HK1040743A1 - Compositions and methods for therapy and diagnosis of prostate cancer - Google Patents

Description

Compositions and methods for the treatment and diagnosis of prostate cancer

Technical Field

The present invention relates generally to the treatment and diagnosis of cancer, such as prostate cancer. The invention more particularly relates to polypeptides comprising at least a portion of a prostate tumor protein and polynucleotides encoding these polypeptides. These polypeptides and polynucleotides may be used in vaccines and pharmaceutical compositions to prevent and treat prostate cancer, and to diagnose and monitor these cancers.

Background

Prostate cancer is the most common cancer in men, with an estimated incidence of 30% in men over 50 years of age. Considerable clinical evidence suggests that human prostate cancer has a tendency to metastasize to bone, and the disease appears to progress inevitably from an androgen-dependent state to an androgen-refractory state, leading to increased patient mortality. This widespread disease is currently becoming the second highest cause of cancer death in american men.

Despite many studies on the treatment of this disease, prostate cancer remains refractory. Typically, treatment is based on surgery and/or radiation therapy, but in a significant proportion of cases these methods are ineffective. Two previously identified prostate-specific proteins, prostate-specific antigen (PSA) and Prostatic Acid Phosphatase (PAP), have limited therapeutic and diagnostic potential. For example, PSA levels do not always correlate well with the presence of prostate cancer, but are positive in a subset of non-prostate cancers, including Benign Prostatic Hyperplasia (BPH). In addition, PSA measurements were related to prostate volume size and did not show metastatic levels.

Despite much research into the treatment of these and other cancers, prostate cancer remains difficult to diagnose and treat effectively. Accordingly, there remains a need in the art for improved methods for detecting and treating these cancers. The present invention fulfills these needs and further provides other related advantages.

Summary of The Invention

Briefly, the present invention provides compositions and methods for the diagnosis and treatment of cancer, such as prostate cancer. In one aspect, the invention provides a polypeptide comprising at least a portion of a prostate tumor protein or a variant thereof. Certain portions and variants are immunogenic such that the ability of the variant to react with antigen-specific antisera is not substantially reduced. In certain embodiments, the polypeptide comprises at least an immunogenic portion of a prostate tumor protein or a variant thereof, wherein the tumor protein comprises an amino acid sequence encoded by the following polynucleotide sequence: (a) 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472; (b) a sequence that hybridizes to any of the above sequences under moderately stringent conditions; and (c) the complement of any of the sequences of (a) or (b). In certain specific embodiments, such polypeptides comprise at least a portion of a tumor protein or a variant thereof, wherein the tumor protein comprises the amino acid sequence recorded in any of SEQ ID NOs 112-114, 172, 176, 178, 327, 329, 331, 336, 339, 376-380 and 383.

The invention also provides polynucleotides encoding the above polypeptides or portions thereof (such as at least the portion encoding 15 amino acid residues of a prostate tumor protein), expression vectors comprising these polynucleotides, and host cells transformed or transfected with these expression vectors.

In another aspect, the invention provides a pharmaceutical composition comprising the polypeptide or polynucleotide described above and a physiologically acceptable carrier.

In a related aspect of the invention, there is provided a vaccine comprising the above polypeptide or polynucleotide and a non-specific immune response enhancer.

The present invention also provides a composition comprising: (a) an antibody or antigen-binding fragment thereof that specifically binds to a prostate tumor protein; and (b) a physiologically acceptable carrier.

In other aspects, the invention provides a composition comprising: (a) antigen presenting cells expressing the above polypeptides; and (b) a pharmaceutically acceptable carrier or excipient. Antigen presenting cells include dendritic cells, macrophages, monocytes, fibroblasts and B cells.

In a related aspect, there is provided a composition comprising: (a) antigen presenting cells expressing the above polypeptides; and (b) a non-specific immune response enhancer.

In other aspects, the invention also provides fusion proteins comprising at least one of the above polypeptides, and polynucleotides encoding these fusion proteins.

In a related aspect, pharmaceutical compositions comprising a fusion protein or a polynucleotide encoding a fusion protein in combination with a physiologically acceptable carrier are provided.

In other aspects, vaccines comprising the fusion protein or the polynucleotide encoding the fusion protein in combination with a non-specific immune response enhancer are also provided.

In other aspects, the invention provides a method of inhibiting the development of cancer in a patient comprising administering to the patient a pharmaceutical composition or vaccine as described above.

In other aspects, the invention also provides methods for removing tumor cells from a biological sample comprising contacting the biological sample with T cells that specifically react with a prostate tumor protein under conditions and for a time sufficient to remove cells expressing the protein from the sample.

In a related aspect, a method of inhibiting the development of cancer in a patient is provided, comprising administering to the patient a biological sample treated as described above.

In other aspects, methods are also provided for stimulating and/or expanding T cells specific for prostate tumor protein, comprising contacting T cells with one or more of the following under conditions and for a time sufficient to stimulate and/or expand T cells: (a) the above-mentioned polypeptide; (b) polynucleotides encoding such polypeptides; and/or (c) antigen presenting cells expressing such polypeptides. Also provided are isolated T cell populations comprising T cells prepared as described above.

In other aspects, the invention provides a method of inhibiting the development of cancer in a patient comprising administering to the patient an effective amount of a population of T cells as described above.

The present invention also provides a method of inhibiting the development of cancer in a patient comprising the steps of: (a) incubating CD4+ and/or CD8+ T cells isolated from a patient with one or more of: a polypeptide comprising at least an immunogenic portion of a prostate tumor protein; (ii) a polynucleotide encoding such a polypeptide; and (iii) antigen presenting cells expressing such polypeptides; and (b) administering to the patient an effective amount of proliferating T cells, and thereby inhibiting the development of cancer in the patient. The proliferating cells may (but need not) be cloned prior to administration to a patient.

In other aspects, the invention provides methods for determining the presence or absence of cancer in a patient comprising: (a) contacting a biological sample obtained from the patient with a binding agent (capable of binding to the polypeptide): (b) detecting the amount of polypeptide bound to the binding agent in the sample; and (c) comparing the amount of the polypeptide to a predetermined threshold value, and thereby determining the presence or absence of cancer in the patient. In a preferred embodiment, the binding agent is an antibody, more preferably a monoclonal antibody. The cancer may be prostate cancer.

In other aspects, the invention also provides methods of monitoring the progression of cancer in a patient. The method comprises the following steps: (a) contacting a biological sample obtained from the patient at a first time point with a binding agent capable of binding to the polypeptide; (b) detecting the amount of polypeptide bound to the binding agent in the sample; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent second time point; and (d) comparing the amount of polypeptide detected in step (c) with the amount detected in step (b), thereby monitoring the development of cancer in the patient.

In other aspects, the invention also provides a method for determining the presence or absence of cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide encoding a prostate tumor protein; (b) detecting the amount of polynucleotide (preferably mRNA) hybridised to the oligonucleotide in the sample; and (c) comparing the amount of polynucleotide hybridized to the oligonucleotide to a predetermined threshold value, and thereby determining the presence or absence of cancer in the patient. In certain embodiments, the amount of mRNA is detected by polymerase chain reaction using, for example, at least one oligonucleotide primer that hybridizes to a polynucleotide encoding a polypeptide as described above or its complement. In other embodiments, the amount of mRNA is detected by hybridization techniques using oligonucleotide probes that hybridize to the polynucleotide encoding the polypeptide described above or its complement.

In a related aspect, there is provided a method of monitoring the development of cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide encoding a prostate tumor protein; (b) detecting the amount of polynucleotide hybridized to the oligonucleotide in the sample; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a second time point; and (d) comparing the amount of polynucleotide detected in step (c) with the amount detected in step (b), and thereby monitoring the development of cancer in the patient.

In other aspects, the invention provides antibodies, such as monoclonal antibodies, that bind to the above polypeptides, and diagnostic kits comprising these antibodies. Also provided are diagnostic kits comprising one or more of the above oligonucleotide probes or primers.

These and other aspects of the invention will be apparent upon reference to the following detailed description and attached drawings. All references disclosed herein are incorporated by reference in their entirety as if each was individually incorporated.

Brief description of the figures and sequence identifiers

Figure 1 illustrates the ability of T cells to kill fibroblasts expressing representative prostate tumor polypeptide P502S, compared to control fibroblasts. The percentage of dissolution is shown as effector: a series of ratios of target cells.

Figures 2A and 2B illustrate the ability of T cells to recognize cells expressing the representative prostate tumor polypeptide P502S. In each case, the number of interferon gamma spots for different numbers of responders is shown. In FIG. 2A, data for P2S-12 peptide pulsed fibroblasts are shown, compared to control E75 peptide pulsed fibroblasts. In FIG. 2B, data for fibroblasts expressing P502S are shown, compared to fibroblasts expressing HER-2/neu.

FIG. 3 shows a peptide competition binding experiment showing that P1S #10 peptide derived from P501S binds to HLA-A2. In the TNF release bioassay, P1S #10 peptide inhibited HLA-A2-restricted presentation of FluM58 peptide to CTL clone D150M 58. D150M58 CTL is specific for HLA-A2 binding to influenza matrix peptide FluM 58.

FIG. 4 illustrates the ability of T cell lines established from P1S #10 immunized mice to specifically lyse P1S #10 pulsed Jurkat A2Kb target cells and P501S transduced Jurkat A2Kb target cells, compared to EGFP transduced Jurkat A2 Kb. Percent dissolution is shown as effector: a series of ratios of target cells.

FIG. 5 illustrates the ability of T cell clones to recognize and specifically lyse Jurkat A2Kb cells expressing the representative prostate tumor polypeptide P501S, and thus indicates that the P1S #10 peptide may be a naturally processed epitope of the P501S polypeptide.

FIGS. 6A and 6B illustrate the specificity of the CD8+ cell line (3A-1) for a representative prostate tumor antigen (P501S). FIG. 6A shows⁵¹Results of Cr release experiments. Percent specific lysis is shown as effector: a series of ratios of target cells. Fig. 6B shows various effectors: target cell ratios 3A-1 cells stimulated with autologous B-LCL transduced with P501S produced levels of interferon-gamma.

SEQ ID NO 1 is the determined cDNA sequence of F1-13

SEQ ID NO 2 is the determined 3' cDNA sequence of F1-12

SEQ ID NO 3 is the determined 5' cDNA sequence of F1-12

SEQ ID NO4 is the determined 3' cDNA sequence of F1-16

SEQ ID NO 5 is the determined 3' cDNA sequence of H1-1

SEQ ID NO 6 is the determined 3' cDNA sequence of H1-9

SEQ ID NO 7 is the determined 3' cDNA sequence of H1-4

SEQ ID NO 8 is the determined 3' cDNA sequence of J1-17

SEQ ID NO 9 is the determined 5' cDNA sequence of J1-17

SEQ ID NO 10 is the determined 3' cDNA sequence of L1-12

SEQ ID NO 11 is the determined 5' cDNA sequence of L1-12

SEQ ID NO 12 is the determined 3' cDNA sequence of N1-1862

SEQ ID NO 13 is the determined 5' cDNA sequence of N1-1862

14 is the determined 3' cDNA sequence of J1-13

SEQ ID NO 15 is the determined 5' cDNA sequence of J1-13

16 is the determined 3' cDNA sequence of J1-19

SEQ ID NO 17 is the determined 5' cDNA sequence of J1-19

18 is the determined 3' cDNA sequence of J1-25

SEQ ID NO 19 is the determined 5' cDNA sequence of J1-25

SEQ ID NO 20 is the determined 5' cDNA sequence of J1-24

21 is the determined 3' cDNA sequence of J1-24

SEQ ID NO 22 is the determined 5' cDNA sequence of K1-58

SEQ ID NO 23 is the determined 3' cDNA sequence of K1-58

SEQ ID NO 24 is the determined 5' cDNA sequence of K1-63

SEQ ID NO 25 is the determined 3' cDNA sequence of K1-63

26 is the determined 5' cDNA sequence of L1-4

27 is the determined 3' cDNA sequence of L1-4

28 is the determined 5' cDNA sequence of L1-14

SEQ ID NO. 29 is the determined 3' cDNA sequence of L1-14

30 is the determined 3' cDNA sequence of J1-12

31 is the determined 3' cDNA sequence of J1-16

32 is the determined 3' cDNA sequence of J1-21

33 is the determined 3' cDNA sequence of K1-48

34 is the determined 3' cDNA sequence of K1-55

35 is the determined 3' cDNA sequence of L1-2

36 is the determined 3' cDNA sequence of L1-6

SEQ ID NO 37 is the determined 3' cDNA sequence of N1-1858

38 is the determined 3' cDNA sequence of N1-1860

SEQ ID NO 39 is the determined 3' cDNA sequence of N1-1861

SEQ ID NO 40 is the determined 3' cDNA sequence of N1-1864

41 is the determined cDNA sequence of P5

42 is the determined cDNA sequence of P8

43 is the determined cDNA sequence of P9

44 is the determined cDNA sequence of P18

SEQ ID NO45 is the determined cDNA sequence of P20

SEQ ID NO 46 is the determined cDNA sequence of P29

47 is the determined cDNA sequence of P30

SEQ ID NO 48 is the determined cDNA sequence of P34

SEQ ID NO 49 is the determined cDNA sequence of P36

SEQ ID NO 50 is the determined cDNA sequence of P38

51 is the determined cDNA sequence of P39

52 is the determined cDNA sequence of P42

53 is the determined cDNA sequence of P47

54 is the determined cDNA sequence of P49

SEQ ID NO 55 is the determined cDNA sequence of P50

56 is the determined cDNA sequence of P53

57 is the determined cDNA sequence of P55

SEQ ID NO 58 is the determined cDNA sequence of P60

SEQ ID NO 59 is the determined cDNA sequence of P64

SEQ ID NO 60 is the determined cDNA sequence of P65

SEQ ID NO 61 is the determined cDNA sequence of P73

SEQ ID NO 62 is the determined cDNA sequence of P75

63 is the determined cDNA sequence of P76

64 is the determined cDNA sequence of P79

SEQ ID NO 65 is the determined cDNA sequence of P84

66 is the determined cDNA sequence of P68

67 is the determined cDNA sequence of P80

SEQ ID NO 68 is the determined cDNA sequence of P82

69 is the determined cDNA sequence of U1-3064

SEQ ID NO 70 is the determined cDNA sequence of U1-3065

71 is the determined cDNA sequence of V1-3692

72 is the determined cDNA sequence of 1A-3905

73 is the determined cDNA sequence of V1-3686

74 is the determined cDNA sequence of R1-2330

75 is the determined cDNA sequence of 1B-3976

76 is the determined cDNA sequence of V1-3679

77 is the determined cDNA sequence of 1G-4736

78 is the determined cDNA sequence of 1G-4738

79 is the determined cDNA sequence of 1G-4741

SEQ ID NO 80 is the determined cDNA sequence of 1G-4744

81 is the determined cDNA sequence of 1G-4734

82 is the determined cDNA sequence of 1H-4774

83 is the determined cDNA sequence of 1H-4781

84 is the determined cDNA sequence of 1H-4785

85 is the determined cDNA sequence of 1H-4787

86 is the determined cDNA sequence of 1H-4796

SEQ ID NO 87 is a 1I-4807 determined cDNA sequence

88 is the determined cDNA sequence of 1I-4810

89 is the determined cDNA sequence of 1I-4811

SEQ ID NO 90 is the determined cDNA sequence of 1J-4876

91 is the determined cDNA sequence of 1K-4884

SEQ ID NO 92 is the determined cDNA sequence of 1K-4896

93 is the determined cDNA sequence of 1G-4761

94 is the determined cDNA sequence of 1G-4762

SEQ ID NO 95 is the determined cDNA sequence of 1H-4766

96 is the determined cDNA sequence of 1H-4770

97 is the determined cDNA sequence of 1H-4771

98 is the determined cDNA sequence of 1H-4772

SEQ ID NO 99 is the determined cDNA sequence of 1D-4297

SEQ ID NO 100 is the determined cDNA sequence of 1D-4309

101 is the determined cDNA sequence of 1D.1-4278

102 is the determined cDNA sequence of 1D-4288

103 is the determined cDNA sequence of 1D-4283

104 is the determined cDNA sequence of 1D-4304

105 is the determined cDNA sequence of 1D-4296

106 is the determined cDNA sequence of 1D-4280

107 is the full-length cDNA sequence determined for F1-12 (also known as P504S)

108 is the predicted amino acid sequence of F1-12

109 is the determined full-length cDNA sequence of J1-17

110 is the full-length cDNA sequence determined for L1-12

111 is the full-length cDNA sequence determined for N1-1862 in SEQ ID NO

112 is the predicted amino acid sequence of J1-17

113 is the predicted amino acid sequence of L1-12

SEQ ID NO 114 is the predicted amino acid sequence of N1-1862

115 is the determined cDNA sequence of P89

116 is the determined cDNA sequence of P90

117 is the determined cDNA sequence of P92

118 is the determined cDNA sequence of P95

119 is the determined cDNA sequence of P98

120 is the determined cDNA sequence of P102

121 is the determined cDNA sequence of P110

122 is the determined cDNA sequence of P111

123 is the determined cDNA sequence of P114

124 is the determined cDNA sequence of P115

125 is the determined cDNA sequence of P116

126 is the determined cDNA sequence of P124

127 is the determined cDNA sequence of P126

128 is the determined cDNA sequence of P130

129 is the determined cDNA sequence of P133

130 is the determined cDNA sequence of P138

131 is the determined cDNA sequence of P143

132 is the determined cDNA sequence of P151

133 is the determined cDNA sequence of P156

134 is the determined cDNA sequence of P157

135 is the P166 determined cDNA sequence

136 is the determined cDNA sequence of P176

137 is the determined cDNA sequence of P178

138 SEQ ID NO 138 determined cDNA sequence of P179

139 is the P185 determined cDNA sequence

140 is the determined cDNA sequence of P192

141 is the determined cDNA sequence of P201

142 is the determined cDNA sequence of P204

143 is the determined cDNA sequence of P208

144 is the determined cDNA sequence of P211

145 is the determined cDNA sequence of P213

146 is the determined cDNA sequence of P219 SEQ ID NO

147 is the determined cDNA sequence of P237

SEQ ID NO. 148 is the determined cDNA sequence of P239

149 is the determined cDNA sequence of P248

SEQ ID NO 150 is the determined cDNA sequence of P251

151 is the determined cDNA sequence of P255

SEQ ID NO 152 is the P256 determined cDNA sequence

153 is the determined cDNA sequence of P259 SEQ ID NO

154 is the determined cDNA sequence of P260

155 is the determined cDNA sequence of P263

156 is the determined cDNA sequence of P264

157 is the determined cDNA sequence for P266

SEQ ID NO 158 is the determined cDNA sequence for P270

159 is the determined cDNA sequence of P272

SEQ ID NO 160 is the determined cDNA sequence of P278

161 is the P105 determined cDNA sequence

162 is the determined cDNA sequence of P107

163 is the determined cDNA sequence of P137 with SEQ ID NO

164 is the determined cDNA sequence of P194

165 is the determined cDNA sequence of P195

166 is the determined cDNA sequence of P196

167 is the P220 determined cDNA sequence of SEQ ID NO

168 is the determined cDNA sequence of P234

169 is the cDNA sequence of P235 determined

170 is the determined cDNA sequence of P243

171 is the determined cDNA sequence of P703P-DE1

172 is the predicted amino acid sequence of P703P-DE1

173 is the determined cDNA sequence of P703P-DE2

174 is the determined cDNA sequence of P703P-DE6

175 is the determined cDNA sequence of P703P-DE13

176 is the predicted amino acid sequence of P703P-DE13

177 is the determined cDNA sequence of P703P-DE14

178 is the predicted amino acid sequence of P703P-DE14

179 is the extended cDNA sequence determined for 1G-4736

SEQ ID NO 180 is the extended cDNA sequence determined for 1G-4738

181 is the determined continued cDNA sequence of 1G-4741

182 is the determined continued cDNA sequence of 1G-4744

183 is the extended cDNA sequence determined for 1H-4774

184 is the determined continuation cDNA sequence of 1H-4781

185 is the extended cDNA sequence determined for 1H-4785

SEQ ID NO:186 is the determined continuation cDNA sequence of 1H-4787

187 is the determined extended cDNA sequence of 1H-4796

188 is the determined continued cDNA sequence of 1I-4807

189 is the determined 3' cDNA sequence of 1I-4810

190 is the determined 3' cDNA sequence of 1I-4811

191 is the determined continuation of the cDNA sequence of 1J-4876

192 is a continuation of the cDNA sequence determined for 1K-4884

193 is a 1K-4896 determined continuation cDNA sequence

194 is the determined continuation of the cDNA sequence of 1G-4761

195 is the extended cDNA sequence determined for 1G-4762

196 is a determined continuation of the cDNA sequence of 1H-4766

197 is the determined 3' cDNA sequence of 1H-4770

198 is the determined 3' cDNA sequence of 1H-4771

SEQ ID NO 199 is the extended cDNA sequence determined for 1H-4772

SEQ ID NO 200 is a continuation of the cDNA sequence determined from 19-4309

SEQ ID NO 201 is a continuation of the cDNA sequence determined for 1D.1-4278

SEQ ID NO 202 is the extended cDNA sequence determined for 1D-4288

203 is the determined continued cDNA sequence of 1D-4283

204 is a determined continuation of the cDNA sequence of 1D-4304

205 is a determined continuation of the cDNA sequence of 1D-4296

SEQ ID NO 206 is the extended cDNA sequence determined for 1D-4280

207 is the determined cDNA sequence of 10-d8fwd

SEQ ID NO 208 is the determined cDNA sequence of 10-H10con

209 is the 11-C8rev determined cDNA sequence

210 is the determined cDNA sequence of 7.g6fwd

211 is the determined cDNA sequence of g6rev 7. SEQ ID NO

212 is the determined cDNA sequence of 8-b5fwd

213 is the determined cDNA sequence of 8-b5rev

214 is the determined cDNA sequence of 8-b6fwd

215 is the determined cDNA sequence of 8-b6rev

216 is the determined cDNA sequence of 8-d4fwd

217 is the determined cDNA sequence of 8-d9rev

218 is the determined cDNA sequence of 8-g3fwd

219 SEQ ID NO is the determined cDNA sequence of 8-g3rev

220 is the determined cDNA sequence of 8-h11rev

221 is the determined cDNA sequence of g-f12fwd

222 is the determined cDNA sequence of g-f3rev

SEQ ID NO 223 is the determined cDNA sequence of P509S

224 is the determined cDNA sequence of P510S

225 is the determined cDNA sequence of P703DE5

226 is the determined cDNA sequence of 9-A11

227 is the determined cDNA sequence of 8-C6

228 is the determined cDNA sequence of 8-H7

229 is the determined cDNA sequence of JPTPN13

230 is the determined cDNA sequence of JPTPN14

231 is the determined cDNA sequence of JPTPN23

232 is the determined cDNA sequence of JPTPN24

233 is a determined cDNA sequence of JPTPN25

234 is the determined cDNA sequence of JPTPN30

235 is the determined cDNA sequence of JPTPN34

236 is the determined cDNA sequence of PTPN35

237 is the determined cDNA sequence of JPTPN36

238 is the determined cDNA sequence of JPTPN38

239 is a determined cDNA sequence of JPTPN39

240 is the determined cDNA sequence of JPTPN40

241 is the determined cDNA sequence of JPTPN41

SEQ ID NO 242 is the determined cDNA sequence of JPTPN42

243 is the determined cDNA sequence of JPTPN45

244 is the determined cDNA sequence of JPTPN46

245 is the determined cDNA sequence of JPTPN51

246 is the determined cDNA sequence of JPTPN56

247 is the determined cDNA sequence of PTPN64

248 is the determined cDNA sequence of JPTPN65

249 is a determined cDNA sequence of JPTPN67

SEQ ID NO 250 is the determined cDNA sequence of JPTPN76

251 is the determined cDNA sequence of JPTPN84

252 is the determined cDNA sequence of JPTPN85

253 is the determined cDNA sequence of JPTPN86

SEQ ID NO 254 is the determined cDNA sequence of JPTPN87

255 is the determined cDNA sequence of JPTPN88

256 is the cDNA sequence determined in JP1F1

SEQ ID NO 257 is the determined cDNA sequence of JP1F2

258 is the determined cDNA sequence of JP1C2

259 is the determined cDNA sequence of JP1B1

260 is the determined cDNA sequence of JP1B2

261 is the determined cDNA sequence of JP1D3

262 is the determined cDNA sequence of JP1A4

SEQ ID NO:263 is the determined cDNA sequence of JP1F5

264 is the determined cDNA sequence of JP1E6

265 is the determined cDNA sequence of JP1D6

266 is the cDNA sequence determined in JP1B5

267 is the determined cDNA sequence of JP1A6

268 is the determined cDNA sequence of JP1E8

269 is the determined cDNA sequence of JP1D7

270 is the determined cDNA sequence of JP1D9

271 is the cDNA sequence determined in JP1C10

272 is the determined cDNA sequence of JP1A9

273 is the determined cDNA sequence of JP1F12

274 is the determined cDNA sequence of JP1E12

275 is the cDNA sequence determined in JP1D11

276 is the determined cDNA sequence of JP1C11

277 is the cDNA sequence determined in JP1C12

278 is the cDNA sequence determined in JP1B12

279 is the determined cDNA sequence of JP1A12

280 is the determined cDNA sequence of JP8G2

281 is the determined cDNA sequence of JP8H1

282 is the determined cDNA sequence of JP8H2

283 is the determined cDNA sequence of JP8A3

284 is the determined cDNA sequence of JP8A4

285 is the determined cDNA sequence of JP8C3

286 is the determined cDNA sequence of JP8G4

287 is the determined cDNA sequence of JP8B6

288 is the determined cDNA sequence of JP8D6

289 is the determined cDNA sequence of JP8F5

290 is the determined cDNA sequence of JP8A8

291 SEQ ID NO. 291 is the determined cDNA sequence of JP8C7

292 is the determined cDNA sequence of JP8D7

293 is a determined cDNA sequence of P8D8

294 is the determined cDNA sequence of JP8E7

295 is the determined cDNA sequence of JP8F8

SEQ ID NO:296 is the determined cDNA sequence of JP8G8

SEQ ID NO:297 is the determined cDNA sequence of JP8B10

298 is the determined cDNA sequence of JP8C10

299 is the determined cDNA sequence of JP8E9

300 is the determined cDNA sequence of JP8E10

301 is the determined cDNA sequence of JP8F9

SEQ ID NO 302 is the determined cDNA sequence of JP8H9

303 is the determined cDNA sequence of JP8C12

304 is the determined cDNA sequence of JP8E11

SEQ ID NO 305 is the determined cDNA sequence of JP8E12

SEQ ID NO 306 is the amino acid sequence of the peptide PS2#12

307 is the determined cDNA sequence of P711P

308 is the determined cDNA sequence of P712P

309 is the determined cDNA sequence of CLONE23

310 is the determined cDNA sequence of P774P

311 is the determined cDNA sequence of P775P

312 is the determined cDNA sequence of P715P

313 is the determined cDNA sequence of P710P

314 is the determined cDNA sequence of P767P

SEQ ID NO 315 is the determined cDNA sequence of P768P

316-325 is the determined cDNA sequence of a previously isolated gene

SEQ ID NO 326 is the determined cDNA sequence of P703PDE5

327 is the predicted amino acid sequence of P703PDE5

328 is the determined cDNA sequence of P703P6.26

329 is the predicted amino acid sequence of P703P6.26

330 is the determined cDNA sequence of P703PX-23

331 is the predicted amino acid sequence of P703PX-23

332 is the determined full-length cDNA sequence of P509S

333 is the determined continued cDNA sequence of P707P (also referred to as 11-C9)

334 is the determined cDNA sequence of P714P

SEQ ID NO 335 is the determined cDNA sequence of P705P (also known as 9-F3)

336 is the predicted amino acid sequence of P705P

337 is the amino acid sequence of peptide P1S #10

338 is the amino acid sequence of peptide p5

339 is the predicted amino acid sequence of P509S

340 is the determined cDNA sequence of P778P

341 is the determined cDNA sequence of P786P

342 is the determined cDNA sequence of P789P

343 is a cloned determined cDNA sequence showing homology with mRNA of human MM46

344 is a cloned determined cDNA sequence showing homology to the mRNA of the human alpha-TNF stimulated ABC protein (ABC50)

345 is a cloned, determined cDNA sequence showing homology to mRNA for human E-cadherin

346 is a cloned, determined cDNA sequence showing homology to mRNA for mitochondrial Serine Hydroxymethyltransferase (SHMT) encoded by the human nucleus

347 is the determined cDNA sequence of a clone showing homology to human natural resistance-associated macrophage protein 2(NRAMP2)

348 is a determined cDNA sequence of a clone showing homology to human phosphoglucomutase-related protein (PGMRP)

349 is a cloned determined cDNA sequence showing homology to mRNA of human proteasome subunit p40

350 is the determined cDNA sequence of P777P

351 is the determined cDNA sequence of P779P

352 is the determined cDNA sequence of P790P

353 SEQ ID NO:353 is the determined cDNA sequence of P784P

354 is the determined cDNA sequence of P776P in SEQ ID NO

355 is the determined cDNA sequence of P780P

356 is the determined cDNA sequence of P544S, SEQ ID NO

357 is the determined cDNA sequence of P745S

358 is the determined cDNA sequence of P782P

359 is the determined cDNA sequence of P783P

360 is an unknown 17984 determined cDNA sequence

361 is the determined cDNA sequence of P787P

362 is the determined cDNA sequence of P788P

363 is an unknown 17994 determined cDNA sequence

364 is the determined cDNA sequence of P781P

365 is the determined cDNA sequence of P785P

366-375 is the cDNA sequence determined for B305D and various splice variants

SEQ ID NO. 376 is the predicted amino acid sequence encoded by the sequence of SEQ ID NO. 366

SEQ ID NO:377 is the predicted amino acid sequence encoded by the sequence of SEQ ID NO:372

378 is the predicted amino acid sequence encoded by the sequence of SEQ ID NO 373

379 is a predicted amino acid sequence encoded by the sequence of SEQ ID NO 374

SEQ ID NO 380 is the predicted amino acid sequence encoded by the sequence of SEQ ID NO 375

381 is the determined cDNA sequence of B716P

382 is the full-length cDNA sequence of P711P determined

383 SEQ ID NO is the predicted amino acid sequence of P711P

384 is the cDNA sequence of P1000C

385 is the cDNA sequence of CGI-82

386 is a cDNA sequence of 23320

SEQ ID NO 387 is the cDNA sequence of CGI-69

388 is the cDNA sequence of L-iditol-2-dehydrogenase

389 cDNA sequence of 23379

390 cDNA sequence of SEQ ID NO 23381

391 is the cDNA sequence of KIAA0122

392 is the cDNA sequence of 23399

393 is the cDNA sequence of the previously identified gene

394 is the cDNA sequence of HCLBP

395 is the cDNA sequence of transglutaminase (Transglutaminase)

396 is the cDNA sequence of a previously identified Gene

397 is the PAP cDNA sequence

SEQ ID NO 398 is the cDNA sequence of the Ets transcription factor PDEF

399 is the cDNA sequence of hTGR

SEQ ID NO 400 is the cDNA sequence of KIAA0295

401 is a cDNA sequence of 22545

402 is a 22547 cDNA sequence

403 is a cDNA sequence of 22548

404 is a 22550 cDNA sequence

405 is a 22551 cDNA sequence

406 is a 22552 cDNA sequence

407 is a 22553 cDNA sequence

408 is a 22558 cDNA sequence

409 cDNA sequence of 22562

410 is a 22565 cDNA sequence

411 is the cDNA sequence of 22567

412 is a 22568 cDNA sequence

413 is a 22570 cDNA sequence

414 is a 22571 cDNA sequence

415 is a cDNA sequence of 22572

416 is a 22573 cDNA sequence

417 is a 22573 cDNA sequence

418 is a 22575 cDNA sequence

419 of the cDNA sequence 22580 in SEQ ID NO

420 is a cDNA sequence of 22581

cDNA sequence of SEQ ID NO 421 is 22582

422 is a 22583 cDNA sequence

423 is a 22584 cDNA sequence

424 is a 22585 cDNA sequence

425 is the cDNA sequence of 22586

426 is a 22587 cDNA sequence

427 is a cDNA sequence of 22588

428 is a 22589 cDNA sequence

cDNA sequence of SEQ ID NO 429 being 22590

430 is a 22591 cDNA sequence

431 is a cDNA sequence of 22592

432 is a 22593 cDNA sequence

433 is a cDNA sequence of 22594

434 is a 22595 cDNA sequence

435 is a 22596 cDNA sequence of SEQ ID NO

436 is the cDNA sequence of 22847

437 is the cDNA sequence of 22848

438 is the cDNA sequence of 22849

439 is the cDNA sequence of 22851

440 is the cDNA sequence of 22852

441 is the cDNA sequence of 22853 of SEQ ID NO

cDNA sequence of SEQ ID NO 442 22854

443 is the cDNA sequence of 22855

444 is a cDNA sequence of 22856

cDNA sequence of SEQ ID NO. 445 is 22857

446 is the cDNA sequence of 23601

SEQ ID NO 447 is the cDNA sequence of 23602

448 is the cDNA sequence of 23605

449 is the cDNA sequence of 23606

450 is the cDNA sequence of 23612

451 is the cDNA sequence of 23614

cDNA sequence of SEQ ID NO 452 is 23618

453 is the cDNA sequence of 23622

454 is a cDNA sequence of a folate hydrolase

455 is the cDNA sequence of LIM protein

456 is the cDNA sequence of a known gene

457 is the cDNA sequence of a known gene

458 is the cDNA sequence of a previously identified gene

SEQ ID NO459 is the cDNA sequence of 23045

460 is the cDNA sequence of 23032

461 is the cDNA sequence of 23054

462-467 is the cDNA sequence of a known gene

468-471 of SEQ ID NO is the cDNA sequence of P710P

472 is the cDNA sequence of P1001C

Detailed Description

As noted above, the present invention relates generally to compositions and methods for the treatment and diagnosis of cancer, such as prostate cancer. The compositions described herein can include prostate tumor polypeptides, polynucleotides encoding these polypeptides, binding agents (such as antibodies), Antigen Presenting Cells (APCs), and/or immune system cells (such as T cells). The polypeptides of the invention typically comprise at least a portion of a prostate tumor protein (such as an immunogenic portion) or a variant thereof. "prostate tumor protein" refers to a protein that is expressed at a level that is at least 2-fold (preferably at least 5-fold) higher in prostate tumor cells than in normal tissues, as determined using representative experiments provided herein. Certain prostate tumor proteins are tumor proteins that detectably react with antisera from prostate cancer patients (in immunological experiments, such as ELISA or Western blots). The polynucleotides of the invention typically comprise a DNA or RNA sequence encoding all or a portion of such a polypeptide. Antibodies are typically immune system proteins or their antigen-binding fragments that are capable of binding to the polypeptides described above. Antigen presenting cells include dendritic cells, macrophages, monocytes, fibroblasts and B cells expressing the above polypeptides. The T cells that can be used in these compositions are typically T cells specific for the polypeptides described above.

The basis of the present invention is the discovery of human prostate tumor proteins. Polynucleotide sequences encoding certain tumor proteins, or portions thereof, are provided in SEQ ID NOS 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382, or 384-472. Polypeptide sequences comprising at least a portion of a tumor protein are provided in SEQ ID NO:112-114, 172, 176, 178, 327, 329, 331, 336, 339, 376-380 and 383. Prostate tumor protein polynucleotides

The present invention includes any polynucleotide or variant thereof described herein that encodes a prostate tumor protein or a portion thereof. Preferred polynucleotides comprise at least 15 contiguous nucleotides, preferably at least 30 contiguous nucleotides, more preferably at least 45 contiguous nucleotides encoding a portion of a prostate tumor protein. More preferably, the polynucleotide encodes an immunogenic portion of a prostate tumor protein. The invention also includes polynucleotides complementary to any of these sequences. Polynucleotides may be single-stranded (coding or antisense) or double-stranded, and may be DNA or RNA molecules (genomic, cDNA or synthetic). RNA molecules include HnRNA molecules that contain introns and correspond to DNA molecules on a one-to-one basis and mRNA molecules that do not contain introns. The polynucleotides of the invention may (but need not) contain other coding or non-coding sequences, and the polynucleotides may (but need not) be linked to other molecules and/or supports.

The polynucleotide may comprise the native sequence (i.e., the endogenous sequence encoding the prostate tumor protein or a portion thereof) or may comprise a variant of such a sequence. A polynucleotide variant may contain one or more substitutions, additions, deletions and/or insertions, but the immunogenicity of the encoded polypeptide is not reduced relative to the native tumor polypeptide. The effect on the immunogenicity of the encoded polypeptide can generally be assessed as described herein. Variants have identity, preferably at least about 70%, more preferably at least about 80%, and most preferably at least about 90% with the polynucleotide encoding the native prostate tumor protein or a portion thereof.

Two polynucleotide or polypeptide sequences are said to be "identical" if the nucleotide or amino acid sequences in the two polynucleotide or polypeptide sequences are identical when aligned for maximum correspondence as described below. Comparisons between two sequences are typically made over a comparison window to identify and compare local regions of sequence similarity. As used herein, a "comparison window" refers to a segment of at least about 20, typically 30 to about 75, 40 to about 50 consecutive positions in which a sequence can be compared to a reference sequence of the same number of consecutive positions after optimal alignment.

Optimal alignment of sequences for comparison can be performed using the Megalign program in the Lasergene module of bioinformatics software (DNASTAR, Inc., Madison, Wis.) using system parameters. This program incorporates various permutations as described in the following references: M.O.Dayhoff (1978) A model of evolution change in proteins-substrates for detecting displacement references.M.O.Dayhoff (eds.) Atlas of Protein Sequence and Structure, national biological Research Foundation, Washington DC, Vol.5, Suppl.3, pp.345-358; hein (1990) Unified Approach to Alignment and phenols, Methods in Enzymology (Methods in Enzymology), volume 183, pp.626-645, Academic Press, Inc., San Diego, Calif.; higgins and P.M.Sharp (1989) CABIOS 5: 151-153; E.W.Myers and W.Muller (1988) CABIOS 4: 11-17; E.D.Robinson (1971) comb.Theor 11: 105; santou and M.Nes (1987) mol.biol.Evol.4: 406-425; sneath and r.r.sokal (1973) Numerical taxomy-the Principles and practice of Numerical taxomy, Freeman Press, San Francisco, CA; wilbur and D.J.Lipman (1983) Proc.Natl.Acad.Sci.USA 80: 726-.

Preferably, the "percent sequence identity" is determined by comparing two optimally aligned sequences over a comparison window of at least 20 positions, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may contain 20% or less additions or deletions (i.e., gaps), typically 5-15%, or 10-12%, as compared to the reference sequence that is optimally aligned and does not contain additions or deletions. This percentage is calculated as follows: determining the number of positions with the same nucleic acid base or amino acid residue in the two sequences to obtain the number of matched positions; the number of matching positions is divided by the total number of positions of the reference sequence (i.e., the window size) and the result is multiplied by 100 to obtain the percentage of sequence identity.

Variants may also/or be substantially homologous to the native gene or to a portion or complement thereof. These polynucleotide variants are capable of hybridizing to naturally occurring DNA sequences (or complementary sequences) encoding native prostate tumor proteins under moderately stringent conditions. Suitable moderately stringent conditions include prewashing in solution 5XSSC, 0.5% SDS, 1.0mM EDTA (pH 8.0); hybridization in 5XSSC at 50-65 ℃ overnight; followed by two washes at 65 ℃ for 20 min each with 2x, 0.5x, and 0.2xSSC containing 0.1% SDS.

One of ordinary skill in the art will appreciate that, due to the degeneracy of the genetic code, there are a wide variety of nucleotide sequences that encode the polypeptides described herein. Some of these polynucleotides have minimal homology to the nucleotide sequence of any native gene. Nonetheless, the present invention expressly includes polynucleotides that vary due to differences in codon usage. In addition, alleles of genes comprising the polynucleotide sequences provided herein are within the scope of the invention. An allele is an endogenous gene that is altered due to one or more mutations, such as deletions, additions and/or substitutions of nucleotides. The resulting mRNA and protein may (but need not) have altered structure or function. Alleles can be identified using conventional techniques, such as hybridization, amplification, and/or database sequence comparison.

Polynucleotides can be prepared using a variety of techniques. For example, polynucleotides can be identified by screening cDNA microarrays (microarray) for tumor-associated expression (i.e., expression in prostate tumors is at least 5-fold higher than in normal tissues as determined using representative experiments provided herein), as described in more detail below. These screens can be carried out using Synteni microarrays (Palo Alto, CA) according to the manufacturer's instructions (and essentially as described in Schena et al [ Proc. Natl. Acad. Sci. USA93: 10614-. Alternatively, the polypeptide can be amplified from cDNA prepared from cells expressing the proteins described herein (such as prostate tumor cells). These polynucleotides can be amplified by Polymerase Chain Reaction (PCR). For this method, sequence-specific primers can be designed based on the sequences provided herein, and can be purchased or synthesized.

The amplified portions can be used to isolate full-length genes from a suitable library, such as a prostate tumor cDNA library, using well-known techniques. In these techniques, libraries are screened using one or more polynucleotide probes or primer pairs (cDNA or genomic) suitable for amplification. Preferably, the library is size selected to contain larger molecules. Random priming libraries may also be preferred for identifying the 5' and upstream regions of genes. Genomic libraries are preferred for obtaining introns and extended 5' sequences.

For hybridization techniques, the partial sequence may be labeled using well-known techniques (e.g., by nick translation or with³²P-terminal tag). The filters containing the denatured bacterial colonies (or lawn containing phage plaques) are then hybridized with labeled probes (see Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor laboratories, Cold Spring Harbor, NY,1989) to screen bacterial or phage libraries. The hybrid colonies or plaques were selected and amplified and the DNA isolated for further analysis. The cDNA clones can be analyzed, for example, by PCR using one primer from the partial sequence and one primer from the vector to determine the amount of the other sequence. Restriction maps and partial sequences can be constructed to identify one or more overlapping clones. The complete sequence can then be determined using conventional techniques, which may involve the construction of a series of deletion clones. The resulting overlapping sequences are then assembled into a single contiguous sequence. Full-length cDNA molecules can be constructed by ligating appropriate fragments using well-known techniques.

Alternatively, a number of amplification techniques can be used to obtain the full-length coding sequence from a partial cDNA sequence. In these techniques, amplification is usually performed by PCR. The amplification step can be carried out using a variety of commercially available kits. Primer design can be performed using, for example, software well known in the art. The primer is preferably 22-30 nucleotides in length, has a GC content of at least 50%, and anneals to the target sequence at a temperature of about 68-72 ℃. The amplified regions can be sequenced as described above and the overlapping sequences assembled into a contiguous sequence.

One such amplification technique is inverse PCR using restriction enzymes to generate fragments of known regions of the gene (see Triglia et al, Nucl. acids Res.16:8186,1988). The fragments are then circularized by intramolecular ligation and used in PCR as a template and divergent primers derived from known regions. In another method, amplification can be performed using primers for the linker sequence and primers specific for known regions to obtain sequences adjacent to the partial sequence. A second round of amplification of the amplified sequence is typically performed using the same adapter primer and a second primer specific for the known region. One variation of this procedure is to use two primers which extend in opposite directions starting from a known region, as described in WO 96/38591. Another such technique is "rapid amplification of cDNA ends" or RACE. This technique involves the use of an inner primer and an outer primer that hybridizes to the polyA region or vector sequence to identify the 5 'and 3' sequences of known sequences. Additional techniques include capture PCR (Lagerstrom et al, PCR Methods application.1: 111-. Other methods using amplification may also be used to obtain full-length cDNA sequences.

In some instances, it is possible to obtain a full-length cDNA sequence by analyzing sequences provided in Expressed Sequence Tag (EST) databases, such as GenBank. Searches for overlapping ESTs can generally be performed using well-known programs (e.g., NCBI BLAST search), and these ESTs can be used to construct contiguous full-length sequences.

Certain nucleic acid sequences of cDNA molecules encoding at least a portion of a prostate tumor protein are provided in: SEQ ID NO 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472. Methods for isolating these polynucleotides are described below. Each of these prostate tumor proteins is overexpressed in prostate tumor tissue.

Polynucleotide variants can generally be prepared by any method known in the art, including chemical synthesis, e.g., solid phase phosphoramidite chemical synthesis. Modifications may also be introduced into a polynucleotide sequence using conventional mutagenesis techniques, such as oligonucleotide-mediated site-specific mutagenesis (see Adelman et al, DNA 2:183, 1983). Alternatively, RNA molecules may be produced by in vitro or in vivo transcription of DNA sequences provided that the DNA encoding the prostate tumor protein or a portion thereof has been inserted into a vector containing a suitable RNA polymerase promoter, such as T7 or SP 6. Certain portions may be used to prepare the encoded polypeptide, as described herein. In addition, a portion of the polynucleotide can be administered to a patient to synthesize the encoded polypeptide in vivo (e.g., by transfecting an antigen presenting cell, such as a dendritic cell, with a cDNA construct encoding a prostate tumor polypeptide, and administering the transfected cell to the patient).

A portion of the sequence complementary to the coding sequence (i.e., the antisense polynucleotide) can also be used as a probe, or to regulate gene expression. cDNA constructs that can be transcribed into antisense RNA can also be introduced into tissue cells to facilitate the production of antisense RNA. As described herein, antisense polynucleotides can be used to inhibit expression of tumor proteins. Antisense technology can be used to control gene expression by a mechanism that forms three helices and impairs the ability of the two helices to open to bind to polymerases, transcription factors or regulatory molecules (see Gee et al, Molecular and immunological applications, Futura Publishing Co., Mt. Kisco, NY; 1994)). Alternatively, antisense molecules can be designed to hybridize to a control region of a gene (e.g., a promoter, enhancer, or transcription initiation site) and block transcription of the gene; or by blocking translation by inhibiting the binding of transcripts to ribosomes.

A portion of the coding sequence or the complement may also be designed as a probe or primer for detecting gene expression. The probes may be labeled with various reporter groups, such as radionuclides and enzymes, and are preferably at least 10 nucleotides, more preferably at least 20 nucleotides, and more preferably at least 30 nucleotides in length. As described above, the length of the primer is preferably 22 to 30 nucleotides.

Any polynucleotide may be further modified to increase in vivo stability. Possible modifications include, but are not limited to, the addition of flanking sequences at the 5 'and/or 3' ends; the use of thioesters of phosphate or 2' O-methyl instead of phosphodiester linkages in the backbone; and/or contain unusual bases such as inosine, queosine, and wybutosine, as well as acetyl-, methyl-, thio-, and other modified forms of adenine, cytosine, guanine, thymine, and uracil.

The nucleotide sequences described herein may be linked to a variety of other nucleotide sequences using established recombinant DNA techniques. For example, polynucleotides can be cloned into a variety of cloning vectors, including plasmids, phagemids, lambda phage derivatives, and cosmids. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. Typically, the vector contains an origin of replication functional in at least one organism, a convenient restriction endonuclease site, and one or more selectable markers. Other elements depend on the design use and are apparent to one of ordinary skill in the art.

In certain embodiments, the polynucleotide may be formulated so as to be capable of entering and being expressed in mammalian cells. These formulations are particularly useful for therapeutic purposes, as described below. One of ordinary skill in the art will appreciate that there are many ways to achieve expression of a polynucleotide in a target cell and that any suitable method may be employed. For example, the polynucleotide may be inserted into a viral vector such as, but not limited to, an adenovirus, an adeno-associated virus, a retrovirus, or vaccinia or other poxvirus (e.g., avian poxvirus). Techniques for inserting DNA into these vectors are well known to those of ordinary skill in the art. Retroviral vectors can also transfer or insert a gene as a selectable marker (to aid in the identification or selection of transduced cells) and/or targeting module (such as ligands encoding receptors on specific target cells, such that the vector has target specificity). Targeting can also be achieved using antibodies by methods known to those of ordinary skill in the art.

Other formulations for therapeutic purposes include colloidal dispersion systems such as macromers, microcapsules, microspheres, beads, and lipid-based systems (including oil-in-water emulsions, micelles, mixed micelles, and liposomes). The preferred colloidal systems for use as delivery vehicles in vitro and in vivo are liposomes (i.e., artificial vesicles). The preparation and use of such systems is well known in the art. Prostate tumor polypeptide

As noted above, in the context of the present invention, the polypeptide may comprise at least an immunogenic portion of a prostate tumor polypeptide or a variant thereof. As described above, "prostate tumor protein" refers to a protein expressed by prostate tumor cells. The protein known as prostate tumor protein may also react detectably with antisera from prostate cancer patients in immunological experiments such as ELISA. The polypeptide may be of any length. There may be other sequences derived from the native protein and/or heterologous sequences, and these sequences may (but need not) have other immunogenic or antigenic properties.

An "immunogenic moiety", as used herein, refers to a portion of a protein that is recognized (i.e., specifically bound) by a B cell and/or T cell surface antigen receptor. These immunogenic portions typically comprise at least 5 amino acid residues, more preferably at least 10 amino acid residues, more preferably at least 20 amino acid residues of the prostate tumor protein or a variant thereof. Certain preferred immunogenic portions include peptides in which the N-terminal leader sequence and/or transmembrane domain have been deleted. Other preferred immunogenic portions may contain short N-and/or C-terminal deletions (e.g., 1-30 amino acids, preferably 5-15 amino acids) relative to the mature protein.

Immunogenic portions can generally be identified using well known techniques, such as those summarized by Paul in Fundamental Immunology, third edition, 243-247(Raven Press,1993) and references thereto. These techniques include the ability to screen polypeptides for antibodies specific for the antigen, anti-serum and/or T cell lines or clones. As used herein, antisera and antibodies are "antigen-specific" if they bind specifically to the antigen (i.e., they react with the protein in an ELISA or other immunoassay and do not detectably react with unrelated proteins). These antisera and antibodies, as described herein, can be prepared using well-known techniques. The immunogenic portion of the native prostate tumor protein is reactive with these antisera and/or T cells to a level substantially no less thanA reactive (e.g., in an ELISA and/or T cell response assay) portion of a full-length polypeptide. These immunogenic portions can react in these experiments at similar or higher levels of reactivity with the full-length polypeptide. These screens can generally be performed using methods well known to those of ordinary skill 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 and contacted with patient serum such that antibodies in the serum bind to the immobilized polypeptide. Unbound polypeptide can then be removed and used (e.g.)¹²⁵I labeled protein a detects bound antibody.

As described above, the composition may comprise a variant of a native prostate tumor protein. Polypeptide "variant", as used herein, refers to a polypeptide that differs from a native prostate tumor polypeptide by one or more substitutions, deletions, additions and/or insertions, but which does not have a substantial decrease in the immunogenicity of the polypeptide. In other words, the ability of a variant to react with antigen-specific antisera may be enhanced or unchanged compared to the native protein, or may be reduced by less than 50%, preferably less than 20%. Such variants can generally be identified by modifying one of the above-described polypeptide sequences and evaluating the reactivity of the modified polypeptide with an antibody or antisera specific for the antigen described herein. Preferred variants include those in which one or more portions, such as the N-terminal leader sequence or transmembrane domain, have been removed. Other preferred variants include those in which a small portion (e.g., 1-30 amino acids, preferably 5-15 amino acids) has been removed from the N-and/or C-terminus of the mature protein. Polypeptide variants preferably exhibit at least about 70%, more preferably at least about 90%, more preferably at least about 95% identity (as determined above) to the identified polypeptide.

Preferably, the variant contains conservative substitutions. "conservative substitution" refers to the substitution of one amino acid for another with similar properties, and one skilled in the art of peptide chemistry would predict that the secondary structure and hydrophilic properties of the polypeptide would be essentially unchanged. Amino acid substitutions may generally be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; while amino acids with uncharged polar head groups that may represent similar hydrophilicity values include leucine, isoleucine, and valine; glycine and alanine; asparagine and glutamine; and serine, threonine, phenylalanine, and tyrosine. Other groups of amino acids that may represent conservative changes include: (1) ala, pro, gly, glu, asp, gln, asn, ser, thr; (2) cys, ser, tyr, thr; (3) val, ile, leu, met, ala, phe; (4) lys, arg, his; and (5) phe, tyr, trp, his. Variants may also/or contain non-conservative changes. In a preferred embodiment, the variant polypeptide differs from the native sequence by a substitution, deletion or addition of 5 or fewer amino acids. Variants may also/or alternatively be modified, for example by deletion or addition of amino acids which have little effect on the immunogenicity, secondary structure and hydrophilic properties of the polypeptide.

As described above, the polypeptide may comprise a signal (or leader) sequence at the N-terminus of the protein that directs protein transfer during or after translation. The polypeptide may also be conjugated to a linker or other sequence to facilitate synthesis, purification or identification of the polypeptide (e.g., polyhistidine), or to enhance binding of the polypeptide to a solid support. For example, the polypeptide may be conjugated to an immunoglobulin Fc region.

Polypeptides can be prepared using a variety of well-known techniques. The recombinant polypeptides encoded by the above-described DNA sequences can be readily prepared from the DNA sequences using a variety of expression vectors known to those of ordinary skill in the art. Expression may be carried out in any suitable host cell transformed or transfected with an expression vector comprising a DNA molecule encoding a recombinant polypeptide. Suitable host cells include prokaryotic cells, yeast, and higher eukaryotic cells. Preferably, the host cell employed is E.coli, yeast or a mammalian cell line (such as COS or CHO). The supernatant from a suitable host/vector system that secretes the recombinant protein or polypeptide into the culture medium is first concentrated using commercially available filters. The concentrate is then purified using a suitable purification matrix, such as an affinity matrix or ion exchange resin. Finally, one or more rounds of reverse phase HPLC may be performed to further purify the recombinant polypeptide.

Polypeptide portions and other variants of less than about 100 amino acids, and often less than about 50 amino acids, can also be produced synthetically using techniques well known to those of ordinary skill in the art. For example, these polypeptides can be synthesized using any commercially available solid phase technique, such as the Merrifield solid phase synthesis method, in which amino acids are added sequentially to a chain of amino acids being extended. See Merrifield, J.Am.chem.Soc.85: 2149-C2146, 1963. Equipment for automated synthesis of polypeptides is commercially available from suppliers such as Perkin Elmer/Applied BioSystems Division (Foster City, CA) and may be operated according to the manufacturer's instructions.

In certain particular embodiments, the polypeptide may be a fusion protein comprising a plurality of the above polypeptides, or comprising at least one of the above polypeptides and an unrelated sequence, such as a known tumor protein. For example, the fusion partner may help provide a T helper epitope (immunological fusion partner), preferably a human recognized T helper epitope, or may help express the protein at a higher yield than the native recombinant protein (expression enhancer). Certain preferred fusion partners are both immunological and expression-enhancing fusion partners. Other fusion partners may be selected to increase the solubility of the protein, or to target the protein to an intracellular compartment of interest. Still further fusion partners include affinity tags to facilitate protein purification.

Fusion proteins can generally be prepared using conventional techniques, including chemical conjugation. Preferably, the fusion protein is expressed as a recombinant protein in an expression system, enabling production at elevated levels relative to the non-fusion protein. Briefly, DNA sequences encoding the polypeptide components may be assembled separately and ligated into an appropriate expression vector. The 3 'end of the DNA sequence encoding one polypeptide component is linked, with or without a peptide linker, to the 5' end of the DNA sequence encoding the second polypeptide component, such that the reading frame of the sequences is identical. This allows translation to a single fusion protein that retains the biological activity of the two component polypeptides.

The peptide linker sequence may be used to separate the first and second polypeptide components by a sufficient distance to ensure that each polypeptide folds into its respective secondary and tertiary structures. Such peptide linker sequences are inserted into the fusion protein using techniques well known in the art. Suitable peptide linker sequences may be selected based on the following factors: (1) the ability to form a flexible extended conformation; (2) the ability to not form secondary structures that can interact with functional epitopes on the first and second polypeptides; and (3) lack of hydrophobic or charged residues that would react with a functional epitope of a polypeptide. Preferred peptide linker sequences contain glycine, asparagine and serine residues. Other nearly neutral amino acids, such as threonine and alanine, can also be used in the linker sequence. Amino acid sequences that can be effectively used as linkers are described in Maratea et al, Gene 40:39-46,1985; murphy et al, Proc.Natl.Acad.Sci.USA 83:8258-8262, 1986; those disclosed in U.S. patent No. 4,935,233 and U.S. patent No. 4,751,180. Linker sequences can generally be 1 to about 50 amino acids in length. Such peptide sequences are not required when the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to separate their functional domains and prevent steric interference.

The ligated DNA sequence is operably linked to suitable transcriptional or translational regulatory elements. The regulatory elements responsible for the expression of the DNA are located only 5' to the DNA sequence encoding the first polypeptide. Similarly, the stop codon and transcription termination signal for termination of translation are located only at the 3' end of the DNA sequence encoding the second polypeptide.

Also provided are fusion proteins comprising a polypeptide of the invention and an unrelated immunogenic protein. Preferred immunogenic proteins are capable of eliciting a memory response. Examples of such proteins include tetanus, tuberculosis and hepatitis proteins (see, e.g., Stoute et al, New Engl. J. Med.336:86-91,1997).

In a preferred embodiment, the immunological fusion partner is derived from protein D (surface protein of the gram-negative bacterium Haemophilus influenzae B, WO 91/18926). Preferably, the protein D derivative comprises approximately the first one-third of the protein (e.g., the first 100-110 amino acids from the N-terminus), and the protein D derivative can be lipidated. In certain preferred embodiments, the N-terminus includes the first 109 residues of the lipoprotein D fusion partner, thereby providing additional foreign T cell epitopes to the polypeptide and increasing the level of expression (and thus functioning as an expression enhancer) in e. The lipid tail ensures optimal display of antigen to antigen presenting cells. Other fusion partners include the nonstructural protein from influenza virus, NS1 (haemagglutinin). Typically, the N-terminal 81 amino acids are used, but different fragments including T helper epitopes may also be used.

In another embodiment, the immunological fusion partner is a protein known as LYTA or a portion thereof (preferably the C-terminal portion). LYTA is obtained from S.pneumoniae synthesizing N-acetyl-L-alanine amidase (known as amidase LYTA, encoded by the LytA Gene, Gene 43:265-292, 1986). LYTA is an autolysin that specifically degrades certain bonds in the peptidoglycan backbone. The C-terminal domain of the LYTA protein is responsible for its affinity for choline or some choline analogs (such as DEAE). This property has been applied to the development of E.coli C-LYTA expression plasmids that can be used to express fusion proteins. Purification of hybrid proteins containing a fragment of C-LYTA at the amino terminus has been described in Biotechnology 10:795-798, 1992. In preferred embodiments, the repeat portion of LYTA may be inserted into the fusion protein. One repeat is found in the C-terminal region, beginning at residue 178. Particularly preferred repeat portions include residues 188-305.

Generally, the polypeptides (including fusion proteins) and polynucleotides described herein are isolated. An "isolated" polypeptide or polynucleotide refers to being separated from its original environment. For example, a naturally occurring protein is isolated if it is separated from some or all of the materials that are present in the natural system. Preferably, these polypeptides are at least about 90% pure, more preferably at least about 95% pure, and most preferably at least about 99% pure. For example, a polynucleotide may be considered isolated if it is cloned into a vector that is not part of its natural environment. Binding agents

The invention also provides agents, such as antibodies and antigen-binding fragments thereof, that specifically bind to prostate tumor proteins. As used herein, antibodies or antigen-binding fragments thereof are said to "specifically bind" to prostate tumor protein if they react at a detectable level (in, e.g., an ELISA) with the prostate tumor protein, but do not react detectably with unrelated proteins under similar conditions. As used herein, "association" refers to non-covalent association between two separate molecules such that a complex is formed. Binding capacity can be assessed, for example, by measuring the binding constant of complex formation. The binding constant is the value obtained by dividing the complex concentration by the product of the concentrations of the components. Generally, when the complex is formed with a binding constant in excess of about 10³L/mol, the two components are said to be "combined". Binding constants can be determined using methods well known in the art.

Using the representative experiments provided herein, the binding agents can also distinguish whether a patient has cancer (such as prostate cancer). In other words, an antibody or other binding agent that binds to prostate tumor protein will produce a signal that indicates the presence of cancer in at least about 20% of patients with the disease and a negative signal that indicates the absence of cancer in at least about 90% of individuals who do not have the cancer. To determine whether a binding agent meets this need, a biological sample (e.g., blood, serum, urine, and/or tumor biopsy) from a patient with or without cancer (as determined using conventional diagnostic tests) can be tested for the presence of a polypeptide that binds to the binding agent as described herein. It is clear that experiments should be performed on a statistically significant number of diseased or non-diseased samples. Each binder should meet the above criteria; however, one of ordinary skill in the art will recognize that binders may be combined to increase sensitivity.

Any agent that meets the above requirements may be used as a binding agent. For example, the binding agent may be a ribosome, RNA molecule or 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 a variety of techniques known to those of ordinary skill in the art. See, for example, Harlow and Lane, Antibodies, Laboratory Manual, Cold Spring Harbor Laboratory, 1988. In general, antibodies can be produced by cell culture techniques, including the production of monoclonal antibodies as described herein, or by transfecting appropriate bacterial or mammalian cell hosts with antibody genes to produce recombinant antibodies. In one technique, an immunogen comprising a polypeptide is first injected into any one of a variety of mammals (e.g., a mouse, rat, rabbit, sheep, or goat). In this step, the polypeptide of the present invention may be used as an unmodified immunogen. Alternatively, particularly for relatively short polypeptides, a better immune response may be elicited if the polypeptide is linked to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin. The immunogen is injected into the animal host, preferably according to a pre-scheduled schedule including one or more boosters, and the animal is periodically bled. Polyclonal antibodies specific for the polypeptide may then be purified from the antiserum, e.g., using affinity chromatography of the polypeptide coupled to a suitable solid support.

Monoclonal antibodies specific for the antigenic polypeptide of interest can be prepared, for example, using the techniques of Kohler and Milstein, Eur.J.Immunol.6:511-519,1976, and modifications thereof. Briefly, these methods involve the preparation of immortalized cell lines capable of producing antibodies with the desired specificity (i.e., reactivity with the polypeptide of interest). These cell lines can be generated, for example, from spleen cells obtained from the above-described immunized animals. The spleen cells are then immortalized, for example, by fusion with a myeloma cell fusion partner, preferably a fusion partner isogenic to the immunized animal. A variety of fusion techniques may be employed. For example, a non-ionic detergent may be mixed with spleen cells and myeloma cells for several minutes, and then plated at low density on selective plates that support growth of heterozygous cells but not myeloma cells. Preferred selection techniques use HAT (hypoxanthine, aminopterin, thymidine) selection. After a sufficient time, usually about 1-2 weeks, colonies of hybrids can be observed. Single colonies were selected and their culture supernatants tested for binding activity to the polypeptide. Hybridoma cells with high reactivity and specificity are preferred.

Monoclonal antibodies can be isolated from the supernatant of growing hybridoma cell colonies. In addition, various techniques can be employed to increase yield, such as injection of the hybridoma cell line into the peritoneal cavity of a suitable vertebrate host (such as a mouse). The monoclonal antibodies can then be harvested from ascites fluid or blood. Contaminants can be removed from the antibody by conventional techniques, such as chromatography, gel filtration, precipitation, and extraction. The polypeptides of the invention may be used in purification processes such as affinity chromatography steps.

In certain embodiments, it may be preferred to use antigen-binding fragments of antibodies. These fragments include Fab fragments which can be prepared using conventional techniques. Briefly, immunoglobulins (Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring harbor Laboratory,1988) can be purified from rabbit serum by affinity chromatography on a protein A bead chromatography column and digested with papain to produce Fab and Fc fragments. The Fab and Fc fragments can be separated by affinity chromatography on a protein a bead column.

The monoclonal antibodies of the invention may be conjugated to one or more therapeutic agents. Suitable agents in this regard include radionuclides, differentiation inducers, drugs, toxins, and derivatives thereof. Preferred radionuclides include⁹⁰Y、¹²³I、¹²⁵I、¹³¹I、¹⁸⁶Re、¹⁸⁸Re、²²¹At, and²¹²and (4) Bi. Preferred drugs include methotrexate, as well as pyrimidine and purine analogs. Preferred differentiation inducers include phorbol esters and butyric acid. Preferred toxins include ricin, abrinToxalbumin, diphtheria toxin, cholera toxin, gelonin (gelonin), pseudomonas exotoxin, shiga toxin, and pokeweed antiviral protein.

The therapeutic agent may be coupled (e.g., covalently bound) to a suitable monoclonal antibody, either directly or indirectly (e.g., via a linking group). If both the reagent and the antibody contain substituents capable of reacting with each other, a direct reaction between them is possible. For example, a nucleophilic group (such as an amino or sulfhydryl group) on one of the two may react with a carbonyl-containing group (such as an anhydride or acid halide) or an alkyl group (such as a halide) containing a readily leaving group on the other of the two.

Alternatively, it may be desirable to couple the therapeutic agent and the antibody via a linking group. The linker group may function as a spacer to space the antibody from the reagent to avoid effects on binding capacity. The linking group may also be used to increase the chemical reactivity of substituents on the reagent or antibody and thereby increase the coupling efficiency. The increase in chemical reactivity may also facilitate the use of reagents or functional groups on reagents that would otherwise not be possible.

It will be apparent to those skilled in the art that a variety of bifunctional or multifunctional reagents (homobifunctional and heterofunctional, such as those described in the catalog of Pierce Chemical co., Rockford, IL) can be employed as linking groups. Coupling can be achieved, for example, by amino, carboxyl, sulfhydryl or oxidized carbohydrate residues. There are numerous references describing these methodologies, such as U.S. Pat. No. 4,671,958 to Rodwell.

If the therapeutic agent is more effective without the antibody moiety of the immunoconjugate of the invention, it may be desirable to use a linking group that can be cleaved during or after entry into the cell. A large number of different cleavable linking groups have been described. Mechanisms by which agents are released from the linker within the cell include cleavage by reducing disulfide bonds (e.g., U.S. Pat. No. 4,489,710 to Spitler), by irradiating photolabile bonds (U.S. Pat. No. 4,625,014 to Senter et al), hydrolysis of derivatized amino acid side chains (e.g., U.S. Pat. No. 4,638,045 to Kohn et al), serum complement-mediated hydrolysis (e.g., U.S. Pat. No. 4,671,958 to Rodwell et al), and acid-catalyzed hydrolysis (e.g., U.S. Pat. No. 4,569,789 to Blattler et al).

It may be desirable to conjugate more than one reagent to the antibody. In one embodiment, the multi-molecule reagent is conjugated to a single molecule antibody. In another embodiment, more than one reagent may be conjugated to one antibody. Regardless of the specific embodiment, immunoconjugates containing more than one agent can be prepared in a variety of ways. For example, more than one agent may be directly conjugated to an antibody molecule, or a linker providing multiple attachment sites may be used. Alternatively, a carrier may be used.

The carrier may carry the agent in a variety of ways, including covalent attachment directly or through a linking group. Suitable carriers include proteins such as albumin (e.g., U.S. patent No. 4,507,234 to Kato et al), peptides, and polysaccharides such as glycosaminoglycans (e.g., U.S. patent No. 4,699,784 to Shih et al). The carrier may also carry the agent by non-covalent association or by encapsulation (such as in liposome vesicles, e.g., U.S. Pat. nos. 4,429,008 and 4,873,088). Carriers specific for radionuclide agents include radiohalogenated small molecules and chelating compounds. For example, U.S. patent No. 4,735,792 discloses representative radiohalogenated small molecules and methods for their synthesis. Radionuclide chelates may be made up of chelating compounds, including those containing nitrogen and sulfur atoms as donor atoms for binding metal or metal oxide radionuclides. For example, U.S. patent No. 4,673,562 to Dayison et al discloses representative chelating compounds and methods for their synthesis.

Various routes of administration can be used for the antibodies and immunoconjugates. Generally, the method of administration may be intravenous, intramuscular, subcutaneous, or performed on the removal of a tumor lesion. It is clear that the exact dosage of antibody/immunoconjugate will vary with the antibody used, the density of antigen on the tumor, and the clearance rate of the antibody. T cells

The immunotherapeutic composition may also/or comprise T cells specific for prostate tumor protein. These cells can generally be prepared in vitro or ex vivo using conventional procedures. For example, T cells can be isolated from bone marrow, peripheral blood, or a portion of bone marrow or peripheral blood of a patient using a cell separation system such as CEPRATETM, which is commercially available from CellPro Inc., Bothell WA (see also U.S. Pat. No. 5,240,856; U.S. Pat. No. 5,215,926; WO 89/06280; WO91/16116 and WO 92/07243). Alternatively, the T cells may be derived from related or unrelated humans, non-human mammals, cell lines or cultures.

T cells can be stimulated with prostate tumor polypeptides, polynucleotides encoding prostate tumor polypeptides, and/or Antigen Presenting Cells (APCs) expressing such polypeptides. Such stimulation is performed under conditions and for a time sufficient to generate T cells specific for the polypeptide. Preferably, the prostate tumor polypeptides and polynucleotides are present in a delivery vehicle (such as microspheres) to facilitate the generation of specific T cells.

A T cell is considered specific for a prostate tumor polypeptide if it kills a target cell that is coated with the polypeptide or that expresses a gene encoding the polypeptide. T cell specificity can be assessed using a variety of conventional techniques. For example, in a chromium release experiment or proliferation experiment, a stimulation index that increases lysis and/or proliferation by more than 2-fold compared to a negative control indicates T cell specificity. These experiments can be performed as described in Chen et al, Cancer Res.54:1065-1070, 1994. Alternatively, detection of T cell proliferation can be accomplished by a variety of known techniques. For example, T cell proliferation can be detected by measuring the rate of increase in DNA synthesis (e.g., by pulsing a culture of T cells with tritium-labeled thymidine and measuring the amount of tritium-labeled thymidine incorporated into the DNA). Contact with prostate tumor polypeptide (100 ng/ml-100. mu.g/ml, preferably 200 ng/ml-25. mu.g/ml) for 3-7 days should result in at least a 2-fold increase in T cell proliferation. Such a 2-3 hour exposure should result in activation of T cells, as described above, which can be measured using conventional cytokine assays, where a 2-fold increase in cytokine release levels (e.g., TNF or TNF-. gamma.) is indicative of T cell activation (see Coligan et al, Current protocols in Immunology, first volume, Wiley Interscience (Greene 1998)). T cells that have been activated in response to prostate tumor polypeptides, polynucleotides, or APCs expressing the polypeptides may be CD 4-and/or CD8 +. Prostate tumor protein-specific T cells can be expanded using conventional techniques. In a preferred embodiment, the T cells are obtained from the patient or a related or unrelated donor and administered to the patient after activation and expansion.

For therapeutic purposes, the number of CD4+ or CD8+ T cells that proliferate in response to a prostate tumor polypeptide, polynucleotide, or APC can be expanded in vitro or in vivo. The in vitro proliferation of these T cells can be performed in a variety of ways. For example, T cells can be exposed to prostate tumor polypeptides, or short peptides corresponding to immunogenic portions of such polypeptides, and/or stimulating cells that synthesize prostate tumor polypeptides, with or without the addition of a T cell growth factor, such as interleukin-2. Alternatively, one or more T cells that proliferate in the presence of prostate tumor protein can be clonally expanded. Methods of cloning cells are well known in the art and include limiting dilution. Pharmaceutical composition and vaccine

In certain aspects, the polypeptides, polynucleotides, T cells, and/or binding agents disclosed herein can be incorporated into a pharmaceutical composition or immunogenic composition (i.e., a vaccine). Pharmaceutical compositions comprise one or more such compounds and a physiologically acceptable carrier. A vaccine may comprise one or more of such compositions and a non-specific immune response enhancer. The non-specific immune response enhancer may be any substance that enhances an immune response to a foreign antigen. Examples of non-specific immune response enhancers include adjuvants, biodegradable microspheres (e.g., polylactactide), and liposomes (in which compounds are incorporated; see, e.g., Fullerton, U.S. Pat. No. 4,235,877). Vaccine preparations are described, for example, in m.f. powell and m.j. newman, eds, "Vaccine Design (the subbunit and adjuvant Vaccine)", Plenum Press (NY, 1995). The pharmaceutical compositions and vaccines within the scope of the present invention may also contain other compounds, both biologically active and inactive. For example, in a composition or vaccine, one or more immunogenic portions of other tumor antigens may be present, either incorporated into the fusion polypeptide or as a separate compound.

The pharmaceutical composition or vaccine may contain DNA encoding one or more of the polypeptides described above, such that the polypeptides may be synthesized in situ. As noted above, DNA may be present in a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacterial and viral expression systems. A number of gene delivery techniques are well known in the art, such as those described by Rolland (Crit. Rev. therapy. drug Carrier Systems 15:143-198,1998) and references cited therein. Suitable nucleic acid expression systems contain DNA sequences required for expression in the patient (such as a suitable promoter and termination signals). Bacterial delivery systems involve the application of bacteria (such as bacillus calmette-guerin) that express immunogenic portions of polypeptides or secrete such epitopes on their cell surface. In a preferred embodiment, the DNA may be introduced using a viral expression system (e.g., vaccinia or other poxvirus, retrovirus, or adenovirus) that may involve a non-pathogenic (defective), replication-competent virus. Suitable systems are disclosed, for example, in Fisher-Hoch et al, Proc. Natl. Acad. Sci. USA 86: 317-; flexner et al, Ann.N.Y.Acad.Sci.569:86-103,1989; flexner et al, Vaccine8:17-21,1990; U.S. Pat. nos. 4,603,112, 4,769,330, and 5,017,487; WO 89/01973; U.S. patent nos. 4,777,127; GB 2,200,651; EP 0,345,242; WO 91/02805; berkner, Biotechniques 6:616-627, 1988; rosenfeld et al, Science 252: 431-; kolls et al, Proc.Natl.Acad.Sci.USA 91:215-219, 1994; Kass-Eisler et al, Proc.Natl.Acad.Sci.USA 90: 11498. 11502, 1993; guzman et al, Circulation88:2838-2848, 1993; and Guzman et al, cir. Res.73: 1202. 1207, 1993. Techniques for incorporating DNA into these expression systems are well known to those of ordinary skill in the art. The DNA may also be "naked" as described in Ulmer et al, Science259: 1745-. Uptake of naked DNA can be increased by coating the DNA onto biodegradable beads that can be efficiently transported into the cell.

While any suitable carrier known to those of ordinary skill in the art may be employed in the pharmaceutical compositions of the present invention, the type of carrier will vary with the mode of administration. The compositions of the invention can be formulated for any suitable mode of administration, including, for example, topical, oral, nasal, intravenous, intracranial, intraperitoneal, subcutaneous, or intramuscular administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, fat, wax or buffer. For oral administration, any of the above carriers or solid carriers can be employed, such as mannitol, lactose, starch, magnesium stearate, sodium saccharin (sodium saccharane), talc, cellulose, glucose, sucrose, and magnesium carbonate. Biodegradable microspheres (e.g., polylactate polyglycolate) can also be employed as carriers for the pharmaceutical compositions of the invention. Suitable biodegradable microspheres are disclosed, for example, in U.S. Pat. nos. 4,897,268 and 5,075,109.

These compositions may also comprise buffers (such as neutral buffered saline or phosphate buffered saline), sugars (such as glucose, mannose, sucrose, or dextran), mannitol, proteins, polypeptides or amino acids (such as glycine), antioxidants, chelating agents (such as EDTA) or glutathione, adjuvants (such as aluminum hydroxide), and/or preservatives. Alternatively, the compositions of the present invention may be formulated as a lyophilizate. The compounds may also be encapsulated within liposomes using well known techniques.

A variety of non-specific immune response enhancers may be employed in the vaccines of the present invention. For example, an adjuvant may be included. Most adjuvants contain substances designed to protect antigens from rapid metabolism, such as aluminium hydroxide or mineral oil, and immune response stimulators, such as lipid a, bordetella pertussis or mycobacterium tuberculosis derived proteins. Suitable adjuvants are commercially available, such as Freund's incomplete and complete adjuvants (Difco Laboratories, Inc., Detroit, MI); MerckAd juvant 65(Merck and Company, Inc., Rahway, NJ); aluminum salts such as aluminum hydroxide gel or aluminum phosphate; calcium, iron or zinc salts; an insoluble suspension of acylated tyrosine; an acylated sugar; a cationically or anionically derivatized polysaccharide; polyphosphazene; biodegradable microspheres; monophosphoryl lipid a and quil a. Cytokines such as GM-CSF or interleukin-2, -7, or-12 may also be used as adjuvants.

In the vaccines provided herein, the adjuvant composition is preferably designed to induce a predominant Th 1-type immune response. High levels of Th1 type cytokines (e.g., IFN-. gamma., IL-2, and IL-12) tend to induce cell-mediated immune responses to the administered antigen. In contrast, high levels of Th 2-type cytokines (e.g., IL-4, IL-5, IL-6, IL-10, and TNF-. beta.) tend to induce humoral immune responses. Following application of the vaccines provided herein, patients will develop immune responses including Th1 and Th2 type responses. In preferred embodiments, where a Th1 type response predominates, the level of Th1 type cytokines will be substantially increased over the level of Th2 type cytokines. The levels of these cytokines can be readily assessed using conventional techniques. For a review of the cytokine family, see Mosmann and Coffman, Ann. Rev. Immunol.7:145-173, 1989.

Preferred adjuvants for eliciting responses predominantly of the Th1 type include, for example, monophosphoryl lipid A, preferably 3-deoxy-acylated monophosphoryl lipid A (3D-MPL), in combination with an aluminium salt. MPL adjuvant is commercially available from Ribi ImmunoChem Research Inc. (Hamilton, MT; see U.S. Pat. Nos. 4,436,727; 4,877,611; 4,866,034 and 4,912,094). CpG-containing oligonucleotides, in which the CpG dinucleotide is unmethylated, also induce a predominantly Th 1-type response. These oligonucleotides are well known and described, for example, in WO 96/02555. Another preferred adjuvant is a saponin, preferably QS21, which may be used alone or in combination with other adjuvants. For example, one enhancement system involves the combination of monophosphoryl lipid A with a saponin derivative, such as QS21 in combination with 3D-MPL as described in WO94/00153, or a less reactogenic composition as described in WO96/33739, where QS21 is quenched with cholesterol. Other preferred formulations comprise oil-in-water emulsions and tocopherols. A particularly effective adjuvant formulation involving QS21, 3D-MPL and tocopherol in an oil-in-water emulsion is described in WO 95/17210. Any of the vaccines provided herein can be prepared using well known methods of combining antigens, immune response enhancers and suitable carriers or excipients.

