CN116802312A - 基于pde4d7相关基因来预测前列腺癌对象对放疗的反应 - Google Patents

基于pde4d7相关基因来预测前列腺癌对象对放疗的反应 Download PDF

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CN116802312A
CN116802312A CN202180053564.XA CN202180053564A CN116802312A CN 116802312 A CN116802312 A CN 116802312A CN 202180053564 A CN202180053564 A CN 202180053564A CN 116802312 A CN116802312 A CN 116802312A
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R·D·霍夫曼
M·施托费尔斯
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Abstract

本发明涉及预测前列腺癌对象对放疗的反应的方法，包括：确定或接收针对从包括以下各项的组中选择的两个或更多个PDE4D7相关基因中的每个的基因表达谱：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述基因表达谱是在从所述对象获得的生物样本中确定的；并且基于针对所述两个或更多个PDE4D7相关基因的所述基因表达谱来确定对放疗反应的预测。

Description

基于PDE4D7相关基因来预测前列腺癌对象对放疗的反应
技术领域
本发明涉及预测前列腺癌对象对放疗的反应的方法，并且涉及用于预测前列腺癌对象对放疗的反应的装置。此外，本发明涉及诊断套件，涉及套件的用途，涉及套件在预测前列腺癌对象对放疗的反应的方法中的用途，涉及一个或多个PDE4D7相关基因中的每个的基因表达谱在预测前列腺癌对象对放疗的反应的方法中的用途，并且涉及对应的计算机程序产品。
背景技术
癌症是一类疾病，其中，一组细胞表现出不受控制的生长、侵袭以及有时候转移。癌症的这三种恶性特性将它们与良性肿瘤区分开来，良性肿瘤是自限性的，不会侵袭或转移。前列腺癌(PCa)是男性第二大最常见的非皮肤恶性肿瘤，2018年全球估计有130万例新确诊病例和360000例死亡(参见BrayF.等人的“Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in185countries”，CA Cancer J Clin，Vol.68，第6期，第394-424页，2018年)。在美国，大约90％的新病例涉及局部癌症，这意味着尚未形成转移(参见ACS(美国癌症协会)，“CancerFacts&Figures 2010”，2010年)。
对于原发性局限性前列腺癌的治疗，有几种根治性疗法可用，其中，最常用的是手术(根治性前列腺切除术，RP)和放疗(RT)。RT是通过外部射束或通过将放射性粒子植入前列腺(近距离放疗)或两者结合进行的。其对于不符合手术条件或已被诊断患有晚期局部或区域阶段肿瘤的患者尤其优选。在美国，高达50％的诊断为局限性前列腺癌的患者接受了根治性RT(见ACS，2010，出处同上)。
在处置之后，测量血液中的前列腺癌抗原(PSA)水平以进行疾病监测。血液PSA水平的升高为癌症复发或进展提供了生化替代量度。然而，报告的无生化进展生存率(bPFS)的差异很大(参见Grimm P.等人的“Comparative analysis of prostate-specificantigen free survival outcomes for patients with low,intermediate and highrisk prostate cancer treatment by radical therapy.Results from the ProstateCancer Results Study Group”(BJU Int,Suppl.1，第22-29页，2012年))。对于许多患者而言，根治性放疗后5年甚至10年的bPFS可能超过90％。遗憾的是，对于处于中度和特别是较高复发风险的患者组，bPFS可能降到5年时40％左右，具体取决于所使用的RT类型(参见Grimm P.等人，2012年，出处同上)。
大量未利用RT进行处置的原发性局限性前列腺癌患者将接受RP(参见ACS，2010，出处同上)。在RP后，最高风险组中平均有60％的患者在5年和10年后经历生化复发(参见Grimm P.等人，2012，出处同上)。在RP后发生生化进展的情况下，主要挑战之一是不确定这是由于复发的局限性疾病，还是由于一个或多个转移，甚至是由于不会导致临床疾病进展的惰性疾病(参见Dal Pra A.等人的“Contemporary role of postoperativeradiotherapy for prostate cancer”(Transl Androl Urol，第7卷，第3期，第399-413页，2018年)和Herrera F.G.和Berthold D.R.的“Radiation therapy after radicalprostatectomy：Implications for clinicians”(Front Oncol，第6卷，第117期，2016年))。RT根除前列腺床中的剩余的癌细胞是在RP后PSA增大之后挽救生存率的主要处置选项之一。挽救性放疗(SRT)的有效性使18％至90％的患者达到了5年的bPFS，具体取决于多种因素(参见Herrera F.G.和Berthold D.R.，2016年，出处同上，以及Pisansky T.M.等人的“Salvage radiation therapy dose response for biochemical failure ofprostate cancer after prostatectomy–A multi-institutional observationalstudy”，Int J Radiat Oncol Biol Phys，Vol.96,No.5，第1046-1053页，2016年)。
清楚的是，对于特定患者组，根治性RT或挽救性RT是无效的。RT能够导致的严重副作用(例如，肠道炎症和功能障碍、尿失禁和勃起功能障碍)甚至使他们的情况更加恶化(参见Resnick M.J.等人的“Long-term functional outcomes after treatment forlocalized prostate cancer”，N Engl J Med，Vol.368,No.5，第436-445页，2013年和Hegarty S.E.等人的“Radiation therapy after radical prostatectomy for prostatecancer：Evaluation of complications and influence of radiation timing onoutcomes in a large,population-based cohort”，PLoS One，ol.10,No.2，2015年)。另外，基于医疗保险报销，一个RT疗程的成本的中位值为18000美元，该成本的差异很大，最高达到约40000美元(参见Paravati A.J.等人的“Variation in the cost of radiationtherapy among medicare patients with cancer”，J Oncol Pract，Vol.11,No.5，第403-409页，2015年)。这些数字不包括在根治性RT和挽救性RT后的后续护理的可观的纵向成本。
对每个患者的RT有效性的改进预测(无论是在根治性背景中还是在挽救性背景中)都将改进治疗选择和提高潜在生存率。这能够通过以下操作来实现：1)为那些预测RT有效的患者优化RT(例如通过剂量递增或不同的开始时间)，以及2)将预测RT无效的患者引导到可能更有效的处置形式的替代方案。另外，这将减少那些免于无效治疗的患者的痛苦并减少在无效治疗上花费的成本。
已经对根治性RT(参见Hall W.A.等人的“Biomarkers of outcome in patientswith localized prostate cancer treated with radiotherapy”，Semin Radiat Oncol，Vol.27，第11-20页，2016年和Raymond E.等人的“An appraisal of analytical toolsused in predicting clinical outcomes following radiation therapy treatment ofmen with prostate cancer：A systematic review”，Radiat Oncol，Vol.12,No.1，第56页，2017年)和SRT(参见Herrera F.G.和Berthold D.R.，2016年，出处同上)的反应预测指标进行了大量的研究。这些指标中的许多指标取决于基于血液的生物标志物PSA的浓度。为在RT(根治性以及挽救性)开始前预测反应而研究的度量包括PSA浓度的绝对值、PSA相对于前列腺体积的绝对值、一定时间内的绝对增大量和倍增时间。其他经常考虑的因素是格里森评分和临床肿瘤分期。对于SRT场景，其他因素是相关的，例如，手术切缘状态、RP后复发时间、手术前/围手术期PSA值和临床病理参数。
虽然这些临床变量在各个风险组中的患者分层方面提供了有限的改进，但是仍然需要更好的预测工具。
已经研究了在组织和体液中种类众多的候选生物标志物，但是验证通常很有限并且通常证明预后信息并且不是预测(治疗特异性)值(参见Hall W.A.等人，2016年，出处同上)。当前，商业组织正在验证少数基因表达板。这些基因表达板中的一个或多个基因表达板可以示出对未来的RT的预测值(参见Dal Pra A.等人，2018年，出处同上)。
总之，对于原发性前列腺癌以及术后环境，仍然强烈需要对RT的反应的更好预测。
发明内容
本发明的目的是提供一种预测前列腺癌对象对放疗的反应的方法，以及一种用于预测前列腺癌对象对放疗的反应的装置，其允许做出更好的处置决策。本发明的另一目的是提供一种诊断套件、套件的使用、套件在预测前列腺癌对象对放疗的反应的方法中的使用、一个或多个PDE4D7相关基因中的每个的基因表达谱在预测前列腺癌对象对放疗的反应的方法中的使用，以及对应的计算机程序产品。
在本发明的第一方面中，提出了一种预测前列腺癌对象对放疗的反应的方法，包括：
确定或接收针对从包括以下项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱的确定的结果：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述(一个或多个)基因表达谱是在从所述对象获得的生物样本中确定的，
基于针对一个或多个所述PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对放疗反应的所述预测，以及
任选地，基于所述预测来向医疗护理人员或所述对象提供所述预测或治疗推荐。
因此，在实施例中，本发明涉及一种预测前列腺癌对象对放疗的反应的方法，包括：
确定针对从包括以下项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的第三(一个或多个)基因表达谱：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述第三(一个或多个)基因表达谱是在从所述对象获得的生物样本中确定的，
基于针对一个或多个所述PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对放疗反应的所述预测，以及
任选地，基于所述预测来向医疗护理人员或所述对象提供所述预测或治疗推荐。
在备选实施例中，本发明涉及一种预测前列腺癌对象对放疗的反应的计算机实施的方法，包括：
接收针对从包括以下项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱的确定的结果：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述(一个或多个)基因表达谱是在从所述对象获得的生物样本中确定的，
基于针对一个或多个所述PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对放疗反应的所述预测，以及
任选地，将所述预测或基于所述预测的治疗推荐提供给医疗护理人员或所述对象。磷酸二酯酶(PDE)提供用于降解第二信使3’-5’-cyclic AMP的唯一手段。这样一来，它们准备提供关键监管角色。因此，其表达中异常变化、活动和细胞内位置全部可以贡献于特定疾病状态的下层分子病理学。实际上，最近已经示出了前列腺癌患者中富集PDE基因中的突变，从而导致提升的cAMP信号传导和前列腺癌的潜在易感性。然而，与每个PDE族内的异构体变体的复杂阵列耦合的不同细胞类型中的各种各样的表达谱使得理解PDE表达中的异常变化与疾病进展挑战期间的功能之间的链接。若干研究已经试图描述前列腺中的PDE补充，其中所有与其他PDE一起识别PDE4表达的显著水平。
使用当前识别的PDE异构体上的序列信息，我们已经分析了19前列腺癌细胞系中的它们的表达，并且异种移植(参见Henderson D.J.等人的“The cAMPphosphodiesterase-4D7(PDE4D7)is downregulated in androgen-independentprostate cancer cells and mediates proliferation by compartmentalizing cAMPat the plasma membrane of VCaP prostate cancer cells”(Br J Cancer，第110卷，第5期，第1278-1287页，2014年))。这样的研究将PDE3B、PDE4B、PDE4D、PDE7A、PDE8A、PDE8B和PDE9A异构体识别为在癌性前列腺细胞中的mRNA水平处异常地表达(参见Henderson D.J.等人，2014年，出处同上)，而PDE1、PDE3A、PDE5A、PDE10A和PDE11A mRNA以较低水平存在(未公布数据)，从而突出显示前列腺上皮细胞中的环状核苷酸信号传导的复杂性。重要地，通过将前列腺癌细胞样本分离成雄激素敏感性和雄激素不敏感性，去势抵抗性前列腺癌(CRPC)细胞表型，我们发现，PDE4D异构体的表达在CRPC样本中下调。特别地，我们发现，雄激素敏感性样本中许多中的最丰富的PDE4异构体，PDE4D7，展现了CRPC细胞模型中的显著程度的下调，从而呈现一种情形，其中，PDE4D7的下调能够直接贡献于驱动cAMP信号传导改变的疾病的恶化。此外，这些观察建议，PDE4D7的测量结果可以告知前列腺癌疾病进展，其中，低水平的表达可以与更具攻击性的表型连接。
基于PDE4D7表达与疾病的病理特征之间的相关性，我们定义的目标是识别患者前列腺组织(通过活检或手术收集的)中的PDE4D7的表达和与个体患者的结果相关的临床有用信息之间的预后关联。临床相关终点或代理终点(其与转移的发展、癌特异性或整体死亡显著相关)通常已经被评价为预后癌生物标志物。使用代理终点的最相关的理由涉及其中确定的临床终点上数据不可用或者队列中的数据的事件的数量对于统计数据分析而言太过限制时的情况。针对PDE4D7预后生物标志物的发展，我们将无BCR(生化性复发)进展生存或手术后二次处置的开始评价为针对转移和前列腺癌死亡的代理终点。使用这些特定终点，我们识别我们的临床队列中的事件的相关数量(例如，针对BCR，>30％)其对于多变量数据分析的是特别相关的。
在我们的评价中，我们选择标准方法多变量分析方法，诸如Cox回归和Kaplan-Meier生存分析，以便研究与确定的预后临床变量相比的连续和/或归类“PDE4D7评分”的附加价值和独立价值，诸如PSA和格里森评分(参见Alves de Inda M.等人的“Validation ofCyclic Adenosine Monophosphate Phosphodiesterase-4D7 for its IndependentContribution to Risk Stratification in a Prostate Cancer Patient Cohort withLongitudinal Biological Outcomes”(Eur Urol Focus，第4卷，第3期，第376-384页，2018年))。我们因此建立了风险模型，其中，我们使用逻辑回归将“PDE4D7评分”与手术后进展的手术前或手术后临床预测因子组合。得到的模型随后在Kaplan-Meier生存和ROC曲线分析中的多个独立患者群组上被测试，以便预测无处置后进展生存(参见Alves de Inda M.等人，2018年，出处同上)。
使用这样的策略，我们开始测试PDE4D7评分对来自手术后设置中的单手术中心的连续管理的患者群组中的回顾性收集、切除的前列腺组织的活检的预后价值(参见Alvesde Inda M.等人，2018年，出处同上)。患者群体包括大约500个个体，其中，承担病理和生物结果两者的纵向随访。这些临床数据可用于所有患者并且在处置后的中值120月的随访期间被收集。“PDE4D7评分”如上所述被确定并且然后使用可用手术后协变量(即，病理格里森评分、pT分级、手术边缘状态、精囊侵袭状态和淋巴结侵袭状态)在单变量和多变量分析两者中被测试，以便调节多变量设置。在该实例中，在初级介入后的无生化进展生存被设置为评价的临床终点。这些临床样本的单变量分析(参见Alves de Inda M.等人，2018年，出处同上)(示出了PDE4D7表达(依据“PDE4D7评分”)和手术后生物性复发(HR＝0.53每单位改变；95％ CI 0.41-0.67；p<0.0001)之间的逆关联)鲁棒地确认我们的先前数据(参见R.等人的“Human phosphodiesterase 4D7(PDE4D7)expression is increased inTMPRSS2-ERG-positive primary prostate cancer and independently adds to areduced risk of post-surgical disease progression”(Br J Cancer，第113卷，第10期，第1502-1511页，2015年)和/>R.等人的“Human PDE4D isoform composition isderegulated in primary prostate cancer and indicative for disease progressionand development of distant metastases”(Oncotarget，第7卷，第43期，第70669-70684页，2016年))。在具有这样的临床变量的多变量分析中，“PDE4D7评分”仍为用于预测临床结果的独立和有效的手段(HR＝0.56每单位改变；95％ CI 0.43-0.73；p<0.0001)。此外，当我们评价具有所验证和临床使用的风险模型CAPRA-S的多变量分析中的“PDE4D7评分”(HR＝0.54 95％ CI 0.42-0.69；p<0.0001)时我们获得了非常相似的结果。CAPRA-S评分(其基于术前PSA和在手术时确定的病理参数)被开发以向临床医师提供旨在帮助预测疾病复发的信息，包括BCR、系统进展和PCSM并且已经在US和其他群体中被评价。
有趣的是，当评估与连续“PDE4D7评分”相比的危害比(HR)时，我们发现了具有针对位于2与5之间的评分值的增加的“PDE4D7评分”的风险中的线性增加。然而，在小于2的PDE4D7评分处，然后手术后进展的风险大幅增加(参见Alves de Inda M.等人，2018年，出处同上)。这还在Kaplan-Meier生存曲线中清楚，其中，分组在最低“PDE4D7评分”类别内的患者展现出最高疾病复发风险。使用逻辑回归分析，我们然后组合CAPRA-S评分与连续“PDE4D7评分”。使用ROC曲线分析测试该模型，我们注意到BCR的处置后进展的2年和5年预测两者的与单独CAPRA-S相比的AUC的4-6％显著改进。因此，我们评价Kaplan-Meier生存分析中的组合的CAPRA-S&“PDE4D7评分”Cox回归组合模型，并且将此与单独的CAPRA-S评分类别进行比较。在施行该操作的情况下，我们确认当使用模型时风险预测的增加值，与单独使用CAPRA-S评分的临床度量相比的组合的“PDE4D7&CAPRA-S”评分(参见Alves de Inda M.等人，2018年，出处同上)。
在前列腺癌的诊断之后，准确风险评估需要在定义的初级处置的分层之前施行。出于这种考虑，我们开始看到是否我们能够转变手术前情况下的“PDE4D7评分”的预后使用，其测试从诊断针活检样本获得的肿瘤组织(参见van Strijp D.等人，“The PrognosticPDE4D7 Score in a Diagnostic Biopsy Prostate Cancer Patient Cohort withLongitudinal Biological Outcomes”，Prostate Cancer，2018:5821616)。在此，针活检被执行在来自单个诊断临床中心的168个患者上，其已经经历作为初级处置的手术。针对每个患者的最小随访时段是在该介入后60个月。用于调节多变量分析中的“PDE4D7评分”的临床协变量是手术时的年龄、术前PSA、PSA密度、活检格里森评分、肿瘤阳性活检评分的百分比、活检中的肿瘤的百分比和临床CT阶段。在此，我们评价了与针对生化性复发的Cox回归分析中的术前CAPRA评分相比的“PDE4D7评分”和组合的“PDE4D7&CAPRA”评分的效用(参见vanStrijp D.等人，2018年，出处同上)。
评价该患者群组，我们发现(参见van Strijp D.等人，2018年，出处同上)“PDE4D7评分”在针对临床变量(HR＝0.43；95％ CI 0.29-0.63；p<0.0001)以及针对临床CAPRA评分(HR＝0.53；95％ CI0.38-0.74；p＝0.0001)进行调节时与多变量分析中的BCR反相关联。Kaplan-Meier分析证明，如前所述，在手术后设置中，“PDE4D7评分”类别显著地与无BCR进展生存(logrank p<0.0001)和无二次处置生存(logrank p＝0.01)相关联。我们然后采用了组合逻辑回归模型，其是在先前队列上开发的。这包括组合的“CAPRA&PDE4D7”评分，证明最高组合的“CAPRA&PDE4D7”组合评分类别内的患者实际上没有在手术后的生化进展或转移到任何二次处置的风险。该逻辑回归模型也使用ROC曲线分析来评价以便预测手术后5年BCR。这揭示了超过单独的CAPRA评分的5％的AUC的增加(AUC＝0.82与0.77，分别地；p＝0.004)。组合的“CAPRA&PDE4D7”评分模型的决策曲线分析确认跨所有决策阈值与任一单独评分相比使用该组合评分的卓越的净收益，以便基于个体患者经历手术后疾病进展的风险阈值决定是否施行介入(例如，手术)(参见van Strijp D.等人，2018年，出处同上)。
本发明基于以下想法，因为PDE4D7生物标志物已经被证明为放疗反应的良好预测因子，识别与PDE47生物标志物高度相关的标志物的能力可能有助于更好地能够预测总体RT反应。
识别的基因ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2如下地被识别：我们在571名前列腺癌患者生成的RNAseq数据中近60000个转录本上识别了一系列与该数据中已知生物标志物PDE4D7的表达有关的基因。571个样本中的这些基因中的任何基因的表达与PDE4D7之间的相关性通过皮尔森相关性完成，并且在正相关的情况下表示为0到1之间的值，或者在负相关的情况下表示为-1到0之间的值。
针对相关系数的公式为：
其中，和分别是所有样本的样本均值AVERAGE(PDE4D7)和AVERAGE(gene)。作为用于计算相关系数的输入数据，我们使用PDE4D7评分(参见Alves de Inda M.等人2018年的文章，出处同上)和RNAseq确定的每个感兴趣基因的TPM基因表达值(见下文)。
在大约60000个转录本中的任何一个的表达与PDE4D7的表达之间确定的最大负相关系数为-0.38，而在大约60000个转录本的任何一个的表达与PDE4D7的表达之间确定的最大正相关系数为+0.56。我们选择了相关性范围为-0.31至-0.38以及+0.41至+0.56的基因。我们识别匹配这些特性的总共77转录本，其在以下表1中列出(按字母顺序排序)。
表1：77转录本的选择，其表达示出了与PDE4D7表达的强负或正相关性。
我们通过在由于术后生化复发接受补救性放疗(SRT)的186名患者的子群组中迭代测试Cox回归组合模型而从这77个转录本中选择了八个基因ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2。测试的临床终点是SRT开始后前列腺癌特异性死亡。
选择八个基因的边界条件是由多变量Cox回归中的p值对于模型中保留的所有基因<0.1的限制给出的。
术语“ABCC5”是指人类ATP结合盒亚家族C成员5基因(Ensembl:ENSG00000114770)，例如，是指NCBI参考序列NM_001023587.2或NCBI参考序列NM_005688.3中定义的序列，特别地，SEQ ID NO:1或SEQ ID No:2中所示的核苷酸序列，其对应于上述ABCC5转录本的NCBI参考序列的序列，并且还涉及相应的氨基酸序列，例如在SEQ ID NO:3或SEQ ID No:4中所示的，其对应于NCBI蛋白质登录参考序列NP_001018881.1和NCBI蛋白质登录参考序列NP_005679中定义的编码ABCC5多肽的蛋白质序列。
术语“ABCC5”还包括显示与ABCC5高度同源性的核苷酸序列，例如，与SEQ ID NO:1或SEQ ID No:2中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的核酸序列，或与SEQ ID NO:3或SEQ ID No:4所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的氨基酸序列，或与SEQ ID NO:3或SEQ ID No:4所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的编码氨基酸序列的核酸序列或与SEQ IDNo:1或SEQ ID No:2中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的由核酸序列编码的氨基酸序列。
术语“CUX2”是指人类同Cut Like源盒2基因(Ensembl:ENSG00000111249)，例如，是指NCBI参考序列NM_015267.3中所定义的序列，特别地，是指SEQ ID No:5中所示的核苷酸序列，其对应于上述CUX2转录本的NCBI参考序列的序列，并且还涉及相应的氨基酸序列，例如，如SEQ ID No:6中所示的，其对应于NCBI蛋白质登录参考序列NP_056082.2中定义的编码CUX2多肽的蛋白质序列。
