGGTCTCT'rCCCACAGCCCAGCCC I ITCTrCCTCTTTGACACCCACTTCCT CTAAATGGTGGTCACATGCTrTGTCTCTT GAAAAAAAG1TTTATGAGTCAGGGTATT TTCAACGCCGGGACAGAAAAATrGAC
AACCTGGC'T=~CAATTAACCACTAAT
GGGTTTCACTTACAGTCCTGACAAATAC
CAGGCACAATrCATCCAGGACAATAGTG
AAGAATTTCATCTCTTCCCCCCAAGCCA
GTCAGTCTGG1TIAATATGCACGGTGG
ATAGCCCATAGCATGCAATGAACTGTGA
GCACCCCTCTGGGAGTCAGCAGAGACAC
ACACACAGGCACCCATACCACACACTGT
GCMTGTATCA
238 1NM000856 "CLONE "CLAS "GENE" 21 SlFICA \L 2
TION"
\L 2) p001000 D I L L SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: {TC {TC {TC "CLONE "CLAS "GENE" 2} SIFICA \L 2)
'LION"
MUTATION \L 2) GATCAAAACAATA'fl'CAAATAATGACAT CAGTCAAAGTrATGATITFGATGGCCATGA
CTCATGTCAATAGGCAACACATAAGCCT
GAGAGTAAGrPAAGGAGAAATTCAGCA
ATAAACAAATTGACATACTATGTCCACT
ATGAGTAAAACCTGCCTCTC'ITAAAACG
'TI17rACTGTACTCCATGGCTCTCCCCCAA TGTGCGYI7CGTGAGAGTCCCCACCCCTG
TGACTCCATCTGTGTGTGGGTTCAGGAG
AGACTCCTGTGTGTA1TCAAAAGAGCCC
CCCATGTGTGTACACACAAGAGACCCAG
TGTGTGTACATGAGAGGCCCCACCCCAT
GTGTGTTCATGAGAGACCCAACCCCTGT
GCGTGTACATGACTCTCCCCATGTGTGT
TCATAAGAGACTTGTGTGTATGGGAGAC
CCTGCCTCTCCITGTGTATATGGAAITACCI'
TCAGAGTATCAAATATT'FrCAGCCCACTG
AGCCATCTTAGAACTTCTCTCCCTT
239 IM000857 p001001 C
ATACATATGTACACACACACTCACAAAC
ACACATATATACACATACATACATACTC
ACACATATATATACACACTAGTACACAC
ATACOCAAATACACACATGCATATACAC
GTACTCACACATACATACCCATACTCAC
ACAAACACATATATACACACATACTCAC
ATATACATTrCATFACATACACACACATAT
ATACATACACACACTTGCATACACACAG
CACACACTCACACACAGAGACACACAG
ACACACAGACACACACACAGAGGAACC
CAAAGGATTGGAAGAA'I'AA'ITTCCTGTG
CTCAGTGGGAAAG'ITACCAGAAAGAC
240 IM000858 AAGTGGTCATGTGGGATGATC pO01005 C
GATCAGGGACCCTGTACCCTGCCCCGTG
241 1 M000859 CAGCCTGTGATTC POOI 006 C SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE m TCDC
T
NO:{T {T (C "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2)
GGACTGTAACCAACTCGGAGAGGAAAG
GGCTTAMrCATI=AGTCTTrACAGTCC
ATGATTGACGGAGGTTAAAGCAGGACG
CTGCT7ACTGACTTAGCTCCCCG-ITGCTr
TATCAGCTACTITCTTAATACAACGCCA
CCCCCGCGGCCGCCACCTCCCTAGGCAA
GACCCACAGGTCAATCCAACAGAGAGG
ATTCCTCAAGTGACACCCTATGTC&AC
GCTATCAATGGCAAAGGTATATTGAGCT
242 1IMOO0860 AAGAATTGATC pOOlOO 7
D
GATCTCAGGCTGCCCGTGGGCGGGGCTG
ACGGAGGGAAGCAGACTAGGCCTCTAC
CATATCCGTGGGAGGGACTrCCAAGGAC
CGAGACTGAAGAAACAGCGAAACAG
GAGACACTGGGAGGAGAGGCGGAGACC
GAGAC'frAGTAG Mm.7675 243 1M000861 pOO1009 B -3 AGAGAAAAGACTATCTTGAC=rIGGAT
ATGCGGGTGCAAAAATGAGAAGACCAC
AGTGCAGCTGTGTGCCCTGCACGGGGCA
GCGAGAGGAGAAAGAAGCAITIACAT
GAAGCACAGAACACGCCTGACAGTTCTC
AACAGCAGCACGTCAGACCACCGCAGC
ACTGCTCGlII=CTCAGCAGACCCCCA
GGAAGCACCACCCAGGATGGACATGTA
GGGGTGCATCCGAGAGAATCAAAATCA
CACAGGGGCCATCCTI=GGTrCGGCAT GAATGATGGGGGCCGCCrGCACTGGCCT CCACCTTCTATGGTrGTrCTrCCTI'GTAT CAATGT1TCAAAAAAAATCCTTGGGCTC
ACAACTGCCTAATGACATCTTCAGGAGT
CAAGTCAAGAAAGAGAAAAGTAGCCGA
CCTGGCACGTGGTAGATAAGACTCAAGG
GTGCAATAAGCAGATGAACTGGCTTAGT
TGGGCTTrCTATTGCTGTGATAAAACAC
CATGACCAAAGCAACTGGGGCGGGGGG
CGGGGGGTGTCATGTTACACTTCCATAT
CACAGTCTATCACTGAGGAJAGTCAGO
AGGATTCAGGCAGGAACC
244 IM000862 p001011 R SEQ SEQLJENCE~tc "SEQUENCE") CLONE CLASS GENE ID {TC (TC {TC
NO:
'CLONE "CLAS "GENE" 2) SIFICA \L 21
TION"
MUTATION \L 2)
GATCGGCCAACACAGGATAGATACCAC
ACAGGATAGGAGGTACAGTGTC'IGGAA
GATTAi-rATCGAGCCCCTGAACGTAGTA
GAAGCTGGCTGI'CG'ITCCAGTGCAAGCT
245 IM000863 GAGCAGATGGTCC p001013 D GATCCACATGAAAGCCAAGCTGCACATr TGCTrCATATGTATGGAGAGGCCTAGGT -rAGCCCA'TGTATrGTTCTTIGGTTGGTGG
TTCAGACTCTAAGAGTCCCAAGGGTCCA
GGTTAGTTGAC71TrGGTrC1TCCTGTG
AAGTTCCTATTCCCMTGGTGCCGCI'CAAT
CCTTCCTCCTATrC'FCAATAAGAGCCCG
CAAGCTCCATCCACTG'IGCTTGTGGG
TATCTGTAA
246 1M000864 p001015 R GCCTCAGCTACATrAGTCAATTrCCCATCT
AGCCTGGGTATCCGAGATGGCAGTAAA
GACACTAGCTGCAAAGCC'ITACTGCCTG
247 1M000865 AGTTTGATC pOOl 0 18
D
GATCCAGTCACAGGAGAGCAACTGGGG
GAGGGAGCAGGACAGAAGCACACCATA
GCCCTTTCAGGGGGCCGGGGGCGAGGG
G'IX3GACAAGAGAAGACAGATAATGACT
CACAGGATGAAGAAGCCTCCCACAGCC
CCTCCGTGAACTGGCCATCTGTTICTGGG
GCCCCAGAGCAGGCGAGTACCGTGAAG
CTTGGGGACTAGCAGCCGGACCACTGAA
CAAGGTCAACCAGCCAGTGTCCCACGA
GGGGAGAAGGTACCAI17GAACTGTCACT
TTGGAAAGTAGCCAGAGCCCATCCCTGG
TCACGACCCAAC
1248 1M000866 I p001 0 19 ID F SEQ SEQLTENCE~tc "SEQUENCE") CLONE CLASS GENE ID T T T NO:{T {T {C "CLONE "CLAS "GENE" \L 2) SIFICA \L 2)
TION"
MUTATION \L 2)
GATCCCTAGAGCTGCTGGTCAGCTGGCC
TGGCTGAAACTACUrCTGTGCAGTGAGA
GACCCTGCCTCAAAACACAGATAATGGA
GACAGATAAATGACATCGTCCGCTGTGT
GTGGGTGTGTATATGTAACACAACACAC
AGTATACACACATACACACCACACTCAT
ACGGTCACACATGCACTCTCAGTGCATG
TGCAACACAACACAGTGTACACACATAC
ATAGACACCACACACATACACATACCAC
249 1M000867 CACACACGCGCACACACACACATAA p001020 R
GATCCTGTGCATCACTGAGCCATCTCC
CCAGCCTACAGTGTAAGTATTCTATACA
TATTAA17rAATCCTGCCGGGTGGTGGT
GGCGCACGCCCTTAATCCCAGCACTCAG
GAGGCAGAGGAAGGTAAA M CTGAGTr
TGAGGCCAGCCTGGTCTACAGAGTGAGT
TCCAGGACAGCCAGAGCTACACAGAGA
AACCCTGTCTCAAAAAACCAAAAAAAC
AAAACAAAACAAAACAAAACAAAAATC
CTATGGAGTATTCTAAAAGTAAAACCGT
ATCATrAGCACTOCCAAATAACAGAAAG
GAAGACCAAAGCAAA
250 1N4000868 p001021 R
GATCCTCTGAAAATGGAGTTACAGATGG
TGTGAGCTGCCATGTGAGTGCTGGGAA
CrGAACTCGGGACCT-[TGGAAGAGCTGC
TGGTGCTC=AACAGCTGAGGTGTCTCT
CCAGCCCCM~GGGTGTGTI=G1TGT TrGTIMG1TrGC I I I CAAGACAGGG 1TrrCTCTGTGTAGCCCTGGCTGTCCTGGA
ACTCACTCTGTTAGACCAGGCTGGCCTC
GAACTCAGAAATCTGCT'CCCAAGTGCT
GGGATTAAAGGCGTGCGCAACCACTGCC
251 1M000869 p001022 IR L-
GATCCAATATAFFCATATGOAGATACAT
252 IM000870 GTATATACATAA p,001023 ID I- SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID ITC {TC {TC
NO:
"CLONE "CLAS "GENE" 2} SIFICA \L 2}
TION"
MUTATION \L 2}
GATCCAGGTCC'ITTCCCCCTTATGGTCCT
ATACACGCCTGGGTACTTAGAGGGTC
AGCTCTGACTGGTGGTGTGGGGAGAAGT
GAGGGG11TACACATGTGACAGAGG'TcCT
AAAAGCTGTCGCCATTGGCACATGACCA
TCCTAAG'I*CTGTGGCAGAAGGCTGCTCA
GAGCCTCTGTCCAGGAACAACCCAACAC
A'ITGCAGAAATAACTGTGCATCTGGGCA
ATGGGGCAACTACTACCTGTCCATCCAG
ATAGCTCTTCTAGAGGCATTCGAAATAA
CACGTAAAGTGGGGTGGTGATGAACAC
ATATAATCTCAGCCCCTGGGAACCGGAG
ACAGGGGAGTCACAAG
253 IM4000871 p0010 24 D GTrCACAGTACYFGCTCACTTGCCTGTC1'C ATGGTITACTCGCCGCTCCYJ7C
[CGTACC
CCC=fCCCCTACAATCCTCCTCGTCTA CTrCATGCGGTATATGTCAAACACCGT
CATATATAACAATGTATGCATGCAGCAT
T-rCT=TTTFCCCATCAGCCTCCCTI'G CTCCCCATCCTCCCGCCCT7CCTCCTrCC 254 1IM000872 TcccAGGATC p00102 6 D AG7FFATGCTTGCAGACAGGAATGTAGCA
TGGCTATCCFCTGAGAGGTTCCACCCAG
CAGGTGACTCAGACAGATACAGATACCC
ACAAGCAAACAGTGGATGGAGClITGCG GGCTC'rA1TGAAGAATAGGAGGAAGG ATTrGACGGCACCAAAGGGAATAGGAAC
TTGACAGGAAGACCAACAAAGTCAACT
AACCTGGACCCTTGGGACTCTrAGAGTC
TGAACCACCAACCAAAGAACATACATG
cGCTAGACCTAGGCCTCTCCATACATA'r 255
GAAGCAAATGTGCAOCTTGGTT'FTCATG
IM000873 TGGATC Ip001027 IR SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ED ITC ITC {TC
NO:
"CLONE "CLAS "GENE" \L 2) SIFICA \L2)
TION"
MUTATION \L 2) GATCGTGGTCTCTTCTC II ICCCTCT ACTTCTTCTTCTIC1TCTrCTTCTrCTTCT TClrCT7CTACTGTCTCTTCTTCT7C 'FrlCTrCTCTTC'1TfCTTCCTCTC TCTCTCTGTCTTT7CTCTGTCTGTGTGTCTC
TGNCTCTCTGTCTCTCTCTATCTCTGTCT
TTCTCTGTCTCTCTGTGTCTGTCTCTCTTT
CTCTGNGNCTCTCCCTGTCTGTCTGTCTC
'fCTC1TrrCTCTCTCTGTCTCTCTCTCTCTG
NCTCTCTNTCTCTGNCTCTCTCTGNCNCT
CTGNCTCTGTCTCTGTCTNTGTNTNTCTrC
TCGCTCTCTNACACACACACAGATGTAC
ATGCAC
256 1M000874 pOOl028 R GATCGGCGGTATCATA1T=ATGTG1TI ATTTCTGTGTCAGAAAG1TIAAAAGGCC
TCAGATFGGAAGTCTGGTGCATGGAA
TGCATATGAGCTI=rCATCTATTGCCC AACAGAn7IAGTCTAAGAACCACCTCTA TrATATAGGGTATGATAAGTAATATAGG TAAGGGAATGCATCCCATrGATAAGTG AAAGTTGAACACACATAGAGT-rGGCTCA
GCCCGGGGTCTAGGCTCTAATGCGCTGG
GGATACCCAGGCCAACTAAACGCTATAG
CAACAGGCATrFGGGGCATGAAGATACTT TTTGTrGHTGTCTTGAATITATATAGOG
GCTTATATCTCAMTACAATTAATCATGA
GTrfGCAGTCAATAAATC7rCATTGCTCA ACATATTTGTACCCTCAAATA'lrI=C TI GTGTGATAT 257 1M000875 p001029 C CTTGTAAACACGATrAFTAAAGATAT AAATGGCTCT1TrACTCTGT-ITAAAAA1T GTrCTTrACCAGTTCTTCGTGTACATrG
GTCTCCAMTCACATGAAATAAAATATT
T-rGMTAATGTrAGATTTTCAATACCAGC TGAGTG7TCGATGTGTGCCTMGGACA 258 TATATFTGTTGTAAAGTGGTCAT17GGG IN4000876 ATC p001031 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID {TC tTC ITC
NO:
"CLONE "CLAS "GENE" 21 S1FICA \L 2)
TION"
MUTATION \L 2) GATCAGATTCAACTCCCGCAT7TCTAGC
CCCAGCATCGTGGAAGGGCTACTGTGTC
=CAAGCACTATGGTGGATACACATA
ATGCCAGCFFCCCTCATfACTGGTGATG TGAGCTGIFl7GCCTAAGGTCcTTTCTrGCC AGGCTT1CTCTGCTGCCAAGGCTCTGAAT TCCCTI17GTAGCTAATGCGTAGCCCTAT TGGCAGACTCTTCCCGTrGGCTGAC'FrCT
GCGTCCCGTCACACAGCAGTACC'ITGYI'
TGTTGTCACCTTGATGMTCTTATATGCA
TTGATGATGGTGAACAGCCCAGCAAGTG
CGCCTGTTTCTCCCTTCCTCCCACT1T GTTCTCAGYI7GTACATGGCAAGGAAAAC
CAATTCCFIT=CATATTTCTFCCCAGAA
AAAAAATCCTCThrFATAAGAGTTCACAT
CCTTGAGCACACATGATAGGAGCTGGTA
259 IM000877 GCCAG p001032 D GATCATGATA2TGTACTGCTGAAGACAA ACATATrAAGATATAAGACTrTGGAGAA ATCAAGTrGGTATUFGACATTGGAGArTA ATCTC1TIGGCTAGCl-M-TGTAGAGCrA GAAGTTrGGTATGTAAGGTATAAGGAAG AGAAGTATI'CATAAGAC17ACCCAGTTG
TCTCTCCTGTAAGCTAAGACCAGCCTFAA
GAAGCTAAAATTATCTAATGTAGiAAC CACAGAGAAAGAAATTGTGGTATGAA1T TTGC'FrG1TCGTGGACATrAACCATnAA CTCAATGATAATCAAATGACAATACATrA
GAGACAAAGATATGCATACTAGTAAAA
260 IM000878 TAGTGATAA Jp001033 ID I-
U
SEQ SEQUENCE~tc "SEQUJENCE") CLONE CLASS GENE NO: ITC {TC {TC "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2}
GATCGTGCTAGAGAATGGTACACTTGGG
TATATTAAGAAATCTrGGTTGAGTGGT GGTGGCACCCTCCT7AA77CCAGCACT CAGGAGTCAAAGGCAGGCAGACAMrGc AGTrAAGGCCTGCCTGGTCTACAAAGT
GAGTTCCAGGAAAGACAGGGCTATAAA
GAGAAATCTrGTCTGAAAAACAAA
AAAACAAAAAACGAAACAGTAACTGAA
ACCGAA AkAA AAAGAAAGAAAGAGA
GAAAGAAAGAAAATCTTACAATGTGGG
AGCTGGAGAGCTGGCTCAGTGGTFAAGA
GCATTGGCTGCTCTrCCAGAAGACCCAG GTTCAATrTTTAGCACCCACATGGTGGG TCACACCTGCCTGTGGCTTCAG'TrCTAG
AG'IMCTGACACTCACACACAAACATAC
261 1M000879 ATTCAAGT p001034 R GATCTTGTA'ITrCTrCTTGGCTTGTCTCC
ATAGGAACAGGCAGCACAGCAGAGGTC
TGGGAGATGGCTCCGAGGGTAAGGGAC
CAAGCAAGGTCACCTGCGCTCACTCCCT
GGAACCCACACAGTGGACAAGAGAGAA
AGACTCTATGGCCTCCACGTGCGTGCGT
GCGTGCTGTGGTGTGCACGTGCCCCTCC
CCCAAATAAAGAAAACTAACGAAAAA
AAATTAAAAGTAAAAAAACAGCACTGC
AGTAGCTCCAGGAATCAACTGGTCAATG
AGTGTATCACATTTGACTATCCGATGAT
GGTTffA1TTACATGTATGCACGTrTr
GCATGTATGTGGGTGCACATGTACAAAC
ACATGTGCCAAGGCCAAAGGACAACM
GGGTGTCCMTCTCAGGAGTCATCGACC
T"TATITTCTGAGACAGGGCCTCTCACTG
GAATCTGACTGGCCAGCAGCCTCCCAAG
GATGCTCCCCAACCTCAGAAGGATGCGC
CTGTCTCTGGCTCCCAGCCCCGGGGG'rr ACACTGGTGGACCACTGGGCTCT1TCA m18 1262 1M000880 ICCTGGGTG 1 0 0 1 0 3 5 B 134 SEQ SEQUENCEjtc "SEQUENCE") CLONE CLASS GENE ID TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 2) 'lION" MUTATION \L 2) GATCTCTCTrAAAATrACATTACAGTA GAAAATGTTTATGAGGCCG I I I IATCT CTAATA~rA1TrATTACCACTCTCCTACC CCCAGAGTCTI7ACAGGCATCAGGGAGJ'G
GACAAAGGCCGGCGGTACTGAATGGTG
ATG3TTA1TfrGAAATAATGAAAAG 263 1IM000881 pOOl 036
D
TACCTGTITGCTCCAACATGGTCAGAAAT
CAGTfrGTFCAAVI=AAGATACAATG AGAGTAACACCCTAAAGACTrCACA'IT
TATGCATAMTGCTACTCTGTGAGCACA
264 ILM000882 TGAACGCTCTCCTrGGGCACGATC p001066 D
GATCGCAGATACTGCAGGTATGTAGTAA
TGAAGTCTGTAAACATACAGAATGGAG
AAGGCCAGAGAGGAAAGTrGCAGGCA17 265 IM000883 GGGTAGTCAGTAGGTAAAATAT p001067 D GATCGCAGCITCTT"CCTrGGTGCTU-rCCC
GTCAGTTCAAGTGCTGTGGCGGGGACIGA
CTACAGAGACTGGAGCAAAAACCAGTA
CCATGACTGCAGCGCCCCCGGGCCCCTG
GCCTGCGGGGTGCCCTACACCTGCTGCA
TCAGGAACACGGTAACTGCATc3GGTGCTF
GGATGTGAGGGTCACCCAG=TGCCAAA
CACTGcccTrCACTCTGCCCAAGTGGAGG
AGGCAGTGGGAGTGGGTGGGACGTGGT
GGCCGGGGCTGAGC7TTGCCTrAGACCAG GGGCCCTAGCAkATGGGAGATGAGTGGG
CAGCTTCCTCTGGGAGTGTGTCAGTGAG
CGTGTGCGTrG'TGIGGGCCTGGCCCAGGC GCTTTGGTTGTAG'FrACTTrGGTTCVrACA
ACAGCT[GGAGGGTCTCAATTGGGGTA
GTGTTGCTTTAGCCACTTAGGGGGACTT
GCCCAAGG'TTGGCAc300CTCYTCCCAGC
AACAGAGAGCCAGAGTGCCCGGCAGGT
GCAGCAGGCTCTACCCAGTCACTGGAGG
CAGAGTACAGTGCAGGTGCTGTGAGCAC
TGGCAGCAGAGCCCTGGGCAGCGGCAT
GCGGTAATGTAAATQ' Mni.281 1 266 1M000884 p001069 B .2
U
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID T T T NO: C {C {T 'CLONE "CLAS "GENE" \L 2} SIFICA \L 2}
TION"
MUTATION \L 2)
CCATGTCAGGTGATTAACCTGTGAGTCT
AAC1TCCAGGAATGCAATGCCTCTGGCA
TCTACAGGCATAAACATAM~GTGGCTT
ACACTCAAACTGACACACCAACACATAT
GTGCACGCGCACACACACACACACCAA
ATTAAAAATAAAATAACCCT1TAAAA AAAATATAGAACCTATAGATAATTGCT7 267 IM000885 TACTGCAGTCACAAACATIMAGGATC p,001070 D
GGGGCACATAGTGAGTTCTAGGATAGCC
AGGGTTATAGAAGCTATAGTGTGAGACC
CTATCTCAAAAAAACAAAACAAAACAA
AAAAACAAAAAAAACCTAAGCCCGTGT
GGTGGTGTGTCTCAGTCTGAGCGC'ITGG
AAGAGAGAGGGAGGTGCATCTCTGAGC
TTGAGGCTAQCCTGGTCTACATAGAGAG
CTCCAAACCAGTCAAAGTAACAAAATG
AAACTGTCTCAACAATGACAACAACAA
ACAAACAAGCACTAGAATAAAAAGAAG
CCAGCATGGTGTCATGTGCCGGTCATCC
TACCACTrGGAAGGAGAGAAGCCAGTG
CAGGAAAATTAGGGATC
.268 1M000886 W001072 ID I SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID ITC {TC {TC
NO:
"CL ONE "CLAS "GENE" 21 SIFICA \L 2}
TION"
MUTATION \2) GATCCCAGGC3TCCTGTAGGCTAGGCAA
GCCCTCTCCCCACCCTGTCCTGGTAGAA
-ErGATCCCGAATGTCAGCATTCCTTCAGT
TAAAGGAATGTGCTCCCTCAGGCTCTCT
CCCATGGTrGCAYIN3CTTCAGCACGCAGG CAGACAC11TGTCCAAGCTAGGcTrcCCTG
TCTCCCATCTGTAGGAAATGCTTGGTAT
GAAGGCCGTGGTGGACCTGGCTAGATGG
GCAGCGCCCAGTGAAGGGCTGTGTCTGG
AGCCTGGGCTGTAATTAGTGGTTTGAAC
TGGGTGCTCTGGGGAGAGGCAAGTAAG
AATrTGC7FrCTG1TFIAGAGCAGGAGi
GAGCTGGCGGCTGGCTGTGCCITAGCCG
GCTGCTCGAAGAGCATh-rGAGGTG'rrCG CCATCTrAATGGGTTAAGACTCTCCTGT GCTAATCTIGGTGGGTrGCT'IMAGGCAC GGTGGTCCCAUI'GTGGlTGTGTGAACAG TACCTrAATGCCAACAC'T[OGGAGGCCT AAGGTATCCCCATCTGCAGGAAcTrGGGG 269 WM000887 TGCACA p001075 D
GATCCTCACACAAATTGAGTAGTACTAA
CAAGAGTGTGAT'CACATAGTCAATAAA
GGTATAGGCCATCTGTGCCCTGGCTTGA
CCTCCGCAGAGCAGAAGCTAACAAAAC
CAAAACAGACTCAGMTCTGcATGCTAA CTrAACCATGATTrCCAGACl'AnMTY
TTATCCTGTGAAAAATATATTAATCI'CT
ATTCTGCAGAGTATCCCTT=TIAAGAG
AACATGAT~rCACTGYTrGACAATAT 270 GCCTAGACACAGAAAAAAATCATITAGT AA793 1M000888 Trp001078 B 16
TTGAGTGCTCAGTGAACTACTUAGGG
CAGCCTAAGGAATACAGTGACCCACCA
GGAAAI'GCCTTGTG=TGGCAGTCTGA
TAGCATCACTCACAGCTGTCGGTCGTGA
271 [M000889 C'11'CATTGGATC p001079 JA Edar GATCCAGGGACAAAGAGCCCATlTCTCCT G'rrCCTrCGTAT 1272 1IMOO0890 I pOOlO8l D I-
U
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE IDITIT
IT
NO:{T C {C "CLONE "CLAS "GENE" 2) SIFICA \L 2}
TDON"
MUTATION \L 2) ACTITCAGGCAAGCTCT-1rGCTCAGTGA
ACCTGCTACCACACACAGACTCCTCCTC
CCTGTrCCCGTCGTTAAAAAAAGTI=A
M~GAGGMTAGAGCAATGGCTCAGTGC
TCAAGACTACTfGCTGfCTACAGG ACCTGGGGCTAGTrCCAACACCCACATG ATGGCTrACAA3TCTCCAGTCTCAGGGG
TCCAGAACTCTI=CTGGCATTGAATG
CACATGATGCATATATAGACAAGCAGGC
ACACACACACACATAAAATAAACA
TCM~TGAATGTAA1TAAAAAGAMA TrAA1TIAATF=ATGTGTATGAATGTr TrGCCTGCATGTATGTCTATGCACTGCAT
GTGTGCCTGGTGCTCAAGGTGTCTGATA
GCCTGGTGCTGGGCTTGGTTCACTCAAC
AGCTGGCCCTATGAAGGCCAGCCGTGAG
GACACCTATCCATGCTGACAGACACAGA
TGCTCAAATGAGACAGCCCCITGTCTAT
GAATGCCCTCTTGAGAATGAACAACCTC
CCTGCAGCAGACCTCCTrCTGGATACCC rGCCCTITCCATAC=ICTGGGTGTCTAGT rcTcrrcc 273 IM000891 p001082 R SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO:{C {C {C "CLONE "?CLAS "GENE" 2) SIFICA \L 2}
TION"
MUTATION \L 2)
GATCACACGCTTCACCTAATTACAAATG
ATTrTCTTAGAGGGGTCTGTATATAACA
GAGATGATAAAATFCAACGGCAGCGCTC
CAACTGCATTrGATATACAGGAAGTACTC ATGAAATrGGAGACACTGATrATCTCTT
TGTGTGGTGTCCACATATGTGGCCATCATL
ATCATATTATTA'FrATTACATGGCTAAA
AAATGGGGTCATAGGTTTCATGACCAGA
ACCAAAATATTCCCCTGTAATITACACA
GGATTGATGGTAAGAAATGAAAACAGT
TTACAThMGAIAATFACTTIACT-rGAC ATAAAATGTGACTrTCATFCC'I1IGCATF CC'TTrCACAGGTAAGGCTACGACAATA GATTCTCAGTTCTCCACCTCTrCTCTATCT
TGTCTACTCTATCAGCAGCAATAGCAAC
AGTYT'CCATGGTCC1TCCATCTGTAAAA
GCAATAAAAAATAACAAAGAAAACCAT
ACAAACCAYI'AGAATATGAGTTGGTATT
CACAACTCTCCTCTCAATAC'CATAT~f
TAAAAATTACTAGAAATATTCATCAATA
274 ATATTTCATrrGTTAGCTCTAGATAATGT 27 PM000892 PFfcCAGG 1001083 ID V SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE IDITIT
T
NO: C {T {C "CLONE "CLAS "GENE" 2} SIFICA \L 2)
TION"
MUTATION \L2) GATCATGGTTATITIGTAGGG1TrATTr ATACATGTCTACATGAATfATGTGCAC
CAGATGTGTGCAGGTGCCCATAGAGGCC
TGCGAGGATGCCAGATACAGATAGITAT
GAGCCACCTAATATAGATG'TGGGAA7T
GAACCCATGTACTCTGCAAGAGCAGCAA
GTACTCTTAACTACTGAGTCATCTGTI-rA GCCCTCCTGTrGGGATTTAATGGTCAGT GTGAAATACTATGAAGATAGAAGGG"17
CCTAGACTCTGGTGTGTAGGGGTGGGGT
ATCTGTGAGATGGGTAAGCTCTGTrGGC
TTTCTAAGAAGGAGAATGAGCAGAAGG
CACACATAGACAIT-rCACACTrCACACA
CATGCATCCAAACACCACACATGCACA
CCACATACCACACGCGCCCTCCTG~rTC TACTATGTAATAATGTrC'TGTAATAAC
TAGTACTCTGCTAATGAAAAGGTCACC
ACTAACTAGATGCTAGCCTTCJ&ACTTTG
GACCAGAACTATGAGCCCAAATAACCT
CTrGCAnrTATAA'FrrAGCCAGCATGTA 275 GAACTGTGTCAATAACAATGGAATAGTG 27 M000893 rGpOOIOB5
R
GATCATCTGGCTAAAATI=ATAATATG
ACTC'TrAAATrCCTTAAGAATTCACAA GGACCTITATGTTGAAATrACTCATATG
TAAGCTI'ACTGGAATGAGATGGCTCCCC
AGlTGAAAACACCATTCTrAAAATACTC
AGAAAATAAGAACGAGGCCAGCCCQGT
CTACAAAGTGAGTrCCAGGACAACCAG AGCTATACAGAGAAACCCTGTCTCAjAAA
CAAAAACAAAAACAAAAACCAAAAAAA
AAACAAAAAAGAAAAAACAA4CAxA&
CAAAAAGAATGTAGATATAAAGAAGA
ATAGTG1TGCTGGAAATAAATAGTAAT ATAAACTTAACAGCAGCCTGTCAA'TrGC AGGGTI=GCACTrGCAGCTCAGAAAG
AAGTGACCCTCCTCAGGAAGTAG
276 1M000894 jp001086 IR I- SEQ SEQUENCE~tc "SEQUIENCE"} CLONE CLASS GENE ID IC (C J NO: C {T {C "CLONE "CLAS "GENE" 2 SJ.FICA TL2)
TION"
IMUTATION \L 21 GTGGG17TGTGTGACTCAGAGAGCAAGCT
TCTACCTCCACAGGCAAGGATGCCTGTG
CACACAGAAA~TGAGATGAAGTCATATGT
GGGGACTGGAGTTGCAGTGGCTCCCAGA
AGGAGGTGTGCAGAGTTCAGGCTGGAG
TCCAGATGAGGAACATCAAATAGAGAG
GCCMTGGAGGGAGTGGGTTCTC17GAT
AAGTAGGACTGCCACCCATATCAAGTAT
AAGACTGCCAATCATACTGAATCTCAGG
TAThrCCCATGTAGCAUrGGGAACATA
TAGCATTTGTCACACTGCTATAGCAAAG
AATCTGTGATGAGGTTGGGAGTGGAGG
GGAACGCCTTTGGTCCTrAGAAAAAGAAC 277 1M000895 CAAAGGTAGGCTGATC p 00 1087 D
CCTGCCCTTGCCAGACCCGACCGCAGCT
CATCGAGGAGGTACCCTCTAAAGTCGTC
ACCTUGAGGAGACAAGCTIC'I'GTCA:I'AGT
GCTCGCAGCCCCGCGGCCCCTGCGCCAG
GTI'GCGGACGCCATC'CCCGCGCCGTC
GCCGCCATCTCCTCCTCCTCCTCCTCCAC
CACCTCCCCCTCACCTGCCACTGACCT
TTCCCCCAGCT-lGGAJGCCACCCTTA
GGAAGCAGAGTCGGTCGGAGACCCGCT