The compositions described herein may be administered as part of a sustained release formulation (e.g., a formulation such as a capsule or sponge that slowly releases the compound after administration). These formulations can generally be prepared using well known techniques and administered by, for example, oral, rectal, or subcutaneous infusion, or by infusion at the intended target site. Sustained release formulations may contain a polypeptide, polynucleotide or antibody dispersed in a carrier matrix and/or contained within a reservoir surrounded by a rate controlling membrane. The carriers used in these formulations are biocompatible and may also be biodegradable; preferred formulations allow for relatively stable release levels of the active ingredient. The amount of active ingredient contained within the sustained release formulation depends upon the site of infusion, the rate and expected duration of release, and the nature of the condition being treated or prevented.

A variety of delivery vehicles may be employed in pharmaceutical compositions and vaccines to facilitate the generation of an antigen-specific immune response against a target tumor cell. Delivery vehicles include Antigen Presenting Cells (APCs), such as dendritic cells, macrophages, B cells, monocytes and other cells that can be processed into potent APCs. These cells may (but need not) be genetically modified to enhance the ability to present antigens, to enhance the activation and/or maintenance of T cell responses, to have anti-tumor effects themselves, and/or to be immunologically compatible with the recipient (i.e., HLA haplotype-matched). APCs can be isolated from a variety of biological fluids and organs, including tumors and peritumoral tissues, and can be autologous, allogeneic, syngeneic, or allogeneic cells.

Certain preferred embodiments of the invention use dendritic cells or their progenitors as antigen presenting cells. Dendritic cells are highly potent APCs (Banchereau and Steinman, Nature 392: 245-. In general, dendritic cells can be identified based on their typical shape (star-shaped in situ, with prominent cytoplasmic processes (dendrites) visible in vitro), and on the differentiation markers of deleted B cells (CD19 and CD20), T cells (CD3), monocytes (CD14), and natural killer cells (CD56), which can be identified using routine experimentation. Dendritic cells can of course be engineered to express specific cell surface receptors or ligands that are not normally found on dendritic cells in vitro or ex vivo, and the invention encompasses such modified dendritic cells. As an alternative to dendritic cells, dendritic cells loaded with secretory vesicle antigens (referred to as exosomes) may be used in vaccines (see Zitvogel et al, Nature Med.4:594-600, 1998).

Dendritic cells and their progenitors can be derived from peripheral blood, bone marrow, tumor-infiltrating cells, tumor-surrounding tissue-infiltrating cells, lymph nodes, spleen, skin, cord blood, or any other suitable tissue or fluid. For example, dendritic cells can be differentiated ex vivo by the combined addition of cytokines (such as GM-CSF, IL-4, IL-13, and/or TNF- α) to a culture of monocytes harvested from peripheral blood. Alternatively, various combinations of GM-CSG, IL-3, TNF- α, CD40 ligand, LPS, flt3 ligand, and/or other compounds that induce dendritic cell maturation and proliferation can be added to the culture medium to differentiate CD34 positive cells harvested from peripheral blood, umbilical cord blood, or bone marrow into dendritic cells.

Dendritic cells can be conveniently divided into "immature" and "mature" cells to distinguish between two well characterized phenotypes in a simple manner. However, this classification should not be construed as excluding all possible intermediate stages of differentiation. Immature dendritic cells are characterized by APC with better antigen uptake and processing capacity, consistent with high expression of Fc γ receptor, mannose receptor and DEC-205 marker. The mature phenotype is typically characterized by low expression of these markers, while the expression of cell surface molecules responsible for T cell activation (such as MHC class i and ii), adhesion molecules (such as CD54 and CD11), and co-stimulatory factors (such as CD40, CD80, and CD86) are high.

APCs can generally be transfected with a polynucleotide encoding a prostate tumor protein (or a portion or other variant thereof) such that the prostate tumor polypeptide or immunogenic portion thereof is expressed on the cell surface. Such transfection may occur ex vivo, and compositions or vaccines comprising these transfected cells may then be used for therapeutic purposes as described herein. Alternatively, a gene delivery vehicle targeting dendritic cells or other antigen presenting cells can be administered to the patient, resulting in transfection occurring in vivo. For example, in vivo and ex vivo transfection of dendritic cells can generally be performed using any method known in the art (such as those described in WO 97/24447), or the gene gun method described by Mahvi et al (Immunology and Cell Biology 75:456-460, 1997). Antigen loading of dendritic cells is achieved by contacting dendritic cells or their progenitors with prostate tumor polypeptide, DNA (naked or contained in a plasmid vector), or RNA; or with recombinant bacteria or viruses expressing the antigen (e.g., vaccinia, fowl pox virus, adenovirus, or lentiviral vector). Prior to loading, the polypeptide may be covalently conjugated to an immunological partner that provides T cell assistance (e.g., a carrier molecule). Alternatively, dendritic cells can be pulsed with a non-conjugated immunological partner alone or in the presence of a polypeptide. Cancer treatment

In other aspects of the invention, the compositions described herein may be used for immunotherapy of cancer (such as prostate cancer). In these methods, pharmaceutical compositions and vaccines are typically administered to the patient. As used herein, "patient" refers to any warm-blooded animal, preferably a human. The patient may or may not have cancer. Accordingly, the pharmaceutical compositions and vaccines described above can be used to prevent the development of cancer or to treat patients suffering from cancer. Cancer can be diagnosed using criteria generally accepted in the art, including the presence of malignant tumors. The pharmaceutical compositions and vaccines can be administered prior to or after surgical resection of the primary tumor and/or treatment, such as radiation therapy or administration of traditional chemotherapeutic drugs.

In certain embodiments, the immunotherapy may be an active immunotherapy, wherein the treatment relies on the in vivo stimulation of the endogenous host immune system to react with the tumor along with the administration of immune response modifiers (such as the polypeptides and polynucleotides disclosed herein).

In other embodiments, the immunotherapy may be a negative immunotherapy, wherein the treatment involves the delivery of an agent (such as effector cells or antibodies) that has a defined tumor immunoreactivity, is capable of directly or indirectly mediating an anti-tumor effect, and does not necessarily rely on the intact host immune system. Examples of effector cells include the above-described T cells, T lymphocytes (such as CD8+ cytotoxic T lymphocytes and CD4+ T helper tumor infiltrating lymphocytes), killer cells (such as natural killer cells and lymphokine-activated killer cells), B cells, and antigen presenting cells (such as dendritic cells and macrophages) that express the polypeptides provided herein. T cell receptors and antibody receptors specific for the polypeptides recorded herein can be cloned, expressed and transferred into other vectors or effector cells for adoptive immunotherapy. The polypeptides provided herein can also be used to generate antibodies or anti-idiotype antibodies for passive immunotherapy (as described above and U.S. patent No. 4,918,164).

Effector cells can be obtained in sufficient quantities for adoptive immunotherapy, typically by in vitro culture as described herein. Culture conditions for expanding single antigen-specific effector cells into billions of cells that retain the ability to recognize antigens in vivo are well known in the art. These in vitro culture conditions are typically stimulated intermittently with antigens, usually in the presence of cytokines (such as IL-2) and non-dividing feeder cells. As described above, the immunoreactive polypeptides provided herein can be used for rapid expansion of antigen-specific T cell cultures to generate sufficient numbers of cells for immunotherapy. In particular, antigen presenting cells, such as dendritic cells, macrophages, monocytes, fibroblasts, or B cells, may be pulsed with an immunoreactive polypeptide or transfected with one or more polynucleotides using conventional techniques well known in the art. For example, antigen presenting cells may be transfected with polynucleotides having promoters suitable for increasing expression in recombinant viruses or other expression systems. Cultured effector cells for therapeutic use must be able to grow, spread widely, and survive for long periods of time in vivo. Studies have shown that cultured effector cells can induce growth in vivo by repeated stimulation with IL-2-supplemented antigens and survive for long periods of time in significant numbers (see, e.g., Cheever et al, Immunological Reviews 157:177,1997).

Alternatively, a vector expressing a polypeptide as recorded herein can be introduced into antigen presenting cells taken from a patient and clonally propagated ex vivo for return to transplantation into the same patient. The transfected cells can be reintroduced into the patient using any method known in the art, preferably by intravenous, intraluminal, intraperitoneal or intratumoral administration in sterile form.

The route of administration, frequency, and dosage of the therapeutic compositions disclosed herein will vary from individual to individual and can be readily established using conventional methods. Generally, pharmaceutical compositions and vaccines can be administered by injection (e.g., intradermally, intramuscularly, intravenously or subcutaneously), intranasally (e.g., by respiration), or orally. Preferably, 1-10 doses can be administered in 52 weeks. Preferably, 6 doses are administered, each at a monthly interval, and booster inoculations can be performed periodically thereafter. Other protocols may be appropriate for individual patients. Suitable dosages of the compounds are those which, when administered as described above, are capable of promoting an anti-tumor immune response and are at least 10-50% greater than the basal (i.e., untreated) level. These responses can be monitored by measuring anti-tumor antibodies in the patient or by vaccine-dependent generation of cytolytic effector cells that can kill patient tumor cells in vitro. These vaccines should also be able to elicit an immune response in vaccinated patients that results in improved clinical outcome (e.g., more frequent remission, complete or partial or longer disease-free survival) compared to unvaccinated patients. Typically, for pharmaceutical compositions and vaccines comprising one or more polypeptides, the amount of each polypeptide in a dose ranges from 100 μ g to 5mg per kg of host. Suitable dose sizes will vary with the size of the patient, but will typically range from about 0.1 to about 5 mL.

In general, appropriate dosages and treatment regimens will provide sufficient quantities of the active compound to provide therapeutic and/or prophylactic effects. Such responses can be monitored by achieving improved clinical results (e.g., more frequent remission, complete or partial or longer disease-free survival) in treated patients as compared to untreated patients. An increase in the preexisting immune response to prostate tumor proteins is often associated with improved clinical efficacy. These immune responses can generally be assessed using conventional proliferation, cytotoxicity or cytokine assays, and can be performed using samples obtained before and after treatment of the patient. Method for detecting cancer

In general, the presence or absence of cancer in a patient can be detected based on the presence of one or more prostate tumor proteins and/or polynucleotides encoding these proteins in a biological sample (e.g., blood, serum, urine, and/or a tumor biopsy sample) obtained from the patient. In other words, these proteins may serve as markers, indicating the presence or absence of cancer (such as prostate cancer). In addition, these proteins can be used to detect other cancers. The binding agents provided herein are generally capable of detecting the level of antigen bound to the agent in a biological sample. Polynucleotide primers and probes can be used to detect mRNA levels encoding tumor proteins, which also indicate the presence or absence of cancer. Typically, prostate tumor sequences are present at levels at least 3-fold higher in tumor tissue than in normal tissue.

Those of ordinary skill in the art are aware of various protocols for using binding agents to detect polypeptide tags in a sample. See Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. Typically, the presence or absence of cancer in a patient can be determined as follows: (a) contacting a biological sample obtained from a patient with a binding agent; (b) detecting the level of polypeptide bound to the binding agent in the sample; and (c) comparing the polypeptide level to a predetermined cut-off value.

In a preferred embodiment, the assay involves binding of the polypeptide using a binding agent immobilized on a solid support and separated from the rest of the sample. The bound polypeptide can then be detected using a detection agent that contains a reporter group and that specifically binds to the binding agent/polypeptide complex. These detection agents may comprise, for example, a binding agent or antibody that specifically binds to the polypeptide or other reagents that specifically bind to the binding agent, such as an anti-immunoglobulin, protein G, protein a, or lectin. Alternatively, a competition assay may be used in which the polypeptide is labelled with a reporter group and allowed to bind to the immobilised binding agent after incubation of the binding agent with the sample. The extent to which the sample component inhibits binding of the labeled polypeptide to the binding agent is indicative of the reactivity of the sample with the immobilized binding agent. As described above, suitable polypeptides for use in these experiments include full-length prostate tumor protein and a portion to which a binding agent can bind.

The solid support may be any material known to those of ordinary skill in the art to which tumor proteins may be attached. For example, the solid support may be a test well in a microtiter plate or nitrocellulose or other suitable membrane. Alternatively, the support may be a bead or a disc, such as glass, glass fibre, latex or a plastics material such as polystyrene or polyvinyl chloride. The support may also be a magnetic particle or fiber optic sensor such as those disclosed in U.S. Pat. No. 5,359,681. The binding agent may be immobilized on the solid support using a variety of techniques known to those skilled in the art (described in detail in the patent and scientific literature). In the present invention, the term "immobilization" refers to non-covalent binding (such as adsorption) and covalent binding (which may be direct linkage between the reagent and a functional group on the support, or may be linkage through a cross-linking agent). Preferably by adsorption in the wells of a microtiter plate or on a membrane. In these cases, adsorption may be achieved by contacting the binding agent in a suitable buffer with the solid support for an appropriate time. The contact time varies with temperature, but is generally from about 1 hour to about 1 day. Typically, one well of a plastic microtiter plate (such as polystyrene or polyvinyl chloride) is contacted with about 10ng-10 μ g, preferably about 100ng-1 μ g, of binding agent, sufficient to immobilize a suitable amount of binding agent.

Covalent attachment of the binding agent to the solid support may generally be carried out by first reacting the support with a bifunctional reagent capable of reacting with a functional group (such as a hydroxyl or amino group) on the support and binding agent. For example, the binding agent can be covalently attached to a support with an appropriate polymer coating using benzoquinone or by condensation of aldehyde groups on the support with amines and reactive H groups on the binding partner, see Pierce Immunotechnology Catalog and handbook,1991, A12-A13.

In certain embodiments, the assay is a dual antibody sandwich assay. This experiment can be performed by first contacting the antibody that has been immobilized on a solid support (typically the wells of a microtiter plate) with the sample so that the antibody in the sample is able to bind to the immobilized antibody. Unbound sample is then removed from the immobilized polypeptide-antibody complex and a detection agent containing a reporter group (preferably a secondary antibody capable of binding to a different site on the polypeptide) is added. The amount of detection agent still bound to the solid support is then determined using methods appropriate for the specific reporter group.

More specifically, once the antibody is immobilized on the support as described above, the remaining protein binding sites on the support are typically blocked. One of ordinary skill in the art will know of any suitable blocking agent, such as bovine serum albumin or tween 20^TM(Sigma Chemical Co., St. Louis, Mo.). The immobilized antibody is then incubated with the sample to allow the polypeptide to bind to the antibody. Prior to incubation, the sample may be diluted with a suitable diluent, such as Phosphate Buffered Saline (PBS). Generally, an appropriate contact time (i.e., incubation time) is a period of time sufficient to detect the presence of a polypeptide in a sample obtained from an individual having prostate cancer. Preferably, the contact time is sufficient to achieve a level of binding that is at least about 95% of the level of binding at equilibrium for bound and unbound polypeptide). One of ordinary skill in the art recognizes that the time required to reach equilibrium can be readily determined by testing the level of binding that occurs after a period of time. An incubation time of about 30 minutes at room temperature is usually sufficient.

This may then be done by using an appropriate buffer (such as containing 0.1% Tween 20)^TMPBS) to remove unbound sample. A secondary antibody containing a reporter group can then be added to the solid support. Preferred reporter groups include those groups noted above.

The detection agent is then incubated with the immobilized antibody-polypeptide complex for a period of time sufficient to detect the bound polypeptide. The appropriate amount of time can generally be determined by testing the level of binding that occurs after a period of time. Unbound detector is then removed and the bound detector is detected using the reporter group. The method employed to detect the reporter group depends on the nature of the reporter group. For radioactive groups, scintillation counting or autoradiographic methods are generally appropriate. Spectrophotometry can be used to detect dyes, luminescent groups, and fluorescent groups. Biotin can be detected using avidin coupled to a different reporter group, usually a radioactive or fluorescent group or an enzyme. The enzyme reporter group can generally be detected by addition of a substrate (usually for a particular length of time) followed by spectrophotometric or other analysis of the reaction product.

To determine the presence or absence of a cancer (such as prostate cancer), the signal detected from the reporter group that remains bound to the solid support is typically compared to a signal corresponding to a predetermined cut-off value. In a preferred embodiment, the cut-off value for cancer detection is the mean signal obtained by incubating the immobilized antibody with a sample of a patient not suffering from cancer. Typically, samples that produce a signal that exceeds a predetermined cut-off value by 3 standard deviations are considered cancer positive. In another preferred embodiment, the cut-off value is determined using a Receiver operator cutter according to the method of Sackett et al (Clinical epidemic: A basic science for Clinical Medicine, Little Brown and Co.,1985, p.106-7). Briefly, in this embodiment, the cut-off value can be determined from a true positive rate (i.e., sensitivity) and false positive rate (100% specificity) pair plot corresponding to each possible cut-off value of the diagnostic reagent results. Of the cut-off values on the graph, the point closest to the top left (i.e., the value encompassing the largest area) is the most accurate cut-off value, and samples whose signal is determined by this method to be higher than the cut-off value can be considered positive. Alternatively, the threshold may be shifted to the left along the graph to minimize false positive rates, or to the right to minimize false negative rates. Typically, samples that produce a signal higher than the threshold value as determined by this method are considered positive for cancer.

In a related embodiment, the experiment is performed in a flow or color strip test format, wherein the binding agent is immobilized on a membrane (such as nitrocellulose). In a flow assay, polypeptides in a sample will bind to the immobilized binding agent as the sample flows through the membrane. Then, as the solution containing the second labeled binding agent flows through the membrane, the second binding agent will bind to the binding agent-polypeptide complex. Detection of the bound second binding agent can then be performed as described above. In the color bar test format, one end of the binding agent-bound membrane is immersed in a solution containing the sample. The sample moves along the membrane, through the zone containing the second binding agent, to the zone of immobilized binding agent. Concentration of the second binding agent in the immobilized antibody region is indicative of the presence of cancer. Typically, concentration of the second binding agent at the site creates a pattern, such as a line that can be easily seen. The absence of such a pattern indicates a negative result. Typically, the amount of binding agent immobilized on the membrane is selected so that when the biological sample contains a polypeptide at a level sufficient to produce a positive signal in a two-antibody sandwich assay, a visually discernible pattern will be produced in the test format described above. Preferred binding agents for use in these experiments are antibodies and antigen-binding fragments thereof. Preferably, the amount of antibody immobilized on the membrane is from about 25ng to about 1. mu.g, more preferably from about 50 to 500 ng. These tests can generally be performed on very small amounts of biological samples.

Of course, there are numerous other protocols that are suitable for use with the tumor proteins or binding agents of the present invention. The above description is intended to be illustrative only. For example, it will be apparent to those of ordinary skill in the art that the above protocols can be readily modified to use prostate tumor polypeptides to detect antibodies in biological samples that bind to such polypeptides. The detection of these prostate tumor protein-specific antibodies may be related to the presence of cancer.

Tumors can also/or alternatively be detected based on the presence of T cells in the biological sample that specifically react with prostate tumor proteins. In certain methods, a biological sample isolated from a patient comprising CD4+ and/or CD8+ T cells is incubated with a prostate tumor polypeptide, a polynucleotide encoding such a polypeptide, and/or an APC that expresses at least an immunogenic portion of such a polypeptide, and then the specific activation of the T cells is detected. Suitable biological samples include, but are not limited to, isolated T cells. For example, T cells may be isolated by the patient by conventional techniques, such as by Ficoll/Hypaque dense gradient centrifugation of peripheral blood lymphocytes. T cells can be incubated with prostate tumor polypeptide (e.g., 5-25. mu.g/ml) in vitro for 2-9 days (usually 4 days) at 37 ℃. It may be desirable to incubate another portion of the T cells in the absence of prostate tumor polypeptide as a control. For CD4+ T cells, activation is preferably detected by assessing proliferation of T cells. For CD8+ T cells, activation is preferably detected by assessing cytolytic activity. A level of proliferation that is at least 2-fold higher and/or a level of cytolytic activity that is at least 20% higher than a disease-free patient is indicative of the presence of cancer in the patient.

As described above, cancer can also/or alternatively be detected based on the level of mRNA encoding prostate tumor protein in the biological sample. For example, at least two oligonucleotide primers can be employed in a Polymerase Chain Reaction (PCR) -based assay to amplify a portion of prostate tumor cDNA derived from a biological sample, wherein at least one oligonucleotide primer is specific for (i.e., capable of hybridizing to) a polynucleotide encoding a prostate tumor protein. The amplified cDNA is then isolated and detected using techniques well known in the art, such as electrophoresis. Similarly, oligonucleotide probes that specifically hybridize to a polynucleotide encoding a prostate tumor protein can be used in hybridization experiments to detect the presence of a polynucleotide encoding a tumor protein in a biological sample.

To be able to hybridize under experimental conditions, the oligonucleotide primers and probes should comprise an oligonucleotide sequence that is at least about 60%, preferably at least 75%, and more preferably at least 90% identical to a portion (at least 10 nucleotides, preferably at least 20 nucleotides in length) of a polynucleotide encoding a prostate tumor protein. Preferably, the oligonucleotide primers and/or probes will hybridize to polynucleotides encoding the polypeptides disclosed herein under moderately stringent conditions as defined above. Oligonucleotide primers and/or probes that can be effectively used in the diagnostic methods described herein are preferably at least 10-40 nucleotides in length. In a preferred embodiment, the oligonucleotide primer comprises at least 10 contiguous nucleotides, more preferably at least 15 contiguous nucleotides, of a DNA molecule having the sequence as recorded in SEQ ID NO 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375 and 381. Techniques for PCR-based and hybridization experiments are well known in the art (see, e.g., Mullis et al, Cold Spring Harbor Symp. Quant. biol.15:263,1987; Erlich eds., PCR Technology, Stockton Press, NY, 1989).

A preferred assay employs RT-PCR, where PCR is used in conjunction with reverse transcription. Typically, RNA is extracted from a biological sample (such as a biopsy specimen) and reverse transcribed to produce cDNA molecules. PCR amplification using at least one specific primer produces cDNA molecules that can be separated and visualized using, for example, gel electrophoresis. Amplification can be performed on biological samples taken from test patients and from individuals who do not have cancer. The amplification reaction can be performed on multiple dilutions of cDNA spanning two orders of magnitude. At each dilution, expression in the test patient sample is increased by 2-fold or more, and is generally considered positive, compared to the same dilution of the non-cancer sample.

In another embodiment, the disclosed compositions can be used as a marker for cancer development. In this embodiment, the above-described experiments for cancer diagnosis can be performed over time and the changes in the levels of reactive polypeptides or polynucleotides assessed. For example, the experiment may be performed every 24 to 72 hours for 6 months to 1 year, and thereafter as needed. Typically, cancer is progressing in patients in which increased levels of the polypeptide or polynucleotide are detected over time. Conversely, if the level of reactive polypeptide or polynucleotide remains stable or decreases over time, the cancer is not progressing.

Certain in vivo diagnostic assays can be performed directly on tumors. One such experiment involves contacting tumor cells with a binding agent. The bound binding agent can then be detected directly or indirectly via a reporter group. These binders may also be used for histological applications. Alternatively, polynucleotide probes may be used for these applications.

As described above, to increase sensitivity, multiple prostate tumor protein markers can be determined in a given sample. Obviously, binding agents specific for the different proteins provided herein can be used in combination in a single experiment. Furthermore, a plurality of primers or probes may be used simultaneously. Tumor protein markers can be selected according to routine experimentation to determine the various combinations that produce the best sensitivity. Furthermore, experiments for the tumor proteins provided herein can be combined with experiments for other known tumor antigens. Diagnostic kit

The invention also provides kits for use in any of the above diagnostic methods. These kits typically comprise two or more components necessary to perform a diagnostic assay. The components may be compounds, reagents, containers and/or devices. For example, a container in the kit may contain a monoclonal antibody or fragment thereof that specifically binds to prostate tumor protein. These antibodies or fragments may be provided adsorbed on a support as described above. The other container or containers may be filled with components to be used in the experiment, such as reagents or buffers. These kits may also/or alternatively comprise the above-described detection agents comprising a reporter group (suitable for direct or indirect detection of antibody binding).

Alternatively, the kit can be designed to monitor the level of mRNA encoding prostate tumor protein in a biological sample. These kits typically comprise at least one oligonucleotide probe or primer as described above that hybridizes to a polynucleotide encoding a prostate tumor protein. Such oligonucleotides may be used, for example, in PCR or hybridization experiments. Other components that may be present in these kits include a second oligonucleotide and/or a diagnostic agent or container that facilitates detection of the polynucleotide encoding the prostate tumor protein. The following examples are offered by way of illustration and not by way of limitation.

Examples

Example 1

Isolation and characterization of prostate tumor polypeptides

This example describes the isolation of certain prostate tumor polypeptides from a prostate tumor cDNA library.

Human prostate tumor cDNA expression libraries were constructed from prostate tumor polyA + RNA using the Superscript plasmid system (BRLLife Technologies, Gaithersburg, MD 20897) for cDNA synthesis and plasmid cloning kits, according to the manufacturer's recommended methods. Specifically, prostate tumor tissue was homogenized with polytron (Kinematica, switzerland) and total RNA was extracted with Trizol reagent (BRL Life Technologies) according to the manufacturer's instructions. Poly A + RNA was then purified using Qiagen oligotex spin column mRNA purification kit (Qiagen, Santa Clarita, CA 91355) according to the manufacturer's recommended protocol. First strand cDNA was synthesized using Not I/Oligo-dT 18 primer. Double-stranded cDNA was synthesized, ligated with EcoRI/Ba XI adaptor (Invitrogen, San Diego, Calif.) and digested with Not I. The cDNA was size-separated using a Chroma Spin-1000 column (Clontech, Palo Alto, Calif.), ligated to EcoRI/Not I sites of pCDNA3.1(Invitrogen), and electroporated into Electro Max E.coli DH10B cells (BRL Life technologies).

Using the same procedure, a normal human pancreatic cDNA expression library was constructed from a panel of six tissue specimens (Clontech). By measuring the number of independent clones,The cDNA library was characterized by the percentage of clones with inserts, the average insert size, and sequence analysis. Prostate tumor library 1.64X 10⁷Individual clones, 70% of which contained inserts with an average insert size of 1745 base pairs. The normal pancreas cDNA library has 3.3X 10⁶Independent clones, 69% of which contained inserts with an average insert size of 1120 base pairs. For both libraries, sequence analysis showed that most clones carried the full-length cDNA sequence, were synthesized from mRNA, with minimal contamination of rRNA and mitochondrial DNA.

cDNA library subtraction (subcoction) was performed using the prostate tumor and normal human pancreas cDNA libraries described above, with minor modifications as described by Hara et al (Blood,84:189-199, 1994). Specifically, a prostate tumor-specific subtracted cDNA library was constructed as follows. Mu.g of the normal human pancreatic cDNA library were digested with EcoRI, Not I and Sfu I, followed by filling in with the DNA polymerase Klenow fragment. After phenol-chloroform extraction and ethanol precipitation, the DNA was dissolved in 100. mu.l of water, heat denatured, and mixed with 100. mu.l (100. mu.g) of optical probe biotin (Vector Laboratories, Burlingame, Calif.) and the resulting mixture was placed on ice and irradiated with 270W of fluorescent light for 20 minutes according to the manufacturer's recommended protocol. Then 50. mu.l of biotin as an optical probe was added thereto, and the biotinylation reaction was repeated. After five extractions with butanol, the DNA was precipitated with ethanol and redissolved in 23. mu.l of water as the driver DNA (driveDNA).

To prepare the tracer DNA (tracer DNA), 10. mu.g of the prostate tumor cDNA library was digested with BamHI and Xho I, phenol-chloroform extracted and passed through a Chroma spin-400 column (Clontech). After ethanol precipitation, the tracer DNA was dissolved in 5. mu.l of water. The tracer DNA was mixed with 15. mu.l of driver DNA and 20. mu.12 Xhybridization buffer (1.5M NaCl/10mM EDTA/50mM HEPES pH 7.5/0.2% SDS), overlaid with mineral oil and fully heat-denatured. The samples were immediately transferred to a 68 ℃ water bath and incubated for 20 hours (Long term hybridization [ LH ]). The reaction mixture was then subjected to streptavidin treatment followed by phenol-chloroform extraction. This step was repeated three more times. The subtracted DNA precipitate was dissolved in 12. mu.l of water, mixed with 8. mu.l of driver DNA and 20. mu.l of 2X hybridization buffer, and hybridized at 68 ℃ for 2 hours (short hybridization [ SH ]). After removal of the biotinylated double stranded DNA, the subtracted DNA was inserted into the BamH I/Xho I site of the chloramphenicol resistance plasmid pBCSK + (Stratagene, La Jolla, CA 92037) and transformed into Electro Max E.coli DHI0B cells by electroporation to create a prostate tumor-specific subtracted cDNA library (prostate minus 1).

To analyze the subtracted cDNA library, 100 independent clones were randomly picked from the subtracted prostate tumor specific library to prepare plasmid DNA and grouped according to insert size. Representative cDNA clones were further characterized by sequencing with a Perkin Elmer/Applied Biosystems Division automatic sequencer model 373A (Foster City, Calif.). 6 cDNA clones, hereinafter F1-13, F1-12, F1-16, H1-1, H1-9 and H1-4, were shown to be abundant in the subtracted prostate specific cDNA library. The 3 'and 5' cDNA sequences determined for F1-12 are provided in SEQ ID NO 2 and 3, respectively; the 3' cDNA sequences of F1-13, F1-16, H1-1, H1-9, and H1-4 are provided in SEQ ID NOs: 1 and 4-7, respectively.

The cDNA sequences of the isolated clones were compared to known sequences in the EMBL and GeneBank databases (published up to 96 years). 4 prostate tumor cDNA clones: f1-13, F1-16, H1-1 and H1-4, determined to encode the following proteins which have been identified: prostate Specific Antigen (PSA), human glandular kallikrein, human tumor expression enhancing genes, and mitochondrial cytochrome C oxidase subunit II. H1-9 is identical to the human autonomously replicating sequence which has been confirmed. No homologous sequence was found for the F1-12 cDNA sequence.

Through subsequent studies, the full-length cDNA sequence of F1-12 was isolated. This sequence is provided in SEQ ID NO 107 and the corresponding deduced amino acid sequence is provided in SEQ ID NO 108.

To clone the less abundant prostate tumor specific genes, the most abundant genes were obtained by using the 3 genes in the normal pancreatic cDNA library and the subtracted prostate tumor specific cDNA library described above: human glandular kallikrein, Prostate Specific Antigen (PSA), and mitochondrial cytochrome C oxidase subunit II, and subtraction of cDNA library from the prostate tumor cDNA library. Specifically, 1. mu.g each of human glandular kallikrein, prostate specific antigen and mitochondrial cytochrome C oxidase subunit II cDNA in pcDNA3.1 was added to the driver DNA, and subtracted as described above to provide a second subtracted cDNA library, which is hereinafter referred to as a potentiated prostate tumor specific subtracted cDNA library with spike.

22 cDNA clones were isolated from a synergistic prostate tumor-specific subtracted cDNA library. The 3 'and 5' cDNA sequences of clones J1-17, L1-12, N1-1862, J1-13, J1-19, J1-25, J1-24, K1-58, K1-63, L1-4 and L1-14 are determined to be provided in sequence in SEQ ID NO 8-9, 10-11, 12-13, 14-15, 16-17, 18-19, 20-21, 22-23, 24-25, 26-27 and 28-29. The 3' cDNA sequences determined for clones J1-12, J1-16, J1-21, K1-48, K1-55, L1-2, L1-6, N1-1858, N1-1860, N1-1861 and N1-1864 are provided in sequence in SEQ ID NO. 30-40. Comparison of these sequences with the sequences in the above gene bank showed NO significant homology to 3 of the 5 most abundant DNA species (J1-17, L1-12 and N1-1862; SEQ ID NOS: 8-9, 10-11 and 12-13). The remaining two most abundant species, one (J1-12; SEQ ID NO:30) identical to the well-established human lung surfactant-associated protein and the other (K1-48; SEQ ID NO:33) share some homology with the 2-arylpropionyl-CoA epimerase mRNA of R. Of the 17 less abundant cDNA clones isolated from the synergistic prostate tumor-specific subtracted cDNA library, 4 (J1-16, K1-55, L1-6 and N1-1864; SEQ ID NOS: 31, 34, 36 and 40, respectively) were identical to the already identified sequences, 2 (J1-21 and N1-1860; SEQ ID NOS: 32 and 38, respectively) showed some homology to the non-human sequences, and 2 (L1-2 and N1-1861; SEQ ID NOS: 35 and 39, respectively) showed some homology to the known human sequences. No significant homology was found for the polypeptides J1-13, J1-19, J1-24, J1-25, K1-58, K1-63, L1-4 and L1-14(SEQ ID NOS: 14-15, 16-17, 20-21, 18-19, 22-23, 24-25, 26-27 and 28-29).

Through subsequent studies, the full-length cDNA sequences of J1-17, L1-12 and N1-1862 were isolated (SEQ ID NO:109-111, respectively). The corresponding deduced amino acid sequence is provided in SEQ ID NO: 112-114. L1-12 is also known as P501S.

In a further experiment, an additional 4 clones were identified by subtraction of the prostate tumor cDNA library with normal prostate cDNA prepared from a pool of three normal prostate polyA + RNAs (prostate subtraction 2). The determined cDNA sequences of these clones (hereinafter referred to as U1-3064, U1-3065, V1-3692 and 1A-3905) are provided in sequence in SEQ ID NOs: 69-72. Comparison of the determined sequences with those in the gene bank showed no significant homology to U1-3065.

Secondary potentiating subtraction (prostate-subtracted potentiation 2) was accomplished by subtraction of the potentiating prostate tumor-specific cDNA library with the normal pancreatic cDNA library and further potentiating subtraction with PSA, J1-17, lung surfactant-associated protein, mitochondrial DNA, cytochrome C oxidase subunit II, N1-1862, autonomously replicating sequences, L1-12 and tumor expression enhancing genes. 4 additional clones were isolated, hereinafter designated V1-3686, R1-2330, 1B-3976 and V1-3679. The determined cDNA sequences of these clones are provided in sequence in SEQ ID NO 73-76. Comparison of these sequences with those within the GenBank revealed no significant homology to V1-3686 and R1-2330.

Further analysis of the three prostate subtractions described above (prostate subtraction 2, a synergistic prostate tumor-specific subtraction cDNA library and prostate subtraction synergy 2) identified 16 additional clones, namely 1G-4736, 1G-4738, 1G-4741, 1G-4744, 1G-4734, 1H-4774, 1H-4781, 1H-4785, 1H-4787, 1H-4796, 1I-4810, 1I-4811, 1J-4876, 1K-4884 and 1K-4896. The determined cDNA sequences of these clones are provided in sequence in SEQ ID NO 77-92. Comparison of these sequences with the sequences in the above gene bank revealed NO significant homology with 1G-4741, 1G-4734, 1I-4807, 1J-4876 and 1K-4896(SEQ ID NOS: 79, 81, 87, 90 and 92). Further analysis of the isolated clones confirmed the extended cDNA sequences of 1G-4736, 1G-4738, 1G-4741, 1G-4744, 1H-4774, 1H-4781, 1H-4785, 1H-4787, 1H-4796, 1I-4807, 1J-4876, 1K-4884 and 1K-4896 provided in sequence in SEQ ID NOs 179-188 and 191-193, and the additional partial cDNA sequences of 1I-4810 and 1I-4811 provided in SEQ ID NOs 189 and 190, respectively.

Additional 3 clones were isolated from additional studies of prostate subtraction synergy 2. Their sequences were determined as described above and compared with the latest GenBank. All three clones showed homology to known genes, which are cysteine-rich proteins, KIAA0242 and KIAA0280 (provided in sequence in SEQ ID NOs: 317, 319 and 320). Further analysis of these clones by Synteni microarray (Synteni, Palo Alto, CA) showed that all 3 clones were overexpressed in most prostate tumors and prostate BPH, as well as in most normal prostate tissues tested, but were expressed at low levels in all other normal tissues.

Subtraction was performed by subtracting normal prostate cDNA library with normal pancreatic cDNA, and one more subtraction was performed (prostate subtraction 3). Thus, 6 additional clones were identified, namely 1G-4761, 16-4762, 1H-4766, 1H-4770, 1H-4771, and 1H-4772(SEQ ID NOS: 93-98). Comparison of these sequences with those in the gene bank showed NO significant homology to 1G-4761 and 1H-4771(SEQ ID NOS: 93 and 97). Further analysis of the isolated clones confirmed the continued cDNA sequences of 1G-4761, 1G-4762, 1H-4766 and 1H-4772, provided in sequence in SEQ ID NOS: 194-196 and 199, and the additional partial cDNA sequences of 1H-4770 and 1H-4771, provided in SEQ ID NOS: 197 and 198, respectively.

Subtraction of the cDNA library of prostate tumor prepared from polyA + RNA pool of 3 prostate cancer patients (prostate subtraction 4) from the cDNA library of normal pancreas identified 8 clones, namely 1D-4297, 1D-4309, 1D.1-4278, 1D-4288, 1D-4283, 1D-4304, 1D-4296 and 1D-4280(SEQ ID NO: 99-107). These sequences were compared with the sequences in the gene bank, and found to have NO significant homology with 1D-4283 and 1D-4304(SEQ ID NOS: 103 and 104). Further analysis of the isolated clones confirmed the continued cDNA sequences of 1D-4309, 1D.1-4278, 1D-4288, 1D-4283, 1D-4304, 1D-4296 and 1D-4280, which are provided in sequence in SEQ ID NO: 200-.

cDNA clones isolated from prostate minus 1 and prostate minus 2 as described above were colony PCR amplified and their mRNA expression levels in prostate tumors, normal prostate and various other normal tissues were determined using microarray technology (Syntei, Palo Alto, Calif.). Briefly, PCR amplification products are spotted onto a slide in a lattice format, each occupying a unique position in the lattice. mRNA is extracted from a tissue sample to be detected, reverse transcription is carried out, and a fluorescence labeling cDNA probe is prepared. The microarray was probed with a labeled cDNA probe, the slide scanned and the fluorescence intensity measured. This intensity correlates with the hybridization intensity. Two clones (P509S and P510S) were found to be overexpressed in prostate tumors and normal prostate, while expressed at low levels in all other normal tissues examined (liver, pancreas, skin, bone marrow, brain, breast, adrenal gland, bladder, testis, salivary glands, large intestine, kidney, ovary, lung, spinal cord, skeletal muscle, and colon). The cDNA sequences determined for P509S and P510S are provided in SEQ ID Nos 223 and 224, respectively. These sequences were compared with sequences in the gene bank and found to have some homology with the ESTs previously identified.

In addition, the full-length cDNA sequence of P509S was isolated. This sequence is provided in SEQ ID NO 332 and the corresponding deduced amino acid sequence is provided in SEQ ID NO 339.

Example 2

Tissue-specific assay for prostate tumor polypeptides

The mRNA expression levels of the prostate tumor polypeptides F1-16, H1-1, J1-17 (also referred to as P502S), L1-12 (also referred to as P501S), F1-12 (also referred to as P504S) and N1-1862 (also referred to as P503S) representative of various normal and tumor tissues were examined by reverse transcription PCR using gene-specific primers.

Briefly, total RNA was extracted from a variety of normal and tumor tissues as described above using Trizol reagent. First strand synthesis was performed using SuperScript II reverse transcriptase (BRL Life technologies) for 1 hour at 42 ℃ using 1-2. mu.g total RNA. The cDNA was then amplified by PCR using gene specific primers. To ensure the semi-quantitative nature of reverse transcription PCR, beta actin was used as an internal control for each tissue examined. First, serial dilutions of first strand cDNA were prepared and tested by reverse transcription PCR using β actin specific primers. Next, a dilution was chosen that allowed linear amplification of the β actin template and was sensitive enough to reflect the initial copy number differences. Using these conditions, the level of β actin was determined in each tissue in each reverse transcription reaction. DNA contamination is minimized by treatment with DNase and ensuring that negative PCR results are obtained when using first strand cDNA prepared without the addition of reverse transcriptase.

The expression levels of mRNA were measured in 4 different types of tumor tissues (prostate tumor from 2 patients, breast tumor, colon tumor and lung tumor from 3 patients) and 16 different normal tissues (including prostate, colon, kidney, liver, lung, ovary, pancreas, skeletal muscle, skin, stomach, testis, bone marrow and brain), and F1-16 was found to be expressed at high levels in prostate tumor tissue, colon tumor and normal prostate, at low levels in normal liver, skin and testis, and not detected in other tissues tested; h1-1 was expressed at high levels in prostate tumors, lung tumors, breast tumors, normal prostate, normal colon, and normal brain, much less in normal lung, pancreas, skeletal muscle, skin, small intestine, and bone marrow, and undetectable in other tissues tested. J1-17(P502S) and L1-12(P501S) appear to be specifically overexpressed in the prostate, with both genes expressed at high levels in both prostate tumor and normal prostate, and at very low or even undetectable levels in all other tissues examined. N1-1862(P503S) was overexpressed in 60% of prostate tumors, and expression was detectable in normal colon and kidney. Therefore, the reverse transcription PCR results reveal that F1-16, H1-1, J1-17(P502S), N1-1862(P503S) and L1-12(P501S) are either prostate specific or have significantly increased expression levels in prostate.

Further reverse transcription PCR results showed that F1-12(P504S) was overexpressed in 60% of prostate tumors, detectable in normal kidneys, and undetectable in all other tissues tested. Similarly, R1-2330 was overexpressed in 40% of prostate tumors, detectable in normal kidney and liver, and undetectable in all other tissues examined. U1-3064 was overexpressed in 60% of prostate tumors, also expressed in breast and colon tumors, but undetectable in normal tissues.

Reverse transcription PCR identification of R1-2330, U1-3064 and 1D-4279 indicated that these 3 antigens were overexpressed in the prostate and/or prostate tumor.

Northern analysis of 4 prostate tumors, 2 normal prostate samples, 2 BPH prostate and normal colon, kidney, liver, lung, pancreas, skeletal muscle, brain, stomach, testis, small intestine and bone marrow showed that L1-12(P501S) was overexpressed in prostate tumors and normal prostate, but undetectable in other normal tissues examined. J1-17(P502S) was detected in 2 prostate tumors and not in other tissues examined. N1-1862(P503S) was overexpressed in 3 prostate tumors, expressed in normal prostate, colon and kidney, and not expressed in other tissues tested. F1-12(P504S) was highly expressed in 2 prostate tumors and undetectable in all other tissues examined.

Representative antigens described herein were tested in prostate tumors, breast tumors, and the following normal tissues using the microarray technique described above: expression levels in prostate, liver, pancreas, skin, bone marrow, brain, breast, adrenal gland, bladder, testis, salivary gland, large intestine, kidney, ovary, lung, spinal cord, skeletal muscle, and colon. L1-12(P501S) was found to be overexpressed in normal prostate and prostate tumors, and somewhat expressed in normal skeletal muscle. Both J1-12 and F1-12(P504S) were overexpressed in prostate tumors and were less or undetectable in all other tissues examined. N1-1862(P503S) was expressed at high levels in prostate tumors and normal prostate, at low levels in normal large intestine and normal colon, and was not detected in all other tissues examined. R1-2330 was overexpressed in prostate tumors and normal prostate and at lower levels in all other tissues examined. 1D-4279 was overexpressed in prostate tumors and normal prostate, expressed at lower levels in normal spinal cord, and undetectable in all other tissues examined.

Further microarray analysis to specifically determine the expression level of P501S (SEQ ID NO:110) in breast tumors revealed moderate overexpression in normal tissues, but negligible or low expression not only in breast tumors, but also in metastatic breast tumors (2/31). This data suggests that P501S may be overexpressed in various breast tumors as well as in prostate tumors.

As described above, the expression levels of 32 ESTs (expressed sequence tags) described by Vasmatzis et al (Proc. Natl. Acad. Sci. USA95:300-304, 1998) in various tumors and normal tissues were examined by microarray technology. 2 of these clones (P1000C and P1001C) were overexpressed in prostate tumors and normal prostate, while low or even undetectable levels were expressed in all other tissues tested (normal aorta, thymus, resting and activated PBMC, epithelial cells, spinal cord, adrenal gland, fetal tissue, skin, salivary glands, large intestine, bone marrow, liver, lung, dendritic cells, stomach, lymph nodes, brain, heart, small intestine, skeletal muscle, colon and kidney). The determined cDNA sequences for P1000C and P1001C are provided in SEQ ID NOs 384 and 472, respectively. The sequence of P1001C shows some homology to the human mRNA of JM27 protein which has been isolated. No significant homology was found to the sequence of P1000C.

Expression of the polypeptide encoded by the full-length cDNA sequence of F1-12(P504S, SEQ ID NO:108) was studied by immunohistochemical analysis. A rabbit anti-P504S polyclonal antibody against the full-length P504S protein was prepared by conventional techniques. The isolation and characterization of polyclonal antibodies was also subsequently performed by techniques well known in the art. Immunohistochemical analysis showed that P504S polypeptide was expressed in 100% of the prostate cancer samples tested (n = 5).

The rabbit anti-P504S polyclonal antibody does not appear to mark benign prostate cells with the same cytoplasmic granule staining, but has a slight nuclear staining. Analysis of normal tissues revealed that the encoded polypeptide was expressed in some but not all normal human tissues. Positive cytoplasmic staining of rabbit anti-P504S polyclonal antibody was found to be present in normal human kidney, liver, brain, colon and lung-associated macrophages, whereas heart and bone marrow were negative.

This data indicates that the P504S polypeptide is present in prostate cancer tissue and that there is a qualitative and quantitative difference between the staining of benign prostate hyperplastic tissue and prostate cancer tissue, indicating that this polypeptide can be selectively detected in prostate tumors and therefore can be used in the diagnosis of prostate cancer.

Example 3

Isolation and characterization of prostate tumor Polypeptides by PCR-based subtraction

cDNA subtraction library was purchased from Clontech, and contains normal prostate cDNA subtracted from 10 other normal tissue cDNAs (brain, heart, kidney, liver, lung, ovary, placenta, skeletal muscle, spleen, and thymus) followed by a first round of PCR amplification. This library was subjected to a second round of PCR amplification according to the manufacturer's recommended protocol. The resulting cDNA fragment was subcloned into the vector pT7 Blue T-vector (Novagen, Madison, Wis.) and transformed into XL-1Blue MRF' E.coli (Stratagene). DNA was isolated from independent clones and sequenced using a Perkin Elmer/Applied Biosystems Division Autosequencer model 373A.

59 positive clones were sequenced. The DNA sequences of these clones were compared with the sequences in the above gene bank and showed no significant homology with 25 of them, namely P5, P8, P9, P18, P20, P30, P34, P36, P38, P39, P42, P49, P50, P53, P55, P60, P64, P65, P73, P75, P76, P79 and P84. The determined cDNA sequences of these clones are provided in sequence in SEQ ID Nos 41-45, 47-52 and 54-65. P29, P47, P68, P80 and P82 (SEQ ID Nos: 46, 53 and 66-68, respectively) were found to have a certain degree of homology with the previously confirmed DNA sequences. To the knowledge of the inventors, these sequences have never been found to be present in the prostate.

Further investigation using the PCR-based methodology described above resulted in the isolation of 180 additional clones, 23 of which were found to have no significant homology to the known sequence. The determined cDNA sequences of these clones are provided in SEQ ID Nos 115-123, 127, 131, 137, 145, 147-151, 153, 156-158 and 160. 23 clones (SEQ ID Nos: 124-. Another 10 clones (SEQ ID NO:161-170) had a certain degree of homology with the known genes. The larger cDNA clone containing the P20 sequence represents a splice variant of the gene P703P. The determined DNA sequences of the variants DE1, DE13 and DE14 are provided in sequence in SEQ ID Nos 171, 175 and 177 and the corresponding deduced amino acid sequences are provided in sequence in SEQ ID Nos 172, 176 and 178. The determined cDNA sequence for the splicing-extending form of P703 is provided in SEQ ID No. 225. The DNA sequences of the splice variants DE2 and DE6 are provided in sequence in SEQ ID Nos. 173 and 174.

mRNA expression levels of each representative clone in tumor tissues [ prostate (n =5), breast (n =2), colon and lung ], normal tissues [ prostate (n =5), colon, kidney, liver, lung (n =2), ovary (n =2), skeletal muscle, skin, stomach, small intestine and brain ], activated and inactivated PBMCs were determined using the reverse transcription PCR method described above. Unless otherwise indicated, expression was measured in only one sample per tissue.

P9 was found to be highly expressed in normal prostate and prostate tumors compared to all normal tissues examined (except normal colon, where there was a comparable level of expression). P20 (part of the P703P gene) was highly expressed in normal prostate and prostate tumors compared to all 12 normal tissues examined. P20 expression was moderately elevated in breast (n =2), colon and lung tumors compared to all normal tissues except lung (1 out of 2 samples). P18 expression was elevated in normal prostate, prostate and breast tumors compared to normal tissues other than lung and stomach. P5 expression was moderately elevated in normal prostate compared to most other normal tissues. However, some increase in expression was observed in normal lung and PBMC. Increased expression of P5 was also observed in prostate tumors (2 out of 5 samples), breast tumors, and 1 lung tumor sample. As for P30, it was similarly expressed in normal prostate and prostate tumors compared to 6 of 12 other normal tissues examined. Increased expression was found in breast tumors, 1 lung tumor sample, 1 colon tumor sample, and also in normal PBMCs. P29 was overexpressed in all 5 prostate tumors and all 5 normal prostates compared to most normal tissues. However, significant expression of P29 was observed in normal colon and normal lung (both 2 samples). P80 was overexpressed in all 5 prostate tumors and all 5 normal prostates and increased expression in colon tumors compared to all other normal tissues examined.

Further studies isolated the following 12 other clones: 10-d8, 10-h10, 11-c8, 7-g6, 8-b5, 8-b6, 8-d4, 8-d9, 8-g3, 8-h11, 9-f12 and 9-f 3. The determined DNA sequences of 10-d8, 10-h10, 11-c8, 8-d4, 8-d9, 8-h11, 9-f12 and 9-f3 are provided in sequence in SEQ ID Nos 207, 208, 209, 216, 217, 220, 221 and 222. The determined forward and reverse DAN sequences of 7-g6, 8-b5, 8-b6 and 8-g3 are provided in SEQ ID Nos 210 and 211, 212 and 213, 214 and 215, 218 and 219. Comparison of these sequences with sequences in the gene bank showed no significant homology to the 9-f3 sequence. Clones 10-d8, 11-c8 and 8-h11 were found to have some homology to previously isolated ESTs, while 10-h10, 8-b5, 8-b6, 8-d4, 8-d9, 8-g3 and 9-f12 have some homology to previously identified genes. Further characterization of 7-66 and 8-63 showed identity with the known genes PAP and PSA, respectively.

The mRNA expression levels of these clones were determined using the microarray technique described above. Clones 7-66, 8-63, 8-B5, 8-B6, 8-D4, 8-D9, 9-F3, 9-F12, 9-H3, 10-A2, 10-A4, 11-C9, and 11-F2 were found to be over-expressed in prostate tumors and normal prostate, while the expression levels were low or undetectable in other tissues tested. 8-F11 is expressed in prostate tumors and normal prostate, bladder, skeletal muscle and colon. 10-H10 is expressed in prostate tumors and normal prostate, bladder, lung, colon, brain and large intestine. 9-B1 has increased expression in prostate tumors, breast tumors, and normal prostate, salivary glands, large intestine, and skin. 11-C8 is expressed in prostate tumors as well as normal prostate and large intestine.

Other cDNA fragments resulting from the above PCR-based normal prostate subtraction were found to be prostate specific by both microarray techniques and reverse transcription PCR. The determined cDNA sequence of this clone (9-A11) is provided in SEQ ID NO: 226. Comparison of this sequence with public databases revealed 99% identity to the known gene HOXB 13.

Upon further analysis, clones 8-C6 and 8-H7 were isolated. The determined cDNA sequences of these clones are provided in sequence in SEQ ID NO 227 and 228. These sequences show some homology to ESTs that have been isolated.

PCR and hybridization based methodologies were applied to obtain the longer cDNA sequence of clone P20 (also known as P703P), thereby obtaining 3 other cDNA fragments that gradually extended the 5' end of the gene. These fragments (P703PDE5, P703P6.26 and P703 PX-23; SEQ ID NOS: 326, 328 and 330; the deduced corresponding amino acid sequences are provided in sequence in SEQ ID NOS: 327, 329 and 331) contain an additional 5' sequence. P703PDE5 was recovered by screening a cDNA library (#141-26) with a portion of P703P as probe. P703P6.26 was recovered from the mixture of the three prostate tumor cDNAs, and P703PX-23 was recovered from the cDNA library (# 438-48). In general, the additional sequences include the entire predicted mature serine protease sequence as well as a portion of the predicted signal sequence. Further investigation of a PCR-based subtraction library (referred to as JP: PCR subtraction) that subtracts a pool of normal tissues from a pool of prostate tumors isolated 13 additional clones, 7 of which did not have any significant homology to the known GenBank sequences. The determined cDNA sequences of these 7 clones (P711P, P712P, neotype 23, P774P, P775P, P710P and P768P) are provided in sequence in SEQ ID NOs 307-311, 313 and 315. The remaining 6 clones (SEQ ID NO:316 and 321-325) showed some homology to the known genes. By microarray analysis, all 13 clones showed 3 or more fold overexpression in prostate tissue, including prostate tumor, BPH and normal prostate, compared to normal non-prostate tissue. Clones P711P, P712P, neo 23 and P768P showed overexpression in most prostate tumor and BPH tissues tested (n =29), and most normal prostate tissues (n =4), but from background to low levels in all normal tissues. Clones P774P, P775P and P710P showed and were relatively low expressed in fewer prostate tumor and BPH samples, negative or low level expression in normal prostate.

The full-length cDNA of P711P was obtained by screening a prostate cDNA library with the partial sequence of SEQ ID NO. 307. Specifically, a directionally cloned prostate cDNA library was constructed using conventional techniques. One million colonies of this library were plated on LB/Amp plates. The colonies were leached using nylon filters, and the cDNA picked up from these filters was denatured and crosslinked to the filters by UV light. The P711P cDNA fragment of SEQ ID NO 307 was radiolabeled and hybridized to these filters. Positive clones were selected, cDNA prepared, and sequenced using an automated PerkinElmer/Applied Biosystems sequencer. The determined full-length sequence of P711P is provided in SEQ ID NO:382 and the corresponding deduced amino acid sequence is provided in SEQ ID NO: 383.

Additional cDNA sequence information was obtained for the two clones described above (11-C9 and 9-F3, hereinafter referred to as P707P and P714P, SEQ ID NOS: 333 and 334, respectively) using PCR and hybridization based methodologies. P707P was found to be a splice variant of the known gene HoxB13 after comparison with the nearest GenBank. In contrast, no significant homology was found with P714P.

Clones 8-B3, P89, P98, P130 and P201 (disclosed in U.S. patent application No. 09/020,956 filed 2/9 of 1998 with a border) were found to have the sequence P705P (SEQ ID NO:335, the corresponding deduced amino acid sequence being provided in SEQ ID NO:336), P705P determined to be a splice variant of the known gene NKX 3.1.

Example 4

Polypeptide synthesis

Polypeptides were synthesized using HPTU (O-benzotriazole-N, N, N ', N' -tetramethyluronium hexafluorophosphate) activation using FMOC chemistry on a Perkin Elmer/Applied Biosystems 430A polypeptide synthesizer. A Gly-Cys-Gly sequence may be added at the amino terminus of the peptide to facilitate conjugation, binding to a fixation surface or labeling of the peptide. The following lysis mixtures may be used: trifluoroacetic acid, ethanedithiol, thioanisole, water, phenol (40: 1: 2: 3), cleaving the peptide from the solid support. After 2 hours of lysis, the peptide can be precipitated in cold methyl-tert-butyl ether. The peptide precipitate was then dissolved in water containing 0.1% trifluoroacetic acid (TFA), lyophilized and purified by C18 reverse phase HPLC. The peptides can be eluted using a gradient of 0% to 60% acetonitrile (containing 0.1% trifluoroacetic acid) in water (containing 0.1% TFA). After lyophilization of the pure fractions, the peptides can be identified by electrospray or other types of mass spectrometry as well as amino acid analysis.

Example 5

Further isolation and characterization of prostate tumor polypeptides by PCR-based subtraction

The cDNA library constructed from prostate primary tumor mRNA as described above was subtracted with cDNA from normal prostate. The subtraction was performed using a PCR-based protocol (Clontech) with some modifications to the protocol to generate larger fragments. In this protocol, the test (tester) and driver double-stranded cDNA were digested with five restriction enzymes (Mlu I, Msc I, PvuII, Sal I and Stu I) that recognize the six-nucleotide restriction sites, respectively. This digestion produced cDNA with an average size of 600bp, rather than 300bp according to Clontech protocol digested with Rsa I. This modification does not affect the subtraction efficiency. Two test populations were then generated with different adaptors, while the driver library was still free of adaptors.

Hybridization of the test and driver libraries is then performed using the excess driver cDNA. In the first hybridization step, the driver cDNA is hybridized separately to one of the two test cDNA populations. This step produces (a) a population of unhybridized test cDNAs, (b) a population of test cDNAs that hybridize to other test cDNAs, (c) a population of test cDNAs that hybridize to driver cDNAs, and (d) a population of unhybridized driver cDNAs. The two separately performed hybridization reactions are then mixed and rehybridized in the presence of additional denatured driver cDNA. Following this second round of hybridization, in addition to populations (a) - (d), a fifth population (e) is produced in which test cDNA containing one adapter hybridizes to test cDNA containing a second adapter. Accordingly, the second hybridization step results in enrichment of differentially expressed sequences, which can be used as a template in PCR amplification (using adaptor-specific primers).

The ends were then filled in and PCR amplified using adaptor specific primers. Only population (e) containing test cDNA that does not hybridize to the driver cDNA is exponentially amplified. A second round of PCR amplification was then performed to reduce background and further enrich for differentially expressed sequences.

This PCR-based subtraction technique normalizes differentially expressed cdnas so that rare transcripts that are overexpressed in prostate tumor tissue can be recovered. Recovery of these transcripts by traditional subtractive methods would be difficult.

In addition to genes known to be overexpressed in prostate tumors, 77 clones were identified. The sequences of these partial cDNAs are provided in SEQ ID NOS: 29-305. Most of these clones had no significant homology to the database sequences. Exceptions are JPTPN23(SEQ ID NO: 231; similar to porcine valosin-containing protein), JPTPN30(SEQ ID NO: 234; similar to mRNA of rat proteasome subunits), JPTPN45(SEQ ID NO: 243; similar to rat norvegicus cytoplasmic NADP-dependent isocitrate dehydrogenase), JPTPN46(SEQ ID NO: 244; similar to human subclone H84D 4 DNA sequence), JP1D6(SEQ ID NO: 265; similar to G.gallus dynein light chain A), JP8D6(SEQ ID NO: 288; similar to human BACclone RG016J 04), JP8F5(SEQ ID NO: 289; similar to human subclone H83 b5 DNA sequence), and JP8E9(SEQ ID NO: 299; similar to human Alu sequence).

Additional 3 clones were obtained from additional studies of the PCR-based subtraction library consisting of prostate tumor pools minus normal prostate pools (called PT-PN PCR subtraction). Comparison of the cDNA sequences of these clones with the recent version of GenBank revealed NO significant homology with the two clones (P715P and P767P; SEQ ID NOS: 312 and 314). Another clone was found to have some homology with the known gene KIAA0056(SEQ ID NO: 318). mRNA expression levels in various tissues were measured using microarray analysis and all 3 clones were found to be overexpressed in prostate tumors and BPH tissues. Specifically, clone P715P was overexpressed 3-fold or more in most prostate tumor and BPH tissues, while expression was increased in most normal prostate samples and in fetal tissues, but was negative to low-level expression in all other normal tissues. Clone P767P was overexpressed in multiple prostate tumors and BPH tissues, but moderately expressed in half normal prostate samples, and background to low levels in all other tested normal tissues.

Further analysis of the PT-PN PCR subtracted library and the DNA subtracted library containing prostate tumor cDNA from which a panel of normal tissue cDNA was subtracted by the above microarray isolated an additional 27 clones determined to be overexpressed in prostate tumors (SEQ ID NO:340-365 and 381). Clones of SEQ ID NOs 341, 342, 345, 347, 348, 349, 351, 355-359, 361, 362 and 364 were also found to be expressed in normal prostate. All 26 clones were found to be expressed at low or undetectable levels in various normal tissues, with the exception of P544S (SEQ ID NO:356), which was found to be expressed in the small intestine. 10 of the 26 clones (SEQ ID NO:340-349) were found to show some homology to the already identified sequences. No significant homology was found with the clone of SEQ ID NO: 350-365.

Example 6

Peptide sensitization of mice and proliferation of CTL cell lines

6.1 this example illustrates the preparation of a CTL cell line specific for cells expressing the P502S gene.

Mice (supplied by Dr. Sherman, The script Research Institute, La Jolla, Calif.) expressing The human HLA A2.1 transgene were immunized with The P2S #12 peptide (VLGWVAEL; SEQ ID NO:306) derived from The P502S gene (also referred to herein as J1-17, SEQ ID NO:8) as described by Theobald et al (Proc. Natl. Acad. Sci. USA92:11993-11997, 1995). 100 μ g P2S #12 and 120 μ g hepatitis B virus protein-derived I-A emulsified with incomplete Freund's adjuvant^bThe bound peptide was used to immunize mice. Three weeks later, these mice were sacrificed and single cell suspensions were prepared using nylon sieves. The cells were then plated at 6X 10⁶The cells/ml were resuspended in complete medium (RPMI-1640; Gibco BRL, Gaithersburg, Md.) containing 10% FCS, 2mM glutamine (Gibco BRL), sodium pyruvate (Gibco BRL), non-essential amino acids (Gibco BRL), 2X 10^-5M2-mercaptoethanol, 50U/ml penicillin and streptomycin, and in irradiated (3000 rads) P2S #12 pulses (5mg/ml P2S #12 and 10mg/ml β 2-microglobulin) LPS immature cells (A2 transgenic splenocytes were cultured for 3 days in the presence of 7 μ g/ml dextran sulfate and 25 μ g/ml LPS). After 6 days, cells (5X 10)⁵One/ml) with 2.5X 10⁶Irradiation of/ml peptide pulses (20,000 rads) EL4A2Kb cells (Sherman et al, Science 258: 815. sup. su 818,1992) and 3X 10⁶A2 transgenic spleen feeder cells/ml were restimulated. Cells were cultured in the presence of 20U/ml IL-2. During the preparation of clonal lines, the cells were restimulated once a week as described above.

By pulsing EL4A2Kb tumor cells (1X 10) with peptide⁴Individual cells/well) as stimuli and a2 transgenic splenocytes (5 × 10)⁵Individual cells/well) as a feeder (cultured in 30U/ml IL-2) and cloned into P2S #12 line. On day 14, cells were restimulated as above. On day 21, growing clones were isolated and maintained. Many of these clones showed human fibroblasts transduced with P502S (Table)Up to HLA a2.1) is significantly more reactive (lytic) than control fibroblasts.

This data demonstrates that P2S #12 displays an epitope naturally processed by the P502S protein expressed in the human HLA a2.1 molecule.

6.2 this example illustrates the preparation of murine CTL lines and CTL clones specific for cells expressing the P501S gene.

The series of experiments was performed similarly to the above. Mice were immunized with the P1S #10 peptide (SEQ ID NO:337) derived from the P501S gene (also referred to herein as L1-12, SEQ ID NO: 110). The P1S #10 peptide was obtained by analysis of the potential HLA-A2 binding sequence as defined by the published HLA-A2 binding motif (K.C. Parker et al, J.Immunol.,152:163,1994) in the predicted polypeptide sequence of P501S. The P1S #10 peptide was synthesized as described in example 4 and tested empirically for HLA-a2 binding using a T cell-based competition assay. The predicted ability of the A2-binding peptide to compete with HLA-A2-specific peptides for presentation to HLA-A2-binding influenza matrix peptide FluM 58-specific HLA-A2-restricted CTL clones (D150M58) was tested. D150M58 CTL secreted TNF in response to self-presentation of fluM58 peptide. In competition experiments, 100-200. mu.g/ml detection peptide was added to D150M58 CTL cultures to bind HLA-A2 on CTL. After 30 minutes, CTLs incubated with the test or control peptides were tested for antigen dose response to fluM58 peptide in standard TNF biological experiments. As shown in FIG. 3, the P1S #10 peptide competes for HLA-A2-restricted presentation of FluM58, demonstrating that the P1S #10 peptide binds to HLA-A2.

Mice expressing the human HLA A2.1 transgene were immunized as described by Theobald et al (Proc. Natl. Acad. Sci. USA92:11993-11997,1995) with the following modifications. 62.5 μ g P1S #10 and 120 μ g of I-A derived from hepatitis B virus protein emulsified with incomplete Freund's adjuvant^bThe bound peptide was used to immunize mice. After 3 weeks, the mice were sacrificed and single cell suspensions were prepared using nylon mesh. The cells were then plated at 6X 10⁶The cells/ml concentration were resuspended in complete medium (as described above) and pulsed in the presence of irradiated (3000 rads) P1S #10 (2. mu.g/ml P1S #10 and 10 mg/ml. beta.)₂Microglobulin) in LPS immature cells (in the presence of 7. mu.g/ml dextran sulphate and 25. mu.g/ml LPSCultured under conditions in which 3-day a2 transgenic spleen cells were cultured). After 6 days, cells (5X 10) were plated as described above⁵Per cell) 2.5X 10⁶Perml peptide pulsed irradiated (20,000 rads) EL4A2Kb cells and 3X 10⁶The/ml A2 transgenic spleen feeder cells restimulated. Cells were cultured in the presence of 20U/ml IL-2. Cells were restimulated once a week during the preparation of clones. After 3 rounds of in vitro stimulation, cell lines were generated that recognized the P1S #10 pulsed Jurkat A2Kb target cells and the P501S transduced Jurkat target cells, as shown in fig. 4.

EL4A2Kb tumor cells (1X 10) pulsed with peptide grown in the presence of 30U/ml IL-2⁴Cells/well) as stimulator cells, A2 transgenic splenocytes as feeder cells (5X 10)⁵Cells/well), a P1S #10 specific CTL line was cloned by limiting dilution analysis. On day 14, restimulation was performed as above. On day 21, surviving clones were isolated and maintained in culture. As shown in FIG. 5, 5 of these clones demonstrated specific cytolytic reactivity against P501S transduced Jurkat A2Kb target cells. This data indicates that P1S #10 represents the naturally processed epitope of the P501S protein expressed in the human HLA-A2.1 molecule.

Example 7

Human T cell ability to recognize prostate tumor polypeptides

This example illustrates the ability of prostate tumor polypeptide-specific T cells to recognize human tumors.

Human CD8+ T cells were sensitized in vitro with a P2S-12 peptide (SEQ ID NO:306) derived from P502S (also known as J1-17) using dendritic cells according to the Van Tsai et al protocol (Critical reviews in Immunology 18:65-75,1998). The resulting CD8 was tested in the interferon-gamma ELISPOT experiment (see Lalvani et al, J.Exp.Med.186:859-865,1997)⁺The ability of small T cell cultures to recognize P2S-12 peptides presented by autologous fibroblasts or fibroblasts transduced to express the P502S gene. Briefly, in the presence of 3. mu.g/ml human beta₂-microglobulin and 1Mu.g/ml P2S-12 peptide or control E75 peptide at 10⁴T cell numbers were measured in duplicate by parallel titration on individual fibroblasts. Furthermore, T cells were also assayed on autologous fibroblasts transduced with the P502S gene or, as a control, on fibroblasts transduced with HER-2/neu. Prior to the experiment, fibroblasts were treated with 10ng/ml interferon gamma for 48 hours to upregulate MHC class I responses. One of the small cultures (#5) demonstrated significant recognition of peptide pulsed fibroblasts in the interferon-gamma ELISPOT experiment, as well as transduced fibroblasts. Figure 2A demonstrates that on fibroblasts pulsed with P2S-12 peptide (solid bars), the number of γ -interferon plaques increases significantly with increasing number of T cells, whereas the control E75 peptide (open bars) does not. This shows that these T cells have the ability to specifically recognize the P2S-12 peptide. As shown in FIG. 2B, this small culture also demonstrated that the number of gamma-interferon plaques increased with the increase in the number of T cells on fibroblasts transduced to express the P502S gene, but not on fibroblasts transduced to express the HER-2/neu gene. These results provide additional conclusive evidence that the P2S-12 peptide is a naturally processing epitope of the P502S protein. Furthermore, this also demonstrates the presence of high affinity T cells in the human T cell pool that are able to recognize this epitope. These T cells should also be able to recognize human tumors expressing the P502S gene.

Example 8

In vivo priming of CTL with prostate antigen by naked DNA immunization

The prostate tumor antigen L1-12, also known as P501S. HLA A2Kb Tg mice (supplied by l.sherman doctor, The Scripps Research Institute, La Jolla, CA) were immunized intramuscularly or intradermally with 100 μ g VR 10132-P501S. Mice were immunized 3 times, each 2 weeks apart. 2 weeks after the last immunization, the immunized splenocytes were cultured with Jurkat A2Kb-P501S transduced stimulator cells. CTL lines were stimulated once a week. CTL activity against P501S transduced target cells was assessed 2 weeks after in vitro stimulation. 2 of 8 mice showed strong anti-P501S CTL responses. These results demonstrate that P501S contains at least one naturally processed a 2-restricted CTL epitope.

Example 9 in vitro Generation of human CTLs by Whole Gene sensitization and stimulation Using prostate tumor antigens

Whole-gene sensitization in vitro using P501S retrovirus-transduced autologous fibroblasts (see, e.g., Yee et al, The Journal of Immunology 157(9):4079-86, 1996) was derived to identify human CTL lines by interferon-gamma ELISPOT assay that specifically recognized autologous fibroblasts transduced with P501S (also known as L1-12) as described above. These CTL lines were shown to be restricted HLA-a2 type i alleles using a panel of HLA-mismatched fibroblast cell lines transduced with P501S. Specifically, Dendritic Cell (DC) cells were differentiated from monocyte cultures derived from PBMC of normal human donors after 5 days of culture in RPMI medium (containing 10% human serum, 50ng/ml human GM-CSF and 30ng/ml human IL-4). After incubation, DCs were infected overnight with recombinant P501S poxvirus with multiplicity of infection (m.o.i) of 5 and matured overnight with the addition of 3 μ g/ml CD40 ligand. The virus was inactivated by UV irradiation. Separation of CD8 using magnetic bead system⁺T cells and primed culture is initiated using conventional culture techniques. Every 7-10 days, cultures were restimulated with autologous primary fibroblasts transduced with the P501S retrovirus. After 4 stimulation cycles, CD8 was identified which specifically produced interferon-gamma when stimulated by autologous fibroblasts transduced with P501S⁺T cell line. P501S specific activity was maintained by continued stimulation of the culture with fibroblasts transduced with P501S in the presence of IL-15. HLA-mismatched fibroblast line series transduced with P501S was prepared to define the restriction alleles of the response. By measuring interferon-gamma in an ELISPOT experiment, the P501S specific response was shown to be restricted by HLA-a2. These results demonstrate that a CD8+ CTL response against P501S can be elicited.

Example 10

Identification of naturally processed CTL epitopes contained within prostate tumor antigens

The nonapeptide P5(SEQ ID NO:338) was derived from the P703P antigen (also known as P20). The p5 peptide is immunogenic in human HLA-A2 donors and is a naturally processed epitope. Antigen-specific CD8⁺T cells can be primed after repeated in vitro stimulation of monocytes pulsed with p5 peptide. These CTLs specifically recognized p 5-pulsed target cells in ELISPOT (described above) and chromium release experiments. Furthermore, immunization of HLA-A2 transgenic mice with P5 resulted in CTL lines recognizing various P703P transduced target cells expressing HLA-A2Kb or HLA-A2. Specifically, HLA-A2 transgenic mice were immunized subepithelially with Freund's incomplete adjuvant containing 100. mu. g p5 peptide and 140. mu.g hepatitis B virus core peptide (Th peptide). After 3 weeks of immunization, splenocytes from immunized mice were stimulated in vitro with peptide-pulsed LPS immature cells. CTL activity was assessed 5 days after the initial in vitro stimulation by chromium release assay. Retrovirus-transduced cells expressing control antigens P703P and HLA-A2Kb were used as target cells. CTL lines were identified that specifically recognized the P5 pulsed target cells as well as the P703P expressing target cells.

The in vitro sensitization experiment proves that the p5 peptide has immunogenicity in human body. Dendritic Cells (DCs) were differentiated from cultures of monocytes derived from PBMCs from normal human donors by culturing in RPMI medium (containing 10% human serum, 50ng/ml human GM-CSF and 30ng/ml human IL-4) for 5 days. After incubation, DCs were pulsed with p5 peptide and were combined with GM-CSF and IL-4 with CD8⁺T cell enriched PBMC cultures. CTL lines were restimulated once a week with p 5-pulsed monocytes. Recognition of p 5-pulsed target cells by CTL was demonstrated 5-6 weeks after the start of CTL culture.

Example 11

Expression of breast tumor-derived antigens in prostate

The isolation of antigen B305D from breast tumors by differential display is described in U.S. patent application No. 08/700,014 filed on 8/20 1996. A number of different spliced forms of the antigen were isolated. The determined cDNA sequences of these splice forms are provided in SEQ ID NO. 366-375 and the predicted amino acid sequences corresponding to the SEQ ID NO. 292, 298 and 301-303 sequences are provided in sequence in SEQ ID NO. 299-306.

The expression level of B305D in various tumor and normal tissues was examined by real-time PCR and by Northern analysis. The results indicate that B305D was expressed at high levels in breast tumors, prostate tumors, normal prostate tissue and normal testis, and at low or undetectable levels in all other tissues examined (colon tumors, lung tumors, ovarian tumors, and normal bone marrow, colon, kidney, liver, lung, ovary, skin, small intestine, stomach).

Example 12

Stimulation of prostate tumor antigen-specific CTL responses in human blood

This example illustrates the ability of prostate tumor antigen to induce a CTL response in normal human blood.

Autologous Dendritic Cells (DCs) were differentiated from monocyte cultures derived from PBMCs from normal donors by culturing in RPMI medium (containing 10% human serum, 50ng/ml GMCSF and 30ng/ml IL-4) for 5 days. After incubation, DCs were infected with recombinant poxvirus expressing P501S (m.o.i. =5) overnight and matured by addition of 2 μ g/ml CD40 ligand for 8 hours. The virus was inactivated by UV irradiation, CD8+ cells were isolated by positive selection using magnetic beads, and primed culture was started in 24-well plates. After 5 stimulation cycles, CD8 was identified which specifically produced interferon-gamma after stimulation with fibroblasts transduced with autologous P501S⁺Is described. Cell line 3A-1 was able to maintain its P501S specific activity following additional stimulation on P501S transduced self B-LCL. The 3A-1 line was shown to specifically recognize self-B-LCL transduced with expression of P501S, but not self-B-LCL transduced with EGFP (by cytotoxicity experiments⁵¹Cr release) and gamma-Interferon production (Interferon-gamma Elispot; see above and Lalvani et al, J.Exp.Med.186:859-865, 1997)). The results of these experiments are presented in fig. 6A and 6B.

Example 13

Identification of prostate tumor antigens by microarray analysis

This example describes the isolation of certain prostate tumor polypeptides from a prostate tumor cDNA library.

The above human prostate tumor cDNA expression libraries were screened using microarray analysis to identify clones that showed at least 3-fold overexpression in prostate tumor and/or normal prostate tissue compared to normal tissue of the non-prostate gland (excluding the testis). 372 clones were identified and 319 of them were successfully sequenced. A summary of these clones (shown in SEQ ID NO:385-400) is given in Table I. Of these sequences, SEQ ID NOS: 386, 389, 390 and 392 correspond to the novel genes, while SEQ ID NOS: 393 and 396 correspond to the previously identified sequences. The other sequences (SEQ ID NOS: 385, 387, 388, 391, 394, 395 and 397-) 400) correspond to known sequences and are shown in Table I.

TABLE I

Overview of prostate tumor antigens

Gene identified previously for known gene
			T cell gamma chain kallikrein vector CGI-82 protein mRNA (23319; SEQ ID NO:385) PSAAld.6 Dehyd.L-iditol-2 dehydrogenase (23376; SEQ ID NO:388) Ets transcription factor PDEF (22672; SEQ ID NO:398) hTGR (22678; SEQ ID NO:398)399) KIAA0295 (22685; SEQ id no:400) prostatic acid phosphatase (22655; 397) transglutaminase (22611; SEQ ID NO:395) HDLBP (23508; 394) CGI-69 protein (23367; SEQ ID NO:387) KIAA0122 (23383; 391) TEEG of SEQ ID NO	P504SP1000CP501SP503SP510SP784PP502SP706P19142.2, bangur.seq(22621；SEQ ID NO:396)5566.1 Wang(23404；SEQ IDNO:393)P712PP778P	23379(SEQ ID NO:389)23399(SEQ ID NO:392)23320(SEQ ID NO:386)23381(SEQ ID NO:390)

CGI-82 showed 4.06-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 43% of prostate tumors, 25% of normal prostate, and undetectable in other normal tissues tested. L-iditol-2 dehydrogenase shows 4.94-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 90% of prostate tumors, 100% of normal prostate, and undetectable in other normal tissues tested. The Ets transcription factor PDEF showed 5.55-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 47% of prostate tumors, 25% of normal prostate, and undetectable in other normal tissues tested. hTGR1 showed 9.11-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 63% of prostate tumors and undetectable in the normal tissues tested (including normal prostate). KIAA0295 showed 5.59-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 47% of prostate tumors, but expressed at low or undetectable levels in the normal tissues tested (including normal prostate tissue). Prostatic acid phosphatase showed 9.14-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 67% of prostate tumors, 50% of normal prostate, and undetectable in all other normal tissues tested. Transglutaminase showed 14.84-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 30% of prostate tumors, 50% of normal prostate, and undetectable in other normal tissues tested. High Density Lipoprotein Binding Protein (HDLBP) showed 28.06-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 97% of prostate tumors, 75% of normal prostate, and undetectable in other normal tissues tested. CGI-69 showed 3.56 fold overexpression in prostate tissue compared to all other normal tissues tested. It is a low abundance gene that is detectable in more than 90% of prostate tumors and in 75% of normal prostate tissue. The expression of this gene in normal tissues is very low. KIAA0122 showed 4.24 fold overexpression in prostate tissue compared to other normal tissues tested. It was overexpressed in 57% of prostate tumors and undetectable in all normal tissues tested (including normal prostate tissue). 19142.2bangur showed 23.25 fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 97% of prostate tumors, 100% of normal prostate, and undetectable in other normal tissues tested. 5566.1Wang showed 3.31-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 97% of prostate tumors, 75% of normal prostate, and also in normal bone marrow, pancreas, and activated PBMCs. The new clone 23379 showed 4.86-fold overexpression in prostate tissue compared to other normal tissues tested. It was detectable in 97% of prostate tumors, 75% of normal prostate, and not in all other normal tissues tested. The new clone 23399 showed 4.09-fold overexpression in prostate tissue compared to other normal tissues tested. It is overexpressed in 27% of prostate tumors and undetectable in all normal tissues tested (including normal prostate tissue). The new clone 23320 showed 3.15-fold overexpression in prostate tissue compared to other normal tissues tested. It can be detected in all prostate tumors, 50% of normal prostate. It is also expressed in the normal colon and trachea. Other normal tissues do not express this gene at high levels.