术语“CUX2”还包括显示与CUX2高度同源性的核苷酸序列，例如，与SEQ ID NO:5中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的核酸序列，或与SEQ ID No:6所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的氨基酸序列，或与SEQ ID No:6所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的编码氨基酸序列的核酸序列或与SEQ ID No:5中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的由核酸序列编码的氨基酸序列。
术语“KIAA1549”是指人类KIAA1549基因(Ensembl:ENSG00000122778)，例如，是指NCBI参考序列NM_020910或NCBI参考序列NM_001164665中定义的序列，特别地，SEQ ID NO:7或SEQ ID No:8中说明的核苷酸序列，其对应于上述KIAA1549转录本的NCBI参考序列的序列，并且还涉及相应的氨基酸序列，例如在SEQ ID NO:9或SEQ ID No:10中所示的，其对应于NCBI蛋白质登录参考序列NP_065961和NCBI蛋白质登录参考序列NP_001158137中定义的编码KIAA1549多肽的蛋白质序列。
术语“KIAA1549”还包括显示与KIAA1549高度同源性的核苷酸序列，例如，与SEQID NO:7或SEQ ID No:8中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的核酸序列，或与SEQ ID NO:9或SEQ ID No:10所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的氨基酸序列，或与SEQ ID NO:9或SEQ ID No:10所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的编码氨基酸序列的核酸序列或与SEQ ID No:7或SEQ ID No:8中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的由核酸序列编码的氨基酸序列。
术语“PDE4D”是指人磷酸二酯酶4D基因(合集：ENSG00000113448)，例如，是指如NCBI参考序列NM_001104631或NCBI参考序列NM_001349242或NCBI参考序列NM_001197218或NCBI参考序列NM_006203或在NCBI参考序列NM_001197221或NCBI参考序列NM_001197220或NCBI参考序列NM_001197223或NCBI参考序列NM_001165899或NCBI参考序列NM_001165899中所定义的序列，特别地，是指如SEQ ID NO:11或SEQ ID NO:12或SEQ ID NO:13或SEQ ID NO:14或SEQ ID NO:15或SEQ ID NO:16或SEQ ID NO:17或SEQ ID NO:18或SEQID NO:19中所示的核苷酸序列，其对应于上述PDE4D转录本的NCBI参考序列的序列，并且还涉及例如，如在SEQ ID NO:20或SEQ ID NO:21或SEQ ID NO:22或在SEQ ID NO:23或SEQ IDNo:24或SEQ ID No:25或SEQ ID No:26或SEQ ID No:27或SEQ ID No:28中所示的对应的氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_001098101和NCBI蛋白质登录参考序列NP_001336171和NCBI蛋白质登录参考序列NP_001184147和NCBI蛋白质登录参考序列NP_006194和NCBI蛋白质登录参考序列NP_001184150和NCBI蛋白质登录参考序列NP_001184149和NCBI蛋白质登录参考序列NP_001184152和在NCBI蛋白质登录参考序列NP_001159371和NCBI蛋白质登录参考序列NP_001184148中定义的编码PDE4D多肽的蛋白质序列。
术语“PDE4D”还包括显示与PDE4D高度同源性的核苷酸序列，例如，与SEQ ID NO:11或SEQ ID NO:12或SEQ ID NO:13或SEQ ID NO:14或SEQ ID NO:15或SEQ ID NO:16或SEQID NO:17或SEQ ID NO:18或SEQ ID No:19中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的核酸序列或者与SEQ ID NO:20或SEQID NO:21或SEQ ID NO:22或SEQ ID NO:23或SEQ ID NO:24或SEQ ID NO:25或SEQ ID NO:26或SEQ ID NO:27或SEQ ID No:28中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的氨基酸序列或与SEQ ID NO:20或SEQ IDNO:21或SEQ ID NO:22或SEQ ID NO:23或SEQ ID NO:24或SEQ ID NO:25或SEQ ID NO:26或SEQ ID NO:27或SEQ ID No:28中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的编码氨基酸序列的核酸序列或者与SEQ ID NO:11或SEQ ID NO:12或SEQ ID NO:13或SEQ ID NO:14或SEQ ID NO:15或SEQ ID NO:16或SEQID NO:17或SEQ ID NO:18或SEQ ID No:19中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的由核酸序列编码的氨基酸序列。
术语“RAP1GAP2”指人类RAP1 GTP酶激活蛋白2基因(ENSG00000132359)，例如，是指如在NCBI参考序列NM_015085或NCBI参考序列NM_001100398或NCBI参考序列NM_001330058中所定义的序列，特别地，如在SEQ ID NO:29或SEQ ID NO:30或SEQ ID NO:31所示的核苷酸序列，其对应于上述RAP1GAP2转录本的NCBI参考序列的序列，并且还涉及例如如在SEQ ID NO:32或SEQ ID NO:33或SEQ ID NO:34中所示的相应的氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_055900和NCBI蛋白质登录参考序列NP_001093868和在的NCBI蛋白质登录参考序列NP_001316987中所定义的编码RAP1GAP2多肽的蛋白质序列。
术语“RAP1GAP2”还包括显示与RAP1GAP2高度同源性的核苷酸序列，例如，与SEQID NO:29或SEQ ID NO:30或SEQ ID No:31所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的核酸序列，或与SEQ ID NO:32或SEQID NO:33或SEQ ID No:34所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的氨基酸序列，或与SEQ ID NO:32或SEQ ID NO:33或SEQID No:34所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的编码氨基酸序列的核酸序列或与SEQ ID NO:29或SEQ ID NO:30或SEQID No:31中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的由核酸序列编码的氨基酸序列。
术语“SLC39A11”是指人类溶质载体家族39成员11基因(Ensembl:ENSG00000133195)，例如，是指如在NCBI参考序列NM_139177或NCBI参考序列NM_001352692中所定义的序列，特别地，如在SEQ ID NO:35或SEQ ID No:36中所示的核苷酸序列，其对应于上述SLC39A11转录本的NCBI参考序列的序列，并且还涉及例如SEQ ID NO:37或SEQ IDNO:38中所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_631916和NCBI蛋白质登录参考序列NP_001339621中定义的编码SLC39A11多肽的蛋白质序列。
术语“SLC39A11”还包括显示与SLC39A11高度同源性的核苷酸序列，例如，与SEQID NO:35或SEQ ID No:36中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的核酸序列，或与SEQ ID NO:37或SEQ ID No:38所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的氨基酸序列，或与SEQ ID NO:37或SEQ ID No:38所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的编码氨基酸序列的核酸序列或与SEQ ID No:35或SEQ ID No:36中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的由核酸序列编码的氨基酸序列。
术语“TDRD1”是指人类都铎域包含1基因(Ensembl:ENSG00000095627)，例如，是指NCBI参考序列NM_198795中定义的序列，特别地，是指SEQ ID No:39中所示的核苷酸序列，其对应于上述TDRD1转录本的NCBI参考序列的序列，并且还涉及例如SEQ ID NO:40中所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考NP_942090中定义的编码TDRD1多肽的蛋白质序列。
术语“TDRD1”还包括显示与TDRD1高度同源性的核苷酸序列，例如，与SEQ ID NO:39中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的核酸序列，或与SEQ ID No:40所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的氨基酸序列，或与SEQ ID No:40所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的编码氨基酸序列的核酸序列或与SEQ ID No:39中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的由核酸序列编码的氨基酸序列。
术语“VWA2”是指人Von Willebrand因子A域包含2基因(Ensembl:ENSG00000165816)，例如，是指NCBI参考序列NM_001320804中定义的序列，特别地，是指SEQID No:41中所示的核苷酸序列，其对应于上述VWA2转录本的NCBI参考序列的序列，并且还涉及例如SEQ ID NO:42中所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考NP_001307733中定义的编码VWA2多肽的蛋白质序列。
术语“VWA2”还包括显示与VWA2高度同源性的核苷酸序列，例如，与SEQ ID NO:41中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的核酸序列，或与SEQ ID No:42所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的氨基酸序列，或与SEQ ID No:42所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的编码氨基酸序列的核酸序列或与SEQ ID No:41中所示的序列至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同的由核酸序列编码的氨基酸序列。
术语“生物样本”或“从对象获得的样本”是指通过本领域技术人员已知的合适方法从对象例如前列腺癌患者获得的任何生物材料。术语“前列腺癌对象”是指患有或疑似患有前列腺癌的人。
还证明了，使用完整模型(使用所有八个基因)对获得显著预测效果不是实质的，并且显著结果能够已经随着PDE4D7相关基因中两个的随机选择而获得。示例和图10-17证明了足以做出显著预测的从整个集合选择的两个或三个基因的随机选择。这些随机选择使得其貌似合理：来自八个PDE4D7相关基因的集合的两个或更多个基因的任何选择允许对前列腺癌对象对放疗的反应的显著预测。
可以以临床上可接受的方式(例如以保存核酸(特别是RNA)或蛋白质的方式)收集所使用的生物样本。
可以以临床上可接受的方式收集所使用的生物样本，例如以保存核酸(特别是RNA)或蛋白质的方式。
所述(一个或多个)生物样本可包括身体组织和/或体液，例如但不限于血液、汗液、唾液和尿液。此外，生物样本可包含源自上皮细胞的细胞提取物或细胞群，所述上皮细胞例如癌性上皮细胞或源自疑似癌性组织的上皮细胞。生物样本可包含源自腺体组织的细胞群，例如，样本可源自男性对象的前列腺。此外，如果需要，可以从获得的身体组织和体液中纯化细胞，然后用作生物样本。在一些实现中，样本可以是组织样本、尿液样本、尿液沉渣样本、血液样本、唾液样本、精液样本、包括循环肿瘤细胞的样本、细胞外囊泡、含有前列腺分泌的外来体的样本，或细胞系或癌细胞系。
在一个特定的实现中，可以获得和/或使用活组织检查或切除样本。这样的样本可以包括细胞或细胞裂解物。
还可以设想将生物样本的内容物提交给富集步骤。例如，样本可以与特定细胞类型(例如前列腺细胞)的细胞膜或细胞器特异性的配体接触，例如用磁性颗粒功能化。由磁性颗粒浓缩的材料可随后用于如上文或下文所述的检测和分析步骤。
此外，细胞，例如肿瘤细胞，可以通过流体或液体样本例如血液、尿液等的过滤过程来富集。这样的过滤过程也可以与基于如上文所述的配体特异性相互作用的富集步骤组合。
术语“前列腺癌”是指男性生殖系统中的前列腺癌，当前列腺细胞发生突变并开始失控增殖时就会发生这种癌症。通常，前列腺癌与前列腺特异性抗原(PSA)水平升高有关。在本发明的一个实施方案中，术语“前列腺癌”涉及显示PSA水平高于3.0的癌症。在另一个实施例中，该术语涉及显示PSA水平高于2.0的癌症。术语“PSA水平”是指血液中PSA的浓度，单位为ng/ml。
术语“非进行性前列腺癌状态”是指个体样本未示出指示“生化复发”和/或“临床复发”和/或“转移”和/或“去势抵抗性疾病”和/或“前列腺癌或疾病特异性死亡”的参数值。
术语“进行性前列腺癌状态”是指个体样本示出指示“生化复发”和/或“临床复发”和/或“转移”和/或“去势抵抗性疾病”和/或“前列腺癌或疾病特异性死亡”的参数值。
术语“生化复发”通常是指指示样本中存在前列腺癌细胞的PSA升高的复发生物学值。然而，也可以使用可用于检测存在或引起对此类存在的怀疑的其他标记。
术语“临床复发”是指临床体征的存在指示所测量的肿瘤细胞的存在，例如使用体内成像。
术语“转移”是指在前列腺以外的器官中存在转移性疾病。
术语“去势抵抗性疾病”是指存在激素不敏感的前列腺癌；即，不再对雄激素剥夺疗法(ADT)产生反应的前列腺癌。
术语“前列腺癌特异性死亡或疾病特异性死亡”是指患者死于前列腺癌。
优选的是，所述一个或多个PDE4D7相关基因包含所述PDE4D7相关基因中的三个或更多个，优选地，六个或更多个，最优选地，所有。
优选地，对所述放疗反应的所述预测的确定包括利用已经根据前列腺癌对象的群体导出的回归函数来将针对两个或更多个，例如，2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因的基因表达谱进行组合。
Cox比例风险回归允许分析几个风险因素对时间对测试事件(如生存)的影响。因此，风险因素可能是二分变量或离散变量，如风险评分或临床阶段，但也可能是连续变量，如生物标志物测量结果或基因表达值。终点(例如，死亡或疾病复发)的概率称为风险。除了关于例如患者群组中的对象是否达到测试终点的信息(例如，患者是否死亡)，在回归分析中也考虑了到达终点的时间。危害建模为：H(t)＝H0(t)·exp(w1·V1+w2·V2+w3·V3+…)，其中，V1、V2、V3…是预测变量，并且H0(t)是基线危害，而H(t)是任何时间t时的危害。危害比(或到达事件的风险)由Ln[H(t)/H0(t)]＝w1·V1+w2·V2+w3·V3+…表示，其中，系数或权重w1、w2、w3…通过Cox回归分析估计，并且可以用与逻辑回归分析类似的方式进行解读。
在一个特定的实现中，对放疗反应的预测如下地确定：
PDE4D7_CORR_模型：
(w1·ABCC5)+(w2·CUX2)+(w3·KIAA1549)+(w4·PDE4D)+ (2)
(w5·RAP1GAP2)+(w6·SLC39A11)+(w7·TDRD1)+(w8·VWA2)
其中，w1到w8是权重，并且ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2是基因的表达水平。
在一个示例中，w1可以是大约-0.1到0.9，例如，0.418，w2可以是大约-0.2到0.8，例如，0.35，w3可以是大约-0.1到0.9，例如，0.43774，w4可以是大约1.3到0.3，比如0.7596，w5可以是大约-1.2至-0.2，例如，-0.7243，w6可以是大约0.0至0.1，例如，0.5361，w7可以是大约-0.2至0.8，例如，0.2686，且w8可以是大约-0.8到0.2，例如，0.3123。
基于放疗反应的预测值，也可以将对放疗反应的预测分类或归类为至少两个风险组中的一个。例如，可能有两个风险组，或三个风险组，或四个风险组，或四个以上的预定义风险组。每个风险组涵盖放疗反应预测值的相应范围(非交叠)。例如，风险组可以指示特定临床事件发生的概率从0到<0.1或从0.1到<0.25或从0.25到<0.5或从0.5到1.0等。
进一步优选地，对所述放疗反应的所述预测的所述确定还基于从所述对象获得的一个或多个临床参数。
如上所述，已经研究了基于临床参数的各种指标。通过使对放疗反应的预测还基于(一个或多个)这样的临床参数，能够可能进一步改进预测。
优选临床参数包括以下一项或多项：(i)前列腺特异性抗原(PSA)水平；(ii)病理性格里森评分(pGS)；iii)临床肿瘤分期；iv)病理学格里森分级组(pGGG)；v)病理阶段；vi)一个或多个病理变量，例如，手术切缘和/或淋巴结浸润和/或前列腺外生长和/或精囊浸润的状态；vii)CAPRA-S；以及viii)另一临床风险评分。
进一步优选地，对所述放疗反应的所述预测的确定包括利用已经根据前列腺癌对象的群体导出的回归函数来将针对一个或多个PDE4D7相关基因的(一个或多个)基因表达谱和从所述对象获得的所述一个或多个临床参数进行组合。
进一步优选地，针对一个或多个PDE4D7相关基因的基因表达谱和从对象获得的一个或多个临床参数与已经从前列腺癌对象的群体导出的回归函数组合。
在一个特定的实现中，对放疗反应的预测如下地确定：
(w9·PDE4D7_CORR_模型)+(w10·pGGG) (3)
其中，w9和w10是权重，PDE4D7_CORR_模型是基于PDE4D7相关基因中的两个或更多个，例如，2个、3个、4个、6个、7个或者所有，PDE4D7相关基因的表达谱的上述回归模型，并且pGGG是病理格里森分级组。
在一个示例中，w9可以是大约0.1到1.1，例如，0.6117，并且w10可以是大约0.1到1.1，例如，0.6127。
优选地，生物样本在放疗开始之前从对象获得。可以以前列腺癌组织中的mRNA或蛋白质的形式确定所述(一个或多个)基因表达谱。替代地，如果基因以可溶形式存在，则可以在血液中测定基因表达谱。
进一步优选的是，所述放疗为根治性放疗或挽救性放疗。
优选地，其中，对放疗反应的预测对于放疗的有效性是负面的或正面的，其中，基于预测推荐治疗，并且如果预测是负面的，则推荐的治疗包括以下中的一项或多项：(i)早于标准提供的放疗；(ii)放射剂量增加的放疗；(iii)(iii)辅助治疗，例如，雄激素阻断治疗；以及iv)作为非辐射治疗的替代治疗。预测为负面的程度可以决定所推荐的治疗偏离标准形式的放疗的程度。
在本发明的另外的方面中，提出了一种用于预测前列腺癌对象对放疗的反应的装置，包括：
输入部，其适于接收指示针对从包括以下项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱的确定的结果的数据：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述(一个或多个)基因表达谱是在从所述对象获得的生物样本中确定的，
处理器，其适于基于针对所述一个或多个PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对所述放疗反应的所述预测，以及
任选地，提供单元，其适于将所述预测或基于所述预测的治疗推荐提供给医疗护理人员或所述对象。
在本发明的另一方面中，提供了一种包括指令的计算机程序产品，当所程序由计算机运行时，所述指令使计算机执行包括以下操作的方法：
接收指示针对从包括以下项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱的确定的结果的数据：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述(一个或多个)基因表达谱是在从所述对象获得的生物样本中确定的，
基于针对一个或多个PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对前列腺癌对象对治疗的反应的预测，并且
任选地，基于所述预测来向医疗护理人员或所述对象提供所述预测或治疗推荐。
在本发明的另一方面中，提出了一种诊断套件，其包括：
至少一个引物和/或探针，用于在从所述对象获得的生物样本中确定针对从包括以下项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或全部，PDE4D7相关基因中的每个的基因表达谱：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，以及
任选地，根据权利要求10所定义的装置或根据权利要求11所定义的计算机程序产品。
在本发明的另一方面中，提出了如权利要求12所定义的套件的使用。
优选地，根据权利要求13所述的用途用在预测前列腺癌对象对放疗的反应的方法中。
在本发明的另一方面中，提出了一种方法，其包括：
接收从前列腺癌对象获得的生物样本，
使用如权利要求12所定义的套件来在从对象获得的生物样本中确定针对从包括以下项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或全部，PDE4D7相关基因中的每个的基因表达谱：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2。
在本发明的另外的方面中，提出了针对从包括以下各项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱在预测前列腺癌对象对放疗的反应的方法中的使用：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，包括：
基于针对一个或多个所述PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对放疗反应的所述预测，以及
任选地，基于所述预测来向医疗护理人员或所述对象提供所述预测或治疗推荐。
应当理解，根据权利要求1所述的方法、根据权利要求10所述的装置、根据权利要求11的所述计算机程序产品、根据权利要求12所述的诊断套件、根据权利要求13所述的诊断套件的用途、根据权利要求15所述的方法，以及根据权利要求16所述的基因表达谱的使用具有相似和/或相同的优选实施例，特别是如从属权利要求中所定义的。
应该理解，本发明的优选实施例也可以是从属权利要求或以上实施例与各自的独立权利要求的任何组合。
本发明的这些和其他方面将根据下文描述的实施例变得显而易见，并且将参考下文描述的实施例得到阐述。
附图说明
在以下附图中：
图1示意性且示例性地示出了预测前列腺癌对象对放疗的反应的方法的实施例的流程图，
图2示出了三个预测模型的ROC曲线分析，
图3示出了三个预测模型的ROC曲线分析，
图4示出了186名患者群组(用于开发PCAI_CORR_模型的训练集)中和PCAI_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)，
图5示出了186名患者群组(用于开发PCAI_CORR&pGGG_模型的训练集)中和PCAI_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)，
图6示出了151名患者群组(用于验证在186名患者训练集上开发的PDE4D7_CORR_模型的测试集)中的PDE4D7_CORR_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)，
图7示出了151名患者群组(用于验证在186名患者训练集上开发的PDE4D7_CORR&pGGG_模型的测试集)中的PCAI_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT
(补救性放疗)，
图8示出了151名患者群组(用于验证在186名患者训练集上开发的PCAI模型的测试集)中的PCAI_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)，并且
图9示出了151名患者群组(用于验证在186名患者训练集上开发的PCAI模型的测试集)中的PCAI_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)。
图10示出了186患者队列中的Kaplan-Meier曲线的PDE4D7_CORR_2.1模型，其中，全部患者在手术后BCR(生化复发)后经受SRT(补救性放疗)。
图11示出了186患者群组中的PDE4D7_CORR_2.2模型的Kaplan-Meier曲线，其中，全部患者在手术后BCR(生化复发)后经受SRT(挽救性辐射处置)。
图12示出了186患者群组中的PDE4D7_CORR_2.3模型的Kaplan-Meier曲线，其中，全部患者在手术后BCR(生化复发)后经受SRT(挽救性辐射处置)。
图13示出了186患者群组中的PDE4D7_CORR_2.4模型的Kaplan-Meier曲线，其中，全部患者在手术后BCR(生化复发)后经受SRT(挽救性辐射处置)。
图14示出了186患者群组中的PDE4D7_CORR_2.5模型的Kaplan-Meier曲线，其中，全部患者在手术后BCR(生化复发)后经受SRT(挽救性辐射处置)。
图15示出了186患者群组中的PDE4D7_CORR_3.1模型的Kaplan-Meier曲线，其中，全部患者在手术后BCR(生化复发)后经受SRT(挽救性辐射处置)。
图16示出了186患者群组中的PDE4D7_CORR_3.2模型的Kaplan-Meier曲线，其中，全部患者在手术后BCR(生化复发)后经受SRT(挽救性辐射处置)。
图17示出了186患者群组中的PDE4D7_CORR_3.3模型的Kaplan-Meier曲线，其中，全部患者在手术后BCR(生化复发)后经受SRT(挽救性辐射处置)。
具体实施方式
放疗反应预测概述
图1示意性且示例性地示出了预测前列腺癌对象对放疗的反应的方法的实施例的流程图。
该方法开始于步骤S100。