CCTCCTCAGAGCAGCGGCCACCAGAGTC
AGGAAGGGGGGGTCCAATCACGTGATC
278 11000896 p001088 R GCTCAATAG'Ffl'MAfACAAAC AAAGCTAAAAGCCTGATGTGTCACJ-rGC CTI'CAGCAGAGCTGrn1TGGGGCCCATTG
TTAATGTTGTGAA'ITAAGTTCTGATGTA
AGTAACCAAGCCACTCCCCACACTTTA
CTrGCAAGAGT[CCAGGCAGATGThAG 1279 1 M000897 jGTCAACCCACCTGACTCTGATC p001089 D
U
SEQ SEQUENCEftc "SEQUENCE") CLONE CLASS GENE ID T T T NO: C {C {T "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2)
GATCACAGTGMTATCTCAGCAACAGAA
AGCAAATGAGGACACACCTGGGTCTCAC
TGATATACTTGGTGATATGTGTAGTrAYr
ATGTCTCACAGTAATTGGACAAGGAAGA
GAGTTCATTGT-rrAGAATGTTGTAACT
GGCATTGTTCTTCTCTCTCTTGTTTTCAT
AAAATCTCACAATATCTACAGCTGTGAG
GTCCAAGGGGCTCATrFGGTGATACCCAC TCMCrTA=~IGTGTGACCAACCTCTITr 280 1M000898 TGGATGTCAAGGGT p001091 C GATCAGT7GCTATTGCT7fGATrGATrGC GAGACTrTAACAAGAGTC1TGTCT
CCTCTCACTCCCTAGCTTCATCITAGAAC,
TTAAACCCACAGCCCAAATGAGTAGTTG
TATGTCATATGCCTCGGCCAGCACGA
CTGAAAGGAAGAAAGGCAGACACTG
GAGTGCAGGAAGAAGACACAAGGCAAA
GCCCAGAATrCAAAAGTAGAAGCACAG 281 1M000899 pOOlO92 C GTACCCTGCATCCCCGGTGTGCC7TcGG
AGTCTGATGCCAGCACTACAGAGCCAAG
CCATAATACAAACCAAATAGAAT-rAACA 282 1M000900 AGAGCTCCATATGATC p00 1093 D
GATCACCTTCCTAGGATGAACGAAGAAG
GATGGCTGGAGGTTAGGGACCCAAGGG
ACTrCCCCCTAGAGCTGGCTGTGTACCC
TAGGCATGTGTGACTGCAGCTGTACAAG
CAGGGTATGTGGGATTCACAGTCCTCA
GGATAAGATGACACTACAGATTAGC
TrTATACCCAACATGGTGGAACCCCATG GTCACACTCTfTCACAGATGGTCACTCC CATrGCCCGAAGCCCAGCCMIATCCAA 283 1M000901I G pOOlO9 4
C
GATCAATAACAGGAAAAGAAAAA\AGA
AGTrACT1CATGTAGCAATGTGGAT AA'rrCCCATCCAGAGAAACAAAACCAGT 284 1N4000902 TCCAG p001095 C
GATCAGGGAAGATGTCACCTCCAACCCA
285 IN4000903 GCCTAGACATGGTGCTGTGACCA P001096 D SEQ SEQIJENCE{tc "SEQUJENCE") CLONE CLASS GENE ID {TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SLFICA\L 2)
TION
MUTATION \L 2)
GATCAAGGAGCAACCCAATAGCTTCTAT
TCCCCCCCTACTAAAATATGACAGTG
ATGGAI-rCTIGGOGATGCACAGATIG'H'CT
CAGAAGYI'ACTGATGAACACACCATGCT
CTAACAAATAGTATCAAACCCACAGTCA
CAGATGGCCCTAGTTAAGCACAGTGCAT
CACAAAG.CAAAGCAAAGAGCCTTGACT
GTGGGAAAGGTACTI7GTGGTGAGGACTA GTOGGGTATGAAAGAAA'1ITAGAGAGGA
TGAAGGTAGTGATAYFCAGTGTGTGTGT
GTGTGTGTGTGTGTGTGTGTGTGTGTGT
GTGTGTGTAAGACTATTAAAGAACACCC
TIrflAAAGAAAGGC1TrCTTGAGTGTC 286 LM000904 ACC p,001097 R GG1TAATAAGCTAGATTATCGTGTATAT
ATAAAGTGTGTATGTATACGMTGGGGA
TITGTACAGAATGCACAGCGTAGTATTCA
GGAAAAAGGAGACTGGGAAATTAATGT
ATAAATTAAAATCAGCTITFAATTAGCT
TAACACACACATACGAAGGCAAAAATG
28~7 M000905 TAACGTTACTIGATC p001098 K IMyc GTGAACGACAGCAGAATCGGGT-rGTACC TCAAAGCAC17ACC1TrTCCCAATACACC
TGATC
288 IM000906 p001099 D
GATCAGTGACAATGTAGCYIGCCTGGA
289 IM000907 AGGATAC'JTGAGTC pOOllOO D
GATCAGCAAAATGGGACATCGAAGTFIG
AACCAAAGTCATAATAAAACATCCTGAG
GTACATAAACACTCTGTAATAGACTAAT
ACAGTTCCTCCAGGCACCAACAGAAACC
7TGACTACTTCCCTTGACTACTTCAGTCA
AATCTTCTGATAAAACCAGACCCAACTI'
290 IM000908 GGAAACGTCCATGTATACAATG p001101 D
GATCATCTGCYFCTACGCCCAATTAAAA
GACGGACTAAGAACATAAAAAGAATCC
AGGCACCTAGGMIGCAGA-AATCTAAAG
291 IM000909 GTTGAGTTCCTTf pOOl 102 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE NO: {TC {TC ITC "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2) GATCACAAGTrATAGTTGAATAACAAGT
CCTGTGTGTGTGTATGTATCCGTATATCA
TAITLC1TATCTGTrACTCATTrCATG GAAACTAGGTGGATGTGTTAACTrGGCT 292 1MN000910 ATrATGAGITrGCTGCTAT p001103 D CTACAATGGTTCAGGC1TGGAATATCA
CTGTATAGGCTGTGTGCCGGCCACCACC
CTTCAGACTGCCACTCACAGGTGCCCGT
GAAGGCTGCCGAGAGGCAGTCCCCATC
AGCCTGTCTCCTACACCCACACACTCTG
TGTGGAGACCACAGGCGCCCAAAGGGT
ATGCTAGTCTCTGCTCTACCGCGTACCCT
CTCCTGAAGGCAGGCAMTCAGAGATTC
CAGMTCACCAGGAAGCTCAGATC
293 1M000911 p001104 C GATC1TTCCCCC1TGTAGTATCAGAGA
GAAAAGCCATGGCATGCATGGCACATG
CTAGGCAAACACTCAAGCATCCTACTCT
GTGATGCAG=TGAAACAAACT1Tr'TT TC1TI1CYI1CTIrG=TITH1CYTT CTTrrCTrrCrrwi 111111111111-i--ri 294 1M000912 TTGAGT pO01l105 R
GATCTCTCCCCATCCTCCTGTGCCTCTT
GTCTGTCATACCTCTACTACTCCATCAGT
TTrGCTGCCTCTGAGTCCCTCTTC117CCTC TCCTATCCCTCCTCCCATCTrCCTCATCT CCAGGTCTCTCGAGGTCT'rCCTTCTTCCC TCTFICTTCCCCTTTCCTCrCACTG rC'TGTATTCCGTTCTTCTCTGT'rGGT CGCTTGCCTCGCACCTC1TCCTCCTGTC CCTCCFI=CATGTACCATAT1TCTCTTC CTCTICTGTGTCTCCTCTT7CCTTCCTCC 1TrACIT-rCCTTCTAACCTTCCTCTIMCTC CTCCTCCGGCAAGC='~GCT-r 1295 JIM000913 1 p001106 IA lGatal SEQ SEQUENCEftc "SEQUENCE"} CLONE CLASS GENE ID (TC (TC ITC 'CLONE "CLAS "GENE" \L 2) SIFICA\TL2)
TION"
MUTATION \L 2} GGTTGT'rCCAGTYFAAATTGGCTCTCTAC AGGAACATGGCTTAGTTCTCCCTlAGCC M~CATGAcccTACACCTCAGACACTAG
TCAAAGTCTAGCTTAATAAAGTG'ITCAG
GATG1TGGTGGAGGGGGGGAGAFGHrA
ATACAGATC
296 1M000914 p00 1107 D V
GGACCACYFJ'AGTATGGGTCATATGTTC
T'AAC'C'ITICATFITCTAATT-Cl'rCC ATCTGCAT7GATTGTGCCCAGTTATCATT
AGTGACIIT]TAGTAAC'ITAAGGGAA
AGTTGTCTFATGCTCTACTTAGTGTCGATT
TAACTTACTCTCCAGACATGGGAGTGCT
TATTMGTTrGCCTACCTCATCCAGGA 297 IM000915 GCTTGTAGATC p00 1108 D 298 11M000916 GATCCGATTrATGAAACCGG'CIAAC p00 1109 D
GATCTGTGGAATGCTATCCAGCTCYIFCC
299 1M000917 AACAAATAC p001110 D TrrAGTATCTGCATCTGACTCTTTCAGCTG 'iTCGYJ'AGGCC'TrCGGAGGGCAGCCAT GCTAGGC-TCCTGTCTrGCAAGCACACCAC AACATCAGTAACAGTCTrCAGGGGTC1-]GA 300 JIM000918 GCCTCCCCTTGAGCTAGATC p00 1111 IR
GATCTGTGGTAATGATTCTGTAAATACA
GATAAACAACGTACACATGGGAATTGTr CCCTGTGTGAAAGTGTrCATCATAAGGT
G'T=ATITATCTACAATATC'ITGGG
301 ITMOO0919 'I AG p001112 D
ACTGCCACA'TTCCCTAACACCTCATCAA
AGAAAACAACACCACAGGTCTCAGGCT
GCCACTCTAGACCTCCGAG7FrGACTCTG
GCTCCTGCTCTCTGCAAGCAAACACGCA
TCCCTCAAGTCTCATGCTGGTTCTCTCA
AGTCT-rCATGCTGGCTCTCTGTAGTTCTG TAAGCITACCCT'rTCAGTGGTGATTrGG 1302 1M000920 GGAGATC P001113 ID I SEQ SEQUENCE~tc "SEQUENCE,)} CLONE CLASS GENE
ID
NO: {TC ITC fTC "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2}
GATCTCCTGGC'=GTAGATAAATGAAG
AGAGTMCTACCAACTGAACTAAAGAG
CGGCACAGGAAATTAAAAAAAACAAAC
AAACTGATAGTTAACTCAATrGAGTAAG TATGGAGTI=GGGACCAAGACATATrA
GGCAAACAGACAGTAAGGCCTAG
303 1M000921 p001114 D GTFCCTGTACTrTATCATGTC1'TACCCCT
ACCTCCCTCCATI=AATCATGTITACTG
GGATGTAATGCATTCGTGTCCA~rCCA
GGATGCTATAACAAGATACC'TFCAGCCT
GTAAGCTATAGAAGAGTGTGGTCCTCAA
CCTTCCTAACTTTGTGACCCTATAATATA
304 1JM000922 GATC p001117 D CCANCGTGCCANACTCA1NANGGArrr TA77CATAGATTCTNTCANACTGCTGTCC
CACATGTGTTCAAAANCAGGTAGGTCTT
305 EM000923 GTCANAT p001119 D
GATCTCAUTGCACAGAAGAGTTAGAAGA
AAGAAAGAAAAGCAGACTGGGAAAAAT
TI=GGAGCGAGCA'FrCAGAGATrGAAC
ATCTATCITAACTTATGCAAAATTCCTATC
AAAAGAAAAAAAAAGCTrCAACAGCTG
GGTAAGTTAAAATGTAACTATAAGGCAA
CACAAGGCAAAGTGTTG1-rCTFGC1-r G'ITTCCGAGATGAGCTCAA'VrAAAATAT
CAATAGCGACAACAATTCTGAGCTGGAC
rAACAAAGAGTAGAACAATACTACCCA ACGCTrGTGGTTAGGTAACCTTACACAA rArrnCCTAATGCTATTCGGCAATAAnT 306 IEM000924 GTCAAGAAAA pOO 1 2 1 D GATCTITrCCTACAAGACTrCTGGGTGA
CCTTGCCAAGCCCAGCCACTGGCTGTGG
TACCTCACCAGGACACTCGGTGGACA'jT
AGGTAGTGCTCCCCA)AGTGCTAGGTGAC
1307 JIMOO0925 IAGTTTATGCTrCAAAGTGACTCCTGCAC p01122 ID I-- SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID {TC (TC fTC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 2}
TION"
MUTATION \L2) GTGCTGACGCGCCCTrGCAMTGGGAGA GCAGTCAAGCTATCTGTACCTrCACCGT
AAGACTACAFITGTCACTGCTGGC'ITCCC
TCCTGTGCAAGGGACGCA'FITGGGTrCAG
ACTATGCATGAAACAGGACAACAAAGG
TAGGGCCATTGGTAGATC
308 JIM000926 p00 1123 D
GATCTCACTGAATATAAAAAGACATCAG
TCCAAGGGTGGAAAMhAACCAAAATAA TACAAT7GTTFGTTG 309 1M000927 p00 1124 D
GAMCWTCAGGAACTAGAGTTACAGACA
310 IM000928 ATGCCCGCCTTGTATr pO01 125 D
GTGGCAGTGACGTCCGTGTGGGAAACG
311 rMO0929 rTAGCAAGTCCGAGCGTGTTCGATC pO17K V~
CAGGAGAGTGTCTCAAAAAGCAGCAAA
GCACCCAGCACCITAGGGTGAAGGACC
A M.CTGGAA'rGTATCCTCCCAGTTGCA
AATGTACACTGTCTCATTCACTCCTGTG
ACATAC'FMGTTTGTGAATGCTAATATC
ACATAGITTCGATC
312 1M000930 p00 1129 C
CCAGCAGAGACCAAGCATCCAAAACAT
GAGCCCATrCAGGCTFCAACCATAGCA GCTCCCATICT'CAATCCTGTTrCACCCCCCA CCCCACCCCCCGCTTCTCTAT'IrAAATCA
CCACTCTCAGTGACCAAAAAGATGCTCA
TGGCAAATGGACTCTTGGCTCTCT=TAC
CTAATACTGAAGGTAACAAGATAATCAA
CTGT17CCTCTCCTTCCCGGGGACCTCAT
CATACAACAT'TCTCCCACATGAAATTAT
CACCACGTCCAATACCCACATCCTCCCC
GTCCTGTAGAGAAACCACATGCCTAGCA
GCAG'I'GGTi-irCCCACCTCTGTGCTCCCTT
CCACCTCGATC
313 IM000931 p001131 D SEQ SEQTJENCE~tc "SEQUENCE") CLONE CLASS GENE
ID
NO: (TC I TC {TC "CLONE "CLAS "GENE" 2} SIFICA \L 2}
TION
MUTATION \L 2}
GATCGCTOTGGTITGGTGTCTGTGTATAT
GCACTGTACATACTAACCAGGTACACAC
ATAAATAMIAATATATAAAAAATAAAG
TGCTTCTAAGAGGCCCCTAGGCAGGGA
CGTATAAAACATICACAAAGCAGCAA
AACAAAATTGATACAATCAAAAAAACA
ACACTATAACCAACATAGGTGAAAACA
GCCAAACACATAATGTACAATCTGGTGT
TCCAGGACAAACATCGTCATATACATG
314 GTATATACATACATACTITICACTCAAT Mm.3 669 IN4000932 AA p001 132 B 2
GATCGCTAAGTGTGCGCGGCCGCCGTCT
GCAGAATGAATGGAGGGAATGAATGAG
GGTGCGCGCGCCCGAGGCCCGGCTrTGCG
TCAGCCATGCGTGCCCGGCATGGACACG
GCCTGGCCTrCCTGGGAGGATGGGACCG GATGCAGTTAGTCCAGGCGTfCAGCATC CCAGGGCCCTrCCTCTGTTGCGTGGTCT
GAGTAATCTGTCTCGCAGAAGATACGCT
M. 1515 315 [TM000933 p001133 B 128 GGAGGTCTCTrGTAGGTGCTTFAGACTCAC GTTACAGTCAYrCAGAGGAGGGAGMT CAGCrGCTAGMTCTGTGCACACCGATC 316 IM000934 p001136 D
GATCGGCTGTCAAGACTGGGGAAGGGT
317 1M000935 CCTCCTAG p,001138 D
AAGCAAGAGGTAATAAAATACATGTGG
ATGGATGACTCAGGGGI-rCAGAGCATAC
ACCGATC
318 1M000936 00O1139 D GATCGGGGACCTrGCATAAAGGGGTCCA AA70964 319 1M000937 GGGCTCTCAGTCCTTGGGAAGG Ip001140 -B -7 SEQ SEQIJENCE~tc "SEQUENCE") CLONE CLASS GENE ID {TC (TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2)
GATCGTGATGACTTCATAACCATCACGT
GTGAAAAGACTTAATGGCGCTGAATTCA
CATGACACTTAAAATGCACAAAGTAACA
AATMTATGTCACATGTATrAAACTACA
GCTAAGTACATGGGGAAAAAGPTAGAC
'lIAGAA'IAACTICATCCAGAGTICATAI'GG 320 1IMOO0938 TAG p001 141 C
GATCGAGGAGTAACCCAATAGCTCCTAT
TCCCCCCTTIACTAAAATATGACCCACTG
ATGGA'FrCTGGGGATGCACAGATG'FrCT
CAGAAGTI'ACTGATGAACACACCATGCT
CTAACAAACAGTATCAAACCCACAGTCA
CAGATGGCCCTAGTFTAAGCACAGTGCAT
CACAAAGCAAAGCAAAGAGCCrrGACT
GTGGGAAAGGTAC'FIGTGGTGAGGACTA
GTGGGGTATGAAAGAAATTAGAGAGGA
TGAAGGTAGTGATATTCAGTGTGTGTGT
GTGTGTGTGTGTGTGTGTGI'GTGTGTGT
GTGTGTGTGTAAGACTATTAAAGAACAC
321 CC3I'-Tfl'AAAGAAAGGc'nTCrrGAGT 114000939 (3TCACC p001144 IR
GATCGGGCCACATCTCAGACACTCCTAT
AGCITACAGAC3AGATACCGiTi~ccTGTTA TGTrGCAGACAACT-rFATCTIGTT-ACTCA
GAGAAAACCTCCAGGTGCCCCTAAAGA
AACTGGGCCCTACATCACATACCCATAC
CACACACATGCAACATGCAAAACATAC
ACACATACATAGACACACACACCACAC
OCACACAGACACATACAGACACACACA
CATACTATACATACAGACACATATGCTA
CACACATACAGACACACACAAGCACAC
ATACTrCACACACAGAGACACACACACC
ACACACACACAC
322 1IM000940 p001 149 R
GCCTGCCTCTGCCTCTCGAGTGCTGGGA
ATAAAGGCGTGCTAGAGCCTFCAC'GG
CTC i cl CTCTCTCTCTCTCTC1-1TIAACCT CC'I1TCCTITAATGAGTTATI1'ATr ATTI1ATGTGCATTTGTGT1TGCCTGTA
TCCGATC
1323 1M000941 Ip001 151 IR I- SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE
ID
NO: ITC I TC {TC "CLONE "CLAS "GENE" \LJ 2} SIFICA \L 2)
TION"
MUTATION L2)
GCTTCAATATTCGAAAAGAATTAGTAAG
324 11M000942 AAAGGCTGTrCGATC p001 152 D CTACCAGGAAGTCAGGGGT17rCCAGGAA
CCCAGAGTTGGCTTCCTCTGCACAGAGG
GACCTCATACCAGTAGATGGTGATATG
CFCCCTTGTTCCTGAGCCTCAGTGGAAG
CGACMTCTATGGATACTCCCTCCCTCGT
GCCTCTCCTTC1TrCCCTCfCTGCTCTCC 325 1M000943 CCCCCCCCCGTCGCCCTCACGATC pOO11 5 4 D
ATACACACCATCAGATATACCTCATTCT
GATATACCTACAGGTACACCAATCACAC
ACACACATTrACTCACATGTACATGCAC
ACACCACATCGGTTAGAACCAAAGACCT
CACACACACCCCTCACACATGT17CATC
TGCATTATCAGTGCCGATC
326 1IMOO0944 p001155 D 327 [M000945 GATGGTCAGGTTATGAATGCCAT pOOl 156 C
AG'JTCTCAGAACCAGCTACTGMIACAC
AGGGCCTCATGCAGCCTTGCTGTCCTCC
ATTCTGCAAGCACAGGATACACACCCCT
328 GAAGGCCAGArrGTCAGGTCAGCCCGAT M000946 c pOO11 57
C
CTrCAAACCGGTCCTGCGAGGAGTCCAC 329 1M000947 AACCTCTGCCTGCCGATC p001158 D
GATCGAGGCCAGCCTGGTCTACAAGTG
AGTCCCAGGACAGCCAGGGCGATACAG
AGAAACCCTGTCTCAAAACAACA&AC
AAACAAGATTCCATTGAGGAACACCCA
GATGGAGACATGGGTGTTCTCCATAGAA
GGGTTAGGGGCTTCCACACCGTTGACAC Miii.8136 330 11M000948 pOO1l59 B 6 GATCGGTGTGCnTCTGCAGTrrTCAGCG AGGACTCTGGGCCCAAAATG1T=AAAG
CAGAAAATTGGTAACACTAGAGATATTG
TCAAAATACGATJfTCCTCTGGTrCAGAA ATGc3CGAGAGGGAGGGCTGGAAGGGTG GAGTGGGAAGGAATTGTCATCAAAGCA AA40894 331 IM000949 TTGflGATAC p001160 B SEQ SEQUENCE~tc "SEQUJENCE") CLONE CLASS GENE ID (TC (TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 21
TION"
MUTATION \L 2)
CTGTCTCAGGCATGAAAACACTAAAAGA
TGACCAAMJCAATAAAGATGAGCTGAA
TGTCTACTCAATTCCCACCATAAGGTCT
332 1M000950 ACAAGATGTAAATGGGCCGATc p00 1161 D GATCGTGGAAACAGAGCCT-rGAATATAA TrGAAGAAACAGAGGGCAGGCAGCAGCC
GCAGCACAGCAGGGGCAGTGTGAGCAG
333 IM000951 GCAGCAACAGGGGG p00 1162 1D CTCcCTACTACCTTCGITCCTGGACNTC
CACTGAGATGAGGCAGGATAAAGGGTC
AAAAGAGACCTGACCTTCTCTGCCAAAG
CCAGGGATTCTGGAAGAATAGAAATG
G'TFCTGGAATTFCACAGATGCAGTGGTCT
AGGATC
334 IIM4000952 p00 1163 C GATCCATAGGTCTCTGCThFCCCCAT7CA
GGGCTGGAGTTATAGATAI'CTGITC'I'ATC
ACCCAGCTTTATGTAGGTTCCAGG
335 1M000953 p001 164 D
TATGTATCTACAAGCCAGAAGAGGGCAT
336 11M000954 TGGATC 00O1166 D GATCCGAG1TCTCTCCGGCCACGTAccTr
TCACATCCCATGCACCCTGGTATGTAAG
AAGAGCCCAGCTCAC
337 IM000955 p001167 D 338 JIM000956 TCCCATAATAT-hFCCTCAGAAGGATC pOO11 6 8 D AAATGTGTATCG'TTrCTGGGTCAGAGCT TTCAGGAACTGAGCATGACrGcrCTACA GTGTC'TrCTCCTTCTGCCTGCTGAAGCC
GTAGGGGACAATAGAACCACAGGATGA
AAGGACTCGGGATC
1339 1MN000957 jp00 1169 ID I--
U
SEQ SEQUENCE{tc "SEQUENCE") CLONE CLASS GENE NO: {TC (TC {TC "CLONE "CLAS "GENE" \L 2) SIFICA \L2)
TDON"
MUTATION L2)
GATCCAATGGCAGCTAGCAGAGTCAGA
GAGCCCTCACrCCAGTrAACTAGGGGAC CCACATGAAG'TrCAAGCTACATATCTGC TACAAATG1T7GAGGGACCTCCTAGCTC CACGCCACATGCTGT1GGTTGGTGGTT
CAGTCTCTGTGAGCCCCACTGGGCTCAG
GTTAGTTGACCTACAGTCT-rCTTGTGGTA TCC'rrGACCCCTCTGACCCCAGAGM~A
ACAATAGCCTCTGACTCTAGAAATCT
ACCTACATTrCCACTAAATrCCTC 340 1LM000958 GGCTCACATAATACCAATGAACT pO001171 R
GATCCATCTGCACAGTCTGTCACCGGGG
TCCAGCAAGTAGCAGCC1TCTGCTGCT
GTCTGTCAGACCCTCCAGGGAGGGAGA
GCTrGTCTTGTGGCCTCCCAACAGGACC
CTGCGTGACGATGCAGGGACAGCAATG
ACAACTCAflCCAGACTCCAGGTCCCTG.
GAGGAGCCTCCCACAAGGGAAAGAGAC
TACTCACTGGTCCTGGGCCCCTC'=GC
GCGCCCCGCCCCCAGACTCAGCGTCTAG
TGTTGCTGGGCTCCCCT
341 11M000959 p001172 K I n)yl
AGGGTAACAGGCTTAGTIGGGGCC-=
CTGTrACAGGAAAACCATGAAATGTCCT
GAAGTGCTCAACAAACAGGGAATATAG
AAAATCATAATGGTrCCTCCCTAGCACA AGGAAGCATGTTrAAAAATrGCAGCAA AATAAAAAAGAACAGATC1TAAGATTG AGGGA=fIACGGGGTGGTACTI=CTr TCTCTrATAAACATTrATTTACTI=GIT A~rCAAGACAGGATC 342 154000960 p001173 D GATCCAGCTGTGCTrAACATACGTAAA
GGTATGGATGCTGAGAGAGTATCTATCG
AAAGCGAAGGCACGCTCCCCAAATTCAA
GAAAGCAGCTGTTrCTAGAACCAAAGAC
ACCACCGCCGCCGCCGCCAGCACCACCC
GCGAGCGCCCGGACCCTGT'rACAGAGTG 343 1M000961 TO pOO 74 C SEQ SEQUENCE {tc "SEQUENCE") CLONE CLASS GENE ID [TC {TC ITC
NO:
"CLONE "CLAS "GENE~ 2) SIFICA \L 2)
TION"
MUTATION \L 2) GATCCTGAAAT7ATCACA'TrrGAATCAA
ATCATGCCCTGCCGAGGATAAATAACCC
AAACGACCGAGAAAACCGAGAAAAAGA
344 1M000962 ACAM1ACTGACCATCCTfC p001175 D GATCCAGTCCAGAGCAATGTrCAGGTCT 345 [M000963 GTGATGGTAT 00O1176 D AAAGGTGCTCrFCAATACTTAACAATCCA
TAAGCT[GTGCTCTC'ITAGTCGTAAAGG
TGGGGTCCATCAAAATCCCATGACACCA
CAGCGAGACCAAACTCCTrCTCTTAC
TCCGAATCACCCATCCCATGTGGGAGAC
GAATAAGAACACAAACTACATCTTCAGT
GACATAGAGTAGCATCTGCAACAGAGG
AAGTGGATGGAGACCYIGcTCTCTGGTCA
AAGACAAAGCATGTGACAGCTGAGCCT
GGCACT7CCTACTrGGGTCACAGCTCAA
ACCCACCTGAACCAACAGCAGAGCCCC
ACAGGGATGGGACTCACATG1TITCCCTC ,irGcCCTGGAGCTTCGTGCATGITGTrA
GAAGCTAACTGGCTAACACGCAGGGGA
ACAGGCAATGTAG'I7GGAGTATGAATCG
AAGTCACTGGGCATGGTCC'TCAGTCAGC
346 1M000964 CAGGATC p00 1177 C CTAGACTAGTATGGCAGAACCTATC17C ITCTAATCAYl'TAGATGAATACTCCACA
TGAGAGAGCCCTGAGAATATCTGTAAAA
AGTAATCCAGGTrCTGTrAC3TCTAGCT
AATC'ITATCTAGGTAATAATAGATAAGG
AATCGGGATTCACGAACACAAATACCTG
TACAAAGCATGTTGTCTCACACGGGACG
AACACITG'FITCTGCTGTGCT-rTATAACGC
TGGGACATACAAAACTAGACTCTGCCTA
AGAAGTGMrGGAAACA1TTGGGTTAAA 1TATAGTCAGATAAAACAACAACCATGA
GTAAATCGAAGAATATAAAACTAGGGA
347 IM000965 TO Jp001178 C I- SEQ SEQUIENCE~tc "SEQUENCE") CLONE CLASS GENE EDIT T T NO:{T {T {C "CLONE "CLAS "GENE" 2} SIFICA \L 2)
TION"
MTATION \L 2} TTCCTGGACAATAATGrITCTTCA'ITA AA'TrFACACTTAGAGCATTGTCTTAATC
CATGAATAA'TCCCAGCTCCTAGCTCAT
TACGTGTGACACAGCAGGGATTCATACA
T7AT7GAATGAATGGATGAGTGAATGA
ATAAAAGAATGAGCATATCAAGAGGAT
348 1000966 c p00 1179 D 349 LM000967 GATCCCTTCTGTC1TIGGTTATCTC pOOl 181 D GATCCACCACTGAGCCACTTCTrCAGCC TGTGACTGTCATTC1TAATCATCCACAC AGACTrCTCCrrGGCAGAJIGCCCAC CTCTTAAGAG1TCACAAAGGTITr=C
TCTGCAGGGCACATGAGAAAACAACTC
TGTCATAAAGAAACCCAGGAAGAAAAC
CAGCAGAGGCAGGTGAGTTAAGCCTGT
GGTGGACA1TCCTTCTGGGGATGACCAG ATGGGAACAGTAAT7CACAGAGGCAGA
GGGGTCTGCAGTCACTCTGCATGCCACA
TGTGTAACCCITAAGAAGTGAGGAATGC
TCTCAACAGGAAAAACACAGCAGCAAA
TGCTATGATACCAAAGCCACAACTCCAT
GGGTCCCTGGAGCCTCTCGAACTAAGCT
GCCAGCTAGGGAGCTAACACTAGCTTG
GATGAAACACAGCTCTGGTAGAG1T 350 1M000968 ,OO 1182 C
GCTGGGAT[TTGAACTCAGGGCCTTCAGA
AGAGCAGTCTGCTCTTACCCGCTGAACC
ATCTCACCAGCCCCCTTCCGTrCTnCC' TCTrCCTrCCTITTr-JTCCACAITGTT TrCAGACTGCACC'-G'TrAGTAGTCTA GGCTGGCTrCCAATrCCCCAATGATTGA
GCTATGGGTATACTGTCTTCACCTACTI
GA1TrMGMIGMTATTTGTT!TTGT 'TTrGAGACAGGG1CTCTGTATAGC CCTGGCTGTrCTGGAACTCACTITGTAG ACCAGGCTGGCC1TGAACTCAGAAATCT GCCTGCCTCTGCCTTrCAAAGTGCTGGGA 351 1MO00969 TC pOOll 8 3 -R SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID {TC {TC {TC
NO:
"CLONE "CLAS 'GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 21 GCTrrCA'IAATATACATCATFACCAG AAACCACAGACATCTTrGTACCAACATA
TAGTAATATI'AATCACAATAGCGATCAC
TC'ITATGTAAGiGAITGAGjAAGACTCCCAG crAATrA'TGCTAATQTlGTAGiAAGAT'GCCA
GATGGATC
352 PM000970 p00 1184 D GATCCCTGC117CTGTAAATCCGCAACGA CAATrGTrTATCTrCTCC1T~TrT A'rT-rGlrITATCTATfATm=CAGAT 353 1M000971 GAAAA p001185 C GATCCT'CCrGcc'i~cTGCCTCCYI'CAGCAA 354 ATCCTACCGGCGTGCGCCACCACTACCG ILM000972 GCGAAAAA p001186 R F GATCCCCC'FrTCTCTCTGTICI'ACGGCCTrC TGTCCTGTG117AGCTGTAGGCCTACTCTG TATGAACAGACCTCAGCcK3AGGGGT]17G GACTTGGGCTrGTGTTTCTTAAGAGAAT GGGGClTCCATGACTGTCCCTCTGTCCCT TfCATCCTAACCCTGCCTCCCGCTAACA GGCAGCCTGTATGMTrGCACTGTrCC TrCCTCCTGACGGTCTGAGTICG'i-i-cccT CAGAGACTGT7GCTGCTGCTTCAGC'FM