Example 14

Identification of prostate tumor antigens by electronic deduction

This example describes the identification of prostate tumor antigens using electron subtraction techniques.

Potential prostate-specific genes were identified in the GenBank human EST database by electron subtraction (similar to that described by Vaspatzis et al, Proc. Natl. Acad. Sci. USA95: 300-. The sequences of various prostate library-derived EST clones (43,482) were obtained from the human EST database published in GenBank. Human EST databases were searched using BLASTN (national Center for Biotechnology information) using each prostate EST sequence as a query sequence. All matches considered identical (matching sequence length > 100 base pairs, identity match > 70% for this region) are arranged together in clusters. Clusters containing more than 200 ESTs were discarded as they might represent repetitive elements or highly expressed genes (such as ribosomal protein genes). If two or more clusters have a common EST, those clusters are arranged together into "super clusters" (supercluster), yielding 4,345 prostate super clusters.

Records of 479 personal cDNA libraries in GenBank were downloaded to generate a database of these cDNA library records. The 479 cDNA libraries were divided into 3 groups, "+" group (normal prostate and prostate tumor libraries, and breast cell lines where expression is desired), "-" group (libraries from other normal adult tissues where expression is not desired), and other groups (fetal tissue, infant tissue, tissues found only in females, cell lines other than prostate tumors, and non-prostate cell lines where expression is considered irrelevant). A summary of these library sets is presented in Table II.

TABLE II

Prostate cDNA library and EST

Libraries	Number of libraries	Number of ESTs
			+ group	25	43,482
Is normal	11	18,875
			Tumor(s)	11	21,769
Cell lines	3	2,838
			Group of	166
Others	287

Each super-cluster is analyzed for ESTs in the super-cluster. The tissue origin of each EST clone was recorded and the super clusters were thus divided into 4 groups: type 1-EST clones found only in the "+" group library; no expression was detected in the "-" or other group libraries; type 2-EST clones found only in the "+" and other groups of libraries; no expression was detected in the "-" group; type 3-EST clones found in the libraries of "+" group, "-" group and others, but the expression in the "+" group was higher than in the "-" group or others; type 4-EST clones found in the "+" group, "-" group and other groups of libraries, but the expression in the "+" group was higher than that in the "-" group. This analysis identified 4,345 breast clusters (see table iii). From these clusters, 3,172 EST clones were ordered to Research Genetics, Inc. and received as glycerol cryopreserved in 96-well plates.

TABLE III

Overview of prostate clusters

Type (B)	Number of super clusters	EST number ordered
			1	688	677
2	2899	2484
			3	85	11
4	673	0
			Total of	4345	3172

The inserts were PCR amplified using amino-linked PCR primers for Synteni microarray analysis. When more than one PCR product is obtained for a particular clone, the PCR product is not used for expression analysis. In total, 2,528 clones from the electron subtraction method were analyzed by microarray analysis to identify electron subtracted mammary clones with higher mRNA in tumors relative to normal tissues. These screens were carried out using Synteni (Palo Alto, CA) microarrays according to the manufacturer's instructions (and essentially as described by Schena et al, Proc. Natl. Acad. Sci. USA93: 10614-. In these assays, clones are arrayed on a chip and then probed with fluorescent probes generated from normal and tumor prostate cDNA, as well as a variety of other normal tissues. The slide was scanned and the fluorescence intensity was measured.

Clones with expression ratios above 3 (i.e., levels of prostate tumor cDNA at least 3-fold higher than normal prostate cDNA) were identified as prostate tumor specific sequences (table iv). The sequences of these clones are provided in SEQ ID NO 401-453 and some of the novel sequences are provided in SEQ ID NO 407, 413, 416-419, 422, 426, 427 and 450.

TABLE IV prostate tumor specific cloning

SEQ ID NO	Sequence name	Note
			401	22545	Previously identified P1000C
402	22547	Previously identified P704P
			403	22548	It is known that
404	22550	It is known that
			405	22551	PSA
406	22552	Prostate secreted protein 94
			407	22553	New
408	22558	Previously identified P509S
			409	22562	Glandular skin-stimulating releasease
410	22565	Previously identified P1000C
			411	22567	PAP
412	22568	B1006C (Breast tumor antigen)
			413	22570	New
414	22571	PSA
			415	22572	Previously identified P706P
416	22573	New
			417	22574	New
418	22575	New
			419	22580	New
420	22581	PAP
			421	22582	Prostate secreted protein 94
422	22583	New
			423	22584	Prostate secreted protein 94
424	22585	Prostate secreted protein 94
			425	22586	It is known that
426	22587	New
			427	22588	New
428	22589	PAP
			429	22590	It is known that
430	22591	PSA
			431	22592	It is known that
432	22593	Previously identified P777P
			433	22594	T cell receptor gamma chain
434	22595	Previously identified P705P
			435	22596	Previously identified P707P
436	22847	PAP
			437	22848	It is known that
438	22849	Prostate secretory protein 57
			439	22851	PAP
440	22852	PAP
			441	22853	PAP
442	22854	Previously identified P509S
			443	22855	Previously identified P705P
444	22856	Previously identified P774P
			445	22857	PSA
446	23601	Previously identified P777P
			447	23602	PSA
448	23605	PSA
			449	23606	PSA
450	23612	New
			451	23614	PSA
452	23618	Previously identified P1000C
			453	23622	Previously identified P705P

Example 15

Further identification of prostate tumor antigens by microarray analysis

This example describes the isolation of other prostate tumor polypeptides from a prostate tumor cDNA library.

The above human prostate tumor cDNA expression libraries were screened using microarray analysis to identify clones that showed at least 3-fold overexpression in prostate tumor and/or normal prostate tissue compared to normal tissue of the non-prostate gland (excluding the testis). 142 clones were identified and sequenced. Some of these clones are shown in SEQ ID NO 454-467. Of these sequences, SEQ ID NO 459-461 corresponds to a novel gene. The others (SEQ ID NOS: 454-458 and 461-467) correspond to known sequences.

Example 16

Further characterization of prostate tumor antigen P710P

This example describes a full-length clone of P710P.

The above prostate cDNA library was screened with the above P710P fragment. 1 million colonies were plated on LB/ampicillin plates. The colonies were leached using nylon filters, and the cDNA picked up from these filters was denatured and cross-linked to the filters by UV light. The P710P fragment was radiolabeled and used for hybridization to filters. Positive cDNA clones were selected, their cDNA recovered, and sequenced by an automated ABI sequencer. 4 sequences are obtained, which are shown in SEQ ID NO 468-471.

From the foregoing, it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not to be restricted except in light of the attached claims.

Sequence Listing <110> Corixa Corporation <120> compositions and methods <130> 210121.42701PC <140> PCT <141> 1999-07-08<160> 472<170> FastSEQ for Windows Version 3.0<210> 1<211> 814<212> DNA <213> Homo sapien <220> <221> misc feature <222> (1) · (814) <223> n = A, T, C or G387400 > 1tttttttttt tttttcacag tataacagct ctttatttct gtgagttcta ctaggaaatc 605 ccagggggtc cagtccctct ccttacttca tccccatccc atgccaaagg aagaccctcc ctccttggct cacagccttc tctaggcttc ccagtgcctc caggacagag tgggttatgt 240tttcagctcc atccttgctg tgagtgtctg gtgcgttgtg cctccagctt ctgctcagtg 63360 ctagagcggc cgccaccgcg gtggagctcc agcttttgtt ccctttagtg agggttaatt gcgcgcttgg cgtaatcatg gtcataactg tttcctgtgt gaaattgtta tccgctcaca 480 540 and ctaactca cattaattgc gttgcgctca ctgncgctgcatgcatgcatgcacg cgg 600 cggaa tgccagctgc attaatgaat cggccaacgc ncggaa gcggtttgcg ttttgggggc tcttccgctt ctcgctcact nantcggcggctct cggctgcggg gaacggtatc 720actcctcaaa ggnggtatta cggttatccn naaatcnggg gatacccngg aaaaaanttt 780aacaaaaggg cancaaaggg cngaaacgta aaaa 814<210> 2<211> 816<212> DNA <213> Homo sapien <220> <221> misc _ feature <222> (1) · (816) <223> n = A, t is set in the position of the base, c or G <400> 2acagaaatgt tggatggtgg agcacctttc tatacgactt acaggacagc agatggggaa 60ttcatggctg ttggagcaat agaaccccag ttctacgagc tgctgatcaa aggacttgga 120ctaaagtctg atgaacttcc caatcagatg agcatggatg attggccaga aatgaagaag 180aagtttgcag atgtatttgc aaagaagacg aaggcagagt ggtgtcaaat ctttgacggc 240acagatgcct gtgtgactcc ggttctgact tttgaggagg ttgttcatca tgatcacaac 300aaggaacggg gctcgtttat caccagtgag gagcaggacg tgagcccccg ccctgcacct 360ctgctgttaa acaccccagc catcccttct ttcaaaaggg atccactagt tctagaagcg 420gccgccaccg cggtggagct ccagcttttg ttccctttag tgagggttaa ttgcgcgctt 480ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt tatccgctca caattccccc 540aacatacgag ccggaacata aagtgttaag cctggggtgc ctaatgatg agctaactcn 600cattaattgc gttgcgctca ctgcccgctt tccagtcggg aaaactgtcg tgccactgcn 660 ttatgaatc ngcccacccc cgggaaagg cgggttgcntt ttgggcctct tccgctttcc 720tcgctcattg atcctngcnc ccggtcttcg gctgcggnga acggttcact cctcaaaggc 780 gg780 gtnccgg ttatcccaca anggggata cccnnga 816.

<210> 3

<211> 773

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(773)

<223> n = A,T,C or G

<400> 3cttttgaaag aagggatggc tggggtgttt aacagcagag gtgcagggcg ggggctcacg 60tcctgctcct cactggtgat aaacgagccc cgttccttgt tgtgatcatg atgaacaacc 120tcctcaaaag tcagaaccgg agtcacacag gcatctgtgc cgtcaaagat ttgacaccac 180tctgccttcg tcttctttgc aaatacatct gcaaacttct tcttcatttc tggccaatca 240tccatgctca tctgattggg aagttcatca gactttagtc canntccttt gatcagcagc 300tcgtagaact ggggttctat tgctccaaca gccatgaatt ccccatctgc tgtcctgtaa 360gtcgtataga aaggtgctcc accatccaac atgttctgtc ctcgaggggg ggcccggtac 420ccaattcgcc ctatantgag tcgtattacg cgcgctcact ggccgtcgtt ttacaacgtc 480gtgactggga aaaccctggg cgttaccaac ttaatcgcct tgcagcacat ccccctttcg 540ccagctgggc gtaatancga aaaggcccgc accgatcgcc cttccaacag ttgcgcacct 600gaatgggnaa atgggacccc cctgttaccg cgcattnaac ccccgcnggg tttngttgtt 660acccccacnt nnaccgctta cactttgcca gcgccttanc gcccgctccc tttcnccttt 720cttcccttcc tttcncnccn ctttcccccg gggtttcccc cntcaaaccc cna 773

<210> 4

<211> 828

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(828)

<223> n = A,T,C or G

<400> 4cctcctgagt cctactgacc tgtgctttct ggtgtggagt ccagggctgc taggaaaagg 60aatgggcaga cacaggtgta tgccaatgtt tctgaaatgg gtataatttc gtcctctcct 120tcggaacact ggctgtctct gaagacttct cgctcagttt cagtgaggac acacacaaag 180acgtgggtga ccatgttgtt tgtggggtgc agagatggga ggggtggggc ccaccctgga 240agagtggaca gtgacacaag gtggacactc tctacagatc actgaggata agctggagcc 300acaatgcatg aggcacacac acagcaagga tgacnctgta aacatagccc acgctgtcct 360gngggcactg ggaagcctan atnaggccgt gagcanaaag aaggggagga tccactagtt 420ctanagcggc cgccaccgcg gtgganctcc ancttttgtt ccctttagtg agggttaatt 480gcgcgcttgg cntaatcatg gtcatanctn tttcctgtgt gaaattgtta tccgctcaca 540attccacaca acatacganc cggaaacata aantgtaaac ctggggtgcc taatgantga 600ctaactcaca ttaattgcgt tgcgctcact gcccgctttc caatcnggaa acctgtcttg 660ccncttgcat tnatgaatcn gccaaccccc ggggaaaagc gtttgcgttt tgggcgctct 720tccgcttcct cnctcantta ntccctncnc tcggtcattc cggctgcngc aaaccggttc 780accncctcca aagggggtat tccggtttcc ccnaatccgg gganancc 828

<210> 5

<211> 834

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(834)

<223> n = A,T,C or G

<400> 5tttttttttt tttttactga tagatggaat ttattaagct tttcacatgt gatagcacat 60agttttaatt gcatccaaag tactaacaaa aactctagca atcaagaatg gcagcatgtt 120attttataac aatcaacacc tgtggctttt aaaatttggt tttcataaga taatttatac 180tgaagtaaat ctagccatgc ttttaaaaaa tgctttaggt cactccaagc ttggcagtta 240acatttggca taaacaataa taaaacaatc acaatttaat aaataacaaa tacaacattg 300taggccataa tcatatacag tataaggaaa aggtggtagt gttgagtaag cagttattag 360aatagaatac cttggcctct atgcaaatat gtctagacac tttgattcac tcagccctga 420cattcagttt tcaaagtagg agacaggttc tacagtatca ttttacagtt tccaacacat 480tgaaaacaag tagaaaatga tgagttgatt tttattaatg cattacatcc tcaagagtta 540tcaccaaccc ctcagttata aaaaattttc aagttatatt agtcatataa cttggtgtgc 600ttattttaaa ttagtgctaa atggattaag tgaagacaac aatggtcccc taatgtgatt 660gatattggtc atttttacca gcttctaaat ctnaactttc aggcttttga actggaacat 720tgnatnacag tgttccanag ttncaaccta ctggaacatt acagtgtgct tgattcaaaa 780tgttattttg ttaaaaatta aattttaacc tggtggaaaa ataatttgaa atna 834

<210> 6

<211> 818

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (818)

<223> n = A,T,C or G

<400> 6tttttttttt tttttttttt aagaccctca tcaatagatg gagacataca gaaatagtca 60aaccacatct acaaaatgcc agtatcaggc ggcggcttcg aagccaaagt gatgtttgga 120tgtaaagtga aatattagtt ggcggatgaa gcagatagtg aggaaagttg agccaataat 180gacgtgaagt ccgtggaagc ctgtggctac aaaaaatgtt gagccgtaga tgccgtcgga 240aatggtgaag ggagactcga agtactctga ggcttgtagg agggtaaaat agagacccag 300taaaattgta ataagcagtg cttgaattat ttggtttcgg ttgttttcta ttagactatg 360gtgagctcag gtgattgata ctcctgatgc gagtaatacg gatgtgttta ggagtgggac 420ttctagggga tttagcgggg tgatgcctgt tgggggccag tgccctccta gttggggggt 480aggggctagg ctggagtggt aaaaggctca gaaaaatcct gcgaagaaaa aaacttctga 540ggtaataaat aggattatcc cgtatcgaag gcctttttgg acaggtggtg tgtggtggcc 600ttggtatgtg ctttctcgtg ttacatcgcg ccatcattgg tatatggtta gtgtgttggg 660ttantanggc ctantatgaa gaacttttgg antggaatta aatcaatngc ttggccggaa 720gtcattanga nggctnaaaa ggccctgtta ngggtctggg ctnggtttta cccnacccat 780ggaatncncc ccccggacna ntgnatccct attcttaa 818

<210> 7

<211> 817

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(817)

<223> n = A,T,C or G

<400> 7tttttttttt tttttttttt tggctctaga gggggtagag ggggtgctat agggtaaata 60cgggccctat ttcaaagatt tttaggggaa ttaattctag gacgatgggt atgaaactgt 120ggtttgctcc acagatttca gagcattgac cgtagtatac ccccggtcgt gtagcggtga 180aagtggtttg gtttagacgt ccgggaattg catctgtttt taagcctaat gtgggacag 240ctcatgagtg caagacgtct tgtgatgtaa ttattatacn aatgggggct tcaatcggga 300gtactactcg attgtcaacg tcaaggagtc gcaggtcgcc tggttctagg aataatgggg 360gaagtatgta ggaattgaag attaatccgc cgtagtcggt gttctcctag gttcaatacc 420attggtggcc aattgatttg atggtaaggg gagggatcgt tgaactcgtc tgttatgtaa 480aggatncctt ngggatggga aggcnatnaa ggactangga tnaatggcgg gcangatatt 540tcaaacngtc tctanttcct gaaacgtctg aaatgttaat aanaattaan tttngttatt 600gaatnttnng gaaaagggct tacaggacta gaaaccaaat angaaaanta atnntaangg 660cnttatcntn aaaggtnata accnctccta tnatcccacc caatngnatt ccccacncnn 720acnattggat nccccanttc canaaanggc cnccccccgg tgnannccnc cttttgttcc 780cttnantgan ggttattcnc ccctngcntt atcancc 817

<210> 8

<211> 799

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (799)

<223> n = A,T,C or G

<400> 8catttccggg tttactttct aaggaaagcc gagcggaagc tgctaacgtg ggaatcggtg 60cataaggaga actttctgct ggcacgcgct agggacaagc gggagagcga ctccgagcgt 120ctgaagcgca cgtcccagaa ggtggacttg gcactgaaac agctgggaca catccgcgag 180tacgaacagc gcctgaaagt gctggagcgg gaggtccagc agtgtagccg cgtcctgggg 240tgggtggccg angcctganc cgctctgcct tgctgccccc angtgggccg ccaccccctg 300acctgcctgg gtccaaacac tgagccctgc tggcggactt caagganaac ccccacangg 360ggattttgct cctanantaa ggctcatctg ggcctcggcc cccccacctg gttggccttg 420tctttgangt gagccccatg tccatctggg ccactgtcng gaccaccttt ngggagtgtt 480ctccttacaa ccacannatg cccggctcct cccggaaacc antcccancc tgngaaggat 540caagncctgn atccactnnt nctanaaccg gccnccnccg cngtggaacc cnccttntgt 600tccttttcnt tnagggttaa tnncgccttg gccttnccan ngtcctncnc nttttccnnt 660gttnaaattg ttangcnccc nccnntcccn cnncnncnan cccgacccnn annttnnann 720ncctgggggt nccnncngat tgacccnncc nccctntant tgcnttnggg nncnntgccc 780ctttccctct nggganncg 799

<210> 9

<211> 801

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(801)

<223> n = A,T,C or G

<400> 9acgccttgat cctcccaggc tgggactggt tctgggagga gccgggcatg ctgtggtttg 60taangatgac actcccaaag gtggtcctga cagtggccca gatggacatg gggctcacct 120caaggacaag gccaccaggt gcgggggccg aagcccacat gatccttact ctatgagcaa 180aatcccctgt gggggcttct ccttgaagtc cgccancagg gctcagtctt tggacccang 240caggtcatgg ggttgtngnc caactggggg ccncaacgca aaanggcnca gggcctcngn 300cacccatccc angacgcggc tacactnctg gacctcccnc tccaccactt tcatgcgctg 360ttcntacccg cgnatntgtc ccanctgttt cngtgccnac tccancttct nggacgtgcg 420ctacatacgc ccggantcnc nctcccgctt tgtccctatc cacgtnccan caacaaattt 480cnccntantg caccnattcc cacntttnnc agntttccnc nncgngcttc cttntaaaag 540ggttganccc cggaaaatnc cccaaagggg gggggccngg tacccaactn ccccctnata 600gctgaantcc ccatnaccnn gnctcnatgg anccntccnt tttaannacn ttctnaactt 660gggaanancc ctcgnccntn cccccnttaa tcccnccttg cnangnncnt cccccnntcc 720ncccnnntng gcntntnann cnaaaaaggc ccnnnancaa tctcctnncn cctcanttcg 780ccanccctcg aaatcggccn c 801

<210> 10

<211> 789

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(789)

<223> n = A,T,C or G

<400> 10cagtctatnt ggccagtgtg gcagctttcc ctgtggctgc cggtgccaca tgcctgtccc 60acagtgtggc cgtggtgaca gcttcagccg ccctcaccgg gttcaccttc tcagccctgc 120agatcctgcc ctacacactg gcctccctct accaccggga gaagcaggtg ttcctgccca 180aataccgagg ggacactgga ggtgctagca gtgaggacag cctgatgacc agcttcctgc 240caggccctaa gcctggagct cccttcccta atggacacgt gggtgctgga ggcagtggcc 300tgctcccacc tccacccgcg ctctgcgggg cctctgcctg tgatgtctcc gtacgtgtgg 360tggtgggtga gcccaccgan gccagggtgg ttccgggccg gggcatctgc ctggacctcg 420ccatcctgga tagtgcttcc tgctgtccca ngtggcccca tccctgttta tgggctccat 480tgtccagctc agccagtctg tcactgccta tatggtgtct gccgcaggcc tgggtctggt 540cccatttact ttgctacaca ggtantattt gacaagaacg anttggccaa atactcagcg 600ttaaaaaatt ccagcaacat tgggggtgga aggcctgcct cactgggtcc aactccccgc 660tcctgttaac cccatggggc tgccggcttg gccgccaatt tctgttgctg ccaaantnat 720gtggctctct gctgccacct gttgctggct gaagtgcnta cngcncanct nggggggtng 780ggngttccc 789

<210> 11

<211> 772

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(772)

<223> n = A,T,C or G

<400> 11cccaccctac ccaaatatta gacaccaaca cagaaaagct agcaatggat tcccttctac 60tttgttaaat aaataagtta aatatttaaa tgcctgtgtc tctgtgatgg caacagaag 120accaacaggc cacatcctga taaaaggtaa gaggggggtg gatcagcaaa aagacagtgc 180tgtgggctga ggggacctgg ttcttgtgtg ttgcccctca ggactcttcc cctacaaata 240actttcatat gttcaaatcc catggaggag tgtttcatcc tagaaactcc catgcaagag 300ctacattaaa cgaagctgca ggttaagggg cttanagatg ggaaaccagg tgactgagtt 360tattcagctc ccaaaaaccc ttctctaggt gtgtctcaac taggaggcta gctgttaacc 420ctgagcctgg gtaatccacc tgcagagtcc ccgcattcca gtgcatggaa cccttctggc 480ctccctgtat aagtccagac tgaaaccccc ttggaaggnc tccagtcagg cagccctana 540aactggggaa aaaagaaaag gacgccccan cccccagctg tgcanctacg cacctcaaca 600gcacagggtg gcagcaaaaa aaccacttta ctttggcaca aacaaaaact ngggggggca 660accccggcac cccnangggg gttaacagga ancngggnaa cntggaaccc aattnaggca 720ggcccnccac cccnaatntt gctgggaaat ttttcctccc ctaaattntt tc 772

<210> 12

<211> 751

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (751)

<223> n = A,T,C or G

<400> 12gccccaattc cagctgccac accacccacg gtgactgcat tagttcggat gtcatacaaa 60agctgattga agcaaccctc tactttttgg tcgtgagcct tttgcttggt gcaggtttca 120ttggctgtgt tggtgacgtt gtcattgcaa cagaatgggg gaaaggcact gttctctttg 180aagtanggtg agtcctcaaa atccgtatag ttggtgaagc cacagcactt gagccctttc 240atggtggtgt tccacacttg agtgaagtct tcctgggaac cataatcttt cttgatggca 300ggcactacca gcaacgtcag ggaagtgctc agccattgtg gtgtacacca aggcgaccac 360agcagctgcn acctcagcaa tgaagatgan gaggangatg aagaagaacg tcncgagggc 420acacttgctc tcagtcttan caccatanca gcccntgaaa accaananca aagaccacna 480cnccggctgc gatgaagaaa tnaccccncg ttgacaaact tgcatggcac tggganccac 540agtggcccna aaaatcttca aaaaggatgc cccatcnatt gaccccccaa atgcccactg 600ccaacagggg ctgccccacn cncnnaacga tganccnatt gnacaagatc tncntggtct 660tnatnaacnt gaaccctgcn tngtggctcc tgttcaggnc cnnggcctga cttctnaann 720aangaactcn gaagncccca cngganannc g 751

<210> 13

<211> 729

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(729)

<223> n = A,T,C or G

<400> 13gagccaggcg tccctctgcc tgcccactca gtggcaacac ccgggagctg ttttgtcctt 60tgtggancct cagcagtncc ctctttcaga actcantgcc aaganccctg aacaggagcc 120accatgcagt gcttcagctt cattaagacc atgatgatcc tcttcaattt gctcatcttt 180ctgtgtggtg cagccctgtt ggcagtgggc atctgggtgt caatcgatgg ggcatccttt 240ctgaagatct tcgggccact gtcgtccagt gccatgcagt ttgtcaacgt gggctacttc 300ctcatcgcag ccggcgttgt ggtcttagct ctaggtttcc tgggctgcta tggtgctaag 360actgagagca agtgtgccct cgtgacgttc ttcttcatcc tcctcctcat cttcattgct 420gaggttgcaa tgctgtggtc gccttggtgt acaccacaat ggctgagcac ttcctgacgt 480tgctggtaat gcctgccatc aanaaaagat tatgggttcc caggaanact tcactcaagt 540gttggaacac caccatgaaa gggctcaagt gctgtggctt cnnccaacta tacggatttt 600gaagantcac ctacttcaaa gaaaanagtg cctttccccc atttctgttg caattgacaa 660acgtccccaa cacagccaat tgaaaacctg cacccaaccc aaangggtcc ccaaccanaa 720attnaaggg 729

<210> 14

<211> 816

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (816)

<223> n = A,T,C or G

<400> 14tgctcttcct caaagttgtt cttgttgcca taacaaccac cataggtaaa gcgggcgcag 60tgttcgctga aggggttgta gtaccagcgc gggatgctct ccttgcagag tcctgtgtct 120ggcaggtcca cgcagtgccc tttgtcactg gggaaatgga tgcgctggag ctcgtcaaag 180ccactcgtgt atttttcaca ggcagcctcg tccgacgcgt cggggcagtt gggggtgtct 240tcacactcca ggaaactgtc natgcagcag ccattgctgc agcggaactg ggtgggctga 300cangtgccag agcacactgg atggcgcctt tccatgnnan gggccctgng ggaaagtccc 360tganccccan anctgcctct caaangcccc accttgcaca ccccgacagg ctagaatgga 420atcttcttcc cgaaaggtag ttnttcttgt tgcccaancc anccccntaa acaaactctt 480gcanatctgc tccgnggggg tcntantacc ancgtgggaa aagaacccca ggcngcgaac 540caancttgtt tggatncgaa gcnataatct nctnttctgc ttggtggaca gcaccantna 600ctgtnnanct ttagnccntg gtcctcntgg gttgnncttg aacctaatcn ccnntcaact 660gggacaaggt aantngccnt cctttnaatt cccnancntn ccccctggtt tggggttttn 720cncnctccta ccccagaaan nccgtgttcc cccccaacta ggggccnaaa ccnnttnttc 780cacaaccctn ccccacccac gggttcngnt ggttng 816

<210> 15

<211> 783

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (783)

<223> n = A,T,C or G

<400> 15ccaaggcctg ggcaggcata nacttgaagg tacaacccca ggaacccctg gtgctgaagg 60atgtggaaaa cacagattgg cgcctactgc ggggtgacac ggatgtcagg gtagagagga 120aagacccaaa ccaggtggaa ctgtggggac tcaaggaang cacctacctg ttccagctga 180cagtgactag ctcagaccac ccagaggaca cggccaacgt cacagtcact gtgctgtcca 240ccaagcagac agaagactac tgcctcgcat ccaacaangt gggtcgctgc cggggctctt 300tcccacgctg gtactatgac cccacggagc agatctgcaa gagtttcgtt tatggaggct 360gcttgggcaa caagaacaac taccttcggg aagaagagtg cattctancc tgtcngggtg 420tgcaaggtgg gcctttgana ngcanctctg gggctcangc gactttcccc cagggcccct 480ccatggaaag gcgccatcca ntgttctctg gcacctgtca gcccacccag ttccgctgca 540ncaatggctg ctgcatcnac antttcctng aattgtgaca acacccccca ntgcccccaa 600ccctcccaac aaagcttccc tgttnaaaaatacnccantt ggcttttnac aaacncccgg 660cncctccntt ttccccnntn aacaaagggc nctngcnttt gaactgcccn aacccnggaa 720tctnccnngg aaaaantncc ccccctggtt cctnnaancc cctccncnaa anctnccccc 780ccc 783

<210> 16

<211> 801

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (801)

<223> n = A,T,C or G

<400> 16gccccaattc cagctgccac accacccacg gtgactgcat tagttcggat gtcatacaaa 60agctgattga agcaaccctc tactttttgg tcgtgagcct tttgcttggt gcaggtttca 120ttggctgtgt tggtgacgtt gtcattgcaa cagaatgggg gaaaggcact gttctctttg 180aagtagggtg agtcctcaaa atccgtatag ttggtgaagc cacagcactt gagccctttc 240atggtggtgt tccacacttg agtgaagtct tcctgggaac cataatcttt cttgatggca 300ggcactacca gcaacgtcag gaagtgctca gccattgtgg tgtacaccaa ggcgaccaca 360gcagctgcaa cctcagcaat gaagatgagg aggaggatga agaagaacgt cncgagggca 420cacttgctct ccgtcttagc accatagcag cccangaaac caagagcaaa gaccacaacg 480ccngctgcga atgaaagaaa ncacccacgt tgacaaactg catggccact ggacgacagt 540tggcccgaan atcttcagaa aagggatgcc ccatcgattg aacacccana tgcccactgc 600cnacagggct gcnccncncn gaaagaatga gccattgaag aaggatcntc ntggtcttaa 660tgaactgaaa ccntgcatgg tggcccctgt tcagggctct tggcagtgaa ttctganaaa 720aaggaacngc ntnagccccc ccaaangana aaacaccccc gggtgttgcc ctgaattggc 780ggccaaggan ccctgccccn g 801

<210> 17

<211> 740

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (740)

<223> n = A,T,C or G

<400> 17gtgagagcca ggcgtccctc tgcctgccca ctcagtggca acacccggga gctgttttgt 60cctttgtgga gcctcagcag ttccctcttt cagaactcac tgccaagagc cctgaacagg 120agccaccatg cagtgcttca gcttcattaa gaccatgatg atcctcttca atttgctcat 180ctttctgtgt ggtgcagccc tgttggcagt gggcatctgg gtgtcaatcg atggggcatc 240ctttctgaag atcttcgggc cactgtcgtc cagtgccatg cagtttgtca acgtgggcta 300cttcctcatc gcagccggcg ttgtggtctt tgctcttggt ttcctgggct gctatggtgc 360taagacggag agcaagtgtg ccctcgtgac gttcttcttc atcctcctcc tcatcttcat 420tgctgaagtt gcagctgctg tggtcgcctt ggtgtacacc acaatggctg aaccattcct 480gacgttgctg gtantgcctg ccatcaanaa agattatggg ttcccaggaa aaattcactc 540aantntggaa caccnccatg aaaagggctc caatttctgn tggcttcccc aactataccg 600gaattttgaa agantcnccc tacttccaaa aaaaaanant tgcctttncc cccnttctgt 660tgcaatgaaa acntcccaan acngccaatn aaaacctgcc cnnncaaaaa ggntcncaaa 720caaaaaaant nnaagggttn 740

<210> 18

<211> 802

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(802)

<223> n = A,T,C or G

<400> 18ccgctggttg cgctggtcca gngnagccac gaagcacgtc agcatacaca gcctcaatca 60caaggtcttc cagctgccgc acattacgca gggcaagagc ctccagcaac actgcatatg 120ggatacactt tactttagca gccagggtga caactgagag gtgtcgaagc ttattcttct 180gagcctctgt tagtggagga agattccggg cttcagctaa gtagtcagcg tatgtcccat 240aagcaaacac tgtgagcagc cggaaggtag aggcaaagtc actctcagcc agctctctaa 300cattgggcat gtccagcagt tctccaaaca cgtagacacc agnggcctcc agcacctgat 360ggatgagtgt ggccagcgct gcccccttgg ccgacttggc taggagcaga aattgctcct 420ggttctgccc tgtcaccttc acttccgcac tcatcactgc actgagtgtg ggggacttgg 480gctcaggatg tccagagacg tggttccgcc ccctcnctta atgacaccgn ccanncaacc 540gtcggctccc gccgantgng ttcgtcgtnc ctgggtcagg gtctgctggc cnctacttgc 600aancttcgtc nggcccatgg aattcaccnc accggaactn gtangatcca ctnnttctat 660aaccggncgc caccgcnnnt ggaactccac tcttnttncc tttacttgag ggttaaggtc 720acccttnncg ttaccttggt ccaaaccntn ccntgtgtcg anatngtnaa tcnggnccna 780tnccanccnc atangaagcc ng 802

<210> 19

<211> 731

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(731)

<223> n = A,T,C or G

<400> 19cnaagcttcc aggtnacggg ccgcnaancc tgacccnagg tancanaang cagncngcgg 60gagcccaccg tcacgnggng gngtctttat nggagggggc ggagccacat cnctggacnt 120cntgacccca actccccncc ncncantgca gtgatgagtg cagaactgaa ggtnacgtgg 180caggaaccaa gancaaannc tgctccnntc caagtcggcn nagggggcgg ggctggccac 240gcncatccnt cnagtgctgn aaagccccnn cctgtctact tgtttggaga acngcnnnga 300catgcccagn gttanataac nggcngagag tnantttgcc tctcccttcc ggctgcgcan 360cgngtntgct tagnggacat aacctgacta cttaactgaa cccnngaatc tnccncccct 420ccactaagct cagaacaaaa aacttcgaca ccactcantt gtcacctgnc tgctcaagta 480aagtgtaccc catncccaat gtntgctnga ngctctgncc tgcnttangt tcggtcctgg 540gaagacctat caattnaagc tatgtttctg actgcctctt gctccctgna acaancnacc 600cnncnntcca agggggggnc ggcccccaat ccccccaacc ntnaattnan tttanccccn 660cccccnggcc cggcctttta cnancntcnn nnacngggna aaaccnnngc tttncccaac 720nnaatccncc t 731

<210> 20

<211> 754

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(754)

<223> n = A,T,C or G

<400> 20tttttttttt tttttttttt taaaaacccc ctccattnaa tgnaaacttc cgaaattgtc 60caaccccctc ntccaaatnn ccntttccgg gngggggttc caaacccaan ttanntttgg 120annttaaatt aaatnttnnt tggnggnnna anccnaatgt nangaaagtt naacccanta 180tnancttnaa tncctggaaa ccngtngntt ccaaaaatnt ttaaccctta antccctccg 240aaatngttna nggaaaaccc aanttctcnt aaggttgttt gaaggntnaa tnaaaanccc 300nnccaattgt ttttngccac gcctgaatta attggnttcc gntgttttcc nttaaaanaa 360ggnnancccc ggttantnaa tccccccnnc cccaattata ccganttttt ttngaattgg 420gancccncgg gaattaacgg ggnnnntccc tnttgggggg cnggnncccc ccccntcggg 480ggttngggnc aggncnnaat tgtttaaggg tccgaaaaat ccctccnaga aaaaaanctc 540ccaggntgag nntngggttt nccccccccc canggcccct ctcgnanagt tggggtttgg 600ggggcctggg attttntttc ccctnttncc tccccccccc ccnggganag aggttngngt 660tttgntcnnc ggccccnccn aaganctttn ccganttnan ttaaatccnt gcctnggcga 720agtccnttgn agggntaaan ggccccctnn cggg 754

<210> 21

<211> 755

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(755)

<223> n = A,T,C or G

<400> 21atcancccat gaccccnaac nngggaccnc tcanccggnc nnncnaccnc cggccnatca 60nngtnagnnc actncnnttn natcacnccc cnccnactac gcccncnanc cnacgcncta 120nncanatncc actganngcg cgangtngan ngagaaanct nataccanag ncaccanacn 180ccagctgtcc nanaangcct nnnatacngg nnnatccaat ntgnancctc cnaagtattn 240nncnncanat gattttcctn anccgattac ccntnccccc tancccctcc cccccaacna 300cgaaggcnct ggnccnaagg nngcgncncc ccgctagntc cccnncaagt cncncnccta 360aactcanccn nattacncgc ttcntgagta tcactccccg aatctcaccc tactcaactc 420aaaaanatcn gatacaaaat aatncaagcc tgnttatnac actntgactg ggtctctatt 480ttagnggtcc ntnaancntc ctaatacttc cagtctncct tcnccaattt ccnaanggct 540ctttcngaca gcatnttttg gttcccnntt gggttcttan ngaattgccc ttcntngaac 600gggctcntct tttccttcgg ttancctggn ttcnnccggc cagttattat ttcccntttt 660aaattcntnc cntttanttt tggcnttcna aacccccggc cttgaaaacg gccccctggt 720aaaaggttgt tttganaaaa tttttgtttt gttcc 755

<210> 22

<211> 849

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(849)

<223> n = A,T,C or G

<400> 22tttttttttt tttttangtg tngtcgtgca ggtagaggct tactacaant gtgaanacgt 60acgctnggan taangcgacc cganttctag ganncnccct aaaatcanac tgtgaagatn 120atcctgnnna cggaanggtc accggnngat nntgctaggg tgnccnctcc cannncnttn 180cataactcng nggccctgcc caccaccttc ggcggcccng ngnccgggcc cgggtcattn 240gnnttaaccn cactnngcna ncggtttccn nccccnncng acccnggcga tccggggtnc 300tctgtcttcc cctgnagncn anaaantggg ccncggnccc ctttacccct nnacaagcca 360cngccntcta nccncngccc cccctccant nngggggact gccnanngct ccgttnctng 420nnaccccnnn gggtncctcg gttgtcgant cnaccgnang ccanggattc cnaaggaagg 480tgcgttnttg gcccctaccc ttcgctncgg nncacccttc ccgacnanga nccgctcccg 540cncnncgnng cctcncctcg caacacccgc nctcntcngt ncggnnnccc ccccacccgc 600nccctcncnc ngncgnancn ctccnccncc gtctcannca ccaccccgcc ccgccaggcc 660ntcanccacn ggnngacnng nagcncnntc gcnccgcgcn gcgncnccct cgccncngaa 720ctncntcngg ccantnncgc tcaanccnna cnaaacgccg ctgcgcggcc cgnagcgncc 780ncctccncga gtcctcccgn cttccnaccc angnnttccn cgaggacacn nnaccccgcc 840nncangcgg 849

<210> 23

<211> 872

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(872)

<223> n = A,T,C or G

<400> 23gcgcaaacta tacttcgctc gnactcgtgc gcctcgctnc tcttttcctc cgcaaccatg 60tctgacnanc ccgattnggc ngatatcnan aagntcganc agtccaaact gantaacaca 120cacacncnan aganaaatcc nctgccttcc anagtanacn attgaacnng agaaccangc 180nggcgaatcg taatnaggcg tgcgccgcca atntgtcncc gtttattntn ccagcntcnc 240ctnccnaccc tacntcttcn nagctgtcnn acccctngtn cgnacccccc naggtcggga 300tcgggtttnn nntgaccgng cnncccctcc ccccntccat nacganccnc ccgcaccacc 360nanngcncgc nccccgnnct cttcgccncc ctgtcctntn cccctgtngc ctggcncngn 420accgcattga ccctcgccnn ctncnngaaa ncgnanacgt ccgggttgnn annancgctg 480tgggnnngcg tctgcnccgc gttccttccn ncnncttcca ccatcttcnt tacngggtct 540ccncgccntc tcnnncacnc cctgggacgc tntcctntgc cccccttnac tccccccctt 600cgncgtgncc cgnccccacc ntcatttnca nacgntcttc acaannncct ggntnnctcc 660cnancngncn gtcanccnag ggaagggngg ggnnccnntg nttgacgttg nggngangtc 720cgaanantcc tcnccntcan cnctacccct cgggcgnnct ctcngttncc aacttancaa 780ntctcccccg ngngcncntc tcagcctcnc ccnccccnct ctctgcantg tnctctgctc 840tnaccnntac gantnttcgn cnccctcttt cc 872

<210> 24

<211> 815

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(815)

<223> n = A,T,C or G

<400> 24gcatgcaagc ttgagtattc tatagngtca cctaaatanc ttggcntaat catggtcnta 60nctgncttcc tgtgtcaaat gtatacnaan tanatatgaa tctnatntga caaganngta 120tcntncatta gtaacaantg tnntgtccat cctgtcngan canattccca tnnattncgn 180cgcattcncn gcncantatn taatngggaa ntcnnntnnn ncaccnncat ctatcntncc 240gcnccctgac tggnagagat ggatnanttc tnntntgacc nacatgttca tcttggattn 300aananccccc cgcngnccac cggttngnng cnagccnntc ccaagacctc ctgtggaggt 360aacctgcgtc aganncatca aacntgggaa acccgcnncc angtnnaagt ngnnncanan 420gatcccgtcc aggnttnacc atcccttcnc agcgccccct ttngtgcctt anagngnagc 480gtgtccnanc cnctcaacat ganacgcgcc agnccanccg caattnggca caatgtcgnc 540gaacccccta gggggantna tncaaanccc caggattgtc cncncangaa atcccncanc 600cccnccctac ccnnctttgg gacngtgacc aantcccgga gtnccagtcc ggccngnctc 660ccccaccggt nnccntgggg gggtgaanct cngnntcanc cngncgaggn ntcgnaagga 720accggncctn ggncgaanng ancnntcnga agngccncnt cgtataaccc cccctcncca 780nccnacngnt agntcccccc cngggtncgg aangg 815

<210> 25

<211> 775

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(775)

<223> n = A,T,C or G

<400> 25ccgagatgtc tcgctccgtg gccttagctg tgctcgcgct actctctctt tctggcctgg 60aggctatcca gcgtactcca aagattcagg tttactcacg tcatccagca gagaatggaa 120agtcaaattt cctgaattgc tatgtgtctg ggtttcatcc atccgacatt gaanttgact 180tactgaagaa tgganagaga attgaaaaag tggagcattc agacttgtct ttcagcaagg 240actggtcttt ctatctcntg tactacactg aattcacccc cactgaaaaa gatgagtatg 300cctgccgtgt gaaccatgtg actttgtcac agcccaagat agttaagtgg gatcgagaca 360tgtaagcagn cnncatggaa gtttgaagat gccgcatttg gattggatga attccaaatt 420ctgcttgctt gcnttttaat antgatatgc ntatacaccc taccctttat gnccccaaat 480tgtaggggtt acatnantgt tcncntngga catgatcttc ctttataant ccnccnttcg 540aattgcccgt cncccngttn ngaatgtttc cnnaaccacg gttggctccc ccaggtcncc 600tcttacggaa gggcctgggc cnctttncaa ggttggggga accnaaaatt tcncttntgc 660ccncccncca cnntcttgng nncncanttt ggaacccttc cnattcccct tggcctcnna 720nccttnncta anaaaacttn aaancgtngc naaanntttn acttcccccc ttacc 775

<210> 26

<211> 820

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(820)

<223> n = A,T,C or G

<400> 26anattantac agtgtaatct tttcccagag gtgtgtanag ggaacggggc ctagaggcat 60cccanagata ncttatanca acagtgcttt gaccaagagc tgctgggcac atttcctgca 120gaaaaggtgg cggtccccat cactcctcct ctcccatagc catcccagag gggtgagtag 180ccatcangcc ttcggtggga gggagtcang gaaacaacan accacagagc anacagacca 240ntgatgacca tgggcgggag cgagcctctt ccctgnaccg gggtggcana nganagccta 300nctgaggggt cacactataa acgttaacga ccnagatnan cacctgcttc aagtgcaccc 360ttcctacctg acnaccagng accnnnaact gcngcctggg gacagcnctg ggancagcta 420acnnagcact cacctgcccc cccatggccg tncgcntccc tggtcctgnc aagggaagct 480ccctgttgga attncgggga naccaaggga nccccctcct ccanctgtga aggaaaaann 540gatggaattt tncccttccg gccnntcccc tcttccttta cacgccccct nntactcntc 600tccctctntt ntcctgncnc acttttnacc ccnnnatttc ccttnattga tcggannctn 660ganattccac tnncgcctnc cntcnatcng naanacnaaa nactntctna cccnggggat 720gggnncctcg ntcatcctct ctttttcnct accnccnntt ctttgcctct ccttngatca780tccaaccntc gntggccntn cccccccnnn tcctttnccc820

<210> 27

<211> 818

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(818)

<223> n = A,T,C or G

<400> 27tctgggtgat ggcctcttcc tcctcaggga cctctgactg ctctgggcca aagaatctct 60tgtttcttct ccgagcccca ggcagcggtg attcagccct gcccaacctg attctgatga 120ctgcggatgc tgtgacggac ccaaggggca aatagggtcc cagggtccag ggaggggcgc 180ctgctgagca cttccgcccc tcaccctgcc cagcccctgc catgagctct gggctgggtc 240tccgcctcca gggttctgct cttccangca ngccancaag tggcgctggg ccacactggc 300ttcttcctgc cccntccctg gctctgantc tctgtcttcc tgtcctgtgc angcnccttg 360gatctcagtt tccctcnctc anngaactct gtttctgann tcttcantta actntgantt 420tatnaccnan tggnctgtnc tgtcnnactt taatgggccn gaccggctaa tccctccctc 480nctcccttcc anttcnnnna accngcttnc cntcntctcc ccntancccg ccngggaanc 540ctcctttgcc ctnaccangg gccnnnaccg cccntnnctn ggggggcnng gtnnctncnc 600ctgntnnccc cnctcncnnt tncctcgtcc cnncnncgcn nngcannttc ncngtcccnn 660tnnctcttcn ngtntcgnaa ngntcncntn tnnnnngncn ngntnntncn tccctctcnc 720cnnntgnang tnnttnnnnc ncngnncccc nnnncnnnnn nggnnntnnn tctncncngc 780cccnnccccc ngnattaagg cctccnntct ccggccnc 818

<210> 28

<211> 731

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (731)

<223> n = A,T,C or G

<400> 28aggaagggcg gagggatatt gtangggatt gagggatagg agnataangg gggaggtgtg 60tcccaacatg anggtgnngt tctcttttga angagggttg ngtttttann ccnggtgggt 120gattnaaccc cattgtatgg agnnaaaggn tttnagggat ttttcggctc ttatcagtat 180ntanattcct gtnaatcgga aaatnatntt tcnncnggaa aatnttgctc ccatccgnaa 240attnctcccg ggtagtgcat nttngggggn cngccangtt tcccaggctg ctanaatcgt 300actaaagntt naagtgggan tncaaatgaa aacctnncac agagnatccn tacccgactg 360tnnnttncct tcgccctntg actctgcnng agcccaatac ccnngngnat gtcncccngn 420nnngcgncnc tgaaannnnc tcgnggctnn gancatcang gggtttcgca tcaaaagcnn 480cgtttcncat naaggcactt tngcctcatc caaccnctng ccctcnncca tttngccgtc 540nggttcncct acgctnntng cncctnnntn ganattttnc ccgcctnggg naancctcct 600gnaacgggta gggncttntc ttttnaccnn gnggtntact aatcnnctnc acgcntnctt 660tctcnacccc cccccttttt caatcccanc ggcnaatggg gtctccccnn cgangggggg 720nnncccannc c 731

<210> 29

<211> 822

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(822)

<223> n = A,T,C or G

<400> 29actagtccag tgtggtggaa ttccattgtg ttggggncnc ttctatgant antnttagat 60cgctcanacc tcacancctc ccnacnangc ctataangaa nannaataga nctgtncnnt 120atntntacnc tcatanncct cnnnacccac tccctcttaa cccntactgt gcctatngcn 180tnnctantct ntgccgcctn cnanccaccn gtgggccnac cncnngnatt ctcnatctcc 240tcnccatntn gcctananta ngtncatacc ctatacctac nccaatgcta nnnctaancn 300tccatnantt annntaacta ccactgacnt ngactttcnc atnanctcct aatttgaatc 360tactctgact cccacngcct annnattagc ancntccccc nacnatntct caaccaaatc 420ntcaacaacc tatctanctg ttcnccaacc nttncctccg atccccnnac aacccccctc 480ccaaataccc nccacctgac ncctaacccn caccatcccg gcaagccnan ggncatttan 540ccactggaat cacnatngganaaaaaaaac ccnaactctc tancncnnat ctccctaana 600aatnctcctn naatttactn ncantnccat caancccacn tgaaacnnaa cccctgtttt 660tanatccctt ctttcgaaaa ccnacccttt annncccaac ctttngggcc cccccnctnc 720ccnaatgaag gncncccaat cnangaaacg nccntgaaaa ancnaggcna anannntccg 780canatcctat cccttanttn ggggnccctt ncccngggcc cc 822

<210> 30

<211> 787

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(787)

<223> n = A,T,C or G

<400> 30cggccgcctg ctctggcaca tgcctcctga atggcatcaa aagtgatgga ctgcccattg 60ctagagaaga ccttctctcc tactgtcatt atggagccct gcagactgag ggctcccctt 120gtctgcagga tttgatgtct gaagtcgtgg agtgtggctt ggagctcctc atctacatna 180gctggaagcc ctggagggcc tctctcgcca gcctccccct tctctccacg ctctccangg 240acaccagggg ctccaggcag cccattattc ccagnangac atggtgtttc tccacgcgga 300cccatggggc ctgnaaggcc agggtctcct ttgacaccat ctctcccgtc ctgcctggca 360ggccgtggga tccactantt ctanaacggn cgccaccncg gtgggagctc cagcttttgt 420tcccnttaat gaaggttaat tgcncgcttg gcgtaatcat nggtcanaac tntttcctgt 480gtgaaattgt ttntcccctc ncnattccnc ncnacatacn aacccggaan cataaagtgt 540taaagcctgg gggtngcctn nngaatnaac tnaactcaat taattgcgtt ggctcatggc 600ccgctttccn ttcnggaaaa ctgtcntccc ctgcnttnnt gaatcggcca ccccccnggg 660aaaagcggtt tgcnttttng ggggntcctt ccncttcccc cctcnctaan ccctncgcct 720cggtcgttnc nggtngcggg gaangggnat nnnctcccnc naagggggng agnnngntat 780ccccaaa 787

<210> 31

<211> 799

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (799)

<223> n = A,T,C or G

<400> 31tttttttttt tttttttggc gatgctactg tttaattgca ggaggtgggg gtgtgtgtac 60catgtaccag ggctattaga agcaagaagg aaggagggag ggcagagcgc cctgctgagc 120aacaaaggac tcctgcagcc ttctctgtct gtctcttggc gcaggcacat ggggaggcct 180cccgcagggt gggggccacc agtccagggg tgggagcact acanggggtg ggagtgggtg 240gtggctggtn cnaatggcct gncacanatc cctacgattc ttgacacctg gatttcacca 300ggggaccttc tgttctccca nggnaacttc ntnnatctcn aaagaacaca actgtttctt 360cngcanttct ggctgttcat ggaaagcaca ggtgtccnat ttnggctggg acttggtaca 420tatggttccg gcccacctct cccntcnaan aagtaattca cccccccccn ccntctnttg 480cctgggccct taantaccca caccggaact canttantta ttcatcttng gntgggcttg 540ntnatcnccn cctgaangcg ccaagttgaa aggccacgcc gtncccnctc cccatagnan 600nttttnncnt canctaatgc ccccccnggc aacnatccaa tccccccccn tgggggcccc 660agcccanggc ccccgnctcg ggnnnccngn cncgnantcc ccaggntctc ccantcngnc 720ccnnngcncc cccgcacgca gaacanaagg ntngagccnc cgcannnnnn nggtnncnac 780ctcgcccccc ccnncgnng 799

<210> 32

<211> 789

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(789)

<223> n = A,T,C or G

<400> 32tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60ttttnccnag ggcaggttta ttgacaacct cncgggacac aancaggctg gggacaggac 120ggcaacaggc tccggcggcg gcggcggcgg ccctacctgc ggtaccaaat ntgcagcctc 180cgctcccgct tgatnttcct ctgcagctgc aggatgccnt aaaacagggc ctcggccntn 240ggtgggcacc ctgggatttn aatttccacg ggcacaatgc ggtcgcancc cctcaccacc 300nattaggaat agtggtntta cccnccnccg ttggcncact ccccntggaa accacttntc 360gcggctccgg catctggtct taaaccttgc aaacnctggg gccctctttt tggttantnt 420nccngccaca atcatnactc agacggcnc gggctggccc caaaaaancn ccccaaaacc 480ggnccatgtc ttnncggggt tgctgcnatn tncatcacct cccgggcnca ncaggncaac 540ccaaaagttc ttgnggcccn caaaaaanct ccggggggnc ccagtttcaa caaagtcatc 600ccccttggcc cccaaatcct ccccccgntt nctgggtttg ggaacccacg cctctnnctt 660tggnnggcaa gntggntccc ccttcgggcc cccggtgggc ccnnctctaa ngaaaacncc 720ntcctnnnca ccatcccccc nngnnacgnc tancaangna tccctttttt tanaaacggg 780ccccccncg 789

<210> 33

<211> 793

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(793)

<223> n = A,T,C or G

<400> 33gacagaacat gttggatggt ggagcacctt tctatacgac ttacaggaca gcagatgggg 60aattcatggc tgttggagca atanaacccc agttctacga gctgctgatc aaaggacttg 120gactaaagtc tgatgaactt cccaatcaga tgagcatgga tgattggcca gaaatgaana 180agaagtttgc agatgtattt gcaaagaaga cgaaggcaga gtggtgtcaa atctttgacg 240gcacagatgc ctgtgtgact ccggttctga cttttgagga ggttgttcat catgatcaca 300acaangaacg gggctcgttt atcaccantg aggagcagga cgtgagcccc cgccctgcac 360ctctgctgtt aaacacccca gccatccctt ctttcaaaag ggatccacta cttctagagc 420ggncgccacc gcggtggagc tccagctttt gttcccttta gtgagggtta attgcgcgct 480tggcgtaatc atggtcatan ctgtttcctg tgtgaaattg ttatccgctc acaattccac 540acaacatacg anccggaagc atnaaatttt aaagcctggn ggtngcctaa tgantgaact 600nactcacatt aattggcttt gcgctcactg cccgctttcc agtccggaaa acctgtcctt 660gccagctgcc nttaatgaat cnggccaccc cccggggaaa aggcngtttg cttnttgggg 720cgcncttccc gctttctcgc ttcctgaant ccttcccccc ggtctttcgg cttgcggcna 780acggtatcna cct 793

<210> 34

<211> 756

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(756)

<223> n = A,T,C or G

<400> 34gccgcgaccg gcatgtacga gcaactcaag ggcgagtgga accgtaaaag ccccaatctt 60ancaagtgcg gggaanagct gggtcgactc aagctagttc ttctggagct caacttcttg 120ccaaccacag ggaccaagct gaccaaacag cagctaattc tggcccgtga catactggag 180atcggggccc aatggagcat cctacgcaan gacatcccct ccttcgagcg ctacatggcc 240cagctcaaat gctactactt tgattacaan gagcagctcc ccgagtcagc ctatatgcac 300cagctcttgg gcctcaacct cctcttcctg ctgtcccaga accgggtggc tgantnccac 360acgganttgg ancggctgcc tgcccaanga catacanacc aatgtctaca tcnaccacca 420gtgtcctgga gcaatactga tgganggcag ctaccncaaa gtnttcctgg ccnagggtaa 480catcccccgc cgagagctac accttcttca ttgacatcct gctcgacact atcagggatg 540aaaatcgcng ggttgctcca gaaaggctnc aanaanatcc ttttcnctga aggcccccgg 600atncnctagt nctagaatcg gcccgccatc gcggtgganc ctccaacctt tcgttnccct 660ttactgaggg ttnattgccg cccttggcgt tatcatggtc acnccngttn cctgtgttga 720aattnttaac cccccacaat tccacgccna cattng 756

<210> 35

<211> 834

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (834)

<223> n = A,T,C or G

<400> 35ggggatctct anatcnacct gnatgcatgg ttgtcggtgt ggtcgctgtc gatgaanatg 60aacaggatct tgcccttgaa gctctcggct gctgtnttta agttgctcag tctgccgtca 120tagtcagaca cnctcttggg caaaaaacan caggatntga gtcttgattt cacctccaat 180aatcttcngg gctgtctgct cggtgaactc gatgacnang ggcagctggt tgtgtntgat 240aaantccanc angttctcct tggtgacctc cccttcaaagttgttccggc cttcatcaaa 300cttctnnaan angannancc canctttgtc gagctggnat ttgganaaca cgtcaccgtt 360ggaaactgat cccaaatggt atgtcatcca tcgcctctgc tgcctgcaaa aaacttgctt 420ggcncaaatc cgactccccn tccttgaaag aagccnatca cacccccctc cctggactcc 480nncaangact ctnccgctnc cccntccnng cagggttggt ggcannccgg gcccntgcgc 540ttcttcagcc agttcacnat nttcatcagc ccctctgcca gctgttntat tccttggggg 600ggaanccgtc tctcccttcc tgaannaact ttgaccgtng gaatagccgc gcntcnccnt 660acntnctggg ccgggttcaa antccctccn ttgncnntcn cctcgggcca ttctggattt 720nccnaacttt ttccttcccc cnccccncgg ngtttggntt tttcatnggg ccccaactct 780gctnttggcc antcccctgg gggcntntan cnccccctnt ggtcccntng ggcc 834

<210> 36

<211> 814

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(814)

<223> n = A,T,C or G

<400> 36cggncgcttt ccngccgcgc cccgtttcca tgacnaaggc tcccttcang ttaaatacnn 60cctagnaaac attaatgggt tgctctacta atacatcata cnaaccagta agcctgccca 120naacgccaac tcaggccatt cctaccaaag gaagaaaggc tggtctctcc accccctgta 180ggaaaggcct gccttgtaag acaccacaat ncggctgaat ctnaagtctt gtgttttact 240aatggaaaaa aaaaataaac aanaggtttt gttctcatgg ctgcccaccg cagcctggca 300ctaaaacanc ccagcgctca cttctgcttg ganaaatatt ctttgctctt ttggacatca 360ggcttgatgg tatcactgcc acntttccac ccagctgggc ncccttcccc catntttgtc 420antganctgg aaggcctgaa ncttagtctc caaaagtctc ngcccacaag accggccacc 480aggggangtc ntttncagtg gatctgccaa anantacccn tatcatcnnt gaataaaaag 540gcccctgaac ganatgcttc cancancctt taagacccat aatcctngaa ccatggtgcc 600cttccggtct gatccnaaag gaatgttcct gggtcccant ccctcctttg ttncttacgt 660tgtnttggac ccntgctngn atnacccaan tganatcccc ngaagcaccc tncccctggc 720atttganttt cntaaattct ctgccctacn nctgaaagca cnattccctn ggcnccnaan 780ggngaactca agaaggtctn ngaaaaacca cncn 814

<210> 37

<211> 760

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(760)

<223> n = A,T,C or G

<400> 37gcatgctgct cttcctcaaa gttgttcttg ttgccataac aaccaccata ggtaaagcgg 60gcgcagtgtt cgctgaaggg gttgtagtac cagcgcggga tgctctcctt gcagagtcct 120gtgtctggca ggtccacgca atgccctttg tcactgggga aatggatgcg ctggagctcg 180tcnaanccac tcgtgtattt ttcacangca gcctcctccg aagcntccgg gcagttgggg 240gtgtcgtcac actccactaa actgtcgatn cancagccca ttgctgcagc ggaactgggt 300gggctgacag gtgccagaac acactggatn ggcctttcca tggaagggcc tgggggaaat 360cncctnancc caaactgcct ctcaaaggcc accttgcaca ccccgacagg ctagaaatgc 420actcttcttc ccaaaggtag ttgttcttgt tgcccaagca ncctccanca aaccaaaanc 480ttgcaaaatc tgctccgtgg gggtcatnnn taccanggtt ggggaaanaa acccggcngn 540ganccncctt gtttgaatgc naaggnaata atcctcctgt cttgcttggg tggaanagca 600caattgaact gttaacnttg ggccgngttc cnctngggtg gtctgaaact aatcaccgtc 660actggaaaaa ggtangtgcc ttccttgaat tcccaaantt cccctngntt tgggtnnttt 720ctcctctncc ctaaaaatcg tnttcccccc ccntanggcg 760

<210> 38

<211> 724

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(724)

<223> n = A,T,C or G

<400> 38tttttttttt tttttttttt tttttttttt tttttaaaaa ccccctccat tgaatgaaaa 60cttccnaaat tgtccaaccc cctcnnccaa atnnccattt ccgggggggg gttccaaacc 120caaattaatt ttgganttta aattaaatnt tnattngggg aanaanccaa atgtnaagaa 180aatttaaccc attatnaact taaatncctn gaaacccntg gnttccaaaa atttttaacc 240cttaaatccc tccgaaattg ntaanggaaa accaaattcn cctaaggctn tttgaaggtt 300ngatttaaac ccccttnant tnttttnacc cnngnctnaa ntatttngnt tccggtgttt 360tcctnttaan cntnggtaac tcccgntaat gaannnccct aanccaatta aaccgaattt 420tttttgaatt ggaaattccn ngggaattna ccggggtttt tcccntttgg gggccatncc 480cccnctttcg gggtttgggn ntaggttgaa tttttnnang ncccaaaaaa ncccccaana 540aaaaaactcc caagnnttaa ttngaatntc ccccttccca ggccttttgg gaaaggnggg 600tttntggggg ccngggantt cnttcccccn ttnccncccc ccccccnggt aaanggttat 660ngnntttggt ttttgggccc cttnanggac cttccggatn gaaattaaat ccccgggncg 720gccg 724

<210> 39

<211> 751

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(751)

<223> n = A,T,C or G

<400> 39tttttttttt tttttctttg ctcacattta atttttattt tgattttttt taatgctgca 60caacacaata tttatttcat ttgtttcttt tatttcattt tatttgtttg ctgctgctgt 120tttatttatt tttactgaaa gtgagaggga acttttgtgg ccttttttcc tttttctgta 180ggccgcctta agctttctaa atttggaaca tctaagcaag ctgaanggaa aagggggttt 240cgcaaaatca ctcgggggaa nggaaaggtt gctttgttaa tcatgcccta tggtgggtga 300ttaactgctt gtacaattac ntttcacttt taattaattg tgctnaangc tttaattana 360cttgggggtt ccctccccan accaaccccn ctgacaaaaa gtgccngccc tcaaatnatg 420tcccggcnnt cnttgaaaca cacngcngaa ngttctcatt ntccccncnc caggtnaaaa 480tgaagggtta ccatntttaa cnccacctcc acntggcnnn gcctgaatcc tcnaaaancn 540ccctcaancn aattnctnng ccccggtcnc gcntnngtcc cncccgggct ccgggaantn 600cacccccnga anncnntnnc naacnaaatt ccgaaaatat tcccnntcnc tcaattcccc 660cnnagactnt cctcnncnan cncaattttc ttttnntcac gaacncgnnc cnnaaaatgn 720nnnncncctc cnctngtccn naatcnccan c 751

<210> 40

<211> 753

<212> DNA

<213> Homo sapien

<220>

<221> misc_featu

<222> (1)...(753)

<223> n = A,T,C or G

<400> 40gtggtatttt ctgtaagatc aggtgttcct ccctcgtagg tttagaggaa acaccctcat 60agatgaaaac ccccccgaga cagcagcact gcaactgcca agcagccggg gtaggagggg 120cgccctatgc acagctgggc ccttgagaca gcagggcttc gatgtcaggc tcgatgtcaa 180tggtctggaa gcggcggctg tacctgcgta ggggcacacc gtcagggccc accaggaact 240tctcaaagtt ccaggcaacn tcgttgcgac acaccggaga ccaggtgatn agcttggggt 300cggtcataan cgcggtggcg tcgtcgctgg gagctggcag ggcctcccgc aggaaggcna 360ataaaaggtg cgcccccgca ccgttcanct cgcacttctc naanaccatg angttgggct 420cnaacccacc accannccgg acttccttga nggaattccc aaatctcttc gntcttgggc 480ttctnctgat gccctanctg gttgcccngn atgccaanca nccccaancc ccggggtcct 540aaancacccn cctcctcntt tcatctgggt tnttntcccc ggaccntggt tcctctcaag 600ggancccata tctcnaccan tactcaccnt ncccccccnt gnnacccanc cttctanngn 660ttcccncccg ncctctggcc cntcaaanan gcttncacna cctgggtctg ccttcccccc 720tnccctatct gnaccccncn tttgtctcan tnt 753

<210> 41

<211> 341

<212> DNA

<213> Homo sapien

<400> 41actatatcca tcacaacaga catgcttcat cccatagact tcttgacata gcttcaaatg 60agtgaaccca tccttgattt atatacatat atgttctcag tattttggga gcctttccac 120ttctttaaac cttgttcatt acgaacactg aaaataggaa tttgtgaaga gttaaaaagt 180tatagcttgt ttacgtagta agtttttgaa gtctacattc aatccagaca cttagttgag 240tgttaaactg tgatttttaa aaaatatcat ttgagaatat tctttcagag gtattttcat 300ttttactttt tgattaattg tgttttatat attagggtag t 341

<210> 42

<211> 101

<212> DNA

<213> Homo sapien

<400> 42acttactgaa tttagttctg tgctcttcct tatttagtgt tgtatcataa atactttgat 60gtttcaaaca ttctaaataa ataattttca gtggcttcat a 101

<210> 43

<211> 305

<212> DNA

<213> Homo sapien

<400> 43acatctttgt tacagtctaa gatgtgttct taaatcacca ttccttcctg gtcctcaccc 60tccagggtgg tctcacactg taattagagc tattgaggag tctttacagc aaattaagat 120tcagatgcct tgctaagtct agagttctag agttatgttt cagaaagtct aagaaaccca 180cctcttgaga ggtcagtaaa gaggacttaa tatttcatat ctacaaaatg accacaggat 240tggatacaga acgagagtta tcctggataa ctcagagctg agtacctgcc cgggggccgc 300tcgaa 305

<210> 44

<211> 852

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(852)

<223> n = A,T,C or G

<400> 44acataaatat cagagaaaag tagtctttga aatatttacg tccaggagtt ctttgtttct 60gattatttgg tgtgtgtttt ggtttgtgtc caaagtattg gcagcttcag ttttcatttt 120ctctccatcc tcgggcattc ttcccaaatt tatataccag tcttcgtcca tccacacgct 180ccagaatttc tcttttgtag taatatctca tagctcggct gagcttttca taggtcatgc 240tgctgttgtt cttcttttta ccccatagct gagccactgc ctctgatttc aagaacctga 300agacgccctc agatcggtct tcccatttta ttaatcctgg gttcttgtct gggttcaaga 360ggatgtcgcg gatgaattcc cataagtgag tccctctcgg gttgtgcttt ttggtgtggc 420acttggcagg ggggtcttgc tcctttttca tatcaggtga ctctgcaaca ggaaggtgac 480tggtggttgt catggagatc tgagcccggc agaaagtttt gctgtccaac aaatctactg 540tgctaccata gttggtgtca tataaatagt tctngtcttt ccaggtgttc atgatggaag 600gctcagtttg ttcagtcttg acaatgacat tgtgtgtgga ctggaacagg tcactactgc 660actggccgtt ccacttcaga tgctgcaagt tgctgtagag gagntgcccc gccgtccctg 720ccgcccgggt gaactcctgc aaactcatgc tgcaaaggtg ctcgccgttg atgtcgaact 780cntggaaagg gatacaattg gcatccagct ggttggtgtc caggaggtga tggagccact 840cccacacctg gt 852

<210> 45

<211> 234

<212> DNA

<213> Homo sapien

<400> 45acaacagacc cttgctcgct aacgacctca tgctcatcaa gttggacgaa tccgtgtccg 60agtctgacac catccggagc atcagcattg cctcgcagtg ccctaccgcg gggaactctt 120gcctcgtttc tggctggggt ctgctggcga acggcagaat gcctaccgtg ctgcagtgcg 180tgaacgtgtc ggtggtgtct gaggaggtct gcagtaagct ctatgacccg ctgt 234

<210> 46

<211> 590

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222>(1)...(590)

<223> n = A,T,C or G

<400> 46actttttatt taaatgttta taaggcagat ctatgagaat gatagaaaac atggtgtgta 60atttgatagc aatattttgg agattacaga gttttagtaa ttaccaatta cacagttaaa 120aagaagataa tatattccaa gcanatacaa aatatctaat gaaagatcaa ggcaggaaaa 180tgantataac taattgacaa tggaaaatca attttaatgt gaattgcaca ttatccttta 240aaagctttca aaanaaanaa ttattgcagt ctanttaatt caaacagtgt taaatggtat 300caggataaan aactgaaggg canaaagaat taattttcac ttcatgtaac ncacccanat 360ttacaatggc ttaaatgcan ggaaaaagca gtggaagtag ggaagtantc aaggtctttc 420tggtctctaa tctgccttac tctttgggtg tggctttgat cctctggaga cagctgccag 480ggctcctgtt atatccacaa tcccagcagc aagatgaagg gatgaaaaag gacacatgct 540gccttccttt gaggagactt catctcactg gccaacactc agtcacatgt 590

<210> 47

<211> 774

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(774)

<223> n = A,T,C or G

<400> 47acaagggggc ataatgaagg agtggggana gattttaaag aaggaaaaaa aacgaggccc 60tgaacagaat tttcctgnac aacggggctt caaaataatt ttcttgggga ggttcaagac 120gcttcactgc ttgaaactta aatggatgtg ggacanaatt ttctgtaatg accctgaggg 180cattacagac gggactctgg gaggaaggat aaacagaaag gggacaaagg ctaatcccaa 240aacatcaaag aaaggaaggt ggcgtcatac ctcccagcct acacagttct ccagggctct 300cctcatccct ggaggacgac agtggaggaa caactgacca tgtccccagg ctcctgtgtg 360ctggctcctg gtcttcagcc cccagctctg gaagcccacc ctctgctgat cctgcgtggc 420ccacactcct tgaacacaca tccccaggtt atattcctgg acatggctga acctcctatt 480cctacttccg agatgccttg ctccctgcag cctgtcaaaa tcccactcac cctccaaacc 540acggcatggg aagcctttct gacttgcctg attactccag catcttggaa caatccctga 600ttccccactc cttagaggca agatagggtg gttaagagta gggctggacc acttggagcc 660aggctgctgg cttcaaattn tggctcattt acgagctatg ggaccttggg caagtnatct 720tcacttctat gggcntcatt ttgttctacc tgcaaaatgg gggataataa tagt 774

<210> 48

<211> 124

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(124)

<223> n = A,T,C or G

<400> 48canaaattga aattttataa aaaggcattt ttctcttata tccataaaat gatataattt 60ttgcaantat anaaatgtgt cataaattat aatgttcctt aattacagct caacgcaact 120tggt 124

<210> 49

<211> 147

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(147)

<223> n = A,T,C or G

<400> 49gccgatgcta ctattttatt gcaggaggtg ggggtgtttt tattattctc tcaacagctt 60tgtggctaca ggtggtgtct gactgcatna aaaanttttt tacgggtgat tgcaaaaatt 120ttagggcacc catatcccaa gcantgt 147

<210> 50

<211> 107

<212> DNA

<213> Homo sapien

<400> 50acattaaatt aataaaagga ctgttggggt tctgctaaaa cacatggctt gatatattgc 60atggtttgag gttaggagga gttaggcata tgttttggga gaggggt 107

<210> 51

<211> 204

<212> DNA

<213> Homo sapien

<400> 51gtcctaggaa gtctagggga cacacgactc tggggtcacg gggccgacac acttgcacgg 60cgggaaggaa aggcagagaa gtgacaccgt cagggggaaa tgacagaaag gaaaatcaag 120gccttgcaag gtcagaaagg ggactcaggg cttccaccac agccctgccc cacttggcca 180cctccctttt gggaccagca atgt 204

<210> 52

<211> 491

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(491)

<223> n = A,T,C or G

<400> 52acaaagataa catttatctt ataacaaaaa tttgatagtt ttaaaggtta gtattgtgta 60gggtattttc caaaagacta aagagataac tcaggtaaaa agttagaaat gtataaaaca 120ccatcagaca ggtttttaaa aaacaacata ttacaaaatt agacaatcat ccttaaaaaa 180aaaacttctt gtatcaattt cttttgttca aaatgactga cttaantatt tttaaatatt 240tcanaaacac ttcctcaaaa attttcaana tggtagcttt canatgtncc ctcagtccca 300atgttgctca gataaataaa tctcgtgaga acttaccacc caccacaagc tttctggggc 360atgcaacagt gtcttttctt tnctttttct tttttttttt ttacaggcac agaaactcat 420caattttatt tggataacaa agggtctcca aattatattg aaaaataaat ccaagttaat 480atcactcttg t 491

<210> 53

<211> 484

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(484)

<223> n = A,T,C or G

<400> 53acataattta gcagggctaa ttaccataag atgctattta ttaanaggtn tatgatctga 60gtattaacag ttgctgaagt ttggtatttt tatgcagcat tttctttttg ctttgataac 120actacagaac ccttaaggac actgaaaatt agtaagtaaa gttcagaaac attagctgct 180caatcaaatc tctacataac actatagtaa ttaaaacgtt aaaaaaaagt gttgaaatct 240gcactagtat anaccgctcc tgtcaggata anactgcttt ggaacagaaa gggaaaaanc 300agctttgant ttctttgtgc tgatangagg aaaggctgaa ttaccttgtt gcctctccct 360aatgattggc aggtcnggta aatnccaaaa catattccaa ctcaacactt cttttccncg 420tancttgant ctgtgtattc caggancagg cggatggaat gggccagccc ncggatgttc 480cant 484

<210> 54

<211> 151

<212> DNA

<213> Homo sapien

<400> 54actaaacctc gtgcttgtga actccataca gaaaacggtg ccatccctga acacggctgg 60ccactgggta tactgctgac aaccgcaaca acaaaaacac aaatccttgg cactggctag 120tctatgtcct ctcaagtgcc tttttgtttg t 151 <210> 55

<211> 91

<212> DNA

<213> Homo sapien

<400> 55acctggcttg tctccgggtg gttcccggcg ccccccacgg tccccagaac ggacactttc 60gccctccagt ggatactcga gccaaagtgg t 91

<210> 56

<211> 133

<212> DNA

<213> Homo sapien

<400> 56ggcggatgtg cgttggttat atacaaatat gtcattttat gtaagggact tgagtatact 60tggatttttg gtatctgtgg gttgggggga cggtccagga accaataccc catggatacc 120aagggacaac tgt 133

<210> 57

<211> 147

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (147)

<223> n = A,T,C or G

<400> 57actctggaga acctgagccg ctgctccgcc tctgggatga ggtgatgcan gcngtggcgc 60gactgggagc tgagcccttc cctttgcgcc tgcctcagag gattgttgcc gacntgcana 120tctcantggg ctggatncat gcagggt 147

<210> 58

<211> 198

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (198)

<223> n = A,T,C or G

<400> 58acagggatat aggtttnaag ttattgtnat tgtaaaatac attgaatttt ctgtatactc 60tgattacata catttatcct ttaaaaaaga tgtaaatctt aatttttatg ccatctatta 120atttaccaat gagttacctt gtaaatgaga agtcatgata gcactgaatt ttaactagtt 180ttgacttcta agtttggt 198

<210> 59

<211> 330

<212> DNA

<213> Homo sapien

<400> 59acaacaaatg ggttgtgagg aagtcttatc agcaaaactg gtgatggcta ctgaaaagat 60ccattgaaaa ttatcattaa tgattttaaa tgacaagtta tcaaaaactc actcaatttt 120cacctgtgct agcttgctaa aatgggagtt aactctagag caaatatagt atcttctgaa 180tacagtcaat aaatgacaaa gccagggcct acaggtggtt tccagacttt ccagacccag 240cagaaggaat ctattttatc acatggatct ccgtctgtgc tcaaaatacc taatgatatt 300tttcgtcttt attggacttc tttgaagagt 330

<210> 60

<211> 175

<212> DNA

<213> Homo sapien

<400> 60accgtgggtg ccttctacat tcctgacggc tccttcacca acatctggtt ctacttcggc 60gtcgtgggct ccttcctctt catcctcatc cagctggtgc tgctcatcga ctttgcgcac 120tcctggaacc agcggtggct gggcaaggcc gaggagtgcg attcccgtgc ctggt 175

<210> 61

<211> 154

<212> DNA

<213> Homo sapien

<400> 61accccacttt tcctcctgtg agcagtctgg acttctcact gctacatgat gagggtgagt 60ggttgttgct cttcaacagt atcctcccct ttccggatct gctgagccgg acagcagtgc 120tggactgcac agccccgggg ctccacattg ctgt 154

<210> 62

<211> 30

<212> DNA

<213> Homo sapien

<400> 62cgctcgagcc ctatagtgag tcgtattaga 30

<210> 63

<211> 89

<212> DNA

<213> Homo sapien

<400> 63acaagtcatt tcagcaccct ttgctcttca aaactgacca tcttttatat ttaatgcttc 60ctgtatgaat aaaaatggtt atgtcaagt 89

<210> 64

<211> 97

<212> DNA

<213> Homo sapien

<400> 64accggagtaa ctgagtcggg acgctgaatc tgaatccacc aataaataaa ggttctgcag 60aatcagtgca tccaggattg gtccttggat ctggggt 97

<210> 65

<211> 377

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(377)

<223> n = A,T,C or G

<400> 65acaacaanaa ntcccttctt taggccactg atggaaacct ggaaccccct tttgatggca 60gcatggcgtc ctaggccttg acacagcggc tggggtttgg gctntcccaa accgcacacc 120ccaaccctgg tctacccaca nttctggcta tgggctgtct ctgccactga acatcagggt 180tcggtcataa natgaaatcc caanggggac agaggtcagt agaggaagct caatgagaaa 240ggtgctgttt gctcagccag aaaacagctg cctggcattc gccgctgaac tatgaacccg 300tgggggtgaa ctacccccan gaggaatcat gcctgggcga tgcaanggtg ccaacaggag 360gggcgggagg agcatgt 377

<210> 66

<211> 305

<212> DNA

<213> Homo sapien

<400> 66acgcctttcc ctcagaattc agggaagaga ctgtcgcctg ccttcctccg ttgttgcgtg 60agaacccgtg tgccccttcc caccatatcc accctcgctc catctttgaa ctcaaacacg 120aggaactaac tgcaccctgg tcctctcccc agtccccagt tcaccctcca tccctcacct 180tcctccactc taagggatat caacactgcc cagcacaggg gccctgaatt tatgtggttt 240ttatatattt tttaataaga tgcactttat gtcatttttt aataaagtct gaagaattac 300tgttt 305