在步骤S102，从第一组被诊断为患有前列腺癌的患者(对象)中的每个获得生物样本。优选地，在获得生物样本后的一段时间内对这些前列腺癌患者执行了前列腺癌监测，例如至少一年，或至少两年，或约五年。
在步骤S104处，例如通过对从每个生物样本中提取的RNA执行RT-qPCR(实时定量PCR)，针对从患者的第一集合获得的生物样本中的每个生物样本获得针对从包括以下各项的组中选择的两个或更多个，例如，2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2。示例性基因表达谱包括两个或更多个基因中每个的表达水平(例如，值)，其可以使用针对一组参考基因(例如B2M、HPRT1、POLR2A和/或PUM1)中的每个的值而被标准化。在一个实现方式中，针对两个或更多个基因中的每个基因的基因表达水平是相对于从包括以下各项的组中选择的一个或多个参考基因标准化的：ACTB、ALAS1、B2M、HPRT1、POLR2A、PUM1、RPLP0、TBP、TUBA1B和/或YWHAZ，例如，这些参考基因中的至少一个或至少两个或至少三个或优选地所有。
在步骤S106处，基于针对患者的第一集合获得的生物样本中的至少一些生物样本获得的两个或更多个基因(ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和/或VWA2)的基因表达谱以及根据监测获得的相应结果来确定用于分配放疗反应的预测的回归函数。在一个特定的实现方式中，如上述公式(1)中所指定的那样确定回归函数。
在步骤S108处，从患者(对象或个体)获得生物样本。患者能够是新的患者或第一集合中的一个患者。
在步骤S110处，例如通过对生物样本执行PCR，针对两个或更多个，例如，2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个获得基因表达谱。在一个实现方式中，针对两个或更多个基因中的每个基因的基因表达水平是相对于从包括以下各项的组中选择的一个或多个参考基因标准化的：ACTB、ALAS1、B2M、HPRT1、POLR2A、PUM1、RPLP0、TBP、TUBA1B和/或YWHAZ，例如，这些参考基因中的至少一个或至少两个或至少三个或优选地所有。这实质上与在步骤S104中相同。
在步骤S112处，使用回归函数来针对患者确定基于两个或更多个基因的基因表达谱的放疗反应的预测。这将稍后在说明书中更详细地描述。
在S114处，可以基于预测向例如患者或其监护人员、医生或另一医疗保健工作人员提供治疗建议。为此目的，可以基于预测的值将预测分类到风险组的预定义集合中的一个风险组中。在一个特定的实现方式中，对放疗反应的预测是针对放疗的有效性为负面的或正面的。如果预测是负面的，则所推荐的治疗包括以下各项中的一项或多项：(i)比标准更早提供的放疗；(ii)具有增加的辐射剂量的放疗；(iii)辅助治疗，例如，雄激素阻断治疗；以及iv)不是辐射治疗的替代治疗。
该方法在S116结束。
在一个实施例中，步骤S104和S110中的基因表达谱是通过使用两个或更多个引物和/或探针和/或其两个或更多个集合检测mRNA表达来确定的。
在一个实施例中，步骤S104和S110还包括分别从第一组患者和患者获得临床参数。临床参数可包括以下一项或多项：(i)前列腺特异性抗原(PSA)水平；(ii)病理性格里森评分(pGS)；iii)临床肿瘤分期；iv)病理学格里森分级组(pGGG)；v)病理阶段；vi)一个或多个病理变量，例如，手术切缘和/或淋巴结浸润和/或前列腺外生长和/或精囊浸润的状态；vii)CAPRA-S；以及viii)另一临床风险评分。然后，用于分配在步骤S106中确定的放疗反应的预测的回归函数还基于从患者的第一集合中的至少一些患者获得的一个或多个临床参数。在步骤S112中，对放疗反应的预测然后还基于从患者获得的一个或多个临床参数(例如，病理格里森分级组(pGGG))，并且是使用回归函数对患者确定的。
基于与RT后的结果的显著相关性，我们预期所识别的分子将提供关于根治性RT和/或SRT的有效性的预测价值。
结果
TPM基因表达值
对于每个基因，基于以下步骤来计算TPM(每百万转录本)表达值：
1、在映射和对齐到人类基因组后，将来自RNAseq fastq原始数据的读取计数除以每个基因的长度(以千碱基为单位)。这得到每千碱基读取(RPK)。
2、将样本中的所有RPK值相加并将该数字除以1000000。这得到“每百万”比例因子。
3、将RPK值除以“每百万”比例因子。这得到针对每个基因的TPM表达值。
每基因的TPM值用于计算每个基因的参考标准化基因表达。
标准化基因表达值
对于Cox回归建模，来自RNAseq数据的所有基于基因TPM(每百万转录本)的表达值通过以下转换进行log2标准化：
TPM_log2＝log2(TPM+1) (4)
在标准化的第二步中，TPM_log2表达值根据四个参考基因的平均平均值(mean(ref_genes))标准化，如下所示：
TPM_log2_norm＝log2(TPM+1)-log2(mean(ref_genes)) (5)
考虑了以下参考基因(表2)：
表2：参考基因。
基因符号 Ensembl_ID
ALAS1 ENSG00000023330
ACTB ENSG00000075624
RPLP0 ENSG00000089157
TBP ENSG00000112592
TUBA1B ENSG00000123416
PUM1 ENSG00000134644
YWHAZ ENSG00000164924
HPRT1 ENSG00000165704
B2M ENSG00000166710
POLR2A ENSG00000181222
对于这些参考基因，我们选择了以下四个B2M、HPRT1、POLR2A和PUM1从而计算：
其中，参考基因的输入数据是它们的RNAseq测量的TPM中的基因表达(每百万转录本)，AVERAGE是数学平均值。
对于感兴趣的基因的多变量分析，我们使用每个基因的参考基因标准化log2(TPM)值作为输入。
Cox回归分析
然后我们开始测试这八个基因的组合是否将呈现更大的预后价值。利用Cox回归，我们在有(PDE4D7_CORR&pGGG_模型)或没有(PDE4D7_CORR_模型)571个前列腺癌患者的队列中的可变病理格里森分级组(pGGG)的存在的情况下将八个基因的表达水平建模为手术后挽救性RT后的前列腺癌特异性死亡。我们了测试了ROC曲线分析以及Kaplan-Meier生存分析中的两个模型。
Cox回归函数推导如下：
PDE4D7_CORR_模型：
(w1·ABCC5)+(w2·CUX2)+(w3·KIAA1549)+(w4·PDE4D)+
(w5·RAP1GAP2)+(w6·SLC39A11)+(w7·TDRD1)+(w8·VWA2)
PDE4D7_CORR&pGGG_模型:
(w9·PDE4D7_CORR_模型)+(w10·pGGG)
权重w1到w10的详细信息如以下表3中所示。
表3:针对两个Cox回归模型(即，PDE4D7相关性模型(PDE4D7_CORR_模型)和PDE4D7相关性&pGGG组合模型(PDE4D7_CORR&pGGG_模型))的变量和权重；NA-不可用。
ROC曲线分析
接下来，我们测试了如上面针对其能力概述的的Cox回归模型以预测在由于术后疾病复发而引起的挽救性辐射治疗(SRT)开始后的5年前列腺癌特异性死亡(PCa Death)。将模型的性能与EAU BCR风险组进行比较(参见Tilki D.等人的“External validation ofthe European Association of Urology Biochemical Recurrence Risk groups topredict metastasis and mortality after radical prostatectomy in a Europeancohort”(Eur Urol，第75卷，第6期，第896-900页，2019年))并且与病理格里森分级组(pGGG)进行比较。
图2示出了三个预测模型的ROC曲线分析。PDE4D7_CORR_模型(AUC＝0.85)是基于与PDE4D7相关的八个基因的Cox回归模型。PDE4D7_CORR&pGGG_模型(AUC＝0.9)是基于与PDE4D7和病理格里森分级组(pGGG)信息相关的八个基因的Cox回归模型。EAU_BCR_Risk(AUC＝0.79)是EAU-BCR风险组(欧洲泌尿外科协会生化复发风险组)。
图3示出了三个预测模型的ROC曲线分析。PDE4D7_CORR_模型(AUC＝0.86)是基于与PDE4D7相关的八个基因的Cox回归模型。PDE4D7_CORR&pGGG_模型(AUC＝0.91)是基于与PDE4D7和病理格里森分级组(pGGG)信息相关的八个基因的Cox回归模型。pGGG(AUC＝0.82)是病理格里森分级组。
Kaplan-Meier生存分析
针对Kaplan-Meier生存曲线分析，基于截止值将风险模型(PDE4D7_CORR_模型和PDE4D7_CORR&pGGG_模型)的Cox函数归类到两个子队列中。针对到低风险和高风险中的组分离的阈值基于PDE4D7_CORR_模型和PDE4D7_CORR&pGGG_模型的平均输出值，分别地，如通过使用整个队列中的每患者的Cox回归模型计算的。
患者类别表示针对两个创建的风险模型(PDE4D7_CORR_模型；PDE4D7_CORR&pGGG_模型)的经历在由于手术后疾病复发(而开始挽救性辐射治疗(SRT)后的前列腺癌特异性死亡(PCa Death)图4至7)和在由手术后疾病复发而开始挽救性辐射治疗(SRT)后的死亡(图8和9)的测试临床终点的增加的风险。
图4示出了186名患者群组(用于开发PCAI_CORR_模型的训练集)中和PCAI_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)，所测试的临床终点是在由于术后疾病复发而进行的挽救性放疗(SRT)开始后的前列腺癌特异性死亡(PCa死亡)(logrank p<0.0001；HR＝9.4；95％CI＝4.1-21.2)。以下补充列表示出了所分析的PDE4D7_CORR_模型类别处于风险中的患者数量，即，在SADT后+20个月的任何时间区间内处于风险中的患者：低风险：106、105、99、93、80、60、55、30、6、3、0；高风险：80、74、66、51、37、24、18、8、1、1、0。
图5示出了186名患者群组(用于开发PCAI_CORR&pGGG_模型的训练集)中和PCAI_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)。所测试的临床终点是在由于术后疾病复发而进行的挽救性放疗(SRT)开始后的前列腺癌特异性死亡(PCa死亡)(logrank p<0.0001；HR＝12.1；95％CI＝4.9-30.2)。以下补充列表示出了所分析的PDE4D7_CORR&pGGG_模型类别处于风险中的患者数量，即，在SADT后+20个月的任何时间区间内处于风险中的患者：低风险：123、123、117、109、94、72、65、34、6、3、0；高风险：63、56、48、35、23、12、8、4、1、1、0。
图6示出了151名患者群组(用于验证在186名患者训练集上开发的PDE4D7_CORR_模型的测试集)中的PDE4D7_CORR_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)。所测试的临床终点是在由于术后疾病复发而进行挽救性放疗(SRT)开始后的前列腺癌特异性死亡(PCa死亡)(logrank p＝0.002；HR＝5.2；95％CI＝1.9-14.3)。以下补充列表示出了所分析的PDE4D7_CORR_模型类别处于风险中的患者数量，即，在SADT后+20个月的任何时间区间内处于风险中的患者：低风险：81、81、80、80、69、51、35、23、14、9、6、31、1、0；高风险：70、68、65、61、51、39、31、20、12、9、6、5、2、0。
图7示出了151名患者群组(用于验证在186名患者训练集上开发的PCAI模型的测试集)中的PCAI_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)。所测试的临床终点是在由于术后疾病复发而进行挽救性放疗(SRT)开始后的前列腺癌特异性死亡(PCa死亡)(logrank p＝0.02；HR＝3.5；95％CI＝1.3-9.8)。以下补充列表指出了所分析的PCAI&临床模型类别处于风险中的患者数量，即，在SRT后+20个月的任何时间区间内处于风险中的患者：低风险：84、83、83、82、70、54、37、27、17、14、9、8、3、0；高风险：67、66、62、59、50、36、29、16、9、4、3、0、0、0。
图8示出了151名患者群组(用于验证在186名患者训练集上开发的PDE4D7_CORR_模型的测试集)中的PDE4D7_CORR_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)。测试的临床终点是由于术后疾病复发而进行的挽救性放疗(SRT)开始后的死亡(对数秩p＝0.002；HR＝3.0；95％CI＝1.5-5.8)。以下补充列表示出了所分析的PDE4D7_CORR_模型类别处于风险中的患者数量，即，在SADT后+20个月的任何时间区间内处于风险中的患者：低风险：81、81、80、80、69、51、35、23、14、9、6、31、1、0；高风险：70、68、65、61、51、39、31、20、12、9、6、5、2、0。
图9示出了151名患者群组(用于验证在186名患者训练集上开发的PCAI模型的测试集)中的PCAI_模型的Kaplan-Meier曲线，所有患者在术后BCR(生化复发)后接受SRT(补救性放疗)。测试的临床终点是由于术后疾病复发而进行的挽救性放疗(SRT)开始后的死亡(对数秩p＝0.0008；HR＝3.4；95％CI＝1.7-7.0)。以下补充列表指出了所分析的PCAI&临床模型类别处于风险中的患者数量，即，在SRT后+20个月的任何时间区间内处于风险中的患者：低风险：84、83、83、82、70、54、37、27、17、14、9、8、3、0；高风险：67、66、62、59、50、36、29、16、9、4、3、0、0、0。
图4至9所示的Kaplan-Meier生存曲线分析指示存在不同的患者风险组。患者的风险组是通过由风险模型DE4D7_CORR_模型或PDE4D7_CORR&pGGG_模型计算的遭受相应临床终点(死亡、前列腺癌特异性死亡)的概率而确定的。取决于患者死于前列腺癌的预测风险(即，取决于患者可能属于哪个风险组)，可能会指示不同类型的干预措施。在较低风险组的护理标准(SOC)中，SRT可能与SADT(挽救雄激素剥夺疗法)相结合，可提供可接受的长期肿瘤控制。对于表现出最终患前列腺癌死亡风险较高的患者组，应用RT和/或与化疗相结合的剂量递增可能会提供改善的纵向生存结果。治疗升级的替代选择是SRT(考虑更高剂量方案)、SADT和化学疗法的早期组合或免疫疗法(例如Sipuleucil-T)或其他实验疗法等替代疗法。
进一步的结果
发明人推测使用完整模型(使用所有八个基因)对获得显著预测效果将不是必需的。因此，两个或三个基因的随机集合选自完整集合以研究是否选自八个PDE4D7相关基因的两个或三个基因的集合将足以做出预测。
本节示出了基于包括两个PDE4D7相关基因的随机选择的组合的五个不同的基因模型并且基于包括三个PDE4D7相关基因的随机选择的组合的三个不同的基因模型的Cox回归模型的额外的结果。在表4和5中显示了针对变量和权重的细节。
表4：包括两个PDE4D7相关基因的随机选择的组合的五个基因Cox回归模型的变量和权重。
表5：包括三个PDE4D7相关基因的随机选择的组合的三个基因Cox回归模型的变量和权重。
对于Kaplan-Meier曲线分析，六个风险模型的Cox回归函数(DE4D7 2.1–2.5&3.1–3.3)根据截止值(见下图说明)而被分为两个亚组(低风险与高风险)。针对终点测试患者队列：在开始SRT(挽救性辐射)之后的前列腺癌特异性死亡(PCa死亡)(图10-17)。
图10示出了PDE4D7_CORR_2.1模型的Kaplan-Meier曲线。测试的临床终点是PCa在SRT开始后由于术后疾病复发而死亡。根据PDE4D7 2.1模型预测的临床终点风险(低风险与高风险)，对象被分为两个群组。值0.4被用作截止值(logrank p＝0.005；HR＝3.1；CI＝1.4-6.7)。以下补充列表显示了分析的PDE4D7.2.1模型类别中处于风险中的对象数量，即，在手术后+20个月的任何时间区间内处于风险中的对象：低风险(<＝0.4)：97、95、90、82、66、50、43、25、5、3、0；高风险(>0.4)：89、84、75、62、51、34、30、13、2、1、0。
图11示出了PDE4D7_CORR_2.2模型的Kaplan-Meier曲线。测试的临床终点是PCa在SRT开始后由于术后疾病复发而死亡。根据PDE4D7 2.2模型预测的临床终点风险(低风险与高风险)，对象被分为两个群组。值-0.05被用作截止值(logrank p＝0.009；HR＝2.9；CI＝1.3-6.3)。以下补充列表显示了分析的PDE4D7 2.2模型类别中处于风险中的对象数量，即，在手术后+20个月的任何时间区间内处于风险中的对象：低风险(<＝-0.05)：101、100、93、84、68、52、46、24、5、3、0；高风险(>-0.05)：85、79、72、60、49、32、27、14、2、1、0。
图12示出了PDE4D7_CORR_2.3模型的Kaplan-Meier曲线。测试的临床终点是PCa在SRT开始后由于术后疾病复发而死亡。根据PDE4D7 2.3模型预测的临床终点风险(低风险与高风险)，对象被分为两个群组。值-1.3被用作截止值(logrank p＝0.0009；HR＝3.7；CI＝1.7-8.3)。以下补充列表显示了分析的PDE4D7 2.3模型类别中处于风险中的对象数量，即，在手术后+20个月的任何时间区间内处于风险中的对象：低风险(<＝-1.3)：86、84、79、72、61、39、34、22、6、3、0；高风险(>-1.3)：100、95、86、72、56、45、39、16、1、1、0。
图13示出了PDE4D7_CORR_2.4模型的Kaplan-Meier曲线。测试的临床终点是PCa在SRT开始后由于术后疾病复发而死亡。根据PDE4D7 2.4模型预测的临床终点风险(低风险与高风险)，对象被分为两个群组。值-0.5被用作截止值(logrank p＝0.0001；HR＝5.2；CI＝2.3-11.7)。以下补充列表显示了分析的PDE4D7 2.4模型类别中处于风险中的对象数量，即，在手术后+20个月的任何时间区间内处于风险中的对象：低风险(<＝-0.5)：106、105、99、90、81、61、55、30、5、2、0；高风险(>-0.5)：80、74、66、55、37、25、19、8、2、2、0。
图14示出了DE4D7_CORR_2.5模型的Kaplan-Meier曲线。测试的临床终点是PCa在SRT开始后由于术后疾病复发而死亡。根据PDE4D7 2.5模型预测的临床终点风险(低风险与高风险)，对象被分为两个群组。值-1.4被用作截止值(logrank p＝0.003；HR＝3.3；CI＝1.5-7.2)。以下补充列表显示了分析的PDE4D7 2.5模型类别中处于风险中的对象数量，即，在手术后+20个月的任何时间区间内处于风险中的对象：低风险(<＝-1.4)：79、77、74、68、56、35、30、18、4、1、0；高风险(>-1.4)：107、102、91、76、61、49、43、20、3、3、0。
图15示出了针对PDE4D7_CORR_3.1模型的Kaplan-Meier曲线。测试的临床终点是PCa在SRT开始后由于术后疾病复发而死亡。根据PDE4D7 3.1模型预测的临床终点风险(低风险与高风险)，对象被分为两个群组。值-1被用作截止值(logrank p＝0.002；HR＝3.5；CI＝1.6-7.6)。以下补充列表显示了分析的PDE4D7 3.1模型类别中处于风险中的对象数量，即，在手术后+20个月的任何时间区间内处于风险中的对象：低风险(<＝-1)：85、83、78、69、56、38、34、20、5、3、0；高风险(>-1)：101、96、87、75、61、46、39、18、2、1、0。
图16示出了PDE4D7_CORR_3.2模型的Kaplan-Meier曲线。测试的临床终点是PCa在SRT开始后由于术后疾病复发而死亡。根据PDE4D7 3.2模型预测的临床终点风险(低风险与高风险)，对象被分为两个群组。值-0.13被用作截止值(logrank p＝0.0004；HR＝4.2；CI＝1.9-9.3)。以下补充列表显示了分析的PDE4D7 3.2模型类别中处于风险中的对象数量，即，在手术后+20个月的任何时间区间内处于风险中的对象：低风险(<＝-0.13)：99、98、94、86、71、54、50、25、4、2、0；高风险(>-0.13)：87、81、71、58、46、30、23、13、3、2、0。
图17示出了PDE4D7_CORR_3.3模型的Kaplan-Meier曲线。测试的临床终点是PCa在SRT开始后由于术后疾病复发而死亡。根据PDE4D7 3.3模型预测的临床终点风险(低风险与高风险)，对象被分为两个群组。值-0.2被用作截止值(logrank p＝0.0002；HR＝4.5；CI＝2.0-10.1)。以下补充列表显示了分析的PDE4D7 3.3模型类别中处于风险中的对象数量，即，在手术后+20个月的任何时间区间内处于风险中的对象：低风险(<＝-0.2)：104、104、98、87、71、54、50、28、6、3、0；高风险(>-0.2)：82、75、67、57、46、30、23、10、1、1、0。
如图10-17所示的Kaplan-Meier分析证明了不同对象/患者风险组也能够使用风险模型区分，其基于两个或三个PDE4D7相关基因的随机选择的组合。
讨论
根治性RT和SRT两者对局限性前列腺癌的疗效有限，导致疾病进展并最终导致患者死亡，尤其是对于那些复发风险高的患者。治疗结果的预测非常复杂，因为许多因素在治疗效果和疾病复发中发挥作用。很可能的是，尚未识别出重要因素，而无法准确确定其他因素的影响。目前正在研究多种临床病理学措施并将其应用于临床环境，以改善反应预测和治疗选择，从而提供一定程度的改善。尽管如此，仍然强烈需要更好地预测对根治性放疗和SRT的反应，以提高这些疗法的成功率。
我们已经识别了如下的分子，其表达与根治性RT和SRT后死亡率显著相关，因此有望提高对这些治疗有效性的预测。对每个患者的RT有效性的改进预测(无论是在根治性背景中还是在挽救性背景中)都将改进治疗选择和提高潜在生存率。这能够通过以下操作来实现：1)为那些预测RT有效的患者优化RT(例如通过剂量递增或不同的开始时间)，以及2)将预测RT无效的患者引导到可能更有效的处置形式的替代方案。另外，这将减少那些免于无效治疗的患者的痛苦并减少在无效治疗上花费的成本。
本领域技术人员通过研究附图、公开以及权利要求书，在实践请求保护的本发明时，可以理解和实现对所公开的实现方式的其他的变型。
在权利要求中，“包括”一词不排除其他元件或步骤，并且词语“一”或“一个”不排除多个。
图1中图示方法的一个或多个步骤可以在可以在计算机上运行的计算机程序产品中实现。计算机程序产品可以包括其上记录(存储)控制程序的非瞬态计算机可读记录介质，例如磁盘、硬盘驱动器等。非瞬态计算机可读介质的常见形式包括例如软盘、软盘、硬盘、磁带或任何其他磁性存储介质、CD-ROM、DVD或任何其他光学介质、RAM、PROM、EPROM、FLASH-EPROM或其他存储芯片或盒式磁带，或计算机可以从中读取和使用的任何其他非瞬态介质。
替代地，该方法的一个或多个步骤可以在瞬态介质中实现，例如可传输的载波，其中，控制程序被体现为使用传输介质的数据信号，例如声波或光波，例如在无线电波和红外数据通信等期间产生的那些。
该示例性方法可以被实现在或实现为一个或多个通用计算机、(一个或多个)专用计算机、经编程的微处理器或微控制器和外围集成电路元件、ASIC或其他集成电路、数字信号处理器、诸如离散元件电路的硬连线电子或逻辑电路、诸如PLD、PLA、FPGA、图形卡CPU(GPU)或PAL的可编程逻辑设备等。一般而言，图示了任何能够实现有限状态机的设备，该有限状态机继而能够实现图1中所示的流程图，能够用于实施用于前列腺癌的患者的治疗选择的风险分层的方法的一个或多个步骤。应当理解，虽然该方法的步骤可以全部由计算机实现，但在一些实施例中，一个或多个步骤可以至少部分地手动执行。
所述计算机程序指令还可以被加载到计算机、其他可编程数据处理装置或其他设备上以令一系列操作步骤在计算机、其他可编程装置或其他设备上执行以产生计算机实施的过程，使得在计算机或其他可编程装置上运行的指令提供用于实施本方中描述的功能/动作。
权利要求书中的任何附图标记都不应被解读为对范围的限制。
本发明涉及一种预测前列腺癌对象对放疗的反应的方法，所述方法包括：确定针对从包括以下各项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2；或接收对针对从包括以下各项的组中选择的一个或多个，例如，1个、2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱的确定的结果：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述(一个或多个)基因表达谱是在从所述对象获得的生物样本中确定的；基于针对一个或多个PDE4D7相关基因的(一个或多个)基因表达谱来确定对放疗反应的预测；并且任选地，将所述预测或基于所述预测的治疗推荐提供给医疗护理人员或所述对象。由于免疫系统和免疫微环境的状态对治疗有效性有影响，因此识别预测这种效应的标志物的能力可能有助于能够更好地预测整体RT反应。发现所识别的基因与RT后的结果呈现显著相关性，因此我们预期它们提供关于根治性RT和/或SRT的有效性的预测价值。
标题为2020PF00491_Sequence Listing_ST25的所附序列表通过引用整体并入本文。
序列表
<110> 皇家飞利浦有限公司
<120> 基于PDE4D7相关基因来预测前列腺癌对象对放疗的反应
<130> 2020PF00491
<160> 42
<170> PatentIn version 3.5
<210> 1
<211> 2009
<212> DNA
<213> 智人
<400> 1
gggaatgctt tgtgcagcgc gcttgcgcgg tgtggcggcc gatgccgcta taaaggcttg 60
ttttgctgca gggctcatgc tcgggagcgt ggttgagcgg ctggcgcggt tgtcctggag 120
caggggcgca ggaattctga tgtgaaacta acagtctgtg agccctggaa cctccactca 180
gagaagatga aggatatcga cataggaaaa gagtatatca tccccagtcc tgggtataga 240
agtgtgaggg agagaaccag cacttctggg acgcacagag accgtgaaga ttccaagttc 300
aggagaactc gaccgttgga atgccaagat gccttggaaa cagcagcccg agccgagggc 360
ctctctcttg atgcctccat gcattctcag ctcagaatcc tggatgagga gcatcccaag 420
ggaaagtacc atcatggctt gagtgctctg aagcccatcc ggactacttc caaacaccag 480
