TW200815476A - Compositions and methods for therapy and diagnosis of prostate cancer - Google Patents

Abstract

Compositions and methods for the therapy and diagnosis of cancer, such as prostate cancer, are disclosed. Compositions may comprise one or more prostate tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a prostate tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as prostate cancer. Diagnostic methods based on detecting a prostate tumor protein, or mRNA encoding such a protein, in a sample are also provided.

Description

200815476 IX. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention generally relates to the treatment and diagnosis of prostate cancer, such as prostate cancer. More particularly, the present invention relates to oxime peptides comprising at least one ym y, σ Η 则 腺 肿瘤 肿瘤 tumor protein, and polynuclear citric acid encoding such a polypeptide. — J uses such peptides and polynucleotides in Ά苗和医华纽, to...〃. And the materials and surveillance of such cancers. #列腺癌' [Prior Art] BACKGROUND OF THE INVENTION Prostate cancer is the most common S Λ d in men, 4. ^. Gua cheek type, in the men over 50 years old, there is an estimated 30 〇 / 〇 Incidence.隹 隹 t ^ 彳 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的^ Τ...going to the state of the system, resulting in a gradual decline in patient mortality. This widespread J^ disease has become the second leading cause of cancer death among Wu nationality men. Although the treatment of this disease has been studied, the prostate is still difficult to treat. It is usually based on 4 Buko/or radiotherapy, but these methods are in most cases ^ 疋 、 ..., effective. Two previously identified lenali-specific egg yolk _, + shell 1 gland-specific antigen (PSA) and prostate phosphatase (PAP> limit the possibility of sputum & sputum therapy and sputum For example, H & 并非 并非 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 Prostate hypertrophy (BPH). In addition, the pSA associated with the glandular mass of the previous and the month is not 127691.doc 200815476 represents the degree of metastasis. ^ & There have been considerable studies on these and other cancers, However, prostate cancer is still not easily diagnosed and treated effectively. Therefore, there is still a need in the art to improve and treat such cancers. The invention will satisfy these needs, and further provide other related benefits. SUMMARY OF THE INVENTION Briefly, the present invention provides compositions and methods for diagnosing and treating cancers such as prostate cancer. In one aspect, the invention provides at least a portion of a prostate tumor protein, or a variant thereof. Peptides. Certain immunogenic portions and other variants are not substantially reduced, as long as the variant has the ability to react with antigen-specific antisera. In certain embodiments, the polypeptide comprises at least one prostate tumor. An immunogenic portion of a protein, or a dimer thereof, wherein the amino acid sequence encompassed by the tumor protein is encoded by a polynucleotide sequence selected from the group consisting of: (a) in sequence recognition, 115- Sequences referred to in any of 171, 173-175, 177, 179-305, 307-3 15, 326, 328, 330, 332-335, 340-375, 381, 382 or 3 84-472, (b a sequence that hybridizes to any of the foregoing sequences under conditions of technical stringency; and (c) a complement of any of the sequences 0) or 卬). In certain specific embodiments, such polypeptides comprise at least a portion of a tumor protein, or a variant thereof, comprising a member selected from the group consisting of sequence recognition 112-114, 172, 176, 178, 327, 329, 331 The amino acid sequence of the sequence referred to in any of 336, 376-380 and 383. Benben is further provided with a polynucleotide encoding the above polypeptide, or a part thereof (such as 127691.doc 200815476 is a portion encoding at least 15 amino acid residues of the prostate tumor protein). A nucleic acid expression vector, and a host cell that transforms or metastasizes an infection using such an expression vector. In other aspects, the invention provides pharmaceutical compositions comprising the above-described polypeptide or polynuclear acid, and a physiologically acceptable carrier. A vaccine is also provided in the related viewpoint of the present invention. Such vaccines include the polypeptides described above or polynucleic acid, as well as non-specific immune response promoters. The invention further provides a pharmaceutical composition comprising: (4) an antibody or antigen-binding fragment thereof that specifically binds to a prostate tumor protein; and (b) a physiologically acceptable carrier. In a still further aspect, the invention provides a pharmaceutical composition comprising () an antigen provided by a cell comprising the above-described compound, and 0) a pharmaceutically acceptable carrier or excipient. The cells providing the antigen include dendritic cells, giant cells, mononuclear cells, fibroblasts, and B cells. The vaccine is provided in a related point of view, and the vaccine comprises: (4) an antigen provided by a cell expressing the above polypeptide, and (8) a non-specific immune response promoter. In other aspects, the invention further provides a fusion protein comprising at least one of the above polypeptides, and a polynuclear bismuth citrate encoding such a fusion protein, in a related view, provided to include and physiologically acceptable loading A mixed protein, or a therapeutic composition of a polynucleotide encoding the fusion protein. In other views, a vaccine is further provided which comprises a fusion protein mixed with a non-specific 127691.doc 200815476 sexual immune response promoter, or a polynuclear acid encoding the fusion protein λ. In a further step-by-step manner, the present invention provides a method of developing cancer in a patient, comprising administering to the patient a pharmaceutical combination vaccine as mentioned above.其他 Ο In other aspects, the invention further provides a method of removing tumor cells from a biological sample comprising contacting the biological sample with a sputum cell that specifically reacts with a prostate tumor protein, wherein the contacting step is Sufficient to allow the conditions and duration of removal of cells expressing the protein f from the side 5 pattern. Providing a method of inhibiting the progression of cancer in a patient in a relevant mirror point comprises administering to the patient a biological sample as described above. = In other methods, a method for providing stimulation and/or expansion of a tau cell specific for a prostate tumor protein, comprising causing the cell to encode such a polypeptide with - or a plurality of peptides (11) Polynucleotides; and/or (in) antigens provided by cells expressing such polypeptides; contacted under conditions *main π 4 sufficient to permit stimulation and/or expansion of T cells. An isolated tau cell group comprising the sputum cells prepared as described above is also provided. In a more advanced aspect, the present invention provides a method of inhibiting the development of cancer in a patient' comprising administering to the patient an effective amount of the above-described tau cell cluster. /, The present invention further provides a method of inhibiting the development of cancer in a patient, comprising the steps of: (a) separating the CD4+ and/or CD8+ T cells from the patient with one or more of: ω includes at least the polypeptide of the immunogenic portion of the prostate tumor protein (11), 'polynuclear polymorphic polymorphic acid of the flat horse; and antigen contact provided by cells expressing the polypeptide 127691.doc 200815476; (b) administering to the patient an effective amount of T-cells that are over-proliferating, and thereby inhibiting the development of cancer in the patient. The cells that have been 'may' but are not necessarily selected for proliferation before being administered to the patient. ζ \ ϋ In a still further aspect, the invention provides a method of determining whether a cancer is present in a patient, comprising: (a) combining a biological sample from the patient with a polypeptide that binds to the polypeptides mentioned above Contacting the agent; (b) detecting the amount of the polypeptide bound to the binding agent in the sample; and (c) comparing the content of the polypeptide to the cutoff value of the pre-tanning, and determining whether there is a Cancer is present. In a preferred embodiment, the binding agent is an antibody, more preferably a monoclonal antibody. The cancer may be prostate cancer. / In other views, the invention also provides methods of monitoring the binding of cancer in a patient. Such methods include the steps of: (4) contacting a biological sample obtained from the patient for the first time with a binding agent that binds to the polypeptides mentioned above: (b) detecting in the sample _, binding to the binding agent The content of the polypeptide; (4) the biological sample obtained from the patient after use, repeating steps (4) and (8); and (4) comparing: the content of the polypeptide detected in the step (4) with the content detected in the step (b) And monitor the progress of cancer in the patient. In other aspects, the invention further provides a method of determining the presence or absence of cancer in a patient, comprising the steps of: (4) contacting the patient from the biomarker with a polypeptide that encodes a prostate tumor protein; (b) Detecting in the sample 'the hybridization with the oligonucleotide, ^=, preferably the content of mRNA; and (4) comparing with the content of the oligonuclear (tetra)hypoic acid, and the cutoff value of Yi, and from the middle ^ Is there cancer in the body? In a political and gentleman's heart, the first order, via the polymerase 127691.doc

-1CU 200815476 A chain reaction to detect the amount of mRNA using, for example, at least one oligonucleic acid primer that hybridizes with the polynuclear decanoate of the above-mentioned polypeptide of the gems or the complement of such a polynucleic acid. In other specific embodiments, hybridization techniques are employed to detect mRNA levels, using oligonucleotides that can hybridize to the complement of a polynuclear or & polynuclear acid: acid encoding the polypeptides mentioned above. .

In a related aspect, 'providing a method of monitoring cancer in a patient' includes the following steps: (4) contacting a biological sample obtained from the patient with an oligo-nucleic acid that can hybridize with a polynuclear acid encoding a prostate tumor protein; (8) detecting the content of the polynuclear acid in the sample, which is hybridized with the nucleus acid; (4) the biological sample obtained from the patient after use, repeating steps (4) and (8); and (4) detecting in step (4) The content of the polynuclear acid is compared with the strontium detected in the step (8), and monitoring the progress of the cancer in the patient. In a further aspect, the present invention provides a & The body 'which binds to the polypeptide described above' and the diagnostic C containing such antibodies are grouped. A diagnostic tool set comprising - or a plurality of the above-described nucleus probes or primers is also provided. These and other aspects of the present invention will become more apparent from the detailed description and drawings. All of the references disclosed herein are hereby incorporated by reference in their entirety in their entirety in their entirety as if they are incorporated herein in their entirety. A brief description of pictures and sequence identification. Sequence identification No. 1 · F1 -13 identified cdnA sequence sequence recognition No. 2 · Fl - 12 identified 3, cdna sequence 127691.doc -11 - 200815476 Sequence identification No. 3: F1-12 determined 5' cDNA sequence sequence recognition No. 4: F1-16 identified 3' cDNA sequence sequence recognition No. 5: H1-1 identified 3' cDNA sequence sequence recognition No. 6: H1-9 determined 3' cDNA sequence sequence identification No. 7 :H1-4 identified 3' cDNA sequence sequence recognition No. 8: Π-17 identified 3' cDNA sequence sequence recognition No. 9: Π-17 identified 5' cDNA sequence sequence recognition No. 10: L1-12 determined 3' cDNA sequence identification No. 11: L1-12 identified 5' cDNA sequence sequence recognition No. 12: N1-1862 identified 3' cDNA sequence sequence recognition No. 13: N1-1862 identified 5' cDNA sequence sequence identification No. 14: Π -13 identified 3' cDNA sequence sequence recognition No. 15: Π-13 identified 5' cDNA sequence sequence recognition No. 16: Π-19 identified 3' cDNA sequence sequence recognition No. 17: J1-19 defined 5' cDNA sequence Sequence recognition No. 18: Π-25 identified 3' cDNA sequence sequence recognition No. 19: Π-25 determined 5' cDNA sequence sequence recognition No. 20 Π-24-determined 5' cDNA sequence sequence recognition No. 21: Π-24-determined 3f cDNA sequence recognition 22nd ·· K1-58 identified 5' cDNA sequence sequence recognition 23·· K1-58 identified 3' cDNA Sequence sequence recognition No. 24: K1-63 identified 5' cDNA sequence sequence recognition No. 25: K1-63 identified 3, cDNA sequence sequence recognition No. 26: L1-4 identified 5' cDNA sequence 127691.doc -12- 200815476 Sequence recognition No. 27 · L1-4 identified 3' cDNA sequence 歹 ij Sequence recognition No. 28: L1-14 identified 5' cDNA sequence 歹 ij Sequence recognition No. 29: L1-14 identified 5' cDNA sequence 歹 J Sequence identification No. 30: J1-12 identified 3' cDNA sequence 歹 ij sequence recognition 3 No. 1: J1-16 identified 3' cDNA sequence sequence recognition No. 32: J1-21 identified 3' cDNA sequence 歹, J sequence recognition No. 33: 31-4 cDNA sequence identified by K1-48 Sequence recognition 34 No. f \ : K1-55 Determined 3' cDNA sequence u Sequence recognition No. 35: L1-2 identified 3' cDNA sequence sequence identification No. 36: L1-6 identified 3' cDNA sequence sequence recognition No. 37: N1-1858 identified 3' cDNA sequence sequence recognition No. 38: N1-1860 identified 3' cDNA sequence sequence recognition No. 39: N1-1861 determination 3' cDNA sequence sequence recognition No. 40: 3YDNA sequence sequence identification identified by N1-1864 No. 41: P5-determined cDNA sequence U-sequence recognition No. 42: P8-determined cDNA sequence 歹 sequence recognition No. 43: P9-determined cDNA sequence Identification No. 44: P18-determined cDNA sequence sequence identification No. 45: P20-determined cDNA sequence sequence identification No. 46: P29-determined cDNA sequence sequence identification No. 47: P30-determined cDNA sequence sequence identification No. 48: P34-determined cDNA sequence Identification No. 49: P36 identified cDNA sequence 识别 sequence recognition No. 50: P3 8 determined cDNA sequence 127691.doc -13- 200815476 Sequence recognition 5 No. 1 sequence recognition No. 52 sequence recognition No. 53 sequence identification No. 54 sequence identification No. 55 sequence Identification No. 56 Sequence Identification No. 57 Sequence Identification No. 58 Sequence Identification No. 59 Sequence Identification No. 60 Sequence Identification 6 No. 1 Sequence Identification No. 62 Sequence Identification No. 63 Sequence Identification No. 64 Sequence Identification No. 65 Sequence Identification No. 66 Sequence Identification No. 67 Sequence Identification No. 68 Sequence Recognition No. 69 Sequence Recognition No. 70 Sequence Recognition No. 71 Sequence Recognition No. 72 Sequence Recognition No. 73 Sequence Recognition No. 74 P3 9 Determined cDNA Sequence 歹 ij P42 Determined cDNA Sequence歹U P47 determined cDNA sequence 歹U P49 determined cDNA sequence 歹J P50 determined cDNA sequence P53 determined cDNA sequence P55 determined cDNA sequence P60 determined cDNA sequence 歹ij P64 determined cDNA sequence 歹U P65 determined cDNA Sequence 歹丨J P73 determined cDNA sequence P75 identified cDNA sequence 歹U P76 determined cDNA sequence 歹ij P79 determined cDNA sequence 歹ij P84 determined cDNA sequence P68 identified cDNA sequence 歹ij P80 determined cDNA sequence P82 determined cDNA sequence UJ U1-3064 Determined cDNA sequence U1-3065 Determined cDNA sequence V1-3692 Determined cDNA sequence 1A-3905 Determined cDNA sequence VI-3686 Determined cDNA sequence R1-233 0 Determined cDNA sequence 127691.doc -14- 200815476 Sequence Identification No. 75: IB-3976 Determined cDNA Sequences Sequence Identification No. 76: V1-3679 Determined cDNA Sequences Sequence Identification No. 77: 1G-4736 Determined cDNA Sequences Identification Number 78: 1G-473 8 Determination cDNA sequence sequence identification No. 79: 1G-4741 identified cDNA sequence sequence recognition No. 80: 1G-4744 identified cDNA sequence sequence recognition No. 81: 1G-4734 identified cDNA sequence identification 82: 1H-4774 defined cDNA Sequence Sequence Identification No. 83: cDNA determined by 1H-4781 Column sequence identification No. 84: 1H-4785 identified cDNA sequence sequence recognition No. 85: 1H-4787 identified cDNA sequence sequence identification No. 86: 1H-4796 identified cDNA sequence sequence recognition No. 87: 11-4807 determined cDNA sequence Identification No. 88: 11-4810 Determination of cDNA sequence sequence identification No. 89: 11-4811 Determination of cDNA sequence sequence recognition No. 90: 1J-4876 identified cDNA sequence sequence recognition No. 91: 1K-4884 identified cDNA sequence sequence recognition 92 No.: 1K-4896 Determined cDNA sequence sequence identification No. 93: 1G-4761 Determined cDNA sequence sequence identification No. 94: 1G-4762 Determined cDNA sequence sequence identification No. 95: 1H-4766 Determined cDNA sequence identification No. 96: 1H-4770-determined cDNA sequence identification No. 97: 1H-4771-determined cDNA sequence identification No. 98: 1H-4772 defined cDNA sequence 127691.doc -15- 200815476 Sequence identification 99: ID-4297 determined cDNA sequence Sequence Identification 100 No. 1D-4309 Defined cDNA Sequence Identification No. 101 1D.1-4278 Determination of cDNA Sequence 歹 J Sequence Identification No. 102 ID-4288 Determination of cDNA Sequence Identification No. 103 ID-4283 Determination of cDNA Sequence Identification 104 ID-430 4 identified cDNA sequence sequence identification No. 105 ID-4296 identified cDNA sequence sequence identification 106 Γ \ sequence identification 107 ID-4280 identified cDNA sequence: F1-12 defined full-length cDNA sequence (also known as P504S) sequence recognition No. 108 F1-12 predicted amino acid sequence sequence identification No. 109: :Π-17-determined full-length cDNA sequence recognition 11 〇#: L1-12 identified full-length cDNA sequence recognition 111 *5 tiger' :N1- 1862 Determination of full-length cDNA sequence identification of No. 112': J1-17 predicted amino acid sequence recognition sequence No. 11 3: U-one sequence identification 114: :L1-12 predicted amino acid sequence: N1-1862 prediction The amino acid sequence recognizes the number 115: :P89 determines the cDNA sequence 歹J sequence recognizes the number 116: :P90 determines the cDNA sequence 歹U sequence recognizes the number 117: :P92 determines the cDNA sequence 歹^ sequence identification 118:P95 The identified cDNA sequence 识别 sequence recognition No. 119: P98 confirmed cDNA sequence 歹 U sequence recognition No. 120: P102 identified cDNA sequence sequence recognition No. 121: P110 determined cDNA sequence 127691.doc -16- 200815476 Sequence identification 122: PI 11 identified cDNA sequence sequence identification number 123: ΡΠ 4 The determined cDNA sequence sequence identification number 124: P115 identified cDNA sequence sequence recognition number 125: P116 determined cDNA sequence sequence identification number 126: P124 determined cDNA sequence sequence identification number 127: P126 determined cDNA sequence sequence identification number 128: P130 The determined cDNA sequence sequence recognizes No. 129: P133-determined cDNA sequence sequence identification No. 130: P138-determined cDNA sequence sequence recognition No. 131: P143-determined cDNA sequence sequence identification No. 132: P151-determined cDNA sequence sequence identification No. 1 3 3 :P1 5 6-determined cDNA sequence sequence identification No. 134: P157-determined cDNA sequence sequence identification No. 135: P1 66-determined cDNA sequence sequence recognition No. 136: P176-determined cDNA sequence sequence recognition No. 137: P178-determined cDNA sequence Identification No. 138·········································································································· The sequence of the cDNA sequence identified by the 143: P2 08 identified cDN A sequence sequence recognition No. 144: P211 identified cDNA sequence identification number 145: P2 13 Determined cDNA sequence 127691.doc -17- 200815476 Sequence recognition No. 146: P219 identified cDNA sequence sequence recognition No. 147: P237 identified cDNA sequence sequence recognition No. 148: P239 identified cDNA sequence sequence identification No. 149: P248 identified cDNA sequence sequence identification No. 150: P251 identified cDNA sequence sequence recognition No. 151: P255 identified cDNA sequence sequence recognition No. 152: P256 identified cDNA sequence sequence recognition No. 153: P259 identified cDNA sequence sequence identification No. 154: P260 determined cDNA sequence sequence identification No. 155: P263 identified cDNA sequence sequence recognition No. 156: P264-determined cDNA sequence sequence recognition No. 157: P266-determined cDNA sequence sequence recognition No. 158: P270-determined cDNA sequence sequence identification No. 159: P272 cDNA sequence sequence identification No. 160: cDNA sequence identified by P278 sequence recognition No. 161: P1 05 identified cDNA sequence sequence recognition No. 162: P107 identified cDNA sequence sequence recognition No. 163: P1 37 identified cDNA sequence sequence identification No. 164: P194 The identified cDNA sequence recognizes the number 165: the cDNA sequence identified by P1 95 recognizes the number 166: the sequence of the cDNA sequence determined by P1 96 Column identification No. 167: cDNA sequence sequence identification identified by P220 No. 168: cDNA sequence identified by P234 sequence recognition No. 169: P235 defined cDNA sequence 127691.doc - 18- 200815476 Sequence recognition No. 170: P243 identified cDNA sequence sequence recognition 171 No.: No.172 identified by P703P-DE1: Amino acid sequence sequence number predicted by P703P-DE1 No. 173: cDNA sequence identified by P703P-DE2 Sequence identification No. 174: P703P-DE6 identified cDNA sequence sequence recognition 175 No.: No.176 identified by P703P-DE13: Amino acid sequence sequence number predicted by P703P-DE13 No. 177: P70 3P-DE14 cDNA sequence identification: No. 178: P703P-DE14 identified cDNA sequence recognition 179: 1G-4736 identified extended cDNA sequence sequence identification number 180: 1G-473 8 defined extended cDNA sequence sequence recognition number 181: 1G-4741 defined extended cDNA sequence sequence recognition 182: 1G-4744 defined extension cDNA Sequence SEQ ID NO: 183: 1H-4774 Determined Extended cDNA Sequence Identification 184: 1H-4781 Determined Extended cDNA Sequence Identification 185: 1H-4785 Defined Extended cDNA Sequence Column Identification No. 186: 1H-4787 Determined Extended cDNA Sequence Identification 187: 1H-4796 Determined Extended cDNA Sequence Identification 188: 11-4807 Determined Extended cDNA Sequence Identification 189: 11-4810 Determined 3 'cDNA sequence sequence recognition No. 190: 11-4811 identified 3fcDNA sequence 歹 sequence identification 191: 1J-4876 defined extended cDNA sequence recognition 192: 1K-4884 defined extended cDNA sequence identification 193: 1K- 4896 Determined Extended cDNA Sequence 127691.doc -19- 200815476 Sequence Identification No. 194: 1G-4761 Determined Extended cDNA Sequence Sequence Identification No. 195: 1G-4762 Determined Extended cDNA Sequence Identification 196: 1H-4766 Defined Extension cDNA sequence identification No. 197: 1H-4770 identified 3' cDNA sequence sequence recognition No. 198: 1H-4771 identified 3' cDNA sequence sequence recognition No. 199: 1H-4772 defined extended cDNA sequence identification 200: 1D- 4309 identified extended cDNA sequence sequence identification No. 201: 1D.1-4278 defined extended cDNA sequence x, sequence recognition 202: ID-4288 identified extended cDNA sequence recognition 203: 1D-4283 defined extended cDNA sequence Identification No. 204: Extended cDNA sequence sequence identified by 1D-4304 No. 205: Extended sequence of cDNA sequence identified by 1D-4296 Sequence number 206: Extended sequence of cDNA sequence identified by 1D-4280 Sequence number 207: 10-d8fwd determined cDNA sequence Sequence Identification No. 208: 10-H10con Determined cDNA Sequence Identification 209: ll-C8rev Determined cDNA Sequence

U Sequence Identification No. 210: 7.g6fwd Determined cDNA Sequence Identification 211: 7.g6rev Determined cDNA Sequence Identification No. 212: 8-b5fwd Determined cDNA Sequence Identification 213: 8-b5rev Determined cDNA Sequence Identification No. 214: 8-b6fwd-determined cDNA sequence identification 215: 8-b6rev-determined cDNA sequence identification 216: 8-d4fwd-determined cDNA sequence recognition 217: 8-d9rev-defined cDNA sequence 127691.doc -20- 200815476 SEQ ID NO: 218: 8-g3fwd-determined cDNA sequence identification 219: 8-g3rev-determined cDNA sequence sequence identification 220: 8-hllrev-determined cDNA sequence identification 221: g-fl2fwd cDNA sequence identification No. 222: cDNA sequence identified by g-f3rev Sequence identification No. 223: P509S identified cDNA sequence sequence recognition No. 224: P510S identified cDNA sequence sequence recognition No. 225: P703DE5 identified cDNA sequence sequence identification No. 226: 9 -A11-determined cDNA sequence identification No. 227: 8-C6-determined cDNA sequence identification 228: 8-H7-determined cDNA sequence 歹 ij sequence recognition No. 229: JPTPN13-determined cDNA sequence sequence identification No. 230 JPTPN14-determined cDNA sequence identification No. 231: JPTPN23-determined cDNA sequence identification No. 23.2: JPTPN24-determined cDNA sequence sequence identification No. 233: JPTPN25-determined cDNA sequence sequence identification No. 234: JPTPN30-determined cDNA sequence identification number 235: JPTPN34-determined cDNA sequence identification No. 236: PTPN35-determined cDNA sequence sequence identification No. 237: JPTPN36-determined cDNA sequence sequence recognition No. 23 8: JPTPN3 8-determined cDNA sequence sequence identification No. 239: JPTPN39-determined cDNA sequence sequence identification 240 No.: JPTPN40-determined cDNA sequence identification No. 241: JPTPN41-determined cDNA sequence -21 - 127691.doc 200815476 Sequence identification No. 242: JPTPN42-determined cDNA sequence sequence identification No. 243: JPTPN45-determined cDNA sequence sequence identification No. 244: JPTPN46 Determined cDNA sequence sequence identification No. 245: JPTPN51 identified cDNA sequence sequence identification No. 246: JPTPN56 identified cDNA sequence sequence recognition No. 247: PTPN64 determined cDNA sequence sequence identification No. 248: JPTPN65 determined cDNA sequence sequence identification No. 249: JPTPN67 The identified cDNA sequence recognizes No. 250: JPTPN76 The sequence of cDNA sequence identification No. 251: JPTPN84 identified cDNA sequence sequence recognition No. 252: JPTPN85 confirmed cDNA sequence sequence recognition No. 253: JPTPN86 confirmed cDNA sequence sequence recognition No. 254: JPTPN87 confirmed cDNA sequence identification number 255: JPTPN88 The identified cDNA sequence recognizes No. 256: JP1F1 determines the cDNA sequence, recognizes the number 257: JP1F2 determines the cDNA sequence, recognizes the sequence 258: JP1C2 determines the cDNA sequence, recognizes the sequence 259: JP1B1 determines the cDNA sequence, recognizes the number 260: JP1B2 The determined cDNA sequence sequence recognizes No. 261: JP1D3 confirmed cDNA sequence sequence recognition No. 262: JP1A4 determined cDNA sequence sequence recognition No. 263: JP1F5 determined cDNA sequence sequence recognition No. 264: JP1E6 determined cDNA sequence sequence identification No. 265: JP1D6 The determined cDNA sequence 127691.doc -22· 200815476 Sequence identification No. 266: JP1B5 identified cDNA sequence sequence recognition No. 267: JP1A6 determined cDNA sequence sequence identification No. 268: JP1E8 determined cDNA sequence identification 269: JP1D7 identified cDNA Sequence sequence recognition No. 270: cDNA sequence sequence identification identified by JP1D9 No. 271: JP1C1 0 identified cDNA sequence sequence recognition No. 272: JP1A9 determined cDNA sequence sequence recognition No. 273: JP1F12 determined cDNA sequence sequence recognition No. 274: JP1E12 determined cDNA sequence sequence recognition No. 275: JP1D11 determined cDNA sequence identification No. 276: JP1C11 identified cDNA sequence sequence recognition No. 277: JP1C12 determined cDNA sequence sequence recognition No. 278: JP1B12 identified cDNA sequence sequence recognition No. 279: JP1A12 determined cDNA sequence sequence recognition No. 280: JP8G2 determined cDNA sequence 歹 ij sequence recognition 281 No.: No. 282 identified by JP8H1: Sequence identification of cDNA sequence identified by JP8H2 No. 283: cDNA sequence identified by JP8 A3 Sequence identification No. 284: cDNA sequence identified by JP8A4 Sequence identification No. 285: Sequence identification of cDNA sequence determined by JP8C3 No. 286: JP8G4 identified cDNA sequence 歹 U sequence recognition No. 287: JP8B6 identified cDNA sequence J J sequence identification No. 288: JP8D6 identified cDNA sequence identification 289: JP8F5 determined cDNA sequence 歹 127691.doc -23- 200815476 Sequence Identification No. 290: cDNA sequence determined by JP8A8 歹 ij Sequence recognition No. 291: cDNA sequence identification identified by JP8C7 292 :JP8D7 identified cDNA sequence 歹 ij sequence recognition No. 293: P8D8 identified cDNA sequence sequence recognition No. 294: JP8E7 determined cDNA sequence 歹 J J sequence recognition No. 295: JP8F8 determined cDNA sequence 歹 U Sequence recognition No. 296: JP8G8 determination cDNA sequence 歹U sequence recognition No. 297: JP8B10 identified cDNA sequence 歹 U sequence recognition No. 298: JP8C10 identified cDNA sequence sequence recognition No. 299: JP8E9 determined cDNA sequence sequence recognition No. 300: JP8E10 determined cDNA sequence sequence recognition 301 No.: JP8F9-determined cDNA sequence sequence identification No. 302: JP8H9-determined cDNA sequence sequence identification No. 303: JP8C12-determined cDNA sequence sequence identification No. 304: JP8E11-determined cDNA sequence sequence identification No. 305: JP8E12-determined cDNA sequence sequence identification 306 No.: Sequence of amino acid sequence of peptide PS2#12 No. 307: cDNA sequence identified by P711P Sequence identification No. 308: cDNA sequence identified by P712P Sequence identification No. 309: CLONE23 confirmed cDNA sequence sequence identification No. 310: P774P identified cDNA Sequence sequence recognition No. 311: cDNA sequence identified by P775P sequence recognition No. 312: P715P identified cDNA sequence sequence identification No. 313: P710P cDNA sequence 127691.doc -24- 200815476 Sequence recognition No. 314: P767P-determined cDNA sequence sequence recognition No. 315: P768P-determined cDNA sequence sequence recognition No. 316-325: Defined cDNA sequence identification of the previously isolated gene No. 326: P703PDE5 identified cDNA sequence sequence recognition No. 327: P703PDE5 predicted amino acid sequence sequence identification No. 328: P703P6.26 identified cDNA sequence J! J Sequence identification No. 329: P703P6.26 identified amino acid sequence sequence identification number 330 :P703PX-23 determined cDNA sequence sequence recognition No.331: P703PX-23 predicted amino acid sequence sequence recognition No. 332: P509S identified full-length cDNA sequence sequence recognition No. 333: P707P defined extended cDNA sequence (also known as 11- C9) Sequence recognition No. 334: cDNA sequence sequence identification identified by P714P No. 335: cDNA sequence determined by P705P (also known as 9-F3) Sequence recognition No. 336: P705P predicted amino acid sequence sequence identification No. 337: peptide P1S# 10 amino acid sequence sequence identification No. 338: amino acid sequence sequence identification of peptide p5 No. 339: P509S predicted amino acid sequence sequence recognition No. 340: P778P determined cDNA sequence sequence recognition 341 No.: 342: cDNA sequence identification identified by P786P: cDNA sequence determined by P789P 歹 U Sequence recognition No. 343: Grafting of the pure species of human MM46 mRNA showing the sequence of DNA sequence identification No. 344: for human TNF -α-stimulated ABC protein 127691.doc -25- 200815476 (ABC5 0) mRNA shows the homologous pure germline of the determined cDNA sequence J, J sequence recognition No. 345: for human E-cadherin (cadherin) The mRNA shows homologous pure germline-determined cDNA sequence sequence recognition No. 346: Determination of homologous pure germline to human nuclear-encoded mitochondrial serine hydroxymethyltransferase (SHMT) cDNA sequence recognition No. 347: Identification of the purely germline of the human natural resistance-related macrophage protein 2 (NRAMP2), the sequence of the identified cDNA sequence, No. 348: for human phosphoglucomutase-related The protein (PGMRP) shows a homologous pure germline. The determined cDNA sequence recognizes No. 349: a pure germline-determined cDNA sequence sequence recognition of the mRNA of the human proteosome subunit p40. number :P777P determined cDNA sequence sequence recognition No. 351: P779P determined cDNA sequence sequence recognition No. 352: P790P determined cDNA sequence sequence recognition No. 353: P784P determined cDNA sequence sequence recognition No. 354: P776P determined cDNA sequence sequence identification No. 355 :P780P identified cDNA sequence sequence recognition No. 356: P544P determined cDNA sequence sequence recognition No. 357: P745P identified cDNA sequence sequence recognition 35 8: P782P determined cDNA sequence sequence recognition No. 359: P783P determined cDNA sequence sequence recognition 360 No.: 17984 identified cDNA sequence sequence recognition No. 361: P787P determined cDNA sequence 127691.doc -26- 200815476 Sequence recognition No. 362: P788P identified cDNA sequence sequence recognition No. 363 · Unknown Π 994 identified cDNA sequence Identification No. 364: P781P determined cDNA sequence sequence recognition No. 365: P785P determined cDNA sequence sequence recognition 3 6 6-3 7 5 · · B 3 0 5 D ligated variant identified a sequence identification 376: by Sequence Identification 366 Sequence-Coordinated Predicted Amino Acid Sequence Identification 377: Predicted Amine F-Mercapto Acid Encoded by Sequence Identification 372 Sequence Sequence Sequence Identification No. 378: Predicted amino acid sequence sequence encoded by sequence recognition No. 373 sequence No. 379: Predicted amino acid sequence sequence encoded by sequence recognition No. 374 sequence No. 380: Recognition of sequence 375 by sequence Sequence-encoded predicted amino acid sequence γ, sequence recognition 3 8 1 : Β 716Ρ determined cDNA sequence

U Sequence Identification No. 382: Full-length cDNA sequence identification identified by P711P No. 383: P711P predicted amino acid sequence sequence recognition No. 384: P1000C cDNA sequence sequence recognition No. 385: CGI-82 cDNA sequence sequence recognition No. 386: 23320 cDNA sequence recognition 387: CGI-69 cDNA sequence recognition 388: L-iditol-2-dehydrogenase cDNA sequence sequence recognition 389: 23379 cDNA sequence 127691.doc -27- 200815476 Sequence identification No. 390: 2338 1 cDNA sequence sequence recognition No. 391: KIAA0122 cDNA sequence sequence recognition No. 392: 23399 cDNA sequence sequence recognition No. 393: Previously confirmed gene cDNA sequence sequence recognition No. 394: HCLBP cDNA sequence Identification No. 395: cDNA sequence identification of transglutaminase: No. 396: cDNA sequence of previously identified gene sequence recognition No. 397: PAP cDNA sequence sequence recognition No. 398: Ets transcription factor PDEF cDNA sequence sequence recognition No. 399 : hTGR cDNA sequence sequence identification No. 400: KIAA0295 cDNA sequence sequence recognition No. 401: 22545 cDNA sequence sequence identification 402: 22547 cDNA sequence sequence identification 403: 2 2548 cDNA sequence sequence identification No. 404: 22550 cDNA sequence sequence recognition No. 405: 22551 cDNA sequence sequence recognition No. 406: 22552 cDNA sequence sequence recognition No. 407: 22553 cDNA sequence sequence recognition No. 408: 22558 cDNA sequence Identification No. 409: 22562 cDNA sequence sequence identification No. 410: 22565 cDNA sequence sequence recognition No. 411: 22567 cDNA sequence sequence recognition No. 412: 22568 cDNA sequence sequence recognition No. 413: 22570 cDNA sequence 127691.doc -28- 200815476 Sequence Identification No. 414: 22571 cDNA Sequence Identification 415: 22572 cDNA Sequence Identification 416: 22573 cDNA Sequence Identification 417: 22573 cDNA Sequence Identification 418: 22575 cDNA Sequence Identification 419 :22580 cDNA sequence identification 420: 22581 cDNA sequence recognition 421: 22582 cDNA sequence recognition 422: 22583 cDNA sequence recognition 423: 22584 cDNA sequence identification 424: 225 85 cDNA Sequence Sequence Identification No. 425: 22586 cDNA Sequence Identification 426: 22587 cDNA Sequence Identification 427: 22588 cDNA Column sequence identification No. 428: 22589 cDNA sequence sequence recognition No. 429: 22590 cDNA sequence sequence recognition No. 430: 22591 cDNA sequence sequence recognition No. 431: 22592 cDNA sequence sequence recognition No. 432: 22593 cDNA sequence sequence identification No. 433 :22594 cDNA sequence recognition 434: 22595 cDNA sequence sequence recognition 435: 22596 cDNA sequence sequence recognition 436: 22847 cDNA sequence sequence recognition 437: 22848 cDNA sequence 127691.doc -29- 200815476 sequence identification No. 438: 22849 cDNA sequence sequence identification No. 439: 22851 cDNA sequence sequence identification No. 440: 22852 cDNA sequence sequence recognition No. 441: 22853 cDNA sequence sequence recognition No. 442: 22854 cDNA sequence sequence identification No. 443: 22855 cDNA sequence identification 444: 22856 cDNA sequence sequence identification 445: 22857 cDNA sequence sequence recognition 446: 23601 cDNA sequence sequence recognition 447: 23602 cDNA sequence sequence recognition 448: 23605 cDNA sequence sequence recognition 449 No.: 23606 cDNA sequence sequence recognition 450: 23612 cDNA sequence sequence recognition 451: 23614 cDNA sequence sequence identification No. 452: 23618 cDNA sequence sequence recognition No. 453: 23622 cDNA sequence sequence recognition No. 454: folate hydrolase DNA sequence sequence recognition No. 455: LIM protein cDNA sequence 歹 ij sequence recognition No. 456: known genes cDNA sequence identification No. 457: cDNA sequence recognition of known genes 45 No. 45: cDNA sequence of previously identified gene sequence recognition 459: 23045 cDNA sequence recognition 460: 23032 cDNA sequence recognition 461: cDNA sequence of 23054-30-127691.doc 200815476 Sequence identification 462-467: cDNA sequence identification of known genes 468-471: cDNA sequence of P710P Sequence recognition 472: P1001C cDNA sequence [Invention] Invention DESCRIPTION As specifically mentioned above, the present invention is generally directed to compositions and methods for treating and diagnosing cancers such as prostate cancer. The compositions described herein may include prostate tumor polypeptides, polynuclear acid encoding such polypeptides, binding agents such as antibodies, antigen-providing cells (APCs), and/or immune system cells (e.g., T cells). Polypeptides of the invention typically include at least a portion (such as an immunogenic portion) of a prostate tumor protein, or a variant thereof. "Prostate tumor protein, which is determined by the representative assays provided herein, is at least twice as high as the amount expressed in normal tissues, more preferably at least five times higher, expressed in prostate tumor cells. Protein. Certain prostate tumor proteins are tumor proteins that can be detected in response to antisera in patients with prostate cancer (in immunoassays, such as ELISA or Western blotting). Polynucleotides of the invention are usually Included in, or complementary to, a DNA or RNA sequence encoding all or 4 of the wounded polypeptides. The antibody is typically a protein of the immune system, or an antigen-binding fragment thereof, which is capable of binding to the polypeptide described above. The cells include dendritic cells, macrophages, mononuclear cells, fibroblasts, and cells which exhibit the above-mentioned polypeptides. T cells which can be used in such compositions are usually T cells specific for the above polypeptides. The present invention is based on the discovery of human prostate tumor proteins. It is identified in the sequence 127691.doc -31- 200815476 1-111, 115-171, 173-175, 1 77, 179-3 05, 3 07-3 15, 326, 328, 330, 332. 335, 3.375, 381, 382 or 384-472, which provides a polynuclear tannin encoding certain tumor proteins or a portion thereof. Sequences. Sequences comprising at least a portion of a polypeptide of a tumor protein are provided in sequence recognitions 112-114, 172, 176, 178, 327, 329, 331, 336, 339, 376-380, and 383. Prostate tumor protein multinuclear Any of the polynucleotides encoding a prostate tumor protein, or a portion thereof, or other variants described herein, are encompassed by the present invention. Preferred polynuclear acid includes at least 15 consecutive cores. The acid, preferably at least 3 consecutive nucleotides, and more preferably at least 45 consecutive p-acids encoding a portion of the prostate tumor protein. More preferably, the prostate tumor protein is encoded. Polynucleic acid of the immunogenic portion. Polynucleic acid which is complementary to any such sequence is also included in the present invention. Polynucleic acid may be single-stranded (password or antisense) or double-stranded, and may be DNA (genomic, cDna or synthetic) or molecule. RNA molecules include a NA molecule, which contains an insertion sequence, and a DNA molecule in a one-to-one format, and an mRNA knife that does not contain an insertion sequence. In the multinuclear acid of the present invention, it may also occur, but not necessarily Additional cryptographic or non-cryptographic sequences are required, and polynucleotides may, but do not, need to be linked to other molecules and/or support materials. ϋ Include natural sequences (ie, encode prostate tumor proteins or endogenous sources) Sexual sequences), or variants of such sequences may be included. A polypeptide variant may contain one or more substitutions, additions, deletions and/or insertions to make it a "tumor protein" that does not reduce the immunogenicity of the encoded polypeptide. 127691.doc -32- 200815476 For coding The effect of the immunogenicity of the polypeptide, which can often be assessed as described herein, is preferably a variant that encodes a native prostate tumor protein or a portion thereof of a polynuclear acid that exhibits at least about 7〇% identity. Sexuality, preferably at least about the same as sex, and more preferably at least about 9% identity 0

ϋ The two polynuclear tannin or polypeptide sequences are said to be “identical”. If the nucleotide or amino acid sequences in the two sequences are identical, the maximum identity is obtained when they are aligned. #同同。 The comparison between the two sequences is usually done by comparing the identity of the sequences on the comparison window and comparing the similarities of the local regions of the sequence. The guardian segment has at least about 20 consecutive positions, typically 3 〇 to about 75, 40 to about 50, wherein after the two sequences are optimally aligned, the sequence can be consecutive to the same number. The reference sequence of the position is compared. In order to compare the sequences optimally in a straight line, it can be used in

The Megalign program in Lasergene Bioinformatics Software (DNASTAR Inc., Madison, WI) operates with preset parameters. The program includes several plans that are arranged in a straight line as described in the following references: Dayhoff, MO (1978) A model of evolutionary change in proteins-Matrices for detecting distant relationships. At Dayhoff, Μ·0·(editor) Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, Washington DC Volume 5, Appendix 3, pp. 345-3 58; Hein J. (1990) Unified Approach to Alignment and Phylogenes Pages 626-645 127691.doc -33 - 200815476

Methods in Enzymology, Volume 183, Academic Press, Inc., San

Diego, CA; Higgins, DG and Sharp, PM (1989) CABIOS 5:151-153; Myers, EW and Muller W. (1988) CABIOS 4:11 -17; Robinson, ED· (1971) Comb. Theor 11: 105; Santou, N. Nes, M. (1987) Mol. Biol. Evol. 4:406-425; Sneath, PHA and Sokal, RR· (1973) Numerical Taxonomy-the Principles and Practice of Numerical Taxonomy, Freeman

Press, San Francisco, CA; Wilbur, W. J. and Lipman, D. (1983) Proc. Natl. Acad., Sci. USA 80: 726-730. Preferably, by comparing the two sequences arranged in a straight line on a comparison window of at least 20 positions, the percentage of sequence identity is determined, 'where the multi-nuclear acid or multi-month too sequence is The portion of the comparison window, which may be 20% or less, usually 5 to 15% or 1 to 12%, compared to a reference sequence in two sequences that are suitably arranged (which does not include addition or deletion) Add or remove (that is, gaps). The percentage is calculated by determining the number of identical nucleic acid bases or amino acid residues present in the two sequences at these positions, resulting in the number of matching positions, dividing the number of matching positions by the reference sequence. The number of total positions (that is, the size of the window), and multiplying the result by 100, gives the percentage of sequence identity. The beta 2 may also be 'or alternatively, substantially homologous to the day's gene, or a part or complement thereof. Such polynucleotide variants are capable of hybridizing under moderately stringent conditions to a naturally occurring sequence (or complement) encoding a native prostate tumor protein. Appropriate moderately stringent conditions include pre-washing with 5Χ SSC, 〇.5% SDS, 1 〇 mM EDTA (10) s 〇); overnight at 127691.doc -34-200815476; followed by a kiss at 6rc Rinse twice with 〇·5Χ and 0.2XSSC for 2 minutes. Those skilled in the art will be aware that due to the degeneracy of the genetic code, there are many nucleotide sequences encoding the polypeptides described herein. Two of these multinuclear ophthalmic acids have the lowest homology to the nucleotide sequence of any native gene. - Multi-nuclear Bodhisattva that does not change as a result of differences in codon usage, and is also specifically intended to be included in the present invention. Furthermore, it is also within the scope of the invention to include a dual gene for a gene comprising a polynuclear acid sequence in the present invention. A dual gene is an endogenous gene that is altered by - or a plurality of mutations, such as the deletion, addition and/or substitution of a nucleic acid. The resulting NA and protein can be 'but not required', with altered structure or function. Standard techniques can be used to identify dual genes (such as hybridization, expansion, and/or library sequence comparison). 8. Any of a variety of sequences can be used to prepare the polynuclear decanoic acid. For example, polynucleic acid can be confirmed by a more detailed description below, by virtue of the performance of tumor-phase 2 (i.e., using the representative assays provided herein, in the performance of the Liege gland tumor, The microarray of the CDNA was screened at least five times higher than in normal tissues. Such screening can be performed using a Synteni microarray (pai〇Alto, CA) according to the manufacturer's instructions (and basically in accordance with (10) et al., Pmc. Nad. Acad. Sci. USA 93: 1〇614 ι〇6ι9, η%, and Heller et al, Proc, Natl. Acad Sci USA94: 2i5〇2(5), 1997 description). Alternatively, the polypeptide may be expanded from cells produced from proteins expressed herein, such as cDNA prepared from prostate tumor cells. Such polypeptides can be expanded via polymerase chain reaction (PCR). Regarding this method 127691.doc -35- 200815476, sequence-specific primers can be designed based on the sequences mentioned herein, and can also be purchased or synthesized. Full length genes can be isolated from appropriate libraries (e.g., prostate tumor CDNA libraries) using well-established techniques using well-established techniques. In such techniques>, one or more polynuclear tannin probes or primers suitable for amplification are used to select (CDNA or genome) libraries. Preferably, the library is a larger molecule of the size 1 of the selected size. In order to confirm the 5, and upstream regions of the gene, random primers

The child is also better. In order to obtain an inserted sequence and an extended 5, sequence, a genomic library is preferred. ^Off: Hybridization technology can use a well-known technique to label a partial sequence (for example, by a gap or by a 32;? end). The bacterial or phage library is then screened by hybridizing a filtrate containing denatured bacterial colonies (or fine moss containing phage spots) to the labeled probe (see Sambruk et al.,

Molecular Cloning ; A Laboratory Manual, Cold Spring

Harbor Laboratories, c〇ld ton η_〇γ, Νγ, i9 called. Hybrid colonies or spots are selected and expanded, and Li A is isolated for further analysis. The eDNA pure lineage can be analyzed to determine the amount of additional sequences, e.g., by PCR' using primers derived from partial sequences and primers derived from vectors. A restriction map and a partial sequence can be generated to confirm one or more partially overlapping pure lines. The complete sequence is then determined using standard techniques, which may involve the deletion of pure lines that produce . The resulting partially overlapping sequences are then assembled into a sequence of soaps. Μ英佑田: σ a , , S uses a well-known technique to connect a suitable piece of & ’ to produce a full-length cDNA molecule. In addition, there are a number of expansion techniques to obtain a full 127691.doc -36 - 200815476 long cipher sequence from a portion of the cDna sequence. In this type of technology, the expansion is usually done via pcR. The steps of the various sets of cores that are available for purchase can be used to design the primers using software such as is well known in the art. Preferably, the length of the primer is 22_3_m with at least a view of the coffee content and is between about 68 ° C and 72. The target sequence is annealed at a temperature of: The extended region can be sequenced as described above, and the partially overlapping sequences are assembled into a continuous sequence. One such expansion technique is reverse phase PCR (see Triglia et al., Nud AC1dS). · Res· 16 : 8 186, 1988), which uses restriction enzymes to generate fragments in known regions of the gene, and then cyclizes the fragments by intramolecular ligation, which is used as a difference in utilization and derived from A template for the pcR of the primer of the known region. In another method, the factor of the crosslinker sequence and the primer specific to the known region can be used to find a region adjacent to the partial sequence by expanding the effect. Sequence. The expanded sequence is typically subjected to a second round of amplification, using the same crosslinker primer, and a second primer specific for the known region. In this program change, it uses two slaves. Primers that are known to begin to extend in the opposite direction of the sequence are described in WO 96/38591. Other such techniques are referred to as "rapid expansion of the cDNA ends" or race. This technique involves the use of internal and external primers. ,its Poly A region or vector sequence hetero-' to confirm the sequence of the 5' and 31 ends of the known sequence. Other techniques include capture PCR (Lagerstom et al, PCR Methods Applic. 1 : 1 1 Bu 19, 1991) and walking PCR (Parker) Etc., Nucl· Acids. Res. 19:305 5-60, 1991). Other methods of amplification can also be used to obtain full-length cDNA sequences. 127691.doc -37- 200815476 In some cases It is possible to obtain full-length cDNA sequences by analyzing sequences provided in the expressed sequence tag (EST) database, such as those available from GenBank, usually using well-known programs (eg, NCBI BLAST studies). Partially overlapping ESTs can be used to generate continuous full-length sequences using such ESTs. Sequence identification l-iii, ι15·171, i73_175, m, m_3()5, 307-3 15, 326, 328, 330 Nucleic acid sequences encoding certain cDNA molecules encoding at least a portion of prostate tumor proteins are provided in 332-335, 340-375, 381, 382, or 3 84-472. The isolation of these polynucleotides is described below. These prostate tumor proteins Excessively expressed in prostate tumor tissues. Polynucleotide k-body can be prepared by any method well known in the art, including chemical synthesis by, for example, solid phase phosphoproline chemical synthesis. Standard mutation-producing techniques can also be used, such as the recruitment of a nucleoside-specific site-specific mutation, and the modification into a polynucleic acid sequence (see Adelman et al., DNA 2: 183, 1983). Alternatively, an RNA molecule can be produced by transcribed a prostaglandin tumor protein or a broad DNA sequence thereof in vitro or in vivo, with the proviso that the (10) VIII is incorporated with an appropriate RNA polymerase promoter gene. (like Ding 7 or 81 > 6) in the vector. Certain portions can be used to prepare the encoded polypeptides described herein. In addition, or in addition, the portion can be administered to a patient to produce a polypeptide encoded in vivo (for example, by transferring the infection-providing cell, such as a dendritic cell, by a cDNa construct encoding a prostate tumor polypeptide. The salt-transferred cells are administered to the patient). ..., 127691.doc -38- 200815476 - A partial sequence complementary to the codon sequence (ie, antisense polynuclear fen) can also be used as a sputum or to regulate gene expression. It is also possible to introduce a cDNA construct transcribed into antisense RNA into the tissue of the tissue to promote the production of antisense RNA. The antisense polynucleic acid described herein can be used to inhibit the expression of tumor protein shellfish. Antisense technology can be used to control gene expression via the formation of triple helices, which jeopardizes the ability of the double helix to fully open the binding of polymerases, transcription factors or regulatory molecules (see - et al, & Η_Γ and Carr, Molecular and Immunologic) Approaches, Futura PubhshmgC〇. (Mt. KiSCO, NY; I·)). Alternatively, antisense molecules that hybridize to a gene-controlled region (eg, a promoter, promoter, or transcriptional initiation site) can be designed and blocked for transcription; or translation can be blocked by inhibiting binding of transcripts to ribosomes. effect. A partial or complementary sequence can also be designed as a probe or primer for detecting gene expression. Various reporter groups can be used to label probes, such as radionuclides and enzymes, and preferably at least 1 nucleotide in length, preferably at least 2 nucleotides in length, optimally At least 3 nucleotides in length, like the primers mentioned above, are preferably 22-3 0 nucleotides. Any polynuclear tannic acid can be further modified to increase its stability in vivo

Qualitative. Possible modifications include, but are not limited to, 'adding the sequence of side J at the 5, and/or 3' ends; using thiophosphate or 2 in the main chain, 〇-甲, and B丄一丞丞The bond of phosphodiacetase, and/or contains non-traditional bases such as muscle bud, ash, queosine and wybutosine, and adenine, 肷6^疋, Guanine, thymus p bite and urine. Bite-based, -, earth, stone, and other modifications. 127691.doc -39- 200815476 The nuclear DNA sequences described herein can be linked to various other nucleotide sequences using established recombinant DNA techniques. For example, polynucleic acid can be selected into any of a variety of selection vectors, including plastids, steroidal bodies, lambda phage derivatives, and plastids. Vectors of particular interest include expression vectors, replication vectors, probe production vectors, and sequencing vectors. Generally, the vector will contain a replication origin that is functional in at least one organism, a suitable restriction endonuclease position, and - or a plurality of selectable markers. Other elements will be based on the intended use and will be apparent to those skilled in the art. In some embodiments, the polynucleotide is tunable to allow it to enter and be expressed in the cells of the mammal. Such formulations are particularly useful for the therapeutic purposes described below. Those skilled in the art will recognize that there are many ways to achieve the expression of a polynucleotide in a target cell, and any suitable method can be used. For example, the polynucleotide can be incorporated into a viral vector such as, but not limited to, adenosis #, glandular disease #, retrovirus or vaccine virus, or other poxvirus (e.g., fowlpox virus). Techniques for incorporating 1) 1^8 into such carriers are well known to those skilled in the art. The retroviral vector may additionally carry or incorporate a gene of a selectable marker (helping to confirm or select a cell into which the foreign gene is introduced), and/or a gene of the target portion, such as a gene encoded on a specific target cell. The gene of the ligand of the body makes the vector more target specific. Antibodies can also be used to accomplish target targeting by familiar methods known to those skilled in the art. Other formulations for therapeutic purposes, including colloidal dispersion systems, such as macromolecular complexes, microcapsules, centrosomes, beads, and lipid-based systems 127691.doc -40-200815476 - including water bags Oil emulsion, gelatin makeup. The preferred membranes of the micelles and vesicles, which are used as a delivery vehicle in vitro and in vivo, are used as microvesicles (ie, artificial membranes). The vesicles/usages are well known in the art. Preparation and characterization of prostate tumor polypeptides In the context of the present invention, polypeptides detailed herein may comprise at least one immunogenic portion of a prostate tumor protein. , ^ , Ώ , 4 k bodies. As in

U mentioned above, "prostate tumor protein,, . ^ ^ 曰 疋 疋 则 则 则 则 则 则 则 腺 腺 腺 腺 腺 腺 腺 腺 腺 腺 腺 腺 腺 腺 腺Proteins belonging to the prostate tumor egg, mussels, also react with antisera derived from patients with prostate cancer in a detectable manner in immunoassays (such as ELISA). The polypeptides described herein can be of any length. There may also be the presence of other sequences derived from natural proteins and/or heterologous sequences, and such sequences may, but need not, have more immunogenic or antigenic properties.

As used herein, the "immunogen portion" is a portion of a protein that can be recognized (i.e., specifically bound) by B-cell and/or T-cell surface antigen receptors. Typically at least 5 amino acid residues, preferably at least 1 , more preferably up to 20 amino acid residues, of the prostate tumor protein, or variant thereof, are included. Certain preferred immunogens Fractions, including peptides in which the N-terminal leader sequence and/or the penetrating membrane functional site have been deleted. Other preferred immunogen portions may contain small N and/or C-terminal deletions relative to mature proteins ( For example, 3 amino acids, preferably 5 丨 5 amino acids. ^ It is generally possible to confirm the part of the immunogen using well-known techniques, such as at 127691.doc -41 - 200815476

ϋ

Paul, Fundamental Immunology, 3rd edition, 243-247 (Raven Press, 1993) and those outlined in the references mentioned herein. Such techniques include screening for polypeptides for their ability to react with antigen-specific antibodies, antisera, and/or T-cell strains or pure germ lines. As used herein, an antiserum and an antibody specifically bind to an antigen (ie, they react with a protein in an ELIS® or other immunoassay and have no detectable response to an unrelated protein), "Antigen-specific". Such antisera and antibodies are prepared as described herein and using well known techniques. The immunogen portion of a native prostate tumor protein is a portion that is reactive with such antiserum and/or T-cells and is substantially not less reactive than the full length polypeptide (eg, in an ELISA and/or T-cell reaction). In the determination of sex). The extent of this immunogen portion in such assays is similar or higher than that of the full length polypeptide. Such screening can generally be accomplished using methods well known to those skilled in the art, such as those described in Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988, for example, 'The polypeptide can be immobilized on a solid support. Topping and contacting it with the patient's serum allows the antibody in the serum to bind to the already immobilized polypeptide. Unbound serum can then be removed and the bound antibody can be detected using, for example, Protein A labeled 125. , as mentioned above, the composition may include a version of the native prostate tumor egg white. As used herein, a polypeptide, variant, f is a polypeptide that differs from the native prostaglandin by one or more substitutions, deletions, additions, and/or insertions that substantially do not detract from the immunogenicity of the polypeptide. . In other words, relative to the natural protein 'can increase or not change the ability of the variant and antigen - 127691.doc •42- 200815476 anti-serum reaction, or relative to natural protein, can be reduced by 50% or less The best is below 2G%. Such variants can generally be confirmed by modifying the sequence of one of the above polypeptides and assessing the reactivity of the modified polypeptide with the antigen-specific antibody or anti-clearing agent interspersed herein. Preferred variants include those in which one or more proteins have been removed, such as the n' terminal leader sequence or the penetrating membrane functional site. Other preferred variants include variants in which a small portion (e.g., 3 to 15 amino acids, preferably 5 to 15 amino acids) is removed from the N- and/or C-terminus of the mature protein. Preferably, the polypeptide variant is at least about 7%, preferably at least large, ', 90', preferably at least about 95% identical (determined as described above) to the identified polypeptide. . ,

Preferably, the variant contains a retention substitution. , a reservative substitution, which is one of the amino acids, substituted with another amino acid having similar properties, such that the formula of the polypeptide and the hydration rabbit are expected to be No change. The substitution of the amino acid can generally be carried out based on the similarity in the polarity, electrical conductivity, solubility, water repellency, hydrophilicity and/or amphoteric nature of the residue. For example, the negatively charged amino acid includes aspartic acid and bisamine I, v positively charged amino acids include lysine and arginine; and have a non-electrical polar head group and have similar Hydrophilic amino acids include chiral acid, isoleucine and valine; glycine and alanine; aspartame and glutamine; and serine, threonine, phenylalanine and cheese Amino acid. Other amino acid groups that may represent retention changes include: (1) ala, pr〇, giy, g, asp, gln, asn, ser, thr; (2) cys, ser, tyr, thr; (3) Val, ile5 'met' ala' phe, (4) lyS, arg, his; and (5) phe, tyr5 trp, his 127691.doc -43- 200815476. Variants may also, or additionally, contain non-retaining changes. In a preferred embodiment, the difference between the variant and the day (four) column is that the five amino acids or the following substitutions, deletions or additions may also (or additionally) be recorded by, for example, deletion or addition. The immunogenicity, secondary structure and hydration properties have the least affected amino acid to modify the variant.

如同 As mentioned above, a polypeptide may contain a signal (or leader) sequence at the end of the protein, which directs the delivery of the protein in a co-transcriptional or transcribed manner. The polypeptide may also be associated with a cross-linking agent or other sequence that readily synthesizes, purifies or confirms the polypeptide (e.g., a poly-case, or a sequence that facilitates binding of the polypeptide to a solid support. For example, the polypeptide can be combined with an immunoglobulin region. Polypeptides can be prepared using any of a variety of well-known techniques. Recombinant polypeptides encoded by the above DNA can be readily prepared from DNA sequences using any of the various expression vectors known to those skilled in the art. The expression of the DNA molecule of the polypeptide is expressed in a suitable sputum cell transformed or transferred to the infection. The host cell of the scorpion includes a prokaryote, a yeast, and a higher eukaryotic cell. Preferably, the host cell used is E. coli, yeast or mammalian cell lines, such as c〇s or CHO. First using commercially available filter paper, centrifuging from a suitable host/vector system for secretion of the recombinant protein or polypeptide into the medium. The supernatant. After centrifugation, the concentrate can be applied to a suitable purification substrate, such as an affinity matrix or ion exchange resin. The recombinant polypeptide can be further purified using one or more reverse phase HPLC steps. A portion having about 100 amino acids or less, usually about 5 amino acids or less, and other variants, can also be synthesized by synthesis, It is produced using techniques well known to those skilled in the art 127691.doc -44 - 200815476, for example, such polypeptides can be synthesized using any commercially available solid phase technique, such as Merrifield solid phase synthesis, where The amino acid is continuously added to the gradually increasing amino acid chain. See Merrifield, J. Am. Chem'Soc. 85: 2149-2146, 1963. Available from suppliers such as Perkin Elmer/Applied BioSystems Division (Foster City , CA) purchased an apparatus for automatically synthesizing a polypeptide, and may operate according to the manufacturer's instructions to select specific specific η υ which includes a plurality of polypeptides described herein, or at least one of which is described herein. Polypeptides, as well as unrelated sequences, such as known tumor proteins. For example, fusion partners can assist in the provision of helper cell epitopes (immunological fusion partners), preferably by humans. Helps the cell epitope, or may contribute to a higher content than the natural recombinant protein == white matter (exhibition enhancer). Some of the preferred fusion partners are immunological and fusion partners. The fusion partner, in order to increase the solubility of the shell - or to make the protein can be better than the intramolecular = better fusion partner including affinity iron, which helps the protein to pass the standard technology Fusion proteins, including chemical binding, allow: 22: Heavy-f protein forms to express the content of the fusion protein without-fusion of the protein, increasing the production and packaging of the polypeptide component in the appropriate I-present vector's - DNA sequence;:: ligated with the y-terminus of the DNA sequence encoding the second polypeptide component 127691.doc -45-200815476 with cross-linking ,, such that the cryptograms of the sequences are in phase. This allows for translation into a single fusion protein that retains the biological activity of the two constituent polypeptides. The peptide crosslinker sequence can be used to separate the first and second polypeptide components by a distance sufficient to ensure that each polypeptide folds into its primary and secondary structure. Such peptide crosslinkers are combined into the fusion protein using standard techniques well known in the art. The appropriate peptide crosslinker sequence can be selected according to the following factors: (1) its ability to adapt to a resiliently extensible configuration; and (2) its inability to adapt to its function on the first and second polypeptides. The antigenic cleavage site produces a parental secondary structure; and (3) lacks a hydrophobic or charged residue that may react with the antigenic epitope of the polypeptide. Preferred peptides Parenteral sequences contain Gly, Asn and Ser residues. Other near-natural amino acids, such as Thr and Ala, can also be used in the crosslinker sequence. Amino acid sequences that can be used as crosslinkers are included in Maratea et al., Gene 4〇: 39, 46,

1985; Murphy et al., Pr〇c _ Acad ^ uSA 83: 8258-8262, 1986; U.S. Patent No. 4,935,233 and U.S. Patent No. 4,751,180. The length of the cross-linking sequence is usually from from to about 50 amino acids. A crosslinker sequence is not required when the first and second polypeptides have non-essential N•terminal amino acid regions that can be used to separate functional functional sites and prevent steric interference. The ligated DNA sequence is operably linked to appropriate transcriptional or translational regulatory elements. The regulatory element responsible for DNA expression is located only at the 5th end of the DNA sequence encoding the first polypeptide. Similarly, the stop codon required to terminate the translation and transcription termination signals occurs only at the 31 end of the DNA sequence encoding the second polypeptide. 127691.doc -46- 200815476 Also mentioned are t, l 3 polypeptides of this formula, and fusion proteins of unrelated immunogenic proteins. Preferably, the immunogenic protein is capable of eliciting a reversing response. Examples of such proteins include tetanus, tuberculosis, and hepatitis proteins (see 'eg St〇 Ute et al., New Engl. J. Med., 336: 86-91, 1997). In specific embodiments of rutting, immunology The fusion partner is derived from the surface egg tart of the gram-negative bacterium Gram-positive influenza haemophilus B (L. 91/18926). Preferably, the derivative of protein D comprises about one-third of the protein (e.g., 100-1 10 amino acids before the end of the bucket), and the derivative of protein D can be lipidated. In certain preferred embodiments, the first residue comprising a lipoprotein D fusion partner on the Ν-terminal is provided to the multi-month with an additional exogenous T] cell epitope. Improve the degree of performance in E. coli (by which it has the function of a performance enhancer). The lipid tail ensures that the antigen is presented to the cell providing the antigen in the most appropriate manner. Other fusion partners include non-structural proteins derived from the influenza virus, NS1 (hemagglutinin). Typically, 81 amino acids of the N-terminus, hydrazine, are used. Different fragments containing helper-cell epitopes can also be used. In other embodiments, the immunological fusion partner is a protein shell called LYTA or a portion thereof (preferably a C-terminal portion). LYTA is derived from Strept〇c〇ccus penum〇nia, which synthesizes N-acetylmercaptoproline guanamine enzyme called 醯feixiao LYTA (encoded by LyiA gene ^ Gene 43 : 265·292, 1986 ). Lyta is an autolysin that specifically degrades certain bonds in the peptide polysaccharide backbone. The C-terminal functional site of the LYTA protein is responsible for the production of pro- biliary or some bile pigment analogs such as deae 127691.doc -47- 200815476 and force. This property has been exploited to develop a plastid of the LYTA of the E. coli c' terminal, which can be used to express fusion proteins. A purification method for a hybrid protein containing a C-LYTA month at an amine terminal has been described (see B-丨.gy Π): 795_798, 1992). In a preferred embodiment, the repetitive portion of LYTA can be fused to protein f. The repeated portion found in the terminal area begins at residue 178. A particularly good repetitive part consists of residues 188-305. η υ In general, the polypeptides (including fusion proteins) and polynucleotides described herein are isolated. " After separation, the polypeptide or polynucleotide is removed from its original environment. For example, if the naturally occurring protein is isolated from the natural system or + JLK ^ φτ λα , IJL·^ and Wang Yi, the substance is separated. Preferably, such polypeptides are at least about (four) purity' more preferably at least about 95% pure, and most preferably at least about (four) pure. If a polynucleotide is selected in a vector that is not part of the natural environment, it is considered to be isolated. Binding Agents The present invention further provides formulations such as antibodies that bind to the prostate tumor protein in a terry manner and antigen-binding fragments thereof. As used herein, if an antibody or antigen-binding fragment thereof, reacts with a prostate tumor protein at a detectable level (eg, in (10) A), but under similar conditions, does not detect detectable == unrelated protein The reaction 'is referred to as specifically binding to the prostate tumor protein shell." When used in this context, "the person" stands for ~, , ° mouth thinking that the two knives are non-covalently linked to form Compound 4 rush. The ability to bind can be assessed by, for example, determining the binding constant formed by the complex; number 127691.doc -48-200815476 is the value obtained by dividing the concentration of the complex by the concentration of the product of the component. In general, in the context of the present invention, two components are said to "in combination", in which case the complex forms a binding constant in excess of about 1 〇3 liters/mole. Binding constants can be determined using methods well known in the art. The binding agent can be used in a representative assay provided herein, in patients with and without cancer, such as prostate cancer. In other words, antibodies or other binding agents that bind to prostate tumor proteins will produce a signal representative of the presence of cancer in at least 2% of patients with the disease, and will have at least approximately no cancer. A negative signal representing the absence of the disease is produced in the individual. To determine if the binding agent is capable of fulfilling this requirement, a biological sample of a patient with and without cancer can be measured for the presence of a polypeptide bound to the binding agent as described herein (eg, The liquid serum, urine and/or tumor biopsy samples (using standard clinical trials) are shown to be statistically significant in the number of samples of the disease and the disease. Each binder should meet the above criteria: however, those skilled in the art will recognize that a combination of modifiers that improve sensitivity can be used in combination. Any formulation that satisfies the above requirements may be a binding agent. For example, the binding agent can be a ribosome, an RNA molecule or a polypeptide with or without a peptide component. In a preferred embodiment, the binding agent is an antibody or antigen-binding fragment thereof. Antibodies can be prepared by any of the techniques known to those skilled in the art. Mai see, for example, Harlow and Lane, Antibodies: A Laboratory Manual, C〇id Spring Harb〇r Lab〇rat〇ry, 1988. In general, antibodies can be produced by cell culture techniques, including the production of a single 127691.doc-49-200815476 strain described herein, or by transferring the gene of the antibody to the appropriate Bacterial or mammalian cell hosts to allow for the production of recombinant antibodies. In one technique, an immunogen comprising a polypeptide is initially injected into any of a variety of mammals, such as mice, rats, rabbits, sheep or goats. In this step, the polypeptide of the present invention acts as an immunogen without modification. In addition, particularly with regard to short polypeptides, if the polypeptide is linked to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin, an immune response to diisoindole can be induced. The immunogen is injected into the animal host, preferably in combination with one or more vaccinations according to a predetermined schedule, and the animal is regularly bled. From the anti-blood sputum, for example, by affinity chromatography, a multi-strain antibody specific for the poly(tetra) is purified using a polypeptide conjugated to a suitable solid support. A single plant specific for the antigenic polypeptide of interest can be prepared using, for example, the techniques of Kohler and Milstein, Eur J Immun〇i 6: 511-519, 1976, and the modified sacral soil, modified method. antibody. Briefly, these methods involve the preparation of an immortalized cell line capable of producing an antibody having the desired specificity (i.e., reactive to the technique of interest), e.g., from the spleen of an animal obtained by immunization as described above. Cells are used to produce such cell lines. Then, for example, the spleen cells are fused with the myeloma cell fusion partner, preferably the same as the immunized animal, and the pelvic cells are made into rabbits, ^, and feng shui. A variety of fusion techniques can be used. For example, in the North Handyman α ^, in a non-ionic detergent, spleen cells and myeloma cells are mixed for a few minutes, iron you ^ ^ knife and then flattened in a selective medium in low density 'its support Hybrid cells grow 'but do not support myeloma cells. A preferred selection technique uses the selection method of ΗΑΤ (sub-yellow, ticket ten, amine base, thymus core 127691.doc -50-200815476). After a sufficient period of time, usually about 2 to 2 weeks, the hybridized colonies are observed. A single colony was selected and tested for binding activity to the polypeptide to test the culture supernatant. Hybridos with high reactivity and specificity are preferred.

单 Individual antibodies can be isolated from the supernatant of growing hybridoma colonies. In addition, various techniques can be used to increase its yield, such as by injecting the hybridoma cell line into a suitable vertebrate host, such as the abdominal cavity of a mouse. However = can be from the ascites fluid or blood (four) monoclonal antibodies. It is possible to remove π stains by conventional techniques, such as chromatography, gel filtration, sinking, and extraction. The polypeptide of the present invention can be used in the purification process, for example, in the step of affinity chromatography. In certain embodiments, it may be preferred to use an antigen-binding fragment of the antibody. Such fragments include Fab fragments, which can be prepared by standard techniques, and can be obtained from rabbit serum by affinity layer. In the protein A beads column, L, purified immunoglobulin ((4) is called Lane, Antibodies. A Laboratory Manual, Cold Spring Harbor LaWatory, i988), and the (4) and & fragments were generated by papain digestion. It can be coupled by affinity chromatography to separate the therapeutic agents on the protein and the beads. Regarding this, a suitable preparation of the monoclonal antibody of the present invention includes a radionuclide, a differentiation inducing agent, a drug 'toxin, and a derivative thereof. Preferred radionuclides include 9〇Υ,]231, i86Re, 188Re, 211 Δ 212 . ^ ϋ 1. Preferred drugs include amine oximes and sputum, as well as guanidine analogs. The flattening inducers include phorbol esters 127691.doc -51 - 200815476 and butyric acid. Preferred toxins include ricin, chicken virulence protein, diphtheria toxin, cholera toxin, gelonine (gelonin, Pseudomonas exotoxin, Shigella toxin, and Pokeweed antiviral protein. may be directly or indirectly ( The therapeutic agent is conjugated (eg, covalently bound) to the appropriate monoclonal antibody, eg, via a cross-linker group. When the formulation and antibody respectively have substituents that are reactive with each other, direct direct interaction between the formulation and the antibody Reaction, for example, having a nucleophilic group on one, such as an amine group or a sulfhydryl group, capable of reacting with a group having a slow group such as a liver or a mercapto group, or Reacting with an alkyl group containing a good release group (eg, a compound). Alternatively, it may be desirable to couple the therapeutic agent to the antibody via a crosslinker group. Separated from the formulation to avoid interference with the ability to bind. The crosslinker group can also promote the chemical reactivity of the substituents above, and thereby increase the coupling efficiency. The reactivity can also contribute to the formulation or Use of functional groups on the formulation Otherwise, it will be impossible. For those skilled in the art, it is obvious that various dual-function or multi-function, homologous or xeno-functional preparations can be used (as described in the catalogue of Pi(10) Chemical Co., Rockford, IL). Those as a crosslinker group. For example, the coupling can be accomplished via an amine group, a sulfhydryl group or an oxidized carbohydrate residue. This is described in the literature on the right winter. For example, U.S. Patent No. 4,671,958 to U.S. Patent No. 4,671,958, the entire disclosure of which is incorporated herein by reference. Or during the period of entry 127691.doc -52- 200815476 'crosslinkers that can be cut. Many different, cuttables have been described

y Crosslinker group. Mechanisms for releasing a formulation from these crosslinker groups in a cell, including by incision of a reduced disulfide bond (e.g., U.S. Patent No. 4,489,7,10, issued to U.S. Pat. </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; For example, U.S. Patent No. 4,671,958 to R.dwe U., et al., and the catalyzed hydrolysis (e.g., U.S. Patent No. 4,569,789 to BlaUler et al.). It is possible to couple more than one formulation to the antibody. In a specific embodiment, a multi-molecule formulation is coupled to an antibody molecule. In other embodiments, more than one type of formulation can be coupled to an antibody. For example, an immunoconjugate with more than one formulation can be prepared in a variety of ways. For example, more than one formulation can be directly coupled to an antibody molecule, or a crossover that provides multiple attachment locations can be used. Agents. Further, may also be used carrier. Formulation vehicle may carry a variety of ways' directly or via a crosslinking agent comprising a divalent venturi. Helmet when carriers include proteins such as albumin or the like (e.g.

U.S. Patent No. 4,5G7,234 to Kat et al., peptides and multi-enzymes such as aminodextran (e.g., U.S. Patent No. 4,699,784 to Shin et al.: covalent bonding) Or by encapsulation, the carrier is formulated, =: 'monthly granule vesicles (for example, U.S. Patent No. 4,429, _t Lidi 4,873 Na). Specially for radioactive (four) ❹, containing radioactive Small molecules and chelating compounds. For example, Japanese Patent No. 127691.doc-53-200815476 4,735,792 discloses a representative radioactive deuterated small molecule, and a synthetic method thereof. The formation of a radionuclide by a chelating compound The chelating compound includes those containing a nitrogen and a sulfur atom as a donor atom for a metal or a metal oxide radionuclide. A representative chelating compound is disclosed, for example, in U.S. Patent No. 4,673,562 to Davi et al. The synthesis method can be used. Various routes of administration of antibodies and immune co-monitoring can be used. Usually, the administration will be intravenous, intramuscular, subcutaneous or in the re-cut tumor base. Actual dose will be The antibody used, the density of the antigen in the tumor, and the clearance rate of the antibody. The tau cell immunotherapy composition may or additionally contain sputum cells specific for prostate tumor proteins. Such cells can usually be used with standard procedures. Prepared in vitro or in vitro. For example, a commercially available cell separation system can be used from the epiphysis, surrounding blood, or the patient's bone marrow or peripheral blood, as described in CellPro Inc., Bothell WA. The CEPRATEtm system is used to separate τ U cells (see also U.S. Patent No. 5,24 M56; U.S. Patent Nos. 5,215,926, WO 89/06280; W0 91/16116 and WO 92/07243). In addition, T cells can be derived from correlation or Unrelated human, non-human mammalian cell lines or cultures. Prostate tumor polypeptides, polynucleotides encoding prostate tumor polypeptides, and/or antigen-providing cells (Apc) expressing such polypeptides can be utilized. Stimulates tau cells. This type of stimulation is accomplished under conditions and for a time sufficient to allow the production of tau cells specific for the polypeptide. Preferably, more prostate tumors are present. Or the presence of a polynucleotide in a delivery vehicle, such as a centrosome, contributes to the production of a specific 127691.doc-54 - 200815476 cell. If the tau cell kills is coated with a polypeptide, or the expression encodes the polypeptide. The stem cells of the gene are considered to be specific for prostate tumor polypeptides. Any of a variety of standard techniques can be used to assess the terry nature of 7 cells, such as 'in chromium release assays or proliferation 敎Compared with the negative control group, the stimulation index increased more than twice in dissolution and/or proliferation, representing the specificity of tau cells. For example, such assays can be performed as described in Chen et al, Cancer Res &gt; 54 Q. 1 〇 65_1070, 1994. In addition, the detection of butyl cell proliferation can also be accomplished by various known techniques. For example, T cell proliferation can be detected by measuring the rate of increase in leg synthesis (eg, a culture of thymocytes labeled with gasified thymus nuclei) and measuring the thymocyte nucleus incorporated into the DNA. The content of the oath). Exposure to prostate tumor polypeptide (1 ng/ml·100 μg/ml, preferably 2 〇〇 ng/ml to 25 μg/3⁄4 liter) for 3-7 days, should produce at least twice the proliferation of τ cells Increase. Following the above exposure for 2 to 3 hours, the activation of the cells should be generated, measured using a standard cytokinin assay, where a twentieth increase in the release of cytokinin (eg, TNF or IFN_Y) represents τ Activation of cells (see c〇ligan et al., Current pr〇t〇c〇is in Immunology, vol., WUey (10) (v) such as "(eg coffee (9) 忉. Activated T cells, reflecting prostate tumor polypeptides, multinuclei The APC of the nucleoside or the polypeptide may be CD4+ and or CD8+. Prostate tumor protein-specific T cells may be expanded using standard techniques. In a preferred embodiment, the T cell line is derived from a patient, or a related or unrelated donation. And after the stimulation and expansion, they are administered to the patient. 127691.doc -55- 200815476: The purpose of treatment can be expanded in vitro or in vivo, and the amount of prostate tumor polypeptide, vegetable acid or Apc can be expanded. Proliferating cm or 8 τ cells. Various methods can be used to complete the proliferation of such cells in vitro: = for example, the butyl cells can be re--with prostate tumors for many months, or equivalent to = The short peptide of the immunogenic part of the polypeptide is contacted with or without human growth cells like 疋 白 _2 _2 2., and 7 or the stimulator of the synthetic prostate tumor polypeptide. Colonization is expanded in number in the presence of prostate tumors - white shells - or a variety of fines (10). Methods for selecting cells are well known in the art and include limited dilution. Pharmaceutical compositions and vaccines. In certain aspects, the polypeptides, polynucleotides, sputum cells, and/or binding agents disclosed herein can be incorporated into a pharmaceutical composition or immunogenic composition (ie, a vaccine). The pharmaceutical composition includes one or A plurality of such compounds, as well as a physiologically acceptable carrier. The vaccine may include one or more such compounds as well as a non-specific immune response promoter. The non-specific immunoreactive U promoter may be Examples of non-specific immune response promoters that can promote an immune response to an exogenous antigen include adjuvants, biodegradable intermediate limbs (eg, poly-paraffin galactosyl #hCtide), and lipid granules. (will be Incorporating therein; see, for example, Fullert〇n, U.S. Patent No. 4,235,877. The preparation of vaccines is generally described, for example, by M F. p〇weii and MJ·Newman, "Vaccine Design subunh _ adjuvant approach"', Plenum press (Νγ, 1995). Pharmaceutical compositions and vaccines within the scope of the invention may also contain other compounds which are biologically active or absent. For example, in a composition or vaccine 127691.doc-56-200815476, immunogenic portions of one or more other tumor antigens that are incorporated into the fusion polypeptide or are present as isolated compounds may be present. The pharmaceutical composition or vaccine may contain DNA encoding one or more of the above polypeptides for the production of the polypeptide. As mentioned above, DNA can be found in any of a variety of delivery systems known to those skilled in the art, including nucleic acid expression systems, bacteria, and viral expression systems. Many gene delivery techniques are well known in the art, such as those described in Rolland^ Crit. Rev. Therap. Drug Carrier Systems 15: 143-198, 1998, and the kite referenced herein. Appropriate nucleic acid expression systems, including the DNA sequences required for expression in the patient (such as appropriate promoter genes and termination signals). Bacterial delivery systems involve the administration of a bacterium that expresses the immunogen portion of the polypeptide on its surface, or that secretes such epitopes (e.g., Bacillus-Calmette-Guerrin). In a preferred embodiment, a viral expression system (eg, a vaccine virus or other poxvirus, retrovirus, or adenovirus) can be used to introduce DNA, which may involve the use of non-pathogenic (defective) A virus that replicates potential. For example, in Fisher-Hoch et al., Proc. Natl. Acad. Sci. USA 86: 3 17-321, 1989; Flexner et al., Ann. Ν·Υ·Acad. Sci. 569:86-103, 1989; Flexner , et al., Vaccine 8: 17-21, 1990; U.S. Patent Nos. 4,603,112, 4,769,330 and 5,017,487; WO 89/01973; U.S. Patent No. 4,777,127; British Patent No. 2,200,651; European Patent No. 0.345,242 ;^¥〇91/02805; Berkner, Biotechniques 6 · 616-627, 1988;

Rosenfeld et al, Science 252:43 1-434, 1991; Kolls et al, Proc·Natl·Acad·Sci. USA 91:215-219, 1994; Kass^Eisler et al, 127691.doc -57- 200815476

Proc. Natl. Acad. Sci. USA 90: 1 1498-1 1502, 1993; Guzman et al., Circulation 88: 2838-2848, 1993; and Guzman et al., Cii*· Res 73: 1202-1207, 1993 Reveal the appropriate system. Techniques for incorporating DNA into such expression systems are well known to those skilled in the art. DNA can also be "naked" as described, for example, in Ulmer et al., 259: 1745-1749, 1993, and reviewed by c〇hen, Science 259 • 1691-1692, 1993. The coating is applied to the biodegradable beads which can effectively transport the cockroaches into the cells to increase the intake of the naked DNA. In the pharmaceutical composition of the present invention, any known one known to the artist can be used. Suitable carriers, the type of carrier will depend on the mode of administration. The compositions of the invention may be formulated into any suitable form of administration including, for example, topical, oral, nasal, intravenous, intracranial, intraperitoneal Intra-, subcutaneous or intramuscular administration. For parenteral administration, such as subcutaneous injection, the carrier usually includes water, saline, alcohol, fat, butterfly or buffer solution. For oral administration, any of the above carriers can be used. Or a solid carrier such as mannitol, lactose, starch, magnesium stearate, sodium starch, talc, cellulose, raisin, sucrose, and carbonate. A biodegradable centrosome (10) such as polylactic acid can also be used. Salt polyglycolic acid As a carrier for the pharmaceutical composition of the present invention, suitable biodegradable centrosomes are described, for example, in U.S. Patent Nos. 4,897,268 and 5, 〇75,109. Such compositions may also include buffer solutions. (eg neutral buffered saline or acid buffered saline), carbohydrates (eg glucose, cheap or dextran), mannitol's protein, peptide, or such as Gan 127691.doc -58- 200815476 An amino acid such as an amine acid, an antioxidant, a chelating agent such as edta or glutathione, an adjuvant such as hydrazine, and/or a preservative. Further, the composition of the present invention may be formulated into a cold. Roll-dried form. The compound may also be encapsulated in the vesicles using well-known techniques. Any of a variety of non-specific immune response promoters may be used in the vaccine of the invention. For example, it may contain an adjuvant, Most adjuvants contain substances designed to protect the antigen from rapid catabolism, such as chlorinated or mineral oils, and stimulators of immune responses, such as lipid rafts, pertussis and blood-loving rods. ® (B〇rtadella pertussis) or Mycobacterium tuberculosis (Myc〇bac(10)_ tuberculosis). Suitable adjuvants are commercially available, such as Fried's incomplete adjuvant and complete adjuvant (Difc〇Lab〇rat〇) Ries, (10) (10), MI); Mark adjuvant 65 (Merck — c〇mpany, ^, called; aluminum salt, such as aluminum hydroxide gel (alum) or aluminum phosphate; calcium, iron or zinc salts; Insoluble suspension of lysine; brewed sugar; polysaccharide derived by cation or anion; polyphosphazenes; biodegradable centrosome; monophosphoryl lipid A And quil Ae can also use cytokinins such as GM_CSF, or interleukin-2, -7 or -12 as adjuvants. Among the vaccines provided herein, it is preferred to design the adjuvant composition to preferentially induce a (f) type of immune response. High levels of cells of the Thi_ type are classified as S (e.g., brain-gamma, 12, and IL_i 2), and there is a tendency for hemiplegia to induce an immune response to the cell cycle of the administered antigen. Conversely, high levels of type 1 cytokinins (e.g., IL-4, IL_5, IL_6, IL_1〇#〇TNF_p) have a tendency to induce humoral immune responses. After the application of the vaccine of 127691.doc-59-200815476 is provided herein, the patient will continue the immune response, which induces a ThnnTh2^M type response. In a preferred embodiment, preferentially a few types of reactions, the Thl-type cytokinin content will increase much more than the Th2-type cytokinin. These cytokinin levels can be readily assessed using standard assays. For a review of the cytokinin family, see Mosmann and Coffman, Ann. Rev. Immun〇i 7: 145-173, 1989. Preferred adjuvants for preferentially inducing a Th1-type reaction include, for example, monophosphoryl lipid A, preferably 3-de-indole-deuterated monophosphoryl lipid octa (3D-MPL), Together with the aluminum salt. MpL adjuvants are commercially available from ImnrnnoChem Research Inc. (Hamilt〇n, Μτ; see U.S. Patent Nos. 4,436,727; 4,877,61 1; 4,866,034 and 4,912,094. Oligonucleotides containing -CPG (where CpG II The nucleotide is also preferentially induced to induce a Th1 reaction. Such nucleotides are well known and described, for example, in WO 96/025 55. Other preferred adjuvants are regioids, preferably For example, it can be used alone &lt; mixed with other adjuvants. 爿#, the promotion system involves a combination of a single 4-base moon mussel A and a saponin derivative, as described in 94/00153. a combination of QS21 and 3Β·Μρ]: or a less reactive composition in which QS21 is annealed with cholesterol as described in W〇96/3 3 739. Other preferred formulations include oil-in-water The emulsion of the Spears of the Moon® 7 4 Temple, another J. The adjuvant formulation involving QS21, 3~MPL and Fertility® in oil-in-water emulsions, as described in WO 95/17210. Any vaccine can be prepared using well-known methods to produce an antigen's immune anti-drug and appropriate carrier or Combination of excipients. 127691.doc 200815476 组合^ The compositions described herein can be delayed in release formulation (ie, like sacs or sea, § weekly formulations such as 4, which act to slowly release after administration) Partial forms of sputum are administered. Such formulations can usually be prepared using established: branching techniques, and by, for example, oral, transrectal, or subcutaneous implantation, or by The county location is implanted. The delayed release formulation may contain polymorphic, multinuclear acid or antibodies dispersed in a carrier matrix, and/or contained in a reservoir surrounded by a membrane of controlled rate. The _ used in the formulation is biocompatible and may also be biodegradable; preferably, the formulation provides for release of the active ingredient in a relatively constant amount. Formulation in delayed release t The s' of the active composition contained will depend on the site of the implant, the rate of release and the expected period, and the nature of the condition to be treated or prevented. Any of the pharmaceutical compositions and vaccines of the invention may be used. Various delivery vehicles, This promotes the production of antigen-specific immune responses to target tumor cells. The delivery vehicle includes cells that provide antigens (ApCs), such as dendritic cells, B cells, mononuclear cells, and others. Cells designed to be effective APCs. Such cells may, but need not, be modified genetically in order to increase their ability to provide antigens, improve the activation and/or persistence of tau cell responses, and have resistance in situ. The tumor is potent and/or immunologically compatible with the recipient (ie, a matching HLA haplotype). ApCs, including tumors and tissues surrounding the tumor, can generally be isolated from any of a variety of biological fluids and organs, and can be autologous, allogeneic (allogogenic), isogenic or xenogeneic. In certain preferred embodiments of the invention, dendritic cells or a subset thereof, 127691.doc-61 - 200815476, are used as cells providing antigen. Dendritic cells are highly potent APCs (Banchereau and Steinman, Nature 392:245-251, 1998) and have been shown to be effective physiological adjuvants for inducing prophylactic or therapeutic anti-tumor immunity (see Timmerman and Levy, Ann). Rev. Med. 50 : 5 07-529, 1999). In general, dendritic cells can be identified on the basis of their typical shape (radial in situ, visible cytoplasmic processes (dendrites) in vitro), and lack of 6 cells (0019 and 0020). The differentiation markers of 1\ cells (CD3), mononuclear spheres (CD14), and natural killer cells (CD56) were determined using standard assays. Of course, dendritic cells can be designed to express specific cell/surface receptors or ligands that are not found in dendritic cells in vivo or in vitro, and are also intended to include such modified dendritic cells. In the present invention. In addition to dendritic cells, another secretory vesicle-loaded antigen-dendritic cell (referred to as an exochromosome) can be used in the vaccine (see Zitvogel et al., Nature Med. 4 594-600, 1998). Dendritic cells and progeny can be obtained from peripheral blood, bone marrow, tumor-infiltrating cells, surrounding tumor-infiltrating cells, lymph nodes, spleen, skin, blood-sucking blood, or any other suitable tissue or fluid. For example, a dendritic can be differentiated in vitro by adding a mixture of cytokinins such as GM-CSF, IL-4, IL-13 and/or TNFa in a mononuclear ball culture obtained from peripheral blood. cell. In addition, CD34-positive cells obtained from peripheral blood, with blood or bone marrow, may also be added to the medium by adding GM-CSF, IL-3, TNFa, CD40 ligand, LPS, flt3 ligand and/or Other compounds that induce dendritic cell maturation and proliferation, which differentiate into dendritic cells 0 127691.doc 200815476 Tree cells are conveniently divided into "immature, and, mature" cells, which allow for simple The method distinguishes two well-characterized phenotypes. However, this oral p-name method should not be interpreted as excluding all possible intermediate stages of differentiation. Immature dendritic cells are characterized by high uptake and antigen handling. The ability, "the FcY and mannose receptor markers are highly correlated. A representative feature of mature phenotypes is the lower expression of these markers, but the same degree of cell surface molecules that activate negative T cells, such as j-th and II, and MHC 'adhesion molecules (eg 〇1:) 54 and CD1 〇, as well as co-stimulatory molecules (such as CD40, (3) (10) and CD86).