<210> 67

<211> 385

<212> DNA

<213> Homo sapien

<400> 67actacacaca ctccacttgc ccttgtgaga cactttgtcc cagcacttta ggaatgctga 60ggtcggacca gccacatctc atgtgcaaga ttgcccagca gacatcaggt ctgagagttc 120cccttttaaa aaaggggact tgcttaaaaa agaagtctag ccacgattgt gtagagcagc 180tgtgctgtgc tggagattca cttttgagag agttctcctc tgagacctga tctttagagg 240ctgggcagtc ttgcacatga gatggggctg gtctgatctc agcactcctt agtctgcttg 300cctctcccag ggccccagcc tggccacacc tgcttacagg gcactctcag atgcccatac 360catagtttct gtgctagtgg accgt 385

<210> 68

<211> 73

<212> DNA

<213> Homo sapien

<400> 68acttaaccag atatattttt accccagatg gggatattct ttgtaaaaaa tgaaaataaa 60gtttttttaa tgg 73

<210> 69

<211> 536

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(536)

<223> n = A,T,C or G

<400> 69actagtccag tgtggtggaa ttccattgtg ttgggggctc tcaccctcct ctcctgcagc 60tccagctttg tgctctgcct ctgaggagac catggcccag catctgagta ccctgctgct 120cctgctggcc accctagctg tggccctggc ctggagcccc aaggaggagg ataggataat 180cccgggtggc atctataacg cagacctcaa tgatgagtgg gtacagcgtg cccttcactt 240cgccatcagc gagtataaca aggccaccaa agatgactac tacagacgtc cgctgcgggt 300actaagagcc aggcaacaga ccgttggggg ggtgaattac ttcttcgacg tagaggtggg 360ccgaaccata tgtaccaagt cccagcccaa cttggacacc tgtgccttcc atgaacagcc 420agaactgcag aagaaacagt tgtgctcttt cgagatctac gaagttccct ggggagaaca 480gaangtccct gggtgaaatc caggtgtcaa gaaatcctan ggatctgttg ccaggc 536

<210> 70

<211> 477

<212> DNA

<213> Homo sapien

<400> 70atgaccccta acaggggccc tctcagccct cctaatgacc tccggcctag ccatgtgatt 60tcacttccac tccataacgc tcctcatact aggcctacta accaacacac taaccatata 120ccaatgatgg cgcgatgtaa cacgagaaag cacataccaa ggccaccaca caccacctgt 180ccaaaaaggc cttcgatacg ggataatcct atttattacc tcagaagttt ttttcttcgc 240agggattttt ctgagccttt taccactcca gcctagcccc taccccccaa ctaggagggc 300actggccccc aacaggcatc accccgctaa atcccctaga agtcccactc ctaaacacat 360ccgtattact cgcatcagga gtatcaatca cctgagctca ccatagtcta atagaaaaca 420accgaaacca aattattcaa agcactgctt attacaattt tactgggtct ctatttt 477

<210> 71

<211> 533

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(533)

<223> n = A,T,C or G

<400> 71agagctatag gtacagtgtg atctcagctt tgcaaacaca ttttctacat agatagtact 60aggtattaat agatatgtaa agaaagaaat cacaccatta ataatggtaa gattggttta 120tgtgatttta gtggtatttt tggcaccctt atatatgttt tccaaacttt cagcagtgat 180attatttcca taacttaaaa agtgagtttg aaaaagaaaa tctccagcaa gcatctcatt 240taaataaagg tttgtcatct ttaaaaatac agcaatatgt gactttttaa aaaagctgtc 300aaataggtgt gaccctacta ataattatta gaaatacatt taaaaacatc gagtacctca 360agtcagtttg ccttgaaaaa tatcaaatat aactcttaga gaaatgtaca taaaagaatg 420cttcgtaatt ttggagtang aggttccctc ctcaattttg tatttttaaa aagtacatgg 480taaaaaaaaa aattcacaac agtatataag gctgtaaaat gaagaattct gcc 533

<210> 72

<211> 511

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (511)

<223> n = A,T,C or G

<400> 72tattacggaa aaacacacca cataattcaa ctancaaaga anactgcttc agggcgtgta 60aaatgaaagg cttccaggca gttatctgat taaagaacac taaaagaggg acaaggctaa 120aagccgcagg atgtctacac tatancaggc gctatttggg ttggctggag gagctgtgga 180aaacatggan agattggtgc tgganatcgc cgtggctatt cctcattgtt attacanagt 240gaggttctct gtgtgcccac tggtttgaaa accgttctnc aataatgata gaatagtaca 300cacatgagaa ctgaaatggc ccaaacccag aaagaaagcc caactagatc ctcagaanac 360gcttctaggg acaataaccg atgaagaaaa gatggcctcc ttgtgccccc gtctgttatg 420atttctctcc attgcagcna naaacccgtt cttctaagca aacncaggtg atgatggcna 480aaatacaccc cctcttgaag naccnggagg a 511

<210> 73

<211> 499

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (499)

<223> n = A,T,C or G

<400> 73cagtgccagc actggtgcca gtaccagtac caataacagt gccagtgcca gtgccagcac 60cagtggtggc ttcagtgctg gtgccagcct gaccgccact ctcacatttg ggctcttcgc 120tggccttggt ggagctggtg ccagcaccag tggcagctct ggtgcctgtg gtttctccta 180caagtgagat tttagatatt gttaatcctg ccagtctttc tcttcaagcc agggtgcatc 240ctcagaaacc tactcaacac agcactctag gcagccacta tcaatcaatt gaagttgaca 300ctctgcatta aatctatttg ccatttctga aaaaaaaaaa aaaaaaaggg cggccgctcg 360antctagagg gcccgtttaa acccgctgat cagcctcgac tgtgccttct anttgccagc 420catctgttgt ttgcccctcc cccgntgcct tccttgaccc tggaaagtgc cactcccact 480gtcctttcct aantaaaat 499

<210> 74

<211> 537

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(537)

<223> n = A,T,C or G

<400> 74tttcatagga gaacacactg aggagatact tgaagaattt ggattcagcc gcgaagagat 60ttatcagctt aactcagata aaatcattga aagtaataag gtaaaagcta gtctctaact 120tccaggccca cggctcaagt gaatttgaat actgcattta cagtgtagag taacacataa 180cattgtatgc atggaaacat ggaggaacag tattacagtg tcctaccact ctaatcaaga 240aaagaattac agactctgat tctacagtga tgattgaatt ctaaaaatgg taatcattag 300ggcttttgat ttataanact ttgggtactt atactaaatt atggtagtta tactgccttc 360cagtttgctt gatatatttg ttgatattaa gattcttgac ttatattttg aatgggttct 420actgaaaaan gaatgatata ttcttgaaga catcgatata catttattta cactcttgat 480tctacaatgt agaaaatgaa ggaaatgccc caaattgtat ggtgataaaa gtcccgt 537

<210> 75

<211> 467

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(467)

<223> n = A,T,C or G

<400> 75caaanacaat tgttcaaaag atgcaaatga tacactactg ctgcagctca caaacacctc 60tgcatattac acgtacctcc tcctgctcct caagtagtgt ggtctatttt gccatcatca 120cctgctgtct gcttagaaga acggctttct gctgcaangg agagaaatca taacagacgg 180tggcacaagg aggccatctt ttcctcatcg gttattgtcc ctagaagcgt cttctgagga 240tctagttggg ctttctttct gggtttgggc catttcantt ctcatgtgtg tactattcta 300tcattattgt ataacggttt tcaaaccngt gggcacncag agaacctcac tctgtaataa 360caatgaggaa tagccacggt gatctccagc accaaatctc tccatgttnt tccagagctc 420ctccagccaa cccaaatagc cgctgctatn gtgtagaaca tccctgn 467

<210> 76

<211> 400

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (400)

<223> n = A,T,C or G

<400> 76aagctgacag cattcgggcc gagatgtctc gctccgtggc cttagctgtg ctcgcgctac 60tctctctttc tggcctggag gctatccagc gtactccaaa gattcaggtt tactcacgtc 120atccagcaga gaatggaaag tcaaatttcc tgaattgcta tgtgtctggg tttcatccat 180ccgacattga agttgactta ctgaagaatg gagagagaat tgaaaaagtg gagcattcag 240acttgtcttt cagcaaggac tggtctttct atctcttgta ctacactgaa ttcaccccca 300ctgaaaaaga tgagtatgcc tgccgtgtgaaccatgtgac tttgtcacag cccaagatng 360ttnagtggga tcganacatg taagcagcan catgggaggt 400

<210> 77

<211> 248

<212> DNA

<213> Homo sapien

<400> 77ctggagtgcc ttggtgtttcaagcccctgc aggaagcaga atgcaccttc tgaggcacct 60ccagctgccc cggcggggga tgcgaggctc ggagcaccct tgcccggctg tgattgctgc 120caggcactgt tcatctcagc ttttctgtcc ctttgctccc ggcaagcgct tctgctgaaa 180gttcatatct ggagcctgat gtcttaacga ataaaggtcc catgctccac ccgaaaaaaa 240aaaaaaaa 248

<210> 78

<211> 201

<212> DNA

<213> Homo sapien

<400> 78actagtccag tgtggtggaa ttccattgtg ttgggcccaa cacaatggct acctttaaca 60tcacccagac cccgccctgc ccgtgcccca cgctgctgct aacgacagta tgatgcttac 120tctgctactc ggaaactatt tttatgtaat taatgtatgc tttcttgttt ataaatgcct 180gatttaaaaa aaaaaaaaaa a 201

<210> 79

<211> 552

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (552)

<223> n = A,T,C or G

<400> 79tccttttgtt aggtttttga gacaacccta gacctaaact gtgtcacaga cttctgaatg 60tttaggcagt gctagtaatt tcctcgtaat gattctgtta tcactttcct attctttatt 120cctctttctt ctgaagatta atgaagttga aaattgaggt ggataaatac aaaaaggtag 180tgtgatagta taagtatcta agtgcagatg aaagtgtgtt atatatatcc attcaaaatt 240atgcaagtta gtaattactc agggttaact aaattacttt aatatgctgt tgaacctact 300ctgttccttg gctagaaaaa attataaaca ggactttgtt agtttgggaa gccaaattga 360taatattcta tgttctaaaa gttgggctat acataaanta tnaagaaata tggaatttta 420ttcccaggaa tatggggttc atttatgaat antacccggg anagaagttt tgantnaaac 480cngttttggt taatacgtta atatgtcctn aatnaacaag gcntgactta tttccaaaaa 540aaaaaaaaaa aa 552

<210> 80

<211> 476

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(476)

<223> n = A,T,C or G

<400> 80acagggattt gagatgctaa ggccccagag atcgtttgat ccaaccctct tattttcaga 60ggggaaaatg gggcctagaa gttacagagc atctagctgg tgcgctggca cccctggcct 120cacacagact cccgagtagc tgggactaca ggcacacagt cactgaagca ggccctgttt 180gcaattcacg ttgccacctc caacttaaac attcttcata tgtgatgtcc ttagtcacta 240aggttaaact ttcccaccca gaaaaggcaa cttagataaa atcttagagt actttcatac 300tcttctaagt cctcttccag cctcactttg agtcctcctt gggggttgat aggaantntc 360tcttggcttt ctcaataaaa tctctatcca tctcatgttt aatttggtac gcntaaaaat 420gctgaaaaaa ttaaaatgtt ctggtttcnc tttaaaaaaa aaaaaaaaaa aaaaaa 476

<210> 81

<211> 232

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(232)

<223> n = A,T,C or G

<400> 81tttttttttg tatgccntcn ctgtggngtt attgttgctg ccaccctgga ggagcccagt 60ttcttctgta tctttctttt ctgggggatc ttcctggctc tgcccctcca ttcccagcct 120ctcatcccca tcttgcactt ttgctagggt tggaggcgct ttcctggtag cccctcagag 180actcagtcag cgggaataag tcctaggggt ggggggtgtg gcaagccggc ct 232

<210> 82

<211> 383

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(383)

<223> n = A,T,C or G

<400> 82aggcgggagc agaagctaaa gccaaagccc aagaagagtg gcagtgccag cactggtgcc 60agtaccagta ccaataacat gccagtgcca gtgccagcac cagtggtggc ttcagtgctg 120gtgccagcct gaccgccact ctcacatttg ggctcttcgc tggccttggt ggagctggtg 180ccagcaccag tggcagctct ggtgcctgtg gtttctccta caagtgagat tttagatatt 240gttaatcctg ccagtctttc tcttcaagcc agggtgcatc ctcagaaacc tactcaacac 300agcactctng gcagccacta tcaatcaatt gaagttgaca ctctgcatta aatctatttg 360ccatttcaaa aaaaaaaaaa aaa 383

<210> 83

<211> 494

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(494)

<223> n = A,T,C or G

<400> 83accgaattgg gaccgctggc ttataagcga tcatgtcctc cagtattacc tcaacgagca 60gggagatcga gtctatacgc tgaagaaatt tgacccgatg ggacaacaga cctgctcagc 120ccatcctgct cggttctccc cagatgacaa atactctcga caccgaatca ccatcaagaa 180acgcttcaag gtgctcatga cccagcaacc gcgccctgtc ctctgagggt ccttaaactg 240atgtcttttc tgccacctgt tacccctcgg agactccgta accaaactct tcggactgtg 300agccctgatg cctttttgcc agccatactc tttggcntcc agtctctcgt ggcgattgat 360tatgcttgtg tgaggcaatc atggtggcat cacccatnaa gggaacacat ttganttttt 420tttcncatat tttaaattac naccagaata nttcagaata aatgaattga aaaactctta 480aaaaaaaaaa aaaa 494

<210> 84

<211> 380

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(380)

<223> n = A,T,C or G

<400> 84gctggtagcc tatggcgtgg ccacggangg gctcctgagg cacgggacag tgacttccca 60agtatcctgc gccgcgtctt ctaccgtccc tacctgcaga tcttcgggca gattccccag 120gaggacatgg acgtggccct catggagcac agcaactgct cgtcggagcc cggcttctgg 180gcacaccctc ctggggccca ggcgggcacc tgcgtctccc agtatgccaa ctggctggtg 240gtgctgctcc tcgtcatctt cctgctcgtg gccaacatcc tgctggtcac ttgctcattg 300ccatgttcag ttacacattc ggcaaagtac agggcaacag cnatctctac tgggaaggcc 260agcgttnccg cctcatccgg 380

<210> 85

<211> 481

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (481)

<223> n = A,T,C or G

<400> 85gagttagctc ctccacaacc ttgatgaggt cgtctgcagt ggcctctcgc ttcataccgc 60tnccatcgtc atactgtagg tttgccacca cctcctgcat cttggggcgg ctaatatcca 120ggaaactctc aatcaagtca ccgtcnatna aacctgtggc tggttctgtc ttccgctcgg 180tgtgaaagga tctccagaag gagtgctcga tcttccccac acttttgatg actttattga 240gtcgattctg catgtccagc aggaggttgt accagctctc tgacagtgag gtcaccagcc 300ctatcatgcc nttgaacgtg ccgaagaaca ccgagccttg tgtggggggt gnagtctcac 360ccagattctg cattaccaga nagccgtggc aaaaganatt gacaactcgc ccaggnngaa 420aaagaacacc tcctggaagt gctngccgct cctcgtccnt tggtggnngc gcntnccttt 480t 481

<210> 86

<211> 472

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(472)

<223> n = A,T,C or G

<400> 86aacatcttcc tgtataatgc tgtgtaatat cgatccgatn ttgtctgctg agaattcatt 60acttggaaaa gcaacttnaa gcctggacac tggtattaaa attcacaata tgcaacactt 120taaacagtgt gtcaatctgc tcccttactt tgtcatcacc agtctgggaa taagggtatg 180ccctattcac acctgttaaa agggcgctaa gcatttttga ttcaacatct ttttttttga 240cacaagtccg aaaaaagcaa aagtaaacag ttnttaattt gttagccaat tcactttctt 300catgggacag agccatttga tttaaaaagc aaattgcata atattgagct ttgggagctg 360atatntgagc ggaagantag cctttctact tcaccagaca caactccttt catattggga 420tgttnacnaa agttatgtct cttacagatg ggatgctttt gtggcaattc tg 472

<210> 87

<211> 413

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(413)

<223> n = A,T,C or G

<400> 87agaaaccagt atctctnaaa acaacctctc ataccttgtg gacctaattt tgtgtgcgtg 60tgtgtgtgcg cgcatattat atagacaggc acatcttttt tacttttgta aaagcttatg 120cctctttggt atctatatct gtgaaagttt taatgatctg ccataatgtc ttggggacct 180ttgtcttctg tgtaaatggt actagagaaa acacctatnt tatgagtcaa tctagttngt 240tttattcgac atgaaggaaa tttccagatn acaacactna caaactctcc cttgactagg 300ggggacaaag aaaagcanaa ctgaacatna gaaacaattn cctggtgaga aatcncataa 360acagaaattg ggtngtatat tgaaananng catcattnaa acgttttttt ttt 413

<210> 88

<211> 448

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(448)

<223> n = A,T,C or G

<400> 88cgcagcgggt cctctctatc tagctccagc ctctcgcctg ccccactccc cgcgtcccgc 60gtcctagccn accatggccg ggcccctgcg cgccccgctg ctcctgctgg ccatcctggc 120cgtggccctg gccgtgagcc ccgcggccgg ctccagtccc ggcaagccgc cgcgcctggt 180gggaggccca tggaccccgc gtggaagaag aaggtgtgcg gcgtgcactg gactttgccg 240tcggcnanta caacaaaccc gcaacnactt ttaccnagcn cgcgctgcag gttgtgccgc 300cccaancaaa ttgttactng gggtaantaa ttcttggaag ttgaacctgg gccaaacnng 360tttaccagaa ccnagccaat tngaacaatt ncccctccat aacagcccct tttaaaaagg 420gaancantcc tgntcttttc caaatttt 448

<210> 89

<211> 463

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(463)

<223> n = A,T,C or G

<400> 89gaattttgtg cactggccac tgtgatggaa ccattgggcc aggatgcttt gagtttatca 60gtagtgattc tgccaaagtt ggtgttgtaa catgagtatg taaaatgtca aaaaattagc 120agaggtctag gtctgcatat cagcagacag tttgtccgtg tattttgtag ccttgaagtt 180ctcagtgaca agttnnttct gatgcgaagt tctnattcca gtgttttagt cctttgcatc 240tttnatgttn agacttgcct ctntnaaatt gcttttgtnt tctgcaggta ctatctgtgg 300tttaacaaaa tagaannact tctctgcttn gaanatttga atatcttaca tctnaaaatn 360aattctctcc ccatannaaa acccangccc ttggganaat ttgaaaaang gntccttcnn 420aattcnnana anttcagntn tcatacaaca naacngganc ccc 463

<210> 90

<211> 400

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(400)

<223> n = A,T,C or G

<400> 90agggattgaa ggtctnttnt actgtcggac tgttcancca ccaactctac aagctgctgt 60cttccactca ctgtctgtaa gcntnttaac ccagactgta tcttcataaa tagaacaaat 120tcttcaccag tcacatcttc taggaccttt ttggattcag ttagtataag ctcttccact 180tcctttgtta agacttcatc tggtaaagtc ttaagttttg tagaaaggaa tttaattgct 240cgttctctaa caatgtcctc tccttgaagt atttggctga acaacccacc tnaagtccct 300ttgtgcatcc attttaaata tacttaatag ggcattggtn cactaggtta aattctgcaa 360gagtcatctg tctgcaaaag ttgcgttagt atatctgcca 400

<210> 91

<211> 480

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(480)

<223> n = A,T,C or G

<400> 91gagctcggat ccaataatct ttgtctgagg gcagcacaca tatncagtgc catggnaact 60ggtctacccc acatgggagc agcatgccgt agntatataa ggtcattccc tgagtcagac 120atgcctcttt gactaccgtg tgccagtgct ggtgattctc acacacctcc nnccgctctt 180tgtggaaaaa ctggcacttg nctggaacta gcaagacatc acttacaaat tcacccacga 240gacacttgaa aggtgtaaca aagcgactct tgcattgctt tttgtccctc cggcaccagt 300tgtcaatacc aacccgctgg tttgcctcca tcacatttgt gatctgtagc tctggataca 360tctcctgaca gtactgaaga acttcttctt ttgtttcaaa agcaactctt ggtgcctgtt 420ngatcaggtt cccatttccc agtccgaatg ttcacatggc atatnttact tcccacaaaa 480

<210> 92

<211> 477

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(477)

<223> n = A,T,C or G

<400> 92atacagccca natcccacca cgaagatgcg cttgttgact gagaacctga tgcggtcact 60ggtcccgctg tagccccagc gactctccac ctgctggaag cggttgatgc tgcactcctt 120cccacgcagg cagcagcggg gccggtcaat gaactccact cgtggcttgg ggttgacggt 180taantgcagg aagaggctga ccacctcgcg gtccaccagg acgcccgact gtgcgggacc 240tgcagcgaaa ctcctcgatg gtcatgagcg ggaagcgaat gangcccagg gccttgccca 300gaaccttccg cctgttctct ggcgtcacct gcagctgctg ccgctnacac tcggcctcgg 360accagcggac aaacggcgtt gaacagccgc acctcacgga tgcccantgt gtcgcgctcc 420aggaacggcn ccagcgtgtc caggtcaatg tcggtgaanc ctccgcgggt aatggcg 477

<210> 93

<211> 377

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (377)

<223> n = A,T,C or G

<400> 93gaacggctgg accttgcctc gcattgtgct gctggcagga ataccttggc aagcagctcc 60agtccgagca gccccagacc gctgccgccc gaagctaagc ctgcctctgg ccttcccctc 120cgcctcaatg cagaaccant agtgggagca ctgtgtttag agttaagagt gaacactgtn 180tgattttact tgggaatttc ctctgttata tagcttttcc caatgctaat ttccaaacaa 240caacaacaaa ataacatgtt tgcctgttna gttgtataaa agtangtgat tctgtatnta 300aagaaaatat tactgttaca tatactgctt gcaanttctg tatttattgg tnctctggaa 360ataaatatat tattaaa 377

<210> 94

<211> 495

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (495)

<223> n = A,T,C or G

<400> 94ccctttgagg ggttagggtc cagttcccag tggaagaaac aggccaggag aantgcgtgc 60cgagctgang cagatttccc acagtgaccc cagagccctg ggctatagtc tctgacccct 120ccaaggaaag accaccttct ggggacatgg gctggagggc aggacctaga ggcaccaagg 180gaaggcccca ttccggggct gttccccgag gaggaaggga aggggctctg tgtgcccccc 240acgaggaana ggccctgant cctgggatca nacacccctt cacgtgtatc cccacacaaa 300tgcaagctca ccaaggtccc ctctcagtcc cttccctaca ccctgaacgg ncactggccc 360acacccaccc agancancca cccgccatgg ggaatgtnct caaggaatcg cngggcaacg 420tggactctng tcccnnaagg gggcagaatc tccaatagan gganngaacc cttgctnana 480aaaaaaaana aaaaa 495

<210> 95

<211> 472

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(472)

<223> n = A,T,C or G

<400> 95ggttacttgg tttcattgcc accacttagt ggatgtcatt tagaaccatt ttgtctgctc 60cctctggaag ccttgcgcag agcggacttt gtaattgttg gagaataact gctgaatttt 120tagctgtttt gagttgattc gcaccactgc accacaactc aatatgaaaa ctatttnact 180tatttattat cttgtgaaaa gtatacaatg aaaattttgt tcatactgta tttatcaagt 240atgatgaaaa gcaatagata tatattcttt tattatgttn aattatgatt gccattatta 300atcggcaaaa tgtggagtgt atgttctttt cacagtaata tatgcctttt gtaacttcac 360ttggttattt tattgtaaat gaattacaaa attcttaatt taagaaaatg gtangttata 420tttanttcan taatttcttt ccttgtttac gttaattttg aaaagaatgc at 472

<210> 96

<211> 476

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(476)

<223> n = A,T,C or G

<400> 96ctgaagcatt tcttcaaact tntctacttt tgtcattgat acctgtagta agttgacaat 60gtggtgaaat ttcaaaatta tatgtaactt ctactagttt tactttctcc cccaagtctt 120ttttaactca tgatttttac acacacaatc cagaacttat tatatagcct ctaagtcttt 180attcttcaca gtagatgatg aaagagtcct ccagtgtctt gngcanaatg ttctagntat 240agctggatac atacngtggg agttctataa actcatacct cagtgggact naaccaaaat 300tgtgttagtc tcaattccta ccacactgag ggagcctccc aaatcactat attcttatct 360gcaggtactc ctccagaaaa acngacaggg caggcttgca tgaaaaagtn acatctgcgt 420tacaaagtct atcttcctca nangtctgtn aaggaacaat ttaatcttct agcttt 476

<210> 97

<211> 479

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(479)

<223> n = A,T,C or G

<400> 97actctttcta atgctgatat gatcttgagt ataagaatgc atatgtcact agaatggata 60aaataatgct gcaaacttaa tgttcttatg caaaatggaa cgctaatgaa acacagctta 120caatcgcaaa tcaaaactca caagtgctca tctgttgtag atttagtgta ataagactta 180gattgtgctc cttcggatat gattgtttct canatcttgg gcaatnttcc ttagtcaaat 240caggctacta gaattctgtt attggatatn tgagagcatg aaatttttaa naatacactt 300gtgattatna aattaatcac aaatttcact tatacctgct atcagcagct agaaaaacat 360ntnnttttta natcaaagta ttttgtgttt ggaantgtnn aaatgaaatc tgaatgtggg 420ttcnatctta ttttttcccn gacnactant tnctttttta gggnctattc tganccatc 479

<210> 98

<211> 461

<212> DNA

<213> Homo sapien

<400> 98agtgacttgt cctccaacaa aaccccttga tcaagtttgt ggcactgaca atcagaccta 60tgctagttcc tgtcatctat tcgctactaa atgcagactg gaggggacca aaaaggggca 120tcaactccag ctggattatt ttggagcctg caaatctatt cctacttgta cggactttga 180agtgattcag tttcctctac ggatgagaga ctggctcaag aatatcctca tgcagcttta 240tgaagccact ctgaacacgc tggttatcta gatgagaaca gagaaataaa gtcagaaaat 300ttacctggag aaaagaggct ttggccgggg accatcccat tgaaccttct cttaaggact 360ttaagaaaaa ctaccacatg ttgtgtatcc tggtgccggc cgtttatgaa ctgaccaccc 420tttggaataa tcttgacgct cctgaacttg ctcctctgcg a 461

<210> 99

<211> 171

<212> DNA

<213> Homo sapien

<400> 99gtggccgcgc gcaggtgttt cctcgtaccg cagggccccc tcccttcccc aggcgtccct 60cggcgcctct gcgggcccga ggaggagcgg ctggcgggtg gggggagtgt gacccaccct 120cggtgagaaa agccttctct agcgatctga gaggcgtgcc ttgggggtac c 171

<210> 100

<211> 269

<212> DNA

<213> Homo sapien

<400> 100cggccgcaag tgcaactcca gctggggccg tgcggacgaa gattctgcca gcagttggtc 60cgactgcgac gacggcggcg gcgacagtcg caggtgcagc gcgggcgcct ggggtcttgc 120aaggctgagc tgacgccgca gaggtcgtgt cacgtcccac gaccttgacg ccgtcgggga 180cagccggaac agagcccggt gaagcgggag gcctcgggga gcccctcggg aagggcggcc 240cgagagatac gcaggtgcag gtggccgcc 269

<210> 101

<211> 405

<212> DNA

<213> Homo sapien

<400> 101tttttttttt ttttggaatc tactgcgagc acagcaggtc agcaacaagt ttattttgca 60gctagcaagg taacagggta gggcatggtt acatgttcag gtcaacttcc tttgtcgtgg 120ttgattggtt tgtctttatg ggggcggggt ggggtagggg aaacgaagca aataacatgg 180agtgggtgca ccctccctgt agaacctggt tacaaagctt ggggcagttc acctggtctg 240tgaccgtcat tttcttgaca tcaatgttat tagaagtcag gatatctttt agagagtcca 300ctgttctgga gggagattag ggtttcttgc caaatccaac aaaatccact gaaaaagttg 360gatgatcagt acgaataccg aggcatattc tcatatcggt ggcca 405

<210> 102

<211> 470

<212> DNA

<213> Homo sapien

<400> 102tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60ggcacttaat ccatttttat ttcaaaatgt ctacaaattt aatcccatta tacggtattt 120tcaaaatcta aattattcaa attagccaaa tccttaccaa ataataccca aaaatcaaaa 180atatacttct ttcagcaaac ttgttacata aattaaaaaa atatatacgg ctggtgtttt 240caaagtacaa ttatcttaac actgcaaaca ttttaaggaa ctaaaataaa aaaaaacact 300ccgcaaaggt taaagggaac aacaaattct tttacaacac cattataaaa atcatatctc 360aaatcttagg ggaatatata cttcacacgg gatcttaact tttactcact ttgtttattt 420ttttaaacca ttgtttgggc ccaacacaat ggaatccccc ctggactagt 470

<210> 103

<211> 581

<212> DNA

<213> Homo sapien

<400> 103tttttttttt ttttttttga cccccctctt ataaaaaaca agttaccatt ttattttact 60tacacatatt tattttataa ttggtattag atattcaaaa ggcagctttt aaaatcaaac 120taaatggaaa ctgccttaga tacataattc ttaggaatta gcttaaaatc tgcctaaagt 180gaaaatcttc tctagctctt ttgactgtaa atttttgact cttgtaaaac atccaaattc 240atttttcttg tctttaaaat tatctaatct ttccattttt tccctattcc aagtcaattt 300gcttctctag cctcatttcc tagctcttat ctactattag taagtggctt ttttcctaaa 360agggaaaaca ggaagagaaa tggcacacaa aacaaacatt ttatattcat atttctacct 420acgttaataa aatagcattt tgtgaagcca gctcaaaaga aggcttagat ccttttatgt 480ccattttagt cactaaacga tatcaaagtg ccagaatgca aaaggtttgt gaacatttat 540tcaaaagcta atataagata tttcacatac tcatctttct g 581

<210> 104

<211> 578

<212> DNA

<213> Homo sapien

<400> 104tttttttttt tttttttttt tttttctctt cttttttttt gaaatgagga tcgagttttt 60cactctctag atagggcatg aagaaaactc atctttccag ctttaaaata acaatcaaat 120ctcttatgct atatcatatt ttaagttaaa ctaatgagtc actggcttat cttctcctga 180aggaaatctg ttcattcttc tcattcatat agttatatca agtactacct tgcatattga 240gaggtttttc ttctctattt acacatatat ttccatgtga atttgtatca aacctttatt 300ttcatgcaaa ctagaaaata atgtttcttt tgcataagag aagagaacaa tatagcatta 360caaaactgct caaattgttt gttaagttat ccattataat tagttggcag gagctaatac 420aaatcacatt tacgacagca ataataaaac tgaagtacca gttaaatatc caaaataatt 480aaaggaacat ttttagcctg ggtataatta gctaattcac tttacaagca tttattagaa 540tgaattcaca tgttattatt cctagcccaa cacaatgg 578

<210> 105

<211> 538

<212> DNA

<213> Homo sapien

<400> 105tttttttttt tttttcagta ataatcagaa caatatttat ttttatattt aaaattcata 60gaaaagtgcc ttacatttaa taaaagtttg tttctcaaag tgatcagagg aattagatat 120gtcttgaaca ccaatattaa tttgaggaaa atacaccaaa atacattaag taaattattt 180aagatcatag agcttgtaag tgaaaagata aaatttgacc tcagaaactc tgagcattaa 240aaatccacta ttagcaaata aattactatg gacttcttgc tttaattttg tgatgaatat 300ggggtgtcac tggtaaacca acacattctg aaggatacat tacttagtga tagattctta 360tgtactttgc taatacgtgg atatgagttg acaagtttct ctttcttcaa tcttttaagg 420ggcgagaaat gaggaagaaa agaaaaggat tacgcatact gttctttcta tggaaggatt 480agatatgttt cctttgccaa tattaaaaaa ataataatgt ttactactag tgaaaccc 538

<210> 106

<211> 473

<212> DNA

<213> Homo sapien

<400> 106tttttttttt ttttttagtc aagtttctat ttttattata attaaagtct cggtcatttc 60atttattagc tctgcaactt acatatttaa attaaagaaa cgttttagac aactgtacaa 120tttataaatg taaggtgcca ttattgagta atatattcct ccaagagtgg atgtgtccct 180tctcccacca actaatgaac agcaacatta gtttaatttt attagtagat atacactgct 240gcaaacgcta attctcttct ccatccccat gtgatattgt gtatatgtgt gagttggtag 300aatgcatcac aatctacaat caacagcaag atgaagctag gctgggcttt cggtgaaaat 360agactgtgtc tgtctgaatc aaatgatctg acctatcctc ggtggcaaga actcttcgaa 420ccgcttcctc aaaggcgctg ccacatttgt ggctctttgc acttgtttca aaa 473

<210> 107

<211> 1621

<212> DNA

<213> Homo sapien

<400> 107cgccatggca ctgcagggca tctcggtcat ggagctgtcc ggcctggccc cgggcccgtt 60ctgtgctatg gtcctggctg acttcggggc gcgtgtggta cgcgtggacc ggcccggctc 120ccgctacgac gtgagccgct tgggccgggg caagcgctcg ctagtgctgg acctgaagca 180gccgcgggga gccgccgtgc tgcggcgtct gtgcaagcgg tcggatgtgc tgctggagcc 240cttccgccgc ggtgtcatgg agaaactcca gctgggccca gagattctgc agcgggaaaa 300tccaaggctt atttatgcca ggctgagtgg atttggccag tcaggaagct tctgccggtt 360agctggccac gatatcaact atttggcttt gtcaggtgtt ctctcaaaaa ttggcagaag 420tggtgagaat ccgtatgccc cgctgaatct cctggctgac tttgctggtg gtggccttat 480gtgtgcactg ggcattataa tggctctttt tgaccgcaca cgcactgaca agggtcaggt 540cattgatgca aatatggtgg aaggaacagc atatttaagt tcttttctgt ggaaaactca 600gaaatcgagt ctgtgggaag cacctcgagg acagaacatg ttggatggtg gagcaccttt 660ctatacgact tacaggacag cagatgggga attcatggct gttggagcaa tagaacccca 720gttctacgag ctgctgatca aaggacttgg actaaagtct gatgaacttc ccaatcagat 780gagcatggat gattggccag aaatgaagaa gaagtttgca gatgtatttg caaagaagac 840gaaggcagag tggtgtcaaa tctttgacgg cacagatgcc tgtgtgactc cggttctgac 900ttttgaggag gttgttcatc atgatcacaa caaggaacgg ggctcgttta tcaccagtga 960ggagcaggac gtgagccccc gccctgcacc tctgctgtta aacaccccag ccatcccttc 1020tttcaaaagg gatcctttca taggagaaca cactgaggag atacttgaag aatttggatt 1080cagccgcgaa gagatttatc agcttaactc agataaaatc attgaaagta ataaggtaaa 1140agctagtctc taacttccag gcccacggct caagtgaatt tgaatactgc atttacagtg 1200tagagtaaca cataacattg tatgcatgga aacatggagg aacagtatta cagtgtccta 1260ccactctaat caagaaaaga attacagact ctgattctac agtgatgatt gaattctaaa 1320aatggttatc attagggctt ttgatttata aaactttggg tacttatact aaattatggt 1380agttattctg ccttccagtt tgcttgatat atttgttgat attaagattc ttgacttata 1440ttttgaatgg gttctagtga aaaaggaatg atatattctt gaagacatcg atatacattt 1500atttacactc ttgattctac aatgtagaaa atgaggaaat gccacaaatt gtatggtgat 1560aaaagtcacg tgaaacaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1620a 1621

<210> 108

<211> 382

<212> PRT

<213> Homo sapien

<400> 108Met Ala Leu Gln Gly Ile Ser Val Met Glu Leu Ser Gly Leu Ala Pro1 5 10 15Gly Pro Phe Cys Ala Met Val Leu Ala Asp Phe Gly Ala Arg Val Val

20 25 30Arg Val Asp Arg Pro Gly Ser Arg Tyr Asp Val Ser Arg Leu Gly Arg35 40 45Gly Lys Arg Ser Leu Val Leu Asp Leu Lys Gln Pro Arg Gly Ala Ala

50 55 60Val Leu Arg Arg Leu Cys Lys Arg Set Asp Val Leu Leu Glu Pro Phe65 70 75 80Arg Arg Gly Val Met Glu Lys Leu Gln Leu Gly Pro Glu Ile Leu Gln

85 90 95Arg Glu Asn Pro Arg Leu Ile Tyr Ala Arg Leu Ser Gly Phe Gly Gln

100 105 110Ser Gly Ser Phe Cys Arg Leu Ala Gly His Asp Ile Asn Tyr Leu Ala

115 120 125Leu Ser Gly Val Leu Ser Lys Ile Gly Arg Set Gly Glu Asn Pro Tyr

130 135 140Ala Pro Leu Asn Leu Leu Ala Asp Phe Ala Gly Gly Gly Leu Met Cys145 150 155 160Ala Leu Gly Ile Ile Met Ala Leu Phe Asp Arg Thr Arg Thr Asp Lys

165 170 175Gly Gln Val Ile Asp Ala Asn Met Val Glu Gly Thr Ala Tyr Leu Ser

180 185 190Ser Phe Leu Trp Lys Thr Gln Lys Ser Ser Leu Trp Glu Ala Pro Arg

195 200 205Gly Gln Asn Met Leu Asp Gly Gly Ala Pro Phe Tyr Thr Thr Tyr Arg

210 215 220Thr Ala Asp Gly Glu Phe Met Ala Val Gly Ala Ile Glu Pro Gln Phe225 230 235 240Tyr Glu Leu Leu Ile Lys Gly Leu Gly Leu Lys Ser Asp Glu Leu Pro

245 250 255Asn Gln Met Ser Met Asp Asp Trp Pro Glu Met Lys Lys Lys Phe Ala

260 265 270Asp Val Phe Ala Lys Lys Thr Lys Ala Glu Trp Cys Gln Ile Phe Asp

275 280 285Gly Thr Asp Ala Cys Val Thr Pro Val Leu Thr Phe Glu Glu Val Val

290 295 300His His Asp His Asn Lys Glu Arg Gly Ser Phe Ile Thr Ser Glu Glu305 310 315 320Gln Asp Val Ser Pro Arg Pro Ala Pro Leu Leu Leu Asn Thr Pro Ala

325 330 335Ile Pro Set Phe Lys Arg Asp Pro Phe Ile Gly Glu His Thr Glu Glu

340 345 350Ile Leu Glu Glu Phe Gly Phe Set Arg Glu Glu Ile Tyr Gln Leu Asn

355 360 365Ser Asp Lys Ile Ile Glu Ser Asn Lys Val Lys Ala Ser Leu

370 375 380

<210> 109

<211> 1524

<212> DNA

<213> Homo sapien

<400> 109ggcacgaggc tgcgccaggg cctgagcgga ggcgggggca gcctcgccag cgggggcccc 60gggcctggcc atgcctcact gagccagcgc ctgcgcctct acctcgccga cagctggaac 120cagtgcgacc tagtggctct cacctgcttc ctcctgggcg tgggctgccg gctgaccccg 180ggtttgtacc acctgggccg cactgtcctc tgcatcgact tcatggtttt cacggtgcgg 240ctgcttcaca tcttcacggt caacaaacag ctggggccca agatcgtcat cgtgagcaag 300atgatgaagg acgtgttctt cttcctcttc ttcctcggcg tgtggctggt agcctatggc 360gtggccacgg aggggctcct gaggccacgg gacagtgact tcccaagtat cctgcgccgc 420gtcttctacc gtccctacct gcagatcttc gggcagattc cccaggagga catggacgtg 480gccctcatgg agcacagcaa ctgctcgtcg gagcccggct tctgggcaca ccctcctggg 540gcccaggcgg gcacctgcgt ctcccagtat gccaactggc tggtggtgct gctcctcgtc 600atcttcctgc tcgtggccaa catcctgctg gtcaacttgc tcattgccat gttcagttac 660acattcggca aagtacaggg caacagcgat ctctactgga aggcgcagcg ttaccgcctc 720atccgggaat tccactctcg gcccgcgctg gccccgccct ttatcgtcat ctcccacttg 780cgcctcctgc tcaggcaatt gtgcaggcga ccccggagcc cccagccgtc ctccccggcc 840ctcgagcatt tccgggttta cctttctaag gaagccgagc ggaagctgct aacgtgggaa 900tcggtgcata aggagaactt tctgctggca cgcgctaggg acaagcggga gagcgactcc 960gagcgtctga agcgcacgtc ccagaaggtg gacttggcac tgaaacagct gggacacatc 1020cgcgagtacg aacagcgcct gaaagtgctg gagcgggagg tccagcagtg tagccgcgtc 1080ctggggtggg tggccgaggc cctgagccgc tctgccttgc tgcccccagg tgggccgcca 1140ccccctgacc tgcctgggtc caaagactga gccctgctgg cggacttcaa ggagaagccc 1200ccacagggga ttttgctcct agagtaaggc tcatctgggc ctcggccccc gcacctggtg 1260gccttgtcct tgaggtgagc cccatgtcca tctgggccac tgtcaggacc acctttggga 1320gtgtcatcct tacaaaccac agcatgcccg gctcctccca gaaccagtcc cagcctggga 1380ggatcaaggc ctggatcccg ggccgttatc catctggagg ctgcagggtc cttggggtaa 1440cagggaccac agacccctca ccactcacag attcctcaca ctggggaaat aaagccattt 1500cagaggaaaa aaaaaaaaaa aaaa 1524

<210> 110

<211> 3410

<212> DNA

<213> Homo sapien

<400> 110gggaaccagc ctgcacgcgc tggctccggg tgacagccgc gcgcctcggc caggatctga 60gtgatgagac gtgtccccac tgaggtgccc cacagcagca ggtgttgagc atgggctgag 120aagctggacc ggcaccaaag ggctggcaga aatgggcgcc tggctgattc ctaggcagtt 180ggcggcagca aggaggagag gccgcagctt ctggagcaga gccgagacga agcagttctg 240gagtgcctga acggccccct gagccctacc cgcctggccc actatggtcc agaggctgtg 300ggtgagccgc ctgctgcggc accggaaagc ccagctcttg ctggtcaacc tgctaacctt 360tggcctggag gtgtgtttgg ccgcaggcat cacctatgtg ccgcctctgc tgctggaagt 420gggggtagag gagaagttca tgaccatggt gctgggcatt ggtccagtgc tgggcctggt 480ctgtgtcccg ctcctaggct cagccagtga ccactggcgt ggacgctatg gccgccgccg 540gcccttcatc tgggcactgt ccttgggcat cctgctgagc ctctttctca tcccaagggc 600cggctggcta gcagggctgc tgtgcccgga tcccaggccc ctggagctgg cactgctcat 660cctgggcgtg gggctgctgg acttctgtgg ccaggtgtgc ttcactccac tggaggccct 720gctctctgac ctcttccggg acccggacca ctgtcgccag gcctactctg tctatgcctt 780catgatcagt cttgggggct gcctgggcta cctcctgcct gccattgact gggacaccag 840tgccctggcc ccctacctgg gcacccagga ggagtgcctc tttggcctgc tcaccctcat 900cttcctcacc tgcgtagcag ccacactgct ggtggctgag gaggcagcgc tgggccccac 960cgagccagca gaagggctgt cggccccctc cttgtcgccc cactgctgtc catgccgggc 1020ccgcttggct ttccggaacc tgggcgccct gcttccccgg ctgcaccagc tgtgctgccg 1080catgccccgc accctgcgcc ggctcttcgt ggctgagctg tgcagctgga tggcactcat 1140gaccttcacg ctgttttaca cggatttcgt gggcgagggg ctgtaccagg gcgtgcccag 1200agctgagccg ggcaccgagg cccggagaca ctatgatgaa ggcgttcgga tgggcagcct 1260ggggctgttc ctgcagtgcg ccatctccct ggtcttctct ctggtcatgg accggctggt 1320gcagcgattc ggcactcgag cagtctattt ggccagtgtg gcagctttcc ctgtggctgc 1380cggtgccaca tgcctgtccc acagtgtggc cgtggtgaca gcttcagccg ccctcaccgg 1440gttcaccttc tcagccctgc agatcctgcc ctacacactg gcctccctct accaccggga 1500gaagcaggtg ttcctgccca aataccgagg ggacactgga ggtgctagca gtgaggacag 1560cctgatgacc agcttcctgc caggccctaa gcctggagct cccttcccta atggacacgt 1620gggtgctgga ggcagtggcc tgctcccacc tccacccgcg ctctgcgggg cctctgcctg 1680tgatgtctcc gtacgtgtgg tggtgggtga gcccaccgag gccagggtgg ttccgggccg 1740gggcatctgc ctggacctcg ccatcctgga tagtgccttc ctgctgtccc aggtggcccc 1800atccctgttt atgggctcca ttgtccagct cagccagtct gtcactgcct atatggtgtc 1860tgccgcaggc ctgggtctgg tcgccattta ctttgctaca caggtagtat ttgacaagag 1920cgacttggcc aaatactcag cgtagaaaac ttccagcaca ttggggtgga gggcctgcct 1980cactgggtcc cagctccccg ctcctgttag ccccatgggg ctgccgggct ggccgccagt 2040ttctgttgct gccaaagtaa tgtggctctc tgctgccacc ctgtgctgct gaggtgcgta 2100gctgcacagc tgggggctgg ggcgtccctc tcctctctcc ccagtctcta gggctgcccg 2160actggaggcc ttccaagggg gcttcagtct ggacttatac agggaggcca gaagggctcc 2220atgcactgga atgcggggac tctgcaggtg gattacccag gctcagggtt aacagctagc 2280ctcctagttg agacacacct agagaagggt ttttgggagc tgaataaact cagtcacctg 2340gtttcccatc tctaagcccc ttaacctgca gcttcgttta atgtagctct tgcatgggag 2400tttctaggat gaaacactcc tccatgggat ttgaacatat gacttatttg taggggaaga 2460gtcctgaggg gcaacacaca agaaccaggt cccctcagcc cacagcactg tctttttgct 2520gatccacccc cctcttacct tttatcagga tgtggcctgt tggtccttct gttgccatca 2580cagagacaca ggcatttaaa tatttaactt atttatttaa caaagtagaa gggaatccat 2640tgctagcttt tctgtgttgg tgtctaatat ttgggtaggg tgggggatcc ccaacaatca 2700ggtcccctga gatagctggt cattgggctg atcattgcca gaatcttctt ctcctggggt 2760ctggcccccc aaaatgccta acccaggacc ttggaaattc tactcatccc aaatgataat 2820tccaaatgct gttacccaag gttagggtgt tgaaggaagg tagagggtgg ggcttcaggt 2880ctcaacggct tccctaacca cccctcttct cttggcccag cctggttccc cccacttcca 2940ctcccctcta ctctctctag gactgggctg atgaaggcac tgcccaaaat ttcccctacc 3000cccaactttc ccctaccccc aactttcccc accagctcca caaccctgtt tggagctact 3060gcaggaccag aagcacaaag tgcggtttcc caagcctttg tccatctcag cccccagagt 3120atatctgtgc ttggggaatc tcacacagaa actcaggagc accccctgcc tgagctaagg 3180gaggtcttat ctctcagggg gggtttaagt gccgtttgca ataatgtcgt cttatttatt 3240tagcggggtg aatattttat actgtaagtg agcaatcaga gtataatgtt tatggtgaca 3300aaattaaagg ctttcttata tgtttaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3360aaaaaaaara aaaaaaaaaa aaaaaaaaaa aaaaaaataa aaaaaaaaaa 3410

<210> 111

<211> 1289

<212> DNA

<213> Homo sapien

<400> 111agccaggcgt ccctctgcct gcccactcag tggcaacacc cgggagctgt tttgtccttt 60gtggagcctc agcagttccc tctttcagaa ctcactgcca agagccctga acaggagcca 120ccatgcagtg cttcagcttc attaagacca tgatgatcct cttcaatttg ctcatctttc 180tgtgtggtgc agccctgttg gcagtgggca tctgggtgtc aatcgatggg gcatcctttc 240tgaagatctt cgggccactg tcgtccagtg ccatgcagtt tgtcaacgtg ggctacttcc 300tcatcgcagc cggcgttgtg gtctttgctc ttggtttcct gggctgctat ggtgctaaga 360ctgagagcaa gtgtgccctc gtgacgttct tcttcatcct cctcctcatc ttcattgctg 420aggttgcagc tgctgtggtc gccttggtgt acaccacaat ggctgagcac ttcctgacgt 480tgctggtagt gcctgccatc aagaaagatt atggttccca ggaagacttc actcaagtgt 540ggaacaccac catgaaaggg ctcaagtgct gtggcttcac caactatacg gattttgagg 600actcacccta cttcaaagag aacagtgcct ttcccccatt ctgttgcaat gacaacgtca 660ccaacacagc caatgaaacc tgcaccaagc aaaaggctca cgaccaaaaa gtagagggtt 720gcttcaatca gcttttgtat gacatccgaa ctaatgcagt caccgtgggt ggtgtggcag 780ctggaattgg gggcctcgag ctggctgcca tgattgtgtc catgtatctg tactgcaatc 840tacaataagt ccacttctgc ctctgccact actgctgcca catgggaact gtgaagaggc 900accctggcaa gcagcagtga ttgggggagg ggacaggatc taacaatgtc acttgggcca 960gaatggacct gccctttctg ctccagactt ggggctagat agggaccact ccttttagcg 1020atgcctgact ttccttccat tggtgggtgg atgggtgggg ggcattccag agcctctaag 1080gtagccagtt ctgttgccca ttcccccagt ctattaaacc cttgatatgc cccctaggcc 1140tagtggtgat cccagtgctc tactggggga tgagagaaag gcattttata gcctgggcat 1200aagtgaaatc agcagagcct ctgggtggat gtgtagaagg cacttcaaaa tgcataaacc 1260tgttacaatg ttaaaaaaaa aaaaaaaaa 1289

<210> 112

<211> 315

<212> PRT

<213> Homo sapien

<400> 112Met Val Phe Thr Val Arg Leu Leu His Ile PheThr Val Asn Lys Gln1 5 10 15Leu Gly Pro Lys Ile Val Ile Val Ser Lys Met Met Lys Asp Val Phe

20 25 30Phe Phe Leu Phe Phe Leu Gly Val Trp Leu Val Ala Tyr Gly Val Ala

35 40 45Thr Glu Gly Leu Leu Arg Pro Arg Asp Ser Asp Phe Pro Ser Ile Leu

50 55 60Arg Arg Val Phe Tyr Arg Pro Tyr Leu Gln Ile Phe Gly Gln Ile Pro65 70 75 80Gln Glu Asp Met Asp Val Ala Leu Met Glu His Ser Asn Cys Ser Ser

85 90 95Glu Pro Gly Phe Trp Ala His Pro Pro Gly Ala Gln Ala Gly Thr Cys

100 105 110Val Ser Gln Tyr Ala Asn Trp Leu Val Val Leu Leu Leu Val Ile Phe

115 120 125Leu Leu Val Ala Ash Ile Leu Leu Val Asn Leu Leu Ile Ala Met Phe

130 135 140Set Tyr Thr Phe Gly Lys Val Gln Gly Asn Ser Asp Leu Tyr Trp Lys145 150 155 160Ala Gln Arg Tyr Arg Leu Ile Arg Glu Phe His Ser Arg Pro Ala Leu

165 170 175Ala Pro Pro Phe Ile Val Ile Ser His Leu Arg Leu Leu Leu Arg Gln

180 185 190Leu Cys Arg Arg Pro Arg Ser Pro Gln Pro Ser Ser Pro Ala Leu Glu

195 200 205His Phe Arg Val Tyr Leu Ser Lys Glu Ala Glu Arg Lys Leu Leu Thr

210 215 220Trp Glu Ser Val His Lys Glu Asn Phe Leu Leu Ala Arg Ala Arg Asp225 230 235 240Lys Arg Glu Ser Asp Ser Glu Arg Leu Lys Arg Thr Ser Gln Lys Val

245 250 255Asp Leu Ala Leu Lys Gln Leu Gly His Ile Arg Glu Tyr Glu Gln Arg

260 265 270Leu Lys Val Leu Glu Arg Glu Val Gln Gln Cys Ser Arg Val Leu Gly

275 280 285Trp Val Ala Glu Ala Leu Ser Arg Ser Ala Leu Leu Pro Pro Gly Gly

290 295 300Pro Pro Pro Pro Asp Leu Pro Gly Ser Lys Asp305 310 315

<210> 113

<211> 553

<212> PRT

<213> Homo sapien

<400> 113Met Val Gln Arg Leu Trp Val Ser Arg Leu Leu Arg His Arg Lys Ala1 5 10 15Gln Leu Leu Leu Val Asn Leu Leu Thr Phe Gly Leu Glu Val Cys Leu

20 25 30Ala Ala Gly Ile Thr Tyr Val Pro Pro Leu Leu Leu Glu Val Gly Val

35 40 45Glu Glu Lys Phe Met Thr Met Val Leu Gly Ile Gly Pro Val Leu Gly

50 55 60Leu Val Cys Val Pro Leu Leu Gly Ser Ala Ser Asp His Trp Arg Gly65 70 75 80Arg Tyr Gly Arg Arg Arg Pro Phe Ile Trp Ala Leu Ser Leu Gly Ile

85 90 95Leu Leu Ser Leu Phe Leu Ile Pro Arg Ala Gly Trp Leu Ala Gly Leu

100 105 110Leu Cys Pro Asp Pro Arg Pro Leu Glu Leu Ala Leu Leu Ile Leu Gly

115 120 125Val Gly Leu Leu Asp Phe Cys Gly Gln Val Cys Phe Thr Pro Leu Glu

130 135 140Ala Leu Leu Ser Asp Leu Phe Arg Asp Pro Asp His Cys Arg Gln Ala145 150 155 160Tyr Ser Val Tyr Ala Phe Met Ile Ser Leu Gly Gly Cys Leu Gly Tyr

165 170 175Leu Leu Pro Ala Ile Asp Trp Asp Thr Ser Ala Leu Ala Pro Tyr Leu

180 185 190Gly Thr Gln Glu Glu Cys Leu Phe Gly Leu Leu Thr Leu Ile Phe Leu

195 200 205Thr Cys Val Ala Ala Thr Leu Leu Val Ala Glu Glu Ala Ala Leu Gly

210 215 220Pro Thr Glu Pro Ala Glu Gly Leu Ser Ala Pro Ser Leu Ser Pro His225 230 235 240Cys Cys Pro Cys Arg Ala Arg Leu Ala Phe Arg Asn Leu Gly Ata Leu

245 250 255Leu Pro Arg Leu His Gln Leu Cys Cys Arg Met Pro Arg Thr Leu Arg

260 265 270Arg Leu Phe Val Ala Glu Leu Cys Ser Trp Met Ala Leu Met Thr Phe

275 280 285Thr Leu Phe Tyr Thr Asp Phe Val Gly Glu Gly Leu Tyr Gln Gly Val

290 295 300Pro Arg Ala Glu Pro Gly Thr Glu Ala Arg Arg His Tyr Asp Glu Gly305 310 315 320Val Arg Met Gly Ser Leu Gly Leu Phe Leu Gln Cys Ala Ile Ser Leu

325 330 335Val Phe Ser Leu Val Met Asp Arg Leu Val Gln Arg Phe Gly Thr

340 345 350Ala Val Tyr Leu Ala Ser Val Ala Ala Phe Pro Val Ala Ala Gly Ala

355 360 365Thr Cys Leu Ser His Ser Val Ala Val Val Thr Ala Ser Ala Ala Leu

370 375 380Thr Gly Phe Thr Phe Ser Ala Leu Gln Ile Leu Pro Tyr Thr Leu Ala385 390 395 400Ser Leu Tyr His Arg Glu Lys Gln Val Phe Leu Pro Lys Tyr Arg Gly

405 410 415Asp Thr Gly Gly Ala Ser Ser Glu Asp Ser Leu Met Thr Ser Phe Leu

420 425 430Pro Gly Pro Lys Pro Gly Ala Pro Phe Pro Asn Gly His Val Gly Ala

435 440 445Gly Gly Ser Gly Leu Leu Pro Pro Pro Pro Ala Leu Cys Gly Ala Ser

450 455 460Ala Cys Asp Val Ser Val Arg Val Val Val Gly Glu Pro Thr Glu Ala465 470 475 480Arg Val Val Pro Gly Arg Gly Ile Cys Leu Asp Leu Ala Ile Leu Asp

485 490 495Ser Ala Phe Leu Leu Ser Gln Val Ala Pro Ser Leu Phe Met Gly Ser

500 505 510Ile Val Gln Leu Ser Gln Ser Val Thr Ala Tyr Met Val Ser Ala Ala

515 520 525Gly Leu Gly Leu Val Ala Ile Tyr Phe Ala Thr Gln Val Val Phe Asp

530 535 540Lys Set Asp Leu Ala Lys Tyr Ser Ala545 550

<210> 114

<211> 241

<212> PRT

<213> Homo sapien

<400> 114Met Gln Cys Phe Ser Phe Ile Lys Thr Met Met Ile Leu Phe Asn Leu1 5 10 15Leu Ile Phe Leu Cys Gly Ala Ala Leu Leu Ala Val Gly Ile Trp Val

20 25 30Ser Ile Asp Gly Ala Ser Phe Leu Lys Ile Phe Gly Pro Leu Ser Ser

35 40 45Ser Ala Met Gln Phe Val Asn Val Gly Tyr Phe Leu Ile Ala Ala Gly

50 55 60Val Val Val Phe Ala Leu Gly Phe Leu Gly Cys Tyr Gly Ala Lys Thr65 70 75 80Glu Ser Lys Cys Ala Leu Val Thr Phe Phe Phe Ile Leu Leu Leu Ile

85 90 95Phe Ile Ala Glu Val Ala Ala Ala Val Val Ala Leu Val Tyr Thr Thr

100 105 110Met Ala Glu His Phe Leu Thr Leu Leu Val Val Pro Ala Ile Lys Lys

115 120 125Asp Tyr Gly Ser Gln Glu Asp Phe Thr Gln Val Trp Asn Thr Thr Met

130 135 140Lys Gly Leu Lys Cys Cys Gly Phe Thr Asn Tyr Thr Asp Phe Glu Asp145 150 155 160Ser Pro Tyr Phe Lys Glu Asn Ser Ala Phe Pro Pro Phe Cys Cys Asn

165 170 175Asp Asn Val Thr Asn Thr Ala Asn Glu Thr Cys Thr Lys Gln Lys Ala

180 185 190His Asp Gln Lys Val Glu Gly Cys Phe Asn Gln Leu Leu Tyr Asp Ile

195 200 205Arg Thr Asn Ala Val Thr Val Gly Gly Val Ala Ala Gly Ile Gly Gly

210 215 220Leu Glu Leu Ala Ala Met Ile Val Ser Met Tyr Leu Tyr Cys Asn Leu225 230 235 240Gln

<210> 115

<211> 366

<212> DNA

<213> Homo sapien

<400> 115gctctttctc tcccctcctc tgaatttaat tctttcaact tgcaatttgc aaggattaca 60catttcactg tgatgtatat tgtgttgcaa aaaaaaaaaa gtgtctttgt ttaaaattac 120ttggtttgtg aatccatctt gctttttccc cattggaact agtcattaac ccatctctga 180actggtagaa aaacatctga agagctagtc tatcagcatc tgacaggtga attggatggt 240tctcagaacc atttcaccca gacagcctgt ttctatcctg tttaataaat tagtttgggt 300tctctacatg cataacaaac cctgctccaa tctgtcacat aaaagtctgt gacttgaagt 360ttagtc 366

<210> 116

<211> 282

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (282)

<223> n = A,T,C or G

<400> 116acaaagatga accatttcct atattatagc aaaattaaaa tctacccgta ttctaatatt 60gagaaatgag atnaaacaca atnttataaa gtctacttag agaagatcaa gtgacctcaa 120agactttact attttcatat tttaagacac atgatttatc ctattttagt aacctggttc 180atacgttaaa caaaggataa tgtgaacagc agagaggatt tgttggcaga aaatctatgt 240tcaatctnga actatctana tcacagacat ttctattcct tt 282

<210> 117

<211> 305

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(305)

<223> n = A,T,C or G

<400> 117acacatgtcg cttcactgcc ttcttagatg cttctggtca acatanagga acagggacca 60tatttatcct ccctcctgaa acaattgcaa aataanacaa aatatatgaa acaattgcaa 120aataaggcaa aatatatgaa acaacaggtc tcgagatatt ggaaatcagt caatgaagga 180tactgatccc tgatcactgt cctaatgcag gatgtgggaa acagatgagg tcacctctgt 240gactgcccca gcttactgcc tgtagagagt ttctangctg cagttcagac agggagaaat 300tgggt 305

<210> 118

<211> 71

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(71)

<223> n = A,T,C or G

<400> 118accaaggtgt ntgaatctct gacgtgggga tctctgattc ccgcacaatc tgagtggaaa 60aantcctggg t 71

<210> 119

<211> 212

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(212)

<223> n = A,T,C or G

<400> 119actccggttg gtgtcagcag cacgtggcat tgaacatngc aatgtggagc ccaaaccaca 60gaaaatgggg tgaaattggc caactttcta tnaacttatg ttggcaantt tgccaccaac 120agtaagctgg cccttctaat aaaagaaaat tgaaaggttt ctcactaanc ggaattaant 180aatggantca aganactccc aggcctcagc gt 212

<210> 120

<211> 90

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(90)

<223> n = A,T,C or G

<400> 120actcgttgca natcaggggc cccccagagt caccgttgca ggagtccttc tggtcttgcc 60ctccgccggc gcagaacatg ctggggtggt

<210> 121

<211> 218

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(218)

<223> n = A,T,C or G

<400> 121tgtancgtga anacgacaga nagggttgtc aaaaatggag aanccttgaa gtcattttga 60gaataagatt tgctaaaaga tttggggcta aaacatggtt attgggagac atttctgaag 120atatncangt aaattangga atgaattcat ggttcttttg ggaattcctt tacgatngcc 180agcatanact tcatgtgggg atancagcta cccttgta 218

<210> 122

<211> 171

<212> DNA

<213> Homo sapien

<400> 122taggggtgta tgcaactgta aggacaaaaa ttgagactca actggcttaa ccaataaagg 60catttgttag ctcatggaac aggaagtcgg atggtggggc atcttcagtg ctgcatgagt 120caccaccccg gcggggtcat ctgtgccaca ggtccctgtt gacagtgcgg t 171

<210> 123

<211> 76

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(76)

<223> n = A,T,C or G

<400> 123tgtagcgtga agacnacaga atggtgtgtg ctgtgctatc caggaacaca tttattatca 60ttatcaanta ttgtgt 76

<210> 124

<211> 131

<212> DNA

<213> Homo sapien

<400> 124acctttcccc aaggccaatg tcctgtgtgc taactggccg gctgcaggac agctgcaatt 60caatgtgctg ggtcatatgg aggggaggag actctaaaat agccaatttt attctcttgg 120ttaagatttg t 131

<210> 125

<211> 432

<212> DNA

<213> Homo sapien

<400> 125actttatcta ctggctatga aatagatggt ggaaaattgc gttaccaact ataccactgg 60cttgaaaaag aggtgatagc tcttcagagg acttgtgact tttgctcaga tgctgaagaa 120ctacagtctg catttggcag aaatgaagat gaatttggat taaatgagga tgctgaagat 180ttgcctcacc aaacaaaagt gaaacaactg agagaaaatt ttcaggaaaa aagacagtgg 240ctcttgaagt atcagtcact tttgagaatg tttcttagtt actgcatact tcatggatcc 300catggtgggg gtcttgcatc tgtaagaatg gaattgattt tgcttttgca agaatctcag 360caggaaacat cagaaccact attttctagc cctctgtcag agcaaacctc agtgcctctc 420ctctttgctt gt 432

<210> 126

<211> 112

<212> DNA

<213> Homo sapien

<400> 126acacaacttg aatagtaaaa tagaaactga gctgaaattt ctaattcact ttctaaccat 60agtaagaatg atatttcccc ccagggatca ccaaatattt ataaaaattt gt 112

<210> 127

<211> 54

<212> DNA

<213> Homo sapien

<400> 127accacgaaac cacaaacaag atggaagcat caatccactt gccaagcaca gcag 54

<210> 128

<211> 323

<212> DNA

<213> Homo sapien

<400> 128acctcattag taattgtttt gttgtttcat ttttttctaa tgtctcccct ctaccagctc 60acctgagata acagaatgaa aatggaagga cagccagatt tctcctttgc tctctgctca 120ttctctctga agtctaggtt acccattttg gggacccatt ataggcaata aacacagttc 180ccaaagcatt tggacagttt cttgttgtgt tttagaatgg ttttcctttt tcttagcctt 240ttcctgcaaa aggctcactc agtcccttgc ttgctcagtg gactgggctc cccagggcct 300aggctgcctt cttttccatg tcc 323

<210> 129

<211> 192

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (192)

<223> n = A,T,C or G

<400> 129acatacatgt gtgtatattt ttaaatatca cttttgtatc actctgactt tttagcatac 60tgaaaacaca ctaacataat ttntgtgaac catgatcaga tacaacccaa atcattcatc 120tagcacattc atctgtgata naaagatagg tgagtttcat ttccttcacg ttggccaatg 180gataaacaaa gt 192

<210> 130

<211> 362

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(362)

<223> n = A,T,C or G

<400> 130ccctttttta tggaatgagt agactgtatg tttgaanatt tanccacaac ctctttgaca 60tataatgacg caacaaaaag gtgctgttta gtcctatggt tcagtttatg cccctgacaa 120gtttccattg tgttttgccg atcttctggc taatcgtggt atcctccatg ttattagtaa 180ttctgtattc cattttgtta acgcctggta gatgtaacct gctangaggc taactttata 240cttatttaaa agctcttatt ttgtggtcat taaaatggca atttatgtgc agcactttat 300tgcagcagga agcacgtgtg ggttggttgt aaagctcttt gctaatctta aaaagtaatg 360gg 362

<210> 131

<211> 332

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(332)

<223> n = A,T,C or G

<400> 131ctttttgaaa gatcgtgtcc actcctgtgg acatcttgtt ttaatggagt ttcccatgca 60gtangactgg tatggttgca gctgtccaga taaaaacatt tgaagagctc caaaatgaga 120gttctcccag gttcgccctg ctgctccaag tctcagcagc agcctctttt aggaggcatc 180ttctgaacta gattaaggca gcttgtaaat ctgatgtgat ttggtttatt atccaactaa 240cttccatctg ttatcactgg agaaagccca gactccccan gacnggtacg gattgtgggc 300atanaaggat tgggtgaagc tggcgttgtg gt 332

<210> 132

<211> 322

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(322)

<223> n = A,T,C or G

<400> 132acttttgcca ttttgtatat ataaacaatc ttgggacatt ctcctgaaaa ctaggtgtcc 60agtggctaag agaactcgat ttcaagcaat tctgaaagga aaaccagcat gacacagaat 120ctcaaattcc caaacagggg ctctgtggga aaaatgaggg aggacctttg tatctcgggt 180tttagcaagt taaaatgaan atgacaggaa aggcttattt atcaacaaag agaagagttg 240ggatgcttct aaaaaaaact ttggtagaga aaataggaat gctnaatcct agggaagcct 300gtaacaatct acaattggtc ca 322

<210> 133

<211> 278

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(278)

<223> n = A,T,C or G

<400> 133acaagccttc acaagtttaa ctaaattggg attaatcttt ctgtanttat ctgcataatt 60cttgtttttc tttccatctg gctcctgggt tgacaatttg tggaaacaac tctattgcta 120ctatttaaaa aaaatcacaa atctttccct ttaagctatg ttnaattcaa actattcctg 180ctattcctgt tttgtcaaag aaattatatt tttcaaaata tgtntatttg tttgatgggt 240cccacgaaac actaataaaa accacagaga ccagcctg 278

<210> 134

<211> 121

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(121)

<223> n = A,T,C or G

<400> 134gtttanaaaa cttgtttagc tccatagagg aaagaatgtt aaactttgta ttttaaaaca 60tgattctctg aggttaaact tggttttcaa atgttatttt tacttgtatt ttgcttttgg 120t 121

<210> 135

<211> 350

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(350)

<223> n = A,T,C or G

<400> 135acttanaacc atgcctagca catcagaatc cctcaaagaa catcagtata atcctatacc 60atancaagtg gtgactggtt aagcgtgcga caaaggtcag ctggcacatt acttgtgtgc 120aaacttgata cttttgttct aagtaggaac tagtatacag tncctaggan tggtactcca 180gggtgccccc caactcctgc agccgctcct ctgtgccagn ccctgnaagg aactttcgct 240ccacctcaat caagccctgg gccatgctac ctgcaattgg ctgaacaaac gtttgctgag 300ttcccaagga tgcaaagcct ggtgctcaac tcctggggcg tcaactcagt 350

<210> 136

<211> 399

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(399)

<223> n = A,T,C or G

<400> 136tgtaccgtga agacgacaga agttgcatgg cagggacagg gcagggccga ggccagggtt 60gctgtgattg tatccgaata ntcctcgtga gaaaagataa tgagatgacg tgagcagcct 120gcagacttgt gtctgccttc aanaagccag acaggaaggc cctgcctgcc ttggctctga 180cctggcggcc agccagccag ccacaggtgg gcttcttcct tttgtggtga caacnccaag 240aaaactgcag aggcccaggg tcaggtgtna gtgggtangt gaccataaaa caccaggtgc 300tcccaggaac ccgggcaaag gccatcccca cctacagcca gcatgcccac tggcgtgatg 360ggtgcagang gatgaagcag ccagntgttc tgctgtggt 399

<210> 137

<211> 165

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (I)...(165)

<223> n = A,T,C or G

<400> 137actggtgtgg tngggggtga tgctggtggt anaagttgan gtgacttcan gatggtgtgt 60ggaggaagtg tgtgaacgta gggatgtaga ngttttggcc gtgctaaatg agcttcggga 120ttggctggtc ccactggtgg tcactgtcat tggtggggtt cctgt 165

<210> 138

<211> 338

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(338)

<223> n = A,T,C or G

<400> 138actcactgga atgccacatt cacaacagaa tcagaggtct gtgaaaacat taatggctcc 60ttaacttctc cagtaagaat cagggacttg aaatggaaac gttaacagcc acatgcccaa 120tgctgggcag tctcccatgc cttccacagt gaaagggctt gagaaaaatc acatccaatg 180tcatgtgttt ccagccacac caaaaggtgc ttggggtgga gggctggggg catananggt 240cangcctcag gaagcctcaa gttccattca gctttgccac tgtacattcc ccatntttaa 300aaaaactgat gccttttttt tttttttttg taaaattc 338

<210> 139

<211> 382

<212> DNA

<213> Homo sapien

<400> 139gggaatcttg gtttttggca tctggtttgc ctatagccga ggccactttg acagaacaaa 60gaaagggact tcgagtaaga aggtgattta cagccagcct agtgcccgaa gtgaaggaga 120attcaaacag acctcgtcat tcctggtgtg agcctggtcg gctcaccgcc tatcatctgc 180atttgcctta ctcaggtgct accggactct ggcccctgat gtctgtagtt tcacaggatg 240ccttatttgt cttctacacc ccacagggcc ccctacttct tcggatgtgt ttttaataat 300gtcagctatg tgccccatcc tccttcatgc cctccctccc tttcctacca ctgctgagtg 360gcctggaact tgtttaaagt gt 382

<210> 140

<211> 200

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(200)

<223> n = A,T,C or G

<400> 140accaaanctt ctttctgttg tgttngattt tactataggg gtttngcttn ttctaaanat 60acttttcatt taacancttt tgttaagtgt caggctgcac tttgctccat anaattattg 120ttttcacatt tcaacttgta tgtgtttgtc tcttanagca ttggtgaaat cacatatttt 180atattcagca taaaggagaa 200

<210> 141

<211> 335

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(335)

<223> n = A,T,C or G

<400> 141actttatttt caaaacactc atatgttgca aaaaacacat agaaaaataa agtttggtgg 60gggtgctgac taaacttcaa gtcacagact tttatgtgac agattggagc agggtttgtt 120atgcatgtag agaacccaaa ctaatttatt aaacaggata gaaacaggct gtctgggtga 180aatggttctg agaaccatcc aattcacctg tcagatgctg atanactagc tcttcagatg 240tttttctacc agttcagaga tnggttaatg actanttcca atggggaaaa agcaagatgg 300attcacaaac caagtaattt taaacaaaga cactt 335

<210> 142

<211> 459

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(459)

<223> n = A,T,C or G

<400> 142accaggttaa tattgccaca tatatccttt ccaattgcgg gctaaacaga cgtgtattta 60gggttgttta aagacaaccc agcttaatat caagagaaat tgtgaccttt catggagtat 120ctgatggaga aaacactgag ttttgacaaa tcttatttta ttcagatagc agtctgatca 180cacatggtcc aacaacactc aaataataaa tcaaatatna tcagatgtta aagattggtc 240ttcaaacatc atagccaatg atgccccgct tgcctataat ctctccgaca taaaaccaca 300tcaacacctc agtggccacc aaaccattca gcacagcttc cttaactgtg agctgtttga 360agctaccagt ctgagcacta ttgactatnt ttttcangct ctgaatagct ctagggatct 420cagcangggt gggaggaacc agctcaacct tggcgtant 459

<210> 143

<211> 140

<212> DNA

<213> Homo sapien

<400> 143acatttcctt ccaccaagtc aggactcctg gcttctgtgg gagttcttat cacctgaggg 60aaatccaaac agtctctcct agaaaggaat agtgtcacca accccaccca tctccctgag 120accatccgac ttccctgtgt 140

<210> 144

<211> 164

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(164)

<223> n = A,T,C or G

<400> 144acttcagtaa caacatacaa taacaacatt aagtgtatat tgccatcttt gtcattttct 60atctatacca ctctcccttc tgaaaacaan aatcactanc caatcactta tacaaatttg 120aggcaattaa tccatatttg ttttcaataa ggaaaaaaag atgt 164

<210> 145

<211> 303

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(303)

<223> n = A,T,C or G

<400> 145acgtagacca tccaactttg tatttgtaat ggcaaacatc cagnagcaat tcctaaacaa 60actggagggt atttataccc aattatccca ttcattaaca tgccctcctc ctcaggctat 120gcaggacagc tatcataagt cggcccaggc atccagatac taccatttgt ataaacttca 180gtaggggagt ccatccaagt gacaggtcta atcaaaggag gaaatggaac ataagcccag 240tagtaaaatn ttgcttagct gaaacagcca caaaagactt accgccgtgg tgattaccat 300caa 303

<210> 146

<211> 327

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(327)

<223> n = A,T,C or G

<400> 146actgcagctc aattagaagt ggtctctgac tttcatcanc ttctccctgg gctccatgac 60actggcctgg agtgactcat tgctctggtt ggttgagaga gctcctttgc caacaggcct 120ccaagtcagg gctgggattt gtttcctttc cacattctag caacaatatg ctggccactt 180cctgaacagg gagggtggga ggagccagca tggaacaagc tgccactttc taaagtagcc 240agacttgccc ctgggcctgt cacacctact gatgaccttc tgtgcctgca ggatggaatg 300taggggtgag ctgtgtgact ctatggt 327

<210> 147

<211> 173

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(173)

<223> n = A,T,C or G

<400> 147acattgtttt tttgagataa agcattgana gagctctcct taacgtgaca caatggaagg 60actggaacac atacccacat ctttgttctg agggataatt ttctgataaa gtcttgctgt 120atattcaagc acatatgtta tatattattc agttccatgt ttatagccta gtt 173

<210> 148

<211> 477

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(477)

<223> n = A,T,C or G

<400> 148acaaccactt tatctcatcg aatttttaac ccaaactcac tcactgtgcc tttctatcct 60atgggatata ttatttgatg ctccatttca tcacacatat atgaataata cactcatact 120gccctactac ctgctgcaat aatcacattc ccttcctgtc ctgaccctga agccattggg 180gtggtcctag tggccatcag tccangcctg caccttgagc ccttgagctc cattgctcac 240nccancccac ctcaccgacc ccatcctctt acacagctac ctccttgctc tctaacccca 300tagattatnt ccaaattcag tcaattaagt tactattaac actctacccg acatgtccag 360caccactggt aagccttctc cagccaacac acacacacac acacncacac acacacatat 420ccaggcacag gctacctcat cttcacaatc acccctttaa ttaccatgct atggtgg 477

<210> 149

<211> 207

<212> DNA

<213> Homo sapien

<400> 149acagttgtat tataatatca agaaataaac ttgcaatgag agcatttaag agggaagaac 60taacgtattt tagagagcca aggaaggttt ctgtggggag tgggatgtaa ggtggggcct 120gatgataaat aagagtcagc caggtaagtg ggtggtgtgg tatgggcaca gtgaagaaca 180tttcaggcag agggaacagc agtgaaa 207

<210> 150

<211> 111

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(111)

<223> n = A,T,C or G

<400> 150accttgattt cattgctgct ctgatggaaa cccaactatc taatttagct aaaacatggg 60cacttaaatg tggtcagtgt ttggacttgt taactantgg catctttggg t 111

<210> 151

<211> 196

<212> DNA

<213> Homo sapien

<400> 151agcgcggcag gtcatattga acattccaga tacctatcat tactcgatgc tgttgataac 60agcaagatgg ctttgaactc agggtcacca ccagctattg gaccttacta tgaaaaccat 120ggataccaac cggaaaaccc ctatcccgca cagcccactg tggtccccac tgtctacgag 180gtgcatccgg ctcagt 196

<210> 152

<211> 132

<212> DNA

<213> Homo sapien

<400> 152acagcacttt cacatgtaag aagggagaaa ttcctaaatg taggagaaag ataacagaac 60cttccccttt tcatctagtg gtggaaacct gatgctttat gttgacagga atagaaccag 120gagggagttt gt 132

<210> 153

<211> 285

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(285)

<223> n = A,T,C or G

<400> 153acaanaccca nganaggcca ctggccgtgg tgtcatggcc tccaaacatg aaagtgtcag 60cttctgctct tatgtcctca tctgacaact ctttaccatt tttatcctcg ctcagcagga 120gcacatcaat aaagtccaaa gtcttggact tggccttggc ttggaggaag tcatcaacac 180cctggctagt gagggtgcgg cgccgctcct ggatgacggc atctgtgaag tcgtgcacca 240gtctgcaggc cctgtggaag cgccgtccac acggagtnag gaatt 285

<210> 154

<211> 333

<212> DNA

<213> Homo sapien

<400> 154accacagtcc tgttgggcca gggcttcatg accctttctg tgaaaagcca tattatcacc 60accccaaatt tttccttaaa tatctttaac tgaaggggtc agcctcttga ctgcaaagac 120cctaagccgg ttacacagct aactcccact ggccctgatt tgtgaaattg ctgctgcctg 180attggcacag gagtcgaagg tgttcagctc ccctcctccg tggaacgaga ctctgatttg 240agtttcacaa attctcgggc cacctcgtca ttgctcctct gaaataaaat ccggagaatg 300gtcaggcctg tctcatccat atggatcttc cgg 333