cacccagtgg acaatgctgg gcttttttcc tgtatgactt tttcgtggct ttcttctctg 540
gcccgtgtgg cccacaagaa gggggagctc tcaatggaag acgtgtggtc tctgtccaag 600
cacgagtctt ctgacgtgaa ctgcagaaga ctagagagac tgtggcaaga agagctgaat 660
gaagttgggc cagacgctgc ttccctgcga agggttgtgt ggatcttctg ccgcaccagg 720
ctcatcctgt ccatcgtgtg cctgatgatc acgcagctgg ctggcttcag tggaccaaat 780
tttcaggatg gctgtattct gcggtcagaa tgagagagtc aagctgggca gaatctctcg 840
ccaagagttc agccttcctt tggagactgc tccatcagtg ccgaggtgtg tgggaacagg 900
cttcactgca ccgccatctt actgagttgc ttcacgtgag gaaaaggggg ctttggccct 960
gtgactcagt tccacatttt ggattgcata ctggaaaaga agccaatctt cttgctagta 1020
aaccagcaac ccggctgtat acagtggtga cccaagcaat ggatataaac ctaaaaatct 1080
gagggagggg agaggtggaa tacagtagtt cttggaatct gaagtctcct atttgatcag 1140
gttatttcct gggacttggc aaaaatctga ttggtgggga tctcctagga cctagtggac 1200
atctggtatt aatttaatct caggaaaaac aagaaattaa cccagagaga gtctgggttt 1260
tggaattcag cgtagctacc tccagaccgt ggtgtctggc ctccattttt gtctgtcatt 1320
cagctctgac ttacagctgc agtcaccttt gctataaggc acctgggtag aagggtggat 1380
gggcttcaca tcaatttttt tcttccttta gggtggggga ttggtttggc tttcttttgt 1440
tgtggttttt tgttttattt ttgtcaagat tgatttttag atgcaaggac ttgaaaagac 1500
ccagaaggat gccaccagtt tttccttgag gcctaggatt ttttattctg tcccgagcag 1560
aggtaattcc tcacaactta gtgcaccagt agcaccagcc attttgagca gagtacctct 1620
ttggggagct tttcgttttg ttttgttttt aattctcttt ccttagcagc aaggtctttt 1680
ttcctagaga atctactccg ttgcagaatc attgcaacct caggagccct cactgattga 1740
gtgctgtcag cctgatatac tactttggac tctggaaaca gatatgggtt ctattctcta 1800
tttctactgt gtgtcgttaa acaaccgtcg gagaccagat gacctgttag atggctagtc 1860
ctgtataact cgactctgta tgtttcaatg tatgttactg caatgcttca cctgctgtac 1920
agtgtttgtg agatgctctt tgaagatggt acttttatat tttttcattt tcaataaaag 1980
tacattcctt cccacaaaaa aaaaaaaaa 2009
<210> 2
<211> 5872
<212> DNA
<213> Homo sapiens
<400> 2
gggaatgctt tgtgcagcgc gcttgcgcgg tgtggcggcc gatgccgcta taaaggcttg 60
ttttgctgca gggctcatgc tcgggagcgt ggttgagcgg ctggcgcggt tgtcctggag 120
caggggcgca ggaattctga tgtgaaacta acagtctgtg agccctggaa cctccactca 180
gagaagatga aggatatcga cataggaaaa gagtatatca tccccagtcc tgggtataga 240
agtgtgaggg agagaaccag cacttctggg acgcacagag accgtgaaga ttccaagttc 300
aggagaactc gaccgttgga atgccaagat gccttggaaa cagcagcccg agccgagggc 360
ctctctcttg atgcctccat gcattctcag ctcagaatcc tggatgagga gcatcccaag 420
ggaaagtacc atcatggctt gagtgctctg aagcccatcc ggactacttc caaacaccag 480
cacccagtgg acaatgctgg gcttttttcc tgtatgactt tttcgtggct ttcttctctg 540
gcccgtgtgg cccacaagaa gggggagctc tcaatggaag acgtgtggtc tctgtccaag 600
cacgagtctt ctgacgtgaa ctgcagaaga ctagagagac tgtggcaaga agagctgaat 660
gaagttgggc cagacgctgc ttccctgcga agggttgtgt ggatcttctg ccgcaccagg 720
ctcatcctgt ccatcgtgtg cctgatgatc acgcagctgg ctggcttcag tggaccagcc 780
ttcatggtga aacacctctt ggagtatacc caggcaacag agtctaacct gcagtacagc 840
ttgttgttag tgctgggcct cctcctgacg gaaatcgtgc ggtcttggtc gcttgcactg 900
acttgggcat tgaattaccg aaccggtgtc cgcttgcggg gggccatcct aaccatggca 960
tttaagaaga tccttaagtt aaagaacatt aaagagaaat ccctgggtga gctcatcaac 1020
atttgctcca acgatgggca gagaatgttt gaggcagcag ccgttggcag cctgctggct 1080
ggaggacccg ttgttgccat cttaggcatg atttataatg taattattct gggaccaaca 1140
ggcttcctgg gatcagctgt ttttatcctc ttttacccag caatgatgtt tgcatcacgg 1200
ctcacagcat atttcaggag aaaatgcgtg gccgccacgg atgaacgtgt ccagaagatg 1260
aatgaagttc ttacttacat taaatttatc aaaatgtatg cctgggtcaa agcattttct 1320
cagagtgttc aaaaaatccg cgaggaggag cgtcggatat tggaaaaagc tgggtacttc 1380
cagagcatca ctgtgggtgt ggctcccatt gtggtggtga ttgccagcgt ggtgaccttc 1440
tctgttcata tgaccctggg cttcgatctg acagcagcac aggctttcac agtggtgaca 1500
gtcttcaatt ccatgacttt tgctttgaaa gtaacaccgt tttcagtaaa gtccctctca 1560
gaagcctcag tggctgttga cagatttaag agtttgtttc taatggaaga ggttcacatg 1620
ataaagaaca aaccagccag tcctcacatc aagatagaga tgaaaaatgc caccttggca 1680
tgggactcct cccactccag tatccagaac tcgcccaagc tgacccccaa aatgaaaaaa 1740
gacaagaggg cttccagggg caagaaagag aaggtgaggc agctgcagcg cactgagcat 1800
caggcggtgc tggcagagca gaaaggccac ctcctcctgg acagtgacga gcggcccagt 1860
cccgaagagg aagaaggcaa gcacatccac ctgggccacc tgcgcttaca gaggacactg 1920
cacagcatcg atctggagat ccaagagggt aaactggttg gaatctgtgg cagtgtggga 1980
agtggaaaaa cctctctcat ttcagccatt ttaggccaga tgacgcttct agagggcagc 2040
attgcaatca gtggaacctt cgcttatgtg gcccagcagg cctggatcct caatgctact 2100
ctgagagaca acatcctgtt tgggaaggaa tatgatgaag aaagatacaa ctctgtgctg 2160
aacagctgct gcctgaggcc tgacctggcc attcttccca gcagcgacct gacggagatt 2220
ggagagcgag gagccaacct gagcggtggg cagcgccaga ggatcagcct tgcccgggcc 2280
ttgtatagtg acaggagcat ctacatcctg gacgaccccc tcagtgcctt agatgcccat 2340
gtgggcaacc acatcttcaa tagtgctatc cggaaacatc tcaagtccaa gacagttctg 2400
tttgttaccc accagttaca gtacctggtt gactgtgatg aagtgatctt catgaaagag 2460
ggctgtatta cggaaagagg cacccatgag gaactgatga atttaaatgg tgactatgct 2520
accattttta ataacctgtt gctgggagag acaccgccag ttgagatcaa ttcaaaaaag 2580
gaaaccagtg gttcacagaa gaagtcacaa gacaagggtc ctaaaacagg atcagtaaag 2640
aaggaaaaag cagtaaagcc agaggaaggg cagcttgtgc agctggaaga gaaagggcag 2700
ggttcagtgc cctggtcagt atatggtgtc tacatccagg ctgctggggg ccccttggca 2760
ttcctggtta ttatggccct tttcatgctg aatgtaggca gcaccgcctt cagcacctgg 2820
tggttgagtt actggatcaa gcaaggaagc gggaacacca ctgtgactcg agggaacgag 2880
acctcggtga gtgacagcat gaaggacaat cctcatatgc agtactatgc cagcatctac 2940
gccctctcca tggcagtcat gctgatcctg aaagccattc gaggagttgt ctttgtcaag 3000
ggcacgctgc gagcttcctc ccggctgcat gacgagcttt tccgaaggat ccttcgaagc 3060
cctatgaagt tttttgacac gacccccaca gggaggattc tcaacaggtt ttccaaagac 3120
atggatgaag ttgacgtgcg gctgccgttc caggccgaga tgttcatcca gaacgttatc 3180
ctggtgttct tctgtgtggg aatgatcgca ggagtcttcc cgtggttcct tgtggcagtg 3240
gggccccttg tcatcctctt ttcagtcctg cacattgtct ccagggtcct gattcgggag 3300
ctgaagcgtc tggacaatat cacgcagtca cctttcctct cccacatcac gtccagcata 3360
cagggccttg ccaccatcca cgcctacaat aaagggcagg agtttctgca cagataccag 3420
gagctgctgg atgacaacca agctcctttt tttttgttta cgtgtgcgat gcggtggctg 3480
gctgtgcggc tggacctcat cagcatcgcc ctcatcacca ccacggggct gatgatcgtt 3540
cttatgcacg ggcagattcc cccagcctat gcgggtctcg ccatctctta tgctgtccag 3600
ttaacggggc tgttccagtt tacggtcaga ctggcatctg agacagaagc tcgattcacc 3660
tcggtggaga ggatcaatca ctacattaag actctgtcct tggaagcacc tgccagaatt 3720
aagaacaagg ctccctcccc tgactggccc caggagggag aggtgacctt tgagaacgca 3780
gagatgaggt accgagaaaa cctccctctc gtcctaaaga aagtatcctt cacgatcaaa 3840
cctaaagaga agattggcat tgtggggcgg acaggatcag ggaagtcctc gctggggatg 3900
gccctcttcc gtctggtgga gttatctgga ggctgcatca agattgatgg agtgagaatc 3960
agtgatattg gccttgccga cctccgaagc aaactctcta tcattcctca agagccggtg 4020
ctgttcagtg gcactgtcag atcaaatttg gaccccttca accagtacac tgaagaccag 4080
atttgggatg ccctggagag gacacacatg aaagaatgta ttgctcagct acctctgaaa 4140
cttgaatctg aagtgatgga gaatggggat aacttctcag tgggggaacg gcagctcttg 4200
tgcatagcta gagccctgct ccgccactgt aagattctga ttttagatga agccacagct 4260
gccatggaca cagagacaga cttattgatt caagagacca tccgagaagc atttgcagac 4320
tgtaccatgc tgaccattgc ccatcgcctg cacacggttc taggctccga taggattatg 4380
gtgctggccc agggacaggt ggtggagttt gacaccccat cggtccttct gtccaacgac 4440
agttcccgat tctatgccat gtttgctgct gcagagaaca aggtcgctgt caagggctga 4500
ctcctccctg ttgacgaagt ctcttttctt tagagcattg ccattccctg cctggggcgg 4560
gcccctcatc gcgtcctcct accgaaacct tgcctttctc gattttatct ttcgcacagc 4620
agttccggat tggcttgtgt gtttcacttt tagggagagt catattttga ttattgtatt 4680
tattccatat tcatgtaaac aaaatttagt ttttgttctt aattgcactc taaaaggttc 4740
agggaaccgt tattataatt gtatcagagg cctataatga agctttatac gtgtagctat 4800
atctatatat aattctgtac atagcctata tttacagtga aaatgtaagc tgtttatttt 4860
atattaaaat aagcactgtg ctaataacag tgcatattcc tttctatcat ttttgtacag 4920
tttgctgtac tagagatctg gttttgctat tagactgtag gaagagtagc atttcattct 4980
tctctagctg gtggtttcac ggtgccaggt tttctgggtg tccaaaggaa gacgtgtggc 5040
aatagtgggc cctccgacag ccccctctgc cgcctcccca cggccgctcc aggggtggct 5100
ggagacgggt gggcggctgg agaccatgca gagcgccgtg agttctcagg gctcctgcct 5160
tctgtcctgg tgtcacttac tgtttctgtc aggagagcag cggggcgaag cccaggcccc 5220
ttttcactcc ctccatcaag aatggggatc acagagacat tcctccgagc cggggagttt 5280
ctttcctgcc ttcttctttt tgctgttgtt tctaaacaag aatcagtcta tccacagaga 5340
gtcccactgc ctcaggttcc tatggctggc cactgcacag agctctccag ctccaagacc 5400
tgttggttcc aagccctgga gccaactgct gctttttgag gtggcacttt ttcatttgcc 5460
tattcccaca cctccacagt tcagtggcag ggctcaggat ttcgtgggtc tgttttcctt 5520
tctcaccgca gtcgtcgcac agtctctctc tctctctccc ctcaaagtct gcaactttaa 5580
gcagctcttg ctaatcagtg tctcacactg gcgtagaagt ttttgtactg taaagagacc 5640
tacctcaggt tgctggttgc tgtgtggttt ggtgtgttcc cgcaaacccc ctttgtgctg 5700
tggggctggt agctcaggtg ggcgtggtca ctgctgtcat caattgaatg gtcagcgttg 5760
catgtcgtga ccaactagac attctgtcgc cttagcatgt ttgctgaaca ccttgtggaa 5820
gcaaaaatct gaaaatgtga ataaaattat tttggatttt gtaaaaaaaa aa 5872
<210> 3
<211> 208
<212> PRT
<213> Homo sapiens
<400> 3
Met Lys Asp Ile Asp Ile Gly Lys Glu Tyr Ile Ile Pro Ser Pro Gly
1 5 10 15
Tyr Arg Ser Val Arg Glu Arg Thr Ser Thr Ser Gly Thr His Arg Asp
20 25 30
Arg Glu Asp Ser Lys Phe Arg Arg Thr Arg Pro Leu Glu Cys Gln Asp
35 40 45
Ala Leu Glu Thr Ala Ala Arg Ala Glu Gly Leu Ser Leu Asp Ala Ser
50 55 60
Met His Ser Gln Leu Arg Ile Leu Asp Glu Glu His Pro Lys Gly Lys
65 70 75 80
Tyr His His Gly Leu Ser Ala Leu Lys Pro Ile Arg Thr Thr Ser Lys
85 90 95
His Gln His Pro Val Asp Asn Ala Gly Leu Phe Ser Cys Met Thr Phe
100 105 110
Ser Trp Leu Ser Ser Leu Ala Arg Val Ala His Lys Lys Gly Glu Leu
115 120 125
Ser Met Glu Asp Val Trp Ser Leu Ser Lys His Glu Ser Ser Asp Val
130 135 140
Asn Cys Arg Arg Leu Glu Arg Leu Trp Gln Glu Glu Leu Asn Glu Val
145 150 155 160
Gly Pro Asp Ala Ala Ser Leu Arg Arg Val Val Trp Ile Phe Cys Arg
165 170 175
Thr Arg Leu Ile Leu Ser Ile Val Cys Leu Met Ile Thr Gln Leu Ala
180 185 190
Gly Phe Ser Gly Pro Asn Phe Gln Asp Gly Cys Ile Leu Arg Ser Glu
195 200 205
<210> 4
<211> 1437
<212> PRT
<213> Homo sapiens
<400> 4
Met Lys Asp Ile Asp Ile Gly Lys Glu Tyr Ile Ile Pro Ser Pro Gly
1 5 10 15
Tyr Arg Ser Val Arg Glu Arg Thr Ser Thr Ser Gly Thr His Arg Asp
20 25 30
Arg Glu Asp Ser Lys Phe Arg Arg Thr Arg Pro Leu Glu Cys Gln Asp
35 40 45
Ala Leu Glu Thr Ala Ala Arg Ala Glu Gly Leu Ser Leu Asp Ala Ser
50 55 60
Met His Ser Gln Leu Arg Ile Leu Asp Glu Glu His Pro Lys Gly Lys
65 70 75 80
Tyr His His Gly Leu Ser Ala Leu Lys Pro Ile Arg Thr Thr Ser Lys
85 90 95
His Gln His Pro Val Asp Asn Ala Gly Leu Phe Ser Cys Met Thr Phe
100 105 110
Ser Trp Leu Ser Ser Leu Ala Arg Val Ala His Lys Lys Gly Glu Leu
115 120 125
Ser Met Glu Asp Val Trp Ser Leu Ser Lys His Glu Ser Ser Asp Val
130 135 140
Asn Cys Arg Arg Leu Glu Arg Leu Trp Gln Glu Glu Leu Asn Glu Val
145 150 155 160
Gly Pro Asp Ala Ala Ser Leu Arg Arg Val Val Trp Ile Phe Cys Arg
165 170 175
Thr Arg Leu Ile Leu Ser Ile Val Cys Leu Met Ile Thr Gln Leu Ala
180 185 190
Gly Phe Ser Gly Pro Ala Phe Met Val Lys His Leu Leu Glu Tyr Thr
195 200 205
Gln Ala Thr Glu Ser Asn Leu Gln Tyr Ser Leu Leu Leu Val Leu Gly
210 215 220
Leu Leu Leu Thr Glu Ile Val Arg Ser Trp Ser Leu Ala Leu Thr Trp
225 230 235 240
Ala Leu Asn Tyr Arg Thr Gly Val Arg Leu Arg Gly Ala Ile Leu Thr
245 250 255
Met Ala Phe Lys Lys Ile Leu Lys Leu Lys Asn Ile Lys Glu Lys Ser
260 265 270
Leu Gly Glu Leu Ile Asn Ile Cys Ser Asn Asp Gly Gln Arg Met Phe
275 280 285
Glu Ala Ala Ala Val Gly Ser Leu Leu Ala Gly Gly Pro Val Val Ala
290 295 300
Ile Leu Gly Met Ile Tyr Asn Val Ile Ile Leu Gly Pro Thr Gly Phe
305 310 315 320
Leu Gly Ser Ala Val Phe Ile Leu Phe Tyr Pro Ala Met Met Phe Ala
325 330 335
Ser Arg Leu Thr Ala Tyr Phe Arg Arg Lys Cys Val Ala Ala Thr Asp
340 345 350
Glu Arg Val Gln Lys Met Asn Glu Val Leu Thr Tyr Ile Lys Phe Ile
355 360 365
Lys Met Tyr Ala Trp Val Lys Ala Phe Ser Gln Ser Val Gln Lys Ile
370 375 380
Arg Glu Glu Glu Arg Arg Ile Leu Glu Lys Ala Gly Tyr Phe Gln Ser
385 390 395 400
Ile Thr Val Gly Val Ala Pro Ile Val Val Val Ile Ala Ser Val Val
405 410 415
Thr Phe Ser Val His Met Thr Leu Gly Phe Asp Leu Thr Ala Ala Gln
420 425 430
Ala Phe Thr Val Val Thr Val Phe Asn Ser Met Thr Phe Ala Leu Lys
435 440 445
Val Thr Pro Phe Ser Val Lys Ser Leu Ser Glu Ala Ser Val Ala Val