U can usually be used to encode a prostate tumor protein (or a portion thereof or other variable polynuclear acid) to transfer APCs to express a portion of the X-linked gland tumor polypeptide or its immunogen on the cell surface. The infection can occur in the live material, and then the composition or vaccine having the force, the worker who has turned the private cells, or the vaccine can be used for the therapeutic purposes described herein. Or other gene delivery vehicles that provide antigen &lt; cells are administered to a patient&apos; resulting in a metastatic infection in vivo. For example, any method known in the art can be used, as described in the purchase (4) (10). 5 4.TC ^Mahvif Λ , Immunology and cell Biology 75 456-460 ' 1997 describes the gene gun method to complete the transfer of dendritic cells in vivo and in vitro. By dendritic cells or sub- Generation of cells with prostate tumor polypeptides, DNA (naked or in plastid vectors) or RNA' or recombinant antigens or viruses with expression antigens (eg vaccine disease: fowlpox, adenovirus or lentivirus (len The tivirus) vector is cultured together, and the large progeny of the cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic cytoplasmic sinus Partners (such as carrier molecules) are covalently linked. In addition, they can also use pulsed dendritic cells in non-common immunological partners, either in the presence of multiple skins. Cancer treatment makes = (4) The composition described herein can be used in the immunotherapy of cancer to produce prostate cancer. In such methods, 'pass: the pharmaceutical composition and vaccine are administered to the patient. When used herein, &quot;

C 妗 妗, means any warm-blooded animal, preferably human. The patient may or may not have cancer. Therefore, the pharmaceutical compositions and vaccines described above can be used to prevent the development of cancer or to treat patients suffering from cancer. Cancers, including the appearance of malignancies, can also be diagnosed using criteria generally accepted in the art. The medical composition and vaccine can be administered before or after surgical removal of the primary tumor, and/or treatment such as administration of radiotherapy or conventional chemotherapeutic drugs. In certain embodiments, the immunotherapy can be an active immunotherapy, wherein the treatment relies on the use of an immune response-modifying agent (such as the neo- and multi-nucleus disclosed herein) to stimulate endogenous The host immune system 'reacts to the tumor. In other specific embodiments, the immunotherapy can be a passive immunotherapy 'where the treatment involves delivering a formulation with 6 established cancers/immunoreactivity (such as effector cells or antibodies)' which can be directly or indirectly regulated Anti-tumor: use, and does not need to rely on the complete host immune system. Shellfish of effector cells include the above-mentioned T cells, τ lymphocytes (such as (10) 屮 cells Qin τ lymphocytes, and (3) 4 + Τ 肿瘤 _ tumor-infiltrating lymphocytes), killer cells (like 127691. Doc-64-200815476 Natural killer cells and lymphokine-activated killer cells, 8 cells and antigen-providing cells (such as dendritic cells and macrophages) to express the polypeptides provided herein. An alternative, T cell receptor, and antibody receptor specific for the polypeptides referred to herein are selected and transferred to other vectors or effector cells for use in the immunotherapy employed. For passive immunotherapy, the polypeptides provided herein can also be used to produce antibodies or antibodies that are resistant to this type (as described above, and as described in U.S. Patent No. 4,918,164). By growing in vitro, as described herein, effector cells are available in amounts sufficient for use with the immunotherapies employed. It is well known in the art to expand the number of single antigen-specific effector cells to millions, and to maintain the identification of antigens in vivo. Such in vitro culture conditions are typically stimulated intermittently with antigen, usually in the presence of cytokinins (such as IL-2) and undivided food cells. As mentioned above, (iv) an immunoreactive polypeptide provided herein rapidly expands the antigen-specific T cell culture to produce a sufficient number of cells for immunotherapy. In particular, cells that provide antigen, such as tree canine cells, giant scorpion cells, mononuclear cells, can be transferred using immunoreactive polypeptide pulses, or one or more polynuclear acid, using standard techniques well known in the art. , fibroblasts or B cells. For example, a cell that provides an antigen can be infected with a poly-η acid transfer infection having a promoter gene suitable for expression in a recombinant virus or other expression system. The cultured effector cells used in the treatment must be able to grow in vivo and be widely distributed&apos; and survive for a long time. Studies have shown that in vivo 127691.doc 200815476 can be used to induce growth of cultured cells by repeated stimulation with an antigen supplemented with IL-2 (see, for example, for example)

Cheever's 'immun〇i〇gicai Reviews 157 : 177,1997) 〇In addition, the vector expressing the polypeptide mentioned in this article can also be introduced into the antigen-producing cells taken from the patient and colonized in vitro. The way to breed, then transplanted back to the same patient. The transferred infected cells can be reintroduced into the patient using any method known in the art, preferably by intravenous, intraluminal, intraperitoneal or intratumoral administration in a sterile form. The route and frequency of administration of the therapeutic compositions disclosed herein, as well as the agents, will vary from subject to subject and can be rapidly established using standard techniques. In general, pharmaceutical compositions and vaccines can be administered by injection (e.g., intradermally, intramuscularly, intravenously or subcutaneously), intranasally (e.g., by inhalation), or via oral administration. Preferably, a dose of between 1 and 1 may be administered over a period of 52 weeks. Preferably, six doses are administered at intervals of .丨 months, and then a continuation of vaccination is given periodically. For each individual patient, another draft of the choice may also be appropriate. The appropriate dose is that when the drug is taken as described above, the rhyme promotes the anti-tumor immune response and has a compound content of at least 1 〇 5 % above the base (i.e., untreated) value. Such reactions can be monitored by measuring the anti-sputum antibodies in the patient's body, or (d) (d) the production of vaccine-dependent effects of lytic effector cells that kill the tumor cells of the patient in vitro. Such vaccines should also be able to elicit an immune response that results in improved clinical outcomes in patients who are vaccinated (eg, more frequent mitigation, complete or partial or long..., disease) compared to patients who are not vaccinated Survival). For pharmaceutical combinations containing one or more polypeptides, the amount of each polypeptide is typically present in a dosage range from about 100 micrograms to 5 milligrams per kilogram of host body weight. The appropriate dose size will vary with the size of the patient, but will typically range from about Hml to about 5 ml. In general, suitable dosages and treatment regimens provide the active compound(s) in an amount sufficient to provide therapeutic and/or prophylactic benefits. Surveillance of such reactions can be monitored by establishing modified = trampoline results (eg, more frequent mitigation, complete or partial or prolonged disease-free survival) in treated patients compared to untreated patients. . Increasing the pre-existing immune response to prostate tumor proteins is often associated with improved clinical outcomes. : Immune-like reactions i can often be assessed using standard sputum, cytotoxic or cytokinin assays, which can be accomplished using samples obtained from patients before or after treatment. Methods for detecting cancer can generally be in biological samples obtained from a patient (eg, blood, serum sputum, urine, and 7 or tumor biopsy samples), or multiple prostate tumor proteins and/or coding such Based on the appearance of the protein's polynuclear acid, it detects cancer in patients. In other words, such proteins can be used as markers to indicate the presence or absence of cancer, such as prostate cancer. In addition, these proteins can be used to detect other cancers. The binding agent generally provided herein allows detection of an antimony containing an antigen bound to the preparation in a biological sample. The poly(n-acid acid primer and probe can be used to detect the content of mRNA encoding the tumor protein 'which also represents cancer. The presence or absence of ... in general, prostate tumor sequence tumor tissue should be present in three levels less than 127691.doc -67-200815476 in normal tissues. There are various assay formats known to those skilled in the art, and binding agents are used to detect the polypeptide label in the sample. See, for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. In general, cancer is present or absent in a patient by contacting a biological sample obtained from the patient with a binding agent; (b) detecting in the sample,

含量 the content of the polypeptide bound to the binding agent; and (c) the content of the polypeptide is determined by comparison with a predetermined cutoff value. In a preferred embodiment, the assay involves the use of a binding agent immobilized on a solid support and removal of the polypeptide from the remaining sample. The bound polypeptide can then be detected using a k/ruthenium containing a reporter group and specifically binding to the binding agent/polypeptide complex. Such detection reagents may contain, for example, a binding agent that specifically binds to a polypeptide or antibody, or other formulation that specifically binds to a binding agent such as anti-immunoglobulin, protein G, protein A or lectin. In addition, it is also possible to make money more ambiguous, in which the &&gt; is marked on the basis of the reporter, and the binding agent which has been fixed by the "Sha" is allowed to be allowed after the binding agent is cultured with the sample. The composition of the sample inhibits the extent to which the labeled polypeptide binds to the binding agent and represents the reactivity of the sample with the already bound binding agent. Suitable polypeptides for use in such assays include full length prostate tumor proteins, as well as portions thereof that bind to the binding agents as described above. The solid support can be any of the materials that can be attached to the tumor protein known to the artist. For example, 151 rpm: b # k —r, .w, the limbs can be smashed on the test wells on the microtiter plate, or the nitrocellulose sputum &amp; In addition, the support is also 127691.doc -68- 200815476 can be beads or discs, such as glass, glass godle fiber, latex, or plastics such as polystyrene or polyvinyl chloride . The support may also be magnetic Ο in the case where the adsorption can be accomplished by contacting the binding agent in a suitable buffer solution with the solid support for a suitable period of time. The contact time can vary with temperature, but is typically between about i hours and about i days. In general, the granules or fiber-optic sensors are, for example, those disclosed in U.S. Patent No. 5,359,681. The bonding agent@ can be placed on a solid support using a variety of techniques known to those skilled in the art and described in detail in the patent and scientific literature. In the context of the present invention, &quot;fix&quot; - means non-covalent bonding, such as adsorption, and covalent bonding (which may be a direct bond between the formulation and the functional groups on the building) Or may be a bond via a crosslinking agent). Immobilization via adsorption onto a microtiter plate or membrane is preferred. In this class, the amount of binder in contact with the pores of the plastic microtiter plate (such as polystyrene or polyvinyl chloride) is between about 10 nanograms and about 10 micrograms, preferably about From 100 nanograms to about i micrograms, it is sufficient to fix the appropriate bismuth-containing binder. Covalent attachment of the binding agent to the solid support can generally be accomplished by first contacting the support with a dual-functional formulation that can interact with the support and a functional group on the binding agent, such as a hydroxyl group. Or both amine groups react. For example, the binding agent can be covalently attached to a support having a suitable polymer coating film using phenylhydrazine, or by condensing an aldehyde group on the support by utilizing an amine group and an active hydrogen on the binding partner. Role to covalently attach (see for example

Pieice Immunotechnology Catalog and Handbook, 1991? A12-A13) 〇 127691.doc 200815476

ϋ In some embodiments, the assay is a two-antibody sandwich assay. The assay can be accomplished by first contacting an antibody that has been immobilized on a solid support, typically a well of a microtiter plate, with a sample to allow binding of the compound to the immobilized antibody. The unbound sample is then removed from the already immobilized polypeptide-antibody complex and a reporter reagent containing the reporter group (preferably a secondary antibody capable of binding to a different portion of the polypeptide) is added. The amount of detection reagent that is still bound to the solid support is then extracted using a method appropriate to the particular reporter group. ~/«V shares are called 又% and 4 teeth; upper, often block the remaining protein binding sites on the support. Any suitable blocker known to the artist can be used, such as bovine serum albumin Tween 2(TM) (Sigma Chemicalc(R), StL〇uis, M〇). After the fall, the immobilized antibody is cultured with the sample, and the polypeptide is allowed to bind to the antibody. The sample may be diluted with a suitable diluent such as phosphate buffered saline (PBS). _ . ^ a ^ ^ 舣g, g, the appropriate contact time, that is, the culture time), for individuals who have enough adenocarcinoma in the eye

In the sample, the time at which the polypeptide is present is detected. B, — 1 乂 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 疋 接触 接触 接触 接触 接触. A degree of binding of 95% is achieved between the polypeptides. Those who are familiar with this will recognize the extent to which the balance is needed during the period of the period. At room temperature, approximately 30 minutes of work can then be removed by rinsing with a suitable buffer solution, like PBS, removing the unbound 疋3 ·1 / ° Tween 2 [secondary antibody added to the solid C. The reporter base can then be included. Preferred reporter groups include those groups mentioned above in 127691.doc -70-200815476. = The detection reagent is combined with the already-prepared antibody-polypeptide complex J &amp; is sufficient to verify the time of binding of the polypeptide. The appropriate time is usually determined by erroneously determining the degree of binding that occurs over a period of time. The H-agent of p,p is then removed and the reporter assay is used to detect the bound assay: the method used to detect the reporter group, depending on the sex of the reporter group. For radioactive groups and t, scintillation counters or methods of self-exposure are generally suitable. Spectrophotometry can be used to detect dyes, luminescent groups, and light-emitting groups. Biotin can be used to detect avidin (usually a radioactive or fluorescent group or enzyme) coupled to a different reporter group. The enzyme reporter group can usually be measured by adding an enzyme to the enzyme (usually lasting a day of nucleus) followed by analysis of a spectroscope or other reaction product. r To determine the presence or absence of a cancer, such as prostate cancer, the signal detected from the reporter group still bound to the solid support is typically compared to a signal that meets the cutoff value. In a preferred embodiment, the cut-off value for cancer detection is the average signal obtained when the antibody that has been immobilized is cultured with a sample obtained from a patient without cancer. Typically, g, a sample that produces a signal that is three standard deviations above the predetermined cutoff value is considered cancer positive. In another preferred embodiment,

Sackett et al., Clinical Epidemology: A Basic Science for Clinical Medicine, Little Brown and Co., 1985, pp. 106-7 ‘Use the Receiver Operator Curve to determine the cutoff value. Briefly, in this particular embodiment, the true positive rate (ie, sensitivity) and false positive rate (100) can be paired from each possible cutoff value that meets the diagnostic test 127691.doc -71 - 200815476 results. The plot of %_specificity determines the cutoff value. The cutoff value on the graph 'the most sinful near the upper left corner (that is, the value covering the largest area) is the most accurate cutoff value, and a sample that produces a signal higher than the cutoff value determined by this method can be considered. It is positive. In addition, you can turn the cutoff value to the left along the graph, minimize the false positive rate, or turn to the right to minimize the false negative rate. Usually a higher yield than the cutoff value determined by this method will be generated.

Samples of U are considered to be cancer positive. &quot; In a related embodiment, the measurement is carried out in the form of a flow-through or strip test in which the binding agent is immobilized on a film such as schloss cellulose. In the flow-through test, when the sample passes through the film, the binding agent which has been fixed in the multi-pad of the sample is combined. Second, when the solution containing the second binding agent is grasped through the film, the labeled binding agent is combined with the binding agent-polypeptide complex. The detection of the combined second binder can then be carried out as described above. In the strip test format, the end 2 of the membrane to which the binder has been incorporated is placed in a solution containing the sample. The hai sample moves along the film' through the area containing the second binder and reaches where the binding agent has been immobilized. Where the antibody is immobilized, the concentration of the second binding agent represents the presence of cancer. Usually, 'the concentration of the second binder at this point' produces a picture which can be read by the naked eye. The absence of such patterns represents a negative result. - Generally, the content of the binding agent immobilized on the membrane is selected so that when the biological sample is contained, it will be sufficient to produce a positive signal in the sandwich assay of the two-antibody. In the format discussed in the text, 'produces a pattern that can be visually distinguished. Preferred binders for use in such assays are antibodies and antigen-binding fragments thereof, 127691.doc-72-200815476. Preferably, the amount of antibody immobilized on the membrane ranges from about 25 nanograms to about 1 microgram, more preferably from about 5 nanograms to about 500 nanograms. Such tests are usually performed using very small amounts of biological samples. Of course, there are many other assays that are suitable for use in tumor proteins or binding agents of the invention. The above description is only intended to illustrate. For example, it is apparent to those skilled in the art that the above draft can be readily modified to use prostate tumor polypeptides to detect antibodies that bind to such polypeptides in biological samples. Detection of such prostate tumor protein-specific antibodies may be associated with the presence of cancer. It is also possible or additionally to detect cancer based on the presence of T cells in a biological sample that specifically react with prostate tumor proteins. In some methods, biological samples containing (2]34+ and /4CD8+ T cells are isolated from a patient, such as a gland tumor polypeptide, a polynucleic acid encoding such a polypeptide, and/or expressing such a polypeptide. At least one immunogenic portion of Apc is cultured together and detects the presence or absence of specific activation of T cells. Suitable biological samples include, but are not limited to, isolated T cells. For example, by routine Techniques (such as Ficoll/Hypaque density gradient centrifugation by peripheral blood lymphocytes) are used to isolate T cells from patients. Tau cells can be combined with prostate tumor polypeptides (eg, 5-25 μg/ml) at 37 t: in vitro. ) Cultivate together for 4 days). It is desirable to culture another aliquot of T cell samples in the absence of a prostate tumor polypeptide for use as a control group. Regarding cD4+ τ cells, it is preferable to detect activation by evaluating the proliferation of tau cells. With regard to CD8 sputum cells, it is preferred to detect activation by cytolytic activity as 127691.doc-73-200815476 two = at least twice as high as in patients without disease, and/or the extent of w-reactivity is tb Patients with no disease are at least as high as sputum, representing cancer in the patient's body. As mentioned herein, cancer can also or additionally be detected based on the amount of m-encoding of the rotatable gland tumor protein in the biological sample. For example, in a rabbit, a polymerase chain reaction using at least two oligo primers is used to expand a tumor that is derived from a prostate tumor in a biological sample, wherein at least one oligonucleotide is introduced before coding. (4) The multinuclear taste of tumor proteins is specific (that is, it is complicated with it. Then, using techniques well known in the art, such as gel electrophoresis, separation and detection have been expanded.) In the hybridization assay, (4) an oligonucleotide probe that specifically hybridizes with a polynuclear acid encoding a prostate tumor protein to detect the presence of a polynuclear acid encoding a tumor protein in a biological sample. Hybridization, the oligo-nucleotide primer and the probe should be in a sequence of four (four), which has at least about township, preferably 75%, and more preferably 2 = about 9〇% identity with the prostaglandin. And the multinuclear acid is at least 10 nucleotides in length, and preferably at least 20 nucleotides. Preferably, the nucleocapsid primer and/or the needle are disclosed in the text. More than a month, too many talents Hybridization under moderately stringent conditions. Oligonucleotide primers and/or probes that are useful in the diagnostic methods described herein are preferably at least 10-40 nucleotides in length. In preferred embodiments In the oligo-nucleotide primer, the sequence includes: 115-171, 173-175, 177, 179_3 〇 5 127691.doc ~ 74 ** 200815476, 307-315, 326, 328, 33 0, 332-33 5. At least one adjacent nucleotide of the DNA molecule of the sequence mentioned in 345-375 and 381, more preferably at least 15 adjacent nucleotides. Regarding the Pcr-based assay, And hybridization assays are well known in the art (see, for example, ""仏 et al, Cold Spring Harbor Symp. Quant. Biol., 51:263, 1987; Erlich ed., PCR Technology, Stockton Press, NY, 1989) Ο u A preferred assay using RT-PCR in which pCR is combined with reverse phase transcription. Typically, A is extracted from a biological sample such as a biopsy tissue and reverse transcribed to produce a cDNA molecule. PCR amplification using at least one specific primer to generate cDNA molecules, which can be used It can be separated and imaged by gel electrophoresis, and the biological sample obtained from the test subject and the individual who does not have cancer can be expanded. The amplification reaction can be performed on several dilutions of cDNA across two stages. In a sample of several dilutions of a test patient, a performance that is increased by a factor of two or more compared to a non-cancer sample of the same dilution is generally considered to be positive. In other specific embodiments The disclosed composition can be used as a marker for cancer. In this embodiment, the above-described assay for cancer diagnosis can be performed over a period of time, and the change in the content of the reactive polypeptide or polynuclear acid can be evaluated. For example, during the period of 6 months to ! years, the measurement is performed every 24 to 72 hours, and then the measurement is performed again when necessary. First, 'cancers' are performed in patients who have detected an increase in nucleoside acid during this period. Conversely, when the ❹m content of the reactive polypeptide is lower, the cancer progresses. ^ 127691.doc -75- 200815476 , "Some diagnostic assays in vivo can be performed directly on the tumor... A follow-up analysis involves contacting the tumor cells with the binding agent 1 to directly or indirectly the reporter's group The bound binding agent is detected. The binding agent can also be used in the fourth method. Alternatively, a polynuclear acid probe can be used in the use of the above (4).

As mentioned above, 'to improve sensitivity, multiple prostate tumor proteins can be assayed in a specific sample. In the single-assay, the binding agents specific for different proteins will be provided herein. mixing. Furthermore, multiple primers or probes can be used simultaneously. Tumor protein π (4) selection can be based on routine experiments to determine the combination that produces the best sensitivity. In addition, or in addition to the detection of tumor proteins, the assays of other known tumor antigens may be mixed herein. Diagnostic Tool Set The present invention further provides a tool set for use in any of the above diagnostic methods. The wn group usually includes two or more known knowledge required to complete the diagnosis. The ingredients can be compounds, reagents, containers and/or equipment. For example, a container in the tool set may contain a monoclonal antibody or μ thereof that binds to the prostate tumor protein. A forced antibody or fragment that is attached to the above-mentioned branch (iv) may be provided. One or more other containers can contain the elements to be used in the assay, such as reagents or buffer solutions. Such X-rays may also or additionally have a detection reagent of 34 which contains a reporter group suitable for direct or indirect detection of antibody binding. The Buco &amp; tool set is set in a biological sample to detect the refractory content of the protein encoded by the prostate. Such a tool group #includes at least one of the above-mentioned oligonucleotide probes or primers which hybridize to a multinuclear acid encoding a prostate tumor protein. For example, such oligonucleotides can be used in PCR or hybridization assays. Other components that may be present in such a tool set include a second oligonucleotide and/or diagnostic reagent, or a container, that facilitates detection of a polypeptide encoding a prostate tumor protein. The following examples are provided for explanation, but are not intended to be limiting. [Embodiment] Example

y Example 1 Isolation and Determining Characteristics of Prostate Tumor Polypeptides This example describes the isolation of certain prostate tumor polypeptides from a prostate tumor CDNA library. A human prostaglandin cDNA expression library was constructed from prostate tumor poly A+ RNA using a cDNA synthesis Superscript plastid system, such as the plastid selection tool set (BRL Life Technologies, Gaithersburg, MD 20897), according to the manufacturer's draft. Specifically, prostate tumor tissue was homogenized using p〇iytron (Kinematica, Switzerland) and all RNA was extracted using Trizol reagent (BRL Life Technologies) according to the manufacturer's instructions. The poly A+ RNA was then purified according to the manufacturer's draft using the Qiagen 〇ligotex spin column mRNA purification tool set (Qiagen, Santa Clarita, CA 91355). The first strand of cDNA was synthesized using a NotI/01ig〇-dTl 8 primer. The synthetic double stranded cDNA' was ligated with EcoR/ΒΑΧΓ conjugate (invitrogen, San Diego, CA) and digested with Notl. The cells were then fractionated by Chr〇ma Spin-1000 column (ClonteclvPaloAlto, CA), and the cDNA was ligated into 127691.doc -77-200815476 to the EcoRI/Notl position of pCDNA3.1 (Invitrogen). Transdermally transformed into ElectroMax E. coli DH10B cells (BRL Life Technologies). A normal human pancreatic cDNA representation library was prepared from a collection of six tissue samples (cl〇ntech) using the same procedure. The characteristics of the cDNA library were determined by determining the number of independent colonies, the percentage of pure lines with insert sequences, the average insert size, and by sequence analysis. The prostate tumor bank contains 1.64χ1〇7 independent colonies, of which 7〇% of the pure lines have insert sequences and the average insert size is 1745 base pairs. The normal pancreatic cDNa pool contains 3 · 3 X 106 independent colonies, of which 69% of the pure lines have the insertion sequence ' and the average insert size is 1120. For both of these libraries, 'sequence analysis showed that most of the pure lines have full-length cDNA sequences, and 攸 mRNA synthesis' has minimal rRNA and mitochondrial DNA contamination, using the above prostate tumors and normal pancreas The cDNA library was subjected to the removal of impurities from the cDNA library as described by Hara et al. (Blood, 84: 189-199, 1994) with several modifications. Specifically, a cDNA library for deducting prostate tumors is generated as follows. The normal pancreatic cDNA library (70 μg) was digested with EcoRI, Not]^SfuI, followed by a filling-filling reaction of the UDNA polymerase Klen〇w fragment. After phenol, gas-extraction and ethanol precipitation, the DNA was dissolved in 1 〇〇 microliter Η&quot;, heat denatured and with 1 〇〇 microliter (1 μg) photoprobe biotin ( Vector Laboratories, Burlingame, CA) Blend. The resulting mixture was irradiated with ice on a 27 〇w sun light for 2 minutes on ice according to the manufacturer's recommendations. Additional light probes (5 〇 127691.doc -78 - 200815476 μl) were added and the biotinylated reaction was repeated. After five extractions with butanol, the DNA was precipitated with ethanol and dissolved in 23 μl of H2 hydrazine to form a manipulator DNA. To form the longitudinal DNA, 10 μg of the prostate tumor cDNA library was digested with BamHI and Xhol, extracted with chloroform, and passed through a Chroma spin-400 column (Clontech). After the ethanol was dissolved, the tracer DNA was dissolved in 5 μl of Η2〇. The tracer DNA was mixed with 15 μl of manipulator DNA and 20 μl of 2χ hybridization buffer solution (l·5MNaCl/10mMEDTA/50mMHEPESpH7·5/0.2% sodium dodecyl sulfate), coated with mineral oil, and completely Heat denaturation. The sample was immediately transferred to a 68 ° C water bath and incubated for 20 hours (long-term hybridization [LH]). The reaction mixture was subjected to treatment with aurein, followed by extraction with phenol/chloroform. Repeat the process more than three times. The subtracted DNA was precipitated, dissolved in 12 μl of H20, mixed with 8 μl of manipulator DNA and 20 μl of 2x hybridization buffer solution, and subjected to hybridization at 68 ° C for 2 hours (short-term hybridization [SH]). After removal of the biotinylated double-stranded DNA, the subtracted cDNA was ligated into the 8&amp;111111/^11〇1 position of chloramphenicol-resistant pBCSK+ (Staragene, La Jolla, 0 8 920 3 7), and It is transformed into ElectroMax E. coli DH10B cells by electroporation to produce a cDNA library deducting prostate tumor-specific cDNA (referred to as π prostate deduction 1). To analyze the deduced cDNA, randomly select self-deducting prostate tumors. The plastid DNA was prepared from 100 independent pure lines in a pool of specificity and grouped based on the size of the inserted sequence. By DNA sequencing, Perkin Elmer/Applied Biosystems Division Automated Sequencer 373 Type A was used ( Foster City, CA), further characterizing the representative cDNA pure lineage 127691.doc-79-200815476. In the cDNA library deducting prostate specificity, it is shown that it is rich in six pure germline 'hereinafter referred to as Fl -13, Fl-12, Fl-16, Hl-1, H1-9 and H1-4. The F1-12-determined 3, and 5' cDNA sequences are provided in sequence recognitions 2 and 3, respectively, and are in sequence F1-13, Fl-16, Hl- are provided in Identification Nos. 1 and 4-7, respectively. l, 3, and cDNA sequences determined by H1-9 and H1-4. Using the EMBL and GenBank databases (published 96), the isolated pure germline cDNA sequences were compared with known sequences in the gene bank. In the pure line of prostate tumor cDNA, four pure lines F丨_丨3, F丨_丨6, Hi_gong and H1-4 encode the following previously identified proteins: prostate specific antigen (PSA), human gland The kallikrein, the human tumor expression promoting gene, and the mitochondrial cytochrome c oxidase subunit η were found to be identical to the previously confirmed human autonomously replicating sequence. The sequence was found to have no significant homology. Subsequent studies led to the isolation of the full-length cDNA of F1-12, which was provided in SEQ ID NO: 107, and the corresponding putative amino acid sequence was provided in SEQ ID NO: 1 〇 8. The prostate tumor-specific gene is not abundant, and the above-mentioned prostate tumor cDNA library is deducted by using the normal pancreatic cDNA library, and the three most abundant genes in the previously deducted prostate tumor-specific cDNA library, human gland kinin freed Enzyme, prostate specific antigen (pSA), and mitochondrial cytochrome c oxidase subunit η, complete subtraction of cDNA library. Specifically, human glandular kallikrein, pSA and in PCDNA3.1 The mitochondrial cytochrome c oxidase subunit „cDNA 1 μg each, added to the operator DNA, and deducted according to the above, provides a second cDN Α library after 127691.doc -80-200815476 Let's call it "the 八0" with the indirect display of prostate tumor specificity. Twenty-two cDNA pure lines were isolated from the cDna library with tracer-deducting prostate tumor specificity. In the sequence identification 8·9, 1 (Μι, ΐ2_ΐ3, ΐ4·ΐ5 ' ' 20-21, 22-23, 24-25, 26-27 and 28-29, respectively, it is called η-17, ΕΜ2. Νΐ-1862, η_13, η-19, η-25 J1 24 Kl-58, Kl-63, L1-4 and L1-14 are purely determined by 3

Ο and 5' cDNA sequences. And in the sequence identification 3〇-4 提供, respectively, they are called Jl]2, Jl-16, Jl_2, K1, K155, L1_2, Li 6, ni i858

, 3, cDNA sequence determined by the pure line of Nl-1860, NH861, and Nl-1864. Comparing these sequences with those in the gene bank as described above, three of the five most abundant DNA species showed no significant homology (1-17, 1^1-12, and: ^1-1862). ; for sequence identification 8-9, 1〇-11 and 12_13 respectively). Among the two most abundant species remaining, one was found to be identical to the previously identified human lung surfactant-associated protein shell and the other was identified ( K1_48; sequence recognition No. 33) has some homology to the mRNA of the 2-arylpropenyl-CoA epimerase of Norwegian rat (R. norvegicus). Four of the 17 less abundant cdNA pure lines isolated from the prostate tumor-specific cDNA library with tracers were found (Jl-16, Kl-55, L1-6, and N1-1864; For sequence recognition 3 ^ , 34 , 3 6 and 40 ) is identical to the previously confirmed sequence and two (Π-21 and N1-1860; sequence recognition 32 and 38 respectively) pairs of non-human sequences were found Some homologousities were shown, and two (L 2N and 1-1861; sequence recognitions 35 and 39, respectively) were found to exhibit some of the same 127691.doc -81 - 200815476 species for known human sequences. For the polypeptides JH3, JH9, J1-24, Jl-25, Kl-58, Kl-63, Ll-4, respectively, sequence identification 14-15, 16-17, 20-2, 18-19, 22-23, 24-25, 26-27, 28-29) did not find the same sex. The post-production study led to the separation of all *CDNA from n_17, (sequence identification 1〇9^11, respectively). A corresponding putative amino acid sequence is provided in sequence identification 112-114. L1-12 is also known as P501S 〇

Ο In a further experiment, normal prostate cDNA prepared from three normal prostate poly A+ RNA collections was used, and the prostate tumor bank (deducted 2u) was subtracted to confirm four additional sequences. These pure germ lines are provided in Sequence Identification No. 72, which are hereinafter referred to as u1-3〇64, 耵1-3065 11-3692, and 1-8-3905, which are determined by the sequence of Comparisons among those in the gene bank showed no significant homology to the 〇Bu 3〇65. Hunting the CDNA library of the prostate tumor with an abnormality in the normal pancreatic DNA library Chen V. , n_17, lung surfactant-related protein, mitochondrial DNA, cytochrome _ chemase arsenic, Ν1_1862, autonomously replicating sequence, 匕12 and swollen silk are now promoted by /, ~ Min, ordering The second deduction with the display (referred to as "prostate deduction 2 with indirects"). Four additional pure lines were isolated, hereinafter referred to as V1_3686, R1_233G, 13976 and heart 679. In the preface (4) No. 73-76, the pure-bred series "fixed c-ship sequences are provided. Comparing these sequences with those in the gene bank shows that there is no significant homologous to ... and R1-2330. Sex. 127691.doc -82- 200815476 Two further analysis of prostate deduction (prostate deduction) 2, the cDNA library with tracer subtraction of prostate specificity, and prostate deduction with tracer 2), the results confirmed sixteen extra pure lines, called 1G-4736, 1G-4738, 1G-474 Bu 1G-4744, 1G-4734, 1H-4774, 1H-478 Bu 1H-4785, 1H-4787, 1H-4796, 11-4810, 11-4811, 1J-4876, 1K-4884 and 1K- 4896. These pure germline-determined cDNA sequences are provided in Sequence Identification No. 77-92, respectively. These sequences are compared to those in the Gene Bank as described above, showing pairs, 11-4807, 1J-4876, and 1Κ- 4876 (sequence identifications 79, 81, 87, 90, and 92, respectively) have no obvious homology. Further analysis of the isolated pure lines is guided by the sequence identifications 179-188 and 191_193 respectively. 1G-4736, 1G-4738, 1G.4741, 1G-4744, 1Η-4774, 1Η-4481, 1Η-4785, 1Η-4878, 1Η-4796, 11-4807, 1JN4876, 1Κ-4884, and 1Κ-4896 extension The cDNA sequence, and the additional cDNA sequence of π·481 (^ π_4811) provided in sequence identifications 189 and 190, respectively. Prostate deduction 2 with tracer His research led to further separate the three purebred lines. According to the sequence identified above, and the nearest gene bank for comparison. All three pure lines were found to be homologous to known genes, which are 畐-cysteine-containing proteins, KIAA0242 and KIAA0280 (sequence recognition 317, 319 and 32 nicknames, respectively). These pure lines were further analyzed by Synteni microarray Palo Alto, CA), confirming that these three pure lines were overexpressed in most prostate tumors and prostate BPH, as well as in most of the prostate tissues examined. But rarely in all other normal organizations 127691.doc -83-200815476. By using the normal pancreatic cDNA, the normal prostate cDNA library is deducted, and the deduction is made outside the order (called, prostate deduction 3,). This resulted in the identification of six additional pure lines called '1G-4761, 1G-4762, 1H-4766, 1H-4770 1H_4771 and 1H·4772 (SEQ ID NO: 93-98). These sequences were compared to those in the gene bank, showing pairs 1G-4761 and 1H-4771 (series recognitions 93 and 97, respectively). Further analysis of the isolated pure lines (Λ' led to the identification of the cDNA sequences extended by 1G-4761, ig-4762, 1H-4766 and 1H-4772, respectively, provided in sequence identifications 194-196 and 199, respectively Additional partial cDNA sequences of 1H-4770 and 1H-4771, respectively, provided in Sequence Identifications 197 and 198. Prostate tumors prepared from a collection of poly A+ RNAs from three prostate cancer patients using normal pancreas Deduction of cDNA library (prostate deduction 4) 'causes the identification of eight pure lines, called 1D_4297, ^4309 ID. 1-4278, ID-4288, ID-4283, ID-4304, ID-4296, and 〇1D_4280 ( Sequence identification 99_1〇7). These sequences were compared with those in the gene bank as described above. It was found that 1]〇_4283 and 11&gt;43〇4 (sequence identification numbers 1 03 and 104, respectively) No significant homology. Further analysis of the isolated pure lines led to the identification of ID-4309, 1D.1-4278, ID-4288, ID-4283, 1D4304, respectively, provided in Sequence Identification No. 200-206, Extended cDNA sequence of 1D-4296 and 1D-4280. Separated in prostate deduction 1 and prostate deduction 2 above Cdna pure lineage, accepting colony pCR expansion, and using microarray technology (Synteni, Palo Alto, cA) to measure its mRNA in prostate tumors, normal prostate 127691.doc-84-200815476, and in various other normal tissues In a nutshell, the PCR amplification product is spotted in slide i in a format such that each product occupies a unique position in the array. The mRNA is extracted from the tissue sample tested, reverse transcribed and fired. Light-labeled cDNA probes. The microarray was probed using labeled cDNA probes, scanned for slides and the intensity of the fluorescence was measured. The intensity is related to the intensity of the hybrid. Two pure lines were found (called P5). 09S and P5 01S) overexpressed in both benign and normal prostates and in all other normal tissues (liver, pancreas, skin, bone marrow, court, adrenal gland, bladder, testicular, salivary gland, large intestine, The kidney, ovary, lung, spinal cord, skeletal muscle, and colon are expressed in low amounts. The cDNA sequences defined by P5〇9s and p51〇St are provided in sequence identifications 223 and 224, respectively. These sequences were compared to those in the gene bank and showed some homology to the previously confirmed. Other studies led to the isolation of the full-length cDNA of P509S. The sequence was provided in Sequence Identification No. 332 and was in the sequence. A corresponding putative amino acid sequence is provided in the identification number. Example 2 Tissue Specificity of Prostate Tumor Polypeptides Gene-specific primers were used to examine representative prostate tumor polypeptides Fl-16, Hl-1, J1-17 (also known as P5〇2S), L1- using RT-PCR. 12 (also known as P501S), F-12 (also known as p5〇4S) and N1-1862 (also known as P503S) 'degree of mRNA expression in various normal and tumor tissues. In other words, extract all of them from various normal and tumor tissues using Trizol reagent as described above! ^ eight. The first strand of synthesis was completed using Sup^Script 127691.doc -85 - 200815476 Π reverse transcriptase (BRL Life Technologies) at a temperature of 42 °c using a total of gram of micrograms. Then, by PCR, the gene A-specific primer is used to expand the drama A. To ensure the semi-quantitative nature of the lamp-coffee, actinin was used as an internal control for each tissue examined. First, serial dilutions of the first 〇〇8 are prepared, and β-actin-specific primers are used to determine 'and then select a linear range-enhancing effect of the actin template' and its sensitivity is sufficient to reflect The dilution of the difference in the number of initial copies uses k conditions to determine the amount of β-actin for each reverse transcription reaction from each tissue. Dna contamination was minimized by treatment with DNase and by ensuring a negative PCR result when using the first strand prepared without the addition of reverse transcriptase. In four different types of tumor tissue (prostate tumors from 2 patients, breast tumors from 3 patients, colon tumors, lung tumors) and sixteen different normal tissues, including prostate, colon, kidney, liver The degree of expression of mRNA was examined in lung, ovary, pancreas, skeletal muscle, skin, stomach, testis, bone marrow, and brain. It was found to be expressed in high levels in prostate tumor tissues, colon tumors, and normal prostate, and was expressed in low levels in normal liver, skin, and pellets, and could not be detected in other tissues examined. It was found that H1-1 is expressed in high levels in prostate tumors, lung tumors, breast tumors, normal prostate, normal colon and normal brain 'in normal lung, pancreas, skeletal muscle, skin, small intestine, bone marrow Low content performance. Jl-17 (P502S:^L^12 (P501S) seems to be over-expressed in the gland, and these two genes are expressed in high levels in prostate tumors and positive slings, but in all other The tested group 127691.doc - 86- 200815476 was found to be low in undetectable content. It was found that Nl-1862 (P5〇3S) was overexpressed in 60% of prostate tumors and was found in normal colon and kidney. Therefore, RT-PCR results indicate that Fl-16, HKi, η 17 (P502S), ΝΝ 1862 (P503S), and Ll-12 (P501S) are prostate-specific or significantly elevated in the prostate. Further RT-PCR studies showed that Fl-12 (P504S) was overexpressed in 60% of prostate tumors, detectable in normal kidneys, but not in all other tissues tested. Ground, showing that Rl_233〇 is overexpressed in 40% of prostate tumors, detectable in normal kidneys and liver, but not in all other tissues tested. U1-3064 was found in 60% of prostate tumors. Excessive performance, but also in breast and colon tumors, In normal tissues can not be detected.

The RT-PCR characteristics of Rl-2330, U1-3064 and 1D-4279 showed that these three antigens were overexpressed in prostate and/or prostate tumors. Northern analysis using four prostate tumors, two normal prostate specimens, two BpH prostates and normal colon, kidney, liver, lung, pancreas, skeletal muscle, brain, stomach, testicles, small intestine and bone marrow, showing L1_12 in Prostate tumors and normal prostates are overexpressed and are not detectable in other normal test tissues. Π-17 (P5 02S) ' was detected in two prostate tumors but not in other tissues tested. N1-1862 (P5 03S) was found to be overexpressed in three prostate tumors and manifested in normal prostate, colon and kidney, but not in other tissues tested. F 1-12 (P504S) was found to be highly expressed in both prostate tumors and not detected in all other test tissues. 127691.doc -87- 200815476 The above-described microarray technology was used to determine the extent of the representative antigens described herein in prostate tumors, breast tumors, and normal tissues: prostate, liver, viscera, Skin; I, bone marrow, brain, breast, adrenal gland, bladder, testicular, salivary gland, large intestine, kidney, nest, lung, spinal cord, skeletal muscle and knot [L1_12 (P501S) was found to be excessive in normal prostate and prostate tumors Performance, and some performance was detected in normal skeletal muscle. It was found that η-12 and -12(1&gt;5048) were over-expressed in prostate tumors.

Now, there are very low or undetectable manifestations in all other tested organizations. Nl-1862 (P503S) was found to have high levels of expression in prostate tumors and normal prostates, and low levels in normal and normal colons, but not in all other tested tissues. which performed. R1 -23 30 was found to be overexpressed in prostate tumors and normal prostate, and very low in all other tested tissues. 1D-4279 was found to be overexpressed in prostate tumors and normal prostate, with very low levels of expression in the normal spinal cord, but was not detectable in all other tested tissues. Further microarray analysis, in particular, the extent to which ρ5〇丨s (sequence recognition i )) is expressed in breast tumors, showing a modest overexpression not only in breast tumors' in metastatic breast tumors (2/3 1 There is also a modest over-performance, which can be neglected to a low level in normal tissues. This data suggests that P5 0 1 S can be overexpressed in a variety of breast tumors, as well as in prostate tumors. By using the microarray technique described above, it is examined by Vasmatzis et al. (Proc.

Natl. Acad. Sci. USA 95: 300-304, 1998) describes the extent of performance of 32 ESTs (presentation of private signatures) in various tumors and normal tissues. Two of these pure lines (called P1000c and P1001c) were found to be overexpressed in prostate tumors and normal anterior collaterals, and in other subjects (normal aorta, thymus, resting, and active PBMC, Epithelial cells, vertebral tract, adrenal gland, fetal tissue, skin, salivary gland, large intestine, bone marrow, liver, lung, dendritic run, stomach, lymph nodes, brain, heart, small intestine, skeletal muscle, colon and kidney), as low as Undetectable content performance. The determined cDNA sequences of pi〇〇〇c and pi〇〇ic are provided in Sequence Identification Nos. 384 and 472, respectively. The mRNA of the human ship 7 protein isolated from the sequence of MP1GG1C showed some homology. No significant homology was found for the sequence of pi〇〇〇c. The expression of the polypeptide encoded by the full-length cDNA sequence of Fl_12 (also known as P504S; sequence recognition No. 1-8) was studied by immunohistochemical analysis. A plurality of antibodies against the rabbit side of the full-length P5G4S protein f were produced by standard techniques. Subsequent separation and formulation of the multi-strain antibody was also carried out by the technique known in the art (10). Immunohistochemical analysis showed that the simple s polypeptide was expressed in 100% of the prostate cancer samples tested (n=5). Rabbit-anti-P504s multi-strain antibodies do not appear to be stained with cytoplasmic granules to indicate benign prostate cells' but can be labeled with light nuclear staining. Analysis of normal tissues revealed that the encoded polypeptides were found to be present in some, but not all, normal human tissues. In normal human kidneys, liver, brain, colon, and lungs, there were II (4) fine shots, and positive cytoplasmic staining of rabbit anti-finger 4S antibody was found, while heart and bone marrow were negative. This data indicates that the polypeptide is present in the tissue of the (IV) adenocarcinoma, and between the tissue of the 127691.doc-89-200815476 prostatic hypertrophy and the prostate cancer tissue, the difference in staining and quantitative indicates that the polypeptide can be It is selectively detected in prostate tumor t and is therefore useful in the diagnosis of prostate cancer. Example 3 By PCR-based deduction, the characteristics of prostate tumor peptides were isolated and determined using ten other normal tissues of Cdna (brain, heart, kidney, visceral u, lung, ovary, placenta, bone) Muscle, spleen and thymus were deducted, and then the first round of PCR amplification was performed by acupuncture moxibustion, which contained the normal cDNA selected from the normal prostate, and was purchased from Clontech. According to the manufacturer's draft, the library accepts a second round of PCR amplification. The resulting cDNA fragment was transcribed into the vector pT7 Blue T-vector (Novagen, Madison, WI) and transformed into XL-1 Blue MRF' E. coli (Stratagene). DNA was isolated from the pure line of the unilateral and used Perkin Elmer/A^^. PPlied

Biosystems Division Automated Sequencer 373A type sequencing. The sequences of 59 positive pure lines were determined. Comparing these purebred $@DNA sequences with those in the gene bank as described above, it is shown that 25 of these purebreds have no significant homology, which are referred to as P5, p8, p9, P18, P20, P30, P34, P36, P38, P39, P42, P49, j&gt; 5〇P53, P55, P60, P64, P65, P73, P75, P76, P79 and p84. These pure lineage-determined cDNA sequences are provided in sequence recognitions 41-45, 47-52 and 54-65, respectively. It was found that P29, P47, P68, P80 and P82 (sequence recognition 46, 53 and 66-68, respectively) showed some degree of homology to previously confirmed DNA sequences. As far as the inventors are aware, none of these sequences are 127691.doc-90-200815476. One has previously been shown to appear in the prostate. Further studies using the PCR-based methodology described above resulted in the isolation of more than 180 additional elite lines and found that 23 of the pure lines showed no significant homology to the known sequences. These pure germline determined cDNA sequences are provided in sequence recognition 丨i 5_丨23, 127, 13 1 , 137, 145, 147-151, 153, 156-158 and 160. Twenty-three pure lines (sequence identifications 124-126, 128-130, 132-136, 138-144, 146, 152, 154, 155 and 159) were found to show some homology to previously confirmed ESTs. It was found that another ten pure lines (sequence recognition 161-17 nickname) have some homology to known genes. The larger cDNA pure line contains the P2〇 sequence, which is equivalent to the junctional variant of the gene, called P7Q3P. In the sequence identifications m, 175 and 177, the DNA sequences defined by the variants DEI, DE13 and DE14 are provided, and the corresponding predicted amino acids are provided in sequence identifications 172, 176 and 178, respectively. sequence. A cDNA sequence defined by the extended form of p7〇3 is provided in Sequence Identification No. 225. DNA sequences designated as ligation variants of DE2 and DE6 are provided in sequence recognitions 173 and 174, respectively. According to the above, a representative pure line was determined by RT-PCR in tumor tissues (prostate (n=5), breast (n=2), colon and lung), normal tissues (prostate (n=5), colon, Renal, liver, lung (n=2), ovarian skeletal muscle, skin, stomach, small intestine and brain), and activation and non-activated PBMc, να expression of privacy. The performance was checked in one sample of each tissue type unless otherwise specified. It was found that Ρ9 is highly expressed in normal prostate and prostate tumors compared with all normal sputum tissues, &amp; normal colon, 127691.doc -91 - 200815476 Ο

U shows comparable performance. A portion of the Ρ20, Ρ703Ρ gene was found to be highly expressed in normal prostate and prostate tumors compared to all twelve tested tissues ❶Ρ20 in breast tumors (η=2), colon tumors, and lung tumors. A moderately increased performance was seen as compared to all normal tissues except for the lungs (Hg in 2). P18 was found to have increased performance in normal prostate, prostate, and breast tumors compared to other normal tissues except the lungs and stomach. A moderately increased performance was observed in the normal prostate compared to most other normal tissues. 2, some increased manifestations were seen in normal lung and PBMC: in the &quot; patterns of prostate tumors (2 of 5), (4) tumors, and - lung tumors, a table showing an increase in P5 was observed. see. As for p3〇, a similar degree of expression was seen in normal prostate and prostate tumors compared to six of the twelve other normal test tissues. In the breast tumor, a lung tumor sample, and a colon tumor sample, increased performance was also seen in normal ^PB^IC. It was found that ρ29 was expressed in the if-neutral tumors in the prostate tumors (5, $) and in the positive and inferior glands (5 of the 5 orders) compared with most of the normal tissues. ^, in the normal colon and normal lung (2 of 2 =, Γ to p29 has a considerable degree of performance. In the Jing ^ he is 1 of 5) and normal anterior gallbladder (5 of 5) ) $, compared with all of its test tissues, has excessive performance, and also seen increased performance in colon tumors. ^ The results stated in the text 'separated twelve additional pure lines, at the post price of 8 sen, 9 he and 94. In sequence identification 2 () 7, fine 127691.doc • 92- 200815476

DNAs identified by 710_d8, 10-hl0, 1 l-c8, 8-d4, 8-d9, 8-hl 1, 9-fl2, and 9-f3, respectively, 209, 216, 217, 220, 221, and 222 sequence. The forward and reverse DNA sequences determined by 7-g6, 8_b5, 8_b6 and 8_g3 are provided in sequence identifications 210 and 211; 212 and 213, 214 and 215, and 218 and 219, respectively. Comparison of these sequences with those in the gene bank revealed no significant homology to the sequence of 9-f3. Pure lines 10-d8, 1 l-c8 and 8 were found, hll showed some homology to previously isolated ESTs and found 10-hlO, 8-b5, 8-b6, 8-d4, 8-d9 , 8-g3 and 9-Π2 show some homology to previously identified genes. The characteristics of 7_〇6 and 8-G3 were further determined, showing the same as the known genes pAp and pSA, respectively. The degree of mRNA expression of these pure lines was determined using the microarray technique described above. 7-G6, 8-G3, 8·Β5, 8-B6, 8_D4, 8 19, 9F3, 9-F12, 9-H3, 10-A2, 10-A4, 11-C9 and: n_F2 were found in prostate tumors and Excessive performance in the normal prostate, but low in other tissues tested, or undetectable. In the prostate tumor and normal prostate, bladder, skeletal muscle and colon, an increased performance of 8_FU was seen. In the prostatic gland tumors and normal prostate, bladder, lung, colon, brain and large intestine, an increased performance of 10-H10 was seen. In prostate tumors, breast tumors, and normal prostate, salivary glands, large intestine, and skin, increased performance was observed, (1), and in prostate tumors and normal prostate, as well as in the large intestine, 11 - C 8 increased performance was seen. Additional micro-eDNA fragments derived from the above-mentioned PCR-based normal prostate depletion were found to be prostate specific by micro-array technology and RT_PCR. The purely germline determined _8-order 127691.doc-93-200815476 column (referred to as 9-AU) is provided in Sequence Identification No. 226. This sequence was compared to those in the published library, showing 99% identity to the known gene HOXB 13. Further studies led to the isolation of pure lineages 8-C6 and 8_H7. These pure germline determined cDNA sequences are provided in Sequence Identification 22 7 and 228, respectively. These sequences were found to exhibit some homology to previously isolated ESTs. Using the PCR and hybridization-based methods, the longer cDna sequence of p2〇 (also known as P703P) was generated, resulting in three additional cDNA fragments that progressively extend the 5' end of the side gene. These fragments, called p7〇3pDE5, P703P6.26, and P703PX-23 (sequence recognition 326, 328, and 33 apos;; and provide predictive counterparts in sequence identifications 3 2 7 , 3 2 9 , and 3 3 1 , respectively The amino acid sequence) contains an additional 5, sequence. The cDNA library (#14146) was screened by using a part of P7〇3p as a probe to restore P703PDE5. P7〇3p6 26 was recovered from a mixture of three prostate tumor cDNAs and Ρ703Ρχ·23 was recovered from the cDna library (#43148). The additional sequences together contain all putative mature serine proteases, along with some of the putative signal sequences. Further studies used a subtraction library of PCR-based prostate tumor collections, deducting the collection of normal tissues (called Jp:pCR subtraction), and isolated an additional pure line, seven of which were not known. The gene bank sequence shares any significant homology. The cDNA sequences defined by these seven pure lines (P711p, p712p, novel 23, p774p, P775P, P710P and P768p) are provided in sequence recognition 3〇7_311, 313 and 315, respectively. The remaining six pure lines (sequence recognition 316 and 321_325) are shown to share some isomorphisms with known genes. By microarray analysis, all 13 pure lines were found in prostate tissue, including prostate tumors, BPH, and normal prostate, which showed a triple compared to normal 127691.doc -94-200815476 non-prostate tissue. Or more overperformance. Pure lines P711P, P712P, novel 23 and p768p, showed excessive in most of the prostate tumors and BPH tissues tested (n=29), and in most normal prostate tissues (n=4). Performance, but does not show background to low levels of performance in all normal tissues. Pure breed p774p,? 7751&gt; and p7i〇p show a lower performance and are expressed in a small number of prostate tumors and specimens, but negative to low in normal prostate. Performance is identified by the use of sequence identification No. 307 Part of the sequence was used to screen the prostate cDNA library and obtain the full-length cDNA of P711P. In particular, a standard technique is used to prepare a library of CDNAs for the selected glands. One million colonies in the library were placed flat on an LB/Amp plate. These colonies were lifted using a nylon filter paper, and the cDNA was denatured by UV light and cross-linked with the filter paper to select cDNA. The p71lp cDna fragment of 3〇7 was identified by radioactive-labeled sequence and used to hybridize to these filter papers. Positive pure lines were selected and cDna (J was prepared using the automated Perkin E1_iVAPPlied Bi〇systems sequencer sequence. The full length sequence determined by P711P is provided in Sequence Identification No. 382 and provided in Sequence Identification No. 383 Corresponding predicted amino acid sequence. Additional cDNA sequence information was derived from the above two pure lines 11-C9 and 9-F3 using PCR and hybridization-based methods, respectively. P707P and P714P (sequence recognition Nos. 333 and 334). After comparison with the nearest gene bank, it was found that P7〇7P is the junction k of the known gene 。13. The opposite 'no significant homology to P714P was found. The purebred strains 8-B3, P89, P98, P130, and P201 were found (as disclosed in U.S. Patent No. 2,956, filed on Feb. 9, 127, 091, pp. , is contained in an adjacent sequence, called p7〇5p (sequence identification number, and provides the predicted amino acid sequence in sequence recognition No. 336,), which is determined to be the known gene NKX3.1. Splicing variant σ Example 4 Synthesis of a peptide available at Perkin Elmer /Applied Bi〇systems 430Α peptide synthesizer, using FMOC chemistry, using HPTU (〇_benzotriazole-N, N, N, Nt-tetramethyl hexafluorophosphate) activation, synthesis Polypeptide. The Gly-Cys-Gly sequence can be attached to the amine terminal of the peptide to provide a method of coupling, binding to a fixed surface, or labeling the peptide. The following incision mixture can be used. Difluoroacetic acid: Ethylene Thiol·· thioanisole··water··phenol (4〇: 1 : 2 2 3) 70% of the solid support was cut into the peptide. After 2 hours of incision, it can be used in ice-cold f-base-third The peptide is allowed to settle in the base-ether. The pellets of the peptide can then be dissolved in water containing 0.1% trifluoroacetic acid (TFA) and lyophilized prior to purification by C18 reverse phase HPLC. The peptide can be eluted using 0%·60% acetonitrile (containing 〇.1〇/〇TFA) in water (containing 0.1% TFA). The pure soluble fraction is then lyophilized. Electrospray or other can be used. Type of negative error analysis' and the characteristics of the peptide were determined by amino acid analysis. Example 5 was further separated and determined by PCR-based subtraction. The characteristics of the adenocarcinoma polypeptide are determined by subtracting the cDNA library derived from the prostate primary tumor mRNA as described above using the cDNA obtained from the normal prostate. This is carried out using pCr-based grass 127691.doc-96-200815476 (clontech). After deducting the effect, Xiao Qi modified to produce a larger fragment in the draft of the Hai, respectively, with five kinds of restriction enzymes (MluI, MscI, pvu„, ~ mouth Stul) that recognize the position of the six-nuclear acid The double-stranded eDNA of the person and the operator. The result of this digestion is the average cDNA size of the pair of test pairs' instead of the average size of the 3GG test pairs generated using digestion according to the cl〇ntech draft. This modification does not affect the result of the deduction. The two tester groups are then produced with different joints, while the manipulator's library still contains no joints. However, using an excess of operator cDNA, the tester and the operator library are crossed. In the first hybridization step, the operator is allowed to hybridize with the mother of the two testers, respectively. As a result, (4) unhybridized tester cDNAs' (b) tester cDNAs hybridized to another tester side, (4) tester cDNAs hybridized with operator cDNAs, and (4) unhybridized operator cDNAs. Two different hybridization reactions are then mixed and hybridization is repeated in the presence of additional denatured operator cDNA. After the second hybridization, in addition to the groups (4) to (4), a fifth group (4) was produced in which the tester cDNA with one conjugate was hybridized with the test cDNA carrying the second conjugate. Thus, the second hybridization step produces a sequence enriched in a different manner that can be used as a template for the expansion of the adaptor-specific primer. The ends were then mounted and the pcR amplification was performed using a adaptor-specific primer. Only group (e), which contains tester cDNA that did not hybridize to the operator's cDNA, was expanded in a number of days. A second pCR expansion step is then performed to reduce the background and further increase the sequence of material time performance. 127691.doc -97- 200815476 PCR-based subtraction techniques normalize 7 in different ways, making rare transcripts that overexpress in prostate tumor tissue can be reversible. Such transcripts will be difficult to recover by traditional deduction methods. In addition to the genes known to be overexpressed in prostate tumors, 77 additional pure lines were identified. The sequences of these partial cDNAs are provided in Sequence Identification Nos. 29 to 3〇5. Most of these sequences do not have significant homology to the sequence 歹 1 n in the database. Except for JPTPN23 (sequence recognition No. 231; a protein similar to valosin in pigs), JpTpN3〇 (sequence recognition No. 234; mRNA similar to rat protein subunit), (sequence recognition No. 243; similar to Norwegian rat Cytosolic NADp-dependent isocitrate dehydrogenase, JPTPN46 (sequence recognition No. 244; similar human passage clonal line H8 4 d4 DNA sequence), JP1D6 (sequence recognition No. 265; similar (g·galhis) kinetics Protein light chain-A); JP8D6 (sequence recognition No. 288; similar to human BAC pure lineage RG016J04), Jp8F5 (sequence recognition No. 289; similar human apes clonal clonal line H8 3 b5 DNA sequence), and JP8E9 ( The sequence recognizes another 1J No. 299; similar to the human aiu sequence). /, his research and use is based on the (^ rule-based deduction library, including the collection of prostate tumors for normal prostate collection (called PT_pNpcR deduction), resulting in two a pure germline outside the jaw. The cDNA sequences of these pure lines were compared with those recently published by Gene Bank's showing the purebredness of the two called Wap (Sequences J 3 3 and 3 14) No significant homogeneity. Find the rest ,, and 屯 germline lines, showing some homology to the known basis ΘΚΙΑΑ〇〇56 (sequence recognition 3丨8). Using microarray analysis, the degree of 127691.doc 200815476 mRNA expression in various tissues was measured and found. The three pure lines are all overexpressed in prostate tumors and facial tissues. Specific r, purebred f, p7i5p, overexpressed in most prostate tumors and BpH tissues by three or more factors And in most normal prostate specimens and in fetal tissues, elevated performance was seen 'but only negative to low levels in all other normal tissues. Pure lineage P767P in several prostate tumors and Excessive performance in BpH tissue, moderate performance in the -half normal prostate sample, and p 纟 in all other normal test tissues, only background to low performance Ο further through the microarray as described above, Analysis of pT_pN pCT deduction library ~, and DNA depletion library containing cDNA from prostate tissue cDNA deducted from normal tissue cDNA, 'to isolate 27 additional pure lines (sequence identification No. 340-365) And No. 381), to determine its excessive performance in prostate tumors. Also found in the sequence of 34 342, 345, 347, 348, 349, 35 1, 355-359, 361, 362 and 364 pure line in the normal prostate Excessive performance in the CJ. All 26 pure lines have only low or undetectable performance in various normal tissues' except for the discovery that P544S (sequence recognition No. 356) is expressed in the small intestine. Of the 26 pure lines, 10 (sequence recognition No. 340-349) were found to show some homology to previously confirmed sequences. No significant homology was found for the pure line of sequence recognition 3 5〇-365. Example 6 First contact with peptide antigen in mice, and propagation of CTL cell lines 6.1 This example explains the preparation of a ct1 cell strain specific for cells expressing the p5〇2s gene. 127691.doc 200815476 According to Theobald et al., with the following modifications, Proc. Natl.

Acad. Sci. USA 92 : 1 1993-1 1997, 1995, vaccination with P2S#12 peptide (VLGWVAEL; sequence recognition 3〇6) shows human hla

All of the transgenic mice (provided by Dr. L. Sherman, The

Scnpps Research Institute, La Jolla, CA), which is derived from the P502S gene (also referred to herein as Jl-17, Sequence Identification No. 8). Mice were immunized with i2 micrograms of P2S# 12 ' and 120 micrograms of hepatitis B virus protein, emulsified I-Ab binding peptide in p-Freed adjuvant. The mice were sacrificed after two weeks and a single cell suspension was prepared using a nylon mesh. The cells were then resuspended at 6×1 〇6 cells/ml in 丨〇% fCS, 2 mM amidoxime (GibcoBRL), sodium pyruvate (GibcoBRL), non-essential amino acid (Gibco BRL), 2χ10 · 5 Μ 2-mercaptoethanol, 50 units / ml of sputum and sulphate in complete medium (RPMI-1640; Gibro BRL, Gaithersburg, MD), and in the irradiation (3000 rad) P2S #12 • pulse ( 5 pg/ml P2S#12, and 1〇mg/ml β2_small globulin) LpS embryo (A2 〇 gene transgenic spleen cells, present in 7 μg/ml dextran sulfate and 25 μg/ml LPS The culture was carried out in the presence of 3 days of culture. Six days later, EL4A2Kb cells (Sherman et al., Science 258: 81 5-81 8, 1992) and 3xl06/ml were irradiated with 2·5 X 1〇6/ml peptide-pulse (20, 〇〇〇rad). The spleen of the A2 gene was fed to the cells, and the cells were stimulated again (5 χΐ〇 ν ml). The cells were cultured in the presence of 20 units/3⁄4 liters of il-2. On the basis of one week, the cells were re-stimulated according to the above, and the selected cell lines were prepared. P2S#12 cell line was selected by limiting dilution analysis, and peptide pulsed EL4 A2Kb tumor cells (lxl〇4 cells/well) were used as stimulators and transfected with A2 127691.doc -100- 200815476 gene. The cells were used as feeders (5 x 105 cells/well) and grown in the presence of 3 〇 units / * liter of IL-2. On the 14th day, the cells were stimulated again as described above. On day 21, the growing pure line was isolated and maintained in the medium. It was confirmed that several of these pure lines were significantly more sensitive (dissolved) to human fibroblasts transduced with P502S (expressing HLa A2.1) than the fibroblasts of the control group. An example is provided in Figure 1. This data indicates that P2S#12 represents the natural processing epitope of P502S protein, which is expressed in molecules associated with human HLA Α2.1. 6.2. This example explains the preparation of the mouse ticks, as well as the performance? The cells of the 5〇13 gene have a specific C T L pure lineage. Perform a series of experiments similar to the above. The mouse was immunized with the P1 S# 10 peptide (SEQ ID NO: 33 7), which was derived from the P50 1 S gene (also referred to herein as L1 -12, sequence recognition 11 nickname). Derived by analyzing the predicted polypeptide sequence of P501S for the possible HLA-A2 binding sequence defined by the published hl A-A2 binding feature (Parker, KC et al, J. Immunol, 152: 163, 1994) P1 S# 1 0 peptide. The p 1 s# 1 〇 peptide was synthesized as described in Example 4, and the binding of HLA-A2 was tested empirically using a T cell-based competitive assay. The predicted A2 binding peptide, which competes with the HLA-A2 specific peptide, is limited in its ability to provide a CTL pure line of HLA-A2 (D150M58) which is specific for the HLA-A2 bound influenza matrix peptide fiuM58. D150M58 CTL secretes TNF, which is a self-providing response to peptide fiuM58. In a competitive assay, 100-200 μg/μl of test peptide was added to the culture D150M5 8 CTL for binding to HLA-A2 on the CTL. After 30 minutes, the CTL was incubated with the test peptide or control peptide 127691.doc -101 - 200815476 and tested for antibody dose response to the fluM58 peptide in a standard TNF bioassay. As shown in Fig. 3, peptide P1S#10 competed with fIuM58 for the limited supply of HLA-A2, confirming that peptide P1S#10 binds to HLA-A2. Mice expressing the transgenic genes of human HLA Α2·1 were immunized as described by Theobald et al. (Proc. Natl. Acad. Sci. USA 92: 1 1993-1 1997, 1995) with the following modifications. Mice were immunized with 62.5 micrograms of P1S#10, and 120 micrograms of I-Ab binding peptide derived from hepatitis B virus protein emulsified in incomplete Freund's adjuvant. The cells were then resuspended in complete medium (as above) at 6χ1〇6 cells/ml and irradiated (3〇00 rad) P1S#10-pulse (2 μg/ml P1S#12, and 1 〇 mg/ml β2-small globulin) LPS embryos (spleen cells transfected with A2 gene, cultured for 3 days in the presence of 7 μg/ml dextran sulfate and 25 μg/ml LPS) were cultured. Six days later, the cells were stimulated again with 2·5χ106/ml of EL4A2Kb cells irradiated with peptide-pulse (20,000 rads) and 3xl〇6/ml Α2 gene-transferred spleen silver-fed cells (5χι 〇5/ ML). The cells were cultured in the presence of 2 单位 units/home liter IL-2. Based on a week, the cells were stimulated again to prepare a selected cell line. After three cycles of in vitro stimulation, a cell line was produced which had a Jurkat A2Kb standard and a P5〇lS-transduced Jurkat stem, as shown in Figure 4. P1S#10-specific CTL cell line was selected by limiting dilution analysis, and peptide pulsed EL4 A2Kb tumor cells (1×1 〇 4 cells/well) were used as stimulators and spleen cells transfected with A2 gene were used. For the feeder (5χ1〇5 cells/well), it was grown in the presence of 30 units/ml IL-2. On day 14, the cells were stimulated again as previously described. On day 21, the surviving pure line 127691.doc -102 - 200815476 ' was isolated and maintained in the medium. As shown in Figure 5, five of these pure lines were confirmed to have specific cytolysis reactivity to the jurkatA2Kb target transduced with P501S. This data indicates that P1S#10 represents the natural processing epitope of the P5〇ls protein, which is expressed in related molecules of human HLA-A2.1. Example 7 The ability of human T cells to recognize prostate tumor polypeptides This example illustrates the ability of T cells specific for prostate tumor polypeptides to recognize human tumors. Human CD8+ T cells were first exposed in vitro to the antigen p2S_12 peptide (SEQ ID NO: 306), which was derived from p5〇2s using dendritic cells according to Van Tsai et al. (Criticai Reviews in Immunology i S: 65_75, 1998). (also known as J1-17). Test the obtained (: 〇8+ τ cell microculture, which is identified by the autologous fibroblasts, or by the interferon £1^§] 〇 ( (Mai Lalvani et al., j Med ρ Med· 186 : 859_865, 密 7), V is able to express the U ability of the p2S_12 peptide provided by the fibroblast of the P502S gene. Briefly, at 3 μg/ml human β2-bioglobulin and 1 μg/ The titration of tau cells was determined in duplicate in ι〇4 fibroblasts in the presence of ml P2S 12 peptide, or control Ε75 peptide. In addition, autologous fibrils transduced with p5〇2s gene The cells were treated with HER-2/neu transduced fibroblasts as a control group, and the cells were simultaneously measured. Prior to the assay, the fibroblasts were treated with 1 μg/ml of γ-interferon for 48 hours. In order to get up, the performance of MHC class I was confirmed. It was confirmed that there was one (#5) in the microculture to strongly recognize the peptide-pulsed fibroblasts, and in the 丫-interferon SPOT test, transduced Fibroblasts. Figure 2Α confirms the apparent increase of 127691.doc -103- 200815476 with P2S-12 pulse On the fibroblasts, the number of γ-interferon spots with an increased number of sputum cells (solid bars), but none of the control Ε75 peptides (open bars) were used. This shows that these sputum cells are specifically identified. The ability of the P2S-12 peptide. As shown in Figure 2, it was also confirmed that these microcultures increased gamma-interferon spots with increased numbers of sputum cells on fibroblasts transduced to express the P502S gene. The number, but the HER-2/neu gene is absent. These results provide additional evidence that the P2S-12 peptide is an epitope for the natural processing of the P5 02S protein. Furthermore, this also confirms that in human sputum cells In the catalogue, there are high-affinity Τ cells capable of recognizing the epitope. These sputum cells should also be able to recognize human tumors that express the P502S gene. Example 8 Using naked DNA to make CTL first contact with antigen in vivo, to prostate antigen Immunization

Like the above prostate tumor antigen L1-12, also known as P501S. HLA A2Kb Tg mice (provided by Dr. L. Sherman, The Scripps Research Intitute, La Jolla, CA) were immunized intramuscularly or intradermally using ^100 μg of VR10132-P501S. Mice were immunized three times at two week intervals. Two weeks after the last immunization, the immunized spleen cells were cultured with Jurkat A2Kb-P501S transduced stimulator cells. CTL cells are stimulated every week. After two weeks of in vitro stimulation, the activity of CTL against the target of P501 S transduction was determined. Two of the eight mice developed a potent anti-P501S CTL response. These results demonstrate that P501S contains at least one naturally processed A2-restricted CTL epitope. 127691.doc -104 - 200815476 Example 9

Using whole-genomes that are in contact with antigens for the first time, and stimulation techniques using prostate tumor antigens, CTLs are produced in vitro using whole-genes in vitro, and retroviral transduction of p5〇iS2 autologous fibroblasts (see, For example, Yee et al., The j〇urnal 〇f Immunology, 157(9): 407, 86, 1996) first contact, derived human CTL cell line, which specifically recognizes p5〇ls (also known as li_i2) The induced autologous fibroblasts were determined by the above-described interferon 彳EUSp〇lv&gt; analysis. Using the squares of the HLA-dismatched fibroblast cells transduced with P501S, these CTL cell lines were shown to be restricted by the 9^8-eight-2 level 1 dual gene. Specifically, it is grown from normal in RpM]^ containing 1% human serum, 5 ng/ml human GM-CSF, and 30 ng/ml human 1]1-4. Dendritic cells (Dc) were differentiated from mononuclear cultures of pBMCs of human donors. After the incubation, DCs were infected with the recombinant p5〇ls vaccine virus at a multiplicity of infection (5 Ι·0·Ι·), and overnight matured by adding a 3 μg/ml CD4 〇 ligand. The virus is inactivated by UV irradiation. The cd8+ τ cells were isolated using a magnetic bead system and the first exposure to the antigen culture was initiated using standard culture techniques. Cultures were re-stimulated using autologous fibroblasts transduced with retroviral P501S every 7 days. After four stimulation cycles, it was confirmed that the CD8+ T cell strain of interferon-1 was specifically produced when stimulated with P501S-transduced autologous fibroblasts. The specific activity of P50 1 S can be maintained by continuously stimulating the culture with P501S_transduced fibroblasts in the presence of IL_15. A square of the fibroblast cell line transducing HLA-dismatched with P5 01 S was generated to define the restriction dual gene of 127691.doc-105-200815476. Measurement of the interferon-γ' by the ELISp〇T assay showed that the specific reaction of P501 S was restricted by HLA-A2. These results confirm that CD8+ CTL pairs can be induced? 5〇1|5 reaction. Example 10 Confirmation of naturally processed CTL epitopes contained within prostate tumor antigens 9-mer peptide 95 (SEQ ID NO: 33 8) is derived from 17〇3? antigen (also known as Ρ20). The ρ5 peptide is immunogenic in human HLA-A2 donors and is an epitope for natural processing. The antigen-specific CD8+ sputum cells are first exposed to the antigen, followed by repeated stimulation in vitro with a single nucleus pulse pulsed with the ρ5 peptide. These CTLs specifically recognize ρ5-pulsed target cells in ELISPOT (as described above) and in the chromium release assay. Furthermore, mice immunized with HLA-A2 gene were immunized with ρ5, resulting in CTL cell lines which were identifiable by various Ρ703Ρ transduced light cells expressing HLA-A2Kb or HLA-A2. Specifically, HLA-A2 gene-transferred mice were subcutaneously immunized in a footpad with 100 μg of p5 peptide and 140 μg of hepatitis B virus core peptide (Th peptide) in Fried's incomplete adjuvant. Three weeks after immunization, peptide-pulsed LPS embryos were stimulated in vitro from spleen cells from immunized mice. Five days after the initial in vitro stimulation, the CTL activity was assessed by a chromium release assay. Cells transduced with retrovirus and expressing control antigens P703P and HLA-A2Kb were used as targets. It was confirmed that the target of p5-pulse was specifically recognized, and the CTL cell line showing the target of P703P.

Experiments in which humans first contacted antigens in vitro confirmed that p5 peptides are immunogenic in humans. By monoclonal culture of PBMC 127691.doc -106-200815476 derived from normal human donors containing 10% human serum, 50 ng/ml human GM-CSF and 3 ng/g human il- Cultured in RPMI medium for 4 days, dendritic cells (DC) were differentiated. After incubation, DCs were pulsed with p5 peptide and incubated with GM-CSF and IL_4, along with CD8+ T cells enriched in PBMC. On a weekly basis, the P5-pulsed mononuclear ball was used to stimulate the CTL plasmid again. Five to six weeks after the start of CTL culture, CTLs were confirmed to recognize P5-pulsed stem cells.

Example 11 Demonstration of breast tumors in the prostate - Derived antigens were isolated from breast tumors by the differential method described in U.S. Patent Application Serial No. 8/700, No. 14, filed on August 20, 1996. Antigen B3 05D. Several different junction forms of the antigen are isolated. These ligated swij sequences are provided in SEQ ID NO: 366-375, and the predicted amino acid sequences are provided in sequences 299-306, respectively, relative to sequence recognition 292, 298, 30 1-303. . The extent of B3〇5D expression in various tumors and normal tissues was examined by real-time PCR and by Northern analysis. The results indicate that B3〇5D is highly expressed in breast tumors, prostate tumors, normal prostate, and normal testicles, and in all other test specimens (colon tumors, lung tumors, ovarian tumors, and bones of the positive f, colon, There are only low or undetectable manifestations in the kidney, Lai, _, ovary, skin, small intestine, and month. Example 12 Pre-induction in human blood This example explains prostate tumor antigen-specific CTL response Tumor antigens are induced in the blood of normal humans 127691.doc -107-200815476 CTL response ability. Mononuclear ball cultures derived from normal donor PBMCs were grown in RPMI medium containing 10% human serum, 50 ng/ml GMCSF and 30 ng/ml IL-4 for five days to differentiate into autologous Dendritic cells (DC). After the incubation, the vaccine virus expressing recombinant P501S, Μ.0.1. was 5, DC was infected overnight, and matured by adding 2 μg/ml of CD40 ligand for 8 hours. The virus was inactivated by UV irradiation, CD8+ T cells were isolated by positive selection using a magnetic bead system, and the first contact antigen culture was initiated on a 24-well plate. After five stimulation cycles, it was confirmed that when interfering with fibroblasts transduced with autologous P 5 0 1 S, the CD8 + cell strain of interferon-γ was specifically produced. On the autologous B-LCL transduced with P501S, the Ρ501 S-specific activity of the cell line 3 A-1 was maintained after an additional stimulation cycle. Determined by cytotoxicity assay (51 chromium release) and interferon-gamma production (interferon jElispot; see above and Lalvani et al, j Εχρ· Med 186: 8 5 9-865, 1997) for display Cell line 3A_i specifically recognizes transduction to express autologous B-lcl of PSOIS, but does not recognize EGFp_transduced autologous B-LCL. The results of these assays are provided in Figures 6A and 6B. Example 13 Confirmation of Prostate Tumor Antigen by Microarray Analysis This example describes the isolation of certain prostate tumor polypeptides from prostate tumors. Screening of the human prostate tumor cdna expression library described above using microarray analysis to demonstrate at least three 127691 in prostate tumors and/or normal prostate tissue compared to normal non-prostate normal tissues (excluding Bi pills) .doc -108 - 200815476 Purely over-performing pure breeds. 372 pure lines were identified and 319 sequences were successfully determined. Table 1 provides an overview of these pure lines, which are not shown in Sequence Identification 385,400. Among these sequences, sequence recognition, (10), 390, and 392 are equivalent to the new Lai gene, and the sequence recognizes the state and the current number in the sequence of the first five. Others (sequence recognition 385, 387, 388, 39, 3, 94, 3, 95, and 397-400) correspond to known sequences, as described in Table 127 691.doc -109 - 200815476 Table i Prostate tumor antigens Overview

Known gene previously confirmed sequence novel gene T-cell γ chain P504S 23379 (sequence recognition No. 389) Kallikrein P1000C 23399 (sequence recognition No. 392) Vector P501S 23320 (sequence recognition No. 386) CGI-82 protein mRNA P503S 23381 (sequence (23319; sequence identification No. 385) recognition No. 390) PSA P510S aldehyde 6 dehydrogenase P784P L-iduroside bee-2-deiL aphid (23376; sequence identification No. 388) P502S Ets transcription factor PDEF (22672; sequence identification No. 398) P706P hTGR (22678; sequence recognition 19142.2 bangur.seq (22621 399); sequence identification number 396) KIAA0295 (22685; sequence 5566.1 Wang (23404; sequence identification 400) recognition number 393) prostate Acid hydrase (22655; sequence recognition No. 397) P712P transaminase (22611; sequence recognition No. 395) HDLBP (23508; sequence identification No. 394) CG1-69 protein (23367; sequence identification No. 387) KIAA0122 ( 23383; Sequence Identification No. 391) TEEG P778P Compared to other normal test tissues, CGI-82 showed 4.06-fold overexpression in prostate tissue. It is overexpressed in 43% of prostate tumors, 25% of normal prostate, but not in other normal test tissues 127691.doc -110- 200815476. Compared to other normal test tissues, the pentitol 1 deaturase showed 4.94-fold overexpression in prostate tissue. It is expressed in 卯% of prostate tumors '1G()_normal prostate (four) degrees, but not in other normal test tissues. The Ets transcription factor PDEF showed a 5.5% overexpression in prostate tissue compared to other normal test tissues. It was overexpressed in 47% of prostate tumors, 25% of normal prostate, but not in other normal test tissues. Compared with other normal test tissues, ^1 (1) showed an overexpression of I&quot; in prostate tissue. It was overexpressed in 63% of prostate tumors and now includes normal test tissues of normal prostate. Undetectable. Compared to other normal test tissues, ΚΙΑΑ0295 showed a 595-fold overexpression in prostate tissue. It was overexpressed in 47% of prostate tumors, but was positive in normal prostate tissue. There was only an undetectable performance in the test tissue. Compared with other normal test tissues, prorenic acid glutamate showed a 9.14-fold overexpression in prostate tissue. It was (4) prostate tumor, 50% normal. Excessive performance in the prostate, but not detectable in other normal test tissues. Transglutaminase showed a 14-84-fold overexpression in prostate tissue compared to other normal test tissues. 30% of prostate tumors, written in normal prostate, are overexpressed but not detectable in other normal test tissues. Compared with other normal test tissues High-density lipoprotein-binding protein (HDLBp) showed 28.06-fold overexpression in prostate tissue. It was overexpressed in 97% of prostate tumors, 75% of normal prostate, but could not be detected in other normal test tissues. Compared with other normal test tissues, cGi_69 showed a 3.56-fold overexpression in glandular tissue at 127691.doc -111 - 200815476. It is a low-rich gene 'more than 90% of prostate tumors and 75 〇 /. It is detectable in normal prostate. The gene has very low performance in normal tissues. Compared with other normal sputum tissues, sputum 122 showed an overexpression of 4.24 times Ο 前列腺 in prostate tissue. It is overexpressed in 57% of prostate tumors, but is not detectable in all normal test tissues including positive stalks. Compared with other normal test tissues, 19142.2 bangur is in prostate tissue. Showing an overexpression of 23.25 times. It is overexpressed in 97% of prostate tumors and 100/〇 hanging hangars. It is in other normal test tissues..., It was found that 5566.1 Wang showed an overexpression of 3.3 times in the other glandular tissue compared with other normal test tissues. It was overexpressed in the prostate gland tumor and 75% normal prostate. It was also overexpressed in normal bone marrow, spleen and activated PBMC. Compared to other normal test tissues, the novel pure line 23379 showed 4.86-fold overexpression in prostate tissue. It was in 97% of the prostate. Tumors and normal prostates are detectable, but are not detectable in all other normal test tissues. Compared with other JL test tissues, the new pure lines are added to the prostate tissue. It shows an overperformance of 4·〇9 times. It is overexpressed in the prostate gland tumors but is not detectable in all normal test tissues including normal prostate tissue. Compared to other normal test tissues, 'the novel pure lineage 23320 showed 315-fold overexpression in prostate tissue. It is manifested in all prostate tumors and 5G% normal prostate tissue and also in normal colon and trachea. Other normal tissues do not express this gene at high levels. 127691.doc -112^ 200815476 Example 14 Confirmation of prostate tumor antigens by electronic subtraction This example describes the use of electron subtraction in the identification of prostate tumor antigens. By electronic deduction (similar to by Vasmatizis et al., pr〇c. Nati.

Acad. Sen· USA 95: 300-304, 1998) identifies possible prostate-specific genes present in the GenBank Human EST database. The sequence of the est pure lineage (43, 482) is derived from various prostate banks obtained from the human EST poor stock library published by GenBank. In the blastn (National Center for Biotechnology Informati〇n) study of human EST data, each prostate EST sequence was used as a problem sequence. All pairs were considered to be the same pair (pair length > 100 bases, density of the same pair within the range &gt; 70%), grouped together (aligned in line). Discard clusters containing more than 2 ESTs, as they may represent repeated features or highly expressed genes, such as those that exhibit nucleocapsid proteins. If there are two or more {) clusters sharing common ESTs, grouping these clusters together into a hypercluster will generate 4,345 prostate superclusters. Download the record of the 479 human cDNA library depicted in GenBank's publication , to generate a database of these cDNA library records. The nine cDna libraries are divided into three groups, plus (normal) prostate and prostate tumor banks, and breast cell strains, which have desired performance, negative group (Minus) (a library from other normal adult organizations, where performance is not what you want), and other groups (=her) (fetal tissue, early childhood tissue, tissue found only in women, non-prostate tumors, As well as cell lines other than prostate cell lines, the performance of 127691.doc-113-200815476 is considered to be irrelevant. A summary of the grouping of these libraries is provided in Table 11.

Table II The number of ESTs in the cDNA library and ESTs library is 25,482. A normal 11 18,875 tumor 11 Γ 21,769 cell line 3 2,838 negative 166 other 287 〇 From the perspective of ESTs in the super-cluster, analyze each super Cluster. Note the organization source of each EST and use it to divide the super cluster into four groups. · Type} EST pure lineage found only in the positive group library; no performance detected in negative or other group library, 2nd Type - EST pure lineage found only in positive and other group libraries; no performance detected in negative group library; type 3 _ fine T pure line in positive, negative and other group libraries; The performance in the group was more pronounced than in the negative or other group 'type 4' - the est pure line found in positive, negative and other groups but the performance of the towel was higher than in the negative group. The analysis identified 4,345 breast clusters (see (4)). From these clusters t, ^search ordered (3), (6), ordered 3,172 pure cultivars, and received the form of frozen glycerol mother liquor in a 96-well culture dish.

Table III

127691.doc 114- 200815476 For Synteni microarray analysis, the insertion sequence was amplified by PCR using an amino-linked PCR primer. When a particular pure line obtains more than one PCR product, the PCR product is not used for performance analysis. The micro-array analysis was used to analyze the electron deduction method, a total of 2,528 pure lines, confirming the electrically depleted breast pure line, with high tumor-to-normal tissue mRNA. Use the Synteni (Palo Alto, CA) micro-car train, according to the manufacturer's instructions (and basically in accordance with Schena et al, Proc. Natl. Acad. Sci. USA 93: 10614-10619, 1996, and Heller et al., Piroc · Natl. Acad. Sci. US A 94: 2150-2155, 1997 Description) Complete this type of screening. In these analyses, pure lines are arrayed on a sheet and then probed with fluorescent probes produced from normal and tumor precursor gland cDNA, as well as various other normal tissues. Scan the slide and measure the fluorescence intensity. A pure line with a performance rate of 3 or more (i.e., the content in the prostate tumor cDNA, which is at least three times the content in the normal prostate cDNA) was confirmed to be a prostate tumor-specific sequence (Table IV). The sequences of these pure lines are provided in Sequence Identification No. 401-453, and some novel sequences are shown in sequence identifications 407, 413, 416-419, 422, 426, 427 and 45 0.

Table IV Prostate-tumor specific pure germline sequence identification number Sequence name review 401 22545 Previously confirmed P1000C 402 22547 Previously confirmed P704P 403 22548 Known 404 22550 Known 405 22551 PSA 406 22552 Prostate secreted protein 94 127691.doc -115- 200815476

407 22553 Novel 408 22558 previously identified P509S 409 22562 glandular kallikrein 410 22565 previously identified P1000C 411 22567 PAP 412 22568 B1006C (mammary tumor antigen) 413 22570 novel 414 22571 PSA 415 22572 previously confirmed P706P 416 22573 new 417 22574 novel 418 22575 novel 419 22580 novel 420 22581 PAP 421 22582 prostate secretory protein 94 422 22583 novel 423 22584 prostate secretory protein 94 424 22585 prostate secretory protein 94 425 22586 known 426 22587 novel 427 22588 Novel 428 22589 PAP 429 22590 Known 430 22591 PSA 431 22592 Known 432 22593 Previously confirmed P777P 433 22594 T cell receptor γ chain 434 22595 Previously confirmed Ρ705Ρ 435 22596 Previously confirmed Ρ707Ρ 436 22847 ΡΑΡ 437 22848 Known 438 22849 Prostate secretory protein 57 439 22851 ΡΑΡ 440 22852 ΡΑΡ 441 22853 ΡΑΡ 442 22854 Previously confirmed P509S 443 22855 Previously confirmed Ρ705Ρ 444 22856 Previously confirmed F774P 127691.doc -116- 200815476

445 22857 PSA 446 23601 Previously confirmed P777P 447 23602 PSA 448 23605 PSA 449 23606 PSA 450 23612 Novel 451 23614 PSA 452 23618 Previously confirmed P1000C 453 23622 Previously confirmed P705P Example 1 5 Further confirmation of prostate tumor by microarray analysis Antigens This example describes the isolation of additional prostate tumor polypeptides from a prostate tumor cDNA library. Screening of the human prostate tumor cDNA expression library described above using microarray analysis confirmed that at least three times overexpression was observed in prostate tumors and/or normal prostate tissue compared to normal tissues of non-prostate (excluding testis). Pure breed. 142 pure lines were identified and sequenced. Some of these pure lines are shown in Sequence Identification 454-467. Sequence recognition Sequences 459-461 are equivalent to novel genes. Others (sequence recognition U 454-458 and 461-467) correspond to known sequences. Example 1 6 Further Characterization of Prostate Tumor Antigen P71 0P This example describes the full-length colonization of P710P. The above P710P fragment was used to screen the above prostate cDNA library. One million colonies were plated on LB/amicomycin discs. These colonies were lifted using a nylon membrane filter, and the cDNA selected through these filter papers was denatured by UV light and crosslinked with the filter paper. The P701P fragment was radioactively labeled, 127691.doc -117-200815476 and used to hybridize to filter paper. A positive cDNA pure line was selected and returned to its cDNA&apos; and sequenced by an automated abi sequencer. Four sequences were obtained and are provided in Sequence Identification 468-471. Example 10 Confirmation of the naturally processed C T L epitope 9-mer peptide contained in the prostate-specific tumor antigen P703P? 5 (Sequence Identification No. 338) is derived from? 703? antigen (also known as P20). The P5 peptide is immunogenic in human HLA-A2 donors and is a natural processing epitope. The antigen-specific human CD8+ T cells can be first exposed to the antigen, followed by repeated stimulation in vitro with a mononuclear ball pulsed with the p5 peptide. These CLTs specifically recognize p5-pulsed and P703P-transduced target cells in ELISPOT (as described above) and chromium release assays. Furthermore, mice immunized with the HLA-A2Kb gene were immunized with p5, resulting in a CTL cell line which identifiable various HLA-A2Kb or HLA-A2 gene transduction target cells of P703P.

Initial studies confirmed that p5 is an antigenic epitope for natural processing using HLA-A2Kb gene transgenic mice. HLA_A2Kb gene-transferred mice were subcutaneously immunized in a footpad with 100 micrograms of p5 peptide and 140 micrograms of hepatitis B virus core peptide (Th peptide) in Fried's incomplete adjuvant. Three weeks after immunization, spleen cells from immunized mice were stimulated in vitro with peptide-pulsed LPS embryos. CTL activity was assessed by a chromium release assay five days after the initial in vitro stimulation. Cells that were retrovirally transduced and showed the control antigen P703I^HLA-A2Kb were used as the stem. The pain recognizes the CTL cell line which specifically recognizes the P5-pulse standard and the P703P 127691.doc-118-200815476. Experiments in which humans first contacted antigens in vitro confirmed that p5 peptides are immunogenic in humans. Cultured in RPMI medium containing 10% human serum, 50 ng/ml human GM-CSF and 30 mM human IL-4 for five days by mononuclear ball culture of PBMC derived from normal human donors , differentiated dendritic cells (DC). After the incubation, DCs were pulsed with 1 μg/ml of p5 peptide and cultured with CD8+ T cells enriched in PBMC. On a weekly basis, CTL cell lines were stimulated again using p5-pulsed mononuclear cells. Five to six weeks after the start of CTL culture, it was confirmed that the CTL recognized the p5-pulsed target cells. In addition, it was also shown that CTL recognizes human cells that have been transduced to express P703P, confirming that p5 is an epitope for natural processing. A further study of a peptide epitope (referred to as peptide 4) derived from the prostate tumor-specific antigen P703P was carried out as follows, which was recognized by CD4 T cells on the cell surface in terms of the relationship of HLA class II molecules. The amino acid sequence of peptide 4 is provided in SEQ ID NO: 78 1 and the corresponding cDNA sequence is provided in SEQ ID NO: 782. Twenty 15-mer peptides partially overlapped by 1 胺 amino acid and derived from the carboxy-terminal fragment of P703P were generated using standard procedures. Dendritic cells (DC) were derived from PMBC of normal female donors using standard GM-CSF and IL-4. CD4 T cells were generated from the same donor as DC using MACS beads and negative selection. DCs were pulsed overnight in a pool of 15-mer peptides at a final concentration of 0.25 μg/ml per peptide. The pulsed DCs were washed and plated in 96-well V-bottom plates at lxl 04 cells/well, and purified CD4 T cells were added at lxl〇5/well. The medium was supplemented with 60 127691.doc -119-200815476 ng/ml IL-6 and 10 ng/ml IL_12 and cultured at 37 C. On a weekly basis, the culture was re-stimulated as above, using the above-made and pulsed DCs as antigen-expressing cells, supplemented with 5 ng/ml IL-7 and 1 〇 unit/ml jiang. After four in vitro stimulation cycles, 96 cell lines (each cell equivalent to one well) were tested for specific proliferation and cytokine production in response to stimulating po〇ls, derived from An irrelevant pool of peptides of mammagl〇bin was used as a control group. A cell line (called F9) was identified from Aggregate #1, confirming the specific proliferation (measured by 3H proliferation assay) and cytokine production (by interferon) in the aggregate of P703P peptide l ELISA assay to measure). The cell strain was further tested for specific recognition of peptide aggregates, specific recognition of individual peptides in the pool, and HLA mismatch analysis to confirm the relevant restriction genes. It was found that the cell line 9 reacted with the peptide aggregate #1 and also reacted with the peptide 4 (sequence recognition No. 781), specifically proliferating and producing interferon-γ. Peptide 4 corresponds to the amino acid 126-140 of sequence identification number 327. Peptide titration experiments were performed to evaluate the sensitivity of the cell line to specific peptides. It was found that the cell line still reacted specifically to peptide 4 at concentrations as low as 0. 25 ng/μl, indicating that the sputum cells are very sensitive. And therefore may have a high affinity for this epitope. To determine the HLA restriction of the Ρ703Ρ reaction, a list of antigen-presenting cells (APCs) is produced, which is particularly compatible with the donors used to produce sputum cells. Pulse APC, and used in cell proliferation and cytokine assays together with cell line 1-F9. APCs at the HLA-DRB0701 and HLA-DQB02 dual genes and donor phase 127691.doc •120·200815476 provide peptides For T cells, it is indicated that the P703P-specific reaction is restricted to one of these dual genes. The antibody blocking assay is used to determine whether the restriction dual gene is HLA-DR0701 or HLA-DQ02. Anti-HLA- is added to the sputum cells. DR blocked antibody L243 or IgG2a matched to an unrelated isoform, and pulsed APC culture with peptide RMPTVLQCVNVSVVS (sequence recognition No. 781) at 250 ng/ml. Standard interferon-y and proliferation assays were performed. The control antibody did not affect the ability of T cells to recognize peptide-pulsed APC in both assays, and the anti-HLA-DR antibody completely blocked the ability of T cells to specifically recognize peptide-pulsed APCs. Determine whether the RMPTVLQCVNVSVVS (sequence identification No. 871) is naturally processed, and check the cell line F9 to recognize the ability to utilize the APC of the recombinant P703P protein pulse. For these experiments, various recombinant P703P sources were used; Escherichia coli derived P703P, Pichia pastoris Pichia-derived P703P, and baculovirus-derived P703P. Unrelated protein control group uses E. coli-derived L3E (a lung-specific antigen) and baculovirus-derived mammaglobin In the interferon-yELISA assay, the cell line 1-F9 was able to effectively recognize P703P in the form of E. coli and Pichia pastoris-derived recombinant P703P, and was less able to effectively recognize the rod-shaped disease-derived P703P. Subsequent Western blot analysis showed that the E. coli and Pichia pastoris P703P protein preparations were intact, but the baculovirus P703P product was degraded by about 75%. P703P peptide RMPTVLQCVNVSVVS (SEQ ID NO: 781) is a naturally occurring peptide epitope determined by P703P and is supplied to tau cells in the case of HLA-DRB-0701 127691.doc -121 - 200815476. In further studies Using a standard procedure to generate twenty-four 15-mer peptides (equivalent to the amino acid 27-154 of sequence identification number 525) which are partially overlapped by 10 amino acids and derived from the Ν-terminal fragment of Ρ703Ρ, and As above, it was judged that it was recognized by CD4 cells. The pool of peptides was pulsed overnight with a final concentration of 10 μg/ml per peptide. A large number of individual CD4 T cell lines (65/480) were confirmed to have significant proliferation and cytokine release (IFN-γ) in the P703P peptide aggregate, but no reaction in the control peptide aggregate. f The CD4 T cell line confirming the specific activity, re-accepted by the appropriate P703P peptide aggregate, and the individual peptides and peptides of each aggregate in the IFN-γ release assay and in the proliferation assay The peptide dose of the pool was titrated and measured again. From the entire set of peptide antigens tested, sixteen immunogenic peptides were identified by T cells. The amino acid sequence 这些J of these peptides is provided in Sequence Identification 799-8 14 and the corresponding cDNA sequence is provided in Sequence ID 783-798. In some cases, peptide-reactive T-cell strains can be mapped to a single peptide.

U maps, however, some may plot more than one peptide in each pool. From each peptide pool, a CD4 T cell line exhibiting a representative recognition pattern was selected with reasonable affinity for the peptide for further analysis (I-1A, -6A; II-4C, -5E; III- 6E, IV-4B, -3F, -9B, -10F, V-5B, -4D and -10F). These CD4 T cell lines were again stimulated with appropriate individual peptides and expressed in baculovirus for the truncated form of the recombinant P703P protein produced in E. coli (sequence recognition of amino acid 96-254 of 525) The full-length P703P produced in the system, and the autologous DC pulsed with the fusion form between the influenza virus NS1 and P703P manufactured in Escherichia coli 127691.doc-122-200815476, were again measured. Among the T cell strains tested, cell line 1-1A specifically recognized the truncated form of P703P (E. coli), but did not recognize other recombinant forms of P703P. This cell line also recognizes peptides used to induce T cells. Cell line 2-4C recognizes the truncated form of P703P (E. coli), as well as the full-length form of P703P produced in baculovirus, and peptides. The remaining T cell strains tested were specific for peptides (II-5E, II-6F, IV-4B, IV-3F, IV-9B, IV-10F, V-5B and V-4D), Or no response to any of the tested antigens (V-10F). These results confirmed that the peptide sequence RPLLANDLMLIKLDE (SEQ ID NO: 814; amino acid 110-124 corresponding to sequence identification No. 525) recognized by the T cell line L·1A, and the peptide sequence SVSESDTIRSISIAS recognized by the T cell line II-4C ( Sequence identification No. 8 11; equivalent to sequence identification 525 amino acid 125-139) and ISIASQCPTAGNSCL (sequence recognition 810; equivalent to sequence recognition 525 amino acid 135-149), may be the natural processing of P703P protein The epitope of the antigen. In a further study, forty-five 15-mer peptides (sequence recognition No. 525) partially overlapped by 10 amino acids and derived from amino acids 47 to 254 spanning P703P were generated by standard procedures and were essentially As above, it was judged that it was recognized by CD4 cells. DCs were prepared from PBMCs of donors with different HLA DRs and the DQ dual genes obtained from them were used in previous experiments. The pool of peptides was pulsed overnight with a final concentration of 0.25 μg/ml per peptide and 10 peptides per collection. _ Identifying twelve cell lines, confirming the specific proliferation and cytokine production (measured by the γ-interferon ELISA assay) in response to the stimulated peptide aggregate. These cell lines were further tested for specific recognition of peptide aggregates by 127691.doc-123-200815476, specific recognition of individual peptides in the aggregate, and specific recognition of recombinant P703P protein. Cell lines 3A5H and 3 A9H react specifically with the recombinant protein and a single individual peptide, as well as peptide aggregates. After re-stimulation on the target receiving the load-specific peptide, only 3 A9H specifically responded to the target exposed to the lysate of fibroblasts infected with adenovirus expressing full length P703P. These results indicate that the cell line 3A9H reacts with an antigen peptide derived from a protein synthesized in mammalian cells. This specific CD4 cell line produces (f-reactive peptide, corresponding to amino acid 155-170 of P703P (SEQ ID NO: 943). The DNA sequence of the peptide is provided in Sequence Identification No. 942. Example 18(d) Preparation of antibodies against P703P and defining characteristics

The rabbit was immunized with a truncated form (P703Ptrl; SEQ ID NO: 172) or a full-length mature form (Ρ703ΡΠ; SEQ ID NO: 523) of the recombinant P703P protein expressed in the above-described bacteria and purified therefrom. Affinity #, purified polyclonal antibodies were generated using the immunogen Ρ703ΡΠ or P703Ptrl attached to a solid support. Rabbit monoclonal antibodies were isolated at Immgenics Pharmaceuticals using SLAM u technology (see, for example, US 5,627,052). Table VII below lists both the multi-strain and monoclonal antibodies produced for P703P.