<210> 155

<211> 308

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(308)

<223> n = A,T,C or G

<400> 155actggaaata ataaaaccca catcacagtg ttgtgtcaaa gatcatcagg gcatggatgg 60gaaagtgctt tgggaactgt aaagtgccta acacatgatc gatgattttt gttataatat 120ttgaatcacg gtgcatacaa actctcctgc ctgctcctcc tgggccccag ccccagcccc 180atcacagctc actgctctgt tcatccaggc ccagcatgta gtggctgatt cttcttggct 240gcttttagcc tccanaagtt tctctgaagc caaccaaacc tctangtgta aggcatgctg 300gccctggt 308

<210> 156

<211> 295

<212> DNA

<213> Homo sapien

<400> 156accttgctcg gtgcttggaa catattagga actcaaaata tgagatgata acagtgccta 60ttattgatta ctgagagaac tgttagacat ttagttgaag attttctaca caggaactga 120gaataggaga ttatgtttgg ccctcatatt ctctcctatc ctccttgcct cattctatgt 180ctaatatatt ctcaatcaaa taaggttagc ataatcagga aatcgaccaa ataccaatat 240aaaaccagat gtctatcctt aagattttca aatagaaaac aaattaacag actat 295

<210> 157

<211> 126

<212> DNA

<213> Homo sapien

<400> 157acaagtttaa atagtgctgt cactgtgcat gtgctgaaat gtgaaatcca ccacatttct 60gaagagcaaa acaaattctg tcatgtaatc tctatcttgg gtcgtgggta tatctgtccc 120cttagt 126

<210> 158

<211> 442

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (442)

<223> n = A,T,C or G

<400> 158acccactggt cttggaaaca cccatcctta atacgatgat ttttctgtcg tgtgaaaatg 60aanccagcag gctgccccta gtcagtcctt ccttccagag aaaaagagat ttgagaaagt 120gcctgggtaa ttcaccatta atttcctccc ccaaactctc tgagtcttcc cttaatattt 180ctggtggttc tgaccaaagc aggtcatggt ttgttgagca tttgggatcc cagtgaagta 240natgtttgta gccttgcata cttagccctt cccacgcaca aacggagtgg cagagtggtg 300ccaaccctgt tttcccagtc cacgtagaca gattcacagt gcggaattct ggaagctgga 360nacagacggg ctctttgcag agccgggact ctgagangga catgagggcc tctgcctctg 420tgttcattct ctgatgtcct gt 442

<210> 159

<211> 498

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (498)

<223> n = A,T,C or G

<400> 159acttccaggt aacgttgttg tttccgttga gcctgaactg atgggtgacg ttgtaggttc 60tccaacaaga actgaggttg cagagcgggt agggaagagt gctgttccag ttgcacctgg 120gctgctgtgg actgttgttg attcctcact acggcccaag gttgtggaac tggcanaaag l80gtgtgttgtt gganttgagc tcgggcggct gtggtaggtt gtgggctctt caacaggggc 240tgctgtggtg ccgggangtg aangtgttgt gtcacttgag cttggccagc tctggaaagt 300antanattct tcctgaaggc cagcgcttgt ggagctggca ngggtcantg ttgtgtgtaa 360cgaaccagtg ctgctgtggg tgggtgtana tcctccacaa agcctgaagt tatggtgtcn 420tcaggtaana atgtggtttc agtgtccctg ggcngctgtg gaaggttgta nattgtcacc 480aagggaataa gctgtggt 498

<210> 160

<211> 380

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(380)

<223> n = A,T,C or G

<400> 160acctgcatcc agcttccctg ccaaactcac aaggagacat caacctctag acagggaaac 60agcttcagga tacttccagg agacagagcc accagcagca aaacaaatat tcccatgcct 120ggagcatggc atagaggaag ctganaaatg tggggtctga ggaagccatt tgagtctggc 180cactagacat ctcatcagcc acttgtgtga agagatgccc catgacccca gatgcctctc 240ccacccttac ctccatctca cacacttgag ctttccactc tgtataattc taacatcctg 300gagaaaaatg gcagtttgac cgaacctgtt cacaacggta gaggctgatt tctaacgaaa 360cttgtagaat gaagcctgga 380

<210> 161

<211> 114

<212> DNA

<213> Homo sapien

<400> 161actccacatc ccctctgagc aggcggttgt cgttcaaggt gtatttggcc ttgcctgtca 60cactgtccac tggcccctta tccacttggt gcttaatccc tcgaaagagc atgt 114

<210> 162

<211> 177

<212> DNA

<213> Homo sapien

<400> 162actttctgaa tcgaatcaaa tgatacttag tgtagtttta atatcctcat atatatcaaa 60gttttactac tctgataatt ttgtaaacca ggtaaccaga acatccagtc atacagcttt 120tggtgatata taacttggca ataacccagt ctggtgatac ataaaactac tcactgt 177

<210> 163

<211> 137

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(137)

<223> n = A,T,C or G

<400> 163catttataca gacaggcgtg aagacattca cgacaaaaac gcgaaattct atcccgtgac 60canagaaggc agctacggct actcctacat cctggcgtgg gtggccttcg cctgcacctt 120catcagcggc atgatgt 137

<210> 164

<211> 469

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(469)

<223> n = A,T,C or G

<400> 164cttatcacaa tgaatgttct cctgggcagc gttgtgatct ttgccacctt cgtgacttta 60tgcaatgcat catgctattt catacctaat gagggagttc caggagattc aaccaggaaa 120tgcatggatc tcaaaggaaa caaacaccca ataaactcgg agtggcagac tgacaactgt 180gagacatgca cttgctacga aacagaaatt tcatgttgca cccttgtttc tacacctgtg 240ggttatgaca aagacaactg ccaaagaatc ttcaagaagg aggactgcaa gtatatcgtg 300gtggagaaga aggacccaaa aaagacctgt tctgtcagtg aatggataat ctaatgtgct 360tctagtaggc acagggctcc caggccaggc ctcattctcc tctggcctct aatagtcaat 420gattgtgtag ccatgcctat cagtaaaaag atntttgagc aaacacttt 469

<210> 165

<211> 195

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(195)

<223> n = A,T,C or G

<400> 165acagtttttt atanatatcg acattgccgg cacttgtgtt cagtttcata aagctggtgg 60atccgctgtc atccactatt ccttggctag agtaaaaatt attcttatag cccatgtccc 120tgcaggccgc ccgcccgtag ttctcgttcc agtcgtcttg gcacacaggg tgccaggact 180tcctctgaga tgagt 195

<210> 166

<211> 383

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(383)

<223> n = A,T,C or G

<400> 166acatcttagt agtgtggcac atcagggggc catcagggtc acagtcactc atagcctcgc 60cgaggtcgga gtccacacca ccggtgtagg tgtgctcaat cttgggcttg gcgcccacct 120ttggagaagg gatatgctgc acacacatgt ccacaaagcc tgtgaactcg ccaaagaatt 180tttgcagacc agcctgagca aggggcggat gttcagcttc agctcctcct tcgtcaggtg 240gatgccaacc tcgtctangg tccgtgggaa gctggtgtcc acntcaccta caacctgggc 300gangatctta taaagaggct ccnagataaa ctccacgaaa cttctctggg agctgctagt 360nggggccttt ttggtgaact ttc 383

<210> 167

<211> 247

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(247)

<223> n = A,T,C or G

<400> 167acagagccag accttggcca taaatgaanc agagattaag actaaacccc aagtcganat 60tggagcagaa actggagcaa gaagtgggcc tggggctgaa gtagagacca aggccactgc 120tatanccata cacagagcca actctcaggc caaggcnatg gttggggcag anccagagac 180tcaatctgan tccaaagtgg tggctggaac actggtcatg acanaggcag tgactctgac 240tgangtc 247

<210> 168

<211> 273

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(273)

<223> n = A,T,C or G

<400> 168acttctaagt tttctagaag tggaaggatt gtantcatcc tgaaaatggg tttacttcaa 60aatccctcan ccttgttctt cacnactgtc tatactgana gtgtcatgtt tccacaaagg 120gctgacacct gagcctgnat tttcactcat ccctgagaag ccctttccag tagggtgggc 180aattcccaac ttccttgcca caagcttccc aggctttctc ccctggaaaa ctccagcttg 240agtcccagat acactcatgg gctgccctgg gca 273

<210> 169

<211> 431

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(431)

<223> n = A,T,C or G

<400> 169acagccttgg cttccccaaa ctccacagtc tcagtgcaga aagatcatct tccagcagtc 60agctcagacc agggtcaaag gatgtgacat caacagtttc tggtttcaga acaggttcta 120ctactgtcaa atgacccccc atacttccgc aaaggctgtg gtaagttttg cacaggtgag 180ggcagcagaa agggggtant tactgatgga caccatcttc tctgtatact ccacactgac 240cttgccatgg gcaaaggccc ctaccacaaa aacaatagga tcactgctgg gcaccagctc 300acgcacatca ctgacaaccg ggatggaaaa agaantgcca actttcatac atccaactgg 360aaagtgatct gatactggat tcttaattac cttcaaaagc ttctgggggc catcagctgc 420tcgaacactg a 431

<210> 170

<211> 266

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(266)

<223> n = A,T,C or G

<400> 170acctgtgggc tgggctgtta tgcctgtgcc ggctgctgaa agggagttca gaggtggagc 60tcaaggagct ctgcaggcat tttgccagnc ctctccanag canagggagc aacctacact 120ccccgctaga aagacaccag attggagtcc tgggaggggg agttggggtg ggcatttgat 180gtatacttgt cacctgaatg aangagccag agaggaanga gacgaanatg anattggcct 240tcaaagctag gggtctggca ggtgga 266

<210> 171

<211> 1248

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(1248)

<223> n = A,T,C or G

<400> 171ggcagccaaa tcataaacgg cgaggactgc agcccgcact cgcagccctg gcaggcggca 60ctggtcatgg aaaacgaatt gttctgctcg ggcgtcctgg tgcatccgca gtgggtgctg 120tcagccgcac actgtttcca gaagtgagtg cagagctcct acaccatcgg gctgggcctg 180cacagtcttg aggccgacca agagccaggg agccagatgg tggaggccag cctctccgta 240cggcacccag agtacaacag acccttgctc gctaacgacc tcatgctcat caagttggac 300gaatccgtgt ccgagtctga caccatccgg agcatcagca ttgcttcgca gtgccctacc 360gcggggaact cttgcctcgt ttctggctgg ggtctgctgg cgaacggcag aatgcctacc 420gtgctgcagt gcgtgaacgt gccggtggtg tctgaggagg tctgcagtaa gctctatgac 480ccgctgtacc accccagcat gttctgcgcc ggcggagggc aagaccagaa ggactcctgc 540aacggtgact ctggggggcc cctgatctgc aacgggtact tgcagggcct tgtgtctttc 600ggaaaagccc cgtgtggcca agttggcgtg ccaggtgtct acaccaacct ctgcaaattc 660actgagtgga tagagaaaac cgtccaggcc agttaactct ggggactggg aacccatgaa 720attgaccccc aaatacatcc tgcggaagga attcaggaat atctgttccc agcccctcct 780ccctcaggcc caggagtcca ggcccccagc ccctcctccc tcaaaccaag ggtacagatc 840cccagcccct cctccctcag acccaggagt ccagaccccc cagcccctcc tccctcagac 900ccaggagtcc agcccctcct ccctcagacc caggagtcca gaccccccag cccctcctcc 960ctcagaccca ggggtccagg cccccaaccc ctcctccctc agactcagag gtccaagccc 1020ccaacccntc attccccaga cccagaggtc caggtcccag cccctcntcc ctcagaccca 1080gcggtccaat gccacctaga ctntccctgt acacagtgcc cccttgtggc acgttgaccc 1140aaccttacca gttggttttt catttttngt ccctttcccc tagatccaga aataaagttt 1200aagagaagng caaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1248

<210> 172

<211> 159

<212> PRT

<213> Homo sapien

<220>

<221> VARIANT

<222> (1)...(159)

<223> Xaa = Any Amino Acid

<400> 172Met Val Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro1 5 10 15Leu Leu Ala Asn Asp Leu Met Leu Ile Lys Leu Asp Glu Ser Val Set

20 25 30Glu Ser Asp Thr Ile Arg Ser Ile Ser Ile Ala Ser Gln Cys Pro Thr

35 40 45Ala Gly Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Gly

50 55 60Arg Met Pro Thr Val Leu Gln Cys Val Asn Val Set Val Val Ser Glu65 70 75 80Glu Val Cys Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Ser Met Phe

85 90 95Cys Ala Gly Gly Gly Gln Xaa Gln Xaa Asp Ser Cys Asn Gly Asp Ser

100 105 110Gly Gly Pro Leu Ile Cys Asn Gly Tyr Leu Gln Gly Leu Val Ser Phe

115 120 125Gly Lys Ala Pro Cys Gly Gln Val Gly Val Pro Gly Val Tyr Thr Asn

130 135 140Leu Cys Lys Phe Thr Glu Trp Ile Glu Lys Thr Val Gln Ala Ser145 150 155

<210> 173

<211> 1265

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(1265)

<223> n = A,T,C or G

<400> 173ggcagcccgc actcgcagcc ctggcaggcg gcactggtca tggaaaacga attgttctgc 60tcgggcgtcc tggtgcatcc gcagtgggtg ctgtcagccg cacactgttt ccagaactcc 120tacaccatcg ggctgggcct gcacagtctt gaggccgacc aagagccagg gagccagatg 180gtggaggcca gcctctccgt acggcaccca gagtacaaca gacccttgct cgctaacgac 240ctcatgctca tcaagttgga cgaatccgtg tccgagtctg acaccatccg gagcatcagc 300attgcttcgc agtgccctac cgcggggaac tcttgcctcg tttctggctg gggtctgctg 360gcgaacggtg agctcacggg tgtgtgtctg ccctcttcaa ggaggtcctc tgcccagtcg 420cgggggctga cccagagctc tgcgtcccag gcagaatgcc taccgtgctg cagtgcgtga 480acgtgtcggt ggtgtctgag gaggtctgca gtaagctcta tgacccgctg taccacccca 540gcatgttctg cgccggcgga gggcaagacc agaaggactc ctgcaacggt gactctgggg 600ggcccctgat ctgcaacggg tacttgcagg gccttgtgtc tttcggaaaa gccccgtgtg 660gccaagttgg cgtgccaggt gtctacacca acctctgcaa attcactgag tggatagaga 720aaaccgtcca ggccagttaa ctctggggac tgggaaccca tgaaattgac ccccaaatac 780atcctgcgga aggaattcag gaatatctgt tcccagcccc tcctccctca ggcccaggag 840tccaggcccc cagcccctcc tccctcaaac caagggtaca gatccccagc ccctcctccc 900tcagacccag gagtccagac cccccagccc ctcctccctc agacccagga gtccagcccc 960tcctccntca gacccaggag tccagacccc ccagcccctc ctccctcaga cccaggggtt 1020gaggccccca acccctcctc cttcagagtc agaggtccaa gcccccaacc cctcgttccc 1080cagacccaga ggtnnaggtc ccagcccctc ttccntcaga cccagnggtc caatgccacc 1140tagattttcc ctgnacacag tgcccccttg tggnangttg acccaacctt accagttggt 1200ttttcatttt tngtcccttt cccctagatc cagaaataaa gtttaagaga ngngcaaaaa 1260aaaaa 1265

<210> 174

<211> 1459

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(1459)

<223> n = A,T,C or G

<400> 174ggtcagccgc acactgtttc cagaagtgag tgcagagctc ctacaccatc gggctgggcc 60tgcacagtct tgaggccgac caagagccag ggagccagat ggtggaggcc agcctctccg 120tacggcaccc agagtacaac agacccttgc tcgctaacga cctcatgctc atcaagttgg 180acgaatccgt gtccgagtct gacaccatcc ggagcatcag cattgcttcg cagtgcccta 240ccgcggggaa ctcttgcctc gtttctggct ggggtctgct ggcgaacggt gagctcacgg 300gtgtgtgtct gccctcttca aggaggtcct ctgcccagtc gcgggggctg acccagagct 360ctgcgtccca ggcagaatgc ctaccgtgct gcagtgcgtg aacgtgtcgg tggtgtctga 420ngaggtctgc antaagctct atgacccgct gtaccacccc ancatgttct gcgccggcgg 480agggcaagac cagaaggact cctgcaacgt gagagagggg aaaggggagg gcaggcgact 540cagggaaggg tggagaaggg ggagacagag acacacaggg ccgcatggcg agatgcagag 600atggagagac acacagggag acagtgacaa ctagagagag aaactgagag aaacagagaa 660ataaacacag gaataaagag aagcaaagga agagagaaac agaaacagac atggggaggc 720agaaacacac acacatagaa atgcagttga ccttccaaca gcatggggcc tgagggcggt 780gacctccacc caatagaaaa tcctcttata acttttgact ccccaaaaac ctgactagaa 840atagcctact gttgacgggg agccttacca ataacataaa tagtcgattt atgcatacgt 900tttatgcatt catgatatac ctttgttgga attttttgat atttctaagc tacacagttc 960gtctgtgaat ttttttaaat tgttgcaact ctcctaaaat ttttctgatg tgtttattga 1020aaaaatccaa gtataagtgg acttgtgcat tcaaaccagg gttgttcaag ggtcaactgt 1080gtacccagag ggaaacagtg acacagattc atagaggtga aacacgaaga gaaacaggaa 1140aaatcaagac tctacaaaga ggctgggcag ggtggctcat gcctgtaatc ccagcacttt 1200gggaggcgag gcaggcagat cacttgaggt aaggagttca agaccagcct ggccaaaatg 1260gtgaaatcct gtctgtacta aaaatacaaa agttagctgg atatggtggc aggcgcctgt 1323aatcccagct acttgggagg ctgaggcagg agaattgctt gaatatggga ggcagaggtt 1380gaagtgagtt gagatcacac cactatactc cagctggggc aacagagtaa gactctgtct 1440caaaaaaaaa aaaaaaaaa 1459

<210> 175

<211> 1167

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (1167)

<223> n = A,T,C or G

<400> 175gcgcagccct ggcaggcggc actggtcatg gaaaacgaat tgttctgctc gggcgtcctg 60gtgcatccgc agtgggtgct gtcagccgca cactgtttcc agaactccta caccatcggg 120ctgggcctgc acagtcttga ggccgaccaa gagccaggga gccagatggt ggaggccagc 180ctctccgtac ggcacccaga gtacaacaga ctcttgctcg ctaacgacct catgctcatc 240aagttggacg aatccgtgtc cgagtctgac accatccgga gcatcagcat tgcttcgcag 300tgccctaccg cggggaactc ttgcctcgtn tctggctggg gtctgctggc gaacggcaga 360atgcctaccg tgctgcactg cgtgaacgtg tcggtggtgt ctgaggangt ctgcagtaag 420ctctatgacc cgctgtacca ccccagcatg ttctgcgccg gcggagggca agaccagaag 480gactcctgca acggtgactc tggggggccc ctgatctgca acgggtactt gcagggcctt 540gtgtctttcg gaaaagcccc gtgtggccaa cttggcgtgc caggtgtcta caccaacctc 600tgcaaattca ctgagtggat agagaaaacc gtccagncca gttaactctg gggactgga 660acccatgaaa ttgaccccca aatacatcct gcggaangaa ttcaggaata tctgttccca 720gcccctcctc cctcaggccc aggagtccag gcccccagcc cctcctccct caaaccaagg 780gtacagatcc ccagcccctc ctccctcaga cccaggagtc cagacccccc agcccctcnt 840ccntcagacc caggagtcca gcccctcctc cntcagacgc aggagtccag accccccagc 900ccntcntccg tcagacccag gggtgcaggc ccccaacccc tcntccntca gagtcagagg 960tccaagcccc caacccctcg ttccccagac ccagaggtnc aggtcccagc ccctcctccc 1020tcagacccag cggtccaatg ccacctagan tntccctgta cacagtgccc ccttgtggca 1080ngttgaccca accttaccag ttggtttttc attttttgtc cctttcccct agatccagaa 1140ataaagtnta agagaagcgc aaaaaaa 1167

<210> 176

<211> 205

<212> PRT

<213> Homo sapien

<220>

<221> VARIANT

<222> (1) ... (205)

<223> Xaa = Any Amino Acid

<400> 176Met Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gln Trp1 5 10 15Val Leu Set Ala Ala His Cys Phe Gln Asn Ser Tyr Thr Ile Gly Leu

20 25 30Gly Leu His Ser Leu Glu Ala Asp Gln Glu Pro Gly Ser Gln Met Val

35 40 45Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Leu Leu Leu

50 55 60Ala Asn Asp Leu Met Leu Ile Lys Leu Asp Glu Ser Val Ser Glu Ser65 70 75 80Asp Thr Ile Arg Ser Ile Ser Ile Ala Set Gln Cys Pro Thr Ala Gly

85 90 95Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Gly Arg Met

100 105 110Pro Thr Val Leu His Cys Val Asn Val Set Val Val Ser Glu Xaa Val

115 120 125Cys Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Set Met Phe Cys Ala

130 135 140Gly Gly Gly Gln Asp Gln Lys Asp Ser Cys Asn Gly Asp Ser Gly Gly145 150 155 160Pro Leu Ile Cys Asn Gly Tyr Leu Gln Gly Leu Val Ser Phe Gly Lys

165 170 175Ala Pro Cys Gly Gln Leu Gly Val Pro Gly Val Tyr Thr Asn Leu Cys

180 185 190Lys Phe Thr Glu Trp Ile Glu Lys Thr Val Gln Xaa Ser

195 200 205

<210> 177

<211> 1119

<212> DNA

<213> Homo sapien

<400> 177gcgcactcgc agccctggca ggcggcactg gtcatggaaa acgaattgtt ctgctcgggc 60gtcctggtgc atccgcagtg ggtgctgtca gccgcacact gtttccagaa ctcctacacc 120atcgggctgg gcctgcacag tcttgaggcc gaccaagagc cagggagcca gatggtggag 180gccagcctct ccgtacggca cccagagtac aacagaccct tgctcgctaa cgacctcatg 240ctcatcaagt tggacgaatc cgtgtccgag tctgacacca tccggagcat cagcattgct 300tcgcagtgcc ctaccgcggg gaactcttgc ctcgtttctg gctggggtct gctggcgaac 360gatgctgtga ttgccatcca gtcccagact gtgggaggct gggagtgtga gaagctttcc 420caaccctggc agggttgtac catttcggca acttccagtg caaggacgtc ctgctgcatc 480ctcactgggt gctcactact gctcactgca tcacccggaa cactgtgatc aactagccag 540caccatagtt ctccgaagtc agactatcat gattactgtg ttgactgtgc tgtctattgt 600actaaccatg ccgatgttta ggtgaaatta gcgtcacttg gcctcaacca tcttggtatc 660cagttatcct cactgaattg agatttcctg cttcagtgtc agccattccc acataatttc 720tgacctacag aggtgaggga tcatatagct cttcaaggat gctggtactc ccctcacaaa 780ttcatttctc ctgttgtagt gaaaggtgcg ccctctggag cctcccaggg tgggtgtgca 840ggtcacaatg atgaatgtat gatcgtgttc ccattaccca aagcctttaa atccctcatg 900ctcagtacac cagggcaggt ctagcatttc ttcatttagt gtatgctgtc cattcatgca 960accacctcag gactcctgga ttctctgcct agttgagctc ctgcatgctg cctccttggg 1020gaggtgaggg agagggccca tggttcaatg ggatctgtgc agttgtaaca cattaggtgc 1080ttaataaaca gaagctgtga tgttaaaaaa aaaaaaaaa 1119

<210> 178

<211> 164

<212> PRT

<213> Homo sapien

<220>

<221> VARIANT

<222> (1)...(164)

<223> Xaa = Any Amino Acid

<400> 178Met Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gln Trp1 5 10 15val Leu Ser Ala Ala His Cys Phe Gln Asn Ser Tyr Thr Ile Gly Leu

20 25 30Gly Leu His Ser Leu Glu Ala Asp Gln Glu Pro Gly Ser Gln Met Val

35 40 45Glu Ala Ser Leu Ser Val Arg His Pro Glu Tyr Asn Arg Pro Leu Leu

50 55 60Ala Asn Asp Leu Met Leu Ile Lys Leu Asp Glu Ser Val Ser Glu Ser65 70 75 80Asp Thr Ile Arg Ser Ile Ser Ile Ala Ser Gln Cys Pro Thr Ala Gly

85 90 95Asn Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Asp Ala Val

100 105 110Ile Ala Ile Gln Ser Xaa Thr Val Gly Gly Trp Glu Cys Glu Lys Leu

115 120 125Ser Gln Pro Trp Gln Gly Cys Thr Ile Ser Ala Thr Ser Ser Ala Arg

130 135 140Thr Ser Cys Cys Ile Leu Thr Gly Cys Ser Leu Leu Leu Thr Ala Ser145 150 155 160Pro Gly Thr Leu

<210> 179

<211> 250

<212> DNA

<213> Homo sapien

<400> 179ctggagtgcc ttggtgtttc aagcccctgc aggaagcaga atgcaccttc tgaggcacct 60ccagctgccc ccggccgggg gatgcgaggc tcggagcacc cttgcccggc tgtgattgct 120gccaggcact gttcatctca gcttttctgt ccctttgctc ccggcaagcg cttctgctga 180aagttcatat ctggagcctg atgtcttaac gaataaaggt cccatgctcc acccgaaaaa 240aaaaaaaaaa 250

<210> 180

<211> 202

<212> DNA

<213> Homo sapien

<400> 180actagtccag tgtggtggaa ttccattgtg ttgggcccaa cacaatggct acctttaaca 60tcacccagac cccgcccctg cccgtgcccc acgctgctgc taacgacagt atgatgctta 120ctctgctact cggaaactat ttttatgtaa ttaatgtatg ctttcttgtt tataaatgcc 180tgatttaaaa aaaaaaaaaa aa 202

<210> 181

<211> 558

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(558)

<223> n = A,T,C or G

<400> 181tccytttgkt naggtttkkg agacamccck agacctwaan ctgtgtcaca gacttcyngg 60aatgtttagg cagtgctagt aatttcytcg taatgattct gttattactt tcctnattct 120ttattcctct ttcttctgaa gattaatgaa gttgaaaatt gaggtggata aatacaaaaa 180ggtagtgtga tagtataagt atctaagtgc agatgaaagt gtgttatata tatccattca 240aaattatgca agttagtaat tactcagggt taactaaatt actttaatat gctgttgaac 300ctactctgtt ccttggctag aaaaaattat aaacaggact ttgttagttt gggaagccaa 360attgataata ttctatgttc taaaagttgg gctatacata aattattaag aaatatggaw 420ttttattccc aggaatatgg kgttcatttt atgaatatta cscrggatag awgtwtgagt 480aaaaycagtt ttggtwaata ygtwaatatg tcmtaaataa acaakgcttt gacttatttc 540caaaaaaaaa aaaaaaaa 558

<210> 182

<211> 479

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(479)

<223> n = A,T,C or G

<400> 182acagggwttk grggatgcta agsccccrga rwtygtttga tccaaccctg gcttwttttc 60agaggggaaa atggggccta gaagttacag mscatytagy tggtgcgmtg gcacccctgg 120cstcacacag astcccgagt agctgggact acaggcacac agtcactgaa gcaggccctg 180ttwgcaattc acgttgccac ctccaactta aacattcttc atatgtgatg tccttagtca 240ctaaggttaa actttcccac ccagaaaagg caacttagat aaaatcttag agtactttca 300tactmttcta agtcctcttc cagcctcact kkgagtcctm cytgggggtt gataggaant 360ntctcttggc tttctcaata aartctctat ycatctcatg tttaatttgg tacgcatara 420awtgstgara aaattaaaat gttctggtty mactttaaaa araaaaaaaa aaaaaaaaa 479

<210> 183

<211> 384

<212> DNA

<213> Homo sapien

<400> 183aggcgggagc agaagctaaa gccaaagccc aagaagagtg gcagtgccag cactggtgcc 60agtaccagta ccaataacag tgccagtgcc agtgccagca ccagtggtgg cttcagtgct 120ggtgccagcc tgaccgccac tctcacattt gggctcttcg ctggccttgg tggagctggt 180gccagcacca gtggcagctc tggtgcctgt ggtttctcct acaagtgaga ttttagatat 240tgttaatcct gccagtcttt ctcttcaagc cagggtgcat cctcagaaac ctactcaaca 300cagcactcta ggcagccact atcaatcaat tgaagttgac actctgcatt aratctattt 360gccatttcaa aaaaaaaaaa aaaa 384

<210> 184

<211> 496

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(496)

<223> n = A,T,C or G

<400> 184accgaattgg gaccgctggc ttataagcga tcatgtyynt ccrgtatkac ctcaacgagc 60agggagatcg agtctatacg ctgaagaaat ttgacccgat gggacaacag acctgctcag 120cccatcctgc tcggttctcc ccagatgaca aatactctsg acaccgaatc accatcaaga 180aacgcttcaa ggtgctcatg acccagcaac cgcgccctgt cctctgaggg tcccttaaac 240tgatgtcttt tctgccacct gttacccctc ggagactccg taaccaaact cttcggactg 300tgagccctga tgcctttttg ccagccatac tctttggcat ccagtctctc gtggcgattg 360attatgcttg tgtgaggcaa tcatggtggc atcacccata aagggaacac atttgacttt 420tttttctcat attttaaatt actacmagaw tattwmagaw waaatgawtt gaaaaactst 480taaaaaaaaa aaaaaa 496

<210> 185

<211> 384

<212> DNA

<213> Homo sapien

<400> 185gctggtagcc tatggcgkgg cccacggagg ggctcctgag gccacggrac agtgacttcc 60caagtatcyt gcgcsgcgtc ttctaccgtc cctacctgca gatcttcggg cagattcccc 120aggaggacat ggacgtggcc ctcatggagc acagcaactg ytcgtcggag cccggcttct 180gggcacaccc tcctggggcc caggcgggca cctgcgtctc ccagtatgcc aactggctgg 240tggtgctgct cctcgtcatc ttcctgctcg tggccaacat cctgctggtc aacttgctca 300ttgccatgtt cagttacaca ttcggcaaag tacagggcaa cagcgatctc tactgggaag 360gcgcagcgtt accgcctcat ccgg 384

<210> 186

<211> 577

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(577)

<223> n = A,T,C or G

<400> 186gagttagctc ctccacaacc ttgatgaggt cgtctgcagt ggcctctcgc ttcataccgc 60tnccatcgtc atactgtagg tttgccacca cytcctggca tcttggggcg gcntaatatt 120ccaggaaact ctcaatcaag tcaccgtcga tgaaacctgt gggctggttc tgtcttccgc 180tcggtgtgaa aggatctccc agaaggagtg ctcgatcttc cccacacttt tgatgacttt 240attgagtcga ttctgcatgt ccagcaggag gttgtaccag ctctctgaca gtgaggtcac 300cagccctatc atgccgttga mcgtgccgaa garcaccgag ccttgtgtgg gggkkgaagt 360ctcacccaga ttctgcatta ccagagagcc gtggcaaaag acattgacaa actcgcccag 420gtggaaaaag amcamctcct ggargtgctn gccgctcctc gtcmgttggt ggcagcgctw 480tccttttgac acacaaacaa gttaaaggca ttttcagccc ccagaaantt gtcatcatcc 540aagatntcgc acagcactna tccagttggg attaaat 577

<210> 187

<211> 534

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(534)

<223> n = A,T,C or G

<400> 187aacatcttcc tgtataatgc tgtgtaatat cgatccgatn ttgtctgstg agaatycatw 60actkggaaaa gmaacattaa agcctggaca ctggtattaa aattcacaat atgcaacact 120ttaaacagtg tgtcaatctg ctcccyynac tttgtcatca ccagtctggg aakaagggta 180tgccctattc acacctgtta aaagggcgct aagcattttt gattcaacat cttttttttt 240gacacaagtc cgaaaaaagc aaaagtaaac agttatyaat ttgttagcca attcactttc 300ttcatgggac agagccatyt gatttaaaaa gcaaattgca taatattgag cttygggagc 360tgatatttga gcggaagagt agcctttcta cttcaccaga cacaactccc tttcatattg 420ggatgttnac naaagtwatg tctctwacag atgggatgct tttgtggcaa ttctgttctg 480aggatctccc agtttattta ccacttgcac aagaaggcgt tttcttcctc aggc 534

<210> 188

<211> 761

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(761)

<223> n = A,T,C or G

<400> 188agaaaccagt atctctnaaa acaacctctc ataccttgtg gacctaattt tgtgtgcgtg 60tgtgtgtgcg cgcatattat atagacaggc acatcttttt tacttttgta aaagcttatg 120cctctttggt atctatatct gtgaaagttt taatgatctg ccataatgtc ttggggacct 180ttgtcttctg tgtaaatggt actagagaaa acacctatnt tatgagtcaa tctagttngt 240tttattcgac atgaaggaaa tttccagatn acaacactna caaactctcc ctkgackarg 300ggggacaaag aaaagcaaaa ctgamcataa raaacaatwa cctggtgaga arttgcataa 360acagaaatwr ggtagtatat tgaarnacag catcattaaa rmgttwtktt wttctccctt 420gcaaaaaaca tgtacngact tcccgttgag taatgccaag ttgttttttt tatnataaaa 480cttgcccttc attacatgtt tnaaagtggt gtggtgggcc aaaatattga aatgatggaa 540ctgactgata aagctgtaca aataagcagt gtgcctaaca agcaacacag taatgttgac 600atgcttaatt cacaaatgct aatttcatta taaatgtttg ctaaaataca ctttgaacta 660tttttctgtn ttcccagagc tgagatntta gattttatgt agtatnaagt gaaaaantac 720gaaaataata acattgaaga aaaananaaa aaanaaaaaa a 761

<210> 189

<211> 482

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(482)

<223> n = A,T,C or G

<400> 189tttttttttt tttgccgatn ctactatttt attgcaggan gtgggggtgt atgcaccgca 60caccggggct atnagaagca agaaggaagg agggagggca cagcccctcg ctgagcaaca 120aagccgcctg ctgccttctc tgtctgtctc ctggtgcagg cacatgggga gaccttcccc 180aaggcagggg ccaccagtcc aggggtggga atacaggggg tgggangtgt gcataagaag 240tgataggcac aggccacccg gtacagaccc ctcggctcct gacaggtnga tttcgaccag 300gtcattgtgc cctgcccagg cacagcgtan atctggaaaa gacagaatgc tttccttttc 360aaatttggct ngtcatngaa ngggcanttt tccaanttng gctnggtctt ggtacncttg 420gttcggccca gctccncgtc caaaaantat tcacccnnct ccnaattgct tgcnggnccc 480cc 482

<210> 190

<211> 471

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (471)

<223> n = A,T,C or G

<400> 190tttttttttt ttttaaaaca gtttttcaca acaaaattta ttagaagaat agtggttttg 60aaaactctcg catccagtga gaactaccat acaccacatt acagctngga atgtnctcca 120aatgtctggt caaatgatac aatggaacca ttcaatctta cacatgcacg aaagaacaag 180cgcttttgac atacaatgca caaaaaaaaa aggggggggg gaccacatgg attaaaattt 240taagtactca tcacatacat taagacacag ttctagtcca gtcnaaaatc agaactgcnt 300tgaaaaattt catgtatgca atccaaccaa agaacttnat tggtgatcat gantnctcta 360ctacatcnac cttgatcatt gccaggaacn aaaagttnaa ancacncngt acaaaaanaa 420tctgtaattn anttcaacct ccgtacngaa aaatnttnnt tatacactcc c 471

<210> 191

<211> 402

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(402)

<223> n = A,T,C or G

<400> 191gagggattga aggtctgttc tastgtcggm ctgttcagcc accaactcta acaagttgct 60gtcttccact cactgtctgt aagcttttta acccagacwg tatcttcata aatagaacaa 120attcttcacc agtcacatct tctaggacct ttttggattc agttagtata agctcttcca 180cttcctttgt taagacttca tctggtaaag tcttaagttt tgtagaaagg aattyaattg 240ctcgttctct aacaatgtcc tctccttgaa gtatttggct gaacaaccca cctaaagtcc 300ctttgtgcat ccattttaaa tatacttaat agggcattgk tncactaggt taaattctgc 360aagagtcatc tgtctgcaaa agttgcgtta gtatatctgc ca 402

<210> 192

<211> 601

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(601)

<223> n = A,T,C or G

<400> 192gagctcggat ccaataatct ttgtctgagg gcagcacaca tatncagtgc catggnaact 60ggtctacccc acatgggagc agcatgccgt agntatataa ggtcattccc tgagtcagac 120atgcytyttt gaytaccgtg tgccaagtgc tggtgattct yaacacacyt ccatcccgyt 180cttttgtgga aaaactggca cttktctgga actagcarga catcacttac aaattcaccc 240acgagacact tgaaaggtgt aacaaagcga ytcttgcatt gctttttgtc cctccggcac 300cagttgtcaa tactaacccg ctggtttgcc tccatcacat ttgtgatctg tagctctgga 360tacatctcct gacagtactg aagaacttct tcttttgttt caaaagcarc tcttggtgcc 420tgttggatca ggttcccatt tcccagtcyg aatgttcaca tggcatattt wacttcccac 480aaaacattgc gatttgaggc tcagcaacag caaatcctgt tccggcattg gctgcaagag 540cctcgatgta gccggccagc gccaaggcag gcgccgtgag ccccaccagc agcagaagca 600g 601

<210> 193

<211> 608

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (608)

<223> n = A,T,C or G

<400> 193atacagccca natcccacca cgaagatgcg cttgttgact gagaacctga tgcggtcact 60ggtcccgctg tagccccagc gactctccac ctgctggaag cggttgatgc tgcactcytt 120cccaacgcag gcagmagcgg gsccggtcaa tgaactccay tcgtggcttg gggtkgacgg 180tkaagtgcag gaagaggctg accacctcgc ggtccaccag gatgcccgac tgtgcgggac 240ctgcagcgaa actcctcgat ggtcatgagc gggaagcgaa tgaggcccag ggccttgccc 300agaaccttcc gcctgttctc tggcgtcacc tgcagctgct gccgctgaca ctcggcctcg 360gaccagcgga caaacggcrt tgaacagccg cacctcacgg atgcccagtg tgtcgcgctc 420caggammgsc accagcgtgt ccaggtcaat gtcggtgaag ccctccgcgg gtratggcgt 480ctgcagtgtt tttgtcgatg ttctccaggc acaggctggc cagctgcggt tcatcgaaga 540gtcgcgcctg cgtgagcagc atgaaggcgt tgtcggctcg cagttcttct tcaggaactc 600cacgcaat 608

<210> 194

<211> 392

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(392)

<223> n = A,T,C or G

<400> 194gaacggctgg accttgcctc gcattgtgct tgctggcagg gaataccttg gcaagcagyt 60ccagtccgag cagccccaga ccgctgccgc ccgaagctaa gcctgcctct ggccttcccc 120tccgcctcaa tgcagaacca gtagtgggag cactgtgttt agagttaaga gtgaacactg 180tttgatttta cttgggaatt tcctctgtta tatagctttt cccaatgcta atttccaaac 240aacaacaaca aaataacatg tttgcctgtt aagttgtata aaagtaggtg attctgtatt 300taaagaaaat attactgtta catatactgc ttgcaatttc tgtatttatt gktnctstgg 360aaataaatat agttattaaa ggttgtcant cc 392

<210> 195

<211> 502

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(502)

<223> n = A,T,C or G

<400> 195ccsttkgagg ggtkaggkyc cagttyccga gtggaagaaa caggccagga gaagtgcgtg 60ccgagctgag gcagatgttc ccacagtgac ccccagagcc stgggstata gtytctgacc 120cctcncaagg aaagaccacs ttctggggac atgggctgga gggcaggacc tagaggcacc 180aagggaaggc cccattccgg ggstgttccc cgaggaggaa gggaaggggc tctgtgtgcc 240ccccasgagg aagaggccct gagtcctggg atcagacacc ccttcacgtg tatccccaca 300caaatgcaag ctcaccaagg tcccctctca gtccccttcc stacaccctg amcggccact 360gscscacacc cacccagagc acgccacccg ccatggggar tgtgctcaag gartcgcngg 420gcarcgtgga catctngtcc cagaaggggg cagaatctcc aatagangga ctgarcmstt 480gctnanaaaa aaaaanaaaa aa 502

<210> 196

<211> 665

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(665)

<223> n = A,T,C or G

<400> 196ggttacttgg tttcattgcc accacttagt ggatgtcatt tagaaccatt ttgtctgctc 60cctctggaag ccttcgcag agcggacttt gtaattgttg gagaataact gctgaatttt 120wagctgtttk gagttgatts gcaccactgc acccacaact tcaatatgaa aacyawttga 180actwatttat tatcttgtga aaagtataac aatgaaaatt ttgttcatac tgtattkatc 240aagtatgatg aaaagcaawa gatatatatt cttttattat gttaaattat gattgccatt 300attaatcggc aaaatgtgga gtgtatgttc ttttcacagt aatatatgcc ttttgtaact 360tcacttggtt attttattgt aaatgartta caaaattctt aatttaagar aatggtatgt 420watatttatt tcattaattt ctttcctkgt ttacgtwaat tttgaaaaga wtgcatgatt 480tcttgacaga aatcgatctt gatgctgtgg aagtagtttg acccacatcc ctatgagttt 540ttcttagaat gtataaaggt tgtagcccat cnaacttcaa agaaaaaaat gaccacatac 600tttgcaatca ggctgaaatg tggcatgctn ttctaattcc aactttataa actagcaaan 660aagtg 665

<210> 197

<211> 492

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(492)

<223> n = A,T,C or G

<400> 197ttttnttttt ttttttttgc aggaaggatt ccatttattg tggatgcatt ttcacaatat 60atgtttattg gagcgatcca ttatcagtga aaagtatcaa gtgtttataa natttttagg 120aaggcagatt cacagaacat gctngtcngc ttgcagtttt acctcgtana gatnacagag 180aattatagtc naaccagtaa acnaggaatt tacttttcaa aagattaaat ccaaactgaa 240caaaattcta ccctgaaact tactccatcc aaatattgga ataanagtca gcagtgatac 300attctcttct gaactttaga ttttctagaa aaatatgtaa tagtgatcag gaagagctct 360tgttcaaaag tacaacnaag caatgttccc ttaccatagg ccttaattca aactttgatc 420catttcactc ccatcacggg agtcaatgct acctgggaca cttgtatttt gttcatnctg 480ancntggctt aa 492

<210> 198

<211> 478

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(478)

<223> n = A,T,C or G

<400> 198tttnttttgn atttcantct gtannaanta ttttcattat gtttattana aaaatatnaa 60tgtntccacn acaaatcatn ttacntnagt aagaggccan ctacattgta caacatacac 120tgagtatatt ttgaaaagga caagtttaaa gtanacncat attgccganc atancacatt 180tatacatggc ttgattgata tttagcacag canaaactga gtgagttacc agaaanaaat 240natatatgtc aatcngattt aagatacaaa acagatccta tggtacatan catcntgtag 300gagttgtggc tttatgttta ctgaaagtca atgcagttcc tgtacaaaga gatggccgta 360agcattctag tacctctact ccatggttaa gaatcgtaca cttatgttta catatgtnca 420gggtaagaat tgtgttaagt naanttatgg agaggtccan gagaaaaatt tgatncaa 478

<210> 199

<211> 482

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (482)

<223> n = A,T,C or G

<400> 199agtgacttgt cctccaacaa aaccccttga tcaagtttgt ggcactgaca atcagaccta 60tgctagttcc tgtcatctat tcgctactaa atgcagactg gaggggacca aaaaggggca 120tcaactccag ctggattatt ttggagcctg caaatctatt cctacttgta cggactttga 180agtgattcag tttcctctac ggatgagaga ctggctcaag aatatcctca tgcagcttta 240tgaagccnac tctgaacacg ctggttatct nagatgagaa ncagagaaat aaagtcnaga 300aaatttacct ggangaaaag aggctttngg ctggggacca tcccattgaa ccttctctta 360anggacttta agaanaaact accacatgtn tgtngtatcc tggtgccngg ccgtttantg 420aacntngacn ncacccttnt ggaatanant cttgacngcn tcctgaactt gctcctctgc 480ga 482

<210> 200

<211> 270

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(270)

<223> n = A,T,C or G

<400> 200cggccgcaag tgcaactcca gctggggccg tgcggacgaa gattctgcca gcagttggtc 60cgactgcgac gacggcggcg gcgacagtcg caggtgcagc gcgggcgcct ggggtcttgc 120aaggctgagc tgacgccgca gaggtcgtgt cacgtcccac gaccttgacg ccgtcgggga 180cagccggaac agagcccggt gaangcggga ggcctcgggg agcccctcgg gaagggcggc 240ccgagagata cgcaggtgca ggtggccgcc 270

<210> 201

<211> 419

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(419)

<223> n = A,T,C or G

<400> 201tttttttttt ttttggaatc tactgcgagc acagcaggtc agcaacaagt ttattttgca 60gctagcaagg taacagggta gggcatggtt acatgttcag gtcaacttcc tttgtcgtgg 120ttgattggtt tgtctttatg ggggcggggt ggggtagggg aaancgaagc anaantaaca 180tggagtgggt gcaccctccc tgtagaacct ggttacnaaa gcttggggca gttcacctgg 240tctgtgaccg tcattttctt gacatcaatg ttattagaag tcaggatatc ttttagagag 300tccactgtnt ctggagggag attagggttt cttgccaana tccaancaaa atccacntga 360aaaagttgga tgatncangt acngaatacc ganggcatan ttctcatant cggtggcca 419

<210> 202

<211> 509

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(509)

<223> n = A,T,C or G

<400> 202tttntttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt 60tggcacttaa tccattttta tttcaaaatg tctacaaant ttnaatncnc cattatacng 120gtnattttnc aaaatctaaa nnttattcaa atntnagcca aantccttac ncaaatnnaa 180tacncncaaa aatcaaaaat atacntntct ttcagcaaac ttngttacat aaattaaaaa 240aatatatacg gctggtgttt tcaaagtaca attatcttaa cactgcaaac atntttnnaa 300ggaactaaaa taaaaaaaaa cactnccgca aaggttaaag ggaacaacaa attcntttta 360caacancnnc nattataaaa atcatatctc aaatcttagg ggaatatata cttcacacng 420ggatcttaac ttttactnca ctttgtttat ttttttanaa ccattgtntt gggcccaaca 480caatggnaat nccnccncnc tggactagt 509

<210> 203

<211> 583

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(583)

<223> n = A,T,C or G

<400> 203tttttttttt ttttttttga cccccctctt ataaaaaaca agttaccatt ttattttact 60tacacatatt tattttataa ttggtattag atattcaaaa ggcagctttt aaaatcaaac 120taaatggaaa ctgccttaga tacataattc ttaggaatta gcttaaaatc tgcctaaagt 180gaaaatcttc tctagctctt ttgactgtaa atttttgact cttgtaaaac atccaaattc 240atttttcttg tctttaaaat tatctaatct ttccattttt tccctattcc aagtcaattt 300gcttctctag cctcatttcc tagctcttat ctactattag taagtggctt ttttcctaaa 360agggaaaaca ggaagagana atggcacaca aaacaaacat tttatattca tatttctacc 420tacgttaata aaatagcatt ttgtgaagcc agctcaaaag aaggcttaga tccttttatg 480tccattttag tcactaaacg atatcnaaag tgccagaatg caaaaggttt gtgaacattt 540attcaaaagc taatataaga tatttcacat actcatcttt ctg 583

<210> 204

<211> 589

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(589)

<223> n = A,T,C or G

<400> 204ttttttttnt tttttttttt ttttttnctc ttcttttttt ttganaatga ggatcgagtt 60tttcactctc tagatagggc atgaagaaaa ctcatctttc cagctttaaa ataacaatca 120aatctcttat gctatatcat attttaagtt aaactaatga gtcactggct tatcttctcc 180tgaaggaaat ctgttcattc ttctcattca tatagttata tcaagtacta ccttgcatat 240tgagaggttt ttcttctcta tttacacata tatttccatg tgaatttgta tcaaaccttt 300attttcatgc aaactagaaa ataatgtntt cttttgcata agagaagaga acaatatnag 360cattacaaaa ctgctcaaat tgtttgttaa gnttatccat tataattagt tnggcaggag 420ctaatacaaa tcacatttac ngacnagcaa taataaaact gaagtaccag ttaaatatcc 480aaaataatta aaggaacatt tttagcctgg gtataattag ctaattcact ttacaagcat 540ttattnagaa tgaattcaca tgttattatt ccntagccca acacaatgg 589

<210> 205

<211> 545

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(545)

<223> n = A,T,C or G

<400> 205tttttntttt ttttttcagt aataatcaga acaatattta tttttatatt taaaattcat 60agaaaagtgc cttacattta ataaaagttt gtttctcaaa gtgatcagag gaattagata 120tngtcttgaa caccaatatt aatttgagga aaatacacca aaatacatta agtaaattat 180ttaagatcat agagcttgta agtgaaaaga taaaatttga cctcagaaac tctgagcatt 240aaaaatccac tattagcaaa taaattacta tggacttctt gctttaattt tgtgatgaat 300atggggtgtc actggtaaac caacacattc tgaaggatac attacttagt gatagattct 360tatgtacttt gctanatnac gtggatatga gttgacaagt ttctctttct tcaatctttt 420aaggggcnga ngaaatgagg aagaaaagaa aaggattacg catactgttc tttctatngg 480aaggattaga tatgtttcct ttgccaatat taaaaaaata ataatgttta ctactagtga 540aaccc 545

<210> 206

<211> 487

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(487)

<223> n = A,T,C or G

<400> 206tttttttttt ttttttagtc aagtttctna tttttattat aattaaagtc ttggtcattt 60catttattag ctctgcaact tacatattta aattaaagaa acgttnttag acaactgtna 120caatttataa atgtaaggtg ccattattga gtanatatat tcctccaaga gtggatgtgt 180cccttctccc accaactaat gaancagcaa cattagttta attttattag tagatnatac 240actgctgcaa acgctaattc tcttctccat ccccatgtng atattgtgta tatgtgtgag 300ttggtnagaa tgcatcanca atctnacaat caacagcaag atgaagctag gcntgggctt 360tcggtgaaaa tagactgtgt ctgtctgaat caaatgatct gacctatcct cggtggcaag 420aactcttcga accgcttcct caaaggcngc tgccacattt gtggcntctn ttgcacttgt 480ttcaaaa 487

<210> 207

<211> 332

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(332)

<223> n = A,T,C or G

<400> 207tgaattggct aaaagactgc atttttanaa ctagcaactc ttatttcttt cctttaaaaa 60tacatagcat taaatcccaa atcctattta aagacctgac agcttgagaa ggtcactact 120gcatttatag gaccttctgg tggttctgct gttacntttg aantctgaca atccttgana 180atctttgcat gcagaggagg taaaaggtat tggattttca cagaggaana acacagcgca 240gaaatgaagg ggccaggctt actgagcttg tccactggag ggctcatggg tgggacatgg 300aaaagaaggc agcctaggcc ctggggagcc ca 332

<210> 208

<211> 524

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(524)

<223> n = A,T,C or G

<400> 208agggcgtggt gcggagggcg ttactgtttt gtctcagtaa caataaatac aaaaagactg 60gttgtgttcc ggccccatcc aaccacgaag ttgatttctc ttgtgtgcag agtgactgat 120tttaaaggac atggagcttg tcacaatgtc acaatgtcac agtgtgaagg gcacactcac 180tcccgcgtga ttcacattta gcaaccaaca atagctcatg agtccatact tgtaaatact 240tttggcagaa tacttnttga aacttgcaga tgataactaa gatccaagat atttcccaaa 300gtaaatagaa gtgggtcata atattaatta cctgttcaca tcagcttcca tttacaagtc 360atgagcccag acactgacat caaactaagc ccacttagac tcctcaccac cagtctgtcc 420tgtcatcaga caggaggctg tcaccttgac caaattctca ccagtcaatc atctatccaa 480aaaccattac ctgatccact tccggtaatg caccaccttg gtga 524

<210> 209

<211> 159

<212> DNA

<213> Homo sapien

<400> 209gggtgaggaa atccagagtt gccatggaga aaattccagt gtcagcattc ttgctccttg 60tggccctctc ctacactctg gccagagata ccacagtcaa acctggagcc aaaaaggaca 120caaaggactc tcgacccaaa ctgccccaga ccctctcca 159

<210> 210

<211> 256

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(256)

<223> n = A,T,C or G

<400> 210actccctggc agacaaaggc agaggagaga gctctgttag ttctgtgttg ttgaactgcc 60actgaatttc tttccacttg gactattaca tgccanttga gggactaatg gaaaaacgta 120tggggagatt ttanccaatt tangtntgta aatggggaga ctggggcagg cgggagagat 180ttgcagggtg naaatgggan ggctggtttg ttanatgaac agggacatag gaggtaggca 240ccaggatgct aaatca 256

<210> 211

<211> 264

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)... (264)

<223> n = A,T,C or G

<400> 211acattgtttt tttgagataa agcattgaga gagctctcct taacgtgaca caatggaagg 60actggaacac atacccacat ctttgttctg agggataatt ttctgataaa gtcttgctgt 120atattcaagc acatatgtta tatattattc agttccatgt ttatagccta gttaaggaga 180ggggagatac attcngaaag aggactgaaa gaaatactca agtnggaaaa cagaaaaaga 240aaaaaaggag caaatgagaa gcct 264

<210> 212

<211> 328

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(328)

<223> n = A,T,C or G

<400> 212acccaaaaat ccaatgctga atatttggct tcattattcc canattcttt gattgtcaaa 60ggatttaatg ttgtctcagc ttgggcactt cagttaggac ctaaggatgc cagccggcag 120gtttatatat gcagcaacaa tattcaagcg cgacaacagg ttattgaact tgcccgccag 180ttnaatttca ttcccattga cttgggatcc ttatcatcag ccagagagat tgaaaattta 240cccctacnac tctttactct ctgganaggg ccagtggtgg tagctataag cttggccaca 300tttttttttc ctttattcct ttgtcaga 328

<210> 213

<211> 250

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(250)

<223> n = A,T,C or G

<400> 213acttatgagc agagcgacat atccnagtgt agactgaata aaactgaatt ctctccagtt 60taaagcattg ctcactgaag ggatagaagt gactgccagg agggaaagta agccaaggct 120cattatgcca aagganatat acatttcaat tctccaaact tcttcctcat tccaagagtt 180ttcaatattt gcatgaacct gctgataanc catgttaana aacaaatatc tctctnacct 240tctcatcggt 250

<210> 214

<211> 444

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(444)

<223> n = A,T,C or G

<400> 214acccagaatc caatgctgaa tatttggctt cattattccc agattctttg attgtcaaag 60gatttaatgt tgtctcagct tgggcacttc agttaggacc taaggatgcc agccggcagg 120tttatatatg cagcaacaat attcaagcgc gacaacaggt tattgaactt gcccgccagt 180tgaatttcat tcccattgac ttgggatcct tatcatcagc canagagatt gaaaatttac 240ccctacgact ctttactctc tggagagggc cagtggtggt agctataagc ttggccacat 300ttttttttcc tttattcctt tgtcagagat gcgattcatc catatgctan aaaccaacag 360agtgactttt acaaaattcc tataganatt gtgaataaaa ccttacctat agttgccatt 420actttgctct ccctaatata cctc 444

<210> 215

<211> 366

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(366)

<223> n = A,T,C or G

<400> 215acttatgagc agagcgacat atccaagtgt anactgaata aaactgaatt ctctccagtt 60taaagcattg ctcactgaag ggatagaagt gactgccagg agggaaagta agccaaggct 120cattatgcca aagganatat acatttcaat tctccaaact tcttcctcat tccaagagtt 180ttcaatattt gcatgaacct gctgataagc catgttgaga aacaaatatc tctctgacct 240tctcatcggt aagcagaggc tgtaggcaac atggaccata gcgaanaaaa aacttagtaa 300tccaagctgt tttctacact gtaaccaggt ttccaaccaa ggtggaaatc tcctatactt 360ggtgcc 366

<210> 216

<211> 260

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(260)

<223> n = A,T,C or G

<400> 216ctgtataaac agaactccac tgcangaggg agggccgggc caggagaatc tccgcttgtc 60caagacaggg gcctaaggag ggtctccaca ctgctnntaa gggctnttnc atttttttat 120taataaaaag tnnaaaaggc ctcttctcaa cttttttccc ttnggctgga aaatttaaaa 180atcaaaaatt tcctnaagtt ntcaagctat catatatact ntatcctgaa aaagcaacat 240aattcttcct tccctccttt 260

<210> 217

<211> 262

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(262)

<223> n = A,T,C or G

<400> 217acctacgtgg gtaagtttan aaatgttata atttcaggaa naggaacgca tataattgta 60tcttgcctat aattttctat tttaataagg aaatagcaaa ttggggtggg gggaatgtag 120ggcattctac agtttgagca aaatgcaatt aaatgtggaa ggacagcact gaaaaatttt 180atgaataatc tgtatgatta tatgtctcta gagtagattt ataattagcc acttacccta 240atatccttca tgcttgtaaa gt 262

<210> 218

<211> 205

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(205)

<223> n = A,T,C or G

<400> 218accaaggtgg tgcattaccg gaantggatc aangacacca tcgtggccaa cccctgagca 60cccctatcaa ctcccttttg tagtaaactt ggaaccttgg aaatgaccag gccaagactc 120aggcctcccc agttctactg acctttgtcc ttangtntna ngtccagggt tgctaggaaa 180anaaatcagc agacacaggt gtaaa 205

<210> 219

<211> 114

<212> DNA

<213> Homo sapien

<400> 219tactgttttg tctcagtaac aataaataca aaaagactgg ttgtgttccg gccccatcca 60accacgaagt tgatttctct tgtgtgcaga gtgactgatt ttaaaggaca tgga 114

<210> 220

<211> 93

<212> DNA

<213> Homo sapien

<400> 220actagccagc acaaaaggca gggtagcctg aattgctttc tgctctttac atttctttta 60aaataagcat ttagtgctca gtccctactg agt 93

<210> 221

<211> 167

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(167)

<223> n = A,T,C or G

<400> 221actangtgca ggtgcgcaca aatatttgtc gatattccct tcatcttgga ttccatgagg 60tcttttgccc agcctgtggc tctactgtag taagtttctg ctgatgagga gccagnatgc 120cccccactac cttccctgac gctccccana aatcacccaa cctctgt 167

<210> 222

<211> 351

<212> DNA

<213> Homo sapien

<400> 222agggcgtggt gcggagggcg gtactgacct cattagtagg aggatgcatt ctggcacccc 60gttcttcacc tgtcccccaa tccttaaaag gccatactgc ataaagtcaa caacagataa 120atgtttgctg aattaaagga tggatgaaaa aaattaataa tgaatttttg cataatccaa 180ttttctcttt tatatttcta gaagaagttt ctttgagcct attagatccc gggaatcttt 240taggtgagca tgattagaga gcttgtaggt tgcttttaca tatatctggc atatttgagt 300ctcgtatcaa aacaatagat tggtaaaggt ggtattattg tattgataag t 351

<210> 223

<211> 383

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(383)

<223> n = A,T,C or G

<400> 223aaaacaaaca aacaaaaaaa acaattcttc attcagaaaa attatcttag ggactgatat 60tggtaattat ggtcaattta atwrtrttkt ggggcatttc cttacattgt cttgacaaga 120ttaaaatgtc tgtgccaaaa ttttgtattt tatttggaga cttcttatca aaagtaatgc 180tgccaaagga agtctaagga attagtagtg ttcccmtcac ttgtttggag tgtgctattc 240taaaagattt tgatttcctg gaatgacaat tatattttaa ctttggtggg ggaaanagtt 300ataggaccac agtcttcact tctgatactt gtaaattaat cttttattgc acttgttttg 360accattaagc tatatgttta aaa 383

<210> 224

<211> 320

<212> DNA

<213> Homo sapien

<400> 224cccctgaagg cttcttgtta gaaaatagta cagttacaac caataggaac aacaaaaaga 60aaaagtttgt gacattgtag tagggagtgt gtacccctta ctccccatca aaaaaaaaat 120ggatacatgg ttaaaggata raagggcaat attttatcat atgttctaaa agagaaggaa 180gagaaaatac tactttctcr aaatggaagc ccttaaaggt gctttgatac tgaaggacac 240aaatgtggcc gtccatcctc ctttaragtt gcatgacttg gacacggtaa ctgttgcagt 300tttaractcm gcattgtgac 320

<210> 225

<211> 1214

<212> DNA

<213> Homo sapien

<400> 225gaggactgca gcccgcactc gcagccctggcaggcggcac tggtcatgga aaacgaattg 60ttctgctcgg gcgtcctggt gcatccgcag tgggtgctgt cagccgcaca ctgtttccag 120aactcctaca ccatcgggct gggcctgcac agtcttgagg ccgaccaaga gccagggagc 180cagatggtgg aggccagcct ctccgtacgg cacccagagt acaacagacc cttgctcgct 240aacgacctca tgctcatcaa gttggacgaa tccgtgtccg agtctgacac catccggagc 300atcagcattg cttcgcagtg ccctaccgcg gggaactctt gcctcgtttc tggctggggt 360ctgctggcga acggcagaat gcctaccgtg ctgcagtgcg tgaacgtgtc ggtggtgtct 420gaggaggtct gcagtaagct ctatgacccg ctgtaccacc ccagcatgtt ctgcgccggc 480ggagggcaag accagaagga ctcctgcaac ggtgactctg gggggcccct gatctgcaac 540gggtacttgc agggccttgt gtctttcgga aaagccccgt gtggccaagt tggcgtgcca 600ggtgtctaca ccaacctctg caaattcact gagtggatag agaaaaccgt ccaggccagt 660taactctggg gactgggaac ccatgaaatt gacccccaaa tacatcctgc ggaaggaatt 720caggaatatc tgttcccagc ccctcctccc tcaggcccag gagtccaggc ccccagcccc 780tcctccctca aaccaagggt acagatcccc agcccctcct ccctcagacc caggagtcca 840gaccccccag cccctcctcc ctcagaccca ggagtccagc ccctcctccc tcagacccag 900gagtccagac cccccagccc ctcctccctc agacccaggg gtccaggccc ccaacccctc 960ctccctcaga ctcagaggtc caagccccca acccctcctt ccccagaccc agaggtccag 1020gtcccagccc ctcctccctc agacccagcg gtccaatgcc acctagactc tccctgtaca 1080cagtgccccc ttgtggcacg ttgacccaac cttaccagtt ggtttttcat tttttgtccc 1140tttcccctag atccagaaat aaagtctaag agaagcgcaa aaaaaaaaaa aaaaaaaaaa 1200aaaaaaaaaa aaaa 1214

<210> 226

<211> 119

<212> DNA

<213> Homo sapien

<400> 226acccagtatg tgcagggaga cggaacccca tgtgacagcc cactccacca gggttcccaa 60agaacctggc ccagtcataa tcattcatcc tgacagtggc aataatcacg ataaccagt 119

<210> 227

<211> 818

<212> DNA

<213> Homo sapien

<400> 227acaattcata gggacgacca atgaggacag ggaatgaacc cggctctccc ccagccctga 60tttttgctac atatggggtc ccttttcatt ctttgcaaaa acactgggtt ttctgagaac 120acggacggtt cttagcacaa tttgtgaaat ctgtgtaraa ccgggctttg caggggagat 180aattttcctc ctctggagga aaggtggtga ttgacaggca gggagacagt gacaaggcta 240gagaaagcca cgctcggcct tctctgaacc aggatggaac ggcagacccc tgaaaacgaa 300gcttgtcccc ttccaatcag ccacttctga gaacccccat ctaacttcct actggaaaag 360agggcctcct caggagcagt ccaagagttt tcaaagataa cgtgacaact accatctaga 420ggaaagggtg caccctcagc agagaagccg agagcttaac tctggtcgtt tccagagaca 480acctgctggc tgtcttggga tgcgcccagc ctttgagagg ccactacccc atgaacttct 540gccatccact ggacatgaag ctgaggacac tgggcttcaa cactgagttg tcatgagagg 600gacaggctct gccctcaagc cggctgaggg cagcaaccac tctcctcccc tttctcacgc 660aaagccattc ccacaaatcc agaccatacc atgaagcaac gagacccaaa cagtttggct 720caagaggata tgaggactgt ctcagcctgg ctttgggctg acaccatgca cacacacaag 780gtccacttct aggttttcag cctagatggg agtcgtgt 818

<210> 228

<211> 744

<212> DNA

<213> Homo sapien

<400> 228actggagaca ctgttgaact tgatcaagac ccagaccacc ccaggtctcc ttcgtgggat 60gtcatgacgt ttgacatacc tttggaacga gcctcctcct tggaagatgg aagaccgtgt 120tcgtggccga cctggcctct cctggcctgt ttcttaagat gcggagtcac atttcaatgg 180taggaaaagt ggcttcgtaa aatagaagag cagtcactgt ggaactacca aatggcgaga 240tgctcggtgc acattggggt gctttgggat aaaagattta tgagccaact attctctggc 300accagattct aggccagttt gttccactga agcttttccc acagcagtcc acctctgcag 360gctggcagct gaatggcttg ccggtggctc tgtggcaaga tcacactgag atcgatgggt 420gagaaggcta ggatgcttgt ctagtgttct tagctgtcac gttggctcct tccaggttgg 480ccagacggtg ttggccactc ccttctaaaa cacaggcgcc ctcctggtga cagtgacccg 540ccgtggtatg ccttggccca ttccagcagt cccagttatg catttcaagt ttggggtttg 600ttcttttcgt taatgttcct ctgtgttgtc agctgtcttc atttcctggg ctaagcagca 660ttgggagatg tggaccagag atccactcct taagaaccag tggcgaaaga cactttcttt 720cttcactctg aagtagctgg tggt 744

<210> 229

<211> 300

<212> DNA

<213> Homo sapien

<400> 229cgagtctggg ttttgtctat aaagtttgat ccctcctttt ctcatccaaa tcatgtgaac 60cattacacat cgaaataaaa gaaaggtggc agacttgccc aacgccaggc tgacatgtgc 120tgcagggttg ttgtttttta attattattg ttagaaacgt cacccacagt ccctgttaat 180ttgtatgtga cagccaactc tgagaaggtc ctatttttcc acctgcagag gatccagtct 240cactaggctc ctccttgccc tcacactgga gtctccgcca gtgtgggtgc ccactgacat 300

<210> 230

<211> 301

<212> DNA

<213> Homo sapien

<400> 230cagcagaaca aatacaaata tgaagagtgc aaagatctca taaaatctat gctgaggaat 60gagcgacagt tcaaggagga gaagcttgca gagcagctca agcaagctga ggagctcagg 120caatataaag tcctggttca cactcaggaa cgagagctga cccagttaag ggagaagttg 180cgggaaggga gagatgcctc cctctcattg aatgagcatc tccaggccct cctcactccg 240gatgaaccgg acaagtccca ggggcaggac ctccaagaaa cagacctcgg ccgcgaccac 300g 301

<210> 231

<211> 301

<212> DNA

<213> Homo sapien

<400> 231gcaagcacgc tggcaaatct ctgtcaggtc agctccagag aagccattag tcattttagc 60caggaactcc aagtccacat ccttggcaac tggggacttg cgcaggttag ccttgaggat 120ggcaacacgg gacttctcat caggaagtgg gatgtagatg agctgatcaa gacggccagg l80tctgaggatg gcaggatcaa tgatgtcagg ccggttggta ccgccaatga tgaacacatt 240tttttttgtg gacatgccat ccatttctgt caggatctgg ttgatgactc ggtcagcagc 300c 301

<210> 232

<211> 301

<212> DNA

<213> Homo sapien

<400> 232agtaggtatt tcgtgagaag ttcaacacca aaactggaac atagttctcc ttcaagtgtt 60ggcgacagcg gggcttcctg attctggaat ataactttgt gtaaattaac agccacctat 120agaagagtcc atctgctgtg aaggagagac agagaactct gggttccgtc gtcctgtcca 180cgtgctgtac caagtgctgg tgccagcctg ttacctgttc ccactgaaaa tctggctaat 240gctcttgtgt atcacttctg attctgacaa tcaatcaatc aatggcctag agcactgact 300g 301

<210> 233

<211> 301

<212> DNA

<213> Homo sapien

<400> 233atgactgact tcccagtaag gctctctaag gggtaagtag gaggatccac aggatttgag 60atgctaaggc cccagagatc gtttgatcca accctcttat tttcagaggg gaaaatgggg 120cctagaagtt acagagcatc tagctggtgc gctggcaccc ctggcctcac acagactccc 180gagtagctgg gactacaggc acacagtcac tgaagcaggc cctgttagca attctatgcg 240tacaaattaa catgagatga gtagagactt tattgagaaa gcaagagaaa atcctatcaa 300c 301

<210> 234

<211> 301

<212> DNA

<213> Homo sapien

<400> 234aggtcctaca catcgagact catccatgat tgatatgaat ttaaaaatta caagcaaaga 60cattttattc atcatgatgc tttcttttgt ttcttctttt cgttttcttc tttttctttt 120tcaatttcag caacatactt ctcaatttct tcaggattta aaatcttgag ggattgatct 180cgcctcatga cagcaagttc aatgtttttg ccacctgact gaaccacttc caggagtgcc 240ttgatcacca gcttaatggt cagatcatct gcttcaatgg cttcgtcagt atagttcttc 300 301

<210> 235

<211> 283

<212> DNA

<213> Homo sapien

<400> 235tggggctgtg catcaggcgg gtttgagaaa tattcaattc tcagcagaag ccagaatttg 60aattccctca tcttttaggg aatcatttac caggtttgga gaggattcag acagctcagg 120tgctttcact aatgtctctg aacttctgtc cctctttgtt catggatagt ccaataaata 180atgttatctt tgaactgatg ctcataggag agaatataag aactctgagt gatatcaaca 240ttagggattc aaagaaatat tagatttaag ctcacactgg tca 283

<210> 236

<211> 301

<212> DNA

<213> Homo sapien

<400> 236aggtcctcca ccaactgcct gaagcacggt taaaattggg aagaagtata gtgcagcata 60aatactttta aatcgatcag atttccctaa cccacatgca atcttcttca ccagaagagg 120tcggagcagc atcattaata ccaagcagaa tgcgtaacag ataaatacaa tggtatatag 180tgggtagacg gcttcatgag tacagtgtac tgtggtatcg taatctggac ttgggttgta 240aagcatcgtg taccagtcag aaagcatcaa tactcgacat gaacgaatat aaagaacacc 300a 301

<210> 237

<211> 301

<212> DNA

<213> Homo sapien

<400> 237cagtggtagt ggtggtggac gtggcgttgg tcgtggtgcc ttttttggtg cccgtcacaa 60actcaatttt tgttcgctcc tttttggcct tttccaattt gtccatctca attttctggg 120ccttggctaa tgcctcatag taggagtcct cagaccagcc atggggatca aacatatcct 180ttgggtagtt ggtgccaagc tcgtcaatgg cacagaatgg atcagcttct cgtaaatcta 240gggttccgaa attctttctt cctttggata atgtagttca tatccattcc ctcctttatc 300t 301

<210> 238

<211> 301

<212> DNA

<213> Homo sapien

<400> 238gggcaggttt tttttttttt ttttttgatg gtgcagaccc ttgctttatt tgtctgactt 60gttcacagtt cagccccctg ctcagaaaac caacgggcca gctaaggaga ggaggaggca 120ccttgagact tccggagtcg aggctctcca gggttcccca gcccatcaat cattttctgc 180accccctgcc tgggaagcag ctccctgggg ggtgggaatg ggtgactaga agggatttca 240gtgtgggacc cagggtctgt tcttcacagt aggaggtgga agggatgact aatttcttta 300t 301

<210> 239

<211> 239

<212> DNA

<213> Homo sapien

<400> 239ataagcagct agggaattct ttatttagta atgtcctaac ataaaagttc acataactgc 60ttctgtcaaa ccatgatact gagctttgtg acaacccaga aataactaag agaaggcaaa 120cataatacct tagagatcaa gaaacattta cacagttcaa ctgtttaaaa atagctcaac 180attcagccag tgagtagagt gtgaatgcca gcatacacag tatacaggtc cttcaggga 239

<210> 240

<211> 300

<212> DNA

<213> Homo sapien

<400> 240ggtcctaatg aagcagcagc ttccacattt taacgcaggt ttacggtgat actgtccttt 60gggatctgcc ctccagtgga accttttaag gaagaagtgg gcccaagcta agttccacat 120gctgggtgag ccagatgact tctgttccct ggtcactttc ttcaatgggg cgaatggggg 180ctgccaggtt tttaaaatca tgcttcatct tgaagcacac ggtcacttca ccctcctcac 240gctgtgggtg tactttgatg aaaataccca ctttgttggc ctttctgaag ctataatgtc 300

<210> 241

<211> 301

<212> DNA

<213> Homo sapien

<400> 241gaggtctggt gctgaggtct ctgggctagg aagaggagtt ctgtggagct ggaagccaga 60cctctttgga ggaaactcca gcagctatgt tggtgtctct gagggaatgc aacaaggctg 120ctcctccatg tattggaaaa ctgcaaactg gactcaactg gaaggaagtg ctgctgccag 180tgtgaagaac cagcctgagg tgacagaaac ggaagcaaac aggaacagcc agtcttttct 240tcctcctcct gtcatacggt ctccctcaag catcctttgt tgtcaggggc ctaaaaggga 300g 301

<210> 242

<211> 301

<212> DNA

<213> Homo sapien

<400> 242ccgaggtcct gggatgcaac caatcactct gtttcacgtg acttttatca ccatacaatt 60tgtggcattt cctcattttc tacattgtag aatcaagagt gtaaataaat gtatatcgat 120gtcttcaaga atatatcatt cctttttcac tagaacccat tcaaaatata agtcaagaat 180cttaatatca acaaatatat caagcaaact ggaaggcaga ataactacca taatttagta 240taagtaccca aagttttata aatcaaaagc cctaatgata accattttta gaattcaatc 300a 301

<210> 243

<211> 301

<212> DNA

<213> Homo sapien

<400> 243aggtaagtcc cagtttgaag ctcaaaagat ctggtatgag cataggctca tcgacgacat 60ggtggcccaa gctatgaaat cagagggagg cttcatctgg gcctgtaaaa actatgatgg 120tgacgtgcag tcggactctg tggcccaagg gtatggctct ctcggcatga tgaccagcgt 180gctggtttgt ccagatggca agacagtaga agcagaggct gcccacggga ctgtaacccg 240tcactaccgc atgttccaga aaggacagga gacgtccacc aatcccattg cttccatttt 300t 301

<210> 244

<211> 300

<212> DNA

<213> Homo sapien

<400> 244gctggtttgc aagaatgaaa tgaatgattc tacagctagg acttaacctt gaaatggaaa 60gtcatgcaat cccatttgca ggatctgtct gtgcacatgc ctctgtagag agcagcattc 120ccagggacct tggaaacagt tgacactgta aggtgcttgc tccccaagac acatcctaaa 180aggtgttgta atggtgaaaa cgtcttcctt ctttattgcc ccttcttatt tatgtgaaca 240actgtttgtc ttttgtgtat cttttttaaa ctgtaaagtt caattgtgaa aatgaatatc 300

<210> 245

<211> 301

<212> DNA

<213> Homo sapien

<400> 245gtctgagtat ttaaaatgtt attgaaatta tccccaacca atgttagaaa agaaagaggt 60tatatactta gataaaaaat gaggtgaatt actatccatt gaaatcatgc tcttagaatt 120aaggccagga gatattgtca ttaatgtara cttcaggaca ctagagtata gcagccctat 180gttttcaaag agcagagatg caattaaata ttgtttagca tcaaaaaggc cactcaatac 240agctaataaa atgaaagacc taatttctaa agcaattctt tataatttac aaagttttaa 300g 301

<210> 246

<211> 301

<212> DNA

<213> Homo sapien

<400> 246ggtctgtcct acaatgcctg cttcttgaaa gaagtcggca ctttctagaa tagctaaata 60acctgggctt attttaaaga actatttgta gctcagattg gttttcctat ggctaaaata 120agtgcttctt gtgaaaatta aataaaacag ttaattcaaa gccttgatat atgttaccac 180taacaatcat actaaatata ttttgaagta caaagtttga catgctctaa agtgacaacc 240caaatgtgtc ttacaaaaca cgttcctaac aaggtatgct ttacactacc aatgcagaaa 300c 301

<210> 247

<211> 301

<212> DNA

<213> Homo sapien

<400> 247aggtcctttg gcagggctca tggatcagag ctcaaactgg agggaaaggc atttcgggta 60gcctaagagg gcgactggcg gcagcacaac caaggaaggc aaggttgttt cccccacgct 120gtgtcctgtg ttcaggtgcg acacacaatc ctcatgggaa caggatcacc catgcgctgc 180ccttgatgat caaggttggg gcttaagtgg attaagggag gcaagttctg ggttccttgc 240cttttcaaac catgaagtca ggctctgtat ccctcctttt cctaactgat attctaacta 300a 301

<210> 248

<211> 301

<212> DNA

<213> Homo sapien

<400> 248aggtccttgg agatgccatt tcagccgaag gactcttctw ttcggaagta caccctcact 60attaggaaga ttcttagggg taatttttct gaggaaggag aactagccaa cttaagaatt 120acaggaagaa agtggtttgg aagacagcca aagaaataaa agcagattaa attgtatcag 180gtacattcca gcctgttggc aactccataa aaacatttca gattttaatc ccgaatttag 240ctaatgagac tggatttttg ttttttatgt tgtgtgtcgc agagctaaaa actcagttcc 300c 301

<210> 249

<211> 301

<212> DNA

<213> Homo sapien

<400> 249gtccagagga agcacctggt gctgaactag gcttgccctg ctgtgaactt gcacttggag 60ccctgacgct gctgttctcc ccgaaaaacc cgaccgacct ccgcgatctc cgtcccgccc 120ccagggagac acagcagtga ctcagagctg gtcgcacact gtgcctccct cctcaccgcc 180catcgtaatg aattattttg aaaattaatt ccaccatcct ttcagattct ggatggaaag 240actgaatctt tgactcagaa ttgtttgctg aaaagaatga tgtgactttc ttagtcattt 300a 301

<210> 250

<211> 301

<212> DNA

<213> Homo sapien

<400> 250ggtctgtgac aaggacttgc aggctgtggg aggcaagtga cccttaacac tacacttctc 60cttatcttta ttggcttgat aaacataatt atttctaaca ctagcttatt tccagttgcc 120cataagcaca tcagtacttt tctctggctg gaatagtaaa ctaaagtatg gtacatctac 180ctaaaagact actatgtgga ataatacata ctaatgaagt attacatgat ttaaagacta 240caataaaacc aaacatgctt ataacattaa gaaaaacaat aaagatacat gattgaaacc 300a 301