450 455 460
Asp Arg Phe Lys Ser Leu Phe Leu Met Glu Glu Val His Met Ile Lys
465 470 475 480
Asn Lys Pro Ala Ser Pro His Ile Lys Ile Glu Met Lys Asn Ala Thr
485 490 495
Leu Ala Trp Asp Ser Ser His Ser Ser Ile Gln Asn Ser Pro Lys Leu
500 505 510
Thr Pro Lys Met Lys Lys Asp Lys Arg Ala Ser Arg Gly Lys Lys Glu
515 520 525
Lys Val Arg Gln Leu Gln Arg Thr Glu His Gln Ala Val Leu Ala Glu
530 535 540
Gln Lys Gly His Leu Leu Leu Asp Ser Asp Glu Arg Pro Ser Pro Glu
545 550 555 560
Glu Glu Glu Gly Lys His Ile His Leu Gly His Leu Arg Leu Gln Arg
565 570 575
Thr Leu His Ser Ile Asp Leu Glu Ile Gln Glu Gly Lys Leu Val Gly
580 585 590
Ile Cys Gly Ser Val Gly Ser Gly Lys Thr Ser Leu Ile Ser Ala Ile
595 600 605
Leu Gly Gln Met Thr Leu Leu Glu Gly Ser Ile Ala Ile Ser Gly Thr
610 615 620
Phe Ala Tyr Val Ala Gln Gln Ala Trp Ile Leu Asn Ala Thr Leu Arg
625 630 635 640
Asp Asn Ile Leu Phe Gly Lys Glu Tyr Asp Glu Glu Arg Tyr Asn Ser
645 650 655
Val Leu Asn Ser Cys Cys Leu Arg Pro Asp Leu Ala Ile Leu Pro Ser
660 665 670
Ser Asp Leu Thr Glu Ile Gly Glu Arg Gly Ala Asn Leu Ser Gly Gly
675 680 685
Gln Arg Gln Arg Ile Ser Leu Ala Arg Ala Leu Tyr Ser Asp Arg Ser
690 695 700
Ile Tyr Ile Leu Asp Asp Pro Leu Ser Ala Leu Asp Ala His Val Gly
705 710 715 720
Asn His Ile Phe Asn Ser Ala Ile Arg Lys His Leu Lys Ser Lys Thr
725 730 735
Val Leu Phe Val Thr His Gln Leu Gln Tyr Leu Val Asp Cys Asp Glu
740 745 750
Val Ile Phe Met Lys Glu Gly Cys Ile Thr Glu Arg Gly Thr His Glu
755 760 765
Glu Leu Met Asn Leu Asn Gly Asp Tyr Ala Thr Ile Phe Asn Asn Leu
770 775 780
Leu Leu Gly Glu Thr Pro Pro Val Glu Ile Asn Ser Lys Lys Glu Thr
785 790 795 800
Ser Gly Ser Gln Lys Lys Ser Gln Asp Lys Gly Pro Lys Thr Gly Ser
805 810 815
Val Lys Lys Glu Lys Ala Val Lys Pro Glu Glu Gly Gln Leu Val Gln
820 825 830
Leu Glu Glu Lys Gly Gln Gly Ser Val Pro Trp Ser Val Tyr Gly Val
835 840 845
Tyr Ile Gln Ala Ala Gly Gly Pro Leu Ala Phe Leu Val Ile Met Ala
850 855 860
Leu Phe Met Leu Asn Val Gly Ser Thr Ala Phe Ser Thr Trp Trp Leu
865 870 875 880
Ser Tyr Trp Ile Lys Gln Gly Ser Gly Asn Thr Thr Val Thr Arg Gly
885 890 895
Asn Glu Thr Ser Val Ser Asp Ser Met Lys Asp Asn Pro His Met Gln
900 905 910
Tyr Tyr Ala Ser Ile Tyr Ala Leu Ser Met Ala Val Met Leu Ile Leu
915 920 925
Lys Ala Ile Arg Gly Val Val Phe Val Lys Gly Thr Leu Arg Ala Ser
930 935 940
Ser Arg Leu His Asp Glu Leu Phe Arg Arg Ile Leu Arg Ser Pro Met
945 950 955 960
Lys Phe Phe Asp Thr Thr Pro Thr Gly Arg Ile Leu Asn Arg Phe Ser
965 970 975
Lys Asp Met Asp Glu Val Asp Val Arg Leu Pro Phe Gln Ala Glu Met
980 985 990
Phe Ile Gln Asn Val Ile Leu Val Phe Phe Cys Val Gly Met Ile Ala
995 1000 1005
Gly Val Phe Pro Trp Phe Leu Val Ala Val Gly Pro Leu Val Ile
1010 1015 1020
Leu Phe Ser Val Leu His Ile Val Ser Arg Val Leu Ile Arg Glu
1025 1030 1035
Leu Lys Arg Leu Asp Asn Ile Thr Gln Ser Pro Phe Leu Ser His
1040 1045 1050
Ile Thr Ser Ser Ile Gln Gly Leu Ala Thr Ile His Ala Tyr Asn
1055 1060 1065
Lys Gly Gln Glu Phe Leu His Arg Tyr Gln Glu Leu Leu Asp Asp
1070 1075 1080
Asn Gln Ala Pro Phe Phe Leu Phe Thr Cys Ala Met Arg Trp Leu
1085 1090 1095
Ala Val Arg Leu Asp Leu Ile Ser Ile Ala Leu Ile Thr Thr Thr
1100 1105 1110
Gly Leu Met Ile Val Leu Met His Gly Gln Ile Pro Pro Ala Tyr
1115 1120 1125
Ala Gly Leu Ala Ile Ser Tyr Ala Val Gln Leu Thr Gly Leu Phe
1130 1135 1140
Gln Phe Thr Val Arg Leu Ala Ser Glu Thr Glu Ala Arg Phe Thr
1145 1150 1155
Ser Val Glu Arg Ile Asn His Tyr Ile Lys Thr Leu Ser Leu Glu
1160 1165 1170
Ala Pro Ala Arg Ile Lys Asn Lys Ala Pro Ser Pro Asp Trp Pro
1175 1180 1185
Gln Glu Gly Glu Val Thr Phe Glu Asn Ala Glu Met Arg Tyr Arg
1190 1195 1200
Glu Asn Leu Pro Leu Val Leu Lys Lys Val Ser Phe Thr Ile Lys
1205 1210 1215
Pro Lys Glu Lys Ile Gly Ile Val Gly Arg Thr Gly Ser Gly Lys
1220 1225 1230
Ser Ser Leu Gly Met Ala Leu Phe Arg Leu Val Glu Leu Ser Gly
1235 1240 1245
Gly Cys Ile Lys Ile Asp Gly Val Arg Ile Ser Asp Ile Gly Leu
1250 1255 1260
Ala Asp Leu Arg Ser Lys Leu Ser Ile Ile Pro Gln Glu Pro Val
1265 1270 1275
Leu Phe Ser Gly Thr Val Arg Ser Asn Leu Asp Pro Phe Asn Gln
1280 1285 1290
Tyr Thr Glu Asp Gln Ile Trp Asp Ala Leu Glu Arg Thr His Met
1295 1300 1305
Lys Glu Cys Ile Ala Gln Leu Pro Leu Lys Leu Glu Ser Glu Val
1310 1315 1320
Met Glu Asn Gly Asp Asn Phe Ser Val Gly Glu Arg Gln Leu Leu
1325 1330 1335
Cys Ile Ala Arg Ala Leu Leu Arg His Cys Lys Ile Leu Ile Leu
1340 1345 1350
Asp Glu Ala Thr Ala Ala Met Asp Thr Glu Thr Asp Leu Leu Ile
1355 1360 1365
Gln Glu Thr Ile Arg Glu Ala Phe Ala Asp Cys Thr Met Leu Thr
1370 1375 1380
Ile Ala His Arg Leu His Thr Val Leu Gly Ser Asp Arg Ile Met
1385 1390 1395
Val Leu Ala Gln Gly Gln Val Val Glu Phe Asp Thr Pro Ser Val
1400 1405 1410
Leu Leu Ser Asn Asp Ser Ser Arg Phe Tyr Ala Met Phe Ala Ala
1415 1420 1425
Ala Glu Asn Lys Val Ala Val Lys Gly
1430 1435
<210> 5
<211> 6855
<212> DNA
<213> Homo sapiens
<400> 5
ggccggaggg cgcccgaggg gccccgggcc gcggcgctca gggcccgggc ggccggcggc 60
ggccccgggg ctggggggag tccagcccgg atattgagtg cagccattga gaaaagccaa 120
actcttgtgt gtgcgcgtct cgatagcccc caagatggcc gccaatgtgg gatcgatgtt 180
tcaatattgg aagcgatttg atctacggcg actccagaag gagcttaatt ccgtcgcttc 240
tgagctgtct gcacggcagg aggagagtga acattctcat aaacatttaa ttgaactccg 300
ccgggaattt aagaaaaatg tacctgagga aatcagagag atggtggctc ctgtattaaa 360
aagcttccaa gccgaggtgg tggcccttag taagagaagt caggaggcgg aggctgcttt 420
tctgagtgtt tacaagcaat taattgaagc accagacccc gtgcctgtgt ttgaggcggc 480
acgcagccta gacgacagac tgcagccccc cagctttgac cccagtgggc agccccggcg 540
agacctccac acttcgtgga agaggaaccc cgagctcctc agccccaaag agcagagaga 600
ggggacgtcg cctgccgggc ccacgctgac cgagggaagc cgcctcccag gcattcccgg 660
gaaagccctc ctgacagaaa ccttgctgca gagaaatgag gcggaaaaac aaaagggcct 720
tcaagaagta cagatcactt tggcggccag actgggggag gcagaggaga aaatcaaagt 780
cctacattca gcgctaaagg ctacgcaggc agagctgcta gagctgcggc ggaagtacga 840
cgaggaggca gcatccaagg cagatgaagt cggcctgatc atgaccaacc tggagaaagc 900
taatcagcga gctgaggctg cccagcggga ggtggaaagt ctccgggaac agctggcctc 960
tgtcaacagc tccatccgcc tggcttgctg ctctccccag gggcccagtg gggataaggt 1020
gaacttcact ctgtgctcgg gccctcggct ggaggccgcg ctggcctcca aggacaggga 1080
gatcctgcgg ctgctgaagg acgtgcagca cctccagagc tcactgcagg agctggagga 1140
ggcatccgcc aaccagatcg ccgacctgga gcggcagctc acggccaagt ccgaggccat 1200
agaaaagctg gaagagaagc tccaggccca gtctgactat gaggaaatta aaacggagct 1260
gagcatcctg aaagccatga agctggcctc cagcacctgc agcctccccc agggcatggc 1320
caagcctgaa gactcactgc ttattgcaaa ggaggccttc ttccccacgc agaaattcct 1380
tctggagaag cccagcctcc tggccagccc tgaggaagac ccatcagagg acgattccat 1440
caaggattca ctgggcacgg agcagtccta cccctcccct cagcagctcc cacctccacc 1500
agggccagaa gaccccctgt ctcccagccc cgggcagccc ctgctgggcc ccagcttggg 1560
gcctgacggc actcggactt tctcgctgtc ccccttcccc agcctggcat caggggagag 1620
actgatgatg cccccagccg ccttcaaggg agaggcgggc ggcctgctgg tgttcccccc 1680
agccttctat ggcgccaagc cccccacagc ccctgccacc ccggcccctg gccctgagcc 1740
actgggcggt cctgagcccg cggatggtgg tgggggcgga gcggcggggc ccggggcaga 1800
ggaggagcag ctggacacgg cagagatcgc cttccaggtg aaggagcagc tgctgaaaca 1860
caacatcggg cagcgggtgt ttgggcatta cgtgctgggg ctgtcgcagg gctcggtcag 1920
cgagatccta gcccggccca agccctggcg caagctcacg gtgaagggca aggagccctt 1980
catcaagatg aagcagttcc tgtcggatga gcagaatgta ctggcgctca ggaccatcca 2040
agtgcggcag cgaggcagca tcaccccgag aatccgcacg cctgagacag gctcagacga 2100
cgccatcaag agcattctag agcaggccaa gaaggagatc gagtcgcaga agggcggcga 2160
gcccaagacc tcggtggccc cgctgagcat cgccaacggc acgacccccg ccagcacctc 2220
ggaggacgcc atcaagagca tcctggagca ggcacgccgt gagatgcagg cgcaacagca 2280
ggcgctgctg gagatggagg tggcgcccag gggccgctcg gtgcccccct cgcccccgga 2340
gcggccatca ctggccaccg cgagccagaa cggggccccg gccttggtga agcaggagga 2400
gggcagcggg ggccccgcgc aggcgccgct cccggtcctg tcccccgccg ccttcgtgca 2460
gagcatcatc cgcaaggtca agtccgagat cggcgacgcc ggctacttcg accaccactg 2520
ggcctccgac cgcggcctgc tcagccgccc ctacgcctcc gtgtcgccct cgctgtcctc 2580
ctcctcctcc tctggctact ctggccagcc caacggccgc gcctggcccc gcggggacga 2640
ggcccctgtg ccccccgagg acgaggcggc ggcaggggcg gaggacgaac cccccaggac 2700
gggcgagctc aaggctgagg gcgcgacggc cgaggcgggc gcgcggctgc cctactaccc 2760
ggcctacgtg ccgcgcaccc tgaagcccac cgtgccgccg ctgacccccg agcagtacga 2820
gctgtacatg taccgtgagg tagacacgct ggagctcacc cgccaggtca aggagaagct 2880
ggccaagaac ggcatctgcc agaggatctt cggggagaag gtgctgggcc tgtcacaggg 2940
cagcgtgagc gacatgctgt cccggccgaa gccatggagc aagctgacgc agaaggggcg 3000
ggagcccttc atccgcatgc agctgtggct ctctgaccag ctcggccagg cagtgggcca 3060
gcagcctggt gcctcccagg ccagtcccac agaaccaagg tcctcaccat ccccaccccc 3120
cagccccaca gagcctgaga agagctccca ggagccgttg agcctgtccc tggagagcag 3180
caaggagaac cagcagccag agggccgctc cagctcctcg ttgagcggga agatgtactc 3240
aggcagccag gccccagggg gcatccagga gatcgtggcc atgtcccccg agctggacac 3300
gtactccatc accaagaggg tgaaggaggt cctcacagac aacaatctag ggcagcggct 3360
gtttggggaa agcatcctgg gtctgacaca gggctccgtg tctgacctgc tgtcccggcc 3420
caaaccctgg cacaagctga gcctgaaggg gcgggagcct tttgtccgca tgcagctgtg 3480
gctcaatgac ccccataacg tggagaagct gagggatatg aagaagctgg agaagaaagc 3540
ctacctgaaa cgtcgctatg gcctcatcag caccggctca gacagtgagt ccccggccac 3600
ccgctcagag tgccccagcc cctgcctgca gccccaggac ctgagcctcc tgcagatcaa 3660
gaagccccgg gtggtgctgg cacccgagga gaaggaggca ctgcggaagg cctatcagct 3720
ggaaccctac ccctcgcagc agaccatcga gctcctctcc ttccagctca acctcaagac 3780
caacaccgtc atcaactggt tccacaacta caggtcccgg atgcgccggg agatgttggt 3840
ggaggggacc caggatgagc cagaccttga tccaagcggg ggtcctggaa tcctaccgcc 3900
aggccactcc cacccagacc ccaccccgca gagccctgac tctgagactg aggaccagaa 3960
gccaaccgtg aaggaactgg agcttcagga gggccctgag gagaacagca cacccctgac 4020
cacccaggac aaggcccaag tgaggatcaa gcaggaacag atggaggagg atgctgagga 4080
agaggcaggc agccagcccc aggactcagg ggagctggac aaaggccaag gtccccccaa 4140
agaggagcat cccgaccctc cgggtaatga tggactccca aaagtggctc ccgggcccct 4200
ccttccaggt ggatccaccc cagactgtcc ctcacttcat ccccaacagg agagtgaggc 4260
cggggagcga cttcacccgg accctttaag ttttaagtca gcctcagagt cctcacgctg 4320
cagcctggag gtgtcactga actcgccctc ggccgcctcc tcaccaggcc tcatgatgtc 4380
tgtgtcacct gtcccctcct cctcagctcc catctcccca tccccacctg gcgccccccc 4440
tgccaaagtg ccgagtgcca gccccactgc tgacatggct ggagccttgc accccagtgc 4500
caaggtgaac cccaacttgc agcggcggca tgagaagatg gccaatctga acaacatcat 4560
ttaccgagta gagcgggctg ccaatcggga ggaggccctg gagtgggagt tctgaaggca 4620
gggtgagggg gcaagggaca taccctggta actaccttcc ttctcgcact tactctcctc 4680
aacaggatgg ggtaagggag ggaggaactc aaccatcaaa atgtggacag caatgttatg 4740
ccgtttacgt tttttgttgt aatcctagtt ctatgaagct gtgtgagcag gtgggtcaaa 4800
tgccattgcc tccacttttc tgcacccccc tgctcctctt caccctgacc cctctgcagg 4860
aggcagaagc aaaatggcac cacatattca cctgaaaact ccaaactctt ttagaaaaat 4920
aaataaatat ttatagacct cttttagata ttttaataaa ggatcctttg gaatttatcc 4980
cagctgatgc tgttttgata ttacagagag ttataaaatc aggatgctgt cacaactgtt 5040
gcgaagtata cactgaagtt gtgtcgtttt tgccactaga tgagattaaa agaagacaat 5100
tattcaaagc catcacaaaa cactataaga ctgaccaaaa tttagataac ctttgaacca 5160
cgattttttt ccacatctgt ctgtgagaca cagcgcaatg ctactgccct tccagaaact 5220
gtgctaaaaa gagaaagtcc aaaagactct aaacaaaaac ctcgacgccg ttgaggatgt 5280
gtttcattct ggtggtctgt tttgcaagct tgataacaga atgtccgtgc cattgtaaat 5340
gttgtagaga tgtgggccgt ggcccaaccg tcctatatga gatgtagcat ggtacagaac 5400
aaactgctta cacaggtctc actagttaga aacctgtggg ccatggaggt cagacatcca 5460
tcttgtccat ctataggcaa gaagtgtttc cagatccttt ggaaaggtgg gcatggggca 5520
ggtgcttgga gagtggcgtt tgagccagag cgaccccatt tcccgtgtga accataggca 5580
caacccagga agtttcccca cttgtaggag tgtgggtatt ccagagcaag actgtggcca 5640
ccatcttccc ctcttggtgt tttccgaaag tgacagtgtt ggtcatccca tgaccactga 5700
agcttagtaa ccagcgccaa aaagtagatt catcaaacta gagaccccag ctccccttct 5760
cgccatcttc tttctcaagt tgaccgtggt gctgtttctg gaaggcatct gcaactccaa 5820
gtccatgcag aactctggaa ggccaagttc atcgcagcat gttcaccata tcccagcctc 5880
caaatctatc ctcctacctt ccaacgcatg acctgttggg gagcagagac ttaaccccca 5940
actcagagga acccttcctc cagcgtcttt ggcatggttt ctagggtgag agttcccaat 6000
ttggatagaa cggccaccat attggttact gaatctctct cccttgtttt tattacgttt 6060
cctttttcaa actgtccatg ggaaggctga attgagtgac tccccagaat gaagatgaga 6120