Table VII Antibody immunogen species/type affinity purified P7〇3P (truncated); #2594 P703Ptrl rabbit/multiple affinity purified P703P (all); 洲?4^ P703PA rabbit/multi-plant 2D4 L- P703Ptrl Rabbit/single plant~8H2 &quot; -- P703Ptrl rabbit/single plant~~7H8 ^ --- P703Ptrl rabbit/single plant coding complementarity determining region of rabbit monoclonal antibody 8H2, 7H8 and 2D4 127691.doc -124- 200815476 The DNA sequences of (CDRs) are provided in sequence identification 506-508, respectively. A map study of epitopes was performed as described above. It was found that the monoclonal antibodies 2D4 and 7H8 were identical to the sequence recognition No. 509 (corresponding to the amino acid 145-1 59 of the sequence recognition No. 1 72) and the sequence recognition No. 5 10 (corresponding to the amino acid 11-25 of the sequence identification 172). The peptide specifically binds. Multiple antibody 2594 was found to bind to the peptide of sequence recognition 5 11-5 14 , while polyclonal antibody 9427 was bound to the peptide of sequence recognition 515-517. The specificity of the anti-P703P antibody was determined by Western blot analysis as follows. (1) a recombinant antigen expressed as a bacterium; (2) a lysate of HEK293 cells and Itk-/- cells that have not been metastasized or infected with a plastid that exhibits full-length P703P; and (3) isolated from these The supernatant of the cell culture was subjected to SDS-PAGE. The protein was transferred to nitrocellulose, and Western blot analysis was carried out using an anti-P703P polyclonal antibody #2594 at an antibody concentration of 1 μg/ml. Proteins were detected using horseradish peroxidase (HRP) conjugated to an anti-rabbit antibody. A 35 kDa immunoreactive band was observed using recombinant P703P. Recombinant P703P showed a slightly higher molecular weight because it was the tagged antigenic epitope. A 30 kDa band consistent with P703P was observed in the lysate and supernatant from cells infected with full-length P703P. To ensure specificity, lysates from HEK293 cells stably transfected with the control plastid were also tested, which was negative for P703P. Other anti-P703P antibodies showed similar scabs. Immunohistochemical studies were performed as described above, using anti-P703P monoclonal antibodies. P703P was found to be highly expressed in normal prostate and prostate tumor tissues, but was not detected in all other test tissues (breast tumor, lung tumor 127691.doc -125-200815476 tumor and normal kidney). Example 21 Preparation of Fusion Protein of Prostate-Specific Antigen This example describes the preparation of a fusion protein of the prostate-specific antigen P703P and a truncated form of the known prostate antigen PSA. The truncated form of psA has 21 amino acid deletions around the active serine position. The expression construct of the fusion protein also has a restriction at the 3' end, which helps to add cDNA to the additional antigen immediately before the stop codon. j The full-length cDNA of PSA was obtained by RT-PCR&apos; from a collection of RNA derived from human prostate tumor tissue using sequence recognition primers Nos. 607 and 608, and cloned into the vector pCR-Bluntll-TOPO. Using the obtained cDNA as a template, two different PSA fragments were produced by PCR using two sets of primers (sequence recognition 609 and 31 ;; and sequence recognition 611 and 612). Using a PCR product of the expected size as a template, by primers, primers Nos. 611 and 613 were identified by sequence, which produced PSA (δ20 8-218 in amino acid) to produce a truncated form of PSA. A mature form of cDNA of P703P carrying a 6-histidine histidine tag at the y-terminus was prepared by PCR using the P703P and 〇 sequence recognition primers 614 and 6-15. Then, by PCR, the truncated form of the modified P703P cDNA and PSA cDNA was used as a template, and the primers of sequence identification Nos. 614 and 615 were obtained to obtain fusion. 703? and? 8 octagonal short form of cDNA (called FOPP). The FOPP cDNA was cloned into the Ndel and Xhol positions of the expression vector pCRX1 and confirmed by DNA sequencing. The determined cDNA sequence of the fusion construct FOPP is provided in Sequence Identification No. 616, and the amino acid sequence is provided in Sequence Identification No. 617. 127691.doc -126- 200815476 The fused FOPP is expressed as a single recombinant protein in E. coli as follows. The expression plasmid pCRX1F〇Pp was transformed into the E. coli strain BL21-CodonPlus RIL. When induced with 1 mM IPTG, the transformant was shown to exhibit FOPP protein. The corresponding pure-bred cultures were inoculated in 25 halo LB cultures containing 50 μg/3⁄4 liters of oxytetracycline and 34 μg/ml of gas, and grown to about 1 at 37C. d 6 〇〇 and store at 4 ° C overnight. The culture was diluted with 1 liter of TBLB containing 50 μg/ml of oxytetracycline and 34 μg/ml of chloramphenicol and grown to an OD600 of 0.4 at 37t. ipTG was added at a final concentration of 1 mM, and the culture was cultured for 3 hours at 3 (rc). The cells were pelleted by centrifugation at 5,000 RPM for 8 minutes. To purify the protein, the cell pellet was suspended in 2 5 ml of 10 mM Tris-Cl ΡΗ8·0, 2 mM PMSF, intact protease inhibitor and 15 μg of lysozyme. The cells were lysed at 4 ° C for 30 minutes, vortexed several times with ultrasound and at 10,00 〇 The lysate was centrifuged for 3 minutes at xg. The inclusions containing inclusion bodies were washed twice with 1 mM Tris-Cl pH 8.0 and 1% CHAPS. The inclusion bodies were dissolved in 40 ml of 10 mM Tris-Cl pH 8.0, 1 〇〇 mM sodium phosphate and 8 M urea. The solution was combined with 8 ml of Ni_NTA (Qiagen) for 1 hour at room temperature. The mixture was poured into a 25 ml column and 50 ml of 10 mM Tris-Cl pH 6 • 3, 100 mM sodium phosphate, 0.5% DOC, and 8 Μ urea rinse. The bound protein was eluted with 35 0 mM imidazole, 10 mM Tris-Cl pH 8.0, 100 mM sodium phosphate, and 8 guanidine urea. The fractions containing FOPP were dialyzed extensively against 1 mM: Tris, Cl pH 4.6, aliquoted and stored at -70 °C. Example 23 127691.doc -127- 200815476 Prostate-specificity in SCID mice with secondary prostate tumors

P703P and P501S When considering the efficacy of antigens in the treatment of prostate cancer, the continuous appearance of antigens in tumors during androgen deprivation therapy is important. The presence of the rituxima-specific antigens P7〇3p and ?5〇18 in prostate tumor samples grown in SCID:fe mice in the presence of ketone was evaluated as follows. Two prostate tumors that had metastasized to the bone were removed from the patient, implanted in SCID mice, and grown in the presence of anthrone. Tumors were evaluated for mRNA expression of P703P, P501S and PSA using quantitative real-time PCR using the SYBR green assay. The performance of P7〇3p and P501S in prostate tumors was used as a positive control group, and the lack of normal small intestine and normal heart was used as a negative control group. In both cases, specific mRNAs were present in late-stage tumors. Because bone metastases are grown in the presence of nicotinic ketone, this means that the emergence of these genes will not be lost during androgen deprivation therapy. Example 24 In patients with sputum adenocarcinoma, it was confirmed that ρ 5 〇1 § and p 7 〇3 p-specific antibodies were detected in the serum of prostate cancer patients and normal healthy donors, and the prostate antigen P50 1 S or P703P was produced. A specific reaction antibody. Western blot analysis and elisa analysis were performed using P501 S peptide (sequence recognition No. 985-987) and P7〇3P peptide (sequence recognition No. 988-990). Sequence identifications 985, 986, and 987 represent the amino acid 23-250, 246-266, and 492-52, respectively, of P501S, sequence identifications 988, 989, 990, 1030, 1031, 1032, 1033, and 1037, respectively, representing p7 〇3P amino acid 110-124, 127691.doc -128- 200815476 140-154, 190-204, 62-76, 91-106, 200-214 and 229-245 ° The results confirmed that some prostate cancer patients have identified P5 An antibody to the same peptide (i.e., a common epitope) of 01S or P703P, and these common epitopes are not recognized by the serum of a normal donor, or are recognized to a significantly lesser extent. The data showed that at least 14 of 48 prostate cancer patients had P501S-specific antibodies, and 3 of 48 prostate cancer patients had P703P-specific antibodies, none of which had antibodies and pairs specific for P501S. Both P703P specific antibodies. ('Example 28 Immunization of mice with recombinant P703P The various P703P recombinant protein formulations were used for immunogenicity studies in vivo. In particular, the group of mice immunized with the P703P formulation is shown in Table XI below, Wherein nC 'amylamined P703P'' represents P703P which is amidated at the C terminal; "truncated -P703P" represents a truncated form of P703P, and ''FOPP&quot; represents a fusion of P703P with PSA.

U 127691.doc -129- 200815476 Table XI Group Antigen Dosage Adjuvant Pathway 1 C'Acetylated P703P 20 μg E. coli AS1 Muscle, Subcutaneous (Foot Pad) 2 Truncated P703P 20 μg AS1 Muscle, Subcutaneous (Footpad) 3 C'Acetylated P703P 20 micrograms of Pichia pastoris AS1 intramuscular, subcutaneous (footpad) 4 P703P 20 micrograms of AS1 intramuscular, subcutaneous (footpad) 5 FOPP 20 micrograms AS1 intramuscular, subcutaneous (Footpad) 6 P703P lO^fu No tail root of subcutaneous 7 C' amidated P703P 20 micrograms E. coli MPL- SE intramuscular, subcutaneous (foot pad) 8 truncated P703P 20 micrograms E. coli MPL- SE intramuscular , subcutaneous (foot pad) 9 C' amidated P703P 20 micrograms of Pichia pastoris MPL- SE intramuscular, subcutaneous (foot pad) 10 P703P 20 micrograms of Pichia pastoris MPL- SE intramuscular, subcutaneous (foot pad) 11 FOPP 20 μg E. coli MPL- SE intramuscular, subcutaneous (foot pad) 12 inexperienced (control group) immunization of each protein at four locations · under two ankles (sq), and in Inside the muscles of both legs (im). Serum plus spleen and lymph node (L N) cells were harvested at intervals of three weeks per immunization 10 days after the last immunization. T cell proliferation and interferon-gamma assays were performed as follows. 250,000 spleen cells or 100,000 LN cells were plated in 96-well plates and stimulated with 1-10 μg/ml of antigen. The antigens tested included the five proteins listed above, the Ρ703Ρ expressed in baculovirus, the NS1 control protein, the PSA (for the F_〇pp group only), and the Ρ703Ρ peptide collection. The peptide assembly consists of 15 amino acid partially overlapping 20-mer peptides, each containing 6-8 peptides. 127691.doc -130· 200815476 Concanavalin agglutinin A was used as a positive control group. On the fourth day after the start of the assay to determine proliferation, the culture was pulsed with H3-thymidine. In order to determine the IFNy content by ELIS A, the supernatant was also withdrawn on the fourth day. Further, Jinqing was also collected, and IgG antibodies against the recombinant proteins listed above were measured by ELISA. All immunogens induced a strong antibody response to the immunogen. In all cases, these reactions reacted with other sources of P703P protein, including strong responses to both P703|&gt; Pichia pastoris and baculovirus forms. AS1 induces a stronger antibody response than MPL-SE. From the standpoint of inducing a reaction against P. cerevisiae and baculovirus forms of P703P, the best immunogen is FOPP, but all immunogens are P703P derived from Escherichia coli, which induces strong reactivity. Antibody response. In both proliferation and interferon-gamma assays, all immunogens elicited quite good anti-immunoassay cell responses, most of the animals that were immunoreactive with their original response, and also produced Ρ703Ρ proteins from other sources. reaction. Furthermore, AS1 induces a better sputum cell response than MPL-SE. Example 29 Analysis of prostate cancer and normal tissues by immunohistochemistry (IHC) analysis of Ρ703Ρ in prostate cancer and normal tissues, analysis of prostate cancer using an array of anti-Ρ703Ρ multiple and monoclonal antibodies by IHC analysis Protein expression of the antigen Ρ703Ρ (see Table X Π). The performance of P703P protein was also analyzed by using the same anti-P703P antibody in 293/Ρ703Ρ transfer transfectants by flow cell counting and Western blot analysis. 127691.doc -131- 200815476 By flow cytometric analysis, PEK-R087 and P7〇3P_2〇59 antibodies were stained with HEK293/P703P 辘 a, 9 a π + tianji\m pa will be infected. Western blot analysis uses P703P-2594 ° Table X Π Anti-P703 antibody

An antibody—P703P-2594 T703P-9245 P703-2D4 P703-8H2 P703-7H8 P703P-2059 P703P-R087 P703P-R080 PA-P703P- 9245 AP-P703P: 9245 Batch number—370-84 690.46 690.88 Rabbit/species/types Rabbit/multiple rabbit/multiple strains of immunogenic bacteria-derived truncated P703P (c-terminal 159 amino acids) Bacterial-derived full-length P703/NS1 fusion-fabricated truncated P703P (c-terminal 159 amino groups) Acid) Bacterial-derived truncated P703P (〇 terminal 159 amino acids) Purified immunogen immunogen

Protein A

Protein A-derived cut-off P703P (c-terminal 159 amino acids) baculovirus-derived full-length form Protein A immunogen 858-130 858409

In order to further evaluate the anterior sputum, 丨~ -- 歹 腺 腺 腺 腺 Ρ Ρ Ρ Ρ Ρ Ρ Ρ , , , Ρ Ρ Ρ Ρ , , , , , , , , , , , , , , , , , , , , , , , , , , 12_24 hours, and 4 packs buried in the money before cutting into 8 pieces. For the best dyeing conditions, in the 0, citric acid reduction solution (PHM), make the heart heat 127691.doc »132- 200815476 reply (SHIER). Slides were incubated with 10% serum/PBS for 5 minutes. Primary antibodies were added to each slide at the indicated concentrations for 25 minutes and then incubated with anti-rabbit biotinylated antibodies for 25 minutes. Endogenous peroxidase activity was blocked by incubation with catalase for three times for 1.5 minutes. The avidin biotin complex/horseradish peroxidase (ABC/HRP) system was used with DAB chromogen to see the performance of the antigen. The slides were contrast-stained with hematoxylin to see the nucleus. As for the Western blot analysis, the cells were cultured in a tee-Xl® containing a lysis buffer on ice to produce a complete lysate. The lysate was then clarified by centrifugation at 4 Torr for 5 minutes at 4 rpm. The sample was diluted with a SDS-PAGE loading buffer solution containing diterpenoid ethanol, and then boiled for 10 minutes before being loaded into the SDS_pAGE gel. The protein was transferred to nitrocellulose and probed with 1 μg/ml of purified anti-P703P rabbit multi-strain serum 2594 (batch 370-84) or rabbit individual P703P-R087. Goat anti-rabbit Ig' co-extracted with HRP was then cultured in an ECL substrate to visualize the dots. For FACS analysis, a single cell suspension of the P703P/HEK293 transformant was produced and the cells were cultured in a permeabilization buffer solution (PBS + saponin + BSA) at room temperature. The cells were then incubated with 10 μg/ml of purified anti-P703P multi-strain serum or monoclonal antibody for 30 minutes. After rinsing three times with the permeabilization buffer solution, the cells were cultured for 30 minutes at room temperature with goat anti-rabbit Ig (H+L)-FITC (Southern Biotechnology) diluted 1:100. After three washes, the cells were resuspended in buffer solution and analyzed by FACS. AP-P703P-127691.doc-133-200815476 9245 antibody against full-length P703 was purified using heat recovery and affinity to obtain optimal IHC results. Using the above procedure, IHC analysis of the antibody showed weak staining on 6/23 metastatic prostate cancer sections. Using this antibody, 24/33 primary prostate cancer sections were positively stained. In addition, staining was observed in malignant glands, benign (normal glandular glands), basal, myoepithelial cells, mast cells in various prostate tumors, and in combination with lipid functional particles. List of normal tissues, including brain, breast, uterus, parotid gland, spleen, liver, ovary, adrenal gland, cervix, tonsils, esophagus, bronchi, lungs, kidneys, testicles, pancreas, skeletal muscle, colon, small intestine, skin and The sigmoid gland sections were all negative. Example 31 Confirmation of the P703P-derived CD4+ T cell epitope by a standard procedure to produce a total of forty 1 amino acid partial overlaps, a 15-mer peptide spanning the amino acid 47 to 254 of the P703P protein sequence . Dendritic (DC) cells were derived from normal female donor pBMCs using standard procedures using GMCSF and IL-4. CD4 τ cells were produced from the same donor as DC using MACS beads and negative selection. DCs were pulsed overnight with a collection of ten 15-mer peptides, each of which was at a final concentration of 25 μg/ml. The pulsed DCs were washed and plated at 1 χ 1 〇 4 cells/well in 96-well round bottom culture plates, and purified T cells were added at 1 χ 1 〇 5 cells/well. The culture was supplemented with 60 house micrograms/ml _6 and 1 ng nanogram/ml IL_12 and cultured at 37t. On a weekly basis, re-stimulate the culture as above, and test for specific proliferation, used as APC, as above produced and pulsed DC, and supplemented with 5 ng/ml than ^ and ... units/ml il_2. After five in vitro stimulation cycles of 127691.doc -134-200815476, the cell lines (each cell equivalent of one well) were assayed for response to the stimulus pool, relative to the sequence derived from p 7 〇3 p Proliferation and cytokine production of irrelevant peptide aggregates. Twelve cell lines were identified, and the specific responses of the stimulated peptide aggregates (measured by standard thymidine proliferation assays) and cytokine production (measured by gamma-interferon ELISA assay) ). These cell lines were further tested for specific recognition of peptide aggregates, specific cognition of individual peptides in the collection, and specific recognition of recombinant P703P protein. Using this method, for the 11th class of 1^11〇, the epitope of the peptide derived from the prostate tumor-specific protein P 7 0 3 P recognized by CD4+ cells was confirmed. This peptide corresponds to the amino acid 145-159 of the P703P protein of sequence identification 525 and has the sequence GNSCLVSGWGLLANG (SEQ ID NO: 992). The cDNA sequence encoding this epitope is set forth in Sequence ID 991. Example 40 Detection of p5〇1 s and P703P-specific antibodies in the serum of prostate cancer patients and normal donors The above confirmation and determination of the characteristics of prostate specific antigen P501s*p7〇3p are respectively identified in Sequence Identification No. 113 (by The sequence identification 11 编码 encoding) and the sequence identification 5 25 (encoded by the sequence identification 524) are exemplified. This example describes the detection of antibodies specific for those proteins in the serum of prostate cancer patients. On a protein basis, effective selection of a gland-specific antibody in a patient's serum is problematic because of protein instability, and/or contamination of a small amount of E. coli-derived protein. However, the carboxy guanylation of recombinant P501S and P703P has provided improved stability of these proteins, which can be confirmed by SDS-PAGE. Therefore, P501 S- and P703P-specific antibodies were screened in the sera of 55 prostate cancer patients and 13 normal male donors using the carboxyammonium P501S and P703P proteins. Incubate and coat at 50 μl with 50 μl of a coating buffer solution (0.1 N carbonate buffer solution; pH 9.5) supplemented with 600 ng of carboxyl amidated P501S or 300 ng of carboxy amidated P703P protein. The plated immunization-culture plate was incubated for at least three hours or overnight at 4 °C. Remove the solution and add at least 150 μl of blocking buffer solution (10% NFDM (skimmed milk powder) / PBS 1:1 mixture) to each well and add Superblock (Pierce) to each well, then Incubate for three hours at room temperature or overnight at 4 °C. After rinsing at least three times with 0.05% Tween 20 containing PBS and rinsing once with PBS, 50 μl of 10% NGS (normal goat serum; Gibco BRL, #162 10-072) diluted PBS was added. Serum from prostate cancer patients or normal donors and incubated for three hours at room temperature or overnight at 4 °C. Rinse at least three times with 0.05% PBS containing Tween and rinse once with PBS.

After U, add 1 〇〇 microliter of HRP-common anti-human IgG (Jackson Immimo Research Laboratories Inc.; #709-036-149) (diluted by 10% NFDM/PBS + Superblock 1: 1 mixture x8000) And incubated at room temperature for 30-60 minutes. After rinsing with 0.05% Tween-containing PBS for at least six times and rinsing once with PBS, 80-100 μl of TMB-plasma solution was force-injected and incubated at room temperature. Between 10 and 30 minutes, after obtaining the appropriate color for the IgG standard, 40-50 microliters (half volume of the substrate) of 0.1% sulfuric acid solution was added to stop the enzyme reaction. The absorbance was then determined using a microtiter plate reader 127691.doc -136-200815476 (Biotec Instruments). Using this method, P501S-specific antibodies were detected in 32/55 prostate cancer patients and 5/13 normal donors. P703-specific antibodies were detected in 24/55 prostate cancer patients and 0/3 normal donors. These results confirm the immunogenicity of P501S and P703P in vivo. In addition, the results also confirmed that the carboxy amidated forms of P501S and P703P retained the antigenic epitopes recognized by rabbit/mouse antibodies as well as antibodies obtained from prostate cancer patients. Example 48 The production of the P703P fusion protein as exemplified confirms and defines the characteristics of the relevant form of the prostate specific antigen P703P which has been described above, and a representative DNA sequence 'represented in sequence identification' in Sequence Identification No. 171 The encoded amino acid sequence is set forth in 197. In this example, the P703P fusion construct is exemplified and the encoded fusion protein is produced. The recombinant fusion protein can be used, for example, in a method of detecting prostate cancer in an individual, and/or in inducing an immune response to prevent and/or treat prostate cancer. Full-length human PAP DNA was obtained by PCR from the prostate cancer tissue cDNA library (PT library) using the primers hPAPF 1 and hPAPRV 1. The sequence of these primers is: hPAPF1 5'CGGCGGATCCGCCGCCACCATGAGAGCTGCACCCCT CCTCCT-31 (preface if 另U〇14) and hPAPRVl

5, CGGCCTCGAGCTAATCTGTACTGTCTTCAGTACCTTG octopidine (2 butyl guanidine-3' (SEQ ID NO: 1015). The PCR product was then cloned into the PCR Bluntll TOPO vector. To modify 127691.doc -137-200815476 hPAP, perform a second PCR, Using the primers FOPP2F1 5, GAGAAAACCGTCCAGGCCAGTAAGGAGTTGAAGTT TGTGTACTTTGGTG-3, (sequence recognition 1016) and HPAPRV1 (sequence recognition 1015), using hPAP/TOPO Bluntll as a template. Also modify FOPP/PCRX1 (DNA containing P703P), using bow | FOPPF1 5, CGGCGGGCATATGCATCACCATCACCATCACATCATA AACGGCGAGGACTGCAG-3' (sequence recognition 1017) and FOPP2RV1 S'CACCAAAGTCACAAACTTCAACTCCTTACTGGCCTG GACGGTTTTCTC-3, (preface 歹U _ ij 1018). Finally, use the primers FOPPF1 and hPAPRV1 with modified hPAP and P703PPCR The product was used as a template for PCR to produce FOPP 2. The PCR product was then cloned into the PCRX1 vector at the restriction enzyme cleavage sites Ndel and Xhol. The E. coli strain Tuner (DE3) pLysS was then transformed using the FOPP2/PCRX1 plastid. And tiling in LB plates containing oxytetracycline and oxytetracycline Using SDS-PAGE analysis and Western blot analysis, antibodies against His-Tag were used to show that the transformant expressed FOPP2 protein when induced by IPTG. To produce a large amount of FOPP2 protein, inoculate the expression culture. 20 ml of STB containing 50 μg/ml of oxytetracycline and 34 μg/ml of chloramphenicol and grown at 37 ° C until the OD600 reading is about 1. The culture is then diluted to 1 liter in 50 liters. Micrograms/ml of oxytetracycline and 34 μg/ml chloramphenicol in STB and grown at 37 ° C until the OD600 reading is about 0.4. Then add IPTG to a final concentration of 1 mM, and at 127691. Doc -138- 200815476 37 The culture was incubated for 2 hours at C. Centrifuge at 5000 RPM for 8 minutes, rinse with PBS 're-centrifugation and store at _7 〇〇c. To purify the protein, re-suspend the cell pellet 25 ml of mM Tris-Cl (pH 8.0) containing 2 mM PMSF and protease inhibitor. The cells were spun several times with ultrasound and the lysate was centrifuged at 4000 RPM for 60 minutes. Rinse inclusion bodies containing 1 CHA mM Tris-HCl (pH 8.0) containing 1% CHAPS

The precipitate was taken twice. Dissolve the inclusion bodies in 40 ml of binding buffer solution (1 〇 mM

Tris HC1' pH 8·〇, 1 mM mM sodium sulphate and 8 Μ urea). At room temperature, mix the "Hai/Valley solution with 1 ml of Nl_NTA tree wax (Qiagen) for a minute. Then pour the mixture into a 25 ml column and rinse the buffer with 50 ml.

(10 mM Tds-ci pH 6 3, 1 mM mM sodium phosphate, 〇·5% D〇c and 8 M urea) rinse. It was then eluted using an elution buffer (1 mM mM Dings, 8·〇, 3 50 mM imidazole, 1 〇 () mM sodium phosphate, and 8 M urea). Beta protein shellfish. The fractions containing F〇pp2 were mixed and dialyzed extensively using a large volume of Tris Cl, pH 8.0, aliquoted and stored at _7 Torr. Your majesty. a FOPP2 sequence, and reveals DNA and amino acid sequences in sequence recognition 1〇19 and 丨〇2〇, respectively. It will be apparent from the foregoing that the specific embodiments of the present invention are described herein, and the invention may be Therefore, the present invention is not intended to be limited, except for the scope of the patent application of the appendix. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the ability of T cells to kill fibroblasts expressing the prostatic prostate tumor polypeptide P502S compared to control fibroblasts. According to a series of effectors of 127691.doc -139« 200815476: light weight ratio, showing the percentage of dissolution. Figures 2A and 2B illustrate the ability of T cells to recognize cells expressing a representative prostate tumor polypeptide P 5 02 S. In each case, the number of gamma-interferon spots was shown for different amounts of reactants. In Fig. 2A, the data obtained from the P2S-12 peptide pulsed fibroblasts were compared with the data of the control Ε75 peptide pulsed fibroblasts. In Figure 2, the data provided by fibroblasts expressing P502S were compared to fibroblasts expressing HER-2/neu. Figure 3 represents a peptide competitive binding assay showing P1S#10 peptide derived from P501S (, binding to HLA-A2. In the bioassay of TNF release, peptide P1S#10 inhibits HLA-A2, limiting fluM58 peptide to CTL pure The performance of the line D150M58. D150M5 8 CTL is specific for HLA-A2 binding to the influenza matrix peptide fluM58. Figure 4 illustrates the T cell line produced from P1S#10 immunized mice, and EGFP-transduced Jurkat A2Kb In comparison, the ability to specifically lyse the P1S#10-pulsed Jurkat A2Kb target and the P501S-transduced Jurkat A2Kb target was shown. The percentage of dissolution was shown by a series of effector to target ratios. () Figure 5 illustrates T The pure cell line recognizes and specifically lyses the ability of the Jurkat A2Kb cells expressing the representative prostate tumor polypeptide P501S, thereby confirming that the P1S#10 peptide may naturally have an epitope of the P501S polypeptide. Figures 6A and 6B illustrate CD8 + The specificity of the cell line (3A-1) for the representative prostate tumor antigen (P5 01S). Figure 6A shows the results of the 51Cr release assay. The percentage of specific lysis is shown by a series of effector: target ratios. Figure 6B shows With P50 1S-transduced autologous B-LCL stimulates 3A-1 cells to produce interferon-1, expressed as a ratio of various effectors: stems. 127691.doc -140- 200815476 Sequence Listing &lt;110&gt; Corixa Corporation &lt;120&gt Immunization therapy and succulent prostate cancer nucleus, and methods of use thereof

ϋ &lt;1.30&gt; 210121.42701PC &lt;140&gt; PCT &lt;141&gt; 199^-07-08 &lt;160&gt; 472 ' &lt;170&gt; FastSEQ for Windows Version 3.0 &lt;210&gt; 1 &lt;211&gt; B14 &lt;212&gt; DNA &lt;213&gt; Human · · &lt;220&gt;&lt;221&gt; misc_. 特敬·· &lt;222&gt; (1).7.(814) &lt;223&gt; n * A#T, C or G &lt; 400 &gt; 1 ttttttttcc tttttcacag tataacagct ctttatttct gtgagttcta ctaggaaatc accaaatctg agggttgtct ggaggactcc aatacacctc cccccatagt gaatcagctt ccagggggtc cagtccctct ccttacttca tccccatccc atgccaaagg aagaccctcc ctcctcggcc cacagccctc tctaggcttc ccagtgcctc caggacagag tgggttatgt tttcagcccc atccttgctg cgagtgtctg gtgcgttgtg cctccagctt ctgctcagtg cttcacggac agtgtccagc acatgtcact ctccactctc tcagtgtgga tccactagtt ctagagcggc cgccaccgcg gtggagctcc agcttttgtt ccctttagtg agggttaatt gcgcgcttgg cgtaatcatg gtcataactg Tttcctgtgt gaaattgtta tccgctcaca attccacaca acatacgagc cggaagcata aagcgtaaag cctggggtgc ctaatgagcg anctaactca cattaattgc gttgcgctca ctgnccgcct tccagtcngg aaaactgtcg tgccagccgc attaatgaat cggcc aacgc ncggggaaaa gcggtttgcg ttttgggggc tcttccgctc ctcgctcact nanccctgcg ctcggtcntt cggctgcggg gaacggtatc actcctcaaa ggnggtatta cggttatccn naaatcnggg gatacccngg aaaaaanttt aacaaaaggg cancaaaggg cngaaacgta aaaa &lt; 210 &gt; 2 &lt; 211 &gt; 816 · &lt; 212 &gt; DNA &lt; 213 &gt; human, &lt; 220 &gt; &lt; 22l &gt; Misc一特教, &lt;222&gt; (1)...(816) &lt; 2 2 3 &gt; n *= A, D, C or G &lt;400&gt; 2 acagaaatgt tggatggtgg agcacctttc tatacgactt acaggacagc agatggggaa ttcatggctg ttggagcaat agaaccccag ttctacgagc tgccgatcaa aggacttgga 60 120 180 240 300 360 420 480 540 600 660 720 780 814 60 120 127691.doc 200815476 ctaaagtctg atgaacttcc caatcagatg agcatggatg attggccaga aatgaagaag 180 aagtttgcag atgtatttgc aaagaagacg aaggcagagt ggtgtcaaat ctttgacggc 240 acagatgcct gtgtgactcc ggttctgact tttgaggagg ttgttcatca tgatcacaac 300 aaggaacggg gctcgtttat caccagtgag gagcaggacg tgagcccccg ccctgcacct 360 ctgctgttaa acaccccagc Catcccttct ttcaaaaggg atccactagt tctagaagcg 420 gccgccaccg cggtggagct ccagcttttg ttcc ctttag tgagggttaa ttgcgcgctt 480 ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt tatccgctca caattccccc 540 aacatacgag ccggaacata aagtgttaag cctggggtgc ctaatgantg agctaactcn 600 cattaattgc gttgcgctca ctgcccgctt tccagtcggg aaaactgtcg tgccactgcn 660 ttantgaatc ngccaccccc cgggaaaagg cggttgcntt ttgggcctct tccgctttcc 720 tcgctcattg atcctngcnc ccggtcttcg gctgcggnga acggttcact cctcaaaggc 780 ggtntnccgg ttatccccaa acnggggata cccnga 816

&lt;210&gt; 3 &lt;211&gt; 773 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc one: special desire &lt;222&gt; (1).7.(773) &lt;223&gt; n = A, T, C branch G

&Lt; 4 00 &gt; 3 cttctgaaag aagggatggc tggggtgttt aacagcagag gtgcagggcg ggggctcacg 60 tcccgctcct cactggtgat aaacgagccc cgttccttgc tgtgaccatg acgaacaacc 120 tccccaaaag tcagaaccgg agtcacacag gcatctgtgc cgccaaagat ttgacaccac 180 tctgccttcg tcttctttgc aaatacatct gcaaacttct tcttcatctc tggccaatca 240 cccacgctca tctgattggg aagttcatca gacttcagtc canntccttt gatcagcagc 300 ccgtagaact ggggttctat tgctccaaca gccatigaatic ccccatctgc tgtcctgtaa 360 gccgcataga aaggcgctcc accatccaac atgtcctgcc cccgaggggg ggcccggtac 420 ccaactcgcc ctatantgag tcgtattacg cgcgctcacc ggccgtcgtt ttacaacgtc 480 gcgaccggga aaaccctggg cgttaccaac ctaatcgcct tgcagcacac ccccctttcg 540 ccagccgggc gtaatancga aaaggcccgc accgaccgcc cttccaacag ttgcgcacct 600 gaacgggnaa atgggacccc cctgttaccg cgcactnaac ccccgcnggg tttngttgtt 660 acccccacnt nnaccgctta cactttgc.ca gcgccttanc gcccgccccc tttcnccttt 720 cttcccctcc tttcncnccn ctttcccccg gggtctcccc cntcaaaccc cna 773 &lt;210&gt; 4 &lt;211&gt; 828 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc_: Feature &lt;222&gt; (1) (828) &lt;223&gt; n - A, T, C or G &lt; 4 00&gt; 4 * cctcctgagc cctactgacc tgtgctttct ggtgtggagt ccagggctgc taggaaaagg 60 aatgggcaga cscaggtgta tgccaatgtt tctgaaatgg gtataatttc gtcctcccct 120 tcggaacacc ggctgtctct gaagacttct cgctcagttt cagtgaggac acacacaaag 180 acg'tgggtga ccatgttgtt tgtggggtgc agagatggga ggggtggggc ccaccctgga 240 agagtggaca gtgacacaag gtggacactc tctacagatc accgaggaca agctggagcc 300 acaatgcatg aggcacacac acagcaagga tgacnctgta aacatagccc acgctgtcct 360 2- 127691.doc 200815476 gngggcactg ggaagcctan atnaggccgt gagcanaaag aaggggagga tccactagtt 420 ctanagcggc cgccaccgcg gtgganctcc ancttttgtt ccctttagtg agggttaatt. 480 gcgcgcttgg cntaatcatg gtcatanctn tttcctgtgt gaaattgtta tccgctcaca 540 attccacaca acatacganc cggaaacata aantgtaaac ctggggtgcc taatgantga 600 ctaactcaca ttaattgcgt tgcgctcact gcccgctttc caatcnggaa acctgtcttg 660 ccncttgcat tnatgaatcn gccaaccccc ggggaaaagc gtttgcgttt tgggcgctct 720 tccgcttcct cnctcantta ntccctncnc tcggtcat Tc cggctgcngc aaaccggttc 780 accncctcca aagggggtat tccggtttcc ccnaatccgg gganancc 828 &lt;210&gt; 5 &lt;211&gt; 834 ^ &lt;212&gt; DNA * &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc-teflux &lt;222&gt; (1).7.(834) &lt;223&gt; n = A, T, C or G &lt; 4 00&gt; 5 ··

U tttttttttt tttttactga tagacggaat ttattaagct tttcacatgt gatagcacat 60 agttttaact gcacccaaag tactaacaaa aactccagca atcaagaatg gcagcatgtt 120 attctataac aatcaacacc tgtggctttt aaaatttggt tttcataaga taatttatac 180 tgaagtaaat ctagccatgc ttttaaaaaa tgctttaggt cactccaagc ttggcagtta 240 acattcggca caaacaataa taaaacaatc acaatttaat aaataacaaa tacaacattg 300 taggccataa ccatacacag cacaaggaaa aggtggtagt gtcgagtaag cagttattag 360 aatagaatac cttggcctct atgcaaatat gtctagacac tttgatccac ccagccctga 420 cattcagttc tcaaagtagg agacaggttc tacagtatca tttcacagtt tccaacacat 480 tgaaaacaag cagaaaatga tgagttgact tttactaatg cattacatcc tcaagagtta. 540 tcaccaaccc ctcagttata aaaaattttc aagctatatt agtcatacaa cttggcgtgc 600 ttatttcaaa ctagtgccaa atggattaag tgaagacaac aacggccccc taatgtgatt 660 gatattggcc atttttacca gcttctaaat ccnaaccttc aggcttttga actggaacat 720 tgnatnacag tgccccanag ttncaaccta ctggaacatc acagtgtgct tgatccaaaa 780 tgtcaccccg tcaaaaatta aatcttaacc tggtggaaaa ataatctgaa atna 834

&lt;210&gt; 6 &lt;211&gt; 818 &lt;212&gt; DNA &lt;213ϊ人颏&lt;220&gt; · &lt;221&gt; misc-features _ &lt;222&gt; (1).7.(Θ18)

tgccgtcgga tttttttctt aagaccctca tcaatagacg gagacataca gaaatagtca 60 aaccacatct acaaaatgcc agtatcaggc ggcggcttcg aagccaaagt gatgtttgga 120 tgtaaagtga aatattagtt ggcggatgaa gcagatagcg aggaaagttg agccaataat 180 ga.cgtgaagt ccgtggaagc ctgtggctac aaaaaatgtt gagccgtaga 240: 6 tttttctttt; &lt; 223 &gt; n «A, T, C, or, G &lt; 400 & gt aatggtgaag ggagactcga agtactctga ggcttgtagg agggtaaaat agagacccag 300 taaaattgta acaagcagtg cttgaattat tcggtttcgg ttgttttcta ttagactatg 360 gtgagctcag gtgattgata ctcctgatgc gagtaatacg gatgtgttta ggagtgggac 420 ttctagggga cttagcgggg tgatgcctgt tgggggccag tgccctccta gttggggggt 480 aggggctagg ctggagtggt aaaaggctca gaaaaatcct gcgaagaaaa aaacttctga 540 3- 127691.doc 200815476

ggtaataaat aggattatcc cgtatcgaag gcctttttgg acaggtggtg tgtggtggcc ttggtatgtg ctttctcgtg ttacatcgcg ccatcattgg tatatggtta gtgtgttggg ttantanggc ctantatgaa gaacttttgg antggaatta aatcaatngc ttggccggaa gtcattanga nggctnaaaa ggccctgtta ngggtctggg ctnggtttta cccnacccat ggaatncncc ccccggacna ntgnatccct attcttaa &lt; 210 &gt; 7 c211 &gt; 817 &lt; 212 &gt; DNA &lt; 213 &gt; Simon &lt; 220 &gt; ♦ &lt;221&gt; misc_j Special Education &lt;222&gt; (1).7.(817) &lt;223&gt; n * A,T,C or G &lt;400&gt; 7 tttttttttt tttttttctt tggctctaga gggggtagag ggggtgctat agggtaaata cgggccctat ttcaaagatt tttaggggaa ttaattctag gacgatgggt atgaaactgt ggtttgctcc acagatttca gagcattgac cgtagtatac ccccggtcgt gtagcggtga aagcggtttg gttcagacgt ccgggaatt.g catctgtttt taagcctaat gtggggacag ctcatgagtg caagacgtct tgtgatgtaa ttattatacn aatgggggct tcaatcggga gtactactcg attgtcaacg tcaaggagtc gcaggtcgcc tggttctagg aacaatgggg gaagtatgta ggaattgaag attaatccgc cgtagtcggt gttctcctag gttcaatacc actggtggcc aactgatttg atggtaaggg gagggatcgt tgaactcgtc tgttatg taa aggatncctc ngggatggga aggcnatnaa ggactangga tnaatggcgg gcangatact: tcaaacngcc tctanttcct gaaacgtctg aaatgttaat aanaactaan tttngccatt gaatnttnng gaaaagggct tacaggacta gaaaccaaat angaaaanta atnntaangg cnttatcntn aaaggtnaca accnctccta tnatcccacc caatngnatt ccccacncnn acnactggat nccccantcc canaaanggc cnccccccgg tgnannccnc ctctcgctcc cctnancgan ggttatccnc ccctngcntt atcancc &lt; 210 &gt; 8 &lt; 211 &gt; 799 &lt; 212 &gt; DNA &lt;213&gt; Person. &lt;220&gt;&lt;221&gt; misc__ Special meal &lt;222&gt; (1).7.(799) &lt;223&gt; n = A, T, C or G &lt;400&gt; 8 catttccggg tttactttct aaggaaagcc gagcggaagc tgccaacgtg ggaatcggtg cataaggaga actttctgct ggcacgcgct agggacaagc gggagagcga cticcgagcgt ctgaagcgca cgtcccagaa ggtggacttg gcactgaaac agctgggaca catccgcgag tacgaacagc gcctgaaagt gctggagcgg gaggtccagc agtgtagccg cgtcctgggg tgggtggccg angcccganc pgctctgcct tgctgccccc angcgggccg ccaccccccg acctgcctgg gtccaaacac tgagccctgc tggcggactt caagganaac ccccacangg ggatttcgct cctanantaa ggctcatctg ggcctcggcc cccccacctg gttggccttg tctttgangt gagccccatg tccatctggg ccactgtcng gaccaccttc ngggagtgtt ctccttacaa ccacannatg cccggctcct cccggaaacc antcccancc tgngaaggat caagncctgn atccactnnt nctanaaccg gccnccnccg cngtggaacc cnccttntgt tccttttcnt tnagggttaa tnncgccttg gccttnccan ngtcctncnc nttttccnnt gttnaaatcg ttangcnccc nccnntcccn cnncnncnan cccgacccnn annttnnann 600 660 720 780 818 60 120 180 240 300 360 420 480 540 600 660 720 78Q 817 60 120 180 24 0 300 360 420 480 540 600 660 720 127691.doc 4- 200815476 ncctgggggt nccnncngat tgacccnncc nccctntant tgcnttnggg nncnntgccc 780 ctttccctct nggganncg 7^9 &lt;210&gt; 9 &lt;211&gt; 801 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc:_ 特微&lt;222&gt; (1) ... (801) &lt;223&gt; n « A, T, C P. G. &lt;400&gt; 9 acgccttgat cctcccaggc tgggactggt tctgggagga Gccgggcatg ctgtggtttg taangatgac actcccaaag gtggtcctga cagtggccca gatggacatg gggctcacct 120 caaggacaag gccaccaggt gcgggggccg aagcccacat gatccttact ctatgagcaa 180 aatcccctgt gggggcttct ccttgaagtc cgcca ncagg gctcagtctt tggacccang 240 caggtcatgg ggttgtngnc caactggggg ccncaacgca aaanggcnca gggcctcngn 300 cacccatccc angacgcggc tacactnctg gacctcccnc tccaccactt tcacgcgctg 360 ttcntacccg cgnatntgtc ccanctgttt cngtgccnac tccancttct nggacgtgcg 420 ctacatacgc ccggantcnc nctcccgctt tgtccctatc cacgcn ^ can caac ^ aattt 480

cnccntantg caccnattcc cacntttnnc agntttccnc nncgngcttc cttntaaaag 540 ggttganccc cggaaaatnc cccaaagggg gggggccngg tacccaactn ccccctnata 600 gctgaantcc ccatnaccnn gnctcnatgg anccntccnt tttaannacn ttctnaactt 660 gggaanancc ctcgnccntn cccccnttaa tcccncctftg cnangnncnt cccccnntcc 720 ncccnnntng gcrxtntnann cnaaaaaggc ccnnnancaa tctcccnncn cctcanttcg 780 ccanccctcg aaatcggccn c Θ01 &lt; 210 &gt; 10 &lt; 211 &gt; 789 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc_: esteem &lt;222&gt; {1).7.(789) &lt;223&gt; π » A, T, C or G &lt; 4 00&gt; 10 cagtctacnc ggccagtgtg gcagctttcc ctgtggctgc cggtgccaca tgcctgtccc 60 acagtgtggc cgtggtgaca gcttcagccg ccctcaccgg gttcaccttc tcagccctgc 120 agatcctgcc ctacacactg gcctccctct accaccggga gaagcaggtg ttcctgccca 180 aataccgagg ggacactgga ggtgctagca gtgaggacag cctgatgacc agcttcctgc 240 caggccctaa gcctggagct cccttcccta atggacacgt gggtgctgga ggcagtggcc '300 tgctcccacc tccacccgcg ctctgcgggg cctctgcctg tgatgtctcc gtacgtgtgg 360 tggtgggtga gcccaccgan gccagggtgg ttccgggccg gggcatctgc ctggacctcg 420 ccaccctgga tagtgcttcc tgctgtccca ngtggcccca tccctgttta tgggccccat 480 tgtccagctc agccagtctg tcactgccta tatggtgtct gccgcaggcc tgggtctggt 540 cccatCtact ttgctacaca ggtantattt gacaagaacg anttggccaa atactcagcg 600 ttaaaaaatt ccagcaacat tgggggtgga aggcctgcct cactgggtcc aactccccgc 660 tqctgttiaac cccatggggc tgccggcttg gccgccaatt tctgttgctg ccaaantnat 720 gtggctctct gctgccacct gttgctggct gaagtgcnta cngcncanct nggggggtn g 760 ggngttccc 789^ 5- 127691.doc 200815476 η &lt;210&gt; 11 &lt;211&gt; 772 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;&lt;221&gt; misc_ special education &lt;222&gt; ) ·Τ: (772)

&Lt; 223 &gt; η »A, T, C or G &lt; 400 &gt; 11 cccaccctac ccaaatatta gacaccaaca cagaaaagct agcaatggat tcccttctac tttgttaaat aaataagtta aatatttaaa tgcctgtgtc tctgtgatgg caacagaagg accaacaggc cacatcctga taaaaggtaa gaggggggtg gatcagcaaa aagacagtgc tgtgggctga ggggacctgg ttcttgtgtg ttgcccctca ggactcttcc cctacaaata actttcatat gttcaaatcc catggaggag tgtttcatcc tagaaactcc catgcaagag ctacattaaa cgaagctgca ggttaagggg cttanagatg ggaaaccagg tgactgagtt tattcagctc ccaaaaaccc ttctctaggt gcgtctcaac taggaggcta gctgttaacc ctgagcctgg gtaatccacc tgcagagtcc ccgcattcca gtgcatggaa cccttctggc ctccctgtat aagtccagac tgaaaccccc ctggaaggnc tccagtcagg cagccctana aactggggaa aaaagaaaag gacgccccan cccccagctg tgcanctacg cacctcaaca gcacagggtg gcagcaaaaa aaccacttta ctttggcaca aacaaaaact ngggggggca accccggcac cccnangggg gttaacagga ancngggnaa cntggaaccc aattnaggca ggcccnccac cccnaatntt gctgggaaat ttttcctccc ctaaattntt tc &lt; 210 &gt; 12 &lt;211&gt; 751 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc_ special &l t;222&gt; (1) .7. (751)' &lt;223&gt; n == A,T,C or G ' &lt;400&gt; 12 gccccaattc cagctgccac accacccacg gtgactgcat tagttcggat gtcatacaaa agctgattga agcaaccctc tactttttgg tcgcgagcct tttgcttggt gcaggtttca ttggccgtgt tggtgacgtt gtcattgcaa cagaatgggg gaaaggcact gttctctttg aagtanggtg agtcctcaaa atccgtatag ttggtgaagc cacagcactt gagccctttc atggtggtgt tccacacttg agtgaagtct tcctgggaac cataatcttt cttgatggca ggcactacca gcaacgtcag ggaagtgctc agccattgtg gt ^ tacacca aggcgaccac agcagctgcn acctcagcaa tgaagatgan gaggangatg aagaagaacg tcncgagggc acacttgctc tcagtcttan caccatanca gcccntgaaa accaananca aagaccacna cnccggctgc gatgaagaaa tnaccccncg ttgacaaact tgcatggcac tggganccac agtggcccna aaaatcttca aaaaggatgc cccatcnatt gaccccccaa atgcccactg ccaacagggg ctgccccacn cncnnaacga tganccnatt Gnacaagatc tncntggtct tnacnaacnt gaaccctgcn tngtggctcc tgttcaggnc cnnggcctga cttctnaann aangaactcn gaagncccca cngganannc g &lt;210&gt; 13 &lt;211&gt; 123 &lt;212&gt; DNA &lt;213&gt; Human One 60 12Q 180 240 300 360 420 480 5 40 600 660 720 772

60 120 180 240 300 360 420 480 540 600 660 720 751 127691.doc -6 - 200815476 Ο

&lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1)·:.{729, &lt;223> η - A, T, C or G &lt;400&gt; 13 gagccaggcg tccctctgcc tgcccactca gtggcaacac ccgggagctg ttttgtcctt tgtggancct cagcagtncc ctctttcaga actcantgcc aaganccctg aacaggagcc accatgcagt gcttcagctt cattaagacc atgatgatcc tcttcaattt gctcatcttt ctgtgtggtg cagccctgtt ggcagtgggc atctgggtgt caatcgatgg ggcatccttt ctgaagatct tcgggccact gtcgtccagt gccatgcagt ttgtcaacgt gggctacttc ctcatcgcag ccggcgttgt * ggtcttagct ctaggtttcc tgggctgcta tggtgctaag actgagagca agtgtgccct cgtgacgttc ttcttcatcc tcctcctcat cttcattgct gaggttgcaa tgctgtggtc gccttggtgt acaccacaat ggctgagcac ttcctgacgt tgctggtaat gcctgccatc aanaaaagat tacgggttcc caggaanact tcactcaagt gttggaacac caccatgaaa gggctcaagt gctgtggctt Cnnccaacta tacggatttt gaagantcac ctacttcaaa gaaaanagtg cctttccccc atttctgttg caattgacaa acgtccccaa cacagccaat tgaaaacctg cacccaaccc aaangggtcc ccaaccanaa attnaaggg &lt;210&gt; 14 .. &lt;211&gt; 816 &lt;212&gt; DNA .· &lt;213>human&lt;220&gt;&lt;221&gt; misc_ Feature &lt;222&gt; (1).7.(816) &lt;223&gt; n = A, T, C or G 60 120 1Θ0 240 300 360 .4,20 480 54 0 600 660 720 729

&Lt; 400 &gt; 14 tgctcttcct caaagttgtt cttgttgcca taacaaccac cataggtaaa gcgggcgcag tgttcgctga aggggtcgta gtaccagcgc gggacgctct ccctgcagag tcctgtgtct ggcaggtcca cgcagtgccc tttgtcactg gggaaatgga cgcgctggag ctcgtcaaag ccactcgtgt atttttcaca ggcagcctcg tccgacgcgt cggggcagtt gggggtgtct tcacactcca ggaaactgtc natgcagcag ccattgctgc agcggaaccg ggtgggctga cangtgccag agcacactgg atggcgcctt tccatgnnan gggccctgng ggaaagtccc tganccccan anctgcctct caaangcccc accttgcaca ccccgacagg ctagaatgga acctccttcc cgaaaggtag ttntccttgt tgcccaancc anccccntaa acaaactctt gcanatctgc tccgnggggg tcntantacc ancgtgggaa aagaacccca ggcngcgaac caancttgtt tggatncgaa gcnataatct nctnttccgc ttggtggaca gcaccantna ctgtrmancc tcagnccntg gtcctcntgg gttgnncttg aacctaatcn ccnntcaact gggacaagge aantngccnt cctttnaatt cccnancntn ccccctggtt tggggttttn cncnccccta ccccagaaan nccgtgttcc cccccaacta ggggccnaaa ccnnttnttc cacaaccctn ccccacccac gggtccngnt ggttng &lt; 210 &gt; 15 &lt; 211 &gt; 783 '&lt;212&gt; DNA &lt;213&gt;Human&lt;220&gt;&lt; 221 &gt; mi sc 一特微&lt;222&gt; (1) . . . (783) &lt;223&gt; n * A, T, C or G 60 120 180 240 300 360 420 4Θ0 540 600 660 720 780 816 127691.doc 200815476 &lt; 400 &gt; 15 ccaaggcctg ggcaggcata nacttgaagg tacaacccca ggaacccctg gtgctgaagg 60 atgtggaaaa cacagattgg cgcctactgc ggggtgacac ggatgtcagg gtagagagga 120 aagacccaaa ccaggtggaa ctgtggggac tcaaggaang cacctacctg ttccagctga 180 cagtgactag ctcagaccac ccagaggaca cggccaacgt cacagtcact gtgctgtcca 240 ccaagcagac agaagactac tgcctcgcat ccaacaangt gggtcgctgc cggggctctt 300 tcccacgctg gtactatgac cccacggagc agatctgcaa gagtttcgtt tatggaggct 360 gcttgggcaa caagaacaac taccttcggg aagaagagtg cattctancc tgtcngggtg 420 tgcaaggtgg gcctttgana ngcanctctg gggctcangc gactttcccc cagggcccct 480 ccatggaaag gcgccatcca ntgttctctg gcacctgtca gcccacccag ttccgctgca 540 ncaatggctg ctgcatcnac antttcctng aattgtgaca acacccccca ntgcccccaa 600 cccccccaac aaagcttccc tgttnaaaaa tacnccantt ggcttttnac aaacncccgg - 660 cncctccntt ttccccnntn aacaaagggc nctngcnttt gaactgcccn aacccn Ggaa 720 tctnccnngg aaaaantncc ccccct.ggtt cctnnaancc cctccncnaa anctnccccc 780 ccc 783 Ο

&lt;210&gt; 16 &lt;211&gt; 801 &lt;212&gt; DNA &lt;213&gt; Person's Union &lt;220&gt;&lt;221&gt; misc_ Desirable &lt;222&gt; (1) .7. (801) &lt;223&gt; = A, T, C table G &lt; 400 &gt; 16 gccccaatcc cagctgccac accacccacg gtgactgcat tagcccggat gtcatacaaa GO agctgaccga agcaaccctc tactctttgg tcgtgagcct tttgcccggt gcaggtttca 120 tcggccgtgc tggtgacgtt gtcattgcaa cagaatgggg gaaaggcact gttctccctg 1B0 aagcagggtg agtcctcaaa atccgtatag ttggtgaagc cacagcactt gagccctttc 240 acggcggtgt tccacacttg agtgaagtct tcctgggaac cacaatcttt cttgatggca 300 ggcactacca gcaacgtcag gaagtgctca gccattgtgg tgtacaccaa ggcgaccaca 360 gcagctgcaa cctcagcaat gaagatgagg aggaggatga agaagaacgc cncgagggca 420 cactcgctcc ccgccttagc accatagcag cccangaaac caagagcaaa gaccacaacg 480 ccngccgcga atgaaagaaa ntacccacgt tgacaaactg catggccacc ggacgacagt 540 tggcccgaan atcttcagaa aagggatgcc ccatcgattg aacacccana tgcccactgc 600 cnacagggct gcnccncncn gaaagaatga gccattgaag aaggatcntc ntggccttaa 660 cgaactgaaa ccntgcatgg tggcccctgt tcagggctct tggcagtgaa ttct Ganaaa 720 aaggaacngc ntnagccccc ccaaangana aaacaccccc gggtgttgcc ctgaattggc 780 ggccaaggan·ccctgccccn g 801 υ &lt;210&gt; 17 &lt;211&gt; 740 &lt;212&gt; DNA &lt;213&gt;Human&lt;220&gt; ' &lt;22 3L&gt; miscj Features&lt;222&gt U) ·:. (740) .· ,. &lt;223&gt; n = A, T, C or G &lt;400&gt; 17 gtgagagcca ggcgtccctc tgcctgccca ctcagtggca acacccggga gctgttttgt 60 127691.doc 8- 200815476 cctttgtgga gcctcagcag ttccctcttt cagaactcac tgccaagagc cctgaacagg 120 agccaccatg cagtgcttca gcttcattaa gaccatgatg atcctcttca atttgctcat 180 ctttctgtgt ggtgcagccc tgttggcagt gggcatctgg gtgtcaatcg atggggcatc 240 ctttctgaag atcctcgggc cactgtcgtc cagtgccatg cagtttgtca acgtgggcta 300 cttcctcatc gcagccggcg tcgtggtctt tgctcttggt ttcctgggct gctatggtgc. 360 taagacggag agcaagtgtg ccctcgtgac gttcttcttc atcctcctcc tcatcttcat 420 tgctgaagtt gcagctgctg tggtcgcctt ggtgtacacc acaatggctg aaccattcct 480 gacgttgctg gtantgcctg ccatcaanaa agattatggg ttcccaggaa aaattcactc 540. aantntggaa caccnccatg aaaagggctc caatttctgn tgg cttCGCC aactataccg 600 gaattttgaa agantcnccc tacttccaaa aaaaaanant tgcctttncc cccnttctgt 660 tgcaatgaaa acntcccaan acngccaatn aaaacctgcc cnnncaaaaa ggntcncaaa 720 caaaaaaant nnaagggttn 740 &lt; 210 &gt; 18 &lt; 211 &gt; 802 &lt; 212 &gt; DNA &lt; 213 &gt;. Human &lt; 220 &gt; &lt; 221 &gt; misc 1. Special desire &lt;222&gt; (1).7. (802)

&lt;223&gt; n = or G

ϋ &lt; 4 0.0) 18 ccgctggttg cgctggtcca gngnagccac gaagcacgtc agcatacaca gcctcaatca 60 caaggcctcc cagctgccgc acattacgca gggcaagagc ctccagcaac actgcatatg 120 ggatacactt tactttagca gccagggtga caactgagag gtgtcgaagc ttatccttct 180 gagcccctgt tagtggagga agattccggg cttcagctaa gtagtcagcg tatgtcccat 240 aagcaaacac tgtgagcagc cggaaggtag aggcaaagtc actctcagcc agccctctaa 300 cattgggcat gtccagcagt tctccaaaca cgtagacacc agnggcctcc agcacctgat 360 ggatgagtgc ggccagcgct: gcccccttgg ccgacctggc taggagcaga aattgctcct 420 ggttctgccc tgtcaccttc acttccgcac tcatcactgc accgagtgtg ggggacccgg 480 gctcaggatg tccagagacg tggttccgcc ccctcnctta atgacaccgn ccanncaacc 540 gtcggccccc gccgantgng ttcgtcgtnc ctgggtcagg gtctgctggc cnctacttgc 600 aancttcgtc nggcccatgg aactcaccnc accggaactn gtangatcca ctnnttccat 660 aaccggncgc caccgcnnnt ggaactccac tcttnttncc tttacttgag ggttaaggtc 720 acccttnncg ttaccttggt ccaaaccntn ccntgtgtcg anatngtnaa tcnggnccna 780 cnccanccnc Atangaagcc ng 802 &lt;210&gt; 19 &lt;211&gt; 731 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1).7.(731) &lt;223&gt; π = or ..G &lt;400&gt; 19 cnaagcttcc aggtnacggg ecgcnaancc tgacccnagg tancanaang cagncngcgg 60 gagcccaccg tcacgnggng gngtctttat nggagggggc ggagccacat cnctggacnt 120 cntgacccca actccccncc ncncantgca gtgatgagtg cagaactgaa ggtnacgtgg 180 caggaaccaa gancaaannc tgctccnntc caagtcggcn nagggggcgg ggctggccac 240 gcncatccnt cnagcgctgn aaagccccnn cctgtctact tgtttggaga acngcnnnga 300 -9 - 127691.doc 200815476 catgcccagn gttanataac nggcngagag tnantttgcc tctcccttcc ggctgcgcan 360 cgngtntgct tagnggacat aacctgacta cttaactgaa cccnngaatc tnccncccct 420 ccactaagct cagaacaaaa aacttcgaca ccactcantt gtcacctgnc tgctcaagta 480 aagtgtaccc catncccaat gtntgctnga ngctctgncc tgcnttangt tcggtcctgg 540 gaagacctat caattnaagc tatgtttctg actgcctctt gctccctgna acaancnacc 600 cnncnntcca agggggggnc ggcccccaat ccccccaacc ntnaattnan tttanccccn 660 cccccnggcc cggcctttta cnancntcnn nnacngggna aaaccnnngc tttncccaac 720 nnaatccncc t 731 &lt;210&gt; 20 &lt;211&gt; 754 &lt;212&gt; DNA &lt;213>People &lt;220&gt;

&lt;221&gt; misc_3 Desirable &lt;222&gt; (1).:.(754) &lt;223&gt; n = A, T, C or G &lt;400&gt; 20 tttttttttt tttttttttt taaaaacccc ctccattnaa tgnaaacttc cgaaattgtc 60 caaccccctc ntccaaatnn ccntttccgg gngggggttc caaacccaan Ttanntttgg 120

arvnttaaatt aaatnttnnt tggnggnnna anccnaatgt nangaaagtt naacccanta 180 tnancttnaa tncctggaaa ccngtngntt ccaaaaatnt ttaaccctta antccctccg 240 aaatngttna nggaaaaccc aanttctcnt aaggttgttt gaaggntnaa tnaaaanccc 300 nnccaattgt ttttngccac gcctgaatta attggnrtcc gntgttttcc nttaaaanaa 360 ggnnancccc ggttancnaa tccccccnnc cccaattata ccganttttt ttngaattgg 420 gancccncgg gaattaacgg ggnnnncccc cnttgggggg cnggnncccc ccccntcggg 4Θ0 ggttngggnc aggncnnaat tgttcaaggg tccgaaaaat ccctccnaga aaaaaanctc 540 ccaggntgag nntngggttt nccccccccc canggcccct ctcgnanagt tggggtttgg 600 ggggcccggg attttntttc ccctnttncc tccccccccc ccnggganag aggctngngt 660 tttgntcnnc ggccccnccn aaganctttn ccganttnan ttaaatccnt gcccnggcga · 720 agtccnttgn agggn-taaan ggccccctnn cggg 754 &lt; 210 &gt; 21 &lt; 211 &gt; 755 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt;220&gt;

&lt;22H&gt; misc_ Desire&lt;222&gt; (1) .7. (755) &lt;223&gt; n = A, T, C or G &lt;400&gt; 21 - atcancccac gaccccnaac nngggaccnc tcanccggnc nnncnaccnc cggccnatca 60 nngtnagnnc actncnnttn naccacnccc cnccnactac gcccncnanc cnacgcncta 120 nncanatncc actganngcg cgangtngan ngagaaanct nataccanag ncaccanacn 180 ccagctgtcc nanaangcct nnnatacngg nnnatccaat ntgnancctc cnaagtattn 240 nncnncanat gattttcctn anccgattac ccntnccccc tancccctcc cccccaacna 300 cgaaggcnct ggnccnaagg nngcgncncc ccgctagntc cccnncaagt cncncnccta 360 aactcanccn nattacncgc ttcntgagta tcactccccg aatctcaccc tactcaactc 420 aaaaanatcn gatacaaaat aatncaagcc tgnttatnac actntgactg ggtctctatt 480 ttagnggccc ntnaancntc ctaatacttc cagtctncct tcnccaattt ccnaanggct 540 ctttcngaca gcatnttttg gttcccnntt gggttcttan ngaattgccc ttcntngaac 600 10- 127691.doc 200815476 gggctcntct tttccttcgg ttancctggn ttcnnccggc cagttattat ttcccntttt aaattcntnc cntttanttt tggcnttcna aacccccggc cttgaaaacg gccccctggt aaaaggttgt tttganaaaa tttttgtttt gttcc &lt; 210 & g t; 22 &lt;211&gt; 849 &lt;212&gt; DNA &lt;213&gt; Person &lt;220&gt;&lt;221&gt; misc one: feature. &lt;222&gt; (1) (849) *

&lt;223&gt; n = A, T, C or G 660 720 755

60 120 180 240 300 360 420 480 540 600 660 720 780 840 849 &lt; 400 &gt; 22 k tttttttttt tttttangtg acgctnggan taangcgacc atcctgnnna cggaanggtc cataactcng nggccctgcc gnnttaaccn cactnngcna tctgtcttcc cctgnagncn cngccntcta nnaccccnnn gggtncctcg tgcgttnttg gcccctaccc cncnncgnng cctcncctcg nccctcncnc ngncgnancn ntcanccacn ggnngacnng ctncntcngg ccantnncgc ncctccncga nccncngccc gtcctcccgn nncangcgg tngtcgtgca ggtagaggct cgantcctag ganncnccct accggnngat nntgctaggg. caccaccttc ggcggcccng ncggtttccn nccccrvncng anaaantggg ccncggnccc cccctccant nngggggact gttgtcgant cnaccgnang ttcgccncgg nncacccttc caacacccgc ncccntcngt ctccnccncc gtctcannca nagcncnntc gcnccgcgcn tcaanccnna cnaaacgccg cttccnaccc angnnttccn tactacaant gtgaanacgt aaaatcanac tgtgaagatn tgnccnctcc cannncnttn ngnccgggcc cgggtcattn acccnggcga cccggggtnc ctttacccct nnacaagcca gccnanngct ccgtcnctng ccanggattc cnaaggaagg ccgacnanga nccgctcccg ncggnnnccc ccccacccgc ccaccccgcc Ccgccaggcc gcgncnccct cgccncngaa ctgcgcggcc cgnagcgncc cga.ggacac n nnaccccgcc &lt;210&gt; 23 &lt;211&gt; 872 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt;misc-feature-&lt;222&gt; (1).7. (872)

n99c9aatcg taatnaggcg 23 ϋ 60 120 180 240 3 00 360 420 480 540 600 660 720 780 gcgcaaacta tacttcgctc gnactcgtgc gcctcgctnc tcttttcctc cgcaaccat.g tctgacnanc ccgattnggc ngataccnan aagntcganc agtccaaact gantaacaca cacacncnan aganaaatcc nctgccttcc anagtanacn attgaacnng agaaccangc; &lt; 223 &gt; n =, or G &lt; 400 & gt tgcgccgcca atntgtcncc gtttattntn ccagcntcnc ctnccnaccc tacntcttcn nagctgtcnn acccctngtn cgnacccccc naggtcggga tcgggtttnn nntgaccgng ^ cnncccctcc ccccntccat nacganccnc ccgcaccacc nanngcncgc nccccgnnct cttcgccncc ctgtcctntn cccctgtngc ctggcncngn accgcattga ccctcgccnn ctncnngaaa ncgnanacgt ccgggttgnn annancgctg tgggnnngcg cctgcnccgc gttccttccn ncnncttcca ccatcttcnt tacngggtct ccncgccntc ccnnncacnc cctgggacgc tntcctntgc cccccttnac tccccccctt cgncgtgncc cgnccccacc ntcatttnca nacgntcttc acaannncct ggntnnctcc cnancngncn gtcanccnag ggaagggngg Ggnnccnntg nttgacgttg nggngangtc cgaanantcc tcnccnccan cnctacccct cgggcgnnct ctcngctncc aacttancaa 127691.doc 200815476

Ntcccccccg ngngcncntc tcagcctcnc ccnccccnct ctctgcantg tnctctgctc tnaccnntac gantnttcgn cnccctcttt cc &lt;210&gt; 24 &lt;211&gt; 815 &lt;212&gt; DNA &lt;213&gt; 'Human•. - · ·_ &lt;220&gt;&lt;221&gt; mi sc one: feature ·· &lt;222&gt; (1).7. (815) &lt;223&gt; n » A,T,C: or *G &lt;400&gt; 24 gcatgcaagc ttgagtattc tatagngtca cctaaatanc ttggcntaat catggtcnta nctgncttcc tgtgtcaaat gtatacnaan tanatatgaa tctnatntga caaganngta tcntncatta gtaacaantg tnntgtccat cctgtcngan canattccca tnnattncgn cgcattcncn gcncantatn taatngggaa ntcnnntnnn ncaccnncat ctaccncncc gcnccctgac tggnagagat ggatnanttc tnntntgacc nacatgttca ccttggattn aananccccc cgcngnccac cggtitngnng cnagccnntc ccaagacctc ctgtggaggt aacctgcgtc aganncatca aacntgggaa acccgcnncc angtnnaagt ngnnncanan gatcccgtcc aggnttnacc atcccttcnc agcgccccct ttngtgcctt anagngnagc gt.gtccnanc cnctcaacat ganacgcgcc agnccanccg caattnggca caatgtcgnc gbacccccta gggggantna tncaaanccc caggattgtc cncncangaa atcccncanc cccnccctac ccnnctttgg gacngtgacc Aantc ccgga gtnccagccc ccccaccggt nnccntgggg gggtgaanct cngnntcanc cngncgaggn ntcgnaagga accggncccn ggncgaanng ancnntcnga agngccncnt cgtataaccc cccctcncca nccnacngnc agntcccccc cngggtncgg aangg & lt ggccngnctc; 210 &gt; 25 &lt; 211 &gt; 775 &lt; 212 &gt; DNA &lt; 213 &gt; al crop-full &lt; 220 &gt; &lt; 221 &gt; misc a To be &lt;222&gt; (1).:.(775) &lt;223&gt; n = A,T,C or G &lt;400&gt; 25 ccgagatgtc tcgctccgtg gccttagctg tgctcgcgct actccctctt tctggcctgg aggctatcca gcgtactcca aagattcagg tttactcacg tcatccagca gagaatggaa agtcaaattt cctgaattgc tatgtgtctg ggtttcatcc atccgacacc gaanttgact tactgaagaa tgganagaga attgaaaaag tggagcattc agact: .tgccc ttcagcaagg actggtcttt ctatctcntg tactacactg aattcacccc cactgaaaaa gatgagtatg cctgccgtgc gaaccatgtg actttgtcac agcccaagat agttaagtgg gaccgagaca tgtaagcagn cnncatggaa gtttgaagat gccgcatttg gattggatga attccaaatt ctgcttgctc gcnctttaat antgatatgc ntatacaccc taccctttat gnccccaaat tgtaggggtt acatnantgt tcncntngga catgatcttc ctttataant ccnccnttcg aattgcccgt cncccngttn ngaatgtttc c nnaaccacg gtcggctccc ccaggtcncc tcttacggaa gggcctgggc cnctttncaa ggttggggga accnaaaatt tcncttntgc ccncccncca cnntcttgng nncncanttt ggaacccttc cnattcccct tggcctcnna nccttnncta anaaaacttn aaancgtngc naaanntttn acttcccccc ctacc &lt; 210 &gt; 26 840 872 60 120 180 240 300 360 420 480 540 600 660 720 780 815 60 120 180 240 300 360 420 480 540 600 660 720 775 127691.doc 12- 200815476

&lt;211&gt; 820 &lt;212&gt; DNA &lt;213&gt; Human: &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1) (820) &lt; 2 2 3 &gt; n A, T , C or .G &lt; 400 &gt; 26 anattantac agtgtaatct tttcccagag gtgtgtanag ggaacggggc ctagaggcat cccanagata ncttatanca acagtgcttt gaccaagagc tgctgggcac atttcctgca gaaaaggtgg cggtccccat cactcctcct ctcccatagc catcccagag gggtgagtag ccatcangcc ttcggtggga gggagtcang gaaacaacan accacagagc anacagacca ntgatgacca tgggcgggag cgagcctctt ccctgnaccg gggtggcana nganagccta nctgaggggt cacactataa acgttaacga ccnagatnan cacctgcttc aagtgcaccc ttcctacctg acnaccagng accnnnaact gcngcctggg gacagcnctg ggancagcta acnnagcact cacctgcccc cccatggccg tncgcntccc tggtcctgnc aagggaagct ccctgttgga attncgggga naccaaggga nccccctcct ccanctgtga aggaaaaann gatggaattt tncccttccg gccnntcccc tcttccttta cacgccccct nntactcntc tccctctntt ntcctgncnc acttttnacc ccnnnatttc ccttn ^ ttga tcggannctn ganattccac tnncgcctnc cntcnatcng naanacnaaa nactntctna cccnggggat gggnncctcg ntcatcctcc ctttttcnct accnccnntt ct Ttgcctct cctcngatca 780tccaaccntc gntggccntn cccccccnnn tcctctnccc 820 &quot; 60 120 180 24*0 300 360 420 480 540 600 660 720 u

&lt;210&gt; 27 &lt;211&gt; 818 &lt;212&gt; DNA &lt;213&gt;Human.·&lt;220&gt;&lt;221>mis0:_Features&lt;222&gt; (1) .7. (818) &lt;223&gt ; π A, T, C or G &lt; 400 &gt; 27 tccgggtgac ggcctcttcc tcctcaggga cctctgactg ccctgggcca aagaatctct tgtttccccc ccgagcccca ggcagcggtg atccagccct gcccaacctg attctgatga ctgcggatgc tgtgacggac ccaaggggca aatagggtcc cagggtccag ggaggggcgc ctgctgagca cttccgcccc tcaccctgcc cagcccctgc catgagctct gggctgggtc tccgcctcca gggttctgct cttccangca ngccancaag tggcgctggg ccacactggc ttcctcctgc cccntccctg gctctgantc tctgtcttcc tgtcctgtgc angcnccttg gacctcagtt tccctcnctc anngaactct gtttctgann tcttcantta actntgantt tacnaccnan cggnctgtnc tgtcnnactt caatgggccn gaccggctaa tccctccctc nctcccttcc anttcnnnna accngcttnc cntcntcccc ccntancccg ccngggaanc ctcctttgcc ctnaccangg gccnnnaccg cccntnnctn ggggggcnng gtnnctncnc ctgntnnccc cnctcncnnt tncctcgtcc cnncnncgcn nngcannttc ncngtcccnn tnnctcttcn ngcnccgnaa ngntcncntn tnnnnngncn ngntnntncn tccctctcnc cnnntgnang tnnttnnnnc ncngnncccc n Nnncnnnnn nggnnntnnn tctncncngc cccnnccccc ngnattaagg cctccnntct ccggccnc &lt;210&gt; 28 &lt;21X&gt; 731 &lt;212&gt; DNA 60 120 180 240 300 360 420 480 540 600 660 720 780 818 127691.doc 13- 200815476

Ο &lt;213&gt; Human · &lt;220&gt;&lt;221&gt; misc_j Desirable &lt;222&gt; (1) . . . (731) &lt;223&gt; η - A#T, C or G &lt;400&gt; 28 aggaagggcg gagggatatt gtangggatt gagggatagg agnataangg gggaggtgtg tcccaacatg anggtgnngt 'tctcttttga angagggttg ngtttttann ccnggtgggt gattnaaccc cattgtatgg agnnaaaggn tttnagggat ttttcggctc ttatcagtat ntanattcct gtnaatcgga aaatnatntt tcnncnggaa aatnttgctc ccatccgnaa attnctcccg ggtagtgcat nttngggggn cngccangtt tcccaggctg ctanaatcgt actaaagntt naagtgggan tncaaatgaa aaectnncac agagnatccn tacccgactg tnnnttncct. tcgccctntg actctgcnng agcccaatac ccnngngnat gtcncccngn nnngcgncnc tgaaannnnc tcgnggctnn gancatcang gggtttcgca tcaaaagcnn cgtttcncat naaggcactt tngcctcatc caaccnctng ccctcnncca tttngccgtc nggttcncct acgctnntng cncctnnntn ganattttnc ccgcctnggg naancctccC gnaatgggta gggncttntc tttcnaccnn gnggtntact aatcnnctnc acgcntnctc cctcnacccc cccccttttt caatcccanc ggcnaatggg gtctccccnn cgangggggg nnncccannc c ·· &lt; 210 &gt; 29 * · &lt; 211 &gt; 822 &lt; 212 &gt; DNA ^ 2 13&gt;Human&lt;220&gt;&lt;221&gt; mi sc1: feature. &lt;222&gt; (1)...(822) * &lt;223&gt; η « or G &lt;400&gt; 29 actagtccag tgtggcggaa ttccattgtg ttggggncnc ttctatgant antnttagat cgctcanacc tcacancctc ccnacnangc ctataangaa nannaataga nctigtncnnt: atntntacnc tcatanncct cnnnacccac tccctcttaa cccntactgt gcctatngcn tnnctantct ntgccgcccn cnanccaccn gtgggccnac cncnngnatt ctcnatcccc tcnccatntn gcctananta ngtncatacc ctatacctac nccaatgcta nnnctaancn tccatnantc annntaacta ccactgacnt .ngactttcnc atnanctcct aatttgaatc tactctgact cccacngcct annnattagc ancntccccc nacnatntct caaccaaatc ntcaacaacc tatctanctg ttcnccaacc nttncctccg atccccnnac aacccccctc ccaaataccc nccacctgac ncctaacccn caccatcccg gcaagccnan ggncatttan ccactggaat cacnatngga naaaaaaaac Ccnaactctc tancncnnat ctccctaana aatnctcctn naatttactn ncantnccat caancccacn tgaaacnnaa cccctgtttt tanatccctC ctttcgaaaa ccnacccttt annncccaac ctttngggcc cccccnctnc ccnaatgaag gncncccaat cnangaaacg nccntgaaaa ancnaggcna anannntccg canatcctat ccctt Anttn ggggnccctt ncccngggcc cc &lt;210&gt; 30 &lt;211&gt; 787 &lt;212&gt; DNA &lt;213&gt; Human · · &lt;220&gt; 60 120 1B0 '240 300 360 420 480 540 600 660 720 731 60 120 180 240 300 360 420 480 540 600 660 720 780 822 127691.doc 14- 200815476

&lt;222&gt; (1) . . . (787). &lt;223&gt; η *= Α,Τ, ί: or G &lt;400) 30 cggccgcctg ctctggcaca tgcctcctga atggcstcaa aagtgatgga ctgcccattg 60 ctagagaaga ccttctctcc tactgtcatt atggagccct gcagactgag ggctcccctt 120 gtctgcagga tttgatgtct gaagtcgtgg agtgtggctt ggagctcctc atctacatna 180 gctggaagcc ctggagggcc tctctcgcca gcctccccct tctctccacg ctctccangg 240 acaccagggg ctccaggcag cccattattc ccagnangac atggtgtttc tccacgcgga 300 cccatggggc ctgnaaggcc agggtctcct ttgacaccat ctctcccgtc ctgcctggca 360 ggccgtggga tccactantt ctanaacggn cgccaccncg gtgggagctc cagcttttgt 420 tcccnttaat gaaggttaat tgcncgcttg gcgtaatcat nggtcanaac tntttcctgt 480 gtgaaattgt ttntcccctc ncnattccnc ncnacatacn aacccggaan cataaagtgt ^ 540 taaagcctgg gggtngcctn nngaatnaac tnaactcaat taattgcgtt ggctcatggc 600 ccgctttccn ttcnggaaaa ctgtcntccc ctgcnttnnt gaatcggcca ccccccnggg 660 aaaagcggtt tgcnttttng ggggntccct ccncttcccc cctcnctaan ccctncgcct 720 cggtcgttnc nggtngcggg gaangggnat nnnctcccnc naagggggng agnnngntac 780 ccccaaa 787 & l t;210&gt; 31 &lt;211&gt; 799

One &lt;212&gt; DNA 〇 &lt;220&gt;

&lt;221&gt;misc_.Features.&lt;222&gt; (1).7.(799) &lt;223&gt; n » A, T, C or G &lt;400&gt; 31 tttttttcct cttttttggc gatgctactg -tttaattgca ggaggtgggg gtgtgtgtac 60 catgtaccag ggccatcaga agcaagaagg aaggagggag ggcagagcgc cctgctgagc 120 aacaaaggac tcctgcagcc ttctctgtct gtctcttggc gcaggcacat ggggaggcct 180 cccgcagggt gggggccacc agtccagggg tgggagcact acanggggtg ggagtgggcg 240 gtggccggtn cnaatggccc gncacanatc cctacgattc ttgacacccg gatttcacca 300 ggggacctcc cgttctccca. nggnaacttc ntnnatctcn aaagaacaca actgtttctc 360 cngcanttct ggctgttcat ggaaagcaca ggtgtccnat tcnggctggg acttggtaca 420 tatggttccg gcccacctct cccntcnaan aagtaattca cccccccccn ccntctnttg 480 cctgggcccc taantaccca caccggaact canttantta ttcatcttng gntgggcttg 540 ntnatcnccn cctgaangcg ccaagttgaa aggccacgcc gtncccnctc cccatagnan 600 nttttnncnt canctaatgc ccccccnggc aacnatccaa tccccccccn tgggggcccc 660 agcccanggc ccccgnctcg ggnnnccngn cncgnantcc ccaggntctc ccantcngnc 720 ccnnngcncc cccgcacgca gaacanaagg ntngagccnc cgcannnnnn nggtnncnac 780 ctcgcccccc ccnncgnng 799 &lt;210&gt; 32 &lt;211&gt; 789 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; inisc_ feature &lt;222&gt; (1) (789) &lt;223&gt; n = A, T, C or G 15-127691.doc 200815476 &lt;400&gt; 32 tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60 ttttnccnag ggcaggttta ttgacaacct cncgggacac * aancaggctg gggacaggac 120 ggcaacaggc tccggcggcg gcggcggcgg ccctacctgc ggtaccaaat ntgcagcctc 180 cgctcccgct tgatnttcct ctgcagctgc aggatgccnt aaaacagggc ctcggccntn 240 ggtgggcacc ctgggatttn aatttccacg ggcacaatgc ggtcgcancc cctcaccacc 300 nattaggaat agtggtntta cccnccnccg ttggcncact ccccntggaa accacttntc 360 gcggctccgg catctggtct taaaccttgc aaacnctgcfg gccctctttt tggttantnt 420 nccngccaca atcatnactc agactggcnc gggctggccc caaaaaancn ccccaaaacc 4ΘΟ ggnccatgtc ttnncggggt tgctgcnatn tncatcacct cccgggcnca ncaggncaac 540 ccaaaagttc ttgnggcccn caaaaaanct ccggggggnc ccagtttcaa caaagtcatc 600 ccccttggcc cccaaatcct ccccccgntt nctgggtttg ggaacccacg cctctnnctt 660 tggnnggcaa gntggntccc ccttcgggcc cccggtgggc ccnnctctaa ngaaaacncc 720 ntcctnnnca ccatcccccc nngnnacgnc tanca Angna tccctttttc tanaaacggg 780 ccccccncg -789 &lt;210&gt; 33 &lt;211&gt; 793 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; : Desire

&lt;222&gt; (1).7.(793) &lt;223&gt; π = A,.T,C anti-G &lt;400&gt; 33 gacagaacat gtcggatggt ggagcacctc tctacacgac ttacaggaca gcagatgggg 60 aattcacggc tgttggagca atanaacccc agttctacga gctgctgaxc aaaggacttg 120 gactaaagtc tgatgaactt cccaatcaga tgagcatgga tgattggcca gaaatgaana 1Θ0 agaagtttgc agatgtattt gcaaagaaga cgaaggcaga gtggtgtcaa atctttgac white 240 gcacagatgc ctgtgtgact ccggttctga ctttcgagga ggttgttcac catgatcaca 300 acaangaacg gggctcgttt atcaccantg aggagcagga cgtgagcccc cgccctgcac 360 ctccgctgtt aaacacccca gccatccctc ccttcaaaag ggacccacta cttctagagc 420 ggncgccacc gcggtggagc tccagctttt gttcccttta gtgagggtta attgcgcgct 480 tggcgtaatc atggtcatan ctgtttcctg tgtgaaattg ttatccgctc acaattccac 540 acaacatacg anccggaagc atnaaatttt aaagcccggn Ggtngcctaa tgantgaact 600 nactcacatt aattggcttt gcgctcactg cccgccttcc agtccggaaa acctgtcctt · 660 gccagctgcc nttaatgaat cnggccaccc cccggggaaa aggcngcttg cttnttgggg 720 cgcncctccc gctttctcgc ttcctgaant ccttcccccc ggtctttcgg cttgcggcna 780 acggtaccna cct 793 &lt;210&gt; 34 &lt;211&gt; 756 ~ &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc -: Feature &lt;222&gt; (1).7. (756) &lt; 223 &gt; n * A, T, C · or G · &lt; 400 &gt; 34 gccgcgaccg gcatgtacga gcaactcaag ggcgagtgga accgtaaaag ccccaatctt 60 ancaagtgcg gggaanagcc gggtcgactc aagccagttc ttctggagct caacttcttg 120 16- 127691.doc 200815476 ccaaccacag ggaccaagct gaccaaacag cagctaattc tggcccgtga catactggag 180 atcggggccc aatggagcat cctacgcaan gacatcccct ccttcgagcg ctacatggcc 240 cagctcaaat gctactactt tgattacaan gagcagctcc ccgagtcagc ctatatgcac 300 cagctcttgg gcctcaacct cctcttcctg ctgtcccaga accgggtggc tgantnccac 360 acgganttgg ancggctgcc tgcccaanga catacanacc aatgtctaca tcnaccacca 420 gtgtcctgga gcaatactga tgganggcag ctaccncaaa gtnttcctgg ccnagggtaa 480 catcccccgc cgagagctac accttcttca ttgacatcct gctcgacact atcagggatg 540 aaaatcgcng ggttgctcca gaaaggctnc aanaanatcc ttttcnctga aggcccccgg 600. atncnctagt nctagaatcg gcccgccatc gcggtgganc ctccaacctt Tcgttnccct 660 ttactgaggg ttnattgc Cg cccttggcgt tatcatggtc acnccngttn cctgtgttga 720 aattnttaac cccccacaat tccacgccna cattng 756

&lt;210&gt; 35 &lt;211&gt; 834 &lt;212&gt; DNA &lt;213&gt; Human _ &lt;220&gt;

&lt;221&gt; misc一·特欲 &lt;222&gt; (1).7.(834) &lt;223&gt; n = A,T,C G

&Lt; 400 &gt; 35 · ggggatccct anatcnacct gnatgcatgg ttgtcggtgt ggtcgctgtc gatgaanatg 60 aacaggatct tgcccttgaa gctctcggct gctgtnttta agttgctcag tctgccgtca 120 cagtcagaca cnctcttggg caaaaaacan caggatntga gtcttgattt cacctccaat: 180 aatcttcngg gctgtctgct cggtgaactc gatgacnang ggcagccggc cgtgtntgat 240 aaantccanc angttctcct tggtgacctc cccttcaaag ttgttccggc cttcatcaaa 300 cccccnnaan angannancc canctttgtc gagctggnat ttgganaaca cgccaccgtt 360. ggaaactgat cccaaatggt atgtcatcca tcgcctctgc tgcctgcaaa aaacttgctt 420 ggcncaaatc cgactccccn tccttgaaag aagccnatca cacccccctc cctggactcc. 480 nncaangact ctnccgctnc cccntccnng ca'gggttggt ggcannccgg gcccncgcgc 54 0 ttcctcagcc agttcacnat nttcatcagc ccctctgcca gccgttntat tccttggggg 600 ggaanccgtc tctcccttcc tgaannaact ttgaccgtng gaatagccgc gcntcnccnt 660 acntnctggg ccgggttcaa antccctccn ttgncnntcn cctcgggcca ttctggattt 720 nccnaacttt ttccttcccc cnccccncgg ngtttggntt Ttccacnggg ccccaactct 780 gctnttggcc anccccctgg gggcntntan cnccccctnt ggtcccntng ggcc 834 &lt ;210&gt; 36 &lt;211&gt; 814 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;#&lt;221&gt; tnisc'Special U &lt;222&gt; (1)·:·(814) &lt;223&gt; n = A, T, C, or ... G &lt; 400 &gt; 36 cggncgcttt ccngccgcgc cccgtttcca tgacnaaggc tcccttcang ttaaatacnn 60 cctagnaaac attaatgggt tgctctacta atacaccata cnaaccagta agcctgccca 120 naacgccaac tcaggccatt cctaccaaag gaagaaaggc tggtctctcc accccctgta 180 ggaaaggcct gccttgtaag acaccacaat ncggctgaat ctnaagtctt gtgttttact 240 aacggaaaaa aaaaataaac aanaggtttt gttctcatgg ctgcccaccg cagcctggca 300 ctaaaacanc ccagcgctca ctt'ctgcttg ganaaatatt ctttgctctt ttiggacatca 360 17- 127691.doc 200815476 ggcttgatgg tatcactgcc acntttccac ccagctgggc ncccttcccc catntttgtc 420 antganctgg aaggcctgaa ncttagtctc caaaagtctc ngcccacaag accggccacc 480 aggggangtc ntttncagtg gatctgccaa anantacccn tatcatcnnt gaataaaaag 540 gcccctgaac ganatgcttc cancancctt taagacccat aatcctngaa ccatggtgcc 600 cttccggtct gatccnaaag gaatgttcct gggtcccant ccctcctttg Ttncttacgt 660 tgtnttggac ccntgctngn atnac Ccaan tganatcccc ngaagcaccc tncccctggc 720 atttganttt cntaaattct ctgccctacn nctgaaagca cnactccctn ggcnccnaan 780 ggngaactca agaaggtctn ngaaaaacca cncn 814 &lt;210&gt; 37 &lt;211&gt; 760 . &lt;212&gt; DNA , ' &lt;213&gt; Human &lt;22D&gt;

&lt;221&gt; misc_: feature &lt;222&gt; (1) .7. (760) &lt;223> n = A, T, C or G &lt; 400> 37 gcatgctgct cttcctcaaa gttgttcttg ttgccataac aaccaccaca ggtaaagcgg 60 η

gcgcagtgtt cgctgaaggg gttgtagtac cagcgcggga tgctctcctt gcagagtcct 120 gtgtctggca ggtccacgca atgccctttg aatggatgcg ctggagctcg 180 tcnaanccac tcgtgtattt ttcacangca gcctcctccg aagcntccgg gcagttgggg 240 gtgtcgtcac actccactaa actgtcgatn cancagccca ttgctgcagc ggaactgggt 300 gggctgacag gtgccagaac acactggatn ggcctttcca tggaagggcc cgggggaaat 360 cncctnancc caaactgcct ctcaaaggcc accttgcaca ccccgacagg ctagaaatgc 420 actccccccc ccaaaggtag ctgtfecttgt tgcccaagca ncctccanca aaccaaaanc 480 ttgcaaaacc tcactgggga cgcLJcgcgg gggtcatnnn taccanggtt ggggaaanaa acccggcngn 540 ganccncctt gtttgaatgc naaggnaata atcctcctgt cttgcttggg tggaanagca 600 caattgaact gttaacntcg ggccgngctc cnctngggtg gtctgaaact aatcaccgcc 660 actggaaaaa ggtangtgcc ttccttgaat tcccaaantt cccctngntt tgggtnntct 720 ctcccctncc ccaaaaatcg tnttcccccc ccntanggcg 760 &lt; 210 &gt; 38 &lt; 211 &gt; 724 &lt; 212 &gt; DNA &lt; 213 &gt; People &lt;220&gt;

&lt;221&gt;〇^5(:_Features&lt;222&gt; (1).7.(724) &lt;223&gt; n = A, T, C or G &lt;400&gt; 38 tttttttttt tttttttttt tttttttttt tttttaaaaa ccccctccat tgaatgaaaa 60 cttccnaaat tgtccaaccc cctcnnccaa atnnccattt ccgggggggg gccccaaacc 120 caaattaatt ttgganttta aattaaatnt tnattngggg aanaanccaa atgtnaagaa 180 aatttaaccc attatnaact taaatncctn gaaacccntg gnttccaaaa atttttaacc 240 cttaaatccc tccgaaattg ntaanggaaa accaaattcn cctaaggctn tttgaaggtt 300 ngatttaaac ccccttnant tnttttnacc cnngnctnaa ntatttngnt tccggtgttt 360 tcctntcaan cntnggtaac tcccgntaat gaannnccct aanccaatta aaccgaactt 420 tttttgaatt ggaaattccn ngggaattna ccggggtttt tcccntttgg gggccacncc 480 cccnctttcg gggtttgggn ntaggttgaa tttttnnang ncccaaaaaa ncccccaana 540 aaaaaactcc caagnnttaa ttngaatntc ccccttccca ggccttttgg gaaaggnggg 600 18- 127691.doc 200815476 tttntggggg ccngggantt cnttcccccn ttnccncccc ccccccnggt aaanggttat ngnntttggt ttttgggccc cttnanggac cttccggatn gaaattaaat ccccgggncg gccg &lt; 210 &gt; 39 &lt; 211 &gt; 751 &lt;; 212 & gt DNA &lt;213&gt;People &lt;220&gt;

&lt;221&gt; misc_ Desirable &lt;222&gt; (1).T.(751)' &lt;223&gt; n » or G 660 720 724

&Lt; 400 &gt; tttttttttt caacacaata tttatttatt ggccgcctta cgcaaaatca ttaactgctt cttgggggtc tcccggcnnt: tgaagggtta ccctcaancn cacccccnga cnnagactnt nnnncncctc 60 120 180 240 300 360 420 480 540 600 66 0 720 751 39 tttttctttg tttatttcat tttactgaaa agctttctaa ctcgggggaa gtacaattac ccctccccan cnttgaaaca ccatntttaa aattnctnng anncnntnnc cctcnncnan cnctngtccn ctcacattta ttgtttcttt gtgagaggga atttggaaca nggaaaggtt: ntttcacttt accaaccccn cacngcngaa cnccacctcc ccccggtcnc naacnaaatt cncaactttc naatcnccan atttttattt tatttcattt acttttgtgg tctaagcaag gctttgttaa taattaattg ctgacaaaaa ngttctcatt acntggcnnn gcntnngtcc ccgaaaatat ttttnntcac c tgattttttt tatttgtttg ccttttttcc ctgaanggaa tcatgcccta tgctnaangc gtgccngccc ntccccncnc gcctgaatcc cncccgggct tcccnntcnc gaacncgnnc taatgctgca ctgctgctgt tttttctigta aagggggttt tggtgggtga ttt§attana tcaaatnatg caggtnaaaa tcnaaaancn ccgggaantn tcaatccccc cnnaaaatgn &lt;21Q&gt; 40 &lt;211&gt; 753 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; mi sc one: special desire &lt;222&gt; (1).7.(753) &lt;223> n = A, T, C or G

&Lt; 400 &gt; 40 gtggtatctt ctgtaagatc agatgaaaac ccccccgaga cgccctatgc acagctgggc tggcctggaa gcggcggctg tctcaaagtt ccaggcaacn cggtcataan cgcggtggcg ataaaaggtg cgcccccgca cnaacccacc accannccgg ttccnctgat gccctanctg aaancacccn cctcctcntt ggancccata tcccnaccan ttcccncccg ncctctggcc tnccctatct gnaccccncn aggtgttcct ccctcgtagg atgccaanca tcatctgggt cagcagcact gcaactgcca ccttgagaca gcagggcttc tacctgcgca ggggcacacc tcgttgcgac acaccggaga tcgtcgctgg gagctggcag ccgttcanct cgcacttctc acttccttga nggaattccc gttgcccngn tnttntcccc tactcaccnt ncccccccnt cntcaaanan gcttncacna tttgtctcan tnt tttagaggaa acacccccat agcagccggg gtaggagggg gatgtcaggc tcgatgtcaa gtcagggccc accaggaact ccaggtgatn agcctggggt ggcctcccgc aggaaggcna naanaccatg angttgggct aaatctcttc gntcttgggc nccccaancc ccggggtcct ggaccntggt tcctctcaag gnnacccanc cttctanngn cccgggtctg ccttcccccc 60 120 180 240 300 360 420 480 540 600 660 720 753 &lt; 210 &gt; 41 127691 .doc 19- 200815476 &lt;211&gt; 341 &lt;212&gt; DNA &lt;213&gt;Personal %&lt;400&gt; 4 1 actatatcca tcacaacaga catgcttcat cccatagact tcttgacata gcttcaaatg 60 agtgaaccca tccttgattt atatacatat atgttctcag tattttggga gcctttccac 120 ttctttaaac cttgttcatt atgaacactg aaaataggaa tttgtgaaga gttaaaaagt 180 tatagcttgt ttacgtagta agtttttgaa gtctacattc aatccagaca cttagttgag 240 tgttaaactg tgatttttaa aaaatatcat ttgagaatat tctttcagag gtattttcat 300 ttttactttt tgattaattg tgttttatat attagggtag t 341 &lt; 210 &gt;. 42 f &lt;211&gt; 101 _ &lt;212&gt; DNA * &lt;213&gt; Human. &lt;400&gt; 42 acttactgaa tttagttctg tgctcttcct tatttagtgt tgtatcataa atactttgat 60 gtttcaaaca ttctaaataa ataattctca gtggcttcat a 101 Ο &lt;210&gt; 43 &lt;211&gt; 305 &lt;212&gt; DNA .. &lt; 213 &gt; buccal &lt; 400 &gt; 4 * 3 acatctttgt tacagtctaa gacgtgttcc taaatcacca ctccttcctg gtcctcaccc 60 tccagggtgg tctcacactg taaCtagagc tattgaggag tctttacagc aaattaagat 120 tcagatgcct tgctaagtct agagttctag agctatgttt cagaaagtct aagaaaccca 180 - cctcttgaga ggtcagtaaa gaggacttaa tatttcacat ctacaaaatg accacaggat 240 tggatacaga acgagagtta Tcctggataa ctcagagctg agtacctgcc cgggggccgc 300 tcgaa 305 &lt;210&gt; 44 &lt;211&gt; 852 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc_ feature &lt;222&gt; (1).7.(852} &lt;223&gt; n := A,T,C or G

&Lt; 400 &gt; 44 acataaatat cagagaaaag cagtctctga aatatttacg tccaggagtt ctttgtttcc 60 gattatttgg tgtgtgtttt ggtttgtgtc caaagtaccg gcagcttcag ttttcatttt 120 ctctccatcc tcgggcattc ttcccaaatt tatataccag tcttcgtcca tccacacgct 180 ccagaatttc tcttttgtag taatatctca tagctcggct gagcttttca taggtcatgc 240 tgctgttgtt cttcttttta ccccatagct gagccactgc ctctgatttc aagaacctga 300 agacgccctc agatcggtct tcccatttta ttaatcctgg gttcttgtct gggttcaaga 360 ggatgtcgcg gatgaattcc cataagtgag tccctctcgg gttgtgcttt ttggtgtggc 420 acttggcagg ggggtcttgc tcctttttca tatcaggtga ctctgcaaca ggaaggtgac 460 t9Qtggttgt catggagatc tgagcccggc agaaagtttt gctgtccaac aaatctactg 54 0 tgctaccata gttggtgtca tataaatagt tctngtcttt ccaggtgttc atgatggaag 600 20- 127691.doc 200815476 gctcagtttg ttcagtcttg acaatgacat tgtgtgtgga ctggaacagg tcactactgc 660 actggccgtt ccacttcaga tgctgcaagt tgctgtagag gagntgcccc gccgtccctg 720 ccgcccgggt gaactcctgc aaactcatgc tgcaaaggtg Ctcgccgttg atgtcgaact 780 cntggaaagg gatacaattg gcatccagct ggctggtgtc caggag gtga tggagccact 840 cccacacctg gt Θ52 &lt; 210 &gt; 45 &lt; 211 &gt; 234 &lt; 212 &gt; DNA &lt; 213 &gt; human face &lt; 400 &gt; 45 acaacagacc cttgctcgct aacgacctca tgctcatcaa gttggacgaa tccgtgtccg 60 agtctgacac catccggagc atcagcattg cttcgcagtg ccctaccgcg gggaactctt Ί20 gcctcgtttc tggctggggt ctgctggcga acggcagaan Gcctaccgtg ctgcagtgcg 180 tgaacgtgtc ggtggtgtct gaggaggtct gcagtaagct ctatgacccg ctgt 234 &lt;210&gt; 46 &lt;211&gt; 590 &lt;212&gt; DNA &lt;213&gt;

&lt;220&gt;&lt;221&gt; misc_f feature &lt;222&gt; (1).7.(590) &lt;223&gt; n = A, T, CG &lt;400&gt; 46 actttttatt taaatgttta taaggcagat ctatgsgaat gatagaaaac atggtgtgta 60 atctgatage aatattttgg agattacaga gttttagtaa ttaccaatta cacagttaaa 120 aagaagataa tatattcca ^ a gcanatacaa aatacctaat gaaagatcaa ggcaggaaaa ΊΘ0 tgantacaac taattgacaa tggaaaatca atcctaatgc gaattgcaca ttatccttta 240 aaageettea aaanaaanaa ttattgcagt ctanttaatc caaacagtgt taaatggtat 300 caggataaan aactgaaggg canaaagaat taactttcac ttcatgtaac ncacccanat 360 ttacaatggc ttaaatgcan ggaaaaagca gtggaagtag ggaagtantc aaggtctttc 420

Tggtctctaa tctgccttac tctttgggtg tggctttgat cctctggaga cagctgccag 4BO ggcccccgtatataccaca tcccagcagc aagatgaagg gatgaaaaag gacacatgct 540 gccctccttt gaggagaetc catctcactg gccaacactc agtcacatgt 590 &lt;210&gt; 47 &lt;211&gt; 774 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc_: feature &lt;222&gt; (1).7.(774) &lt;223&gt; n = A, T, C* or G &lt;400&gt; 47 acaagggggc ataaegaagg agtggggana gattttaaag aaggaaaaaa aacgaggccc 60 tgaacagaat tttcctgnac aacggggctc caaaataatt ttcttgggga ggttcaagac 120 gcttcactgc ttgaaactta aatggatgtg ggacanaatt ttctgtaatg accctgaggg 180 cattacagac gggactctgg gaggaaggac aaacagaaag gggacaaagg ctaatcccaa 240 aacatcaaag aaaggaaggt ggcgtcatac ctcccagcct acacagttct ccagggctct 300 -21 - 127691.doc 200815476 cctcatccct ggaggacgac agtggaggaa caactgacca tgtccccagg ctcctgtgtg 360 ctggctcctg gtcttcagcc cccagctctg gaagcccacc ctctgctgat cctgcgtggc 420 ccacactcct tgaacacaca tccccaggtt atattcctgg acatggctga acctcctatt 480 cctacttccg agatgccttg ctccctgcag cctgtcaaaa tcccactcac cctccaaacc 540 acggcatggg aagcctttct gacttgcctg attactccag catcttggaa caatccctga 600 ttccccactc cttagaggca agatagggtg gttaagagta gggctggacc acttggagcc 660 aggctgctgg cttcaaattn tggctcattt acgagctatg ggaccttggg caagtnatct 720 tcacttctat gggcntcatt ttgttctacc tgcaaaatg g gggataataa tagt 774 &lt;210&gt; 4Θ &lt;211&gt; 124 &lt;212> DNA &lt;213 &gt; Human·, . &lt;220&gt; - &lt;221&gt; rnisc_ 特彼&lt;222&gt; (1).7. (124)

&lt;223&gt; n == A#T, C or G &lt;400&gt; 4Θ canaaattga aattttataa aaaggcattt ttctcttata tccataaaat gatataattt 60 ttgcaantat anaaatgtgt cataaattat aatgtccctt aattacagct caacgcaact 120

Tggt · · · 124 &lt;210&gt; 49 &lt;211&gt; 147 ... &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc-feature- &lt;222&gt; (1).7. )

&lt;223&gt; n = A, T, C or G &lt;400&gt; 49 gccgatgcta ccattttatt gcaggaggtg ggggtgtttt tattactccc tcaacagctt 60 tgcggctaca ggtggtgtct gactgcatna aaaanttttt tacgggtgat tgcaaaaatt 120 ttagggcacc catatcccaa gcantgt 147 &lt;210&gt; 50 &lt;211&gt; 107 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 50 - acatcaaatt aataaaagga ctgttggggt tctgctaaaa cacatggctt gacatattgc 60 atggtttgag gttaggagga gttaggcata tgttttggga gaggggt 107 &lt;210&gt; 51 ' .