<210> 251

<211> 301

<212> DNA

<213> Homo sapien

<400> 251gccgaggtcc tacatttggc ccagtttccc cctgcatcct ctccagggcc cctgcctcat 60agacaacctc atagagcata ggagaactgg ttgccctggg ggcaggggga ctgtctggat 120ggcaggggtc ctcaaaaatg ccactgtcac tgccaggaaa tgcttctgag cagtacacct l80cattgggatc aatgaaaagc ttcaagaaat cttcaggctc actctcttga aggcccggaa 240cctctggagg ggggcagtgg aatcccagct ccaggacgga tcctgtcgaa aagatatcct 300c 301

<210> 252

<211> 301

<212> DNA

<213> Homo sapien

<400> 252gcaaccaatc actctgtttc acgtgacttt tatcaccata caatttgtgg catttcctca 60ttttctacat tgtagaatca agagtgtaaa taaatgtata tcgatgtctt caagaatata 120tcattccttt ttcactagga acccattcaa aatataagtc aagaatctta atatcaacaa 180atatatcaag caaactggaa ggcagaataa ctaccataat ttagtataag tacccaaagt 240tttataaatc aaaagcccta atgataacca tttttagaat tcaatcatca ctgtagaatc 300a 301

<210> 253

<211> 301

<212> DNA

<213> Homo sapien

<400> 253ttccctaaga agatgttatt ttgttgggtt ttgttccccc tccatctcga ttctcgtacc 60caactaaaaa aaaaaaataa agaaaaaatg tgctgcgttc tgaaaaataa ctccttagct 120tggtctgatt gttttcagac cttaaaatat aaacttgttt cacaagcttt aatccatgtg 180gatttttttt cttagagaac cacaaaacat aaaaggagca agtcggactg aatacctgtt 240tccatagtgc ccacagggta ttcctcacat tttctccata ggaaaatgct ttttcccaag 300g 301

<210> 254

<211> 301

<212> DNA

<213> Homo sapien

<400> 254cgctgcgcct ttcccttggg ggaggggcaa ggccagaggg ggtccaagtg cagcacgagg 60aacttgacca attcccttga agcgggtggg ttaaaccctg taaatgggaa caaaatcccc 120ccaaatctct tcatcttacc ctggtggact cctgactgta gaattttttg gttgaaacaa 180gaaaaaaata aagctttgga cttttcaagg ttgcttaaca ggtactgaaa gactggcctc 240acttaaactg agccaggaaa agctgcagat ttattaatgg gtgtgttagt gtgcagtgcc 300t 301

<210> 255

<211> 302

<212> DNA

<213> Homo sapien

<400> 255agcttttttt tttttttttt tttttttttt ttcattaaaa aatagtgctc tttattataa 60attactgaaa tgtttctttt ctgaatataa atataaatat gtgcaaagtt tgacttggat 120tgggattttg ttgagttctt caagcatctc ctaataccct caagggcctg agtagggggg 180aggaaaaaggactggaggtg gaatctttat aaaaaacaag agtgattgag gcagattgta 240aacattatta aaaaacaaga aacaaacaaa aaaatagaga aaaaaaccac cccaacacac 300aa 302

<210> 256

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 256gttccagaaa acattgaagg tggcttccca aagtctaact agggataccc cctctagcct 60aggaccctcc tccccacacc tcaatccacc aaaccatcca taatgcaccc agataggccc 120acccccaaaa gcctggacac cttgagcaca cagttatgac caggacagac tcatctctat 180aggcaaatag ctgctggcaa actggcatta cctggtttgt ggggatgggg gggcaagtgt 240gtggcctctc ggcctggtta gcaagaacat tcagggtagg cctaagttan tcgtgttagt 300t 301

<210> 257

<211> 301

<212> DNA

<213> Homo sapien

<400> 257gttgtggagg aactctggct tgctcattaa gtcctactga ttttcactat cccctgaatt 60tccccactta tttttgtctt tcactatcgc aggccttaga agaggtctac ctgcctccag 120tcttacctag tccagtctac cccctggagt tagaatggcc atcctgaagt gaaaagtaat 180gtcacattac tcccttcagt gatttcttgt agaagtgcca atccctgaat gccaccaaga 240tcttaatctt cacatcttta atcttatctc tttgactcct ctttacaccg gagaaggctc 300c 301

<210> 258

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 258cagcagtagt agatgccgta tgccagcacg cccagcactc ccaggatcag caccagcacc 60aggggcccag ccaccaggcg cagaagcaag ataaacagta ggctcaagac cagagccacc 120cccagggcaa caagaatcca ataccaggac tgggcaaaat cttcaaagat cttaacactg 180atgtctcggg cattgaggct gtcaataana cgctgatccc ctgctgtatg gtggtgtcat 240tggtgatccc tgggagcgcc ggtggagtaa cgttggtcca tggaaagcag cgcccacaac 300t 301

<210> 259

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 259tcatatatgc aaacaaatgc agactangcc tcaggcagag actaaaggac atctcttggg 60gtgtcctgaa gtgatttgga cccctgaggg cagacaccta agtaggaatc ccagtgggaa 120gcaaagccat aaggaagccc aggattcctt gtgatcagga agtgggccag gaaggtctgt 180tccsgctcac atctcatctg catgcagcac ggaccggatg cgcccactgg gtcttggctt 240ccctcccatc ttctcaagca gtgtccttgt tgagccattt gcatccttgg ctccaggtgg 300c 301

<210> 260

<211> 301

<212> DNA

<213> Homo sapien

<400> 260ttttttttct ccctaaggaa aaagaaggaa caagtctcat aaaaccaaat aagcaatggt 60aaggtgtctt aacttgaaaa agattaggag tcactggttt acaagttata attgaatgaa 120agaactgtaa cagccacagt tggccatttc atgccaatgg cagcaaacaa caggattaac 180tagggcaaaa taaataagtg tgtggaagcc ctgataagtg cttaataaac agactgattc 240actgagacat cagtacctgc ccgggcggcc gctcgagccg aattctgcag atatccatca 300c 301

<210> 261

<211> 301

<212> DNA

<213> Homo sapien

<400> 261aaatattcga gcaaatcctg taactaatgt gtctccataa aaggctttga actcagtgaa 60tctgcttcca tccacgattc tagcaatgac ctctcggaca tcaaagctcc tcttaaggtt 120agcaccaact attccataca attcatcagc aggaaataaa ggctcttcag aaggttcaat 180ggtgacatcc aatttcttct gataatttag attcctcaca accttcctag ttaagtgaag 240ggcatgatga tcatccaaag cccagtggtc acttactcca gactttctgc aatgaagatc 300a 301

<210> 262

<211> 301

<212> DNA

<213> Homo sapien

<400> 262gaggagagcc tgttacagca tttgtaagca cagaatactc caggagtatt tgtaattgtc 60tgtgagcttc ttgccgcaag tctctcagaa atttaaaaag atgcaaatcc ctgagtcacc 120cctagacttc ctaaaccaga tcctctgggg ctggaacctg gcactctgca tttgtaatga 180gggctttctg gtgcacacct aattttgtgc atctttgccc taaatcctgg attagtgccc 240catcattacc cccacattat aatgggatag attcagagca gatactctcc agcaaagaat 300c 301

<210> 263

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 263tttagcttgt ggtaaatgac tcacaaaact gattttaaaa tcaagttaat gtgaattttg 60aaaattacta cttaatccta attcacaata acaatggcat taaggtttga cttgagttgg 120ttcttagtat tatttatggt aaataggctc ttaccacttg caaataactg gccacatcat 180taatgactga cttcccagta aggctctcta aggggtaagt angaggatcc acaggatttg 240agatgctaag gccccagaga tcgtttgatc caaccctctt attttcagag gggaaaatgg 300g 301

<210> 264

<211> 301

<212> DNA

<213> Homo sapien

<400> 264aaagacgtta aaccactcta ctaccacttg tggaactctc aaagggtaaa tgacaaascc 60aatgaatgac tctaaaaaca atatttacat ttaatggttt gtagacaata aaaaaacaag 120gtggatagat ctagaattgt aacattttaa gaaaaccata scatttgaca gatgagaaag 180ctcaattata gatgcaaagt tataactaaa ctactatagt agtaaagaaa tacatttcac 240acccttcata taaattcact atcttggctt gaggcactcc ataaaatgta tcacgtgcat 300a 301

<210> 265

<211> 301

<212> DNA

<213> Homo sapien

<400> 265tgcccaagtt atgtgtaagt gtatccgcac ccagaggtaa aactacactg tcatctttgt 60cttcttgtga cgcagtattt cttctctggg gagaagccgg gaagtcttct cctggctcta 120catattcttg gaagtctcta atcaactttt gttccatttg tttcatttct tcaggaggga 180ttttcagttt gtcaacatgt tctctaacaa cacttgccca tttctgtaaa gaatccaaag 240cagtccaagg ctttgacatg tcaacaacca gcataactag agtatccttc agagatacgg 300c 301

<210> 266

<211> 301

<212> DNA

<213> Homo sapien

<400> 266taccgtctgc ccttcctccc atccaggcca tctgcgaatc tacatgggtc ctcctattcg 60acaccagatc actctttcct ctacccacag gcttgctatg agcaagagac acaacctcct 120ctcttctgtg ttccagcttc ttttcctgtt cttcccaccc cttaagttct attcctgggg 180atagagacac caatacccat aacctctctc ctaagcctcc ttataaccca gggtgcacag 240cacagactcc tgacaactgg taaggccaat gaactgggag ctcacagctg gctgtgcctg 300a 301

<210> 267

<211> 301

<212> DNA

<213> Homo sapien

<400> 267aaagagcaca ggccagctca gcctgccctg gccatctaga ctcagcctgg ctccatgggg 60gttctcagtg ctgagtccat ccaggaaaag ctcacctaga ccttctgagg ctgaatcttc 120atcctcacag gcagcttctg agagcctgat attcctagcc ttgatggtct ggagtaaagc 180ctcattctga ttcctctcct tcttttcttt caagttggct ttcctcacat ccctctgttc 240aattcgcttc agcttgtctg ctttagccct catttccaga agcttcttct ctttggcatc 300t 301

<210> 268

<211> 301

<212> DNA

<213> Homo sapien

<400> 268aatgtctcac tcaactactt cccagcctac cgtggcctaa ttctgggagt tttcttctta 60gatcttggga gagccggttc ttctaaggag aaggaggaag gacagatgta actttggatc 120tcgaagagga agtctaatgg aagtaattag tcaacggtcc ttgtttagac tcttggaata 180tgctgggtgg ctcagtgagc ccttttggag aaagcaagta ttattcttaa ggagtaacca 240cttcccattg ttctactttc taccatcatc aattgtatat tatgtattct ttggagaact 300a 301

<210> 269

<211> 301

<212> DNA

<213> Homo sapien

<400> 269taacaatata cactagctat ctttttaact gtccatcatt agcaccaatg aagattcaat 60aaaattacct ttattcacac atctcaaaac aattctgcaa attcttagtg aagtttaact 120atagtcacag accttaaata ttcacattgt tttctatgtc tactgaaaat aagttcacta 180cttttctgga tattctttac aaaatcttat taaaattcct ggtattatca cccccaatta 240tacagtagca caaccacctt atgtagtttt tacatgatag ctctgtagaa gtttcacatc 300t 301

<210> 270

<211> 301

<212> DNA

<213> Homo sapien

<400> 270cattgaagag cttttgcgaa acatcagaac acaagtgctt ataaaattaa ttaagcctta 60cacaagaata catattcctt ttatttctaa ggagttaaac atagatgtag ctgatgtgga 120gagcttgctg gtgcagtgca tattggataa cactattcat ggccgaattg atcaagtcaa 180ccaactcctt gaactggatc atcagaagaa gggtggtgca cgatatactg cactagataa 240tggaccaacc aactaaattc tctcaccagg ctgtatcagt aaactggctt aacagaaaac 300a 301

<210> 271

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,c or G

<400> 271aaaaggttct cataagatta acaatttaaa taaatatttg atagaacatt ctttctcatt 60tttatagctc atctttaggg ttgatattca gttcatgctt cccttgctgt tcttgatcca 120gaattgcaat cacttcatca gcctgtattc gctccaattc tctataaagt gggtccaagg 180tgaaccacag agccacagca cacctctttc ccttggtgac tgccttcacc ccatganggt 240tctctcctcc agatganaac tgatcatgcg cccacatttt gggttttata gaagcagtca 300c 301

<210> 272

<211> 301

<212> DNA

<213> Homo sapien

<400> 272taaattgcta agccacagat aacaccaatc aaatggaaca aatcactgtc ttcaaatgtc 60ttatcagaaa accaaatgag cctggaatct tcataatacc taaacatgcc gtatttagga 120tccaataatt ccctcatgat gagcaagaaa aattctttgc gcacccctcc tgcatccaca 180gcatcttctc caacaaatat aaccttgagt ggcttcttgt aatctatgtt ctttgttttc 240ctaaggactt ccattgcatc tcctacaata ttttctctac gcaccactag aattaagcag 300g 301

<210> 273

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 273acatgtgtgt atgtgtatct ttgggaaaan aanaagacat cttgtttayt atttttttgg 60agagangctg ggacatggat aatcacwtaa tttgctayta tyactttaat ctgactygaa 120gaaccgtcta aaaataaaat ttaccatgtc dtatattcct tatagtatgc ttatttcacc 180ttytttctgt ccagagagag tatcagtgac ananatttma gggtgaamac atgmattggt 240gggacttnty tttacngagm accctgcccg sgcgccctcg makcngantt ccgcsananc 300t 301

<210> 274

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 274cttatatact ctttctcaga ggcaaaagag gagatgggta atgtagacaa ttctttgagg 60aacagtaaat gattattaga gagaangaat ggaccaagga gacagaaatt aacttgtaaa 120tgattctctt tggaatctga atgagatcaa gaggccagct ttagcttgtg gaaaagtcca 180tctaggtatg gttgcattct cgtcttcttt tctgcagtag ataatgaggt aaccgaaggc 240aattgtgctt cttttgataa gaagctttct tggtcatatc aggaaattcc aganaaagtc 300C 301

<210> 275

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 275tcggtgtcag cagcacgtgg cattgaacat tgcaatgtgg agcccaaacc acagaaaatg 60gggtgaaatt ggccaacttt ctattaactt atgttggcaa ttttgccacc aacagtaagc 120tggcccttct aataaaagaa aattgaaagg tttctcacta aacggaatta agtagtggag 180tcaagagact cccaggcctc agcgtacctg cccgggcggc cgctcgaagc cgaattctgc 240agatatccat cacactggcg gncgctcgan catgcatcta gaaggnccaa ttcgccctat 300a 301

<210> 276

<211> 301

<212> DNA

<213> Homo sapien

<400> 276tgtacacata ctcaataaat aaatgactgc attgtggtat tattactata ctgattatat 60ttatcatgtg acttctaatt agaaaatgta tccaaaagca aaacagcaga tatacaaaat 120taaagagaca gaagatagac attaacagat aaggcaactt atacattgag aatccaaatc 180caatacattt aaacatttgg gaaatgaggg ggacaaatgg aagccagatc aaatttgtgt 240aaaactattc agtatgtttc ccttgcttca tgtctgagaa ggctctcctt caatggggat 300g 301

<210> 277

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 277tttgttgatg tcagtatttt attacttgcg ttatgagtgc tcacctggga aattctaaag 60atacagagga cttggaggaa gcagagcaac tgaatttaat ttaaaagaag gaaaacattg 120gaatcatggc actcctgata ctttcccaaa tcaacactct caatgcccca ccctcgtcct 180caccatagtg gggagactaa agtggccacg gatttgcctt angtgtgcag tgcgttctga 240gttcnctgtc gattacatct gaccagtctc ctttttccga agtccntccg ttcaatcttg 300c 301

<210> 278

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 278taccactaca ctccagcctg ggcaacagag caagacctgt ctcaaagcat aaaatggaat 60aacatatcaa atgaaacagg gaaaatgaag ctgacaattt atggaagcca gggcttgtca 120cagtctctac tgttattatg cattacctgg gaatttatat aagcccttaa taataatgcc 180aatgaacatc tcatgtgtgc tcacaatgtt ctggcactat tataagtgct tcacaggttt 240tatgtgttct tcgtaacttt atggantagg tactcggccg cgaacacgct aagccgaatt 300c 301

<210> 279

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 279aaagcaggaa tgacaaagct tgcttttctg gtatgttcta ggtgtattgt gacttttact 60gttatattaa ttgccaatat aagtaaatat agattatata tgtatagtgt ttcacaaagc 120ttagaccttt accttccagc caccccacag tgcttgatat ttcagagtca gtcattggtt 180atacatgtgt agttccaaag cacataagct agaanaanaa atatttctag ggagcactac 240catctgtttt cacatgaaat gccacacaca tagaactcca acatcaattt cattgcacag 300a 301

<210> 280

<211> 301

<212> DNA

<213> Homo sapien

<400> 280ggtactggag ttttcctccc ctgtgaaaac gtaactactg ttgggagtga attgaggatg 60tagaaaggtg gtggaaccaa attgtggtca atggaaatag gagaatatgg ttctcactct 120tgagaaaaaa acctaagatt agcccaggta gttgcctgta acttcagttt ttctgcctgg 180gtttgatata gtttagggtt ggggttagat taagatctaa attacatcag gacaaagaga 240cagactatta actccacagt taattaagga ggtatgttcc atgtttattt gttaaagcag 300t 301

<210> 281

<211> 301

<212> DNA

<213> Homo sapien

<400> 281aggtacaaga aggggaatgg gaaagagctg ctgctgtggc attgttcaac ttggatattc 60gccgagcaat ccaaatcctg aatgaagggg catcttctga aaaaggagat ctgaatctca 120atgtggtagc aatggcttta tcgggttata cggatgagaa gaactccctt tggagagaaa 180tgtgtagcac actgcgatta cagctaaata acccgtattt gtgtgtcatg tttgcatttc 240tgacaagtga aacaggatct tacgatggag ttttgtatga aaacaaagtt gcagtacctc 300g 301

<2t0> 282

<211> 301

<212> DNA

<213> Homo sapien

<400> 282caggtactac agaattaaaa tactgacaag caagtagttt cttggcgtgc acgaattgca 60tccagaaccc aaaaattaag aaattcaaaa agacattttg tgggcacctg ctagcacaga 120agcgcagaag caaagcccag gcagaaccat gctaacctta cagctcagcc tgcacagaag 180cgcagaagca aagcccaggc agaaccatgctaaccttaca gctcagcctg cacagaagcg 240cagaagcaaa gcccaggcag aacatgctaa ccttacagct cagcctgcac agaagcacag 300a 301

<210> 283

<211> 301

<212> DNA

<213> Homo sapien

<400> 283atctgtatac ggcagacaaa ctttatarag tgtagagagg tgagcgaaag gatgcaaaag 60cactttgagg gctttataat aatatgctgc ttgaaaaaaa aaatgtgtag ttgatactca 120gtgcatctcc agacatagta aggggttgct ctgaccaatc aggtgatcat tttttctatc 180acttcccagg ttttatgcaa aaattttgtt aaattctata atggtgatat gcatctttta 240ggaaacatat acatttttaa aaatctattt tatgtaagaa ctgacagacg aatttgcttt 300g 301

<210> 284

<211> 301

<212> DNA

<213> Homo sapien

<400> 284caggtacaaa acgctattaa gtggcttaga atttgaacat ttgtggtctt tatttacttt 60gcttcgtgtg tgggcaaagc aacatcttcc ctaaatatat attaccaaga aaagcaagaa 120gcagattagg tttttgacaa aacaaacagg ccaaaagggg gctgacctgg agcagagcat 180ggtgagaggc aaggcatgag agggcaagtt tgttgtggac agatctgtgc ctactttatt 240actggagtaa aagaaaacaa agttcattga tgtcgaagga tatatacagt gttagaaatt 300a 301

<210> 285

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 285acatcaccat gatcggatcc cccacccatt atacgttgta tgcttacata aatactcttc 60aatgatcatt agtgttttaa aaaaaatact gaaaactcct tctgcatccc aacctctaac 120caggaaagca aatgctattt acagacctgc aagccctccc tcaaacnaaa ctatttctgg 180attaaatatg tctgacttct tttgaggtca cacgactagg caaatgctat ttacgatctg 240caaaagctgt ttgaagagtc aaagccccca tgtgaacacg atttctggac cctgtaacag 300t 301

<210> 286

<211> 301

<212> DNA

<213> Homo sapien

<400> 286taccactgca ttccagcctg ggtgacagag tgagactccg tctccaaaaa aaactttgct 60tgtatattat ttttgcctta cagtggatcattctagtagg aaaggacagt aagatttttt 120atcaaaatgt gtcatgccag taagagatgt tatattcttt tctcatttct tccccaccca 180aaaataagct accatatagc ttataagtct caaatttttg ccttttacta aaatgtgatt 240gtttctgttc attgtgtatg cttcatcacc tatattaggc aaattccatt ttttcccttg 300t 301

<210> 287

<211> 301

<212> DNA

<213> Homo sapien

<400> 287tacagatctg ggaactaaat attaaaaatg agtgtggctg gatatatgga gaatgttggg 60cccagaagga acgtagagat cagatattac aacagctttg ttttgagggt tagaaatatg 120aaatgatttg gttatgaacg cacagtttag gcagcagggc cagaatcctg accctctgcc 180ccgtggttat ctcctcccca gcttggctgc ctcatgttat cacagtattc cattttgttt 240gttgcatgtc ttgtgaagcc atcaagattt tctcgtctgt tttcctctca ttggtaatgc 300t 301

<210> 288

<211> 301

<212> DNA

<213> Homo sapien

<400> 288gtacacctaa ctgcaaggac agctgaggaa tgtaatgggc agccgctttt aaagaagtag 60agtcaatagg aagacaaatt ccagttccag ctcagtctgg gtatctgcaa agctgcaaaa 120gatctttaaa gacaatttca agagaatatt tccttaaagt tggcaatttg gagatcatac 180aaaagcatct gcttttgtga tttaatttag ctcatctggc cactggaaga atccaaacag 240tctgccttaa ttttggatga atgcatgatg gaaattcaat aatttagaaa gttaaaaaaa 300a 301

<210> 289

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 289ggtacactgt ttccatgtta tgtttctaca cattgctacc tcagtgctcc tggaaactta 60gcttttgatg tctccaagta gtccaccttc atttaactct ttgaaactgt atcatctttg 120ccaagtaaga gtggtggcct atttcagctg ctttgacaaa atgactggct cctgacttaa 180cgttctataa atgaatgtgc tgaagcaaag tgcccatggt ggcggcgaan aagagaaaga 240tgtgttttgt tttggactct ctgtggtccc ttccaatgct gtgggtttcc aaccagngga 300a 301

<210> 290

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 290acactgagct cttcttgata aatatacaga atgcttggca tatacaagat tctatactac 60tgactgatct gttcatttct ctcacagctc ttacccccaa aagcttttcc accctaagtg 120ttctgacctc cttttctaat cacagtaggg atagaggcag anccacctac aatgaacatg 180gagttctatc aagaggcaga aacagcacag aatcccagtt ttaccattcg ctagcagtgc 240tgccttgaac aaaaacattt ctccatgtct cattttcttc atgcctcaag taacagtgag 300a 301

<210> 291

<211> 301

<212> DNA

<213> Homo sapien

<400> 291caggtaccaa tttcttctat cctagaaaca tttcatttta tgttgttgaa acataacaac 60tatatcagct agattttttt tctatgcttt acctgctatg gaaaatttga cacattctgc 120tttactcttt tgtttatagg tgaatcacaa aatgtatttt tatgtattct gtagttcaat 180agccatggct gtttacttca tttaatttat ttagcataaa gacattatga aaaggcctaa 240acatgagctt cacttcccca ctaactaatt agcatctgtt atttcttaac cgtaatgcct 300a 301

<210> 292

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 292accttttagt agtaatgtct aataataaat aagaaatcaa ttttataagg tccatatagc 60tgtattaaat aatttttaag tttaaaagat aaaataccat cattttaaat gttggtattc 120aaaaccaaag natataaccg aaaggaaaaa cagatgagac ataaaatgat ttgcnagatg 180ggaaatatag tasttyatga atgttnatta aattccagtt ataatagtgg ctacacactc 240tcactacaca cacagacccc acagtcctat atgccacaaa cacatttcca taacttgaaa 300a 301

<210> 293

<211> 301

<212> DNA

<213> Homo sapien

<400> 293ggtaccaagt gctggtgcca gcctgttacc tgttctcact gaaaagtctg gctaatgctc 60ttgtgtagtc acttctgatt ctgacaatca atcaatcaat ggcctagagc actgactgtt 120aacacaaacg tcactagcaa agtagcaaca gctttaagtc taaatacaaa gctgttctgt 180gtgagaattt tttaaaaggc tacttgtata ataacccttg tcatttttaa tgtacctcgg 240ccgcgaccac gctaagccga attctgcaga tatccatcac actggcggcc gctcgagcat 300g 301

<210> 294

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 294tgacccataa caatatacac tagctatctt tttaactgtc catcattagc accaatgaag 60attcaataaa attaccttta ttcacacatc tcaaaacaat tctgcaaatt cttagtgaag 120tttaactata gtcacaganc ttaaatattc acattgtttt ctatgtctac tgaaaataag 180ttcactactt ttctgggata ttctttacaa aatcttatta aaattcctgg tattatcacc 240cccaattata cagtagcaca accaccttat gtagttttta catgatagct ctgtagaggt 300t 301

<210> 295

<211> 305

<212> DNA

<213> Homo sapien

<400> 295gtactctttc tctcccctcc tctgaattta attctttcaa cttgcaattt gcaaggatta 60cacatttcac tgtgatgtat attgtgttgc aaaaaaaaaa gtgtctttgt ttaaaattac 120ttggtttgtg aatccatctt gctttttccc cattggaact agtcattaac ccatctctga 180actggtagaa aaacrtctga agagctagtc tatcagcatc tgacaggtga attggatggt 240tctcagaacc atttcaccca gacagcctgt ttctatcctg tttaataaat tagtttgggt 300tctct 305

<210> 296

<211> 301

<212> DNA

<213> Homo sapien

<400> 296aggtactatg ggaagctgct aaaataatat ttgatagtaa aagtatgtaa tgtgctatct 60cacctagtag taaactaaaa ataaactgaa actttatgga atctgaagtt attttccttg 120attaaataga attaataaac caatatgagg aaacatgaaa ccatgcaatc tactatcaac 180tttgaaaaag tgattgaacg aaccacttag ctttcagatg atgaacactg ataagtcatt 240tgtcattact ataaatttta aaatctgtta ataagatggc ctatagggag gaaaaagggg 300c 301

<210> 297

<211> 300

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(300)

<223> n = A,T,C or G

<400> 297actgagtttt aactggacgc caagcaggca aggctggaag gttttgctct ctttgtgcta 60aaggttttga aaaccttgaa ggagaatcat tttgacaaga agtacttaag agtctagaga 120acaaagangt gaaccagctg aaagctctcg ggggaanctt acatgtgttg ttaggcctgt 180tccatcattg ggagtgcact ggccatccct caaaatttgt ctgggctggc ctgagtggtc 240accgcacctc ggccgcgacc acgctaagcc gaattctgca gatatccatc acactggcgg 300

<210> 298

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 298tatggggttt gtcacccaaa agctgatgct gagaaaggcc tccctggggc ccctcccgcg 60ggcatctgag agacctggtg ttccagtgtt tctggaaatg ggtcccagtg ccgccggctg 120tgaagctctc agatcaatca cgggaagggc ctggcggtgg tggccacctg gaaccaccct 180gtcctgtctg tttacatttc actaycaggt tttctctggg cattacnatt tgttccccta 240caacagtgac ctgtgcattc tgctgtggcc tgctgtgtct gcaggtggct ctcagcgagg 300t 301

<210> 299

<211> 301

<212> DNA

<213> Homo sapien

<400> 299gttttgagac ggagtttcac tcttgttgcc cagactggac tgcaatggca gggtctctgc 60tcactgcacc ctctgcctcc caggttcgag caattctcct gcctcagcct cccaggtagc 120tgggattgca ggctcacgcc accataccca gctaattttt ttgtattttt agtagagacg 180gagtttcgcc atgttggcca gctggtctca aactcctgac ctcaagcgac ctgcctgcct 240cggcctccca aagtgctgga attataggca tgagtcaaca cgcccagcct aaagatattt 300t 301

<210> 300

<211> 301

<212> DNA

<213> Homo sapien

<400> 300attcagtttt atttgctgcc ccagtatctg taaccaggag tgccacaaaa tcttgccaga 60tatgtcccac acccactggg aaaggctccc acctggctac ttcctctatc agctgggtca 120gctgcattcc acaaggttct cagcctaatg agtttcacta cctgccagtc tcaaaactta 180gtaaagcaag accatgacat tcccccacgg aaatcagagt ttgccccacc gtcttgttac 240tataaagcct gcctctaaca gtccttgctt cttcacacca atcccgagcg catcccccat 300g 301

<210> 301

<211> 301

<212> DNA

<213> Homo sapien

<400> 301ttaaattttt gagaggataa aaaggacaaa taatctagaa atgtgtcttc ttcagtctgc 60agaggacccc aggtctccaa gcaaccacat ggtcaagggc atgaataatt aaaagttggt 120gggaactcac aaagaccctc agagctgaga cacccacaac agtgggagct cacaaagacc 180ctcagagctg agacacccac aacagtggga gctcacaaag accctcagag ctgagacacc 240cacaacagca cctcgttcag ctgccacatg tgtgaataag gatgcaatgt ccagaagtgt 300t 301

<210> 302

<211> 301

<212> DNA

<213> Homo sapien

<400> 302aggtacacat ttagcttgtg gtaaatgact cacaaaactg attttaaaat caagttaatg 60tgaattttga aaattactac ttaatcctaa ttcacaataa caatggcatt aaggtttgac 120ttgagttggt tcttagtatt atttatggta aataggctct taccacttgc aaataactgg 180ccacatcatt aatgactgac ttcccagtaa ggctctctaa ggggtaagta ggaggatcca 240caggatttga gatgctaagg ccccagagat cgtttgatcc aaccctctta ttttcagagg 300g 301

<210> 303

<211> 301

<212> DNA

<213> Homo sapien

<400> 303aggtaccaac tgtggaaata ggtagaggat cattttttct ttccatatca actaagttgt 60atattgtttt ttgacagttt aacacatctt cttctgtcag agattctttc acaatagcac 120tggctaatgg aactaccgct tgcatgttaa aaatggtggt ttgtgaaatg atcataggcc 180agtaacgggt atgtttttct aactgatctt ttgctcgttc caaagggacc tcaagacttc 240catcgatttt atatctgggg tctagaaaag gagttaatct gttttccctc ataaattcac 300c 301

<210> 304

<211> 301

<212> DNA

<213> Homo sapien

<400> 304acatggatgt tattttgcag actgtcaacc tgaatttgta tttgcttgac attgcctaat 60tattagtttc agtttcagct tacccacttt ttgtctgcaa catgcaraas agacagtgcc 120ctttttagtg tatcatatca ggaatcatct cacattggtt tgtgccatta ctggtgcagt 180gactttcagc cacttgggta aggtggagtt ggccatatgt ctccactgca aaattactga 240ttttcctttt gtaattaata agtgtgtgtg tgaagattct ttgagatgag gtatatatct 300c 301

<210> 305

<211> 301

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(301)

<223> n = A,T,C or G

<400> 305gangtacagc gtggtcaagg taacaagaag aaaaaaatgt gagtggcatc ctgggatgag 60cagggggaca gacctggaca gacacgttgt catttgctgc tgtgggtagg aaaatgggcg 120taaaggagga gaaacagata caaaatctcc aactcagtat taaggtattc tcatgcctag 180aatattggta gaaacaagaa tacattcata tggcaaataa ctaaccatgg tggaacaaaa 240ttctgggatt taagttggat accaangaaa ttgtattaaa agagctgttc atggaataag 300a 301

<210> 306

<211> 8

<212> PRT

<213> Homo sapien

<400> 306Val Leu Gly Trp Val Ala Glu Leu1 5

<210> 307

<211> 637

<212> DNA

<213> Homo sapien

<400> 307acagggratg aagggaaagg gagaggatga ggaagccccc ctggggattt ggtttggtcc 60ttgtgatcag gtggtctatg gggcttatcc ctacaaagaa gaatccagaa ataggggcac 120attgaggaat gatacttgag cccaaagagc attcaatcat tgttttattt gccttmtttt 180cacaccattg gtgagggagg gattaccacc ctggggttat gaagatggtt gaacacccca 240cacatagcac cggagatatg agatcaacag tttcttagcc atagagattc acagcccaga 300gcaggaggac gcttgcacac catgcaggat gacatggggg atgcgctcgg gattggtgtg 360aagaagcaag gactgttaga ggcaggcttt atagtaacaa gacggtgggg caaactctga 420tttccgtggg ggaatgtcat ggtcttgctt tactaagttt tgagactggc aggtagtgaa 480actcattagg ctgagaacct tgtggaatgc acttgaccca sctgatagag gaagtagcca 540ggtgggagcc tttcccagtg ggtgtgggac atatctggca agattttgtg gcactcctgg 600ttacagatac tggggcagca aataaaactg aatcttg 637

<210> 308

<211> 647

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(647)

<223> n = A,T,C or G

<400> 308acgattttca ttatcatgta aatcgggtca ctcaaggggc caaccacagc tgggagccac 60tgctcagggg aaggttcata tgggactttc tactgcccaa ggttctatac aggatataaa 120ggngcctcac agtatagatc tggtagcaaa gaagaagaaa caaacactga tctctttctg 180ccacccctct gaccctttgg aactcctctg accctttaga acaagcctac ctaatatctg 240ctagagaaaa gaccaacaac ggcctcaaag gatctcttac catgaaggtc tcagctaatt 300cttggctaag atgtgggttc cacattaggt tctgaatatg gggggaaggg tcaatttgct 360cattttgtgt gtggataaag tcaggatgcc caggggccag agcagggggc tgcttgcttt 420gggaacaatg gctgagcata taaccatagg ttatggggaa caaaacaaca tcaaagtcac 480tgtatcaatt gccatgaaga cttgagggac ctgaatctac cgattcatct taaggcagca 540ggaccagttt gagtggcaac aatgcagcag cagaatcaat ggaaacaaca gaatgattgc 600aatgtccttt tttttctcct gcttctgact tgataaaagg ggaccgt 647

<210> 309

<211> 460

<212> DNA

<213> Homo sapien

<400> 309actttatagt ttaggctgga cattggaaaa aaaaaaaagc cagaacaaca tgtgatagat 60aatatgattg gctgcacact tccagactga tgaatgatga acgtgatgga ctattgtatg 120gagcacatct tcagcaagag ggggaaatac tcatcatttt tggccagcag ttgtttgatc 180accaaacatc atgccagaat actcagcaaa ccttcttagc tcttgagaag tcaaagtccg 240ggggaattta ttcctggcaa ttttaattgg actccttatg tgagagcagc ggctacccag 300ctggggtggt ggagcgaacc cgtcactagt ggacatgcag tggcagagct cctggtaacc 360acctagagga atacacaggc acatgtgtga tgccaagcgt gacacctgta gcactcaaat 420ttgtcttgtt tttgtctttc ggtgtgtaag attcttaagt 460

<210> 310

<211> 539

<212> DNA

<213> Homo sapien

<400> 310acgggactta tcaaataaag ataggaaaag aagaaaactc aaatattata ggcagaaatg 60ctaaaggttt taaaatatgt caggattgga agaaggcatg gataaagaac aaagttcagt 120taggaaagag aaacacagaa ggaagagaca caataaaagt cattatgtat tctgtgagaa 180gtcagacagt aagatttgtg ggaaatgggt tggtttgttg tatggtatgt attttagcaa 240taatctttat ggcagagaaa gctaaaatcc tttagcttgc gtgaatgatc acttgctgaa 300ttcctcaagg taggcatgat gaaggagggt ttagaggaga cacagacaca atgaactgac 360ctagatagaa agccttagta tactcagcta ggaatagtga ttctgagggc acactgtgac 420atgattatgt cattacatgt atggtagtga tggggatgat aggaaggaag aacttatggc 480atattttcac ccccacaaaa gtcagttaaa tattgggaca ctaaccatcc aggtcaaga 539

<210> 311

<211> 526

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(526)

<223> n = A,T,C or G

<400> 311caaatttgag ccaatgacat agaattttac aaatcaagaa gcttatrctg gggccatttc 60ttttgacgtt ttctctaaac tactaaagag gcattaatga tccataaatt atattatcta 120catttacagc atttaaaatg tgttcagcat gaaatattag ctacagggga agctaaataa 180attaaacatg gaataaagat ttgtccttaa atataatcta caagaagact ttgatatttg 240tttttcacaa gtgaagcatt cttataaagt gtcataacct ttttggggaa actatgggaa 300aaaatgggga aactctgaag ggttttaagt atcttacctg aagctacaga ctccataacc 360tctctttaca gggagctcct gcagccccta cagaaatgag tggctgagat tcttgattgc 420acagcaagag cttctcatct aaaccctttc cctttttagt atctgtgtat caagtataaa 480agttctataa actgtagtnt acttatttta atccccaaag cacagt 526

<210> 312

<211> 500

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(500)

<223> n = A,T,C or G

<400> 312cctctctctc cccaccccct gactctagag aactgggttt tctcccagta ctccagcaat 60tcatttctga aagcagttga gccactttat tccaaagtac actgcagatg ttcaaactct 120ccatttctct ttcccttcca cctgccagtt ttgctgactc tcaacttgtc atgagtgtaa 180gcattaagga cattatgctt cttcgattct gaagacaggc cctgctcatg gatgactctg 240gcttcttagg aaaatatttt tcttccaaaa tcagtaggaa atctaaactt atcccctctt 300tgcagatgtc tagcagcttc agacatttgg ttaagaaccc atgggaaaaa aaaaaatcct 360tgctaatgtg gtttcctttg taaaccanga ttcttatttg nctggtatag aatatcagct 420ctgaacgtgt ggtaaagatt tttgtgtttg aatataggag aaatcagttt gctgaaaagt 480tagtcttaat tatctattgg 500

<210> 313

<211> 718

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)..,(718)

<223> n = A,T,C or G

<400> 313ggagatttgt gtggtttgca gccgagggag accaggaaga tctgcatggt gggaaggacc 60tgatgataca gaggtgagaa ataagaaagg ctgctgactt taccatctga ggccacacat 120ctgctgaaat ggagataatt aacatcacta gaaacagcaa gatgacaata taatgtctaa 180gtagtgacat gtttttgcac atttccagcc cttttaaata tccacacaca caggaagcac 240aaaaggaagc acagagatcc ctgggagaaa tgcccggccg ccatcttggg tcatcgatga 300gcctcgccct gtgcctgntc ccgcttgtga gggaaggaca ttagaaaatg aattgatgtg 360ttccttaaag gatggcagga aaacagatcc tgttgtggat atttatttga acgggattac 420agatttgaaa tgaagtcaca aagtgagcat taccaatgag aggaaaacag acgagaaaat 480cttgatggtt cacaagacat gcaacaaaca aaatggaata ctgtgatgac acgagcagcc 540aactggggag gagataccac ggggcagagg tcaggattct ggccctgctg cctaactgtg 600cgttatacca atcatttcta tttctaccct caaacaagct gtngaatatc tgacttacgg 660ttcttntggc ccacattttc atnatccacc ccntcntttt aannttantc caaantgt 718

<210> 314

<211> 358

<212> DNA

<213> Homo sapien

<400> 314gtttatttac attacagaaa aaacatcaag acaatgtata ctatttcaaa tatatccata 60cataatcaaa tatagctgta gtacatgttt tcattggtgt agattaccac aaatgcaagg 120caacatgtgt agatctcttg tcttattctt ttgtctataa tactgtattg tgtagtccaa 180gctctcggta gtccagccac tgtgaaacat gctcccttta gattaacctc gtggacgctc 240ttgttgtatt gctgaactgt agtgccctgt attttgcttc tgtctgtgaa ttctgttgct 300tctggggcat ttccttgtga tgcagaggac caccacacag atgacagcaa tctgaatt 358

<210> 315

<211> 341

<212> DNA

<213> Homo sapien

<400> 315taccacctcc ccgctggcac tgatgagccg catcaccatg gtcaccagca ccatgaaggc 60ataggtgatg atgaggacat ggaatgggcc cccaaggatg gtctgtccaa agaagcgagt 120gacccccatt ctgaagatgt ctggaacctc taccagcagg atgatgatag ccccaatgac 180agtcaccagc tccccgacca gccggatatc gtccttaggg gtcatgtagg cttcctgaag 240tagcttctgc tgtaagaggg tgttgtcccg ggggctcgtg cggttattgg tcctgggctt 300gagggggcgg tagatgcagc acatggtgaa gcagatgatg t 341

<210> 316

<211> 151

<212> DNA

<213> Homo sapien

<400> 316agactgggca agactcttac gccccacact gcaatttggt cttgttgccg tatccattta 60tgtgggcctt tctcgagttt ctgattataa acaccactgg agcgatgtgt tgactggact 120cattcaggga gctctggttg caatattagt t 151

<210> 317

<211> 151

<212> DNA

<213> Homo sapien

<400> 317agaactagtg gatcctaatg aaatacctga aacatatatt ggcatttatc aatggctcaa 60atcttcattt atctctggcc ttaaccctgg ctcctgaggc tgcggccagc agatcccagg 120ccagggctct gttcttgcca cacctgcttg a 151

<210> 318

<211> 151

<212> DNA

<213> Homo sapien

<400> 318actggtggga ggcgctgttt agttggctgt tttcagaggg gtctttcgga gggacctcct 60gctgcaggct ggagtgtctt tattcctggc gggagaccgc acattccact gctgaggctg 120tgggggcggt ttatcaggca gtgataaaca t 151

<210> 319

<211> 151

<212> DNA

<213> Homo sapien

<400> 319aactagtgga tccagagcta taggtacagt gtgatctcag ctttgcaaac acattttcta 60catagatagt actaggtatt aatagatatg taaagaaaga aatcacacca ttaataatgg 120taagattggg tttatgtgat tttagtgggt a 151

<210> 320

<211> 150

<212> DNA

<213> Homo sapien

<400> 320aactagtgga tccactagtc cagtgtggtg gaattccatt gtgttggggt tctagatcgc 60gagcggctgc cctttttttt tttttttttg ggggggaatt tttttttttt aatagttatt 120gagtgttcta cagcttacag taaataccat 150

<210> 321

<211> 151

<212> DNA

<213> Homo sapien

<400> 321agcaactttg tttttcatcc aggttatttt aggcttagga tttcctctca cactgcagtt 60tagggtggca ttgtaaccag ctatggcata ggtgttaacc aaaggctgag taaacatggg 120tgcctctgag aaatcaaagt cttcatacac t 151

<210> 322

<211> 151

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(151)

<223> n = A,T,C or G

<400> 322atccagcatc ttcctgtt tcttgccttc ctttttcttc ttcttasatt ctgcttgagg 60tttgggcttg gtcagtttgc cacagggctt ggagatggtg acagtcttct ggcattcggc 120attgtgcagg gctcgcttca nacttccagt t 151

<210> 323

<211> 151

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(151)

<223> n = A,T,C or G

<400> 323tgaggacttg tkttcttttt ctttattttt aatcctctta ckttgtaaat atattgccta 60nagactcant tactacccag tttgtggttt twtgggagaa atgtaactgg acagttagct 120gttcaatyaa aaagacactt ancccatgtg g 151

<210> 324

<211> 461

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(461)

<223> n = A,T,C or G

<400> 324acctgtgtgg aatttcagct ttcctcatgc aaaaggattt tgtatccccg gcctacttga 60agaagtggtc agctaaagga atccaggttg ttggttggac tgttaatacc tttgatgaaa 120agagttacta cgaatcccat cttggttcca gctatatcac tgacagcatg gtagaagact 180gcgaacctca cttctagact ttcacggtgg gacgaaacgg gttcagaaac tgccaggggc 240ctcatacagg gatatcaaaa taccctttgt gctacccagg ccctggggaa tcaggtgact 300cacacaaatg caatagttgg tcactgcatt tttacctgaa ccaaagctaa acccggtgtt 360gccaccatgc accatggcat gccagagttc aacactgttg ctcttgaaaa ttgggtctga 420aaaaacgcac aagagcccct gccctgccct agctgangca c 461

<210> 325

<211> 400

<212> DNA

<213> Homo sapien

<400> 325acactgtttc catgttatgt ttctacacat tgctacctca gtgctcctgg aaacttagct 60tttgatgtct ccaagtagtc caccttcatt taactctttg aaactgtatc atctttgcca 120agtaagagtg gtggcctatt tcagctgctt tgacaaaatg actggctcct gacttaacgt 180tctataaatg aatgtgctga agcaaagtgc ccatggtggc ggcgaagaag agaaagatgt 240gttttgtttt ggactctctg tggtcccttc caatgctgtg ggtttccaac caggggaagg 300gtcccttttg cattgccaag tgccataacc atgagcacta cgctaccatg gttctgcctc 360ctggccaagc aggctggttt gcaagaatga aatgaatgat 400

<210> 326

<211> 1215

<212> DNA

<213> Homo sapien

<400> 326ggaggactgc agcccgcact cgcagccctg gcaggcggca ctggtcatgg aaaacgaatt 60gttctgctcg ggcgtcctgg tgcatccgca gtgggtgctg tcagccgcac actgtttcca 120gaactcctac accatcgggc tgggcctgca cagtcttgag gccgaccaag agccagggag 180ccagatggtg gaggccagcc tctccgtacg gcacccagag tacaacagac ccttgctcgc 240taacgacctc atgctcatca agttggacga atccgtgtcc gagtctgaca ccatccggag 300catcagcatt gcttcgcagt gccctaccgc ggggaactct tgcctcgttt ctggctgggg 360tctgctggcg aacggcagaa tgcctaccgt gctgcagtgc gtgaacgtgt cggtggtgtc 420tgaggaggtc tgcagtaagc tctatgaccc gctgtaccac cccagcatgt tctgcgccgg 480cggagggcaa gaccagaagg actcctgcaa cggtgactct ggggggcccc tgatctgcaa 540cgggtacttg cagggccttg tgtctttcgg aaaagccccg tgtggccaag ttggcgtgcc 600aggtgtctac accaacctct gcaaattcac tgagtggata gagaaaaccg tccaggccag 660ttaactctgg ggactgggaa cccatgaaat tgacccccaa atacatcctg cggaaggaat 720tcaggaatat ctgttcccag cccctcctcc ctcaggccca ggagtccagg cccccagccc 780ctcctccctc aaaccaaggg tacagatccc cagcccctcc tccctcagac ccaggagtcc 840agacccccca gcccctcctc cctcagaccc aggagtccag cccctcctcc ctcagaccca 900ggagtccaga ccccccagcc cctcctccct cagacccagg ggtccaggcc cccaacccct 960cctccctcag actcagaggt ccaagccccc aacccctcct tccccagacc cagaggtcca 1020ggtcccagcc cctcctccct cagacccagc ggtccaatgc cacctagact ctccctgtac 1080acagtgcccc cttgtggcac gttgacccaa ccttaccagt tggtttttca ttttttgtcc 1140ctttccccta gatccagaaa taaagtctaa gagaagcgca aaaaaaaaaa aaaaaaaaaa 1200aaaaaaaaaa aaaaa 1215

<210> 327

<211> 220

<212> PRT

<213> Homo sapien

<400> 327Glu Asp Cys Ser Pro His Ser Gln Pro Trp Gln Ala Ala Leu Val Met1 5 10 15Glu Asn Glu Leu Phe Cys Ser Gly Val Leu Val His Pro Gln Trp Val

20 25 30Leu Ser Ala Ala His Cys Phe Gln Asn Ser Tyr Thr Ile Gly Leu Gly

35 40 45Leu His Ser Leu Glu Ala Asp Gln Glu Pro Gly Ser Gln Met Val Glu

50 55 60Ala Ser Leu Ser Val Arg His Pro Glu Tyr Ash Arg Pro Leu Leu Ala65 70 75 80Asn Asp Leu Met Leu Ile Lys Leu Asp Glu Ser Val Ser Glu Ser Asp

85 90 95Thr Ile Arg Ser Ile Ser Ile Ala Ser Gln Cys Pro Thr Ala Gly Asn

100 105 110Ser Cys Leu Val Ser Gly Trp Gly Leu Leu Ala Asn Gly Arg Met Pro

115 120 125Thr Val Leu Gln Cys Val Asn Val Ser Val Val Ser Glu Glu Val Cys

130 135 140Ser Lys Leu Tyr Asp Pro Leu Tyr His Pro Ser Met Phe Cys Ala Gly145 150 155 160Gly Gly Gln Asp Gln Lys Asp Ser Cys Asn Gly Asp Ser Gly Gly Pro

165 170 175Leu Ile Cys Asn Gly Tyr Leu Gln Gly Leu Val Ser Phe Gly Lys Ala

180 185 190Pro Cys Gly Gln Val Gly Val Pro Gly Val Tyr Thr Asn Leu Cys Lys

195 200 205Phe Thr Glu Trp Ile Glu Lys Thr Val Gln Ala Ser

210 215 220

<210> 328

<211> 234

<212> DNA

<213> Homo sapien

<400> 328cgctcgtctc tggtagctgc agccaaatca taaacggcga ggactgcagc ccgcactcgc 60agccctggca ggcggcactg gtcatggaaa acgaattgtt ctgctcgggc gtcctggtgc 120atccgcagtg ggtgctgtca gccacacact gtttccagaa ctcctacacc atcgggctgg 180gcctgcacag tcttgaggcc gaccaagagc cagggagcca gatggtggag gcca 234

<210> 329

<211> 77

<212> PRT

<213> Homo sapien

<400> 329Leu Val Ser Gly Ser Cys Ser Gln Ile Ile Asn Gly Glu Asp Cys Ser1 5 10 15Pro His Ser Gln Pro Trp Gln Ala Ala Leu Val Met Glu Asn Glu Leu

20 25 30Phe Cys Ser Gly Val Leu Val His Pro Gln Trp Val Leu Ser Ala Thr

35 40 45His Cys Phe Gln Asn Ser Tyr Thr Ile Gly Leu Gly Leu His Ser Leu

50 55 60Glu Ala Asp Gln Glu Pro Gly Ser Gln Met Val Glu Ala65 70 75

<210> 330

<211> 70

<212> DNA

<213> Homo sapien

<400> 330cccaacacaa tggcccgatc ccatccctga ctccgccctc aggatcgctc gtctctggta 60gctgcagcca 70

<210> 331

<211> 22

<212> PRT

<213> Homo sapien

<400> 331Gln His Asn Gly Pro Ile Pro Ser Leu Thr Pro Pro Ser Gly Ser Leu1 5 10 15Val Ser Gly Ser Cys Ser

20

<210> 332

<211> 2507

<212> DNA

<213> Homo sapien

<400> 332tggtgccgct gcagccggca gagatggttg agctcatgtt cccgctgttg ctcctccttc 60tgcccttcct tctgtatatg gctgcgcccc aaatcaggaa aatgctgtcc agtggggtgt 120gtacatcaac tgttcagctt cctgggaaag tagttgtggt cacaggagct aatacaggta 180tcgggaagga gacagccaaa gagctggctc agagaggagc tcgagtatat ttagcttgcc 240gggatgtgga aaagggggaa ttggtggcca aagagatcca gaccacgaca gggaaccagc 300aggtgttggt gcggaaactg gacctgtctg atactaagtc tattcgagct tttgctaagg 360gcttcttagc tgaggaaaag cacctccacg ttttgatcaa caatgcagga gtgatgatgt 420gtccgtactc gaagacagca gatggctttg agatgcacat aggagtcaac cacttgggtc 480acttcctcct aacccatctg ctgctagaga aactaaatga atcagcccca tcaaggatag 540taaatgtgtc ttccctcgca catcaccttg gaatgatcca cttccataac ctgcatggct 600agaaattcta caatgcaggc ctggcctact gtcacagcaa gctagccaac atcctcttca 660cccaggaact ggcccggaga ctaaaaggct ctggcgttac gacgtattct gtacaccctg 720gcacagtcca atctgaactg gttcggcact catctttcat gagatggatg tggtggcttt 780tctccttttt catcaagact cctcagcagg gagcccagac cagcctgcac tgtgccttaa 840cagaaggtct tgagattcta agtgggaatc atttcagtga ctgtcatgtg gcatgggtct 900ctgcccaagc tcgtaatgag actatagcaa ggcggctgtg ggacgtcagt tgtgacctgc 960tgggcctccc aatagactaa caggcagtgc cagttggacc caagagaaga ctgcagcaga 1020ctacacagta cttcttgtca aaatgattct ccttcaaggt tttcaaaacc tttagcacaa 1080agagagcaaa accttccagc cttgcctgct tggtgtccag ttaaaactca gtgtactgcc 1140agattcgtct aaatgtctgt catgtccaga tttactttgc ttctgttact gccagagtta 1200ctagagatat cataatagga taagaagacc ctcatatgac ctgcacagct cattttcctt 1260ctgaaagaaa ctactaccta ggagaatcta agctatagca gggatgattt atgcaaattt 1320gaactagctt ctttgttcac aattcagttc ctcccaacca accagtcttc acttcaagag 1380ggccacactg caacctcagc ttaacatgaa taacaaagac tggctcagga gcagggcttg 1440cccaggcatg gtggatcacc ggaggtcagt agttcaagac cagcctggcc aacatggtga 1500aaccccacct ctactaaaaa ttgtgtatat ctttgtgtgt cttcctgttt atgtgtgcca 1560agggagtatt ttcacaaagt tcaaaacagc cacaataatc agagatggag caaaccagtg 1620ccatccagtc tttatgcaaa tgaaatgctg caaagggaag cagattctgt atatgttggt 1680aactacccac caagagcaca tgggtagcag ggaagaagta aaaaaagaga aggagaatac 1740tggaagataa tgcacaaaat gaagggacta gttaaggatt aactagccct ttaaggatta 1800actagttaag gattaatagc aaaagayatt aaatatgcta acatagctat ggaggaattg 1860agggcaagca cccaggactg atgaggtctt aacaaaaacc agtgtggcaa aaaaaaaaaa 1920aaaaaaaaaa aaaaatccta aaaacaaaca aacaaaaaaa acaattcttc attcagaaaa 1980attatcttag ggactgatat tggtaattat ggtcaattta ataatatttt ggggcatttc 2040cttacattgt cttgacaaga ttaaaatgtc tghgccaaaa ttttgtattt tatttggaga 2100cttcttatca aaagtaatgc tgccaaagga agtctaagga attagtagtg ttcccatcac 2160ttgtttggag tgtgctattc taaaagattt tgatttcctg gaatgacaat tatattttaa 2220ctttggtggg ggaaagagtt ataggaccac agtcttcact tctgatactt gtaaattaat 2280cttttattgc acttgttttg accattaagc tatatgttta gaaatggtca ttttacggaa 2340aaattagaaa aattctgata atagtgcaga ataaatgaat taatgtttta cttaatttat 2400attgaactgt caatgacaaa taaaaattct ttttgattat tttttgtttt catttaccag 2460aataaaaacg taagaattaa aagtttgatt acaaaaaaaa aaaaaaa 2507

<210> 333

<211> 3030

<212> DNA

<213> Homo sapien

<400> 333gcaggcgact tgcgagctgg gagcgattta aaacgctttg gattcccccg gcctgggtgg 60ggagagcgag ctgggtgccc cctagattcc ccgcccccgc acctcatgag ccgaccctcg 120gctccatgga gcccggcaat tatgccacct tggatggagc caaggatatc gaaggcttgc 180tgggagcggg aggggggcgg aatctggtcg cccactcccc tctgaccagc cacccagcgg 240cgcctacgct gatgcctgct gtcaactatg cccccttgga tctgccaggc tcggcggagc 300cgccaaagca atgccaccca tgccctgggg tgccccaggg gacgtcccca gctcccgtgc 360cttatggtta ctttggaggc gggtactact cctgccgagt gtcccggagc tcgctgaaac 420cctgtgccca ggcagccacc ctggccgcgt accccgcgga gactcccacg gccggggaag 480agtaccccag ycgccccact gagtttgcct tctatccggg atatccggga acctaccagc 540ctatggccag ttacctggac gtgtctgtgg tgcagactct gggtgctcct ggagaaccgc 600gacatgactc cctgttgcct gtggacagtt accagtcttg ggctctcgct ggtggctgga 660acagccagat gtgttgccag ggagaacaga acccaccagg tcccttttgg aaggcagcat 720ttgcagactc cagcgggcag caccctcctg acgcctgcgc ctttcgtcgc ggccgcaaga 780aacgcattcc gtacagcaag gggcagttgc gggagctgga gcgggagtat gcggctaaca 840agttcatcac caaggacaag aggcgcaaga tctcggcagc caccagcctc tcggagcgcc 900agattaccat ctggtttcag aaccgccggg tcaaagagaa gaaggttctc gccaaggtga 960agaacagcgc taccccttaa gagatctcct tgcctgggtg ggaggagcga aagtgggggt 1020gtcctgggga gaccaggaac ctgccaagcc caggctgggg ccaaggactc tgctgagagg 1080cccctagaga caacaccctt cccaggccac tggctgctgg actgttcctc aggagcggcc 1140tgggtaccca gtatgtgcag ggagacggaa ccccatgtga cagcccactc caccagggtt 1200ccaaagaac ctggcccagt cataatcatt catcctgaca gtggcaataa tcacgataac 1260cagtactagc tgccatgatc gttagcctca tattttctat ctagagctct gtagagcact 1320ttagaaaccg ctttcatgaa ttgagctaat tatgaataaa tttggaaggc gatccctttg 1380cagggaagct ttctctcaga cccccttcca ttacacctct caccctggta acagcaggaa 1440gactgaggag aggggaacgg gcagattcgt tgtgtggctg tgatgtccgt ttagcatttt 1500tctcagctga cagctgggta ggtggacaat tgtagaggct gtctcttcct ccctccttgt 1560ccaccccata gggtgtaccc actggtcttg gaagcaccca tccttaatac gatgattttt 1620ctgtcgtgtg aaaatgaagc cagcaggctg cccctagtca gtccttcctt ccagagaaaa 1680agagatttga gaaagtgcct gggtaattca ccattaattt cctcccccaa actctctgag 1740tcttccctta atatttctgg tggttctgac caaagcaggt catggtttgt tgagcatttg 1800ggatcccagt gaagtagatg tttgtagcct tgcatactta gcccttccca ggcacaaacg 1820gagtggcaga gtggtgccaa ccctgttttc ccagtccacg tagacagatt cacagtgcgg 1920aattctggaa gctggagaca gacgggctct ttgcagagcc gggactctga gagggacatg 1980agggcctctg cctctgtgtt cattctctga tgtcctgtac ctgggctcag tgcccggtgg 2040gactcatctc ctggccgcgc agcaaagcca gcgggttcgt gctggtcctt cctgcacctt 2100aggctggggg tggggggcct gccggcgcat tctccacgat tgagcgcaca ggcctgaagt 2160ctggacaacc cgcagaaccg aagctccgag cagcgggtcg gtggcgagta gtggggtcgg 2220tggcgagcag ttggtggtgg gccgcggccg ccactacctc gaggacattt ccctcccgga 2280gccagctctc ctagaaaccc cgcggcggcc gccgcagcca agtgtttatg gcccgcggtc 2340gggtgggatc ctagccctgt ctcctctcct gggaaggagt gagggtggga cgtgacttag 2400acacctacaa atctatttac caaagaggag cccgggactg agggaaaagg ccaaagagtg 2460tgagtgcatg cggactgggg gttcagggga agaggacgag gaggaggaag atgaggtcga 2520tttcctgatt taaaaaatcg tccaagcccc gtggtccagc ttaaggtcct cggttacatg 2580cgccgctcag agcaggtcac tttctgcctt ccacgtcctc cttcaaggaa gccccatgtg 2640ggtagctttc aatatcgcag gttcttactc ctctgcctct ataagctcaa acccaccaac 2700gatcgggcaa gtaaaccccc tccctcgccg acttcggaac tggcgagagt tcagcgcaga 2760tgggcctgtg gggagggggc aagatagatg agggggagcg gcatggtgcg gggtgacccc 2820ttggagagag gaaaaaggcc acaagagggg ctgccaccgc cactaacgga gatggccctg 2880gtagagacct ttgggggtct ggaacctctg gactccccat gctctaactc ccacactctg 2940ctatcagaaa cttaaacttg aggattttct ctgtttttca ctcgcaataa aytcagagca 3000aacaaaaaaa aaaaaaaaaa aaaactcgag 3030

<210> 334

<211> 2417

<212> DNA

<213> Homo sapien

<400> 334ggcggccgct ctagagctag tgggatcccc cgggctgcac gaattcggca cgagtgagtt 60ggagttttac ctgtattgtt ttaatttcaa caagcctgag gactagccac aaatgtaccc 120agtttacaaa tgaggaaaca ggtgcaaaaa ggttgttacc tgtcaaaggt cgtatgtggc 180agagccaaga tttgagccca gttatgtctg atgaacttag cctatgctct ttaaacttct 240gaatgctgac cattgaggat atctaaactt agatcaattg cattttccct ccaagactat 300ttacttatca atacaataat accaccttta ccaatctatt gttttgatac gagactcaaa 360tatgccagat atatgtaaaa gcaacctaca agctctctaa tcatgctcac ctaaaagatt 420cccgggatct aataggctca aagaaacttc ttctagaaat ataaaagaga aaattggatt 480atgcaaaaat tcattattaa tttttttcat ccatccttta attcagcaaa catttatctg 540ttgttgactt tatgcagtat ggccttttaa ggattggggg acaggtgaag aacggggtgc 600cagaatgcat cctcctacta atgaggtcag tacacatttg cattttaaaa tgccctgtcc 660agctgggcat ggtggatcat gcctgtaatc tcaacattgg aaggccaagg caggaggatt 720gcttcagccc aggagttcaa gaccagcctg ggcaacatag aaagacccca tctctcaatc 780aatcaatcaa tgccctgtct ttgaaaataa aactctttaa gaaaggttta atgggcaggg 840tgtggtagct catgcctata atacagcact ttgggaggct gaggcaggag gatcacttta 900gcccagaagt tcaagaccag cctgggcaac aagtgacacc tcatctcaat tttttaataa 960aatgaataca tacataagga aagataaaaa gaaaagttta atgaaagaat acagtataaa 1020acaaatctct tggacctaaa agtatttttg ttcaagccaa atattgtgaa tcacctctct 1080gtgttgagga tacagaatat ctaagcccag gaaactgagc agaaagttca tgtactaact 1140aatcaacccg aggcaaggca aaaatgagac taactaatca atccgaggca aggggcaaat 1200tagacggaac ctgactctgg tctattaagc gacaactttc cctctgttgt atttttcttt 1260tattcaatgt aaaaggataa aaactctcta aaactaaaaa caatgtttgt caggagttac 1320aaaccatgac caactaatta tggggaatca taaaatatga ctgtatgaga tcttgatggt 1380ttacaaagtg tacccactgt taatcacttt aaacattaat gaacttaaaa atgaatttac 1440ggagattgga atgtttcttt cctgttgtat tagttggctc aggctgccat aacaaaatac 1500cacagactgg gaggcttaag taacagaaat tcatttctca cagttctggg ggctggaagt 1560ccacgatcaa ggtgcaggaa aggcaggctt cattctgagg cccctctctt ggctcacatg 1620tggccaccct cccactgcgt gctcacatga cctctttgtg ctcctggaaa gagggtgtgg 1680gggacagagg gaaagagaag gagagggaac tctctggtgt ctcgtctttc aaggacccta 1740acctgggcca ctttggccca ggcactgtgg ggtggggggt tgtggctgct ctgctctgag 1800tggccaagat aaagcaacag aaaaatgtcc aaagctgtgc agcaaagaca agccaccgaa 1860cagggatctg ctcatcagtg tggggacctc caagtcggcc accctggagg caagccccca 1920cagagcccat gcaaggtggc agcagcagaa gaagggaatt gtccctgtcc ttggcacatt 1980cctcaccgac ctggtgatgc tggacactgc gatgaatggt aatgtggatg agaatatgat 2040ggactcccag aaaaggagac ccagctgctc aggtggctgc aaatcattac agccttcatc 2100ctggggagga actgggggcc tggttctggg tcagagagca gcccagtgag ggtgagagct 2160acagcctgtc ctgccagctg gatccccagt cccggtcaac cagtaatcaa ggctgagcag 2220atcaggcttc ccggagctgg tcttgggaag ccagccctgg ggtgagttgg ctcctgctgt 2280ggtactgaga caatattgtc ataaattcaa tgcgcccttg tatccctttt tcttttttat 2340ctgtctacat ctataatcac tatgcatact agtctttgtt agtgtttcta ttcmacttaa 2400tagagatatg ttatact 2417

<210> 335

<211> 2984

<212> DNA

<213> Homo sapien

<400> 335atccctcctt ccccactctc ctttccagaa ggcacttggg gtcttatctg ttggactctg 60aaaacacttc aggcgccctt ccaaggcttc cccaaacccc taagcagccg cagaagcgct 120cccgagctgc cttctcccac actcaggtga tcgagttgga gaggaagttc agccatcaga 180agtacctgtc ggcccctgaa cgggcccacc tggccaagaa cctcaagctc acggagaccc 240aagtgaagat atggttccag aacagacgct ataagactaa gcgaaagcag ctctcctcgg 300agctgggaga cttggagaag cactcctctt tgccggccct gaaagaggag gccttctccc 360ggcctccct ggtctccgtg tataacagct atccttacta cccatacctg tactgcgtgg 420gcagctggag cccagctttt tggtaatgcc agctcaggtg acaaccatta tgatcaaaaa 480ctgccttccc cagggtgtct ctatgaaaag cacaaggggc caaggtcagg gagcaagagg 540tgtgcacacc aaagctattg gagatttgcg tggaaatctc asattcttca ctggtgagac 600aatgaaacaa cagagacagt gaaagtttta atacctaagt cattccccca gtgcatactg 660taggtcattt tttttgcttc tggctacctg tttgaagggg agagagggaa aatcaagtgg 720tattttccag cactttgtat gattttggat gagctgtaca cccaaggatt ctgttctgca 780actccatcct cctgtgtcac tgaatatcaa ctctgaaaga gcaaacctaa caggagaaag 840gacaaccagg atgaggatgt caccaactga attaaactta agtccagaag cctcctgttg 900gccttggaat atggccaagg ctctctctgt ccctgtaaaa gagaggggca aatagagagt 960ctccaagaga acgccctcat gctcagcaca tatttgcatg ggagggggag atgggtggga 1020ggagatgaaa atatcagctt ttcttattcc tttttattcc ttttaaaatg gtatgccaac 1080ttaagtattt acagggtggc ccaaatagaa caagatgcac tcgctgtgat tttaagacaa 1140gctgtataaa cagaactcca ctgcaagagg gggggccggg ccaggagaat ctccgcttgt 1200ccaagacagg ggcctaagga gggtctccac actgctgcta ggggctgttg cattttttta 1260ttagtagaaa gtggaaaggc ctcttctcaa cttttttccc ttgggctgga gaatttagaa 1320tcagaagttt cctggagttt tcaggctatc atatatactg tatcctgaaa ggcaacataa 1380ttcttccttc cctcctttta aaattttgtg ttcctttttg cagcaattac tcactaaagg 1440gcttcatttt agtccagatt tttagtctgg ctgcacctaa cttatgcctc gcttatttag 1500cccgagatct ggtctttttt tttttttttt tttttccgtc tccccaaagc tttatctgtc 1560ttgacttttt aaaaaagttt gggggcagat tctgaattgg ctaaaagaca tgcattttta 1620aaactagcaa ctcttatttc tttcctttaa aaatacatag cattaaatcc caaatcctat 1680ttaaagacct gacagcttga gaaggtcact actgcattta taggaccttc tggtggttct 1740gctgttacgt ttgaagtctg acaatccttg agaatctttg catgcagagg aggtaagagg 1800tattggattt tcacagagga agaacacagc gcagaatgaa gggccaggct tactgagctg 1860tccagtggag ggctcatggg tgggacatgg aaaagaaggc agcctaggcc ctggggagcc 1920cagtccactg agcaagcaag ggactgagtg agccttttgc aggaaaaggc taagaaaaag 1980gaaaaccatt ctaaaacaca acaagaaact gtccaaatgc tttgggaact gtgtttattg 2040cctataatgg gtccccaaaa thggtaacct agacttcaga gagaatgagc agagagcaaa 2100ggagaaatct ggctgtcctt ccattttcat tctgttatct caggtgagct ggtagagggg 2160agacattaga aaaaaatgaa acaacaaaac aattactaat gaggtacgct gaggcctggg 2220agtctcttga ctccactact taattccgtt tagtgagaaa cctttcaatt ttcttttatt 2280agaagggcca gcttactgtt ggtggcaaaattgccaacataagttaatag aaagttggcc 2340aatttcaccc cattttctgt ggtttgggct ccacattgca atgttcaatg ccacgtgctg 2400ctgacaccga ccggagtact agccagcaca aaaggcaggg tagcctgaat tgctttctgc 2460tctttacatt tcttttaaaa taagcattta gtgctcagtc cctactgagt actctttctc 2520tcccctcctc tgaatttaat tctttcaact tgcaatttgc aaggattaca catttcactg 2580tgatgtatat tgtgttgcaa aaaaaaaaaa aagtgtcttt gtttaaaatt acttggtttg 2640tgaatccatc ttgctttttc cccattggaa ctagtcatta acccatctct gaactggtag 2700aaaaacatct gaagagctag tctatcagca tctgacaggt gaattggatg gttctcagaa 2760ccatttcacc cagacagcct gtttctatcc tgtttaataa attagtttgg gttctctaca 2820tgcataacaa accctgctcc aatctgtcac ataaaagtct gtgacttgaa gtttagtcag 2880cacccccacc aaactttatt tttctatgtg ttttttgcaa catatgagtg ttttgaaaat 2940aaagtaccca tgtctttatt agaaaaaaaa aaaaaaaaaa aaaa 2984

<210> 336

<211> 147

<212> PRT

<213> Homo sapien

<400> 336Pro Ser Phe Pro Thr Leu Leu Ser Arg Arg His Leu Gly Ser Tyr Leu1 5 10 15Leu Asp Ser Glu Asn Thr Ser Gly Ala Leu Pro Arg Leu Pro Gln Thr

20 25 30Pro Lys Gln Pro Gln Lys Arg Ser Arg Ala Ala Phe Ser His Thr Gln

35 40 45val Ile Glu Leu Glu Arg Lys Phe Ser His Gln Lys Tyr Leu Ser Ala

50 55 60Pro Glu Arg Ala His Leu Ala Lys Asn Leu Lys Leu Thr Glu Thr Gln65 70 75 80 Val Lys Ile Trp Phe Gln Asn Arg Arg Tyr Lys Thr Lys Arg Lys Gln

85 90 95Leu Ser Ser Glu Leu Gly Asp Leu Glu Lys His Ser Ser Leu Pro Ala

100 105 110Leu Lys Glu Glu Ala Phe Ser Arg Ala Ser Leu Val Ser Val Tyr Asn

115 120 125Ser Tyr Pro Tyr Tyr Pro Tyr Leu Tyr Cys Val Gly Ser Trp Ser Pro

130 135 140Ala Phe Trp145

<210> 337

<211> 9

<212> PRT

<213> Homo sapien

<400> 337Ala Leu Thr Gly Phe Thr Phe Ser Ala1 5

<210> 338

<211> 9

<212> PRT

<213> Homo sapien

<400> 338Leu Leu Ala Asn Asp Leu Met Leu Ile1 5

<210> 339

<211> 318

<212> PRT

<213> Homo sapien

<400> 339Met Val Glu Leu Met Phe Pro Leu Leu Leu Leu Leu Leu Pro Phe Leu1 5 10 15Leu Tyr Met Ala Ala Pro Gln Ile Arg Lys Met Leu Ser Ser Gly Val

20 25 30Cys Thr Ser Thr Val Gln Leu Pro Gly Lys Val Val Val Val Thr Gly

35 40 45Ala Asn Thr Gly Ile Gly Lys Glu Thr Ala Lys Glu Leu Ala Gln Arg

50 55 60Gly Ala Arg Val Tyr Leu Ala Cys Arg Asp Val Glu Lys Gly Glu Leu65 70 75 80Val Ala Lys Glu Ile Gln Thr Thr Thr Gly Asn Gln Gln Val Leu Val

85 90 95Arg Lys Leu Asp Leu Ser Asp Thr Lys Ser Ile Arg Ala Phe Ala Lys

100 105 110Gly Phe Leu Ala Glu Glu Lys His Leu His Val Leu Ile Asn Asn Ala

115 120 125Gly Val Met Met Cys Pro Tyr Ser Lys Thr Ala Asp Gly Phe Glu Met

130 135 140His Ile Gly Val Asn His Leu Gly His Phe Leu Leu Thr His Leu Leu145 150 155 160Leu Glu Lys Leu Lys Glu Ser Ala Pro Ser Arg Ile Val Asn Val Ser

165 170 175Ser Leu Ala His His Leu Gly Arg Ile His Phe His Asn Leu Gln Gly

180 185 190Glu Lys Phe Tyr Asn Ala Gly Leu Ala Tyr Cys His Ser Lys Leu Ala

195 200 205Asn Ile Leu Phe Thr Gln Glu Leu Ala Arg Arg Leu Lys Gly Ser Gly

210 215 220Val Thr Thr Tyr Ser Val His Pro Gly Thr Val Gln Ser Glu Leu Val225 230 235 240Arg His Ser Ser Phe Met Arg Trp Met Trp Trp Leu Phe Ser Phe Phe

245 250 255Ile Lys Thr Pro Gln Gln Gly Ala Gln Thr Ser Leu His Cys Ala Leu

260 265 270Thr Glu Gly Leu Glu Ile Leu Ser Gly Asn His Phe Ser Asp Cys His

275 280 285Val Ala Trp Val Ser Ala Gln Ala Arg Asn Glu Thr Ile Ala Arg Arg

290 295 300Leu Trp Asp Val Ser Cys Asp Leu Leu Gly Leu Pro Ile Asp305 310 315

<210> 340

<211> 483

<212> DNA

<213> Homo sapien

<400> 340gccgaggtct gccttcacac ggaggacacg agactgcttc ctcaagggct cctgcctgcc 60tggacactgg tgggaggcgc tgtttagttg gctgttttca gaggggtctt tcggagggac 120ctcctgctgc aggctggagt gtctttattc ctggcgggag accgcacatt ccactgctga 180ggttgtgggg gcggtttatc aggcagtgat aaacataaga tgtcatttcc ttgactccgg 240ccttcaattt tctctttggc tgacgacgga gtccgtggtg tcccgatgta actgacccct 300gctccaaacg tgacatcact gatgctcttc tcgggggtgc tgatggcccg cttggtcacg 360tgctcaatct cgccattcga ctcttgctcc aaactgtatg aagacacctg actgcacgtt 420ttttctgggc ttccagaatt taaagtgaaa ggcagcactc ctaagctccg actccgatgc 480ctg 483

<210> 341

<211> 344

<212> DNA

<213> Homo sapien

<400> 341ctgctgctga gtcacagatt tcattataaa tagcctccct aaggaaaata cactgaatgc 60tatttttact aaccattcta tttttataga aatagctgag agtttctaaa ccaactctct 120gctgccttac aagtattaaa tattttactt ctttccataa agagtagctc aaaatatgca 180attaatttaa taatttctga tgatggtttt atctgcagta atatgtatat catctattag 240aatttactta atgaaaaact gaagagaaca aaatttgtaa ccactagcac ttaagtactc 300ctgattctta acattgtctt taatgaccac aagacaacca acag 344

<210> 342

<211> 592

<212> DNA

<213> Homo sapien

<400> 342acagcaaaaa agaaactgag aagcccaaty tgctttcttg ttaacatcca cttatccaac 60caatgtggaa acttcttata cttggttcca ttatgaagtt ggacaattgc tgctatcaca 120cctggcaggt aaaccaatgc caagagagtg atggaaacca ttggcaagac tttgttgatg 180accaggattg gaattttata aaaatattgt tgatgggaag ttgctaaagg gtgaattact 240tccctcagaa gagtgtaaag aaaagtcaga gatgctataa tagcagctat tttaattggc 300aagtgccact gtggaaagag ttcctgtgtg tgctgaagtt ctgaagggca gtcaaattca 360tcagcatggg ctgtttggtg caaatgcaaa agcacaggtc tttttagcat gctggtctct 420cccgtggcct tatgcaaata atcgtcttct tctaaatttc tcctaggctt cattttccaa 480agttcttctt ggtttgtgat gtcttttctg ctttccatta attctataaa atagtatggc 540ttcagccacc cactcttcgc cttagcttga ccgtgagtct cggctgccgc tg 592

<210> 343

<211> 382

<212> DNA

<213> Homo sapien

<400> 343ttcttgacct cctcctcctt caagctcaaa caccacctcc cttattcagg accggcactt 60cttaatgttt gtggctttct ctccagcctc tcttaggagg ggtaatggtg gagttggcat 120cttgtaactc tcctttctcc tttcttcccc tttctctgcc cgcctttccc atcctgctgt 180agacttcttg attgtcagtc tgtgtcacat ccagtgattg ttttggtttc tgttcccttt 240ctgactgccc aaggggctca gaaccccagc aatcccttcc tttcactacc ttcttttttg 300ggggtagttg gaagggactg aaattgtggg gggaaggtag gaggcacatc aataaagagg 360aaaccaccaa gctgaaaaaa aa 382

<210> 344

<211> 536

<212> DNA

<213> Homo sapien

<400> 344ctgggcctga agctgtaggg taaatcagag gcaggcttct gagtgatgag agtcctgaga 60caataggcca cataaacttg gctggatgga acctcacaat aaggtggtca cctcttgttt 120gtttaggggg atgccaagga taaggccagc tcagttatat gaagagaagc agaacaaaca 180agtctttcag agaaatggat gcaatcagag tgggatcccg gtcacatcaa ggtcacactc 240caccttcatg tgcctgaatg gttgccaggt cagaaaaatc caccccttac gagtgcggct 300tcgaccctat atcccccgcc cgcgtccctt tctccataaa attcttctta gtagctatta 360ccttcttatt atttgatcta gaaattgccc tccttttacc cctaccatga gccctacaaa 420caactaacct gccactaata gttatgtcat ccctcttatt aatcatcatc ctagccctaa 480gtctggccta tgagtgacta caaaaaggat tagactgagc cgaataacaa aaaaaa 536