CTCTCAGCTTCTCTCAGGGCTTCCGCTCT
GGAGTITCTCCTGCTTCTCTGTITTACn7r TCAAAGCTCAGCCTCCATCTrCTGCACC
TGCGGAGTCATFCACTGAYI'CCCAGCTGT
GGCCTGTCACCC1TCCC1TrCMC'CC
TCCTGTGCCACCACCATGCACCCTCCCC
TTCTGTCTGTI'GTGTrGTCCTAACCTT7C TTCTCCCCATGCACCCTCCCCT-rCTGTCT G11'GTGl7GTCCTAACCITrTCTTCTCCTC
TCTGTGCTCTGCAGGTTTAGGGTCTCI'G
TATGAMhGTACCTGCA1TrA'ITGAAGC
TCCACTCTTCTCMJCCCTCTCTTATC
355 1M000973 pOOl! 87
D
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE
ID
NO: ITC {TC {TC "CLONE "CLAS "GENE" SIFICA \L 2)
TION"
-MUTATION \L 2) GATCCTGCAATACCTCjTCGTGGGCATAT
ATCTAGAAGATGTITTCAACTGGTAATA
GAACACATGCTCTACTATGTTCATAGCA
GCCTTI7TATAATAGCCAGAAGCTGGA
AAGAATCCAGATGTCCCTCAAGAGAGG
AATGGGTACAGAAAATGTGATACATTrA 356 IM000974 CAA p001188 R
ATCTAAACTATAATAGT'TGCAGGGCTAG
TTCATTGTCAGGTGCGTGGCGAAAGAGT
GCAAATCCCGGGGGTTCTTC-FCAGAA
TCAACGAGGCAATACACTrGAACATGTA
TGYTTGTAATCTGCGGGGCATCACCC
GTCCTCCAGGATC
357 IM000975 p001190 D
GATCCCCCAGAAGTGATAGTAACAGT
GAGGTGAATGCAAGCAATAAGCTACCT
AAATCATTAAAACTTCCTA=TIATAGC
ATCTATTAGTrGCACACAGCAGTGATGG 358 ILM000976 GTrCATT p 0 0 1 19 2 K Irf4
GGACCTCTGTACAAATGTCGGGAGATAA
GGGAAGAAAAAGACGACAGAGATAGCA
GTCAGGATGTAATGTGTACTAGATGAGT
GGTTCAAGCAATAGGATGGAAAGGGCT
TAGCAGGAGAGAT=~AAGGATGGAG
GCAGTAGAT'rACATCTGGGAAATGTCAC 359 JIM000977 TGGAACTGGATC p00 1194 D
GATCACCAGGCTGGGGAGGCCACCTAA
GGAAGTGGCACGGGCACGGGCAC1rCC
CCAGAGCACCCTCTGGGCACTCTGAGAG
GGGCAGAGATGTACTGCAGTAGGCTGQG
360 [M000978 CGCGGAGGAG p00 1196 D
ATATAAAATATCGAACGTCCTCTGGCTT
GTAAATATCATGTTAACCTTCAAAGCGT
TCGAAAGCGCAGGAAATCTGAGTCAAC
AGAATAGTATGTAAG FrrATTnTATAG
AACCTGCCTGAACTGCAAGGGAGGGGC
GGGGCGTGGACCCAGGCCTGGCTGCCAA
361
TCTGCGCTGCCAGTGAACTAAGCCTGAT
IM000979 c pOOll 9 7 D SEQ SEQUiENCE~tc "SEQUENCE") CLONE CLASS GENE, ID T T T NO:{T {T C 'CLONE "CLAS "GENE" 2) S1FICA \L 2)
TION"
MUTATION \L 2)
GATCAAGTCCTGGTCAGTACCAAGTTAA
AAAAAAAACTATATAAAAGCTATAYLAG
GGGACAGCTGTGGC1TTTFGTAGAAAAGA
AGGTCCTGGTGCTATGACCTGCAGATGC
CCATGTGGAAGTCTTCAGATGAAGACTT
TCTCATGGAGTAAACATAC1CTGTITGTTT GACCATGTGGACTrGGTTCAAAA'rGCCC A'TGGATGCTCCTI'GGGTACCAGGC1TC
AGTGGGAGTCCCAAGCCCATGTCTI'AT
TTGAGCATGAGCAGTACTGATGCT-rACC TAGTCTI'An'Cll7CCTTGCCCCCTGCCT GGACCGTCTCTGG'I7ACAAGGATGCTGC AGTGGGAAGCGGTATGACCG'TACC7IT[
ATGGGACTGAGACCAACTAAGGGGAGG
CI'GAGGAGGCTGCAGTGAAGY[ATrGTT
GGCACTGTGGGCTAAGATGGAAGATAA
CATGTTAACAAACT1CAAGTGCGGAGGTC 362 LM00980 TCAGAAGTAAAATTGCCTGGY[AGTAD
GATCAATT'GGTAACCAAGCCTTGAACTG
GTATCTCCCACCTGGCTCAATATAGGCT
CTM~CAAAGGCTAAATTrAAGACCAAGG ACACAGAAGGGTAGCTCGCrGGGCAAA 364 LM000982 CGTGATCCCTGCTGATAGTGTAG pOOl202 D CTCTCGTGTGGAGATAT7AAAGGTG
[GA
365 IM000983 ACCACTAAGCCCTGATC p 001203 A lgcp2
GATCAAGCAGAGGGGTAAAAXAAGGGC
AAGCTCAGTGTTAGACAAGCTCATAAGC
CAAAGCTGTGAACTCTCCAACGCCT
366 IM000984 -1p0012 05
D
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ED {TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2) GATCACTrCAACATCAAGAAGTTACCCA GCCCCGGGAAGAAGTACA1TCGAGGA AGCAGTG1TrCATI=GAGTCTGCTC
CCATCCCGTITCTCTGCAGCTGGGTAAA
CTrGAAGCTGGGCTAGCCTCTGGGTAGA
AGGCAGCTAATGACAACTACCTTGCCTG
TCCCACGGAGCCCGGACAGAACCTGAG
ATAACACACCTAGCTTGCTGAGTAAAGG
CAGGTrACTGTGTGAATGACTGTGAGCT GTTCCAGCTCTGCAGAGCAGGjAAGTCTG 367 IM000985 ACTGTGGAGATAAGAGATAT 0001207 D GTCATGAM~GTAATrCCCTGTCCAACTC TCArrGCTTAGGTCAAAATGGC-FAACT CCTAGCCTACTrCAGTGTAAAAGTCATG 368 1M000986 CGTAATGATC p001209 D
GATCAGGCTGGCCTCAAACTCAGAAATC
CACCTGCCTCTGCCTCCTGAGTGCGGGG
A'ITAAAGGCGTGCGCCACCACTGCCTGG
CTGC-IC1TI1r=CTT1TC1GTGT
GTGTGGGGTAGTGGTGGTGGTGGTGGTO
TrCGAACC 369 EM000987 p001210 A Hsc7Ot
ATGTGTGTGTGTGGGATGTGTGTGCCAT
TGTGTGTGTGTGAGTGAGTGTGTGTGTG
TGTCTGTGTATGTrGTGGAACAGATTCC TGTGTATGrICCTTCTTCACACATGTTr
TCAGAAGTGAAACCAGOCTATGAAGAC
CGCCAGGCAGCTCTGCAAAGCAGTACTG
AGAAGGTGGGACACTGCGGGGGTGAGA
370 11M000988 ACAGTATGCATGATC p,001212 R GATCACACTCCATGAAGCTrCTCTTCTG
CAACAGGAAACAAATAGCAAGCAAAAC
CACTGGTAATCATTrATGTGGTGTCTAAC
AGAGAGCGGTGACAGGGGTGGAAAACT
GAATGACA M AAAAGGAGCTGGAGAT GT'rGG1TrAAGGCGTGTGGGGGCAGCCT 371 M4000989 ACAGCATGGAATrGGTCCATAA p00l213 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID ITC {TC (TC
NO:
"CLONE 'CLAS "GENE" 2) SIFICA \L 2
TION"
MUTATION \L 21 AACCATCATGGTAGCTrCTGcT-'c~icTrcc ACGAAGATGGTrGMTCCACAGTTGCCC TCTCTACAGAGTGGTCCTGTAT7AAGTC
ACAGGTGCCATCCI'GGTGATC
372 1IMOO0990 p001214 D
GATCTAACCACCCG'TITCCTGCCCGGTC
TTAGATAGACCTCTTGGCCCCCACGCAC
GTAGACAATGGAGTAGACAAGACTTCG
AGGGGAAAGAGGCTI'CCCAAGATGACC
CAGCTCAflGGC'ITGACTCCCAACGCCA CCCAC7TACACAGTGAGTATCTCTGGTC 373 1M000991 'IGrCTGT p001215 A lFarp
GATCTATGTCATCTTCCAGGACTCAGAG
'rrAAGAGAGTrACCAAGTGAGAGCTCTC ATCACC17CTGAAGCAGTTrGAGAATTGG
AACCCAGAAAGATGCACATGCACGGGC
ACACACACACCCACGGGCACACACCCA
CCCACCCATGCAGAGAGAGAGAGAGAG
374 1M000992 p00 1216 D
TAGGTTGTGCCTGGCCTGTGCAGGACAT
GCCTATGGGGTCTTCATCCCTCTCACTrA CTAATG3TCACTACTGACAAGCACTA
GTAAGAAAGTAGGTGCCTGTAAGAGAC
TGGAGCAGCCTGCTGCTGAC1TCAGCAC
CTGGGAGGCCTCAGTAGCAAAGCYI'AGG
G'ITAGCAATCC'n7GGGGCTGTGGCTGGC
TGAGCTCTGGGGTACCGITIAAGAGGAA
AGCTGGAGTCCAGGFTCTCCAGGCCCTG
GGTGCATCCCACAACCTCTCTCTCTCTCC
TACCACTCGCAGCCUTGGCTAAGGAT
GAGGACCGGGACCTGGAGTTATC'FGAG
ATC
1375 1M000993 L-pOOI 2 1 7 A Snn SEQ SEQUENCE~tc "?SEQUENCE")} CLONE CLASS GENE ID {TC {TC ITC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L2)
TION"
MUTATION \L 2)
GATCTCTCCCCATCCTCCTGTTGCCTCTT
GTCTGTCATACCTCTACTACTCCATCAGT
TGCTGCCTCTGAGTCCCTC1TCTTCCTC TCCTATCCCTCCTCCCATC1TCCTCATCT CCAGGTCTCTCCAGGTCTTCCTrCT-rCCC TCCTTFCCGCCTICCTC1TCCACTG TC1-TGTATrCCCTTC1TCTCTGTrGGT CCCTTrCCCTCGCACCTCTITCCTCCTGTC CCTCCTT=CATGTACCATATTTCTCT7C 376 1M000994 CTCT17CTGTGTCTC p00121 8 A Gatal
GATCTTAGATGGCCAAATGTTGTGAACG
TCCTAGATGTGTCGTGAGCACTCAGG
GTTrGAGAGCCCTGGTTATrAGCAAGTG
AAGTGGATGTATACACAAGCAGAAGGC
TGAAAGTAGACCCCGGTCTCTAATCCTA
TATAAAAACCAACTCCAAATGGACAATA
GAAATAAGTGCAAGACTAACTCCAGGG
377 1M000995 TCACTGGAGGGATACAAAGGGAGATGC p001219 D
GAATGAATATATATATGGGACTAAATGC
CATGCCATAACCAAGAGAACTIAAAGA
AGAAAGTGTYITAGTTATGMIACTC1TrC
AAAGAGTCCAGCTGCCAAAGGGATGCT
GTCAGGAGTAGCTGAGAGCATACATCTG
GACCCATTAACAAAGAAGGGATGCTTCC
378 E1M000996 CCAGCAAGATC p001220 D 379 1M4000997 GGAGGAGGGGCACCTTCTCAGAGATC p001221 D
GATCTTAAAGCI'AATAGGTGTGTGTGTG
rGTGTGTGTGTGTGTGTGTGTGTGTGGTC
AGTGGTAAAATTGTCTACCAAGCTCTAG
G'rTCACCCCTCACAGAGCCGGAGAGAA
AAGGAGAAATCAACTCAAGTCAACCCA
AACAAAACAAAGGACTCAACA
380 JEM000998 I p001222 IR SEQ SEQUENCEftc "SEQUENCE") CLONE CLASS GENE ID {TC (TC (TC
NO:
"CLONE 'CLAS "GENE" 2) SIFICA L 2}
TION"
MUTATION \L 2) GATCTG'ITCCCAAATCCTCAGTrACTCTrc
TGGGAAATGGCTI'CTGTATGTACACATG
TTCTCTAGCTATGTAATAAAAGACCTCT
C'ITCCTrGGCAAAACUrAACTCTACCTTA
GAAAACTUTGATIGAGTACTAGAAAGAT
GACATGTCCACAAACGTC'FrAAGTGAT
TCAGGGTTCACAACAAAGAAGGAGATG
CTATATTGTCTrTCATGACATAGCGTCTA AGTCCCATrAGCATAACT-TCTATAACACA 381 1lM000999 CAAGTGGG[ p001223 ID ACACTAGC'ITCGAAAC'F7TTAGT'TGTCT GTCCCTGAGCCCYI17GTGGTACTI'CCTCC TCAGAGCCCA6CTCCAGCAGTCCCCT7A
GCGGGTGTTTTAGCAACCACACCCTCT
GACTGTGGGTTGCTCTGCAGTGGCTT
AAGGTrGAATACGAAATGCCTTrCCACA
AAGAGACACTACAGAATCT]TAGGTGTCG
AGACAATGGGCATrGAGAAGGAATTG GAACC1TCAGATrc 382 1IMOO1000 p001224 D I-
GATCTAAAGGGAAACCCTGTC'ITITG
AATCTGAGCCAGCACAATA'TGTATrTC
C'FCAATACGTGGTGAATGTTGTATTAG
CAACAATAAATGGAAGCAGGGAATCTC
TCATCTCATGAGTGATATrACAATGTCT
GTCTGGAAACAAACGGCTAATCAAGTTA
GTCACT'rACTGTrrCThFAGAAAACACAG
TACTFIGAAATGCATACCTAGCAGAGAA
TATAAAGTA'TFACTG'rrGGACTAGACT 383 ILNM001001 GGGCCCCCGGGTGTGAGGG pOOl2 2 5 D
GATCTATCTCATCCTGT'ATAGCCGGAA
ACATGATAGGAGGATTGGGCAACTCTCC
AGjTCCCYI1l'CTCT7GGGTAAAGTCTGAA Ac3CAAATCGCCCGGACCCALrCTCCTGTC
TCTGCAGCCTGTCCGAGTTGCCTCTIGCC
ACTCACTAACTTCACTCCTF]AA1TTAAA 384 EM00 1002 AAGCCAGCACAMTATFGACCGTCT pOO 122 6
C
SEQ SEQLJENCE~tc "SEQUJENCE") CLONE CLASS GENE NO: {TC {TC {TC "CLONE "CLAS "GENE" 2) SIFICA \L2)
TION"
MUTATION \L 2)
GCATGTCTCCAGACTCTCAGCTGCTTCCT
GTCTGCTCCTGCTGGATGCT'rCATGAAG ATGGAGTGAAGCAGTGGTCAGCTrGTCT
GTCTCAGCTGTTCTATGTGCATGTGTGC
ACTTGCTGGAGC'ITATGTGCACCACAAG
CACGCAGGTGCACACAGAAGCCAGAGA
385 1N4001003 TC p001227 D
GATCGAACACGCTCGGACTTGCTAAACG
386 MO~l004 TTCCCACACGGACAGTCACTGCCAA 386____EM001004______ p001229 K Nnyc
GATCGTGAGTTCAAGACCAGCCTAAAAT
ACAlCAGTGAGCCTCTGTC1TrTAAGAAAc
AAACAAACAACAACAGCAAACAAAAJ
ATAT'rGCTCAAGACCCAATGTTCCTCGG ACTA ATAGGAATCAGAGTTGCTGTr CTTCTCAGGGCATGCCAGTTrAA-rITGAA
AGACAAGGTGTAGAGGCAAGGAJAG
TGATI=ACT-rGGATAACCACCTCATGG
AGCAGTCAGGGGAACTCTAGCCTCAAA
GCTCT'rGCAGAAGITATAT 387 IM001605 p001230 D GTAGAAGC1TFIAGAAATACGTTrGIT
ATCTATCTATCCATCTATCCACCCATTAT
CATCTATTATCTATAITrAACATCTrATCT' AAGTATCTG1TTATCTATCTACCTGTCTA
TACCTACCTATCTACCTACCTACCTATAG
CGATC
388 1M001006 p001233 R GATCGTGCATGCATGGGTGTG1TTGGG 389 IM001007 GAGAGGTrCTGT pOOl 23 5 D GTrACTAT'rCATCTGAGGTrCTCTrMGT
TGTATITGAACAGGAGGAAGGAACCAG
GAGCTCAAGGATGTAGCTGGAAATGCTA
TAAAACTGGGATGCCCTAGAGAATCACA
CGGACAATCCTGCTAACCCATGGAT'rGT ACACTCCAATATACAAGATAACATG1TTT 390
GTGCAGGCATGCCACCATGATGTTCGAT
IMOO1008 c pOOl 2 39 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ED {TC {'IC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA \L 21
TION"
MUTATION \L 2)
GATCGACCGCAGATGAGGTCTATGCAGG
AAAAACGATGTCTGGAATIT7AAAA
TTGCTCAGCAACTCACTGCCACGTATAC
391 1M001009 TGGAGAGCCAC'fl'AGGGAT p001240 K [yc CCAAGTATACGTGGCAGTGAG7ITGCTGA GCAATFlTAATAAAA7TCCAGACATCGT TIMrCT'GCATAGACCTCATCTGCGGI'CG 392 1iM001010 ATC pOO 1242 K Myc
GATCGTAGAGAGATIGGACCCAAATATC
AGCCAGAGAATTrAGACCAGAAAATGGA
ACCAAAGTACCTGTCAGTCCAAGGATGT
393 M001011 AGTGGCACTAC p001244 D F
GTCCCCAAATGTAAACAAAACTATCAAA
AGAAATTGGGCATGCCAGAA=TrC TICACATTAAGGGAAT-CTGAAAT-rGAA ATCT7GCTAAGGGAAGGGTGGCTTGAGA ATA'FrAACAGAATCCTAGGTrGAAGGAG
CAGGAATAGAGGATC
394 1M001012 p00l2 4 6 D
CAGCTAGCCCATGGAGCTGCTGGGACAC
GAGGCCGCAGGCTGAGCATAATGGGGA
AGAGATGGCAGATI'CATTCACCCACTTG
AGGAGACCACAAT7AGTCAGAGGCATG CTGGGCCTGGTCAGAGTlGCTCAAATAAA CATfCACAGGACCAAAGTAATAAGCAYI' GGTG1TACAGAGATAAATCC'ITAGCAG
GGACACGGGACCCCAGAAAACCGGA-AG
GACATCOTTCCCATCATGAGAACAAGGA
CAGCAAACAGTCACTGAGGGTATACTAC
TGACCAG'FrCCAACAGGGATGGTCAGAA
G'TGAACGCTGGATATATCATGAGCTCT
GACCTAAATATTCTGAGTATTCCCCATG
flTGAATGGACTGAATACTCACATTTTCT
AAATGCTGAATACTGAA'TICATAGCA
ACCATCATAAGGCATGGTGGCAGAATA
ATATCTCTCACTCAGAAAGCAAAGTATT
CTAAGTflGGGGATC 1395 1rM001013 I p001247 ID F SEQ SEQUENCEftc "SEQUENCE") CLONE CLASS GENE ID (TC {TC ITC
NO:
"CLONE "CLAS "GENE" T\ 2) SIFICA \L 2)
TION"
MUTATION \L 2)
GATCCCGTGGGGACTGAGCCTGCAGCTC
AGTGGTAAAGCAGATGTCTAACGTGGTA
CAGGGTCCCAGATGAGATGACACAAGT
ACCTGTCAGTACTCCGGGAACACTGGGT
GGGAC1T=ATATGMTAMTGTATrCTT 396 IM00I014 p001248 D AGTCCATGT3TACTGAGAGAGGAGTTA GGTrfTAGAAAGCCTrCCTCAGATGTCCC
TCAAAGAAGCTGCTACAACTGCCCTCAT
397 IMOOlO15 CCCAAGTTGCCAAGGATC p001249 D
AGATITGCGTGAGTTCTGATGCATGCTGG
CCATGATGTGAGGCAGGGGCAGTGGTrG GATTCGGAGTCAGAAAACMrCCCGTCT ACTGCCGTAATCCCAGCTAAATTrCCTA 398 JIMOO 1016 TCCTCGTTGTAGCTGTTGGTGAGGATC GATCCTTCCGAATCTGCCATrGAAT A1TrrAAAACACACCTCACTGCAGACTAA
ACACATTGCAAGCACTGGGAGCAGAGG
TGGCTAGTGAGCACCACTCTAGATGGTC
399 1M001017 CTTC p001253 D GATCCTCCTGCGTCTACCTrCGGGTGGG AT'rGCAGGCATGGACCACCATGCTrGGC 1TGTGTGGTACTG3ACATTGAACCCAG AACTC1TTrGAGCACTAGGCAAGCACATC CrGAACACCAGTAAAACA'II-CAAAGA
GAAAAGAAAAMTAAAACATACACCTAT
CTACATCCATIrrCCACCATGTTAGTAAA CCAGGGACA1TrGAAGTGTGGTCInrA
TAAAAACACCCGGGTGCTTATCTCCCAC
400 IM001018 GCTCT pOOl 2 5 4 R
CCAGCGGTGCTCACTACTGCATGTAACC
01 IM001019 AGCTCCAGGATC pO01255 ID SEQ SEQUENCE{tc "SEQUENCE") CLONE CLASS GENE ID (TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA\L 2)
TION'
MUTATION \L 21
GTCTCAAAGAACAAAAATAAAAGAGGA
AATrAGTAACGAGTCCTGAGAGATAGA
AGAGTA'TCAGCCTGGGACCAGAGCTCT
GTCT1TACAGTC17GCCATTCTGTGGGGC CTGGGACACAGCATCCTYFGGTrCT1AGA ATGCCATAGGCCTCCTGAGGGAGCCTrT
TCTGTAGGCACTTCTCCCACATTC'ITGGA
TGGATGCGATI17ATTCTGTGTCAGGGGA CTAGGGTrGCTGGATGTGTGGGTCGAATG ACTGTT1GTTCTGTCACFI'GGGAATYITGG
GATAGGAGAATI'CTGAGTGCAAGGCTA
GTCTGCACTTGAACGTACATATCGGGTT
'ITAAGCCAGCCTCTGAGCTACCACAGTG
AGACTCTCTCT'rAACTfAAAATCAACATA AATAGTCTTAGTATGGAGAGGTrAGGGG 402 M4001020 ATC p001257 C CG'IIccCGGAAAATGTGAAAAGAAG
AAGCACGAGACGAAACCCCCTCGAGAA
TGAGAAAATTAAATCTAGAACCCAAATG
GCGTCCAACAAGAACAYI7AGCTCT7GAA
AATGAATAITGCGCCTGCGCAGCCACCG
CGCGGCCAGCTGCTCAACTGCAGCTAGA
403 ITMOO1021 GCCCGACCCCAAGCGATC pOO1 26 0 C
GTGTCACATGTATGAACAGCATCACATG
GTATGAATGGTATCATATGGTATGACGT
GAATGTGTGCACCGGCACTGATC
405 IMOO 1023 ATACCACCCACTCCC~aAAGAAAAIGATC p001263 D GACTGATATTAGTAGGiTrGTTCTGTAAG GGCCGTGAAAT1TIAGCTAGAAG7FrCT
TGCTTFCATFAACAGTGGCAAGTATGAG
TCCATCTCATGGGGTGGGTC117GAATA
CAATCAGAAGGTGGTGAGTTATCGCCAT
AACATCTGTGCCGCTATTGTACCAGTGG
ACATAG'VrGCCAGGCAGGCGAT7ACTGT AG(-CTTAGGTCATiiccTGAAGCTCTCT
GGGGTCTGTTAGGTGAGACTGATGATAA
CTCTrCTCTTCCcYTrAGTGTACACAGCAC
CTITAGCACTATGAAAGCGAGGCAGTA
'TGATC
1406 M001024 1 pOOl 264 ID I
U
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID TIT
IT
NO: C {T {C "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 2} GTrCCGATGMTGTATCTCGTTrGAATTA TCCATCAG1TGATTAAGTTGATGGTCAT
CTAGGCTGATTCCCCTACATGGCCATCT
CAATATTGCTFC=~IAATAAGACCTGGA
CAA1TAACAGCACCAGTTGACATGCCAA CITGGA'rrGGGGGAGGGGTCTTAAAGGG CCCCGCCClTAGATGAAGAGCTATACGC
AATTAATGACTGTCAGAAAGGGAGAAT
GGCTICCCAGAGATGAACCCCCTAATG
407 IM00 1025 GATTACCCAGTACCAAGTGATC p001265 A RadS2
ATCAACCTATGGGGCCGT-AGACCCCT
GGTCTrGGGTGGGGTGGATATG7TAT'rC ITTTrGCTGTGGTGGCAGCAATI=GTT TGCMTTG1TT=GATACAGITCTC GTCATGTAflCCTGGT'TGCCTGGAATrC AC1TCTATAGACCAGAATGGCCTCAAT
TACAGTGAACCGCCTGCCTCTGGCTC
AGATTACTGGAArrACAcGM~GTGCTA
FCTCACTAGTTGGTGTGTGATC
408 1M001026 pOO12 66
C
GATCAAGTCCCCAGTTAAATGCyrTTr-TT GATAGGTTGCC1TGGTGATGTCTCTrCAT
AGTAATAGAAAAGCAACCTAAGACAAG
AGGAGAGAGTOGGGIMAAGAACGAGGA
GAGAGAGGAACTCAGAGGGTCCTGGAG
GTCCCGGGAA
409 IEMO01027 p001267 C
CTCACACATACATTCATACATACACACA
CATATATACATACACACACTrGCATACA
CACAGCACACACTCACACACAGAGACA
CACAGACACACAGACACACACACAGAG
GAACCCAAAGGATTGGAAGAATAAT'17JC CCGTGCTCAGCGGGAAAGTrACCAGAA 410 IIMO01028 AGACAAGTGGTCATGTGGGATGATC pOOl 270
C
GATCATCACCAGTGTAGTGTTGGCT-IA
ACGGTGCACGCCTITAATCCTAGCACT-r
GGGAGGTGGAAACAGGTAGGTGTGCTT
ACT7CAGTGAGTGAAT-rCCAGGCCAGGC
AGGGATACAGAGTGAGAACCTGTTATCT
AAATAAATAAATAAA
1411 IIM001029 p001271 -C SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE {D TC {TC {TC
NO:
"CLONE "CLAS "GENE" 2) S1FJCA\L 2)
TION
MUTATION \L 2) CACCCACGGCTTGCTrCITTFCTCTATGT
GTAATTGAAGCACATACCCGGTGGGAGC
CATGTAAAGCCTGTGTCCATGATC
412 1M001030 p001272 D GATCATGTGTrAATGAAACTGTCAGGGG
TGGGTAAGATGGCTCAGTAGGTAAAGG
CAC'rrGCCT~CTAGCCGGAGACCTGAG GTrCCTCCTGGGGCCCACAGGGAAAAGG
AGATAACCAGCTCTCTGTCCTCTGACCT
CCTGGGCCCCTCCCTCACAAACAAACAA
ACAAACACACACACAAACGACCAGACC
Al1TCCCACAGTAGCTGTGGTGCGTTAC AC'FGTAACGGGCACCATGTGAGGGYlTG
GGC'IT'ATCACATCTCCGCTAGTCATACT
TGGTGT-ITCCTGCGTCT'rGCTTACAGTTG
T-I'CTAATGGGTGGGCGGTGATATCGAAT
TGTGGYT=AGCATGTATITrCCTGTGCTC 413 1M001031 TGCTAAGACCACTrACAArACAG pO001274 R CCTrAACGCTCCCTrGATGTCCACTCCCG TTrTCTGCAGCGAT'rTA'FrGCTTAGTC
TATCTATAAGGTGTATGCAAGCTGCAAA
GTCAAGTATrCC1TTGTACTrGAGCAA GTc'ICCTIAAGTA'IrIATOCI-rCATAACGT-r GTGATATGCTrGAGcAAAT-rrGAGI'C'IA TrCATAA1TAAGCCACTGT7CTGATAA 414 1MOO1032 AAGACCCTAGAGTGCTATATCTGATC p001277 D
AAA-AGAGTGTCAGATGTCAGAACTGACT
AGCTGGGCTGACACTGAGGAATGAAGG
TTGGGGATATATGCACCTCCTGAAAACA
415 IM001033 GGAAGCCTM~GTTGGTFGATC p 0 0 l 2 79 D GATCAACC'ITAGTACACAGCAGAGTGTTr TTCTGGGAAGCTCATGGAGACCCAC1TI' TGTCATCCCATAGAGGTrACTACAAATC TGAGCATGAGAATAACTACT7GCTG=r~
AATACAAAGAACCATTAGCAGTCAATGC
CCCAAGT7CTAAGGGCACAGACTTCATA
CGAGAAAAAAAAACAAAGCAAAACAAA
AACTATCACATGCTACTATCTGTACTGG
GGAATGCATACAA=GrTTAGGTAT 1416 1M001034 I p001281 ID SEQ SEQUENCE{tc "SEQUENCE") CLONE CLASS GENE ID {TC {TC (TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA TL 2)
'RON"
MUTATION \L 2)
GATGAGTAGAGAGCAGAGGGGTCTATG
AGGGAGGTAGAGCAGCCTGGGAGGCCT
GAGGAAGGAGGGACAAGGGCAGAGTCT
TGGTCACTGTrGGTCTAATTGCCTrCAG AAGGCTTGCAGACTCTGG'T17GGAGTTC
CAGGTGGGTGGCTG
417 1EM001035 p001282 C
CAAGTAGGGTGTGTGTGTGTGTGTGT
GTGTAGCCAGTGTC1ICTCAATCACTCT CCACCTrAATATITTrTGAGACAGAA TCTCTCACTGAACCTGTATGCTGTCAA'rr
GTCATGGCTGACTGGCCAAGGAGCCCG
AAGAAT-rTATCTCTATGCTCAATCCAAC 418 EN4001036 CCCCAGATC pOOl 285 R
GATCACATGGACCGATTGCCGCGGGACA
TCGCACAGGAGCGTATGCACCACGATAT
CGTGCGGC1TIGOATGAGTACAACCTG
GTGCGCAGCCCACAGCTGCATGGCACTG
CCCTGGGTGGCACACCCACTCTGTCTCC
CACACTCTGCTCGCCCAATGGCTACCTG
GGCAATCTCAAGTCCGCCACACAGGGCA
AGAAGGCCCGCAAGCCCAGCACCAAAG
GGCTGGTGTGGTAGCAAGGAAGCTAA
GGACCTCAAGGCACGGAGGAAGAAGTC
CCAGGATGGCAAGGGCTGCCTGT1TGGAC
AGCTCGAGCATGCTGTCGCCTGTGGACT
CCCTCGAGTCACCCCATGGCTACTTGTC
AGATGTGGCCTCGCCACCCCTCCTCCCC
TCCCCATrCCAGCAGTCTrCCATCCATGC
CTCTCAGCCACCTGCCTGGTATGCCTGA
CACTCACCTGGGCATCAGCCACTrGAAT
GTGGCAGCCAAGCCTGAGATGGCAGCA
CTGGCTGGAGGTAGCCGGTrGGCCTG
AGCCACCCCCGCCACGCCTCTCCCACCT
GCCTGTAGCCTCCAGTGCCAGCACAGTG
CTGAGTACCAATGC
419 PM001037 pOOl 28 9 K Notch] SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE pIC {TC {TC "CLONE "CLAS "GENE" 21 SIFICA \L 21
TION"
\L 21
GATCTAACTCAGGCTGTTCAGCTTGGCC
AACAAGCTCAAATATCCATrCCGCTGTC
ACATCGGGCCCCATGTGATGCTTFATAT
ACTAAATAGAACAAGCAAArrGATACTA GATGGGACAGTCTGCTIACCCAGM1'GG
TGTITGGTGGGGGAGGTGAGACATATCC
CACAGTCCCAGAGCAACTGTCACTGCAG