&Lt; 211 &gt; 204 &lt; 212 &gt; DNA of human &lt; 400 &gt; 51 gtcctaggaa gtctagggga cacacgactc tggggtcacg gggccgacac acttgcacgg 60 22- 127691.doc 200815476 cgggaaggaa aggcagagaa gtgacaccgt cagggggaaa tgacagaaag gaaaatcaag gccttgcaag gtcagaaagg ggactcaggg cttccaccac agccctgccc cacttggcca cctccctttt gggaccagca atgt &lt; 210 &gt; 52 &lt;211&gt; 491 &lt;212&gt; DNA &lt;213&gt; Human · · &lt;220&gt;&lt;221&gt; misc_: Desirable &lt;222&gt; (1) (491)

agggtctcca tttgatagtt acaaagataa gggtattttc ccatcagaca aaaacttctt tcanaaacac atgttgctca atgcaacagt caatcttatt atcacccttg 52 catttatctt caaaagacta ggtttttaaa gcatcaattt ttcctcaaaa gataaataaa gtcttttctt tggataacaa t ataacaaaaa aagagataac aaacaacata cttttgttca attttcaana tctcgtgaga tnctttttct; &lt; 223 &gt; n = &gt; A, T, C or G 21810 112 o &lt; 400 & gt tcaggtaaaa ttacaaaatt aaatgactga tggtagcttt acttaccacc tttttttttt aattatattg ttaaaggtta agttagaaat agacaatcat cttaantatt canatgtncc caccacaagc tcacaggcac aaaaacaaat gtattgtgta gtataaaaca ccttaaaaaa tttaaatatt ctcagcccca tttctggggc agaaactcat ccaagttaat / 1 / V Γ% / V / V fv · «284062c6cf \ 11233444 u &lt;. 210 &gt; 53 &lt; 211 &gt; 484

&lt;'212&gt; DNA &lt;213&gt; Human r * &lt;220&gt;

&lt;221&gt;misc-feature&lt;222&gt; (1).7.(484) &lt;223&gt; n « A,T,(: or G &lt;400&gt; acataatcta gcattaacag actacagaac caatcaaatc gcactagtat agccttgant aatgattggc tancttgant cant 53 gcagggctaa ttgctgaagC ccttaaggac cctacataac anaccgctcc tcctttgtgc aggtcnggta ctgtgtattc ttaccataag ttggtatttt actgaaaatt actatagtaa tgtcaggata tgatangagg aatnccaaaa caggancagg atgctattta tatgcagcat agtaagtaaa ttaaaacgtt anactgcttt aaaggctgaa catattccaa cggatggaat ttaanaggtn tttctttctg gttcagaaac aaaaaaaagt ggaacagaaa ttaccttgct ctcaacactt gggceagccc tacgatctga cttcgataac attagctgct gttgaaatct gggaaaaanc gcctctccct cttttccncg ncggatgttc 28406288 11233444 &lt;. 210 &gt; 54 &lt; 211 &gt; 151 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 54 actaaacctc gtgcttgtga actccataca gaaaacggtg ccatccctga acacggctgg ccactgggca tactgctgac aaccgcaaca acaaaaacac aaatccttgg cactggctag tctatgtcct ctcaagtgcc tttttgtttg t 23· 2 5 1 1 127691.doc 200815476

&lt;210&gt; 55 &lt;211&gt; 91 &lt;212&gt; DNA &lt;213&gt; Human·. &lt;400&gt; 55 acctggcttg tctccgggtg gttcccggcg ccccccacgg tccccagaac ggacactttc gccctccagt ggatactcga gccaaagtgg t &lt;210&gt; 56 &lt;211&gt; 133 &lt;212&gt ; DNA &lt;213&gt; Human 4 · &lt;400&gt; 56 ggcggatgtg cgttggttat atacaaatat gtcattttat gtaagggact tgagtatact tggatttttg gtatctgtgg gttgggggga cggtccagga accaataccc catggatacc aagggacaac tgt &lt;210&gt; 57 &lt;211&gt; 147 - &lt;212&gt; DNA &lt;213&gt;&lt;220&gt;&lt;221&gt;misc-feature&lt;222&gt; (1) (147) &lt;223&gt; n = A, T, C or G &lt;400&gt; 57 actctggaga acctgagccg ctgctccgcc tctgggatga ggtgatgcan gcngtggcgc gactgggagc tgagcccttc Cccctgcgcc tgcctcagag gattgttgcc gacntgcana tctcantggg ctggatncat gcagggt &lt;210&gt; 5Θ &lt;211&gt; 198 &lt;212&gt; DNA &lt;213&gt; Human ···· &lt;220&gt;&lt;221&gt; misc one: feature &lt;222&gt; (1) ... (198) · ~ &lt;223&gt; n = A, T, C or G &lt;400&gt; 58 acagggatat aggtttnaag ttattgtnat tgtaaaatac attgaatttt ctg Tatactc tgattacata catttatcct ttaaaaaaga tgtaaatctt aatttttatg ccatctatta atttaccaat gagttacctt gtaaatgaga agtcatgata gcactgaatt ttaactagtt ttgacttcta agtttggt &lt;210&gt; 59 &lt;211&gt; 330 &lt;212&gt; DNA &lt; 213 &gt; human 60 91 60 120 133 60 120 147 60 120 180 198 127691. Doc 24- 200815476

&Lt; 400 &gt; 59 acaacaaatg ggttgtgagg aagtcttatc agcaaaactg gtgatggcta ctgaaaagat ccattgaaaa ttatcattaa tgattttaaa tgacaagtta tcaaaaactc actcaatctt cacctgtgct agcttgctaa aatgggagtt aactctagag caaatatagt atcttctgaa tacagtcaat aaatgacaaa gccagggcct acaggtggtt tccagacttt ccagacccag cagaaggaat ctattttatc acatggatct ccgtctgtgc tcaaaatacc taatgatatt tttcgtcttt attggacttc tttgaagagt &lt; 210 &gt; 60 &lt; 211 &gt; 175 &lt; 212 &gt; DNA &lt; 213 &gt; al Yan &lt;. 400 &gt; 60 accgtgggtg ccttctacat tcctgacggc tccttcacca acatctggtt ctacttcggc gtcgtgggct ccttcctctt catcctcatc cagctggtgc tgctcatcga ctttigcgcac tcctggaacc agcggtggct gggcaaggcc gaggagtgcg attcccgtgc ccggt &lt; 210 &gt; 61 &lt; 211 &gt;. 154 _ &lt; 212 &gt; DNA &lt;213&gt; 颜·** 60 120 180 240 300 330 60 120 175 軎&lt;400&gt; 61 &quot; accccacttt tcctcctgtg agcagtctgg acttctcact gctacatgat gagggtgagt ggttgttgct cttcaacagt atcctcccct tcccggatct gctgagccgg acagcagtgc tggactgcac agccccgggg ccccacatcg ctgc &lt;210&gt; 62 &lt;211&gt; 30 &lt;212&g t; DNA &lt; 213 &gt; human face · i ·. &lt;400&gt; 62 cgctcgagcc ctatagtgag tcgtattaga &lt;210&gt; 63 &lt;211&gt; 89 &lt;212&gt; DNA &lt;213&gt; _人颜:- &lt;400&gt; 63 acaagtcatt tcagcaccct ttgctcccca aaactgacca tcttttatat ttaatgcttc ctgtatgaat aaaaatggtt atgtcaagc &lt; 210 &gt; 64 &lt; 211 &gt; 97 &lt; 212 &gt; DNA * &lt; 213> human 60 120 154 30 60 89 &lt; 400 &gt; 64 accggagtaa ctgagtcggg acgctgaatc tgaatccacc aataaataaa ggttctgcag aatcagcgca tccaggattg Gtcct'tggat ctggggt 60 97 127691.doc 25- 200815476 &lt;210&gt; 65 &lt;211&gt; 377 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc_ Desire&lt;222&gt; (1).:.(377} &lt;223>n = A, T, C or G &lt;400&gt; 65 * acaacaanaa ntcccttctt taggccactg atggaaacct: ggaaccccct tttgatggca 60 gcatggcgtc ctaggccttg acacagcggc tggggttcgg gctnccccaa accgcacacc -120 ccaaccctgg tctacccaca nttctggcta tgggctgtct ctgccactga acatcagggt 180 tcggtcataa natgaaatcc caanggggac agaggtcagt agaggaagct caatgagaaa 240 ggtgctgttt gctcagccag aaaacagctg cctggcattc gccgctgaac tatgaacccg 300 tgggggtgaa ctacccccan gaggaatcat gcctgggcga tgcaanggtg ccaacaggag 360 gggcgggagg agcatgt 377

f'i .V &lt; 210 &gt; 66 &lt; 211 &gt; 305 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 66 acgccttccc ctcagaattc agggaagaga ctgtcgcctg cctccctccg ttgttgcgtg 60 agaacccgtg tgccccttcc caccatatcc accctcgctc catccttgaa ctcaaacacg 120 aggaaccaac tgcaccctgg ccctctcccc agtccccagt tcaccctcca tccctcacct 180 ccctccactc taagggatat caacactgcc cagcacaggg gccctgaatt tatgtggttt 240 ticaiiatatitt: tttaataaga tgcactttat gtcattcttc aataaagtct gaagaattac 300 cgttt 305 &lt; 210 &gt; 67 &lt; 211 &gt; 385 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 67 accacacaca ctccacttgc ccttgtgaga cactttgtcc cagcacttta ggaatgctga 60 ggtcggacca gccacatctc atgtgcaaga ttgcccagca gacatcaggt ctgagagttc 120 cccttctaaa aaaggggact tgcttaaaaa agaagtctag ccacgattgt gtagagcagc 180 tgtgctgtgc tggagattca cttttgagag agttctccCc tgagacctga tctttagagg 240 ctgggcagtc ttgcacatga gatggggctg gtctgatctc agcactcctt agtctgcttg 300 cctctcccag ggccccagcc tggccacacc tgcttacagg gcaccctcag atgcccatac 360 catagcttcc gtgctagtgg accgt 385 &lt; 210 &gt; 68.

&lt;211&gt; 73 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 68 acttaaccag atatattttt accccagatg gggatattct ttgtaaaaaa tgaaaataaa 60 gtttttttaa tgg 73 127691.doc 200815476 &lt;210&gt; 69 &lt;211&gt; 536 &lt;212&gt; DNA &lt;;213&gt; Human face.· &lt;220&gt;

&lt;221&gt; misc_ feature &lt;222&gt; (1).: (536) &lt;223&gt; η « Α,Τ,Ο or G &lt;400&gt; 69 actagtccag tgtggtggaa ttccattgtg ttgggggctc tcaccctcct ctcctgcagc 60 tccagctttg tgctctgcct ctgaggagac catggcccag catctgagca ccctgctgct 120 cctgctggcc accctagctg tggccctggc ctggagcccc aaggaggagg ataggataat ~ 180 cccgggtggc atctataacg cagacctcaa tgatgagtgg gtacagcgtg cccttcactc 240 cgccaccagc gagtataaca aggccaccaa agatgactac tacagacgtc cgctgcgggt 300 actaagagcc aggcaacaga ccgttggggg ggtgaattac ttcttcgacg tagaggtggg 360 ccgaaccata tgtaccaagt cccagcccaa cttggacacc tgtgccttcc atgaacagcc 420 agaactgcag aagaaacagt tgtgctcttt cgagatctac gaagttccct ggggagaaca 480 gaangtccct gggtgaaatc caggtgtcaa gaaatcctan ggacctgttg ccaggc 536 &lt;210&gt; 70

&Lt; 211 &gt; 477 - &lt; 212 &gt; DNA * &lt; 2U &gt; human, ·· &lt; 400 &gt; 70 atgaccccca acaggggccc cctcagccct cctaatgacc tccggccceg ccatgtgatc 60 ccacctccac cccataacgc tcctcatact aggcctacta accaacacac caaccataca 120 ccaatgatgg cgcgatgtaa cacgagaaag cacataccaa ggccaccaca caccacctgt 100 ccaaaaaggc cttcgatacg ggataatcct atttatcacc tcagaagttc tcctcttcgc 240 agggattctt .ctgagccttt raccactcca gcccagcccc taccccccaa ctaggagggc 300 accggccccc aacaggcacc accccgctiaa atcccctaga agtcccactc ctaaacacat 360 ccgtattact cgcatcagga gtatcaatca cctgagctca ccatagtcta atagaaaaca 420 accgaaacca aattattcaa agcactgctt attacaattc taccgggtcc ccacctt 477 &lt; 210 &gt; 71 &lt; 211 &gt; 533 &lt; 212 &gt; DNA &lt; 213 &gt; People &lt;220&gt;

&lt;221&gt; misc_: feature &lt;222&gt; (1).7.(533) &lt;223&gt; n = A, T, C or G

&Lt; 400 &gt;. 71 agagctatag gtacagtgcg atctcagctt tgcaaacaca tcttctacat agatagtact 60 aggtattaac agatatgtaa, agaaagaaat cacaccatta ataatggtaa gattggttta 120 tgcgatttca gtggtatttt tggcaccctt atatatgttt tccaaacttt cagcagtgat 180 attatttcca taacttaaaa agtgagtttg aaaaagaaaa tctccagcaa gcatctcatt 240 taaataaagg tttgtcatct ttaaaaatac agcaatacgt gactttttaa aaaagctgtc 300 aaataggtgt gaccctacta ataattatta gaaatacatt taaaaacatc gagtacctca 360 agtcagtttg Ccttgaaaaa tatcaaatat aactcttaga gaaatgtaca taaaagaatg 420 ctccgtaatc ttggagtang aggttccctc ctcaattttg tacttttaaa aagtacatgg 480 taaaaaaaaa aattcacaac agtatataag gctgtaaaat gaagaattct gcc 533 127691.doc 27- 200815476 &lt;210&gt; 72 &lt;211&gt; 511 &lt;212&gt; DNA &lt;213>human &lt;220&gt;

&lt;222&gt; (1) .7. (511) &lt;223&gt; n *= A,T,C or G &lt;400&gt; 72 tattacggaa aaacacacca cataattcaa ctancaaaga anactgcttc agggcgtgta 60 aaatgaaagg cttccaggca gttatctgat taaagaacac taaaagaggg acaaggccaa 120 aagccgcagg atgtctacac tatancaggc gctatttggg ttggctggag gagctgtgga 18Ci aaacatggan agattggtgc cgganatcgc cgtggctatt cctcattgtt attacanagt 240 gaggttctct gtgtgcccac tggtttgaaa accgttctnc aataatgata gaatagtaca 300 cacatgagaa ctgaaatggc ccaaacccag aaagaaagcc caactagatc ctcagaanac 360 gcttctaggg acaacaaccg atgaagaaaa gatggcctcc ttgtgccccc gtctgttatg 420 atttctctcc attgcagcna naaacccgtt cctctaagca aacncaggtg atgatggcna 480 aaatacaccc cctcttgaag naccnggagg a 511 ft &lt; 210 &gt; 73

&lt;211&gt; 499 &lt;212&gt; DNA &lt;213&gt;Human &lt;220&gt;&lt;221&gt; misc_ Tough &lt;222&gt; (1).7.(499)

. &Lt; 223 &gt; n = A, T, C or G &lt; 400 &gt; 73 cagcgccagc actggtgcca gtaccagtac caataacagt gccagtgcca gtgccagcac .60 cagtggtggc ttcagtgctg gtgccagcct gaccgccact ctcacatttg ggctcctcgc 120 tggccttggt ggagctggtg ccagcaccag tggcagctct ggtgcctgtg gtctctccta 180 caagtgagat tttagacacc gctaatcctg ccagtctctc tcttcaagcc agggtgcatc 240 ctcagaaacc tactcaacac agcactctag gcagccacta tcaatcaatt gaagttgaca 300 ctctgcatta aatctattcg ccatttctga aaaaaaaaaa aaaaaaaggg cggccgctcg 360 antctagagg gcccgtttaa acccgctgat cagcctcgac tgtgccttct anttgccagc 420 catctgttgt ttgcccctcc cccgntgcct tccttgaccc tggaaagtgc cactcccact 480 gtcctttcct aantaaaat 499 &lt; 210 &gt; 74 &lt; 211 &gt; 537 * &lt; 212 &gt; DNA &lt; 213 &gt; human &lt;220&gt; ' &lt;221&gt; mi SC One Desire. &lt;222&gt; (1).7.(537)

&Lt; 223 &gt; n = A, T, C or G &lt; 400 &gt; 74 tttcatagga gaacacactg aggagatact tgaagaattt ggattcagcc gcgaagagat 60 127691.doc 28- 200815476 ttatcagctt aactcagata aaatcattga aagtaataag gtaaaagcta gtctctaact 120 tccaggccca cggctcaagt gaatttgaat actgcattta cagtgtagag taacacataa 180 cattgtatgc atggaaacat ggaggaacag tatcacagtg tcctaccact ctaatcaaga 240 aaagaattac agactctgat tccacagtga tgattgaatt ctaaaaatgg taatcattag 300 ggcttttgat ttataanact ttgggtactt atactaaatt atggtagtta tactgccttc 360 cagtttgctt gatatatttg ttgatattaa gattcttgac ttatattttg aatgggttct 420 actgaaaaan gaatgatata ttcttgaaga catcgatata catttattta cactcttgat 480 tctacaatgt agaaaatgaa ggaaatgccc caaattgtat ggtgataaaa gtcccgt 537 &lt; 210 &gt; 75 &lt; 211 &gt; 467 &lt; 212 &gt; DNA · &lt;213&gt; Human · &lt;220&gt;

&lt;221&gt; misc_: Desirable &lt;222&gt; (1).:.(467) &lt;223&gt; n *= W or G &lt;400&gt; 75 caaanacaat tgttcaaaag atgcaaatga tacactactg ctgcagctca caaacacctc 60

tgcatattac acgtacctcc tcctgctcct caagtagtgt ggtctatttt gccatcatca 120 cctgctgtct gcttagaaga acggctttct gctgcaangg agagaaatca taacagacgg 180 tggcacaagg aggccatctt ttccccatcg gttattgtcc ctagaagcgt cttccgagga 240 tctagttggg ctttctttct gggtttgggc catttcantt cccatgtgtg tactatccta 300 tcatcattgt ataacggctc tcaaaccngt gggcacncag agaacctcac tctgtaataa 360 caatgaggaa tagccacggc gatctccagc accaaatccc tccatgttnt tccagagctc 420 ctccagccaa cccaaatagc cgctgctatn gtgcagaaca tccctgn 467 &lt;210&gt; 76 &lt;211&gt; 400 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc_ 梓&lt;222&gt; (1) . . . (400) &lt;223&gt; n = A, T, C or G &lt;400&gt; 76 aagctgacag cattcgggcc gagacgtctc gctccgtggc cttagccgtg ctcgcgctac 60 tctctctttc tggcctggag gctatccagc gtactccaaa gattcaggct tactcacgtc 120 atccagcaga gaatggaaag tcaaatctcc tgaatcgcta tgtgtctggg tttcatccat 180 ccgacatcga agttgactta ctgaagaatg gagagagaat tgaaaaagtg gagcattcag 240 acttgtcctt cagcaaggac tggtcttcct atctcttgta ctacactgaa ttcaccccca 300 ctgaaaaaga tgagtatgcc tgccgtgtga accatgtgac tttgtcacag cccaagatng 360

Ttnagtggga tcganacatg taagcagcan catgggaggt 40Q

&Lt; 210 &gt; 77 &lt; 211 &gt; 248 &lt; 212 &gt; DNA &lt; 213 &gt; al pigment * &lt; 400 &gt; 77 ctggagtgcc ttggcgttcc aagcccctgc aggaagcaga atgcaccttc tgaggcacct 60 29- 127691.doc 200815476 ccagctgccc cggcggggga tgcgaggctc ggagcaccct tgcccggctg tgattgctgc caggcactgt tcatctcagc ttttctgtcc ctttgctccc ggcaagcgct tctgctgaaa gttcatatct ggagcctgat gtcttaacga ataaaggtcc catgctccac ccgaaaaaaa aaaaaaaa &lt; 210 &gt; 78 &lt; 211 &gt; 201 &lt; 212 &gt; DNA &lt; 213 &gt; who is eligible &lt; 400 &gt; 78 actagtccag tgtggtggaa ttcc ^ ttgtg ttgggcccaa cacaatggct acctttaaca tcacccagac cccgccctgc ccgtgcccca cgctgctgct aacgacagta tgatgcttac tctgctactc Ggaaactatt tttatgtaat taatgtatgc tttcttgttt ataaatgcct gatttaaaaa aaaaaaaaaa a &lt;210&gt; 79 &lt;211&gt; 552 &lt;212&gt; DNA &lt;213&gt;People 2 8 4 4 112 2 ooo -.l 6 2 8 0 Ο &lt;220&gt;&lt;221&gt;misc-feature&lt;222&gt; (1).7.(552) &lt;223&gt; n * A#T, C or 79 aggtttttga gctagtaatt ctgaagatta taagtatcta gtaactactc gctagaaaaa tgttccaaaa tatggggttc taatacgtta aa &lt;400&gt; tccttttgtt tttaggcagt cctccttctc tgcgatagta atgcaagtta ctgttccttg taatattcta tccccaggaa cngttttggt aaaaaaaaaa gacaacccta ccctcgtaat atgaagttga agtgcagatg agggttaact attataaaca gttgggctat atttatgaat atatgccctn gacctaaact gactctgtta aaattgaggt aaagtgtgtt. aaattactet ggactttgtt acataaanta antacccggg aannaacaag gcgtcacaga tcactttcct ggataaatac atatatatcc aatatgctgt agtttgggaa tnaagaaata anagaagttt gcntgactta cttctgaatg attctttatt aaaaaggtag actcaaaatt tgaacctact gccaaattga tggaatttta tgantnaaac tttccaaaaa 284062845 112334455 ϋ &lt;210&gt; 80 &lt;211&gt; 476 &lt;212&gt; DNA &lt;213&gt; Human

&lt;220&gt;&lt;221&gt; misc_: feature &lt;222&gt; (1)·Τ·(476) &lt;223&gt; n = A, T, C or G &lt;400&gt; 80 . ' acagggattt gagatgctaa ggccccagag atcgtttgat ccaaccctct tattttcaga ggggaaaatg gggcctagaa gttacagagc atctagctgg tgcgctggca cccctggcct cacacagact cccgagtagc tgggactaca ggcacacagt cactgaagca ggccctgttt gcaattcacg ttgccacctc caacttaaac attcctcata tgtgatgtcc ttagtcacta aggttaaact ttcccaccca gaaaaggcaa cttagataaa atcttagagt actttcatac tcttctaagt cctcttccag cctcactttg agtcctcctt gggggttgat aggaantntc 2 8 4 0 6 112 3 3 127691.doc 30- 200815476 tcttggcttt ctcaataaaa tctctatcca tctcatgttt aatttggtac gcntaaaaat 420 gctgaaaaaa ttaaaatgtt ctggtttcnc tttaaaaaaa aaaaaaaaaa aaaaaa 476 &lt;210&gt; 81 &lt;211&gt; 232 &lt;212&gt; DNA &lt;213&gt;People;&lt;220&gt;&lt;221&gt; misc-special education. &lt;222&gt; (1) ..."232)

&Lt; 223 &gt; ri = A, T, C or G &lt;. 400 &gt; 81, tttttttttg tatgccntcn ctgtggngtt attgtcgctg ccaccctgga ggagcccagt 60 ttcttctgta tctttctttt ctgggggatc ttcctggctc tgcccctcca ttcccagcct 120 ctcatcccca tcttgcactt ttgctagggt tggaggcgct ttcctggtag cccctcagag 180 actcagtcag cgggaataag tcctaggggc ggggggtgtg gcaagccggc ct 232.

ϋ &lt;210&gt; 82 &lt;211&gt; 383 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; miscj feature &lt;222&gt; (1).7.(383) &lt;223> n « A, T, C or G &lt;400&gt; B2 aggcgggagc agaagctaaa gccaaagccc aagaagagtg gcagtgccag cactggtgcc 60 agtaccagta ccaataacat gccagtgcca gtgccagcac cagtggtggc ttcagtgctg 120 gcgccagccc gaccgccact ctcacatttg ggctcttcgc tggccttggt ggagctggtg 180 ccagcaccag cggcagctct ggtgcctgtg gtttctccta caagtgagat tttagatatt 240 gttaatcctg ccagtctttc tcttcaagcc agggtgcatc cccagaaacc tacccaacac 300 agcaccccng gcagccacta tcaatcaatt gaagtcgaca ctctgcatta 360 ccacctcaaa aaaaaaaaaa aaa 383 & lt aatctatctg; 210 &gt; Θ3 &lt; 211 &gt; 494 &lt; 212 &gt; DNA &lt;213&gt;People&lt;220&gt;

&lt;221&gt; mi sc 一.特敬&lt;222&gt; (1)...(494) &lt;223&gt; n = A, T, C or .G &lt;400&gt; 83 , accgaattgg gaccgctggc ttataagcga tcatgtcctc cagtattacc tcaacgagca 60 gggagatcga gtctatacgc tgaagaaatt tgacccgatg ggacaacaga cctgctcagc 120 ccatcctgct cggttctccc cagatgacaa atactctcga caccgaatca ccatcaagaa 180 acgcttcaag gtgctcatga cccagcaacc gcgccctgtc ctctgagggt ccttaaactg 240 atgtcttttc cgccacctgt tacccctcgg agactccgta accaaactct tcggactgtg 300 agccctgatg cctttttgcc agccatactc tttggcntcc agtctctcgt ggcgatcgat 360 -31 - 127691.doc 200815476 tatgcttgtg tgaggcaatc atggtggcat cacccatnaa gggaacacat ttganttttt tttcncatat tttaaattac Naccagaata nttcagaata aatgaattga aaaactctta aaaaaaaaaa aaaa &lt;210&gt; 84 &lt;211&gt; 380 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;&lt;221&gt; tnisc-features &lt;222&gt;(1)...&lt;380)

&lt;223&gt; n » A, T, C or G 0 0 4 2 8 9 84 tatggcgtgg gccgcgtctt acgtggccct ccggggccca tcgccatctt ttacacattc ccccatccgg 2 8 4 o 6 Θ 1 1 2 3 3 3 &lt;400&gt; gctggtagcc agtatcctgc gaggacatgg gcacaccctc gtgctgctcc ccatgttcag agcgttnccg ccacggangg ctaccgtccc cacggagcac ggcgggcacc cctgctcgtg ggcaaagtac gctcctgagg tacctgcaga agcaactgct tgcgtctccc gccaacatcc agggcaacag cacgggacag tcttcgggca cgtcggagcc agtacgccaa tgctggtcac cnatctctac tgacttccca gattccccag cggcttctgg ctggctggtg ttgctcattg tgggaaggcc u &lt; 210 &gt; 85 &lt; 211 &gt; 481 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 220 &gt;

&lt;221&gt; misc^ Feature &lt;222&gt; (1).T.(481) &lt;223&gt; n = A, T, C or G &lt;4 00 &gt; gagttagctc tnccaccgtc ggaaaccctc tgtgaaagga gtcgattctg ctatcacgcc ccagattctg aaagaacacc t 85 ctccacaacc atactgtagg aatcaagtca tctccagaag catgtccagc nttgaacgtg cattaccaga tcctggaagt ttgatgaggt tttgccacca ccgtcnatna gagtgctcga aggaggttgt ccgaagaaca nagccgtggc gctngccgct cgtctgcagc cctcctgcac aacctgtggc tcttccccac accagctctc ccgagccttg aaaaganatt cctcgtccnt ggcctctcgc cttggggcgg tggttccgtc acttttgatg tgacagtgag tgtggggggc gacaactcgc tggtggnngc ttcataccgc ctsataccca tcccgctcgg actttattga gtcaccagcc gnagtctcac ccaggnngaa gcntnccttt 28406288 11233444 &lt; 210 &gt; 86 &lt; 211 &gt; 472 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; Features

&lt;222&gt; (1).7.(472) &lt;223&gt; n = A#T, C or G &lt;400&gt; 86 -32 127691.doc 200815476 aacatcttcc tgtataatgc tgtgtaatat cgatccgatn ttgtctgctg agaattcatt 60 acttggaaaa gcaacttnaa gcctggacac tggtattaaa attcacaata tgcaacactt 120 taaacagtgt gtcaatctgc tcccttactt tgtcatcacc agtctgggaa traagggtatg 180 ccctattcac acctgttaaa agggcgctaa gcatttttga ttcaacatct ttttttttga 240 cacaagtccg aaaaaagcaa aagtaaacag ttnttaattt gttagccaat tcactttctt 300 catgggacag agccatttga tttaaaaagc aaattgcata atattgagct ttgggagctg 360 atatntgagc ggaagantag cctttctact tcaccagaca caactccttt catattggga 420 tgttnacnaa agttatgtct cttacagatg ggatgctttt gtggcaattc tg 472 &lt; 210 &gt; 87 &lt;211&gt; 413 &lt;212&gt; DNA * &lt;213&gt; Human · * &lt;220&gt;

&lt;221&gt; misc-·•Features &lt;222&gt; (1) .7. (413) .* &lt;223&gt; n A,T,C or 'G &lt;400&gt; 87 agaaaccagt atctctnaaa acaacctctc ataccttgtg gacctaattc tgcgtgcgcg 60

tgtgtgtgcg cgcatattac atagacaggc acatcttttt tacttitcgta aaagcttatg 120 cctctctggt atctatatct gtgaaagttt taatgatctg ccataatgtc ttggggacct 180 ttgtcttctg tgtaaacggt actagagaaa acacctatnt tatgagtcaa r.ctagttngt 240 tttattcgac atgaaggaaa tttccagatn acaacactna caaactctcc cttgactagg 300 ggggacaaag aaaagcanaa ctgaacatna gaaacaattn cctggtgaga aattncataa 360 acagaaattg ggtngtatat tgaaananng caccatcnaa acgttttttt ttt 413 &lt; 210 &gt; 8Θ &lt;211&gt; 448 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;

&lt;221>misc_ 特启&lt;222&gt; (1)····(448) &lt;223> n = A, T, C or G &lt;400&gt; 88 cgcagcgggc cctctctatc tagccccagc ctctcgcctg ccccactccc cgcgtcccgc 60 gtcccagccn accatggccg ggcccctgcg cgccccgctg ctcctgctgg ccatcctggc 120 cgtggccctg gccgtgagcc ccgcggccgg ctccagtccc ggcaagccgc cgcgcctggt 180 gggaggccca tggaccccgc gtggaagaag aaggtgtgcg gcgtgcactg gactttgccg 240 tcggcnanta caacaaaccc gcaacnactt ttaccnagcn cgcgctgcag gttgtgccgc 300 cccaancaaa ttgttactng gggtaantaa ttcttggaag ttgaacctgg gccaaacnng 360 tttaccagaa ccnagccaat tngaacaatt ncccctccat aacagcccct tttaaaaagg 420 gaancantcc tgntcttttc caaacttt 448 &lt; 210 &gt; 89 &lt; 2U &gt; 463 &lt;212&gt; DNA &lt;213&gt; Human.. &lt;220&gt;&lt;221&gt; misc_: Special Desire 33-127691.doc 200815476

&Lt; 222 &gt; (1) (463) &lt;... 223 &gt; η = A, T, C or G &lt; 400 &gt; 89 gaattttgtg cactggccac tgtgatggaa ccattgggcc aggatgcttt gagtttatca gtagtgattc tgccaaagtt ggtgttgtaa catgagtatg taaaatgtca aaaaattagc agaggtctag gtctgcatat cagcagacag tttgtccgtg tattttgtag ccttgaagtt ctcagtgaca agttnnttct gatgcgaagt tctnattcca gtgttttagt cctttgcatc tttnatgttn agacttgcct ctntnaaatt gcttttgtnt tctgcaggta ctatctgtgg tttaacaaaa tagaannact tctctgcttn gaanatttga atatcttaca tctnaaaatn aattctctcc ccatannaaa acccangccc ttggganaat ttgaaaaang gntccttcnn aattcnnana anttcagntn tcatacaaca naacngganc ccc

&lt;210&gt; 90 &lt;211&gt; 400 &lt;212&gt; DNA &lt;213&gt;. Person SR &lt;22Q&gt;

C 60 120 1Θ0 240 300 360 420 463

&lt;221&gt; misc-characteristic &lt;222&gt;&lt;1) (400) &lt;223&gt; n * A, Tf CG &lt;400&gt; 90 agggattgaa ggtctnctnt cttccactca ctgtctgtaa ccttcaccag tcacatcttc tcctttgtta agacttcacc cgttctccaa caatgtcctc ctgtgcatcc attttaaata gagccatctg tctgcaaaag actgtcggac gcntntcaac Taggacctct tggtaaagtc tccttgaagt tacttaatag ttgcgttagt tgttcancca ccagactgta ttggattcag tcaagtttcg acttggctga ggcattggtn atatctgcca ccaactctac tcttcataaa tcagtataag tagaaaggaa acaacccacc cactaggtta aagttgctgt tagaacaaat ctctcccact tctaatcgcc tnaagtcccc aattctgcaa 60 120 180 24Q 300 360 400 Ο

&lt;210&gt; 91 &lt;211&gt; 480 &lt;212&gt; OHA &lt; 213 &gt; Human &lt;220&gt;&lt;221&gt; misc-special $ &lt;222&gt; {1).7.(480) &lt;223&gt; A, T # C or · G &lt; 400 &gt; 51 - gagctcggat ccaataatct ttgtctgagg gcagcacaca taCncagtgc catggnaact ggtctacccc acatgggagc agcatgccgt agntatataa ggtcattccc tgagtcagac atgcctcttt gactaccgtg tgccagtgct ggtgatcctc acacacctcc nnccgctctt tgtggaaaaa ctggcacttg nctggaacta gcaagacatc acttacaaat tcacccacga gacacctgaa aggtgtaaca ^ agcgactct cgcattgctt tttgtccctc cggcaccagt tgtcaatact aacccgctgg tttgcctcca tcacatttgt gatctgtagc Tctggataca tctcctgaca gtactgaaga acttcttctt ttgtttcaaa agcaactctt ggtgcctgtt ngatcaggtt cccatttccc agtccgaatg ttcacatggc atatnttact tcccacaaaa 60 120 1Θ0 240 300 360 420 480

&lt;210&gt; 32 &lt;211&gt; 477 &lt;212&gt; DNA 127691.doc -34- 200815476 &lt;213&gt; People &lt;220&gt;

&lt;221&gt;misc-feature&lt;222&gt; (1) (477) &lt;223&gt; n = A, T, C or G &lt;400&gt; 92 atacagccca natcccacca cgaagatgcg cttgttgact gagaacctga tgcggtcact 60 ggtcccgctg tagccccagc gactctccac ctgctggaag cggttgatgc tgcactcctt 120 cccacgcagg cagcagcggg gccggtcaat gaactccact cgtggcttgg ggttgacggt 180 taantgcagg aagaggctga ccacttcgcg gtccaccagg atgcccgact gtgcgggacc 240 tgcagcgaaa ctcctcgatg gtcatgagcg ggaagcgaat gangcccagg gccttgccca 300 gaaccttccg cctgttctct ggcgtcacct gcagctgctg ccgctnacac tcggcctcgg 360. accagcggac aaacggcgtt gaacagccgc acctcacgga tgcccantgt gtcgcgctcc 420 aggaacggcn ccagcgtgtc caggtcaatg tcggtgaanc ctccgcgggt aatggcg 477 &lt; 210 &gt; 93 &lt;211&gt; 377 &lt;212&gt; DNA &lt;213&gt;

&lt;220&gt;

&lt;221&gt; misc" feature &lt;222&gt; (1) . . . (377) &lt;223&gt; n = A, T, C or G &lt;4〇0&gt; 93 gaacggctgg accttgcctc gcactgcgcc gctggcagga acaccttggc aagcagctcc 60 agtccgagca gccccagacc gctgccgccc .gaagctaagc cugcccctgg cctccccctc 12 0 cgccccaatg cagaaccant agtgggagca ccgcgtccag agttaagagt gaacactgcn · 180 tgattttact, tgggaatctc ctctgttata tagctcttcc caatgctaat ttccaaacaa 240 caacaacaaa acaacatgtt tgcctgttna gttgtataaa agtangtgat tctgtatnca 300 aagaaaacat taccgttaca tatactgctt gcaanttctg tatttactgg tnctctggaa 360 ataaacatat tattaaa 377 &lt; 210 &gt; 94 &lt; 211 &gt; 495 &lt;2X2&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221>misc_ feature&lt;222&gt; (1) .7. (495.) &lt;223&gt; Π = A, T, C or G &lt;400&gt; 94 ccctctgagg ggttagggtc cagcccccag tggaagaaac aggccaggag aantgcgtgc 60 cgagctgang cagatttccc acagtgaccc cagagccctg ggccatagtc tctgacccct 120 ccaaggaaag accaccttct ggggacatgg gctggagggc aggacctaga ggcaccaagg 180 gaaggcccca ttccggggct gttccccgag gaggaaggga aggggctctg tgtgcccccc 240 acgaggaana ggccctgant cctgggatca nacacccctt cacgtgtatc cccacacaaa 300 tgcaagctca ccaaggtccc ctctcagtcc cttccctaca ccctgaacgg ncactggccc 360 acacccaccc agancancca cccgccatgg ggaatgtnct caaggaatcg cngggcaacg 420 tggactccng tcccnnaagg gggcagaatc tccaacagan gganngaacc cctgctnana 480 35- 127691.doc 200815476 Aaaaaaaana aaaaa &lt;210&gt; 95 &lt;211&gt; 472 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc-feature &lt;222&gt; (1) (472)

1 &lt; 223 &gt; n = A, T # C * G &lt; 400 &gt; 95 ggttacttgg tttcattgcc accacttagt ggatgtcatt tagaaccatt tcgtctgctc cctctggaag ccttgcgcag agcggacttt gtaattgttg gagaataact gctgaatttt tagctgtttt gagttgattc gcaccactgc accacaactc aatatgaaaa ctatttnact tatttattat cttgtgaaaa gtatacaatg aaaattctgt tcatactgta tttatcaagt atgatgaaaa gcaatagata tatattcttt tattatgttn aattatgatt gccattatta atcggcaaaa /tgtggagtgt atgttctttt cacagtaata tatgcctttt gtaacttcac ttggttattt tattgtaaat gaattacaaa attcttaatt taagaaaacg gtangttata tttanttcan taatttcttt ccttgtttac gttaatitttig aaaag swallow atgc at . &lt;210&gt; 96 ·, &lt;211&gt; 476 &lt;212&gt; DNA &quot;&lt;213:, human &lt;220&gt;&lt;221&gt;misc_features&lt;222&gt; (1)...(476)..........

&lt;223&gt; n = A, T, C or G 495

Vo 120 180 240 300 360 420 4 72

6Q 120 180 240 300 360 420 476 &lt;400&gt; 96 ccgaagcatt: tcttcaaact gcggcgaaac ttcaaaatta ccttaactca tgatttttac actcctcaca gcagatgatg agctggatac atacngtggg tgtgctagtc tcaattccca gcaggtactc ctccagaaaa tacaaagtct: atcttcctca &lt;210&gt; 97 &lt;211&gt; 479 &lt;212&gt; DNA &lt;213&gt; people Yan tntctacttt tgtcattgac tatgtaactt ctacragctt acacacaatc cagaactcat aaagagtcct: ccagcgtctt agttctataa actcataccc ccacactgag ggagcccccc acngacaggg caggcttgca nangtctgtn aaggaacaat acctgcagca agttgacaat taccttcccc cccaagtctt tatatagccc ctaagtcttt gngcanaatg ttctagntat cagtgggacc naaccaaaat aaatcactat attcttatct tgaaaaagtn acatctgcgt ttaatcttcc agcttc

&lt;220&gt; % &lt;221>misc_特微&lt;222&gt; (1)...(479) &lt;223&gt; n = A, T#C or G &lt;400&gt; 97 actctttcta atgctgatat gatcttgagt ataagaatgc atatgtcact agaatggata aaataatgct gcaaacttaa tgttcttatg caaaatggaa cgctaatgaa acacagctta 36- 60 120 127691.doc 200815476 caatcgcaaa tcaaaactca caagtgctca tctgttgtag atttagtgta ataagactta 180 gattgtgctc cttcggatat gattgtttcc canatcttgg gcaatnttcc ttagtcaaat 240 caggctacta gaattctgtt attggatatn. tgagagcatg aaatttttaa naatacactt 300 gtgattatna aattaatcac aaatttcact tatacctgct atcagcagct agaaaaacat 360 ntnnttttta natcaaagta ttttgtgtct ggaantgtnn aaatgaaatc tgaatgtggg 420 ttcnatctta ttttttcccn gacnactant tnctttttta gggnctattc tganccatc 479 &lt; 210 &gt; 98 &lt; 211 &gt; 461 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 98 agtgacttgt cctccaacaa aaccccttga tcaagcttgt ggcaccgaca atcagaccta -60 tgctagttcc tgccatctat tcgctactaa atgcagactg gaggggacca aaaaggggca 120 tcaactccag ctggattatt ttggagcctg Caaatctatt cccacttgta cggactttga 180 agtgactcag tctcctctac ggatgagaga ctggctcaag aatatcctca tgcagcttta 240 tgaagccact ctgaacacgc tggttatcta gatgagaaca gagaaataaa gtcagaaaat 300 ttacctggag aaaagaggct ttggctgggg accatcccat tgaacctcct cttaaggact 360 ttaagaaaaa ctaccacatg ttgcgtatcc tggtgccggc .cgtctatgaa ctgaccaccc 420 cctggaacaa tcttgacgct cctgaacttg cccctctgcg a 461

&lt;210&gt; 99 ·· &lt;211&gt; 171 ·- &lt;212&gt; DNA ·· &lt;213 &gt;human&lt;.400&gt; 99 gtggccgcgc gcaggtgttt cctcgtaccg cagggccccc tccccccccc aggcgtccct 60 cggcgcccct gcgggcccga ggaggagcgg ccggcgggtg gggggagtgt gacccaccct 120 cggtgagaaa agccttctct . agcgacctga gaggcgtgcc ttgggggtac c 171 &lt; 210 &gt; 100 &lt; 211 &gt; 269 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 100 cggccgcaag cgcaactcca gctggggccg tgcggacgaa gactctgcca gcagttggtc 60 cgactgcgac gacggcggcg gcgacagtcg caggtgcagc gcgggcgcct ggggtcttgc 120 aaggctgagc tgacgccgca gaggtcgtgt cacgccccac gaccttgacg ccgtcgggga 180 cagccggaac agagcccggt gaagcgggag gcctcgggga gccccccggg aagggcggcc 240 cgagagacac g'caggtgcag gtggccgcc 269 &lt; 210 &gt; 101 &lt; 211 &gt; 405 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 101 tttttttctc tcttggaatc tactgcgagc acagcaggtc agcaacaagt ttattttgca 60 gctagcaagg taacagggta Gggcatggtt acatgttcag gticaactitcc tttgtcgtgg 120 ttgattggcc tgtctttacg ggggcggggt ggggtagggg aaacgaagca aataacatgg 180 agtgggtgca Ccctccctgt agaacctggc tacaaagctt ggggcagttc acctggtctg 240 tgaccgticat ttccctgaca tcaatgttat tagaagccag gacatctttt agagagtcca 300 -37- 127691.doc 200815476

ϋ

ctgttctgga gggagattag ggtttcttgc caaatccaac aaaatccact gaaaaagttg gatgatcagt acgaataccg aggcatattc tcatatcggt ggcca &lt; 210 &gt; 102 &lt; 211 &gt; 470 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 102 tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt ggcacttaat ccatttttat ttcaaaatgt ctacaaattt aatcccatta tacggtattt tcaaaatcta aattattcaa attagccaaa tccttaccaa ataataccca aaaatcaaaa atatacttct ttcagcaaac ttgttacata aattaaaaaa atatatacgg ctggtgtttt caaagtacaa tcatcttaac accgcaaaca ttttaaggaa ctaaaataaa aaaaaacact ccgcaaaggt taaagggaac aacaaattct tttacaacac cattataaaa atcatatctc aaatcttagg ggaatatata cttcacacgg gatcttaact tttactcact ttgtttattt ctttaaacca ttgtttgggc ccaacacaat ggaatccccc ctggactagt &lt; 210 &gt; 103 &lt; 211 &gt; 581 &lt; 212 &gt; DNA ·· * &lt;213&gt;Human- &lt;400&gt; 103 .. ttttettttt ttttttttga cccccctctc ataaaaaaca agttaccatt tcattttact tacacatatt tattttataa ttggtattag atattcaaaa ggcagctttt aaaatcaaac taaatggaaa ctgccttaga tacataatcc ttagg3atta gcttaaaatc tgcc taaagt gaaaatcctc tctagccctt ttgactgtaa acttttgact cttgtaaaac acccaaattc attcttcttg tctttaaaat tatctaatct ttccattcct tccccattcc aagtcaactc gcttctccag cctcattccc tagctcctat ccactattag taagcggctt ctttcctaaa agggaaaaca ggaagagaaa tggcacacaa aacaaacatc ttatattcat atttctacct acgttaataa aatagcactt tgtgaagcca gctcaaaaga aggcctagat cctttcatgt ccattttagt cactaaacga taccaaagtg ccagaacgca aaaggcttgt gaacatttac tcaaaagcta atataagata ttccacatac tcatctttct g &lt; 210 &gt; 104 &lt; 211 &gt; 578 &lt; 212 &gt; DNA &lt; 213 &gt; human * &lt; 4 00 &gt;. 104 tttttttttt tttttttttt tttttctctt cttttttttt gaaatgagga tcgagttttc cactctctag atagggcacg aagaaaactc atctttccag ctttagiaata acaatcaaat ctcttatgct atatcatatt ttaagttaaa ccaataagtc actggcttat cttctcctga aggaaatctg ttcattcttc tcattcatat agttatatca agtactacct tgcatattga gaggtttttc ttctctattt acacatatat ttccatgtga atttgtatca aacctttatt Ttcatgcaaa ctagaaadta atgtttcttt tgcataagag aagagaacaa tacagcatta caaaactgct caaattgttt gttaagttat ccattataat tagttggcag gagccaacac aa Atcacatt tacgacagca ataataaaac tgaagtacca gttaaatatc caaaataatt aaaggaacat ttttagcctg ggtataatita gctaattcac tttacaagca tttattagaa tgaattcaca tgttattatt cctagcccaa cacaatgg &lt;210&gt; 105 &lt;211&gt; 538 &lt;212&gt; DNA 360 405 60 120 180 24Θ 300 360 420 470 60 120 180 240 300 360 420 4Θ0 54 0 581 60 120 180 240 300 360 420 480 540 578 127691.doc 38- 200815476 &lt; 213 &gt; human &lt; 400 &gt; 105 tttttttttt tttttcagta ataatcagaa caatatttat ttttatattt aaaattcata 60 gaaaagtgcc ttacatttaa taaaagtttg tttctcaaag tgatcagagg aattagatat 120 gtcttgaaca ccaatattaa tttgaggaaa atacaccaaa atacattaag taaattattt 180 aagatcatag agcttgtaag tgaaaagata aaatttgacc tcagaaactc tgagcattaa 240 · aaatccacta ttagcaaata aattactatg gacttcttgc tttaattttg tgatgaatat 300 ggggtgtcac tggtaaacca acacattctg aaggatacat tacttagtga tagattctta 360 tgtactttgc taatacgtgg atatgagttg acaagtttct ctttcttcaa tcttttaagg 420 ggcgagaaat gaggaagaaa agaaaaggat tacgcatact gttctttcta tggaaggatt 480 agatacgttt cctttgccaa ta.ttaaaaaa ataat Aatgt ttaccactag tgaaaccc 538 &lt;210&gt; 106 &lt;211&gt; 473 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 106 tttttttttt ttttttagtc aagttcctat ttttattata attaaagtct tggtcattcc 60 atttattagc tctgcaacct acatatttaa attaaagaaa cgttttagac aactgtacaa 120

tttataaatg taaggtgcca ttattgagta atatacccct ccaagagtgg atgtgtcccc 1Θ0 tctcccacca actaatgaac agcaacatta gttcaatt-tt attagtagat atacactgct 240 gcaaacgcta attctcttct ccatccccat gtgatattgt gtatatgtgt gagctggtag 300 aatgcatcac aatctacaat caacagcaag atgaagctag gctaggcttt cggtgaaaat 360 agactgtgtc tgtctgaatc aaatgatctg acctatcctc ggtggcaaga actcttcgaa 420 ccgctccctc aaaggcgctg ccacacttigt ggccctttgc acccgttcca aaa 473 &lt; 210 &gt; 107 &lt; 211 &gt; 1621 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 107 cgccatggca ccgcagggca tctcggtcat ggagctgtcc ggcctggccc cgggcccgtc 60 ctgtgctacg gtcctggctg acttcggggc gcgtgtggta cgcgcggacc ggcccggctc 120 ccgctacgac gtgagccgct tgggccgggg caagcgctcg ccagcgctgg acccgaagca 180 gccgcgggga gccgccgtgc tgcggcgccc gcgcaagcgg t'cggatgtgc tgctggagcc 240 cttccgccgc Ggtgtcatgg agaaacccca gccgggccca gagatcctgc agcgggaaaa 300 cccaaggcct atttatgcca ggccgagtgg acttggccag ccaggaagct tctgccggtc 360 agctggccac gatatcaact atttggcttt gtcaggtgtt ctctcaaaaa ttggcagaag 420 tggtgagaat · ccgtatgccc cgctgaacct cctggctgac tttgctggtg gtggccttat 480 gtgtgcactg ggcattacaa tggctccttt tgaccgcaca cgcactgaca agggtcaggt 540

cattgatgca aatatggtgg aaggaacagc a kernel atttaagt tctrtttctgt ggaaaactca 600 gaaatcgagt ctgtgggaag cacctcgagg acagaacatg ttggatggtg gagcaccttt 660 ccacacgacc tacaggacag cagatgggga attcatggct gtcggagcaa tagaacccca 720 gttctacgag ctgctgatca aaggacttgg actaaagcct gatgaactrc ccaatcagac 780 gagcatggac gattggccag aaatgaagaa gaagtttgca gatgtatttg caaagaagac 840 gaaggcagag tggtgtcaaa tctttgacgg cacagatgcc tgtgtgactc cggttctgac 900 ttctgaggag gttgttcatc atgatcacaa caaggaacgg ggctcgttta tcaccagtga 960 ggagcaggac gtgagccccc gccctgcacc tctgccgtta aacaccccag ccatcccttc 1020 tttcaaaagg gaccctttca taggagaaca cactgaggag atacttgaag aatttggatc 1080 cagccgcgsa gagatttatc agcttaactc agataaaatc attgaaagta ataaggtaaa 1140 agctagtctc taacttccag gcccacggct caagtgaatt tgaatactgc atttacagtg 1200 tagaataaca cataacattg tatgcacgga aacatggagg aacagcatta cagtgtccta 1260 127691.doc 39- 200815476 ccactctaat caagaaaaga attacagact ctgattctac agtgatgatt gaattctaaa aatggttatc attagggctit Ttgatttata aaactttggg tacttatact aaatt atggt agttattctg ccttccagtt tgcttgatat atttgttgat attaagattc ttgacttata ttttgaatgg gttctagtga aaaaggaatg atatattctt gaagacatcg atatacattt atttacactc ttgattctac aatgtagaaa atgaggaaat gccacaaatt gtatggtgat aaaagtcacg tgaaQcaaaa aaaaaaiasiaa aaassaaskaa adaaaaaaea aaasaaaaaa a &lt; 210 &gt; 108 &lt; 211 &gt; 382 &lt; 212 &gt; protein lease &lt; 213 &gt; al bully &lt;400&gt; 108

Met Ala Leu Gin Gly lie Ser Val Met Glu Leu Ser Gly Leu Ala Pro 1 5 10 15

Gly Pro Phe Cys Ala Met Val Leu Ala Asp Phe Gly Ala Arg Val Val 20 25 30

Arg Val Asp Arg Pro Gly Ser Arg Tyr Asp Val Ser Arg Leu Gly Arg 35 40 45

Gly Lys Arg Ser Leu Val Leu Asp Leu Lys Gin Pro Arg Gly Ala Ala 50 55 .60

Val Leu Arg Arg Leu Cys Lys Arg Ser Asp Val Leu Leu Glu .Pro Phe

65 70 75 80

Arg Arg Gly Val Met Glu Lys Leu Gin Leu*Gly Pro Glu lie Leu Gin 85 9Q 95

Arg Glu Asn Pro Arg Leu lie Tyr Ala Arg Leu Ser Gly Phe Gly Gin 100 105 no

Ser Gly Ser Phe Cys Arg Leu Ala Gly His Asp lie Asn Tyr Leu Ala 115 120 125

Leu Ser Gly Val Leu Ser Lys lie Gly Arg Ser Gly Glu Asn Pro Tyr 130 135 140

Ala Pro Leu Asn Leu Leu Ala Asp Phe Ala Gly Gly Gly Leu Met Cys 145 150 155 160

Ala Leu Gly lie lie Met Ala Leu Phe Asp Arg Thr Arg Thr Asp Lys 165 170 175

Gly Gin Val lie Asp Ala Asn Met Val Glu Gly Thr Ala Tyr Leu Ser 180 185 190

Ser Phe Leu Trp Lys Thr Gin Lys Ser Ser Leu Trp Glu Ala Pro Arg 195 200 205

Gly Gin Asn Met Leu Asp Gly Gly Ala Pro Phe Tyr Thr Thr Tyr Arg 210 215 220

Thr Ala Asp Gly Glu Phe Met Ala Val Gly Ala He Glu Pro Gin Phe 225 230 235 240

Tyr Glu Leu Leu He Lys Gly Leu Gly Leu Lys Ser Asp Glu Leu Pro 245 250 255

Asn Gin Met Ser Met Asp Asp Trp Pro Glu Met Lys Lys Lys Phe Ala 260 265 270

Asp Val Phe Ala Lys -Lys Thr Lys Ala Glu Trp Cys Gin lie Phe Asp 275 280 285

Gly Thr Asp Ala Cys Val Thr Pro Val Leu Thr Phe Glu Glu Val Val 290 295 300

His His Asp His Asn Lys Glu Arg Gly Ser Phe lie Thr Ser Glu Glu 305 310 315 320

Gin Asp Val Ser Pro Arg Pro Ala Pro Leu Leu Leu Asn Thr Pro Ala 40- 1320 1380 1440 1500 1560 1620 1621 127691.doc 200815476

325 330 335 lie Pro Ser Phe Lys Arg Asp Pro Phe He Gly Glu His Thr Glu Glu 340 345 350 lie Leu Glu Glu Phe Gly Phe Ser Arg Glu Glu He Tyr Gin Leu Asn 355 360 365 Ser Asp Lys lie He Glu Ser Asn Lys val Lys Ala Ser Leu 370 375 380 &lt; 210 &gt; 109 &lt; 211 &gt; 1524 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 109 ggcacgaggc tgcgccaggg cctgagcgga ggcgggggca gcctcgccag cgggggcccc gggcctggcc atgcctcact gagccagcgc ctgcgcccct acctcgccga cagctggaac cagtgcgacc tagtggctct cacctgcttc ctcctgggcg tgggctgccg gctgaccccg ggtttgtacc acctgggccg cactgtcctc tgcatcgact tcacggtttt cacggtgcgg ctgcttcaca tcttcacggt, caacaaacag ctggggccca agatcgtcat cgtgagcaag atgatgaagg acgtgttctt cttcctcttc ttccccggcg tgtggctggt agcccatggc gtggccacgg aggggctcct gaggccacgg gacagtgact tcccaagtat cctgcgccgc gtcctctacc gcccctacct gcagatcttc gggcagattc cccaggagga catggacgtg gccctcatgg agcacagcaa ctgctcgtcg;, gagcccggct tctgggcaca cccccctggg gcccaggcgg gcacctgcgt ictcccagtac ^ gccaactiggc tggtggtgct gctcctcgcc atctccctgc tcgtggccaa c atccc- ^ ccg gtcaactcgc tcattgccac gttcagttac acattcggca aagtacaggg caacagcgat ctictaccgga aggcgcagcg ttaccgcctc atccgggaat tccactctcg gcccgcgccg gccccgccct ttatcgtcat cr.cccacttg cgccccctgc ccaggcaatc gcgcaggcga ccccggagcc cccagccqtc ccccccggcc ctcgagcatt tccgggttta cctctctaag gaagccgagc ggaagctgcc aacgtgggaa tcggcgcata aggagaactc tccgctggca cgcgctaggg acaagcgaga gagcgactcc gagcgcctga agcgcacgtc ccagaaggtg gacttggcac tgaaacagcc gggacacatc cgcgagtacg aa.cagcgcct gaaagcgctg gagcgggagg tccagcagtg tagccgcgtc ccggggtggg nggccgaggc cccgagccgc tctgccttgc tgcccccagg tgggccgcca ccccccgacc tgcctgggtc caaagaccga gccctgctgg cggacttcaa ggagaagccc ccacagggga ttttgctcct agagtaaggc tcacctgggc ctcggccccc gcacctggtg gcctcgccct tgaggtgagc cccatgtcca tctgggccac tgtcaggacc acctctggga gtgtcatcct cacaaaccac agcatgcccg gctcccccca gaaccagtcc cagcctggga ggatcaaggc ctggaccccg ggccgttacc catctggagg ctgcagggtc cttggggtaa cagggaccac agacccctca ccactcacag .attcctcaca ctggagaaat aaagccattc cagaggaaaa aaaaaaaaaa 60 120 18Q 240 300 360 420 48a 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1524

U &lt; 210 &gt; 110 &lt; 211 &gt; 3410 - &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 110 gggaaccagc ctgcacgcgc tggctccggg cgacagccgc gcgcctcggc caggatctga gtgacgagac gtgtccccac tgaggcgccc cacagcagca ggtgttgagc atgggctgag aagctggacc ggcaccaaag ggctggcaga aatgggcgcc cggccgattc ctaggcagtt ggcggcagca aggaggagag gccgcagctC ctggagcaga gccgagacga agcagttctg gagtgcctga acggccccct gagccctacc cgectggccc actatggtcc agaggctgtg ggtgagccgc ctgctgcggc accggaaagc ccagctcttg ctggtcaacc tgctaacctt tggcctggag gtgtgtccgg ccgcaggcat cacctacgtg ccgcctccgc tgctggaagt gggggtagag gagaagtcca tgaccatggt gctgggcatt ggtccagtgc tgggcctggt: 60 120 1Θ0 240 300 360 420 480 127691.doc -41 - 200815476

ϋ ctgtgtcccg ctcctaggct cagccagtga ccactggcgt ggacgctatg gccgccgccg gcccttcatc tgggcactgt ccttgggcat cctgctgagc ctctttctca tcccaagggc cggctggcta gcagggctgc tgtgcccgga tcccaggccc ctggagctgg cactgctcat cctgggcgtg gggctgctgg acttctgtgg ccaggtgtgc ttcactccac tggaggccct gctctctgac ctcttccggg acccggacca ctgtcgccag gcctactccg tctatgcctt catgatcagt cttgggggct gcctgggcta cctcctgcct gccattgact gggacaccag tgccctggcc ccctacctgg gcacccagga ggagtgcctc tttggcctgc tcaccctcat cttcctcacc tgcgtagcag ccacactgct ggtggctgag gaggcagcgc tgggccccac cgagccagca gaagggccgt cggccccctc cttgtcgccc cactgctgtc catgccgggc ccgcttggct ttccggaacc tgggcgccct gcttccccgg ctgcaccagc tgtgctgccg catgccccgc accctgcgcc ggctcttcgt ggctgagctg tgcagctgga tggcactcat gaccttcacg ctgttttaca cggatttcgt gggcgagggg ctgtaccagg gcgtgcccag agctgagccg ggcaccgagg cccggagaca ctatgatgaa ggcgttcgga tgggcagcct ggggctgttc ctgcagtgcg ccatctccct ggtcttctct ctggtcatgg accggctggt gcagcgattc ggcactcgag cagtctattt ggccagtgtg gcagctttcc ccgtggctgc cggtgcc aca tgcctgtccc acagtgtggc cgtggtgaca gcttcagccg ccctcaccgg gttcaccttc tcagccctgc agatcctgcc ctacacactg gcctccctct accaccggga gaagcaggtg ttcctgccca aataccgagg ggacactgga ggtgctagca gtgaggacag cctgatgacc agcctcctgc caggccctaa gcctggagct cccttcccta atggacacgt gggtgctgga ggcagtggcc tgctcccacc tccacccgcg ctctgcgggg cccccgcctg tgatgtctcc gtacgtgtgg tggtgggtga gcccaccgag gccagggtgg tcccgggccg gggcatctgc ctggacctcg ccatcctgga tagcgccttc ctgctgtccc aggcggcccc .atccctgttc atgggctcca ttgtccagct cagccagtct gtcactgcct atatggtgr, c tgccgcaggc ctgggtctgg tcgccattta ctttgc.taca caggtagtat ccgacaagac] cgactcggcc aaatactcag cgtagaaaac tcccagcaca ttggggtgga gggcctgcct cactgggccc cagctccccg ctcctgttag ccccatgggg ctaccgggct ggccgccagt ttccgttgct gccaaagtaa tgtggctctc tgctgccacc cr.gtgctgct gaggcgcgza gccgcacagc tgggggctgg ggcgcccctc tcctctctcc ccagtcccca gggccgcccg actggaggcc tcccaagggg gcctcagtct ggacttatac agcgaggcca gaagggctcc atgcaccgga atgcggggac tctgcaggtg gattacccag gcccagggtt aacagctagc ctcctagctg a gacacacct agagaagggt ttttgggagc tgaataaacc cagtcacctg gtttcccatc tctaagcccc ttaacctgca gcttcgttta atgtagcccc cgcacgggag tttctaggat gaaacactcc cccatgggat ttgaacatat gacttatttg caggggaaga gccctgaggg gcaacacaca agaaccaggt cccctcagcc cacagcaccg tccttttgct gatccacccc cctctcacct tttatcagga tgtggcctgt tggtccttcc gccgccatca cagagacaca ggcacttaaa tatttaactt atttatttaa caaagcagaa gggaatccac tgctagcttt tccgcgttgg tgtctaatat ttgggtaggg tgggggaccc ccaacaatca ggtcccctga gatagctggt cattgggctg atcattgcca gaatcccctt ctcctggggc ctggcccccc aaaatgccta acccaggacc ttggaaattc tactcacccc aaacgataat tccaaatgct gtcacccaag gttagggtgt tgaaggaagg tagagggtgg ggcctcaggc ctcaacggct tccctaacca cccctcttct ctcggcccag cctggtcccc cccacttcca ctcccctcta ctctctctag gactgggctg atgaaggcac tgcccaaaac tccccctacc cccaactttc ccctaccccc aactttcccc accagcccca caaccjptgtc gcaggaccag aagcacaaag tgcggtttcc caagcctttg tccatctcag cccccagagt atatctgtgc ttggggaatc ccacacagaa actcaggagc accccctgcc tgagctaagg gaggccctat ctctcagggg tggagctact gggtttaagt gccgtttgca ataatgtcgc cttatttatt tagcggggtg aatatcttat actgtaagtg agcaatcaga gtataatgcc catggtgaca aaattaaagg ccttcttata tgtttaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaara aaaaaaaaaa aaaaaaaaaa aaaaaaataa aadaaadadd 540 600 660 720 780 840 900 960 1020 1080 1140 1200 126Θ 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2 04 0 2100 2160 2220 2280 2340 2400 '2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3410 &lt;210&gt; 111 &lt;211&gt; 1289 &lt;212&gt; DNA &lt;213&gt; Human 127691.doc -42- 200815476 &lt;4〇0&gt; 111

60 120 180 240 300 360 420 480 540 600 660 • 720 780 640 900 960 1020 1080 1140 1200 1260 1289 agccaggcgt ccctctgcct gcccactcag tggcaacacc cgggagctgt tttgtccttt gtggagcctc agcagttccc tctttcagaa ctcactgcca agagccctga acaggagcca ccatgcagtg cttcagcttc attaagacca tgatgatcct cttcaatttg ctcatctttc tgtgtiggtgc agccctgttg gcagtgggca tctgggtgtc aatcgatggg gcatcctttc tgaagatctt cgggccactg tcgtccagtg ccatgcagtt tgtcaacgtg ggctacttcc tcatcgcagc cggcgttgtg gtctttgctc ttggtttcct gggctgctat ggtgctaaga ctgagagcaa gtgtgccctc gtgacgttct tcttcatcct cctcctcatc ttcattgctg aggttgcagc tgctgtggtc gccttggtgt acaccacaat ggctgagcac ttcctgacgt tgctggtagt gcctgccatc aagaaagatt atggttccca ggaagacttc actcaagtgt ggaacaccac catgaaaggg ctcaagtgct gtggcttcac caactatacg gattttgagg actcacccta cttcaaagag aacagtgcct ttcccccatt ctgttgcaat gacaacgtca ccaacacagc caatgaaacc tgcaccaagc aaaaggctca cgaccaaaaa gtagagggtt gcttcaatca gcttttgtat gacatccgaa ctaatgcagt caccgtgggt Ggtgtggcag ctggaattgg gggcctcgag ctggctgcca tgattgtgtc c atgtatctg tactgcaatc tacaataagt ccacttctgc ctctgccact actgctgcca catgggaact gtgaagaggc accctggcaa gcagcagtga ttggggg &amp; gg ggacaggatc taacaatgtc acttgggcca gaatggacct gccctttctg ctccagactt ggggctagat agggaccact ccttttagcg atgcctgact ttccttccat tggtgggtgg atgggtgggg ggcattccag agcctctaag gtagccagtt ctgttgccca ttcccccagt ctattaaacc ctcgatatgc cccctaggcc tagtggtgat cccagtgctc tactggggga tgagagaaag gcattttata gcctgggcat aagtgaaatc agcagagcct; ctgggtggat gtgtagaagg cacttcaaaa cgcataaacc tgttacaatg ttaaaaaaaa aaaaaaaaa &lt;210&gt; 112 &lt;211&gt; 315 &lt;212&gt; Protein goods &lt;213&gt; Human face &lt;400&gt;

Met Val Phe Thr Val Arg Leu Leu His lie Phe. Thr Val Asn Lys Gin 1 5 10 15

Leu Gly Pro Lys lie Val lie Val Ser Lys Met Met Lys Asp Val Phe 20 25 30

Phe Phe Leu Phe Phe' Leu Gly Val Trp Leu Val Ala Tyr Gly Val Ala 35 40 45

Thr Glu Gly Leu Leu Arg Pro Arg Asp Ser Asp Phe Pro Ser lie Leu 50 55 60

Arg Arg Val Phe Tyr Arg Pro Tyr Leu Gin lie Phe Gly Gin lie Pro 65 70 75 80

Gin Glu Asp Met Asp Val Ala Leu Met Glu His Ser Asn Cys Ser Ser 85 90 95

Glu Pro Gly Phe Trp Ala His Pro Pro Gly Ala Gin Ala Gly Thr Cys· 100 105 110

Val Ser Gin Tyr Ala Asn Trp Leu Val Val Leu Leu Leu Val lie Phe 115 120 125

Leu Leu Val Ala Asn lie Leu Leu Val Asn Leu Leu lie Ala Met Phe 130 , 135 140

Ser Tyr Thr Phe Gly Lys Val Gin Gly Asn Ser Asp Leu Tyr Trp Lys .145 150 155 160

Ala Gin Arg Tyr Arg Leu lie Arg Glu Phe His Ser Arg Pro Ala Leu 165 170 175

Ala Pro Pro Phe lie Val lie Ser His Leu Arg Leu Leu Leu Arg Gin 180 185 190

Leu Cys Arg Arg Pro Arg Ser Pro Gin Pro Ser Ser Pro Ala Leu Glu 127691.doc 43- 200815476 195 200 205

His Phe Arg Val Tyr Leu Ser Lys Glu Ala Glu Arg Lys Leu Leu Thr 210 215 220

Trp Glu Ser Val His Lys Glu Asn Phe Leu Leu Ala Arg Ala Arg Asp 225 230 235 240

Lys Arg Glu Ser Asp Ser Glu Arg Leu Lys Arg Thr Ser Gin Lys Val 245 250 255

Asp Leu Ala Leu Lys Gin Leu Gly His lie Arg Glu Tyr Glu Gin Arg 2G0 265 270

Leu Lys Val Leu Glu Arg Glu Val Gin Gin Cys Ser Arg Val Leu Gly 275 280 285

Trp Val Ala Glu Ala Leu Ser Arg Ser Ala Leu Leu Pro Pro Gly Gly 290 295 300

Pro Pro Pro Pro Asp Leu Pro Gly Ser Lys Asp 305 310 315 &lt;210&gt; 113 &lt;211&gt; 553 • &lt;212&gt; Protein &lt;213&gt;People &lt;40Q&gt; 113 ..

Met Val Gin Arg Leu Trp Val Ser Arg Leu Leu Arg His Arg Lys Ala 1 5 10 * 15

Gin Leu Leu Leu Val Asn Leu Leu Thr Phe Gly Leu Glu Val Cys Leu 2a 25 30

Ala Ala Gly lie Thr Tyr Val Pro Pro Leu Leu Leu Glu Val Gly Val 35 40 45

Glu Glu Lys Phe Met Thr Met Val Leu Gly lie Gly Pro Val Leu Gly 50 5S 60

Leu Val Cys Val Pro Leu Leu Gly Ser Ala Ser Asp His Trp Arg Gly 65 70 75 Θ0 ·

Arg Tyr Gly Arg Arg Arg Pro Phe He Trp. Ala Leu Ser Leu Gly lie 85 90 95

Leu Leu Ser Leu Phe Leu He Pro Arg Ala Gly Trp Leu Ala Gly Leu 100 105 110

Leu Cys Pro Asp Pro Arg Pro Leu Glu Leu Ala Leu Leu lie Leu Gly 115 120 125

Val Gly Leu Leu Asp Phe Cys Gly Gin Val Cys Phe Thr Pro Leu Glu 130 135 140

Ala Leu Leu Ser Asp Leu Phe Arg Asp Pro Asp His Cys Arg Gin Ala 145 150 155 160

Tyr Ser Val Tyr Ala Phe Met lie Ser Leu Gly Gly Cys Leu Gly Tyr 165 170 175

Leu Leu Pro Ala lie Asp Trp Asp Thr Ser Ala Leu Ala Pro Tyr Leu 180 185 190

Gly Thr Gin Glu Glu Cys Leu Phe Gly Leu Leu Thr Leu lie Phe Leu 195 ^ 200 205

Thr Cys Val Ala Ala Thr Leu Leu Val Ala Glu Glu Ala Ala Leu Gly 210 215 220

Pro Thr Glu Pro Ala Glu Gly Leu Ser Ala Pro Ser Leu Ser Pro His 225 230 235 240

Cys Cys Pro Cys Arg Ala Arg Leu Ala Phe Arg Asn Leu Gly Ala Leu 245 250 255

Leu Pro Arg Leu His Gin Leu Cys Cys Arg Met Pro Arg Thr Leu Arg 127691.doc 44- 200815476 260 265 270

Arg Leu Phe Val Ala Glu Leu Cys Ser Trp Met Ala Leu Met Thr Phe 275 280 285

Thr Leu Phe Tyr Thr Asp Phe Val Gly Glu Gly Leu Tyr Gin Gly Val 290 295 300

Pro Arg Ala Glu Pro Gly Thr Glu Ala Arg Arg His Tyr Asp Glu Gly 305 310 315 320

Val Arg Met Gly Ser Leu Gly Leu Phe Leu Gin Cys Ala L Le Ser Leu 325 330 335

Val Phe Ser Leu Val Met Asp Arg Leu Val Gin Arg Phe Gly Thr Arg 340 345 350

Ala Val Tyr Leu. Ala. Ser Val Ala Ala Phe Pro Val Ala Ala Gly Ala 355 * 360 365

Thr Cys Leu Ser His Ser Val Ala Val Val Thr Ala Ser Ala Ala Leu 370 375 380

Thr Gly Phe Thr Phe Ser Ala Leu Gin He Leu Pro Tyr Thr Leu Ala 385 390 395 400

Ser Leu Tyr His Arg Glu Lys Gin Val Phe Leu Pro Lys Tyr Arg Gly 405 410 415

Asp Thr Gly Gly Ala Ser Ser Glu Asp Ser Leu Met Thr Ser Phe Leu 420 425 430

Pro Gly Pro Lys Pro Gly Ala Pro Phe Pro Asn Gly His Val-Gly Ala 435 440 445

Gly Gly Ser Gly Leu Leu Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro

Ala Cys Asp Val Ser Val Arg Val Val Val Gly Glu Pro Thr Glu Ala 465 470 475 480

Arg Val Val Pro Gly Arg Gly lie Cys Leu Asp Leu Ala lie Leu Asp 4B5 490 495

Ser Ala Phe Leu Leu Ser Gin Val Ala Pro Ser Leu Phe Met Gly Ser 5 00 - - ~ -....... 505 510 lie Val Gin Leu Ser Gin Ser Val Thr Ala Tyr Met Val Ser Ala Ala 515 520 525

Gly Leu Gly Leu Val Ala He Tyr Phe Ala Thr Gin Val Val Phe Asp 530 535 540

Lys Ser Asp Leu Ala Lys Tyr Ser Ala 545 550 &lt;210&gt; 114 &lt;211&gt; 241 &lt;212&gt; Protein &lt;213&gt;People &lt;400&gt;

Met Gin Cys Phe Ser Phe lie Lys Thr Met Met lie Leu Phe Asn Leu 1 5 10 15

Leu lie Phe Leu Cys Gly Ala Ala Leu Leu Ala Val Gly lie Trp Val 20 25 30

Ser lie Asp Gly Ala'Ser Phe Leu Lys He Phe Gly Pro Leu Ser Ser 35 40 45

Ser Ala Mec Gin Phe Val Asn Val Gly Tyr Phe Leu lie Ala Ala Gly 50 55 60

Val Val Val Phe Ala Leu Gly Phe Leu Gly Cys Tyr Gly Ala Lys Thr 65 70 75 80

Glu Ser Lys Cys Ala Leu Val Thr Phe Phe Phe lie Leu Leu Leu lie 127691.doc 45- 200815476 85 90 95 Phe He Ala Glu Val Ala Ala Ala Val Val Ala Leu Val Tyr Thr Thr 100 105 110 Met Ala Glu His Phe Leu Thr Leu Leu Val Val Pro Ala lie Lys Lys 115 120 125 Asp Tyr Gly Ser Gin Glu Asp Phe Thr Gin Val Trp Asn Thr Thr Met 130 135 140 Lys Gly Leu Lys Cys Cys Gly Phe Thr Asn Tyr Thr Asp Phe Glu Asp 145 150 155 ISO Ser Pro Tyr Phe Lys Glu Asn Ser Ala Phe Pro Pro Phe Cys Cys Asn 165 170 175 Asp Asn Val Thr Asn Thr Ala Asn Glu Thr Cys Thr Lys Gin Lys Ala 180 185 190 His Asp Gin Lys Val Glu Gly Cys Phe Asn Gin Leu Leu Tyr Asp lie 195 200 205 Arg Thr Asn Ala Val Thr Val Gly Gly Val Ala Ala Gly He Gly Gly 210 215 220 Leu Glu Leu Ala Ala Met lie Val Ser Met Ίγτ Leu Tyr Cys Asn Leu 225 230 235 240 Gin

&Lt; 210 &gt; 115 &lt; 211 &gt; 366 .- &lt; 212 &gt; DNA .. &lt; 213 &gt; al crop-* &lt; 400 &gt; 115 gctccttctc tcccctcctc tgaatttaat tctttcaacc tgcaatttgc aaggattaca catttcaccg tgatgtatat tgtgttgcaa aaaaaaaaaa gtgtctttgt ttaaaattac ttggtttgtg aacccatctt gctttttccc cattggaact agtcattaac ccatctctga actggtagaa aaacatctga agagctagtc tatcagcatc tgacaggtga attggatggt cctcagaacc atttcaccca gacagcctgt ttctatcctg tttaataaat tagtttgggt tctctacatg cataacaaac cctgctccaa tctgtcacat aaaagtctgt gacttgaagt tcagtc &lt; 210 &gt;. 116 &lt; 211 &gt; 282 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 220 &gt; &lt; 221 &gt; misc_ wherein &lt;222&gt; (1)...(282) _ &lt;223&gt; n = A, T, C or G &lt;400&gt; 116 acaaagacga accatttcct atattatagc aaaattaaaa tctacccgta ttetaatact gagaaatgag atnaaacaca atnttataaa gtctacttag agaagatcaa gtgacctcaa agactttact attttcatat tttaagacac atgatttatc ctattttagt aacctggttc atacgttaaa caaaggataa Tgtgaacagc agagaggatt tgttggcaga aaatctatgt tcaatctnga actatctana tcacagacat ttctattcct tt &lt;210&gt; 117 &lt ;211&gt; 305 60 120 180 240 300 360 366 60 120 180 240 282 127691.doc 46 - 200815476 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc 1. feature &lt;222&gt; (1).7.(305) &lt;223&gt; n = A, T, C or G &lt;400&gt; 117 acacatgtcg cttcactgcc ttcttagatg cttctggtca acatanagga acagggacca 60 tatttatcct ccctcctgaa acaattgcaa aataanacaa aatatatgaa acaattgcaa 120 aataaggcaa aatatatgaa acaacaggtc tcgagatatt ggaaatcagt caatgaagga 180 tactgatccc tgatcactgt cctaatgcag gatgtgggaa acagatgagg tcacctctgt 240 gactgcccca gcttactgcc tgtagagagt ttctangctg cagttcagac agggagaaat 300 tgggt 305 &lt; 210 &gt; 118 &lt; 211 &gt; 71 &lt; 212 &gt; DNA &lt; 213 &gt; human

&lt;220&gt;&lt;221>misc_:Special desire- &lt;222&gt;(1)...(71&gt;One&lt;223&gt; n = A, T, C or G a &lt;400&gt; 118 accaaggtgt ntgaacccct gacgtgggga tctctgattc ccgcacaatc tgagtggaaa 60 aanccctggg t 71 &lt;210&gt; 119 . &lt;211&gt; 212 &lt;212&gt; DNA &lt;213&gt; Human 颏. &lt;220&gt;&lt;221&gt; misc_ gas contending &lt;222&gt; (1).7..(212) &lt;;223&gt; n » A, T, C or G &lt;400&gt; 119 actccggttg gtgtcagcag cacgtggcat tgaacatngc aatgtggagc ccaaaccaca 60 gaaaatgggg tgaaattggc caactttcta tnaacttatg ttggcaantt tgccaccaac 120

Agtaagctgg cccttctaat aaaagaaaat tgaaaggttt ctcaccaanc ggaactaant 180 aatggancca aganactccc aggcctcagc gt 212 &lt;210&gt; 120 &lt;211&gt; 90 ^ &lt;212&gt; DNA 'human &lt;220&gt;

&lt;221&gt; misc-characteristic &lt;222&gt; (1).7.(90) &lt;223&gt; n = A, T, C or G 47- 127691.doc 200815476

&lt;400&gt; 120 actcgttgca natcaggggc cccccagagt caccgttgca ggagtccttc tggtcttgcc ctccgccggc gcagaacatg ctggggtggt &lt;210&gt; 121 &lt;211&gt; 218 &lt;212&gt; DNA &lt;213&gt; Human face.·&lt;220&gt;&lt;221&gt;misc-feature&lt;; 222 &gt; ⑴ ... (218} &lt; 223 &gt; n = A, T \ C or G &lt; 400 &gt; 121 tgtancgtga anacgacaga nagggt-tgtc aaaaatggag aanccttgaa gtcattttga gaataagatt tgctaaaaga tttggggcta aaacatggtt attgggagac atttctgaag atatncangt aaattangga atgaactcat ggttcttttg ggaattcctt tacgatngcc agcatanacc tcatgtgggg atancagcta cccttgta _ . &lt;210&gt; 122 -&lt;211&gt; 171 &lt;212&gt; DNA , - &lt;213&gt; Human &lt;400&gt; 122 tagaggtgta tgcaactgta aggacaaaaa tcgagactca actggcttaa ccaataaagg cacccgccag ctcatggaac aggaagtcgg atggtggggc atcttcagtg ctgcatgagt caccaccccg gcggggtcat ctgtgccaca ggtccctgtt gacagtgcgg t &lt;210&gt; 123 &lt;211&gt; 76 &lt;212&gt; DNA &lt;213 &gt; Person's amount &lt;220&gt;&lt;221&gt; miscjm &lt;222&gt; (1) (76) &lt;223&gt; n « A#T, C or G &lt;400&gt; 123 tgtagcgtga agacna caga atggtgtgtg ctgcgctatc caggaacaca tttattatca ttatcaanta ttgtgt &lt; 210 &gt; 124 &lt; 211 &gt; 131 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 124 · acctttcccc aaggccaatg tcctgtgtgc taactggccg gctgcaggac agctgcaatt caatgtgctg ggtcatatgg aggggaggag actctaaaat agccaatttt attctcttgg ttaagatttg t 60 90 60 120 180 218 60 120 171 60 76 60 120 131 127691.doc 48- 200815476 &lt;210&gt; 125 &lt;211&gt; 432 &lt;212&gt; DNA &lt;213&gt;Human* &lt;400&gt; 125 actttatcta ctggctatga aatagatggt ggaaaattgc gttaccaact ataccactgg 60 cttgaaaaag aggtgatagc tcttcagagg acttgtgact tttgctcaga tgctgaagaa 120. ctacagtctg catttggcag aaatgaagat gaatttggat taaatgagga tgctgaagat i8〇ttgcctcacc aaacaaaagt: gaaacaactg agagaaaatt ttcaggaaaa aagacagtgg 24 0 ctcttgaagt atcagtcact tttgagaatg tttcttagtt actgcatact: tcatggatcc 300 catggtgggg gtcttgcatc tgta ^ gaatg gaattgattt tgcttttgca agaatctcag 360 caggaaacat cagaaccact attttctagc cctctgtcag agcaaacctc agtgcctctc 420 ctctttgctt Gt 4 32^. &lt;210&gt; 126 &lt;211&gt; 1 12 &lt;212&gt; DNA &lt;213>human &lt;400&gt; 126 acacaacttg aacagcaaaa tagaaactga gctgaaattt ctaatfcact ttctaaccat 60

Agcaagaatg acatttcccc ccagggatca ccaaatattt ataaaaattt gt 112 &lt;210&gt; 127 ..