aggtgaatat aatcaatgcc aatgtaatgc cagcgggtga gatggccgat ggaggtttca 6180
aagatgtagc tagcattttg aaaccatatg ggcaaaaccc ggcaaccaga aggggacaga 6240
taaggaccgt tccagaaatc ccaactctca cacccagccc aggctgcagt ctccacacca 6300
aacagtcaac aaaacacaaa ccctgaagga aaaccttttc catacaccca ggctatgcat 6360
tgaagagttt tccactgtat acatttttat ccagatgaag gtatttttat attttgacaa 6420
taggaaacag tgaccatttt cagagtaatc aaatctggaa caaatgaaac atcttttagc 6480
caccaccacc ctgttgcaat taagacaacc gtgggggaac acaccacttt ttactgttga 6540
aaccaacaca acgttgaaat ccaggcttat acgcagactc cgattcctag agaactaaat 6600
ttggctttag tgtgacggga tttgattaag cacttagtat agtcttttga acacggaaat 6660
cctgttgtac ttaaagctag cggacccgtg aacaactttg tcaggttcac gtcctataac 6720
ggttaaaaaa cacacacaca catacacaaa ccgtttctat gagagattga tgaactttgt 6780
ttaaaatttt aaaaaaagga acacgttctg taaacgagtc gctaaataca gaattgtata 6840
ataaaaaaaa aaaaa 6855
<210> 6
<211> 1486
<212> PRT
<213> Homo sapiens
<400> 6
Met Ala Ala Asn Val Gly Ser Met Phe Gln Tyr Trp Lys Arg Phe Asp
1 5 10 15
Leu Arg Arg Leu Gln Lys Glu Leu Asn Ser Val Ala Ser Glu Leu Ser
20 25 30
Ala Arg Gln Glu Glu Ser Glu His Ser His Lys His Leu Ile Glu Leu
35 40 45
Arg Arg Glu Phe Lys Lys Asn Val Pro Glu Glu Ile Arg Glu Met Val
50 55 60
Ala Pro Val Leu Lys Ser Phe Gln Ala Glu Val Val Ala Leu Ser Lys
65 70 75 80
Arg Ser Gln Glu Ala Glu Ala Ala Phe Leu Ser Val Tyr Lys Gln Leu
85 90 95
Ile Glu Ala Pro Asp Pro Val Pro Val Phe Glu Ala Ala Arg Ser Leu
100 105 110
Asp Asp Arg Leu Gln Pro Pro Ser Phe Asp Pro Ser Gly Gln Pro Arg
115 120 125
Arg Asp Leu His Thr Ser Trp Lys Arg Asn Pro Glu Leu Leu Ser Pro
130 135 140
Lys Glu Gln Arg Glu Gly Thr Ser Pro Ala Gly Pro Thr Leu Thr Glu
145 150 155 160
Gly Ser Arg Leu Pro Gly Ile Pro Gly Lys Ala Leu Leu Thr Glu Thr
165 170 175
Leu Leu Gln Arg Asn Glu Ala Glu Lys Gln Lys Gly Leu Gln Glu Val
180 185 190
Gln Ile Thr Leu Ala Ala Arg Leu Gly Glu Ala Glu Glu Lys Ile Lys
195 200 205
Val Leu His Ser Ala Leu Lys Ala Thr Gln Ala Glu Leu Leu Glu Leu
210 215 220
Arg Arg Lys Tyr Asp Glu Glu Ala Ala Ser Lys Ala Asp Glu Val Gly
225 230 235 240
Leu Ile Met Thr Asn Leu Glu Lys Ala Asn Gln Arg Ala Glu Ala Ala
245 250 255
Gln Arg Glu Val Glu Ser Leu Arg Glu Gln Leu Ala Ser Val Asn Ser
260 265 270
Ser Ile Arg Leu Ala Cys Cys Ser Pro Gln Gly Pro Ser Gly Asp Lys
275 280 285
Val Asn Phe Thr Leu Cys Ser Gly Pro Arg Leu Glu Ala Ala Leu Ala
290 295 300
Ser Lys Asp Arg Glu Ile Leu Arg Leu Leu Lys Asp Val Gln His Leu
305 310 315 320
Gln Ser Ser Leu Gln Glu Leu Glu Glu Ala Ser Ala Asn Gln Ile Ala
325 330 335
Asp Leu Glu Arg Gln Leu Thr Ala Lys Ser Glu Ala Ile Glu Lys Leu
340 345 350
Glu Glu Lys Leu Gln Ala Gln Ser Asp Tyr Glu Glu Ile Lys Thr Glu
355 360 365
Leu Ser Ile Leu Lys Ala Met Lys Leu Ala Ser Ser Thr Cys Ser Leu
370 375 380
Pro Gln Gly Met Ala Lys Pro Glu Asp Ser Leu Leu Ile Ala Lys Glu
385 390 395 400
Ala Phe Phe Pro Thr Gln Lys Phe Leu Leu Glu Lys Pro Ser Leu Leu
405 410 415
Ala Ser Pro Glu Glu Asp Pro Ser Glu Asp Asp Ser Ile Lys Asp Ser
420 425 430
Leu Gly Thr Glu Gln Ser Tyr Pro Ser Pro Gln Gln Leu Pro Pro Pro
435 440 445
Pro Gly Pro Glu Asp Pro Leu Ser Pro Ser Pro Gly Gln Pro Leu Leu
450 455 460
Gly Pro Ser Leu Gly Pro Asp Gly Thr Arg Thr Phe Ser Leu Ser Pro
465 470 475 480
Phe Pro Ser Leu Ala Ser Gly Glu Arg Leu Met Met Pro Pro Ala Ala
485 490 495
Phe Lys Gly Glu Ala Gly Gly Leu Leu Val Phe Pro Pro Ala Phe Tyr
500 505 510
Gly Ala Lys Pro Pro Thr Ala Pro Ala Thr Pro Ala Pro Gly Pro Glu
515 520 525
Pro Leu Gly Gly Pro Glu Pro Ala Asp Gly Gly Gly Gly Gly Ala Ala
530 535 540
Gly Pro Gly Ala Glu Glu Glu Gln Leu Asp Thr Ala Glu Ile Ala Phe
545 550 555 560
Gln Val Lys Glu Gln Leu Leu Lys His Asn Ile Gly Gln Arg Val Phe
565 570 575
Gly His Tyr Val Leu Gly Leu Ser Gln Gly Ser Val Ser Glu Ile Leu
580 585 590
Ala Arg Pro Lys Pro Trp Arg Lys Leu Thr Val Lys Gly Lys Glu Pro
595 600 605
Phe Ile Lys Met Lys Gln Phe Leu Ser Asp Glu Gln Asn Val Leu Ala
610 615 620
Leu Arg Thr Ile Gln Val Arg Gln Arg Gly Ser Ile Thr Pro Arg Ile
625 630 635 640
Arg Thr Pro Glu Thr Gly Ser Asp Asp Ala Ile Lys Ser Ile Leu Glu
645 650 655
Gln Ala Lys Lys Glu Ile Glu Ser Gln Lys Gly Gly Glu Pro Lys Thr
660 665 670
Ser Val Ala Pro Leu Ser Ile Ala Asn Gly Thr Thr Pro Ala Ser Thr
675 680 685
Ser Glu Asp Ala Ile Lys Ser Ile Leu Glu Gln Ala Arg Arg Glu Met
690 695 700
Gln Ala Gln Gln Gln Ala Leu Leu Glu Met Glu Val Ala Pro Arg Gly
705 710 715 720
Arg Ser Val Pro Pro Ser Pro Pro Glu Arg Pro Ser Leu Ala Thr Ala
725 730 735
Ser Gln Asn Gly Ala Pro Ala Leu Val Lys Gln Glu Glu Gly Ser Gly
740 745 750
Gly Pro Ala Gln Ala Pro Leu Pro Val Leu Ser Pro Ala Ala Phe Val
755 760 765
Gln Ser Ile Ile Arg Lys Val Lys Ser Glu Ile Gly Asp Ala Gly Tyr
770 775 780
Phe Asp His His Trp Ala Ser Asp Arg Gly Leu Leu Ser Arg Pro Tyr
785 790 795 800
Ala Ser Val Ser Pro Ser Leu Ser Ser Ser Ser Ser Ser Gly Tyr Ser
805 810 815
Gly Gln Pro Asn Gly Arg Ala Trp Pro Arg Gly Asp Glu Ala Pro Val
820 825 830
Pro Pro Glu Asp Glu Ala Ala Ala Gly Ala Glu Asp Glu Pro Pro Arg
835 840 845
Thr Gly Glu Leu Lys Ala Glu Gly Ala Thr Ala Glu Ala Gly Ala Arg
850 855 860
Leu Pro Tyr Tyr Pro Ala Tyr Val Pro Arg Thr Leu Lys Pro Thr Val
865 870 875 880
Pro Pro Leu Thr Pro Glu Gln Tyr Glu Leu Tyr Met Tyr Arg Glu Val
885 890 895
Asp Thr Leu Glu Leu Thr Arg Gln Val Lys Glu Lys Leu Ala Lys Asn
900 905 910
Gly Ile Cys Gln Arg Ile Phe Gly Glu Lys Val Leu Gly Leu Ser Gln
915 920 925
Gly Ser Val Ser Asp Met Leu Ser Arg Pro Lys Pro Trp Ser Lys Leu
930 935 940
Thr Gln Lys Gly Arg Glu Pro Phe Ile Arg Met Gln Leu Trp Leu Ser
945 950 955 960
Asp Gln Leu Gly Gln Ala Val Gly Gln Gln Pro Gly Ala Ser Gln Ala
965 970 975
Ser Pro Thr Glu Pro Arg Ser Ser Pro Ser Pro Pro Pro Ser Pro Thr
980 985 990
Glu Pro Glu Lys Ser Ser Gln Glu Pro Leu Ser Leu Ser Leu Glu Ser
995 1000 1005
Ser Lys Glu Asn Gln Gln Pro Glu Gly Arg Ser Ser Ser Ser Leu
1010 1015 1020
Ser Gly Lys Met Tyr Ser Gly Ser Gln Ala Pro Gly Gly Ile Gln
1025 1030 1035
Glu Ile Val Ala Met Ser Pro Glu Leu Asp Thr Tyr Ser Ile Thr
1040 1045 1050
Lys Arg Val Lys Glu Val Leu Thr Asp Asn Asn Leu Gly Gln Arg
1055 1060 1065
Leu Phe Gly Glu Ser Ile Leu Gly Leu Thr Gln Gly Ser Val Ser
1070 1075 1080
Asp Leu Leu Ser Arg Pro Lys Pro Trp His Lys Leu Ser Leu Lys
1085 1090 1095
Gly Arg Glu Pro Phe Val Arg Met Gln Leu Trp Leu Asn Asp Pro
1100 1105 1110
His Asn Val Glu Lys Leu Arg Asp Met Lys Lys Leu Glu Lys Lys
1115 1120 1125
Ala Tyr Leu Lys Arg Arg Tyr Gly Leu Ile Ser Thr Gly Ser Asp
1130 1135 1140
Ser Glu Ser Pro Ala Thr Arg Ser Glu Cys Pro Ser Pro Cys Leu
1145 1150 1155
Gln Pro Gln Asp Leu Ser Leu Leu Gln Ile Lys Lys Pro Arg Val
1160 1165 1170
Val Leu Ala Pro Glu Glu Lys Glu Ala Leu Arg Lys Ala Tyr Gln
1175 1180 1185
Leu Glu Pro Tyr Pro Ser Gln Gln Thr Ile Glu Leu Leu Ser Phe
1190 1195 1200
Gln Leu Asn Leu Lys Thr Asn Thr Val Ile Asn Trp Phe His Asn
1205 1210 1215
Tyr Arg Ser Arg Met Arg Arg Glu Met Leu Val Glu Gly Thr Gln
1220 1225 1230
Asp Glu Pro Asp Leu Asp Pro Ser Gly Gly Pro Gly Ile Leu Pro
1235 1240 1245
Pro Gly His Ser His Pro Asp Pro Thr Pro Gln Ser Pro Asp Ser
1250 1255 1260
Glu Thr Glu Asp Gln Lys Pro Thr Val Lys Glu Leu Glu Leu Gln
1265 1270 1275
Glu Gly Pro Glu Glu Asn Ser Thr Pro Leu Thr Thr Gln Asp Lys
1280 1285 1290
Ala Gln Val Arg Ile Lys Gln Glu Gln Met Glu Glu Asp Ala Glu
1295 1300 1305
Glu Glu Ala Gly Ser Gln Pro Gln Asp Ser Gly Glu Leu Asp Lys
1310 1315 1320
Gly Gln Gly Pro Pro Lys Glu Glu His Pro Asp Pro Pro Gly Asn
1325 1330 1335
Asp Gly Leu Pro Lys Val Ala Pro Gly Pro Leu Leu Pro Gly Gly
1340 1345 1350
Ser Thr Pro Asp Cys Pro Ser Leu His Pro Gln Gln Glu Ser Glu
1355 1360 1365
Ala Gly Glu Arg Leu His Pro Asp Pro Leu Ser Phe Lys Ser Ala
1370 1375 1380
Ser Glu Ser Ser Arg Cys Ser Leu Glu Val Ser Leu Asn Ser Pro
1385 1390 1395
Ser Ala Ala Ser Ser Pro Gly Leu Met Met Ser Val Ser Pro Val
1400 1405 1410
Pro Ser Ser Ser Ala Pro Ile Ser Pro Ser Pro Pro Gly Ala Pro
1415 1420 1425
Pro Ala Lys Val Pro Ser Ala Ser Pro Thr Ala Asp Met Ala Gly
1430 1435 1440
Ala Leu His Pro Ser Ala Lys Val Asn Pro Asn Leu Gln Arg Arg
1445 1450 1455
His Glu Lys Met Ala Asn Leu Asn Asn Ile Ile Tyr Arg Val Glu
1460 1465 1470
Arg Ala Ala Asn Arg Glu Glu Ala Leu Glu Trp Glu Phe
1475 1480 1485
<210> 7
<211> 12379
<212> DNA
<213> Homo sapiens
<400> 7
gacccgagag ccgctgagcc gcgaggccgg gccggggcgc cggccgggaa tgccgggggc 60
gcggcgccga cgccgaggcg cggccatgga ggggaagccc cgcgccgggg tcgcgctggc 120
cccggggccg agcggccgac ggccttccgc ccgctgcgcc cgccgccgcc gcccggggct 180
gctgcttcct ggcctctggc tgctgctgct ggcccggccg gcctcgtgcg ccccagatga 240
gctctctccg gaacagcaca acctttcttt atactccatg gagctcgtgc tgaagaaaag 300
cactgggcac agcgctgcac aagtggcctt aacagaaact gctcccggct cccagcacag 360
cagtcctctc catgtcacag ccccgccgtc tgccactact tttgatacag ccttttttaa 420
ccaaggaaaa cagaccaaaa gtacagcaga tcccagcatc tttgtggcaa cttacgtgtc 480
agtgacgagt aaagaggtgg ccgtcaatga cgatgagatg gataactttc tgccagatac 540
tcactggacc actccacgga tggtttctcc aatacagtat atcacagtca gcccaccagg 600
gctgcccagg gaagcattag aacctatgct cactccatca ttacccatgg tttctttaca 660
agatgaagaa gtgacatcgg gctggcagaa cacaacgcga caaccagcgg catatgctga 720
gtccgccagt catttccaca cctttcggtc agcttttcgc acctctgagg gcatcgttcc 780
aactcctggc aggaatttgg tgctttatcc tactgatgct tacagtcatt tatcaagcag 840
gactctgcca gagattgtgg cttccctaac agagggtgtg gaaaccaccc tttttttaag 900
ctcccggtct ttaatgccac agccgttagg cgacggcatt actataccgt tgccctcctt 960
gggggaggtc tcacagcctc cagaggaggt ttgggccaca agtgcagaca gatacactga 1020
tgtgaccact gtgttgagtc aaagcctaga agaaaccatc tctccaagaa cataccccac 1080
tgtgactgca tcgcacgcag cccttgcatt cagcaggaca cattctccat tgctttcaac 1140
tcctcttgca tttgcgtcct ctgcttcacc aactgatgtt tcatctaacc cctttctccc 1200
tagcgactcc agcaaaacat ccgaattgca tagcaattca gccctccccg gtcctgtgga 1260
caacactcat atcctgagcc cggtgtcctc attcagacca tacacttggt gtgcggcctg 1320
cactgtgcct tcacctcagc aagttctggc cacgagcctc atggagaaag acgtgggatc 1380
aggggatggt gccgagactc tgtgcatgac cgtgctggaa gaaagcagca tctctctaat 1440
gagtagcgtc gtagcagact tctctgaatt tgaggaagat cctcaagtat ttaatacgct 1500
tttcccctcc agacctatcg tcccactttc ttctagatcc atggaaatct cagagacgag 1560
tgttggcatt tctgccgagg tggatatgag tagtgttaca accacacagg ttccccctgc 1620
ccacggccgc ctctctgtgc cggcgtcact tgatcctact gctggctcct tgtctgttgc 1680
tgaaacccaa gtgacgccat ccagcgtgac cactgcattt ttctcggtca tcaccagcat 1740
tctccttgac tcatctttct ctgtcatagc aaacaaaaac acaccgtcgc ttgccgtcag 1800
agacccgagt gtttttacgc cttatagtct ggttccttca gtggagtctt cacttttctc 1860
tgaccaagaa cgttccagtt tttctgagca taaacccaga ggtgctttgg attttgcatc 1920
cagctttttc tcaacacccc cgctggaact cagcggctcc atctcttcgc cttcggaagc 1980
acctgcgtct ctgtctctga tgccgagtga cttgtccccc ttcacatctc agtctttttc 2040
tcccttggtt gagacattta cattgtttga ctctagtgat ctgcagtcat ctcagctgtc 2100
tcttcccagt tccacaaatc ttgagttttc gcagctccag ccaagttccg agctgccttt 2160
aaacaccatc atgttgctac ctagccgttc tgaggtgtca ccatggtcaa gcttcccttc 2220
tgattctctc gagtttgttg aagcgtctac ggtttcactg acggattcag aagctcattt 2280
tacctcagct ttcattgaaa ctacctccta tcttgagtct tcactcattt cccatgaatc 2340
cgcagtcact gcactggtgc cccccggctc tgagtctttt gacattttga ctgccgggat 2400
tcaagcaaca tcaccattga ccactgtcca cacaacgccc attttaactg agtcttcttt 2460
gttctcaact ctgacacctc ctgacgacca aatcagtgct ctagacggtc acgtgtctgt 2520
cctggcctct ttctccaaag ccattcccac tggtacggtg ttgatcactg acgcgtacct 2580
gccatcagga tcctcgtttg tttctgaagc aacccccttc cctctgccca cagagctgac 2640
cgtcgtgggc ccatcactca cacccacaga ggtgccactg aacacctcca cggaagtgag 2700
cacaaccagc accggtgctg ccactggtgg tcccctcgac tccaccctga tgggtgacgc 2760
cgcaagtcag agccccccag agagtagtgc tgctcctccc ctgccatccc tgcgtcccgt 2820
gactgccttc actctcgaag caacagtcga cacaccaaca ctggctactg ccaagccgcc 2880
atatgtttgt gatatcacag tccccgatgc ctatctgatc acaactgtgc tggccagaag 2940
agctgtgcag gagtacatca ttacagcaat caaagaagta ctgaggattc acttcaaccg 3000
tgcagtggaa ctgaaggttt acgaactatt tactgacttc acttttctgg taacatccgg 3060
tcctttcgtt tacacggcaa tatccgtcat aaatgtgctt ataaacagta agcttgtccg 3120
tgaccagact cctttaatcc tgtctgtgaa accttctttc cttgtgccag agtccaggtt 3180
ccaagttcaa acagtacttc agtttgtgcc tccgagtgtg gatactggct tctgcaactt 3240
cacccagcgc attgagaaag gcctaatgac agctctcttt gaagtgagaa aacaccacca 3300