GGTICCCAGGGGAGGAGCCAGGTGTGAA
GCTGGCAGTGTGTGAGGTACCCTGGGGA
AAkATGAAI'GGTrTACT p001292 D
AGGCCTGGTAGTGACCAGCAAGTACTGA
ACGCTCGCTCTATGCCAGACACAGACCC
TCTRFCCTCGTC17ATCCTA1TATCC ATACTGAACAGACAAGGAAkATGAAGGC
TTAGATGAGTCACCCGAC'ITGCTGAGAT
c p001293 D
AGTGGGGCCTGAAAATCACATCTGGGCA
AACCCTGAGGCCTGCCAAGTCCTCATCA
GAGGGATGCCCTCTTCATCCCAGGTGCT
117CTGACTATAAAATAAGGTGAAITAC[A CCTCCCCTGAGG~rACACCTFCCAGiGG'F[I AAGCTGGIfTAGAGAACCCAGGGACACA
CTGGGAAACAGCCCACAACAGCAGGAG
CTGGAGCACTCACCCAGGGATGTCCATG
GGGTCCAGCTCCCTGCGCTGGCGCCCAC
GACTGGTrACCAGGAAGCAGTGAAGAGG
TGGCCCAACCCACTGTAGAGCGCTTGAT
TGGGTGCTTGCGCAGCTC1TCCTCOTGG
CCATAGTACGGGAAGATC
EM00 1040 pOO1 2 97 tMoichi AGTGGAACCAGATlCCTCCTACGCMTG CACTGCACTTFCGTITCTCTrCTGTACC ATrFCTAATGGAGGCCAGAGTAGCAACTG TATAGACAAATCAAATCG7FITACTCTTC CAGIC'TTGCGGCTAACAGfCII-CCIF GTTCfCCTC'TAGCCTCAYI'rCC1ITF 423 IM00 1041 CTCAGATC p01298 B A1604147
U
SEQ SEQUENCE~tc "SEQUJENCE") CLONE CLASS GENE ED ITC (TC {TC
NO:
"CLONE "CLAS "GENE" 2) SIFICA\L 2)
TION"
MUTATION \L2}
GATC'ITCTGCTITCATCTGAGTAGGCTTA
GACTGGTTGTATTATTATATTA'rrACT TGTTGTTGTTGTTA1TIGGTGGGAGTAG
TAGTAGCAGTAGGTGTGTGTGTGTGTOT
GTGTGTGTGTGTGTGTGTAGATGTCACA
GCATGTATATGGAGGCCAGAGAACAGC
TCTAGCGGTrGC'FrCTCTCCTTCC1TCC
ACTGTGGTCCAGGGAATAGAACTCAGGT
CATCAGGCTGGGCAGCTGTCACCI7AA
TGCTCTGAGTTATCTCACCAACGTTAAT
AAAAGGCTrCAAACAGCAG-TrTGGGC TGGGCCTGGTrGTGCAGACCTGGAATTG
CAGMMC~AGGATGCTAGGCAGGAGG
ACTGGAAGCTCAAGTTGTGTCGGGGAAA
CTTAGTAAGTCCCTATTCTCGTCCCGCAC
GCGCCCAAAAAGCCAAGACCAAGACCA
AGCAG17GGTACAGCAGAAAAAGCAC GAGAGTCTCCTCCTCCTCCTGCTCCTGTrF
TAATGATGCAGAACCC
424 1M001042 p001300 R GATCTGTGCATrA'JTCTGTTGGAAATGT GACAAGATrCTGTTGAGAATCTCATACT CTATGAACTCTTAAAAAAAAAAGGTrTC TGCTGTrnTGAGACAAAATACTrATAL AGG1TATGATGTAGrrAAGGCCCTGAA TGTCCCCCAAAGACATGTGTGT7GAGGG
TGGTCTCCACTCCGTGGTCTITGGGA
GGTGTI=ATGTrAGCTGGTGAGGCATA
GTGGCAGGGGAGGAGAGTTGGGTCATA
GTCCTM~GAAGAGGCTAT-FCAGGC-1CT 425 EM00 1043 GGTGCCTAA p001303 D
GATCTGACTGTGATAGGAGGGTCCTGGG
GCCACCCTGACATAGGCCTGGTCTATGA
ATGCTCTCATGGACTGGGCCGT17GTC 426 U%4001044 A p001305 D SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID ITC {TC ITC
NO:
"CLONE "CLAS "GENE" 21 SIFICA \L 2}
TION"
MUTATION \L 2)
CTGCCTCTCTCCCTGGTCCCTCCTGAGG
TTCTGGACCCTCAAAAGGCCC'I=CCCA
CCCCAGCCrrCAGGCCTG'rAACCCAGCC TCGGTTTCICTrCCCAITGCCAAAGCACA ATGGCTGTTATAATTAACGGArrATCTC
AGCGCGACAGCTGCGCCCCTGAAAAT
427 1M001045 TAG&I17GAATAACAAGATC p001306 C
GATCTTGGACCACCACGTCAAGCCTCT'T
GTACATTTCMGAAAAACAAAGCTTGG
'TTCCCCCTAGTCACCACGGTGAAAAAAA
428 1M001046 CCCAGGACAGTAAAGGTCCCAA pOOl 3
O
7
D
7AGTACCTCTGGTGGAATCACCATGCC TGACCTAAAGCT17ACTACAGAGCAATT
GTGATAAAAACTGGATGGTACTGGTATA
GTGACAGACAAGTAGACCAATGGA.ATA
GAA'rFGAAGACCCAGAAATGAACCCAC
ATACCTATGGTCATCGATC
429 1M001047 p001308 R
GATCGCACCGATTGCCAGTATAGTACCT
AGAGTGTCAAGTTGGCCTCTCAGGGAAG
AGAGAACATGTA1T'AGGGTAAGACGCA 430 IM4001048 AGCCCCAGTAAAAACATGTGAG p0013 ii D GATCGC'ITCACCAAGTGTGAACTGTrGG
TAGGGACAGAGCAGACCACAAGCCCCT
cT-rrGCATACATGGGGGCGTCCTAGT
GTAGGTGGCTAGGGATGGTGGACAGGA
GAGGAGGGAAGACAGTATCACATA.AGA
ACAATAGTrGGAGGGCAGGGGAGGAAGC CMrCTCATGGCTGGGGTGAAGTCACTTC
CGTAGCCAGAGCTGACTGAGAATATCAC
TGCTICCTAGTAAGGAAACACCGGAAG
TCGGAAGATGATAAACGCGAAACTCACT
ACATCATAGACACCA'ITCTGTC~rCATC AACAGAGAAA1TrATAA 431 PM001049 p001313 D GATCGGTCCAc'ITcTGTGTFGCTAGGCCC
CGGCATAGTCTCACAGGAGAGAGCTATA
TCTGGGTCCTTTCAGCAAAATGTTGCTA
432 1M001050 iOTGTATGCAATGGTG pOOl 3 l 6
IR
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ED {TC ITC {TC
NO:
"CLONE "CLAS "GENE" 2} SIFICA \L 2}
TION"
MUTATION TL2) AGGGTACAGCGAAGC1TGAAAAAAGCA
AGGAGTGCTCTGGGACCGGGAGTGATG
GAGAAAGTCTGAAGCCCCMIGCACACC
CCTACAATGGGMTGCGCCAAGAGAGGC
GCCGGCAACTCTACGCGGCGTGGGOCTC
TCCCCAGCGCTCTAGGTrCTACTGTGCT GAGCCACACTAGnCTCTCCCTAGACC
TGAAGAGACCCCAGAAGTCTGAGAGTC
CCMrGG'FrCTCCATCTCTCACCACCCCC CACTCTCGTGCTlTAACTCTGAGGAGGG
CCACTCAAGTITCATTCATAAGAACAAGG
GC1T7GCTCTTrAAAGGAGCCGCATACCG
AAAGCGTFGTGTGACTGAGGGTTCACA
TGCACAGAGCTCCGCGTGTCTCGACATC
CTCTCTCTCCGATC
433 IM001051 p001317 D
ATCTCAGGAAACTCCTAGCAGCTITAGT
434 ACc3CATCGTGCTG'=CCAGCTGTCGGT WOO01052 A1TIACACAGGTITGAGCGATC p001318 D CCTrCAGGATrrAC1TGGATGA17CATrA GAGAATCTTGTC1TITAGACTATAAAGCA CTTGTrGAAGAAGGTTACAATGTAGCAA GCAACCTrGTI=GGAATGTAT1TGGTA CA1TGTGCTCTrCCCTGGTCTGGTGCMT CATTrCACATATIrGCTCTrAATAGAAG TAGGGTrCAGTGCTGGGGA'TT7CATrG CTGTTrCTCCA~rGACCTC1TrGAGCTGA AGTTATTrC1TATrAGAAAGTCAGGGTAG 435 IMOOI053 GCGATC p001319 D
CCAGCAGGCAGCGAGACGCAFI=CGCG
TGGCGGTGGTGAGCTCTGTrCGAGGG GATGAGCCCC17GCAACGGCACCGG'rrG
GTCCACGAGGCACTGTCGGAGGAGCTG
GCTGGACCGGTACATGCCCTGGCCATCC
AGGCGAAGACCCCCGCCCAGTGGAGAG
AAAACCCACAGTJ7GGACATFAGTCCCCC
CTGCCTAGGTGGGAGCAAGAAAACTCG
AGGGACCTG'TrAATAAATACCTGGATTG Mm. 1045 436 ]14001054 GGAGAACGATC p001321 B 31 GTI I CCTGCATAGACCTCATCTGCGGTjo 437 'Irvloolos CGATC 01322 lK SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID ITC {TC {TFC
NO:
"CLONE "CLAS "GENE" 21 SIFICA \L 2)
TION"
MUTATION \L 2)
AAACTAGGAAAGGGTATAGCA'IMGAA
ATGTAAATAAAGAAAATATCTAA'TT'AA
AAACAAAAAAGAAAGACAAAGGAAAAT
TAAAAAAAAAAAAAAAAGAAACAAAAG
CCACTGCAGGACTGCCCAACAGTCTACT
GAAAACTGTGAGCCflA7IFCCTAGATGA
GCCTCTGATGCCTCCACTTACAAGCTAC
CYTCACTCCTCCATCTATCTCCT=[G11'
ATGTCCCGCGATC
438 IEM001056 p001324 R
GATCGGACTCGAAGAGCAGAAGAAACA
AAACTCAAAGCAGGGA'ITlAGGTCAAAA TTAAAAAGGGThrGCACACAAAAGGAA
ACCATCCGAAGAGACAACCTACAAAGT
439 IM001057 GAGAGAAACTTG~hrGAAC p,001325 D GTCTGAGAAATTGTCTFrAATGTAGTGA
CTGTGGAGCCTTGCAGGGAI'ACCCACGA
TGGGGGTGTCATTCATATGTCACTGCAC
440 1IMOO1058 CTGGAAGACCGATC p001326 ID GATCGCACAGCCTGCYI17CTCAACAGTA
GGTAGGACCAACAGCCTAGGTGGCACC
ACCCACAGTGAGCTGGGCCTTCCACATC
AATCATCAATCAAGAAAAATAGCACAA
AACCCTrTCCCGAAGGCCAATCTGCTGG AGGCA'IMICTCAG'I1GAGATFrCCCTCTT
CCCAAATGACTGCATAAAACTFGTGTCA
441 TGTTGACATGAAACTAGCCAGCACAGGG 1MO01059 TGT p001327 K lPvtI GATCGGGTAATTTAGTAATAGTrCATGA TATrCATTACTCGGCGTAAATCAGGAAA AACAnTrCTAGATGAATGTGGTATCTC 442 AGTGCACAGM'IT(YTFAGTfAGAAAAC 1IMOO1060 AAAT p001328 D F GATCGAGGAGGGGAAGTCCIT7CCTTCCT 443 IM00 1061 TCGT-rCCTrCCT-rC 00O1329 R SEQ SEQUENCE~tc "SEQUENCE"} CLONE CLASS GENE NO:* {TC fTC {TC "CLONE "CLAS "GENE" 2) SIFICA \L 2}
TION"
MUTATION \L 2) GATCGGGGGTrCAAGGTCCTCCTCGGGG
TACCTATTAGGAGGGCAGCCCAGGCTAC
GTGAGACrCTGTGTCAATAAAAATAAAA
ATAAAAAGCTGGGTGGTGGTGGCGCAC
444 11M001062 GC p001330 R
GATCGACCTGCCTCTGTCTTAAGCAAGA
AGGGAGATAGATATGCATAGTA'IMAGT
GTAATGAAAGTTACGTTGTAT-rACGCTG 445 EM001063 AGGT17ATCACA p00133 1 D
ATCTAAGTAGTATAATGTAAGACGAT
446 IM001064 C 00O1332 D GATCGTCGTCTAACTrAGCTGGC'TrTAT
AGTGATATAACAAAATATTAGAGGATGC
=GGTrGAAAAAGAAG=hATTrGCAT 447 IM001065 CACAGTTC Ip001333 D GATCGAACACGCTCGGACTrGCTAAACG 448 IM001066 TTCC p001334 K iNyc GATCGTdATCA1T1TATAACAGTAGTG
AGGAGATGTCCCCTGGGGCCGCCCTGGC
TCTGGAGAGGGAAGCCACATGCTCCAA
GGGGCTATGGTGAGGACCACAGCCMTA
449 Irm00 1067 CAMTfGCTT p001338 ID
GATCATGCACTGTCTGGGATAGTGATGG
GCTGTGTCCTITGTTGGCCAAGAGGAAG
TGGCAAAAGGCAAAG77GCTGTFGGCTC
CAGGAGTCAGTCTGGGGACGGGGCTGA
GATGCTGTGGGACAGACTCTGGAAAGG
GCAG
1450 I1M001068 pO10l 339 ID V- SEQ SEQUENCE~tc "SEQUJENCE") CLONE CLASS GENE ID T T IT NO: C {T {C "CLONE "CLAS "GENE" 2) SIFICA \L 2)
TION"
MUTATION \L 21 GATCGTGGCCACTGAGAGACC1TTCT
GGCCACCAGATGCACACAGCTGCATGA
ACATCTGCATACACAMrAACACATACA AAGTTGAAGAGAAGCACGTGTGTC7FrGT
GGTCTGACCACTTCCTGGGCACCACCAA
GCTGCTCTGACAACGGATTCCCACTGGG
TTCGGCCATCTTGCTTCCTCCCCTCAGAG
'IfnGCCCATGTCCTCTGTCTI=CATAGC
CACAGCCTTGCCCAAGATAAGATACATC
451 1M001069 CAACTGTACAGTGCTCCAIl p001341 D
GATCGTACCAGGAGCTCCAAGCGTACCC
CTGATGCTACAACCTCAlITCCTGAGCCT
TGATTCTGTGGACTCTAG
452 P1001070 p001342 IC
GAACAAGGAAGGAAATAAAGAATAAAG
GACATCTGACACTACCAAAGTI'AGGTCA
GGATGTGTCTTACAGATGGCCACTCAAC
AGCCTATAGAAAGCACCGCACAGACCA
GCACGGTCT1TICTCCCAGGTGTCTCTG AGGTACTGC1Tr=rCCAGGGATC 453 IIM001071 p001344 D
GATCCCGAGTCCT=CATGGTGTGGTTCT
ATTGTG'CCCTAGGGC'1ITCAGCAGGCAGA
AGGAGAAAGACACTGTAGAGCAGCCCC
454 LM00 1072 CAAp001345 ID GATCCTGGGA3T=CTGGjGCAATrGGAG
GCCACAA'ITAGATAGMTCCGGAATCG
ATGTCCCT-rAAAGACCAGCGCCTGGACT CTACTGAGTAAACTCCCArITCAAG1TC CTCCTC1TCCTCTAIT-1I'GAACAACGTGTA TCATTAAATTATAAAATTGTGI'rG'frGT TGTrG7rGITrCAAAAATTrAACTAT'rG
GGGGAGGGGCAGTTGCCCGAGGACAAC
ITc3TGAGAACCAGGThITGCCTrCCACA 455 CTTAGGGGTCCCTGGAA'TGGAACTTATG 1M001073 T pOOl34 6
R
SEQ SEQUENCE~tc "SEQUENCE") CLONE CLASS GENE ID {TC ITC {TC
NO:
'CLONE "CLAS "GENE" \L 2) SIFICA \L 2)
TION"
MUTATION \L 2)
AGAGGAGAAATGGGGGTGCGAGAGGAC
AAAGTCTGTGCCCCACAGCGCTGGGGCC
AGAGCCCAGGAGGGCCTCATGGGAGAG
GTTGCCTGAAGGCAGTAAGAGAGGCAG
AGGATGCTI7GGGCCAGAGAGGTTCCCCA CAA~rGCTTGGATC 456 1M001074 p001348 D
GATCCCAAACAACTGGAACAGGGG'ITAT
457 B4001075 CCCAAAAGCTGTrGCCTG p,001349 D
GATCCAACTCCTCTTCACAAAGAGACTA
TGTGCAGGATGGAGAAGAAGATGTATC
CAAGCATATCCTGTGAAA1TrATGTCAA TGCTGTGAAA1TrGTCCCAGCACTCACA ATCCAGATTTCTGCTrTMAGGTGGCTITr TrCTAT-TCAT-rCTGGCTTGATAGA AG1TFGAGGTGACAT1T=AAGACCTGT Min.1238 458 1M001076 GCCACTAAAAT1TCAGACCCTATTTG p001350 B 02
GATCGGTTAGFJTGACCAGCCATACTAT
AACTrAGTGCAACCCTTTACTTrGGTGG GTGGTACTAGGAATrAAACCCAGGACCT TCACATATACTAGTATCATrGAGTFFACA TCTAGCCC1TIAACCAATrCCC'TTT AACCCTITIATCC1TG 459 [MOO 1077 p001351 D V- CTCAAGAT-TCTGrrGTCTGAGAATCTCTC
CCTCTGCTTGGGGACCCAMTATAATGA
GGTGATACTTCATCTGAAGTAATGGCCA
GGCCACGGTGTGAGACTC1TGAATGTCA 1460 1MN001078 ICATGCTGGATC Ip001352 ID I- Breast TABLE 2 SEQUENCE {tc "SEQUENCE") SEQ ID SAGRESH CLASS. GENE CATGTGAGACTTG'I1AATTTAGATTT A'rrCTGTAGTGIT[GATATGAGTAT AAATAAGACAA1fTAAATITCTATA'ITA GAAAGTGGCTT'TACATrGAATATG
CITCAGGATATGCGTGAGAATTTGG
IM000127 CGATGTGTAATC 461 D
CCTTACTGCAGAGATGACTCGGCCAA
CGGCTNCGAGCTCCTGACCACTTCCT
CAGGTTTGG=ITFGTrAGTTICTC
ACAGCAATGGGAAGCATAATCAATA
CAACTTCCCAGAATGCGACCTGTGAC
AAGACCAATGAGCAGACTCAAGGCT
GGGCACATAAAAGCACCAAAAAAAA
AAAAAAATTCCC'1TGCAAT'n'ATrGTT 1M000 128 CATO 462 D
GCTGCTCATCACCAAAGGAAGTCAGG
ACTGGAACTCAAGCAGGTCAGGAAG
IMOOO 129 CAGGAG'I17cATGCAGAGGCCATG 463 R CATGGCAAGATGGAGACTTrGTCTAC FgI3/Fgf IM000130 CAGGGCCACTCCAAGCACCCAGCTG 464 K 4 GTGAAAGGGCAGAAATAAUfCCTGA IMOOO 131 AGGTTGTCCTCTGCCTTCT'ACATG 465 C
CATGACTATG'ITTCTFJTTAGGTATATC
TGAATAGTATGGATCTAAATGATGAA
GTITACACCATTCTACAAATGGGCA
CAGAACACAGGGCATAGATACAAAT
GGCAAGGTGAACCCAGATCTCTGTGC
ITATCTGCAATATAACAACACTAAGA
AATA'ITAGGTCTCTCTGTGGIITCCT
IM000132 TAAATrCTA 466 D
GTA'ITTCCTGTCAGAGGAAAAGAGTT
1TCAAAAAAC1T1AAAATFITfTAT-IT
GTAGCCTGGACCAGFITCATAGCAA
CCTGTCATCCATATCCTCAGATTCACT
TATGAGFITGTCTGCCCATTAAGATC
TIFTAAAATGGTTCTAACAGCTTACTT
CAT7GTTrCAITAGTAAAGGG'ITTATA TCTACACTfTGATA MTIGCTFACTCCA IM000133 TACATG 467 D LMOOl 34
CATGAGATGAAAAAGAAGCCFTIGGA
CTTGAA11TTGCUGCAAATGCGTA
CTGCAGTTGATGGAAATI'
AGGGTCCCTrCAACTTCCTCAGAGCC
AAGGCTGACT[TACTACCG'ITCCCCAA
IM000135 GATCTCATG 469 D
CATGCCTCTGOAAAGTACCTTAAACA
IM000 136 TAGAATCCGCTCGTAGTG 470 K Myb CCAGATCCCATT'AACAGATGGTrGTG IM000137 AGTCACCATG 471 K WntJ CATGACTrCTTTCAMTUCTGTGTG TCTGTCTTCCTGTG'TFrGCCTGCCCCT CTC1TTCTCTTCTAACAGCCCCCT"TGA
ACCAAGTGATGCGCTGTC'ITCGGAAA
TACCAATCCCGGACTCCCAGCCCCCT
IM000 138 CCTCCATFTCTGTCCCCAGT 472 K Braf
CATGGGAATGTAATGTA'TAATGAAT
AT-rATATAAAAGAGGCTAAATAGC1T
GGCT'ITAAMTCTCACTTGCCTACTC
AATTGAGAAGT'TTATGGATCACCAAA
IM000139 AGT 473 D CATGTCCTTA FTCTAGGAAGCCCCCT 7TITUACCCCTGCCTCTGAGAGAAAC IM000140 AG 474 D
CATGAAGACCCAAATCCATATGAATA
CACACATAAAATATM~ATITCTCTA
IM000141 TAA=TATGCCCACC 475 D GAAAGCATFrGAAATATACTGGCCTFrA IM000 142 TTAATGGCACATG 476 D
CATGTGCACACACCCCACAAATGACC
TCAGATGTCAGTGGTACTGAAACTGA
GAAACTGATGATAGAGCCAGTAAAA
ATAGTGAAAGTGCCTGTITTGAGAGT
TTATA1T'ACAATAC1TrAATATCTA
ACTACACACACATACACCTGAAAAG
GGCTCAGAATACACAGGCCTGAGAT
EM000143 GGCTCTCAAGAACCAGCCTC 477 D
GGCCTTCCACTGGTCAAAGCTGAGAC
TGCAGAAAAGGTTGATAGCCTCCCAG
GGGCAATGACACCCTTTCTGCTTGAG
CTrCCCCCCGCCCCCCTCTCAGGATGT IM000 144 AGTCATG 478 K Wntl
CATGCCAGTCCACATCTGCTTCTATG
ACAAATGCCACATCCCAACGACAAA
CTCACTCATTCTTCCTGTATCAATTrA
CGCATACACATAATAC=ITGCTCAA
GGTACATrCATATTrCCGGCAAACAG IM000 145 ACAGCTATAG 479 D
CATGTCACTCACTUGGAGAAAGAGTT
CTAATrATTTATCACGGCATFIrCAC AACTATAGAAATAAAGTTAATTTC1T Mm.605 52 TN4000146 TGGAAATAAAGTT7GAAGTrTGTAAMF
CCAGATGGGCTCAGGTTGCTGTT
CTCCTCCITAAAAGAAAAAAGGAAA
GAAAAG2FIAAACCTGCAACAGCATC
AGCAGAGCTCACCCCTCCTCACCTGC
AGCCCTGGTTGCCT'CTCTTCC'ITTCAT
IM000147 G 481 D GAAAACACTFGTITCTGGGIfTCAGGGGT TACTTAGCCfl'GGAATCAGAGTCTAC CCAGAGTCTrACCTGCTTCTACCCAA-A
GCAGGTGGAAGAAGCTGCCCAGGAC
GGGGCTCAGAGTCTACATTFGAACTC
CCTGTGCCAAGAAGTCTGGATAGAGT
ATAGTGTCTGTATATTCTAAACTTITCT
GGAACAACCCCTGCFI'ACAATACTCT
IMOOO 148 TTCCAACTCTGAGGCCATG 482 D ACCTCTGTGCCAGCTTCTCGGACATT Fgl3/Fg/ 1M000149 TAACAACTCTGGATCATG 483 K 4
CTGGCAGTAACACACTTAAACTGCTA
GCACCTrGGGAAGTGGAAATAAGATC
AGGAGCTCAA'ICAAGGTCAI'CCTCAG
CTAAACAAGACCCCCCCCAAAAAAA
AAGAAGAAGATGGCCTAGAAAGAGA
ACTCAGCAGCTGCTGATCTPACAGAT
GACTAGAGTTTGGFITACCAGCACCCA
IM000150 CATG 484 D
CATGCCTGGTCCCTGCTGAGTGCAGA
AGAGGGTGTCAGATTCCTTGGAACTG
GAGTTATATACAGTCGTGTGTCACTG
TGGGTGCTFGGGAACTGAACCTGTGTC
CTCTGCAAAAACAAGAGGTCTTGGIT
GTTGTTGTTTTGTTTGAAACAGGGTTI'
IMOOO 151 CTCTATrGTGGCCCTG 485 C
GCAGGAGCCCTTGTGCAGGCCACAAC
CTGCACAGCTGTACAAGGCCTGCCTG
ACTGCCTGAACAGATGTGTGGGATCT
TGCCCCCCTTGTGCAGGCGTACAGAT Fgl3/Fgf IMOOO 152 GCAGACTGCTCAGAGACACACATG 486 K 4
CATGGGCTAGACCTACACTGAGFTGT
IMOOO 153 GCTAAAGAAGTGAC 487 D
CATGTCCTCCACAGCTGAGCACCCTC
AACTGTCTCCCAGGGCCTCTGTFTCTA
TCCAGGGTCTGCAGGGTCTCTGCCCC
ACGCCTAGCCCCTGAGAAATCTTAAG
CAGTCTGAAAACTACGCCACTGAACT
GCTAAAACCCTGGAGTCACTGATGGA FgJ3/Fgf 1M000 154 A 488 K 4 IM000155 TAG'I'GCTAGACTCTGCC'1ITCACCITG
GCATAGATTCACCTTCCAGATAT
U
CCAGGGCACTTGCAAAGAAGCCAGG
CATCATCAGGGGTITrGGACTrCCAGC CAGAGTCTGAG1TGTCACTTGAATGT
GCTGCATTTGTTGGATTCAGCCCCA
GTCTCCCGACTCTITTGTGAG MTAGG
ATAATAATCACAACAGCACCCCTTCT
TATTTGATGGCTAATAAGCTCTAGGC
CAGTGTCTTIAGCTCCATTCATG
CATGTA'1TCTGAGAGTAGAATITATA
CCCAGAGAATACCTAAGAAGTGAAC
TGACGCCGGGCGTGGTGGCGCACGCC
M[AATCCCAGCAGTTGGGAGGCAGA
GGCAGGTGAATTITCTGAGThrGAGGC
CAGCCTGGTCTACAAAGTGAGTTCCA
IM000156 GGACAGCCAGG 490 D
GCCTGGTGTGGTAGCTCACACCTTTA
ATCCCAGCACTCATCTCTGTGATTTG
CTAGGCCAGCCTGGTATACACAGTGA FgJ3/Fgf IM000157 GTFACAGATCAGCCATG 491 K 4
CGACATCCAACTTCTGGAAGGAGAG
ATGGGAAGGGGCATTTGGGGTGCTA
GGAAGGGATGGGAGGTGTCCCTAGA
IM000 158 GCAGTGCTCATG 492 K Wnt3
CATGAAATAATGCCTITCAGAACTGCA
TTAGAAATCACAAATAGCCCTGAATG
CCCTCTAGATGCTTCTTGAGAACA
ATTATGTGTTAAAGTCCTAAGGCCCT
TGTCAGCCGACCATATGGAAAGGGA
IM000159 GAACTAAGTGAAATGGGAGTF 493 D
ACTGACAAGAATAGAGAGAAGTTCA
IM000 160 GTCATG 494 D
GTGTCCTGCTCCTGTCTGGGTCAAGG
TCATAAAAGATGAGCCAAGGCTGACT
TCAGTGCCCACCTGGGGAGACTGATG
TC7ITCACAGGAATGCTCACCTGGAAG
GTGTCCTCTGGGTGCATCTGTGTCAC
ATTrCGGTATAGAAGGAAGAATGCCA ACAATACTCTAAAAATATfAGAGGCC FfGAGAGTCCTCAGTGGTAT'TCCACC
AACATCAAAGCTGCATCGTAATATGC
CAGCCTGGTCCTCACCTTTCCTGCGCT
TCCCAGGAAAACATCAGCCTTTAACC
IM000161 TCAGCCCATAGGGGAGATG 495 D
AGGATCTITATAAAAATAACAGTGACC
CAAAACATAATTIIGCCATCAAGAA
TCTCAAAATCAAGTCTCATCGAAGTC
TACTCTTCTI'ATFGTATCTrAAACAC
ACACACACGCACACATCACACAAGC
ACACACACAAGAATTCACACACATAC
1M00062 49 Wnt IM000162 496 Wntl CATGGTA7TCTGATGA'TAGTACCAAC
ATACTGCTGCAGCTAGCTGTATCTGG
AAATCCCAACCTCAGCCAAGTATI[G
TGGITTGAAATAACCTATACTTCTCAC
IM000 163 ATCAAACAC 497 D ACTGTGACCTGAGCACTFCThTGTCFI'
ATCAATAGCTCACGTGCCCAGGCCGG
GTGACCAGTCTCTAGGATGYFCTCCA Fgl3/Fgf 1M00I14 TG 498 K 4
CATGCACACAAACTGGCCCTGAACTT
TrGACTFCCAGGCCICTGCCTfCTCTGC
GCGCACACACACACTCGCACTCCTGT
ATATGAAGCGTATATGTGYITCTGTG
GGAACTGTITTTATCAGGTGAAGCAC
TITCCTTTGTITCTYIGCTACCCACCTCCA
GGGCTCCAGGATCTCCAGACAGCCAA
GCCTAAGACAGGCCCAGCTTCCTCTG
TATCTCTGTGATGAGAACCTJ'GGCAT
AGAGCTGCCCTCACCCTCGGGATAGG
GCTYITTCCCCGGAACGAGCCAGG
CACCTCAACAGCTCCTGGGGAGGAAT Fg/3/Fg/ IM000 165 AGGGGACT 499 K 4
CATGGCACTATGAAGGAAATGAAGA
TACAAAAGArI-FCCCATACAAAGGGT IM000166 CAACTGTITCAATTJ'GGCAIIFTAYI 500 D
CATGATAGAAGACCACGTCI'GGGATG
GGGTAAGGGTTTCTCAGAGTACCTTG
CCCTGGGGCCACATCCTAAATCTACA
IM000 167 ACAAAGCT 501 D
CATGCAAAAGAATTCCAAATGAITI
ACAGATCTTAGCCCTCTAAGAGATAG
ATATAGCACAAGTCCTGACTCCTGAG
GTAGGTACACACTGACTTCCT'TCCAC
AAGCAcTrGCCTCAGCCCGGAGATGA
AGGTCACATCAATAGAGACAAGTCA
GGTTAACCGTGAGCAACCTCAAGACA
AGGAGGAGCACAGCATAGGTCGGTG
GAAGTGTITGCATAAGCCTAAGGCCT
GGGCCCAGTCACCAGCA'GCAGAG
GAAAAGGAAAAACAGATAGTAGGTG
IM000168 CCTTGGTGTGT 502 C CATGCAGTITACCAATCTF['rCCACT CTrrAAAAAGACAAAAAATATTAGA
ATACTGGGCTGAGGAATGGCTCATCA
G'1TAAGAGCGCTGCTCTTTTGAAGGA CTCCCGTrCTIGIf[CCAAATGCCCACCT IM000169 GGAGGCTATCCTGTAGcTrAGAGGT 503 D AGGAAGTGCTGAATFAGAGAGGTnTG
GGGAGAGCCCAACAATCTGACCTATT
TATACCCTGCCAGGCCCTGCCCATG IM000170 Sl OOa4
CATGGTGCTGGAGGATCATCCATCCT
IM000 171 GACATTCTGGGA 505 R C2ITTAACCCA1TITATGGTGTGACCAG AAACCACAGATCTFTACCTAGGC1TCA
GAGACATGACCCGAGGAAAGCTCCAT
IM000 172 TAAAATCCTCATCATG 506 D
CATGTAYFCATAAGTGGATAITAGCA
IM000173 AGAAAGTACAGGCTAAT 507 D
CCTCTGGAAGTCAAGTGCAGCMTGC
TTATTTG1TTAAGCCATCCACCATCCA
GTTATTAGATCTGAATTCATCTTAG
GGTCAGCTTTGTTGTAGATTTAGGAT
GTGGCCCCAGGGCAAGGTACTCTGAG
AAACCCTrACCCCATCCCAGACGTGG IM000174 TCTTCTATCATG 508 D GII ITCM1C II1TI IIIIIrAAAAGAA
ACAGTCTCAAGTAGCCCAGGCAGTCG
CTAAACTTATTATATAGCCCAGGACA
GTCTITGAATTfCCTGAAGGTCCCTCCTC
TACCTCGTAGTCCTGAGACCGA'ITGC
IMOOO 175 ATG 509 D
AGAGACCCAGAAATACCAAGGTGAT
TTCCAACTGCCTGACCTGGGAGGCAA
IMOOOI 76 GCATG 510 D CATGTAAGATGTTCAC=1JCCAGTGT
CTG=FGTGCTGCCTTCAAACTGTTGA
CCTGATGTAAAAATGTTTGCATCAGC
TCAGGTGTATAGAATTGGACTGATITC
CAGGAGAGTCAAATATAGAGAATAT
IM000177 CTAGTGTCCAAGAT 511 D CATGCTAATGGAGTTTAT-rCTTrAGGA CTGCCTCCTGCATCCATITGATTGACTr IM000 178 AAATATGTGCACACT 512 D