&lt;211&gt; 54 &lt;212&gt; DNA &lt;213&gt;Human&lt;400&gt; 127 accacgaaac cacaaacaag atggaagcat caatccactt gccaagcaca gcag 54 &lt;210&gt; 128 &lt;211&gt; 323 &lt;212&gt; DNA &lt;213&gt; 400 &gt; 128 acctcactag taattgctct gttgtttcat ttttttctaa tgtctcccct ctaccagctc 60 acctgagata acagaacgaa aatggaagga cagccagatt tctcctttgc tctctgctca 120 ttctctccga agcctaggtt acccattttg gggacccatt ataggcaata aacacagttc 180 ccaaagcatc tggacagttt cttgttgtgt tttagaatgg ttttcctttt tcttagcctt 240 ttcctgcaaa aggctcactc agtcccttgc ttgctcagtg gactgggctc cccagggcct 300 aggctgcctt cctttccatg tcc 323 &lt;. 210 &gt; 129 &lt;211&gt; 192 &lt;212&gt; DNA . &lt;213&gt;People&lt;220&gt;&lt;221&gt; misc_ tribute &lt;222&gt; (1).7.(192)

&lt;223&gt; n = A, D, C or G 49- 127691.doc 200815476 &lt;400&gt; 129 acatacatgt gtgtatattt ttaaatatca cttttgtatc actctgactt tttagcatac 60 tgaaaacaca ctaacataat ttntgtgaac catgatcaga tacaacccaa atcattcatc 120 tagcacattc atctgtgata naaagatagg tgagtttcat ttccttcacg ttggccaatg 180 gataaacaaa gt 192 &lt;210&gt; 130 &lt;211&gt; 362 &lt;212&gt; DNA &lt;213>human-. &lt;220&gt;

&lt;221&gt;misc··特欲&lt;222&gt; (1).7.(362) &lt;223&gt; n = A, T, C or G &lt;400&gt; 130 ccctttttta tggaatgagt agactgtatg tttgaanatt tanccacaac ctctttgaca 60 tataatgacg caacaaaaag Gtgctgttta gtcctatggt ccagtttatg cccctgacaa 120 gtttccattg tgttttgccg atcttctggc taatcgtggt atcctccatg ttattagtaa 180 ttctgtattc cattttgtta acgcctggta gatgtaacct gct'dngaggc taactttata 240 Ο

Cttacttaaa agctcttatt ttgtggtcat taaaatggca atttatgtgc agcactttat 300 tgcagcagga agcacgtgtg ggttggttgt aaagctcttt gctaatctta aaaagtaatg 360 gg 362 &lt;210&gt; 131 •&lt;211&gt; 332 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt;&lt;222&gt; (1).7.(332) &lt;223&gt; n = A, T, C or G &lt;400&gt; 131 cctcccgaaa gatcgtgtcc actcctgtgg acatcctgct ttaatggagt ttcccatgca 60 gtangactgg tatggttgca gctgtccaga taaaaacatt tgaagagctc caaaatgaga 120 gtcctcccag gttcgccctg ctgctccaag tctcagcagc agcctctttt aggaggcatc 180 ttctgaacta gattaaggca gcttgtaaat ctgatgtgat ctggtttatc atccaactaa 240 cttccatctg ctatcactgg agaaagccca gactccccan gacnggtacg gattgtgggc 300 atanaaggat'tgggtgaagc tggcgttgtg gt 332 &lt; 210 &gt; 132 &lt; 211 &gt; 322 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 220 &gt; &lt; 221 &gt; Misc— &lt;222&gt; (1).7.(322)

&Lt; 223 &gt; n * A, T, C or G &lt; 400 &gt; 132 actttcgcca tcttgtatat ataaacaatc ttgggacatt ctcctgaaaa ctaggtigtcc 60 50- 127691.doc 200815476 agtggctaag agaactcgat ttcaagcaat tctgaaagga aaaccagcat gacacagaat 120 ctcaaattcc caaacagggg ctctgtggga aaaatgaggg aggacctttg tatctcgggt 180 tttagcaagt taaaatgaan atgacaggaa aggcttattt atcaacaaag Agaagagttg 240 ggatgcttct aaaaaaaact ttggtagaga aaataggaat gctnaatcct agggaagcct 300 gtaacaatct acaattggtc ca 322

&lt;210&gt; 133 &lt;211&gt; 278 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1).7. (278) &lt;223&gt; n = A , T, C or G Ο &lt; 400 &gt;. 133 acaagccttc acaagtttaa ctaaattggg attaatcttt ctgtanttat ctgcataatt 60 cttgtttttc tttccatctg gctcctgggt tgacaatttg tccattgcta 120 ccatttaaaa aaaatcacaa atctttccct ttaagctatg ttnaattcaa actattcctg 180 ctattcctgt tttgtcaaag aaattatatt tttcaaaata tgtncatttg ttcgatgggt 240 cccac ^ aaac actaataaaa accacagaga ccagcctg 278 ϋ tggaaacaac

&lt;210&gt; 134 ·- &lt;211&gt; 121 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;&lt;221&gt; misc__ &lt;222&gt; (1).7.(121) &lt;223&gt; n = A, TrC or G &lt;400&gt; 134 ' gtttanaaaa cttgtttagc tccatagagg aaagaatgtt aaactttgta ttttaaaaca 60 tgattccccg aggttaaact tggctttcaa atgttatctt tacctgtatt ttgcct:r.tgg 120 t 121 &lt;210&gt; 135 &lt;211&gt; 350 &lt;212&gt; DNA &lt;213&gt;Human&lt;220&gt;&lt;221&gt;misc_.Desire&lt;222&gt; (1) .7. (350) &lt;223&gt; n * A, T, C or G &lt;400&gt; 135 - acttanaacc acgcctagca catcagaatc cctcaaagaa catcagcata atcctatacc 60 atancaagcg gtgactggtt aagcgtgcga caaaggtcag ctggcacatt acttgtgtgc 120 aaactcgaca cttttgttct aagtaggaac tagtatacag tncctaggan tggtactcca 180 gggtgccccc caactcctgc agccgctcct ctgtgccagn ccctgnaagg aactttcgct 240 ccacctcaat caagccctgg gccatgctac ctgcaattgg ctgaacaaac gtttgctgag 300 ttcccaegga tgcaaagcct ggcgctcaac tcctggggcg tcaactcagt 350 127691.doc -51 - 200815476 &lt; 210 &gt; 136 &lt;211&gt; 399 &lt;212&gt; DNA &lt;213&gt; Human & l t;220&gt;

&lt;221&gt;misc-feature&lt;222&gt; (1)····(399) &lt;223&gt; η = A, T, C or G &lt;400&gt; 136 tgtaccgtga agacgacaga agttgcatgg cagggacagg gcagggccga ggccagggtt 60 gctgtgattg tatccgaata ntcctcgtga gaaaagataa tgagatgacg tgagcagcct 120 gcagacttgt gtctgccttc aanaagccag acaggaaggc cctgcctgcc ttggctctga · .180 cctggcggcc agccagccag ccacaggtgg gcttcttcct tttgtggtga caacnccaag 240 aaaactgcag aggcccaggg tcaggtgtna gtgggcangt * gaccataaaa caccaggtgc 300 tcccaggaac ccgggcaaag gccatcccca cctacagcca gcatgcccac tggcgtgatg 360 ggtgcagang gatgaagcag ccagntgttc tgctgtggt 399 &lt; 210 &gt; 137 &lt; 211 &gt; 165

&lt;212&gt; DNA * * &lt;213&gt; Human - &lt;220&gt;--&lt;221&gt; mi sc - feature &lt;222&gt; (1)··. (165)

. &Lt; 2 2 3 &gt; n = A, T, C or G &lt; 40Q &gt; 137 actggtgtgg tngggggtga tgctggtggt anaagttgaa gtgacttcan gatggtgtgt 60 ggaggaagtg tigtgaiacgtia gggatgtaga ngtcttggcc gtgctaaatg agcttcggga 120 ttggccggtc ccactggtgg tcactgtcac tggtggggtt cctgt · 165 &lt; 210 &gt; 138 &lt;211&gt; 338 . &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;&lt;221&gt; misc_ tribute &lt;222&gt; (1).7.(338)

&Lt; 223 &gt; n * A, T, C or G ϋ &lt; 400 &gt; 138 actcactgga atgccacatt cacaacagaa tcagaggtct gtgaaaacat taatggctcc 60 ttaacttctc cagtaagaat cagggacttg aaatggaaac gttaacagcc acatgcccaa 120 tgctgggcag tctcccatgc cttccacagt gaaagggcct gagaaaaatc acatccaatg 180 tcatgtgttt ccagccacac caaaaggtgc ttggggtgga gggctggggg catananggt 240 cangcctcag gaagcctcaa gttccactca Gctttgccac tgtacattcc ccatntttaa 300 aaaaaccgat gccttttttt tttttttttg taaaattc 338 &lt;210&gt; 139 &lt;211&gt; 382 127691.doc 52- 200815476

&Lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 139 gggaatcttg gtttttggca tctggtttgc ctatagccga ggccactttg acagaacaaa gaaagggact tcgagtaaga aggtgattta cagccagcct agtgcccgaa gtgaaggaga attcaaacag acctcgtcat tcctggtgtg agcctggtcg gctcaccgcc tatcatctgc atttgcctta ctcaggtgct accggactct ggcccctgat gtctgtagtt tcacaggatg ccttatttgt cttctacacc ccacagggcc ccctacttct tcggatgtgt ttttaataat gtcagctatg tgccccatcc tccttcatgc cctccctccc tttcctacca Ctgctgagtg gcctggaact tgtttaaagt gt &lt;210&gt; 140 · &lt;211&gt; 200 &lt;212&gt; DNA &lt;213&gt;Human&lt;220&gt;&lt;221&gt; misc one particular desire. &lt;222&gt; (1)·:·(200 ) &lt; 223 &gt; n * A, T, C or G &lt; 400 &gt; 140 ·· * accaaanctt ctttctgttg tgttngattt tactataggg gtttngcttn ttctaaanat actcttcatc taacancttt tgttaagtgt caggctgcac ttcgctccat anaattattg tcctcacatt tcaacttgta tgtgtttgtc tcttanagca tcggtgaaat cacatatttt atatccagca taaaggagaa • &lt; 210 &gt; 141 &lt;211&gt; 335 &lt;212&gt; DNA &lt;213&gt; Human · . &lt;220&gt;&lt;221&gt; misc__ Special Education &lt;222&gt; . (1) .7 {335) &lt; 223 &gt; n = A, T, C or G &lt; 400 &gt;. 141 actccatccc caaaacactc atatgttgca aaaaacacat agaaaaataa agtttggtgg gggtgctgac taaacttcaa gtcacagact tttatgtgac agattggagc agggtttgtt acgcatgtag agaacccaaa ctaatctact aaacaggata gaaacaggct gtctgggtga aatggttctg agaaccatcc aattcacctg tcagatgctg Atanactagc tcttcagatg tttttctacc agttcagaga tnggttaatg actanttcca atggggaaaa agcaagacgg attcacaaac caagtaattt taaacaaaga cactt . &lt;210&gt; 142 &lt;211&gt; 459 &lt;212&gt; DNA human 60 120 180 240 300 360 382 60 120 180 200 60 120 180 240 300 335

&lt;220&gt;&lt;221&gt; misc__ feature. &lt;222&gt; {1).7.(459) &lt;223> n = A, T, C or G 127691.doc 53- 200815476 &lt;400&gt; 142 accaggttaa tattgccaca tatatccttt ccaattgcgg gctaaacaga cgtgtattta 60 gggttgttta aagacaaccc agcttaatat caagagaaat tgtgaccttt catggagtat 120 ctgatggaga aaacactgag ttttgacaaa tcttatttta ttcagatagc agtctgatca 180 cacatggtcc aacaacactc aaataataaa tcaaatatna tcagatgtta aagattggtc 240 ttcaaacatc atagccaatg atgccccgct tgcctataat ctctccgaca taaaaccaca 300 tcaacacctc agtggccacc aaaccattca gcacagcttc cttaactgtg agctgtttga 360 agctaccagt ctgagcacta ttgactatnt ttttcangct ctgaatagct ctagggatct 420 cagcangggt gggaggaacc agctcaacct Tggcgtant 459

&lt;210&gt; 143 &lt;211&gt; 140 &lt;212&gt; DNA &lt;213 &gt; shemale, &lt;400&gt; 143 acatttcct.t ccaccaagtc aggactcctg gcttctgtgg gagttcttat cacctgaggg 60 aaatccaaac agtctctcct agaaaggaat agtgtcacca accccaccca tctccctgag 120 accatccgac ttccctgtgt 140 &lt;210&gt ; 144 &lt;211&gt; 164 ·* ·

ϋ &lt;212&gt; DNA &lt;213&gt;Person&lt;220&gt;&lt;221&gt; misc-feature &lt;222&gt; (1) (164)

&lt;223&gt; n = Α,Τ/CG &lt;400&gt; 144 acttcagcaa caacatacaa taacaacatt aagtgcacat tgccatcttt gtcattttct 60 atctatacca ctctcccttc tgaaaacaan aatcactanc caatcactta tacaaatttg 120 •aggcaattaa tccatatttg ttttcaataa ggaaaaaaag atgt 164 &lt;210&gt; 145 &lt;21X&gt; 303 &lt;212&gt ; DNA &lt;213&gt; Person &lt;220&gt;&lt;221&gt; misc_: Feature &lt;222&gt; (1) (303) &lt;223&gt; η * A, T, C or G · &lt;400&gt; acgtagacca tccaactttg tattcgtaat ggcaaacatc cagnagcaat tcctaaacaa 60 actggagggt atttataccc aattatccca titcattaaca tgccctcctc ctcaggctat 120 gcaggacagc tatcataagt cggcccaggc atccagatac taccatttgt ataaacttca 180 gtaggggagt ccatccaagt gacaggtcta atcaaaggsg gaaatggaac ataagcccag 240 tagtaaaatn ttgcttagct gaaacagcca caaaagactt accgccgtgg tgattaccat 300 caa 303 &lt; 210 &gt; 146 -54- 127691.doc 200815476 &lt;211&gt; 327 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc_: feature &lt;222&gt; (1) (327) &lt;223&gt; n * or G o 6 2 8 4 0 1 1 2 .3 &lt;40〇3 actgcagctc actggcctgg ccaagtcagg cctgaacagg agacttgccc taggggtgag 146 aattagaagt agtgactcat gctgggattt gagggtggga ctgggcctgt ctgtgtgact ggtctctgac tgqtctggtt gtttcctttc ggagccagca cacacctact ctatggt, tttcatcanc ggttgagaga cacattctag tggaacaagc gatgaccttc ttctccctgg gctcctttgc caacaatatg tgccactttc tgtgcctgca gctccatgac caacaggcct ctggccactt taaagtagcc ggatggaatg &lt; 210 &gt; 147 &lt; 211 &gt; 173 &lt; 212 &gt; DNA &lt; 213 &gt; shall o &lt;220&gt;

&lt;221&gt;misc-feature&lt;222&gt; (1) (173) &lt;223&gt; n = W or G &lt;400&gt; 147 0 0 3 6 2 7 acattgttitt tttgagataa agcattgana gagctctcct taacgcgaca caatggaagg actggaacac atacccacat ctttgttctg agggataatt· ttctgataaa gtcttgccgt atattcaagc Acacatgtta tatattattc agttccatgt ttacagccta get

&lt;210&gt; 148 &lt;211&gt; 477 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc_feature &lt;222&gt; (1). T. (477) &lt;223&gt; n * * A, T, C or G o &lt; 400 &gt; acaaccactc atgggacata gccccactac gtggtcctag nccancccac tagattatnt caccactggc ccaggcacag 148 tatctcatcg ttatttgatg ctgctgcaat tggccatcag ctcaccgacc ccaaattcag aagccttctc gctacctcat aatttttaac ctccatttca aatcacattc tccangcctg ccatcctctt tcaattaagt cagccaacac cttcacaatc ccaaactcac tcacacatat ccttcctgtc caccttgagc acacagctac tactattaac acacacacac acccctttaa tcactgtgcc atga ^ taata Ctgaccctga ccctgagctc ctccttgctc actctacccg acacncacac ttaccatgct tttccatcct cacccatact: agccattggg cattgctcac tctaacccca acatgtccag acacacatat atggtgg 00000007 62840627

&lt;210&gt; 149 &lt;211&gt; 207 &lt;212&gt; DNA 127691.doc 55- 200815476 &lt;213 &gt; human effect &lt;400&gt; 149 acagttgtat tataatatca agaaataaac ttgcaatgag agcatttaag agggaagaac 60 taacgtactt tagagagcca aggaaggttt ctgtggggag tgggatgtaa ggtggggcct 120 gatgataaat aagagtcagc caggtaagtg Ggtggtgtgg tatgggcaca gtgaagaaca 180 tttcaggcag agggaacagc agtgaaa 207 &lt;210&gt; 150 &lt;211&gt; 111 &lt;212&gt; DNA &lt;213 &gt; human. &lt;220&gt;., &lt;221>misc&lt;222&gt; (1 ) . . . (111)

&lt;223&gt; n = A, T, C or G &lt;400&gt; 150 accttgatct cattgctgct ctgatggaaa cccaactatc taatttagct aaaacatggg 60 cactcaaatg tggtcagtgt ttggacttgt taactantgg catctttggg t ill

&lt;210&gt; 151 &lt;211&gt; 196 ··

&Lt; 212 &gt; DNA &lt; 213: &gt; al Europium &lt; 400 &gt; 151 agcgcg'gcag gtcatattga acattccaga tacctatcat tactcgatgc tgttgataac 60 agcaagatgg cttcgaactc agggccacca ccagctattg gaccttacta tgaaaaccac 120 ggataccaac cggaaaaccc- ctatcccgca cagcccactg tggtccccac tgtctacgag 18 0 gtgcatccgg ctcagt 196 &lt;.210&gt; 152 &lt;211&gt; 132.

&lt;212&gt; DNA &lt;213&gt; Person no. &lt;400&gt; 152 acagcactct cacatgtaag aagggagaaa ttcctaaatg taggagaaag ataacagaac 60 ctcccccttt tcatctagtg gtggaaaccfgatgctttat gttgacagga atagaaccag 120 gagggagttt gt 132 &lt;210&gt; 153

&lt;211&gt; 285 ** &lt;212&gt; DNA &lt;213&gt;People &lt;220&gt;&lt;221&gt; mi sc-feature &lt;222&gt; (1) (285)

&Lt; 223 &gt; n »A, T, C or G &lt; 400 &gt; 153 acaanaccca nganaggcca ctggccgtgg tgtcatggcc tccaaacacg aaagtgticag 56- 127691.doc 200815476 cttctgctct tatgtcctca tctgacaact ctttaccatt tttatcctcg ctcagcagga 120 gcacatcaat aaagtccaaa gtcttggact tggccctggc ttggaggaag tcatcaacac iq〇cctggctsgt gagggtgcgg cgccgctcct ggatgacggc atctgtgaag tcgtgcacca 240 gtctgcaggc cctgtggaag cgccgtccac acggagtnag gaatt 285 &lt; 210 &gt; 154 &lt; 211 &gt; 333 &lt; 212 &gt; DNA &lt; 213 &gt; • al chin &lt; 400 &gt; 154 accacagtcc tgttgggcca gggcttcatg accctttctg tgaaaagcca tattatcacc 60 accccaaatt tttccttaaa * tatcttcaac tgaaggggtc agcctcttga ctgcaaagac 120 cctaagccgg ttacacagct aactcccact ggccctgatt tgtgaaattg ctgctgcctg i8〇attggcacag gagtcgaagg tgttcagctc ccctcctccg tggaacgaga ctctgatttg -2¾0 agtttcacaa attctcgggc cacctcgtca ttgctcctct gaaataaaat ccggagaatg 3〇〇gtcaggcctg tctcatccat atggatcttc egg 333 &lt; 210 &gt; 155 &lt; 211 &gt; 308 &lt; 212 &gt; DNA &lt; 2U &gt; human

&lt;220&gt;&lt;221&gt; mi§C:_ feature &lt;222&gt; (1).7.(308)

n * A, T, C or G &lt; 400 &gt;. 155 accggaaata ataaaaccca catcacagcg tcgtgtcaaa gatcatcagg gcatggatgg 60 gaaagtgctt cgggaactgt aaagcgccta acacatgatc gatgattttt gttataatat 120 ccgaaccacg gtgcatacaa actctcctgc ccgctcctcc tgggccccag ccccagccce 180 atcacagccc accgctctgt tcacccaggc ccagcatgta gtggccgatc cctcttggct 240 gcccttagcc cccanaagtc tetetgaage caaccaaacc tctangtgta aggeatgetg 300 gccctggt 30Θ &lt; 210 &gt; 156 &lt; 211 &gt; 295 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 156 accttgctcg gtgcttggaa cataccagga actcaaaata tgagatgata acagtgccta 60 ttatcgacta ccgagagaac tgtcagacac tcagttgaag accttctaca caggaactga 120 gaataggaga ttatgtccgg ccctcatatc ccctcctacc ccccttgcct cattctatgt 180 ctaatatatt cccaatcaaa Taaggttagc acaaccagga aatcgaccaa ataccaatat 240 aaaaccagac gtctatcctt aagaccccca aatagaaaac aaactaacag actat 295 &lt;210&gt; 157 ' &lt;211&gt; 126 &lt;212&gt; DNA &lt;213&gt;human&lt;400&gt; 157 acaagtttaa atagtgctgt cactgtgcat gegetgaa^t gtgaaatcca ccacattcct 60 57- 127691 .doc 200815476

Gaagagcaaa acaaattctg tcatgtaatc tctatcttgg gtcgtgggta tatctgtccc 120 cttagt 12S &lt;210&gt; 158 &lt;211&gt; 442 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt; · &lt;221&gt; misc--expressive &lt;222&gt; (1) ... (442) &lt; 223 &gt;. n - A, T, C or &lt; 400 &gt; 158 acccactggt cttggaaaca cccatcctta atacgatgat ttttctgtcg tgtgaaaatg 60 aanccagcag gctgccccta gtcagtcctt ccttccagag aaaaagagat ttgagaaagt 12a gcctgggtaa ttcaccatta atttcctccc ccaaactctc tgagtcttcc cttaatattt i8〇ctggtggttc tgaccaaagc aggtcatggt ttgttgagca Tttgggatcc cagtgaagta 240 natgtttgta gccttgcata cttagccctt cccacgcaca aacggagtgg cagagtggtg 300 ccaaccctgt tttcccagtc cacgtagaca gattcacagt gcggaattct ggaagctgga 360 η

Ca 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。

&lt;221&gt; mi sc 一特欲&lt;222&gt; U) .7. (49Θ) &lt;223&gt; n = ATC ^ G &lt;400&gt; 159 acttccaggt aacgttgttg tttccgttga gcctgaactg atgggtgacg ttgtaggttc 60 tccaacaaga actgaggttg cagagcgggt agggaagagt gctgttccag ttgcacctgg 120 gctgctgtgg actgttgttg attcctcact acggcccaag gttgtggaac tggcanaaag 1Θ0 gtgcgttgtt gganttgagc tcgggcggct gtggcaggtt gtgggctctt caacaggggc 240 tgctgtggtg ccgggangtg aangtgctgt gtcacttgag cttggccagc tctggaaagt 300 antanattct tcctgaaggc cagcgcttgC ggagctggca ngggtcantg ttgtgtgtaa 360 cgaaccagtg ctgctgtggg tgggtgtana tcctccacaa agcctgaagt tatggtgtcn 420 tcaggtaana atgtggtttc agtgtccctg ggcngctgtg gaaggttgta nattgtcacc 460 aagggaataa gctgtggt .. 4 98 &lt.;210&gt; 160 &lt;211&gt; 380 &lt;212&gt; DNA &lt;213&gt; class. &lt;220&gt;

&lt;221>mi sc-expressive&lt;222&gt; {1) (380) &lt;223&gt; n - A, T, C ^ G &lt; 400 &gt; 160 58-127691.doc 200815476 acctgcatcc agcttccctg ccaaactcac aaggagacat caacctctag acagggaaac 60 agcttcagga tacttccagg agacagagcc accagcagca aaacaaatat tcccatgcct 120 ggagcatggc a.tagaggaag ctganaaatg tggggtctga ggaagccatt tgagtctggc 180 cactagacat ctcatcagcc acttgtgtga agagatgccc catgacccca gatgcctctc 240 ccacccttac ctccatctca cacacttgag ctttccactc tgtataattc taacatcctg 300 gagaaaaatg gcagttcgac cgaacctgtt cacaacggta gaggctgatt tctaacgaaa 360 cttgtagaat gaagcccgga 380 Ο u &lt; 210 &gt; 161 &lt; 211 &gt; 114 &lt;212&gt; DNA &lt;213&gt; human none &lt;400&gt; 161 · g actccacatc ccctctgagc aggcggttgt cgttcaaggt gtatttggcc ttgcctgtca 60 cactgtccac tggcccctta cccacttggt gcttaatccc ccgaaagagc atgt 114 &lt;210&gt; 162 &lt;211&gt; 177 &lt;212&gt; DNA &lt;213&gt;Human • · * &lt;400&gt; 162 actttctgaa tcgaaLcaaa tgatacctag tgtagtttta atatcctcat atatatcaaa 60 gttttactac tctgataatt ctgtaaacca ggtaaccaga acatcca Gtc atacagctct 120 tggtgatata taacttggca ataacccagt ctggtgatac ataaaactac tcactgt 177 &lt;210&gt; 163 &lt;211&gt; 137 &lt;212&gt; DNA &lt;213&gt; Shemale.··. &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; ) . . . (137) &lt;223&gt; n « A,T,C or G &lt;400&gt; 163 catttacaca gacaggcgtg aagacattca cgacaaaaac gcgaaattct atcccgtgac 60 canagaaggc agctacggct arctcctacat cctggcgtgg gtggccttcg cctgcacctc 120 catcagcggc atgatgt 137 &lt;210&gt; 164 &lt;211&gt ; 469 ^ &lt;212&gt; DNA ' &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc - Feature &lt;222&gt; (1) (469) &lt;223&gt; n = A, T, C or G &lt; 40Q &gt; 164 cttatcacaa tgaatgttct cctgggcagc gctgtgatct ttgccacctt: cgtgacttta 60 tgcaatgcat catgctattt catacctaat gagggagt-tc caggagattc aaccaggaaa 120 127691.doc 59- 200815476 tgcatggatc tcaaaggaaa caaacaccca ataaactcgg agtggcagac tgacaactgt 180 gagacatgca cttgctacga aacagaaatt tcatgttgca cccttgtttc tacacctgtg 240 ggttatgaca aagacaactg ccaaagaatc ttcaagaagg aggactgcaa gtatatcgtg 300 Gtggagaaga agga Cccaaa aaagacctgt tctgtcagtg aatggataat ctaatgtgct 360 tctagtaggc acagggctcc caggccaggc ctcattctcc tctggcctct aatagtcaat 420 gattgtgtag ccatgcctat cagtaaaaag atntttgagc aaacacttt 469 &lt;210&gt; 165 &lt;211&gt; 195 &lt;212&gt; DNA &lt;213&gt; Personal &lt;220&gt;&lt;221&gt; misc_ Features &lt;222&gt; (1).7.(195) &lt;223&gt; n = A, T, C or &lt;3 &lt;400&gt; 165 acagttttct atanatatcg acattgccgg cacutgtgt cagtttcata aagctggtgg 60 atccgctgcc atccactatt ccttggctag agtaaaaatt attcttatag cccatgtccc 120 tgcaggccgc ccgcccgtag ttctcgttcc Agtcgtcttg gcacacaggg tgccaggact 180 tcctctgaga tgagt .· · 195

&lt;210&gt; 166 &lt;211&gt; 383 &lt;212&gt; DNA &lt;213 &gt; Person's amount &lt;220&gt;

&lt;221&gt; mi sc a feature &lt;222&gt; (1).7.(383) &lt;223&gt; n *= or G &lt;400&gt; 166 acatctcagt agtgtggcac atcagggggc catcagggtc acagccactc atagcctcgc 60 cgaggtcgga gtccacacca ccggtgtagg tgtgcccaat cttgggctcg gcgcccacct 120 ttggagaagg . gatatgctgc acacacatgt ccacaaagcc tgtgaactcg ccaaagaatt 180 cttgcagacc agcctgagca aggggcggat gttcagcttc agctcctcct tcgccaggtg 240 gatgccaacc tcgtctangg tccgtgggaa gctggtgtcc acntcaccta caacctgggc 300 gangatctta taaagaggcc ccnagataaa ctccacgaaa cttctctggg agctgctagt 360 n9999 ^ cttt ttggtgaact ttc 3Θ3 &lt; 210 &gt; 167 &lt; 211 &gt; 247 _ &lt; 212 &gt; DNA ~ &lt;213&gt;Human&lt;220&gt;&lt;221&gt; mi sc-features. &lt;222&gt; (1)二·"247)

&Lt; 223 &gt; n »A, T, C or G &lt; 400 &gt; 167 acagagccag accttggcca taaacgaanc agagattaag actaaacccc aagccganat 60 tggagcagaa actggagcaa gaagtgggcc tggggctgaa gcagagacca aggccactgc 120 60- 127691.doc 200815476 tatanccata cacagagcca actctcaggc caaggcnatg gttggggcag anccagagac 180 tcaatctgan tccaaagtgg tggctggasc sctggtcatg acanaggcag Tgactctgac 240 tgangtc 247 &lt;210&gt; 168 &lt;211&gt; 273 &lt;212&gt; DNA &lt;213 &gt; person # &lt;220&gt;&lt;221&gt; misc-feature &lt;222&gt; (1) (273) 180 aattcccaac ttccttgcca caagcttccc aggctctctc ccctggaaaa ctccagcttg 240 agtcccagat acactcatgg tttcactcat ccctgagaag ccctttccag tagggtgggc: 168 acttctaagt tttctagaag tggaaggatt gtantcatcc tgaaaatggg tttacttcaa 60 aatccctcan ccttgttctt cacnactgtc tatactgana gtgtcatgtt tccacaaagg 120 gctgacacct gagcctgnat; · &lt; 223 &gt; n «A, T, C or G &lt; 400 & gt Gctgccctgg gca 273 &lt;210&gt; 169 &lt;211&gt; 431

^ ' &lt;212&gt; DNA &lt;213&gt;.Human &lt;220 &gt;

4221&gt; misc_: Feature &lt;222&gt; (1)...(431) &lt;223> n = AT, C or G &lt;400&gt; 169 acagccttgg cttccccaaa. ctccacagtc ccagtgcaga aagatcatct cccagcagtc 60 agctcagacc agggtcaaag gatgtgacat caacagtttc tggtttcaga acaggttcta 120 ctactgccaa atgacccccc atacttcctc aaaggctgtg gtaagttttg cacaggtgag 180 ggcagcagaa agggggtant tactgatgga caccatcttc tctgtatact ccacactgac 240 ctcgccatgg gcaaaggccc ctaccacaaa aacaatagga tcactgctgg gcaccagctc 300 acgcacacca ctgacaaccg ggatggaaaa agaantgcca accttcatac atccaactgg 360 aaagtgacct gatactggat tcttaattac cttcaaaagc ttctgggggc catcagccgc 420 tcgaacactg a 431 &lt; 210 &gt; 170 &lt; 211 &gt; 266 &lt; 212 & gt DNA -

&lt;213&gt;, People &lt;220&gt;&lt;221&gt; misc One: Extraordinary &lt;222&gt; (1) . . . (266)

&Lt; 223 &gt; n = A, T, C or G &lt; 400 &gt; 170 acctgcgggc tgggctgtta tgcctgtgcc ggctgctgaa agggagttca gaggtggagc 60 tcaaggagct ctgcaggcat tttgccaanc ctctccanag canagggagc aacctacact 120 ccccgctaga aagacaccag attggagtcc tgggaggggg agttggggtg ggcatttgat 1B0 -61 &gt; 127691.doc 200815476 gtatacttgt cacctgaatg aangagccag Agagagaanga gacgaanatg anattggcct tcaaagctag gggtctggca ggtgga &lt;210&gt; 171 &lt;211&gt; 1248 &lt;212&gt; DNA &lt;213&gt; human face &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1) (1248)

&lt;223&gt; n = A, T, C or G 240 266

&Lt; 400 &gt; 171 ggcagccaaa tcataaacgg cgaggactgc agcccgcact cgcagccctg gcaggcggca ctggtcatgg aaaacgaatt gttctgctcg ggcgtcctgg tgcatccgca gtgggtgctg tcagccgcac actgtttcca gaagtgagtg cagagctcct acaccatcgg gctgggcctg cacagtcttg aggccgacca agagccaggg agccagatgg tggaggccag cctctccgta cggcacccag agtacaacag acccttgctc gctaacgacc tcatgctcat caagttggac gaatccgtgt ccgagtctga caccatccgg agcatcagca ttgcttcgca gtgccctacc gcggggaact cttgcctcgt ttctggctgg ggtctgctgg cgaaeggcag aatgcctacc gtgctgcagt gcgtgaacgt gtcggtggtg tctgaggagg tctgcagtaa gctctatgac 60 12Q 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1248 ccgctgtacc aacggtgact ggaaaagccc actgagtgga attgaccccc ccctcaggcc cccagcccct ccaggagtcc ctcagaccca ccaacccntc gcggtccaat aaccttacca aagagaagng accccagcat ccggggggcc cgtgtggcca tagagaaaac aaatacatcc caggagtcca cctccctcag agcccctcct ggggtccagg attccccaga gccacctaga gttggttctt caaaaaaaaa Gttctgcgcc cctgatctgc agttggcgtg cgtccaggcc tgcggaagga ggcccccagc acccaggagt ccctc agacc cccccaaccc cccagaggtc ctntccctgt catttttngt aaaaaaaaad ggcggagggc aacgggtact ccaggtgtct agttaactct attcaggaat ccctcctccc ccagaccccc caggagtcca ctcctccctc caggtcccag acacagtgcc ccctttcccc aaaaaaaaaa aagaccagaa tgcagggcct: acaccaacct ggggactggg atctgttccc tcaaaccaag cagcccctcc gaccccccag agactcagag cccctcntcc cccttgtggc tagatccaga aaaaaaaa ggactcctgc tgtgtctttc ctgcaaattc aacccatgaa agcccctcct ggtacagatc tcccccagac cccctcctcc gtccaagccc ctcagaccca acgttgaccc aataaagttt &lt; 210 &gt; 172 &lt;211&gt; 159 &lt;212&gt; Protein Brahman&lt;213&gt; Human &lt;220&gt; · &lt;221&gt; ^ Ο &lt;222&gt; (1) (159) . * &lt;223&gt; Xaa »any amine Acid &lt;400&gt; 172

Met Val Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro 1 5 10 15

Leu Leu Ala Asn Asp Leu Met Leu lie Lys Leu Asp Glu Ser Val Ser 20 25 30

Glu Ser Asp Thr lie Arg Ser lie Ser lie Ala Ser Gin Cys Pro Thr 35 40 45

Ala Gly Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Gly 50 55 60 62- 127691.doc 200815476

Arg Met Pro Thr Val Leu Gin Cvs Val Asn Val Ser Val Val Ser Glu 65 70 75 80

Glu Val CyS Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Ser Met Phe 85 * 90 95

Cys Ala Gly Gly Gly Gin Xaa Gin Xaa Asp Ser Cys Asn Gly Asp Ser 100 105 110

Gly Gly Pro Leu lie Cys Asn Gly Tyr Leu Gin Gly Leu Val Ser Phe .115 120 125

Gly Lys Ala Pro Cys Gly Gin Val Gly Val Pro Gly Val iyr Thr Asn 130 135 . 140

Leu Cys Lys Phe Thr Glu Τΐφ lie Glu Lys Thr Val Gin Ala Ser 145 150 155

U &lt;210&gt; 173 &lt;211&gt; 1265 &lt;212&gt; DNA &lt;213&gt; Person &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1).7. (1265)

&Lt; 2 2 3 &gt; n «A, D, C or G ggcagcccgc tcgggcgtcc tacaccatcg gtggaggcca ctcatgctca attgcctcgc gcgaacggtg cgggggccga acgtgtcggt gcacgtcctg ggcccctgat gccaagttgg aaaccgtcca atcccgcgga tccaggcccc ccagacccag ccctccntca gaggccccca cagacccaga tagatttccc ttttcatttt aaaas 173 actcgcagcc tggcgcatcc ggctgggcct gcctctccgc tcaagttgga agcgccctac agctcacggg cccagagctc ggcgtctgag cgccggcgga ccgcaacggg cgtgccaggt ggccagttaa aggaattcag cagcccctcc gagtccagac gacccaggag acccctcctc ggtnnaggtc ctgnacacag cngtcccttt ctggcaggcg gcagtgggtg gcacagtctt acggcaccca cgaatccgtg cgcggggaac tgtgtgtccg tgcgtcccag gaggcctgca gggcaagacc tacctgcagg gtctacacca ctctggggac gaatatccgt tccctcaaac cccccagccc tccagacccc cttcagagtc ccagcccctc tgccccctcg cccctagatc gcactggtca ctgccagccg gaggccgacc gagtacaaca tccgagtctg tcctgcctcg ccctcttcaa gcagaatgcc gcaagcccta agaaggactc gccttgtgtc acctctgcaa tgggaaccca tcccagcccc caagggtaca ctcctccctc ccagcccctc agaggtccaa ttccntcaga Tggnangttg cagaaat^aa tggaaaacga cacacr.gttc aagag ccagg gaccctcgcc acaccatccg ctCctggctg ggaggccccc taccgcgctg tgacccgctg ctgcaacggt tctcggaaaa attcactgag tgaaactgac tcctccctca gatccccagc agacccagga ctccctcaga gcccccaacc cccagnggtc acccaacctt gtttaagaga attgttctgc ccagaactcc gagccagatg cgctaacgac gagcatcagc gggtctgctg tgcccagtcg cagtgcgtga taccacccca gactccgggg gccccgtgtg tggatagaga ccccaaatac ggcccaggag ccctcctccc gtccagcccc cccaggggtt cctcgttccc caatgccacc accagttggt ngngcaaaaa 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1265 &lt;210&gt; 174 &lt;211&gt; 1459 &lt;212&gt; DNA &lt;213&gt;Human&lt;220&gt;&lt;221&gt; mi SC-feature&lt;222&gt; (1 ) . . . (1459) -63- 127691.doc 200815476

&lt;223&gt; η * A, T, C or G

· &Lt; 400 &gt; ggtcagccgc tgcacagtct tacggcaccc acgaatccgt ccgcggggaa gtgtgtgtct ctgcgtccca ngaggtctgc agggcaagac cagggaaggg atggagagac ataaacacag agaaacacac gacctccacc atagcctact cttatgcatt gtctgtgaat aaaaatccaa gtacccagag aaaccaagac gggaggcgag gtgaaatcct aatcccagct gaagtgagtt caaaaaaaaa 174 acactgtttc tgaggccgac agagtacaac gtccgagtct ctcttgcctc gccctcttca ggcagaatgc antaagctct cagaaggact tggagaaggg acacagggag gaataaagag acacacagaa caatagaaaa gttgacgggg catgatatac ttttttaaat gtataagtgg ggaaacagtg tctacaaaga gcaggcagat gtctgtacta acttgggagg gagatcacac aaaaaaaaa cagaagtgag caagagccag agacccttgc gacaccatcc gtttctggct aggaggtcct ctaccgtgct atgacccgct cctgcaacgt ggagacagag acagtgacaa aagcaaagga atgcagttga tcctcttata agccctacca cttcgttgga tgttgcaacc acctgtgcat acacagattc ggctgggcag cacttgaggt aaaatacaaa ctgaggcagg cactatactc tgcagagctc ggagccagat tcgctaacga ggagcatcag ggggtctgct ctgcccagtc gcagtgcgtg gtaccacccc gagagagggg acacacaggg ctagagagag agagagaaac ccttccaaca acttttgact ataacataaa attt tttgat ctcctaaaat tcaaaccagg atagaggtga ggtggctcat aaggagctca agttagctgg agaattgctt cagctggggc ctacaccatc ggtggaggcc cctcatgctc cattgcttcg ggcgaacggt gcgggggctg aacgtgtcgg ancatgttct aaaggggagg ccgcatggcg aaactgagag agaaacagac gcatggggcc ccccaaaaac tagtcgattt atttctaagc ttttctgatg gttgtrcaag aacacgaaga gcctgtaatc agaccagcct atatggtggc gaatacggga aacagagtaa gggctgggcc agcctctccg atcaagttgg cagtgcccta gagctcacgg acccagagct tggtgtctga gcgccggcgg gcaggcgact agatgcagag aaacagagaa atggggaggc tgagggcggt ctgactagaa atgcatacgt tacacagttc tgcttatcga Ggcdaactgt gaaacaggaa ccagcacctt ggccaaaatg aggcgcctgt ggcagaggtt gactctgtct 60 120 180 240 300 360 420 480 540 βΟΘ 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1459 &lt;210&gt; 175 &lt;211&gt; 1167 &lt;212&gt; DNA &lt;213&gt;;人倒&lt;220&gt;

&lt;221&gt;misc-detail&lt;222&gt; (1) (1167) &lt;223&gt; n = A, T, C or G u &lt;4 00&gt; gcgcagccct gtgcatccgc ctgggcccgc ctctccgtac aagtcggacg tgccctaccg atgcctaccg ccctatgacc gactcctgca gtgtccttcg tgcaaattca acccatgaaa gcccctcctc gcacagatcc ccntcagacc 175 ggcaggcggc agtgggtgct acagtcttga ggcacccaga aatccgtgtc cggggaactc tgctgcactg cgctgtacca acggtgactc gaaaagcccc ctgagtggat ttgaccccca cctcaggccc ccagcccctc caggagtcca actggtcatg gtcagccgca ggccgaccaa gcacaacaga cgagtctgac ttgcctcgtn cgtgaacgtg ccccagcatg tggggggccc gtgtggccaa agagaaascc aacacatcct aggagtccag ctccctcaga gcccctcctc gaaaacgaat cactgtttcc gagccaggga ctcttgctcg accatccgga tctggctggg tcggtggtgt ttctgcgccg ctgatctgca cttggcgtgc gtccagncca gcggaangaa gcccccagcc cccaggagtc cntcagacgc tgttctgctc Agaactccta gccag.atggt ctaacgacct gcatcagcac gtctgctggc ctgaggangt gcggagggca acgggtactt caggtgtcta gttaactctg ttcaggaata cctcccccct cagacccccc aggagtccag gggcgtcctg caccatcggg ggaggccagc. catgctcatc tgcttcgcag gaacggcaga ctgcagt Aag agaccagaag gcagggcctt caccaacctc gggactggga cctgttccca caaaccaagg agcccctcnt accccccagc 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 127691.doc 64- 200815476

· « '1 r ccntcntccg tcagacccag gggtgcaggc ccccaacccc tcntccntca gagtcagagg tccaagcccc caacccctcg ttccccagac ccagaggtnc aggtcccagc ccctcctccc tcagacccag cggtccaatg ccacctagan tntccctgta cacagtgccc ccttgtggca ngttgaccca accttaccag ttggtttttc attttttgtc cctttcccct agatccagaa ataaagtnta agagaagcgc aaaaaaa &lt; 210 &gt; 176 &lt; 211 &gt; 205 &lt; 212 &gt; protein cargo &lt;213&gt; Human &lt;220&gt;&lt;221&gt; Change ίί &lt;222&gt; (1)...(205) . &lt;223&gt; Xaa = any amino acid, &lt;400&gt; 176 Met Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gin Trp 15 10 15 Val Leu Ser Ala Ala His Cys Phe Gin Asn Ser Tyr Thr lie Gly Leu 20 25 30 Gly Leu His Ser Leu Glu Ala Asp Gin Glu Pro Gly Ser Gin Met Val 35 40 -45 · Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Leu Leu Leu 50 55 ** 60 Ala Asn Asp Leu Met Leu lie Lys Leu Asp Glu Ser Val Ser Glu Ser 65 70 75 80 Asp Thr lie Arg Ser lie Ser lie Ala Ser Gin Cys Pro Thr Ala Gly 05 90 95 Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Gly Arg Met 100 105 110 Pro Thr Val Leu His Cys Val Asn Val Ser Val Val Ser Glu Xaa Vel 115 120 * 125 Cys Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Ser Met Phe Cys Ala 130 135 140 Gly Gly Gly Gin Asp Gin Lys Asp Ser Cys Asn Gly Asp Ser Gly Gly 145 150 155 160 Pro Leu lie Cys Asn Gly Tyr Leu Gin Gly Leu Val Ser Phe Gly Lys 165 170 175 Ala Pro Cys Gly Gin Leu Gly Val Pro Gly Val Tyr Thr Asn Leu Cys 180 . 185 190 Lys Phe Thr Glu Trp lie Glu Lys Thr Val Gin Xaa Ser 195 200 205 &lt;210&gt; 177 _ &lt;211&gt; 1119 &lt;212&gt; DNA &lt;213&gt;.People&lt;400&gt; 177 gcgcactcgc agccctggca ggcggcactg gtcatggaaa acgaatcgtt ctgctcgggc gtcctggtgc atccgcagtg ggtgctgtca gccgcacact gtttccagaa ctcctacacc • atcgggctgg gcctgcacag tcttgaggcc gaccaagagc cagggagcca gatggtggag gccagcctct ccgtacggca cccagagtac aacagaccct tgctcgctaa cgacctcatg ctcatcaagt tggacgaacc cgtgtccgag tctgacacca tccggagcat cagcattgct 960 1020 1080 1140 1167 60 120 180 240 300 127691.doc 65- 200815476 tcgcagtgcc ctaccgcggg gaactcttgc ctcgtttctg g ctggggtct gctggcgaac gatgctgtga ttgccatcca gtcccagact gtgggaggct gggagtgtga gaagctttcc caaccctggc agggttgtac catttcggca acttccagtg caaggacgtc ctgctgcatc ctcactgggt gctcactact gctcactgca tcacccggaa cactgtgatc aactagccag caccatagtt ctccgaagtc agactatcat gattactgtg ttgactgtgc tgtctattgt actaaccatg ccgatgttta ggtgaaatta gcgtcacttg gcctcaacca tcttggtatc cagttatcct cactgaattg agatttcctg cttcagtgtc agccattccc acataatttc tgacctacag aggtgaggga tcatatagct cttcaaggat gctggtactc ccctcacaaa tteatttetc ctgttgtagt gaaaggtgcg ccctctggag cctcccaggg tgggtgtgca ggtcacaatg atgaatgtat gatcgtgttc ccattaccca aagcctttaa atccctcatg ctcagtacac cagggcaggt etageattte ttcatttagt gtatgctgtc cattcatgca accacctcag gactcctgga ttctctgcct agttgagctc ctgcatgctg cctccttggg gaggtgaggg agagggccca tggttcaatg ggatctgtgc agttgtaaca cattaggtgc ttaataaaca gaagctgtga tgttaaaaaa aaaaaaaaa &lt; 210 &gt; 178 &lt; 211 &gt; 164 &lt; 23L2 &gt; protein 1Ϊ &lt; 213 &gt; al chin &lt;22Q&gt;

&lt;221&gt;Changes. &lt;222&gt; (1) (164) ’· * &lt;223&gt; Xaa = any amino acid &lt;40Q&gt; 178 *-

Met Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gin Trp 1 5 10 15

Val Leu Ser Ala Ala His Cys Phe Gin Asn Ser Tyr Thr lie Gly Leu 20 25 30

Gly Leu His Ser Leu Glu Ala Asp Gin Glu Pro Gly Ser Gin Mec Val 35 40 45

Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro Leu Leu 50 55 60

Ala Asn Asp Leu Met Leu He Lys Leu Asp Glu Ser Val Ser Glu Ser 65 70 75 80

Asp Thr lie Arg Ser lie Ser lie Ala Ser Gin Cys Pro Thr Ala Gly 85 90 95

Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Asp Ala Val 100 105 110 lie Ala lie Gin Ser Xaa Thr Val Gly Gly Trp Glu Cys Glu Lys Leu 115 120 125

Ser Gin Pro Trp Gin Gly Cys Thr He Ser Ala Thr Ser Ser Ala Arg 130 135 140

Thr Ser Cys Cys lie Leu Thr Gly Cys Ser Leu Leu L*eu Thr Ala Ser 145 150 155 160

Pro Gly Thr Leu &lt;210&gt; 179 &lt;211&gt; 250 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 179-66 - 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1119 127691.doc 200815476 ctggagtgcc tt ^ gtgtttc aagcccctgc aggaagcaga atgcaccttc tgaggcacct ccagctgccc ccggccgggg gatgcgaggc tcggagcacc cttgcccggc tgtgattgct gccaggcact gttcatctca gcttttctgt ccctttgctc ccggcaagcg cttctgctga aagttcatat ctggagcctg atgtcttaac gaataaaggt cccatgctcc acccgaaaaa aaaaaaaaaa &lt; 210 &gt; 180 &lt; 211 &gt; 202 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 180 actagtccag tgtggtggaa ttccattgtg ttgggcccaa cacaatggct acctttaaca tcacccagac cccgcccctg cccgtgcccc acgctgctgc taacgacagt atgatgctta ctctgctact cggaaactat ttttatgtaa ttaatgtatg ctttcttgtt tataaatgcc tgatttaaaa aaaaaaaaaa aa o 6 2 Θ 4 5 112 2 o 6 2 8 1, -1 &lt; 210 &gt; 181 &lt; 211 &gt; 558 &lt;212&gt; DNA &lt;213&gt; Human 〇&lt;220&gt;

&lt;221&gt; misc_ feature &lt;222&gt; (1).7.(558) &lt;223&gt; n * A, T, C or G &lt;400&gt; 181 e cccytttgkt naggtttkkg aatgtttagg cagtgctagt ttattcctcc ttcttctgaa ggcagtgtga aaattatgca ctactctgtt attgatdaca ttctatcccc aaaaycagtt caaaaaaaaa cagtataagt agttagtaat ccttggctag tcctatgttc aggaatatgg ttggtwaata aaaaaaaa agacamccck aactccyccg gactaacgaa atcr.aagcgc cacccagggt aaaaaattat taaaagttgg kgttcatttt ygtwaacatg agacctwaan caacgattct gttgaaaatt .agacgaaagc taactaaatt aaacaggact gctacacata acgaacatta tcmtaaataa ctgtgtcaca gttatcactt gaggcggata gtgctatata aettcaacat ttgttagctt aatcactaag cscrggatag acaakgctcc gacttcyngg ccctnattct aatacaaaaa catccattca gctgttgaac gggaagccaa aaatatggaw awgtwcgagc gacttatttc 2840628 4 5 1123344 5 5 o

&lt;210&gt; 1B2 &lt;211&gt; 479 &lt;212&gt; DNA &lt;213&gt; Person &lt;220&gt;&lt;221&gt; misc_ &lt;222&gt; (1).7. (479) &lt;223>n = eight , Shi, (: or G &lt; 400 &gt; 182 acagggwttk grggatgcta agsccccrga rwtygtttga tccaaccctg gcttwttctc agaggggaaa atggggccta gaagttacag mscatytagy tggcgcgmtg gcacccccgg cstcacacag astcccgagc agccgggact acaggcacac agtcactgaa gcaggccctg ttwgcaattc acgttgccac ccccaactta aacacccctc atacgtgacg tccttagtca ctaaggttaa actttcccac ccagaaaagg caacttagat aaaatcttag agtactttca o 6 2 8 4 112 127691 .doc -67- 200815476 tactmttcta agtcctcttc cagcctcact kkgagtcctm cytgggggtt gataggaant ntctcttggc tttctcaata aartctctet ycatctcatg tttaatttgg tacgcatara awtgstgara aaattaaaat gttctggtty mactttaaaa araaaaaaaa aaaaaaaaa &lt; 210 &gt; 183 &lt; 211 &gt; 384 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 183 aggcgggagc Agaagtataaa gccaaagccc aagaagagtg gcagtgccag cactggtgcc agtaccagta ccaataacag tgccagtgcc agtgccagca ccagtggtgg cttcagtgct ggtgccagcc tgaccgccac tctcacattt gggctcttcg ctgg Cctgtg tggagctggt gccagcacca gtggcagctc tggtgcctgt ggtttctcct acaagtgaga ttttagatat tgttaatcct gccagtcttt ctcttcaagc cagggtgcat cctcagaaac ctactcaaca cagcactcta ggcagccact atcaatcaat tgaagttgac actctgcatt aratctattt gccatttcaa aaaaaaaaaa aaaa

&lt;210&gt; 184 &lt;211&gt; 496 &lt;212&gt; DNA

360 420 47S 60 120 180 240 300 360 384 &lt;213&gt; Human · &lt;220&gt;

&lt;221>misc-detail&lt;222&gt;(1).:.&lt;496)&lt;223&gt; n = A, T, C or G &lt;40O&gt; 184 accgaattgg gaccgccggc agggagaccg agtccatacg cccatcctgc tcggttctcc aacgctccaa ggtgcccatg cgatgtcttt tccgccacct tgagccctga tgcctttttg attatgcttg tgtgaggcaa tttttctcat attttaaatt taaaaaaaaa aaaaaa ttataagcga tcacgtyync ctgaagaaat ttgacccgat ccagatgaca aatactctsg acccagcaac cgcgccctgt gttacccctc ggagactccg ccagccatac tctctggcat tcatggcggc atcacccaca actacmagaw tattwmagaw ccrgtatkac cccaacgagc gggacaacag acctgctcag acaccgaatc accatcaaga cccctgaggg tcccttaaac taaccaaact cttcggactg ccagtctctc gtggcgattg aagggaacac atttgacttt waaatgawtt gaaaaactst 60 120 180 240 300 360 420 480 496 Ο &lt; 210 &gt; 185 &lt; 211 &gt; 384 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 185 gctggtagcc tatggcgkgg cccacggagg ggctcctgag gccacggrac agtgacttcc caagtatcyt gcgcsgcgtc ttctaccgtc cctacctgca gatcttcggg cagattcccc aggaggacat ggacgtggcc ctcatggagc acagcaactg ytcgtcggag cccggcttct gggcacaccc tcctggggcc caggcgggca cctgcgtc tc ccagtatgcc aactggctgg tggtgctgcc cctcgtcatc ttcctgctcg tggccaacat cctgctggtc aacttgctca ttgccatgtt cagttacaca ttcggcaaag tacagggcaa cagcgatctc tactgggaag gcgcagcgtc accgcctcat ccgg 60 120 180 240 300 360 384 &lt; 210 &gt; 1Θ6 &lt; 211 &gt; 577 127691.doc 68- 200815476 &lt; 212 &gt; DNA &lt; 213 &gt; People

&lt;220&gt;&lt;221&gt; misc-specific desire &lt;222&gt; (1) (577) &lt;223&gt; n * or G &lt;400&gt; 186 gagttagctc ctccacaacc ttgatgaggt cgtctgcagt ggcctctcgc ttcataccgc tnccatcgtc atactgtagg tttgccacca cytcctggca tcttggggcg gcntaatatt ccaggaaact ctcaatcaag tcaccgtcga tgaaacctgt gggctggttc tgtcttccgc tcggtgtgaa aggatctccc agaaggagtg ctcgatcttc cccacacttt tgatgacttt attgagtcga ttctgcatgt ccagcaggag gttgtaccag ctctctgaca gtgaggtcac cagccctatc atgccgttga mcgtgccgaa garcaccgag ccttgtgtgg gggkkgaagc ctcacccaga ttctgcatta ccagagagcc gtggcaaaag acattgacaa actcgcccag gtggaaaaag amcamctcct ggargtgctn gccgctcctc gtcmgttggt ggcagcgctw tccttttgac acacaaacaa gttaaaggca ttttcagccc ccagaaantt gtcatcatcc aagatntcgc acagcactna tccagttggg attaaat &lt; 210 &gt; 187 &lt;211&gt; 534 &lt;212&gt; DNA ·· ' &lt; 213 &gt; 铕 ·· &lt;220&gt;·-&lt;221>misc-feature&lt;222&gt; (1) (534) &lt; 2 2 3 &gt; n = A, T, C or G 60 120 180 240 300 -360 420 480 540 577 &lt;4C0&gt; 187 aacaccttcc tgtataatgc tgtgtaat at cgatccgatn tcgtctgstg agaatycatw actkggaaaa gmaacattaa agcctggaca ctggtattaa aattcacaat atgcaacact tcaaacagtg tgtcaatctg ctcccyynac tttgtcatca ccagcctggg aakaagggta tgccctattc acacctgtta aaagggcgct aagcattttt gattcaacat cttttctttt gacacaagtc cgaaaaaagc aaaagtaaac agttatyaat ttgttagcca attcactttc ttcatgggac agagccatyt gatttaaaaa gcaaattgca taatattgag cctygggagc tgatatttga gcggaagagt agcctttcta cttcaccaga cacaactccc tttcacattg ggatgttnac naaagcwatg tctctwacag atgggatgct tttgtggcaa ttctgttctg aggatctccc agtttattta ccacttgcac aagaaggcgt Tttcttcctc aggc 60 120 180 240 300 360 420 480 534 o &lt;210&gt; 188 &lt;211&gt; 761 &lt;212&gt; DNA &lt;213&gt; Human

&lt;220&gt;&lt;221&gt;&lt;222&gt; (1) (761) &lt;223&gt; n = or G &lt;400&gt; 188 •agaaaccagt atctctnaaa acaacctctc ataccttgtg gacctaattt tgtgtgcgtg tgtgtgtgcg cgcatattat atagacaggc acatcttttt tacttttgta aaagcttatg cctctctggt atctataccc gtgaaagttt taatgatctg ccataatgtc ttggggacct 60 120 180 127691.doc 69- 200815476 4062840626 2334456677 ttgtcttctg tttattcaac ggggacaaag acagaaatwr gcaaaaaaca cttgcccttc ctgactgata atgcttaatt tttttctgtn tgtaaatggt gaaaataata acaacactna raaacaatwa catcattaaa atgaaggaaa aaaagcaaaa ggtagtatat tgtacngact attacatgtt aagctgtaca cacaaatgct ttcccagagc acattgaaga actagagaaa Cttccagatn ctgamcataa tgaarnacag tcccgttgag tnaaagtggt aataagcagt aatttcatta tgagatntta aaaananaaa acacctatnt taatgccaag gtggtgggcc Gtgcctaaca taaatgtttg gattttatgt aaanaaaaaa tatgagtcaa caaactctcc cctggtgaga rmgttwtktt ttgttttttt aaaatattga agcaacacag ctaaaataca agtatnaagt tctagttngt ctkgackarg arttgcataa wttctccctt tatnataaaa aatgatggaa taatgttgac ctttgaacta gaaaaantac o &lt;210&gt; 189 &lt;211&gt; 482 &lt;212&gt; DNA &lt;213&gt;People &lt;220&gt;

&lt;221&gt;misc一特欲&lt;222&gt; (1)...(482) &lt;223&gt; n = A,T,C · or 'G &lt;4 00&gt; tttttttttt caccggggct aagccgcctg aaggcagggg tgataggcac gtcattgtgc aaatttggcc gttcggccca cc 189 tttgccgatn atnagaagca ctgccttctc ccaccagccc aggccacccg cctgcccagg ngtcatngaa gctccncgtc ccactattct agaaggaagg tgtccgtctc a9999tggga gtacagaccc cacagcgtan ngggcantct caasaantat attgcaggan agggagggca ctggtgcagg atacaggggg ctcggctcct etccggaaaa cccaanttng tcacccrmct gtgggggtgt cagccccttg cacatgggga tgggangtgt gacaggtnga gacagaatgc gctnggtctt ccnaattgct atgcaccgca ctgagcaaca gaccttcccc gcataagaag tctcgaccag tttccctctc ggcacncttg tgcnggnccc 2 Θ 406 2 B 8 1 1233 4 4 4 &lt;210&gt; 190 &lt;211&gt; 471 &lt;212&gt; DNA &lt;213&gt; Person's amount_ &lt;220&gt;

&lt;221&gt; nr\isc_ Desirable. &lt;222&gt; (1).7.(471) &lt;223&gt; n = A, T, C or .G y &lt;400&gt; tttttttttt aaaactctcg aatgcctggt cgcttttgac taagtactca tgaaaaattt ctacatcnac tctgtaattn 190 ttttaaaaca catccagtga caaatgatac atacaatgca tcacatacat cacgtatgca cttgatcatt anttcaacct gtttttcaca gaactaccat aatggaacca caaaaaaaaa taagacacag atccaaccaa gccaggaacn ccgtacngaa acaaaattta acaccacatt ttcaatctta aggggggggg ttctagtcca agaacttnat aaaagttnaa aaatnttnnt ttageagaat acagctngga cacatgcacg gaccacatgg gtcnaaaatc tggtgatcat ancacncngt tatacactcc agtggttctg atgtnctcca aaagaacaag attaaaattt agaactgcnt gantnctcta acaaaaanaa c oooooool 62840627

&lt;210&gt; 191 &lt;211&gt; 402 &lt;212&gt; DNA 127691.doc 70-200815476 &lt;213&gt; Person &lt;220&gt;&lt;221&gt; misc__ Feature &lt;222&gt; (1).7. (402) aacaatgtcc 191 gagggattga aggtctgttc tastgtcggro ctgttcagcc accaactcta acaagttgct 60 gtcttccact cactgtctgt aagcttttta acccagacwg tatcttcata aatagaacaa 120 attcttcacc agtcacatct tctaggacct ttttggattc agttagtata agctcttcca 180 cttcctttgt taagacttca tctggtaaag tcttaagttt tgtagaaagg aactyaattg 240 ctcgttctct; &lt; 2 23 &gt; n = A, D, C or G &lt; 400 & gt Tctccttgaa gtatttggct gaacaaccca cctaaagtcc 300 ctttgtgcat ccattttaaa tatacttaat agggcattgk tncactaggt taaattctgc *360 aagagtcatc tgtctgcaaa agttgcgtta gtatatctgc ca 402 &lt;210&gt; 192 &lt;211&gt; 601 &lt;212&gt; DNA &lt; 213:►

&lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1).7.(601) &lt;223&gt; n « A#T, C or G &lt;400&gt; 192 gagctcggat ccaacaatct ttgtctgagg gcagcacaca tatncagcgc catggnaacc 60 ggcctacccc acatgggagc agcatgccgt agntacacaa ggtcaCtccc tgagccagac 120 atgcytyttt gaytaccgcg cgccaagtgc tggcgattct yaacacacyt ccatcccgyt 180 ctcctgtgga aaaactggca cctktctgga actagcarga catcacttac aaattcaccc 240 acgagacact tgaaaggtgc aacaaagcga ytctcgcatt gctttttgtc cctccggcac 300 cagttgtcaa tactaacccg ctggcctgcc tccaccacat ttgtgatctg tagctctgga 360 tacatctcct gacagtactg aagaacctct tctttcgttt caaaagcarc tcttggcgcc 420 tgctggatca ggt, tcccatc tcccagccyg aatgttcaca tggcatattt wacttcccac 4Θ0 aaaacatcgc Gatttgaggc tcagcaacag caaaccctgt tccggcattg gctgcaagag 540 cctcgatgta gccggccagc gccaaggcag gcgccgtgag ccccaccagc agcagaagca 600 g 601

&lt;210&gt; 193 &lt;211&gt; 608 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt;misc-feature&lt;222&gt; (1).7.(608) &lt;223&gt; n * A, T, C or G &lt; 400 &gt; 193 atacagccca natcccacca cgaagatgcg cttgttgact gagaacctga tgcggtcact 60 ggtcccgctg tagccccagc gactccccac ccgctggaag cggttgatgc tgcactcytt 120 cccaacgcag gcagmagcgg gsccggtcaa tgaactccay tcgtggcttg gggtkgacgg 180 tkaagtgcag gaagaggctg accacctcgc ggtccaccag gatgcccgac tgtgcgggac 240 ccgcagcgaa acccctcgat ggtcatgagc gggaagcgaa tgaggcccag ggcctcgccc 300 127691.doc -71 - 200815476 agaaccttcc gcctgttctc tggcgtcacc tgcagctgct gccgctgaca ctcggcctcg 360 gaccagcgga caaacggcrt tgaacagccg cacctcacgg atgcccagtg tgtcgcgctc 420 caggammgsc accagcgtgt ccaggtcaat gtcggtgaag ccctccgcgg gtratggcgt 480 ctgcagtgtt tttgtcgatg ttctccaggc acaggctggc cagctgcggt tcatcgaaga 540 gtcgcgcctg cgtgagcagc atgaaggcgt tgtcggctcg cagttcttct tcaggaactc 600 cacgcaat 608 &lt; 210 &gt; 194 &lt; 211 &gt; 392 &lt;2:L2&gt; DNA Human &lt;220&gt;

&lt;221&gt; misc a special desire &lt;222&gt; (1)·:.(392) &lt;223&gt; n two A, T*, C or G &lt;400&gt; 194 gaacggctgg accttgcccc gcattgtgct tgctggcagg gaataccttg gcaagcagyt 60 ccagtccgag cagccccaga ccgccgccgc ccgaagctaa gcctgcctct ggccttcccc 120 tccgcctcaa tgcagaacca gtagtgggag cactgtgttt agagttaaga gtgaacactg 180 tttgatctta cttgggaatt tcctctgtta tatagctttt cccaatgcta atitcccaaac 240 aacaacaaca aaataacatg ttcgcctgct aagtcgtrata aaagtagacg atcctgtact 300 taaagaaaat attactgtta catataccgc ttgcaatttc tgtatttatt gktncustigg 360 aaataaacat agttaccaaa ggttgtcant cc eleven 392 &lt; 210 &gt; 195 &lt; 211 &gt; 502 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;&lt;221&gt; misc^^^

&lt;222&gt; (1) (502) &lt;223&gt; n * A, T, C or G &lt; 400 &gt; 195 ccsctkgagg ggtkaggkyc cagttyccga gtggaagaaa caggccagga gaagtgcgtg 60 ccgagctgag gcagatgttc ccacagtgac ccccagagcc stgggstaca gcytctgacc 120 cctcncaagg aaagaccacs ttctggggac atgggctgga gggcaggacc Tagaggcacc 180 aagggaaggc cccattccgg ggstgttccc cgaggaggaa gggaaggggc tctgtgtgcc 240 ccccasgagg aagaggccct gagtcctggg accagacacc ccttcacgtg catccccaca 300

caaatgcaag ctcaccaagg tcccctctca gccccctccc stacaccctg amcggccact 360 gscscacacc cacccagagc acgccacccg ccatggggar tgcgcccaag garccgcngg 420 gcarcgtgga catctngccc cagaaggggg cagaatctcc aatagangga ctgarcmstt 480 gctnanaaaa aaaaanaaaa aa 502 &lt; 210 &gt; 196 &lt; 211 &gt; 665 · '&lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 220 &gt;&lt;221&gt;misc一.特欲&lt;222&gt;(1)...(6&amp;5) 127691.doc 72- 200815476 &lt;223&gt; η *= A,T,C or G &lt;400&gt; 196 Ggttacttgg tttcattgcc accacttagt ggatgtcatt tagaaccatt ttgtctgctc 60 cctctggaag ccttgcgcag agcggacttt gtaattgttg gagaataact gctgaatttt 120 wagctgtttk gagttgatts gcaccactgc acccacaact tcaatatgaa aacyawttga 180

actwatttat tatcttgtga aaagtataac aatgaaaatt ttgttcatac tgtattkatc 24Q aagtatgatg aaaagcaawa gatatatatt cttttattat gctaaattat gattgccatt 300 attaatcggc aaaatgtgga gtgtatgttc ttttcacagt aatatatgcc ctatgagttt 540 ttcttagaat gtataaaggt tgtagcccat cnaacctcaa agaaaaaaat ttttgtaact 360 tcacttggtc attttattgt aaatgartta caaaattctt aatttaagar aatggtatgt 420 watatttatt tcattaattt .ctttcctkgt ttacgtwaat tttgaaaaga wtgcatgatt 480 tcttgacaga aatcgatctt gatgctgtgg aagtagttitg acccacatcc gaccacatac 600 Tttgcaatca ggctgaaatg tggcatgctn ttctaattcc aactttataa actagcaaan 660 aagtg 665 &lt;210&gt; 197 &lt;211&gt; 492 &lt;212&gt; DNA &lt;213:&gt; People &lt;22Q&gt;&lt;221&gt; misc_ 4^^

&lt;222&gt; (1)...(4^2) &lt;223&gt; n = A, T, C or G &lt;400&gt; 197 ttttnccttt ttctttttgc aggaaggatc ccatttaccg tggatgcacc ttcacaatat 60 atgtctattg gagcgatcca ttatcagtga aaagtatcaa gtgttcataa natttttagg 120 aaggcagatc cacagaacat gctngtcngc ttgcagtctt acctcgcana gatnacagag 180 aattacagtc naaccagtaa acnaggaatt tacttttcaa aagattaaac ccaaaccgaa * 240 caaaattcca ccctgaaact taccccatcc aaatattgga ataanagtca gcagcgatac 300 attctcttct gaactttaga ttctctagaa aaacacgtas tagtgatcag gaagagctct 360 tgttcaaaag tacaacnaag caatgttccc ctaccacagg ccttaattca aactttgatc 420 catttcactc ccatcacggg agtcaacgct acctgggaca cttgtatttt gttcatnctg 4Θ0 ancntggctt aa 492 &lt; 210 &gt; 198 &lt;211&gt; 47S &lt;212&gt; DNA &lt;213&gt; Human

&lt;220&gt;&lt;221&gt; misc_4^

&lt;222&gt; (1) (478) &lt;223> π = A, T, C or G &lt; 400 &gt; 198 · ttcnttttgn atctcantct gtannaanta ttttcattac gtctattana aaaatatnaa 60 tgtntccacn acaaatcatn ctacntnagt aagaggccan ctacatcgta caacatacac 120 t^agtatatt ttgaaaagga caagtttaaa gtanacncat attgccganc atancacatt 180 tatacatggc ttgattgata tttagcacag canaaactga gtgagttacc agaaanaaat 240 natatatgtc aatcngattt aagatacaaa acagatccta tggtacatan catcntgtag 300 gagttgtggc tttacgttta ccgaaagtca atgcagttcc tgtacaaaga gatggccgta 360 agcattctag tacctctacc ccatggttaa gaaccgtaca cttatgttta catatgtnca 420 73- 127691.doc 200815476 gggtaagaat tgtgttaagt naanttatgg agaggtccan gagaaaaatt tgatncaa 478 &lt; 210 &gt; 199 &lt;211&gt; 482 &lt;212&gt; DNA &lt;213&gt;Human&lt;220&gt;&lt;221&gt;misc1·特教&lt;222&gt; (1) (482) &lt;223&gt; n » A, T, C or G &lt;400&gt; 199 agtgacttgt cctccaacaa aaccccttga tcaagtttgt ggcactgaca atcagaccta 60 tgctagctcc tgtcatctat tcgctactaa atgcagactg gaggggacca aaaaggggca ~120 tcaactccag ctggattatt ttggagcc tg caaatctatt cctacttgta cggactttga 180 agtgattcag tttcctctac ggatgagaga ctggctcaag aatatcctca tgcagcttta 24 0 tgaagccnac tctgaacacg ctggttatct nagatgagaa ncagagaaat aaagtcnaga 300 aaatttacct ggangaaaag aggctttngg ctggggacca tcccattgaa ccttctctta 360 anggactitta agaanaaact accacatgtn tgtngtatcc tggtgccngg ccgtttantg 420 aacntngacn ncacccttnt ggaatanant cttgacngcn tcctgaactt gctcctctgc 480 ga 482

&lt;210&gt; 200 &lt;211&gt; 270 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; mi:sc ·te micro&lt;222&gt; (1).7.(270) &lt;223&gt ; n = A, T, C or G &lt; 4〇0 &gt; 200 cggccgcaag tgcaactcca gctggggccg tgcggacgaa gattctgcca gcagttggtc 60 cgactgcgac gacggcggcg gcgacagtcg caggtgcagc gcgggcgcct ggggtcttgc 120 aaggccgagc tgacgccgca gaggtcgtgt: cacgtcccac gaccttgacg ccgtcgggga 180 cagccggaac agagcccggt gaangcggga ggcctcgggg agcccctcgg gaagggcggc 240 ccgagagata cgcaggtgca ggtggccgcc 270 &lt;210&gt; 201 &lt;211&gt; 419 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt;misc-feature&lt;222&gt; (1).7.(419) &lt;223&gt; n = A, T, C/G &lt;400&gt; 201 ttctttttct ttttggaatc tactgcgagc acagcaggtc agcaacaagt ttattttgca 60 gctagcaagg taacagggta gggcatggtt acatgttcag gtcaacttcc Tttgtcgtgg 120 ttgattggtt tgtctttatg ggggcggggt ggggtagggg aaancgaagc anaantaaca 180 tggagtgggt gcaccctccc tgtagaacct ggttacnaaa gcctggggca gttcacctgg 240 74- 127691.doc 200815476

tctgtgaccg tcattttctt: gacatcaatg ttattagaag tcaggatatc ttttagagag tccactgtnt ctggagggag attagggttt cttgccaana tccaancaaa atccacntga aaaagttgga tgatncangt acngaatacc ganggcatan ttctcatant cggtggcca &lt; 210 &gt; 202 &lt; 211 &gt; 509 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 220 &gt; &lt; 221 &gt; misc a Laid Micro&lt;222&gt; (1).:.(509) · &lt;223&gt; n = A,T,C or G 0 0 9 0 6 1 &lt;400&gt; 202 tttntttttt tttttttttt tttttttttt tttttttttt tttttttttt Cttttttttt tggcacttaa tccattttta tttcaaaatg tccacaaant ttnaatncnc cattatacng gtnattttnc aaaatctaaa nnttattcaa atntnagcca aantccttac ncaaatnnaa tacncncaaa aatcaaaaat atacntntct ttcagcaaac ttngtcacat aaactaaaaa aatatatacg gctggtgttt tcaaagtaca attatcttaa cactgcaaac atntttnnaa ggaactaaaa taaaaaaaaa cactnccgca aaggttaaag ggaacaacaa actcnttcta caacancnnc nattataaaa atcatatctc aaatcttagg ggaatatata ccccacacng ggatcttaac ttttaccnca ctctgtttat ttttttanaa ccattgtntt gggcccaaca caatggnaat nccnccncnc tggactagt - 284o &amp; 20ao 11233445 · 0 &lt; 210 &gt; 203 &lt; 2 11&gt; 583 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc_: Feature &lt;222&gt; (1) (583) &lt;223&gt; n = A, T, C or u &lt; 4 00 &gt; tttttttttt tacacatatt taaatggaaa gaaaatctcc atttttcttg gcttctctag agggaaaaca tacgttaata tccattttag acccaaaagc 203 ttttccctga tat cttataa ctgccticaga tctagccccc tctttaaaac cctcattccc ggaagagana aaatagcatc tcactaaacg taatataaga cccccctctt ttggcattag cacataatcc ctgaccgtaa tatctaatct tagctcttat acggcacaca tcgtgaagcc atatcnaaag tatctcacat ataaaaaaca atattcaaaa tcaggaatta acttttgact ttccattttt ctactattag aaacaaacat agctcaaaag tgccagaatg actcatcttt agttaccacc ggcagcttct gcttaaaatc cttgtaaaac tccctactcc taagcggctt tteatattea aaggettaga caaaaggtcc ctg ttactccact aetaatcsaac tgcctaaagt atccaaattc aagtcaactt ttttcctaaa tatttctacc tccttttatg gtgaacattt 284062Θ48 112334455 &lt; 210 &gt; 204 &lt; 211 &gt; 589 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 220 &gt; &lt; 221 &gt; &lt; 222 &gt; (1)...(589) 75- 127691.doc 200815476

&lt;223&gt; η = A, *T, C or G

&Lt; 400 &gt; 204 ttttttttnt tttttttttt ttttttnctc tttcactctc tagatagggc atgaagaaaa aatctcttat gctatatcat attttaagtt tgaaggaaat ctgttcattc ttctcattca tgagaggttt ttcttctcta tttacacata attttcatgc aaactagaaa ataatgtntt cattacaaaa ctgctcaaat tgtttgttaa ctaatacaaa tcacatttac ugacnagcaa aaaataatta aaggaacatt tttagcctgg ttattnagaa tgaattcaca tgttattatt &lt; 210 &gt; 205 &lt; 211 &gt; 545 &lt; 212 &gt; DNA &lt;2Work 3&gt; Person &lt;220&gt;&lt;221&gt; misc_ Feature &lt;222&gt; "1) (545)

&Lt; 223 &gt; n = A # T, C or G &lt; 400 &gt; 205 cttttntttc ttctttcagc aataatcaga agaaaagtgc cttacactta ataaaagctt tngtcttgaa caccaatact aatctgagga ctaagatcat agagcttgta agtgaaaaga aaaaatccac tattagcaaa caaattacta atggggcgcc actggtaaac caacacattc tatgcacttt gccanatnac gtggatatga aaggggcnga ngaaatgagg aagaaaagaa aaggattaga tatgcttcct ttgccaacat aaccc &lt; 210 &gt; 206 &lt;211&gt; 487 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; 1^5〇_Features &lt;222&gt; (1) (487)

&Lt; 223 &gt; n = A # T, CG ttcttttttt ttganaatga ggatcgagtt ctcatctttc cagctttaaa ataacaatca aaactaatga gtcactggct tatcttctcc tatagttata tcaagtacta ccttgcatat tatttccatg tgaatttgta tcaaaccttt cttttgcata agagaagaga acaatatnag gnttatccat tataattagt tnggcaggag taataaaact gaagtaccag ttaaatatcc gtataattag ctaattcact ttacaagcat ccntagccca acacaatgg acaatattta tttttatact taaaactcac gtcxctcaaa gtigatcagag gaattagata aaacacacca aaatacatta agtaaatcat caaaacccga cctcagaaac tctgagcatt tggacttctt gctttaattt tgtgacgaac tgaaggatac attacttagc gatagatcct gctgacaagt ttctctttct tcaatctttc aaggatcacg cacactgttc tttctatngg taaaadaaca ataatgttta ctactagcga 60 120 180 240 3 00 360 420 480 540 583 60 120 180 240 300 360 420 480 540 545 &lt;. 400 &gt; tttttttttt cattcattag caatttataa cccttctccc accgctgcaa ttggtnagaa tcggtgaaaa 206 ttttttagtic ctctgcaact atgtaaggtg accaactaat acgctaattc tgcatcanca tagactgtgt aagtttctna tiacatatcta ccatcattga gaancagcaa tcttctccat atctnacaat ctgtctgaat tttttattat aattaaagaa gtanatata t: cattagttta ccccatgtng caacagcaag caaatgacct aattaaagtc acgttnttag tcctccaaga attttattag atattgtgta atgaagctag gacctatcct ttggtcattt acaactgtna gtggatgtgt tagatnatac catgtgtgag gcntgggctt cggtggcaag 60 120 180 240 300 360 420 -76- 127691.doc 200815476 ttcaaaa 437 &lt; 210 &gt; 207 &lt; 211 &gt; 332 &lt; 212 &gt; DNA ' &lt;213&gt; Person &lt;220&gt;&lt;221&gt; misc_ Feature &lt;222&gt; (1).7.(332)

&Lt; 223> n »A, T, C or G &lt; 400 &gt; 207 - 'tgaattggct aaaagactgc actttcanaa ctagcaactc ttatttcttt cctttaaaaa 60 tacatagcat taaatcccaa atcctattta aagacctgac agcttgagaa ggtcactact 120 gcatttatag gaccttctgg tggttctgct gttacntttg aantctgaca atccttgana 180 atctttgcat gcagaggagg taaaaggtat tggactttca cagaggaana acacagcgca 240 gaaatgaagg ggccaggctt Actgagcccg cccactggag ggctcatggg tgggacacgg 300 aaaagaaggc agcctaggcc ctggggagcc ca 332

&lt;210&gt; 20B &lt;211&gt; 524 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc one: feature &lt;222&gt; (1) .7. (524) &lt;223&gt; = A, T, C, or 0 &lt; 400 &gt; 208 agggcgtggt gcggagggcg ttactgtctt gtctcagtaa caataaatac aaaaagaccg 60 gttgtgttcc ggccccatcc aaccacgaag tcgatttctc ttgtgtgcag agcgactgac 120 tttaaaggac atggagcttg tcacaatgtc acaatgtcac agtgtgaagg gcacactcac 180 tcccgcgtga tccacatcta gcaaccaaca acagcccatg agcccatact tgtaaatact 240 tttggcagaa tacttntcga aacttgcaga tgacaactaa gatccaagat atttcccaaa 300 gtaaatagaa gtgggtcata ataccaacta cctgttcaca tcagcttcca tttacaagtc 360 atgagcccag acactgacac caaactaagc ccacttagac tcctcaccac cagtctgtcc 420 tgtcatcaga caggaggctg tcacctcgac caaattctca ccagtcaatc atctatccaa 480 aaaccattac ctgatccact tccggtaatg caccaccttg gtga 524 &lt; 210 &gt; 209 &lt; 211 &gt;.. 159 - &lt; 212 &gt; DNA &lt; 213 &gt; al Eu · &lt;400&gt; 209 gggtgaggaa atccagagtt .gccatggaga aaattccagc gtcagcattc ttgctccttg 60 tggccctctc ctacactctg gccagagata ccacagtcaa acctggag Cc aaaaaggaca 120 caaaggactc tcgacccaaa ctgccccaga cccccccca 159

&lt;210&gt; 210 &lt;211&gt; 256 &lt;212&gt; DNA 77 - 127691.doc 200815476 &lt;220&gt;&lt;22l&gt; misc a special respect &lt;222&gt; (1) . . . (256) &lt;223&gt; n «A, T, C or G &lt; 400 &gt; 210 actccctggc agacaaaggc agaggagaga gctctgttag ttctgtgttg ttgaactgcc 60 actgaatttc tttccacttg gactattaca tgccanttga gggactaatg gaaaaacgta 120 tggggagatt ttanccaatt tangtntgta aatggggaga ctggggcagg cgggagagat 180 ttgcagggtg naaatgggan ggctggtttg ttanatgaac agggacatag gaggtaggca 240 ccaggatgct aaatca 256.

&lt;210&gt; 211 &lt;211&gt; 264 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc_ tribute &lt;222&gt; (1) . . . (264) &lt;223&gt; n = A, T, C or G &lt; 400 &gt; 211 acattgtttt tttgagataa agcattgaga gagctctcct taacgtgaca caatggaagg 60 actggaacac atacccacat ctttgttctg agggataatt ttctgataaa gtcttgctgt 120 acattcaagc acatatgtta tatattattc agttccatgt tcatagccta gttaaggaga 180 ggggagacac attcngaaag aggactgaaa gaaatactca agtnggaaaa cagaaaaaga 240 aaaaaaggag caaatgagaa gcct 264

&lt;210&gt; 212 &lt;211&gt; 32Θ &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1) . . . (328) &lt;223&gt; n = A , T, C or G

U &lt; 400 &gt; 212 acccaaaaat ccaatgctga atatttggct tcattattcc canactcttt gactgtcaaa 60 ggactcaatg ttgtctcagc ttgggcactt cagttaggac ccaaggatgc cagccggcag 120 gtttatatat gcagcaacaa tattcaagcg cgacaacagg tcatcgaact tgcccgccag 180 ttnaacccca ttcccattga cttgggatcc ttatcatcag ccagagagat tgaaaattta 240 cccctacnac tctctaccct ctgganaggg ccagtggtgg tagctacaag cttggccaca 300 ttcctttctc ctttactcct ttgtcaga 328 &lt; 210 &gt; 213 &lt;211&gt; 250 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221>misc__ Special 127691.doc 78- 200815476

&lt;222&gt; (1) . . . (250) &lt;223&gt; η = A,T,C Sheep G &lt;400&gt; 213 acttatgagc agagcgacat atccnagtgt agactgaata aaactgaatt ctctccagtt 60 taaagcattg ctcactgaag ggatagaagt gactgccagg agggaaagta agccaaggct 120 cattatgcca aagganatat acatttcaat tctccaaact tcttcctcat Tccaagagtt 180 ttcaatattt gcatgaacct gctgataanc catgttaana aacaaatatc tctctnacct 240 tctcatcggt 25〇&lt;210&gt; 214 &lt;211&gt; 444 &lt;212&gt; DNA &lt;213&gt;People&lt;22Q&gt;

&lt;221&gt; misc - special respect &lt;222&gt; (X)...(444) &lt;223> n = A, T, C or G

&Lt; 400 &gt; 214 .- acccagaacc caatgctgaa tatttggctt cattattccc agatcctttg attgtcaaag 60 gatttaatgt tgtctcagct tgggcacttc agttaggacc taaggatgcc agccggcagg 120 tttatacacg cagcaacaat attcaagcgc gacaacaggt tattgaactt gcccgccagt 180 cgaactccat tcccattgac ttgggatcct tatcatcagc canagagatt gaaaatttac 240 ccctacgact:. Ctctactctc tggagagggc cagtggtggt agctataagc ttggccacat 300 tctcttctcc tttattcctc tgtcagagat gcgattcatc catatgctan aaaccaacag 360 agtgactttt acaaaattcc tataganatt gtgaataaaa ccttacccat agttgccact 420 actttgctct ccctaatata cctc 444 &lt;210&gt; 215 &lt;211&gt; 366 &lt;212&gt; DNA &lt;2X3&gt;People&lt;220&gt;

&lt;221&gt; misc_ 4 佘敬 &lt;222&gt; (1)...(366) &lt;223&gt; n = A#T, C or G &lt;400&gt; 215 actcacgagc agagcgacat atccaagtgt anactgaata aaactgaatc ctctccagtt 60

taaagcattg ctcactgaag ggatagaagt gactgccagg agggaaagta agccaaggct 120 catcatgcca aagganatat acatttcaat tctccaaact tcttccccat tccaagagtt '180 ttcaatattt gcatgaacct gctgataagc catgttgaga aacaaatatc tctctgacct 240 tctcatcggt aagcagaggc tgtaggcaac atggaccata gcgaanaaaa aacttagtaa 300 tccaagctgc cctctacact gtaaccaggt ttccaaccaa ggtggaaatc tcctatactt 360 ggtgcc 366 &lt; 210 &gt; 216 &lt; 211 &gt; 260 &lt;212&gt; DNA &lt;213&gt;People 127691.doc 79- &lt;220&gt; 200815476

&lt;221&gt; misc__ 特ίΐ &lt;222&gt; (1).7.(260) &lt;223>η - A,T,C or · G &lt;400&gt; 216 ctgtataaac agaactccac tgcangaggg agggccgggc caggagaatc tccgcttgtc 60 caagacaggg gcctaaggag ggtctccaca ctgctnntaa Gggctnttnc atttttttat 120 taataaaaag tnnaaaaggc ctcttctcaa cttttttccc ttnggctgga aaatttaaaa 180 atcaaaaatt tcctnaagtt ntcaagctat catatatact ntatcctgaa aaagcaacat: 240 aattcttcct tccctccttt .· 260 &lt;210&gt; 217 &lt;211&gt; 262 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;

&lt;221&gt; miscj Desire &lt;222&gt; (1).7.(262) &lt;223> n * A, T, C or G

&Lt; 400 &gt; 217 - acctacgtgg gtaagtttan aaatgttata atttcaggaa naggaacgca tataattgta 60 tcttgcctat aattttctat tttaataagg aaatagcaaa ttggggtggg gggaatgtag 120 ggcattctac agtttgagca aaatgcaatt aaatgtggaa ggacagcact gaaaaatttt 180 atgaataatc tgtatgatta t.atgtctcta gagtagattt ataattagcc acttacccca 240 atatccttca tgcttgcaaa gt 262

&lt;210&gt; 218 &lt;211&gt; 205 &lt;212&gt; DNA &lt;213&gt; Person &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1).7.(205)

&Lt; 223 &gt; n: = A, T, C or G &lt; 400 &gt; 218 accaaggtgg tgcattaccg gaantggatc aangacacca tcgtggccaa cccctgagca 60 cccctatcaa ctcccttctg tagtaaactt ggaaccttgg aaatgaccag gccaagactc 120, aggcctcccc agttctactg acctttgtcc ttangtntna ngtccagggt tgctaggaaa 180 anaaatcagc agacacaggt gtaaa - · 205 &lt; 210 &gt; 219 &lt;211&gt; 114 &lt;212&gt; DNA . , &lt;213&gt; Human &lt;400&gt; 219 tactgttttg tctcagtaac aataaataca aaaagactgg ttgtgttccg gccccatcca 60 accacgaagt tgatttctct tgtgtgcaga gtgactgatt ttaaaggaca tgga H4 &lt;210&gt; 220 80- 127691.doc 200815476 &lt;;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 220 actagccagc acaaaaggca gggtagcctg aattgctttc tgctctttac atttctttta 60 aaataagcat ttagtgctca gtccctactg agt 93 &lt;210&gt; 221 &lt;211&gt; 167 &lt;212&gt; DNA &lt;213&gt; People's &lt;;220&gt;&lt;221&gt; misc one: special education &lt;222&gt; (1)...(167)

&lt;223&gt; n » A, T, C or G &lt;400&gt; 221

U actangtgca ggcgcgcaca aatatttgcc gatattccct tcatcttgga ttccatgagg 60 tcttttgccc agcctgtggc tctactgtag taagtttctg ctgatgagga gccagnatgc 120 cccccactac cttccctgac gctccccana aatcacCcaa cctctgt 167 &lt; 210 &gt; 222 &quot; &lt; 211 &gt;. 351 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 222 agggcgcggt gcggagggcg gtaccgacct .cattagtagg aggatgcatt ctggcacccc 60 gttcttcacc tgtcccccaa tcctcaaaag gccatactgc ataaagtcaa caacagataa 120 atgtctgctg aattaaagga tggatgaaaa aaattaataa tgaatttttg cataatccaa 180 ttttctcttt tatatttcta gaagaagttt cctcgagccc attagatccc gggaatcctt 240 taggtgagca cgattagaga gcttgtaggt tgctcttaca tatatctggc acatttgagt 300 ctcgtatcaa aacaatagat tggtaaaggt ggtattattg tattgataag t 351

&lt;210&gt; 223 &lt;211&gt; 383 &lt;212&gt; DNA &lt;213&gt; People None &lt;220&gt;

&lt;221&gt; mi sc - feature &lt;222&gt; (1).7.(383) &lt;223&gt; n = A, T, C or G &lt;400&gt; 223 aaddcaaaca aacaaaaaaa acaattcttc attcagaaaa attatcttag ggactgatat 60 tggtaattat ggtcaattta atwrtrttkt ggggcatttc cttacattgt cttgacaaga 120 ttaaaatgtc tgtgccaaaa tttcgtattt tatttggaga cttcttatca aaagtaatgc 180 tgccaaagga agtctaagga attagtagtg ttcccmtcac ttgtttggag tgtgctattc 240 taaaagattt tgatttcctg gaatgacaat tatattttaa ctttggtggg ggaaanagtt 300 ataggaccac agtcttcact tctgatactt gtaaattaat cttttattgc acttgttttg 360 accattaagc tatatgttta aaa 383 -81 - 127691.doc 200815476 Ο Ο &lt; 211 &gt; 320 ' &lt; 212 &gt; DNA &lt; 213 &gt; · human &lt; 400 &gt; 224 cccctgaagg cttcttgtta gaaaatagta cagttacaac caataggaac aacaaaaaga aaaagtttgt gacattgtag tagggagtgt gtacccctta ctccccatca aaaaaaaaat ggatacatgg ttaaaggata raagggcaat attttatcat atgttctaaa agagaaggaa gagaaaatac tactttctcr aaatggaagc ccttaaaggt gctttgatac tgaaggacac aaatgtggcc gtccatcctc ctttaragtt gcatgacttg gacacggtaa ctgttgcagt cttaractcm gcattgtgac · &Lt; 210 &gt; 225 &lt; 211 &gt; 1214 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 40Q &gt; 225 gaggactgca gcccgcactc gcagccctgg caggcggcac tggtcacgga aaacgaattg ttctgctcgg gcgtcctggt gcatccgcag tgggtgctgt cagccgcaca ctgtttccag aactcctaca ccatcgggct gggcctgcac agtcttgagg ccgaccaaga gccagggagc cagatggtgg aggccagcct ctccgtacgg cacccagag.t acaacagacc cttgctcgct aacgacctca tgctcatcaa gttggacgaa tccgtgtccg agtctgacac catccggagc atcagcattg cttcgcagtg ccctaccgcg gggaactctt gcctcgtttc tggctggggt ctgctggcga acggcagaat gcctaccgtg ctgcagtgcg tgaacgtgtc ggtggtgtct gaggaggtct gcagtaagct ccatgacccg ctgtaccacc ccagcatgtt ctgcgccggc ggagggcaag accagaagga ctcctgcaac ggtgactctg gggggcccct gatctgcaac gggcacctgc agggccttgt gtctttcgga aaagccccgt gtggccaagt tggcgtgcca ggcgcctaca ccaacctctg caaattcact gagtggatag agaaaaccgt ccaggcc'agt caactccggg gactgggaac ccatgaaatt gacccccaaa Cacaccctgc ggaaggaatt caggaatatc tgttcccagc ccctcctccc ccaggcccag gagtccaggc ccccagcccc ccctccccca aaccaagggt acagaticccc· agcccctcct ccctcagac c caggagtcca gaccccccag cccctcctcc ctcagaccca ggagtccagc ccctcctccc tcagacccag gagcccagac cccccagccc ctcctccctc agacccaggg gcccaggccc ccaacccctc cccccccaga ctcagaggtc caagccccca acccctcctt ccccagaccc agaggtccag gccccagccc ctcctccctc agacccagcg gtccaatgcc acctagactc tccctgtaca cagcgccccc ttgtggcacg ttgacccaac cttaccagtt ggtttttcat tttttgtccc tctcccctag atccagaaat aaagtctaag agaagcgcaa aaaadaaaaa aaaaaaaaaa aaaaaaaaaa aaaa &lt; 210 &gt; 226 &lt; 211 &gt; 119 &lt;212&gt; DNA . &lt;213&gt; Human &lt;400&gt; 226 acccagcatg tgcagggaga cggaacccca tgtgacagcc cactccacca gggttcccaa agaacccggc ccagtcataa cbattcatcc tgacagtggc aataatcacg ataaccagt &lt;210&gt; 227 &lt;211&gt; 818 &lt;212> DNA &lt;213&gt; Human &lt;400&gt; 227 60 120 180 240 300 320 60 120 180 240 300 360 420 4Θ0 540 600 6 60 720 780 840 900 960 1020 1080 1140 1200 1214 60 119 127691.doc 82- 200815476 acaattcata gggacgacca atgaggacag ggaatgaacc cggctctccc ccagccctga 60 tttttgctac atatggggtc ccttttcatt cttcgcaaaa Acactgggtt ttctgagaa c 120 acggacggtt: cttagcacaa tttgtgaaat ctgcgtaraa ccgggctttg caggggagat 180 aatcttcctc ctctggagga aaggtggtga ttgacaggca gggagacagt gacaaggcta 240 gagaaagcca cgctcggcct tctctgaacc aggatggaac ggcagacccc tgaaaacgaa 300 gcttgtcccc ttccaatcag ccacttctga gaacccccat ctaacttcct actggaaaag 360 agggcctcct caggagcagt ccaagagttt tcaaagataa cgtgacaact accatctaga 420 ggaaagggtg caccctcagc agagaagccg agagcttaac tctggtcgtt tccagagaca 480 acctgctggc tgtcttggga tgcgcccagc ctttgagagg ccactacccc atgaacttct 540 gccatccact: ggacatgaag ctgaggacac tgggcttcaa cactgagttg tcatgagagg 600 4 gacaggctct gccctcaagc cggctgaggg cagcaaccac tctcctcccc tttctcacgc 660 aaagccattc ccacaaatcc agaccatacc atgaagcaac gagacccaaa cagtttggct 720 caagaggata tgaggactgt ctcagcctgg ctttgggctg acaccatgca cacacacaag 780 gtccacttct aggttttcag cctagatggg agtcgtgt 818 &lt; 210 &gt; 228 &lt; 211 &gt; 744 &lt; 212 &gt; DNA &lt;213&gt;Human&lt;400&gt; 228 actggagaca ctgttgaact tgatcaagac ccagaccacc ccaggcctcc ttcgtgggat 60 gtcatgacgt ctgacatacc t Ttggaacga gcctcctgct tggaagatgg aagaccgtgt 120 tcgtggccga cctggcctct cctggcctgt ttcctaagat gcggagtcac acttcaatgg 180 taggaaaagt ggctccgtaa aacagaagag cagtcactgt ggaactacca aatggcgaga 240 tgctcggtgc acattggggt gctttgggat aaaagattta tgagccaact attctctggc 300

accagactct aggccagttt gttccactga agctcttccc acagcagtcc acctctgcag 36G gctggcagct gaatggcttg ccggtggctc tgtggcaaga tcacactgag atcgatgggt 420 gagaaggcta ggatgcttgt ctagtgttct tagctgtcac gttggctccc tccaggttgg 480 ccagacggcg ttggccactc ccttctaaaa cacaggcgcc ctcccggtga cagcgacccg 540 ccgcggcatg ccttggccca ttccagcagc cccagttacg catttcaagt ttggggtttg 600 ttctcttcgt taatgttcct ctgtgttgtc agctgtcttc atttcctggg ctaagcagca 660 ttgggagatg tggaccagag atccactcct taagaaccag tggcgaaaga cactttcttt 720 ctccaccctg Aagtagctgg tggt 744

&lt;210&gt; 229 &lt;211&gt; 300 &lt;212&gt; DNA &lt;213&gt; • Person &lt;400&gt;

cgagtctggg ttttgtctat aaagtttgat ccctcctttt ctcatccaaa tcatgtgaac 60 cattacacat cgaaataaaa gaaaggtggc agacttgccc aacgccaggc tgacatgtgc 120 tgcagggttg ttgtttttta attattattg ttagaaacgt cacccacagt ccctgctaat 180 ttgtacgtga cagccaactc tgagaaggcc ccacttttcc acctgcagag gatccagtct 240 caccaggccc ctccttgccc tcacactgga gtctccgcca gtgtgggcgc ccactgacat 300 &lt; 210 &gt; 230, &lt; 211 &gt; 301 · &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 230 cagcagaaca aatacaaata tgaagagtgc aaagatctca taaaatctat gctgaggaat 60 -83- 127691.doc 200815476 caatataaag tcctggttca cactcaggaa cgagagctga cccagttaag ggagaagttg 180 cgggaaggga gagatgcctc cctctcattg aatgagcatc tccaggccct cctcactccg 240 gatgaaccgg acaagtccca ggggcaggac ctccaagaaa cagacctcgg ccgcgaccac 300 g 301 &lt;210&gt; 231 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 231 . g gcaagcacgc tggcaaatct ctgccaggtc agctccagag aagccattag tcattttagc 6a caggaactcc aagtccacat ccttggcaac tggggacttg cgcaggttag ccttgaggat 120 ggcaacacgg gacttctcat caggaagtgg gatgtagatg agctgatcaa gacggccagg 180 tctgaggatg gcaggatcaa tgatgtcagg ccggttggta ccgccaatga tgaacacatt 240 tttttttgtg gacatgccat ccatttctgt caggatctgg ttgatgactc ggtcagcagc 300 c 301 Γ &lt; 210 &gt; 232 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 232 agtaggtatt tcgtgagaag ttcaacacca aaactggaac atagttctcc ttcaagtgtt 60 ggcgacagcg gggcttcctg attctggaat ataactttgt gtaaattaac agccacctat 120 agaagagtcc atctgctgtg aaggagagac agagaacr.ct gggttccgtc gccccgtcca 180 cgcgccgtac caagtgctgg tgccagcctg ttacctgttc ccactgaaaa tccggccaac 240 gctctzgcgt atcacttctg attctgacaa tqaatcaatc aatggcctag agcactgact * 300 g 301 &lt; 210 &gt; 233 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human ϋ &lt; 4〇0 &gt; 233 atgactgacc ccccagtaag gctctctaag gggtaagtag gaggatccac aggatttgag 60 acgccaaggc cccagagatc gtttgatcca accctcttat ttccagaggg gaaaatgggg 120 cctagaagct acagagcatc tagctggtgc gctggcaccc ctggcctcac acagactccc 180 gagcagctgg gactacaggc acacagtcac tgaagcaggc cctgttagca attctatgcg 2 40 tacaaatcaa catgagatga gtagagactt tattgagaaa gcaagagaaa atcctatcaa&quot; 300 c 301 &lt;210&gt; 234 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human '* &lt;400&gt; 234 aggtcctaca caccgagact catccatgat tgatatgaat ttaaaaatta caagcaaaga 60 cattttattc atcatgatgc tttcttttgt ttcttctttt cgttttcttc tttttctttt 120 tcaattccag caacatactt ctcaatttct tcaggattta aaatcttgag ggattgatct 180 cgccccatga cagcaagttc aacgtctttg ccacctgact gaaccacttc caggagtgcc 240 ccgatcacca gcttaatggt cagatcatct gcttcaatg ^ cttcgtcagt atagttcctc 300 127691.doc 84- 301200815476 t Ο ο &lt; 210 &gt; 235 &lt; 211 &gt; 283 &lt; 212 &gt; DNA &lt; 213 &gt; al Somen ·, · &lt; 400 &gt; 235 tggggctgtg catcaggcgg * gtttgagaaa tattcaattc tcagcagaag ccagaatttg aattccctca tcttttaggg aatcatttac caggtttgga gaggattcag acagctcagg tgctttcact aatgtctctg aacttctgtc cctctttgtt catggatagt ccaataaata atgttatctt tgaactgatg ctcataggag agadtataag aactctgagt: gatatcaaca ttagggactc aaagaaatat tagatttaag cccacactgg tea &lt; 210 &gt; 236 &lt;211&gt; 301 &lt;212 &Gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 236 ·· aggtcctcca ccaactgcct gaagcacggt caaaattggg aagaageata gtgeageata aatactttta aatcgatcag atttccctaa cccacatgca atettettea ccagsagagg ccggagcagc atcactaata ccaagcagaa tgcgtaacag ataaatacaa eggeatatag tgggtagacg gcttcatgsg tacagcgcac tgtggtatcg taatctggac tcgggttgta aagcatcgcg taccagtcag aaagcatcaa tactcgacat gaaegaatat aaagaacacc a &lt; 210 &gt; 237 &lt; 211 &gt; 301 &lt; 212 &gt; DNA Simon &lt; 400 &gt; 237 cagtggtagt ggtggtggac gtggcgctgg tcgtggtgcc ctttttggtg cccgtcacaa actcaatttt tgttcgctcc tttttggcct tttccaactt gtccatctca atcttccggg ccctggctaa tgcctcatag taggagccct cagaccagcc atggggatca aacacatccc tcgggtagtt ggcgccaagc tcgtcaatgg cacagaatgg atcagcttct cgcaaatcta gggttccgaa attetttett cctttggata aegtagttea tatccat kernel cc ctcctttatc t &lt;210&gt; 238 ^ &lt;211&gt; 301 ~ &lt;212&gt; DNA &lt;213 &gt; human face &lt;400&gt; 238 gggcaggttt tttttttttt ttctttgatg gtgcagaccc ttgctttatt tgtctgactt gtccacagtt cagccccctg ctcagaaaac caacgggcca getaaggaga ggaggag Gea .ccttgagact teeggagteg aggctctcca gggttcccca gcccatcaac cattctctgc accccctgcc tgggaagcag ctccctgggg ggtgggaatg ggtgactaga agggatttca gtgtgggacc cagggtctgt tcttcacagt aggaggtgga agggatgact aatttcttta t 60 120 -180 240 283 60 120 180 240 300 301 60 120 180 240 300 301 60 120 180 240 300 301 &lt;210&gt; &lt; 211 &gt; 239 _ 127691.doc -85- 200815476 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 239 ataagcagct agggaattct ttatttagta atgtcctaac ataaaagttc acataactgc 60 ttctgtcaaa ccatgatact gagctttgtg acaacccaga aataactaag agaaggcaaa 120 cataatacct tagagatcaa gaaacattta cacagttcaa ctgtttaaaa atagctcaac 180 attcagccag tgagtagagt gtgaatgcca gcatacacag tatacaggtc cttcaggga 239 &lt; 210 &gt; 240 &lt; 211 &gt; 300 &lt; 212 &gt; DNA &lt; 213 &gt; al crop-full &lt; 400 &gt; 240 ggtcctaatg aagcagcagc ttccacattt taacgcaggt ttacggtgat actgtccttt 60 gggatctgcc ctccagtgga acctttcaag gaagaagtgg gcccaagcta agttccacat 120 gctgggtgag ccagatgact tctgttccct ggtcactttc Ttcaatgggg cgaatggggg 180 ctgccaggtt tttaaaatca tgct tcatct tgaagcacac ggtcacttca ccctcctcac 240 gctgtgggtg tactttgatg aaaataccca ctttgttggc ctttctgaag ctataatgtc 300 Γ_ &lt; 210 &gt; 241 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; Simon &lt; 400 &gt; 241 gaggtctggt gctgaggtct ctgggctagg aagaggagtt ctgtggagct ggaagccaga 60 cccctctgga ggaaactcca gcagctatgt tggtgtctct gagggaatgc aacaaggctg 120 cccccccatg tattggaaaa ctgcaaactg gactcaactg gaaggaagtg ctgctgccag 180 tgtgaagaac cagcctgagg tgacagaaac ggaagcaaac aggaacagcc agtcttttct 240 tcctcctcct gccatacggt ctctctcaag catcctttgc tgtcaggggc ctaaaaggga 300 g 301 &lt; 210 &gt; 242 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 242 ccgaggtcct gggatgcaac caatcactct gtttcacgtg acttttatca ccatacaact 60 tgtggcattc cctcattttc cacattgtag aatcaagagt gtaaataaat gtatatcgat 120

gtcCtcaaga atatatcact cctttctcac tagaacccat tcaaaatata agtcaagaat 180 cttaatatca acaaatatat caagcaaact ggaaggcaga ataactacca taatttagta 240 taagtaccca aagttttata aatcaaaagc cctaatgata accattttta gaattcaatc 300 a 301 &lt;210&gt; 243 — &lt;211&gt; 301 ' &lt;212&gt; DNA &lt;213&gt; Person. &lt;400&gt ; 243 aggtaagtcc cagtttgaag ctcaaaagat ctggtatgag cataggctca tcgacgacat 60 ggtggcccaa gctatgaaat cagagggagg cttcatctgg gcctgtaaaa actatgacgg 120 127691.doc 86- 200815476 tgacgtgcag tcggactctg tggcccaagg gtatggctct ctcggcatga tgaccagcgt gctggtttgt ccagatggca agacagtaga agcagaggct gcccacggga ctgtaacccg tcactaccgc acgttccaga aaggacagga gacgtccacc aatcccattg cttccatttt t &lt; 210 &gt; 244 &lt; 211 &gt; 300 &lt; 212 &gt; DMA &lt; 213 &gt; human &lt; 40Q &gt; 244 gctggtttgc aagaatgaaa tgaatgattc tacagctagg acttaacctt gaaatggaaa gtcatgcaat cccatttgca ggatictgtct gtgcacatgc ctctgtagag agcagcattc ccagggacct tggaaacagt tgacactgta aggtgcttgc tccccaagac acatcctaaa aggtgttgta atggtgaaaa cgtcttcctt ctttattgcc cctt Cttatt catgtgaaca actgtttgtc tctcgcgtat cttttttaaa ctgtaaagtt caattgtgaa aatgaatatc &lt;210&gt; 245 &lt;211&gt; 301 0&lt;212&gt; DNA · · · &lt;213&gt;People&lt;4〇〇&gt; 245 .· gtctgagcat ttaaaatgct accgaaatta cccccaacca atgttagaaa agaaagaggt tatatactca gataaaaaat gaggtgaatt actatccatt gaaatcatgc tcttagaatt aaggccagga gatattgtca ttaatgtara cttcaggaca ctagagtata gcagccccat gttttcaaag agcagagatg caattaaata ttgtttagca tcaaaaaggc cactcaatac agctaataaa atgaaagacc taatttctaa agcaattctc tacaatctac aaagtctcaa 9 &lt; 210 &gt; 246 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 246 ggtctgtccc acaacgcctg cctcttgaaa gaagtcggca ctttctagaa tagctaaata acctgggctc attttaaaga actatttgta gctcagattg gttttcctat ggccaaaata agtgcttctt gtgaaaatta aataaaacag ttaattcaaa gccctgatat atgtcaccac taacaatcat actaaatata ttctgaagta caaagtttga catgctctaa agtgacaacc caaatgtgtc ttacaaaaca cgtccctaac aaggtatgct ttacactacc aatgcagaaa o ^ &lt; 210 &gt; 247 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al.铕 &lt; 400 &gt; 247 aggtcctttg gcagggctca tggatcagag ctcaaactgg agggaaaggc atttcgggta gcctaagagg gcgactggcg gcagcacaac caaggaaggc aaggttgttt cccccacgct gtgtcctgtg txcaggtgcg acacacaatc ctcatgggaa caggatcacc catgcgctgc cctcgatgat caaggttggg gcttaagtgg atcaagggag gcaagttctg ggttccttgc cttttcaaac catgaagtca ggctctgtat ccctcctttt cctaactgat attctaacca a 8 4 0 0 12 3 3 6- · - 2 8 4 o -1 1 2 3 ooooo 1 6 2 8 4 0 0 2 8 4 0 0 112 3 3 o 6 2 8 4 112 o 1 oo 127691.doc 87- 200815476 &lt;210&gt; 248 &lt;211&gt; 301 &lt;212&gt ; DNA &lt; 213 &gt; human &lt; 400 &gt; 248 aggtccttgg agatgccatt tcagccgaag gactcttctw ttcggaagta caccctcact attaggaaga ttcttagggg taatttttct gaggaaggag aactagccaa ctcaagaatt acaggaagaa agtggtttgg aagacagcca aagaaataaa agcagattaa attgtatcag gtacattcca gcctgttggc aactccataa aaacatttca gattttaatc ccgaatttag ctaatgagac tggatttttg ttttttatgt tgtgtgtcgc agagctaaaa actcagttcc 2 8 4 0 0 112 3 3 &lt;210&gt; 249 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human o &lt;400&gt; 249 gtccagagga a gcacctggt gctgaactag gcttgccctg ctgtgaactt gcacttggag ccctgacgct gctgttctcc ccgaaaaacc cgaccgacct ccgc ^ atctc cgtcccgccc ccagggagac acagcagtga ctcagagctg gtcgcacact gtgcctccct cctcaccgcc catcgtaatg aactattttg aaaattaatt ccaccatcet ttcagattct ggatggaaag actgaatctc tgactcagaa tcgtttgctg aaaagaatga t-.gtgactttc ttagccattt aooooo 1 6 2 8 4 0 0 &lt; 210 &gt; 250 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al crop-full &lt; 400 &gt; 250 ggtctgtgac aaggacttgc aggctgtggg aggcaagtga cccttaacac tacacttctc ctcatcttta ttggcttgat aaacataatt atttctaaca ctagcttatt tccagttgcc cacaagcaca tcagcaccct tccctggctg gaatagtaaa ctaaagtatg gtacatctac ctaaaagact accatgtgaa ataatacata ctaatgaagt attacatgat ttaaagacta caataaaacc aaacatgctt ataacattaa 'gaaaaacaat aaagatacat gactgaaacc a 2 Θ 4 ο o 112 3 3 u &lt;210&gt; 251 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt;Human&lt;400&gt; 251 gccgaggtcc tacacttggc agacaacctc atagagcata ggcaggggtc ctcaaaaatg cattgggacc aatgaaaagc cctctggagg ggggcagtgg ccagtttccc ggagaaccgg cca ctgtcac ttcaagaaat aatcccagct cctgcatcct rcgccctggg tgccaggaaa cctcaggctc ccaggacgga ctccagggcc ggcaggggga tgcttctgag actctcttga tcccgtcgaa cctgcctcat ctgtctggat cagtacacct aggcccggaa aagatatcct 2 8 4 0 0 112 3 3 &lt; 210 &gt; 252 &lt; 211 &gt; 301 127691.doc 88- 200815476 &lt; 212 &gt; DNA &lt; 2 13 &gt; human &lt; 400 &gt; 252 gcaaccaatc actctgtttc acgtgacttt tatcaccaca caatttgtigg catttcctca 60 ttttctacat tgtagaatca agagtgtaaa taaatgtata tcgatgtctt caagaatata 120 tcattccttt ttcactagga acccattcaa aatataagtc aagaatctta atatcaacaa 180 atatatcaag caaactggaa ggcagaataa ctaccataat ttagtataag tacccaaagt 240 tttataaatc aaaagcccta atgataacca tctctagaat tcaatcatca ctgtagaatc 300 a 301 &lt; 210 &gt; 253 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 253 ttccctaaga agatgttatt ttgttgggtt ttgttccccc cccatctcga ttctcgtacc 60 caactaaaaa aaaaaaataa agaaaaaatg tgctgcgttc tgaaaaataa ctccttagct 120 tggtctgatt gttttcagac cttaaaatat aaacttgtct cacaagcttt aatccatgtg 180

gatttttcct cttagagaac cacaaaacat aaaaggagca agccggactg aatacctgtt 240 tccatagtgc ccacagggta ttcctcacat ttcctccaiza ggaaaatgct ttttcccaag 300 g 301 &lt; 210 &gt; 254 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 254 - cgccgcgcct ttcccttggg ggaggggcaa ggccagaggg ggtccaagtg cagcacgagg 60 aacttgacca attcccttga agcgggtggg ttaaaccctg caaatgggaa caaaatcccc 120 ccaaatctct tcaccttacc ctggcggact cccgactgca gaacctcctg gttgaaacaa 180 gaaaaaaata aagctttgga cttttcaagg ttgctcaaca ggtactgaaa gactggcctc 240 actcaaactg agccaggaaa agctgcagat ttactaatgg gtgcgttagt gtgcagtgcc 300 t 301 &lt; 210 &gt; 255 &lt; 211 &gt; 302 &lt; 212 &gt; DNA &lt; 213 &gt; · human .