gggaacgtat aacctcacgg tgcagatctt gaatatcacc atcagttcct caagggtgac 3360
tcctcggcgg ggcccggtga atatcatctt tgcggttaaa agcacacagg gatttttgaa 3420
tgggtcggaa gtgagcgagc tgctcagaaa cttgagtgtg gtggagttca gtttctatct 3480
gggataccca gtgctgcaga tcgcagagcc cttccagtat ccacagctca acttatctca 3540
gttgctgaag tcctcttggg tcagaacagt tctcctgggc gtcatggaga agcaactcca 3600
gaatgaagtg tttcaagccg agatggaacg caagctggcc cagctgctca gcgaggtttc 3660
caccagaagg cggatgtgga gaagggccac tgtagctgca gggaacagtg tggtgcaggt 3720
ggtaaatgtg tcgaggctgg agggagatga caatccggta cagctcatct actttgtgga 3780
ggatcaagat ggagaaagac tcagtgcagt caagtcttcg gacctgatta acaaaatgga 3840
cctccagaga gcagccatca tcttgggtta ccgaattcaa ggtgtcattg cccagcctgt 3900
cgacagggtg aagaggccgt ctccggaatc ccagagcaac aacttgtggg tcattgttgg 3960
cgtggtcatc ccagtgctgg tggtgatggt gattgttgtc atcctctact ggaaactatg 4020
ccgcacagac aagctagact ttcagcctga cactgtggcc aacattcagc agcgtcagaa 4080
gctgcagatc cctagtgtga agggcttcga ttttgctaag cagcatctgg gtcagcacaa 4140
taaagacgac atattgatta ttcatgagcc agcgccactg ccaggacctc tgaaggacca 4200
caccacgccc tcggaaaatg gagacgtgcc aagccccaag tcaaagatcc cttccaagaa 4260
tgttcgtcac agaggaagag tttctccctc agatgctgac tctacggtca gtgaagagtc 4320
cagcgagagg gacgcaggag ataagacgcc gggagccgtc aacgatggca ggtcccacag 4380
agctccgcag agcgggccac cactgcccag ttcgggaaat gagcagcact catcagcctc 4440
catcttcgag cacgtggaca ggatctcccg ccccccggag gctagccggc gggtccccag 4500
taagatccag cttatcgcca tgcagccgat cccggcacct cccgtccagc gcccctcccc 4560
agccgaccga gtggcggaaa gcaataaaat caacaaagag attcagaccg cgctgcggca 4620
caagtctgag atcgagcacc atcgcaacaa gatccgcctg cgcgccaagc gccgcgggca 4680
ctacgagttc ccggtggtag acgacctgtc ctcgggcgac actaaggagc gacaccgggt 4740
gtaccgcagg gcacagatgc agatcgacaa gatcctggac cccacggcca gcgtgccctc 4800
cgtgttcata gagcccagga agagctcacg gataaaacgt tctcccaagc ctcgccggaa 4860
acaccaggtc aacggctgtc ctgccgacgc tgagaaggac cggctcatca ccacagacag 4920
cgatggcacc tacaggaggc cccccggcgt ccacaactca gcctacatcg gatgcccatc 4980
ggatcctgac ctcccagccg atgtgcagac accatcctcg gtggaactgg ggaggtatcc 5040
agcccttccc ttcccggcct cccagtacat cccaccccag ccgtccatcg aggaggcacg 5100
ccagaccatg cactccctcc tggacgacgc ctttgccctc gtggccccca gcagccagcc 5160
tgccagcacc gcaggtgtag gccccggagt cccacccggc ctgcccgcaa acagcacccc 5220
ttcccaggaa gagaggcgag ccacccagtg ggggtccttc tacagcccag cccagacggc 5280
caacaatccc tgcagtagat acgaagacta tggaatgact cccccgacgg gtccattgcc 5340
aagaccaggt tttggccccg gtttgctgca gtctacagag ctggtgcccc ctgaccctca 5400
gcagccacag gcctccgccg aagccccatt tgctgccaga gggatctact cggaggagat 5460
gccgtcggtg gcccggcctc ggcctgtcgg gggtaccaca ggctcccaga tccagcacct 5520
gacacaggtg gggattgcca gcagaattgg agctcagcca gtggaaatcc cgccaagcag 5580
aggcagccag tatggggggc caggctggcc ttcgtacggg gaggacgaag cggggcgaag 5640
agaggccgtg ccaaggactt caggcaggga gccctcagct ccttccggga acctccccca 5700
ccggggactg cagggccctg ggctgggtta ccccaccagc tccacggaag acctccagcc 5760
tggccactcc tcggcctctc tcatcaaagc aatccgcgag gagctcctcc ggctctccca 5820
gaaacagagc accgtgcaga acttccacag ctgatcggcc tcgcctcgca gatttgccaa 5880
gtatccgctt cctgtggaag caagaccaaa aggaaatcaa ctgagtgggt gtttggaaga 5940
ggaaggagca actctcgggc agcctgccca agggagggag caagttgcaa tttagaagat 6000
gccatacgtc gtgtgacagc tcatgagcct ttcactgggc tggcaattgt ctgaacactt 6060
gggttcagtt gaaatatatg tattttggcc aaaagccagc agcacttcac aaaaacaaaa 6120
cacaaaccta agctaacaaa atgactgcat tcgtctcttt tttaaaggta gagattaaac 6180
tgtatagaca gcatagggat gaaaggaacc aagcgtttct gtgggattga gactggtacg 6240
tgtacgatga acctgctgct ttgttttctg agaagaggtt tgaagacatt ttattaacag 6300
cttaattttt ctcttttact ccataggaac ttattttaat agtaacatta acaacaagaa 6360
tactaagact gtttgggaat tttaaaaagc tactagtgag aaaccaaatg ataggttgta 6420
gagcctgatg actccaaaca aagccatcac ccgcattctt cctccttctt ctggtgctac 6480
agctccaagg gcccttcacc ttcatgtctg aaatggaact ttggcttttt cagtggaaga 6540
atatgttgaa ggtttcattt tgttctagaa aaaaaaaatc cctcccaaag tggggcaaaa 6600
agctttatat ttatttgatt atccaaaata cagatcaaag tttagatcta cattcttcat 6660
tgtatttgct gtttcttaat tgggcacaca caactcctgg tcatgtccca gttcagcacc 6720
gatcgctaag gccgatcctg tagaatgcgg ctttcaagag gtcctaactg atcctttctt 6780
ccactttgct gttgatttgt tcacaaatta tgtctgaatg agaaatcttc tgtaagcaga 6840
agttatttaa taattcccag caccacgaaa ttgttataca tacatcccta ccagtcacat 6900
tccctgtgtt cagagcctgg aaatgaaatt gagttcagtt cagcctctct gtaatgaatc 6960
aagaaatgta aaagagcttt gagaccccaa gggaaaggag agagttgctt ctcatttctg 7020
attttattgt gctgttactc tgtcgagtgg ctattaaaat tgtcttatgc tctttgggct 7080
aagaggggat catctcgctt aagatgtact cctgatgtaa acatttcccc cactttccaa 7140
ataatggtaa agaaaacagt ggcaagggct gttctgtttt ctggtacctg agtgaaactc 7200
agaagaaaag caggcttagc taagagattt tcactattaa cctgttttta ttagatcagc 7260
gaagacagtc atgcatcgct taatgatggg gatgcattct gagaaatgtg tcattaggct 7320
gttttgttgc tgtgccaaca tcctagattg tacttacaca acctacatgg tatagcctac 7380
tacacacctg ggctgtgtgg catggcctat tcctcttagg ctacaaacct gtacagcatg 7440
ttactgtact gaacacaatg gtaagtattt gtgtatctaa acatagctaa acatagaaaa 7500
ggtatggtaa aaatacaatt ttataatctt atgggactac catcaatatg tagaccgtca 7560
ttgaccaaaa catcctgatg tgtgcatgac tgtacttttc attaaataac agataagggg 7620
ctatagaatt tggggctctg actgatcaaa acctgtgtat ctgtgtcaag ttttaagacc 7680
cctgaaacag ctaaaacagg tttccaaagt gtaatcactg gatttcaaaa ccatgtttta 7740
gcccttcatt aatgaagcct gttgtacaga tttagagtct tacaatatga gggaagttgg 7800
ttctgggaag gtaagatgta gccagttttc atctgggcac ctctgaaaga gaaggagtgc 7860
aggagagtaa gtctctcaag gacgttcaac aaaggaccag cagcatctta tcaggcgatc 7920
ctcagaggct ccaaggagca ttggagagaa tgcccctttc tgggcttgat gtcttggttt 7980
tggtttaata ccaaatttct cttggtcttg gtttaatacc cgactcctcc caaattgaac 8040
gattatcttt gtatgtcact caaaaatacc aggtttcctg aatatgttat taagaatttc 8100
agatatccaa gcagaatttt attatggaca ccttgtaatg aattcaaatc gtgtgacagc 8160
aaacgggata aatggcccct tctcacccag ttccgctcag ggccatacag gcttgcacat 8220
agagtgtgct aaaaatggta acctcctttg agcattgcag aaagagggtt ctgtttcaaa 8280
ttgggctgac cgtaaaagca attttgatgt ctttcaaact accataaagg gattttaact 8340
gtatttttat tcttagaaac aatacacctt taaacagatg tcaagaccaa agatgatgta 8400
taataaacag ccggtggtta tggtgtggtg tgagcaggcc cccggatcac cagccctctg 8460
ctggtggtca taaagcacac acagtttgta cttgcttcct ctcgacgcct gccacaacag 8520
ttttgccagt caccaaactc agaaaaaact agctgtgtga gcagcaccgt accctagcgg 8580
tcttcagaca ttaagttcac gtcatccact gaaaggaagg gtccttgcgt tgacagcgtg 8640
tggctttgga gtccgtttat ggaagcactc tacaatgaac agttgaattt tatgtctatt 8700
cttttttcct attttaaaag ttctagtggt aacacaaact gtaaatttga gtcagaatgt 8760
ttggagaaat gttgtttttt tttttttcag agactacttt gtcactcact gaccatgtct 8820
ggttccttct ctgaacttca ttctccccat aagccaaaca agaacagacc tcccccgcca 8880
cctcccaggc accgtagttg tgagaatcag atgtgatcat gtgtgcagat gtcctgtgag 8940
gagggagcat aaagcactgt gaaaatgtag catgctgtct atgtggacgc cctaggatga 9000
gtgatgtgaa acgctgcact actgcggtga atgggttcac acatgggtaa tgagcaaaac 9060
cgaaagctcg gtgtgactca gtttcctcac tcccattttg ctttaatttc acttccttca 9120
ccaattttcc gattgcattt attaagcatc tttctgctcc cgactttctg gtgtctctgg 9180
caccaaataa cccagcagac atgagccttg ccttctgaga ttttagaatc taagatagca 9240
cgagtgggta tagaagatgg aagataccga taaataacat ggtttaagtg tcaataaaat 9300
tcattcgaag agatcaggcg cggtggctca cgcctgtaat cccagcattt tgggaggctg 9360
aggcaggtgg atcacttgag atcaagagct taaaaccagc ccaggcaaca tggcaaaacc 9420
ccgtctctac aaaaaaatac aaaaactagc tgggtgtggt ggcgcatgcc tgtagtccca 9480
gctgaggcac gataattgct tgaacccggg gggtggaggt tgcagtgagc tgagattgca 9540
ccactgtact ccaacctggg cgacagagca agactgtgtc tcaaaaagaa aaaaatttgt 9600
tcaaaagaca taaatgaatt aggcacccag aagaagttgc atgtttggaa atgcaatatc 9660
ttggggagac gtcaacttct gaagtgactt tgaaggcagg gcagctaccc aggcaaatgg 9720
cgtggaagga agagctgaga gtgggcctgg gaaaggctgt agggaaggag tgaagctgtc 9780
actgaaatga acttgatctt gatctgcttt gatatgggga cagaatcccc gactgcacta 9840
ttgagggagt ttcagaagag aaggaagagg tgctggaagg atgcttttgc agtcatgcag 9900
caaggaaacg accagggctg tgaagatcta cagaggaagt actccagtgt gggggaggca 9960
agggaagagg acgaaaatga tgagaatgac actgaggtca ttgtttagag cagatctcaa 10020
gcagccgttt ggccacgcca tatcctttgt ggagcatagt gggttatcta tctgtctgtc 10080
tgtctatgta tctgtctatc tatctatata tatattcagc ttctttactg ctacctacac 10140
atttttctcc aaattttatt aatttcatag tgttttgatt tgggtggcag atgactttta 10200
agcagtgggt gtttgccggc cagatctttc ctggcatgcg gactgtgagg caaagcacgg 10260
gtgaaggtag gcgctaaagg ctttgggcta aagccagcac gcggttctgt gctataggag 10320
tctcccgttt cccgtggaca ggttcagcgt tccttctttc gcacaacttt tttctaagtg 10380
ttccagtgac caagccagtc attcggacac tgatttgcag tgcattggca gtaattcaca 10440
aattagttgt tatataagtc tctctcatcc ctttcacact agattctcag acatgaatga 10500
atttgtcgtt tggaaggaaa gctgggtaac gttttgggca caggggaagg aggactccgg 10560
tcttaactcc cacgctaact ttagctcaag tggagttttc accgtggtca tttctacctc 10620
cggagcaagg tgccagcgcc agtactagag cctgcttatc cacatttgcc ctggacagga 10680
gcaggaggaa gtccacttct gtaccggcag acagagcatg tgaacacaaa acacatttct 10740
atggcatagt caactgaact tcatttttac atttaatcta acatgttaac acgttctaac 10800
agggtttcta tgagcagctg ctgtaacata ctcatcaact atgatagact taacacttgt 10860
tacctaatga acaaggagga tgtgcatttc gggtttcttt tgatattcgt ggaggtgatt 10920
gtcagtgttt aaacaggact actttctcca ctatgaagat gacttggaaa tcgcaacatc 10980
atggtacatt gctaagtcca tgcttgtgtg tgtgacagta ggcttgataa tttatcttaa 11040
aacacagcag cattgaaatt taggaaaaga atattaaatg cctttggaaa catgaaacaa 11100
agttaggagc cagtaagaaa gtgacagaag caatgaatgt cttaatgcag tatagttaaa 11160
atggcttccc acagggtaga taattatcca ggatccttcc ttttccttct tcctccaggt 11220
ttttcagggg tcacttcaca tttctaaaga aagagtgaat aggctgggca tggtggctca 11280
agcctctaat ctcaacgctt tgggaggctg aggcaggagg atcgcttgag gccaggagtt 11340
tgagaccacc ttgggcaaca taacgagacc ccgtctctac aaaaaaaatt taaaaattag 11400
ctgagcatgg tggcatgtgc cagtagtccc agctactcga aaggctaaga ctggaggatc 11460
gcttgagcca atgagttgga ggctgcagtg agctataatc acgccactgc actccagcct 11520
gggctgcagg gtgaggtcct gtctctggaa aaaaaaaaaa aaaaaaaagg aataggtaaa 11580
agggacagag gtgaaatttt gagtgacttg agtctcttgc agtccctgat tacacagaac 11640
ctttctgggc tacttggagc atcacgaata gtctttcctg tacttaccag atttcaagta 11700
ttcataactt gactccctaa gtgtacaagt tgggaatagt acagggccaa gttcaagtcg 11760
catatgctgt actgttcctc ctgcaaatgt ggggaaagaa gagggagata ctagaggaac 11820
tgaggctcca cccattcatt cagttgctct aagcaccaga ggacttgttt cagaaaaggg 11880
gagtgggaac gccctcgact ttgccctcct ccggagcatc tctgggacgc agggagtctg 11940
gctagcgtta ataggaaagg ttgctcggca gagctgccct ggagtactga cttgtctctc 12000
cctcctttgt caaggtccat gtttttctgg ctcttcctgc acactcatcc ctagattatg 12060
agcgttaatg tacgaaatgt gcagagcaaa ttgaggccaa ctgtggcatc aatactgcaa 12120
cttaaacttg acaatcatgg tttgctggtc ctcaaacagg cactgaaatc tcagtatggg 12180
tatacgattt aataatcggc ccctcccttc tatttgtcgg ttttatgttt ctatccttca 12240
atagctgcac tgttttctaa tgtgctgtag agtttttgaa ataatttatg caagtatttg 12300
gtttccatgt ttacaattta tacagctttc ctagcatttt aaatggaaat gtcaataaat 12360
gctatgaatt ggtgtcaaa 12379
<210> 8
<211> 12498
<212> DNA
<213> Homo sapiens
<400> 8
ctctccggcc tccctccgcg ccggtgcgcg gcgccccgtc ccagccgcag ccgcagcggc 60
cgcccctccc ggacccgaga gccgctgagc cgcgaggccg ggccggggcg ccggccggga 120
atgccggggg cgcggcgccg acgccgaggc gcggccatgg aggggaagcc ccgcgccggg 180
gtcgcgctgg ccccggggcc gagcggccga cggccttccg cccgctgcgc ccgccgccgc 240
cgcccggggc tgctgcttcc tggcctctgg ctgctgctgc tggcccggcc ggcctcgtgc 300
gccccagatg agctctctcc ggaacagcac aacctttctt tatactccat ggagctcgtg 360
ctgaagaaaa gcactgggca cagcgctgca caagtggcct taacagaaac tgctcccggc 420
tcccagcaca gcagtcctct ccatgtcaca gccccgccgt ctgccactac ttttgataca 480
gcctttttta accaaggaaa acagaccaaa agtacagcag atcccagcat ctttgtggca 540
acttacgtgt cagtgacgag taaagaggtg gccgtcaatg acgatgagat ggataacttt 600
ctgccagata ctcactggac cactccacgg atggtttctc caatacagta tatcacagtc 660
agcccaccag ggctgcccag ggaagcatta gaacctatgc tcactccatc attacccatg 720
gtttctttac aagatgaaga agtgacatcg ggctggcaga acacaacgcg acaaccagcg 780
gcatatgctg agtccgccag tcatttccac acctttcggt cagcttttcg cacctctgag 840
ggcatcgttc caactcctgg caggaatttg gtgctttatc ctactgatgc ttacagtcat 900
ttatcaagca ggactctgcc agagattgtg gcttccctaa cagagggtgt ggaaaccacc 960
ctttttttaa gctcccggtc tttaatgcca cagccgttag gcgacggcat tactataccg 1020