ACTAGGTGACTGTCTCAGGGTCTCAC
TGTGTAGTCCTGGCCTAGAACTCTCT
ATGGAGACGAGGCAGAGCTCACACTC
AGATCCAGATGCCTCAGCCTCCTAAG
TGCTGGGATTrAAAGGCCAGTCCCAGC ATACCCTGCCCCTGTrCTGACArITG
AACCCCTCCTTTAGACAGTAGGGAAA
CTGAGGCCTGAGATATGAGAC=IJ
IM000179 AGGGGCATG 513 R-
AAACTTCAGAAAGCGGGGGGTACCA
AGGAGACTCAAT7IAAGATCTCTCCTC
GATCTTGAAACCATCCCCAGCCCTTC
GCAAAGCACAITTfGACGGACAGGGTT
CTCTTGTCTTGGGCAACACATCCCGG
CTACGCTCTGCAGGGTGAAGCTGTTA
AGAACGTTCCATG imoool 80 54514
GATAAGCCTCTACAAAGCTGGAGAG
GGCAGTCCAAAGAAAC'ITGAAAAGA
TFTAAAAGACAGTGCCTAAGGACACA
AACGTTICCATAAAGAGCCTATGA
CATFATITI'-ACTGCTGCTAATGAAACT
GACC'rrGAAGGAACAAGTGTTTAGGG
TTAGCCTAAAC'TFGGAAT'GGTGAA
GGCAATGTGTCAGCTAGACAAATTFAG
AGAAAGAACTCAACAGATGAGTCAA
TGAATT'TCTAAACTAGCTTGACYF
AGGATTITrCAGCACAGGAACAAAAG CACATACTGTCCCTCTGGTrTGGCATG IM000181
CATGGAAAATGATAAAAACCACAGT
CTAGAACATATrAGAGGAGTGAGFFA CCCTGAAGAACACAHrCGYIGGAAAC IMOQO 182 GGATATTGTGTAA 516 R CATGCCCGGCTCTArJ'ACTATTrC'T C'F1TCTIr=GTTTCAGGATCCAGIT
TCC'FIGATAAATITTCTI'GAATGTFG
T&L'TGT1TTC=IGCTGAITrT CTTCAATACTGCTGCTT1TTCTCTCCA IMOOG 183 GGFFCAGGA'IGAGA 517 D CATGCTGTCACTAAGcTrGTGCTCUTC CAAGGAGATGAAGAGACTAGcTrGGT
ACCCTTGCTATGCCAGGCTITTFCTT
IMOOO 184 GTTrATACACACCTAATG 518 D
CATGATCTAATCTGAAC'YI'GTATCCC
AACCCTTTATAAACAAGTGAATGrG'r
AATCTAAACTAGTATAAGCTCU'GAA
TAATAGCTGAGTGAATTGCCT1rTGAT IM000 185 ACACGTMFCCAAATTAGTAGCC 519 D
GTCAACCACAGCAGTACTGTITACTFI'
CTGTGGGGGAGACGTCTCCCCTCCTC
IM000186 ATG 520 D
GGCAGTGAGCTTGCCCACTCTGCTACAGGACC
TCGGTGACCCACTATATACAGCCCTCTTCACT
ACGGCTCACAATCGGAGT17AAGACCCAGTG
AAGTAAACCCAGCAGGACCCTTI'ACAAAGCG
IM000 187 AGGACATO 521 D
CIUGTCCAAACCAGCTTAGTCAACAG
CCTCCTATGTGGGCTCCATCTTACCCT
CCTCATCTAGCTGATGAATGTACCTG
CCTCTGTTCCCI-FCCTCCITGGTCTGA
GCTGAGCCFFCTTJGGGACTGAGAGCC
'1TCATCCACCACAGGCAGACTATCYT
TAGATCATCATAGCCCCAGGTC'ITCA
TTGCAGTGCAAAAGTGCAGACVFITAC
AM11CCATITTATGCTCCCTflTGTAA
CGGCTCCTTACCGGACTGCAGCATAA
GTGGCTGAGTATCCAATCACAATAGA
IM000188
ACACTTAGTITGTTTGC'TTGTCTAACTC
TCTCAGTTACACCATTGAGTATGTTA
CACAGGGCTGCTTrGTAGCTGTCACT
GAGGCGACAAGGCAAGGGGACTAAG
GCAGGACTCAGATGAGCCTGT1TIA CT1TCCCGTTGTCCC M CACTTTGGGT
TGAGCATG
ATATAGACTCAATCAAGGTATTATFC
TGGAACAAACAACTAGTAACAAAAA
TAGTGCAATTGCAAGTATGATAACAC
AAGGCAGCCTITACCAGGTL'TGTCGG
AAGGAAATTGTTCTTTGAAATCTGAA
TTCCAGAGAAAAAGTCAAATGTAAA
IMOOI 189 CTAGAAGTG17IGCATG 523 D
CATGTATGTGCGTGTGTGAGTGCATC
AACACAAGTGGATAGATGCGTGTGTG
T-fTGTGTGTCTGACTGTTFAAGTAGGT GGCATCTGTCCTAGTCCTGACTTTrrG ATAAGTCTACACGnrrGATAAGAGGA
TCTCTCTCACCACTCAGGYTCCTCCCC
CCACCTCCACCCCAGTACACAGCCAT
GCCCCTCTGATCCCATTTTAGGGACA
TAACACCCGCTCCCAGACTGAGCTA
ATGCGTITGGACGCTCCAAAACTGATC
TGAACCCTCTCTGACCCTGCCCTCCTC BF 1638 IM000190 CCAGGACAGGGCAA 524 B CATGA=]ECAGTITICFGCCATATr CCACGTCCTACAGTGGACATMfCTAA AT=TCCACCTfl=CAGTTICGTCG IM000191 CCATATflTCACGTGCTAAAGTG 525 R
AAGTATGTCTGCTATGAGTCAAAAGT
IM000192 CTTATITTGCATCACATG 526 D
CATGCCGCAGTGGCCAGCAGCCCTGG
TrCCAGGATTCTCAGAGATAACAAGG
AGCCAGTGACCCTTCTTCAAGCACC
AAAGAAAAGGTAACCGACCCCACAA
AGACCTGAGTATGAATGG'TrFCTGCA GCTAAGGCACTFTCCTMfGAGGTCAGC
GCAGTTCGGGGCTGAGAAAAGAGCT
TGCCCTGGCTTAGAGCC1TTCTCTGG
CTCACTGTCCCAGCCAGGACCCATCC
ATCAGCCCACAGTGGGGTGGCATAGT
GCAATCCTAGAGAGATGTrCAAAGG FgI3/g 1M000193 GACATATC 527 K 4
AYTCTCTGGGTTFCCTGTGGTGCTCT
GGACCCCTCTCGGTCCTACAATCCTF
CCTCCCCATCTTCCAGTGCTCTGCCTA
GTATITIGGCTGTGAOTCTCTGCATCT
GT'CCATG IM0001 94
CATGCCCCTCTCGACCCTGGGAGCAT
TCACCATCTTATAAACTGA'ITCTTFTC
IM000 195 TGGGAAGATGATG 529 D CATGAAACACAC'ITTTAACT1TCCAC ATACThITAAAAGTGTACCTTCCCAT
T-FICGCCCCTAGACCCAAATTGGA
TGTTTCTGGCTCCCTCTCGTI'CGTAGC
TTTCCTGTGATGTAGAAACGCIT-AG
IM000 196 AAACCACACC 530 D
GTTTCCCACGGTGGAAGAGGCAAAC
AAGATCCCTTGGGCCTGCcTrCTTGT IM000 197 GGCACTAATCTTACTCATG 531 D
ATGTGGTGTTI'AAATGAGAATGTGGC
CCATAGGCTCATATGTTGAATACNTA
TJrTrcCAGTACTTGGAAGTAMTGGG
GAGGACTAGAGGTGTGACYITITGAA
GGGGGTGTAFITATIGTGGATGTACTAA
[M000 198 GAACCTTTAAATCCCTCTGACCATG 532 D 1M000 199 GCATCATAGTTGTACCATG 533 D CATGGGTTAACAGTG GGCCCTAAACT IM000200 TGAACTAGAAAACTTrAAAGATG 534 K WntJ CAAGTCTGTCTGTCTCC7ITACTAGCCT
=FIGCTGTTCTGACTCTCAAATGGTTC
CTrAATTGGCCATITrGTCCCCTAAAT
AGGGGCGATITAGGATCAACACTCAA
GCAATGTTCCAGATGGGGTCTIGACGT
TCCTCACTGGGGTCCCAGGGCTCCTC
TGACTTrGGTCACAGAAAGGTCAGCCC
TCTGACCTGGGATAGATGTCTGGATG
ACCTCTGACCTCAGCTCATAAACCTG
ACTGTGGAGATTGAGACTGGAGGGA
CTCAGGGCAGTGGCTCAcLrGGACAGT
GCCAGGGTGTGCAGTGGTAGGCAGA
CTTCTATGTCAGGTGCTCCTGTGCCTC Fgt'3/Fgf IM000201 CATG 535 K 4
GCACATATCTGAGCATCTCAAGAAGC
TGAAGCAGCAGAATCATCCGCTCGAA
GCAAGTGTAAGCCAATAAGAAGACT
CTGTCTCAGAAGAAACTGAAACGAA
GAGAGACAAAAACAACTITrCTIGGGGC
TGAAGAGATGGCTCAGCAATTAAAA
GCCCAITCTGCTCACTCAGAGGCCCT
CTGTGAGCTGTCTCCAGATG'ITTAAC
IM000202 AAGCACAGCTAACA7FJTGGCATG 536 R
CACATTCATTAAAGAGACTTTATTAA
AGCTCAAAGCACATATTGCACCTCAC
ACAATAATFJGTGGGAGACTTCAACAC
ACCACTTI7CATCAATGGACAGATCAT G IM000203
GGGGAGAGGCTTCAATGAGCCCCCTC
ACATTTFGCA1TIAAATAGCAGCATCA
AGCGCTTCGCGTGCCACACACCAGTG
GGCTCCCAGATGTCAAGCCGGAGTCA
GTCAGATGGCCAGTGCCCAGCTGTCC
TCCCTATGTCGTGCGGGAGCAGGCAG
TGACCTTAAAGAGAGAGCGCTCACG
CTCCTGGAGCCCGACTCTGGGTCCCT
IM000204 CATG 538 D CTfGTCCGCCACCCCGCCTGCCTCATT
ACCTGGCTCACTCAGTAACGTGAAAG
CCTTrACAGAAATCTCCAGGTCCTCAG
GGGGAAAGGAAGTCATCTTCTTCCTC
ATCCTCGGAGGACAGAAGTCGGATG
GTAAGCATCTGTGCTGTGCTCCTCTA
ACTGTGACGCCGGGTTCCCATGACAT
IM000205 G 539 K Braf
ATATAGTATGACTGCCTCAAAACAAA
ACAACAACAAGAAAACCCCAAGATA
TCTAAAGGAGGAACMTCCAAAAGA
CAGAAATG TCCATAGACCrrGACAAA IM000206 GGAACATG 540 C GTCAAGTGGATGTTTCTCATFTrCAAT GATTITrGAGTIrTTTGACATATrCA
CGTCCTACAGTGGACATFCTAAATA
TTCCACATII IICAGTITCCTCGCCA TATTTCACGTCCTAAAGTGTGTA1TrC TCAFITCCGTGATI=CAG=r~CTC GCCATATrTCCAGGTCCTTrAGTGTGG AM~CGCAT-TTCACGTTr'AGTG ATFI7GTCATTM~CAAGnTGTCAAGT IM000207 GGATGTTTCTCATFJTI ICCATG 541 R CATGAAGrAGAATAATFGGGATAAA
GCTIIATCATTATCAATI'GGT-=GA
AATTrATTGTATrGATATCTTGTAAACT GAATATTTfATTGGTACATAAGTCTGG 'ITATGG'TTGACTACTTn'AAGTT-AAG AG1TIGAT-rCTTCCAGGTAAATGGG IM000208 TGTTfGTAATG 542 R
CATGCAGCCGGGGTGGGATTI'GAAG
AT-TATGCCTAGTGAATATTTAATAT
AAACACGGTGTGATCGAA'ITGATAGC
IM000209 ITG'1TGAAAACTAGAGCGAAACC 543 D
GGACAGGGTCTCTCTCTCTTGU-GTTC
AT-rGMIICATATATCATCGTCGGCCTG
CTITACAGACTGCATTGTGTTCCCCTGT
CTCTGCCTCCCATCTCACTGTAGAAG
TAATGGGATTACAGATAGATGCTACT
GTGTCTGAAAG'ITAAATTrCCTAGGCC
CCATG
IM00021 0
AGTGGGAGGGAGCGCCACTCTTGGA
GCTAGGCAGGAACTGTIGTTACTTCA
AAAACTAACAAGACAATCTCACATTC
CTGAGC'TGAAGACCAGATGCAGCCA
GGGACAGGGTTCTGCCCTGGCCACTA
GATGGGCTGCIGGCGCTGCTAAAGC
ACTGCACAAAACTGGACGAGGTGCA
CCAAGAGTCCCGTGTI17GGCCCTCAG
GGCAGACTAGAGAGCAGGACJTITCTC
CTGGGAGCAGAAACTGAGCCTGGGG Fgf3/Fg/ IM000211 TCTTCATG 545 K 4 CATGCTCATAA'rrCTGCAGTrGCCT7CT
CATAACACAGGATAAAACACTCTAAC
C1T-AACATTATAC1'TGAAAACT'TAT
GTGGTFTITCCTACCAGAGTCATATC
AAACCAGTCTCCCTCTCCACTCACAA
IM000212 GGATCCAGTCACAATGGCCTITITA 546 D
CTGTAGGACCTGGAATATGGTGAGAA
AACTGAAAATCACGGAAAATGAGAA
ATACACAC3TITAGGACGTGAAATATG
GCGAGGAAAACTGAAAAAAGTGGAA
AATATAGAAATGY7CACTGTAGGACA IM000213 TG 547 R CATGGCGAGATTrCTGTGTCCAAGCTG
CCTCTACTCGTGACAT-TCCAAGATGC
CI'CTGAGGTGGGAACTGTGAAATAGG
IM000214 -ACAGAGCCCCACAGTCCCCTCTT 548 K Wnt3
CATGGGGGGGGGTACCAAGAAGGGA
CTGCTGTGA'ITGGGATGTAAATAAAT
AAATAAATAGAATAAACAAAACCCA
AAAACAAACAGAAACCTAAACTCAA
TAACTGCAGAAATGACTCTTGCTCTT
TTCTGGTAAGGTFTAGAAGCAGGTTAC
AAATCTATATrAGAGATGGAGGCATT
TCACACCAGCATAGGTATAGGAAGTA
GATGAAATGAGGACTACACTAGAGT
CTGThITGTCACAACCAATTCTGAGTG IM0002 15 ATTTrCACTGAGATAT 549 D
CTCTGAGAAACCTACCCCATTCTCCC
TCCTrTCTCCCATAAGCAACCACCTC
CACAGCATTATCAAAAGACTGCTGAC
AGATTGGTGGCTCAGCAGGGAGAGT
CAGAGCTGTTTC11TAGGTCTAAGTTfG
TAGCTCCACAGTAGTATG'TTCTCCAT
IM000216 G 550 D CATGGAACACTCAAAGcTrGGCCAGG GCCCA1TTACCAGGTATCCTTTGCCTT CTCAGCTGATGGGCATCAACACATrA
A'TCACATATGACTCGMJGTGTCAT
ATCAATAGTAT IM000217
U
GTGGT1TITGTGGTAGAGAGACACAG
AAGAAACTGAAGTCCTTGGAACATA
ATTATCACTGTGG1TGAATGTFITGTGT
TCCTATAACATCCTATGTAGGAACTG
AACCTATAAAAGTAGTGGCTCCGAAG
GTGGTGTCCTFAAATGTGAACTGGGC
TACAAGA1TTGGCCCTTGTGAATGGC
TT'TATGGAAGAGGCTGTCACTIT
GTCTCTTCCTCCATTATCT-rGGAAGAC ACAACAGTfCAAGGTCTCATCTGGGA
AACAGAGACCTT'TACCAGACCCTAAA
TCTGCCAGTGGTGTCTTGATCCTGGT
CTTTCTGTCCITAGGAGCTATAATGC
ATG IM000218 552
GGCCACAGCCAGTCCACCTGTATGCA
GCTGGGTGCTTGGAGTGGCCCTGGTA Fg/3/Fgf IM000219 GACAAAGTCTCCATGTITGCCATG 553 K 4
CCTTAGGGCGCAAAATCCTFTCCTCCC
ATTC'ITCCATAAGAGTCCCCAATCTC
CATCCACTGFI7CACCTGTGGGTGTGT
GTATCTGTCTAAGTCAGCTGCTAGGT
IM000220 GGAGATGCTCAAAGGAGAACATG 554 R
GACAGTAAAGAAGACAAAGAAGTGA
GTAGAGCTGGATGAAAACTAGGAAG
TTrCAGACAAAGACTGCGGGAATGAN
GTGTAGAGTCTAGAGCCCAAACAGTT
IM000221 AAACATG 555 D CTGCTACATFTCTrAGCTCTAGCTAACT
AGCATCAATGTCCCAACCCF-CTA
TGTATGACTCCAAAGCCAGTGTCACA
IM000222 TG 556 R
CATGGTCTCTAGAGCTAAGAGATACC
AATGCTGCGGCAGGCAGTTYITTA
CAATCATITACAGT1TGACAGTGTCT
GGCCGTGTGCCAAGGCTGGCCTTCAT
CCCTGAGCTCGGTGATGCTTCTGTCC
TGGTCTTCTGGCTCGTCACAGCTTAA
IM000223 GAAAGTAGCTGCTTCTC 557 D
GATGGAAAATGATAAAAACCAGACT
GTAGAACATATTAGATGAGTGAGTTrA
GACTGAAAAACACATTCGTTGGAAAG
GGGATTTGTGTATATCAATGAGTAGT
IM000224 TA 1558 R
CATGGAAAGATAATGTGTAAATTTGG
GT[GCCGTGGAAAACTITFGGTTTCT
CCATCAATGGTAATTGAGAGTITGGC
TGGGTATAGTAGCCTGGGCTGGCAIT
TFTGflCTC'ITAAGGTCTGTATGAAGT CTGTCCAGGATC'FrCTGACTCTCATA
ATGTCTGGTGTAAAGTCTGGTGTAAT
IM000225
TCTGACAGGCCTGCCTTTATATG-A
CTTGACC'FrUITCCCTTACTGCTTTTA
ATATTCTA
GGTAAGAGTGGGAGAAAATGGGGGT
GGGGGGTGGGGACACTGCAGAA&JCC
TGGGAGAAAAAATCCAACTAJA
1M4000226
TCAGGAAACACATG
CACCCCCATCCCGCAGTTCCCAGAGG
1M000227 GAACAGTCCCAGCAAAAATACATG
CATGGAGATGCAATGAAAGCACACA
ATFATFGCTGAACCAAACAGAJ4AGCTC
AAAACTAGGCACAGAAAAGAGATAC
AAACACAAATCTGAACAAAy]TGACCT
TCTGCCTATAGCATAACTAATATCTC
AGAGATAAAAGTGGTCThPATATACC
AGGGCGAAAGAGGTCTAAAAAGAGA
GGAATAAAAAATATGGCATAMflCCT
GTCATATGCAGAACCTATATGAGT'CT
TITGTTTMGTTTCITrrCAAITACAGCCT
ATGTAGCTCTAGCTGTCCTAGAACT
ACTITrjGTAGACCAGGCT IM000228 CTGTTCTACAATGCCGG'I11CCAACG
TATGTGTFITI'CAGTGTAACTCACTCA
TCTAATATGTCTACAGTGTGGTy= 1M000229 ATCATTITfCCATG 563 R
GACAGGCTCCAATCAGATATACCAAG
GGCAGGAAGCACGTGACAAAATCAG
ATGCCTGGAGACAAGTGTAATAAAA~
GAAGCAACAGAAAACAAGGTTAC'IT
GGCATTGTCACAACCCAACTCTCCCA
CCATAGCAAGTGATGGATACACCATC
ACACCAGAAAAGCAAGATATGGATC
IM000230 TAAAGTCACTTCTCATG 564 R
CATGGGTCCCTGAAGGGTCTCTCCT-
TAGCAAACCCCTGTACAGTrGAAGTG ANTTFCAGGTACCCATTrGGTCTTAG IM000231 c 565 D
CCCCACTCCTCACAGGGCTCCCCACA
TCTGCCCTGGGACACCCCACTrcCTCA
CAGGGCTCCCCACAI'CTGCCCTGGCA
CCCCTCCAI1TrCAGGCACCTGAAG~ TCCCTACTFFTCTAAAGGCCA~j'CyrCT ACCTCAGGTCTTGCTCTAGGACTGTC FgJ3/Fgf IM000232 AACATG 566 K 4
CAGGACAGCCAGGGCTACACAGAGA
AACCCTGTCTCAAAAAACAAACAAA
CAAAAAAAAGACCATTATGCATTCCT
1M000233 GCGGCTCTGACATG 567 R IM000234 1M00234CATGGGCAGCACCTCGTGGAACACTA
U
TITATAAGTGTCCTCCAGTCAGGTCAA
_______CAGCGTAAGAT
CCTGTACA'TCTGTGflAAGGACAGA FgI/Fg/r IM000235 GGGCCTGCTGCATG 569 K 4 CATGGA GGCGCAGGAGTTATTGTCTA
AAGTTGTGAAGATGAAGCCTAGATTG
IM000236 TATTGGAGATCCGGGTAT 570 D GCAGATATTrCCACCTCTGCCTTCCA IM000237 CAGTCCTTCGTCCCATG 571 C CATACGCTTACAATGTGTTGTTATTrrC
TGG'ITCTCGTCTGCCTTCMTATAAAA
ACAAATCCAGTAAGGTGGAGTAGGC
AGCCTITACTCAGGGACTGTCACCAT
IM000238 G 572 D TITCTGTATATATrGTGTGGTCAGAAA ACCGTGGTITCCTGGTGTCAAiAcjT TAACAC M CAGTAATCACTCATrCT
AAACCAGACAAACCTTTAATGTTTCA
TCTGGAAAGGTACTCATrCAAACCAA TGCTCTCTfAAAACCAGAc3TAM~AA ACAGCCAACTGCATGTUTCAGGcrITrG ATAGAAAATCAGCTrGATCTAAAATA GTCACTGAA2ITCTGATATCATAGACA IM000239 TG 573 D
TCCACCCACCCACCCACCTGCCCACC
CAGACAAATGTTGACTGAGCATTCAT
ATACTCCATTCACTTCTAAGTAGAGA
GCCTAAGAATATGAGAAAATCCTCAT
AGCAAAGAAATGCCTCT-ciCAACTCci
AGTAAAAACTCGAGTATGGGATGGA
AGAGTTGAGAAAACAGATGATAGTA
IN4000240 TGAGAGCCTATG. 574 D
AGGAGCCTAGCAGAATTGCCCTCTGA
GAAGCTCCACCCAGCAGAAACAAAT
GCAGAGACCGATCGATAAACACTGG
ACAGAGCACAGAGTCTTGTGGAAGA
GTTGGGGGAAGAATTGAGGAACCCA
AATGGGATAGGGACTCCACAAGAAG
IM000241 AAAAAGAGAGTCAACTAACATG 575 R-
CATGTCCTACAGTGGATATIMCTAAA
TI=CCTCC ITIIIICAG1TrCGTCGC
CATATITTGAAGTCCNAAAGTGTGTAT
TrTCTCATAT-rCTciTGATTTCAG=m
CTCGCCATAT'TCCAGGTCCTACAGTG
IM000242 TG 576 R
CATGTGGAGGCCAGAAGTCAACATAT
AGTCTCCTTCCCAATTACTI-GTCACTG
GAGAGC
IM000243 G~rCAGTAGCCAGCAGGGGGGATAG
GACCAGCCCAAATTCTCCCTTTGCTT
GGCCTTGACTACTAGTCTGGGAAGGG
ATAAGTGGGCTAACCAGAAGTCTrCC
ACATCTCTAAGTGATTAAAAATGGAA
GACGTGATCTCTGGTCMTTCATAAAC
AGGCN1TI'CTCAAAGTTGGTCTGTGC AGT-fTGTGGGAAAAAATGAAATGTAC IM000244 TICATG 558 D
CTACAGAGTGAGGTCAAGCTCGAGG
ATAGCCAGGCAGGGATGCACAGGGA
AACCCTGTCTCAAAAATCAAAACCAA
CCCAACAAACAAAAACAAAAATGGA
IM000245 AGGATAGAAGAGAGATAATCCATG 579 D
CATGTACTGAATCCCTGAAGTTGATG
CTGAGCACCATCTTrGTGCTGnTCTAC IM000246 CGCAMhACTGGGG 580' D
CATGTGTCACTCAAAGGCTGCTGAGA
ATCAGGCTGTACCTGTATTCCTAAGC
CATCCACAGCCATCCTGACCCACAGC
AAATGCTGGCAGT1CGCCCCACAGCTG
GACTCCG'TCCTCCCTCCACTCCTATA
GCCGAGGCTATCCACACAGGCTATTT
CAGTGCCCTFAAGCCTTGCTACCCTTA
IM000247 TGTATACATTGAGGACAATGAT 581 D
AGAAACCACTGCCAAATCAATACATT
YI'AATTGGAAGTG'T'ATGAAGCCCA
GGAGAGATCCCTAAATGTATTAATTG
CYI7CCTGAGGAAATATAAAACTCACA IM000248 G'TACTAAAGCCATG 582 C ATC'31CTACACAGATGAAACTGACAA
AGTACAAATAAAGATTATATACCAAA
ATGAAAAAAAGTAAACAGCACACAT
TrATAGATGCATCTAGCATCCCCCAA
AGCTCAACACCATCCATAC'ITGAAGA
CTGCAGTGGTCCCTCTAGACAGTATG
CTCCAGGTCAGCCCTCAGCACJ'rGAG AATAAACAGC'ITCATIMACTCAGCCT FgJ3/Fgf IM000249 GTrGTCAGGATCCATG 583 K 4
ACTGCCTCAAAACAAAACAACAACA
ACAAAACCCCAAGATATCTAAAGGA
GGAACATTCCAAAAGACAGAAATGT
IM000250 CCATG 584 C
CATGAGCTGTCGATAGTGACCTGCAGT'CAAGG
AAATCTGAGGGCTTCCTAATTAACAGAGGAG
CTCTAAATGAGAGTAACGCGCTCCACAAACCC
CCTCACACTCGGTAAG'FGTCACGGTGCAGATA
1M000251 IAT 585 C IM000252
SGCCGCG'IA'IGTGTTCTITCA:FAGAAGAAT
TAGCACATAATGGAATGTGCGTATCTGAAGITG
CACAACTGAGGAGTAITrATrAI'TACATACCT
'TACAAGATATCTI=CTGAGGGAGCAACCTG
AAAACATAAGGAGAAAAACATAAGAACTGCC
ACTCTAAGGGTTGGTGAAATGGCACAGCCTG
GCGGTAGGACACACAGATG
CATGGAGAAACCTGGGCTrATTCAAGCAGMT CCTrGITrACCCTGCCCAGGGTrGCCAGTGA AGGGGCTCCTCCATCACTAACTAAAGGTCTrA 1M000253 TCGTATGCTGGTTCCTCTCCACCCCACCAT 587 D TATAGGAATAGAAATCAGAACTATCAGTTr G=nGC'rCAAATGTCAACACATAAM~AAA IM000254 MIACAAACGCCTrGCACAMTGCATG 588 C
GAAGACAAAAGATGTGTCAAATACCTOGGCA
AAAGGGGGTGGTGGTGCTCTCGCAACTCC
TGAAAGACACCTCTGCTCAGCACACTAGM~C
CAGGTTCCTGGGTTAGGA1TGGGTGAGATTG GTCGGCGATGGMTGGTrCCTCCATTCTGCTG C1rCTCCCTFGATACATTGAGTTACAGCAGCCC IM000255 ACGCGTACACACTCTCGCACATG 589 K Wntl
GAAGAGGAAATAAGOCAATAGCTAGACTGGA
AAAACGAGCCAGCCTAAGAAGCTGCAGAGTA
GTCTGTGGGGTTCTG='~GG1TAGCTGCCTI IM000256 AGTGCTCATG 590 D CATGGATAGAGGATGGAAGTrfGAAA~
ACCTGCTATITAAGAACATAGCCCTGT
IM000257 CCATTAGTGAGAGTG 591 D CATGTGGCCCAGGGGCACTrGGAGCCTrAGAT AGCTGCc=rATGGCTCCTGGTGGCCTTGGAT
GTGGGTGGGTGACAGGAAACAGGAAGAGCTG
GATAGTGGGGGTCCCGAGGAGGAGCTAGCT
GTGCTCTCTATGCAC11TGCTCTCCTGGGGCTA
CCCCCGTCTCAGGGGAAGGCCTGTGACTGGCT
AAGCAACAAGTGTGGGCTGAGACCTI-CTCTG
TGACACTCTGGTGCTACTCTGGCCATAGCACA Fg/3/Fgf IM000258 GATCTCTAGGAACGCACTCT 592 K 4 TATATGGATATGT17ATGTGAGGGTAGGCACT CCTGGAGGGTGGAGGCATTAAYrAGATCCTCT IM000259 GCAGGTGAGCCACCTGACATG 593 D
ATATGTGGACTGTAGTCATCTTGAACATCTGT
AACAAAATATATAGAT-rAGGAGG'LMAGACA IN4000260 IGCAGACATG 594 D
GTGCCTCTTGTCTGCCAAGCTGGTAT-GTAGC
1M000261 1TG 595 D A'ITrGTGACATCT-TAGGAGC'ITAGGTTGGTCT
TCGAGACACAGGGCTGTCCCCTGTAAAGCAG
GTTCCATCAGTGACTCCAGGGTI=AGCAGTT
CAGTGGCGTAGTMCAGACTGCrA.AGATy-
CTCAGGGGCTAGGCGTGGGGCAGAGACCCTG
CAGACCCTGGCTAGAACAGAGGCCCTGGGAG
IM000262 Fgf3/Fgf 4 206
ACAGTT'GAGGGTGCTCAGCITGTGGAGGACAT
G
CATGACGACTTGAAAAATGACGAAATCACTA
IM000263 AAACA597 R
CCTAAGTCTGACCGTGCCACTTCCCAGTCTTC
CC'TACACTTCAATGC'ITIAGGCACAACAAAT Mm. 102 IM000264 I TGTACCCCTCATG 598 B 899
CCCCCCAGCCTGCTCCCTCCCCGGAGGGAGTC
IM000265 CCCAGTrGTGACATG 599 D GnTFAGGTGATAGGGTACTGCCCAGCAG'rAG GTGGTGCCCAGGATrcTrATicCTCAAAA'fI'GCA IM000266 CAAACAGAACATG 600 D CATGTTGTGTAGATACCTACA'rAATfATAATr IM00 0267 CATIAACTGTAAMTGCTAC 601 D CATGGGMTGAGCCTTrGTCCTGAGCTGGAGGA AGAGAGTGACCCAAAGGGACCTrGGTAGCAG
CCAGGGATGTGTFGGGGAGCAGAGAAACITI
TATGAACTTCAGflTAGTACTGAAACTTCCC 11M000268 TTICCCTAGACTTCCTIG 602 D CATGGGACAkACTCCTTTCCTTCTGGGTCAG
GGGAGAGAGACCTCCTATCTAAACTGTATAG
GCCATrGCTGTAGCCCTTAGGTCACTUCCGGG IM000269 GCGGGGAGGAGGAGGTTAAGACCC'IAT 603 D CA'GXAAAFGAAAGAACAGAGTAGCAATfTGG
GGAGAAAAGCCTGCCGAGCGGACTTAATCTTI
IM000270 CCCAAGTGCTATCAGT 604 D A'I'GC7FFG'r1'YITCCCGCCCAT-rACCTGCTITrTG T'ITGAGATAATAG1TFFGTTAC1TFTATCAACTrA GTAGCGACTAGITTACA'IT'GG1TTCATAAAT
AAGATCCATTTTAATCTGAGTMLCCATCCTTG
ATiTA11TGATTCATATTTrAATrGTCTAGT7
CCCATCCCTGGGCAGGACTTTTGGGAAAGTC
TTGCAGGTGACTATG'L1I'GAGAAMGA1'TTATGT
TGTATTAGCACAGGTACAITCGACAGTGCTGG
TTCCTTCTGGAGCGCCTCGGGTGTGGGTCCTT
1M000271 TTCCTCAGC 605 D CATGAGFIGATFI'ATrCCTGAATTCTACCTCT 1M000272 CTTGGGTCTATFrCTITCTITTGTrCTAGAG 606 R
GGGATAAGACTGGATAGTAAGCCGGGCGTGG
IM000273 TGGTGCATG 607 D
CAGAAGGTAGTG'ITTCACAACAGTCCTCCCGA
TGATCAA'G'ITACACTAAACCATATAGGA
A'[FCACCCTGAGAGGAGTTrCGAAAGCC'lCA
AAA~CTGTACTGATATAAAGCAAATCTCVIIFT'
GGATTCCCAATCAAAATGATFI7rGGCAGAACIT
TAAGGCCACAAAAATTGTGTCTGAACAACCCC
TCTGAGCCCAG=hFGTTAGCfl'AAATTAAGG IM000274
GCCATG
CCTCAAACTAAGAAGCATCCM1TCGAAGCTG
CTGGGATTAAGGGAGTATGCCACCACCACCA
GCTATGGCA1TTTTTC1TrAA1rACTAT 1Tn'GCTTrGTATATrATGG'1TCCAGYITGTG IM000275 GGTI=ATAAGCM~GAGTGTGMhCTGCATG 609 D GTCCACMhAGOACGTGGAATATGGTAAGAA IM000276 AACTGAAAATCATG 610 R
CATGGTCAGCTCTCACTGCCCCATCCCCTGTC
TCCAGTITCACGCACTGTATCCTGTGTCTTrTCTC TGTGGCTAGACTCTTCTCT'rGGGGGAGGGGAG TCTrGTATATCGATGTGTGCTCACGCACATAG AGGCTAAAGATrAATCTAGGTTATCATTCA IM000277 TCGTCTCATTGX2 611 D CATGTGTrCCTGATnTAG~rGGATTnr
CTCCCAGG=CTGCAGTGTCCCCACCCCCCA