&Lt; 400 &gt; 255 - agcttttittt ttttttcctt ttcattaaaa aatagtgctc tttattataa 60 atcactgaaa tgtttctttt ccgaatacaa atataaatac gtgcaaagtt tgacttggat 120 tgggattttg ttgagttctc caagcacctc ctaataccct caagggcctg agtagggggg 180 aggaaaaagg actggaggtg gaatctttat aaaaaacaag agtgattgag gcagattgta 240 aacaccatta aaaaacaaga aacaaacaaa a'aaatagaga aaaaaaccac cccaacacac 300 aa 302 &lt; 210 &gt; 256 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human-89-127691.doc 200815476 &lt;220&gt;

&lt;221&gt; misc_5 Desirable &lt;222&gt; (1) . . . (301) ' &lt;223&gt; n = A#T, C or G &lt;400&gt; 256 gttccagaaa acattgaagg tggcttccca aagtctaact agggataccc cctctagcct 60 aggaccctcc tccccacacc tcaatccacc aaaccatcca caatgcaccc agacaggccc 120 acccccaaaa gcctggacac cttgagcaca cagttatgac caggacagac tcatctctat 180 aggcaaatag ctgctggcaa actggcatta cctggtttgt ggggatgggg gggcaagtgt 240 gtggcctctc ggcctggtta gcaagaacat tcagggtagg cctaagttan tcgtgttagt 300 t 301 &lt; 210 &gt; 257 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt;400&gt; 257 gttgtggagg aactctggct tgctcattaa gtcctactga ttttcactat cccctgaatt 60 tccccactta tttttgtctt tcactatcgc aggccttaga agaggtctac ctgcctccag 120

C tcttacctag tccagtctac cccctggagt tagaatggcc atcctgaagt gaaaagtaat 180 gtcacattac tcccttcagt gatttcttgt agaagtgcca- atccctgaat gccaccaaga 240 tcctaatctt cacatcttta atcttatctc tttgactcct ctttacaccg gagaaggccc 300 C · '301 &lt; 210 &gt; 258 &lt; 211 &gt; 301 &lt; 212 &gt; DNA, 213 &gt; A class &lt; 220 &gt; * &lt;221&gt; mi sc a special desire &lt;222&gt; (1).7.(301)

&Lt; 223 &gt; n =, or G &lt; 400 &gt; 258 cagcagcagt agatgccgta tgccagcacg cccagcactc ccaggatcag caccagcacc 60 aggggcccag ccaccaggcg cagaagcaag ataaacagta ggctcaagac cagagccacc 120 cccagggcaa caagaatcca ataccaggac tgggcaaaat cttcaaagat cttaacactg 180 atgtcccggg cattgaggct gtcaataana cgctgatccc ctgctgtacg gtggtgtcat 240 tggtgacccc tgggagcgcc ggcggagtaa cgttggtcca tggaaagcag cgcccacaac 300 t 301

&lt;210&gt; 259 &lt;211&gt; 301 ·

&lt;212&gt; DNA &lt;213&gt;People &lt;&lt;220&gt;

&lt;221&gt; misc 1. esteem &lt;222&gt; (1).7.(301) &lt;223&gt; n = A, T#C or G &lt;400&gt; 259 -90- 127691.doc 200815476 tcatatatgc aaacaaatgc agactangcc tcaggcagag actaaaggac atctcttggg gtgtcctgaa gtgatttgga cccctgaggg cagacaccta agtaggaatc ccagtgggaa gcaaagccat aaggaagccc aggattcctt gtgatcagga agtgggccag gaaggtctgt tccagctcac atctcatctg catgcagcac ggaccggatg cgcccactgg gtcttggctt ccctcccatc ttctcaagca gtgtccttgt tgagccattt gcatccttgg ctccaggtgg c 60 120 180 240 300 301

&Lt; 210 &gt; 260 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 260 ttttttttct ccctaaggaa aaagaaggaa caagtctcat aaaaccaaat aagcaatggt aaggtgtctt aacttgaaaa agattaggag tcactggttt acaagttaca attgaatgaa agaactgtaa cagccacagt tggccatttc atgccaatgg cagcaaacaa caggattaac tagggcaaaa caaataagtg tgtggaagcc ctgataagtg cttaataaac agactgatcc actgagacat cagcacctgc ccgggcggcc gctcgagccg aattctgcag atatccatca c &lt; 210 &gt; 261 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al amount &lt; 400 &gt; 261 aaacatccga gcaaaccctg taactaacgt gtctccataa aaggccttga actcagtgaa tctgctccca cccacgattc cagcaacgac ctctcggaca tcaaagcccc tcttaaggtt agcaccaact attccataca attcatcagc aggaaataaa ggctcctcag aaggtccaat Ggtgacaccc aatttcttct gataatttag attcctcaca accttcccag tcaagtgaag ggcatgacga ccatccaaag cccagcggtc acttactcca gaccctctgc aatgaagatc a . 60 120 180 240 300 301 60 120 180 240 300 301

&Lt; 210 &gt; 262 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213> Human &lt; 400 &gt; 262 gaggagagcc cgttacagca tttgcaagca cagaatactc caggagcatt tgtaactgtc tgtgagcccc tcgccgcaag tctctcagaa atttaaaaag atgcaaatcc ctgagccacc cctagacctc ctaaaccaga tcctctgggg ctggaacctg gcactctgca tttgtaatga gggctttctig gtgcacacct aattttgtgc atctttgccc taaaccctgg atcagcgccc catcatcacc Cccacattat aatgggatag atccagagca gatactctcc agcaaagaat c . &lt;210&gt; 263 &lt;211&gt; 301 ' - &lt;212&gt; DNA &lt;213&gt;Human&lt;220&gt;&lt;221&gt; misc-characteristics &lt;222&gt; (1).. (301) &lt;223&gt; n = A, T, C, or G 60 120 180 240 300 301 127691.doc -91- 200815476 &lt;400&gt; 263 tttagcttgt ggtaaatgac tcacaaaact gattttaaaa tcaagttaat gtgaattttg 60 aaaattacta cttaatccta attcacaata acaatggcat taaggtttga cttgagttgg 120 Ttcttagtat tatttatggt aaataggctc ttaccacttg caaataactg gccacatcat 180 taatgactga cttcccagta aggctctcta aggggtaagt angaggatcc acaggatttg 240 agatgctaag gccccagaga tcgtttgatc caaccctctt attttcagag gggaaaatgg 300 g 301 &lt; 210 &gt; 264 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 264 · aaagacgtta aaccactcta ctaccacttg tggaactctc aaagggtaaa tgacaaascc 60 aatgaatgac tctaaaaaca atatttacat ttaatggttt gtagacaata aaaaaacaag 120 gtggatagat ctagaattgt aacattttaa gaaaaccata scatttgaca gatgagaaag 180 ctcaattata gatgcaaagt tataactaaa ctactatagt agtaaagaaa tacatttcac 240 acccttcata taaattcact atcttggctt gaggcactcc ataaaatgta tcacgtgcat 300 a 301 &lt; 210 &gt; 265 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; Simon &lt; 400 &gt; 265 tgcccaagtt atgtgtaagt gtacccgcac ccagaggtaa aactacactg tcatctttgt 60 cttcttgcga cgcagtattt cttctctggg gagaagccgg gaagtcttct cccggcCcca 120 catattcttg gaagtctcta atcaactttt gt-cccatttg cttcatttct tcaggaggga 180 ttttcagctt gtcaacatgc tctctaacaa cacttgccca tittctgtiaaa gaatccaaag 240 cagtccaagg ctttgacatg ccaacaacca gcataactag agtatccttc agagatacgg 300 c 301 &lt; 210 &gt; 266 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; who is eligible &lt;4〇0&gt; 266 taccgtctgc ccttcctccc atccaggcca tctg Cgaatc tacatgggtc ctcctrattcg 60 acaccagatc actctttcct ctacccacag gcttgctatg agcaagagac acaacctcct 120 ctcttctgtg ttccagcttc ttttcctgtt cttcccaccc cttaagttct attcctgggg 180

Atagagacac caatacccat aacctctctc ctaagcctcc ttataaccca gggtgcacag 240 cacagacccc tgacaactgg taaggccaat gaactgggag ctcacagctg gctgtgcccg 300 a 301 &lt;210&gt; 267 &lt;211&gt; 301 '

&Lt; 212 &gt; DNA &lt; n3 &gt;. Human &lt; 400 &gt; 267 aaagagcaca ggccagctca gcctgccctg gccatctaga ctcagcctgg ccccacgggg 60 92- 127691.doc 200815476 gttctcagtg ctgagtccat ccaggaaaag ctcacctaga ccttctgagg ctgaatcttc 120 atcctcacag gcagcttctg agagcctgat attcctagcc ttgatggtct ggagtaaagc 180 ctcattctga ttcctctcct tcttttcttt caagttggct ttcctcacat ccctctgttc 240 aattcgcttc agcttgtctg ctttagccct catttccaga agcttcttct ctttggcatc 300 t 301 &lt; 210 &gt; 268 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 4Q0 &gt; 268 aatgtctcac tcaactactt cccagcctac cgtggcctaa ttctgggagt tttctcctta '150 gatcttggga gagctggttc ttctaaggag aaggaggaag gacagatgta actttggatc 120 tcgaagagga Agtctaatgg aagtaattag tcaacggtcc ttgtttagac tcttggaata 180 tgctgggtgg ctcagtgagc cctttcggag aaagcaagta ttattcttaa ggagtaacca 240 cttcccattg ttctaccttc taccatcatc aattgtacat tatgtattct ttggagaact 300 a 301 Ο

&Lt; 210 &gt; 269 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 269 taacaatata cactagctat ctttttaact gtccatcatt agcaccaatg aagattcaat 60 aaaattacct ttattcacac atctcaaaac aattctgcaa actcttagtg aagtttaact 120 atagtcacag accttaaata ttcacattgt tttctatgtc tactgaaaat aagttcacta 180 cttttctgga trattctttac aaa grasshopper Tcttat taaaattcct ggtatnatica cccccaatta 240 tacagtagca caaccacctt atgtagtittc tacatgatag ctctgtagaa gttitcacatc* 300 t 301 &lt;210&gt; 270 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt;human cheek &lt;400&gt; 270 cattgaagag cttttgcgaa acatcagaac acaagtgctt ataaaattaa ttaagcccta 60 cacaagaata catattcctt ttatttctaa ggagttaaac atagatgtag ctgatgtgga 120 gagcttgctg gtgcagtgca tattggataa cactattcat ggccgaattg atcaagtcaa 180 ccaactcctt gaactggatc atcagaagaa gggtggtgca cgatatactg cactagataa 240 tggaccaacc aactaaattc tctcaccagg ctgtatcagt aaactggctt aacagaaaac 300 a 301 &lt; 210 &gt; 271 &lt; 211 &gt; 301 &lt; 212 &gt; DNA who, without &lt; 220 &gt;

&lt;221&gt; misc one: feature &lt;222&gt; (1) (301) &lt;223&gt; n » or G -93- 127691.doc 200815476 &lt;4〇0&gt; 271 aaaaggttct cataagatta acaatttaaa taaatatttg atagaacatt ctttctcatt $ 〇tttatagccc atctttaggg ttgatattca gttcatgctt cccttgctgt tcttgatcca 120 gaattgcaat cacttcatca gcctgtattc gctccaattc tctataaagt gggtccaagg i8〇tgaaccacag agccacagca cacctctttc ccttggtgac tgccttcacc ccatganggt 240 tctctcctcc agatganaac tgatcatgcg cccacacttt gggttttata gaagcagtca 300 c 301 &lt; 210 &gt; 272 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; Simon &lt; 400 &gt; 272 ..- taaattgcca agccacagat aacaccaatc aaatggaaca aatcactgtc ttcaaatgtc g〇ttatcagaaa accaaatgag cctggaatct tcataatacc taaacatgcc gtatttagga 120 tccaataatt ccctcatgac gagcaagaaa aatcctttgc gcacccctcc tgcatccaca ie〇gcatcttctc caacaaatat aaccttgagt ggcttcttgt aatctatgtt ctttgttttc 240 ctaaggactt ccattgcatc tcctacaata tttcctctac gcaccactag aattaagcag 3〇〇g 301 f,

&lt;210&gt; 273 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt; • &lt;221&gt; misc_ Desirable &lt;222&gt; (1)U〇l) &lt;223&gt; n » HC or G &lt ; 400 &gt; 273 ♦ acatgtgtgt atgtgtatct ctgggaaaan aanaagacac cntgtttayt atctctttgg 60 agagangctg ggacatggat aatcacwtaa cccgctayta tyactttaac ctgactygaa 120 gaaccgccta aaaataaaat ttaccatgtc dcatactccc tatagtatgc ttatttcacc 180 ccytccctgt ccagagagag tatcagtgac ananatttma gggtgaamac atgmattggt 240 gggacctnty tttacngagm accctgcccg sgcgcccccg makcngantt ccgcsananc 300 t 301 ϋ

&lt;210&gt; 274 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human &lt;&lt;220&gt;&lt;221&gt; misc - esteem &lt;222&gt; (1).7.(301) &lt;223&gt;; n - A, T, C or * G &lt; 400> 274 cttatacact ctttctcaga ggcaaaagag gagatgggta atgtagacaa ttctttgagg 60 aacagtaaat gattattaga gagaangaat ggaccaagga gacagaaatc aactcgtaaa 120 t'gattcccct cggaatctga atgagatcaa gaggccagct titagctztgtig gaaaagtcca 180 tctaggtatg gttgcattct cgtcttcttt cctgcagtag ataatgaggc aaccgaaggc 240 aactgtgctt cttttgataa gaagctttct tggtcacatc Aggaaattcc aganaaagtc 300 127691.doc 94- 200815476 c 301 &lt;210&gt; 275 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213>People&lt;220&gt;&lt;221&gt; Special Education &lt;222&gt; (1) . . . (301).

&Lt; 223 &gt; η - A, T, C or G • · &lt; 400 &gt; 275 ccggtgtcag cagcacgtgg cattgaacat tgcaatgtgg agcccaaacc acagaaaatg -60 gggtgaaatt: ggccaacttt ctattaactt atgttggcaa ttctgccacc aacagtaagc 120 tggcccttct aataaaagaa aattgaaagg tttctcacta aacggaatta agtagtggag 180 tcaagagact cccaggcctc agcgtacctg cccgggcggc cgctcgaagc cgaattctgc 240 Agatacccac cacactggcg gncgctcgan catgcatcca gaaggnccaa ttcgccctat 300 a 301

Ο &lt; 210 &gt; 276 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 4〇0 &gt; 276 cgtacacata ctcaataaat aaatgactgc attgtggtat tattaccaca ctgattatat 60 ctaccacgtg acctccaatt agaaaatgta tccaaaagca aaacagcaga tatacaaaat 120 caaagagaca gaagatagac attaacagat aaggcaactc acacattgag aatccaaacc 180 caacacatcc Aaacatttgg gaaatgaggg ggacaaatgg aagccagacc aaactcgtgt 240 aaaactaccc agcacgtccc ccttgcccca tgcctgagaa ggctctcctt caatggggat* 300 g 301 &lt;210&gt; 277 &lt;211&gt; 301

&lt;212&gt; DNA &lt; 213 &gt; Human Face &lt;220&gt; . &lt;221&gt; mi sc- ‘Special Desire &lt;222&gt; (1).T.(3Q1)

&Lt; 223 &gt; n = * A, T \ C or G &lt; 400 &gt; 277 - cttgccgatg tcagtattct attacttgcg ttatgagtgc tcacctggga aattctaaag 60 atacagagga cttggaggaa gcagagcaac tgaatttaat ttaaaagaag gaaaacattg 120 gaaccatggc actcccgata ctttcccaaa tcaacactct caacgcccca ccctcgtcct 180 caecatagcg gggagactaa agtggccacg gaettgeett angtgtgcag tgcgttctga 240 gttcnctgtc gattacatct Gaccagtctc ctttttccga agtccntccg ttcaatcttg 300 C 301 &lt;210&gt; 278 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human 127691.doc -95- 200815476 &lt;220&gt;

&lt;221&gt; misc a special desire &lt;222&gt; (1).7.(301) &lt;223>η * A,T,C or G &lt;400&gt; 278 taccactaca ctccagcctg ggcaacagag caagacctgt ctcaaagcat aaaatggaat 60 aacatatcaa atgaaacagg gaaaatgaag ctgacaattt atggaagcca gggcttgtca 120 cagtctctac tgttattatg cattacctgg gaatttatat aagccctcaa taataatgcc 180 aatgaacatc tcatgtgtgc tcacaatgtt ctggcactat tataagtgct tcacaggttt 240 tatgtgttct tcgtaacttt atggantagg tactcggccg cgaacacgct aagccgaatt 300 c 301 &lt; 210 &gt; 279 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 220 &gt;

&lt;221&gt; misc_ feature &lt;222&gt; (1).7.(301) &lt;223&gt; n = A, T, C or G

&Lt; 400 &gt; 279 aaagcaggaa tgacaaagct tgcttttctg gtatgttcta ggtgtatcgt gacttttact 60 gctatattaa tcgccaacat aagtaaatat agactatata tgtatagtgc ctcacaaagc 120 ttagaccttc accctccagc caccccacag tgcttgatac ttcagagtca gccatcggct 180 atacatgtgc agttccaaag cacataagcc agaanaanaa acacctctag ggagcactac 240 catctgtttt cacacgaaac gccacacaca cagaactcca acatcaattt cattgcacag 300 a 301

&Lt; 210 &gt; 280 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 280 ggtaccggag ttttcctccc ctgcgaaaac gtaactactg ttgggagtga attgaggatg 60 tagaaaggcg gtggaaccaa actgcggtca acggaaacag gagaatatgg tcctcactct 120 tgagaaaaaa acctaagatt agcccaggta gttgcctgta actccagttt ttccgcctgg 180 gtttgatata gtctagggtt ggggttagat ' Taagatctaa attacatcag gacaaagaga 240 cagactatta actccacagt taattaagga ggtatgttcc atgtttactt gttaaagcag 300 t 301

&Lt; 210 &gt; 281 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 281 aggtacaaga aggggaacgg gaaagagctg ctgctgtggc atcgttcaac ttggatatcc 60 .gccgagcaac ccaaatcctg aatgaagggg catcttctga aaaaggagat ctgaatctca 120 atgtggtagc aatggcttta tcgggttata cggatgagaa gaactccctt tggagagaaa 180 tgtgtagcac actgcgatta cagctaaata acccgtattt gcgtgtcatg tttgcatttc 240 127691 .doc 96- 200815476 tgacaagtga aacaggatct tacgatggag ttttgtatga aaacaaagtt gcagtacctc 9 . &lt;210&gt; 282 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213 &gt; human &lt;400&gt; 2B2 caggtactac agaactaaaa tactgacaag caagtagttt cttggcgtgc acgaattgca tccagaaccc aaaaattaag·aaattcaaaa agacattttg tgggcacctg ctagcacaga agcgcagaag caaagcccag gcagaaccat gctaaectta cagctcagcc tgcacagaag cgcagaagca aagcccaggc agaaccatgc taaccttaca gctcagcctg cacagaagcg cagaagcaaa gcccaggcag aacatgctaa ccttacagct cagcctgcac agaagcacag a &lt; 2i〇 &gt; 283 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al crop-0 &lt; 400 &gt; 2B3 atctgtatac Ggcagacaaa etctatarag tgtagagagg tgagcgaaag ga tgcaaaag cactttgagg gcctcataac aacacgctgc ttgaaaaaaa aaatgtgtag ttgacactca gtgcacctcc agacatagta aggggtcgct ctgaccaatc aggtgatcat ttcttctacc acttcccagg ttetatgeaa aaattccgtt aaattetata atggtgatat gcacctctca ggaaacatat acatittttiaa aaatctact: t taegtaagaa ctgacagacg aatittgettit: 9 &lt; 210 &gt; 284 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al Amount &lt; 400 &gt; 284 caggcacaaa acgccaccaa geggettaga atttgaacat ttgcggtccc tatctactct gcttcgtgcg cgggcaaagc aacacctccc ctaaatatac attaccaaga aaagcaagaa gcagatcagg ttcccgacaa aacaaacagg ccaaaagggg gccgacccgg ageagageat ggtgagaggc aaggeaegag agggcaagct tgttgtggac agatctgtgc etaetttatt actggagtaa aagaaaacaa agttcattga .tgccgaagga tatatacagt gttagaaact a &lt; 210 &gt; 285 _ &lt; 211 &gt; 301

U &lt;212&gt; DNA &lt;213&gt;Human &lt;220&gt; · &lt;221>misc-special board &lt;222&gt;(1&gt; ...(301)

&lt;223&gt; n = A, T, C or G &lt; 400 &gt; 285 acatcaccat gaccggatcc cccacccatt atacgttgta tgtttacata aatactcttc aatgatcatt agtgctttaa aaaaaatact gaaaactcct tctgcatccc aatctctaac 127691.doc 97-300 301 60 120 180 .240 300 301 60 120 180 240 300 301 60 120 180 240 300 301 60 120 200815476 caggaaagca aatgctattt acagacctgc aagccctccc tcaaacnaaa ctatttctgg attaaatatg tctgacttct tttgaggtca cacgactagg caaatgctat ttacgatctg caaaagctgt ttgaagagtc aaagccccca tgtgaacacg atttctggac cctgtaacag t

&lt;210&gt; 286 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 286 taccactgca ttccagcctg tgtatattat ttttgcctta atcaaaatgt gtcatgccag aaaataagct accatatagc gtttctgttc attgtgtatg t &lt;210&gt; 2Θ7 &lt;211&gt; 301 &lt;212&gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 287 tacagatctg ggaactaaat cccagaagga acgtagagat aaacgatttg gctatgaacg ccgtggttat cccctcccca gttgcatgtc tcgtgaagcc t ggtgacagag tgagactccg cagtggatca ttctagtagg taagagatgt tatattcttt ttataagtct caaatttttg cttcatcacc tatactaggc tctccaaaaa aaactttgct aaaggacagt aagatttttt tctcatttct tccccaccca cccttcacta aaatgtgatt aaattccatt ttttcccttg attaaaaatg agdgtggctg cagatattac aacagctttg cacagtttag gcagcagggc gcttggctgc cccatgttat atcaagattt tctcgtctgc gatacatgga gaatgttggg ttttgagggt tagaaatatg cagaatcctg accctctgcc cacagtattc cattttgttc tttcctctca ctggtaatgc &lt; 210 &gt; 288 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; who is eligible &lt; 400 &gt; 288 gtacacccaa ccgcaaggac agctgaggaa tgtaatgggc agccgctttt aaagaagtag agtcaatagg aagacaaat t ccagttccag ctcagtctgg gtatctgcaa agctgcaaaa gacctttaaa gacaatttca agagaatatt.tccctaaagc tggcaacctg gagatcatac aaaagcacct gcttttgtga ctcaacttag ctcatctggc cactggaaga atccaaacag tctgccttaa ttttggatga acgcacgatg gaaattcaat aatttagaaa gttaaaaaaa a

Q &lt;210&gt; 289 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt;People &lt;220&gt;

&lt;221>misc_: Feature &lt;222&gt; (1).7.(301) &lt;223&gt; n = A, T, C or G &lt;400&gt; 289 -98- 127691.doc 200815476 ggtacactgt ttccatgtta tgtttctaca cattgctacc tcagtgctcc tggaaactta 60 gcttttgatg tctccaagta gtccaccttc atttaactct ttgaaactgt atcatctttg 120 ccaagtaaga gtggtggccc atttcagctg ctttgacaaa atgactggct cctgacttaa ie〇cgttctataa atgaatgtgc tgaagcaaag tgcccatggt ggcggcgaan aagagaaaga 240 tgtgttttgt ttcggactct ctgtggtccc ttccaatgct gtgggtttcc aaccagngga 300 a 301 &lt; 210 &gt; 290 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt;213&gt;People&lt;220&gt;

&lt;22l&gt; mi sc I. Feature &lt;222&gt; (1) (301) &lt;223&gt; n = A, T, C or G &lt; 400 &gt; 290 acaccgagcc cttcttgata aacatacaga atgcttggca tatacaagat tctatactac 60 tgactgatct gttcatttct ctcacagctc Ctacccccaa aagctcttcc accctaagtg 120 ttctgacctc cttttctaat cacagtaggg atagaggcag anccacctac aatgaacatg 180 gagttctacc aagaggcaga aacagcacag aaccccagtt ttaccacccg ctagcagtgc 240

tgccctgaac aaaaacatcc ctccacgtct catccccttc atgcctcaag taacagtgag 300 a 301 &lt; 210 &gt; 291 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al crop-full &lt; 400 &gt; 291 caggcaccaa tttcttctat cctagaaaca ttccatctca tgttgtcgaa acataacaac 60 catatcagct tctatgctct acccgctatig gaaaatctga cacattctgc 120 ttcactcttt tgtttatagg Tgaatcacaa aatgcattct tatgtacccc gtagttcaat 180 agccatggct gcttacttca tctaattcat ttagcacaaa gacattatga aaaggcctaa 240 acatgagctt cacttcccca ctaactaact: agcacctgtt atttcctaac cgtaacgcct 3〇〇a 301 &lt;210&gt; 292 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt;.People · &lt;220&gt ; *

&lt;221&gt; mi sc-feature&lt;222&gt; (1) . . . (301) &lt;223> n - A, T, C or G &lt;400&gt; 292 . acccttcagt agtaatgtct aataataaac aagaaatcaa ccctataagg tccatatagc 6〇tgtactaaat aattcttaag tttaaaagat aaaataccat cattctaaat gttggtattc 120 aaaaccaaag natataaccg aaaggaaaaa cagatgagac ataaaatgat ttgcnagatg 180 ggaaatatag tastcyacga atgtcnatta aatcccagtt ataatagtgg ctacacactc 240 tcactacaca cacagacccc acagtcctat ataccacaaa cacatttcca taacttgaaa 300 a 301 99- 127691.doc 200815476 &lt; 210 &gt; 293 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt;. 293 ggtaccaagt gctggtgcca gcctgttacc tgttctcact gaaaagtctg gctaatgctc 60 ttgtgtagtc acttctgatt ctgacaatca atcaatcaat ggcctagagc actgactgtt 120 aacacaaacg tcactagcaa agtagcaaca gctttaagtc taaatacaaa gctgttctgc 180 gtgagaattt tttaaaaggc tacttgtata ataacccttg tcatttttaa tgtacctcgg 240 ccgcgaccac gctaagccga attctgcaga tatccatcac actggcggcc gctcgagcat 300 g 301 &lt;210&gt; 294 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human &lt;22Q&gt; η

&lt;221&gt; mi sc a feature &lt;222&gt; (1).7.(301) &lt;223&gt; n = A, T, C or G &lt;4〇0&gt; 294 tgacccataa caatatacac tagctanctt tttaactg'tc catcattagc accaatgaag 60 atccaataaa attaccttta tccacacatc tcaaaacaat tctgcaaatt cctagtgaag 120 tttaactata gtcacaganc ttaaatattc acattgtttc ctacgcccac cgaaaataag 180 cccaccacct tcctgggata ttctttacaa aatcttatta aaattcctgg cattatcacc 240 cccaattaca cagtagcaca accaccttat gtagttttta catgatagcc ccgtagaggt 300 t 301 &lt; 210 &gt; 295 &lt; 211 &gt; 305 &lt; 212 &gt; DNA &lt; 21 3 &gt; human &lt; 400 &gt; 295 gtaccctetc tctcccctcc tctgaattta attctctcaa ctcgcaatcc gcaaggatta 60 cacattticac tgtgatgtat attgtgttgc aaaaaaaaaa gtgtctctgt ttaaaattac 120 ttggtctgcg aatccatctt gctttttccc cactggaact agtcattaac ccatctctga 180 accggcagaa aaacrtctga agagetagte tatcagcatc tgacaggtga attggatggt 240 tctcagaacc atttcaccca gacagcctgt ttctatcctg tttaacaaac tagtttgggt 300 tetet 305

&Lt; 210 &gt; 296 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 296 aggtactacg ggaagctgct aaaataatat ttgatagtaa aagtatgtaa tgtgctatct 60 cacctagtag taaactaaaa ataaactgaa actttatgga atetgaagee attttccttg 120 actaaataga attaataaac caatatgagg aaacatgaaa ccatgcaatc tactatcaac 180 tctgaaaaag tgattgaacg aaccacttag Ctttcagatg atgaacactg ataagteatt 240 127691.doc 100- 200815476 tgtcattact ataaatttta aaatctgtta ataagatggc ctatagggag ga &lt;210&gt; 297 &lt;211&gt; 300 &lt;212&gt; DNA &lt;213 &gt; Human &lt;220&gt;&lt;221&gt;_ misc_ Feature &lt;222&gt; (1)...(300} &lt;223&gt; n » A,T,C or *G &lt;400&gt; 297 actgagtttt aaccggacgc caagcaggca aggctggaag gtcttgctcc ctttgtgcta 60 aaggctttga aaaccttgaa ggagaatcat tttgacaaga agtacttaag agtctagaga 120 acaaagangt gaaccagctg aaagctctcg g^ Iggaanctt acatgtgttg ttaggcctgt 18Ο tccatcattg ggagtgcact ggccatccct caaaatttgt ctgggctggc ctgagtggtc 240 accgcacctc ggccgcgacc acgccaagcc gaattctgca gatatccatc acactggcgg 300

&lt;210&gt; 298 &lt;211&gt; 301 &lt;212&gt; DNA \ &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc_ Feature &lt;222) (1) (301) &lt;223&gt; = A, T, C or G &lt; 400 &gt; 298 catggggctt gccacccaaa agccgatgct gagaaaggcc tccctggggc cccccccgcg 60 ggcacctgag agacctggcg ttccagtgtt 120 tgaagctctc tctggaaatg ggtcccagcg ccgccggctg agaccaatca cgggaagggc ccggcggtgg cggccacccg gaaccaccct 180 gccccgcccg cttacacccc actaycaggc tttccctggg catcacnact tgccccccta 240 caacagtgac ccgtgcatcc tgctgtggcc tgctgtgtcc gcaggcggct cccagcgagg 300 t 301 &lt;210&gt; 299 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human &lt;40O&gt; 299 **

gccctgagac ggagtctcac tcttgttgcc cagactggac tgcaatggca gggcctctgc 60 tcactgcacc ccctgccccc caggctcgag caactctcct gccccagcct cccaggtagc 120 tgggattgca ggcccacgcc accataccca gctaattttt tcgtattttt agtagagacg 180 gagttccgcc acgctggcca .gctggtctca aactcctgac ctcaagcgac ctgcctgcct 240 cggcctccca aagtgctgga attataggca tgagtcaaca cgcccagcct aaagatattt 300 t 301 &lt; 210 &gt; 300 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; human -101 »127691.doc 200815476 &lt; 400 &gt; 300 attcagtttt atttgctgcc ccagtatctg taaccaggag tgccacaaaa tcttgccaga 60 tatgtcccac acccactggg aaaggctccc acctggctac ttcctctatc agctgggtca 120 gctgcattcc acaaggttct cagcctaatg agtttcacta cctgccagtc tcaaaaccta 18D gtaaagcaag accatgacat tcccccacgg aaatcagagt ttgccccacc gtcttgttac 240 tataaagcct gcctctaaca Gtccttgctt cttcacacca atcccgagcg catcccccat 300 g 301 &lt;210&gt; 301 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 301 ttaaattttc gagaggataa aaaggacaaa taatctagaa atgtgtcttc ttcagtctgc 60 agaggacccc aggtctccaa gcaa . Ccacac ggtcaagggc atgaataatt aaaagttggt 120 gggaactcac aaagaccctc agagccgaga cacccacaac agtgggagct cacaaagacc 180 ctcagagctg agacacccac aacagtggga gctcacaaag accctcagag ctgagacacc 240 cacaacagca cctcgttcag ctgccacatg tgtgaataag gatgcaatgt ccagaagtgt 300 t 301 Γ &lt; 210 &gt; 302 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt; 213 &gt; al. europium &lt; 400 &gt; 302 aggtacacat ttagcttgcg gtaaatgact cacaaaactg attttaaaat caagttaacg 60 tgaatcttga aaattactac ttaatcctaa ttcacaataa caatggcatt aaggtttgac 120 ttgagtcggt tcttagtatt atttatggta aacaggctct taccacttgc aaacaactgg 180 ccacatcacc aatgaccgac tticccagtaa ggctctctaa ggggtaagca ggaggatcca 240 caggacttga gatgctaagg ccccagagac cgtttgatcc aaccccctca tcttcagagg 300 9 301 &lt; 210 &gt; 303 &lt;211&gt; 301 &lt;212&gt; DNA &lt;213&gt;Personality &lt;400&gt; 303 aggcaccaac cgtggaaata ggtagaggac cattttttct ttccatatca actaagttgc SO atattgtttt ttgacagttt aacacacctt cttccgtcag agattctttc acaatagcac 120 tggctaatgg aactaccgct tgcatgttaa aaatggtggt ttgtgaaatg accataggcc. 180 agt aacgggt atgtttttct aaccgatctc ttgctcgttc caaagggacc tcaagacttc 240 caccgatttc atatctgggg tctagaaaag gagctaatct gttttccctc ataaattcac 300 c 301 &lt; 210 &gt; 304 &lt; 211 &gt; 301 '&lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 304 acatggatgt cattttgcag actgtcaacc tgaatccgta tttgcttgac atcgcctaat 60 127691.doc 102- 200815476 tattagtttc agtttcagct tacccacttt ttgtctgcaa catgcaraas agacagtgcc 120 ctttttagtg tatcatatca ggaatcatct cacattggtt tgtgccatta ctggtgcagt 180 gactttcagc cacttgggta aggtggagtt ggccatatgt ctccactgca aaattactga 240 ttttcctttt gtaattaata agtgtgtgtg tgaagattct ttgagatgag gtatatatct 300 c 301 &lt; 210 &gt; 305 &lt; 211 &gt; 301 &lt; 212 &gt; DNA &lt;213&gt; human

&lt;220&gt; * &lt;221&gt; misc a special desire &lt;222&gt; (1) · · · (301) &lt;223>n = A work C or G &lt;400&gt; 305 gangtacagc gtggtcaagg taacaagaag aaaaaaatgt gagtggcatc ctgggatgag 60 cagggggaca gacctggaca gacacgttgt Catttgctgc tgtgggtagg aaaatgggcg 120 taaaggagga gaaacagata caaaatctcc aactcagtat taaggtattc tcatgcctag 180 aatattggta gaaacaagaa tacactcata tggcaaataa ctaaccatgg tggaacaaaa 240 ttctgggatt taagttggat accaangaaa ctgtattaaa agagctgttc atggaataag 300 η

a 301 &lt;210&gt; 306 &lt;211&gt; 8 &lt;212&gt; Protein '&lt;213&gt; Human &lt;400&gt; 306

VAL &gt; 211 &lt;211&gt; attgaggaat. gatacttgag cccaaagagc attcaatcat tgttttattt gccttmtttt 1Θ0 cacaccattg gtgagggagg gattaccacc ctggggttat gaagatggtt gaacacccca 240 cacatagcac cggagatatg agatcaacag tttcttagcc atagagattc acagcccaga 300 gcaggaggac gcttgcacac catgcaggat gacatggggg atgcgctcgg gattggcgtg 360 aagaagcaag gactgttaga ggcaggcttt acagcaacaa gacggtgggg caaactccga 420 tttccgtggg ggaatgtcat ggtcttgctt tactaagttt tgagactggc aggtagtgaa 480 actcattagg ctgagaacct, tgtggaatgc acttgaccca sctgatagag gaagtagcca 540 9gtgggagcc tttcccagtg ggtgtgggac atatctggc stone agatetttgtg gcactcctgg 600 ttacagatac tggggcagca aataaaactg aatcttg 637 &lt;210&gt; 308 &lt;211&gt; 647 &lt;212&gt; DNA &lt;213&gt; Human 103-127691.doc 200815476 &lt;220&gt;&lt;221&gt; One feature &Lt;222&gt; (1) .7. (647) &lt;223&gt; η « A,T#C or t3 &lt;400&gt; 308 acgattttca ttatcatgta aatcgggtca ctcaaggggc caaccacagc tgggagccac 60 tgctcagggg aaggttcata tgggactttc tactgcccaa ggttctatac aggatataaa 120 ggngcctcac agtatagatc tggtagcaaa gaagaagaaa caaacactga tctctttctg 180 ccacccctct gaccctttgg aactcctctg accctttaga acaagcctac ctaatatctg 240 ctagagaaaa gaccaacaac ggcctcaaag gatctcttac catgaaggtc tcagctaatt 300 cttggctaag atgtgggttc cacattaggt tctgaatatg gggggaaggg tcaatttgct 360 cattttgtgt gtggataaag tcaggatgcc caggggccag agcagggggc tgcttgcttt 420 gggaacaatg gctgagcata taaccatagg ttatggggaa caaaacaaca tcaaagtcac '480 tgtatcaatt gccatgaaga cttgagggac ctgaatctac cgattcatct taaggcagca 540 ggaccagttt gagtggcaac aatgcagcag cagaatcaat ggaaacaaca Gaatgattgc 600 aatgtccttt tttttctcct gcttctgact tgataaaagg ggaccgt 647 &lt;210&gt; 309 &lt;211&gt; 460 &lt;212&gt; DNA &lt;213&gt; Humans &lt;4〇0&gt; 309 accctatagt ttaggctgga catcggaaaa aaaaaaaagc cagaacaaca tgtgatagat 60 aatatgatcg gctg cacact tccagactga tgaatgatga acgtgatgga ctattgtatg 120 gagcacacct tcagcaagag ggggaaatac tcatcactct tggccagcag ttgtttgatc 180 accaaacatc atgccagaat actcagcaaa ccttcttagc tcctgagaag tcaaagtccg 240 ggggaattta ttcctggcaa ttttaattgg actccttatg cgagagcagc ggctacccag 300 ccggggtggt ggagcgaacc cgtcactagt ggacatgcag tggcagagct cctggtaacc 360 acctagagga atacacaggc acatgtgtga tgccaagcgt gacacctgta gcactcaaat 420 tcgcctcgtt tttgtctttc ggtgtgtaag attcttaagt 460 &lt;. 210 &gt; 310 &lt; 211 &gt; 539 &lt; 212 &gt; DNA &lt; 213 &gt; al crop-full &lt; 400 &gt; 310 acgggactta tcaaataaag ataggaaaag aagaaaactc aaatatcata ggcagaaatg 60 ccaaaggttt taaaatatgt caggattgga agaaggcatg gataaagaac aaagttcagt 120 taggaaagag a.aacacagaa ggaagagaca caataaaagt cattatgtat tctgtgagaa 180 gtcagacagc aagatttgtg ggaaatgggt tggtttgttg Tatggtatgt actttagcaa 240 taacctttat ggcagagaaa gctaaaatcc ttcagcctgc gtgaa^igatc acttgctgaa· 300

ttcctcaagg taggcatgat gaaggagggt ttagaggaga cacagacaca atgaactgac 360 ctagatagaa agccttagta tacccagcta ggaatagtga ttctgagggc acactgtgac 420 atgattacgt cattacatgt atggtagtga tggggatgat aggaaggaag aacttatggc 480 atattctcac ccccacaaaa gtcagttaaa tattgggaca ctaaccatcc aggtcaaga 539 &lt; 210 &gt; 311 &lt; 211 &gt; 526 &lt; 212 &gt; DNA &lt; 213 &gt; al Amount 104 - 127691.doc 200815476 &lt;220&gt;&lt;221&gt; misc - special desire &lt;222&gt; (1).:·(526) &lt;223&gt; n = A, T, C or G &lt;400&gt; 311 caaatttgag ccaatgacat agaatttcac aaatcaagaa gcttattctg gggccatttc 60 ttttgacgtt ttctctaaac tactaaagag gcattaatga tccataaatt atattatcta 120 catttacagc atttaaaatg tgttcagcat gaaatattag ctacagggga agctaaataa 180 attaaacatg gaataaagat ttgtccttaa atataatcta caagaagact ttgatatttg 240 tttttcacaa gtgaagcatt cttataaagt gtcataacct ttttggggaa actatgggaa 300 aaaacgggga aactctgaag ggttttaagt atcttacctg aagctacaga ctccataacc 360 tctctttaca gggagctcct gcagccccta cagaaatgag tggctgagat tcttgattgc 420 acagcaagag cttctcatct aaaccctttc Cctttttagt atctgtgtat caagtataaa 480 agttctataa actgtagtnt acttatttta atccccaaag cacagt 526 &lt;210&gt; 312 &lt;211&gt; 500 . &lt;212&gt; DNA Human &lt;220&gt; n &lt;221&gt; mise_ Desirable &lt;222&gt; (1).7. 500) &lt; 223 &gt; n * A, T, C or G &lt; 400 &gt; 312 cctctctctc cccaccccct gactctagag aactgggctt tcccccagta ctccagcaat 60 tcatctccga aagcagttga gccactttat tccaaagtac accgcagatg ttcaaactct 120 ccacttctct ttcccttcca cctgccagtt ttgctgaccc tcaacccgtc atgagtgtaa iso gcactaagga cactatgctt-cttcgatcct gasgacaggc cctgcccacg gatgactctg 240. gcttcccagg aaaatatttt tcctccaaaa tcagtaggaa atctaaactt accccctctt 300 tgcagatgcc tagcagcttc agacatttgg ttaagaaccc atgggaaaaa a ^ aaaatcct 360 tgctaatgtg gtttcctttg taaaccanga ttctcattcg nctggcatag aatatcagct 420 ctgaacgtgt ggtaaagatt tttgtgtttg aatataggag aaatcagttt gccgaaaagt 480 tagtcttaat tatctattgg 500 3 8 XX 3 7 &lt; 210 &gt; &lt; 211 &gt; &lt; 212 &gt; DNA &lt;213 &gt; shemale &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1).7.(718) &lt;223&gt; n = A, T, C &Lt; 400 &gt; ggagatttgc tgatgataca ctgctgaaat gt pregnant gtgacat aaaaggaagc gcctcgccct ttccttaaag 313 gtggtttgca gaggtgagaa ggagataatt gtctttgcac acagagatcc gtgcctgntc gatggcagga gccgagggag ataagaaagg aacatcacta atttccagcc ctgggagaaa ccgcttgtga aaacaga kernel cc accaggaaga ctgctgactt gaaacagcaa ctcttaaata tgcccggccg gggaaggaca tgttgtggac tccgcatggc taccatccga gacgacaata tccacacaca ccatcttggg ttagaaaatg acttatttga gggaaggacc ggccacacat taatgtccaa caggaagcac tcatcgatga aattgatgtg acgggattac 60 120 180 240 300 360 420 105- 127691.doc 200815476 agatttgaaa tgaagtcaca aagtgagcat taccaatgag aggaaaacag acgagaaaat 480 cttgatggtt cacaagacat gcaacaaaca aaatggaata ctgtgatgac acgagcagcc 540 aactggggag gagataccac ggggcagagg tcaggattct ggccctgctg cctaactgtg 600 cgttatacca atcacttcta tttctaccct caaacaagct gtngaatatc tgacttacgg 660 ttcttntggc ccacattttc atnatccacc ccntcntttt aannttantc caaantgt 718 &lt;210&gt; 314 &lt;211&gt; 358 &lt;212&gt; DNA &lt;213&gt;People&lt;400&gt; 314 gtttatttac attacagaaa aaacatcaa g acaatgtata ctatttcaaa tatatccata 60 cataatcaaa tatagccgta gtacatgttt tcattggtgt agattaccac aaatgcaagg 120 caacatgtgt agatctcttg tcctattctt ttgtctataa tactgtattg tgtagtccaa 180 gctctcggta gtccagccac tgtgaaacat gctcccttta gattaacctc gtggacgctc 240 ttgttgtatt gctgaactgt agtgccctgt attttgcttc tgtctgtgaa ttctgttgct 300 tctggggcat ttccttgtga tgcagaggac caccacacag atgacagcaa tctgaatt 358

&Lt; 210 &gt; 315 &lt; 211 &gt; 341 &lt; 212 &gt; DNA &lt; 213 &gt; al chin &lt; 400 &gt; 315 taccacctcc ccgctagcac cgacgagccg catcaccatg gtcaccagca ccatgaaggc 60 ataggtgatg atgaggacat ggaatgggcc cccaaggatg gtctgtccaa agaagcgagt 120 gacccccatt ctgaagacgt ctggaacctc taccagcagg atgatgatag ccccaatgac 180 agtcaccagc tccccgacca gccggatatc . gtccttaggg gccatgtagg cttcctgaag 240 tagctcccgc tgcaagaggg cgttgtcccg ggggctcgtg cggctattgg ccctgggctc 300 gagggggcgg tagatgcagc acatggtgaa gcagatgatg t 341 &lt; 210 &gt; 316 · · &lt; 211 &gt; 151 &lt; 212 &gt; DNA &lt; 213 &gt; al chin &lt; 400 &gt; 316 agactgggca agactcctac gccccacact gcaatttggt cttgttgccg tatccattca 60 cgcgggcctt ccccgagttt ctgattataa acaccactgg agcgatgcgt tgaccggact 120 catccaggga gctctggttg caatattagt t 151 &lt; 210 &gt; 317 &lt; 211 &gt; 151 &lt; 212 &gt; DNA &lt;.. ggcatttatc 317 agaaccagtg gatcctaatg ..aaatacctga aacatatatt; 213 &gt; human &lt; 400 & gt Aatggctcaa 60 atcttcattt atctccggcc ttaaccctgg ctcctgaggc tgcggccagc agatcccagg 120 ccagggctct gttcttgcca ca Cctgcttg a 151

&lt;210&gt; 318 &lt;211&gt; 151 &lt;212&gt; DNA -106- 127691.doc 200815476

&Lt; 213 &gt; human &lt; 400 &gt; 318 actggtggga ggcgctgttt agttggctgt tttcagaggg gtctttcgga gggacctcct gctgcaggct ggagtgtctt tattcctggc gggagaccgc acattccact gctgaggctg tgggggcggt ttatcaggca gtgataaaca t &lt; 210 &gt; 319 &lt; 211 &gt; 151 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 319 aactagtgga tccagagcta taggtacagt gtgatctcag ctttgcaaac acattttcca catagatagt actaggtatt aatagatatg taaagaaaga aatcacacca ttaataatgg taagattggg tttatgtgat ctcagtgggt a &lt; 210 &gt; 320 &lt; 211 &gt; 150 &lt; 212 &gt; DNA &lt; 213 &gt; al crop-· · r &lt;. 400 &gt; 320 aactagtgga tccaccagtc cagtgtggtg gaatt.Qcatt gtgttggggt tctagatcgc gagcggctgc cctctrcctt ttcccttttg ggggggaatt tttttttttt aatagccatt gagtgttcta cagctcacag caaataccat &lt; 210 &gt; 321 &lt; 211 &gt; 151 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 321 agcaactttg tttttcatcc aggtcacttt aggcttagga tttcctctca cactgcagct tagggtggca tcgtaaccag ctatggcata ggtgttaacc Aaaggctgag taaacatggg tgcctctgag aaaccaaagc cttcacacac t &lt;2i〇&gt; 322 &lt;211&gt; 151 &lt;21 2&gt; DNA &lt;213&gt; Human &lt;220&gt; _ &lt;221&gt; misc__: feature (J &lt; 222 &gt; (1) .7. (151) &lt;223&gt; n = A, TC or G &lt;400&gt; 322 atccagcatc ttctcctgtt tcttgccttc ctttttcttc ttcttasatt ctgcttgagg tt: t999ctcg gtcagtttgc cacagggctt ggagatggtg acagtcttct ggcattcggc attgtgcagg gcccgcttca nacttccagt t &lt; 210 &gt; 323 &lt; 211 &gt; 151 &lt; 212 &gt; DNA 60 120 151 60 120 151 60 120 150 60 120 151 60 120 151 127691 .doc 107- 200815476 &lt;213&gt;莩&lt;220&gt;&lt;221&gt; misc a tribute &lt;222&gt; (1)...(151)

&lt;223&gt; η = A, T#C ^ G &lt;400&gt; 323 tgaggacttg tkttcttttt ctttattttt aatcctctta ckttgtaaat atattgccta 60 nagactcant tactacccag tttgtggttt twtgggagaa atgtaactgg acagttagct 120 gttcaatyaa aaagacactt ancccatgtg g 151 - public &lt;210&gt; 324 &lt;211&gt; 461 &lt;;212&gt; DNA U13&gt; Human &lt;220&gt;&lt;221&gt;1^5&lt;:_SpecialDesire&lt;222&gt; (1)...(461) · * Ο

&Lt; 223 &gt; n »A, T, C or G · &lt;. 400 &gt; 324 acctgtgtgg aatttcagct ttcctcatgc aaaaggattt tgtatccccg gcctacttga 60 agaagtggtc agctaaagga atccaggttg tcggctggac tgttaatacc tttgatgaaa 120 agagt'tacta cgaatcccac ctcggttcca gctatatcac tgacagcatg gtagaagact 180 gcgaacccca cttctagacc ttcacggtgg gacgaaacgg gtccagaaac tgccaggggc 240 ccccitacagg gatatcaaaa taccctttgc gccacecagg ccctggggaa tcaggtgact 300 cacacaaacg caatagttgg tcactgcact tttacctgaa ccaaagctaa acccggcgtc 360 gccaccatgc accatggcat gccagagtitc aacactgttg ctcttgaaaa ttgggtctga 420 aaaaacgcac aagagcccct gccctgcccc agctgangca c 461 &lt; 210 &gt; 325 &lt; 211 &gt; 400 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 325 acaccgcttc catgttacgt ttctacacat tgctacctca gtgcccctgg aaacttagct 60 tctgatgtct ccaagtagtc caccttcatt taactctttg aaactgtatc atctttgcca 120 agtaagagtg gtggcctatt tcagctgctt tgacaaaatg actggctcct gacttaacgt 180 tctacaaatg aatgtgctga agcaaagtgc ccacggtggc ggcgaagaag agaaagatgt;. 240 gttttgcttt ggactctctg tggtcccttc caatgctgtg g gtttccaac caggggaagg 300 gtcccttttg cattgccaag tgccataacc atgagcacta cgctaccatg gttccgcctc 360 ccggccaagc aggctggctt gcaagaatga aatgaatgat 400 &lt; 210 &gt; 326 &lt; 211 &gt; 1215 &lt; 212 &gt; DNA &quot; &lt; 213 &gt; human &lt; 400 &gt; 326 ggaggactgc agcccgcact cgcagccctg gcaggcggca ctggtcatgg aaaacgaatc 6〇 Gccctgctcg ggcgtcctgg tgcatccgca gtgggtgctg tcagccgcac actgtttcca 120 gaactcctac accatcgggc tgggcctgca cagtcttgag gccgaccaag agccagggag 180 -108- 127691.doc 200815476

ccagatggtg gaggccagcc tctccgtacg gcacccagag tacaacagac ccttgctcgc taacgacctc atgctcatca agttggacga atccgtgtcc gagtctgaca ccatccggag catcagcatt gcttcgcagt gccctaccgc ggggaactct tgccccgttt ctggctgggg tctgctggcg aacggcagaa tgcctaccgt gctgcagtgc gtgaacgtgt cggtggtgtc tgaggaggtc tgcagtaagc tctatgaccc gctgtaccac cccagcatgt tctgcgccgg cggagggcaa gaccagaagg actcctgcaa cggtgacttt ggggggcccc tgatctgcaa cgggtacttg cagggccttg tgtctttcgg aaaagccccg tgtggccaag ttggcgtgcc aggtgtctac accaacctct gcaaattcac tgagtggata gagaaaaccg tccaggccag ttaactctgg ggactgggaa cccatgaaat tgacccccaa atacatcctg cggaaggaat tcaggaatat ctgttcccag cccctcctcc ctcaggccca ggagtccagg cccccagccc ctcctccctc aaaccaaggg tacagatccc cagcccctcc tccctcagac ccaggagtcc agacccccca gcccctcctc cctcagaccc aggagtccag cccctcctcc ctcagaccca ggagtccaga ccccccagcc cctcctccct cagacccagg ggtccaggcc cccaacccct cctccctcag actcagaggt ccaagccccc aacccctcct tccccagacc cagaggtcca ggtcccagcc cctcctccct cagacccagc ggcccaatgc cacctagact ctccctgtac acagtgcccc Cttgtggc^c gttgacccaa ccttaccagt tggtttttca ttttttgtcc ctttccccta gatccagaaa taaagtctaa gagaagcgca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa &lt;210&gt; 327 · · &lt;211&gt; 220 _ &lt;2:L2&gt;protein &lt;213&gt; Human... 240 300 360 420 480 54 0 600 660 720 780 84 0. .9. 00 960 1020 ΙΟβΟ 1140 1200 1215

U &lt;400&gt; 327 Glu Asp Cys Ser Pro His Ser Gin Pro Trp Gin Ala Ala Leu Val Met 1 5 10 15 Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gin Trp Val . 20 25 30 Leu Ser Ala Ala His Cys Phe Gin Asn Ser Tyr Thr lie Gly Leu Gly 35 40 45 Leu His Ser Leu Glu Ala Asp Gin Glu Pro Gly Ser Gin Met Val Glu 50 55 60 Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro Leu Leu Ala 65 70 75 80 Asn Asp Leu Met Leu He Lys Leu Asp Glu Ser Val Ser Glu Ser Asp 85 90 95 Thr He Arg Ser lie Ser He Ala Ser Gin Cys Pro Thr Ala*Gly Asn 100 105 110 Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Gly Arg Met Pro 115 120 125 Thr Val Leu Gin Cys Val Asn Val Ser Val Val Ser Glu Glu Val Cys . 130 135 140 Ser Lys Leu Tyx Asp Pro Leu Tyr His Pro Ser Met Phe Cys Ala Gly 145 150 155 160 Gly Gly Gin Asp Gin Lys Asp Ser Cys Asn Gly Asp Ser Gly Gly Pro 165 ' 170 175 Leu lie Cys Asn Gly Tyr Leu Gin Gly Leu Val Ser Phe Gly Lys Ala 180 185 190 • Pro Cys Gly Gin Val Gly Val Pro Gly Val iyr&gt;Thr Asn Leu Cys Lys 195 20 0 205 Phe Thr Glu Trp lie Glu Lys Thr Val Gin Ala Ser 210 215 220 &lt;210&gt; 328 127691.doc 109- 200815476 &lt;211&gt; 234 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 328 cgctcgtctc tggtagctgc agccaaatca taaacggcga ggactgcagc ccgcactcgc agccctggca ggcggcactg gtcatggaaa acgaattgtt ctgctcgggc gtcctggtgc atccgcagtg ggtgctgtca gccacacact gtttccagaa ctcctacacc atcgggctgg gcctgcacag tcttgaggcc gaccaagagc cagggagcca gatggtggag gcca &lt; 210 &gt; 325 &lt; 211 &gt; 77 &lt; 212 &gt; protein &lt; 213 &gt; human 60 120 180 234 Γ u &lt;400&gt; 329 Leu Val Ser Gly Ser Cys Ser Gin lie lie Asn Gly Glu Asp Cys Ser 1 5 10 ' 15 Pro His Ser Gin Pro Trp Gin Ala Ala Leu Val Met Glu Asn Glu Leu 20 25 30 Phe Cys Ser Gly Val Leu Val His Pro Gin Trp Val Leu Ser Ala Thr 35 40 * 45 · His Cys Phe Gin Asn Ser Tyr Thr lie Gly.^Leu Gly Leu His Ser Leu 50 55 60 Glu Ala Asp Gin Glu Pro Gly Ser Gin Met Val. Glu Ala 65 70 75 &lt;210&gt; 330 &lt;211&gt; 70 &lt;212&gt; DNA &lt;213&gt; Person &lt;400&gt; 330 cccaacacaa tggcc Cgatc ccatccccga ctccgccctc aggatcgctc gtctctggca gccgcagcca &lt;210&gt; 331 &lt;211&gt; 22 &lt;212&gt; Egg &lt;213&gt; Human &lt;400&gt; 331 Gin His Asn Gly Pro lie Pro Ser Leu Thr Pro Pro Ser Gly Ser Leu 1 5 10 * 15 * Val Ser Gly Ser Cys Ser 20 &lt;210&gt; 332 &lt;211&gt; 2507 &lt;212&gt; DNA &lt;213&gt; Human &lt;4〇0&gt; 332 tggtgccgct gcagccggca gagatggttg agctcatgtt cccgctgttg ctcctccttc tgcccttcct tctgtatatg gctgcgcccc aaatcaggaa aatgctgtcc Agtggggtgt 60 70

60 12Q 127691.doc -110- 200815476

u tagttgtggt cacaggagct aatacaggta agagaggagc tcgagtatat ttagcttgcc aagagatcca gaccacgaca gggaaccagc atactaagtc tattcgagct tttgctaagg ttttgatcaa caatgcagga gtgatgatgt agatgcacat aggagtcaac cacttgggtc aactaaagga atcagcccca tcaaggatag gaaggatcca cttccataac ctgcagggcg gtcacagcaa gctagccaac atcctcttca ctggcgttac gacgtattct gtacaccctg catctttcat gagatggatg tggtggcttt gagcccagac cagcctgcac tgtgccttaa atttcagtga ctgtcatgtg gcatgggtct ggcggctgtg ggacgtcagt tgtgacctgc cagttggacc caagagaaga ctgcagcaga ccttcaaggt tttcaaaacc cttagcacaa tggtgtccag ttaaaactca gtgtaccgcc tttactttgc ttctgttact gccagagtta ctcatatgac ctgcacagct cattttcctt agctacagca gggatgattt atgcaaattt ctcccaacca accagtcttc actccaagag taacaaagac tggctcagga gcagggcttg agctcaagac cagcctggcc aacatggtga ctttgtgcgt cctcctgttc atgt.gtgcca cacaataatc agagatggag caaaccagtg caaagggaag cagattctgt atatgtcggt ggaagaagta aaaaaayaga aggagaacac gtcaaggatc aaccagccct tcaaggacca aaatatgcta acacagctat ggaggaattg aacaaaaacc agtgtggcaa aaaaaaaaaa aacaaaa aaa acaattcttc attcagaaaa ggtcaattca ataatatttt ggggcacccc tgtgccaaaa tttcgtactt tatttggaga agcctaagga attagtagtg ttcccaccac tgatttcctg gaatgacaat tatattttaa agtcttcact tctgatactt gtaaattaat gaaatggtca ttttacggaa ataaatgaat taatgtttta cttaatttat ccttgatcat ttttcgcttt catttaccag acaaaadaaa aaaaaaa gtacatcaac tgttcagctt cctgggaaag tcgggaagga gacagccaaa gagctggctc gggatgtgga aaagggggaa ttggtggcca aggtgttggt gcggaaactg gacctgtctg gcttcttagc tgaggaaaag cacctccacg gtccgtactc gaagacagca gatggctttg acttcctcct aacccatctg ctgctagaga tatacgttta taaatgtgtc ttccctcgca catcacctgg agaaattcta caatgcaggc ctggcctact cccaggaact ggcccggaga ctaaaaggct gcacagtcca atctgaactg gttcggcact tctccttttt catcaagact cctcagcagg cagaaggtct tgagattcta agtgggaatc ctgcccaagc tcgtaatgag actatagcaa ctttgttcac aattcagt tgggcctccc aatagactaa .caggcagtgc ctacacagta cttcttgtca aaatgattct agagagcaaa accttccagc cttgcctgct agattcgtct aaatgtctgt catgtccaga ctagagatat cataatagga taagaagacc ctgaaagaaa ctactaccta ggagaatcta gaactagctt tc ggccacactg caacctcagc ttaacatgaa cccaggcatg gtggatcacc ggaggtcagt aaccccacct ctactaaaaa ttgtgtatat agggagtatt tccacaaagt tcaaaacagc ccatccagtc tttatgcaaa tgaaatgctg aactacccac caagagcaca tgggtagcag tggaagataa tgcacaaaat gaagggacca actagtcaag gattaatagc aaaagayact agggcaagca cccaggaccg atgaggtctc aaaaaaaaaa aaaaatccta aaaacaaaca attatctcag ggactgatat tggtaattat cttacatcgt cttgacaaga ttaaaatgtc ctccccatca aaagtaatgc tgccaaagga ttgttcggag tgtgctattc taaaagattt ctttggtggg ggaaagagtt ataggaccac cccttactgc acttgtcttg accattaagc aaattagaaa Aattctgata atagtgcaga atcgaactgt caatgacaaa taaaaattct aacaaaaacg taagaactaa aagtttgatt &lt;210&gt; 333 &lt;211&gt; 3030

&Lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400> 333 gcaggcgact tgcgagctgg gagcgattta ggagagcgag ctgggtgccc .cctagattcc gctccatgga gcccggcaat tacgccaccc tgggagcggg aggggggcgg satctggtcg cgcctacgct gatgcctgct gtcaactatg cgccaaagca atgccaccca tgccctgggg cctatggtta ctttggaggc gggtactact cctgtgccca ggcagccacc ctggccgcgc aaacgccccg gattcccccg gcctgggcgg ccgcccccgc acctcatgag ccgaccctcg tggatggagc caaggatatc gaaggcttgc cccactcccc Tctgaccagc cacccagcgg cccccctgga tctgccaggc tcggcggagc tgccccaggg gacgtcccca gctcccgtgc cctgccgagt gtcccggagc tcgctgaaac accccgcgga gactcccacg gccggggaag 180 240 300 360 420 480 54 0 600 660 720 780 840 900 960 1020 · 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 I860 1920 .1980 2040 2100 2160 2220 2280 2340 2400 2460 2507 60 120 180 240 300 360 420 480 111 - 127691.doc 200815476

agtaccccag ycgccccact gagtttgcct tctatccggg atatccggga acctaccagc ctatggccag ttacctggac gtgtctgtgg tgcagactct gggtgctcct ggagaaccgc gacatgactc cctgttgcct gtggacagtt accagtcttg ggctctcgct ggtggctgga acagccagat gtgttgccag ggagaacaga acccaccagg tccctttcgg aaggcagcat ttgcagactc cagcgggcag caccctcctg acgcctgcgc ctttcgtcgc ggccgcaaga aacgcattcc gtacagcaag gggcagttgc gggagctgga gcgggagtat gcggctaaca agttcatcac caaggacaag aggcgcaaga tctcggcagc caccagcctc tcggagcgcc agattaccat ctggtttcag aaccgccggg tcaaagagaa gaaggttctc gccaaggtga agaacagcgc taccccttaa gagatctcct tgcctgggtg ggaggagcga aagtgggggt gtcctgggga gaccaggaac ctgccaagcc caggctgggg ccaaggactc tgctgagagg cccctagaga caacaccctt cccaggccac tggctgctgg actgttcctc aggagcggcc tgggtaccca gtatgtgcag ggagacggaa ccccatgtga cagcccactc caccagggtt cccaaagaac ctggcccagt cataatcatc catcctgaca gtggcaataa tcacgataac cagtactagc tgccatgatc gttagcctca tattttctat ctagagctct gtagagcact ttagaaaccg ctttcatgaa ttgagctaat tatgaataaa tttggaaggc gatcccttcg cagggaagct ttctcccaga cccccctcca ttacacctct caccctggta acagcaggaa gactgaggag aggggaacgg gcagattcgc tgtgtggctg tgatgcccgt ttagcatttt tctcagctga cagctgggta ggtggacaat tgtagaggct gtctcttcct ccctccttgt ccaccccata gggtgtaccc actggtcttg gaagcaccca tccttaatac gatgattttt ctgtcgtgtg aaaatgaagc cagcaggctg cccctagtca gtccttcctt ccagagaaaa agagatttga gaaagtgccc gggtaaccca ccattaattt cctcccccaa actctccgag tcttccctta atacttctgg tggttctgac caaagcaggt catggtttgt tgagcatttg ggaccccagc gaagtagatg tttgtagcct tgcatactta gccctcccca ggcacaaacg gagtggcaga gtggtgccaa ccccgttttc ccagtccacg tagacagatt cacagtgcgg aactctggaa gctggagaca gacgggctct ttgcagagcc gggactctga gagggacacg agggcccctg cctccgtgtt catcctctga tgtcctgtac ctgggctcag r.gcccggtgg gactcatctc ctggccgcgc agcaaagcca gcgggctcgt gccggtcctt cctgcacctt aggccggggg tggggggccc gccggcgcat tctccacgac cgagcgcaca ggcctgaagc ctggacaacc cgcagaaccg aagctccgag cagcgggccg gtggcgagta gtggggtcgg ccgcgagcag tcggcggtgg gccgcggccg ccactacctc gaggacatct ccctcccgga gccagccctc ctagaaac cc cgcggcggcc gccgcagcca agcgctcatg gcccgcggtc gggcgggatc ctagccctgt ctcctctcct 'gggaaggaac gagggtggga cgtgacttag acacctacaa atctacctac caaagaggag cccgggactg agggaaaagg ccaaagagtg cgagcgcatg cggactgggg gttcagggga agaggacgag gaggaggaag atgaggtcga cctcctgatt taaaaaatcg tccaagcccc gtggcccagc ttaaggtcct cggttacatg cgccgcccag agcaggtcac tttctgccct ccacgtcctc cctcaaggaa gccccatgtg ggcagctctc aacaccgcag gctctcaccc ctctgcctct acaagcccaa acccaccaac gaccgggcaa gcaaaccccc tccctcgccg acttcggaac tggcgagagt tcagcgcaga tgggcccgtg gggagggggc aagatagacg agggggagcg gcatggcgcg gggcgacccc ttggagagag gaaaaaggcc acaagagggg ctgccaccgc cactaacgga gacggccctg gtagagaccc ttgggggtcc ggaacctctg gactccccat gccctaactc ccacactctg ctaccagaaa ctcaaacttg aggattttct ctgttttcca ctcgcaataa aytcagagca aacaaaaaaa aaaaaaaaaa aaaacccgag &lt; 210 &gt; 334 ~ &lt; 211 &gt; 2417 &lt; 212 &gt; DNA &lt; 213 &gt; human, &lt; 400 &gt; 334 ' ggcggccgct ctagagctag tgggatcccc cgggctgcac gaattcggca cgagtgagtc ggagttttac ctgtattgtt ttaatttcaa ca agcctgag gactagccac aaatgtaccc agtttacasa tgaggaaaca ggtgcaaaaa ggttgttacc tgtcaaaggt cgtatgtggc agagccaaga tctgagccca gttatgtctg atgaacttag cctatgctct ttaaacttct gaatgctgac caccgaggat atctaaactt agatcaattg caccctccct ccaagaccat 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 I860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3030 60 120 180 240 300 127691.doc 112- Ο 200815476 ttacttatca atacaataat accaccttta ccaatctatt gttttgatac gagactcaaa tatgccagat atatgtaaaa gcaacctaca agctctctaa tcatgctcac ctaaaagatt cccgggatct aataggctca aagaaacttc ttctagaaat ataaaagaga aaattggatt atgcaaaaat tcattattaa tttttttcat ccatccttta attcagcaaa catttatctg Ttgttgactt tatgcagtat ggccttttaa ggattggggg acaggtgaag aacggggtgc cagaatgcat cctcctacta atgaggtcag tacacatttg cattttaaaa tgccctgtcc agctgggcat ggtggatcat gcctgtaatc tcaacattgg aaggccaagg caggaggatt gcttcagccc aggagttcaa gaccagcctg ggcaacaCag aaagacccca tctctcaatc aatcaatcaa tgccctgtct ttgaaaataa aactctttaa gaaaggttta atgggcaggg catgcctata atacagcact ttgggaggct gaggcaggag gatcacttta gcccagaagt tcaagaccag .cctgggcaac aagtgacacc tcatctcaat tttttaataa aatgaataca tacataagga aagataaaaa gaaaagttta atgaaagaat acagtataaa acaaatctct tggacctaaa agtatttttg ttcaagccaa atattgtgaa tcacctctct gtgttgagga tacagaatat ctaagcccag gaaactgagc agaaagttca tgtactaact aatcaacccg aggcaaggca aaaatgagac taactaatca atccgaggca aggggcaaat tagacggaac ctgactctgg tctattaagc gacaactttc cctctgttgt atttttcttt tgtggtagct tattcaatgt aaaaggataa aaactctcta aaactaaaaa caatgttcgt caggagttac aaaccatgac caactaatta tggggaatca taaaatatga ctgtatgaga tcttgatggt ttacaaagtg tacccactgt caatcacttt aaacattaat gaacttaaaa acgaacttac ggagattgga atgtttcttt cctgttgtat tagttggctc aggctgccat aacaaaatac cacagactgg gaggcttaag taacagaaat tcacttctca cagttc-cggg ggctggaagt ccacgatcaa ggtgcaggaa aggcaggctt cattctgagg cccctctctt ggctcacatg tggccaccct cccactgcgt gctcacatga cctctttgtg ctcctggaaa gagggcg tgg gggacagagg gaaagagaag gagagggaac tctctggcgt ctcgcctctc aaggacccca acctgggcca ctttggccca ggcactgtgg ggtggggggt tgtggctgcc ctgctctgag tggccaagac aaagcaacag aaaaatgtcc aaagctgtgc agcaaagaca agccaccgaa cagggatctg cccaccagtg cggggacctc caagtcggcc accccuaagg caagccccca cagagcccat gcaaggcggc agcagcagaa gaagggaatt gcccctgccc ccggcacatc cctcaccgac ccggcgatgc tggacactgc gatgaatggc aatgtggacg agaaLdtgat ggactcccag aaaaggagac ccagctgctc aggtggctgc aaaccattac agccctcatc ctggggagga actgggggcc tggttctggg tcagagagca gcccagcgag ggtgagagcc acagcctgcc ctgccagctg gatccccagt cccggccaac cagcaaccaa ggctgagcag accaggctcc ccggagctgg tcttgggaag ccagccctgg ggtgagtcgg ctcctgctgc ggtaccgaga caatattgtc ataaattcaa tgcgcccttg tatccctctt tccttctcat ctgtccacac ccataatcac tatgcatact agtctttgtt agtgttccca ttcmacccaa tagagacacg ctatacc &lt; 210 &gt; 335 &lt; 211 &gt; 2984 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 335 360 420 480 540 600 660 720 780 840 900 960 1020 1080: 1140 1200 1260 1320 1380 1440 1500 15^0 1620 1 680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 234 0 2400 2417

60 120 180 240 300 360 420 480 540 600 660 720 stccctccct aaaacacccc cccgagctgc agtacctgtc aagtgaagat agctgggaga gggcctccct gcagccggag ctgccttccc tgcgcacacc aatgaaacaa taggtcattt ccccactctc aggcgccctt cttctcccac ggcccctgaa atggtcccag cttggagaag ggcccccgtg cccagctttt cagggcgtct aaagctatcg cagagacagt tttttgcttc ctttccagaa ccaaggcttc actcaggtga cgggcccacc aacagacgct cafctcctctt tataacagct tggtaatgcc ctatgaaaag gagatttgcg gaaagtttta tggctacctg ggcacttggg cccaaacccc tcgagttgga tggccaagaa ataagactaa tgccggccct atccttacta agctcaggtg cacaaggggc tggaaatccc atacctaagt tttgaagggg gtctta-tctg taagcagccg gaggaagttc cctcaagctc gcgaaagcag gaaagaggag cccatacctg acaaccatta caaggtcagg asacccttca cattccccca agagagggaa ttggactctg cagaagcgcc agccatcaga acggagaccc ccctcctcgg gccttctccc tactgcgtgg tgatcaaaaa gagcaagagg ctggtgagac gtgcatactg aatcaagtgg 113- 127691.doc 200815476 tattttccag cactttgtat gattttggat gagctgtaca cccaaggatt ctgttctgca actccatcct cctgtgtcac Tgaatatcaa ctctgaaaga gcaaacctaa caggagaaag g acaaccagg atgaggatgt caccaactga attaaactta agtccagaag cctcctgttg gccttggaat atggccaagg ctctctctgt ccctgtaaaa gagaggggca aatagagagt ctccaagaga acgccctcat. gctcagcaca tatttgcatg ggagggggag atgggtggga ggagatgaaa atatcagctt ttcttattcc tttttattcc ttttaaaatg gtatgccaac ttaagtattt acagggtggc ccaaatagaa caagatgcac tcgctgtgat tttaagacaa gctgtataaa cagaacccca ctgcaagagg gggggccggg ccaggagaat ctccgcttgt ccaagacagg ggcctaagga gggtctccac actgctgcta ggggctgttg cattttttta ttagtagaaa gtggaaaggc ctcttctcaa cttttttccc ttgggctgga gaatttagaa tcagaagttt cctggagttt 'tdaggctatc atatatactg tatcctgaaa ggcaacataa ttcttccttc cctcctttta aaattttgtg ttcctttttg cagcaattac tcactaaagg gcttcatttt agtccagatt tttagtctgg ctgcacctaa cttatgcctc gcttatttag cccgagatct ggtctttttt tttttttttt tttttccgtc tccccaaagc tttatctgtc ttgacttttt aaaaaagttt gggggcagat tctgaattgg ctaaaagaca tgcattttta aaactagcaa ctcttatttc tttcctttaa aaatacatag cattaaatcc caaatcctat ttaaagacct gacagcttga gaaggtcact actgcattta taggaccttc cggtggttct gctgttacg t ttgaagtctg acaatccttg agaatctttg catgcagagg aggtaagagg tattggattt tcacagagga agaacacagc gcagaatgaa gggccaggct tactgagctg tccagtggag ggcccatggg tgggacatgg aaaagaaggc agcctaggcc ctggggagcc cagtccactg agcaagcaag ggactgagtg agccttttgc aggaaaaggc caagaaaaag gaaaaccatt ctaaaacaca acaagaaact gtccaaatgc tttgggaact gcgtttattg cctataatgg gtccccaaaa tgggtaacct agacctcaga gagaacgagc agagagcaaa ggagaaatct ggctgtcctt ccattttcat tctgttatct caggtgagct ggtagagggg agacactaga aaaaaatgaa acaacaaaac aatnactaat gaggtacgct gaggcctggg agtctcccga ctccactact . tiaattccgtc tagtgagaaa cctttcaatc tccttttatt agaag.ggcca gcttactgtt ggtggcaaaa- ctgccaacaf aagttaacag aaagttggcc aatcccaccc cattctccgt ggtttgggct ccacattgca atgttcaatg ccacgtgctg ccgacaccga ccggagtact agccagcaca aaaggcaggg tagcctgaat tgctttccgc cccctacatt ccccccaaaa Laagcattta gcgctcagtc cctactgagt actctttctc ccccctcctc tgaacttaat. dagger ctttcaact tgcaatttgc aaggattaca catttcactg tgatgtacat tgtgtcgcaa aaaaaaaaaa aagtgtcttt gttcaaaatt acttggtttg cgaacccacc cc gccttttc cccattggaa ctagccatta acccatctct gaactggtag aaaascacct gaagagctag tctatcagca tctgacaggt gaattggatg gtcctcagaa ccatcrcacc cagacagcct gtctctaccc tgcttaataa attagtctgg gttccctaca tgcaceacaa accctgcccc aatctgtcac ataaaagtct gtgactr.gaa gtttagtcag cacccccacc aaactttact tttctatgtg ttttttgcaa catacgagcg ttttgaaaat aaagtaccca tgcctttatt agaaaaaaaa aadaaddaaa aaaa 780 840 900 960 1020 1080 1140 1200 1260 132,0 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 282C 2680 2940 2984 u &lt;210&gt; 336 &lt;211&gt; 147 &lt;212&gt; Protein &lt;213&gt; Human &lt;400&gt;; 336 Pro Ser Phe Pro Thr 1 5 Leu Asp Ser Glu Asn 20

Leu Leu Ser Arg Arg His Leu Gly Ser Tyr Leu 10 15 Thr Ser Gly Ala Leu Pro Arg Leu Pro Gin Thr 25 30 Pro Lys Gin Pro Gin Lys Arg Ser Arg Ala Ala Phe Ser His Thr Gin 35 40 45 Val lie Glu Leu Glu Arg Lys Phe Ser His Gin Lys Tyr Leu Ser Ala 50 55 60 Pro Glu Arg Ala His Leu Ala Lys Asn Leu Lys Leu Thr Glu Thr Gin 65 70 75 80 127691.doc -114- 200815476

Val Lys lie Trp Phe Gin Asn Arg Arg Tyr Lys Thr Lys Arg Lys Gin 05 90 95

Leu Ser Ser Glu Leu Gly Asp Leu Glu Lys His Ser Ser Leu Pro Ala 100 105 110

Leu Lys Glu Glu Ala Phe Ser Arg Ala Ser Leu Val Ser Val Tyr Asn 115 120 125

Ser Tyr Pro Tyr Tyr Pro Tyr Leu Tyr Cys Val Gly Ser Trp Ser Pro 130 135^ 140

Ala Phe Trp , 145 &lt;210&gt; 337 &lt;211&gt; 9 &lt;212&gt;protein &lt;213&gt; human &lt;400&gt;

Ala Leu Thr Gly Phe Thr Phe Ser Ala 1 5

&lt;210&gt; 338 &lt;211&gt; 9 .- Protein &lt;213&gt; People &lt;400&gt; 338

Leu Leu Ala Asn Asp Leu Met Leu lie 1 5 &lt;210&gt; 339 &lt;211&gt; 318 &lt;212&gt; • Protein &lt;213&gt;People &lt;400&gt;

Met Val Glu Leu Met Phe Pro Leu Leu Leu Leu Leu Leu Pro Phe Leu 1 5 10 15

Leu Tyr Met Ala Ala Pro Gin lie Arg Lys Met Leu Ser Ser Gly Val 20 25 30 ϋ

Cys Thr Ser Thr Val Gin Leu Pro Gly Lys Val Val Val Val Gly 35 40 45

Ala Asn Thr Gly lie Gly Lys Glu Thr Ala Lys Glu Leu Ala Gin. Arg 50 55 60

Gly Ala Arg Val Tyr Leu Ala Cys Arg Asp Val Glu Lys Gly Glu Leu 65 70 75 80

Val Ala Lys Glu lie Gin Thr Thr Thr Gly Asn Gin Gin Val Leu Val 85 90 95

Arg Lys Leu Asp Leu Ser Asp Thr Lys Ser lie Arg Ala Phe Ala Lys 100 105 110

Gly Phe Leu Ala Glu Glu Lys His Leu His Val Leu lie Asn Asn Ala 115 120 125

Gly Val Met Met Cys Pro Tyr Ser Lys Thr Ala Asp Gly Phe Glu Met 130 135 140

His lie Gly Val Asn His Leu Gly His Phe Leu Leu Thr His Leu Leu 127691.doc -115- 200815476 145 150 155 160 Leu Glu Lys Leu Lys Glu Ser Ala Pro Ser Arg lie Val Asn Val Ser 165 170 175 Ser Leu Ala His His Leu Gly Arg lie His Phe His Asn Leu Gin Gly 180 185 190 Glu Lys Phe Tyr Asn Ala Gly Leu Ala Tyr Cys His Ser Lys Leu Ala 195 200 205 Asn lie Leu Phe Thr Gin Glu Leu Ala Arg Arg Leu Lys Gly Ser Gly 210 215 220 Val Thr Thr Tyr Ser Val His Pro Gly Thr Val Gin Ser Glu Leu Val 225 230 235 240 Arg His Ser Ser Phe Met Arg Trp Met Trp Trp Leu Phe Ser Phe Phe 245 250 255 lie Lys Thr Pro Gin Gin Gly Ala Gin Thr Ser Leu His Cys Ala Leu 260 265 270 Thr Glu Gly Leu Glu lie Leu Ser Gly Asn His Phe Ser Asp Cys His 275 280 285 Val Ala Trp Val Ser Ala Gin Ala Arg Asn Glu Thr lie Ala Arg Arg 290 295 300 Leu Trp Asp Val Ser Cys Asp Leu Leu Gly Leu Pro lie Asp 305 310 315 Ο &lt;210&gt; 340 &lt;211&gt; 483 &lt;212&gt; DNA &lt;213&gt;Human&quot;&lt;400&gt; 340 gccgaggtct gccctcacac ggaggacacg agactgctcc c ccaagggct cctgcctgcc cggacaccgg cgggaggcgc Cgtttagttg gctgccctca gaggggtct ^ tcggagggac cccccgccgc aggctggagc gtctttattc ccggcgggag accgcacatc ccactgctga ggctgtgggg gcggcttatc aggcagtgat aaacataaga tgccatttcc ttgactccgg cccccsatcc tctctttggc tgacgacgga gtccgtggtg tcccgatgca actgacccct:.. gccccaaacg tgacatcact gatgctcttc tcgggggcgc tgatggcccg cttggtcacg tgcccaacct cgccattcga ctcttgctcc aaactgtatg aagacacccg actgcacgtt ccccccgggc ctccagaatt taaagtgaaa ggcagcaccc ctaagctccg actccgacgc c [ g 60 120 180 240 300 360 420 4 80 483 &lt;210&gt; 341 &lt;211&gt; 344 &lt;212&gt; DNA &lt;213&gt; Humans &lt;400&gt; 341 ctgctgccga gtcacagact tcattataaa tagcctccct aaggaaaaca cactgaatgc tattcccact aaccattcta tttttataga aatagctgag agcc'cctaaa Ccaactctct gctgccttac aagtattaaa tattttacct ctttccataa agagtagctc aaaatacgca actaatttaa taatttccga tgatggtttt atctgcagta atatgcatat cacccaccag aacttaccta atgaaaaact gaagagaaca aaatttgtaa ccaccagcac ttaagcactc ctgattccta acattgtctt- taatgaccac aagacaacca acag &lt;210 &gt; 342 &lt;211&gt; 592 &lt;212&gt; DNA &lt;213&gt; Human 60 120 180 240 300 344 127691.doc 116- 200815476 &lt;400&gt; 342 acagcaaaaa agaaactgag aagcccaaty cgctttcttg ttaacatcca cttatccaac caatgcggaa acttcttata cttggttcca ctatgaagtt ggacaattgc tgctatcaca cctggcaggt aaaccaatgc caagagagtg atggaaacca ttggcaagac tttgttgatg accaggattg gaattttata aaaatattgt tgacgggaag ttgctaaagg gtgaattact tccctcagaa gagtgtaaag aaaagtcaga gatgctataa tagcagctat tttaattggc aagtgccact gtggaaagag ttcctgtgtg tgctgaagtt ctgaagggca gtcaaattca tcagcatggg ctgtttggtg caaatgcaaa agcacaggtc tttttagcat gctggtctct cccgtgtcct tatgcaaaca atcgtcttct tctaaatttc tcctaggctt cactttccaa agttctcctt ggtttgtgat gtcttttctg ctttccatta attctataaa atagtatggc ttcagccacc cactcttcgc cttagcttga ccgtgagtct cggccgccgc tg &lt; 210 &gt; 343 &lt;211&gt; 382 &lt;212&gt; DNA &lt;213&gt; Person's amount 60 120 180 240 300 360 420 460 540 592 , Γ &lt;400&gt; 343 ttcttgacct cctcctcctt caagctcaaa caccacctcc cctattcagg accggcactt cttaatgttt gtggctttct ccccagcc tc ticttaggagg ggtaatggtg gagctggcat cttgtaactc tccctcctcc tttcttcccc cttctccgcG cgcctttccc atcctgccgt agactccttg atcgtcagtc tgtgccacac ccagtgattg ctttggttnc tgcccccttt ctgactgccc aaggggctca gaaccccagc aatccctt-cc tctcactacc ttcttttttg ggggtagctg gaAgggactg aaattgtggg gggaaggtag oaggcacatc aacaaagagg aaaccaccaa gctgaaaaaa aa &lt; 210 &gt; 344 &lt; 211 &gt; 536 ...... * &lt; 212 &gt; DNA &lt; 213 &gt; al Eu 60 120 180 240 300 360 382 &lt; 400 &gt; 3 4 4 ctgggcctga caataggcca gtttaggggg agtcctccag cacccccacg ccgaccccac ccttctcacc caaccaaccc qtctggccta agccgtaggg cataaacttg atgccaagga agaaacggac tgcccgaacg atcccccgcc acctgatcca gccactaaca tgagcgacta caaatcagag gctggatgga taaggccagc gcaatcagag gttgccaggt cgcgccccct gaaatcgccc Gttatgtcat: caaaaaggat gcaggcttcc acctcacaat ccagttatat tgggatcccg cagaaaaatc tctccataaa ccctctcacc ccctctcatt tagactgagc gagugatgag aaggtggtca gaagagaagc gtcacatcaa caccccttac attcttctta cctaccacga aatcatcatc cgaataacaa agtcctgaga cctctcgttt agaacaaaca ggtcacactc gagtgcggct gc Agccatta gccctacaaa ctagccccaa aaaaaa 60 120 180 240 300 360 420 480 536