<210> 345

<211> 251

<212> DNA

<213> Homo sapien

<400> 345accttttgag gtctctctca ccacctccac agccaccgtc accgtgggat gtgctggatg 60tgaatgaagc ccccatcttt gtgcctcctg aaaagagagt ggaagtgtcc gaggactttg 120gcgtgggcca ggaaatcaca tcctacactg cccaggagcc agacacattt atggaacaga 180aaataacata tcggatttgg agagacactg ccaactggct ggagattaat ccggacactg 240gtgccatttc c 251

<210> 346

<211> 282

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(282)

<223> n = A,T,C or G<400> 346cgcgtctctg acactgtgat catgacaggg gttcaaacag aaagtgcctg ggccctcctt 60ctaagtcttg ttaccaaaaa aaggaaaaag aaaagatctt ctcagttaca aattctggga 120agggagacta tacctggctc ttgccctaag tgagaggtct tccctcccgc accaaaaaat 180agaaaggctt tctatttcac tggcccaggt agggggaagg agagtaactt tgagtctgtg 240ggtctcattt cccaaggtgc cttcaatgct catnaaaacc aa 282

<210> 347

<211> 201

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1) ... (201)

<223> n = A,T,C or G

<400> 347acacacataa tattataaaa tgccatctaa ttggaaggag ctttctatca ttgcaagtca 60taaatataac ttttaaaana ntactancag cttttaccta ngctcctaaa tgcttgtaaa 120tctgagactg actggaccca cccagaccca gggcaaagat acatgttacc atatcatctt 180tataaagaat ttttttttgt c 201

<210> 348

<211> 251

<212> DNA

<213> Homo sapien

<400> 348ctgttaatca caacatttgt gcatcacttg tgccaagtga gaaaatgttc taaaatcaca 60agagagaaca gtgccagaat gaaactgacc ctaagtccca ggtgcccctg ggcaggcaga 120aggagacact cccagcatgg aggagggttt atcttttcat cctaggtcag gtctacaatg 180ggggaaggtt ttattataga actcccaaca gcccacctca ctcctgccac ccacccgatg 240gccctgcctc c 251

<210> 349

<211> 251

<212> DNA

<213> Homo sapien

<400> 349taaaaatcaa gccatttaat tgtatctttg aaggtaaaca atatatggga gctggatcac 60aacccctgag gatgccagag ctatgggtcc agaacatggt gtggtattat caacagagtt 120cagaagggtc tgaactctac gtgttaccag agaacataat gcaattcatg cattccactt 180agcaattttg taaaatacca gaaacagacc ccaagagtct ttcaagatga ggaaaattca 240actcctggtt t 251

<210> 350

<211> 908

<212> DNA

<213> Homo sapien

<400> 350ctggacactt tgcgagggct tttgctggct gctgctgctg cccgtcatgc tactcatcgt 60agcccgcccg gtgaagctcg ctgctttccc tacctcctta agtgactgcc aaacgcccac 120cggctggaat tgctctggtt atgatgacag agaaaatgat ctcttcctct gtgacaccaa 180cacctgtaaa tttgatgggg aatgtttaagaattggagac actgtgactt gcgtctgtca 240gttcaagtgc aacaatgact atgtgcctgt gtgtggctcc aatggggaga gctaccagaa 300tgagtgttac ctgcgacagg ctgcatgcaa acagcagagt gagatacttg tggtgtcaga 360aggatcatgt gccacagtcc atgaaggctc tggagaaact agtcaaaagg agacatccac 420ctgtgatatt tgccagtttg gtgcagaatg tgacgaagat gccgaggatg tctggtgtgt 480gtgtaatatt gactgttctc aaaccaactt caatcccctc tgcgcttctg atgggaaatc 540ttatgataat gcatgccaaa tcaaagaagc atcgtgtcag aaacaggaga aaattgaagt 600catgtctttg ggtcgatgtc aagataacac aactacaact actaagtctg aagatgggca 660ttatgcaaga acagattatg cagagaatgc taacaaatta gaagaaagtg ccagagaaca 720ccacatacct tgtccggaac attacaatgg cttctgcatg catgggaagt gtgagcattc 780tatcaatatg caggagccat cttgcaggtg tgatgctggt tatactggac aacactgtga 840aaaaaaggac tacagtgttc tatacgttgt tcccggtcct gtacgatttc agtatgtctt 900aatcgcag 908

<210> 351

<211> 472

<212> DNA

<213> Homo sapien

<400> 351ccagttattt gcaagtggta agagcctatt taccataaat aatactaaga accaactcaa 60gtcaaacctt aatgccattg ttattgtgaa ttaggattaa gtagtaattt tcaaaattca 120cattaacttg attttaaaat cagwtttgyg agtcatttac cacaagctaa atgtgtacac 180tatgataaaa acaaccattg tattcctgtt tttctaaaca gtcctaattt ctaacactgt 240atatatcctt cgacatcaat gaactttgtt ttcttttact ccagtaataa agtaggcaca 300gatctgtcca caacaaactt gccctctcat gccttgcctc tcaccatgct ctgctccagg 360tcagccccct tttggcctgt ttgttttgtc aaaaacctaa tctgcttctt gcttttcttg 420gtaatatata tttagggaag atgttgcttt gcccacacac gaagcaaagt aa 472

<210> 352

<211> 251

<212> DNA

<213> Homo sapien

<400> 352ctcaaagcta atctctcggg aatcaaacca gaaaagggca aggatcttag gcatggtgga 60tgtggataag gccaggtcaa tggctgcaag catgcagaga aagaggtaca tcggagcgtg 120caggctgcgt tccgtcctta cgatgaagac cacgatgcag tttccaaaca ttgccactac 180atacatggaa aggaggggga agccaaccca gaaatgggct ttctctaatc ctgggatacc 240aataagcaca a 251

<210> 353

<211> 436

<212> DNA

<213> Homo sapien

<400> 353tttttttttt tttttttttt ttttttacaa caatgcagtc atttatttat tgagtatgtg 60cacattatgg tattattact atactgatta tatttatcat gtgacttcta attaraaaat 120gtatccaaaa gcaaaacagc agatatacaa aattaaagag acagaagata gacattaaca 180gataaggcaa cttatacatt gacaatccaa atccaataca tttaaacatt tgggaaatga 240gggggacaaa tggaagccar atcaaatttg tgtaaaacta ttcagtatgt ttcccttgct 300tcatgtctga raaggctctc ccttcaatgg ggatgacaaa ctccaaatgc cacacaaatg 360ttaacagaat actagattca cactggaacg ggggtaaaga agaaattatt ttctataaaa 420gggctcctaa tgtagt 436

<210> 354

<211> 854

<212> DNA

<213> Homo sapien

<400> 354ccttttctag ttcaccagtt ttctgcaagg atgctggtta gggagtgtct gcaggaggag 60caagtctgaa accaaatcta ggaaacatag gaaacgagcc aggcacaggg ctggtgggcc 120atcagggacc accctttggg ttgatatttt gcttaatctg catcttttga gtaagatcat 180ctggcagtag aagctgttct ccaggtacat ttctctagct catgtacaaa aacatcctga 240aggactttgt caggtgcctt gctaaaagcc agatgcgttc ggcacttcct tggtctgagg 300ttaattgcac acctacaggc actgggctca tgctttcaag tattttgtcc tcactttagg 360gtgagtgaaa gatccccatt ataggagcac ttgggagaga tcatataaaa gctgactctt 420gagtacatgc agtaatgggg tagatgtgtg tggtgtgtct tcattcctgc aagggtgctt 480gttagggagt gtttccagga ggaacaagtc tgaaaccaat catgaaataa atggtaggtg 540tgaactggaa aactaattca aaagagagat cgtgatatca gtgtggttga tacaccttgg 600caatatggaa ggctctaatt tgcccatatt tgaaataata attcagcttt ttgtaataca 560aaataacaaa ggattgagaa tcatggtgtc taatgtataa aagacccagg aaacataaat 720atatcaactg cataaatgta aaatgcatgt gacccaagaa ggccccaaag tggcagacaa 780cattgtaccc attttccctt ccaaaatgtg agcggcgggc ctgctgcttt caaggctgtc 840acacgggatg tcag 854

<210> 355

<211> 676

<212> DNA

<213> Homo sapien

<400> 355gaaattaagt atgagctaaa ttccctgtta aaacctctag gggtgacaga tctcttcaac 60caggtcaaag ctgatctttc tggaatgtca ccaaccaagg gcctatattt atcaaaagcc 120atccacaagt catacctgga tgtcagcgaa gagggcacgg aggcagcagc agccactggg 180gacagcatcg ctgtaaaaag cctaccaatg agagctcagt tcaaggcgaa ccaccccttc 240ctgttcttta taaggcacac tcataccaac acgatcctat tctgtggcaa gcttgcctct 300ccctaatcag atggggttga gtaaggctca gagttgcaga tgaggtgcag agacaatcct 360gtgactttcc cacggccaaa aagctgttca cacctcacgc acctctgtgc ctcagtttgc 420tcatctgcaa aataggtcta ggatttcttc caaccatttc atgagttgtg aagctaaggc 480tttgttaatc atggaaaaag gtagacttat gcagaaagcc tttctggctt tcttatctgt 540ggtgtctcat ttgagtgctg tccagtgaca tgatcaagtc aatgagtaaa attttaaggg 600attagatttt cttgacttgt atgtatctgt gagatcttga ataagtgacc tgacatctct 660gcttaaagaa aaccag 676

<210> 356

<211> 574

<212> DNA

<213> Homo sapien

<400> 356tttttttttt tttttcagga aaacattctc ttactttatt tgcatctcag caaaggttct 60catgtggcac ctgactggca tcaaaccaaa gttcgtaggc caacaaagat gggccactca 120caagcttccc atttgtagat ctcagtgcct atgagtatct gacacctgtt cctctcttca 180gtctcttagg gaggcttaaa tctgtctcag gtgtgctaag agtgccagcc caaggkggtc 240aaaagtccac aaaactgcag tctttgctgg gatagtaagc caagcagtgc ctggacagca 300gagttctttt cttgggcaac agataaccag acaggactct aatcgtgctc ttattcaaca 360ttcttctgtc tctgcctaga ctggaataaa aagccaatct ctctcgtggc acagggaagg 420agatacaagc tcgtttacat gtgatagatc taacaaaggc atctaccgaa gtctggtctg 480gatagacggc acagggagct cttaggtcag cgctgctggt tggaggacat tcctgagtcc 540agctttgcag cctttgtgca acagtacttt ccca 574

<210> 357

<211> 393

<212> DNA

<213> Homo sapien

<400> 357tttttttttt tttttttttt tttttttttt tacagaatat aratgcttta tcactgkact 60taatatggkg kcttgttcac tatacttaaa aatgcaccac tcataaatat ttaattcagc 120aagccacaac caaracttga ttttatcaac aaaaacccct aaatataaac ggsaaaaaag 180atagatataa ttattccagt ttttttaaaa cttaaaarat attccattgc cgaattaara 240araarataag tgttatatgg aaagaagggc attcaagcac actaaaraaa cctgaggkaa 300gcataatctg tacaaaatta aactgtcctt tttggcattt taacaaattt gcaacgktct 360tttttttctt tttctgtttt tttttttttt tac 393

<210> 358

<211> 630

<212> DNA

<213> Homo sapien

<400> 358acagggtaaa caggaggatc cttgctctca cggagcttac attctagcag gaggacaata 60ttaatgttta taggaaaatg atgagtttat gacaaaggaa gtagatagtg ttttacaaga 120gcatagagta gggaagctaa tccagcacag ggaggtcaca gagacatccc taaggaagtg 180gagtttaaac tgagagaagc aagtgcttaa actgaaggat gtgttgaaga agaagggaga 240gtagaacaat ttgggcagag ggaaccttat agaccctaag gtgggaaggt tcaaagaact 300gaaagagagc tagaacagct ggagccgttc tccggtgtaa agaggagtca aagagataag 360attaaagatg tgaagattaa gatcttggtg gcattcaggg attggcactt ctacaagaaa 420tcactgaagg gagtaatgtg acattacttt tcacttcagg atggccattc taactccagg 480gggtagactg gactaggtaa gactggaggc aggtagacct cttctaaggc ctgcgatagt 540gaaagacaaa aataagtggg gaaattcagg ggatagtgaa aatcagtagg acttaatgag 600caagccagag gttcctccac aacaaccagt 630

<210> 359

<211> 620

<212> DNA

<213> Homo sapien

<400> 359acagcattcc aaaatataca tctagagact aarrgtaaat gctctatagt gaagaagtaa 60taattaaaaa atgctactaa tatagaaaat ttataatcag aaaaataaat attcagggag 120ctcaccagaa gaataaagth ctctgccagt tattaaagga ttactgctgg tgaattaaat 180atggcattcc ccaagggaaa tagagagatt cttctggatt atgttcaata tttatttcac 240aggattaact gttttaggaa cagatataaa gcttcgccac ggaagagatg gacaaagcac 300aaagacaaca tgatacctta ggaagcaaca ctaccctttc aggcataaaa tttggagaaa 360tgcaacatta tgcttcatga ataatatgta gaaagaaggt ctgatgaaaa tgacatcctt 420aatgtaagat aactttataa gaattctggg tcaaataaaa ttctttgaag aaaacatcca 480aatgtcattg acttatcaaa tactatcttg gcatataacc tatgaaggca aaactaaaca 540aacaaaaagc tcacaccaaa caaaaccatc aacttatttt gtattctata acatacgaga 600ctgtaaagat gtgacagtgt 620

<210> 360

<211> 431

<212> DNA

<213> Homo sapien

<400> 360aaaaaaaaaa agccagaaca acatgtgata gataatatga ttggctgcac acttccagac 60tgatgaatga tgaacgtgat ggactattgt atggagcaca tcttcagcaa gagggggaaa 120tactcatcat ttttggccag cagttgtttg atcaccaaac atcatgccag aatactcagc 180aaaccttctt agctcttgag aagtcaaagt ccgggggaat ttattcctgg caattttaat 240tggactcctt atgtgagagc agcggctacc cagctggggt ggtggagcga acccgtcact 300agtggacatg cagtggcaga gctcctggta accacctaga ggaatacaca ggcacatgtg 360tgatgccaag cgtgacacct gtagcactca aatttgtctt gtttttgtct ttcggtgtgt 420agattcttag t 431

<210> 361

<211> 351

<212> DNA

<213> Homo sapien

<400> 361acactgattt ccgatcaaaa gaatcatcat ctttaccttg acttttcagg gaattactga 60actttcttct cagaagatag ggcacagcca ttgccttggc ctcacttgaa gggtctgcat 120ttgggtcctc tggtctcttg ccaagtttcc cagccactcg agggagaaat atcgggaggt 180ttgacttcct ccggggcttt cccgagggct tcaccgtgag ccctgcggcc ctcagggctg 240caatcctgga ttcaatgtct gaaacctcgc tctctgcctg ctggacttct gaggccgtca 300ctgccactct gtcctccagc tctgacagct cctcatctgt ggtcctgttg t 351

<210> 362

<211> 463

<212> DNA

<213> Homo sapien

<400> 362acttcatcag gccataatgg gtgcctcccg tgagaatcca agcacctttg gactgcgcga 60tgtagatgag ccggctgaag atcttgcgca tgcgcggctt cagggcgaag ttcttggcgc 120ccccggtcac agaaatgacc aggttgggtg ttttcaggtg ccagtgctgg gtcagcagct 180cgtaaaggat ttccgcgtcc gtgtcgcagg acagacgtat atacttccct ttcttcccca 240gtgtctcaaa ctgaatatcc ccaaaggcgt cggtaggaaa ttccttggtg tgtttcttgt 300agttccattt ctcactttgg ttgatctggg tgccttccat gtgctggctc tgggcatagc 360cacacttgca cacattctcc ctgataagca cgatggtgtg gacaggaagg aaggatttca 420ttgagcctgc ttatggaaac tggtattgtt agcttaaata gac 463

<210> 363

<211> 653

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(653)

<223> n = A,T,C or G

<400> 363acccccgagt ncctgnctgg catactgnga acgaccaacg acacacccaa gctcggcctc 60ctcttggnga ttctgggtga catcttcatg aatggcaacc gtgccagwga ggctgtcctc 120tgggaggcac tacgcaagat gggactgcgtcctggggtga gacatcctct ccttggagat 180ctaacgaaac ttctcaccta tgagttgtaa agcagaaata cctgnactac agacgagtgc 240ccaacagcaa ccccccggaa gtatgagttc ctctrgggcc tccgttccta ccatgagasc 300tagcaagatg naagtgttga gantcattgc agaggttcag aaaagagacc cntcgtgact 360ggtctgcaca gttcatggag gctgcagatg aggccttgga tgctctggat gctgctgcag 420ctgaggccga agcccgggct gaagcaagaa cccgcatggg aattggagat gaggctgtgt 480ntgggccctg gagctgggat gacattgagt ttgagctgct gacctgggat gaggaaggag 540attttggaga tccntggtcc agaattccat ttaccttctg ggccagatac caccagaatg 600cccgctccag attccctcag acctttgccg gtcccattat tggtcstggt ggt 653

<210> 364

<211> 401

<212> DNA

<213> Homo sapien

<400> 364actagaggaa agacgttaaa ccactctact accacttgtg gaactctcaa agggtaaatg 60acaaagccaa tgaatgactc taaaaacaat atttacattt aatggtttgt agacaataaa 120aaaacaaggt ggatagatct agaattgtaa cattttaaga aaaccatagc atttgacaga 180tgagaaagct caattataga tgcaaagtta taactaaact actatagtag taaagaaata 240catttcacac ccttcatata aattcactat cttggcttga ggcactccat aaaatgtatc 300acgtgcatag taaatcttta tatttgctat ggcgttgcac tagaggactt ggactgcaac 360aagtggatgc gcggaaaatg aaatcttctt caatagccca g 401

<210> 365

<211> 356

<212> DNA

<213> Homo sapien

<400> 365ccagtgtcat atttgggctt aaaatttcaa gaagggcact tcaaatggct ttgcatttgc 60atgtttcagt gctagagcgt aggaatagac cctggcgtcc actgtgagat gttcttcagc 120taccagagca tcaagtctct gcagcaggtc attcttgggt aaagaaatga cttccacaaa 180ctctccatcc cctggctttg gcttcggcct tgcgttttcg gcatcatctc cgttaatggt 240gactgtcacg atgtgtatag tacagtttga caagcctggg tccatacaga ccgctggaga 300acattcggca atgtcccctt tgtagccagt ttcttcttcg agctcccgga gagcag 356

<210> 366

<211> 1851

<212> DNA

<213> Hcmo sapien

<400> 366tcatcaccat tgccagcagc ggcaccgtta gtcaggtttt ctgggaatcc cacatgagta 60cttccgtgtt cttcattctt cttcaatagc cataaatctt ctagctctgg ctggctgttt 120tcacttcctt taagcctttg tgactcttcc tctgatgtca gctttaagtc ttgttctgga 180ttgctgtttt cagaagagat ttttaacatc tgtttttctt tgtagtcaga aagtaactgg 240caaattacat gatgatgact agaaacagca tactctctgg ccgtctttcc agatcttgag 300aagatacatc aacattttgc tcaagtagag ggctgactat acttgctgat ccacaacata 360cagcaagtat gagagcagtt cttccatatc tatccagcgc atttaaattc gcttttttct 420tgattaaaaa tttcaccact tgctgttttt gctcatgtat accaagtagc agtggtgtga 480ggccatgctt gttttttgat tcgatatcag caccgtataa gagcagtgct tggccatta 540atttatcttc attgtagaca gcatagtgta gagtggtatt tccatactca tctggaatat 600ttggatcagt gccatgttcc agcaacatta acgcacattc atcttcctgg cattgtacgg 660cctttgtcag agctgtcctc tttttgttgt csaggacatt aagttgacat cgtctgtcca 720gcacgagttt tactacttct gaattcccat tggcagaggc cagatgtaga gcagtcctct 780tttgcttgtc cctcttgttc acatccgtgt ccctgagcat gacgatgaga tcctttctgg 840ggactttacc ccaccaggca gctctgtgga gcttgtccag atcttctcca tggacgtggt 900acctgggatc catgaaggcg ctgtcatcgt agtctcccca agcgaccacg ttgctcttgc 960cgctcccctg cagcagggga agcagtggca gcaccacttg cacctcttgc tcccaagcgt 1020cttcacagag gagtcgttgt ggtctccaga agtgcccacg ttgctcttgc cgctccccct 1080gtccatccag ggaggaagaa atgcaggaaa tgaaagatgc atgcacgatg gtatactcct 1140cagccatcaa acttctggac agcaggtcac ttccagcaag gtggagaaag ctgtccaccc 1200acagaggatg agatccagaa accacaatat ccattcacaa acaaacactt ttcagccaga 1260cacaggtact gaaatcatgt catctgcggc aacatggtgg aacctaccca atcacacatc 1320aagagatgaa gacactgcag tatatctgca caacgtaata ctcttcatcc ataacaaaat 1380aatataattt tcctctggag ccatatggat gaactatgaa ggaagaactc cccgaagaag 1440ccagtcgcag agaagccaca ctgaagctct gtcctcagcc atcagcgcca cggacaggar 1500tgtgtttctt ccccagtgat gcagcctcaa gttatcccga agctgccgca gcacacggtg 1560gctcctgaga aacaccccag ctcttccggt ctaacacagg caagtcaata aatgtgataa 1620tcacataaac agaattaaaa gcaaagtcac ataagcatct caacagacac agaaaaggca 1680tttgacaaaa tccagcatcc ttgtatttat tgttgcagtt ctcagaggaa atgcttctaa 1740cttttcccca tttagtatta tgttggctgt gggcttgtca taggtggttt ttattacttt 1800aaggtatgtc ccttctatgc ctgttttgct gagggtttta attctcgtgc c 1851

<210> 367

<211> 668

<212> DNA

<213> Homo sapien

<400> 367cttgagcttc caaataygga agactggccc ttacacasgt caatgttaaa atgaatgcat 60ttcagtattt tgaagataaa attrgtagat ctataccttg ttttttgatt cgatatcagc 120accrtataag agcagtgctt tggccattaa tttatctttc attrtagaca gcrtagtgya 180gagtggtatt tccatactca tctggaatat ttggatcagt gccatgttcc agcaacatta 240acgcacattc atcttcctgg cattgtacgg cctgtcagta ttagacccaa aaacaaatta 300catatcttag gaattcaaaa taacattcca cagctttcac caactagtta tatttaaagg 360agaaaactca tttttatgcc atgtattgaa atcaaaccca cctcatgctg atatagttgg 420ctactgcata cctttatcag agctgtcctc tttttgttgt caaggacatt aagttgacat 480cgtctgtcca gcaggagttt tactacttct gaattcccat tggcagaggc cagatgtaga 540gcagtcctat gagagtgaga agacttttta ggaaattgta gtgcactagc tacagccata 600gcaatgattc atgtaactgc aaacactgaa tagcctgcta ttactctgcc ttcaaaaaaa 660aaaaaaaa 668

<210> 368

<211> 1512

<212> DNA

<213> Homo sapien

<400> 368gggtcgccca gggggsgcgt gggctttcct cgggtgggtg tgggttttcc ctgggtgggg 60tgggctgggc trgaatcccc tgctggggtt ggcaggtttt ggctgggatt gacttttytc 120ttcaaacaga ttggaaaccc ggagttacct gctagttggt gaaactggtt ggtagacgcg 180atctgttggc tactactggc ttctcctggc tgttaaaagc agatggtggt tgaggttgat 240tccatgccgg ctgcttcttc tgtgaagaag ccatttggtc tcaggagcaa gatgggcaag 300tggtgctgcc gttgcttccc ctgctgcagg gagagcggca agagcaacgt gggcacttct 360ggagaccacg acgactctgc tatgaagaca ctcaggagca agatgggcaa gtggtgccgc 420cactgcttcc cctgctgcag ggggagtggc aagagcaacg tgggcgcttc tggagaccac 480gacgaytctg ctatgaagac actcaggaac aagatgggca agtggtgctg ccactgcttc 540ccctgctgca gggggagcrg caagagcaag gtgggcgctt ggggagacta cgatgacagt 600gccttcatgg agcccaggta ccacgtccgtggagaagatc tggacaagct ccacagagct 660gcctggtggg gtaaagtccc cagaaaggat ctcatcgtca tgctcaggga cactgacgtg 720aacaagaagg acaagcaaaa gaggactgct ctacatctgg cctctgccaa tgggaattca 780gaagtagtaa aactcstgct ggacagacga tgtcaactta atgtccttga caacaaaaag 840aggacagctc tgayaaaggc cgtacaatgc caggaagatg aatgtgcgtt aatgttgctg 900gaacatggca ctgatccaaa tattccagat gagtatggaa ataccactct rcactaygct 960rtctayaatg aagataaatt aatggccaaa gcactgctct tatayggtgc tgatatcgaa 1020tcaaaaaaca aggtatagat ctactaattt tatcttcaaa atactgaaat gcattcattt 1080taacattgac gtgtgtaagg gccagtcttc cgtatttgga agctcaagca taacttgaat 1140gaaaatattt tgaaatgacc taattatctm agactttatt ttaaatattg ttattttcaa 1200agaagcatta gagggtacag tttttttttt ttaaatgcac ttctggtaaa tacttttgtt 1260gaaaacactg aatttgtaaa aggtaatact tactattttt caatttttcc ctcctaggat 1320ttttttcccc taatgaatgt aagatggcaa aatttgccct gaaataggtt ttacatgaaa 1380actccaagaa aagttaaaca tgtttcagtg aatagagatc ctgctccttt ggcaagttcc 1440taaaaaacag taatagatac gaggtgatgc gcctgtcagt ggcaaggttt aagatatttc 1500tgatctcgtg cc 1512

<210> 369

<211> 1853

<212> DNA

<213> Homo sapien

<400> 369gggtcgccca gggggsgcgt gggctttcct cgggtgggtg tgggttttcc ctgggtgggg 60tgggctgggc trgaatcccc tgctggggtt ggcaggtttt ggctgggatt gacttttytc 120ttcaaacaga ttggaaaccc ggagttacct gctagttggt gaaactggtt ggtagacgcg 180atctgttggc tactactggc ttctcctggc tgttaaaagc agatggtggt tgaggttgat 240tccatgccgg ctgcttcttc tgtgaagaag ccatttggtc tcaggagcaa gstgggcaag 300tggtgctgcc gttgcttccc ctgctgcagg gagagcggca agagcaacgt gggcacttct 360ggagaccacg acgactctgc tatgaagaca ctcaggagca agatgggcaa gtggtgccgc 420cactgcttcc cctgctgcag ggggagtggc aagagcaacg tgggcgcttc tggagaccac 480gacgaytctg ctatgaagac actcaggaac aagatgggca agtggtgctg ccactgcttc 540ccctgctgca gggggagcrg caagagcaag gtgggcgctt ggggagacta cgatgacagy 600gccttcatgg akcccaggta ccacgtccrt ggagaagatc tggacaagct ccacagagct 660gcctggtggg gtaaagtccc cagaaaggat ctcatcgtca tgctcaggga cackgaygtg 720aacaagargg acaagcaaaa gaggactgct ctacatctgg cctctgccaa tgggaattca 780gaagtagtaa aactcstgct ggacagacga tgtcaactta atgtccttga caacaaaaag 840aggacagctc tgayaaaggc cgtacaatgc caggaagatg aatgtgcgtt aatgttgctg 900gaacatggca ctgatccaaa tattccagat gagtatggaa ataccactct rcactaygct 960rtctayaatg aagataaatt aatggccaaa gcactgctct tatayggtgc tgatatcgaa 1020tcaaaaaaca agcatggcct cacaccactg ytacttggtr tacatgagca aaaacagcaa 1080gtsgtgaaat ttttaatyaa gaaaaaagcg aatttaaaat gcrctggata gatatggaag 1140ractgctctc atacttgctg tatgttgtgg atcagcaagt atagtcagcc ytctacttga 1200gcaaaatrtt gatgtatctt ctcaagatct ggaaagacgg ccagagagta tgctgtttct 1260agtcatcatc atgtaatttg ccagttactt tctgactaca aagaaaaaca gatgttaaaa 1320atctcttctg aaaacagcaa tccagaacaa gacttaaagc tgacatcaga ggaagagtca 1380caaaggctta aaggaagtga aaacagccag ccagaggcat ggaaactttt aaatttaaac 1440ttttggttta atgttttttt tttttgcctt aataatatta gatagtccca aatgaaatwa 1500cctatgagac taggctttga gaatcaatag attctttttt taagaatctt ttggctagga 1560gcggtgtctc acgcctgtaa ttccagcacc ttgagaggct gaggtgggca gatcacgaga 1620tcaggagatc gagaccatcc tggctaacac ggtgaaaccc catctctact aaaaatacaa 1680aaacttagct gggtgtggtg gcgggtgcct gtagtcccag ctactcagga rgctgaggca 1740ggagaatggc atgaacccgg gaggtggagg ttgcagtgag ccgagatccg ccactacact 1800ccagcctggg tgacagagca agactctgtc tcaaaaaaaa aaaaaaaaaa aaa 1853

<210> 370

<211> 2184

<212> DNA

<213> Homo sapien

<400> 370ggcacgagaa ttaaaaccct cagcaaaaca ggcatagaag ggacatacct taaagtaata 60aaaaccacct atgacaagcc cacagccaac ataatactaa atggggaaaa gttagaagca 120tttcctctga gaacctcaac aataaataca aggatgctgg attttgtcaa atgccttttc 180tgtgtctgtt gagatgctta tgtgactttg cttttaattc tgtttatgtg attatcacat 240ttattgactt gcctgtgtta gaccggaaga gctggggtgt ttctcaggag ccaccgtgtg 300ctgcggcagc ttcgggataa cttgaggctg catcactggg gaagaaacac aytcctgtcc 360gtggcgctga tggctgagga cagagcttca gtgtggcttc tctgcgactg gcttcttcgg 420ggagttcttc cttcatagtt catccatatg gctccagagg aaaattatat tattttgtta 480tggatgaaga gtattacgtt gtgcagatat actgcagtgt cttcatctct tgatgtgtga 540ttgggtaggt tccaccatgt tgccgcagat gacatgattt cagtacctgt gtctggctga 600aaagtgtttg tttgtgaatg gatattgtgg tttctggatc tcatcctctg tgggtggaca 660gctttctcca ccttgctgga agtgacctgc tgtccagaag tttgatggct gaggagtata 720ccatcgtgca tgcatctttc atttcctgca tttcttcctc cctggatgga cagggggagc 780ggcaagagca acgtgggcac ttctggagac cacaacgact cctctgtgaa gacgcttggg 840agcaagaggt gcaagtggtg ctgccactgc ttcccctgct gcaggggagc ggcaagagca 900acgtggtcgc ttggggagac tacgatgaca gcgccttcat ggatcccagg taccacgtcc 960atggagaaga tctggacaag ctccacagag ctgcctggtg gggtaaagtc cccagaaagg 1020atctcatcgt catgctcagg gacacggatg tgaacaagag ggacaagcaa aagaggactg 1080ctctacatct ggcctctgcc aatgggaatt cagaagtagt aaaactcgtg ctggacagac 1140gatgtcaact taatgtcctt gacaacaaaa agaggacagc tctgacaaag gccgtacaat 1200gccaggaaga tgaatgtgcg ttaatgttgc tggaacatgg cactgatcca aatattccag 1260atgagtatgg aaataccact ctacactatg ctgtctacaa tgaagataaa ttaatggcca 1320aagcactgct cttatacggt gctgatatcg aatcaaaaaa caagcatggc ctcacaccac 1380tgctacttgg tatacatgag caaaaacagc aagtggtgaa atttttaatc aagaaaaaag 1440cgaatttaaa tgcgctggat agatatggaa gaactgctct catacttgct gtatgttgtg 1500gatcagcaag tatagtcagc cctctacttg agcaaaatgt tgatgtatct tctcaagatc 1560tggaaagacg gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact 1620ttctgactac aaagaaaaac agatgttaaa aatctcttct gaaaacagca atccagaaca 1680agacttaaag ctgacatcag aggaagagtc acaaaggctt aaaggaagtg aaaacagcca 1740gccagaggca tggaaacttt taaatttaaa cttttggttt aatgtttttt ttttttgcct 1800taataatatt agatagtccc aaatgaaatw acctatgaga ctaggctttg agaatcaata 1860gattcttttt ttaagaatct tttggctagg agcggtgtct cacgcctgta attccagcac 1920cttgagaggc tgaggtgggc agatcacgag atcaggagat cgagaccatc ctggctaaca 1980cggtgaaacc ccatctctac taaaaataca aaaacttagc tgggtgtggt ggcgggtgcc 2040tgtagtccca gctactcagg argctgaggc aggagaatgg catgaacccg ggaggtggag 2100gttgcagtga gccgagatcc gccactacac tccagcctgg gtgacagagc aagactctgt 2160ctcaaaaaaa aaaaaaaaaa aaaa 2184

<210> 371

<211> 1855

<212> DNA

<213> Homo sapien

<220>

<221> misc_feature

<222> (1)...(1855)

<223> n = A,T,C or G

<400> 371tgcacgcatc ggccagtgtc tgtgccacgt acactgacgc cccctgagat gtgcacgccg 60cacgcgcacg ttgcacgcgc ggcagcggct tggctggctt gtaacggctt gcacgcgcac 120gccgcccccg cataaccgtc agactggcct gtaacggctt gcaggcgcac gccgcacgcg 180cgtaacggct tggctgccct gtaacggctt gcacgtgcat gctgcacgcg cgttaacggc 240ttggctggca tgtagccgct tggcttggct ttgcattytt tgctkggctk ggcgttgkty 300tcttggattg acgcttcctc cttggatkga cgtttcctcc ttggatkgac gtttcytyty 360tcgcgttcct ttgctggact tgacctttty tctgctgggt ttggcattcc tttggggtgg 420gctgggtgtt ttctccgggg gggktkgccc ttcctggggt gggcgtgggk cgcccccagg 480gggcgtgggc tttccccggg tggggtggg ttttcctggg gtggggtggg ctgtgctggg 540atccccctgc tggggttggc agggattgac ttttttcttc aaacagattg gaaacccgga 600gtaacntgct agttggtgaa actggttggt agacgcgatc tgctggtact actgtttctc 660ctggctgtta aaagcagatg gtggctgagg ttgattcaat gccggctgct tcttctgtga 720agaagccatt tggtctcagg agcaagatgg gcaagtggtg cgccactgct tcccctgctg 780cagggggagc ggcaagagca acgtgggcac ttctggagac cacaacgact cctctgtgaa 840gacgcttggg agcaagaggt gcaagtggtg ctgcccactg cttcccctgc tgcaggggag 900cggcaagagc aacgtggkcg cttggggaga ctacgatgac agcgccttca tggakcccag 960gtaccacgtc crtggagaag atctggacaa gctccacaga gctgcctggt ggggtaaagt 1020ccccagaaag gatctcatcg tcatgctcag ggacactgay gtgaacaaga rggacaagca 1080aaagaggact gctctacatc tggcctctgc caatgggaat tcagaagtag taaaactcgt 1140gctggacaga cgatgtcaac ttaatgtcct tgacaacaaa aagaggacag ctctgacaaa 1200ggccgtacaa tgccaggaag atgaatgtgc gttaatgttg ctggaacatg gcactgatcc 1260aaatattcca gatgagtatg gaaataccac tctacactat gctgtctaca atgaagataa 1320attaatggcc aaagcactgc tcttatacgg tgctgatatc gaatcaaaaa acaaggtata 1380gatctactaa ttttatcttc aaaatactga aatgcattca ttttaacatt gacgtgtgta 1440agggccagtc ttccgtattt ggaagctcaa gcataacttg aatgaaaata ttttgaaatg 1500acctaattat ctaagacttt attttaaata ttgttatttt caaagaagca ttagagggta 1560cagttttttt tttttaaatg cacttctggt aaatactttt gttgaaaaca ctgaatttgt 1620aaaaggtaat acttactatt tttcaatttt tccctcctag gatttttttc ccctaatgaa 1680tgtaagatgg caaaatttgc cctgaaatag gttttacatg aaaactccaa gaaaagttaa 1740acatgtttca gtgaatagag atcctgctcc tttggcaagt tcctaaaaaa cagtaataga 1800tacgaggtga tgcgcctgtc agtggcaagg tttaagatat ttctgatctc gtgcc 1855

<210> 372

<211> 1059

<212> DNA

<213> Homo sapien

<400> 372gcaacgtggg cacttctgga gaccacaacg actcctctgt gaagacgctt gggagcaaga 60ggtgcaagtg gtgctgccca ctgcttcccc tgctgcaggg gagcggcaag agcaacgtgg 120gcgcttgrgg agactmcgat gacagygcct tcatggagcc caggtaccac gtccgtggag 180aagatctgga caagctccac agagctgccc tggtggggta aagtccccag aaaggatctc 240atcgtcatgc tcagggacac tgaygtgaac aagarggaca agcaaaagag gactgctcta 300catctggcct ctgccaatgg gaattcagaa gtagtaaaac tcstgctgga cagacgatgt 360caacttaatg tccttgacaa caaaaagagg acagctctga yaaaggccgt acaatgccag 420gaagatgaat gtgcgttaat gttgctggaa catggcactg atccaaatat tccagatgag 480tatggaaata ccactctrca ctaygctrtc tayaatgaag ataaattaat ggccaaagca 540ctgctcttat ayggtgctga tatcgaatca aaaaacaagg tatagatcta ctaattttat 600cttcaaaata ctgaaatgca ttcattttaa cattgacgtg tgtaagggcc agtcttccgt 660atttggaagc tcaagcataa cttgaatgaa aatattttga aatgacctaa ttatctaaga 720ctttatttta aatattgtta ttttcaaaga agcattagag ggtacagttt ttttttttta 780aatgcacttc tggtaaatac ttttgttgaa aacactgaat ttgtaaaagg taatacttac 840tatttttcaa tttttccctc ctaggatttt tttcccctaa tgaatgtaag atggcaaaat 900ttgccctgaa ataggtttta catgaaaact ccaagaaaag ttaaacatgt ttcagtgaat 960agagatcctg ctcctttggc aagttcctaa aaaacagtaa tagatacgag gtgatgcgcc 1020tgtcagtggc aaggtttaag atatttctga tctcgtgcc 1059

<210> 373

<211> 1155

<212> DNA

<213> Homo sapien

<400> 373atggtggttg aggttgattc catgccggct gcctcttctg tgaagaagcc atttggtctc 60aggagcaaga tgggcaagtg gtgctgccgt tgcttcccct gctgcaggga gagcggcaag 120agcaacgtgg gcacttctgg agaccacgac gactctgcta tgaagacact caggagcaag 180atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240ggcgcttctg gagaccacga cgactctgct atgaagacac tcaggaacaa gatgggcaag 300tggtgctgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg 360ggagactacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatc2g 420gacaagctcc acagagctgc ctggtggggt aaagtcccca gaaaggatct catcgtcatg 480ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 546tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat 600gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa 660tgtgcgttaa tgttgccgga acatggcact gatccaaata ttccagatga gtatggaaat 720accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta 780tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgta 840catgagcaaa aacagcaagt cgtgaaattt ttaatcaaga aaaaagcgaa tttaaatgca 900ctggatagat atggaaggac tgctctcata cttgctgtat gttgtggatc agcaagtata 960gtcagccttc tacttgagca aaatattgat gtatcttctc aagatctatc tggacagacg 1020gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac 1080aaagaaaaac agatgctaaa aatctcttct gaaaacagca atccagaaaa tgtctcaaga 1140accagaaata aataa 1155

<210> 374

<211> 2000

<212> DNA

<213> Homo sapien

<400> 374atggtggttg aggttgattc catgccggct gcctcttctg tgaagaagcc atttggtctc 60aggagcaaga tgggcaagtg gtgctgccgt tgcttcccct gctgcaggga gagcggcaag 120agcaacgtgg gcacttctgg agaccacgac gactctgcta tgaagacact caggagcaag 180atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240ggcgcttctg gagaccacga cgactctgct atgaagacac tcaggaacaa gatgggcaag 300tggtgctgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg 360ggagactacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatctg 420gacaagctcc acagagctgc ctggtggggt aaagtcccca gaaaggatct catcgtcatg 480ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 540tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat 600gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa 660tgtgcgttaa tgttgctgga acatggcact gatccaaata ttccagatga gtatggaaat 720accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta 780tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgta 840catgagcaaa aacagcaagt cgtgaaattt ttaatcaaga aaaaagcgaa tttaaatgca 900ctggatagat atggaaggac tgctctcata cttgctgtat gttgtggatc agcaagtata 960gtcagccttc tacttgagca aaatattgat gtatcttctc aagatctatc tggacagacg 1020gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac 1080aaagaaaaac agatgctaaa aatctcttct gaaaacagca atccagaaca agacttaaag 1140ctgacatcag aggaagagtc acaaaggttc aaaggcagtg aaaatagcca gccagagaaa 1200atgtctcaag aaccagaaat aaataaggat ggtgatagag aggttgaaga agaaatgaag 1260aagcatgaaa gtaataatgt gggattacta gaaaacctga ctaatggtgt cactgctggc 1320aatggtgata atggattaat tcctcaaagg aagagcagaa cacctgaaaa tcagcaattt 1380cctgacaacg aaagtgaaga gtatcacaga atttgcgaat tagtttctga ctacaaagaa 1440aaacagatgc caaaatactc ttctgaaaac agcaacccag aacaagactt aaagctgaca 1500tcagaggaag agtcacaaag gcttgagggc agtgaaaatg gccagccaga gctagaaaat 1560tttatggcta tcgaagaaat gaagaagcac ggaagtactc atgtcggatt cccagaaaac 1620ctgactaatg gtgccactgc tggcaatggt gatgatggat taattcctcc aaggaagagc 1680agaacacctg aaagccagca atttcctgac actgagaatg aagagtatca cagtgacgaa 1740caaaatgata ctcagaagca attttgtgaa gaacagaaca ctggaatatt acacgatgag 1800attctgattc atgaagaaaa gcagatagaa gtggttgaaa aaatgaattc tgagctttct 1860cttagttgta agaaagaaaa agacatcttg catgaaaata gtacgttgcg ggaagaaatt 1920gccatgctaa gactggagct agacacaatg aaacatcaga gccagctaaa aaaaaaaaaa 1980aaaaaaaaaa aaaaaaaaaa 2000

<210> 375

<211> 2040

<212> DNA

<213> Homo sapien

<400> 375atggtggttg aggttgattc catgccggct gcctcttctg tgaagaagcc atttggtctc 60aggagcaaga tgggcaagtg gtgctgccgt tgcttcccct gctgcaggga gagcggcaag 120agcaacgtgg gcacttctgg agaccacgac gactctgcta tgaagacact caggagcaag 180atgggcaagt ggtgccgcca ctgcttcccc tgctgcaggg ggagtggcaa gagcaacgtg 240ggcgcttctg gagaccacga cgactctgct atgaagacac tcaggaacaa gatgggcaag 300tggtgctgcc actgcttccc ctgctgcagg gggagcggca agagcaaggt gggcgcttgg 360ggagactacg atgacagtgc cttcatggag cccaggtacc acgtccgtgg agaagatctg 420gacaagctcc acagagctgc ctggtggggt aaagtcccca gaaaggatct catcgtcatg 480ctcagggaca ctgacgtgaa caagaaggac aagcaaaaga ggactgctct acatctggcc 540tctgccaatg ggaattcaga agtagtaaaa ctcctgctgg acagacgatg tcaacttaat 600gtccttgaca acaaaaagag gacagctctg ataaaggccg tacaatgcca ggaagatgaa 660tgtgcgttaa tgttgctgga acatggcact gatccaaata ttccagatga gtatggaaat 720accactctgc actacgctat ctataatgaa gataaattaa tggccaaagc actgctctta 780tatggtgctg atatcgaatc aaaaaacaag catggcctca caccactgtt acttggtgta 840catgagcaaa aacagcaagt cgtgaaattt ttaatcaaga aaaaagcgaa tttaaatgca 900ctggatagat atggaaggac tgctctcata cttgctgtat gttgtggatc agcaagtata 960gtcagccttc tacttgagca aaatattgat gtatcttctc aagatctatc tggacagacg 1020gccagagagt atgctgtttc tagtcatcat catgtaattt gccagttact ttctgactac 1080aaagaaaaac agatgctaaa aatctcttct gaaaacagca atccagaaca agacttaaag 1140ctgacatcag aggaagagtc acaaaggttc aaaggcagtg aaaatagcca gccagagaaa 1200atgtctcaag aaccagaaat aaataaggat ggtgatagag aggttgaaga agaaatgaag 1260aagcatgaaa gtaataatgt gggattacta gaaaacctga ctaatggtgt cactgctggc 1320aatggtgata atggattaat tcctcaaagg aagagcagaa cacctgaaaa tcagcaattt 1380cctgacaacg aaagtgaaga gtatcacaga atttgcgaat tagtttctga ctacaaagaa 1440aaacagatgc caaaatactc ttctgaaaac agcaacccag aacaagactt aaagctgaca 1500tcagaggaag agtcacaaag gcttgagggc agtgaaaatg gccagccaga gaaaagatct 1560caagaaccag aaataaataa ggatggtgat agagagctag aaaattttat ggctatcgaa 1620gaaatgaaga agcacggaag tactcatgtc ggattcccag aaaacctgac taatggtgcc 1680actgctggca atggtgatga tggattaatt cctccaagga agagcagaac acctgaaagc 1740cagcaatttc ctgacactga gaatgaagag tatcacagtg acgaacaaaa tgatactcag 1800aagcaatttt gtgaagaaca gaacactgga atattacacg atgagattct gattcatgaa 1860gaaaagcaga tagaagtggt tgaaaaaatg aattctgagc tttctcttag ttgtaagaaa 1920gaaaaagaca tcttgcatga aaatagtacg ttgcgggaag aaattgccat gctaagactg 1980gagctagaca caatgaaaca tcagagccag ctaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2040

<210> 376

<211> 329

<212> PRT

<213> Homo sapien

<400> 376Met Asp Ile Val Val Ser Gly Ser His Pro Leu Trp Val Asp Ser Phe1 5 10 15Leu His Leu Ala Gly Ser Asp Leu Leu Ser Arg Ser Leu Met Ala Glu

20 25 30Glu Tyr Thr Ile Val His Ala Ser Phe Ile Ser Cys Ile Ser Ser Ser

35 40 45Leu Asp Gly Gln Gly Glu Arg Gln Glu Gln Arg Gly His Phe Trp Arg

50 55 60Pro Gln Arg Leu Leu Cys Glu Asp Ala Trp Glu Gln Glu Val Gln Val65 70 75 80Val Leu Pro Leu Leu Pro Leu Leu Gln Gly Ser Gly Lys Ser Asn Val

85 90 95Val Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe Met Asp Pro Arg Tyr

100 105 110His Val His Gly Glu Asp Leu Asp Lys Leu His Arg Ala Ala Trp Trp

115 120 125Gly Lys Val Pro Arg Lys Asp Leu Ile val Met Leu Arg Asp Thr Asp

130 135 140Val Asn Lys Arg Asp Lys Gln Lys Arg Thr Ala Leu His Leu Ala Ser145 150 155 160Ala Asn Gly Asn Ser Glu Val Val Lys Leu Val Leu Asp Arg Arg Cys

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

180 185 190Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met Leu Leu Glu His Gly

195 200 205Thr Asp Pro Asn Ile Pro Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr

210 215 220Ala val Tyr Asn Glu Asp Lys Leu Met Ala Lys Ala Leu Leu Leu Tyr225 230 235 240Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly Leu Thr Pro Leu Leu

245 250 255Leu Gly Ile His Glu Gln Lys Gln Gln Val Val Lys Phe Leu Ile Lys

260 265 270Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr Gly Arg Thr Ala Leu

275 280 285Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile Val Ser Pro Leu Leu

290 295 300Glu Gln Asn Val Asp Val Ser Ser Gln Asp Leu Glu Arg Arg Pro GLu305 310 315 320Ser Met Leu Phe Leu Val Ile Ile Met

325

<210> 377

<211> 148

<212> PRT

<213> Homo sapien

<220>

<221> VARIANT

<222> (1)...(148)

<223> Xaa = Any Amino Acid

<400> 377Met Thr Xaa Pro Ser Trp Ser Pro Gly Thr Thr Ser Val Glu Lys Ile1 5 10 15Trp Thr Ser Ser Thr Glu Leu Pro Trp Trp Gly Lys Val Pro Arg Lys

20 25 30Asp Leu Ile Val Met Leu Arg Asp Thr Asp Val Asn Lys Xaa Asp Lys

35 40 45Gln Lys Arg Thr Ala Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu

50 55 60Val Val Lys Leu Xaa Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp65 70 75 80Asn Lys Lys Arg Thr Ala Leu Xaa Lys Ala Val Gln Cys Gln Glu Asp

85 90 95Glu Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro

100 105 110Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala Xaa Tyr Asn Glu Asp

115 120 125Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp Ile Glu Ser

130 135 140Lys Asn Lys Val145

<210> 378

<211> 1719

<212> PRT

<213> Homo sapien

<400> 378Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys1 5 10 15Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe

20 25 30Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp

35 40 45His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp

50 55 60Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val65 70 75 80Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn

85 90 95Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg G1y Ser

100 105 110Gly Lys Ser Lys Val Gly Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe

115 120 125Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His

130 135 140Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu Ile Val Met145 150 155 160Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln Lys Arg Thr Ala

165 170 175Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val Val Lys Leu Leu

180 185 190Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr

195 200 205Ala Leu Ile Lys Ala Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met

210 215 220Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp Glu Tyr Gly Asn225 230 235 240Thr Thr Leu His Tyr Ala Ile Tyr Asn Glu Asp Lys Leu Met Ala Lys

245 250 255Ala Leu Leu Leu Tyr Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly

260 265 270Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys Gln Gln Val Val

275 280 285Lys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr

290 295 300Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile305 310 315 320Val Ser Leu Leu Leu Glu Gln Asn Ile Asp Val Ser Ser Gln Asp Leu

325 330 335Ser Gly Gln Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val

340 345 350Ile Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln Met Leu Lys Ile

355 360 365Ser Ser Glu Asn Ser Asn Pro Glu Asn Val Ser Arg Thr Arg Asn Lys

370 375 380Pro Arg Thr His Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser385 390 395 400Ser Val Lys Lys Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys

405 410 415Cys Arg Cys Phe Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly

420 425 430Thr Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys

435 440 445Met Gly Lys Trp Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly

450 455 460Lys Ser Asn Val Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys465 470 475 480Thr Leu Arg Asn Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys

485 490 495Cys Arg Gly Ser Gly Lys Ser Lys Val Gly Ala Trp Giy Asp Tyr Asp

500 505 510Asp Ser Ala Phe Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu

515 520 525Asp Lys Leu His Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp

530 535 540Leu Ile Val Met Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln545 550 555 560Lys Arg Thr Ala Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val

565 570 575Val Lys Leu Leu Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn

580 585 590Lys Lys Arg Thr Ala Leu Ile Lys Ala Val Gln Cys Gln Glu Asp Glu

595 600 605Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp

610 615 620Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala Ile Tyr Asn GluAsp Lys625 630 635 640Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp Ile Giu Ser Lys

645 650 655Asn Lys His Gly Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys

660 665 670Gln Gln Val Val Lys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala

675 680 685Leu Asp Arg Tyr Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly

690 695 700Ser Ala Ser Ile Val Ser Leu Leu Leu Glu Gln Asn Ile Asp Val Ser705 710 715 720Ser Gln Asp Leu Ser Gly Gln Thr Ala Arg Glu Tyr Ala Val Ser Ser

725 730 735His His His Val Ile Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln

740 745 750Met Leu Lys Ile Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys

755 760 765Leu Thr Ser Glu Glu Glu Ser Gln Arg Phe Lys Gly Ser Glu Asn Ser

770 775 780Gln Pro Glu Lys Met Ser Gln Glu Pro Glu Ile Asn Lys Asp Gly Asp785 790 795 800Arg Glu Val Glu Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly

805 810 815Leu Leu Glu Asn Leu Thr Asn Gly Val Thr Ala Gly Asn Gly Asp Asn

820 825 830Gly Leu Ile Pro Gln Arg Lys Ser Arg Thr Pro Glu Asn Gln Gln Phe

835 840 845Pro Asp Asn Glu Ser Glu Glu Tyr His Arg Ile Cys Glu Leu Val Ser

850 855 860Asp Tyr Lys Glu Lys Gln Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn865 870 875 880Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Leu

885 890 895Glu Gly Ser Glu Asn Gly Gln Pro Glu Leu Glu Asn Phe Met Ala Ile

900 905 910Glu Glu Met Lys Lys His Gly Ser Thr His Val Gly Phe Pro Glu Asn

915 920 925Leu Thr Asn Gly Ala Thr Ala Gly Asn Gly Asp Asp Gly Leu Ile Pro

930 935 940Pro Arg Lys Ser Arg Thr Pro Glu Ser Gln Gln Phe Pro Asp Thr Glu945 950 955 960Asn Glu Glu Tyr His Ser Asp Glu Gln Asn Asp Thr Gln Lys Gln Phe

965 970 975Cys Glu Glu Gln Asn Thr Gly Ile Leu His Asp Glu Ile Leu Ile His

980 985 990Glu Glu Lys Gln Ile Glu Val Val Glu Lys Met Asn Ser Glu Leu Ser

995 1000 1005Leu Ser Cys Lys Lys Glu Lys Asp Ile Leu His Glu Asn Ser Thr Leu

1010 1015 1020Arg Glu Glu Ile Ala Met Leu Arg Leu Glu Leu Asp Thr Met Lys His1025 1030 1035 104Gln Ser Gln Leu Pro Arg Thr His Met Val Val Glu Val Asp Ser Met

1045 1050 1055Pro Ala Ala Ser Ser Val Lys Lys Pro Phe Gly Leu Arg Ser Lys Met

1060 1065 1070Gly Lys Trp Cys Cys Arg Cys Phe Pro Cys Cys Arg Glu Ser Gly Lys

1075 1080 1085Ser Asn Val Gly Thr Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr

1090 1095 1100Leu Arg Ser Lys Met Gly Lys Trp Cys Arg His Cys Phe Pro Cys Cys1105 1110 1115 112Arg Gly Ser Gly Lys Ser Asn Val Gly Ala Ser Gly Asp His Asp Asp

1125 1130 1135Ser Ala Met Lys Thr Leu Arg Asn Lys Met Gly Lys Trp Cys Cys His

1140 1145 1150Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Lys Val Gly Ala Trp

1155 1160 1165Gly Asp Tyr Asp Asp Ser Ala Phe Met Glu Pro Arg Tyr His Val Arg

1170 1175 1180Gly Glu Asp Leu Asp Lys Leu His Arg Ala Ala Trp Trp Gly Lys Val1185 1190 1195 120Pro Arg Lys Asp Leu Ile Val Met Leu Arg Asp Thr Asp Val Asn Lys

1205 1210 1215Lys Asp Lys Gln Lys Arg Thr Ala Leu His Leu Ala Ser Ala Asn Gly

122 1225 1230Asn Ser Glu Val Val Lys Leu Leu Leu Asp Arg Arg Cys Gln Leu Asn

1235 1240 1245Val Leu Asp Asn Lys Lys Arg Thr Ala Leu Ile Lys Ala Val Gln Cys

1250 1255 1260Gln Glu Asp Glu Cys Ala Leu Met Leu Leu Glu His Gly Thr Asp Pro1265 1270 1275 128Asn Ile Pro Asp Glu Tyr Gly Asn Thr Thr Leu His Tyr Ala Ile Tyr

128 1290 1295Asn Glu Asp Lys Leu Met Ala Lys Ala Leu Leu Leu Tyr Gly Ala Asp

1300 1305 1310Ile Glu Ser Lys Asn Lys His Gly Leu Thr Pro Leu Leu Leu Gly Val

1315 1320 1325His Glu Gln Lys Gln Gln Val Val Lys Phe Leu Ile Lys Lys Lys Ala

1330 1335 1340Asn Leu Asn Ala Leu Asp Arg Tyr Gly Arg Thr Ala Leu Ile Leu Ala1345 1350 1355 136Val Cys Cys Gly Ser Ala Ser Ile Val Ser Leu Leu Leu Glu Gln Asn

1365 1370 1375Ile Asp Val Ser Ser Gln Asp Leu Ser Gly Gln Thr Ala Arg Glu Tyr

1380 1385 1390Ala Val Ser Ser His His His Val Ile Cys Gln Leu Leu Ser Asp Tyr

1395 1400 1405Lys Glu Lys Gln Met Leu Lys Ile Ser Ser Glu Asn Ser Asn Pro Glu1410 1415 1420Gln Asp Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Phe Lys Gly1425 1430 1435 144Ser Glu Asn Ser Gln Pro Glu Lys Met Ser Gln Glu Pro Glu Ile Asn

1445 1450 1455Lys Asp Gly Asp Arg Glu Val Glu Glu Glu Met Lys Lys His Glu Ser

1460 1465 1470Asn Asn Val Gly Leu Leu Glu Asn Leu Thr Asn Gly Val Thr Ala Gly

1475 1480 1485Asn Gly Asp Asn Gly Leu Ile Pro Gln Arg Lys Ser Arg Thr Pro Glu

1490 1495 1500Asn Gln Gln Phe Pro Asp Asn Glu Ser Glu Glu Tyr His Arg Ile Cys1505 1510 1515 152Glu Leu Val Ser Asp Tyr Lys Glu Lys Gln Met Pro Lys Tyr Ser Ser

1525 1530 1535Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu Glu Glu

1540 1545 1550Ser Gln Arg Leu Glu Gly Ser Glu Asn Gly Gln Pro Glu Lys Arg Ser

1555 1560 1565Gln Glu Pro Glu Ile Asn Lys Asp Gly Asp Arg Glu Leu Glu Asn Phe

1570 1575 1580Met Ala Ile Glu Glu Met Lys Lys His Gly Ser Thr His Val Gly Phe1585 1590 1595 160Pro Glu Asn Leu Thr Asn Gly Ala Thr Ala Gly Asp Gly Asp Asp Gly

1605 1610 1615Leu Ile Pro Pro Arg Lys Ser Arg Thr Pro Glu Ser Gln Gln Phe Pro

1620 1625 1630Asp Thr Glu Asn Glu Glu Tyr His Ser Asp Glu Gln Asn Asp Thr Gln

1635 1640 1645Lys Gln Phe Cys Glu Glu Gln Asn Thr Gly Ile Leu His Asp Glu Ile

1650 1655 1660Leu Ile His Glu Glu Lys Gln Ile Glu Val Val Glu Lys Met Asn Ser1665 1670 1675 168Glu Leu Ser Leu Ser Cys Lys Lys Glu Lys Asp Ile Leu His Glu Asn

16 1690 1695Ser Thr Leu Arg Glu Glu Ile Ala Met Leu Arg Leu Glu Leu Asp Thr

1700 1705 1710Met Lys His Gln Ser Gln Leu

1715

<210> 379

<211> 656

<212> PRT

<213> Homo sapien

<400> 379Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys1 5 10 15Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe

20 25 30Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp

35 40 45His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp

50 55 60Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val65 70 75 80Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn

85 90 95Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser

100 105 110Gly Lys Ser Lys Val Gly Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe

115 120 125Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His

130 135 140Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu Ile Val Met145 150 155 160Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln Lys Arg Thr Ala

165 170 175Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val Val Lys Leu Leu

180 185 190Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr

195 200 205Ala Leu Ile Lys Ala Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met

210 215 220Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp Glu Tyr Gly Asn225 230 235 240Thr Thr Leu His Tyr Ala Ile Tyr Asn Glu Asp Lys Leu Met Ala Lys

245 250 255Ala Leu Leu Leu Tyr Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly

260 265 270Leu Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys Gln Gln Val Val

275 280 285Lys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr

290 295 300Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile305 310 315 320Val Ser Leu Leu Leu Glu Gln Asn Ile Asp Val Ser Ser Gln Asp Leu

325 330 335Ser Gly Gln Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val

340 345 350Ile Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln Met Leu Lys Ile

355 360 365Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu

370 375 380Glu Glu Ser Gln Arg Phe Lys Gly Ser Glu Asn Ser Gln Pro Glu Lys385 390 395 400Met Ser Gln Glu Pro Glu Ile Asn Lys Asp Gly Asp Arg Glu Val Glu

405 410 415Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly Leu Leu Glu Asn

420 425 430Leu Thr Asn Gly Val Thr Ala Gly Asn Gly Asp Asn Gly Leu Ile Pro

435 440 445Gln Arg Lys Ser Arg Thr Pro Glu Asn Gln Gln Phe Pro Asp Asn Glu

450 455 460Ser Glu Glu Tyr His Arg Ile Cys Glu Leu Val Ser Asp Tyr Lys Glu465 470 475 480Lys Gln Met Pro Lys Tyr Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp

485 490 495Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Leu Glu Gly Ser Glu

500 505 510Asn Gly Gln Pro Glu Leu Glu Asn Phe Met Ala Ile Glu Glu Met Lys

515 520 525Lys His Gly Ser Thr His Val Gly Phe Pro Glu Asn Leu Thr Asn Gly

530 535 540Ala Thr Ala Gly Asn Gly Asp Asp Gly Leu Ile Pro Pro Arg Lys Ser545 550 555 560Arg Thr Pro Glu Ser Gln Gln Phe Pro Asp Thr Glu Asn Glu Glu Tyr

565 570 575His Ser Asp Glu Gln Asn Asp Thr Gln Lys Gln Phe Cys Glu Glu Gln

580 585 590Asn Thr Gly Ile Leu His Asp Glu Ile Leu Ile His Glu Glu Lys Gln

595 600 605Ile Glu Val Val Glu Lys Met Asn Ser Glu Leu Ser Leu Ser Cys Lys

610 615 620Lys Glu Lys Asp Ile Leu His Glu Asn Ser Thr Leu Arg Glu Glu Ile625 630 635 640Ala Met Leu Arg Leu Glu Leu Asp Thr Met Lys His Gln Ser Gln Leu

645 650 655

<210> 380

<211> 671

<212> PRT

<213> Homo sapien

<400> 380Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys1 5 10 15Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe

20 25 30Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp

35 40 45His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp

50 55 60Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val65 70 75 80Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn

85 90 95Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser

l00 105 110Gly Lys Ser Lys Val Gly Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe

115 120 125Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His

130 135 140Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu Ile Val Met145 150 155 160Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gln Lys Arg Thr Ala

165 170 175Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val Val Lys Leu Leu

180 185 190Leu Asp Arg Arg Cys Gln Leu Asn Val Leu Asp Asn Lys Lys Arg Thr

195 200 205Ala Leu Ile Lys Ala Val Gln Cys Gln Glu Asp Glu Cys Ala Leu Met

210 215 220Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp Glu Tyr Gly Asn

230 235 240

J His Tyr Ala Ile Tyr Asn Glu Asp Lys Leu Met Ala Lys

245 250 255

Leu Leu Tyr Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly

260 265 270

Thr Pro Leu Leu Leu Gly Val His Glu Gln Lys Gln Gln Val Val

275 280 285Jys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr

290 295 300Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile305 310 315 320Val Ser Leu Leu Leu Glu Gln Asn Ile Asp Val Ser Ser Gln Asp Leu

325 330 335Ser Gly Gln Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val

340 345 350Ile Cys Gln Leu Leu Ser Asp Tyr Lys Glu Lys Gln Met Leu Lys Ile

355 360 365Ser Ser Glu Asn Ser Asn Pro Glu Gln Asp Leu Lys Leu Thr Ser Glu

370 375 380Glu Glu Ser Gln Arg Phe Lys Gly Ser Glu Asn Ser Gln Pro Glu Lys385 390 395 400Met Ser Gln Glu Pro Glu Ile Asn Lys Asp Gly Asp Arg Glu Val Glu

405 410 415Glu Glu Met Lys Lys His Glu Ser Asn Asn Val Gly Leu Leu Glu Asn

420 425 430Leu Thr Asn Gly Val Thr Ala Gly Asn Gly Asp Asn Gly Leu Ile Pro

435 440 445Gln Arg Lys Ser Arg Thr Pro Glu Asn Gln Gln Phe Pro Asp Asn Glu

450 455 460Ser Glu Glu Tyr His Arg Ile Cys Glu Leu Val Ser Asp Tyr Lys Glu465 470 475 480Lys Gln Met Pro Lys Tyr Ser Ser Glu Asn Ser Agn Pro Glu Gln Asp

485 490 495Leu Lys Leu Thr Ser Glu Glu Glu Ser Gln Arg Leu Glu Gly Ser Glu

500 505 510Asn Gly Gln Pro Glu Lys Arg Ser Gln Glu Pro Glu Ile Asn Lys Asp

515 520 525Gly Asp Arg Glu Leu Glu Asn Phe Met Ala Ile Glu Glu Met Lys Lys

530 535 540His Gly Ser Thr His Val Gly Phe Pro Glu Asn Leu Thr Asn Gly Ala545 550 555 560Thr Ala Gly Asn Gly Asp Asp Gly Leu Ile Pro Pro Arg Lys Ser Arg

565 570 575Thr Pro Glu Ser Gln Gln Phe Pro Asp Thr Glu Asn Glu Glu Tyr His

580 585 590Ser Asp Glu Gln Asn Asp Thr Gln Lys Gln Phe Cys Glu Glu Gln Ash

595 600 605Thr Gly Ile Leu His Asp Glu Ile Leu Ile His Glu Glu Lys Gln Ile

610 615 620Glu Val Val Glu Lys Met Asn Ser Glu Leu Ser Leu Ser Cys Lys Lys625 630 635 640Glu Lys Asp Ile Leu His Glu Asn Ser Thr Leu Arg Glu Glu Ile Ala

645 650 655Met Leu Arg Leu Glu Leu Asp Thr Met Lys His Gln Ser Gln Leu

660 665 670

<210> 381

<211> 251

<212> DNA

<213> Homo sapien

<400> 381ggagaagcgt ctgctggggc aggaaggggt ttccctgccc tctcacctgt ccctcaccaa 60ggtaacatgc ttcccctaag ggtatcccaa cccaggggcc tcaccatgac ctctgagggg 120ccaatatccc aggagaagca ttggggagtt gggggcaggt gaaggaccca ggactcacac 180atcctgggcc tccaaggcag aggagagggt cctcaagaag gtcaggagga aaatccgtaa 240caagcagtca g 251<210> 382<211> 3279<212> DNA<213> Homo sapiens<400> 382cttcctgcag cccccatgct ggtgaggggc acgggcagga acagtggacc caacatggaa 60atgctggagg gtgtcaggaa gtgatcgggc tctggggcag ggaggagggg tggggagtgt 120cactgggagg ggacatcctg cagaaggtag gagtgagcaa acacccgctg caggggaggg 180gagagccctg cggcacctgg gggagcagag ggagcagcac ctgcccaggc ctgggaggag 240gggcctggag ggcgtgagga ggagcgaggg ggctgcatggctggagtgag ggatcagggg 300cagggcgcga gatggcctca cacagggaag agagggcccc tcctgcaggg cctcacctgg 360gccacaggag gacactgctt ttcctctgag gagtcaggag ctgtggatgg tgctggacag 420aagaaggaca gggcctggct caggtgtcca gaggctgtcg ctggcttccc tttgggatca 480gactgcaggg agggagggcg gcagggttgt ggggggagtg acgatgagga tgacctgggg 540gtggctccag gccttgcccc tgcctgggcc ctcacccagc ctccctcaca gtctcctggc 600cctcagtctc tcccctccac tccatcctcc atctggcctc agtgggtcat tctgatcact 660gaactgacca tacccagccc tgcccacggc cctccatggc tccccaatgc cctggagagg 720ggacatctag tcagagagta gtcctgaaga ggtggcctct gcgatgtgcc tgtgggggca 780gcatcctgca gatggtcccg gccctcatcc tgctgacctg tctgcaggga ctgtcctcct 840ggaccttgcc ccttgtgcag gagctggacc ctgaagtccc ctccccatag gccaagactg 900gagccttgtt ccctctgttg gactccctgc ccatattctt gtgggagtgg gttctggaga 960catttctgtc tgttcctgag agctgggaat tgctctcagt catctgcctg cgcggttctg 1020agagatggag ttgcctaggc agttattggg gccaatcttt ctcactgtgt ctctcctcct 1080ttagccttag ggtgattctg ggggtccact tgtctgtaat ggtgtgcttc aaggtatcac 1140atcatggggc cctgagccat gtgccctgcc tgaaaagcct gctgtgtaca ccaaggtggt 1200gcattaccgg aagtggatca aggacaccat cgcagccaac ccctgagtgc ccctgtccca 1260cccctacctc tagtaaattt aagtccacct cacgttctgg catcacttgg cctttctgga 1320tgctggacac ctgaagcttg gaactcacct ggccgaagct cgagcctcct gagtcctact 1380gacctgtgct ttctggtgtg gagtccaggg ctgctaggaa aaggaatggg cagacacagg 1440tgtatgccaa tgtttctgaa atgggtataa tttcgtcctc tccttcggaa cactggctgt 1500ctctgaagac ttctcgctca gtttcagtga ggacacacac aaagacgtgg gtgaccatgt 1560tgtttgtggg gtgcagagat gggaggggtg gggcccaccc tggaagagtg gacagtgaca 1620caaggtggac actctctaca gatcactgag gataagctgg agccacaatg catgaggcac 1680acacacagca aggttgacgc tgtaaacata gcccacgctg tcctgggggc actgggaagc 1740ctagataagg ccgtgagcag aaagaagggg aggatcctcc tatgttgttg aaggagggac 1800tagggggaga aactgaaagc tgattaatta caggaggttt gttcaggtcc cccaaaccac 1860cgtcagattt gatgatttcc tagcaggact tacagaaata aagagctatc atgctgtggt 1920ttattatggt ttgttacatt gataggatac atactgaaat cagcaaacaa aacagatgta 1980tagattagag tgtggagaaa acagaggaaa acttgcagtt acgaagactg gcaacttggc 2040tttactaagt tttcagactg gcaggaagtc aaacctatta ggctgaggac cttgtggagt 2100gtagctgatc cagctgatag aggaactagc caggtggggg cctttccctt tggatggggg 2160gcatatccga cagttattct ctccaagtgg agacttacgg acagcatata attctccctg 2220caaggatgta tgataatatg tacaaagtaa ttccaactga ggaagctcac ctgatcctta 2280gtgtccaggg tttttactgg gggtctgtag gacgagtatg gagtacttga ataattgacc 2340tgaagtcctc agacctgagg ttccctagag ttcaaacaga tacagcatgg tccagagtcc 2400cagatgtaca aaaacaggga ttcatcacaa atcccatctt tagcatgaag ggtctggcat 2460ggcccaaggc cccaagtata tcaaggcact tgggcagaac atgccaagga atcaaatgtc 2520atctcccagg agttattcaa gggtgagccc tttacttggg atgtacaggc tttgagcagt 2580gcagggctgc tgagtcaacc ttttattgta Caggggatga gggaaaggga gaggatgagg 2640aagcccccct ggggatttgg tttggtcttg tgatcaggtg gtctatgggg ctatccctac 2700aaagaagaat ccagaaatag gggcacattg aggaatgata ctgagcccaa agagcattca 2760atcattgttt tatttgcctt cttttcacac cattggtgag ggagggatta ccaccctggg 2820gttatgaaga tggttgaaca ccccacacat agcaccggag atatgagatc aacagtttct 2880tagccataga gattcacagc ccagagcagg aggacgctgc acaccatgca ggatgacatg 2940ggggatgcgc tcgggattgg tgtgaagaag caaggactgt tagaggcagg ctttatagta 3000acaagacggt ggggcaaact ctgatttccg tgggggaatg tcatggtctt gctttactaa 3060gttttgagac tggcaggtag tgaaactcat taggctgaga accttgtgga atgcagctga 3120cccagctgat agaggaagta gccaggtggg agcctttccc agtgggtgtg ggacatatct 3180ggcaagattt tgtggcactc ctggttacag atactggggc agcaaataaa actgaatctt 3240gttttcagac cttaaaaaaa aaaaaaaaaa aaaagtttt 3279<210> 383<211> 155<212> PRT<213> Homo sapiens<400> 383Met Ala Gly Val Arg Asp Gln Gly Gln Gly Ala Arg Trp Pro His Thr

5 10 15Gly Lys Arg Gly Pro Leu Leu Gln Gly Leu Thr Trp Ala Thr Gly Gly

20 25 30His Cys Phe Ser Ser Glu Glu Ser Gly Ala Val Asp Gly Ala Gly Gln

35 40 45Lys Lys Asp Arg Ala Trp Leu Arg Cys Pro Glu Ala Val Ala Gly Phe

50 55 60Pro Leu Gly Ser Asp Cys Arg Glu Gly Gly Arg Gln Gly Cys Gly Gly65 70 75 80Ser Asp Asp Glu Asp Asp Leu Gly Val Ala Pro Gly Leu Ala Pro Ala