IM000278 Ic 612 D ATGGTGTCTGTrCATAGCAGTAAAACCFrAAC
TAAGACACTGATATAACTCACCI=CCCAGCC
TCAAAGTCTCTACCATCTCAGGATCCACTCAC
TCATTCACCAAACTTCATCAAATGCCCACTGT
1M000279 GCTATCATCAGTACAGAATAAAITCATG 613 R
CATGAGACTGTCACAAGCTCCTGGGATGGGG
ACCTTACCAGAAAGCCACCAAATCAGAGGCA
TCCGTGTAGTCTTGTIrC CAGGCCCTGAGTGCCAGGCAGGAGCAGGCAA Fg/3/Fgf IM000280 AGTrCACCTGGGAGGATGCCCTGGAT 614 K 4 GTrGGTCTMCAAAGAAAACAAAGGTC ATrGCAGC'ITIGTACCATGAGGTGATGGT AGGAATPrGAGATATATAATCTA=~GAAGATA 1M000281 TATATTATGGCATG 615 D
CCGCTGCTCTCTCACCAACCCAGTGTGTCTGC
TI=AGCCCAGACGGGGGAGGGGGTAAGGGG
IM000282 GTGGTCTGTCTCATG 616 K Wntl GTGTCCCTCCTGTCGrAGGCAGTACCCA IM000283 ATCAAACCATG 617 C AGCTGGTACAATGGT7AGAGCAGAGCTGCAG
AAGCAATACAAGAGATCCTGQCTCAGCTAGG
TGCAAGCTGGAATAGACTCCTGACAGn7GTCC IM000284 TATGAACTCCATACACAGGCATG 618 D
ATGGATCCCTGGGOGCAGTCTCTGGATGGTG
CTC~CGCCGACAAA-GCC
IM000285 GTAACTCCTTCCATG 619 R CATGATGCACTrAGCAATCCTCAATTGAGACI TCAAGTGAGCCTAGGCTGTGACAAAATGACT Fgf3Fgf IM000286 GT7fAAAACT 620 K 4 IM000287 10087CATGTAAAGCTAGTrCAACATACTATA rrICAGTGTAGAAGAGGTGAGGTTATCTCAC''
GCCAGGATAAGCTA'ITGAACAAGCAAGGG'ITI
CTCACTTACTGTAAGTGGAAGTGTT=CTTA
CTTCAAAAAGTCATAATGAAYI=AAGCTGC
ATAAATAThFTAGTTA1T
TAAGC'TTTCTCTTACACAATCCCCCGGAAAC
CCACAGTrTAGGTGACAAAGACCGAGGCAGCT ALrTCCTAGGCCTGGTAAGT'GGGCACCCACCAT 1M000288 TFACAAAGAGCTCA(GGA'ITTGGCTCACACATG 622 D
CATGAAGAI'GAACCOGGCTTCTCTGGCA
ACTAGGCrCAGAAAGGATAGGACCACCAc3CC
GAGTAGCTGTCAGATGGAGCTGAAGACCTGA
GGGAAAGAATGCTTGTGGGAAGAAGCTGGCTr CC-fFrGGTI-1-GTTG'rrGCTGG3TIGTGACC IM000289 GGATC1TGCTCJTGTGACCCTACCTIAACATr 623 K WntJ CATGGAM'IAMTrACTGCAmTGAATTrATG GAAAAI'ATATIAT'GAAAAOTC'rr1rAGAAAAAG GCAGAGGACGAAAAAAACCAAAGAAU['FTrAA TTrATCTGAGACCAAGAAAACTCT1TAAGAAAA AGCAGTAGMTFAAACTACGTG'FrGTTAAAAT
AGTCCTGTAITAGATATAAAGTCCCTCAGAGGG
AAGAGATrTGTTGAATAAAYI'CAGACACTCAA IM000290 GAGAA 624 D ATTAAACAc3CCCAGTGCACTCAG3AAGTGAAT G'I7GAGAAGTGGGTAATCTGGGGACAAACAG AGGGAAGAATAGTGCCCTTGGCACGTGCAAA Fg/3/Fg/ IM000291 GGAG'TI'GGGAACAAACATG 625 K 4 CATGTATrGACAGT'GAGGTCAGGAGTGCCCAG GGAGCT-rGCATrGGCAGAACAGCC71TCCTGG
CCAAGCCTAGTGTCATCAAGTATATATTGGAC
CAGACMTATAAAACTTGGGTTCCACTCTGGC
TGGACCAGCCTCAAGGCGTCGCCTCTCCAGGC
CTACCTCCCAGAGAGAGGCAGCATTI'GGA
IM000292 GGA'JTGAA 626 D CATGGG3AACI1TGrcCAAGCAAGGGACTCTGC TACACCITCAAGGGACGCTFGCTrAATACIGGGIT
TCAACCTTGGGCAGCGTGCACAGCAGGAGTG
GOAGGGCTCTGATGAGGAGAGCCACCCACAC
IM000293 TGTGAGATCTAGGAGATAAGGTCACATCCAC 627 D
CCCTCCAGCAAAYITGAAATACGAAAGACTCA
AACACATTAGAACCATTCCAATAAAAACTTGC
IM000294 A'J1GCCCCCAGGCCCCTCCCACCACCATGj 628 D
CAAGAGTATATATCCAAGAAAAATACAGCTG
IM000295 IAGTrOACTGTPAG'F-FCTGTM~GGCCrF7CATIG 1629 D
GGTAAAAACTCTACCAGTFTAAACTAC
ATTFCCCAGCCTGCCTCCAATGAATTT
AAT'FflGTGTFTMrAGGGMTCTGI1TAT TGTI'G'TI=GAGACAGGGATTrCACA AAGATCTGCCTGCCITCTGCTTrCCTGA IM000296
GTGCTAAAATTAAAGGTATGCATG
GTAGTAACTGrI=CTGTATTAC=r1GTTG AAAATrAGATTGTrCCTGGTGAC=IGTGTGC 1M000297 TATATTCTCTGCATG 631 D CATG'1CTGCTTCTAC1TrATCCACCCTGCAC ACACTGACTGCTATGT-rCCTGTACCTrTTCCAT CTCTCCATrGAATATTCACTCCAACAGTGGCA IM000298 TTGGAAArrGCAGTGGAGATACC 632 D
ACGATGGTCITGCCCM~CTCACACCATCAAT
AGTCACTCAGAGCTGTG1GTrATCTGAAGT IM000299 GTGTrGCAGTCCAACIr7GCCCCATG 633 D-
GGAGTGTAAGCGTCGGTGTGTCACCCGTGAG
IM000300 A'rrAAGTCAAAGTGTACATG 634 K Wntl
TAGACGCAGTCTTGCACTGGCCTGGG
ACTCGCTITATI'AGG'TrTGACTG'ATC
TGGCCAACAAACACCAGGAAATGGG
GTGACAGGTGGTTGTGAGCCCTCTGA
AATGGGCAYJTGGGACCTGAACCTGGG
IM000301 TCCTCTGTAAGAGACATG 635 D TCACCCCAGCTGGGGCTGTGCTGAAGACTCTG Fg/3/Fgf IM000302 AAGGGGAAGATAGGCCTATGGTNACATG 636 K 4
GTTGGGCTGAGCCACAAGTACACCTCCACTCA
CTGAGCCATCTAGCAGGTCCCAAACAAGGTG
AC=IIGTCATCCAGCAAGACATAGCCATCTA Fg[3/Fg/ IM000303 TGCCAGTCATCCT7GTCATG 637 K 4 TAACATATTTGC ITG'FATGAAGGAAAATGTf GGATGTGTGTGCCTGTGG1TGAGTACTGCAAG
TAGTGTCAGGGAAGAGAAACCTAGCTTGAAC
AGTCCCCTCATCTCCTrCATATCCTCACTCCTT
GTCAGGCCCTGTATTAGGTAGTGCTTCCCTAC
CTCCCTAATGCTGTGACCCM7CAATAGA IM000304 G1TCCTCATG 638 C
CATGTGAGCACAGGTACCTATGGAAA
CCAAAAGTGTAGGATCCCTrrAGAACT GGAAT'FATAGGCAGCTGTACGCTAT'r
GATGTGGGTGCTGGAAACTGAACTCG
AGGCTTCYrGAAGAGCATCAACTGCT 1M000305 CTTAGCTGG 639 D
CATGTAGAGACTGCCATATCCAGGGATCCACC
CCATAATCAGCATCCAAACGCTGACACCATTG
CATACACTAGCAAGA11TATrGAAAGGACCC
AGATGTAGCTGTCTCTTGTGAGACTATGCCGG
GGCCTAGGAAACACAGAAGTGGATGCTCACA
GTCAGCAAATGGATGGATCATAGGGCTCCCA
ATGGAGGAGCTAGAGAAAGTAGCCAAGGAGC
TAAAGGGATCTGCAACCCTATAGGTGAAACA
IIN000306 A 640 R IM000307 1M00307CATGTCCTAGAGTTGTTCCAGCACAGAAGCTI'
TTGGGAGAGACCACCATTACTGAAACGCAGC
AGATGCTGCAGCT
CTGCTrGTTGTGGGGACGAGCCAGACACCCTC Fg/3Fgf IM000308 CACAGGTGCAGTGGTGCAACATG 642 K 4
CATGATGMTGTGCAGGAATAGAAACCCTGAC
TAAGACAGAGGATATTrCAAGAT'CCAAACTAG IM000309 CAGG'ITAGCT'GTGGTTCC 643 R
CATGAAGCACACATTACCCTGTGACYTGC'TT
IM00031 0 'IIA'TAAT 644 D CATGTCGTCCTCT-rGTCTrGTrAGTrCTCTATTCT TGTGATTCCGCAGCTCTCCATAGAGTGCAGITr CTATGTCCTGCCTGCAAGGTCCA'flGGC1TAC
TAGGGTCTGCCCCTCCCAGAAGAGTAGCTCAT
TfAGAATGCAT'TACTGGTGTGCTGTCTTGCAT IM000311 CITTYFACCCAT 645 D ATCTATGTATGCACTACTAATrACTGTITAG TTE7ATATATGCCCTAATAAT[rACCCCArrGAA AAC'n7AAA'Ir1TG1TrlCAAAAGTGTGGTCTCA TTGGAGGTGTlAATGTACAATGTC1TICTCATI IM000312 IG 646 D
CATGGCCAGCTGAGCGGGCTGCJAACCTGCCCT
TCTGC'fl'CCTGTCCCTGCACCT'CAGCACCGCT IM0003 13 GTGCACTrGGTACTAGACCTCAATCACCGCAG 647 D
CATGTGCGTCCCCCCCAAACACGCAAGCGCAC
IM0003 14 ACCCACAAAGAGAAGAGACAGGG 649 D CATGGCCACTTrGGAGAGAAGGGGGAAGGGAA LM0003 15 TGCGGAGAGAGCGGGAGCAAGAG 649 C
CTTAAGCACTGATCAATGGCCAAGGTPTGCCG
AC'FIGGGATCTGGGGTATAGACATCCACCCAC
TGAGACCCTCTAACAAAACCAGATGTGGAGG
TACGAAGCCTGGCTCAGGGGCCTGTCCTTTGT
CATCAGAAT-I'CACCAGCTGCAGCTCCTGGGTC FgJ3/FgJ IM0003 16 AGCTIFYG'VrFrGGCAMG 650 K 4
GTGTATTGATATGCAAATGTGTFAAAATATGAI
IM0003 17 TyrAAAATT~ccCCATG 651 D GCAAAGTrGTCCACAC=rGGTCT-rCGTTCTTCT IM000318 TGAGTrCATG 652 R ATAGCAGGT CTGGATACCCCAACATACCAG AAAAGCAAGATTCAGATCTAAAATCAC-1TCTC IM000319 ATG 1653 C IN4000320
CATGTCCTGGCITTGTAAAGGGTCCTGCTGGG
FTrAMYCACTGGGTC1TAAACTCCGATTrGTG AGCCGTAGTrGAAGAGGGCTGTATATAGTGG
TCACCGAGGITCCTGTFAGCAGAGTGGGCAAGC
TCACTGCCTGCTACCAGCAGTTCACTATGT1T ATGGTCTGCTGCCTGCTGGTGGT-rTATAGATG CTGTGTCGTAAGAGAAAAG'FrCAGGGTAGCCT
GGAGTGAATGGAGT'TGGGGTATCAGGGAGGT
CTM GTACACTGGGGTGAGCTAGGCCTGTGGA
AAGCITTCTGGGGGTITCCCC
CATGCTCCCAGGCACCAGGCTTGCT1TrGCATA GGTG43GACAGGGTCCCAATACTCAGCCTGGG
GTGCCAATGAGGCTCAGGCCACACACCCTCTT
GGTAGGAGTCACTGTAGTGGGGTCTGTGAGA
GCCAGTAACTrGTGAGGGTGTGAAC-ITAGCTC AGGACAGAGGCCAGCAGGAAGCTrCCCTAC AGAGAGTGTTTrCGTC'TITCCYTrCTGGTT TGT-ITCTTrGGGAAGGGAACAATMTCGCTI-17 AGT1GGCTrGTATATCCTACTGAAACC1Tr IM000321 AAG 655 D
CATGTATTAAGTCCCTCGTGAGGAAG
1M000322 GGT -656 D
CATGAGTCAGAGGCTTCTACTCCATAAAAC
TGATCTGGGTATAGAATrGTGTrCTCAAGAAA
TAGTAAGTTATAATCAACTAAGTCATCTCCTG
TCTCATTITMCTCCAAATCGGGTCCTCGAA
TTGTITATAAGAAGATTCAATCAATCAAGAGTA
TCCCTIT7CCCAA1TrrGTGTGCTAAGTGGAAAC AGGTC1TAGCACATCAATCACATAAAGITCAA IN4000323 'TAAGAAGGAA'TrTAAAGATCAG 657 D
GCTATGAGTCTCCACTTGTAAACAAT
TATACTCAAACATAITCAGGACACAC
TTGGGCTTCCTCCATCAAGCCAGGCA
GGTTTG=h1CTTGTTfGTF=GAGAT IM000324 AGATGGATGGGCCAGCTTCATG 658 C CCCACCCCTAGCAACCAGTTfCCTCCTCTGAAT GGAAGACATCTGATACCAAC=rGAGCInrCA IM000325 CATG 659 D ATCNNCGAATCATrCTAGGCTTIGTGG 1M000326 GACCATG 660 D ACTATTCTCAACAATAAATGAACTrCTGGOGGG AATCACCAATCCTGA T7CAAACGGTACTGTA IM000327 GAGCAATCATG 661 R CCTAGGCACCCACCACAATAG'rAATCCATCT T-TGAATI=GACCCAGTGT'rGCCAAGTATTC ATrGCAACAGCI-=CAAATG=rI-ICI-JC IM000328 CCAAATAAA1TCCATG 662 D AGAGGCTACCCCTTCAAGTGGC17GCCTAGTA TAGGTATrACAGACAGAGAAC'TCGAGTAATr IM000329 TCCTCAAGCCACATG 663 D ACTCTGAACTITGCTTrGCCTGGTATrrGCC TCTC1TATCCCATTGACCCTGTACAGAA&AGC
TGAGGAAGCAGGTGCAACCAGGCATCTCAGG
CACCCAGTITAAGAAGTAGATGAAATACTGTA
ATGTACATG
IM000330 CATGATrITCAGTMTrGCCATATTCCACGT CCTACAGTGGACATTTCTAAATMrCCACCTTY 17rCAG=nCCTCGCCATAITTCACGTCCTAAA IM000331 GTGTGT 665 R CATGAGACAGTCCCAGATCCCTCACCATAiG IM000332 AGCTACCATATIAC 666 D
CATGCGACCATCCATCAGGAGTTGGAGGTGCC
A'TCGGCTCT'GCCTTACAGAAAAGGAArcI'GAG A1TFAGAAACCCCAGGTGACCCACTCAGGGCC
ACCGGGGCAGTAAAAAGAATCTAAGATGTAA
AGTCAGTGGAAACTCCTCCCAACCAGCAGAG Fgf3/Fgf IM000333 ACTCCTCCCAGCCAGCTCI7GAT 667 K 4
GGGAAGCAAGAGGCAGTAAGAAAGGGGAAA
IM000334 CTGGGGAGGTAACCAAAGTCACATG 668 D
CATGCTAACAAAGAATGGGGAA.AGCTCTCTA
GGCTFCCACCT[AAACAATGAGGAAG3GGAAG IM000335 AAGGAAAG 669 D CATGT-rGGTGGGACTTATGGGTA7GCTJ7CT
GATATFI'ACTAGGAGGCACAATCTCACAGAAA
AC'rCCCTG3ATCTTACAATCC'rrFCTGCCCCCTCT
MTGCAATGTTCCCTGAGCCTCAAGTATGGAG
TTA1TrATAGCTGTATrCArGAGACCAGAA IM000336 TCCACAGGTATGC 670 R IM000337 CTCACACAGATATGCATG 671 D
AGAAGTGATCYICTTCTGTGTGTCCCTGITCAC
IM000338 CGGGAGGCAATCAGACGGiTCCCiCATG 672 D I I CC I i IGTIGGACGAATATrATTrGAAA IM000339 TATGTAGTGTGCATG 673 D CATGAGATATGATITrAGATCTGAATCTTGCT TTTCAGGTGTCTrGGCATA'TCAGAACTCGCT GTGGTGc3GTGAACTGGoG1TCTGA'I'G3ATGCCCA A159706 1M000340 T-rGGTC3CTGGTTC 674 B 2
CATGGAAAGGTAMIGGAAATAGGCTGTITTG
IM000341 TGTGTAACTC 675 D
CCCTAGGACTCACCTGGTAGGAAAGAAGTAA
1rCTTCCAAGTTGTCCCCTGACATCCACAAGC 1M000342 ACATAGTGTCAGGCATG 676 D CATGCCA'TrCATACATACTGGCAATGGATATA TAGAAAATGAGACTCCTTrCAATATTrGTGTGA IM000343 TGACAGAT 677 D
AGAAACCATTITACACTGCCAGGTUTGGGGCCT
LIM000344 GGCTATGCATG 678 D GATCCCTInAACTTCTTGGATAGTT-rCTCTAGC TCCTCCAi-rGGGGGCCCTGTGAT'CCA'TCCAAT
AGCTGACTGTGAGCATCCACTATGTGTITUGC
TAGGCCCTGGCATAGTCTCATAAGAGACAGCT
R IM000345 ATATCAGGGTCC=rCAGCAAACTCTrGCTAG TGAATGCAATGGTGTCATCATrT7GGAGGCTGA
TTATGGGATGGATCCCTGGATATGGCAGTCTC
TAGATGGTCCATCCTITGTCTCAGCTCCAAA
CTTTGTCTCTGTAACTCC'TrCCATG
AGGGTGGTCTGTGCAACCCAGGCTGGAACCC
AGCACAATAAATAGmrTATITACATAACCGA
ACGCGTGGCTCTGCGGCCACATTMCGGTGCAA
ATTAMTACACAGTGATGAGGAGGCAGGACA
GGAAGGGGTGGGAGGAGGCTGAGGGAGGCAT
IM000346 G 680 K Wntl CATGTGTGTrCT1TrGTGATTGGG7rACCTCAC IM000347 TCAGGATGATA1TrCT 681 R CATGAGGCCAAGGGAGAGGCAAATrCCTGTG M000348 TGAATCAATTATCATCTCACAGAGAACATAcc 682 D
AGTAGTATGCCACAGGGAGAAAGGGTATTTA
TCAAAGGGACAGGAGCTAG'ITGTGGTGACCTT
ACCTATCTGCTrGCCTCTGCCTCCACGGTGCT GGGATTrGAAGGTGTGCACCACCACACCCAGC TICAGA1T1TI1ATTrATGNGTATrCC 1M000349 TGM~CACCTGCATG 683 R CATGCATATACAGGATATAACCTfGTAAGTA AGAATAAAGCACATAAAAAATAC1TCAGTA IM000350 ATATrGTCCAAACCACTT 684 D CATGTGTGTGYTGTG1TTGCGGAGTGTGGGG GCGGGAGGGAAAGGTGGCCAGGCTGTCACTC FGF8 AGAGATCAGGATGACAGGCGCTCCCTCATCTA
{TC
GGCGCGGGAGCTCTGATTGCAGATCGAGJA
AACAAAATAGCAATTG IFGF8" \L 2} IM00035 1 685 K CATGAAGATGAACCGGGCTTGTTrGTCTGGCA ACTAGGCTCAGAAkAGGATAGGTCCACCAGCC
GAGTAGCTGTCAGATGGAGCTGAAGACCTGA
IM000352 GGGAAAGAATGcTTGTGGGAAGA 686 K Wntl
TCAGTTCCAAGAGATGACACAGCCGC
IM000353 AGTGATG 687 R
CAGAGACTGAAGGAAAGACCATCCAGTGAGT
GGCCCAACTTrGGGATCCATCCCATrGAAAGG IM000354 ATCAAATCCAGACACTATfACTGATACCATG 688 R CCCTACAGTGACACTrACTCCAATAAGGCCAC IM000355 ACATCCTAGTAGTGCCAGTCCCCATG 689 R GGCCTCTATTGCTCGGITCAGATrAAGTACCTG GCT'rGACTGAGAGCGGCTCMTCATTCCTAAA 11M000356 ATGGTrcTCATG 1690 D IM000357 1M00357AGTAGATGGCAGAGAATAATCAAACTCAGGG
CTGAAATTAACCATG
CCAACCCAACAGCTGGGAAGGGTTGGAAGTA
GCCCCGAGGCTGG'IAGTCCCCT'TCCAGATGG
GGAGGTTAGACTGGGGCTAGCCAGGCTGCTC
CAGATAGACTTrCCGATTCGCAI-rAGAAATGAA
AAGAGGAGAGGAAAGOGAAAAGGAAGAAAG
IM000358 GCTACAAGCATG 692 C
CATGGGGT'CTGGAGCCAGC'I'ATICAAACCCAG
GA'TGTCYFAACTGTGGTGGCTrGGATGAGiAA TGGCCGCCATAGGCGCATAGATI1GAATTCIT IM000359 GGTCCCTAGTI' 693 R ACGGTGGGCTGATA1TICTAGAITCTCCTAGT IM000360 GCCTATCCCCTATTATCATrG 694 C CATGAAT1TI'GAGATAT-fCTCTGAAC IM000361 cAAAcAATAi-r 695 D
GGAGAAATTATGCCTTAAAITAAAAAGCAAA
TATTGAAAAATTAAATATAATTCCATrFAAA'r
CATAATGGACCAACAACAGAACACATCTATCT
ATGTATCTATCTATGTFATCTATGTA'ITI'AT'CTA
1M000362 CCTATCTATCTGAAAAG3CAAAAACITACA'L'(G 696 D GCAAGGACAACTIGACAGTGAAGCAAC'rAT T-ITCATCTTGACTCTCACTCGGC1TrAACGTIC IM000363 CAITCAGGAAACAGGCATG 697 D
CATGAGAAGTCACAATTCCACCACTT
AAAATCAGTGCTTGGAAGGATACTGT
AGGCCAAGAGGTAAGTAGAGGGGAC
AGCAGTGCACGTT1TICAAAGTGTGG
GTGTGTGTTGTGGGTGTGTGTCTGTC
TGCCTGTGCGTGTATGTGGGTCAGTA
IM000364 CAGGAAAAGC 698 D
CAAGAITAAACTCTTAATGGGAI'CTAGGGAGT
CAY[CTGTAGAGAGCACYTGACTAGAAGGT-rA
AGTCTTAGATCCAGATCCCAGCACAAACATAA
TACATCGTATACTCACACACACACACACACAC
IM000365 ACACACACGCAGTCGTCATG 699 D CATGTCTCAA AA A AA A AA AAGAATCACTlGG ATrGTACATAGTAGTTAATAATATGTAATTAG TCTAACTGTGAAGGGGCAC117ATTAG'IMCTA
CTFATGTAGTGTAAATGAACTATG'FCGCTATTA
IM000366 GAAATTC 700 D GAAGGTTGAAATCTGTAATcrATrC'TTCTATGG
CATCATTCACCTCTCTAATACAGCTGTAGAGA
AAAATGTCTGAAGATrCGGTrCTACTCTCG'Fr IM000367 CTFFGAGGTCTGCCAACCCATG 701 D
CATGGCTGGACTATAGAGCTCTAGCTTCAGTT
GCTGGGATGTTCAGTGCATCACCACAGAGAG
IM00368GGT-rC'rAAGTGGTGATGG'Y'GGTAG'rGGAAAG 1M00368GTGGACCCTCCAGACAAAGGAAGCACTCACC ACGACCCTGCTCACCTGTGAACCTTTCCTrITC
AGACTGATTCCTGAGATCAGCCAGGCAGGGC
TACCAACCAGGGACTCGTAATGAAAATTrAG
GGATATGG
CATGGTCTGGTGAGTATGGCACCAGATAGGAT
GTTATGCCCG1TrTATTCAAGAAACAAGG AATCTTGTT7CTATCATAATAGGAAGAATA
GAGCAGTCCTGGCTAAATGAAAGGTGGNAAA
IM000369 GTTGGMTGAGTATCTCMTCC 703 D IM000370 AAAATCCAATACACA1TCATG 704 D CCCTTTGTrrGTGCAMTCAGCTAATCTCATCCC TGTTTGGGTCCTGGAACCCTCTTGCTfCCCTGG
CATCTAGGACTTGCTAGTGGCTACCCCCAGCT
CCCCAnCCCCATTGCTACACACCTCTGTrCA AA'FrCCTGACCCTGTGTATATCATCGCAGTCTC
TTCTAATACCTGACCTGAACCCCCTITICCCC
TCCTCTA1TCTCTTCC17GCAAGTCCCTCCCA IM000371 CCTTCTACC'FrCCATG 705 R
CATGGGTCATCTGATGTIACCAAGCAACA
GTGATGAATCTATAAATAGAACCATCAGTTCA
AGAAACACAACTAGATrCC1TrCCATACCT TGCTIMG1TTCTTACATCTCCCCCTGCCCTG TGOTI=C=rAATCTG1TI=ACAATCCA IM000372 AATFGTATCCCCTrCTCTGTC 706 D TrGGOCCTITrGCATACCCTGTTCTGGCTAAGA IM000373 CAA17GTCACCTGACTGGGCATG 707 D IM000374 AAGTGGATGT-17CTCATI=CCATG 708 R TATAAGCAATCCCAAAAA1TCTACCTGGGAAC TCCTAGAGCTGATAACACCTrCAGTGAGCCAA GTATCTGGGTATAGGA'ITAATTr1AAAAAAAT
AGAAAATCAGTATCTCTCTTACATACAAATAA
CAAAAGGGCTGAAAAAGAAATrAAGGAAATA
AAACC=~CACAATAGCCATAAATAATATAAA
CTATCTTGGGATAACTCTAACCAGGCAAGCAA
AAGACCTGTATGATCAAATCTTrGAAGAAGA
AAATTGAAAAAGGTATCAGAGGAGGTAAAGA
IA4000375 TCTCCCATG 709 R IM000376 CATGGGCTCTGCTTAAGAAACCCCGGAG 710 C CATGC1TrAGGCC=F~CACGATCTFrANNGG
GGACCGNGAGAGNT*NGGTGCTGGATGATCTC
ITGAGAGAGCITATCGTCCTCAAACTcICTGATA
TTCAAGCTGTTCGCAGCTGCAGCAGCAAAGT
CCCGGTCT=GTCACCGATCTGTGAACAGCAA
CAATGAGCACG'IMCATAACAGACAGOAAAT
IM000377 GGATGCT 711 A inDall IM0003 78 GGCGTACCTGTGTATATGCATGCATG 712 D
GTGCTAGGCTCACTCAAGATAAAAIT
1M000379 ITGCTAITI'CAGCTCCCTGGATAATAA 713 D
AATCTATCCTCTCACAGCTIGITGACTC
TCACAGGGGTGCAGGCAGGACGACA
TCAAGAGAGTGATGGCCTCTAACAAG
TGT-rCTGCCCACFTCCTCYITCCGGGTC
AAAGACTAGATCTAGACTGGTGGGG
CTGTTGATTrCACTATGAATGTGCCTG
ACACCATCCCACACFAGCATCATAG
ACAcYIGGGGGACTGGTGATACACTA
TGATGCCTGACACCATCCCACACTTIA
ACATGATG
CTATCGCGAGGGTGAGGGCAGTTCTA
TGCCAAGGTF[CTCATCACAGAGATAC
AGAGGAAGCTGGGCCTGTCT[AGGGT
TGGCTGTCTGGAGATCCTGGAGCCCT
GGAGGTGGGTAGCAAGAACAAAGGA
AGTACTTCACCTGATAAAAACAGTrC
CCAGAGAAACACATATACGCTTCATA
TAGAGGAGTGCGAGTGTGTGTGTGCG
CGCAGAGAGGCAGAGGCCTGGAAG'r CAAAAGTTCAGGGCCAGTTTGTGTGC Fgl3/Fgf IM000380 ATG 714 K 4
GGGGTTGACTAGAAGAAGGAGGCGATTAGGG
TGTATCATATGAGAGAAGAATAA'k&AGGA AAAAATAAATIT'ACAAGGjAUAAAAAGTAAT
TACATFACATACATACATACATACATFCCATACA
TACATACATACAAGTTAAACTGTrATGGTAGC IM000381 ATO 715 D AGGATGATATIMCTAGTTCCATCCA'FrGCCT AAGAATrCrrGAAFrCATTGCTTfTAATAGCT GAGTAGTACTCCA1TFGTAAGTATACCA'FAT TGTCTGTATCCA'TrCCTCTGTTGAAGGACATCT GGGTTCI=CCAGCI'CTGGCTA't'ATAAATIG IM000382 AAG'TrGCTATGAACATAGTGAAGCATG 716 R CATGCCTGCAGGTCACAGCC-FlGCGCGCCT'CC AGITGCCCAGCGTfCAfiAGTGACACAGACTCTG
TCAGGATGGTTCAAATGCAAATCTCTGCAACT
GCGTTrAGCCGCTTCTAACCAAGACAGAAAGCT
GCCGTCCTGTCCTITCGTGTCTFGTCCCCATACCC
CATATCGGGTAGCTrrC1TTCAGCATTGTCCA GACACCATCATATGCCTACAITCGCACAAGTF7C TCTGAGGCCAGATAATTrGGCAGCACTCCTGrT
GTGTGCCGAGAGTGCAGAAAAGGGCTATCCC
GAAAAGGTGTGATCTGGAAAGAAGGAJAAA
IM000383 c 717 D
ATCFI=GGCCAGAGCAAGCAGGGACTGAGT
GAGCAGAGGTGACAGGAGCGAGCAAGGCTGA
CAAAGTCTT'CCATA'ITCCTACTAGGATGACCC
ATTAAGCCCCATTTAAAGCATrCCATTGCM1
CCAAATACAAAGTCCCAAAATCCACATTCMT
IM000384 CAAATAAAAGCATG 718 C I M000385__1TAACATATGGT1ITAAAAATCCATAATGAG 1719 1 D
CATATGATAGAGAAGTCATCAGAGCTCTTCAG
CTCCACATCATCTGTCCCCAGAAGTAT*TACTA
CTCCTAACTTGCTGAGCCAAGGCACAGATATr CTrFGTGTAAGCATCTCTG=ATCCTGTGI'T
GCCACGCAGGAGCACGCACACTGCTTCCTGTC
TGAGG'ITGT7CCATATCAGCATG
CATGCCAGGGCTTGAATTAACACAAGTGCCCC
IM000386 AGAT 720 D IM000387 CCTGTCTGTATATGCAGATG 721 D
CATGGAAAATGAGAAACATCCACTTGACGAC
ITGAAGAATGACGAAATCACTGGAAATCGTG
AAAAATGAGAAATGCACACTGTAGGACCTGG
AATATGGCGAGAAAAGTGAAAATCACGGAAA
ATGAGAAATACACACTAGTACGTGAAATAT
IM000388 GGCGAGGAAAACTGAAAAAGGTGG 722 R
CATGAAGGTAAATTATGACCATCAGGGTTCAG
ACCTCAGCTCGACCGGAGACCAGCCTGCAAN
TCCCCACAGCCCTCCCTAAAGTGG'TAAAAG
IM000389 ACAGAAAAGAATTAAATATCTGA 723 R GATGCACTAGCAAGA=rIGCTGAAAGGACCC IM000390 AGAT 724 R IM000391 GACACATACAGACACATG 725 D GTAAATGTATTAGGT-rCAGAACTGGCACTGCT ICACTTATGTTCACAGTTG1TTGGGTAAAACTA
GAACCAAACACAAAAGCAAAAGAGCCAAGCA
GCAGAGCAGGGAGCAAGGGGCTTGGGGAAAA
CACTCACCTCTGTrGTGTCTTCTrCTAGCTGTC
AGGGCAT'TGAGTGGCAAGGAGTGGAAAGGAA
C=TGGGCA1TCCGAGTCAGGAAAAGTGTAGC AAAATAACACTATGGAGQTrAGCAAGTGTTCT IM000392 AGACGGGCAGAATAAATACATG 726 D
GTITAGGTCATGGTGGTACACTCTCCAAGGA
CAGTATAAATrGATTTICTGTATCCTTCTT TGTTC'rGGCCATAAGGCACTrGGAGTGCATT
AATATGTACTTATT-ATACTATGTC=TTG
TCMIGGCTrAAAAGAAACAGGGTCAAGTGAC IM000393 CATG 727 C AG1T~rC1TAAAAAAATAAAGTAGGAATGAA
ACTGGAACAAAAATGCAATAAATI=AAAGC
IM000394 ATCACCGCTAAAACATG 728 D IM000395 CATGA'r=CAGTn7T'GCCATATTCCAG 729 R
GAGAGGAGCCTGGGGAAATGAAGGT
CCAGCAACAGGCCCAAAGTGGGATC
CAGCTLTAAGGGGAGGCCCCAAGGCC
TGACACTATACTGAGGCTATGGAGC
1M000396. ACTCATAAAAATGGACCCAGCATG 730 R IM0003 97 1CATGGCAGCCTTGGAGTATCAGGCTG r731 1 D
CTG'ITCCCAATGTGGGATGCAGAGGG.