&Lt; 210 &gt; 345 &lt; 211 &gt; 251 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 345 60 120 180 240 251 acctttcgag gtctctctca ccacccccac agccaccgtc accgtgggat gtgccggatg tgaatgaagc ccccatcttt gtgcctcctg aaaagagagt ggaagtigccc gaggactttg gcgtgggcca ggaaatcaca tcctacactg cccaggagcc agacacattt atggaacaga aaacaacaxa tcggactcgg Agagacactg ccaactggct ggagattaat ccggacactg gtgccactcc c 117- 127691.doc 200815476 &lt;210&gt; 346 &lt;211&gt; 282 &lt;212&gt; DNA &lt; 213 &gt; Human Effect &lt;220&gt;

&lt;221&gt; misc_ special education &lt;222&gt; (1): (282) &lt;223>n * A, T, C or G &lt;400&gt; 346 cgcgtctctg acactgtgat catgacaggg gttcaaacag aaagtgcctg ggccctcctt 60 ctaagtcttg ttaccaaaaa aaggaaaaag aaaagatctt ctcagttaca aattctggga 120 agggagacta Tacctggctc ttgccctaag tgagaggtcc tccctcccgc accaaaaaat 1Θ0 agaaaggctt tctatcccac tggcccaggt agggggaagg agagtaactt tgagtctgtg 240 ggtctcattt cccaaggcgc cttcaatgct catnaaaacc aa 282

&lt;210&gt; 347 &lt;211&gt; 201 &lt;212&gt; DNA

&lt;213&gt; People. * &lt;220&gt; * &lt;22l&gt; misc_ • Special Micro &lt;222&gt; (1).7.(201)

&Lt; 223 &gt; n = A, T, C or G &lt; 400 &gt; 347 acacacataa tattacaaaa tgccatctaa ttggaaggag ctttctacca ttgcaagtca 60 taaatataac ctttaaaana ntactancag cttttaccta ngctcctaaa tgctcgtaaa 120 tctgagactg actggaccca cccagaccca gggcaaagat acatgttacc atatcacctc '1Θ0 cttctcttgc c 201 &lt; 210 &gt; 348 &lt;211&gt; 251 &lt;212&gt; DNA &lt; 213 &gt;Human&lt;40O&gt; 34Θ ctgctaatca caacatttgt gcatcacctg tgccaagtga gaaaatgttc taaaatcaca 60 agagagaaca gtgccagaat gaaactgacc ctaagtccca ggtgcccctg ggcaggcaga 120 aggagacact cccagcatgg aggagggctt atcttttcat cctaggccag gtccacaatg 180

U ggggaaggct tcattataga actcccaaca gcccacctca ctcctgccac ccacccgatg 240 gccctgcctc c . 251 &lt;210&gt; 349 &lt;211&gt; 251 &lt;212&gt; DNA &lt;213&gt; Humans &lt;4〇0&gt; 349 caaaaatcaa gccattcaac tgtacctttg aaggtaaaca atatatggga gctggatcac 60 aacccctgag gatgccagag ctatgggtcc Agaacatggt gtggtatcat caacagagtc 120 cagaagggtc tgaactctac gtgttaccag agaacacaat gcaattcatg cattccactt 1B0 agcaaccttg caaaatacca gaaacagacc ccaagagtct ttcaagatga ggaaaaccca 240 127691.doc -118- 200815476 actcctggtt t 251 &lt;210&gt; 350 &lt;211&gt; 908 &lt;212&gt; DNA &lt;213&gt;; 400 &gt; 350 ctggacactt tgcgagggcc tttgctggct gctgctgctg cccgtcatgc tactcatcgt 60 agcccgcccg gcgaagctcg ctgctttccc tacctcctta agtgactgcc aaacgcccac 120 cggctggaat tgctctggtt atgatgacag agaaaatgat ctcttcctct gtgacaccaa 180 cacctgtaaa tttgatgggg aatgtttaag aattggagac actgtgacct gcgtccgtca 240 gttcaagtgc aacaatgact atgtgcctgt gtgtggctcc aatggggaga gctaccagaa 300 tgagtigttac ctgcgacagg ctgcatgcaa acagcagagt gagatacttg tggtgccaga 360 r aggatcatgt gccacagtcc atgaaggctc tggagaaact agtcaaaagg agacatccac 420 ctgtgatatt tgccagtttg gtgcagaatg tgacgaagat gccgaggatg cctggtgtgt 480 gtgtaatatt gactgttccc aaaccaactt caatcccctc tgcgctcccg acgggaaatc 540 ttatgataac gcatgccaaa tcaaagaagc atcgtgtcag aaacaggaga aaatcgaagt 600 catgtctttg ggtcgatgtc aagataacac aactacaact actaagtctg aagatgggca 66〇ttatgcaaga acagattatg cagagaatgc taacaaatta gaagaaagtg ccagagaaca 720 ccacatacct tgtccggaac atcacaatgg cttctgcatg catgggaagt gtgagcaccc 780 tatcaatatg caggagccat cttgcaggtg tgatgccggt tatactggac aacactgtga 840

ϋ aaaaaaggac tacagtgttc tatacgttgt tcccggtcct gtacgatttc agtatgtctt 900 aatcgcag a 908 &lt;210&gt; 351 &lt;211&gt; 472 &lt;212&gt; DNA • &lt;213&gt;human&lt;400&gt; 351- ----- ccagtcatct gcaagcggta agagcctatt taccataaac aatactaaga accaactcaa 60 gtcaaacccc aatgccattg ttattgtgaa ttaggactaa gtagcaacct tcaaaatcca 120 cactaacccg actctaaaat cagwtttgyg agtcatctac cacaagctaa atgtgtacac 180 tacgataaaa acaaccattg tactcctgtt tttctaaaca gtcctaattt ccaacactgt 240 atataccctc cgacatcaac gaactctgtt ctctcttact ccagcaataa agtaggcaca 300 gacccgccca caacaaactE: gccccctcat gccctgcctc tcaccacgct ctgctccagg 360 tcagcccccc tctggcctgt ttgtctcgtc aaaaacctaa tctgctcctt gcttttcttg 420 gcaatacaca tctagggaag atgttgcttt gcccacacac gaagcaaagc aa 472 &lt;210&gt; 352 &lt;211&gt; 251 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 352 .. ctcaaagcca atctctcggg aatcaaacca gaaaagggca aggatcctag gcatgotgga 60 tgcggacaag gccaggccaa tggctgcaag catgcagaga aagaggcaca tcggagcgtg 120 caggccgcgt tccgtcctta cgatgaagac cacgatg Cag tctccaaaca ttgccactac 180 atacatggaa aggaggggga agccaaccca gaaatgggct ttctctaatc ctgggatacc 240 aacaagcaca a ' 251

&lt;210&gt; 353 &lt;211&gt; 436 &lt;212&gt; DNA 119-127691.doc 200815476 &lt;213&gt;People&lt;400&gt; 353 ttttcttttt tttttttttt ttttttacaa caatgcagtc atttacttat tgagtatgtg 60 cacattatgg tattattact atactgatta tatttatcat gcgacttctai attaraaaat 120 gtatccaaaa gcaaaacagc agatatacaa aattaaagag acagaagata gacattaaca 180 gataaggcaa cttatacatt gacaatccaa atccaacaca tttaaacatt tgggaaatga 240 gggggacaaa tggaagccar atcaaatttg tgtaaaacta ttcagtatgt ttcccttgct 300 tcatgtctga raaggctctc ccttcaatgg ggatgacaaa ctccaaatgc cacacaaatg 360 ttaacagaat actagattca cactggaacg ggggtaaaga agaaattatt ttctataaaa 420 gggctcctaa tgtagt 436 &lt; 210 &gt; 354 &lt; 211 &gt; 854 &lt; 212 &gt; DNA &lt;2i3&gt;Human&lt;400&gt; 354 ccccttctag ttcaccagtt ttctgcaagg atgctggtta, gggagtgtct gcaggaggag 60 caagcctgaa accaaatcta ggaaacatag gaaacgagcc aggcacaggg ctggtgggcc 120

atcagggacc accctttggg ttgatatctt gcttaacctg catctttr.ga gtaagatcat ISO ccggcagtag aagctgttcc ccaggtacat ttctctagct catgtacaaa aacatcctga 240 aggactttgt caggtgcctt gctaaaagcc agatgcgt ^ c ggcacttcct tggtctgagg 300 ccaaccgcac acctacaggc actgggctca tgctcncaag tatcttgtcc tcactttagg 360 gcgagtgaaa gacccccact acaggagcac ctcjggagaga tcatataaaa gctgactctt: 420 gagcacatgc agcaatgggg tagatgtgtg tggtgcgtcc tcattcctgc aagggtgctt 480 gcnagggagc gcttccagga ggaacaagtc cgaaaccaat cacgaaataa atgguaggtg 540 cgaaccggaa aactaatcca aaagagagat cgtgatatca gtgtggttga cacaccttgg 600 caacatggaa ggctctaacc tgcccatatt: tgaaacaata atccagcttt ttgtaataca 660 aaacaacaaa ggattgagaa ccatggcgcc taatgcataa aagacccagg aaacataaat 720 acatcaaccg cataaatgca aaatgcatgt gacccaagaa ggccccaaag tggcagacaa · 780 caccgcaccc antetccctt ccaaaacgtg ageggeggge ctgctgcttt caaggctgtc 840 acacgggacg tcag 854 &lt; 210 &gt; 355 &lt;211&gt; 676 &lt;212&gt; DNA &lt;213&gt;Human&lt;400&gt; 355 gaaaccaagc atgagetaaa ttccctgtta aaacccctag gggtgac aga tctcttcaac 60 caggccaaag ccgatctttc tggaatgcca ccaaccaagg gcctatactt atcaaaagcc 120 u atccacaagt catacctgga tgtcagcgaa gagggeaegg aggeageage agccacCggg 180 gacagcatcg ctgtaaaaag cctaccaatg agagcccagt tcaaggcgaa ccaccccttc 240 ctgcccttta taaggcacac tcataccaac acgatcctac tctgtggcaa gcttgcccct · 300 ccccaatcag acggggttga gtaaggetea gagttgeaga tgaggtgcag agacaatcct 360 gtgacttticc cacggccaaa aagctgttca cacctcacgc acccctgtgc ctcaotrr〇e - tzo tcacccgcaa aataggtcta ggatttcttc caaccattcc atgagttgtg aagetaagge 480 ttegetaate atggaaaaag gtagactcat gcagaaagcc ttcctggctt tcttatctgt 540 ggtgcctcat ttgagtgccg cccagtgaca cgatcaagtc aatgagt〇aa attttaaggg 600 atcagactcc cttgacctgt atgtatctgt gagatettga ataagcgacc tgacatccct 660 geetaaagaa aaccag 676 &lt;. 210 &gt; 356 &lt; 211 &gt; 574 120- 127691.doc 200815476 &lt;212&gt; DNA &lt;213&gt;Human&lt;400&gt; 356 tttttttttt tttttcagga aaacattctc ttactttatt tgcatctcag caaaggttct 60 catgtggcac ctgactggca tcaaaccaaa gttcgtaggc caacaaagat gggccactca 120 caagctcccc atttgtagat ctcagtgcct atgagtatct gacacctgtt cctctcttca 180 gtctcttagg gaggcttaaa cctgtctcag gtgtgctaag agtgccagcc caaggkggtc 240 aaaagtccac aaaactgcag tctttgctgg gatagtaagc caagcagtgc ctggacagca 3〇〇gagttctttt cttgggcaac agataaccag acaggactct aatcgtgctc ttattcaaca 360 ttcttctgtc tctgcctaga ctggaataaa aagccaatct ctctcgtggc acagggaagg 420 agatacaagc tcgtttacat gtgatagatc taacaaaggc atctaccgaa gcctggtctg 480 gatagacggc acagggagcc cttaggccag cgctgctggt tggaggacat tcctgagtcc 540 agctttgcag cctttgtgca acagtacttt ccca 57 orders · &lt;210&gt; 357 &lt;211&gt; 393 &lt;212&gt; DNA &lt;213&gt; human &lt;400&gt;

ttttttcttt tttttcttct tttttttctt tacagaatat aratgcttta tcactgkact 6〇taatatggkg kcttgtccac catacttaaa aatgcaccac tcacaaatac ttaattcagc 120 aagccacaac caaracttga ttttatcaac aaaaacccct aaatataaac ggsaaaaaag 180 atagatataa ttatcccagt tttcttaaaa cttaaaarat attccattgc cgaattaara 240 araaracaag tgtcatatgg aaagaagggc attcaagcac actaaaraaa cctgaggkaa 300 gcataacctg tacaaaatca aactgccctc tttggcattt taacaeattt gcaacgkcct 360 tttttttctt tttccgtttt cttcttttt.c tac 393 &lt; 210 &gt; 358 &lt; 211 &gt; 630 &lt; 212 &gt; DMA al europium &lt; 400 &gt; 358 acagggcaaa caggaggacc cttgctctca cggagcttac actctagcag gaggacaata 60 ttaatgccca taggaaaacg atgagtctat gacaaaggaa gcagatagtg tcttacaaga 120 gcatagagta gggaagccaa tccagcacag ggaggtcaca gagacatccc taaggaagtg 180 gagtttaaac tgagagaagc aagtgcttaa actgaaggat gtgttgaaga agaagggaga 240 Gtagagacaat tcgggcagag ggaacctcat agaccctaag gtgggaaggc tcaaagaact 300 gaaagagagc cagaacagct ggagccgctc tccggtgtaa agaggagtca aagagataag 360 attaaagatg tgaagattaa gatcttggtg-gcattcaggg att Ggcactt ctacaagaaa 420 tcactgaagg gagtaatgtg acatcacttt tcacttcagg atggccactc taactccagg 480 gggtagactg gactaggtaa gactggaggc aggtagacct cttccaaggc ctgcgatagt 540

gaaagacaaa aacaagtggg gaaattcagg ggatagtgaa aatcagtagg actcaatgag 600 caagccagag gttcccccac aacaaccagt $ 30 &lt; 210 &gt; 359 &lt; 211 &gt; 620 &lt; 212 &gt; DNA &lt; 213 &gt; al europium &lt; 400 &gt; 359 acagcacccc aaaatataca tctagagact aarrgtaaat gctctatagt gaagaagtaa 60 caattaaaaa atgctactaa tatagaaaac ctataaccag aaaaataaac attcagggag 120 127691.doc -121 - 200815476 ctcaccagaa gaataaagtg ctctgccagt tattaaagga ttactgctgg tgaattaaat 180 atggcattcc ccaagggaaa tagagagatt cttctggatt atgttcaata tttatttcac 240 aggattaact gttttaggaa cagatataaa gcttcgccac ggaagagatg gacaaagcac 300 aaagacaaca tgatacctta ggaagcaaca ctaccctttc aggcataaaa tttggagaaa 360 tgcaacatta tgcttcatga ataatatgta gaaagaaggt ctgatgaaaa tgacatcctt 420 aatgtaagat aactttataa gaattctggg tcaaataaaa ttctttgaag aaaacatcca 480 Aatgtcattg acttatcaaa tactatcttg gcatataacc tatgaaggca aaactaaaca 540 aacaaaaagc tcacaccaaa caaaaccatc aacttatttt gtattctata acatacgaga 600 ctgtaaagat gtgacagtgt 620

&Lt; 210 &gt; 360 &lt; 211 &gt; 431 &lt; 212 &gt; DNA &lt; 213 &gt; buccal &lt; 40O &gt; 360 aaaaaaaaaa agccagaaca acatgtgata gataatatga ttggccgcac acttccagac 60 tgatgaacga tgaacgtgat ggactactgc atggagcaca tcttcagcaa gagggggaaa 120 tactcatcat ttttggccag cagttgtttg atcaccaaac atcacgccag aatactcagc 180 aaaccttctt agctcttgag aagtcaaagt Ccgggggaat ttattcctgg caatcttaat 240 tggactcctt atgtgagagc agcggctacc cagctggggt ggcggagcga acccgtcact 300 agtggacatg cagcggcaga gctcctggta accacctaga ggaatacaca ggcacatgtg 360

tgacgccaag cgtgacacct gtagcactca aacttgtctt gtttttgtct ttcggtgtgt 420 agatccctag c, a 431 &lt; 210 &gt; 361 c211 &gt; 351 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 361 acactgactt ccgatcaaaa gaatcatcat cctcacctcg acctctcagg gaattactga * 60 accttcccct cagaagatag ggcacagcca ttgccttggc ctcacttgaa gggtctgcat 120 . tcgggccctc tggtcccccg ccaagcctcc cagccactcg agggagaaat accgggaggt 180 ttgacttcct ccggggcttt cccgagggct tcaccgtgag ccctgcggcc ctcagggctg 240 caatcctgga ttcaacgtct gaaacctcgc tctctgcctg ctggacttct gaggccgtca 300 ctgccaccct gccccccagc cctgacagcc cctcatctgt ggtcctgctg t 351 &lt; 210 &gt; 362 &lt; 211 &gt; 463 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 362 acttcatcag gccacaatgg gtgcctcccg tgagaatcca agcacctttg gactgcgcga 60 cgtagatgag ccggccgaag atcttgcgca tgcgcggctt cagggcgaag ttcttggcgc 120 ccccggtcac agaaatgacc aggttgggtg tttccaggtg ccagtgctgg gtcagcagcc 180 cgcaaaggat ttccgcgtcc gtgtcgcagg acagacgtat atacttccct tccttcccca 240 gtgtctcaaa ctgaacatcc ccaaaggcgt cggtaggaaa ttccttg. gtg tgtttcttgt 300 agttccactt ctcactttgg ttgatctggg tgccttccat gtgctggctc cgggcatagc 3 &lt; 5〇cacacttgca cacattctcc ctgataagca cgatggtgtg gacaggaagg aaggatttca 420 ttgagcccgc ctacggaaac tggtattgtt agcttaaata gac 463 &lt; 210 &gt; 363 &lt; 211 &gt; 653 122- 127691.doc 200815476 &lt; 212 &gt; DNA &lt; 213 &gt;人铕&lt;220&gt;&lt;221&gt; mi sc一特欲&lt;222&gt; (1)...(653} * &lt;223&gt; n *= A,T,C or G &lt;400&gt; 363 acccccgagt ncctgnctgg catactgnga acgaccaacg acacacccaa gctcggcctc 60 ctcttggnga ttctgggtga catcttcatg aatggcaacc gtgccagwga ggctgtcctc 120 tgggaggcac tacgcaagat gg ^ actgcgt cctggggtga gacatcctct ccttggagat 180 ctaacgaaac ttctcaccta tgagttgtaa agcagaaata cctgnactac agacgagtgc 24Q ^ ccaacagcaa ccccccggaa gtatgagttc ccctrgggcc tccgttccta ccatgagasc 300 tagcaagatg naagtgttga gantcattgc agaggttcag aaaagagacc cntcgtgact 3 $ 0 ggtctgcaca gttcatggag gctgcagatg aggccttgga tgccctggat gctgccgcag 420 Ctgaggccga agcccgggct gaagcaagaa cccgcatggg aactggagat gaggctgtgt 480 ntgggccctg gagctgg Gat gacattgagc tcgagctgct gacctgggac gaggaaggag 540 attttggaga tccntggtcc agaattccac tcaccctctg ggccagatac caccagaatg 600 cccgctccag attccctcag acctttgccg gtcccatcat tggtcstggt ggt 653

&lt;210&gt; 364 &lt;211&gt; 401 &lt;212&gt; DNA &lt;213&gt; human none &lt;400&gt; 364 accagaggaa agacgttaaa ccactctact accacttgtg gaacccccaa agggtaaatg 60 acaaagccaa tgaatgactc taaasacaat atttacacnt aacggcttgt agacaataaa 120

aaaacaaggt ggatagaccc agaactgcaa cattccaaga aaaccacagc actcgacaga 18Q tgagaaagct caattataga tgcaaagtca caactaaact actacagcag taaagaaata 240 cattccacac ccttcatata aatccactac ctcggcttga ggcactccat aaaatgtatc 300 acgcgcatag taaatctcca tacccgctat ggcgccgcac cagaggactc ggactgcaac 360 aagcggatgc gcggaaaatg aaatcttctc caacagccca g 401 &lt; 210 &gt; 365 &lt; 211 &gt; 356 &lt; 212 &gt; DNA &lt;213&gt;Human&lt;400&gt; 365 ccagtgccat atttgggctt aaaattccaa gaagggcact tcaaatggcc ttgcatttgc 60 atgtttcagt gctagagcgt aggaatagac cccggcgccc actgcgagat gttcttcagc 120

U taccagagca tcaagtctcc gcagcaggtc attctcgggt aaagaaatga cttccacaaa 180 ctccccatcc cctggctttg gcttcggcct cgcgttctcg gcaccatccc cgttaatggt 240 gaccgtcacg atgcgtatag tacagctcga caagcctggg tccatacaga ccgctggaga 300 acatccggca atgtcccctc tgcagccagt ttcttcttcg agctcccgga oaqcao &lt; 210 &gt; 366 &lt; 211 &gt; 1851 * &lt; 212 &gt; DNA &lt; 213 &gt; who is eligible &lt;400&gt; 366 tcatcaccat tgccagcagc ggcaccgtta gtcaggcttt ccgggaatcc cacatgagca 60 123- 127691.doc 200815476

CJ cttccgtgtt cttcattctt cttcaatagc cataaatctt ctagctctgg ctggctgttt tcacttcctt taagcccttg tgactcttcc tctgatgtca gctttaagtc ttgttctgga ttgctgtttt cagaagagat ttttaacatc tgtttttctt tgtagtcaga aagtaactgg caaattacat gatgatgact agaaacagca tactctctgg ccgtctttcc agatcttgag aagatacatc aacattttgc tcaagtagag ggctgactat acttgctgat ccacaacata cagcaagtat gagagcagtt cttccatatc tatccagcgc atttaaattc gcttttttct tgattaaaaa tttcaccact tgctgttttt gctcatgtat accaagtagc agtggtgtga ggccatgctt gttttttgat tcgatatcag caccgcataa gagcagtgct ttggccatta atttatcttc attgtagaca gcatagtgta gagtggtatt tccatactca tctggaatat ttggatcagt acgcacattc atcttcctgg cattgtacgg cctttgtcag agctgtcctc gccatgttcc agcaacatta tttttgttgt caaggacatt aagttgacat cgtctgtcca gcacgagttt taccacttct. gaattcccat tggcagaggc cagatgtaga gcagtcctct tttgctcgtc cctcttgttc acatccgtgt ccctgagcat gacgatgaga tcctttctgg ggactttacc ccaccaggca gctctgtgga gcttgtccag atcttctcca acctgggatc catgaaggcg ctgtcatcgt agtctcccca agcgaccacg ttgctcttgc cgctcc tggacgtggt cctg cagcagggga agcagtggca gcaccacttg cacctcttgc tcccaagcgt cttcacagag gagtcgttgt ggtctccaga agtgcccacg ttgctcttgc cgctccccct gtccatccag ggaggaagaa atgcaggaaa tgaaagatgc atgcacgatg gtatactcct cagccatcaa acttctggac agcaggtcac ttccagcaag gtggagaaag ctgtccaccc acagaggatg agatccagaa accacaatat ccattcacaa acaaacactt ttcagccaga cacaggcact gaaatcatgt catctgcggc aacatggtgg aacccaccca atcacacatc aagagatgaa gacactgcag tatatctgca caacgtaata ctcttcatcc ataaeaaaat aatataattt tcctctggag ccatatggat gaactatgaa ggaagaaccc cccgaagaag ccagtcgcag agaagccaca ctgaagctct gtcctcagcc atcagcgcca cggacaggar tgtgcttctt ccccagtgat gcagcctcaa gttatcccga agctgccgca gcacacggtg gctcccgaga aacaccccag ctcttccggt ccaacac ^ gg caagtcaata aatgtgataa tcacataaac agaattaaaa gcaaagccac ataagcatct caacagacac agaaaaggca tctgacaaaa tccagcatcc ttgtatttat cgtcgcagtc ctcagaggaa atgcttctaa etcttcccca tttagtatta tgttggccgt gggcttgcca caggtggttc tc3tcacctt aaggtatgtc ccctctatgc ctgttttgct gagggtctca actctcgtgc c &lt; 210 &gt; 367 &lt; 211 & g t; 668 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 367 cttgagcctc caaataygga agactggccc ttacacasgt caatgttaaa aegaatgeat ctcagcattt tgaagataaa attrgtagat ctataccttg tttettgate cgatatcagc accrtataag ageagegett tggccattaa ettatettte actrtagaca gcrtagtgya gagtggcatt tccateictca tctggaatat ttggatcagt gccatgttcc agcaacatta acgcacattc atcttcctgg cattgtacgg cetgtcagta tcagacccaa aaacaaatta catatctcag gaattcaaaa taacattcca cagctttcac caaccagtta tatttaaagg agaaaaccca tttttatgcc atgtatcgaa atcaaaccca cctcatgctg atatagttgg ctactgcata cctttatcag agctgtcctc tttttgttgt: caaggacatt aagtcgacat cgtctgtcca gcaggagttt tactacttct gaattcccat tggcagaggc cagatgtaga gcagtcctat gagagtgaga agactettta ggaaatcgta gtgcaccagc tacaqcr ^ ta gcaatgattc atgtaactgc aaacactgaa tagcccgcta ttactccgcc ttcaaaaaaa aaaaaaaa &lt; 210 &gt; 368 '&lt; 211 &gt; 1512 &lt;212>DNA&lt;213&gt; Human 120 180 240 300 360 420 480 540 600 660 720 7B0 840 900 ^ 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1851 6 0 120 180 240 300 360 420 480 540 600 660 668 127691.doc 124- Ο 200815476 &lt; 400 &gt; 368 gggtcgccca gggggsgcgt gggctctcct cgggtgggtg tgggttttcc ctgggtgggg tgggctgggc trgaaccccc tgctggggtt ggcaggtttt ggctgggatt gacttttycc ttcaaacaga ttggaaaccc ggagttacct gctagttggt gaaactggtt ggtagacgcg acccgttggc tactactggc ttctcctggc tgttaaaagc agatggtggt tgaggctgat tccatgccgg ctgctccttc tgtgaagaag ccatttggtc ccaggagcaa gatgggcaag tggtgctgcc gttgcttccc ctgccgcagg gagagcggca agagcaacgt gggcacttct ggagaccacg acgactctgc tatgaagaca ctcaggagca agatgggcaa gtggtgccgc cactgcttcc cctgctgcag ggggagtggc aagagcaacg tgggcgcttc tggagaccac gacgaytctg ctatgaagac actcaggaac aagatgggca agtggtgctg ccactgcttc ccctgctgca gggggagcrg caagagcaag gtgggcgctt ggggagacta cgatgacagt gccttcatgg agcccaggta * ccacgtccgt ggagaagatc tggacaagct ccacagagct gcccggtggg gtaaagtccc cagaaaggat ctcatcgtca tgctcaggga cactgacgtg aacaagaagg acaagcaaaa gaggactgct Ctacatctgg cctctgccaa tgggaattca gaagtagtaa aactcstgct ggacagacga tgtcaactta atgtcct cga caacaaaaag aggacagctc tgayaaaggc cgtacaatgc caggaagatg aatgtgcgct aatgttgctg gaacatggca ccgatccaaa tattccagat gagtatggaa ataccactct rcaccaygct rtctayaatg aagataaatt aatggccaaa gcactgctct tatayggcgc tgatatcgaa tcaaaaaaca aggtatagac ctactaattt tatcttcaaa atactgaaat gcattcattt taacattgac gcgtgtaagg gccagtcttc cgtatttgga agctcaagca taacttgaat gaaaacattt tgaaacgacc ta * attatctm agactttatt ttaaatattg ttaccttcaa agaagcacta gagggtacag cttccttttt ttaaatgcac Ctctggtaaa cactttcgtt gaaaacaccg aatccgtaaa aggtaatact tactattttt Caatttttcc ctcctaggat tttcctcccc caatgaacgt aagacggcaa aatttgccct gaaataggtc ccacacgaaa accccaagaa aagtcaaaca tgtr.ccagtg aatagagatc ccgccccncc ggcaagcccc taaaaaacag taacagatac gaggtgatgc gcccgtcagt ggcaaggtcc aagacattcc tgatctcgtg cc

&lt;210&gt; 369 &lt;211&gt; 1853 &lt;212&gt; DNA &lt;213&gt; .乂 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1512

60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 102σ 1080 1140 1200 1260

gggtcgccca tgggctgggc ttcaaacaga atctgccggc tccatgccgg tggtgctgcc ggagaccacg cactgcttcc gacgaytctg ccctgctgca gccttcatgg gcctggtggg aacaagargg gaagtagtaa aggacagctc gaacatggca rtctayaatg tcaaaaaaca gtsgtgaaat ractgctctc gcaaeianrc C 369 gggggsgcgt trgaatcccc ttggaaaccc tactactggc ccgccccttc gccgcctccc acgactrccgc cctgctgcag ctatgaagac • gggggagcrg ak.cccaggta gtaaagtccc acaagcaaaa eactcscgct tgayaaaggc ctgatccaaa aagataaatt agcatggcct ctttaatyaa acacccgccg gatgcacctc gggctttcct tgctggggtt ggagttacct ttctcctggc cgcgaagaag ctgccgcagg tatgaagaca ggggagtggc actcaggaac caagagcaag ccacgtccrt cagaaaggat gaggactgct ggacagacga cgtacaatgc tattccagat aatggccaaa cacaccactg gaaaaaagcg tacgttgtgg ctcaagacct cgggtgggtg ggcaggtttt gctagttggt tgttaaaagc ccattcggcc gagagcggca ctcaggagca aagagcaacg aagatgggca gtgggcgctt ggagaagatc ctcatcgtca ctacatctgg tgtcaactta caggaagatg gagtatggaa gcactgctct ytacttggtr aatttaaaat atcagcaagt ggaaagacgg tgggttttcc ggccgggact gaaactggtt agacggcggc ccaggagcaa agagcaacgt agatgggcaa tgggcgcttc agtggtgctg ggggagacta tggacaagct tgctcaggga cctctgccaa atgtccttga aatgtgcgtt ataccactct tatayggtgc tacatgagca gcrctggata acagtcagcc ccagagagca ctgggtgggg gacttttytc ggtagacgcg tgaggttgat gatgggcaag gggcacttct gtggtgccgc tggagaccac ccactgcttc cgatgacagy ccacagagct cackgaygtg tgggaattca caacaaaaag aatgtcgctg rcaccaygct tgatatcgaa aaadcagcaa gatatggaag ycctacctga tgctgtttct -125 · 127691.doc 200815476 agtcatcatc atgtaatttg ccagctactt cctgactaca aagaaaaaca gatgttaaaa 1320 atctcttctg aaaacagcaa tccagaacaa gacttaaagc tgacatcaga ggaagagtca 1380 caaaggctta aaggaagtga aaacagccag ccagaggcat ggaaactttt aaatttaaac 1440 ttttggttta atgttctttt tttttgcctt aataatatta gatagtccca aatgaaatwa 1500 cctatgagac taggctttga gaatcaatag atcctttttt taagaatctt ttggctagga 1560 gcggtgtctc acgcctgtaa ttccagcacc ttgagaggct gaggtgggca gatcacgaga 1620 tcaggagatc gagaccatcc tggctaacac ggtgaaaccc catctctact aaaaatacaa 1680 aaacttagct gggtgtggcg gcgggtgcct gtagtcccag ctactcagga rgctgaggca 1740 ggagaat ggc atgaacccgg gaggtggagg ttgcagtgag ccgagatccg ccactacact 1800 ccagcctggg tgacagagca agaccccgtc tcaaaaaaaa aaaaaaaaaa aaa 1853 &lt; 210 &gt; 370 &lt; 211 &gt; 2184 &lt; 212 &gt; DNA &lt; 213 &gt; al betray Ο t &lt; 400 &gt; 370 ggcacgagaa ttaaaaccct cagcaaaaca ggcacagaag ggacatacct caaagtaata 60 aaaaccacct atgacaagcc cacagccaac ataatactaa atggggaaaa gttagaagca 120 tttcccctga gaactgcaac aataaataca aggatgctgg actttgtcaa atgcctcttc 180 tgcgcctgtt gagatgccta tgtgactttg cctr.taaccc cgt ^ tatgtg attatcacat 240 tcatt-gactt gcccgcgtta gaccggaaga gccggggtgt ttcccaggag ccaccgtgcg 300 ctgcggcagc ttcgggataa cccgaggctg caccactggg gaagaaacac aytcctgtcc 360 gcggcgctga tggccgagga cagagcttca gtgcggctcc tctgcgactg gcttcctcgg 420 ggagctcctc ccccacagtc catccatacg Gctccagagg aaaattatat tattttgtta 480 tggacgaaga gcaccacgct gtgcagatat actgcagtgt ccccatcccc tgatgcgtga 540 ttgggcaggc tccaccatgc tgccgcagat aacatgattc cagtacctgc gtctggctga 600 aaagtgtctg tttgtgaatg gatattgcgg tttctggatc tcatcctctg tgggtggaca 660 gctttctcca cc tcgctgga agtgaccr.gc tgtccagaag ctcgacggcc gaggagtata 720 ccatcgtgca tgcatctttc atcccctgca ccccttcctc cccggacgga cagggggagc 7Θ0 ggcaagagca acgcgggcac tcccggagac cacaacgact cctctgtgaa gacgcctggg 940 agcaagaggt gcaagtggtg ctgccaccgc ctcccctgct gcaggggagc ggcaagagca 900 acgcggccgc ttggggagac cacgacgaca gcgccttcat ggatcccagg taccacgtcc 960 acggagaaga tctggacaag ctccacagag ctgcctggtg gggtaaagtc cccagaaagg. 1020 atcccatcgc cacgcccagg gacacggatg tgaacaagag ggacaagcaa aagaggactg 1080 ctctacaccc ggcctccgcc aatgggaact cagaagtagt aaaacccgtg ctggacagac 1140 gatgtcaacc taatgtcctt gacaacaaaa agaggacagc tctgacaaag gccgtacaat 1200 gccaggaaga tgaacgcgcg ctaatgctgc tggaacatgg cactgatcca aatattccag 1260 atgagtacgg aaataccact ctacactatg ctgcctacaa tgaagataaa ct3atggcca 1320 aagcactgct cctacacggt gccgataccg aatcaaaaaa caagcatggc ctcacaccac 1380 tgctacccgg tatacatgag caaaaacagc aagcggtgaa actcttaacc aagaaaaaag 1440 cgaatttaaa tgcgctggat agatacggaa 'gaactgctct cacacttgct gtatgttgtg 1500 gatcagcaag tacagtca gc cccctactcg agcaaaatgt tgatgtatct tctcaagatc 1560 tggaaagacg gccagagagc atgctgttcc tagtcaccat catgtaatct gccagttacc 1620 ttctgactac adca. tcaagaacct tttggctagg agcggtgtct aaagaaaaac agatgttaaa aatctcttcc gaaaacagca atcca ^ 1680 agacttaaag ctgacaccag aggaagagtc acaaaggctt oadggaagcg aaaacagcca 1740 gccagaggca tggaaacttc taaacccaaa cctctggttt aatgttttct ttttttgcct 1800 taataatact agacagtccc aaatgaaatw acccatgaga ctaggctttg agaatcaata 1860 gatcctctct cacgcctgta attccagcac 1920 cttgagaggc tgaggtgggc ^ agatcacgag accaggagat cgagaccatc ctggctaaca 1980 cggtgaaacc ccatctccac caaaaacaca aaaacttagc tgggtgtggt ggcgggtgcc 2040 tgtagcccca gctactcagg argctgaggc aggagaatgg cacgaacccg ggaggtggag 2100 gctgcagtga gccgagaccc gccactacac tccagcctgg gtgacagagc aagactctgt 2160 ctcaaaaaaa aaaaaaaaaa aaaa 2184 127691.doc 126- 200815476 &lt; 210 &gt; 371 &lt; 211 &gt; 1655 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;

&lt;221&gt; misc^ 特敬 &lt;222&gt; (1)··· {1B55) &lt;223&gt; n = A, T, C or G

&Lt; 400 &gt; tgcacgcatc cacgcgcacg gccgcccccg cgtaacggct ttggctggca tcttggattg tcgcgttcct gctgggtgtt gggcgtgggc atccccctgc gtaacntgct ctggctgtta agaagccatt cagggggagc gacgcttggg cggcaaaagc gtaccacgtc ccccagaaag aaagaggact gctggacaga ggccgcacaa aaatattcca attaatggcc gatccactaa agggccagtc acccaaccat cagtccttct aaaaggtaac cgtaagacgg acatgtttca tacgaggtga 371 ggccagtgcc ttgcacgcgc cacaaccgtc tggccgccct tgtagccgcc acgcctcctc ttgctggacc ttctccgggg tttccccggg tggggtcggc agctggcgaa aaagcagacg tggtcccagg ggcaagagca agcaagaggc aacgcggkcg crcgqagaag gatcccatcg gctctacatc cgacgtcaac tgccaggaag gacgagtacg aaagcaccgc tttcacctcc ctccgcaccc ctaagacmt tcctcaaatg acttactatt caaaatctgc gcgaacagag tgcgcccgtc cgcgccacgt ggcagcggct agactggcct gtaacggctt tggctcggct cccggatkga tgacctttty gggktkgccc cgggcgtggg agggactgac accggttggt gcggctgagg agcaagatgg acgtgggcac gcaagtggtg cctggggaga atctggacaa ccacgcccag cggcccccgc ctaacgtcct atigaatgtigc gaaacaccac tcccacacgg aaaacaccga ggaagcccaa attc caaaca cacccctggc ccc caatccc cccgaaacag atcctgcccc agcggcaagg acaccgacgc tggctggott gtaacggctt gcacgtgcat ccgcatcytt cgtttccccc tctgccgggt ttcctggggt tcttcctggg ctttttcctc agacgcgatc ttgattcaBt gcaagtggtg tcctggagac ctgcccactg ctacgatgac gctccacaga ggacaccgay caatgggaat cgacaacaaa gttTaatgctg tccacaccat tgccgatatc aacgcactca gcataacttg ttgtcacttt aaatactttt tcccccctag gccccacatg cctggcaagc tttaagatac cccctgagat gtaacggctt gcaggcgcac gctgcacgcg tgctkggctk ttggackgac ttggcattcc gggcgtgggk gtggggtggg aaacagattg tgctggtact gccggctgct cgccactgcc cacaacgact cttcccccgc agcgccttca gctgcccggt gtgaacaaga tcagaagcag aagaggacag ccggaacatg gctgcctaca gaatcaaaaa ttttaacatt aatgaaaata caaagaagca gtcgaaaaca gatttccctc aaaactccaa tcctaaaaaa ttctgatctc gtgcacgccg gcacgcgcac gccgcacgcg cgttaacggc ggcgtcgkty gtttcytyty tctggggtgg cgcccccagg ccgtgctggg gaaacccgga actgcttccc tcttictgtga tcccctgctg cccctgcgaa tgcBggggag tggakcccag ggggtaaagc rggacaagca caaaactcgc ctctgacaaa gcaccgatcc atgaagacaa acaaggtaca gacgtgtgta ttttgaaatg Tcagagggca ccgaatttgc ccctaatgaa gaaaagtcaa cagtaataga gtgcc 60 120 ISO 240, 3 00 360 420 480 54Q 600 660 720 78D 840 900 96 0 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1855

&Lt; 210 &gt; 372 &lt; 211 &gt; 1059 &lt; 212 &gt; DNA al chin &lt; 4 00 &gt; gcaacgtggg ggtgcaagtg gcgcctgrgg aagacctgga atcgtcatgc catccggccc 372 cacccctgga gtgccgccca agactmcgat caagccccac ccagggacac ccgccaacgg gaccacaacg ctgcttcccc gacagygcct agagccgccc tgaygtgaac gaattcagaa acccctccgt tgccgcaggg tcatggagcc cggtggggta aagarggaca gt3gta3aac gaagacgctt gagcggcaag caggtaccac aagtccccag agcaaaagag tcstgctgga gggagcaaga agcaacgtgg gtccgtggag aaaggatctc gactgctcca cagacgatgc 60 120 180 240 300 360 127691.doc 127- 200815476 caacttaatg tccttgacaa caaaaagagg acagctctga yaaaggccgt acaatgccag 420 gaagatgaat gtgcgttaat gttgctggaa catggcactg atccaaatat tccagatgag 4Θ0 tatggaaata ccactctrca ctaygctrtc tayaatgaag ataaattaat ggccaaagca 540 ctgctcttat ayggtgctga tatcgaatca aaaaacaagg tacagatcta ctaattttat 600 cttcaaaata Ctgaaatgca tccactttaa cattgacgtg tgtaagggcc agtcttccgt 660 atttggaagc t.caagcataa cctgaatgaa aatattttga aatgacctaa ttatctaaga 720 ctttatttta aatattgtta ttttcaaaga agcatcagag ggtacagttt ttttc tttta 780 aatgcacctc tggtaaatac ttttgttgaa aacactgaat ttgtaaaagg taatacttac 840 tatttttcaa tttttccctc ctaggatttt tttcccctaa tgaatgtaag atggcaaaat 900 ttgccctgaa ataggtttta catgaaaact ccaagaaaag ttaaacatgt ttcagtgaat 960 agagatcctg ctcctttggc aagttcctaa aaaacagtaa tagatacgag gtgatgcgcc 1020 tgtcagtggc a.aggtttaag atatttccga tctcgtgcc 1059 &lt; 210 &gt; 373 &lt; 211 &gt; 1155 &lt; 212 &gt; DNA &lt;213&gt;People&lt;400&gt; 373 atggtggttg aggttgatcc catgccggct gcctcttctg tgaagaagcc acttggtccc 60 aggagcaaga tgggcaagcg gcgctgccgc tgctcccccc gccgcaggga gagcggcaag 120

agcaacgtgg gcacttccgg agaccacgac gactctgcta tgaagacact caggagcaag 1Θ0 atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240 ggcgcttctg gagaccacga cgactctgct atgaagacac tcaggaacaa gatgggcaag 300 tggtgctgcc actgcttccc ctgccgcagg gggagcggca agagcaaggc gggcgcttgg 360 ggagactacg atgacagtgc cttcatggag cccaggcacc acgtccgtgg agaagatctg 420 gacaagctcc acagagccgc ctggtggggt aaagccccca gaaagg; 3t: ct: catcgtcatg 480

ctcagggaca ctgacgcgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 54C tctgccaatg ggaattcaga agtagcaaaa cccctgctgg acagacgatg tcaactcaar. 600 gcccctgaca acaaaaagag gacagccctg ataaaggccg tacaatgcca ggaagatgaa 660 cgtgcgttaa tgttgctgga acatggcacc gaticcaaaiia tcccagatga gtatggaaat 720 accactctgc actacgctat ctacaatgaa gacaaatcaa tggccaaagc accgctctca 780 cacggcgccg acatcgaatc aaaaaacaag cacggcccca caccactgtc acctggtgta 840 cacgagcaaa aacagcaagc cgcgaaaccc tcaaccaaga aaaadgcgaa ttcaaatgca 500 ctggacagat atggaaggac tgctctcata ctcgctgtat gccgtggatc agcaagtata 960 gccagccccc tacttgagca aaacatcgat gcatctcctc aagatctatc tggacagacg 1020 gccagagagt acgctgtctc tagccatcac catgcaatcc gccagtcact ttctgactac 1080 aaagaaaaac agatgctaaa aatctcttct gaaaacagca acccagaaaa tgcctcaaga 1140 accagaaata aataa 1155 &lt; 210 &gt; 374 &lt; 211 &gt; 2000 &lt; 212 &gt; DNA al chin &lt;400&gt; 374 - acggcggccg aggtcgactc catgccggct gcctcttctg tgaagaagcc atttggtctc 60 aggagcaaga tgggcaagtg gtgctgccgt tgcctcccct gctgcaggga gagc ggcaag 120 agcaacgtgg gcacctctgg agaccacgac gactctgcta tgaagacacc caggagcaag 180 atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240 ggcgcccccg gagaccacga cgaccctgct atgaagacac tcaggaacaa gatgggcaag 300 tggcgccgcc actgctcccc ctgccgcagg gggagcggca agagcaaggc gggcgcttgg 360 ggagactacg atgacagtgc cttcatggag cccay ^ t: cx〇〇a〇0tr: cotaq agaagatctg 420 gacaagctcc acagagctgc ccggtggggc Aaagtcccca gaaaggatcc catcgtcatg *.〇〇ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 540 128- 127691.doc 200815476

tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa tgtgcgttaa tgttgctgga acatggcact gatccaaata ttccagatga gtatggaaat accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgca catgagcaaa aacagcaagt cgtgaaattt ttaatcaaga aaaaagcgaa tttaaatgca ctggatagat atggaaggac cgctctcata cttgctgtat gttgtggatc agcaagtata gtcagccttc tacttgagca aaatattgat gtatcttctc aagatctatc tggacagacg gccagagagc acgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac aaagaaaaac agatgctaaa aatctcttct gaaaacagca atccagaaca agacttaaag ctgacatcag aggaagagtc acaaaggttc aaaggcagtg aaaatagcca gccagagaaa atgtctcaag aaccagaaat aaataaggat ggtgatagag aggttgaaga agaaatgaag aagcatgaaa gtaataatgt 9ggat: tact: a gaaaacct_ga ctaatggtgt cactgctggc aatggtgata atggattaat tcctcaaagg aagagcagaa cacctgaaaa tcagcaattt cctgacaacg aaagtgaaga gtatcacaga atttgcgaat tagtctctga ctacaaagaa aaacaga cgc caaaatactc ttctgaaaac agcaacccag aacaagactt aaagctgaca tcagaggaag agtcacaaag gcttgagggc agtgaaaatg gccagccaga gctagaaaat Cttatggcta tcgaagaaat gaagaagcac ggaagtactc atgtcggatt cccagaaaac ccgactaatg gtgccactgc tggcaatggt gatgatggac caatccctcc aaggaagagc agaacacccg aaagccagca atttcctgac actgagaatg aagagtacca cagcgacgaa caaaatgatia ctcagaagca attttgtgaa gaacagaaca ctggaatatt acacgatgag attctgatcc acgaagaaaa gcagatagaa gtggttgaaa aaatgaattc tgagctttct ctcagttgca agaaagaaaa agacatcttg catgaaaata acacgctgcg ggaagaaatt gccatgccaa gactggagct agacacaacg aaacatcaga gccagccaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa - &lt; 210 &gt; 375 a &lt; 211 &gt; 2040 &lt; 212 &gt; DNA &lt; 213 &gt; al chin &lt; 400 &gt; 375 atggtggttg aggttgattc catgccggct gcctctcctg tgaagaagcc atttggtctc aggagcaaga tgggcaagcg gtgctgccgt tgcttccccc gctgcaggga gagcggcaag agcaacgcgg gcacttctgg agaccacgac gactctgcta Tgaagacact caggagcaag acgggcaagc ggtgccgcca ctgcttcccc cgccgcaggg agagcggcaa gagcaacgtg ggcgcccctg gagaccacga cgactctgct atga agacac tcaggaacaa gatgggcaag cggcgccgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg ggagaccacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatctg gacaagcccc acagagctgc ctggcggggt aaagtcccca gaaaggatct catcgtcatg cccagggaca ctgacgcgaa caagaaggac aagcaaaaga ggactgctct acatctggcc tctgccaatg ggaacccaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat gcccccgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa cgtgcgtcaa tgctgccgga acatggcact gatccaaata ttccagatga gtatggaaat accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta tatggtgctg atatcgaacc aaaaaacaag cacggcccca caccactgtt acttggtgta catgagcaaa aacagcaagt cgtgaaattt ttaatcaaga aaaaaotoa ^ tt: t: a »ats〇〇ccggacagat atggaaggac tgctctcata cttgctguat gttgtggatc agcaagtata gccagccccc tactcgagca aaatattgat gtatcttctc aagatctatc tggacagacg gccagagagt atgccgtttc tagtcatcat catgtaattt gccagttact ttctgactac aaagaaaaac agatgctaaa aatctcttct gaaaacagca atccagaaca agacttaaag ctgacatcag aggaagagtc acaaaggttc aaa ggcagtg aaaatagcca gccagagaaa atgcctcaag aaccagaaat: aaataaggat ggtgatagag aggttgaaga agaaatgaag aagcacgaaa gcaataatgt gggattacta gaaaacctga ctaatggtgt cactgctggc aatggtgata atggattaat tcctcaaagg aagagcagaa cacctgaaaa tcagcaattt 600 660 720 780 840 900 960 1020 1080 '1140 1200 1260 1320 1380 1440 ** 1500 1560 1620 1680 1740 1800 1860 1920 I960 2000 60 120 180 240 300 360 420 480 540 600 660 720 780 840 ?〇〇960 1020 1080 1140 1200 1260 1320 1380 127691.doc 129- 200815476 Ο

cctgacaacg aaagtgaaga gtatcacaga atttgcgaat tagtttctga ctacaaagaa aaacagatgc caaaatactc ttctgaaaac agcaacccag aacaagactt aaagctgaca tcagaggaag agtcacaaag gcttgagggc agtgaaaatg gccagccaga gaaaagatct caagaaccag aaataaataa ggatggtgat agagagctag aaaattttat ggctatcgaa gaaatgaaga agcacggaag tactcatgtc ggattcccag aaaacctgac taatggtgcc actgctggca atggtgatga tggattaatt cctccaagga agagcagaac acctgaaagc cagcaatttc ctgacactga gaatgaagag tatcacagtg acgaaceaaa cgatactcag aagcaatttt gtgaagaaca gaacactgga atattacacg atgagattct gattcatgaa gaaaagcaga tagaagtggt tgaaaaaatg aattctgagc tttctcttag ttgtaagaaa gaaaaagaca tcttgcatga aaatagtacg ttgcgggaag aaattgccat gctaagactg gagctagaca caatgaaaca tcagagccag ctaaaaaaaa aaaaaaaaaa aaaaaaaaaa &lt; 210 &gt; 376 · &lt; 211 &gt; 329 &lt; 212 &gt; protein &lt; 213 &gt; human &lt; 400 &gt; 376 Met Asp lie Val Val Ser Gly Ser His Pro Leu Trp Val Asp Ser Phe 15 10 15 Leu His Leu Ala Gly Ser Asp Leu Leu Ser Arg Ser Leu Met Ala Glu 20 25 . 30 Glu Tyr Thr lie Val His Ala Ser Phe Lie ger Cys lie Ser Ser Ser 35 40 45 Leu Asp Gly Gin Gly Glu Arg Gin Glu GLrv Arg Gly His Phe Trp Arg 50 55 60 Pro Gin Arg Leu Leu Cys Glu Asp Ala Trp Glu Gin Glu Val Gin Val 65 70 75 80 Val Leu Pro Leu Leu Pro Leu Leu Gin Gly Ser Gly Lys Ser Asn Val 85 90 95 Val Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe Met Asp Pro Arg Tyr 100 105 110 His val His Gly Glu Asp Leu Asp Lys Leu His Arg Ala Ala Trp Trp 115 120 125 Gly Lys Val P.ro Arg Lys Asp Leu He Val Met Leu Arg Asp Thr Asp 130 135 140 Val Asn Lys Arg Asp Lys Gin Lys Arg Thr Ala Leu His Leu Ala Ser 145 150 155 160 Ala Asn Gly Asn Ser Glu Val Val Lys Leu Val Leu Asp Arg Arg Cys 165 170 175 Gin Leu Asn Val Leu Asp Asn Lys Lys Arg Thr Ala Leu Thr Lys Ala 1Θ0 185 190 Val Gin Cys Gin Glu Asp Glu Cys Ala Leu Met Leu Leu Glu His Gly 195 200 205 Thr Asp Pro Asn lie Pro Asp Glu Tyr Gly Asn Thr Jhr Leu His Tyr 210 215 220 Ala Val Tyr Asn Glu Asp Lys Leu Met Ala Lyc Λΐ〇Leu Leu Leu Tyr 225 230 235 240 Gly Ala Asp lie Glu Ser Lys Asn Lys His Gly Leu Thr Pro Leu Leu 245 250 255 Leu Gly lie His Glu Gin Lys Gin Gin Val Val Lys Phe Leu lie Lys 260 265 270 Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr Gly Arg Thr Ala Leu 275 280 285 lie Leu Ala Val Cys Cys Gly Ser Ala Ser lie Val Ser Pro Leu Leu 1440 1500 1560 1620 1660 1740 1800 1860 1920 1900 2040 127691.doc 130- 200815476 290 295 300 Glu Gin Asn Val Asp Val Ser Ser Gin Asp Leu Glu Arg Arg Pro Glu 305 310 315 320 Ser Met Leu Phe Leu Val lie lie Met 325

&lt;210&gt; 377 &lt;211&gt; 148 &lt;212&gt; Protein c213&gt; Human &lt;220&gt;&lt;221&gt; Variation &lt;222&gt; (1) (148) &lt;223&gt; Xaa *any amino acid &lt;400&gt;; 377 Met Thr Xaa Pro Ser Trp Ser Pro Gly Thr Thr Ser Val·Glu Lys lie 15 10 15 Trp Thr Ser Ser Thr Glu Leu Pro Trp Trp Gly Lys Val Pro Arg Lys 20 25 30 Asp Leu lie Val Met Leu Arg Asp Thr Asp Val Asn Lys. Xaa Asp Lys 35 40 * 45 Gin Lys Arg Thr Ala Leu His Leu Ala Ser Ala*Asn Gly Asn Ser Glu 50 55 60 Val Val Lys Leu Xaa Leu Asp Arg Arg Cys Gin Leu Asn Val Leu Asp 65 70 75 80 Asn Lys Lys Arg Thr Ala Leu Xaa Lys Ala Val Gin Cys Gin Glu Asp 85 90 95 Glu Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro Asn lie Pro 100 105 110 Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala Xaa Tyr Asn Glu Asp 115 120 125 Lys Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp lie Glu Ser 130 135 140 Lys Asn Lys Val 145 &lt;210&gt; 378 &lt;211&gt; 1719 &lt;212&gt; Protein &lt;;213&gt; 人颜· ϋ &lt;400&gt; 378 Met val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys 1 5 10 &quot; 15 Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe 20 25- 30 Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp 35 40 45 His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp 50 55 60 Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val 65 70 75 80 Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn 127691.doc -131 - 200815476 85 90 95

Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser 100 105 110

Gly Lys Ser Lys Val Gly Ala Trp Gly Asp Tyx Asp Asp Ser Ala Phe 115 120 125

Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His 130 135 140

Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu lie Val Met 145 150 155 160

Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gin Lys Arg Thr Ala 165 170 175

Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val Val Lys Leu Leu 180 185 190

Leu Asp Arg Arg Cys Gin Leu Asn Val Leu Asp Asn Lys Lys Arg Thr 195 200 205

Ala Leu lie Lys Ala Val Gin Cys Gin Glu Asp Glu Cys Ala Leu Met 210 215 220

Leu Leu Glu His Gly Thr Asp Pro Asn lie Pro Asp Glu Ίγτ Gly Asn 225 230 235 240

Thr Thr Leu His Tyr Ala lie Tyr Asn Glu Asp Lys Leu Met Ala Lys 245 250 255

Ala Leu Leu Leu Tyr Gly Ala Asp lie Glu Ser&quot;Lys Asn Lys His Gly 260 265· 270

Leu Thr Pro Leu Leu Leu Gly Val His Glu Gin Lys Gin Gin Val Val 275 280 .. 285

Lys. Phe Leu lie Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr 290 295 300

Gly Arg Thr Ala Leu lie Leu Ala Val Cys Cys Gly Ser Ala Ser lie 305 310 315 320

Val Ser Leu Leu Leu Glu Gin Asn lie Asp Val Ser Ser Gin Asp Leu 325 330 335

Ser Gly Gin Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val .340 345 350 lie Cys Gin Leu Leu Ser Asp Tyr Lys Glu Lys Gin Met Leu Lys lie 355 360 365

Ser Ser Glu Asn Ser Asn Pro Glu Asn Val Ser Arg Thr Arg Asn Lys 370 375 380

Pro Arg Thr His Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser 385 390 395 400

Ser Val Lys Lys Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys 405 410 415

Cys Arg Cys Phe Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly 420 425 430

Thr Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys 435 440 _ 445

Met Gly Lys Trp Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly 450 455 460

Lys Ser Asn Val Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys 465 470 475 480

Thr Leu Arg Asn -Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys 485 490 453

Cys Arg Gly Ser Gly Lys Ser Lys val Gly Ala Trp Gly Asp Tyr Asp 500 505 510

Asp Ser Ala Phe Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu 515 520 525 127691.doc -132- 200815476

Asp Lys Leu His Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp 530 535 540

Leu lie Val Met Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gin 545 550 555 560

Lys Arg Thr Ala Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val 565 570 575

Val Lys Leu Leu Leu Asp Arg Arg Cys Gin Leu Asn Val Leu Asp Asn 580 585 590

Lys Lys Arg Thr Ala Leu lie Lys Ala Val Gin Cys Gin Glu Asp Glu 595 600 605

Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro Asn lie Pro Asp 610 * 615 620

Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala He Tyr Asn Glu Asp Lys 625 630 635 640

Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp lie Glu Ser Lys. 645 650 655

Asn Lys His Gly Leu Thr Pro Leu Leu Leu Gly Val His Glu Gin Lys 660 665 670

Gin Gin Val Val Lys Phe Leu He Lys Lys Lys Ala Asn Leu Asn Ala Ο 675 680 685

Leu Asp Arg Tyr Gly Arg Thr Ala Leu lie Leu Ala Val Cys Cys Gly 690 695 .. 700

Ser Ala Ser lie Val Ser Leu Leu Leu Glu Gin Asn He Asp Val Ser 705 710 .. 715 720

Ser Gin Asp Leu Ser Gly Gin Thr Ala Arg Glu Tyr Ala Val Ser Ser 725 730 735

His His His His lie Cys Gin Leu Leu Ser Asp Tyr Lys Glu Lys Gin 740 745 750

Met Leu Lys lie Ser Ser Glu Asn Ser Asn Pro Glu Gin Asp Leu Lys 755 760 765

Leu Thr Ser Glu Glu Glu Ser Gin Arg Phe Lys Gly Ser Glu Asn Ser 770 775 780

Gin Pro Glu Lys Met Ser Gin Glu Pro Glu lie Asn Lys Asp Gly Asp 785 790 *795 800

Arg Glu Val Glu Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly 805 810 815

Leu Leu Glu Asn Leu Thr Asn Gly Val Ding hr Ala Gly Asn Gly Asp Asn 820 825 830

Gly Leu lie Pro Gin Arg Lys Ser Arg Thr Pro Glu Asn Gin Gin Phe 835 B40 845

Pro Asp Asn Glu Ser Glu Glu Tyr His Arg lie Cys Glu Leu Val Ser 850 855 860

Asp Tyr Lys Glu Lys Gin.Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn 865 870 875 .. ΘΘ0

Pro Glu Gin Asp Leu Lys Leu Thr Ser Glu Glu Glu Ser Gin Arg Leu 885 890 835

Glu Gly Ser Glu Asn Gly Gin Pro Glu Leu Glu Asn Phe Met Ala lie 900 905 910

Glu Glu Met Lys Lys His Gly Ser Thr His Val Gly Phe Pro Glu Asn 915 920 925

Leu Thr Asn Gly Ala Thr Ala Gly Asn. Gly Asp Asp Gly Leu lie Pro 930 935 940 .

Pro Arg Lys Ser Arg Thr Pro Glu Ser Gin Gin Phe Pro Asp Thr Glu 945 950 955 960

Asn Glu Glu Tyr His Ser Asp Glu Gin. Asn Asp Thr Gin Lys Gin Phe 127691.doc -133- 200815476 965 970 975

Cys Glu Glu Gin Asn Thr Gly lie Leu His Asp Glu He Leu He His 980 985 990

Glu Glu Lys Gin lie Glu Val Val Glu Lys Met Asn Ser Glu Leu Ser 995 1000 1005

Leu Ser Cys Lys Lys Glu Lys. Asp He Leu His Glu Asn Ser Thr Leu 1010 1015 1020

Arg Glu Glu He Ala Met Leu Arg Leu Glu Leu Asp Thr Met Lys His 1025 1030 1035 104

Gin Ser Gin Leu Pro Arg Thr His Met Val Val Glu Val Asp Ser Met • 1045 1050 1055

Pro Ala Ala Ser Ser Val Lys Lys Pro Phe Gly Leu Arg Ser Lys Met 1060 1065 1070

Gly Lys Trp Cys Cys Arg Cys Phe Pro Cys Cys Arg Glu Ser Gly Lys 1075 1080 1085

Ser Asn Val Gly Thr Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr 1090 1095 1100

Leu Arg Ser Lys Met Gly Lys Trp Cys Arg His Cys Phe Pro Cys Cys 1105 1110 1115 112

Arg Gly Ser Gly Lys Ser Asn Val Gly Ala Ser Gly Asp His Asp Asp

1125 1130 .. - 1135

Ser Ala Met Lys Thr Leu Arg Asn Lys Met Gly Lys Trp Cys Cys His 1140 1145 1150

Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Lys Val Gly Ala Trp 1155 1160-1165

Gly Asp Tyr Asp Asp Ser Ala Phe Met Glu Pro Arg Tyr His Val Arg 1170 1175 1180

Gly Glu Asp Leu Asp Lys Leu His Arg Ala Ala Trp Trp Gly Lys Val 118b 1190 1195 120

Pro Arg Lys Asp*Leu lie Val Met Leu Arg Asp Thr Asp Val Asn Lys 1205 1210 1215*

Lys Asp Lys Gin Lys Arg Thr Ala Leu His Leu Ala Ser Ala Asn Gly 1220 1225 1230

Asn Ser Glu Val Val Lys Leu Leu Leu Asp Arg Arg Cys Gin Leu Asn 1235 1240 1245

Val Leu Asp Asn Lys Lys Arg Thr Ala Leu lie Lys Ala Val Gin Cys 1250 1255 1260

Gin Glu Asp Glu Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro 1265 1270 1275 128

Asn lie Pro Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala He Tyr 1285 ' 1290 1295

Asn Glu Asp Lys Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp

1300 1305 1310

He Glu Ser Lys Asn Lys His Gly Leu Thr Pro Leu Leu Leu Gly Val 1315 1320 &quot; 1325

His Glu Gin Lys Gin Gin Val Val Lys Phe Leu lie Lys Lys Lys Ala 1330 1335 1J40 .

Asn Leu Asn Ala Leu Asp Arg Tyr Gly Arg Thr Ala Leu He Leu Ala 1345 ^ 1350 1355 136

Val Cys Cys Gly' Ser Ala Ser lie Val Ser Leu Leu Leu Glu Gin Asn 1365 1370 1375 lie Asp Val Ser Ser Gin Asp Leu Ser Gly Gin Thr Ala Arg Glu Tyr 1380 1385 1390

Ala Val Ser Ser His His His Val lie Cys Gin Leu Leu Ser Asp Tyr 1395 1400 1405 127691.doc -134- 200815476

Lys Glu Lys Gin Met Leu Lys lie Ser Ser Glu Asn Ser Asn Pro Glu 1410 1415 1420

Gin Asp Leu Lys Leu Thr Ser Glu Glu Glu Ser Gin Arg Phe Lys Gly 1425 1430 1435 144

Ser Glu Asn Ser Gin Pro Glu Lys Met Ser Gin Glu Pro Glu lie Asn 1445 1450 1455

Lys Asp Gly Asp Arg Glu Val Glu Glu Glu Met Lys Lys His Glu Ser 1460 1465 1470

Asn Asn Val Gly Leu Leu Glu Asn Leu Thr Asn Gly Val Thr Ala Gly 1475 1480 1485

Asn Gly Asp Asn .Gly Leu lie Pro Gin Arg Lys Ser Arg Thr Pro Glu 1490 1495 1500

Asn Gin Gin Phe Pro Asp Asn Glu Ser Glu Glu Tyr His Arg lie Cys 1505 1510 151S 152

Glu Leu Val Ser Asp Tyr Lys Glu Lys Gin Met Pro Lys Tyr Ser Ser 1525 1530 1535

Glu Asn Ser Asn Pro Glu Gin Asp Leu Lys Leu Thr Ser Glu Glu Glu 1540 1545 1550

Ser Gin Arg Leu Glu Gly Ser Glu Asn Gly Gin-Pro Glu Lys Arg Ser 1555 1560 1565

Gin Glu Pro Glu lie Asn Lys Asp Gly Asp Arg Glu Leu Glu Asn Phe 1570 1575 1580

Met Ala lie Glu Glu Met Lys Lys His Giy Ser Thr His Val Gly Phe 1585 1590 1595 160

Pro Glu Asn Leu Thr Asn Gly Ala Thr Ala Gly Asn Gly Asp Asp Gly 1605 1610 1615

Leu lie Pro Pro Arg Lys Ser Arg Thr Pro Glu Ser Gin Gin Phe Pra 1620 1625 1630

Asp Thr Glu 'Asn Glu Glu Tyr His Ser Asp Glu Gin Asn Asp Thr Gin 1635 1640 1645

Lys Gin Phe Cys Glu Glu Gin Asn Thr Gly lie Leu His Asp Glu lie 1650 1655 · 1660

Leu He His Glu Glu Lys Gin lie Glu Val Val Glu Lys Met Asn Ser 1665 1670 1675 16&amp;

Glu Leu Ser Lea SBr Cys Lys Lys Glu Lys Asp lie Leu His Glu Asn 1685 1690 1695

Ser Thr Leu Arg Glu Glu lie Ala Met Leu Arg Leu Glu Leu Asp Thr 1700 1705 1710

Met Lys His Gin Ser Gin Leu

&lt;210&gt; 379 • &lt;211&gt; 656 &lt;212&gt; Protein &lt;213&gt; People - &lt;400&gt; 379

Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys 15 10 15

Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe 20 ' 25 30

Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp 35 40 45

His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp 50 55 60 127691.doc 135- 200815476

Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val 65 70 75 80

Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn 85 90 95

Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser 100 105 110

Gly Lys Ser Lys Val Gly Ala Trp Gly Asp Tyx Asp Asp Ser Ala Phe 115 120 125

Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His 130 135 140

Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu He Val Met 145 150 155 160

Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gin Lys Arg Thr Ala 165 170 175

Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val Val Lys Leu Leu ... 180 105 190

Leu Asp Arg Arg Cys Gin Leu Asn Val Leu Asp Asn Lys Lys Arg Thr 195 200 205

Ala Leu He Lys Ala Val Gin Cys Gin Glu Asp Glu Cys Ala Leu Met 210 215 220

Leu Leu Glu His Gly Thr Asp Pro Asn lie Pro Asp Glu Tyr Gly Asn 225 230 235 240

Thr Thr Leu His Tyr Ala lie Tyr Asn Glu Asp. Lys Leu Met Ala Lys 245 250 255

Ala Leu Leu Leu Tyr Gly Ala Asp lie··Glu Ser Lys Asn Lys His Gly 260 265 270

Leu Thr Pro Leu Leu Leu Gly Val His Glu Gin Lys Gin Gin Val Val 275 280 285

Lys Phe Leu lie Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr 290 295 300

Gly Arg Thr Ala Leu lie Leu Ala Val Cys Cys Gly Ser Ala Ser lie 305 310 315 320

Val Ser Leu Leu Leu Glu Gin Asn lie Asp Val Ser Ser Gin Asp Leu 325 330 335

Ser Gly Gin Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val 340 345 350 lie Cys Gin Leu Leu Ser Asp Tyx Lys G'lu Lys Gin Met Leu Lys lie 355 360* 365

Ser Ser Glu Asn Ser Asn Pro Glu Gin Asp Leu Lys Leu Thr Ser Glu 370 375 380

Glu Glu Ser Gin Arg Phe Lys Gly Ser Glu Asn Ser Gin Pro Glu Lys 385 390 395 400

Met Ser Gin Glu Pro Glu lie' Asn Lys Asp Gly Asp Arg Glu Val Glu

405 410 41S

Glu Glu Met Lys Lys His Glu Ser Asn Asn val Gly Leu Leu Glu Asn 420 425 430

Leu Thr Asn Gly Val Thr Ala Gly Asn Gly Asp Asn Gly Leu lie *Pro 435 440 • One 445

Gin Arg Lys Ser Arg Thr Pro Glu Asn Gin Gin Phe Pro Asp Asn Glu 450 455 460

Ser Glu Glu Tyr His Arg lie Cys Glu Leu Val Ser Asp Tyr Lys Glu 465 470 475 480

Lys Gin Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn Pro Glu Gin Asp 485 490 495

Leu Lys Leu Thr Ser Glu Glu Glu Ser Gin Arg Leu Glu Gly Ser Glu 127691.doc 136- 500200815476

505 510 Phe Met Ala lie Glu Glu Met Lys • 525 Phe Pro Glu Asn Leu Thr Asn Gly 540 Gly Leu lie Pro Pro Arg Lys Ser 555 560 Pro Asp Thr Glu Asn Glu Glu Tyr 570 575 Gin Lys Gin Phe Cys' Glu Glu Gin 585 590 lie Leu lie His Glu Glu Lys Gin -, 605 Ser Glu Leu Ser Leu Ser Cys Lys 620 Asn Ser Thr Leu Arg Glu Glu lie 635 640 Thr Met Lys His Gin Ser Gin Leu 650 655

Asn Gly Gin Pro Glu Leu Glu Asn 515 520

Lys His Gly Ser Thr His Val Gly 530 535

Ala Thr Ala Gly Asn Gly Asp Asp 545 550

Axg Thr Pro Glu Ser Gin Gin Phe 565

His Ser Asp Glu.Gin Asn Asp Thr 580

Asn Thr Gly lie Leu His Asp Glu 595 600 lie Glu Val Val Glu Lys Met Asn 610 615

Lys Glu Lys Asp lie Leu His Glu 625 630

Ala Met Leu Arg Leu Glu Leu Asp 645 &lt;210&gt; 380 &lt;211&gt; 671 &lt;212&gt; Peptone Human &lt;400&gt; 380

Met Val Val Glu Val Asp Ser Met 1:5 Pro Phe Gly Leu Arg Ser Lys Met 20

Pro Cys Cys Arg Glu Ser Gly Lys 35 40

His Asp Asp Ser Ala Met Lys Thr 50 55

Cys Arg His Cys Phe Pro Cys Cys 65 70

Gly Ala Ser Gly Asp His Asp Asp 85

Lys Mec Gly Lys Trp Cys Cys His 100

Gly Lys Ser Lys Val Gly Ala Trp 115 120

Met Glu Pro Arg Tyr His Val Arg 130 135

Arg Ala Ala Trp Trp Gly Lys Val 145 150

Leu Arg Asp Thr Asp Val Asn Lys 165

Leu His Leu Ala Ser Ala Asn Gly 180

Leu Asp Arg Arg Cys Gin Leu Asn 195 200

Ala Leu lie Lys Ala Val Gin Cys 210 215

Leu Leu Glu His Gly Thr Asp Pro

Pro Ala Ala Ser Ser Val Lys Lys 10 15

Gly Lys Trp Cys Cys Arg Cys Phe 25 30

Ser Asn Val Gly Thr Ser Gly Asp 45

Leu Arg Ser Lys Mec Gly Lys Trp 60

Arg Gly Ser Gly Lys Ser Asn Val 75 80

Ser Ala Mec Lys Thr Leu Arg Asn 90 95

Cys Phe Pro Cys Cys Arg Gly Ser 105 110

Gly Asp Tyr Asp Asp Ser Ala Phe 125

Gly Glu Asp Leu Asp Lys Leu His Ί40

Pro Arg Lys Asp Leu He Val Met 155 160

Lys Asp Lys Gin Lys Arg Thr Ala — 170 175

Asn Ser Glu Val Val Lys Leu Leu 185 190

Val Leu Asp Asn Lys Lys Arg Thr 205

Gin Glu Asp Glu Cys Ala Leu Mec 220

Asn lie Pro Asp Glu Tyr Gly Asn 127691.doc -137- 200815476 225 230 235 240

Thr Thr Leu His Tyr Ala lie Tyr Asn Glu Asp Lys Leu Met Ala Lys 245 250 255

Ala Leu Leu Leu Tyr Gly Ala Asp lie Glu Ser Lys Asn Lys His Gly 260 265 270

Leu Thr Pro Leu Leu Leu Gly Val His Glu Gin Lys Gin Gin Val Val 275 280 285

Lys Phe Leu lie Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr 290 295 300

Gly Arg Thr Ala Leu He Leu Ala Val Cys Cys Gly Ser Ala Ser lie 305 ^ 310 315 320

Val Ser Leu Leu Leu Glu Gin Asn He Asp Val Ser Ser Gin Asp Leu 325 330 335

Ser Gly Gin Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val 340 345 350 lie Cys Gin Leu Leu Ser Asp Tyr Lys Glu Lys Gin Met Leu Lys lie 355 360 365

Ser Ser Glu Asn Ser Asn Pro Glu Gin Asp Leu Lys Leu Thr Ser Glu 370 375 380

Glu Glu Ser Gin Arg Phe Lys Gly Ser Glu Asn Ser Gin Pro Glu Lys 385 390 395 . 400

Met Ser Gin Glu Pro Glu lie Asn Lys Asp Gly Asp Arg Glu Val Glu 405 .- 410 415

Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly Leu Leu Glu Asn 420 425 430

Leu Thr Asn Gly Val Thr Ala Gly Asn Gly Asp Asn Gly Leu He Pro 435 440 445

Gin Arg Lys Ser Arg Thr Pro Glu Asn Gin Gin Phe Pro Asp Asn Glu 450 455 460

Ser Glu Glu Tyr His Arg lie Cys Glu Leu Val Ser Asp Tyr Lys Glu 465 470 475 460

Lys Gin Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn Pro Glu Gin Asp 485 490 495

Leu Lys Leu Thr Ser Glu Glu Glu Ser Gin 'Arg Leu Glu Gly Ser Glu 500 505 510

Asn Gly Gin Pro Glu Lys Arg Ser Gin Glu Pro Glu lie Asn Lys Asp 515 520 525

Gly Asp Arg Glu Leu Glu Asn Phe Mec Ala lie Glu Glu Met Lys Lys 530 535 540

His Gly Ser Thr His Val Gly Phe Pro Glu Asn Leu Thr Asn Gly Ala 545 550 555 560

Thr Ala Gly Asn Gly Asp Asp Gly Leu lie Pro Pro Arg Lys Ser Arg 565 570 575

U

Thr Pro Glu Ser Gin Gin Phe Pro Asp Thr Glu Asn Glu Glu Tyr His 580 585 590 ·

Ser Asp Glu Gin Asn Asp Thr Gin Lys Gin Phe Cys Glu Glu Gin Asn 595 600 605

Thr Gly lie Leu His Asp Glu He Leu lie wis oiu ciu Lvs Gin He 610 615 620

Glu Val Val Glu'Lys Met Asn Ser Glu Leu Ser Leu Ser Cys Lys Lys 625 630 635 640

Glu Lys Asp lie Leu His Glu Asn Ser Thr Leu Arg Glu Glu lie Ala 645 650 655

Met Leu Arg Leu Glu Leu Asp Thr Met Lys His Gin Ser Gin Leu 660 665 670 · 127691.doc -138- 200815476 &lt;210&gt; 381 &lt;211&gt; 251 &lt;212&gt; DNA &lt; 213 &gt; Human Face &lt; 400 &gt; 381 oooo 1 6 2 8 4 5 112 2 Λ ggagaagcgt ctgctggggc aggaaggggt ttccctgccc tctcacctgt ccctcaccaa ggtaacatgc ttcccctaag ggtatcccaa cccaggggcc tcaccatgac ctctgagggg ccaatatccc aggagaagca ttggggagtt gggggcaggt gaaggaccca ggactcacac atcctgggcc tccaaggcag aggagagggt cctcaagaag gtcaggagga aaatccgtaa caagcagtca g &lt; 210 &gt; 382 &lt; 211 &gt; 3279 &lt; 212 &gt; DNA &lt; 213 &gt; human oo &lt; 400 &gt; 382 cttcctgcag atgctggagg cactgggagg gagagccctg gggcctggag cagggcgcga gccacaggag a &amp; gaaggaca gactgcaggg gcggctccag ccccagtctc gaactgacca ggacatctag gcatcctgca ggaccttgcc gagccctgtc cacccctgcc agagatggag ctacccctag atcatggggc gcatcaccgg cccctacctc tgctggacac gacccgtgct tgtatgccaa ctctgaagac tgtttgtggg caaggtggac acacacagca ccagataagg cagggggaga cgtcagattt tcattatggt Tagattagag tttactaagt: gtagctgatc cccccacgct gtgtcagga a ggacatcctg cggcacctgg ggcgtgagga gacggcctca gacactgctt gggcccggct agggagggcg gccttgcccc tcccctccac tacccagccc tcagagagta gatggccccg ccttgtgcag ccctctgttg tgttcctgag ttgcctaggc ggtgattctg cctgagccat aagtggatca tagtaaattc ctgaagcttg tcccggcgtg tgttcctgaa ttctcgctca gtgcagagat actctctaca aggttgacgc ccgtgagcag aactgaaagc gatgatttcc ctgttacatc tgtggagaaa tttcagactg cagctgatag ggtgaggggc gtgatcgggc cagaaggtag gggagcagag ggagcgaggg cacagggaag ttcctctgag caggtgtcca gcagggttgt cgcccgggcc tccatcctcc tgcccacggc gccctgaaga gccctcatcc gagctggacc gactccctgc agccgggaat agtcattggg ggggtccact gtgccctgcc aggacaccat aagtccacct gaactcaccc gagtccaggg atgggtataa gcttcagtga gggaggggtg gatcaccgag tgtaaacata aaagaagggg tgactaatca tagcaggact gataggatac acagaggaaa gcaggaagcc aggaactagc acgggcagga tctggggcag gagcg &amp; gcaa ggagcagcac ggctgcatgg agagggcccc gagtcaggag gaggccgtcg ggggggagtg ctcacccagc atctggcctc cctccatggc ggtggcccct tgctgacctg ctgaagcccc ccatattctt tgctctcagt gccaatcttt cgtctgtaac cgaaaagcct cgca gccaac cacgttctgg ggccgaagct ccgctaggaa tttcgtcctc ggacacacac gggcccaccc gacaagctgg gcccacgccg aggatcctcc caggaggttc tacagaaata atactgaaac: acttgcagtc aaacctacca caggtggggg acagtggacc ggaggagggg acacccgctg ctgcccaggc ctggagtgag tcctgcaggg ctgtggatgg ctggcccccc acgacgagga ctccctcaca agcgggtcat tccccaacgc gcgatgcgcc tctgcaggga ccccccat'ag gcgggagtgg catctgcctg ctcactgtgt ggtgtgcttc gctgtgcaca ccctgagtgc catcacttgg cgagcctcct aaggaacggg

Cccttcggaa aaagacgtgg tggaagagtg agccacaacg tcctgggggc tatgttgttg gttcaggtcc aagagctatc cagcaaacaa acgaagactg ggctgaggac ccttcccctt caacatggaa tggggagcgt caggggaggg ctgggaggag. Ggatcagggg ccccacccgg cgctggacag tttgggacca tgacctgggg gtcccccggc tccgatcact cctggagagg tgcgggggca ctgtcctcct gccaagaccg gctctggaga cgcggctctg ctctcctcct aaggcatcac ccaaggcggc ccctgtccca cctttctgga gagtcctact cagacacagg cactggctgt gtgaccacgt gacagtgaca catgaggcac actgggaagc aaggagggac cccaaaccac atgctgtggt aacagatgea gcaacttggc cttgtggagt tggatggggg 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 126 0 1320 1380 14 4 0 1500 1560 1620 1680 1740 1B00 1860 1920 1980 2040 2100 2160 127691.doc -139- 200815476 gcatatccga cagttattct ctccaagtgg agacttacgg acagcatata Attctccctg 2220 caaggatgta tgataatatg tacaaagtaa ttccaactga ggaagctcac ctgatcctta 2280 gtgtccaggg tttttactgg gggtctgtag gacgagtatg gagtacttga ataattgacc 2340 tgaagtcctc agacctgagg ttccctagag ttcaaacaga tacagcatgg tccagagtcc 2400 cagatgtaca aaaacaggga ttcatcacaa atcccatctt tagcatgaag ggtctggcat 2460 ggcccaaggc cccaagtata tcaaggcact tgggcagaac atgccaagga atcaaatgtc 2520 atctcccagg agttattcaa gggtgagccc tttacttggg atgtacaggc tttgagcagc. 2580 gcagggctgc tgagtcaacc ttttattgta caggggatga gggaaaggga gaggatgagg 2640 aagcccccct ggggatttgg tttggtcttg tgatcaggtg gtctatgggg ctatccctac 2700 aaagaagaat ccagaaatag gggcacattg aggaatgata ctgagcccaa agagcattca 2760 atcattgttt tatttgcctt cttttcacac cattggtgag ggagggatta ccaccctggg 2820 gttatgaaga tggttgaaca ccccacacat agcaccggag atatgagatc aacagtttct 2S60 tagccataga gattcacagc ccagagcagg aggacgctgc acaccatgca ggatgacatg 2940 ggggatgcgc tcgggattgg tgtgaagaag caaggactgt tagaggcagg ctttatagta 3000 acaagacggt ggggcaaact ctgatttccg tgggggaatg tcacggtctt gctttactaa 3060 gttttgagac tggcaggtag tgaaactcat. taggctgaga accttgtgga atgcagctga 3120 cccagctgat agaggaagta gccaggcggg agcctttccc agtgggcgtg ggacatatcc 3180 ggcaagattt tgtggcactc ctggttacag atactggggc agcaaataaa actgaatctt 324 0 gtcttcagac cttaaaaaaa aaaaaaaaaa aaaagtttt 3279 Γ &lt;210&gt; 383 * &lt;211&gt; 155 &lt;212&gt;protein &lt;213&gt; Person 铕 .- &lt;400&gt; 383

Met Ala Gly Val Arg Asp Gin Gly G.ln Gly Ala Arg Trp Pro His Thr 5 10 15

Gly Lys Arg Gly Pro Leu Leu Gin Gly Leu Thr Trp Ala Thr Gly Gly 20 25 * 30

His Cys Phe Ser Ser Glu Glu Ser Gly Ala Val Asp Gly Ala Gly Gin 35 40 45

Lys Lys Asp Arg Ala Trp Leu Arg Cys Pro Glu Ala Val Ala Gly Phe 50 55 · 60

Pro Leu Gly Ser Asp Cys Arg Glu Gly Gly Arg Gin Gly Cys Gly Gly 65 70 75 80

Ser Asp Asp Glu Asp Asp Leu Gly Val Ala Pro Gly Leu Ala Pro Ala 85 90 95

Trp Ala Leu Thr Gin Pro Pro Ser Gin Ser Pro Gly Pro Gin Ser Leu 100 105 110

Pro Ser Thr Pro Ser Ser lie Trp Pro*Gin Trp Val lie Leu lie Thr 115 120 125

Glu Leu Thr lie Pro Ser Pro Ala His Gly Pro Pro Trp Leu Pro Asn 130 135 140

Ala Leu Glu Arg Gly His Leu Val Arg Glu 145 150 127691.doc -140- 200815476 &lt;210&gt; 384 &lt;211&gt; 557 &lt;212&gt; DNA &lt;213&gt; Personnel 60 120 180 240 300 360 42 0'. 480 540 557 &lt; 400 &gt; 384 ggatcctcta aaagatgtgt ggggaagggt tctgcctcct acttaacctt ctctgtagag tccccaagac ccttcttatt tcaattgtga aaaaaaaaaa gagcggccgc tctgtcttgg cccttttgca ggccaagcag gaaatggaaa agcagcattc acatcctaaa tatgtgaaca aaatgaatat aaaaaaa ctactactac actctctgtg ttgccaagtg gctggtttgc gtcttgcaat ccagggacct aggtgtcgta actgtttgtc catgcaaata taaattcgcg gtcccttcca ccataaccat aagaatgaaa cccatttgca tggaaacagt atggtgaaaa tttttttgta aattatgcga gccgcgtcga acgctgtggg gagcactact tgaatgattc Ggatccgtct tggcactgta cgtcttcctt tcttttttaa tttttttttc cgaagaagag tttccaacca ctaccatggt tacagctagg gtgcacatgc aggtgcttgc ctttattgcc actgtaaagt aaagtaaaaa

ί \ β

&Lt; 210 &gt; 385 &lt; 211 &gt; 337 &lt; 212 &gt; DNA &lt; 213 &gt; al chin ·· · &lt; 400 &gt; 385 ** ttcccaggtg acgtgcgagg gaagacacat ctactatcct tgatggggct gatcccttta 60 gtttctctag cagcagatgg gttaggagga agtgacccaa ytiggttgact cctatgtgca 120 tctcaaagcc atctgctgtc ttcgagtacg gacacatcau cactcctgca ttgctgatca 180 aaacgtggag gtgccttccc tcagctaaga agcccttagc aaaagctcga acagacctag 240 tatcagacag gtccagtttc cgcaccaaca cctgctggct ccctgtcgtg gtctggatct 300 ctttggccac caattccccc tcttccacat cccggca 337 &lt; 210 &gt; 386 * &lt; 211 &gt; 300 &lt; 212 &gt; DNA &lt; 213 &gt; al jie &lt; 400 &gt; 386 gggcccgcta ccggcccagg ccccgcctcg cgagccctcc tccccgggtg cccgcccgca 60 gcccgctcgg cccagagggt gggcgcgggg ctgcctctac cggctggcgg ctgtaaccca 120 gcgaccttgg cccgaaggct ctagcaagga cccaccgacc ccagccgcgg cggcggcggc 180 gcggacttcg cccggtgtgt ggggcggagc ggactgcgtg tccgcggacg ggcagcgaag 240 atgttagcct tcgctgccag gaccgcggac cgatcccagg gccgcggtgt aacctcagcc 300 &lt; 210 &gt; .387 &lt; 211 &gt; 537 &lt; 212 &gt; DNA * &lt;213&gt;人联一&lt;4 〇0 &gt; 387 gggccgagtc gggcacc'aag ggactctttg caggcttcct tcctcggatc atcaaggctg 60 cccccccctg tgccatcatg atcagcacct atgagttcgg caaaagcttc ttccagaggc 120 tgaaccagga ccggcttctg ggcggctgaa aggggcaagg aggcaaggac cccgcctctc 180 ccacggatgg ggagagggca ggaggagacc cagccaagtg ccttttcctc agcactgagg 240 gagggggctt gtttcccttc cctcccggcg acaagctcca gggcagggct gtccctccgg 300 127691.doc -141 - 200815476 Ο

gcggcccagc acttcctcag acacaactcc cttacccacc ccccaagttc aagaccaaat gtttgctgta gctgggcatg tctccaggaa ctgacccttg ttaattcctt aagtctaaag &lt; 210 &gt; 388 &lt; 211 &gt; 520 &lt; 212 &gt; DNA _ &lt; 213 &gt; Human · &lt; 400 &gt; 388 aggataattt ttaaaccaat caaatgaaaa tgaggttaaa ccagtttigca ttcccctaat gtttgaagac tgcctcttct acagcttctg ggaccccctc cccaacatgc cccagcccac ccaggaaact gctacttgtg gacctcacca acttccccca ccccagaaga ttagcatccc tcatactcaa ttgatggtta ttagacaatt atctttcctc ttctcattac cagtaaaggc atgaacttgt cttattttaa tggtgggtct &lt; 210 &gt; 3Θ9 &lt; 211 &gt; 365 &lt; 212 &gt; DNA &lt; 213 &gt; al. _ &lt; 4Q0 &gt; 3Θ9 cgttgcccca gtttgacaga aggaaaggcg gagttaaggc tggatttcag atctgcctgg aacgactttc caaacaatct Caccagcgcc aagcctatgg ccagctgtct ttgtgttccc cccaggaaac cttcagacta ccctcctctg tgagggtcag tggaagaacc tagactccca gggag &lt;210&gt; 390 &lt;211&gt; 221 &lt;212&gt; DNA &lt;213&gt;Human&lt;220&gt;&lt;221&gt;misc-devil&lt;222&gt; (1) .7.(221) &lt;223y n = or G &lt;400&gt; 390 tgcctctcca tcctggcccc gacttctctg tacacggntt ctcatgggtg tggaacatct gctctangag tctgancnga ntcgctgccc tcaaagtcta gagggagtgg aggagttaag &lt; 210 &gt; 391 &lt; 211 &gt; 325 &lt; 212 &gt; DNA &lt; 213> human ttcctgctgc tccagtcgtg gggatcatca 360 cttccagctg cccccttcgt gtctccctgt 420 ccaagaagcc ctcagcctgg tgtagtctcc 480 atgatgaact tcaaaaaaaa aaaaaaa 537 aaacaaacaa acaaaaaagg aaatgtcatg 60 gtggaaaaag taagaggact actcagcact 120 agaattgtgt tatttcactc gccaagtgaa 180 ccctaagcat ggccccttgc caccaggcaa 240 gagaccagga gggtttggtt agctcacagg 300 atactagact catactcaac tcaactaggc 360 ccatttcttt ctggttatta taaacagaaa 420 tcttggtatc tttctgctgg aacgatttct 480 tttttctggt 520 gagctractc aaagcccaga gggagtggag 60 ctccagccgc agtgtgccct ccgctccccc 120 ctccagctca ggcgccccag aagcgtctcg 180 tctcacccgc ccgtcctcac agctgagact 240 ccttcagcaa ggggcgttgc ccacatcccc 300 ttgctagagg Tagaaagggg aagggtgctg 360 365 tcaggaaagt ggggacggac cccatccgca 60 ctgcttgcgg tttcaggaag gcctctggct 120 cantntgaca naaggaaagg cggagcccat 180 gctggatttc a 221 127691.doc •142- 200815476 &lt;220&gt;&lt;221&gt; misc" Features &lt;222&gt; (1) .7. (325)

gccagtaccc tgtcccgacg 391 tggagcaggt cccgaggcct ccctagagcc tggggccgac tctgtgncga tgcangcttt 60 ctctcgcgcc cagcctggag ctgctcctgg catctaccaa caatcagncg aggcgagcag 120 tagccagggc actgctgcca acagccagtc cnnataccat catgtnaccc ggtgngctct 180 naanttngat ntccanagcc ctacccatcn tagttctgct ctcccaccgg ntaccagccc 240 cactgcccag gaatcctaca; &lt; 223 &gt; n »A, T, C or G &lt; 400 & gt Tctctaccta ccagtacgat 300 ★ gagacctccg gctactacta tgacc 325

&lt;210&gt; 392 &lt;211&gt; 277 &lt;212&gt; DMA &lt;213&gt; children. C:

&lt;220&gt; · * &lt;221&gt; misc_ special education &lt;222&gt; (1) .7. (277)

&Lt; 223 &gt; n = A, T, C or · G &lt; 400 &gt; 392 acatt'gtcca actccttcct ttatatcttt taacatctcc atggngaaag gttcacatct 60 agccccacct nggcnagngn ctcctacttg agtctcttcc ccggcctgnn ccagtngnaa 120 antaccanga accgncatgn cttaanaacn ncctggtttn tgggttnntc aatgactgca 180 ngcagtgcac caccctgtcc actacgtgat gctgtaggac taaagtctca cagtgggcgg 240 ccgaggatac agcgccgcgt cctgtgttgc tggggaa 277 &lt; 210 &gt; 393 &lt; 211 &gt; 566 &lt; 212 &gt; DNA &lt; 213 &gt; al camphene &lt; 400 &gt; 393 actagtccag tgtggtggaa ttcgcggccg cgtcgacgga caggccagct gtctggctca 60 gcgatctaca ttctgaagtt gtctgaaaat gtcttcatga ttaaattcag cctaaacgtt 120 tcgccgggaa cactgcagag acaatgctgt gagtttccaa ccttagccca. tctgcgggca 180 gagaaggtct agtttgtcca tcagcattat catgatatca ggactggtta cctggttaag 240 gaggggccta ggagatctgt cccttttaga gacaccttac ttataatgaa gtatctggga 300 999tggtt: ct caaaagtaga aatgtcctgt attccgatga tcatcctgta aacattttat 360 cacttattaa tcatccctgc ctgtgtctat tattatattc atatctctac gctggaaact 420 ccctgcccca atgtctactg tgcctttgtt tttgctagtt tgcgttgttg Aaaaaaaaaa 480 cactccctgc ctgagtttta atttttgtcc aaagttattt taatctatac aattaaaagc 540 tcctgcctat caaaaaaaaa aaaaaa 566 &lt;210&gt; 3S4 &lt;211&gt; 384 &lt;212&gt; DNA &lt;213 &gt; Person 143 _ 127691.doc &lt;220&gt; 200815476 &lt;222&gt; 1)...(384)

aggacgatgg gaaccagccc 394 gaacatacat gtcccggcac ctgagctgca gtctgacatc atcgccatca cgggcctcgc 60 tgcaaattng gaccgggcca aggctggact gctggagcgt gtgaaggagc tacaggccna 120 gcaggaggac cgggctttaa ggagttttaa gctgagtgtc actgtagacc ccaaatacca 180 tcccaagatt atcgggagaa agggggcagt aattacccaa atccggttgg agcatgacgt 240 gaacatccag tttcctgata; &lt; 223 &gt; η «A # T, C or G &lt; 400 & gt caggaccaaa ttaccatcac 300 agggtacgaa aagaacacag aagctgccag ggatgctata ctgagaatcg tgggtgaact 360 tgagcagatg gtttctgagg acgt 384 &lt; 210 &gt; 395 &lt; 211 &gt; 399 &lt; 212 &gt; DMA &lt; 213 &gt; al Yan &lt; 400 &gt; 395 ggcaaaactg tgtgacctca ataagacctc gcagatccaa ggtcaagtat cagaagtgac 60 tctgaccttg gactccaaga Cctacaccaa cagcctggct atattiagatg atgagccagt 120

tatcagaggt ttcatcattg cggaaattgt ggagtctaag gaaatcatgg cctctgaagt 180 actcacgtct ttccagtacc ctgagctctc tatagagttg cctaacacag gcagaattgg 240 ccagctactt gtctgcaatt gtatcttcaa gaacaccctg gccatccctt tgactgacgt 300 caagctctct ttggaaagcc tgggcatctc ctcactacag acctccgacc acgggacggt 360 gcagcctggt gagaccaccc aatcccaaat aaaatgcac 399 &lt; 210 &gt; 396 &lt; 211 &gt; 403 &lt; 212 &gt; DNA &lt;213&gt;Rental&lt;220&gt;&lt;221&gt;misc-feature&lt;222&gt; (1) II. (403&gt;

&Lt; 223 &gt; n = A, T, C or G &lt; 400 &gt; 396 tggagttntc agtgcaaaca agccataaag cttcagtagc aaattaccgt ctcacagaaa 60 gacatctcca acccctgctc cagctgctga taaaacaaat catgtgtcta gcctgactcc 120 agacaaggac aacctgttcc ttcataactc tctagagaaa aaaaggagtc gttagcagat 180 actaaaaaaa gtggatgaat aatctggata tttttcctaa aaagattcct tgaaacacat 240 taggaaaatg gagggcctta tgatcagaat gctagaatta Gtccattgtg ctgaagcagg 300 gtttagggga gggagcgagg gataaaagaa ggaaaaaaag aagagtgaga aaacctattc 360 atcaaagcag gtgctaccac tcaatgttag gccctgctct ttt 403 &lt;210&gt; 397 &lt;211&gt; 100 ^ &lt;212&gt; DNA - &lt;213&gt;•&lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1)...(100)

&lt;223&gt; n = A, T, C or G 144- 127691.doc 200815476 &lt;400&gt; 397 actagtncag tgtggtggaa ttcgcggccg cgtcgaccta naanccacct ctatagcaaa 60 tccatccccg ctcctggttg gtnacagaat gactgacaaa 100 &lt;210&gt; 398 &lt;211&gt; 278 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;&lt;221&gt; misc one: feature &lt;222&gt; (1) ... (27Θ)

&lt;223&gt; n « A,T,C &lt;400&gt; 398 Ο

gcggccgcgt cgacagcagt tccgccagcg ctcgcccctg ggtggggatg tgctgcacgc 60 ccacctggac atctggaagt cagcggcctg gatgaaagag cggacttcac ccggggcgat 120 tcactactgt gcctcgacca gtgaggagag ctggaccgac agcgaggtgg actcatcatg 180 ctccgggcag cccatccacc tgtggcagtt cctcaaggag ttgctactca agccccacag 240 ctatggccgc ttcattangt ggctcaacaa ggagaagg · · 278 &lt; 210 &gt; 399 &lt; 211 &gt; 298 a &lt; 212 &gt; DNA &lt;213> Human &lt;220&gt;&lt;221&gt; misc_ Feature &lt;222&gt; (1) (29Θ) &lt;223&gt; n = A, T, C or G · &lt;400&gt; 399 acggaggcgg aggaagcgnc cccgggatcg anaggatggg tcctgncatt gaccncctcn 60 9999tgccng catggagcgc atgggcgcgg gcctgggcca cggcatggat cgcgcgggcc 120 ccgagatcga gcgcatgggc ctggtcatgg accgcatggg ctccgtggag cgcacgggcc 180 ccggcattga gcgcatgggc ccgctgggcc tcgaccacat ggcctccanc attgancgca 240 tgggccagac catggagcgc attggctctg gcgtggagcn catgggtgcc ggcacggg 298 &lt; 210 &gt; 400 &lt; 211 &gt; 548.