85 90 95Trp Ala Leu Thr Gln Pro Pro Ser Gln Ser Pro Gly Pro Gln Ser Leu

100 105 110Pro Ser Thr Pro Ser Ser Ile Trp Pro Gln Trp Val Ile Leu Ile Thr

115 120 125Glu Leu Thr Ile Pro Ser Pro Ala His Gly Pro Pro Trp Leu Pro Asn

130 135 140Ala Leu Glu Arg Gly His Leu Val Arg Glu145 150<210> 384<211> 557<212> DNA<213> Homo sapiens<400> 384ggatcctcta gagcggccgc ctactactac taaattcgcg gccgcgtcga cgaagaagag 60aaagatgtgt tttgttttgg actctctgtg gtcccttcca atgctgtggg tttccaacca 120ggggaagggt cccttttgca ttgccaagtg ccataaccat gagcactact ctaccatggt 180tctgcctcct ggccaagcag gctggtttgc aagaatgaaa tgaatgattc tacagctagg 240acttaacctt gaaatggaaa gtcttgcaat cccatttgca ggatccgtct gtgcacatgc 300ctctgtagag agcagcattc ccagggacct tggaaacagt tggcactgta aggtgcttgc 360tccccaagac acatcctaaa aggtgttgta atggtgaaaa cgtcttcctt ctttattgcc 420ccttcttatt tatgtgaaca actgtttgtc tttttttgta tcttttttaa actgtaaagt 480tcaattgtga aaatgaatat catgcaaata aattatgcga tttttttttc aaagtaaaaa 540aaaaaaaaaa aaaaaaa 557<210> 385<211> 337<212> DNA<213> Homo sapiens<400> 385ttcccaggtg atgtgcgagg gaagacacat ttactatcct tgatggggct gattccttta 60gtttctctag cagcagatgg gttaggagga agtgacccaa gtggttgact cctatgtgca 120tctcaaagcc atctgctgtc ttcgagtacg gacacatcat cactcctgca ttgttgatca 180aaacgtggag gtgcttttcc tcagctaaga agcccttagc aaaagctcga atagacttag 240tatcagacag gtccagtttc cgcaccaaca cctgctggtt ccctgtcgtg gtctggatct 300ctttggccac caattccccc ttttccacat cccggca 337<210> 386<211> 300<212> DNA<213> Homo sapiens<400> 386gggcccgcta ccggcccagg ccccgcctcg cgagtcctcc tccccgggtg cctgcccgca 60gcccgctcgg cccagagggt gggcgcgggg ctgcctctac cggctggcgg ctgtaactca 120gcgaccttgg cccgaaggct ctagcaagga cccaccgacc ccagccgcgg cggcggcggc 180gcggactttg cccggtgtgt ggggcggagc ggactgcgtg tccgcggacg ggcagcgaag 240atgttagcct tcgctgccag gaccgtggac cgatcccagg gctgtggtgt aacctcagcc 300<210> 387<211> 537<212> DNA<213> Homo sapiens<400> 387gggccgagtc gggcaccaag ggactctttg caggcttcct tcctcggatc atcaaggctg 60ccccctcctg tgccatcatg atcagcacct atgagttcgg caaaagcttc ttccagaggc 120tgaaccagga ccggcttctg ggcggctgaa aggggcaagg aggcaaggac cccgtctctc 180ccacggatgg ggagagggca ggaggagacc cagccaagtg ccttttcctc agcactgagg 240gagggggctt gtttcccttc cctcccggcg acaagctcca gggcagggct gtccctctgg 300gcggcccagc acttcctcag acacaacttc ttcctgctgc tccagtcgtg gggatcatca 360cttacccacc ccccaagttc aagaccaaat cttccagctg cccccttcgt gtttccctgt 420gtttgctgta gctgggcatg tctccaggaa ccaagaagcc ctcagcctgg tgtagtctcc 480ctgacccttg ttaattcctt aagtctaaag atgatgaact tcaaaaaaaa aaaaaaa 537<210> 388<211> 520<212> DNA<213> Homo sapiens<400> 388aggataattt ttaaaccaat caaatgaaaa aaacaaacaa acaaaaaagg aaatgtcatg 60tgaggttaaa ccagtttgca ttcccctaat gtggaaaaag taagaggact actcagcact 120gtttgaagat tgcctcttct acagcttctg agaattgtgt tatttcactt gccaagtgaa 180ggaccccctc cccaacatgc cccagcccac ccctaagcat ggtcccttgt caccaggcaa 240ccaggaaact gctacttgtg gacctcacca gagaccagga gggtttggtt agctcacagg 300acttccccca ccccagaaga ttagcatccc atactagact catactcaac tcaactaggc 360tcatactcaa ttgatggtta ttagacaatt ccatttcttt ctggttatta taaacagaaa 420atctttcctc ttctcattac cagtaaaggc tcttggtatc tttctgttgg aatgatttct 480atgaacttgt cttattttaa tggtgggttt tttttctggt 520<210> 389<211> 365<212> DNA<213> Homo sapiens<400> 389cgttgcccca gtttgacaga aggaaaggcg gagcttattc aaagtctaga gggagtggag 60gagttaaggc tggatttcag atctgcctgg ttccagccgc agtgtgccct ctgctccccc 120aacgactttc caaataatct caccagcgcc ttccagctca ggcgtcctag aagcgtcttg 180aagcctatgg ccagctgtct ttgtgttccc tctcacccgc ctgtcctcac agctgagact 240cccaggaaac cttcagacta ccttcctctg ccttcagcaa ggggcgttgc ccacattctc 300tgagggtcag tggaagaacc tagactccca ttgctagagg tagaaagggg aagggtgctg 360gggag 365<210> 390<211> 221<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(221)<223> n = A,T,C or G<400> 390tgcctctcca tcctggcccc gacttctctg tcaggaaagt ggggatggac cccatctgca 60tacacggntt ctcatgggtg tggaacatct ctgcttgcgg tttcaggaag gcctctggct 120gctctangag tctgancnga ntcgttgccc cantntgaca naaggaaagg cggagcttat 180tcaaagtcta gagggagtgg aggagttaag gctggatttc a 221<210> 391<211> 325<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1) ...(325)<223> n = A,T,C or G<400> 351tggagcaggt cccgaggcct ccctagagcc tggggccgac tctgtgncga tgcangcttt 60ctctcgcgcc cagcctggag ctgctcctgg catctaccaa caatcagncg aggcgagcag 120tagccagggc actgctgcca acagccagtc cnnataccat catgtnaccc ggtgngctct 180naanttngat ntccanagcc ctacccatcn tagttctgct ctcccaccgg ntaccagccc 240cactgcccag gaatcctaca gccagtaccc tgtcccgacg tctctaccta ccagtacgat 300gagacctccg gctactacta tgacc 325<210> 392<211> 277<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(277)<223> n = A,T,C or G<400> 392atattgttta actccttcct ttatatcttt taacattttc atggngaaag gttcacatct 60agtctcactt nggcnagngn ctcctacttg agtctcttcc ccggcctgnn ccagtngnaa 120antaccanga accgncatgn cttaanaacn ncctggtttn tgggttnntc aatgactgca 180tgcagtgcac caccctgtcc actacgtgat gctgtaggat taaagtctca cagtgggcgg 240ctgaggatac agcgccgcgt cctgtgttgc tggggaa 277<210> 393<211> 566<212> DNA<213> Homo sapiens<400> 393actagtccag tgtggtggaa ttcgcggccg cgtcgacgga caggtcagct gtctggctca 60gtgatctaca ttctgaagtt gtctgaaaat gtcttcatga ttaaattcag cctaaacgtt 120ttgccgggaa cactgcagag acaatgctgt gagtttccaa ccttagccca tctgcgggca 180gagaaggtct agtttgtcca tcagcattat catgatatca ggactggtta cttggttaag 240gaggggtcta ggagatctgt cccttttaga gacaccttac ttataatgaa gtatttggga 300gggtggtttt caaaagtaga aatgtcctgt attccgatga tcatcctgta aacattttat 360catttattaa tcatccctgc ctgtgtctat tattatattc atatctctac gctggaaact 420ttctgcctca atgtttactg tgcctttgtt tttgctagtt tgtgttgttg aaaaaaaaaa 480cattctctgc ctgagtttta atttttgtcc aaagttattt taatctatac aattaaaagc 540ttttgcctat caaaaaaaaa aaaaaa 566<210> 394<211> 384<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(384)<223> n = A,T,C or G<400> 394gaacatacat gtcccggcac ctgagctgca gtctgacatc atcgccatca cgggcctcgc 60tgcaaattng gaccgggcca aggctggact gctggagcgt gtgaaggagc tacaggccna 120gcaggaggac cgggctttaa ggagttttaa gctgagtgtc actgtagacc ccaaatacca 180tcccaagatt atcgggagaa agggggcagt aattacccaa atccggttgg agcatgacgt 240gaacatccag tttcctgata aggacgatgg gaaccagccc caggaccaaa ttaccatcac 300agggtacgaa aagaacacag aagctgccag ggatgctata ctgagaattg tgggtgaact 360tgagcagatg gtttctgagg acgt 384<210> 395<211> 399<212> DNA<213> Homo sapiens<400> 395ggcaaaactg tgtgacctca ataagacctc gcagatccaa ggtcaagtat cagaagtgac 60tctgaccttg gactccaaga cctacatcaa cagcctggct atattagatg atgagccagt 120tatcagaggt ttcatcattg cggaaattgt ggagtctaag gaaatcatgg cctctgaagt 180attcacgtct ttccagtacc ctgagttctc tatagagttg cctaacacag gcagaattgg 240ccagctactt gtctgcaatt gtatcttcaa gaataccctg gccatccctt tgactgacgt 300caagttctct ttggaaagcc tgggcatctc ctcactacag acctctgacc atgggacggt 360gcagcctggt gagaccatcc aatcccaaat aaaatgcac 399<210> 396<211> 403<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(403)<223> n = A,T,C or G<400> 396tggagttntc agtgcaaaca agccataaag cttcagtagc aaattactgt ctcacagaaa 60gacattttca acttctgctc cagctgctga taaaacaaat catgtgttta gcttgactcc 120agacaaggac aacctgttcc ttcataactc tctagagaaa aaaaggagtt gttagtagat 180actaaaaaaa gtggatgaat aatctggata tttttcctaa aaagattcct tgaaacacat 240taggaaaatg gagggcctta tgatcagaat gctagaatta gtccattgtg ctgaagcagg 300gtttagggga gggagtgagg gataaaagaa ggaaaaaaag aagagtgaga aaacctattt 360atcaaagcag gtgctatcac tcaatgttag gccctgctct ttt 403<210> 397<211> 100<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1) ...(100)<223> n = A,T,C or G<400> 397actagtncag tgtggtggaa ttcgcggccg cgtcgaccta naanccatct ctatagcaaa 60tccatccccg ctcctggttg gtnacagaat gactgacaaa 100<210> 398<211> 278<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (278)<223> n = A,T,C or G<400> 398gcggccgcgt cgacagcagt tccgccagcg ctcgcccctg ggtggggatg tgctgcacgc 60ccacctggac atctggaagt cagcggcctg gatgaaagag cggacttcac ctggggcgat 120tcactactgt gcctcgacca gtgaggagag ctggaccgac agcgaggtgg actcatcatg 180ctccgggcag cccatccacc tgtggcagtt cctcaaggag ttgctactca agccccacag 240ctatggccgc ttcattangt ggctcaacaa ggagaagg 278<210> 399<211> 298<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (298)<223> n = A,T,C or G<400> 399acggaggtgg aggaagcgnc cctgggatcg anaggatggg tcctgncatt gaccncctcn 60ggggtgccng catggagcgc atgggcgcgg gcctgggcca cggcatggat cgcgtgggct 120ccgagatcga gcgcatgggc ctggtcatgg accgcatggg ctccgtggag cgcatgggct 180ccggcattga gcgcatgggc ccgctgggcc tcgaccacat ggcctccanc attgancgca 240tgggccagac catggagcgc attggctctg gcgtggagcn catgggtgcc ggcatggg 298<210> 400<211> 548<212> DNA<213> Homo sapiens<400> 400acatcaacta cttcctcatt ttaaggtatg gcagttccct tcatcccctt ttcctgcctt 60gtacatgtac atgtatgaaa tttccttctc ttaccgaact ctctccacac atcacaaggt 120caaagaacca cacgcttaga agggtaagag ggcaccctat gaaatgaaat ggtgatttct 180tgagtctctt ttttccacgt ttaaggggcc atggcaggac ttagagttgc gagttaagac 240tgcagagggc tagagaatta tttcatacag gctttgaggc cacccatgtc acttatcccg 300tataccctct caccatcccc ttgtctactc tgatgccccc aagatgcaac tgggcagcta 360gttggcccca taattctggg cctttgttgt ttgttttaat tacttgggca tcccaggaag 420ctttccagtg atctcctacc atgggccccc ctcctgggat caagcccctc ccaggccctg 480tccccagccc ctcctgcccc agcccacccg cttgccttgg tgctcagccc tcccattggg 540agcaggtt 548<210> 401<211> 355<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(355)<223> n = A,T,C or G<400> 401actgtttcca tgttatgttt ctacacattg ctacctcagt gctcctggaa acttagcttt 60tgatgtctcc aagtagtcca ccttcattta actctttgaa actgtatcat ctttgccaag 120taagagtggt ggcctatttc agctgctttg acaaaatgac tggctcctga cttaacgttc 180tataaatgaa tgtgctgaag caaagtgccc atggtggcgg cgaagaagan aaagatgtgt 240tttgttttgg actctctgtg gtcccttcca atgctgnggg tttccaacca ggggaagggt 300cccttttgca ttgccaagtg ccataaccat gagcactact ctaccatggn tctgc 355<210> 402<211> 407<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (407)<223> n = A,T,C or G<400> 402atggggcaag ctggataaag aaccaagacc cactggagta tgctgtcttc aagaaaccca 60tctcacatgc ggtggcatac ataggctcaa aataaaggaa tggagaaaaa tatttcaagc 120aaatggaaaa cagaaaaaag caggtgttgc actcctactt tctgacaaaa cagactatgc 180gaataaagat aaaaaagaga aggacattac aaaggtggtc ctgacctttg ataaatctca 240ttgcttgata ccaacctggg ctgttttaat tgcccaaacc aaaaggataa tttgctgagg 300ttgtggagct tctcccctgc agagagtccc tgatctccca aaatttggtt gagatgtaag 360gntgattttg ctgacaactc cttttctgaa gttttactca tttccaa 407<210> 403<211> 303<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(303)<223> n = A,T,C or G<400> 403cagtatttat agccnaactg aaaagctagt agcaggcaag tctcaaatcc aggcaccaaa 60tcctaagcaa gagccatggc atggtgaaaa tgcaaaagga gagtctggcc aatctacaaa 120tagagaacaa gacctactca gtcatgaaca aaaaggcaga caccaacatg gatctcatgg 180gggattggat attgtaatta tagagcagga agatgacagt gatcgtcatt tggcacaaca 240tcttaacaac gaccgaaacc cattatttac ataaacctcc attcggtaac catgttgaaa 300gga 303<210> 404<211> 225<212> DNA<213> Homo sapiens<400> 404aagtgtaact tttaaaaatt tagtggattt tgaaaattct tagaggaaag taaaggaaaa 60attgttaatg cactcattta cctttacatg gtgaaagttc tctcttgatc ctacaaacag 120acattttcca ctcgtgtttc catagttgtt aagtgtatca gatgtgttgg gcatgtgaat 180ctccaagtgc ctgtgtaata aataaagtat ctttatttca ttcat 225<210> 405<211> 334<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(334)<223> n = A,T,C or G<400> 405gagctgttat actgtgagtt ctactaggaa atcatcaaat ctgagggttg tctggaggac 60ttcaatacac ctccccccat agtgaatcag cttccagggg gtccagtccc tctccttact 120tcatccccat cccatgccaa aggaagaccc tccctccttg gctcacagcc ttctctaggc 180ttcccagtgc ctccaggaca gagtgggtta tgttttcagc tccatccttg ctgtgagtgt 240ctggtgcggt tgtgcctcca gcttctgctc agtgcttcat ggacagtgtc cagcccatgt 300cactctccac tctctcanng tggatcccac ccct 334<210> 406<211> 216<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(216)<223> n = A,T,C or G<400> 406tttcatacct aatgagggag ttganatnac atnnaaccag gaaatgcatg gatctcaang 60gaaacaaaca cccaataaac tcggagtggc agactgacaa ctgtgagaca tgcacttgct 120acnaaacaca aatttnatgt tgcacccttg tttctacacc tgtgggttat gacaaagaca 180actgccaaag aatnttcaag aaggaggact gccant 216<210> 407<211> 413<212> DNA<213> Homo sapiens<400> 407gctgacttgc tagtatcatc tgcattcatt gaagcacaag aacttcatgc cttgactcat 60gtaaatgcaa taggattaaa aaataaattt gatatcacat ggaaacagac aaaaaatatt 120gtacaacatt gcacccagtg tcagattcta cacctggcca ctcaggaagc aagagttaat 180cccagaggtc tatgtcctaa tgtgttatgg caaatggatg tcatgcacgt accttcattt 240ggaaaattgt catttgtcca tgtgacagtt gatacttatt cacatttcat atgggcaacc 300tgccagacag gagaaagtct tcccatgtta aaagacattt attatcttgt tttcctgtca 360tgggagttcc agaaaaagtt aaaacagaca atgggccagg ttctgtagta aag 413<210> 408<211> 183<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(183)<223> n = A,T,C or G<400> 408ggagctngcc ctcaattcct ccatntctat gttancatat ttaatgtctt ttgnnattaa 60tncttaacta gttaatcctt aaagggctan ntaatcctta actagtccct ccattgtgag 120cattatcctt ccagtattcn ccttctnttt tatttactcc ttcctggcta cccatgtact 180ntt 183<210> 409<211> 250<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1) ... (250)<223> n = A,T,C or G<400> 409cccacgcatg ataagctctt tatttctgta agtcctgcta ggaaatcatc aaatctgacg 60gtggtttggg ggacctgaac aaacctcctg taattaatca gctttcagtt tctcccccta 120gtccctcctt caacaacata ggaggatcct ccccttcttt ctgctcacgg ccttatctag 180gcttcccagt gcccccagga cagcgtgggc tatgtttaca gcgcntcctt gctggggggg 240ggccntatgc 250<210> 410<211> 306<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(306)<223> n = A,T,C or G<400> 410ggctggtttg caagaatgaa atgaatgatt ctacagctag gacttaacct tgaaatggaa 60agtcttgcaa tcccatttgc aggatccgtc tgtgcacatg cctctgtaga gagcagcatt 120cccagggacc ttggaaacag ttggcactgt aaggtgcttg ctccccaaga cacatcctaa 180aaggtgttgt aatggtgaaa accgcttcct tctttattgc cccttcttat ttatgtgaac 240nactggttgg ctttttttgn atctttttta aactggaaag ttcaattgng aaaatgaata 300tcntgc 306<210> 411<211> 261<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(261)<223> n = A,T,C or G<400> 411agagatattn cttaggtnaa agttcataga gttcccatga actatatgac tggccacaca 60ggatcttttg tatttaagga ttctgagatt ttgcttgagc aggattagat aaggctgttc 120tttaaatgtc tgaaatggaa cagatttcaa aaaaaaaccc cacaatctag ggtgggaaca 180aggaaggaaa gatgtgaata ggctgatggg caaaaaacca atttacccat cagttccagc 240cttctctcaa ggngaggcaa a 261<210> 412<211> 241<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(241)<223> n = A,T,C or G<400> 412gttcaatgtt acctgacatt tctacaacac cccactcacc gatgtattcg ttgcccagtg 60ggaacatacc agcctgaatt tggaaaaaat aattgtgttt cttgcccagg aaatactacg 120actgactttg atggctccac aaacataacc cagtgtaaaa acagaagatg tggaggggag 180ctgggagatt tcactgggta cattgaattc ccaaactacc cangcaatta cccagccaac 240a 241<210> 413<211> 231<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(231)<223> n = A,T,C or G<400> 413aactcttaca atccaagtga ctcatctgtg tgcttgaatc ctttccactg tctcatctcc 60ctcatccaag tttctagtac cttctctttg ttgtgaagga taatcaaact gaacaacaaa 120aagtttactc tcctcatttg gaacctaaaa actctcttct tcctgggtct gagggctcca 180agaatccttg aatcanttct cagatcattg gggacaccan atcaggaacc t 231<210> 414<211> 234<212> DNA<213> Homo sapiens<400> 414actgtccatg aagcactgag cagaagctgg aggcacaacg caccagacac tcacagcaag 60gatggagctg aaaacataac ccactctgtc ctggaggcac tgggaagcct agagaaggct 120gtgagccaag gagggaggt cttcctttgg catgggatgg ggatgaagta aggagaggga 180ctggaccccc tggaagctga ttcactatgg ggggaggtgt attgaagtcc tcca 234<210> 415<211> 217<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(217)<223> n = A,T,C or G<400> 415gcataggatt aagactgagt atcttttcta cattctttta actttctaag gggcacttct 60caaaacacag accaggtagc aaatctccac tgctctaagg ntctcaccac cactttctca 120cacctagcaa tagtagaatt cagtcctact tctgaggcca gaagaatggt tcagaaaaat 180antggattat aaaaaataac aattaagaaa aataatc 217<210> 416<211> 213<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(213)<223> n = A,T,C or G<400> 416atgcatatnt aaagganact gcctcgcttt tagaagacat ctggnctgct ctctgcatga 60ggcacagcag taaagctctt tgattcccag aatcaagaac tctccccttc agactattac 120cgaatgcaag gtggttaatt gaaggccact aattgatgct caaatagaag gatattgact 180atattggaac agatggagtc tctactacaa aag 213<210> 417<211> 303<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(303)<223> n = A,T,C or G<400> 417nagtcttcag gcccatcagg gaagttcaca ctggagagaa gtcatacata tgtactgtat 60gtgggaaagg ctttactctg agttcaaatc ttcaagccca tcagagagtc cacactggag 120agaagccata caaatgcaat gagtgtggga agagcttcag gagggattcc cattatcaag 180ttcatctagt ggtccacaca ggagagaaac cctataaatg tgagatatgt gggaagggct 240tcantcaaag ttcgtatctt caaatccatc ngaaggncca cagtatanan aaacctttta 300agt 303<210> 418<211> 328<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(328)<223> n = A,T,C or G<400> 418tttttggcgg tggtggggca gggacgggac angagtctca ctctgttgcc caggctggag 60tgcacaggca tgatctcggc tcactacaac ccctgcctcc catgtccaag cgattcttgt 120gcctcagcct tccctgtagc tagaattaca ggcacatgcc accacaccca gctagttttt 180gtatttttag tagagacagg gtttcaccat gttggccagg ctggtctcaa actcctnacc 240tcagnggtca ggctggtctc aaactcctga cctcaagtga tctgcccacc tcagcctccc 300aaagtgctan gattacaggc cgtgagcc 328<210> 419<211> 389<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(389)<223> n = A,T,C or G<400> 419cctcctcaag acggcctgtg gtccgcctcc cggcaaccaa gaagcctgca gtgccatatg 60acccctgagc catggactgg agcctgaaag gcagcgtaca ccctgctcct gatcttgctg 120cttgtttcct ctctgtggct ccattcatag cacagttgtt gcactgaggc ttgtgcaggc 180cgagcaaggc caagctggct caaagagcaa ccagtcaact ctgccacggt gtgccaggca 240ccggttctcc agccaccaac ctcactcgct cccgcaaatg gcacatcagt tcttctaccc 300taaaggtagg accaaagggc atctgctttt ctgaagtcct ctgctctatc agccatcacg 360tggcagccac tcnggctgtg tcgacgcgg 389<210> 420<211> 408<212> DNA<213> Homo sapiens<400> 420gttcctccta actcctgcca gaaacagctc tcctcaacat gagagctgca cccctcctcc 60tggccagggc agcaagcctt agccttggct tcttgtttct gctttttttc tggctagacc 120gaagtgtact agccaaggag ttgaagtttg tgactttggt gtttcggcat ggagaccgaa 180gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 240gccaactcac ccagctgggc atggagcagc attatgaact tggagagtat ataagaaaga 300gatatagaaa attcttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 360acgttgaccg gactttgatg aagtgctatg acaaacctgg caagcccg 408<210> 421<211> 352<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(352)<223> n = A,T,C or G<400> 421gctcaaaaat ctttttactg atnggcatgg ctacacaatc attgactatt acggaggcca 60gaggagaatg aggcctggcc tgggagccct gtgcctacta naagcacatt agattatcca 120ttcactgaca gaacaggtct tttttgggtc cttcttctcc accacnatat acttgcagtc 180ctccttcttg aagattcttt ggcagttgtc tttgtcataa cccacaggtg tagaaacaag 240ggtgcaacat gaaatttctg tttcgtagca agtgcatgtc tcacaagttg gcangtctgc 300cactccgagt ttattgggtg tttgtttcct ttgagatcca tgcatttcct gg 352<210> 422<211> 337<212> DNA<213> Homo sapiens<400> 422atgccaccat gctggcaatg cagcgggcgg tcgaaggcct gcatatccag cccaagctgg 60cgatgatcga cggcaaccgt tgcccgaagt tgccgatgcc agccgaagcg gtggtcaagg 120gcgatagcaa ggtgccggcg atcgcggcgg cgtcaatcct ggccaaggtc agccgrgatc 180gtgaaatggc agctgtcgaa ttgatctacc cgggttatgg catcggcggg cataagggct 240atccgacacc ggtgcacctg gaagccttgc agcggctggg gccgacgccg attcaccgac 300gcttcttccg ccggtacggc tggcctatga aaattat 337<210> 423<211> 310<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (310)<223> n = A,T,C or G<400> 423gctcaaaaat ctttttactg atatggcatg gctacacaat cattgactat tagaggccag 60aggagaatga ggcctggcct gggagccctg tgcctactan aagcncatta gattatccat 120tcactgacag aacaggtctt ttttgggtcc ttcttctcca ccacgatata cttgcagtcc 180tccttcttga agattctttg gcagttgtct ttgtcataac ccacaggtgt anaaacaagg 240gtgcaacatg aaatttctgt ttcgtagcaa gtgcatgtct cacagttgtc aagtctgccc 300tccgagttta 310<210> 424<211> 370<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(370)<223> n = A,T,C or G<400> 424gctcaaaaat ctttttactg ataggcatgg ctacacaatc attgactatt agaggccaga 60ggagaatgag gcctggcctg ggagccctgt gcctactaga agcacattag attatccatt 120cactgacaga acaggtcttt tttgggtcct tcttctccac cacgatatac ttgcagtcct 180ccttcttgaa gattctttgg cagttgtctt tgtcataacc cacaggtgta gaaacatcct 240ggttgaatct cctggaactc cctcattagg tatgaaatag catgatgcat tgcataaagt 300cacgaaggtg gcaaagatca caacgctgcc cagganaaca ttcattgtga taagcaggac 360tccgtcgacg 370<210> 425<211> 216<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(216)<223> n = A,T,C or G<400> 425aattgctatn ntttattttg ccactcaaaa taattaccaa aaaaaaaaaa tnttaaatga 60taacaacnca acatcaaggn aaananaaca ggaatggntg accntgcata aatnggccga 120anattatcca ttatnttaag ggttgacttc aggntacagc acacagacaa acatgcccag 180gaggntntca ggaccgctcg atgtnttntg aggagg 216<210> 426<211> 596<212> DNA<213> Homo sapiens<400> 426cttccagtga ggataaccct gttgccccgg gccgaggttc tccattaggc tctgattgat 60tggcagtcag tgatggaagg gtgttctgat cattccgact gccccaaggg tcgctggcca 120gctctctgtt ttgctgagtt ggcagtagga cctaatttgt taattaagag tagatggtga 180gctgtccttg tattttgatt aacctaatgg ccttcccagc acgactcgga ttcagctgga 240gacatcacgg caacttttaa tgaaatgatt tgaagggcca ttaagaggca cttcccgtta 300ttaggcagtt catctgcact gataacttct tggcagctga gctggtcgga gctgtggccc 360aaacgcacac ttggcttttg gttttgagat acaactctta atcttttagt catgcttgag 420ggtggatggc cttttcagct ttaacccaat ttgcactgcc ttggaagtgt agccaggaga 480atacactcat atactcgtgg gcttagaggc cacagcagat gtcattggtc tactgcctga 540gtcccgctgg tcccatccca ggaccttcca tcggcgagta cctgggagcc cgtgct 596<210> 427<211> 107<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(107)<223> n = A,T,C or G<400> 427gaagaattca agttaggttt attcaaaggg cttacngaga atcctanacc caggncccag 60cccgggagca gccttanaga gctcctgttt gactgcccgg ctcagng 107<210> 428<211> 38<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(38)<223> n = A,T,C or G<400> 428gaacttccna anaangactt tattcactat tttacatt 38<210> 429<211> 544<212> DNA<213> Homo sapiens<400> 429ctttgctgga cggaataaaa gtggacgcaa gcatgacctc ctgatgaggg cgctgcattt 60attgaagagc ggctgcagcc ctgcggttca gattaaaatc cgagaattgt atagacgccg 120atatccacga actcttgaag gactttctga tttatccaca atcaaatcat cggttttcag 180tttggatggt ggctcatcac ctgtagaacc tgacttggcc gtggctggaa tccactcgtt 240gccttccact tcagttacac ctcactcacc atcctctcct gttggttctg tgctgcttca 300agatactaag cccacatttg agatgcagca gccatctccc ccaattcctc ctgtccatcc 360tgatgtgcag ttaaaaaatc tgccctttta tgatgtcctt gatgttctca tcaagcccac 420gagtttagtt caaagcagta ttcagcgatt tcaagagaag ttttttattt ttgctttgac 480acctcaacaa gttagagaga tatgcatatc cagggatttt ttgccaggtg gtaggagaga 540ttat 544<210> 430<211> 507<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(507)<223> n = A,T,C or G<400> 430cttatcncaa tggggctccc aaacttggct gtgcagtgga aactccgggg gaattttgaa 60gaacactgac acccatcttc caccccgaca ctctgattta attgggctgc agtgagaaca 120gagcatcaat ttaaaaagct gcccagaatg ttntcctggg cagcgttgtg atctttgccn 180ccttcgtgac tttatgcaat gcatcatgct atttcatacc taatgaggga gttccaggag 240attcaaccag gatgtttcta cncctgtggg ttatgacaaa gacaactgcc aaagaatntt 300caagaaggag gactgcaagt atatcgtggt ggagaagaag gacccaaaaa agacctgttc 360tgtcagtgaa tggataatct aatgtgcttc tagtaggcac agggctccca ggccaggcct 420cattctcctc tggcctctaa tagtcaatga ttgtgtagcc atgcctatca gtaaaaagat 480ttttgagcaa aaaaaaaaaa aaaaaaa 507<210> 431<211> 392<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(392)<223> n = A,T,C or G<400> 431gaaaattcag aatggataaa aacaaatgaa gtacaaaata tttcagattt acatagcgat 60aaacaagaaa gcacttatca ggaggactta caaatggaag tacactctan aaccatcatc 120tatcatggct aaatgtgaga ttagcacagc tgtattattt gtacattgca aacacctaga 180aagagatggg aaacaaaatc ccaggagttt tgtgtgtgga gtcctgggtt ttccaacaga 240catcattcca gcattctgag attagggnga ttggggatca ttctggagtt ggaatgttca 300acaaaagtga tgttgttagg taaaatgtac aacttctgga tctatgcaga cattgaaggt 360gcaatgagtc tggcttttac tctgctgttt ct 392<210> 432<211> 387<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(387)<223> n = A,T,C or G<400> 432ggtatccnta cataatcaaa tatagctgta gtacatgttt tcattggngt agattaccac 60aaatgcaagg caacatgtgt agatctcttg tcttattctt ttgtctataa tactgtattg 120ngtagtccaa gctctcggna gtccagccac tgngaaacat gctcccttta gattaacctc 180gtggacnctn ttgttgnatt gtctgaactg tagngccctg tattttgctt ctgtctgnga 240attctgttgc ttctggggca tttccttgng atgcagagga ccaccacaca gatgacagca 300atctgaattg ntccaatcac agctgcgatt aagacatact gaaatcgtac aggaccggga 360acaacgtata gaacactgga gtccttt 387<210> 433<211> 281<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)... (281)<223> n = A,T,C or G<400> 433ttcaactagc anagaanact gcttcagggn gtgtaaaatg aaaggcttcc acgcagttat 60ctgattaaag aacactaaga gagggacaag gctagaagcc gcaggatgtc tacactatag 120caggcnctat ttgggttggc tggaggagct gtggaaaaca tggagagatt ggcgctggag 180atcgccgtgg ctattcctcn ttgntattac accagngagg ntctctgtnt gcccactggt 240tnnaaaaccg ntatacaata atgatagaat aggacacaca t 281<210> 434<211> 484<212> DNA<213> Homo sapiens<400> 434ttttaaaata agcatttagt gctcagtccc tactgagtac tctttctctc ccctcctctg 60aatttaattc tttcaacttg caatttgcaa ggattacaca tttcactgtg atgtatattg 120tgttgcaaaa aaaaaaaagt gtctttgttt aaaattactt ggtttgtgaa tccatcttgc 180tttttcccca ttggaactag tcattaaccc atctctgaac tggtagaaaa acatctgaag 240agctagtcta tcagcatctg acaggtgaat tggatggttc tcagaaccat ttcacccaga 300cagcctgttt ctatcctgtt taataaatta gtttgggttc tctacatgca taacaaaccc 360tgctccaatc tgtcacataa aagtctgtga cttgaagttt agtcagcacc cccaccaaac 420tttatttttc tatgtgtttt ttgcaacata tgagtgtttt gaaaataaag tacccatgtc 480ttta 484<210> 435<211> 424<212> DNA<213> Homo sapiens<400> 435gcgccgctca gagcaggtca ctttctgcct tccacgtcct ccttcaagga agccccatgt 60gggtagcttt caatatcgca ggttcttact cctctgcctc tataagctca aacccaccaa 120cgatcgggca agtaaacccc ctccctcgcc gacttcggaa ctggcgagag ttcagcgcag 180atgggcctgt ggggaggggg caagatagat gagggggagc ggcatggtgc ggggtgaccc 240cttggagaga ggaaaaaggc cacaagaggg gctgccaccg ccactaacgg agatggccct 300ggtagagacc tttgggggtc tggaacctct ggactcccca tgctctaact cccacactct 360gctatcagaa acttaaactt gaggattttc tctgtttttc actcgcaata aattcagagc 420aaac 424<210> 436<211> 667<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(667)<223> n = A,T,C or G<400> 436accttgggaa nactctcaca atataaaggg tcgtagactt tactccaaat tccaaaaagg 60tctggccat gtaatcctga aagttttccc aaggtagcta taaaatcctt ataagggtgc 120agcctcttct ggaattcctc tgatttcaaa gtctcactct caagttcttg aaaacgaggg 180cagttcctga aaggcaggta tagcaactga tcttcagaaa gaggaactgt gtgcaccggg 240atgggctgcc agagtaggat aggattccag atgctgacac cttctggggg aaacagggct 300gcaggtttg tcatagcact catcaaagtc cggtcaacgt ctgtgcttcg aatataaacc 360tgttcatgtt tataggactc attcaagaat tttctatatc tctttcttat atactctcca 420agttcataat gctgctccat gcccagctgg gtgagttggc caaatccttg tggccatgag 480gattccttta tggggtcagt gggaaaggtg tcaatgggac ttcggtctcc atgccgaaac 540accaaagtca caaacttcaa ctccttggct agtacacttc ggtctagcca gaaaaaaagc 600agaaacaaga agccaaggct aaggcttgct gccctgccag gaggaggggt gcagctctca 660tgttgag 667<210> 437<211> 693<212> DNA<213> Homo sapiens<400> 437ctacgtctca accctcattt ttaggtaagg aatcttaagt ccaaagatat taagtgactc 60acacagccag gtaaggaaag ctggattggc acactaggac tctaccatac cgggttttgt 120taaagctcag gttaggaggc tgataagctt ggaaggaact tcagacaGct ttttcagatc 180ataaaagata attcttagcc catgttcttc tccagagcag acctgaaatg acagcacagc 240aggtactcct ctattttcac ccctcttgct tctactctct ggcagtcaga cctgtgggag 300gccatgggag aaagcagctc tctggatgtt tGtacagatc atggactatt ctctgtggac 360catttctcca gGttacccta ggtgtcacta ttggggggac agccagcatc tttagctttc 420atttgagttt ctgtctgtct tcagtagagg aaacttttgc tcttcacact tcacatctga 480acacctaact gctgttgctc ctgaggtggt Gaaagacaga tatagagctt acagtattta 540tcctatttct aggcactgag Ggctgtgggg taccttgtgg tgccaaaaca gatcctgttt 600taaggacatg ttgcttcaga gatgtctgta actatctggg ggctctgttg gctctttacc 660ctgcatcatg tgctctcttg gctgaaaatg acc 693<210> 438<211> 360<212> DNA<213> Homo sapiens<400> 438ctgcttatca caatgaatgt tctcctgggc agcgttgtga tctttgccac cttcgtgact 60ttatgcaatg catcatgcta tttcatacct aatgagggag ttccaggaga ttcaaccagg 120atgtttctac acctgtgggt tatgacaaag acaactgcca aagaatcttc aagaaggagg 180actgcaagta tatctggtgg agaagaagga cccaaaaaag acctgttctg tcagtgaatg 240gataatctaa tgtgcttcta gtaggcacag ggctcccagg ccaggcctca ttctcctctg 300gcctctaata gtcaataatt gtgtagccat gcctatcagt aaaaagattt ttgagcaaac 360<210> 439<211> 431<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(431)<223> n = A,T,C or G<400> 439gttcctnnta actcctgcca gaaacagctc tcctcaacat gagagctgca cccctcctcc 60tggccagggc agcaagcctt agccttggct tcttgtttct gctttttttc tggctagacc 120gaagtgtact agccaaggag ttgaagtttg tgactttggt gtttcggcat ggagaccgaa 180gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 240gccaactcac ccagctgggc atggagcagc attatgaact tggagagtat ataagaaaga 300gatatagaaa attcttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 360acgttgaccg gactttgatg agtgctatga caaacctggc agcccgtcga cgcggccgcg 420aatttagtag t 431<210> 440<211> 523<212> DNA<213> Homo sapiens<400> 440agagataaag cttaggtcaa agttcataga gttcccatga actatatgac tggccacaca 60ggatcttttg tatttaagga ttctgagatt ttgcttgagc aggattagat aaggctgttc 120tttaaatgtc tgaaatggaa cagatttcaa aaaaaaaccc cacaatctag ggtgggaaca 180aggaaggaaa gatgtgaata ggctgatggg caaaaaacca atttacccat cagttccagc 240cttctctcaa ggagaggcaa agaaaggaga tacagtggag acatctggaa agttttctcc 300actggaaaac tgctactatc tgtttttata tttctgttaa aatatatgag gctacagaac 360taaaaattaa aacctctttg tgtcccttgg tcctggaaca tttatgttcc ttttaaagaa 420acaaaaatca aactttacag aaagatttga tgtatgtaat acatatagca gctcttgaag 480tatatatatc atagcaaata agtcatctga tgagaacaag cta 523<210> 441<211> 430<212> DNA<213> Homo sapiens<400> 441gttcctccta actcctgcca gaaacagctc tcctcaacat gagagctgca cccctcctcc 60tggccagggc agcaagcctt agccttggct tcttgtttct gctttttttc tggctagacc 120gaagtgtact agccaaggag ttgaagtttg tgactttggt gtttcggcat ggagaccgaa 180gtcccattga cacctttccc actgacccca taaaggaatc ctcatggcca caaggatttg 240gccaactcac ccagctgggc atggagcagc attatgaact tggagagtat ataagaaaga 300gatatagaaa attcttgaat gagtcctata aacatgaaca ggtttatatt cgaagcacag 360acgttgacg gactttgatg agtgctatga caaacctggc agcccgtcga cgcggccgcg 420aatttagtag 430<210> 442<211> 362<212> DNA<213> Homo sapiens<400> 442ctaaggaatt agtagtgttc ccatcacttg tttggagtgt gctattctaa aagattttga 60tttcctggaa tgacaattat attttaactt tggtggggga aagagttata ggaccacagt 120cttcacttct gatacttgta aattaatctt ttattgcact tgttttgacc attaagctat 180atgtttagaa atggtcattt tacggaaaaa ttagaaaaat tctgataata gtgcagaata 240aatgaattaa tgttttactt aatttatatt gaactgtcaa tgacaaataa aaattctttt 300tgattatttt ttgttttcat ttaccagaat aaaaactaag aattaaaagt ttgattacag 360tc 362<210> 443<211> 624<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(624)<223> n = A,T,C or G<400> 443tttttttttt gcaacacaat atacatcaca gtgaaatgtg taatccttgc aaattgcaag 60ttgaaagaat taaattcaga ggaggggaga gaaagagtac tcagtaggga ctgagcacta 120aatgcttatt ttaaaagaaa tgtaaagagc agaaagcaat tcaggctacc ctgccttttg 180tgctggctag tactccggtc ggtgtcagca gcacgtggca ttgaacattg caatgtggag 240cccaaaccac agaaaatggg gtgaaattgg ccaactttct attaacttgg cttcctgttt 300tataaaatat tgtgaataat atcacctact tcaaagggca gttatgaggc ttaaatgaac 360taacgcctac aaaacactta aacatagata acataggtgc aagtactatg tatctggtac 420atggtaaaca tccttattat taaagtcaac gctaaaatga atgtgtgtgc atatgctaat 480agtacagaga gagggcactt aaaccaacta agggcctgga gggaaggttt cctggaaaga 540ngatgcttgt gctgggtcca aatcttggtc tactatgacc ttggccaaat tatttaaact 600ttgtccctat ctgctaaaca gatc 624<210> 444<211> 425<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(425)<223> n = A,T,C or G<400> 444gcacatcatt nntcttgcat tctttgagaa taagaagatc agtaaatagt tcagaagtgg 60gaagctttgt ccaggcctgt gtgtgaaccc aatgttttgc ttagaaatag aacaagtaag 120ttcattgcta tagcataaca caaaatttgc ataagtggtg gtcagcaaat ccttgaatgc 180tgcttaatgt gagaggttgg taaaatcctt tgtgcaacac tctaactccc tgaatgtttt 240gctgtgctgg gacctgtgca tgccagacaa ggccaagctg gctgaaagag caaccagcca 300cctctgcaat ctgccacctc ctgctggcag gatttgtttt tgcatcctgt gaagagccaa 360ggaggcacca gggcataagt gagtagactt atggtcgacg cggccgcgaa tttagtagta 420gtaga 425<210> 445<211> 414<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(414)<223> n = A,T,C or G<400> 445catgtttatg nttttggatt actttgggca cctagtgttt ctaaatcgtc tatcattctt 60ttctgttttt caaaagcaga gatggccaga gtctcaacaa actgtatctt caagtctttg 120tgaaattctt tgcatgtggc agattattgg atgtagtttc ctttaactag catataaatc 180tggtgtgttt cagataaatg aacagcaaaa tgtggtggaa ttaccatttg gaacattgtg 240aatgaaaaat tgtgtctcta gattatgtaa caaataacta tttcctaacc attgatcttt 300ggatttttat aatcctactc acaaatgact aggctctcc tcttgtattt tgaagcagtg 360tgggtgctgg attgataaaa aaaaaaaaag tcgacgcggc cgcgaattta gtag 414<210> 446<211> 631<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(631)<223> n = A,T,C or G<400> 446acaaattaga anaaagtgcc agagaacacc acataccttg tccggaacat tacaatggct 60tctgcatgca tgggaagtgt gagcattcta tcaatatgca ggagccatct tgcaggtgtg 120atgctggtta tactggacaa cactgtgaaa aaaaggacta cagtgttcta tacgttgttc 180ccggtcctgt acgatttcag tatgtcttaa tcgcagctgt gattggaaca attcagattg 240ctgtcatctg tgtggtggtc ctctgcatca caagggccaa actttaggta atagcattgg 300actgagattt gtaaactttc caaccttcca ggaaatgccc cagaagcaac agaattcaca 360gacagaagca aaatacaggg cactacagtt cagacaatac aacaagagcg tccacgaggt 420taatctaaag ggagcatgtt tcacagtggc tggactaccg agagcttgga ctacacaata 480cagtattata gacaaaagaa taagacaaga gatctacaca tgttgccttg catttgtggt 540aatctacacc aatgaaaaca tgtactacag ctatatttga ttatgtatgg atatatttga 600aatagtatac attgtcttga tgttttttct g 631<210> 447<211> 585<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(585)<223> n = A,T,C or G<400> 447ccttgggaaa antntcacaa tataaagggt cgtagacttt actccaaatt ccaaaaaggt 60cctggccatg taatcctgaa agttttccca aggtagctat aaaatcctta taagggtgca 120gcctcttctg gaattcctct gatttcaaag tctcactctc aagttcttga aaacgagggc 180agttcctgaa aggcaggtat agcaactgat cttcagaaag aggaactgtg tgcaccggga 240tgggctgcca gagtaggata ggattccaga tgctgacacc ttctgggga aacagggctg 300ccaggtttgt catagcactc atcaaagtcc ggtcaacgtc tgtgcttcga atataaacct 360gttcatgttt ataggactca ttcaagaatt ttctatatct ctttcttata tactctccaa 420gttcataatg ctgctccatg cccagctggg tgagttggcc aaatccttgt ggccatgagg 480attcctttat ggggtcagtg ggaaaggtgt caatgggact tcggtctcca tgccgaaaca 540ccaaagtcac aaacttcaac tccttggcta gtacacttcg gtcta 585<210> 448<211> 93<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(93)<223> n = A,T,C or G<400> 448tgctcgtggg tcattctgan nnccgaactg accntgccag ccctgccgan gggccnccat 60ggctccctag tgccctggag agganggggc tag 93<210> 449<211> 706<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(706)<223> n = A,T,C or G<400> 449ccaagttcat gctntgtgct ggacgctgga cagggggcaa aagcnnttgc tcgtgggtca 60ttctgancac cgaactgacc atgccagccc tgccgatggt cctccatggc tccctagtgc 120cctggagagg aggtgtctag tcagagagta gtcctggaag gtggcctctg ngaggagcca 180cggggacagc atcctgcaga tggtcgggcg cgtcccattc gccattcagg ctgcgcaact 240gttgggaagg gcgatcggtg cgggcctctt cgctattacg ccagctggcg aaaggggat 300gtgctgcaag gcgattaagt tgggtaacgc cagggttttc ccagtcncga cgttgtaaaa 360cgacggccag tgaattgaat ttaggtgacn ctatagaaga gctatgacgt cgcatgcacg 420cgtacgtaag cttggatcct ctagagcggc cgcctactac tactaaattc gcggccgcgt 480cgacgtggga tccncactga gagagtggag agtgacatgt gctggacnct gtccatgaag 540cactgagcag aagctggagg cacaacgcnc cagacactca cagctactca ggaggctgag 600aacaggttga acctgggagg tggaggttgc aatgagctga gatcaggccn ctgcncccca 660gcatggatga cagagtgaaa ctccatctta aaaaaaaaaa aaaaaa 706<210> 450<211> 493<212> DNA<213> Homo sapiens<400> 450gagacggagt gtcactctgt tgcccaggct ggagtgcagc aagacactgt ctaagaaaaa 60acagttttaa aaggtaaaac aacataaaaa gaaatatcct atagtggaaa taagagagtc 120aaatgaggct gagaacttta caaagggatc ttacagacat gtcgccaata tcactgcatg 180agcctaagta taagaacaac ctttggggag aaaccatcat ttgacagtga ggtacaattc 240caagtcaggt agtgaaatgg gtggaattaa actcaaatta atcctgccag ctgaaacgca 300agagacactg tcagagagtt aaaaagtgag ttctatccat gaggtgattc cacagtcttc 360tcaagtcaac acatctgtga actcacagac caagttctta aaccactgtt caaactctgc 420tacacatcag aatcacctgg agagctttac aaactcccat tgccgagggt cgacgcggcc 480gcgaatttag tag 493<210> 451<211> 501<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(501)<223> n = A,T,C or G<400> 451gggcgcgtcc cattcgccat tcaggctgcg caactgttgg gaagggcgat cggtgcgggc 60ctcttcgcta ttacgccagc tggcgaaagg gggatgtgct gcaaggcgat taagttgggt 120aacgccaggg ttttcccagt cncgacgttg taaaacgacg gccagtgaat tgaatttagg 180tgacnctata gaagagctat gacgtcgcat gcacgcgtac gtaagcttgg atcctctaga 240gcggccgcct actactacta aattcgcggc cgcgtcgacg tgggatccnc actgagagag 300tggagagtga catgtgctgg acnctgtcca tgaagcactg agcagaagct ggaggcacaa 360cgcnccagac actcacagct actcaggagg ctgagaacag gttgaacctg ggaggtggag 420gttgcaatga gctgagatca ggccnctgcn ccccagcatg gatgacagag tgaaactcca 480tcttaaaaaa aaaaaaaaaa a 501<210> 452<211> 51<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(51)<223> n = A,T,C or G<400> 452agacggtttc accnttacaa cnccttttag gatgggnntt ggggagcaag c 51<210> 453<211> 317<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(317)<223> n = A,T,C or G<400> 453tacatcttgc tttttcccca ttggaactag tcattaaccc atctctgaac tggtagaaaa 60acatctgaag agctagtcta tcagcatctg gcaagtgaat tggatggttc tcagaaccat 120ttcacccana cagcctgttt ctatcctgtt taataaatta gtttgggttc tctacatgca 180taacaaaccc tgctccaatc tgtcacataa aagtctgtga cttgaagttt antcagcacc 240cccaccaaac tttatttttc tatgtgtttt ttgcaacata tgagtgtttt gaaaataagg 300tacccatgtc tttatta 317<210> 454<211> 231<212> DNA<213> Homo sapiens<400> 454ttcgaggtac aatcaactct cagagtgtag tttccttcta tagatgagtc agcattaata 60taagccacgc cacgctcttg aaggagtctt gaattctcct ctgctcactc agtagaacca 120agaagaccaa attcttctgc atcccagctt gcaaacaaaa ttgttcttct aggtctccac 180ccttcctttt tcagtgttcc aaagctcctc acaatttcat gaacaacagc t 231<210> 455<211> 231<212> DNA<213> Homo sapiens<400> 455taccaaagag ggcataataa tcagtctcac agtagggttc accatcctcc aagtgaaaaa 60cattgttccg aatgggcttt ccacaggcta cacacacaaa acaggaaaca tgccaagttt 120gtttcaacgc attgatgact tctccaagga tcttcctttg gcatcgacca cattcagggg 180caaagaattt ctcatagcac agctcacaat acagggctcc tttctcctct a 231<210> 456<211> 231<212> DNA<213> Homo sapiens<400> 456ttggcaggta cccttacaaa gaagacacca taccttatgc gttattaggt ggaataatca 60ttccattcag tattatcgtt attattcttg gagaaaccct gtctgtttac tgtaaccttt 120tgcactcaaa ttcctttatc aggaataact acatagccac tatttacaaa gccattggaa 180cctttttatt tggtgcagct gctagtcagt ccctgactga cattgccaag t 231<210> 457<211> 231<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(231)<223> n = A,T,C or G<400> 457cgaggtaccc aggggtctga aaatctctnn tttantagtc gatagcaaaa ttgttcatca 60gcattcctta atatgatctt gctataatta gatttttctc cattagagtt catacagttt 120tatttgattt tattagcaat ctctttcaga agacccttga gatcattaag ctttgtatcc 180agttgtctaa atcgatgcct catttcctct gaggtgtcgc tggcttttgt g 231<210> 458<211> 231<212> DNA<213> Homo sapiens<400> 458aggtctggtt ccccccactt ccactcccct ctactctctc taggactggg ctgggccaag 60agaagagggg tggttaggga agccgttgag acctgaagcc ccaccctcta ccttccttca 120acaccctaac cttgggtaac agcatttgga attatcattt gggatgagta gaatttccaa 180ggtcctgggt taggcatttt ggggggccag accccaggag aagaagattc t 231<210> 459<211> 231<212> DNA<213> Homo sapiens<400> 459ggtaccgagg ctcgctgaca cagagaaacc ccaacgcgag gaaaggaatg gccagccaca 60ccttcgcgaa acctgtggtg gcccaccagt cctaacggga caggacagag agacagagca 120gccctgcact gttttccctc caccacagcc atcctgtccc tcattggctc tgtgctttcc 180actatacaca gtcaccgtcc caatgagaaa caagaaggag caccctccac a 231<210> 460<211> 231<212> DNA<213> Homo sapiens<400> 460gcaggtataa catgctgcaa caacagatgt gactaggaac ggccggtgac atggggaggg 60cctatcaccc tattcttgg ggctgcttct tcacagtgat catgaagcct agcagcaaat 120cccacctccc cacacgcaca cggccagcct ggagcccaca gaagggtcct cctgcagcca 180gtggagttg gtccagcctc cagtccaccc ctaccaggct taaggataga a 231<210> 461<211> 231<212> DNA<213> Homo sapiens<400> 461cgaggtttga gaagctctaa tgtgcagggg agccgagaag caggcggcct agggagggtc 60gcgtgtgctc cagaagagtg tgtgcatgcc agaggggaaa caggcgcctg tgtgtcctgg 120gtggggttca gtgaggagtg ggaaattggt tcagcagaac caagccgttg ggtgaataag 180agggggattc catggcactg atagagccct atagtttcag agctgggaat t 231<210> 462<211> 231<212> DNA<213> Homo sapiens<400> 462aggtaccctc attgtagcca tgggaaaatt gatgttcagt ggggatcagt gaattaaatg 60gggtcatgca agtataaaaa ttaaaaaaaa aagacttcat gcccaatctc atatgatgtg 120gaagaactgt tagagagacc aacagggtag tgggttagag atttccagag tcttacattt 180tctagaggag gtatttaatt tcttctcact catccagtgt tgtatttagg a 231<210> 463<211> 231<212> DNA<213> Homo sapiens<400> 463tactccagcc tggtgacaga gcgagaccct atcaccgccc cccaccccac caaaaaaaaa 60actgagtaga caggtgtcct cttggcatgg taagtcttaa gtcccctccc agatctgtga 120catttgacag gtgtcttttc ctctggacct cggtgtcccc atctgagtga gaaaaggcag 180tggggaggtg gatcttccag tcgaagcggt atagaagccc gtgtgaaaag c 231<210> 464<211> 231<212> DNA<213> Homo sapiens<400> 464gtactctaag attttatcta agttgccttt tctgggtggg aaagtttaac cttagtgact 60aaggacatca catatgaaga atgtttaagt tggaggtggc aacgtgaatt gcaaacaggg 120cctgcttcag tgactgtgtg cctgtagtcc cagctactcg ggagtctgtg tgaggccagg 180ggtgccagcg caccagctag atgctctgta acttctaggc cccattttcc c 231<210> 465<211> 231<212> DNA<213> Homo sapiens<400> 465catgttgttg tagctgtggt aatgctggct gcatctcaga cagggttaac ttcagctcct 60gtggcaaatt agcaacaaat tctgacatca tatttatggt ttctgtatct ttgttgatga 120aggatggcac aatttttgct tgtgttcata atatactcag attagttcag ctccatcaga 180taaactggag acatgcagga cattagggta gtgttgtagc tctggtaatg a 231<210> 466<211> 231<212> DNA<213> Homo sapiens<400> 466caggtacctc tttccattgg atactgtgct agcaagcatg ctctccgggg tttttttaat 60ggccttcgaa cagaacttgc cacataccca ggtataatag tttctaacat ttgcccagga 120cctgtgcaat caaatattgt ggagaattcc ctagctggag aagtcacaaa gactataggc 180aataatggag accagtccca caagatgaca accagtcgtt gtgtgcggct g 231<210> 467<211> 311<212> DNA<213> Homo sapiens<400> 467gtacaccctg gcacagtcca atctgaactg gttcggcact catctttcat gagatggatg 60tggtggcttt tctccttttt catcaagact cctcagcagg gagcccagac cagcctgcac 120tgtgccttaa cagaaggtct tgagattcta agtgggaatc atttcagtga ctgtcatgtg 180gcatgggtct ctgcccaagc tcgtaatgag actatagcaa ggcggctgtg ggacgtcagt 240tgtgacctgc tgggcctccc aatagactaa caggcagtgc cagttggacc caagagaaga 300ctgcagcaga c 311<210> 468<211> 3112<212> DNA<213> Homo sapiens<400> 468cattgtgttg ggagaaaaac agaggggaga tttgtgtggc tgcagccgag ggagaccagg 60aagatctgca tggtgggaag gacctgatga tacagagttt gataggagac aattaaaggc 120tggaaggcac tggatgcctg atgatgaagt ggactttcaa actggggcac tactgaaacg 180atgggatggc cagagacaca ggagatgagt tggagcaagc tcaataacaa agtggttcaa 240cgaggacttg gaattgcatg gagctggagc tgaagtttag cccaattgtt tactagttga 300gtgaatgtgg atgattggat gatcatttct catctctgag cctcaggttc cccatccata 360aaatgggata cacagtatga tctataaagt gggatatagt atgatctact tcactgggtt 420atttgaagga tgaattgaga taatttattt caggtgccta gaacaatgcc cagattagta 480catttggtgg aactgagaaa tggcataaca ccaaatttaa tatatgtcag atgttactat 540gattatcatt caatctcata gttttgtcat ggcccaattt atcctcactt gtgcctcaac 600aaattgaact gttaacaaag gaatctctgg tcctgggtaa tggctgagca ccactgagca 660tttccattcc agttggcttc ttgggtttgc tagctgcatc actagtcatc ttasataaat 720gaagttttaa catttctcca gtgatttttt tatctcacct ttgaagatac tatgttatgt 780gattaaataa agaacttgag aagaacaggt ttcattaaac ataaaatcaa tgtagacgca 840aattttctgg atgggcaata cttatgttca caggaaatgc tttaaaatat gcagaagata 900attaaatggc aatggacaaa gtgaaaaact tagacttttt tttttttttt ggaagtatct 960ggatgttcct tagtcactta aaggagaact gaaaaatagc agtgagttcc acataatcca 1020acctgtgaga ttaaggctct ttgtggggaa ggacaaagat ctgtaaattt acagtttcct 1080tccaaagcca acgtcgaatt ttgaaacata tcaaagctct tcttcaagac aaataatcta 1140tagtacatct ttcttatggg atgcacttat gaaaaatggt ggctgtcaac atctagtcac 1200tttagctctc aaaatggttc attttaagag aaagttttag aatctcatat ttattcctgt 1260ggaaggacag cattgtggct tggactttat aaggtcttta ttcaactaaa taggtgagaa 1320ataagaaagg ctgctgactt taccatctga ggccacacat ctgctgaaat ggagataatt 1380aacatcacta gaaacagcaa gatgacaata taatgtctaa gtagtgacat gtttttgcac 1440atttccagcc cctttaaata tccacacaca caggaagcac aaaaggaagc acagagatcc 1500ctgggagaaa tgcccggccg ccatcttggg tcatcgatga gcctcgccct gtgcctggtc 1560ccgcttgtga gggaaggaca ttagaaaatg aattgatgtg ttccttaaag gatgggcagg 1620aaaacagatc ctgttgtgga tatttatttg aacgggatta cagatttgaa atgaagtcac 1680aaagtgagca ttaccaatga gaggaaaaca gacgagaaaa tcttgatggc ttcacaagac 1740atgcaacaaa caaaatggaa tactgtgatg acatgaggca gccaagctgg ggaggagata 1800accacggggc agagggtcag gattctggcc ctgctgccta aactgtgcgt tcataaccaa 1860atcatttcat atttctaacc ctcaaaacaa agctgttgta atatctgatc tctacggttc 1920cttctgggcc caacattctc catatatcca gccacactca tttttaatat ttagttccca 1980gatctgtact gtgacctttc tacactgtag aataacatta ctcattttgt tcaaagaccc 2040ttcgtgttgc tgcctaatat gtagctgact gtttttccta aggagtgttc tggcccaggg 2100gatctgtgaa caggctggga agcatctcaa gatctttcca gggttatact tactagcaca 2160cagcatgatc attacggagt gaattatcta atcaacatca tcctcagtgt ctttgcccat 2220actgaaattc atttcccact tttgtgccca ttctcaagac ctcaaaatgt cattccatta 2280atatcacagg attaactttt ttttttaacc tggaagaatt caatgttaca tgcagctatg 2340ggaatttaat tacatatttt gttttccagt gcaaagatga ctaagtcctt tatccctccc 2400ctttgtttga ttttttttcc agtataaagt taaaatgctt agccttgtac tgaggctgta 2460tacagccaca gcctctcccc atccctccag ccttatctgt catcaccatc aacccctccc 2520atgcacctaa acaaaatcta acttgtaatt ccttgaacat gtcaggcata cattattcct 2580tctgcctgag aagctcttcc ttgtctctta aatctagaat gatgtaaagt tttgaataag 2640ttgactatct tacttcatgc aaagaaggga cacatatgag attcatcatc acatgagaca 2700gcaaatacta aaagtgtaat ttgattataa gagtttagat aaatatatga aatgcaagag 2760ccacagaggg aatgtttatg gggcacgttt gtaagcctgg gatgtgaagc aaaggcaggg 2820aacctcatag tatcttatat aatatacttc atttctctat ctctatcaca atatccaaca 2880agcttttcac agaattcatg cagtgcaaat ccccaaaggt aacctttatc catttcatgg 2940tgagtgcgct ttagaatttt ggcaaatcat actggtcact tatctcaact ttgagatgtg 3000tttgtccttg tagttaattg aaagaaatag ggcactcttg tgagccactt tagggttcac 3060tcctggcaat aaagaattta caaagagcaa aaaaaaaaaa aaaaaaaaaa aa 3112<210> 469<211> 2229<212> DNA<213> Homo sapiens<400> 469agctctttgt aaattcttta ttgccaggag tgaaccctaa agtggctcac aagagtgccc 60tatttctttc aattaactac aaggacaaac acatctcaaa gttgagataa gtgaccagta 120tgatttgcca aaattctaaa gcgcactcac catgaaatgg ataaaggtta cctttgggga 180tttgcactgc atgaattctg tgaaaagctt gttggatatt gtgatagaga tagagaaatg 240aagtatatta tataagatac tatgaggttc cctgcctttg cttcacatcc caggcttaca 300aacgtgcccc ataaacattc cctctgtggc tcttgcattt catatattta tctaaactct 360tataatcaaa tacactttta gtatttgctg tctcatgtga tgatgaatct catatgtgtc 420ccttctttgc atgaagtaag atagtcaact tattcaaaac tttacatcat tctagattta 480agagacaagg aagagcttct caggcagaag gaataatgta tgcctgacat gttcaaggaa 540ttacaagtta gattttgttt aggtgcatgg gaggggttga tggtgatgac agataaggct 600ggagggatgg ggagaggctg tggctgtata cagcctcagt acaaggctaa gcattttaac 660tttatactgg aaaaaaaatc aaacaaaggg gagggataaa ggacttagtc atctttgcac 720tggaaaacaa aatatgtaat taaattccca tagctgcatg taacattgaa ttcttccagg 780ttaaaaaaaa agttaatcct gtgatattaa tggaatgaca ttttgaggtc ttgagaatgg 840gcacaaaagt gggaaatgaa tttcagtatg ggcaaagaca ctgaggatga tgttgattag 900ataattcact ccgtaatgat catgctgtgt gctagtaagt ataaccctgg aaagatcttg 960agatgcttcc cagcctgttc acagatcccc tgggccagaa cactccttag gaaaaacagt 1020cagctacata ttaggcagca acacgaaggg tctttgaaca aaatgagtaa tgttattcta 1080cagtgtagaa aggtcacagt acagatctgg gaactaaata ttaaaaatga gtgtggctgg 1140atatatggag aatgttgggc ccagaaggaa ccgtagagat cagatattac aacagctttg 1200ttttgagggt tagaaatatg aaatgatttg gttatgaacg cacagtttag gcagcagggc 1260cagaatcctg accctctgcc ccgtggttat ctcctcccca gcttggctgc ctcatgtcat 1320cacagtattc cattttgttt gttgcatgtc ttgtgaagcc atcaagattt tctcgtctgt 1380tttcctctca ttggtaatgc tcactttgtg acttcatttc aaatctgtaa tcccgttcaa 1440ataaatatcc acaacaggat ctgttttcct gcccatcctt taaggaacac atcaattcat 1500tttctaatgt ccttccctca caagcgggac caggcacagg gcgaggctca tcgatgaccc 1560aagatggcgg ccgggcattt ctcccaggga tctctgtgct tccttttgtg cttcctgtgt 1620gtgtggatat ttaaaggggc tggaaatgtg caaaaacatg tcactactta gacattatat 1680tgtcatcttg ctgtttctag tgatgttaat tatctccatt tcagcagatg tgtggcctca 1740gatggtaaag tcagcagcct ttcttatttc tcacctggaa atacatacga ccatttgagg 1800agacaaatgg caaggtgtca gcataccctg aacttgagtt gagagctaca cacaatatta 1860ttggtttccg agcatcacaa acaccctctc tgtttcttca ctgggcacag aattttaata 1920cttatttcag tgggctgttg gcaggaacaa atgaagcaat ctacataaag tcactagtgc 1980agtgcctgac acacaccatt ctcttgaggt cccctctaga gatcccacag gtcatatgac 2040ttcttgggga gcagtggctc acacctgtaa tcccagcact ttgggaggct gaggcaggtg 2100ggtcacctga ggtcaggagt tcaagaccag cctggccaat atggtgaaac cccatctcta 2160ctaaaaatac aaaaattagc tgggcgtgct ggtgcatgcc tgtaatccca gccccaacac 2220aatggaatt 2229<210> 470<211> 2426<212> DNA<213> Homo sapiens<400> 470gtaaattctt tattgccagg agtgaaccct aaagtggctc acaagagtgc cctatttctt 60tcaattaact acaaggacaa acacatctca aagttgagat aagtgaccag tatgatttgc 120caaaattcta aagcgcactc accatgaaat ggataaaggt tacctttggg gatttgcact 180gcatgaattc tgtgaaaagc ttgttggata ttgtgataga gatagagaaa tgaagtatat 240tatataagat actatgaggt tccctgcctt tgcttcacat cccaggctta caaacgtgcc 300ccataaacat tccctctgtg gctcttgcat ttcatatatt tatctaaact cttataatca 360aattacactt ttagtatttg ctgtctcatg tgatgatgaa tctcatatgt gtcccttctt 420tgcatgaagt aagatagtca acttattcaa aactttacat cattctagat ttaagagaca 480aggaagagct tctcaggcag aaggaataat gtatgcctga catgttcaag gaattacaag 540ttagattttg tttaggtgca tgggaggggt tgatggtgat gacagataag gctggaggga 600tggggagagg ctgtggctgt atacagcctc agtacaaggc taagcatttt aactttatac 660tggaaaaaaa atcaaacaaa ggggagggat aaaggactta gtcatctttg cactggaaaa 720caaaatatgt aattaaattc ccatagctgc atgtaacatt gaattcttcc aggttaaaaa 780aaaaagttaa tcctgtgata ttaatggaat gacattttga ggtcttgaga atgggcacaa 840aagtgggaaa tgaatttcag tatgggcaaa gacactgagg atgatgttga ttagataatt 900cactccgtaa tgatcatgct gtgtgctagt aagtataacc ctggaaagat cttgagatgc 960ttcccagcct gttcacagat cccctgggcc agaacactcc ttaggaaaaa cagtcagcta 1020catattaggc agcaacacga agggtctttg aacaaaatga gtaatgttat tctacagtgt 1080agaaaggtca cagtacagat ctgggaacta aatattaaaa atgagtgtgg ctggatatat 1140ggagaatgtt gggcccagaa ggaaccgtag agatcagata ttacaacagc tttgttttga 1200gggttagaaa tatgaaatga tttggttatg aacgcacagt ttaggcagca gggccagaat 1260cctgaccctc tgccccgtgg ttatctcctc cccagcttgg ctgcctcatg tcatcacagt 1320attccatttt gtttgttgca tgtcttgtga agccatcaag attttctcgt ctgttttcct 1380ctcattggta atgctcactt tgtgacttca tttcaaatct gtaatcccgt tcaaataaat 1440atccacaaca ggatctgttt tcctgcccat cctttaagga acacatcaat tcattttcta 1500atgtccttcc ctcacaagcg ggaccaggca cagggcgagg ctcatcgatg acccaagatg 1560gcggccgggc atttctccca gggatctctg tgcttccttt tgtgcttcct gtgtgtgtgg 1620atatttaaag gggctggaaa tgtgcaaaaa catgtcacta cttagacatt atattgtcat 1680cttgctgttt ctagtgatgt taattatctc catttcagca gatgtgtggc ctcagatggt 1740aaagtcagca gcctttctta tttctcacct ggaaatacat acgaccattt gaggagacaa 1800atggcaaggt gtcagcatac cctgaacttg agttgagagc tacacacaat attattggtt 1860tccgagcatc acaaacaccc tctctgtttc ttcactgggc acagaatttt aatacttatt 1920tcagtgggct gttggcagga acaaatgaag caatctacat aaagtcacta gtgcagtgcc 1980tgacacacac cattctcttg aggtcccctc tagagatccc acaggtcata tgacttcttg 2040gggagcagtg gctcacacct gtaatcccag cactttggga ggctgaggca ggtgggtcac 2100ctgaggtcag gagttcaaga ccagcctggc caatatggtg aaaccccatc tctactaaaa 2160atacaaaaat tagctgggcg tgctggtgca tgcctgtaat cccagctact tgggaggctg 2220aggcaggaga attgctggaa catgggaggc ggaggttgca gtgagctgta attgtgccat 2280tgcactcgaa cctgggcgac agagtggaac tctgtttcca aaaaacaaac aaacaaaaaa 2340ggcatagtca gatacaacgt gggtgggatg tgtaaataga agcaggatat aaagggcatg 2400gggtgacggt tttgcccaac acaatg 2426<210> 471<211> 812<212> DNA<213> Homo sapiens<400> 471gaacaaaatg agtaatgtta ttctacagtg tagaaaggtc acagtacaga tctgggaact 60aaatattaaa aatgagtgtg gctggatata tggagaatgt tgggcccaga aggaaccgta 120gagatcagat attacaacag ctttgttttg agggttagaa atatgaaatg atttggttat 180gaacgcacag tttaggcagc agggccagaa tcctgaccct ctgccccgtg gttatctcct 240ccccagcttg gctgcctcat gtcatcacag tattccattt tgtttgttgc atgtcttgtg 300aagccatcaa gattttctcg tctgttttcc tctcattggt aatgctcact ttgtgacttc 360atttcaaatc tgtaatcccg ttcaaataaa tatccacaac aggatctgtt ttcctgccca 420tcctttaagg aacacatcaa ttcattttct aatgtccttc cctcacaagc gggaccaggc 480acagggcgag gctcatcgat gacccaagat ggcggccggg catttctccc agggatctct 540gtgcttcctt ttgtgcttcc tgtgtgtgtg gatatttaaa ggggctggaa atgtgcaaaa 600acatgtcact acttagacat tatattgtca tcttgctgtt tctagtgatg ttaattatct 660ccatttcagc agatgtgtgg cctcagatgg taaagtcagc agcctttctt atttctcacc 720tctgtatcat caggtccttc ccaccatgca gatcttcctg gtctccctcg gctgcagcca 780cacaaatctc ccctctgttt ttctgatgcc ag 812<210> 472<211> 515<212> DNA<213> Homo sapiens<220><221> misc_feature<222> (1)...(515)<223> n = A,T,C or G<400> 472acggagactt attttctgat attgtctgca tatgtatgtt tttaagagtc tggaaatagt 60cttatgactt tcctatcatg cttattaata aataatacag cccagagaag atgaaaatgg 120gttccagaat tattggtcct tgcagcccgg tgaatctcag caagaggaac caccaactga 180caatcaggat attgaacctg gacaagagag agaaggaaca cctccgatcg aagaacgtaa 240agtagaaggt gattgccagg aaatggatct ggaaaagact cggagtgagc gtggagatgg 300ctctgatgta aaagagaaga ctccacctaa tcctaagcat gctaagacta aagaagcagg 360agatgggcag ccataagtta aaaagaagac aagctgaagc tacacacatg gctgatgtca 420cattgaaaat gtgactgaaa atttgaaaat tctctcaata aagtttgagt tttctctgaa 480gaaaaaaaaa naaaaaaaaa aaanaaaaan aaaaa 515

Claims (79)

1. An isolated polypeptide comprising at least an immunogenic portion of a prostate tumor protein, or a variant thereof, wherein said tumor protein comprises an amino acid sequence encoded by a polynucleotide sequence selected from the group consisting of:

(a) 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109, 111, 115-;

(b) a sequence that hybridizes to any of the above sequences under moderately stringent conditions; and

(c) a complement of any of (a) or (b).

2. The isolated polypeptide of claim 1, wherein the polypeptide comprises an amino acid sequence encoded by any one of the polynucleotide sequences set forth in seq id no:2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 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, or any of the complementary sequences of the above polynucleotide sequences.

3. An isolated polypeptide comprising a sequence as set forth in any one of SEQ ID NOs 108, 112, 113, 114, 172, 176, 178, 327, 329, 331, 339 and 383.

4. An isolated polynucleotide encoding at least 15 amino acid residues of a prostate tumor protein or a variant thereof which differs by one or more substitutions, deletions, additions and/or insertions, but which does not have a substantially reduced ability to react with antigen-specific antisera, wherein said tumor protein comprises an amino acid sequence encoded by a polynucleotide comprising any one of the following sequences: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109, 111, 115-.

5. 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 comprising any one of the following sequences: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109, 111, 115-.

6. An isolated polynucleotide comprising a sequence as set forth in any one of: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109, 111, 115-.

7. An isolated polynucleotide comprising a sequence that hybridizes under moderately stringent conditions to the sequence of any one of seq id no:2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109, 111, 115-.

8. An isolated polynucleotide complementary to the polynucleotide of any one of claims 4-7.

9. An expression vector comprising the polynucleotide of any one of claims 4-7.

10. A host cell transformed or transfected with the expression vector of claim 9.

11. An expression vector comprising the polynucleotide of claim 8.

12. A host cell transformed or transfected with the expression vector of claim 11.

13. A pharmaceutical composition comprising the polypeptide of claim 1 in combination with a physiologically acceptable carrier.

14. A vaccine comprising a polypeptide according to claim 1 in combination with a non-specific immune response enhancer.

15. The vaccine of claim 14 wherein the non-specific immune response enhancer is an adjuvant.

16. The vaccine of claim 14 wherein the non-specific immune response enhancer induces a predominantly class i response.

17. A pharmaceutical composition comprising the polynucleotide of claim 4 in combination with a physiologically acceptable carrier.

18. A vaccine comprising a polynucleotide according to claim 4 in combination with a non-specific immune response enhancer.

19. The vaccine of claim 18 wherein the non-specific immune response enhancer is an adjuvant.

20. The vaccine of claim 18 wherein the non-specific immune response enhancer induces a predominantly class i response.

21. An isolated antibody or antigen-binding fragment thereof that specifically binds to a prostate tumor protein comprising an amino acid sequence encoded by any one of the following polynucleotide sequences: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 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, or any of the complementary sequences of the above polynucleotide sequences.

22. A pharmaceutical composition comprising the antibody or fragment thereof of claim 18 in combination with a physiologically acceptable carrier.

23. A pharmaceutical composition comprising an antigen presenting cell expressing a polypeptide of claim 1 in combination with a pharmaceutically acceptable carrier or excipient.

24. The pharmaceutical composition of claim 23, wherein the antigen presenting cell is a dendritic cell or a macrophage.

25. A vaccine comprising antigen presenting cells expressing a polypeptide of claim 1 in combination with a non-specific immune response enhancer.

26. The vaccine of claim 25 wherein the non-specific immune response enhancer is an adjuvant.

27. The vaccine of claim 25 wherein the non-specific immune response enhancer induces a predominantly class i response.

28. The vaccine of claim 25, wherein the antigen presenting cell is a dendritic cell.

29. A method of inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of the polypeptide of claim 1, and thereby inhibiting the development of cancer in the patient.

30. A method of inhibiting the development of cancer in a patient comprising administering to the patient an effective amount of the polynucleotide of claim 4, and thereby inhibiting the development of cancer in the patient.

31. A method of inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of the antibody or antigen-binding fragment thereof of claim 21, and thereby inhibiting the development of cancer in the patient.

32. A method of inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of an antigen presenting cell that expresses a polypeptide of claim 1, and thereby inhibiting the development of cancer in the patient.

33. The method of claim 32, wherein the antigen presenting cell is a dendritic cell.

34. The method of any one of claims 29-32, wherein the cancer is prostate cancer.

35. A fusion protein comprising at least one polypeptide of claim 1.

36. The fusion protein of claim 35, wherein the fusion protein comprises an expression enhancer that increases its expression in a host cell transfected with a polynucleotide encoding the fusion protein.

37. The fusion protein of claim 35, wherein the fusion protein comprises a T helper epitope that is not present in the polypeptide of claim 1.

38. The fusion protein of claim 35, wherein the fusion protein comprises an affinity tag.

39. An isolated polynucleotide encoding the fusion protein of claim 35.

40. A pharmaceutical composition comprising the fusion protein of claim 32 in combination with a physiologically acceptable carrier.

41. A vaccine comprising the fusion protein of claim 35 in combination with a non-specific immune response enhancer.

42. The vaccine of claim 41 wherein the non-specific immune response enhancer is an adjuvant.

43. The vaccine of claim 41 wherein the non-specific immune response enhancer induces a predominantly class I response.

44. A pharmaceutical composition comprising the polynucleotide of claim 40 in combination with a physiologically acceptable carrier.

45. A vaccine comprising a polynucleotide according to claim 40 in combination with a non-specific immune response enhancer.

46. The vaccine of claim 45 wherein the non-specific immune response enhancer is an adjuvant.

47. The vaccine of claim 45 wherein the non-specific immune response enhancer induces a predominantly class I response.

48. A method of inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 40 or claim 44.

49. A method of inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of the vaccine of claim 41 or claim 45.

50. A method for removing tumor cells from a biological sample comprising contacting the biological sample with T cells that specifically react with a prostate tumor protein under conditions and for a time sufficient to remove cells expressing the prostate tumor protein from the sample, wherein the tumor protein comprises an amino acid sequence encoded by a polynucleotide sequence selected from the group consisting of:

1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472 of SEQ ID NO; and

(ii) a polynucleotide complementary to the above-mentioned polynucleotide.

51. The method of claim 50, wherein the biological sample is blood or a fraction thereof.

52. A method of inhibiting the development of cancer in a patient, comprising administering to the patient a biological sample treated by the method of claim 50.

53. A method for stimulating and/or expanding T cells specific for prostate tumor protein comprising contacting T cells with one or more of the following under conditions and for a time sufficient to stimulate and/or expand T cells:

a polypeptide of claim 1;

(ii) a polypeptide encoded by a polynucleotide comprising a sequence provided by any one of SEQ ID NOs 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472;

(iii) a polynucleotide encoding the polypeptide of (i) or (ii); and/or

(iv) antigen presenting cells expressing the polypeptide of (i) or (ii).

54. An isolated population of T cells comprising T cells prepared by the method of claim 53.

55. A method of inhibiting the development of cancer in a patient, comprising administering to the patient an effective amount of the T cell population of claim 54.

56. A method of inhibiting the development of cancer in a patient comprising the steps of:

(a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of:

a polypeptide of claim 1;

(ii) a polypeptide encoded by a polynucleotide comprising any one of the sequences of SEQ ID NOs 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472;

(iii) a polynucleotide encoding the polypeptide of (i) or (ii); or

(iv) antigen presenting cells expressing the polypeptide of (i) or (ii);

allowing the T cells to proliferate; and are

(b) Administering to the patient an effective amount of proliferating T cells, and thereby inhibiting the development of cancer in the patient.

57. A method of inhibiting the development of cancer in a patient comprising the steps of:

(a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of:

a polypeptide of claim 1;

(ii) a polypeptide encoded by a polynucleotide comprising any one of the sequences of SEQ ID NOs 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472;

(ii) a polynucleotide encoding the polypeptide of (i) or (ii); or

(vi) antigen presenting cells expressing the polypeptide of (i) or (ii); allowing the T cells to proliferate;

(b) cloning at least one proliferating cell; and are

(c) Administering to the patient an effective amount of the clonal T cells, and thereby inhibiting the development of cancer in the patient.

58. A method for determining the presence or absence of cancer in a patient comprising the steps of:

(a) contacting a biological sample isolated from a patient with a binding agent that binds to a prostate tumor protein, wherein the tumor protein comprises an amino acid sequence encoded by a polynucleotide sequence selected from the group consisting of:

1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472 of SEQ ID NO; and

(ii) a polynucleotide complementary to the above-mentioned polynucleotide;

(b) detecting the amount of polypeptide bound to the binding agent in the sample; and are

(c) Comparing the amount of the polypeptide to a predetermined threshold and thereby determining the presence or absence of cancer in the patient.

59. The method of claim 58 wherein the binding agent is an antibody.

60. The method of claim 59, wherein the antibody is a monoclonal antibody.

61. The method of claim 58, wherein the cancer is prostate cancer.

62. A method of monitoring the progression of cancer in a patient, comprising the steps of:

(a) contacting a biological sample obtained from a patient at a first time point with a binding agent that binds to a prostate tumor protein, wherein the tumor protein comprises an amino acid sequence encoded by any one of the following polynucleotide sequences: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472, or a polynucleotide complementary thereto;

(b) detecting the amount of polypeptide bound to the binding agent in the sample;

(c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent second time point; and are

(d) Comparing the amount of polypeptide detected in step (c) with the amount detected in step (b), and thereby monitoring the progression of the cancer in the patient.

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. The method of claim 62, wherein the cancer is prostate cancer.

66. A method for determining the presence or absence of cancer in a patient comprising the steps of:

(a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide encoding a prostate tumor protein, wherein said tumor protein comprises an amino acid sequence encoded by any of the following polynucleotide sequences: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472, or a polynucleotide complementary to any of the above polynucleotides;

(b) detecting the amount of polynucleotide hybridized to the oligonucleotide in the sample; and are

(c) Comparing the amount of polynucleotide hybridized to the oligonucleotide to a predetermined threshold value, and thereby determining the presence or absence of cancer in the patient.

67. The method of claim 66, wherein the amount of polynucleotide hybridized to the oligonucleotide is determined using polymerase chain reaction.

68. The method of claim 66, wherein the amount of polynucleotide hybridized to the oligonucleotide is determined using a hybridization assay.

69. A method of monitoring the progression of cancer in a patient, comprising the steps of:

(a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide encoding a prostate tumor protein, wherein said tumor protein comprises an amino acid sequence encoded by any of the following polynucleotide sequences: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 or 384-472, or a polynucleotide complementary to any of the above polynucleotides;

(b) detecting the amount of polynucleotide hybridized to the oligonucleotide in the sample;

(c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent second time point; and are

(d) Comparing the amount of polynucleotide detected in step (c) with the amount detected in step (b), and thereby monitoring the progression of the cancer in the patient.

70. The method of claim 69, wherein the amount of polynucleotide hybridized to the oligonucleotide is determined using polymerase chain reaction.

71. The method of claim 69, wherein the amount of polynucleotide hybridized to the oligonucleotide is determined using a hybridization assay.

72. A diagnostic kit comprising:

(a) one or more antibodies of claim 21; and

(b) a detector comprising a reporter group.

73. The kit of claim 72, wherein the antibody is immobilized on a solid support.

74. The kit of claim 73, wherein the solid support comprises nitrocellulose, latex, or a plastic material.

75. The kit of claim 72, wherein the detection agent comprises an anti-immunoglobulin, protein G, protein A, or lectin.

76. The kit of claim 72, wherein the reporter group is selected from the group consisting of: radioisotopes, fluorescent groups, luminescent groups, enzymes, biotin and dye particles.

77. An oligonucleotide comprising 1O-40 nucleotides that is hybridizable under moderately stringent conditions to a polynucleotide encoding a prostate tumor protein, wherein said tumor protein comprises an amino acid sequence encoded by any one of the polynucleotide sequences set forth in seq id no:2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 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, 468-471-472 or the recorded polynucleotide sequence, or the complementary sequence of any of the above polynucleotides.

78. The oligonucleotide of claim 77, wherein the oligonucleotide comprises 10 to 40 nucleotides of any one of the sequences of SEQ ID NOs 2, 3, 8 to 29, 41 to 45, 47 to 52, 54 to 65, 70, 73, 74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109, 111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227-305, 307-315, 326, 328, 330, 332, 334, 350-365, 381, 382, 384, 386, 389, 390, 392, 396, 401, 402, 407, 408, 410, 413, 415-419, 422, 426, 427, 432, 434, 435, 442, 446, 450, 452, 459, 461, 468, 471 or 471.

79. A diagnostic kit comprising:

(a) the oligonucleotide of claim 77; and

(b) diagnostic agents for use in polymerase chain reaction or hybridization assays.