CACTGCCAGCCTGGTTATCACGCACC
ACTGTCACACAGGGAAGCGCCCCY[
ccc
GGAG'J-TCTTCT'CAATFAACAGAGTAAAMTC
TCCCTCAGCAGTTCTCCCAGGAAACCCATAj\G IM000398 CTAGCCATG 732 D
CCTTAGATGTTGTCTAATCGACAAAATACTI'
IM000399 TATATGTGAAAAGGAAAGCATG 733 D
AATAATCAGATITCCAGAGCTCCCAG
GAACTAAACCAACAACCAACGAATA
IM000400 CACATG 734 R ATCCAGTAATCATTCATCTrATrGTrCCACAC
AGGAAAACCTGTAATAGATGGUTCATCAGCIT
TATT'rATAACTICTATCT-rGAAAGCAACTGG AATGCCCTTCAGTrAGGTFAAGCAGATACACITAG
GCTCACCTCAACTATAGGCACAATGAAAGGA
ATGAAATGTCAACTCACGAAAGGTAAGTACA
IM000401 CATG 735 D
CCTGGCCATATTTCACGTCCTAAAGTGTGTAT
TACTCA3TTCCGiTGAY=FCAG1YFFrC'CGCC
ATATTCCAGGTCCTI'CAG'GITCATTTCTCATT
1T-rCAAGFTTAGTGATFCGTCGTTITCA IM000402 AGITCGTICAAGTGGATGTITicTrCA=h1CCATG 736 R
CATGCAAGAACAGGACAAATGTCTGTGAAGA
AAATGAGTGAGCGTIGAACAGGAGGTCAAGGA
TCCGGTCCCAGGCAGCTCTCAGTCTrGGGCAAG CATTTCTAAAC1TGCCTTCCT-rCCTGTTFGGGG fgJ3/Fg/ IM000403 GTGAAGGTCTG 737 K 4
AATAGGAGTAGATGAGAATGAAGAT-ITCA
A1TI'AAAGGACCAGCAAATAGCTFFCAGCAAA A'rATAGAAGAAAACTTCCCATACCTAAAGA IM000404 AAGATGCCCATG 738 R CATGCAGCCCCA'TAGTGATTGATCCTGTfrCC IM000405 ATATAA 739 D
CATGGGCTCTCTGCTGATAATGCTGA
GGCTG7TI'FGTGCTGTAGTCTGCGCTTr
TTGCGCCCTCTCAGAAAAACTGTATG
TCATAGG3AGTITGCTGGCTATTGGGTA
CATAAGCAAAGCCACCCTA'ITGTGCC
AGTGCCTITAGACAGTGAGAGAAGAA
AGGCCCCTGGTTAGAAATCTTA'rCAG
GACTGGGAATGTAACTCAGTITGATAA
GAGTGC'ITGCTFAGCGTGCACACAGC
CCTGGG'ITCAAGCGCCTAGTAGTACA
GAAACTGAGTGTGGCTTCACACACCT
GTAATCCCAGCACIYFGGAGAGATAGA
TGGAGGAGGATTAGAAGTTCAAGG'TT
I M000406 IATC1TTAGTCACATAGTATTGGTAGG 740 1 R I
CAGCCAGCCTGGAATACTTGAGATAC
TTACAGGAAGGAAGGAAGGAAGGAA
AGAAGGAG*3GAGAGAGGACAGGAG
GAAGGAGATAGATATACACAGAAAG
AGACAGAGAAACAGAGATTCAGGAG
ACAGAAAGACATACGGAGACACAGT
GAGA
CATGTGGTTGCTGGGGATTGAACTCAGGAGCT
CTGGAAGAGCAGTCAATGCTCTTAACCGCTGA
GCCATCTCTCCAGCTCCC'I=AGACTrCTTAG TAGCAGCATAATrCTTGCTrGGM~CAGTTCT
GACAACCACAGCAGTCAGGAGTGAGTAAG
IM000407 AGG 741 R CCTCATAATGT1TGTITGAGCATITU
TITAAAACCTAACTTGTCTT=GCTTAT
CTATTGTGGTITICTTAGTGTGTGTGTG
TGTGTGTGTGTATGCGCGCGTGTGCT
IM000408 CTGGTCTTCGTGCACATG 742 D ATrGTGACATCTTAGGAGCTTAGGTTGGTCT
TCGAGACACAGGGCTGTCCCTGTAAAGCAGG
TTCGATCAGTGACTCCAGGGTI=AGCAGTrC AGTGGCGTAGTI=CAGACTGCT'rAAGATJTTC
TCAAGGGCTAGGCGTGGGGCAGAGACGCTGC
AGACCTGGCTAGAACAGANGCCCTGGc3AGA FgJ3/Fg IM000409 CAGTTGAGGGTGCTCAACTGTGGAGGACATG 743 K 4
CATGTATGCACAACCAAAACT-TATAAATATGA
GAATrCACTrATAGTCCTAGTCC1TAATACA GAATrrAGCArTCCGATATAAAACAACAGATr IM000410 AAACCCCAACAG'ErAGAATAGAGCAG 744 D AATAGGAGTAGATGAGAATGAAGAT17TCAA CTTrAAAGGGCCAGCAAATATCTrCAACAAAAT AATAGAAGAAAACT-rCCCCAACCTAAAGAAA IM000411I GAGATGCCCATG 745 R
CATGCACAGCCTACTCCTGGGTGATGGTACCA
GCTCCAGCCTCTGTTCTGCACGCTrGTGCCTTC 1M000412 AACCTGGCAACCTCC 746 K WntJ
CATGAAAACCTGTCTCAGAAAACAAAAACAC
G'ITGAGAGCCAGCATAGAAGGCATAGGAGGT
AATGTGTGTGTGTCTGTATATATGACAAGAGC
IM00041 3 AGACCTGTGCTGAACCAGTTAACTAC=r1G 747 D CATGCTACTAACCAG11TGAGGCAGTACCAGT GTTrGAAGATGCTGTCMI7ATCCAATGGATGG
TI=AGCTCCTTGTCAAAGATCAGGTGATCA
TAGGGTGTGAGTTMTrrCTGGGTCTFCAGTT ATATTrCCAT'rGATCTACTGGCCTGTAATTGTA TM000414 CCAATAC 748 R GGTrAGGAATTCTGGACAGTTGGTACT'rGGTT TGAATATAGTAGGTGACAAGCTGTGCCTrGAG IM000415 ITGGGGTGGCAAGCAGGGrrCTCTGCAGCAGG 74 C 220
ATGCAGTGTACATG
CATGAAAATGYFAAGTCCTGACAGACAGGGT
GCCATCTGCCAAoAA'YrrGAGTAATCTAGKA IM000416 CAGAAAT 750 D IM000417 CATGGGGTFTGTGGATCTG 751 D
CAGAACAAATAAGCTGGAAAGGATGAAGCAG
CCACAACATAACTGCTGT-rGGC'TCTTTGTGT ACATT-1TAAACC1W[CUCTGAAAGiAGTGACCA ATGCTI=AACTGCTGAGT'rATCTCACCCGAC ITACTIYTCTCTCTCTCTCTCTCTfT-CC1TCTFrC CTAAAATrAATGT3TGTGTATGTGTGTGTGT GTGTATGAirCAGAAACC7hrATGTGGTGjGT IM0004 18 AGAAGACCATCTGCAGc3ATTCATG 752 D
CATGGTCCCACAAGCCTAGAATGATF
1M000419 CGTGGAT 753 D
GGGGTCCAGGAGAGAAACTTGAGTC
IM000420 ATG 754 D GGAAAGAGATIAC'TCAAGACCAACTT-rACCAC C1TCA1TrAGCCAGGACTGCTCTATrC1TCCT ATI'ACTGCTAAGAAACAAGATrCC1TGT1TCT
TGAGATAAGAAACGGGCATAACATCCTATCT
IM000421 GGTGCCATACTCACCAGACCATG 755 D GTCCTCCCAAAGAATAGTGTrAACTGAGCTC T'rTGGGTGGCAATAAATGAATTGCTCTGGTGG
GACAGGCAGTGCACATATGGGGAGGGGGAGA
IM000422 CACATG 756 D 1M000423 CATGTTC'JTACTTCTTGTrG 757 D GiGGTAITATGAATTATATATATATGTGTGTATA IM000424 TATGTATACAGGCATG 758 D
CATGCGCCCTAAGACTCATCTCCACGAATGAC
GTGACGACCTAATTGCATCCT-FCTAACCCAC
TGATTAGGCAAACCACCCTCCAAAGGGCTCGC
TGAGTI'CcCTC1TCGGGAAGAGGTGTGTTGAGT IM000425 ACGCTGGAATGGATAT-rCGAGGGCTGAGG 759 R CATCTCTCGAGCCCTTGCCCAGCCTTVIC~r AAAATTGTA'WTAAA1ATTICTGITACA IM000426 CAGGTGTGTGAGTGTrGAACATG 760 D
CATGTGGACCTGGGGGCTAAGTCAGGGTGAA
GCT-rCCACAGCTAAGTGGCTGGAGGCTGCCCT
AAAAGCTCAGGAGGCACCGCAAGCAAGCCTT
GAAAAAGCTTrACCCACCAGCTTGACCTTAGAC rrCTGGCCTCAGGCTGTGACAATACATTGCT GCTGITAAAGAACCATATGGI1'GGTGAITG'1IT TTGTTTGTTTCTGGTTC'r=GTGTTGGTG1TI- T'rGCGGGGTGTGTGTGTGTGTGTGTGTG TGTGTGTGTGTGTGTGTGTrGCAGTGCTAGAG Fg/3/Fgf IM000427 ATAAGATCTGA 761 K 4 GTCTAAAG1T=CAAATGATGGATAAGrrTGTrT
AAACCTCCTIAAGATCTCAAGCACAAAAAG
AAAGACATGAAATACGAATAGTAGAAAGGAA
AGGAGA1TfCGAACTAGAGGGCCCCAAGAGTC ATAAAGAGAAGAA1TAAACAACTGTACCCA CAAATTCAITAGCATAGATCAAGTAGTCCA1T IM000428 TCT7CATG 762 C
CATGTATGTTCTCGATGCCTTGGCCT
IM000429 G 763 D
AAAGACATTAACTCTTGAGAACCAAGGGGTA
GGACAGTATAGACTGAA=IIGCCTCCCCTCT
TCATAAGTrrGTCACTGCTAACCTCATCAGA IM000430 ACTTAAGCATATAACC1TCATG 764 D-
CATGGAGAACTAGCAAGAGCAGGATGGCGTT
1M00043 1 TCTCTAGAATGCCGTATAG 765 D
CATGGTGAC'ITCCATCMTAGAACCATAATC
IM000432 ANGTTAAT 766 D
CATGCTTATATCCCTCAAAAAT]TACAGTTA
AACTGAAAATGCTrACrACTTTITCTTAC YTATATCTAGTATCGATAAGAACfrGTCCCAAA IM000433 GGACAC 767 D
CTGGGTCITAGTCCTCTGAGGTCCCTAGCACA
TCAGAGGTTCATCAGTTCCAAGAGATGACACA Fgf3/Fgf IM000434 GCCGCAGTCATG 768 K 4 CATGGAGAATGCACAGTCAAAACGC1TGCAT IM000435 CCT 769 D
CACCCCCTCCGCCTTACATCAATCC
TGGGTGCACAATGGGACTGTGGATGA
CTGATGTCTGCGCAAACAACTfGCGG Fgf3/Fg/ IM000436 GGAAGTCTAGCTGACAAACGCTCATG 770 K 4
ATGTATCCAATGGCAAAGCACGGGGOAGGCT
TCATC=GAAGAGAAGAGTGCTCTTGGTAGGC
TATCCTITITrGAGACAACTAGAAATAGGAG CAIT17CAACAATCTGGACATATGTCCTCCCAC AAGAACTrG17GAGAATGGGTCTGAATTAACT GGAAATAAAAGTGAACACATrCTCCTATACAC IM000437 ATG 771 D
TCACTCCATTYAGTTCAAATGCTAC
AACTCCTTTGAGCACCACTGTCA'Tr 1M000438 CAAGACC'FrATTCTGTGAATACCATG 772 C CATGCTTAGCCCAGGGAATGACACTATrCGAG GTGTGGCCTrArJ7GGAGCAGGTGTGGCCTrGT
TGGAAGAAGTGTGTCACTCACTGTTGGGGTGG
GAMrGAGAGCTrCCTCCTAGCTGCTTGAGGA IM000439 TGCCGGTCTT 773 R CATGAGCTGGGTGAACGACAGCAAAGGMTG Mm.202 IM000440 M~CTCITIAAGGAAGACAATGGTGTGAAAT 74 B TGGTTrGATCCTITGGGGGAAATG7ITGGCCCCT
T
CATGATCTCACTGTGAGGGCTGGCTACCTTGG
AGCTICACTGTACTIGAAA'I'AT[IC'GGCCGAYFG
CCTC3TCGCTGGTr7ATGGGCACACACAGTIA CTrGTCTATGAGTCTITGTrAGGCTGAGCCTA
GTGGTGCAGGCCTGTCATCTCCCCTACTIAC
1M000441 TITAGGCTCTGAGGCAGGAGGAT 775 D
TCTGGTAACTL'GGGGGTCTGATAAAA
CAGTTGGGGGATITCTI=CflCGC
GTCTGAAGCCAATGTTATI'ACAGGTG
TGTGCTTGTCTCTCCCACACCCTGCCC
CTGTTGCCTAACACACGCGGCACACA
IM000442 CATG 776 D CATGACTCTlCCTCCAGAGTTAGAGGTGGAGC
CAGGACAAAGTCTAAAGAAAAGAAACCCCAA
TrcAAAAAGGGAAGCTGGTATCATCCAACCTTI 1M000443 AAATTACTCCACATCCGTCCAGAG 777 D
CATGTCTGTCCCAAAAGGAAGTTCCFICCTCT
GTCCTCCACATCTGACCAGCACCATCA3TCAA TCTGCAACCCAAACCAGACATTrACATCATCT ATGCCTCC1ICCTGCTTGTCTCCCCTCAACCA
GCACCCAGCAAGCTYCAGGTATCCCCTTAGT
GT7GTCAGGATCTCTCCAGT7CTCCAGACCCC 1M000444 AATTCTGTrCTCACTCTACACTGCTAGC 778 D AAAGCTAACTTrCTCATCACCTACCTAATAGCC TGAGAGCCCTGTGTAGAAAAAT-7AAGGAGTTI' IM000445 AGTTCCY[-CATG 779 C
CATGCAGACAAAGTAAATAAGAAAACAAATTI
IM000446 AAATGTAOGCTGGACGOATAGATGGT 780 D
CTCAGCTCCTAGGCAACAC'TGTAGACCCACA
GCCCCTTCACACACACACACACACACACACAC
ACACACACACACACGGCTGGGGATGCAACCC
ATCTCGTCC'11I'ACACGTGCTCTACCATCACAC CACACATTTCCAGCAC1TTATCTGAAGT'GMh IM000447 CC1TIA'rGTGCATG 781 K Wnt]
CATAACCACTATAACCAGCCTGCTTACYTGGC
'TfGTTTCGAGGGC=h~GTIAGAGCTCM~ CTI=rACCCTTCTCCGTGTGTGTGTGTGTGTG
TGTGTGTGTGTGTGTGTGTGTGTCTGTCTGTCT
IM000448 GTCTGTCITGjTCTGTCTTAGTrGYIG'L'ACATIG 782 C CATGTGGTCCACGGTI1ACTTfACTAGGGAG
CAACCTGTACCACAGGGAGAGAGGCCTAAGG
AGAGGAAAGGAGCTGACCCAGAACTFGAAAAG
IM000449 GCACACACCATTCTGCCAGCACTTCCC 783 C CATGTCCTACAGTGGACATI-IrfCTAAATrCCC FFCTf1TCAG=1CCTCGCCATATTTCACGT IM000450 ,CCrAAAGTGTGTATCTCTCAFI=CCGTTAMh 784 R TCAGGTATCTCGCCATATTCCAG'FrCCTACAG TGTGCATCTCATTCTrCACG1TI1CAGTGA TTTCGTCATITTATCAAGTCGTCAAGTGAA1Tr 1TrCAT1TTCTCTGA1TICAG=TICTCGCC CATGTrGCCTCAAGACAGATCTCCACTITTAAA GACATAGCTAAAGGCCTGGAAGCTrAGTCAAT TAAGC17CCTGCCCAGACACTCCTCCCTGAA
AAAGGTA'ITTAACCTCAGGCCCACCCTGAGAA
IM00045 1 GTGGGOTATGATI=ACTCATCCAcTrrc 785 R CATGGTrrCTA1TACTGTG1TGAAGCACCCTG ACCAAAGCCAA'rrGGGGGACGAAAGGGTITA TrGGCTrAAAC117CCAAATCAGTGTrrATCAT IM000452 TAAAGGAAGTCAGGGTAG 786 R
GGAAGTGTCAGACGGCTCTCAGGGAGATACA
CATAGC1TJAY[GGATAACTGCAGCTTGAAGA IM000453 CATG 787 D CATGTACCTATGTGTGTGTAAGATITFGCCTAT'r T-rCACACAG1rAAGAAAGCATCGT'rATGAAAA TCATTACAACT1rCCAGATAAACAGATCCACT ilI000454 CAGCCACAGAT 788 D GCCC1TCTCTCTGAACTI=CAGTTrCCTGGATA AAGTCAGTGTrCCACCTCTATACCTGACTAGT IM000455 TTrrcCTAAAT-CTGAGTCAAGCATATT-rCATG 789 D
GACCTCGTGGGCGGGCCTGAGGAGACAGTGC
AGATGAGGTGTCAGTAAGGAGGATGGAAGCA
AGAAAGATGGAGGAGATGATGGAGAAGCTGA
AGAAGGCACTGAAGAAGGCACAGGGAAGAA
IM000456 GAGTGCATG 790 D CrGCCGTrGAGAGCGTCCAGATCCCCTGACT TGAGTGGGTCCACCTrGTITTGG1TrGGTrCGC IM000457 AGTGTCGGCTGTGGAGCCCCAGGCCITGCATG 791 C
TTCTTAT)CCACTGAGCCACACTGCTAATACTG
IM000458 TGATGTC1TITIAAGACTCACCATG 792 D GGGTTCAACACATTMIGGAGA1TGATCAAAA 1M000459 TTAAAACATG 793 D
CATGAAGGAGAGTCTGAGGCTACATCCACCA
GGCTCTATGATCTCCCTCTGCTGCATCCAGGA
CA1TCTCCT'rCTGGATGAAGATGATGCTGGCG
CTGGCGCTGGCGCTGACGCTGATGCTGCTCGC
IM000460 TrrCTGCGTCCT 794 C
CCYJIGTCCTCAAATTACAAAACTCCC
TAGGGTCTMF-CTCTGGGCTACAAAA
TTCTGCAAATGGACTCAGGAGGAATC
AATGTGGAAATrCACTTrGCITrCC
CAATCAGCAAAATAATG'IMGCCAAA
ATCGT'TAGATTCTFrCCCCTAAGTAGA129 GCTACTGCCGACTTGAAAGCAGTGGTA429 IM000461 ITCCAGAACCCGAGCCCAGGGGCTGCC 795 B 8
ACTFCCTAITGCATG
CCCTTGTCCTCAAAYITACAAACTTCCT
TAGGGITLYTLT1TGGCTNCAAAATT
TTNCAAAGGGCTTCAGGAGGAATAAT
GGTGGGAAA'11ACTHGCTIrTCCA
ATCAACAAAAAAATGGTTGGCCAAA
TCGGTAGAAflCTITfCCCTAAATAAG
CTACTGCCGACTTFGAAAGCAGTGGGT
TCAGAACCCGACCCAAGGGCTGCCCT
IM000462 1ITCTATGCATG 796 D
CATGTATCITAAGAACAGAGCCAGTGCTCTCC
IM000463 CTCTCCCAC~rGAT 797 D
CATGCAGANTAAAGTACATATATGTAAAPAAA
IM000464 TAAAAATfAAATGTFFF 798 D
GTGCTCTCCCTTGCCTCTCCTCTCCTG
AGTITTCTCTGTAGGTGTAAGGGCTGG
AGGTGGGCCCAAGAACCAGAGATCA
GAGGAGGGAACTTCCGGAGCAGAGG
CCCTGGGAGCAGTGYFAAGCAGGCTrr
TGGCCAGGI'CTGGAGG'I'GTCCAGGCA
GGGAGGTGGAGCTGGAAGAGACCAA
TTAGTCAAACGGCTGCAATTGGCCAT
TTGGAAGCAATTAACAGGGTCTCCAT
TACCATATI'ATGCCCCTCCACCCCCTC
CACACTCTACTAGGCTCTGCTCTGTA
TGGAAGGGGGAAGGTGGAGGCTCAN
CTCAAGCCAGGGAGACTACAATGGA
GGCCCAGTGCTCGCCAGGATGCACAC
ACTCAGGCACCCTCCGTGTGAGGAGG
GGAGGGCAGGGCAGCATCTGAAGCA
ACCTGTCATTCACAGCCTGANAGANG
GTGGGAACAANGGCTTNCAAAGCCA
AGAANGCANGTGGNTAGAAATGCAN
GAAAACCTCTCTGGTAAGAAAGGC'I'G
AANGAAGCAGCTAGGGTTrGTAAAAC Fgf3/Fgf IM000465 AAGANCAT 799 K 4
CTCCCTCTCCCTCTAGCTGCICCTAGCAGGGGC
CAATACAACTGCAGGGAATCAAGGAAGAGCC
rL=CCTGAACTGTCCTGGATGCCCCAGTCCA ACAGCAACTCCCAC'FrGCCCTGGCTTGG1TG
CTCCACTGT'CCTGAAGGCACAGTGTGATATCC
CAGACCTCCAGCGAGACAGCCCAACCTGCAA
GCCTGATGGGAGGGGTGGCCTGAGACAACA A15 5005 IM000466 GTACCTACATG 800 B 7
CATGGACTCCAGGGTCAGGGTGTAAGAAAAA
GGTGGAGCCTGCTAGGTGTGGTGACACACAC
CTIfTAACCCCAGAACTCAGAAAGCTGAGGCA GGTGACTIAGCCAGGAGTTrCAAGGTCATCTAGT TCATCAGATCTATAGAGTGAAACACGCCAGGCT F]/g IM000467 ACAITGAGATC 801 K4
GCTCAACACTJTAAAAGCGCCTGCAGAGGGGT
GGGGGTTrAATCCCAGCACACACATAGTGGG TCAGGGAATCTGAAGCCCTCTrCTGGCCACTG IM000468 CGTGAACTGCATG 802 D
GTGGGAAGCTATACGAAAGTAAAACACACTC
TAAGAAAGAGAACAGGCTGCCTGGGAGAGGG
AGGTGCCAGGGGCTTAGACAGGAAGGTAGTT
TTCAAAAAGTGAAAAC'ITAAGCTATCTGAATG
AATGATACAAAATAAAAGAAGACACAAGAAT
TrCCAGTCACCTGAGATATCTCACACTCCTGT
TCTTTCAACCTTCTAGCTGAAAGGAGAAAGAG
IM000469 CCATG 803 D CATGGAAGGAGTrACAGAGACAATGMTGGA
GCTGAGACGAAAGGATGGACCATCTAGAGAC
TGCCATATCCAGGGATCCATC1TATAATCAGC
CTCCAAACCCTGACACCATTGCATACACCAGC
AAGATI=GCTGAAAGGACCCTGATATAGCTG
TCTCTTGTGAGGCTATGCTGGGGCCTAGCAAA
IM000470 CACAGT 804 R CATGCTTrAGATGACCGCAATATGTGTGGTAC TCTrCAGAC1T[AAAGATTTGCTGAATATCCT ATI'CCCCTrAAATTGTGATCACCCTAGCTAGA TCTAATCTrAGATCTCGAAAGTTCTACAATTT GCCTCAAMTGArrAGTGTI=CCTCCTTGAAG IM000471 AC 805 D
CTTGCCTTGGGAAGTGAGGGGTTCTAATGAAG
GTTFGCAAGCCTGTCCACCCAGGGCCCTGCTAA
AGAAGGAATGGTCCCCAGCCTGTITGTCCCC
TCTGTGGCTTCTrAGTTCTGGACACTGAGCCA GTCTGGGCAGCAGGCAATrCACACTGTGAATT
TCTGTGGAAAGCA=IIGGGGGTTCTGAAAGC
CCTGTACATrCTGTGFAAGGACAGAGGGCCT FgI3/Fgf IM000472 CCTGCATG 806 K 4
CATGGGGGCTATGTCCTAGGGTAGACACCCCC
m7ATCCCTCACCTCCTrCCCTGTCTrAGCAGT
GGTGTCCCCCACTGTGACTCTACTGCATCTGG
GAGCTGTCTCCCGGGGGACTTCCTCCTGCTGG
AGTGAGTAGGTGGCTAGGGCGAAGCCTGTGT
AAGAGGCAGGAGGTGTM~GCACAACTCCAA
AGGGTGCAGATCCTGCTGGCTCCAGCTrCCCA FgJ3/Fgf IM000473 GGGCCAGACCCCCAAATACcc1TCACCCAGC 807 K 4 GTGTATGTrCTCTGGTGAAAGTGTrAACCAGC TCACTCCGTGAAGAGCACGCTGCTrCAGATC AGTGTITCAGAGTCTTGAATAATI'GGTI1TAG
AATCATAAAATTGCAGTCCTITACAAAGGACT
IM000474 GGAAGTGAGTCATG 808 D CATGTGAATTCTCTATTrGCAATGTGCTTGGT-r GATACTrCCATACTCTACCCAGAGCCTGTTAG IM00475AAAAATCACTC'TCCCCACCCTATrCTTCACC 1M00475AGTCAATATGTATCTAGTATTCTAAACITCCT CCCTCGTAAGGjCAGjTGGGGAAG
CATGTGTACTCTCACCATCAGAATFATGAGGA
ACCCACAATTTCTrCACATTTATAACTGAGC AGI'cTIGAGGTIArFrGCC'I-1-AGCAACAGAAA IM000476 CTGAACTCAAAACAATCGGCACAC 810 C
CCATIATCAGACCAACC'ICCCACACAACAGTA
GGCCACCAGGTGGGGGCAAAGTCCTGGGTAA
GG1TIC'TTGGCACTGTAAT1TGAATCCCAATA IM000477 ATAATGACTGTG'I1ATTTGCTCATG 811 D TAAAACC1TAGGGAGCTGATAAAAATCTATC AAAACAACACTcTrGTCTCTCGTATCCAGCCAT 1M000478 CCATG 812 C TCTGCCCAGCC'FflTGCTrCCTFCCCTGGTAACA AA 1177 IM00 0479 GGATGCTAA'FrAGAATTCATG 813 B 84
CATGTAAAAAAAAACTTCAT-TAACAA
CTACAACAAAGCAGAGACC'GGCCC
TTGGATTGGGGCCCCTCTGAGAGCTA
IM000480 TAGGCTGGGATACTGG 814 D
GTGCGTGATAACCAGGCTGGCAGTGCCCTCTIG
CATCCCACATrGGGAACAGCAGCCTGATACTFC 1M000481 CAAGGCTGCCATG 815 D
ATGTCAACATTGAGTCCAGTAAGGACATCGTA
TATGCTGGTCA7FrATrATAGCTCrfAAGGGTrC
ATACATGAGACAGACCACCCCCTI'ACCCCCTC
CCCCGTCTGGGCTAAAAGCAGACACACTGGG
IM000482 TFGGTGAGAGAGCAGCAG 816 K WntI
CATGAGACAGACCACCCCCITACCCCCTCCCC
CGTCTGGGCTAAAAGCAGACACACTGGGITG
IM0 00483 GTGAGAGAGCAGCAG 817 K Wntl CATGAGAAAAATrGTCTCTAATTCTCT'TGYI GAATFMrGTGTGG'I1TIYGA'I'ATICAGGTGA'' IM000484 GTGGCCTCATACAATGAATGTGG 818 R CCAGTGAAGTAAACCCAGCAGGACCC1TPrAC 1M000485 AAAGCCAGGACATG 819 D TCGGGGGAAAGITIAn'TITATACCYFCCCGCT CTGGATrAAG(GGAGGGTAGGAAAGGATrGGA
TGAAGCTAGAGACAGAGTGGCAGGAAGGTGG
TAGACCTGAAATTrGTCAGACAACCACTTATCG YI7000AAGGGTATAAGGTGACCACAGCACTA GCAGACTGTrc~iGGACGTAGTAAGGAG'FI'CCT GCAGGGGAGGAGTGGGTCAGCCTrGAATCC IM000486 CATATGGTGG'I1TCACAAGTCAGCCTACATG 820 D CATGTG1TTTAGCAACTGTGCTCATThITCTGC
TGCTGCI'AGGAATAAAATCAAATCTAGTANA
A'ITGCT'1TAATACAAAGTTrATTGTCATCCATCT
CTGAAGATCTGAAGTATTGCTOGGGGGGTCTCC
1M000487 AACTCACCGACC 821 D
CAAGGGCCTCTCCTCCCACTGATGGTCGACCA
GGCCATGCTCTGCTACATATGCAGCTAGAGAC
ACAGGTCTGGGGGGGGGTACTGGTTAGTTCA
TATTGTTGTCCCTCCTATAGGGITGCAGACCA
CTTTAGGTCCCTGGGTACT-rCTCTAGCTCCTT CA'TAGGGGCCCTGTGTrCCATCCAATAGATG ACTGTGAGCTTCT-FATAAGCATAAAC1TCAC IM000488 TTACCACATG 822 R CATGGTGTrAGCCTCCAGGCAGGAAGCATACC AGAGGAGAACTCCACAGGAAGCC'rrGrr GTGCTGTTrAAAAACAAAGTATGATGGGGCTA
GAAGAGGCTTTAAGAGGTCCTCTGGAGAAAA
IM000489 GAATCTATTTTCCAT7 823 D
CATGAGAGGTTTAAGTCCTGAAAGACCATC
ATACCTAGAGTCTATACAACAAATAAACTTGG
AATACAGTGAAGCTAGTAAAAATAACrCCTG 1M000490 AGCTTATGG 824 D
CACAGTCAGGAAGCAGAAAGATGAACG'ITGA
CTCTCAGCTCTCCTrCTCCCTAGT-rCTATGG Fg/3/Fgfr IM000491 AGGTCTCCAGCCCATG 825 K 4 CATGATAAAAGTCTTGGAAAGATCAAGAA~r
CAAGGCCCATAAATAAACATAOTACAAGCAA
TATACAGCAAACACAGTAGCCAACATCAAAC
TAAATAGAGAGAAACT-rGAAACAATCCCACT
AAAATCAGGGACTAGACAAAGTTGCCCACTC
TCTCITAACTGTTCAATAGAGTACTCAAAAT
IM000492 CCTAGC 826 R CATGGTAGCTrrTCTAGTGAGGTCTCT IM000493 TCC 827 D
AGTACCCTTAGCCAATAAACCATCCCTCTAGT
CCCTGTTT G II II TAAAGACAGG Fg/3/Fgf IM000494 GTCTCACCATG 828 K 4
CATGAGCTAGGCCATCTGCAAGCTGGTCTCGT
CrrGACCAGGAGTACACAGAAGCCTGGCTCA IM000495 GGACTTGGTAAC 829 D GTrGMTATGCAGATCTCTCAGCGUTAGC(AT CTATGGGA1Tl IGGAAGACCyf-CAGTl ATCTTCCA1TTCTGAGGCTGMTCTAGGCAAC GGAGTGGTACCCTFIAATCTnCCCCTGAC C1TICTGCCTATGAAGATG'rrGACTAGTGAG CCCGTGGGGATGTGTA~rATCTGnACAMA MIATGGC1TGGTAGCGACTCCTG~fGTGT'G 1M000496 TCAGCTrCATG 830 D
CATGCCTCCCTCAGCCTCCTCCCACC
CCTI'CCTGTCCTGCCTCCTCATCACTG
TGTAAATAATrGCACCGAAATGTGG
CCGCAGAGCCACGCGTTGGGTTATGT
AAATAAAACTAMrATTGTGCTGGGT IM000497 TC 831 K WntJ TCTAAGTCCAGTC=rCACACACACTGACrlTF IM000498 GGTCATCTGTAATCACAACArIG 832 D GATGCACACAAACTGGCCCTGAACmprGAC-r TCCAGGCCTC'rGCCTCTCTGCGCGCACACACA CACTCGCAC'ICCTIGTATATGAAGCGTATATGT Fgf3/Fgf rM000499 GTYI7CTCTGGGAACTGrITIATCAGGTGAAG 833 K 4
GGGCTGAAGGAAAATG'TGTGTCATC
IM000500 YT7GTGGCATG 834 D
CATGTACCACTT[GCTAATCCCCTA
AGCGCCCCTTGGTAAGCATCTAAAGT
GATATATCTCYJIGGTCTACTGAAGTT
CTGCCCTGTCTCCATCGGGGATTCTC
GGGAGGCTAAAA'ITATAGACTAYTTG
IM000501 TGAAAG 835 D 1M000502 CATGTCCTTATGATATGGAAAAA 836 D
CATGTGCGAAGAGCCATTACAGGCTC
AGACTAACATCTGCCTGTAAACAACG
GTTGCTAAGTTCCAGGGAAGCGTAA
IM000503 G 837 D CCAGATGACCTTGAACTCAGAGATCTCCfl-TGC C'ITAGCCTCCTGGGA~rCATAGCCGCTATIGCC 1M000504 TCAAGATCTCCATG 838 R
CATGTAGITGCAAACAAGACATCCCTIGGTAT
IM000505 ATCCAGAACC'rGAGCTATGC 839 D GGATATAGTGTCAAACAGTCTGATGTAT-fCA'I' AGGTMGTATCCATAGTTATCAAATrCTC''CAT 1M000506 G 840 D CATGTACCACACACAGACTrGGTA.AI'AGTTA GATGATAA1TACAAAAGCAACAAAITAAAACC 1M000507 AACAAAACAAAACAAAGCTTGGTAATA 841 D GT'rAGGAGCACGAACI'GCTC1TCAGAGGACC 1M000508 TGGGMTAATTFCCCAACACTCACATG 842 R CATcGICAA'rGATAAACA'FrCCAAAACACCA AAACCATCCrCTCTGTACAGGCTATGATGATr CAACTGCTGCCC7ZrCCTCAfflTCTTGTTCCCAA IMOO0509 CTCCTACTGAATATTTCCTGCAT 843 D
CATGATAGAAGACCACGTCTGGGATGGGGTA
AGGGM~CTCAGAGTACCTfGCCCTGGGGCCA IM0005 10 CATCCTAAATCTACAACAAAGCTGACCCTA 844 D CAAGT1TIGTAAGGGAGCTAAGAAAGGCATT OTTGGTFAGG'TrGGAAAGAGGGGGCAGGACC
TGGCTCTCGCTTCAGCCCACTCCCCTCTGCCCC
CCAGCCTCAAACACT1TACCCTAGCATAGCA IM000511 GAAACATG 845 D W00012)CATGAACTCAGTGGGCAGATGAAGAGfyI=G 84K 1M005 12TGTGAACTGGGGCTIrrGCCCTTATCATCCTGT 86 K FJ/g GTGTTCTCCTGGTGACCCTCAAGCTTGGCTGC 4 AATGATCCCCAC1TACAGAT
GTTTAITACTCCAATGATTCGCACAGCCGGGT
TGCAAGTCTAAGGCAGGCTGTCTGCCTrCCTG GAGGTACrACCCCACCTCCCCCTCTGGGGGA IM000513 GCTCCACTTGGCCATG 847 R CATGAFICrAG1TTGCCATAT-FCCACGT TCTACAGTAGACAflCTAATCCAJLCTp' TTCAG1TrCCTCGCCATA1TTCACGTCCTAAA GTGTGAAT17CTCATTCCGTGATITCAGTF- IM000514 TTCTCGCCATATTCCAGGTC 848 R GTAACCACTCA1TACCTGCCCCAATGATGTC TGGGCCAAGGCACTrAAATrCATATCTACT IM000515 GTGACTATAGGTGCCCATG 849 D CATGACACTGCTCACTGTrGCTCTCTAACCn IM000516 GGTCCAG 850 D GNGCTrGGCAGAGTAGAGAAACTC1TrGGGA IM0005 17 AACTrGGTTCAGATCCAGACATG 851 C CACCTCTGCCTCAGTirTCCCTGATTAT IM0 005 18 CAACAAGTGCTCATG 852 D
CATGTAACTCAAGAAAGTGTAGTAGGCGTAGT
GGTAAATGCCTrTGATCCCAGCACTTGGGAGG TAGAGGCAGGTGGGATCTCTACA~FlC&G
ACTGGTCTGGTCTATATAGTGAGFTCCAGGCC
AACCTCACATrGAATrCATCTCA4ACAAT IM000519 AAAAATAGAGGAAGATATAGTCAGGCAC 853 R GAAGACATTCATTITI=CTrGGGAGGGGATA 1M000520 GAATCCAAGGCTCCAAAGCAGAGUTCATG 854 D
GACCACGCTGGCCTCGAACTCAGAAATCTGCC
TGCCTCTGCCTCCCAAGTGCTGGGAIh&AGG CTGTGCCACCACTGTGCTrACTGATCTCMIGA TGTCCCAGTTATAGCTCTTGGGflCCCCACCC A MTGTAGGGGGACCCAGGACACCTCAGAGC TCTCCCAAGTCTAAAAAGGGCAGGyrCTOG CTCCCTTAATGCCT'rATCAAGCACAACAGAAC TCAGGGGCAGAAATGrrFCCCAGGAAGAACT IM000521 TAGCTGTGGGGAGAGTCATG 855 R CAT=RCTIT7ATAGCTGAGTGUTATCCACTG CAAAAAMTGAATATrCCACTATUCTGU7GAT GAATGTTAGGCTGGTCACGTTCTTC~p.'
GTGAATGGAGCAGCAATAAACATAAGTGGGC
IM000522 ATG 856 D
CTCCATTGGGCCGAGTGAAGCTGTGGTTCAGA
GAAACTCTATGGACAAGCTGACnCCAGAAC ATrGACCTGTCTTGAGATCAACAGCGTAG IM000523 GAAAGCCATG 857 D 1M000524 CATGGGAAAGTAATCCGTGGCTAACACAAAG 1858 D
GGGAAATAAAGTAATATT
CATGTAGGACCCTGAATGCCAGCAATGAACA
ATAGCAGCTFGGTMCGGACTCTTGC'v-FrCTC CTCCCTCCACTACTAACTfACiCCTCACCG1TrGC ATCTFIGTGACTCAGAGGTCTG'rrrCCAGGC 'FrCCTTCCT-rCCAGTGTTCT'rCTAATGCATCTA IM000525 AAGTGAAGGGGTGG 859 D
CATGCAAAGCCTCTGCAGGGCCGACAGCAAG
GAAGGCCCT'rCTAGATCTCCAGCACTCIc3TcA
AAAGCCATCACTCGGGAGGCAGGCAACCACA
ATGTAGGGAAGACCTGTAAAGCCT'rCAGAGA
GGAACAGCTIGGCAGCCCCTGGGTCACTCAGA
GTGGCCAACAGCTACTC'rGTGGAGACAGCA
GGAGGAGGCCTAGACTATAGAAGGATGGAGG
1M000526 AC 860 D CATGCACACAAACTGGCCCTGAACTrrGACT
TCCAGGCCTCTGCCTCTCTGCGCTCACACACA
CACTCGCACTCCTrGTIATATrGAAGCGTATATGT Fgf3/Fgf IM000527 GMITCTGGG 861 K 4 CATGAAACATTATTfN=1fGGAAGI' IM000528 CTGCAGGTAAACTrAAATAGG'rTAJ\ 862 R AGCAAGAACAAAGGAAGTAC7FrCACCTGATA
AAAACAGTTCCCAGAGAAACACATATACOCT
TCATAI'ACAGGAGTFGCGAGTGTGTGTGTGAGC
GCAGAGAGGCAGAGGCCTGGAAGTCAAAGT Fgf3Fgf IM000529 TCAGGGCCAG'ITGTGTGCATG 863 K 4 GAT-FYTrA1TCCTFAGCATCCTGATTGGAGA FgJ3Fgf IM000530 TGCCTGGGTGCACATG 864 K 4
CATGTAGAGACTGCCATATCGAGGGATCCACC
CCATAATCAGCATCCAAACACTGACACCATTG
CATACACTAGCAAGAThI'TAT'TGAAAGGACGC IM000531I AGATCJ'rAG 865 R GACCTGTACCCTACCCTCTGATGGAGGCCA'[c TA'1TGCCTGTCCCCAGGAGTCCCCAAACTGC
TCAAAGAACAGACTGTGGGCTCTGGAAAGCT
AGCAGGITGACCCCGGGGGATGTTCTGAGCAG
TGCCTrACTGAAGFITATCCAGGCCCTAGGGjT
CCCCTCAACTGCTCACACAGCCTAGGGTGGGT
CTCTTGAGGAGTCACT'rGTCACT-TCTG1'I'GCYF
CCCAAGAGACCCAGGGAAAAAAGGAAGGAA
IM000532 GGCCATG 866 D ATCTCACTCGTrAAAATGAACAAAGGGACTGC AGAGATGGCTCTGAGCT1TfAAGACCAT'AGCC
TGCPVITCCAGAGAGCCCAGGCTTCATI-CCC
AGCCCACATATGGCAGI-rCACAACCA'rCTACA ACTCTAGTTCCTGGGGATCTCACACT1-~JGTCT TCTGTGGGCACTGCGCAAATGTGCACAGAAAT Fg(3/Fgf IM000533 ACACGCAAGGAAAACACCCATG 867 K 4
AAGAAACACTCTTAGCTGGGCCTGGAAGTGC
1M000534 ACATG 868 D CTAAAGCAGATTATrATACrrTUCTACTGAC
CATAATGCAACCACTATATATAAA&CAGAACA
TACTATAAGTGAATAACArTAGGATACAAA&J ATGTATAAAAGGGGAGAGAGGATAACCAT'rG TGAAGTATGTIAAATAAAATGTIT7GGGATn-T GAGGAAArrAATAAATrAGTACCCTnTGC 1M000535 'I1TGGGGAAAGAAAGGCAGCATG 869 D
CAGCCCCAAACCCATCAGCCTGAGACTGATGC
ACAGGAGGCAGGCCAGTI'AGT-rATTCTCTGGG CCCCTCTA I I IIGCCTrCTGTAGGTTAATCCCA CCGCTCCCAGTGCTGGAAAGTGCAAGCATrGT 1M000536 GGGAAGTTAAAAACGTGCCACCATG 870 D
CATGGACAATGCACCCCTCAAGCAGTGTCTTC
CATACAGACAAGCATATrATICTATACAG Fg/3Fgf IM000537 ACAGCAAC'FIGCTGAGGTGTAAGG 871 K 4 GGATGAAGAAGCCCkAAGGTATAGGTCAGTC TTGCTCTGACTrCTCACAGTAAAAATACAACT
CCCAGGGACTAAAATGACACAGAACAGCUTA
GCCTCTGGACA7ITGCTTFrGGATrGCAAAGTG ATAAGTGAAAAAGTAATAAGTCTATCTAGAfT GGAAAACATrTGGTAACnTCAMIAAACACAC 1M000538 TGCCCATG 872 D CATGTCCTACATTGGACATyfCTA =r~CCATCTTITCAGTT1CCTCAC
CATATTCACGTCCTAAAGTGTGTAT
TTCTTCACGTGTArrCGTrGGTTGUTGG
TTTAGTTCCTGGGAGCTCTGGAAATC
IM000539 TGAFI'ATT 873 R TGGAAAATGAGAAACATCCACTrGACGACTT
GAAAAATGAGGAAATCACTAAAAAACGTGAA
AAATGAGAAATGCACACTGAGGGACCTGGAA
TATGGCGAGAAAACTGAAAATCACGGAAAAJT
GAGAAATACACAG1TAGGACGTGTAATATGT CGAGGAAAACTGAAAAGGGTGGAGAAmIAG
AAATGTCCACTGTAGGACGTGGAATATGGCA
IN4000540 Ac3AAAACTGAAAATCATG 874 R
TGACATACAGAAAGAACACAAATACCTGTAG
CTGCTGTGACAGGACCAACCA'rrCTAAATATC
AAAGCAGCTGTTGACACCTAAGGACTGGTCTG
ACTGCTAGATCTAGGAGTrCAACUrGCAAA IM000541 GCTGGCTITGATGCTCATG 875 C TTATATATATATATCG1TrTCrnACTCCTGA 1M000542 ATCAGTGACATG 876 D
CATGTCAGCCCTCAGCMTACACAGGTGTCAA
AAAAAAACCOCGGTTC
GTCTGCCA1'rAGCTGTTATTGTGTACAT-rAAG IM000543 TAATCCGTrACCGCAT~G 877 D
TCACCCCAGTATTCAAGGAGGTGCCACAGGA
CTCAAAGGATACAGAAGTFACATA'1-'AAAXC
CCAATCTCGTAGAGGATTCAGAGGAACTAAG
TT~GGAGGGGCACAGATTGTAGTACCATTFAA
GCCCCTCTGTrCCTCGTGGAGAACCACTACTG
TCCAGCAAGGCGGGAAGGACCCAAATCAAGC
AAATGAGACTrGTTcTrGG
CATGATANATCCCITFGTGAGCAT
TCCATAGCCTCAGTAATAGTGTCTGA
CCTTGGGACCACGCTGTATCCCACTN
TGGGACCTITCYI=CNTCAGGCTACTC
TCCATF1rCCATrfNCTGTAAII'CTTTCA
ACAGAAACA'TATGGGTCANAGGTG
TGACTGTGGGAGGACAACCCCATCCC
TCAC'ITGATGTCCTGTCTTCCTGCTGG
AGGTGGGCTFATAAGTCCCTNCCC
CTACTGNCCAGCAYITCATCAAAGAT
CCCTCCCTAGGAATCCT'GGGAACCTC
IM000544 TC 878 D GATAAGCT-fATCTTGAACTrGAATGTATATGG
AGAAGCAGAAACCTGAAACAGCCCACAGA
ACTGAAGAAGGATGAAGGGAC'r*C'rCAOC IM000545 T'GGAATA'FCAITG 879 D CATGTTCCCAGCTGcJGCAAGGCCTCGGG'ITICC
TCGGTGAAGAGTGTGGACCAGCCGATFGAGCC
CTCCGACG'IOCTGGATGAAACGGCTGGC'FFrTG MTAGTITGTrTAACCTCCCCAACGAGACTr TGATCAGCTCCACcTrcGAAAATGTUCGCGAAA
GATGCGGAGAGCCTGAGGGACTGCGGGGCAG
CAACGGGCTCCGGCCTAGCCGGGCCCGCCGG A14 1328 IM000546 CCCCCAGA 880 B3 8 ACCAAGTGT[AATAATGTACTGArG'(GCyToIC IM000 547 CCTGTGGCAGTACAC1TrGTCCTCTrACACATG 881 C CC~rACTGCAGAGATGACTCGGCCAACGGC'1 CGAGCCCCTGACCAC'TCCTCAGGTIrGGT'FI TGTTrAGiTflTCTCACAGCAAITGGGAAGCAT
AATCAATACAACTT-CCCAGAATGCGACCTGTG
ACAAGGCGAATGAGCAGACTCAAGGCT(JGUC
ACATAAAAGCACCA A AA AA AAAACTCCCI7 IM000548 GCAGTTA117G'FCATG 882 D
GACTGAGCCTGCCTGGGGCCGTAGGG
AAGGGGGGGTTGGACCCTCTGGTATT
TGCAGTTACCACTOACAGGEITTT=C
CGAGATGCCAGTGTCAGGGTGTITCGG
TGCTGACCCCCCAGGGACCGTGCAGC
CCCGATGGCTGTCI'CGGTCCTCTCM4 CM-fICCGCCACCCCTGGGATATI'CA
GGACTCANTCCCCGCAACAGCTCTGA
CTGAGGTCAGCTCTGTGACCAGGGNC
CCTGTCCCCGGTGTGNNGTGTATFIG
IM000549 CATG 883 K Wnl] CATGTAGAAGGCAGAGGACAACC1TCAGGGA IM000550 TTAnTICTGCCCGAC 884 C GT-rCCTCGAT'rCFGCTGC'ITCTCCGTGATACAT TGAGT'rACAGCAGCCCACGCGTACACACTCTC 1M000551 GCACATG 885 K W,tl
CATGCCACCAACAAATAAGTAAGTA&AAG
AAGGAAGGAAGGAAGGAAGGAAAGAAAGAA
I1M000552 AACA1TrAAATCTGTAAT 886 D CGGAGC~rAGGTCTATCAMTAAAGATACAAC CAAATAGGCAGAATCATrCCTGAGGAOCCC
ATF=CMTATCTCAGGTCCTGCAGATTTCTCC
CTGGTA'TrATCAGGGAGGAGCAc3CAGCTGAG CTATCCTATCTCCrTTACTAATAGAAAAAACG
CCMIAGGGCTTGAGCACAGGACCTGTAMJIC
AGGGGAATGTTGACAATCCATAACTCCAGGG
TGGACTACTAAGCCCTGCAAGGTGAGTGIAC
IM000553 CCCGGCCGAGAATAAGGCCCATG 887 R CATGGCCTGAGAGTGGAAGAGTAUrGTA GCAGGGGTrGT[CCAGAAAGM~AGAATATAC AGACACTATACTCTATCCAGACT7C-FGGCAC AGGGAGTTrCAAATGTAGACTCTGAGCCCCGTC CTGGGGCAGCTrC'TCCACCTGC I IGGGTAG AAGCAGGCAX3ACTCTGGGTAGACTCTGA1TCC
AAGGCTAAGTAACCCCTGAACCCAGAACAGT
IM000554 G=T~C 888 D CCAGATATCATACTGAGTTCGTAGGTGGyT]- IM000555 AATTAATCACGGGCCCCTGGCATGj 889 D
TTGGTGATCCAAACCCAAAGAGACAAATGCT
GAATGTCACTCTCAT=CTFGUrCTAGCTCC AATCTrCAGATATGAGTAAGCAACACATA
ATTFATGAAGGGACCATACTGGGATGTAGGGG
IM000556 GCTTGCATG 890 D
CATGAGCACTGCTCTAGGGACACCTC
CCATCCCT'TCCTAGCACCCCAAATGC
CCCT'rCCCATCTCTCCTTrCCAGAAGnT 1M000557 GGA 891 K Wnt-3
ATATAGCTGTCTCCTGAGGGCCTATGCCAGTG
CCTGGCAAATACAGAAGTGGATGCTCACJ&AT
CATCCAT-rGGACAGAGCACAGAGTCCCCAAT
GAAGGAGCTAGAGAAAGTACCCAAG(JAGCTG
AAGGGGTCTGAAGCCCCATAGGAGGJ&ACATC
AATATGAACTAACCAGTGCCCCCAAGpCCT TAGAAC7AAACCACCAATCAAAGAAAACACA IM000558 TG 892 R CATGATAAGGTTAGAG=1GTGAGCTCCP.