&Lt; 212 &gt; DNA &lt; 213 &gt; human ^ &lt; 400 &gt; 400 acatcsacta cttcctcact ttaaggtatg gcagttccct tcotcccctc ttcctgcctt 60 gtacatgtac atgtatgaaa cttccttccc ttaccgaact ctctccacac atcacaaggt 120 caaagaacca cacgcttaga agggtaagag ggcaccctat gaaatgaaat ggtgatttct 180 tgagtctctt ttttccacgt &quot; ctaaggggcc arggcaggac ttagagttgc gagttaagac 240 tgcagagggc tagagaatta tttcatacag gctttgaggc cacccatgtc acttatcccg 300 tataccctct caccatcccc ttgtctactc tgatgccccc aagatgcaac tgggcagcta 360 gttggcccca taattctggg cctttgttgt ttgttttaat tacttgggca tcccaggaag 420 ctttccagtg atctcctacc atgggccccc ctcctgggat caagcccctc ccaggccctg 4Θ0 tccccagccc ctcctgcccc agcccacccg cttgccttgg cgctcagccc tcccattggg 540 agcaggtt 548 145- 127691.doc 200815476

&lt;210&gt; 401 &lt;211&gt; 355 &lt;212&gt; DNA &lt;213&gt; 乂 class: ·,. &lt;220&gt;&lt;221&gt; misc one. Hold against &lt;222&gt; (1).7. ) &lt; 223 &gt; n dagger A, T, C or G &lt; 400 &gt; 401 actgtttcca tgttatgttt ctacacattg ctacctcagt gctcctggaa acttagcttt 60 tgatgtctcc aagtagtcca ccttcattta actctttgaa actgtatcat ctttgccaag 120 taagagtggt ggcctatttc agctgctttg acaaaatgac tggctcctga cttaacgttc 180 tataaatgaa tgtgctgaag caaagtgccc atggtggcgg cgaagaagan aaagatgtgt 240 tttgttttgg actctctgtg gtcccttcca Atgctgnggg tttccaacca ggggaagggt 300 cccttttgca ttgccaagtg ccataaccat gagcactact ctaccatggn tctgc 355 &lt;210&gt; 402 &lt;211&gt; 407 &lt;212&gt; DNA .. . &lt;213&gt;People&lt;220&gt;&lt;221&gt; misc_ Desirable &lt;222&gt; (1).7.(407) &lt;223&gt; n = A, T, C or G &lt;400&gt; 402 atggggcaag ccggataaag aaccaagacc cactggagta tgcCgtcttc aagaaaccca 60 ccccacatgc ggtggcatac ataggctcaa aataaaggaa tggagaaaaa tatttcaagc 120 aaacggaaaa cagaaaaaag caggtgttgc actcctactt tctgacaaaa cagactatgc 180 gaacaaagat aaaaa agaga aggacattac aaaggtggtc ctgacctttg ataaatctca 240 tcgcctgata ccaacctggg ctgttttaat tgcccaaacc aaaaggataa tttgctgagg 300 ttgtggagct tctcccctgc agagagtccc tgatctccca aaatttggtt gagatgtaag 360 gntgatctcg ctgacaactc cttttctgaa gtcttactca cttccaa 407 &lt; 210 &gt; 403 &lt; 211 &gt; 303 &lt; 212 &gt; DNA &lt; 213 &gt; human u &lt; 220 &gt;&lt;221>misc-extraorative&lt;222&gt; (1).7.(303) &lt;223&gt; n » A, T, C or G &lt;400&gt; 403 cagtatttat agccnaactg'aaaagctagt tcctaagcaa gagccatggc atggtgaaaa tagagaacaa gacctactca gtcatgaaca gggatcggat atcgtaatta tagagcagga tcttaacaac gaccgaaacc cattatttac gga agcaggcaag tctcaaatcc aggcaccaaa 60 tgcaaaagga gagtctggcc aatctacaaa 120 aaaaggcaga caccaacatg gatctcatgg 180 agatgacagt gatcgtcatt tggcacaaca 240 ataaacctcc attcggtaac catgttgaaa 300 303 127691.doc -146- 200815476 &lt; 210 &gt; 404 &lt; 211 &gt; 225 &lt; 212 &gt; DNA &lt;213 &gt; Human &lt;40O&gt; 404 aagtgtaact tttaaaaatt tagtggattt tgaaaattct tagaggaaag taaaggaaaa 60 attgttaatg cactcattta cctttacatg gtgaaa Gttc tctcttgatc ctacaaacag 120 acattttcca ctcgtgtttc catagttgtt aagtgtatca gatgtgttgg gcatgtgaat 180 ctccaagtgc ctgtgtaata aataaagtat ctttatttca ttcat 225 &lt;210&gt; 405 . &lt;211&gt; 334 &lt;212&gt; DNA · &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misC-: Special respect &lt;222&gt; (1)...(334)

&lt;223&gt; n = A, T, C or G

tctggaggac 〇0 tctccttact 120 ttctctaggc 180 ccgtgagtgt 240 cagcccatgt 300 334 &lt; 400 &gt;. 405 gagctgttat tccaatacac tcacccccar ttcccagtgc ctggcgcggt cactccccac actgtgagtt ctccccccat cccatgccaa ctccaggaca tgtgcctcca tctctcanng ctactaggaa agtgaatcag aggaagaccc gagtgggtta gcttctgctc tggatcccac atcatcaaat cctccagggg tccctccttg tgtcttcagc agtgcttcac ccct ctgagggttg gtccagtccc gctcacagcc cccatccttg ggacagtgtc &lt; 210 &gt; 406 &lt;211&gt; 216 &lt;212> DNA &lt;213&gt; Human &lt;220&gt;&lt;22 1 &gt; misc^ earning · &lt;222&gt; (1)...(216)

&Lt; 223 &gt; n = A, T, C or G &lt; 400 &gt; 4 06 ϋ tttcacacct aatgagggag ttganatnac atnnaaccag gaaatgcatg gatctcaang 60 gaaacaaaca cccaataaac tcggagtggc agactgacaa ccgtgagaca tgcacttgct 120 acnaaacaca aatttnatgt tgcacccttg tttccacacc tgtgggttat gacaaagaca 180 accgccaaag aatnttcaag aaggaggact gccant 216 &lt; 210 &gt; 407 &lt; 211 &gt; 413 &lt; 212 &gt; DNA • a &lt; 213 &gt; human * &lt; 400 &gt; 407 gctgacttgc tagtatcatc tgcattcatt gaagcacaag aacttcatgc cttgactcat 60 gtaaatgcaa taggattaaa aaataaattt gatatcacat ggaaacagac aaaaaatatt 120 gcacaacatt gcacccagtg tcagattcta cacctggcca ctcaggaagc aagagttaat 180 cccagaggtc tatgtcctaa tgtgrtatgg caaatggacg tcatgcacgt : accctcattt 240 -147- 127691.doc 200815476 atgggcaacc 300 tttcctgtca 360 aag 413 ggaaaattgt catttgtcca tgtgacagtt gatacttatt cacatttcat tgccagacag gagaaagtct tcccatgtta aaagacattt attatcttgt tgggagttcc agaaaaagtt aaaacagaca atgggccagg ttctgtagta &lt;210&gt; 408 &lt;211&gt; 183 &lt;212&gt; DNA &lt;213&gt;颉&lt;220&gt;&lt;221&gt; misc Feature &lt; 222 &gt; (1) ... (183)

&lt;223&gt; n = A,T,C &lt;400&gt; 408 ggagctngcc ctcaattcct ccatntctat gttancatat ttaatgtctt ttgnnattaa 60 tncttaacca gttaatcctt aaagggctan ntaatcctta actagtccct ccattgtgag 120 cattatcctt ccagtattcn ccttctnttt tatttactcc ttcctggcta cccatgtact 180 ntt 183

&lt;210&gt; 409 one &lt;211&gt; 250 -

&lt;212&gt; DNA &lt;213&gt; Human ··_ &lt;220&gt;&lt;221&gt; misc-feature &lt;222&gt; (1) (250)

&Lt; 223 &gt; nA, T, C or G &lt; 400 &gt; 409 cccacgcatg ataagctctt tatttctgta agtcctgcta ggaaatcatc aaatctgacg 60 gtggtttggg ggacctgaac aaaccccctg taattaatca gctctcagtt cctcccccta 120 gtccctcctt caacaacata ggaggaccct ccccttcttt ccgcccacgg ccttatctag 180 gcctcccagt gcccccagga cagcgtgggc tatgtttaca gcgcntcctt gctggggggg 240 ggccntatgc 250 &lt; 210 &gt; 410 &lt;211&gt; 306 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;-&lt;221&gt; misc_ feature &lt;222&gt; (1) (306)

&Lt; 223 &gt; n = A, T, C or G &lt; 400 &gt; 410 ~ tgaaatggaa 60 gagcagcatt 120 cacatcctaa 180 ttatgtgaac 24 0 aaaatgaata 300 306 · ggctggtttg caagaatgaa atgaatgatt ctacagctag gacttaacct agtcttgcaa tcccatttgc aggacccgtc tgtgcacatg cctctgtaga cccagggacc ttggaaacag ttggcactgt aaggtgcttg ctccccaaga aaggtgttgc aatggtgaaa accgcttcct Tctttattgc cccttctcat nactggttgg ctttctttgn atctttttta aactggaaag ttcaattgng tcntgc 148- 127691.doc 200815476 Ο u &lt;2Ι0&gt; 411 &lt;211&gt; 261 &lt;212&gt; DNA &lt;213 &gt;People&lt;220&gt;&lt;221&gt;misc_;222&gt; (1)...(261) &lt;223&gt; η *= A,T,C or G &lt;400&gt; 411 _agagatatcn cttaggtinaa agttcataga gttcccatga act this atgac cggccacaca 6〇&quot; ggatctcttg tatctaagga ttccgagatt ttgcttgagc aggattagat Aaggccgtcc 120 tttaaatgtc tgaaatggaa cagatttcaa aaaaaaaccc cacaatctag ggtgggaaca 18Q aggaaggaaa gangtigaatia ggctgatggg caaaaaacca atttacccat cagttccagc 240 cctctctcaa ggngaggcaa a 261 &lt;210&gt; 412 &lt;211&gt; 241 .. . &lt;212&gt; DNA &lt;213 &gt; Human... &lt;220&gt;&lt;221&gt; misc a special desire &lt;222&gt;. (1) .7. (241) &lt;223&gt; n = A, T, C or G &lt;400&gt; 412 gttcaatgct acctgacatt tctacaacac cccactcacc gatgtattcg ttgcccagtg 60 ggaacatacc agcctgaacc tggaaaaaat: aattgtgttt: cttgcccagg aaatactacg 120 actgaccctg atggctccac aaacataacc cagtgtaaaa acagaagacg tggaggggag 1B0 ctgggagatt tcactgggta cattgaactc ccaaactacc cangcaatta cccagccaac 240 a 241 &lt; 210 &gt; 413 &lt; 211 &gt; 231 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; "1) ·: · (231) · &lt;223&gt; n = A#T, C or G &lt;400&gt; 413 aactctcaca acccaagtga ctcatctgtg tgcttgaatc ctttccactg tctcatctcc 60 ctcatccaag Tttctagtac, cttctctttg ttgtgaagga taatcaaacc gaacaacaaa 120 aagtttactc tccccatttg gaacctaaaa acrctcttct tcctgggcct gagggctcca 180 agaatcctcg aatcanttct cagatcattg gggacaccan atcaggaacc t 231 &lt;210&gt; 414 &lt;211&gt; 234 &lt;212&gt; DNA &lt;213&gt; People 127691.doc 149-200815476 &lt;400&gt; 414 actgtccatg aagcactgag cagaag ctgg aggcacaacg caccagacac tcacagcaag 60 gatg ^ agctg aaaacataac ccactctgtc ctggaggcac tgggaagcct agagaaggct 120 gtgagccaag gagggagggt cttcctttgg catgggatgg ggatgaagta aggagaggga 180 ctggaccccc tggaagctga ttcactatgg ggggaggtgt attgaagtcc tcca 234 &lt; 210 &gt; 415 &lt; 211 &gt; 217 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt;220&gt;&lt;221&gt; misc_: feature ~ * &lt;222&gt; (1)...(217)

&Lt; 223 &gt; n »A, T, C or G &lt; 400 &gt; 415 Ο ϋ gcataggatt aagaccgagt atcttttcta cattctttta actttctaag gggcacttct 60 caaaacacag accaggtagc aaatctccac tgctctaagg ntctcaccac cactttctca 120 cacctagcaa tagtagaatt cagtcctact tctgaggcca gaagaatggt tcagaaaaat 180 antggattat aaaaaataac aattaagaaa aataatc '217 &lt; 210 &gt; 416 &lt;211&gt; 213 ·· &lt;212&gt; DNA &lt;213&gt;乂铕&lt;220&gt;.&lt; 2 21 &gt; mi sc-4 competing &lt;222&gt; (1) (213)

&Lt; 223 &gt; n =, or G &lt; 400 &gt; 416 atgcatatnt aaagganact gcctcgcttt tagaagacat ctggnctgct ctctgcatga 60 ggcacagcag taaagctctt tgattcccag aatcaagaac tctccccttc agactattac 120 cgaatgcaag gtggttaatc gaaggccact: aattgatgct caaatagaag gatattgact 180 atattggaac agatggagtc tctactacaa aag 213 &lt; 210 &gt; 417 &lt; 211 &gt; 303 &lt;2\2&gt;DNA·&lt;213&gt; Human* &lt;220&gt;&lt;221&gt; misc_: special respect &lt;222&gt; (1).7.(303)

&Lt; 223 &gt; n »A, T, C or G &lt; 400 &gt; 417 nagtcttcag gcccatcagg gaagttcaca ctggagagaa gtcatacata tgtactgtat 60 gtgggaaagg ctttactctg agttcaaatc ttcaagccca tcagagagtc cacactggag 120 agaagccata caaatgcaat gagtgtggga agagcttcag gagggattcc cattatcaag 180 ttcacctagt ggtccacaca ggagagaaac cctataaatg tgagatatgt gggaagggct 240 tcantcaaag ttcgtatctt caaatccatc ngaaggncca Cagtatanan aaacctttta 300 agt 303 150- 127691.doc 200815476 &lt;210&gt; 418 &lt;211&gt; 328 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;

&lt;221&gt; misc one: feature &lt;222&gt; (1).7.(328) &lt;223&gt; π » A, T, C or G &lt;400&gt; 418 * tttttggcgg tggtggggca gggacgggac angagtctca ctctgttgcc caggctggag 60 tgcacaggca tgatctcggc tcactacaac Cccccccctcc catgtccaag cgattcttgt 120 gccLcagcct tccctgtagc tagaattaca ggcacatgcc accacaccca gctagttttc 180 gtatttttag cagagacagg gtttcaccat gttggccagg ctggtctcaa actcctnacc 240 tcagnggtca ggctggtctc aaactcctga ccccaagtga cctgcccacc tcagcctccc 300 aaagtgctan gattacaggc cgtgagcc 328 Ο

&lt;21Q&gt; 419 '* * &lt;211&gt; 389 ..

&lt;212&gt; DNA &lt;213&gt; Human - &lt;220&gt;&lt;221&gt;misc-feature&lt;222&gt; (1) (389) &lt;223&gt; n « A#T#C ^ G &lt; 400 &gt; 419 cctcctcaag acggcctgtg gtccgcctcc cggcaaccaa gaagcctgca gtgccatatg 60 acccctgagc catggactgg agcctgaaag gcagcgtaca ccctgcccct gatcttgccg 120 cttigtctcct ctctgcggcc ccatitcatag cacagntgtt: gcactgaggc ttgtgcaggc 180 cgagcaaggc caagctggcc caaagagcaa ccagtc'aacc ccgccacggt gtgccaggca 24 0 ccggcccccc agccaccaac ctcacccgcc cccgcaaacg gcacatcagt tctcctaccc 300 caaaggtagg accaaagggc acctgctctt ctgaagcccc dtgctictatc agccatcacg 360 tggcagccac tcnggctgtg ccgacgcgg 389 &lt; 210 &gt; 420 &lt; 211 &gt; 408. &lt; 212 &gt; DNA &lt; 213> human &lt; 400 &gt; 420 gttcctccca tggccagggc gaagtgtact gtcccactga gccaactcac gatatagaaa acgctgaccg actcctgcca agcaagcctt agccaaggag, cacctttccc ccagctgggc attcttgaat gactttgatg gaaacagctc agccctggcc ttgaagtttg actgacccca atggagcagc gagtcctata Aagcgctatg tcctcaacat tcttgcttct tgactttggt taBaggaatc attacgaact aacatgaaca acaaacctgg ga Gagctgca gcttttcttc gtttcggcat ctcatggcca tggagagtat ggtttatatt caagcccg cccctcctcc 60 tggctagacc 120 ggagaccgaa 180 caaggatttg 240 ataagaaaga 300 cgaagcacag 360 127691.doc &lt;210&gt; 421 &lt;211&gt; 352 151 - 200815476 &lt;213&gt;Human &lt;220&gt;

&lt;221&gt; mi sc-feature&lt;222&gt; (1)...(352> &lt;223&gt; n » A, T\C or G &lt;400&gt; 421 gctcaaaaat gaggagaatg ttcactgaca ctccttcttg ggtgcaacat cactccgagt ctttttactg aggcctggcc gaacaggtct aagattcttt gaaatttctg ttattgggtg atnggcatgg tgggagccct tttttgggtc ggcagttgtc tttcgtagca tttgtttcct ctacacaatc gtgcctacta cttcttctcc tttgtcataa agtgcatgcc ttgagatcca attgactatt naagcacatt accacnatat cccacaggtg tcacaagttg tgcatttcct acggaggcca 60 agattatcca 120 acttgcagtc 180 tagaaacaag 240 gcangtctgc 300 &lt; 210 &gt; 422 &lt; 211 &gt; 337 &lt; 212 &gt; DNA &lt; 213 &gt; human

&Lt; 400 &gt;. 422 .. atgccaccac gctggcaatg cagcgggcgg tcgaaggcct gcacatccag cccaagctgg 60 cgatgatcga cggcaaccgt tgcccgaagt tgccgatgcc agccgaagcg gtggccaagg 120 gcgatagcaa ggtgccggcg atcgcggcgg cgtcaaccct ggccaaggtc agccgtgatc 180 gcgaaacggc agctgtcgaa ttgatctacc cgggttatgg catcggcggg cataagggct 240 atccgacacc ggtgcacctg gaagcctcgc agcggccggg gccgacgccg actcaccgac 300 gcttcttccg ccggtacggc tggcctacga aaattat 337

&lt;210&gt; 423 &lt;211&gt; 310 &lt;212&gt; DNA &lt;213&gt;human;&lt;220&gt;&lt;221&gt; misc_ feature &lt;222&gt; (1) (310) &lt;223&gt; n = A, T # C or G &lt; 400 &gt; 423 gctcaaaaat cctcctactg atatggcacg gctacacaat caccgactat tagaggccag 60 aggagaatga ggcctggcct gggagccctg tgcctactan aagcncatca gattatccat 120 tcactgacag aacaggtctt ttttgggtcc ttcttctcca ccacgatata cccgcagtcc 1Θ0 tcctcctcga agactctttg gcagttgtct ttgtcataac ccacaggtgt anaaacaagg 240 gtgcaacatg aaatttctgc tccgtagcaa gtgcatgtct cacagccgcc aagtccgccc 300 tccgagttta 310 &lt;210&gt; 424 &lt;211&gt; 370 &lt;212&gt; DNA &lt;213&gt; Personnel: &lt;220&gt;

&lt;221&gt; mi sc a special arrival &lt;222&gt; (1) (370) &lt;223) n * or G 152- 127691.doc 200815476 η ο &lt;400&gt; 424 gctcaaaaat ctttttactg ataggcatgg ctacacaatc attgactatt agaggccaga 60 ggagaatgag gcctggcctg ggagccctgt gcctactaga agcacattag attacccatt 120 cactgacaga acaggtctcc ttcgggtcct tcttctccac cacgatatac ttgcagtcct 180 ccttcttgaa gattctttgg cagttgtctt tgtcataacc cacaggtgta gaaacatcct 240 ggttgaatct cctggaactc cctcattagg tatgaaatag catgatgcat tgcataaagt 300 cacgaaggtg gcaaagatca caacgctgcc cagganaaca ttcattgtga taagcaggac 360 tccgtcgacg 370 &lt; 210 &gt; 425 &lt; 211 &gt; 216 &lt;212&gt; DNA · * &lt;213&gt; Human- &lt;220&gt;&lt;221&gt;misc-detail&lt;222&gt; (1).7.(216) &lt;223&gt; n = A, T, C or G &lt ; 4 00&gt; 4 2 5 aactgccatn ncccattttg ccactcaaaa taattaccaa aaaaaaaaaa tnttaaatga 60 taacaacnca acatcaaggn aaananaaca ggaatggptg accntgcata aatnggccga 120 anattaccca ctatnttaag ggttgacttc aggntacagc acacagacaa acatgcccag 180 gaggntntca ggaccgctcg atgtnttntg aggagg 216 &lt;210&g t; 42G · &lt; 211 &gt; 596 &lt; 2X2 &gt; DNA &lt; 213 &gt; human &lt; 4O0 &gt; 426 * cctccagcga ggataaccct gttgccccgg gccgaggttc tccattaggc tctgattgat 60 cggcagccag cgatggaagg gtgtcctgat caccccgact gccccaaggg tcgccggcca 120 gctctccgtc tcgctgagtc ggcagtagga cctaatccgt taattaagag tagatggtga 180 gccgcccccg tattttgatt aacctaatgg ccttcccagc acgacccgga ttcagctgga 240 gacaccacgg caacttttaa tgaaatgatt tgaagggcca ttaagaggca cctcccgcca 300 tcaggcagtc cacctgcact gataacttct tggcagctga gctggccgga gctgtggccc 360 aaacgcacac ccggccttcg gtcctgagat acaactctta atctcctagt catgcttgag 420 ggcggacggc cccttcagct ttaacccaat ctgcactgcc ttggaagcgt agccaggaga 480 acacacccat atactcgtgg gcttagaggc cacagcagat gtcattggtc tactgcctga 540 gtcccgccgg tcccatccca ggaccttcca tcggcgagta cctgggagcc cgtgct 596 &lt; 210 &gt; 427 - &lt;211&gt; 107 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt;misc-feature&lt;222&gt; (1).7.(107) •&lt;223&gt; Π * A,T , C or G &lt;400&gt; 427 gaagaattca agtcaggttt attcaaaggg cttacngaga atccta Nacc caggncccag 60 127691.doc 153- 200815476 cccgggagca gccttanaga gctcctgttt gactgcccgg ctcagng &lt;210&gt; 428 &lt;211&gt; 38 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;

&lt;221&gt; misc two specials &lt;222&gt; (1)./.(38) &lt;223&gt; n = A, T, C or G &lt;400&gt; 428 gaacttccna anaangactt tattcactat tttacatt &lt;210&gt; 429 &lt; 211 &gt; 544 &lt; 212 &gt; DNA · &lt; 213 &gt; al crop-107 38 η cgctgcattt 60 atagacgccg 120 cggttttcag 180 tccactcgtt 240 tgctgcttca 300 ccgtccatcc 360 tcaagcccac 420 ctgccttgac 480 gtaggagaga 540 544 &lt; 400 &gt; 429 ctttgctgga attgaagagc atatccacga tttiggatggt gccttccact agatactaag tgatgtgcsg gagcttagtt accccaacaa ttat cggaataaaa ggctgcagcc actcttgaag ggctcatcac tcagttacac cccacatttg ttaaaaaatc caaagcagta gtcagagaga gtggacgcaa ctgcggttca gactttctga ctgtagaacc ctcactcacc agatgcagca tgccctttca ttcagcgatt tacgcatatc gcatga.cctc gattaaaatc tttat-ccaca tgacttggcc atcctctcct gccatctccc tgatgtcctt tcaagagaag cagggatttt ctgatgaggg cgagaattgt atcaaatcat gtggctggaa gttggttctg ccaactcctc gacgttctca ttctttacr.t ttgccaggtg &lt; 210 &gt; 430 &lt;211&gt; 507 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc_

&Lt; 222 &gt; (1) .7 (507) &lt;. 223 &gt; n = HC or G ο &lt; 400 &gt; 430 cttatcncaa gaacactgac gagcatcaat cctccgtgac attcaaccag caagaaggag tgtcagtgaa cattctcctc ttctgagcaa tggggctccc acccatcttc ctaaaaagct tttatgcaat gatgtttcta gactgcaagc tggataatct tggcctctaa aaaaaaaaaa aaacttggct caccccgaca gcccagaatg gcatcatgct Ccnctgtggg atatcgtggt aatgtgcttc tagtcaatga aaaaaaa gtgcagtgga ctctgattta

Ctntcctggg atttcatacc tfatgacaaa ggagaagaag tagtaggcac ttgtgtagcc aactccgggg atcgggctgc cagcgttgtg taatgaggga gacaactgcc gacccaaaaa agggctccca atgectatea gaattttgaa 60 agtgagaaca 120 atctttgccn 180 gctccaggag 240 aaagaatntt 300 agacctgttc 360 ggccaggcct 420 gtaaaaagat 480 507 127691.doc &lt; 210 &gt; 431 &lt; 211 &gt; 392 -154-

200815476 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;

&lt;221&gt; misc_: special effect &lt;222&gt; (1) (392) &lt;223> n = A, T, C or G &lt;400&gt; 431 gaaaattcag aatggataaa aacaaatgaa gtacaaaata tttcagattt acatagcgat aaacaagaaa gcacttatca ggaggactta caaatggaag tacactctan aaccatcatc tatcatggct aaatgtgaga ttagcacagc tgtattattt gtacattgca aacacctaga aagagatggg aaacaaaatc ccaggagttt tgtgtgtgga gtcctgggtt ttccaacaga catcattcca gcattctgag atcagggnga ttggggatca ttctggagtt ggaatgttca acaaaagtga tgttgttagg taaaatgtac aacttctgga tctatgcaga cattgaaggt gcaatgagtc tggcttttac tctgctgttt ct

&lt;210&gt; 432 &lt;211&gt; 387 &lt;212&gt; DNA &lt;213&gt; Human ··· &lt;220&gt; . . . &lt;221&gt; misc 1. Devotion &lt;222&gt; (1) (387) ) - &lt; 223 &gt; n = A, T, C or G &lt; 40O &gt; 432 ggtatccnca cataatcaaa tatagccgta gcacatgttt tcattggngt agattaccac aaatgcaagg caacatgtgt agatctcttg tcttattctt ttgtctataa tactgcattg ngtagtccaa gctcccggna gcccagccac t.gngaaacat gccccctcta gattaacctc gtggacnctn ttgtcgnatt gtccgaactg tagngccctg tatttcgctc ccgtctgnga attctgttgc ttctggggca tccccttgng atgcagagga Ccaccacaca gatgacagca atctgaattg ntccaaccac agccgcgatt aagacatact gaaatcgtac aggaccggga acaacgtata gaacactgga gtcctcc &lt;210&gt; 433 &lt;211&gt; 281 &lt;212&gt; DNA &lt;213&gt;Human&lt;220&gt;&lt;221&gt;misc__Features&lt;222&gt; (1).7 .(281) **

&lt;223&gt; η »Α,Τ,ί: or G 60 120 180 240 , 30〇&quot; 360 392 60 120 1Θ0 2^0 300 360 387 60 120 180 240 281 &lt;400&gt; 433 ttcaactagc anagaanact ctgattaaag aacactaaga caggcnctat ttgggttggc atcgccgtgg ctattcctcn tnnaaaaccg ntatacaaca &lt; 210 &gt; 434 &lt; 211 &gt; 484 .gcttcagggn gtrgtaaaatg gagggacaag gctagaagcc tggaggagct gtggaaaaca ttgntattac accagngagg atgatagaat aggacacaca aaaggcttcc acgcagttat gcaggatgtc tacactatag tggagagatt ggcgccggag ntctctgtnt gcccactggt t -155- 127691.doc 200815476

ϋ &lt; 212 &gt; DNA &lt; 213 &gt;. and europium &lt; 400 &gt; 434 ttttaaaaca agcatttagt gctcagtccc aatccaattc tttcaacttg caatttgcaa tgttgcaaaa aaaaaaaagt gtctttgttt tttttcccca ttggaactag tcattaaccc agctagtcta tcagcatctg acaggtgaat cagcctgttt ctatcctgtt taataaatta tgctccaatc tgtcacataa aagcctgtga tttacttttc tatgtgtttt ttgcaacata ttta &lt; 210 &gt; 435 &lt; 211 &gt; 424 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 435 gcaccgctca gagcaggtca ctttctgcct gggcagctct caatatcgca ggtccttact cgaccgggca agtaaacccc ctcccccgcc atgggcctgt ggggaggggg caagatagac ctcggagaga ggaaasaggc cacaagaggg ggnagagacc cttgggggtc tggaacccct gctaccagaa acttaaactt gaggatcttc aaac &lt; 210 &gt; 436 &lt; 211 &gt; 667 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;22l&gt; Feature &lt;222&gt; (1).7.(667) &lt;223&gt; n = A, T, C or G &lt;400&gt; Accctgggaa nactctcaca atacaaaggg tcccggccac gtaatcctga aagtcccccc agcctcttcc ggaattcctc tgatttcaaa cagcccctga aaggcaggta tagcaactga acgggccgcc agagtaggat aggattccag gccaggtttg tcatagcact cacc aaagtc tgttcatgtt tataggactc acccaagaat agcccacaac gctgctccat gcccagctgg gatcccctta tggggtcagc gggaaaggtg • accaaagtca caaacttcaa ctccttggct agaaacaaga agccaaggcc aaggcttgct tgctgag &lt; 2X0 &gt; 437 tactgagtac tctttctctc ccctcctctg 60 ggattacaca tttcactgtg atgtatattg 120 aaaattactt ggtttgtgaa tccatcttgc 180 atctctgaac tggtagaaaa acatctgaag 240 tggatggttc tcagaaccat ttcacccaga 300 gtttgggttc tctacatgca taacaaaccc 360 cttgaagttt agtcagcacc cccaccaaac 420 ^ tgagtgtttt gaaaataaag tacccatgtc 480 484 tccacgtccc ccttcaagga agccccatgt 60 cctccgcctc tacaagctca aacccaccaa 120 gacttcggaa ctggcgagag ttcagcgcag 180 gagggggagc ggcatggtgc ggggtgaccc 240 gccgccaccg ccactaacgg agatggccct 300 ggacccccca tgctctaact cccacactct 360 tccgcttctc actcgcaata aattcagagc 420 424 tcgtagactt taccccaaat tccaaaaagg 60 aaggtagcta taSaatcctt ataagggtgc 120 gtctcactct caagttctcg aaaacgaggg 180 cccccagaaa gaggaactgt Gtgcaccggg 240 atgctgacac cttctggggg aaacagggct 300 cggtcaacgt ctgtgcttcg aatataaacc 360 tttctatatc tctttct tat atactctcca 420 g ^ agtcggc caaatccttg tggccacgag 480 tcaatgggac ttcggcctcc atgccgaaac 540 agtacacttc ggtctagcca gaaaaaaagc 600 gccctgccag gaggaggggt gcagctctca 660 667 127691.doc -156- 200815476 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 437 ctacgtctca accctcattt ttaggtaagg aatcttaagt ccaaagatat taagtgactc 60 acacagccag gtaaggaaag ctggattggc acactaggac tctaccatac cgggttttgt 120 taaagctcag gttaggaggc tgataagctt ggaaggaact tcagacagct ttttcagatc 180 ataaaagata actcttagcc catgttcttc tccagagcag acctgaaatg acagcacagc 240 aggtactcct ctattttcaq ccctcttgct tctactctct ggcagtcaga cctgtgggag 300 gccatgggag aaagcagctc tctggatgtt tgtacagatc atggactatt ctctgtggac 360 cattcctcca ggttacccta ggtgtcacta ttggggggac agccagcatc tttagctttc 420.

acttgagttt ctgtctgtct tcagtagagg aaactcttgc tcttcacact ccacatctga 4BD acacctaact gctgttgctc ctgaggtggt gaaagacaga tatagagctt acagtattta 540 tcctatttct aggcactgag ggctgtgggg taccttgtgg tgccaaaaca gatcctgttt 600 taaggacatg ttgcttcaga gatgtctgta actatctggg ggctctgttg gctctttacc 660 ctgcatcatg tgctctcttg gctgaaaatg acc 693 &lt; 210 &gt; 438 &lt; 211 &gt; 360 · ·

&Lt; 212 &gt; DNA &lt; 213> human * &lt; 400 &gt; 4 38 ccgcttatca caatgaatgt tctcctgggc agcgttgcga ccttcgccac cttcgtgacc 60 ccacgcaatg catcatgcta tttcatacct aatgagggag ctccaggaga ttcaaccagg 120 acgtttctac acctgtgggt tacgacaaag acaactgcca aagaatcttc aagaaggagg 180 actgcaagta tatctggtgg agaagaagga cccaaaaaag acctgttctg tcagtgaatg 240 gataatctaa tgtgcttcta gtaggcacag ggctcccagg ccaggcccca Ttcccctctg 300 gcccccaaca gtcaataatt gcgcagccac gcctaccagt aaaaagattc ttgagcaaac 360 &lt;210&gt; 439 &lt;211&gt; 431 * &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;&lt;221&gt;misc_features&lt;222&gt; (1) . . (431)

&Lt; 223 &gt; n * A, T, C or G &lt; 400 &gt; 439 _ gttcctnnta actcctgcca gaaacagccc tcctcaacat gagagctgca cccctcctcc 60 cggccagggc agcaagcctt agccttggct tcttgtttct gcttttttto t99ct〇yacc 120 gaagtgcacc agccaaggag ttgaagtttg tgactttggc gtctcggcat ggagaccgaa 180 gccccactga cacctctccc actgacccca taaaggaatc ctcatggcca caaggatttg 240 gccaactcac ccagctgggc atggagcagc atcacgaact tggagagcac ataagaaaga 300 gatacagaaa attcttgaat gagtcctata aacacgaaca ggtttatatt cgaagcacag 360 acgctgaccg gactttgatg agtgctatga ca ^ acctagc agcccgtcga cgcggccgcg 420 aatccagtag t 431 &lt; 210 &gt; 440 &lt; 211 &gt; 523 &lt; 2i2 &gt; DMA &lt; 213 &gt; human 157- 127691.doc 200815476 &lt; 400 &gt; 440 agagataaag cttaggtcaa agttcataga gttcccatga actatatgac tggccacaca 60 ggatcttttg tatttaagga ttctgagatt ttgcttgagc aggattagat aaggctgttc 120 tttaaatgtc tgaaatggaa cagatttcaa aaaaaaaccc cacaacctag ggtgggaaca 180 aggaaggaaa gatgtgaata ggctgatggg caaaaaacca atttacccat cagttccagc 240 cttctctcaa ggagaggcaa agaaaggaga tacagtggag acatctggaa agtt ttctcc 300 actggaaaac tgctactatc tgtttttata tttctgttaa aatatatgag gctacagaac 360 taaaaattaa aacctctttg tgtccctcgg tcctggaaca tttatgttcc tcctaaagaa 420 acaaaaatca aactttacag aaagatttga tgtatgtaat acatatagca gctcttgaag 480 tatatatatc atagcaaata agtcatctga tgagaacaag eta 523 &lt; 210 &gt; 441 _ &lt; 211 &gt; 430 '

&lt;212&gt; DNA &lt;213>human * &lt;400&gt; 441 gttcctccta actcctgcca gaaacagctc tcctcaacat gagagetgea cccctcctcc 60 tggccagggc agcaagcctt ageettgget tcctgtttct gctttttttc tggctagacc 120

Gaagtgtact agccaaggag tcgaagtttg tgactttggt gtttcggcat ggagaccgaa 18Q

gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 24Q gccaactcac ccagctgggc atggageage attatgaact tggagagtatL ataagaaaga 300 gacatagaaa atccttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 3β0 acgttgaccg gacnctgatg agegetatga caaacctggc agcccgtcga cgcggccgcg 420 aatetagtag 430 &lt; 210 &gt; 442 &lt; 211 &gt;. 362 .- &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 40O &gt; 442 ctaaggaact agcagcgctc ccatcacttg tttggagtgt gccatcctaa aagattttga 60 ttccccggaa tgacaatcac attccaactt tggcggggga aagagccata ggaccacagt 120 ctticacttct gatacccgca aatcaatctt ttatcgcact tgctttgacc attaagetat 1Θ0 atgettagaa acggccattt tacggaaaaa ttagaaaaac tctgacaata gcgcagaata 240 aatgaaccaa tgtcccaccc aattcatatt · gaactgtcaa tgacaaacaa aaattctttt: 300 cgactaccct ttgttcccac ccaccagaat aaaaactaag aatcaaaagc Tcgactacag 360 cc 362 &lt;210&gt; 443 &lt;211&gt; 624 &lt;212&gt; DNA ~ &lt;213&gt; Human &lt;220&gt;&lt;221&gt; misc - esteem &lt;222&gt; (1) .7. (624) , -

&Lt; 223 &gt; n »A # T, C Λ G &lt; 4 00 &gt; 4 4 3 ctccttcttt gcaacacaat gtgaaatgtg taacccttgc aaattgcaag 60 ttgaaagaat taaatccaga ggaggggaga gaaagagtac tcagtaggga ctgagcacta 120 aacgcctact ttaaaagaaa tigtaaagage agaa accounting gcaat tcaggctacc ccgccttttg 180 tgctggctag tactccggtc ggtgtcagca gcacgtggca ttgaacattg caatgtggag atacatcaca 240 127691.doc -158- 200815476 agaaaatggg gtgaaattgg ccaactttct attaacttgg cttcccgtct 300 tgtgaataat atcacctact tcaaagggca gttatgaggc ttaaatgaac 360 aaaacactta aacatagata acataggtgc aagtactatg tatctggtac 420 tccctattac taaagtcaac gctaaaatga atgtgtgtgc atatgctaat 480 9a999cactt aaaccaacta agggcctgga gggaaggttt cctggaaaga 540 gctgggtcca aatcttggtc tactatgacc ttggccaaat tatttaaact 600 ctgctaaaca gate 624 cccaaaccac tataaaatat taacgcctac Atggtaaaca agtacagaga ngatgcttgt ttgtccctat &lt;210&gt; 444 &lt;211&gt; 425 &lt;212&gt; DNA &lt;213&gt; Human &lt;220&gt;&lt;221&gt; Features &lt;222&gt; (1) (425)

&lt;223&gt; n « A, T, C or G &lt;400&gt; 444 gcacatcatc nntcctgcat cctttgagaa taagaagatc agtaaatagt tcagaagtgg 60 gaagctctgt ccaggcccgt gtgtgaaccc aatgttttgc ttagaaatag aacaagtaag 120

u ttcattgcta tagcacaaca caaaatttgc ataagtggtg gtcagcaaat ccttgaatgc 180 tgcttaatgt gagaggttgg taaaat: cctC cgtgcaacac &quot; tctaactccc tgaacgtttt 240 gctgtgctgg gacctgtgca tgccagacaa ggccaagctg gctgaaagag caaccagcca 300 cctctgcaat ccgccacctc ctgctggcag gatttgtttt tgcancctgt gaagagccaa 360 ggaggcacca gggcacaagt: gagcagactt atggtcgacg cggccgcgaa tttagtagta 420 gtaga 425 &lt; 210> 445 &lt;211&gt; 414 ....... &lt;212&gt; DNA · &lt;213&gt;People&lt;220&gt;&lt;221&gt; misc one:}Intrinsic &lt;222&gt; (1) (414)

&Lt; 223 &gt; Π - A, T, CG &lt; 400 &gt; 445 catgcccacg nccccggatc accctgggca cctagtgttt ctaaatcgtc taccactctc 60 ttccgtcttc caaaagcaga gatggccaga gtctcaacaa actgtatctt caagtctttg 120 tgaaatcccc cgcatgtggc agactaccgg atgtagtttc ccttaactag catataaacc 180 tggcgtgctt cagataaacg aacagcaaaa tigtggtggaa ttaccatttg gaacattgtg 240 aacgaaaaat tgtgtctcta gatcacgtaa caaataacta tctcctaacc actgatctcc 300 ggacttttac aatcctactc acaaatgact aggcccctcc ccttgcattt cgaagcagtg 360 tgggtgctgg attgataaaa aaaaaaaaag tcgacgcggc cgcgaattta gtag 414 &lt;210&gt; 446 ~ &lt;211&gt; 631 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;&lt;221&gt; misc__ 4 Temple sign &lt ;222&gt; (1)...(631) -159- 127691.doc 200815476 &lt;223&gt; η e A,T,C or G &lt;40Q&gt; 446 acaaattaga anaaagtgcc agagaacacc tctgcatgca tgggaagtgt gagcattcta atgctggtta tactggacaa cactgtgaaa ccggtcctgt acgatttcag tatgtcttaa ctgtcatctg tgcggtggtc ctctgcatca Actgagattt gtaaactttc caaccttcca gacagaagca aaatacaggg cactacagtt taatctaaag ggagcatgtt tcacagtggc cagta ttata gacaaaagaa taagacaaga aatctacacc aatgaaaaca tgtactacag aatagtatac attgtcttga tgtttttcct acataccttg tccggaacat tacaatggct 60 tcaatatgca ggagccatct tgcaggtgtg 120 aaaaggacta cagtgttcta tacgttgttc 180 tcgcagctgt gattggaaca attcagattg 240 caagggccaa actttaggta atagcattgg 300 ggaaatgccc cagaagcaac agaattcaca 360 cagacaatac aacaagagcg tccacgaggt 420 tggactaccg agagcttgga ctacacaata 480 gatctacaca tgttgccttg catttgtggt 540 ctatatttga ttatgtatgg atatatttga 600 g 631 &lt;21Q&gt; 447 &lt;211&gt; 585 &lt;212&gt; DNA &lt;213&gt; Human n &lt;220&gt;

&lt;221&gt;misc-feature&lt;222&gt; (1).7.(585) &lt;223> n = A, T, C Table G ccaaaaaggt 60 caagggtgca 120 aaacgagggc 180 cgcaccggga 240 aacagggctg 300 atataaacct 360 tactctccaa 420 ggccatgagg 480 tgccgaaaca 540 &lt; 400 &gt; 447 ccttgggaaa cctggccatg gccccctctg agttcctgaa cgggctgcca ccaggtttgt gtccatgttt gctcacaatg attcctzctisit ccaaagtcac antntcacaa taatcctgaa gaacccccct aggcaggtat gagtaggata catagcactc ataggactca ctgctccatg ggggccagtg aaacctcaac tataaagggt agttttccca gatcccaaag agcaactgat ggattccaga atcaaagtcc ttcaagaatc cccagctggg ggaaaggtgt tccttggcca cgcagacttt aggcagctat cctcactctc cttcagaaag tgctgacacc ggccaacgtc ttctacatct tgagtcggcc caatgggact gtacacttcg actccaaatt aaaatcctta aagttcttga aggaactgtg Ttctggggga tgtgcttcga ctttcttaca aaatccctgc tcggtctcca gtcta &lt;210&gt; 448 &lt;211&gt; 93 &lt;212&gt; DNA &lt;213&gt; Human ϋ &lt;220&gt;&lt;22l&gt; misc_ feature &lt;222&gt; (1).7.(93)

&lt;223&gt; n = or G &lt;400&gt; 448 , ~ tgctcgtggg tcattctgan nnccgaactg accntgccag ccctgccgan gggccnccat 60 ggctccctag tgccctggag agganggggc tag 93 &lt;210&gt;

&lt;211&gt; 706 &lt;212&gt; DNA &lt;213&gt; Personnel 127691.doc -160- 200815476 &lt;220&gt;&lt;221&gt; misc__.Features &lt;222&gt; (1).7.(706) ^

&Lt; 223 &gt; η - A, T, C or G &lt; 400 &gt; 449 ccaagttcat gctntgtgct ggacgctgga cagggggcaa aagcnnttgc tcgtgggtca 60 ttctgancac cgaactgacc atgccagccc tgccgatggt cctccatggc tccctagtgc 120 cctggagagg aggtgtctag tcagagagta gtcctggaag gtggcccctg ngaggagcca 180 cggggacagc atcctgcaga tggtcgggcg cgtcccattc gccattcagg ctgcgcaact 240 9ttgggaagg gcgatcggtg cgggcctctt cgctattacg ccagctggcg aaagggggat 300 gtgctgcaag gcgattaagt t.gggtaacgc cagggttttc ccagtcncga cgttgtaaaa 360 cgacggccag tgaattgaat ttaggcgacn ccatagaaga gctatgacgt cgcatgcacg 420 cgtacgtaag cttggacccc ctagagcggc cgcccactac tactaaattc gcggccgcgt 480 cgacgtggga tccncactga gagagtggag agtgacatgt gctggacnct gtccatgaag 540 cactgagcag aagctggagg cacaacgcnc cagacactca cagctactca ggaggctgag 600 aacaggttga acctgggagg tggaggttgc aatgagccga gatcaggccn ctgcncccca 660 gcatggatga cagagtgaaa ctccatctca Aaaaaaaaaa aaaaaa 706 &lt;210&gt; 450 &lt;211&gt; 493 &lt;212&gt; DNA .

&Lt; 213 &gt; ^ &lt; 400 &gt; 4 50 gagacggagt gccactctgt tgcccaggcc ggagtgcagc aagacactgt ccaagaaaaa 〇0 acagtctcaa aaggtaaaac aacataaaaa gaaacatcct atagtggaaa 120 aaacgaggct gagaacctca caaagggatc taagagagtc ttacagacat gtcgccaata tcaccgcacg 180 agcccaagta caagaacaac ccctggggag aaaccaccat ttgacagtga ggcacaattc 240 caagtcaggt agtgaaar.gg gcggaactaa actcaaatta atxctgccag ctgaaacgca 3 00 agagacactg tcagagagtt aaaaagtgag ccccatccat gaggt; gatcc cacagtcttc 360 tcaagtcaac acatctgtga actcacagac caagccccta aaccactgtt caaactctgc 420 tacacatcag aaccacctgg agagctctac aaactcccat tgccgagggt cgacgcggcc 480 gcgaattcag tag 493 &lt; 210 &gt; 451 &lt; 211 &gt; 501 &lt; 212 &gt; DNA &lt; 213: &gt; human &lt;220&gt;&lt;221&gt; misp a special desire &lt;222&gt; (1).7.(501)

aacccgcggc taagttgggc 120 aacgccaggg ttttcccagt cncgacgtcg caadacgacg gccagtgaat tgaacttagg 180 tgacnctata gaagagctac gacgccgcac gcacgcgcac gtaagcttgg atcctctaga 240 gcggccgcct actactacta: 451 gggcgcgtcc cactcgccat tcaggctgcg caBctgctgg gaagggcgat cggtgcgggc 60 ctcttcgcta tcacgccagc tggcgaaagg gggatgtgcc gcaaggcgat; 400 &gt; - &lt;; 223 & gt A, T # C or G & lt n cgcgtcgacg tgggatccnc actgagagag 300 tggagagtga catgtgctgg acnccgccca cgaagcactg agcagaagct ggaggcacaa 360 cgcnccagac actcacagct vHctc3ggagg ccgagaacag gttgaacctg ggaggtggag 420 gttgcaatga gctgagatca ggccnctgcn ccccagcatg gacgacagag tgaaactcca 480 127691.doc 161 - 200815476 tctcaaaaaa aaaaaaaaaa a 501 &lt; 210 &gt; 452 &lt; 211 &gt; 51 &lt; 212 &gt; DNA &lt;213&gt; shemale &lt;220&gt;&lt;221&gt; raise a daring &lt;222&gt; (1)...(51)

&lt;223&gt; n = A, T, C or G &lt;4〇0&gt; 452 agacggtttc accnccacaa cncctttcag gatgggnntt ggggagcaag c 51 &lt;210&gt; 453 &lt;211&gt; 317 &lt;212&gt; DNA &lt;213&gt; Human · &lt;220&gt; f)

&lt;221&gt; misc_: feature &lt;222&gt; (1).7.(317) &lt;223&gt; n = A, T, C or G &lt; 4 00&gt; 4 53·

cacatcttqc tttttcccca ttggaactag tcattaaccc atctctgaac tggtagaaaa 6Q acacctgaag agctagtcca tcagcacctg gcaagegaat tggacggttc tcagaaccat 120 ttcacccana cagcctgctc ctatcctgtt taataaatta gtctgggctc tctacatgca 180 caacaaaccc tgctccaacc cgccacataa -aagtctgtga ettgaagett anccagcacc 240 cccaccaaac cctacctttc tacgtgtttt c.tgcaacata tgagtgtttt gaaaataagg 300 cacccatgtc ctcacca 317 &lt; 210 &gt; 4 54 &lt; 211 &gt; 231 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 454 u ttcgaggtac taagccacgc agaagaccaa ccctcccttc aatcaactct cagagtgtag tttcctccta cagatgagtc ageattaata 60 cacgcccttg aaggagcctc gaattctcct ccgctcactc agtagaacca 120 acccttccgc atcccagctt gcaaacaaaa ttgttcttct: aggtctccac 180 tcagtgtccc aaagctcctc acaattccat gaacaacagc c 231 &lt; 210 &gt; 455 &lt;211&gt; 231 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 455 taccaaagag ggcataataa tcagtctcac agtagggttc accatccncc aagtgaaaaa 60 cattgttccg aacgggcttc ccacaggcta cacacacaaa acaggaaaca tgccaagttt 120 gcttcaacgc attgatgact cctccaagga ccttcctttg gcat Cgacca cattcagggg 180 caaagaattt cccacagcac agctcacaat acagggctcc tttcticctct. a 231 127691.doc -162- 200815476 &lt;210&gt; 456 &lt;211&gt; 231 &lt;212&gt; DNA &lt;213&gt; human. &lt;400&gt; 456 ttggcaggta cccttacaaa gaagacacca taccttatgc gttattaggt ggaataatca 60 tcccattcag tattatcgtt attattcttg gagaaaccct gtctgcttac tgtaaccttt 120 tgcactcaaa Ctcctttatc aggaataact acatagccac tatttacaaa gccattggaa 180 cctttttatt tggtgcagct gctagtcagt ccctgactga cattgccaag t 231 &lt;210&gt; 457 &lt;211&gt; 231 &lt;212&gt; DNA &lt;213&gt;People&lt;220&gt;

&lt;221>misc_ feature &lt;222&gt; (1).7.(231) &lt;223&gt; n = A, T, C or G

ttgttcacca 60 catacagttt 120 cttcgtaccc 1Θ0 g 231 &lt; 400 &gt; 457 cgaggtaccc gcacccctta tatttgacct agccgcctaa aggggtctga atatgatctt tattagcaat atcgatgccc aaatctctnn gctataatta ctctttcaga cacttcctct tttantagtc gattttcctc agaccctrtga gaggtgtcgc gatagcaaaa cattagagct gaccaccaag cggctcttgc &lt; 210 &gt; 45Θ &lt; 211 &gt; 231 &lt; 212 &gt; DNA &lt; 213 &gt; al crop-full &lt; 400 &gt; 453 aggcccggct ccccccactt ccactcccct ctactccctc taggaccggg ctgggccaag 60 agaagagggg cggtcaggga agccgttgag acctgaagcc ccacccccta ccttccttca 120 acaccccaac cttgggcaac agcatttgga attaccatct gggatgagta gaatttccaa 180 ggtcctgggc taggcacttt ggggggccag accccaggag aagaagatcc c 231 &lt; 210 &gt; 459 &lt; 211 &gt; 231 &lt; 212 &gt; DNA &lt;213&gt; head

&Lt; 400 &gt; 459 - ggtaccgagg ctcgctgaca cagagaaacc ccaacgcgag gaaaggaatg gccagccaca 60 ccctcgcgaa acctgtggtg gcccaccagc cctaacggga caggacagag agacagagca 120 gccctgcacc gttttccctc caccacagcc atcctgtccc tcactggccc tgtgccttcc 180 actatacaca gtcaccgtcc caangagaaa csragaaggag cacccticcac a 231 &lt; 210 &gt; 460 &lt; 211 &gt; 231 &lt; 212 &gt; DNA &lt; 213 &gt; al Qiu &lt; 400 &gt; 460 163- 127691.doc 200815476 gcaggtataa catgctgcaa caacagatgt gactaggaac ggccggtgac atggggaggg 60 cctatcaccc tattcttggg ggctgcttct tcacagtgat catgaagcct agcagcaaat 120 cccacctccc cacacgcaca cggccagcct ggagcccaca gaagggtcct cctgcagcca 180 gtggagcttg gtccagcctc cagtccaccc ctaccaggct taaggataga a 231 &lt; 210 &gt; 461 &lt; 211 &gt; 231 &lt; 212 &gt; DNA &lt; 213 &gt; al Yan &lt; 400 &gt; 461 cgaggtttga gaagctctaa tgtgcagggg agccgagaag caggcggcct agggagggtc 60 gcgtgtgctc cagaagagtg tgtgcatgcc agaggggaaa caggcgcctg tgtgtcctgg 120 gtggggttca gtgaggagtg ggaaattggt tcagcagaac caagccgttg ggtgaataag 180 agggggattc catggcactg atagagccct atagtttc Ag agctgggaat t 231

&lt;210&gt; 462 &lt;211&gt; 231 &lt;212&gt; DNA &lt;213&gt; human .

& Lt DNA ^; aggtaccctc attgtagcca tgggaaaatt gatgttcagt ggggatcagt gaattaaatg 60 gggtcatgca agtataaaaa tcaaaaaaaa aagacttrat gcccaatctc atatgatgtg 120 gaagaactgt tagagagacc aacagggtag tgggttagag atttccagag tcttacattt 180 tctagaggag tcttctcact catccagtgt tgtatttagg a 231 & lt - 462;; 210 &gt; 463 &lt; 211 &gt; 231 &lt; 212 & gt &lt; 400 &gt; 213> human amount &lt; 40O &gt; 463 tactccagcc tggtgacaga gcgagacccc atcaccgccc cccaccccac caaaaaaaaa 60 actgagtaga caggtgtccc cttggcatgg taagtcttaa gtcccctccc agatctgtga 120 catttgacag gtgtctttcc ctctggacct cggtgtcccc atctgagtga gaaaaggcag 180 tggggaggtg gatcttccag tcgaagcggt:. atagaagccc gtgtgaaaag c 231 &lt; 210 &gt; 464 &lt; 211 &gt; 231 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 464 gtactctaag attttatcta agttgccttt tctgggtggg aaagtttaac cttagtgact 60 aaggacacca catatgaaga atgtttaagt tggaggtggc aacgtgaatt: gcaaacaggg 120 cctgcttcag tgactgtgtg cctgtagtcc cagctactcg ggagtctgtg tgaggccagg 180 ggtgccagcg caccagctag atgctctgta acttctaggc cccattttcc c 231 &lt; 210 &gt; 465 &lt;2ll&gt; 231 &lt;212&gt; DNA &lt;213&gt; Human &lt;400&gt; 4 65 127691.doc 164- 200815476

υ catgttgttg tagctgtggt aatgctggcc gcatctcaga cagggttaac ttcagctcct 60 gtggcaaatt agcaacaaat tctgacatca tatttatggt ttctgtatct ttgttgatga 120 aggatggcac aatttttgct tgcgttcata atatactcag attagttcag ctccatcaga 180 taaactggag acatgcagga cattagggta gtgttgtagc tctggtaatg a 231 &lt; 210 &gt; 466 &lt; 211 &gt; 231 &lt; 212 &gt; DNA &lt; 213 &gt; al # &lt; 400 &gt; 466 caggtacctc tttccattgg acactgtgct agcaagcatg ctctccgggg tttttttaat ggccttcgaa cagaacctgc cacacaccca ggtacaatag tttctaacat ttgcccagga cctgtgcaat caaatattgt: ggagaattcc ccagctggag aagtcacaaa gactataggc aataatggag accagtccca caagatgaca accagtcgtt gtgtgcggct g &lt; 210 &gt; 467 &lt; 21X &gt; 311 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 467 * gtacaccctg gcacagtcca acctgaactg gttcggcacc catctttcat gagatggatg 60 tggtggcttt tctccttcct catcaagact cctcagcagg gagcccagac cagcctgcac 120 tgtgccttaa cagaaggtcc tgagattcta agtgggaatc attitcagcga ctgtcatgtg 180 gcacgggtct ctgcccaagc tcgcaatgag actatagcaa ggcggctgtg ggacgccagt 240 tgtgacctgc tgggccticcc aac Agactaa caggcagngc cagttggacc caagagaaga 300 ctgcagcaga c 311 &lt;210&gt; 468 &lt;2i:l&gt; 3112 &lt;212&gt; DNA &lt;213&gt; Human. &lt;400&gt; 468 cattgtgttg ggagaaaaac agaggggaga tctgtgtggc tgcagccgag ggagaccagg 60 aagatccgca tggtgggaag gacccgacga cacagagttt gacaggagac aattaaaggc 120 tggaaggcac tggatgcctg acgatgaagt ggactttcaa actggggcac tactgaaacg 180 atgggatggc cagagacaca ggagatgagt tggagcaagc tcaataacaa agtggttcaa 240 cgaggacttg gaactgcatg gagccggagc tgaagtttag cccaattgtt tactagtcga 300 gtgaatgtgg acgatcggac gatcacttct · catctctgag cctcaggttc cccatccata 360 aaatgggata cacagtatga tctataaagt gggatatagt atgatctact tcactgggtt 420 atttgaagga tgaattgaga caattcattt caggtgccta gaacaatgcc cagattagta 480 catctggtgg aaccgagaaa tggcacaaca ccaaatttaa tatratgtcag atgttactat 540 Gattatcatt caatctcaca gtcctgccac ggcccaattt accctcactt gtgcctcaac 600 aaattgaact getaacaaag gaatctctgg tcctgggtaa tggctgagca ccactgagca 660 tttccattcc agttggcccc tcgggttcgc tagctgcatc actagtcatc ttaaataaat 720 gaagttt taa catttctcca gcgattcctt tatctcacct ttgaagatac tatgttatgt 780 gattaaataa agaacttgag aagaacaggt ttcattaaac ataaaatcaa tgtagacgca 840 aattttctgg atgggcaaca cttatgtcca caggaaatgc cttaaaatat gcagaagata 900 accaaatggc aatggacaaa gtgaaaaact tagacttttt tttttttttc ggaagtatct 960 ggatgttcct tagtcactta aaggagaact gaaaaatagc agtgagttcc acataatcca 1020 acctgtgaga ttaaggctct:. ttgtggggaa ggacaaagat ctgtaaattt acagtttccc 1080 tccaaagcca acgtcgaact ttgaaacata tcaaagctct tcttcaagac aaataatcta 1140 tagtacatct ttcttatggg acgcacttat gaaaaatggt ggctgtcaac atctagtcac 1200 60 120 180 *' 231 127691.doc 165- 200815476 Ο

tttagctctc ggaaggacag ataagaaagg aacatcacta atttccagcc ctgggagaaa ccgcttgtga aaaacagatc aaagtgagca atgcaacaaa accacggggc atcatttcat cttctgggcc gatctgtact ctcgtgttgc gatctgtgaa cagcacgatc actgaaattc atatcacagg ggaatttaac ctttgcttga tacagccaca atgcacctaa cctgcctgag ttgactatct gcaaatacca ccacagaggg aacctcatag agcttctcac tgagtgcgct tttgtccttg ccccggcaat &lt; 210 &gt; 469 &lt; 211 &gt; 2229 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 469 agctcttcgt tatttccttc tgatttgcca tttgcactgc aagcatatta aacgtgcccc tataatcaaa ccttccttgc agagacaagg ttacaagtta ggagggatgg tttataccgg tggaaaacaa ttaaaaaaaa gcacaaaagt ataatccact aaaatggttc cattgtggct ctgctgactt gaaacagcaa cctttaaata tgcccggccg gggaaggaca ctgttgtgga ttaccaatga caaaatggaa agagggtcag atttctaacc caacattctc gtgacctttc tgcctaatat caggccggga attacggagt atttcccacc atcaactttt tacacatttt ttttttttcc gcctctcccc acaaaatcta aagctcttcc tactccatgc aaagtgcaac * Aatgtctatg taccctacac agaattcatg ttagaatttt tagttaattg aaagaattta attttaagag tggactttat taccatctga ga tgacaata tccacacaca ccatcttggg ttagaaaatg catttatttg gaggaaaaca tactgtgatg gattctggcc ctcaaaacaa catatatcca tacactgtag gtagctgact agcatctcaa gaatcatcta tctgtgccca ttttctaacc gttttccagt agtataaagt atccctccag acctgtaact ttgcctccta aaagaaggga ttgattataa gggcacgttt aatatacttc cagtgcaaat ggcaaatcac aaagaaacag caaagagcaa aaagttttag aaggtcttta ggccacacat taacgtctaa caggaagcac tcatcgatga aattgacgtg aacgggatta gacgagaaaa acatgaggca ctgctgccta agccgttgta gccacactca aataacatca gttttcccta gatctttcca atcaacatca ctctcaagac tggaagaatt gcaaagatga taaaatgctt ccttatctgt ccttgaacat aacccagaat cacatatgag gagtccagat gcaagcctgg actcccccat ccccaaaggt accggccact ggcacccttg aaaaaaaaaa aatctcatat ttcaactaaa ctgctgaaat gtagtgacat aaaaggaagc gcctcgccct ttccttaaag cagatttgaa tcttgatggc gccaagctgg aactgtgcgt atatctgatc tttttaatat ctcattttgt aggagcgttc gggttatact tcctcagtgt ctcaaaatgt caatgttaca ccaagtcctt agccttgtac catcaccatc gtcaggcata gatgtaaagc attcatcatc aaatacatga gacgtgaagc ctccatcaca aacctttatc tatctcaacc t gagccacct aaaaaaaaaa ttattcctgt taggtgagaa ggagataatt gtttttgcac acagagatcc gtgcctggtc gatgggcagg acgaagccac ttcacaagac ggaggagata tcataaccaa tctacggttc ttagttccca tcaaagaccc tggcccaggg tactagcaca ctttgcccac cattccatta tgcagctatg tatccctccc tgaggctgta aacccctccc cattattcct tttgaataag acatgagaca aacgcaagag aaaggcaggg atatccaaca catttcatgg tcgagacgtg tagggctcac aa 1260 1320 1380 1440 1500 1560 1620 icao 1740 1800 1860 1920 1980 204a 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3112 aaattctcta aattaactac aaattctaaa atgaattctg tacaagatac acaaacatcc tacaccttta atgaagcaag aagagcttct gattccgttt ggagaggctg aaaaaaaatc aatatgtaat agttaatcct gggaaatgaa ccgtaatgat ttgccaggag aaggacaaac gcgcactcac tgaaaagctt tacgaggttc cccctgtggc gtatttgctg acagtcaact caggcagaag aggtgcacgg tggctgtata aaacaaaggg taaattccca gtgatattaa tttcagtatg catgctgtgc tgaaccctaa acacctcaaa Catgaaatgg gtcggacatc cctgcctttg ccttgcattt cctcatgcga tatccaaaac gaataatgta gaggggttga cagcctcagt ga gggataaa tagctgcatg tggaacgaca ggcaaagaca gctagtaagt agtggctcac gttgagataa ataaaggtta gtgatagaga ctteacatcc catatattta tgatgaatct tttacatcat tgcctgacat tggtgatgac acaaggctaa ggacttagtc taacattgaa ttttgaggtc ctgaggatga ataaccccgg aagagtgccc 60 gtgaccagta 120 cctttgggga 180 tagagaaatg 240 caggcttaca 300 tctaaactct 360 catatgtgtc 420 tctagattta 480 gtccaaggaa 540 agataaggct 600 gcattttaac 660 atctttgcac 720 ttcttccagg 780 ttgagaatgg 840 tgttgattag 900 aaagatcttg 960 127691.doc 166- 200815476 agatgcttcc cagcctgttc acagatcccc tgggccagaa cactccttag gaaaaacagt 1020 cagctacata ttaggcagca acacgaaggg tctttgaaca aaatgagtaa tgttattcta 1080 cagtgtagaa aggtcacagt acagatctgg gaactaaata ttaaaaatga gtgtggctgg 1140 atatatggag aatgttgggc ccagaaggaa ccgtagagat cagatattac aacagctttg 1200 ttttgagggt tagaaatatg aaatgatttg gttatgaacg cacagtttag gcagcagggc 1260 cagaatcctg accctctgcc ccgtggttat ctcctcccca gcttggctgc ctcatgtcac 1320 cacagtattc cattttgttt gttgcatgtc ttgtgaagcc atcaagattt tctcgtctgt 1380 tttcctctc a ttggtaatgc tcactttgtg acttcatttc aaatctgtaa tcccgttcaa 1440 ataaatatcc acaacaggat ctgttttcct gcccatcctt taaggaacac atcaattcat 1500 tttctaatgc ccttccctca caagcgggac caggcacagg gcgaggctca tcgatgaccc 1560 aagatggcgg ccgggcattt ctcccaggga tctccgcgcc tccttttgcg cttcctgtgt 1620 gtgtggatat ttaaaggggc tggaaatgtg caaaaacat; g tcactactta gacattatat 1680 tgtcatcttg ctgtttctag tgatgttaat tatctccatt tcagcagatg tgtggcctca 1740- *

gatggtaaag tcagcagcct ttcttatttc tcacctggaa atacatacga ccatttgagg 1800 agacaaatgg caaggtgtca gcataccctg aacttgagtc gagagccaca cacaatatta I860 ttggtttccg agcatcacaa acaccctctc tgtttcttca ctgggcacag aattttaata 1920 cttatttcag tgggctgttg gcaggaacaa atgaagcaat ctacataaag tcactagtgc 1980 agtgcctgac acacaccatt ctcttgaggt cccctctaga gatcccacag gtcatatgac 2040 ttcttgggga gcagtggctc acacctgtaa tcccagcact tcgggaggct gaggcaggtg 2100 ggtcacctga ggtcaggagt tcaagaccag cctggccaat atggtgaaac cccatctcta 2160 ctaaaaatac aaaaattagc tgggcgtgct ggtgcatgcc cgtaatccca gccCcaacac 2220 aacggaact 2229 &lt; 210 &gt; 470 .. &lt; 211 &gt; 2426 &lt; 212 &gt; DNA &lt; 213 &gt; human &lt; 400 &gt; 470 gtaaattctt tattgccagg agtgaaccct aaagtggctc acaagagtgc cctatttctt 60 ccaattaact acaaggacaa acacatctca aagctgagac aagcgaccag tatgatttgc 120 caaaattcca Aagcgcactc accatgaaat ggacaaaggc tacccccggg gatttgcact 1Θ0 gcacgaaccc tgtgaaaagc ttgttggata ttgcgacaga gacagagaaa tgaagtatat 240 tatataagat actatgaggc cccctgcctt tgcttcacac cccaggc tta caaacgtgcc 300 ccataaacat tccctctgtg gctcttgcat ttcatatatt tatctaaact cttataatca 360 aattacactt ctagtatttg ctgcctcatg tgatgatgaa tcccatatgt gtcccttctt 420 tgcacgaagt aagatagtca acttattcaa aactttacat cattccagat ctaagagaca 480 aggaagagct tctcaggcag aaggaataat gtacgcctga cacgcccaag gaattacaag 540 ttagactctg tctaggtgca atcaaacaaa ggggagggat aAaggactta tgggaggggc tgatggcgac gacagacaag gccggaggga 600 tggggagagg ctgtggctgt atacagcctc agtacaaggc caagcattcc aacttcatac 660 cggaaaaaaa gccatctttg cactggaaaa 720 caaaatatgt aattaaattc ccatagctgc atgtaacatt gaattcctcc aggttaaaaa 780 aaaaagtcaa tcccgtgata ttaacggaat gacattctga ggccttgaga atgggcacaa .84 0 aagtgggaaa tgaatttcag tatgggcaaa gacactgagg atgacgtcga ttagacaatc 900 cactccgtaa tgatcatgct gtgtgctagt aagtataacc ctggaaagat cttgagatgc 960 tccccagcct gttcacagat cccccgggcc agaacactcc ttaggaaaaa cagtcagcta 1020 cataccaggc agcaacacga agggtctttg aacaaaatga gtaacgttat tctacagtgt 1080 agaaaggtca cagtacagat ctgggaacta aatattaaaa Atgagtgtgg ctggatatat 1 140 ggagaatgtt gggcccagaa ggaaccgtag agatcagata ctacaacagc tttgttttga 1200 gggtcagaaa tacgaaatga tttggttatg aacgcacagt ttaggcagca gggccagaat 1260 · cctgaccctc tgccccgtgg ttatctcctc cccagcttgg ctgcctcatg tcatcacagt 1320 attccatttt gtttgttgca tgtcttgtga agccatcaag attttctcgt ctgttttcct 1380 ctcatcggca acgctcactt tgtgacttca tttcaaatct gtaatcccgt tcaaataaat. 1440 acccacaaca ggatctgttt ccctgcccat cctttaagga acacatcaat tcattttcta 1500 atgccccccc ctcacaagcg ggaccaggca cagggcgagg ctcatcgatg acccaagatg 1560 167- 127691.doc 200815476 gcggccgggc atttctccca gggatctctg tgcttccttt tgtgcttcct gtgtgtgtgg 1620 atatttaaag gggctggaaa tgtgcaaaaa catgtcacta cttagacatt atattgtcat 1680 cttgctgttt ctagtgatgt taattatctc catttcagca gatgtgtggc ctcagatggt 1740 aaagtcagca gcctttctta tttctcacct ggaaatacat acgaccattt gaggagacaa 1800 acggcaaggt gtcagcatac cctgaacttg agttgagagc tacacacaat attattggtt i860 tccgagcatc acaaacaccc tctctgtttc ttcactgggc acagaatttt aacacttatt 1920 Tcagtgggct gttggcagga acaaatgaag caatctacat aaagtcacta gtgcagtgcc 1980 tgacacacac cattctcttg aggtcccctc tagagatccc acaggtcata tgacttcttg 2040 gggagcagtg gctcacacct gtaatcccag cactttggga ggctgaggca ggtgggtcac 2100 ctgaggtcag gagttcaaga ccagcctggc caatatggtg aaaccccatc tctactaaaa 2160 atacaaaaat tagctgggcg cgctggtgca tgcctgtaat cccagctact tgggaggctg 2220 aggcaggaga attgctggaa catgggaggc ggaggttgca gtgagctgta attgtgccat 2280 tgcactcgaa cctgggcgac agagtggaac tctgtttcca aaaaacaaac aaacaaaaaa 234P ggcatagtca gatacaacgt gggtgggatg tgtaaataga agcaggatat Aaagggcatg 2400 gggtgacggt tttgcccaac acaatg 2426 &lt;210&gt; 471 &lt;211&gt; 812 &lt;212&gt; DNA &lt;213&gt; Human

U

&Lt; 400 &gt; 471 gaacaaaacg agtaatgtta ttctacagtg tagaaaggtc acagtacaga tctgggaact 60 aaatattaaa aatgagtgtg gctggatata tggagaatgt tgggcccaga aggaaccgta 120 gagatcagat actacaacag ctttgctccg agggttagaa acatgaaatg atttggttat 180 gaacgcacag ttcaggcagc agggccagaa tcctgacccc ctgccccgtg gttacctccc 240 ccccagcttg gctgcctcat gtcatcacag tattccattc tgtttgttgc atgtcttgtg 300 aagccatcaa gattttcccg tctgtttccc tctcattggt aacgctcact ccgtgactcc 360 actccaaacc tgtaatcccg ttcaaacaaa catccacaac aggacctgtc ctcctgccca 420 tcccccaagg aacacatcaa ttcactcccc aacgcccttc cctcacaagc gggaccaggc 480 acagggcgag gcccatcgat gacccaagat-ggcggccggg cacttctccc agggacctcc 540 gtgctccccc tcgtgcttcc cgtgtgtgtg gacattcaaa ggggctggaa atgtgcaaaa 600 acacgtcact acttagacat tatactgtca ccccgctgtc tctagtgatg ttaattatct 660 ccacctcagc agatgtgtgg ccccagatgg taaagtcagc agcctttctt atttctcacc 720 tctgtatcat caggtccttc ccaccatgca gatcttcctg gtccccctcg gctgcagcca 780 cacaaatctc ccctctgttt ttctgatgcc Ag 812 &lt;210&gt; 472 &lt;211&gt; 515 &lt ;212&gt; DNA &lt;213&gt;People&lt;220&gt; ^ &lt;221&gt; misc_ feature &lt;222&gt; (1)···· 515) &lt;223&gt; n = A, T, C or G &lt;400&gt; acggagacct cctatgactt gtcccagaac caatcaggat agtagaaggt ccctgatgta agatgggcag accttctgat attgtctgca tatgtatgtt tttaagagtc cggaaatagt 60 tcctatcatg cttattaata aataatacag cccagagaag atgaaaatgg 120 tattggtcct tgcagcccgg tgaatctcag caagaggaac caccaactga 180 attgaacctg gacaagagag agaaggaaca cctccgatcg aagaacgtaa 240 gatcgccagg aaatggatct ggaaaagact cggagtgagc gtggagatgg 300 aaagagaaga ctccacctaa tcctaagcat gctaagacta aagaagcagg 360 ccataagtta aaaagaagac aagctgaagc tacacacatg gctgatgtca 420 127691 .doc 168- 200815476 cattgaaaat gtgactgaaa atttgaaaat tctctcaata aagttcgagt tttctctgaa gaaaaaaaaa naaaaaaaaa aaanaaaaan aaaaa 480 515 〇u 127691.doc 169-

Claims (1)

200815476 X. Patent Application Range: 1. An isolated polypeptide comprising at least an immunogenic portion of a prostate tumor protein or a variant thereof, wherein the tumor protein comprises an amino group encoded by a polynucleotide selected from the group consisting of: Acid sequence: (4) in sequence identification 225, 227-305, 307_315, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410 a sequence referred to in any one of 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 468-471 or 472; b) a sequence that hybridizes to any of the above sequences under moderate stringency; and (c) a sequence that is complementary to any of (a) or (b). 2. According to the scope of the patent application! An isolated polypeptide, wherein the polypeptide comprises by sequence recognition 225, 227-305, 307_315, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446 '450, 452, 453, 459-461, 468-471 or 472 An amino acid sequence encoded by a polynucleic acid sequence as mentioned, or a sequence complementary to any of the above polynucleotide sequences. 3. An isolated polypeptide comprising the sequences referred to in any of Sequence Recognition Nos. 339 and 383. 4. An isolated polynucleotide encoding a prostate tumor protein 127691.doc 200815476 at least 15 amino acid residues or variants thereof, differing in one or more substitutions, deletions, additions and/or insertions, Such that the ability of the variant to react with antigen-specific antisera is substantially not reduced, wherein the tumor protein comprises an amino acid sequence encoded by a polynucleotide, the polynucleic acid comprising SEQ ID 225, 227-305, 307-3 15, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426 a sequence referred to in any one of 427, 432, 434, 435, 442_444, 446, 450, 452, 453, 459-461, 468-471 or 472, or a sequence complementary to any of the above sequences. An isolated polynucleotide encoding a prostate tumor protein or a variant thereof, wherein the tumor protein comprises an amino acid sequence encoded by a polynucleotide, the polynucleic acid being included in sequence recognition 225, 227-305 , 307-315, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426 a sequence referred to in any one of 427, 432, 434, 435, 442-444, 446, 450, 452, 453, 459-461, 468-471 or 472, or a sequence complementary to any of the above sequences. 6. An isolated polynuclear acid sequence comprising sequence recognition 225, 227-305, 307-3 15, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444 '446, 450, 452, 453 '459-461, 468- 127691.doc -2- 200815476 4 The sequence mentioned in any of 1 1 or 4 7 2 . 7. An isolated polynucleotide sequence comprising under moderately stringent conditions, and in sequence recognition 225, 227-305, 307-315, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450, 452, 453, A sequence hybridizing sequence as referred to in any one of 459-461, 468-471 or 472. f 8· An isolated polynucleotide which is complementary to the polynuclear:y:acid according to any one of the items of the invention. 9. A performance vector comprising the polynucleotide according to any one of claims 4 to 7. 10. A host cell which is transformed or transferred by infection according to the performance of claim 9 of the scope of the patent application. 11. A performance vector comprising a polynucleotide according to item 8 of the scope of the patent application. Ϋ12. A host cell which is transformed or transferred by infection according to the performance vector of the scope of the patent application. A pharmaceutical composition comprising a polypeptide according to the scope of the patent application and a physiologically acceptable carrier. A vaccine comprising a polypeptide according to claim i in combination with a non-specific immune response promoter. 15. The vaccine according to item 14 of the Shenqing patent scope, wherein the non-specific immunostimulating agent is an adjuvant. 127691.doc 200815476 i6. The vaccine according to claim 14, wherein the non-specific immune response promoter preferentially induces a type j response. 17. A pharmaceutical composition comprising a polypeptide according to item 4 of the scope of the patent application and a physiologically acceptable carrier. 18. A vaccine comprising a polypeptide according to item 4 of the patent application and a non-specific immune response promoter. 19. The vaccine according to claim 18, wherein the non-specific immunostimulating agent is an adjuvant. 20. According to the vaccine of claim 18, the non-specific immunostimulating agent preferentially induces the type I reaction. An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to an allelic tumor protein, including a sequence recognition 225, 227-305, 307-3 15, 332, 3 ;H, M0_ 365, 381, 382, 384, 386, 389, 39〇, 392, 393, 401, 4G2, 4〇7, 4G8, 41G, 413, 415·4ΐ9, w❻, 427, 432, 434, An amino acid sequence encoded by a polynuclear acid sequence as referred to in any one of 435, 442-444, 446, 450, 452, 453, 459-461, 468_471 or 472, or any of the polynucleotide sequences described above Complementary sequence. A pharmaceutical composition comprising an antibody or a fragment thereof according to the scope of the patent application (4) and a physiologically acceptable carrier. 23. A pharmaceutical composition comprising a providing antigen &cell; and a pharmaceutically acceptable carrier or excipient according to the polypeptide of claim 1 of the scope of the patent application. y 127691.doc 200815476 24. 25. 26. 27. 〇28. 29. 30. y 31. 32. 33. The pharmaceutical composition according to claim 23, wherein the antigen-providing cell is a dendritic cell or Giant scorpion cells. A vaccine comprising a cell-providing antigen and a non-specific immune response promoter which exhibit a polypeptide according to the scope of the patent application. The vaccine according to claim 25, wherein the non-specific immunostimulating agent is an adjuvant. According to the vaccine of claim 25, wherein the non-specific immunostimulating agent preferentially induces the type I reaction. A vaccine according to claim 25, wherein the antigen-providing cell is a dendritic cell. A method of inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of a polypeptide according to the scope of the patent application, and thereby inhibiting the development of cancer in the patient. A method of inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of polynucleic acid according to item 4 of the patent application, and thereby inhibiting the development of cancer in the patient. A method of inhibiting the development of cancer in a patient, which comprises administering to the patient an effective amount of an antibody or an antigen-binding fragment according to claim 21 of the patent application, and thereby inhibiting the development of cancer in the patient. Two methods for inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of an antigen-producing cell according to the polypeptide of the scope of the patent application, and thereby inhibiting the development of cancer in the patient . According to the method of claim 32, wherein the cells provided are dendritic cells. The method of any one of claims 29 to 32, wherein the cancer is prostate cancer. 35. A fusion protein comprising at least one polypeptide according to claim 1 of the patent application. The fusion protein according to claim 35, wherein the fusion protein comprises a performance enhancer which enhances the expression of the fusion protein in a host cell which is metastatically infected with a polypeptide encoding the fusion protein. 37. The fusion protein according to claim 35, wherein the fusion protein comprises a helper T epitope which is not found in the polypeptide of claim 1 of the scope of claim. 38. The fusion protein according to claim 35, wherein the fusion protein comprises an affinity tag. 39. An isolated polynuclear acid encoding a fusion protein according to claim 35 of the scope of the patent application. A pharmaceutical composition comprising a fusion protein according to claim 35 in combination with a physiologically acceptable carrier. 41_ A vaccine comprising a fusion protein according to claim 35, which is mixed with a non-specific immune response promoter. 42. The vaccine according to claim 41, wherein the non-specific immunostimulating agent is an adjuvant. 43. The vaccine according to claim 41, wherein the non-specific immunostimulating agent preferentially induces a type I reaction. 44. A pharmaceutical composition comprising a polynucleic acid and a physiologically acceptable carrier according to item 4 of the scope of the patent application. 127691.doc 200815476 The fusion protein of the 40th item, wherein the non-specific vaccine is a vaccine according to the patent and a non-specific immune response promoter. 46. The vaccine response promoter according to item 45 of the patent application scope is an adjuvant. 47. According to the 45th item of the patent application, the non-specific immune response promoter is preferentially induced to the j-type reaction. 48. A method for inhibiting the development of cancer in a patient, #includes the patient U Inject the effective amount of the pharmaceutical composition according to Article 4 q or 4 of the patent application. '49·: A method for suppressing cancer in a patient's fetus (4), which has been vaccinated according to claim 41 or 45 of the patent. 5〇· A method for removing tumor cells from a biological sample, comprising: contacting a biological sample with a T cell capable of reacting with a prostate tumor protein, Beneficial, wherein the tumor protein comprises: An amino acid sequence encoded by a polynucleotide sequence selected from the group consisting of: (1) in the sequence recognition 225_305, 307-315, 332-335, 340-375, Ml, 382 or 384-472 And a polyhydric acid; and (11) a sequence complementary to the polynucleotide of the above; the step of contacting is performed under conditions and for a time sufficient to permit removal of the J-adenosperm protein from the sample. . 51. A liquid or part thereof according to item 5 of the scope of the patent application. Wherein the biological sample is blood 52. A method of inhibiting the development of cancer in a patient, comprising administering to the patient 127691.doc 200815476 a biological sample treated according to the method of claim 50 of the patent application. 53. A method of stimulating and/or amplifying a butyl cell specific for a prostate tumor, comprising 'making a 5 HAI T cell with a condition and time sufficient to allow stimulation and/or enlargement of the T cell. Multiple: (i) a polypeptide according to item 1 of the scope of the patent application; (ii) provided by any one of the sequence identifications 225-305, 307-315, 332-335, 340-375, 381, 382 or 384_472 a sequence of a polynucleic acid-encoded polypeptide; (iii) a multinuclear acid encoding a polypeptide of (i) or (ii); and/or (iv) an antigen-producing cell contact of the polypeptide of (1) or (ii). 54. An isolated tau cell group comprising tau cells prepared according to the method of claim 53 of the patent application. 55. A method of inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of a T cell group according to claim 54 of the patent application. 56. A method of inhibiting the development of cancer in a patient, comprising the steps of: (a) cultivating CD4+ and/or CD8+ T cells isolated from the patient with at least one member selected from the group consisting of: (i) The polypeptide of claim 1; (ii) encoded by a polynucleotide comprising a sequence provided by any one of sequence identifications 225-305, 307-315, 332_335, 340_3 75, 381, 382 or 384-472 a polypeptide; (111) a polynucleotide encoding a polypeptide of (1) or (Π); or (iv) a cell providing antigen of (i) or (Π), such that the T cell is thinned; and 127691.doc 200815476 (b) administering to the patient an effective amount of proliferating tau cells and thereby inhibiting the development of cancer in the patient. 5 7 A method for inhibiting the development of cancer in a patient, comprising the steps of: Ο) cultivating CD4 + and/or CD8 + Τ cells isolated from the patient with at least one member selected from the group consisting of: (i) a polypeptide according to item 1 of the patent application; (ii) provided by any one of the sequence identifications 225-305, 307-3 15, 332-335, 3 40-3 75, 381, 382 or 384-472 a sequence of a polynucleotide encoding a polynucleic acid; (iii) a polynucleic acid encoding a polypeptide of (1) or (ii); or (iv) a cell providing an antigen of the polypeptide of (1) or (ii) such that the T cell proliferate; b) selecting at least one cell that has proliferated; and (0) administering to the patient an effective amount of the selected tau cells, thereby inhibiting the development of cancer in the patient. 5 8 · A method for the presence or absence of a patient, comprising the steps of: (a) contacting a biological sample obtained from the patient with a binding agent that binds to a prostate tumor protein, wherein the tumor protein comprises a polynuclear alumina selected from the group consisting of Sequence-encoded amino acid sequence: (1) in sequence a polynuclear acid provided by any one of 225-305, 307-3 15, 332-335, 340_375, 381, 382 or 384_472; and (ii) a sequence complementary to the polynucleotide described above; 127691.doc 200815476 The content of the polypeptide bound to the binding agent; (C) comparing the content of the polypeptide with a predetermined cutoff value, and determining whether the cancer is present or not in the patient. 59. According to the scope of the patent application 58 In the case of the formula, the binding agent is an antibody. 60. According to the scope of the patent application, item 59, the ^ ^ ^ ^ Κ 法 method, wherein the antibody is a monoclonal antibody. η (b) detection in the test The method of claim 5, wherein the cancer is prostate cancer 0 62. A method for monitoring cancer in a patient, comprising the following steps: (4) obtaining the first time from the The biological sample of the patient is contacted with a binding agent that binds to the prostate tumor protein, wherein the tumor protein comprises a multinucleus as mentioned in any of sequence identifications 225-305, 307_315, 332_335, 34〇375, 38b382 or 384_472 Acid, or any The above multinuclear: y: acid-complementary sequence-encoded amino acid sequence; (b) detecting the content of the polypeptide bound to the binding agent in the sample; (4) repeating steps (4) and (b)' obtained from the patient after use a biological sample; and (d) comparing the amount of the polypeptide detected in step (c) with the amount detected in the step, and monitoring the cancer in the patient from the towel. 63. The method of claim 62, wherein the binding agent is an antibody. 64. The method of claim 63, wherein the antibody is a monoclonal antibody. [65] According to the method of claim 62, wherein the cancer is prostate 127691.doc -10 - 200815476 66. A method for determining whether a cancer is in the presence or absence of a body, including the following steps (4) contacting a biological sample obtained from the patient with an oligonucleotide that hybridizes to a polynuclear acid encoding a prostate tumor protein, wherein the tumor protein is comprised by sequence recognition 225-3〇5, 3〇7-315 , 332-340 375, 381, 382 or 384-472, the ribonium sequence referred to in any one of the above, or any amino acid encoded by a sequence complementary to the above multinuclear acid; (b) detection In the sample, the content of the multinuclear acid that hybridizes with the nucleus acid; and (4) comparing the content of the polynuclear phthalic acid hybridized with the oligonucleoside acid to a predetermined cutoff value, and determining the cancer from the towel The presence or absence of the patient. 67. The method of claim 66, wherein a polymerase chain reaction is used to determine the amount of polynucleic acid that hybridizes to the oligonucleic acid. 68. The method according to claim 66, wherein a hybridization assay is used to determine the amount of polynucleotide that hybridizes to the oligonucleotide. 69. A method for monitoring cancer in a patient, comprising the steps of: (4) contacting a biological sample obtained from the patient with an oligonucleotide that can hybridize with a polynuclear acid encoding a prostate tumor protein, wherein The tumor protein includes any of the multi-nuclear ophthalmic acids mentioned in any of the sequence identifications 225-305, 307-315, 340-375, 381, 382 or 384-472, or any of the sequences encoded by the multi-core money complementary to the above 127691. .doc -11 · 200815476 Amino acid sequence; biological sample obtained from the patient after the use of polynucleic acid which is hybridized with 5 oligo-nucleotide; (b) Determination of the content in the sample; (C) The steps (a) and (b) and (a) are detected in the step of the polyacid content and in step (b:: to the combination of 1 ' and from which the cancer is monitored in the patient's body. 70. The method of claim &lt;+, item, wherein a polymerase chain reaction is used to determine the amount of polynucleic acid in the nucleus of the nucleus. 71. The method of claim 69, wherein a hybridization assay is used to determine the amount of polynuclear _ hybridized to the oligonucleic acid. 72. A diagnostic tool set comprising: () or an antibody according to the second aspect of the patent application; and (b) a detection reagent comprising a reporter group. 73. (4) Please consult the tool group in item 72 of the patent scope, in which the antibody is immobilized on a solid support. 7 4 · According to the patented group of 73 patented whistle, the solid support includes nitrocellulose, latex or plastic material. 75. The health care kit according to item 72 of the patent application, wherein the detection reagent comprises anti-immunoglobulin, protein G, protein raft or lectin. 76. The tool set according to claim 72, wherein the reporter group is selected from the group consisting of a radioisotope, a fluorescent group, a luminescent group, an enzyme, a biotin, and a dye particle. 127691.doc -12- 200815476 77 - an oligonucleotide, comprising ι〇 to 40 nucleotides, which hybridizes under moderately stringent conditions to a polynucleic acid encoding a prostate tumor protein, wherein the tumor protein comprises In sequence identification 225, 227-305, 307-3 15 , 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, Polynucleotide referred to in any of 413, 415-419, 422, 426, 427, 432, 434, 435 '442-444, 446, 450, 452, 453, 45 9-461, 468-471 or 472 Or the sequence complementary to the above-described polynuclear decanoic acid encodes the amino acid sequence of hydrazine. 78. The oligonucleotide according to claim 77, wherein the oligonucleotide comprises 10-40 in sequence recognition 225, 227-305, 307-315, 332, 334, 350-365, 381, 382 , 384, 386, 389, 390, 392, 393, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442-444, 446, 450 The multinuclear acid accepting acid mentioned in any one of 452, 453, 459_461, 468_471 or 472. 79. A diagnostic tool set comprising: (4) an oligonucleotide according to claim 77; and (8) a diagnostic reagent used in each chain reaction or hybridization analysis of the polymerized oxime. 127691.doc •13·