AACCTITGCTCAGCAAGCGTrooGTTy'rGCA GCCGAGCTGCCATC17CTCATCCCCGATAGA GCCAGCCGCCCfGTCGTGTCGTAGH I14000559 AGAGGAGGCATTATAGAGCGGACC-1A&ACAT .893 D TrOCCTTGGAGCCTGAGGGATGGGGA'FrGGCT
GAATGTGAAT
CAGAAcTrGTGCTCTIAGGAAGCCAGACGC'I'A TGCCTTAGGCCCTG'rrCGCTGCAGACCI'1GCTC IM000560 TGiTGCTIACAGTGTAAAAGCGAAGATCATG 894 D
GAGAATTAGAAAAGAGAI'AACAAAGGCGAGA
IM000561 AAGAGAGGCGTGTGAGAGCATG 895 D
GTTITCCAGAYIG(TCCTAGTAGCGTGGGCTGCAG
IM000562 GAACAGCCAGCATG 896 C
GGGGGTGGGGGTGGTAAGAGAAGATTAAITA
GCCTAGCATATATAAGGTITGGATTrCAATCT'
TCAACTCCACCCCTTAAAGAATAAATAAACAA
GTAGATAGATTATAGACAGACAGcTrAGATGG
ATAGACAGATAGCTACATAGATACATAGATA
GATGATAGATAATrAGACAGACAGACAGATAA
ATGATAGATAGATGATAGGAAGTCCCAGUTA
ACAAATGGAAATAAAAAGACAAAAGTCCCCTr IM000563 TTGTCCATG 897 D GTATATGGAATATGGCAAGAAAACTGAAAATr IM000564 CATG 898 R
CATGGTAAAGGTCAGGAGTACACCTGTGCTTC
TGTGTTCT-rCTGTGTTGGCTGACAGCTGGGCA
GAAGTGAGTTCAGGAGGNCAACCCATACGAT
GAGACAAGCCGGGGCAAAGTGGGATATGTGG
ACCGCAGCACATCAGAAGGGTGTGCCCGACA AAI 1113 IM000565 TAC899 B 54 CATGAAGTATA'T7A'IAGAGGGGAACTAGTCT TACTGCTGAGCAGCGTGTTG'rCI'ICTIACAGAG GATrGTTT"IGTGTrTCTGGAAThFTAAAATTACTTlA
AAGTIAATAGTGTCAATGAAACGTTGTCCGGTG
ACTrGCTTCYTTAAATGATCACTrGTTrAGACA IM000566 GGGA 900 R
AATAATCAGATTTCCAGAGCTCCCAG
GAACTAAACCAACAACCAACGAATA
IM000567 CACATG 901 R CATGAT'ITGATAGGGTT1TGGTTCTCTGGA ATCTAACTrC1TGAGTr=GTGTATIA'rTGGA IM000568 TA11'AGCCC1'Cr 902 R GCAAAT'AGTCG-'fTGTACCGAACT'TCCACACA GTAATGTAGTGAAYVIA1TAAAA'flTATF7CCTrT AATCTITrTAAAGTCCAGACTCTATCCCCCT CC~rGTCCACCCTCTGATTGTTCCACATCCCAT IM000569 ACCTCCTTGCCTCATG 903 R TTCCATCTCT'GTA7ITCTGT-rGCTGATGCTCAC ATCTATGTTTCCAGA'IIC'I-rrCCTAGITG1TF'C TATICTICCACTGTTIGCCTCACTFGGG'TMI1 TA~rGTGTCCACT17CC1TVIAGGTCrrGGAT IM000570 ,GGT1T'rGAATTCCATCACCTrnTrGG-TGT 904 C GTTrCCTGCAATrCITrAAGGGA1TTGTGT TTCCTCF=AATGTCT7CTACCTGT1GGT1-AT G1TICCTGTAATTC1rAAGGGATI=IGTGT T'rCCTcTIAATGTCTrCTACTGTITAGCAGT G1TCTCCTGCATrTCMIAAGTGAGTrATTTAA GTCCTTCrGATTCCTCTACCATCATCATG CATGAG=r~CTACTTrATAAAATTATATA AAGTCAT1AGTAGAACCTAGCMTAT7AAT T1TACCAATTAATATAAGGCCACTGATATrAT TGACTrTrGTCACTACAAAATACAGCAATGAA ATAAT=flCTTCTAGGCTCCTCCTCACAA CTAGTTCITCAGCTCACATrAATAC'Ir=CA AGTrGTAAGGGACCTCAGGGACAGGGGGC IM00057 1 905 CATGAGCTrATAG1CAGTAAGAGAGCATAG ATAGAATATAGGTGCCTGTGCGCTGCTCrT TGGTrGTAT1TTAAATCCTrrATCTCTGAGAAGT CGGAACTGTrrGGCAACAGACAATATGGTAGC IM000572 c 906 D
CTGACACAGGTATGCCCAGTCCATAGTGTGCA
GAGCACAGATGGCCAAGGATAACTAGGAATG
AGACCTACTAACCCAAACTCCAAACAT-rATG AAACTIAAAAAAATGAC1TCAGTTGAAc=r 1M000573 GCAGGTAACCACATCATG 907 D ATGTGTCC'TrrAACA1TCTTGCTTI'AGTAGA ACATCCTCTGACCCGTATCTGATTrCAGTGAAA AATFCCTrCACGAGTCTGCCTrAGCAAAACAT CCIrGACCTGTGTCTGCTrCAGGAAAACACC IM000574 CCTTCACATG 908 R
CATGTTGGTAACAGATACAACAAGCAGACTT
AAACTAATAAGAAAACAGCTATGATTAATAT
GTTrTATAACTTAGCTGAAGAGAATGTATGGAG C1T-rGAAG-rAATCT=rCATATACACAGGAA
TGCCTTCAAAAAGCATTGCAGCAGATF[CA&A
IM000575 GGATTAAACTCAT 909 D CATGTGGCGAACCAGCATCACTTGCTTTr CCTACTAACCCAGGACATCCATCAnrATII
AATAGCATCCACCCTAGTAGATATAAGGTGAT
ACCTTATTrGTGAMrCA1TTGCCTrCTCTGAA GATCACTAACAATCAAAATCTGGTrCATM-yI TTTATGAATrCTCATTTGTCTJ-I
IIGCTAAATAT
ATGTCACAATC11CAAMAAAAGCAA TTGTI=G1TAATAATGAGCTAACTI=CATAC 1M000576 AT-rGAAG 910 D
TTGCTGTGGGCCTAATTCAAGGCTGA
TAGATCACCACAGAAGGACACTG1T
TCCTCCGGGCAGCAGGAAGTACAGG
GTAGGGACTCTAGAATCACTGCCCTA A166396 IM000577 GGGCATG 911 B 9 GTACTrGAAGTTITrAGCTAGAGCAAAAAGAC IM000578 tAATGGAAGGAGATCAAGGGAATACAAAGTGG 912 R GAAAGAAGTCAcJAGTATCA'fl7ATc3TCCAGG'I'
GATATGATAGITATACATAAATGACCCTAITAGA
Y[FACACCTAAGACCTCTACAGTGGATAAATAC
TAAAATATrrACTACACAGAAATCACCCCATG CATGCAAGGTATGAAcTrCACTAATAA IM000579 GGGGATA 913 D CATGGTrICACACTCCATAATATCTTGTTFCTCAC
TAATTCCTCTAATCCCATAATATACACCAATA
A1i-i-AACAAGGGAATTTCTIACATTGA3TrGTA ATAAGGGAGATACTGTGTGAACfACCCAC
AAAAGTCTCCAATAGAAGTGTGGATACCACA
GGAAGTC1GTGACAACCA117AAAATJTGGGT
CTGATAAGAAGATAACCCITAAATATATAGA
IM000580 ITATGTAAAG 914 D
GATGGGCTGGGGAAAGGCAGAGAGAAGAACA
TCTGGATTGTTCCTAACMhGCC1TrAAAATGA GACTTCAATAATACTTAGACGTACCAGCTfCT CACAGTCAGT'rAAAATGTrGACACACAGACCTC IM000581 TCAGCAGACTGAATGGGTGAG 915 D AGAGATGGTTGGGA3TTAAGT-FlACCA
GGGTAGGGTCACCACAATCAACCCTT
IM000582 GATGCCTTTrATAGGAAGAAACATG 916 D CATGGAAGTCTAAAAGACATrAGGTTCTGGAT GGAAGAAGAGAAAA11'ATC'T7AAGFI=AGA
AAAGGGATGATAAAACAAGTCTTAAATCTTCT
CAATT-frGCCATAATTCA11GAATrAATA~rG
GTAAATGCTTGTGTGGTCCCATAAAGTTCA
TGTGTTATATCACTAAGTAGTrATTTGTAAAA 1M000583 TTATAAATAGCCTCTAT 917 C CTTGTGAATTG1TTAACTGThFTGAAAAAGTA
GATGTTTCTCTATTFATTIT-FGGGACAATTAT
CAGAATrTGAAACAAACTGTGTATCTCTrATr IM0005 84 I'ACJ-TCTGCTTAACCCCCATG 918 D CATGG'IrGCTATA'FrCATrAACACAAATCATr TAAAATCCTTrAATGTAAAATGGGCACATrTTC AAAATrAAAATAT'ATIGAAAACCAA'rAAAGAT
AGAAAATTI'AGGAAAAAAAATAATCCAAGCA
AGATGTrAAGATCCAACCACAGCAGCAT'ATII'A
GCAGCAGGACAAAAATAAGGACAACAACCAA
GAAAGGGATrGTGGTTAATGTATGCCTCATTG GAAGGGATAATAGGATGTAAAAGTG'rGAGAA
TAAAGAGAAAAAAATCTCTMIAAAATGTAA
GTTAAAATAATAAAAATAAT-hrAAAAATTFGGTr G1TCTCAGGGCTGGATAATA'fl'ACTAACAAAA CCAGGGAATTATrAATAAAAAATCTCTTATCA IM000585 GTTAT 919 D AACAAGITI'AAATrGGGGCATAGTGGATGAC A1TIGTGATCCCAGCAGTTGGAAGGTAGAAAT AGGTAAATAAGAGTTCAAGGTCATrCTCAG 1M000586 n-ATIGTAGTTGTACArICTAGCGATGTAGTTr 920 D
GAGTTCAAGGCCATG
GTCCTCCAATGTGCATCTCA1T1TCACGTT IM000587 TITCAGGT-fCTCGCCATAFIcCATG 921 R AAITGCAFrGAATCTGTGGA1TrCTA1TAACA AGATGOCCATFIr=CCTATGTTAATCGTACT
GATCCATCAGGATGGCAGTCMJCCATCTTCT
GATATCGGCCTCAA'ITrCTTCAGGGGCITT IM000588 GAAGTTATCGCCATG 922 R GGCTAGGTACTCCTAAACG1TCCTCTGCTATC IM000589 CTAGGCCCAATAGAAAAAAAGTGGCCCATG 923 D AATAATACTrCACTGTACTrAAAATATTAT
CTCCTATCTCACTCTAATAC'CTGTGAAAGA
AGCAATATCGTCTCTITGTAGATAAAAATGGC
TGAGAAGGGCACCTTrCAAGACACTAAGTGAC IM000590 TAACTCAGACTCAGAAGTTCAGAGACCATG 924 D CATGCTCTACTATGTrCACAGCAGTCT-A-TrrA TAAC3TCCAGATACTGGAAGCAACTCAGATGT
TCCTCAATGTAAGAATGGATACAGAAAAT
ATGGTACAMTACACAATGGGGTACAACTCAG
IM000591 CrTTAAGiAACAATGAC 925 R
AAAACCCAAGAACAATTAAGCTGTA
GTJ'CCCAAGTGTAATTATATTATGGT
TGMrCTGCTTGCTTrATATCCCTATA TACAAMTATGATFCAAGTAHrAGTG IM000592 GGAATAGACTAATGGCATG 926 C IM000593 CATGCCAAGCCTI'CTGGTATCACCCTAAAGGC 927 C- CATGCTCTTCTCTGCTGrrCTrACTGAAy-Tfl AATAAGAACAATrCCACACAGTGAAGCA CTGCTCAATrAAGAGATATTCCTACCAGGCAT CTTrGGAATCCTGCAA.GCACCTCTTCTCTGTr CCrGATGACCCTCAAM~GGTrGTGTCCAGAG
GTGGTGOGGAGGAGGGGAGGGGAAACGAA
GCrrATTTrrAATGCAAGTCAATMAJ~' IM000594 CAATGTTCTCGAT 928 D CATGCTAGGCAAATGCTCCACTGAATGAATrA CATITCCAATCTIAGATGCA=r-AAAGAG AAAAGATrGAGTACTGAAG-II-GAATAGAAT
ACAGGAATAAGGGACTAAACATATATATAGC
CTTATATAGAGAAATArAAGTAAGTAGTAAC 1M000595 Ti-rGCrGTGTGTGTGTGTGTG~rGCACAC 929 D CATGCCA'TrAGTCTATTCCCACTAATACTUGA ATCATAAATrGTATATAGGGATATAJ&AGCAA GCAGAAACAACCATAATATAATrACACTTGG 1M000596 GAACTACAGCTAArrGTC1-GGGT= 930 C
CATGCACAGCTGGTGAGTGAGTTGTCTTCTGG
TACAAAAATCTCCTCACAGGCACATrACAAG
TGCCTATATCTTGCTAGCITCAAGAACACA
I M000597 JAGAAGGGACACACAAAAGCTCrCTGAGTT 931 _A D
CCITCTCCTGCTGI'I'AFUTG
ATCGTCAAAGTTIAGCAAAATTATAAATGI'GAA
1M000598 ArrCATG 932 D
CATGAAKFATGTTTGTTITATITCTTT
TGTACATCATTCAATGCAGTAATCTA
AAGT1TGGGGTC'I1IGGTCTTATATCTT GGAACTTCAGTGACYT'ATrIGGTTrCTA 1M000599 ACG 933 D AGAGACAGTCACAAAAGGGGCCCATFFCTTG'11
AAGAATGGGGCAGTGGAGAAGTTCGGGTTAG
TGGAGTAGCCTGCCTCAcYITCCTCCTGTCTTC F-gf3/Fgf IM000600 TGTAG'ITAAATGTGjTTAATGGITFAACATG 934 K 4 1M000601 CATGTAGCATITFATCTI'AGCCAGCAC 935 D CATGTACAGACTATGAACAGiGAAATGTTTTTG
CAAATAACTCTGTGCATTAGAATMTTCAG
AAATATAACCA1TITGACAG1TGTAGG1TIACA C11TIAAAATTACAAAATCAATAAAATTGATC TACAAACCGAGGCCIFACAAAACCCIrGCTGG IM000602 ATATrGAAGACGGGATAATATTAAAG 4-56 936 D AAYPCCCACCACCCACAGGGTGGCTCCATrAAC
CATCTIGTAACTCCAGTCTCAGGGAGTCCAAGG
CCCTCMTTGGCTTGCAAGGGCTrGCACACAC Fg/3Fg/ IM000603 ACAGCGCACACATG 937 K 4
CATGGTGAATGAT-FG=I~GATGTG'ITCTTGG
AMTGGTU'I'CGAGAAYI=ATTGACTATI1TrGG CA'rrAATACTCATAAGGGAAA'FrGGTCTGAAG TTC1TCCTTGTTGAGTC'1ATGAGGGTATCA
ATATAA'GTGGATTCATAGAGCAAGTTAGAT
TGTGTTCCTTrCTGTrTATIT'1GTGGAA'rAIT TrGAAGAGTATTGGTrAIrAGA'r(YTrCCTTGAA GGTATGATAGAAfFrGAACTAAACCCATATG GTTFCTGGATfTTGGFGGAAGACCAATG ACTGCTITCTATTTC1TrAGGTGT7ATGGGACTG TATAGATGGTTTATCTGAACCAGiAThr-AAcT-r
TGGTATTFTGT-I'ATGTG'LT[AGAAAATTGCCCAT
TTCATCCATAMhCCCAGTTGTGTTGAGTATAG GCTM~GTAGTAGGATATAATGMTI1GAAT 'TTGCTCAGTATG'TCATATCTCCC=rCC AT17CTGAT1TGTTAATGTGGATACTATCTCT GTGTCCTCTGTTTAGTCTGGCTAAGGGTTF-c 1M000604 TATCTGTTGA'FITrCTG 938 R CATGGG'I'T'AACAGTGGGCCCTAAAC'JTIGAAC'r' AGAAAACrrAAAGATGCTCATAGGGAAGAAG AAAAGAGCAGAAAGCTrAGCT-rCTAGACAGG GGTAAGGC'FrAGAGCTCAATAAAAAAGGAAC IM000605 Iccc 939 K Wntl
CATGGCCTGTCTCAGTTTACTTCACAGCTGAA
IM000606 I CAAGAGGCAGAGAGTGACAGGTAG 940 K Wntl
U-
CATGCTCGCCAGTCCCAGAACCTGGA
AGGCTGAGGCAGGAGGATTAAA.JAG
CCTFTGGGGACACCAGGCTTGGTGGCA
CCGGTCGTAAATCCAGCACTGGGGAG
TITAAGAAGCAAGTGAGTCACATCTGT
GAGTCTGAGGGTATGTTGGTCTACGT
AACGAGCTCTAGTATAGCGAGCCTGG
GATACATAGTAAGCAGT[CTAGTATA
GCCAGCCTGOGATACACAGTAACGA
GTITCTAGTATAGCCAGCCTGGGATAC
I1M000607 ACC 941 D
CATATGCGTATTCACATTTGTGTGGGAACGTC
GTTGGAGAAAGCAGGAGCAGGAGTrACAGAC
AGTATAAGCTGCCTGACCTGGGTGCTGGGA
ACACCTCAGGTCCTCTGGAAGAGCAGTAAGTC
CCCTTAACCAATGAACCATCTATCCGTCCAGC
CTACATTAATrGnrC'ATT-rACTTGTCT IM000608 GCATG 942 R
CACACACACACACACACGGGTGGGGATCCAA
CCCATCTCGTCCTTACACGTGCTCTACCATCA
CGCCACACA'TrTCCAGCACN'TrATCTGAAGT IM000609 GTrCC I I rAITTGTGCATG 943 K Wntl
CATGCCTGGTGCCTGCAGAGGTCAGAAAGTGT
TGGATGCCCTGGAATTAGAGTAACACATAGn~ ATAAGATGCTGCGTGGGTGCTGGGATmfGAAJC
CCUTGTCCTCTGCAAGAGCAGCCAGTGCCT
AACCACCGAGCCATCCCTCCAGCCCCTGATA
CTCACTCTTCACGGCTCAATCGTAGG
TAflGAGGCTGCCAAGTGACGCAAGAGCACC
TAGGAAGGCAGCCACATCGGTGGCACTCTGG
AAGCACTGCGAGGATGACTGCACACAI-JGCC
IM000610 GGTTGTC 944 K Notch] CATGCTGGCCATTATTGATmAAGTTATAC
TCTAGACCTTTGTAAATATTAGCCATTGCATA
TTACAGAAATrrCTTAGCAGAGATAGTCTCTC
ACTCTTAGTGATGAGCAAGCTGGAGTCAGCA
TTATTCTCCCAGCTAAGATACAGAAJ-rACAGA
CGMIATGACGGACACATCTGGATGTAGTTJA
IM000611 CTTAGTCCAC 945 D
CCCCCCCCGCCCCTGCCAGACCGCAGCCCGA
IM000612 GCACAGCATG 946 D CATGCCTCCCTCAGCCTCCTCCACCCCTrCCTG TCCTGCCTCCTCATCACTGTGTAATAAM1GC ACCGAAATGTGGCCGCAGAGCCACGCGTrCG GTTATGTAAATAAAACTATrATGTGCTGGG Fg/3/Fgf 1M000613 TFCCAGCCTGGGTTGCAGAGACCACCGT 947 K 4
CATGAATTCAATGGTGTGCTGCTATA.AATGC
AAATAAACCATATATATCATATTACACTC&AT
TlTAAATATT1CCTAATATrAATAAAGGTG IM000614 IATGGGGAACTr 948 D
CATGTCTAC'TTIATL'GCATATFAGGAT
GTCAGGTCCTGCTCGTTTCCTGGGAC
CAMhGCCTGGAAGACATFFCCATT CITIACTCTGAGATAGTTCCTGTCrT TGTTGYITGAGGTGTG7TFC'rrGTATTC U AGCAAAATGCTGGATCTTGTTITGCGA ATCCAGTCTIGT-rAGCTTATGTCTFF-If ACAGGTGAA'FrGAGTCCAT[AATATT GAGAGATATTAAAGAGAAATGAC[Tl TGGTlCCTGATATALTG1TITCTAG TFAG3TTGTGTGC'TTGGGACTCTCTC CCT1TGACTGTGJTGTGAGATGCTTA Cl ATATCTfTGTCCTATCTTTGGTGCAGGT GTCTTCCTTGTGI'TAGAGTI=CATTfC CAGGTTTCTCTGTAGTG-rATG'ITAG AAGACATATACTGCTrGAATrAGrI' CI ~T-TGCCTGGAATA=FTGrI=CTCCAT
CTATGTTIGATTGAGAGTTFCTGGGT
AAAATAGCCTANCCTGGCATTTGTGT
TcTrc'iTAAAAGTCTGTATGACC'FCTG 1N4000615 ACTANGC=1TCTGGCC 949 D CATGGTGAATGATTG'TflGATGTIGT TCTTGGATITTGGTTTCGAGAATTTrTAT TGACTA3TIGGCATFAATACTCATA AGGGAAATfl'GGTGTGAAGTTCTTcCC
T-G'TTGAGTCTTTATGAGGGTATCAA
TATAATTGTGGATTCATAGAGCAAGT
TGGATflGTGTTCC'TGCTGTTTATAIfT TGTGGAATATTrrTGAAGAGTA1TGG'T ATTAGATTTTC7ETGAAGG'rATGATA GAATrCTGAACTAAACCCATATGGrT
CTGGA=II-ITGGTTGGAAGACCA
ATGACTGCTCTATCTITAGGTGT[
ATGGGACTGTATAGATGGMIIATCTG
AACCAGATTTlAACTTTGGTAMIGTT ATCTGM~AGAAAA'ITrGCCCAT[CA
TCCATATICCCAGTTGTGTTGAGTAT
AGGC=TGTAGTAGGATATAATGAT
TFITGAATLTCCTCAGTATG1TPCT TATATCTCCCTTGATTrCTGATM
GTFTAATGTGGATAGTATCTCCGTGTG
IM000616 CCC 950 R CCATGTCAGGTGGTrAACCTGTGAGTCTAACT
TCCAGGAATGCAATGCCTCTGGCATCTACAGG
CATAAACATACrGTGGCTrACACCAACTG
ACACACCAACACATATGTGCAGGCGCACACA
CACACACACCAAATTAAAAATAAAATAACCC
TFrrAAfiAATATAGAATCTATAGATAATT 1M0006 17 GCTTTACTGCACTCACAAACI1TrAGGATC 951 D IM000618 ACACTAACACAAAGAAGGGGATC 952 D

Claims (18)

  1. 2. The method according to claim 1, wherein the expression product is a mRNA having a sequence of SEQ ID NO: 1587.
  2. 3. A method of diagnosing carcinoma, lymphoma, prostate cancer, colon cancer, stomach cancer or breast cancer comprising: a) determining the level of an expression product comprising a nucleotide sequence at least 98% identical to SEQ ID NO: 1587, or a full complement thereof, in a patient sample; and b) comparing the level of the expression product in to a level of the expression product in a second sample, the second sample comprising a normal tissue, wherein a difference between the level of the expression products in (a) and the level of the expression products in the second sample indicates that the patient has carcinoma, lymphoma, prostate cancer, colon cancer, stomach cancer or breast cancer. 242
  3. 4. A method of diagnosing prostate, colon, stomach or breast cancer in a patient Ucomprising: contacting a polynucleotide that hybridizes under highly stringent conditions to a nucleotide sequence which encodes a polypeptide encoded for by a nucleotide sequence at least 98% identical to SEQ ID NO: 1587 with nucleic acids of a patient prostate, colon, stomach or breast sample under binding conditions suitable to form a duplex, wherein the polypeptide has protein phosphatase activity; and S(b) comparing the amount of the duplex formed to the amount of duplex formed when the polynucleotide is contacted with nucleic acids of a normal, non-cancerous control, wherein increased levels of the amount of duplex formed upon contacting the polynucleotide with the nucleic acids of the patient sample compared to the amount of duplex formed upon contacting the polynucleotide and the nucleic acids of the non-cancerous control indicates that the patient has prostate, colon, stomach or breast cancer. The method according to claim 4, wherein hybridization is performed at 50 'C to 'C in 5 X SSC (9mM saline/0.9 mM sodium citrate).
  4. 6. A method of screening drug candidates comprising: a) providing a cell that expresses a carcinoma associated (CA) gene comprising or encoding a nucleotide sequence at least 98% identical to SEQ ID NO: 1587; b) adding a drug candidate to the cell; and c) determining the effect of the drug candidate on the expression of the CA gene.
  5. 7. The method according to claim 6, wherein the determining in step comprises comparing the level of expression in the absence of the drug candidate to the level of expression in the presence of the drug candidate.
  6. 8. A method for screening for a bioactive agent capable of binding to a CA protein (CAP), wherein the CAP is encoded by a gene comprising or encoding a nucleotide sequence at least 98% identical to SEQ ID NO: 1587, the method comprising: a) combining the CAP and a candidate bioactive agent; and b) determining the binding of the candidate agent to the CAP.
  7. 9. A method for screening for a bioactive agent capable of modulating the activity of a CA protein (CAP), wherein the CAP is encoded by a gene comprising or encoding a nucleotide sequence at least 98% identical to SEQ ID NO: 1587, the method comprising: a) combining the CAP and a candidate bioactive agent; and b) determining the effect of the candidate agent on the bioactivity of the CAP. A method of evaluating the effect of a candidate anti-cancer drug comprising: a) administering the drug to a patient; b) removing a sample from the patient; and c) determining alterations in the sample in the expression or activation of a gene comprising or encoding a nucleotide sequence at least 98% identical to SEQ ID NO: 1587.
  8. 11. A method for inhibiting the activity of a CA protein (CAP), wherein the CAP is encoded by a gene comprising or encoding a nucleotide sequence at least 98% identical to SEQ ID NO: 1587, the method comprising binding an inhibitor to the CAP.
  9. 12. A method of treating carcinoma, lymphoma, prostate cancer, colon cancer, stomach cancer or breast cancer, comprising administering to a patient an inhibitor of a CA protein (CAP) wherein the CAP is encoded by a gene comprising or encoding a nucleotide sequence at least 98% identical to SEQ ID NO: 1587.
  10. 13. A method of neutralizing the effect of a CA protein (CAP), wherein the CAP is encoded by a gene comprising or encoding a nucleotide sequence at least 98% identical to SEQ ID NO: 1587, comprising contacting an agent specific for the CAP protein with the CAP protein in an amount sufficient to effect neutralization.
  11. 14. A method of diagnosing carcinoma, lymphoma, prostate cancer, colon cancer, stomach cancer or breast cancer or a propensity to carcinoma, lymphoma, prostate cancer, colon cancer, stomach cancer or breast cancer by sequencing at N least one CA gene of an individual, the gene comprising or encoding a ri nucleotide sequence at least 98% identical to SEQ ID NO: 1587.
  12. 15. A method of determining CA gene copy number comprising adding a CA gene probe to a sample genomic DNA from an individual under conditions suitable (N for hybridization, the CA gene probe comprising a nucleotide sequence at least 98% identical to SEQ ID NO: 1587.
  13. 16. The method according to any one of claims 1, 3, 12 and 14 wherein the cancer is lymphoma, colon cancer, stomach cancer or breast cancer.
  14. 17. The method according to any one of claims 1, 3, 12 and 14 wherein the cancer is colon cancer.
  15. 18. The method according to any one of claims 1-3, wherein the level of the expression product in the sample is increased at least 100% relative to the control.
  16. 19. The method of any of claims 1-3, wherein the level of the expression product in the sample is increased at least 150% relative to the control. A polypeptide which specifically binds to a protein encoded by a gene comprising a nucleotide sequence at least 98% identical to SEQ ID NO: 1587.
  17. 21. A polypeptide according to claim 15, comprising an antibody which specifically binds to a protein encoded by a gene comprising or encoding a nucleotide sequence of SEQ ID NO: 1587.
  18. 22. A biochip comprising one or more nucleic acid segments of SEQ ID NO: 1587 or fragments thereof.
AU2007240202A 2001-12-26 2007-12-10 Novel compositions and methods for cancer Abandoned AU2007240202A1 (en)

Priority Applications (1)

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US10/035,832 2001-12-26
AU2002367390A AU2002367390A1 (en) 2001-12-26 2002-12-26 Novel compositions and methods for cancer
AU2007240202A AU2007240202A1 (en) 2001-12-26 2007-12-10 Novel compositions and methods for cancer

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