ttgccctcct tgggggaggt ctcacagcct ccagaggagg tttgggccac aagtgcagac 1080
agatacactg atgtgaccac tgtgttgagt caaagcctag aagaaaccat ctctccaaga 1140
acatacccca ctgtgactgc atcgcacgca gcccttgcat tcagcaggac acattctcca 1200
ttgctttcaa ctcctcttgc atttgcgtcc tctgcttcac caactgatgt ttcatctaac 1260
ccctttctcc ctagcgactc cagcaaaaca tccgaattgc atagcaattc agccctcccc 1320
ggtcctgtgg acaacactca tatcctgagc ccggtgtcct cattcagacc atacacttgg 1380
tgtgcggcct gcactgtgcc ttcacctcag caagttctgg ccacgagcct catggagaaa 1440
gacgtgggat caggggatgg tgccgagact ctgtgcatga ccgtgctgga agaaagcagc 1500
atctctctaa tgagtagcgt cgtagcagac ttctctgaat ttgaggaaga tcctcaagta 1560
tttaatacgc ttttcccctc cagacctatc gtcccacttt cttctagatc catggaaatc 1620
tcagagacga gtgttggcat ttctgccgag gtggatatga gtagtgttac aaccacacag 1680
gttccccctg cccacggccg cctctctgtg ccggcgtcac ttgatcctac tgctggctcc 1740
ttgtctgttg ctgaaaccca agtgacgcca tccagcgtga ccactgcatt tttctcggtc 1800
atcaccagca ttctccttga ctcatctttc tctgtcatag caaacaaaaa cacaccgtcg 1860
cttgccgtca gagacccgag tgtttttacg ccttatagtc tggttccttc agtggagtct 1920
tcacttttct ctgaccaaga acgttccagt ttttctgagc ataaacccag aggtgctttg 1980
gattttgcat ccagcttttt ctcaacaccc ccgctggaac tcagcggctc catctcttcg 2040
ccttcggaag cacctgcgtc tctgtctctg atgccgagtg acttgtcccc cttcacatct 2100
cagtcttttt ctcccttggt tgagacattt acattgtttg actctagtga tctgcagtca 2160
tctcagctgt ctcttcccag ttccacaaat cttgagtttt cgcagctcca gccaagttcc 2220
gagctgcctt taaacaccat catgttgcta cctagccgtt ctgaggtgtc accatggtca 2280
agcttccctt ctgattctct cgagtttgtt gaagcgtcta cggtttcact gacggattca 2340
gaagctcatt ttacctcagc tttcattgaa actacctcct atcttgagtc ttcactcatt 2400
tcccatgaat ccgcagtcac tgcactggtg ccccccggct ctgagtcttt tgacattttg 2460
actgccggga ttcaagcaac atcaccattg accactgtcc acacaacgcc cattttaact 2520
gagtcttctt tgttctcaac tctgacacct cctgacgacc aaatcagtgc tctagacggt 2580
cacgtgtctg tcctggcctc tttctccaaa gccattccca ctggtacggt gttgatcact 2640
gacgcgtacc tgccatcagg atcctcgttt gtttctgaag caaccccctt ccctctgccc 2700
acagagctga ccgtcgtggg cccatcactc acacccacag aggtgccact gaacacctcc 2760
acggaagtga gcacaaccag caccggtgct gccactggtg gtcccctcga ctccaccctg 2820
atgggtgacg ccgcaagtca gagcccccca gagagtagtg ctgctcctcc cctgccatcc 2880
ctgcgtcccg tgactgcctt cactctcgaa gcaacagtcg acacaccaac actggctact 2940
gccaagccgc catatgtttg tgatatcaca gtccccgatg cctatctgat cacaactgtg 3000
ctggccagaa gagctgtgca ggagtacatc attacagcaa tcaaagaagt actgaggatt 3060
cacttcaacc gtgcagtgga actgaaggtt tacgaactat ttactgactt cacttttctg 3120
gtaacatccg gtcctttcgt ttacacggca atatccgtca taaatgtgct tataaacagt 3180
aagcttgtcc gtgaccagac tcctttaatc ctgtctgtga aaccttcttt ccttgtgcca 3240
gagtccaggt tccaagttca aacagtactt cagtttgtgc ctccgagtgt ggatactggc 3300
ttctgcaact tcacccagcg cattgagaaa ggcctaatga cagctctctt tgaagtgaga 3360
aaacaccacc agggaacgta taacctcacg gtgcagatct tgaatatcac catcagttcc 3420
tcaagggtga ctcctcggcg gggcccggtg aatatcatct ttgcggttaa aagcacacag 3480
ggatttttga atgggtcgga agtgagcgag ctgctcagaa acttgagtgt ggtggagttc 3540
agtttctatc tgggataccc agtgctgcag atcgcagagc ccttccagta tccacagctc 3600
aacttatctc agttgctgaa gtcctcttgg gtcagaacag ttctcctggg cgtcatggag 3660
aagcaactcc agaatgaagt gtttcaagcc gagatggaac gcaagctggc ccagctgctc 3720
agcgaggttt ccaccagaag gcggatgtgg agaagggcca ctgtagctgc agggaacagt 3780
gtggtgcagg tggtaaatgt gtcgaggctg gagggagatg acaatccggt acagctcatc 3840
tactttgtgg aggatcaaga tggagaaaga ctcagtgcag tcaagtcttc ggacctgatt 3900
aacaaaatgg acctccagag agcagccatc atcttgggtt accgaattca aggtgtcatt 3960
gcccagcctg tcgacagggt gaagaggccg tctccggaat cccagagcaa caacttgtgg 4020
gtcattgttg gcgtggtcat cccagtgctg gtggtgatgg tgattgttgt catcctctac 4080
tggaaactat gccgcacaga caagctagac tttcagcctg acactgtggc caacattcag 4140
cagcgtcaga agctgcagat ccctagtgtg aagggcttcg attttgctaa gcagcatctg 4200
ggtcagcaca ataaagacga catattgatt attcatgagc cagcgccact gccaggacct 4260
ctgaaggacc acaccacgcc ctcggaaaat ggagacgtgc caagccccaa gtcaaagatc 4320
ccttccaaga atgttcgtca cagaggaaga gtttctccct cagatgctga ctctacggtc 4380
agtgaagagt ccagcgagag ggacgcagga gataagacgc cgggagccgt caacgatggc 4440
aggtcccaca gagctccgca gagcgggcca ccactgccca gttcgggaaa tgagcagcac 4500
tcatcagcct ccatcttcga gcacgtggac aggatctccc gccccccgga ggctagccgg 4560
cgggtcccca gtaagatcca gcttatcgcc atgcagccga tcccggcacc tcccgtccag 4620
cgcccctccc cagccgaccg agtggcggaa agcaataaaa tcaacaaaga gattcagacc 4680
gcgctgcggc acaagtctga gatcgagcac catcgcaaca agatccgcct gcgcgccaag 4740
cgccgcgggc actacgagtt cccggtggta gacgacctgt cctcgggcga cactaaggag 4800
cgacaccggg tgtaccgcag ggcacagatg cagatcgaca agatcctgga ccccacggcc 4860
agcgtgccct ccgtgttcat agagcccagg aagagctcac ggataaaacg ttctcccaag 4920
cctcgccgga aacaccaggt caacggctgt cctgccgacg ctgagaagga ccggctcatc 4980
accacagaca gcgatggcac ctacaggagg ccccccggcg tccacaactc agcctacatc 5040
ggatgcccat cggatcctga cctcccagcc gatgtgcaga caccatcctc ggtggaactg 5100
gggaggtatc cagcccttcc cttcccggcc tcccagtaca tcccacccca gccgtccatc 5160
gaggaggcac gccagaccat gcactccctc ctggacgacg cctttgccct cgtggccccc 5220
agcagccagc ctgccagcac cgcaggtgta ggccccggag tcccacccgg cctgcccgca 5280
aacagcaccc cttcccagga agagaggcga gccacccagt gggggtcctt ctacagccca 5340
gcccagacgg ccaacaatcc ctgcagtaga tacgaagact atggaatgac tcccccgacg 5400
ggtccattgc caagaccagg ttttggcccc ggtttgctgc agtctacaga gctggtgccc 5460
cctgaccctc agcagccaca ggcctccgcc gaagccccat ttgctgccag agggatctac 5520
tcggaggaga tgccgtcggt ggcccggcct cggcctgtcg ggggtaccac aggctcccag 5580
atccagcacc tgacacaggt ggggattgcc agcagaattg gagctcagcc agtggaaatc 5640
ccgccaagca gaggcagcca gtatgggggg ccaggctggc cttcgtacgg ggaggacgaa 5700
gcggggcgaa gagaggccac acacatgctc ggacatcaag agtattcttc ttcaccgcta 5760
tttcaggtgc caaggacttc aggcagggag ccctcagctc cttccgggaa cctcccccac 5820
cggggactgc agggccctgg gctgggttac cccaccagct ccacggaaga cctccagcct 5880
ggccactcct cggcctctct catcaaagca atccgcgagg agctcctccg gctctcccag 5940
aaacagagca ccgtgcagaa cttccacagc tgatcggcct cgcctcgcag atttgccaag 6000
tatccgcttc ctgtggaagc aagaccaaaa ggaaatcaac tgagtgggtg tttggaagag 6060
gaaggagcaa ctctcgggca gcctgcccaa gggagggagc aagttgcaat ttagaagatg 6120
ccatacgtcg tgtgacagct catgagcctt tcactgggct ggcaattgtc tgaacacttg 6180
ggttcagttg aaatatatgt attttggcca aaagccagca gcacttcaca aaaacaaaac 6240
acaaacctaa gctaacaaaa tgactgcatt cgtctctttt ttaaaggtag agattaaact 6300
gtatagacag catagggatg aaaggaacca agcgtttctg tgggattgag actggtacgt 6360
gtacgatgaa cctgctgctt tgttttctga gaagaggttt gaagacattt tattaacagc 6420
ttaatttttc tcttttactc cataggaact tattttaata gtaacattaa caacaagaat 6480
actaagactg tttgggaatt ttaaaaagct actagtgaga aaccaaatga taggttgtag 6540
agcctgatga ctccaaacaa agccatcacc cgcattcttc ctccttcttc tggtgctaca 6600
gctccaaggg cccttcacct tcatgtctga aatggaactt tggctttttc agtggaagaa 6660
tatgttgaag gtttcatttt gttctagaaa aaaaaaatcc ctcccaaagt ggggcaaaaa 6720
gctttatatt tatttgatta tccaaaatac agatcaaagt ttagatctac attcttcatt 6780
gtatttgctg tttcttaatt gggcacacac aactcctggt catgtcccag ttcagcaccg 6840
atcgctaagg ccgatcctgt agaatgcggc tttcaagagg tcctaactga tcctttcttc 6900
cactttgctg ttgatttgtt cacaaattat gtctgaatga gaaatcttct gtaagcagaa 6960
gttatttaat aattcccagc accacgaaat tgttatacat acatccctac cagtcacatt 7020
ccctgtgttc agagcctgga aatgaaattg agttcagttc agcctctctg taatgaatca 7080
agaaatgtaa aagagctttg agaccccaag ggaaaggaga gagttgcttc tcatttctga 7140
ttttattgtg ctgttactct gtcgagtggc tattaaaatt gtcttatgct ctttgggcta 7200
agaggggatc atctcgctta agatgtactc ctgatgtaaa catttccccc actttccaaa 7260
taatggtaaa gaaaacagtg gcaagggctg ttctgttttc tggtacctga gtgaaactca 7320
gaagaaaagc aggcttagct aagagatttt cactattaac ctgtttttat tagatcagcg 7380
aagacagtca tgcatcgctt aatgatgggg atgcattctg agaaatgtgt cattaggctg 7440
ttttgttgct gtgccaacat cctagattgt acttacacaa cctacatggt atagcctact 7500
acacacctgg gctgtgtggc atggcctatt cctcttaggc tacaaacctg tacagcatgt 7560
tactgtactg aacacaatgg taagtatttg tgtatctaaa catagctaaa catagaaaag 7620
gtatggtaaa aatacaattt tataatctta tgggactacc atcaatatgt agaccgtcat 7680
tgaccaaaac atcctgatgt gtgcatgact gtacttttca ttaaataaca gataaggggc 7740
tatagaattt ggggctctga ctgatcaaaa cctgtgtatc tgtgtcaagt tttaagaccc 7800
ctgaaacagc taaaacaggt ttccaaagtg taatcactgg atttcaaaac catgttttag 7860
cccttcatta atgaagcctg ttgtacagat ttagagtctt acaatatgag ggaagttggt 7920
tctgggaagg taagatgtag ccagttttca tctgggcacc tctgaaagag aaggagtgca 7980
ggagagtaag tctctcaagg acgttcaaca aaggaccagc agcatcttat caggcgatcc 8040
tcagaggctc caaggagcat tggagagaat gcccctttct gggcttgatg tcttggtttt 8100
ggtttaatac caaatttctc ttggtcttgg tttaataccc gactcctccc aaattgaacg 8160
attatctttg tatgtcactc aaaaatacca ggtttcctga atatgttatt aagaatttca 8220
gatatccaag cagaatttta ttatggacac cttgtaatga attcaaatcg tgtgacagca 8280
aacgggataa atggcccctt ctcacccagt tccgctcagg gccatacagg cttgcacata 8340
gagtgtgcta aaaatggtaa cctcctttga gcattgcaga aagagggttc tgtttcaaat 8400
tgggctgacc gtaaaagcaa ttttgatgtc tttcaaacta ccataaaggg attttaactg 8460
tatttttatt cttagaaaca atacaccttt aaacagatgt caagaccaaa gatgatgtat 8520
aataaacagc cggtggttat ggtgtggtgt gagcaggccc ccggatcacc agccctctgc 8580
tggtggtcat aaagcacaca cagtttgtac ttgcttcctc tcgacgcctg ccacaacagt 8640
tttgccagtc accaaactca gaaaaaacta gctgtgtgag cagcaccgta ccctagcggt 8700
cttcagacat taagttcacg tcatccactg aaaggaaggg tccttgcgtt gacagcgtgt 8760
ggctttggag tccgtttatg gaagcactct acaatgaaca gttgaatttt atgtctattc 8820
ttttttccta ttttaaaagt tctagtggta acacaaactg taaatttgag tcagaatgtt 8880
tggagaaatg ttgttttttt ttttttcaga gactactttg tcactcactg accatgtctg 8940
gttccttctc tgaacttcat tctccccata agccaaacaa gaacagacct cccccgccac 9000
ctcccaggca ccgtagttgt gagaatcaga tgtgatcatg tgtgcagatg tcctgtgagg 9060
agggagcata aagcactgtg aaaatgtagc atgctgtcta tgtggacgcc ctaggatgag 9120
tgatgtgaaa cgctgcacta ctgcggtgaa tgggttcaca catgggtaat gagcaaaacc 9180
gaaagctcgg tgtgactcag tttcctcact cccattttgc tttaatttca cttccttcac 9240
caattttccg attgcattta ttaagcatct ttctgctccc gactttctgg tgtctctggc 9300
accaaataac ccagcagaca tgagccttgc cttctgagat tttagaatct aagatagcac 9360
gagtgggtat agaagatgga agataccgat aaataacatg gtttaagtgt caataaaatt 9420
cattcgaaga gatcaggcgc ggtggctcac gcctgtaatc ccagcatttt gggaggctga 9480
ggcaggtgga tcacttgaga tcaagagctt aaaaccagcc caggcaacat ggcaaaaccc 9540
cgtctctaca aaaaaataca aaaactagct gggtgtggtg gcgcatgcct gtagtcccag 9600
ctgaggcacg ataattgctt gaacccgggg ggtggaggtt gcagtgagct gagattgcac 9660
cactgtactc caacctgggc gacagagcaa gactgtgtct caaaaagaaa aaaatttgtt 9720
caaaagacat aaatgaatta ggcacccaga agaagttgca tgtttggaaa tgcaatatct 9780
tggggagacg tcaacttctg aagtgacttt gaaggcaggg cagctaccca ggcaaatggc 9840
gtggaaggaa gagctgagag tgggcctggg aaaggctgta gggaaggagt gaagctgtca 9900
ctgaaatgaa cttgatcttg atctgctttg atatggggac agaatccccg actgcactat 9960
tgagggagtt tcagaagaga aggaagaggt gctggaagga tgcttttgca gtcatgcagc 10020
aaggaaacga ccagggctgt gaagatctac agaggaagta ctccagtgtg ggggaggcaa 10080
gggaagagga cgaaaatgat gagaatgaca ctgaggtcat tgtttagagc agatctcaag 10140
cagccgtttg gccacgccat atcctttgtg gagcatagtg ggttatctat ctgtctgtct 10200
gtctatgtat ctgtctatct atctatatat atattcagct tctttactgc tacctacaca 10260
tttttctcca aattttatta atttcatagt gttttgattt gggtggcaga tgacttttaa 10320
gcagtgggtg tttgccggcc agatctttcc tggcatgcgg actgtgaggc aaagcacggg 10380
tgaaggtagg cgctaaaggc tttgggctaa agccagcacg cggttctgtg ctataggagt 10440
ctcccgtttc ccgtggacag gttcagcgtt ccttctttcg cacaactttt ttctaagtgt 10500
tccagtgacc aagccagtca ttcggacact gatttgcagt gcattggcag taattcacaa 10560
attagttgtt atataagtct ctctcatccc tttcacacta gattctcaga catgaatgaa 10620
tttgtcgttt ggaaggaaag ctgggtaacg ttttgggcac aggggaagga ggactccggt 10680
cttaactccc acgctaactt tagctcaagt ggagttttca ccgtggtcat ttctacctcc 10740
ggagcaaggt gccagcgcca gtactagagc ctgcttatcc acatttgccc tggacaggag 10800
caggaggaag tccacttctg taccggcaga cagagcatgt gaacacaaaa cacatttcta 10860
tggcatagtc aactgaactt catttttaca tttaatctaa catgttaaca cgttctaaca 10920
gggtttctat gagcagctgc tgtaacatac tcatcaacta tgatagactt aacacttgtt 10980
acctaatgaa caaggaggat gtgcatttcg ggtttctttt gatattcgtg gaggtgattg 11040
tcagtgttta aacaggacta ctttctccac tatgaagatg acttggaaat cgcaacatca 11100
tggtacattg ctaagtccat gcttgtgtgt gtgacagtag gcttgataat ttatcttaaa 11160
acacagcagc attgaaattt aggaaaagaa tattaaatgc ctttggaaac atgaaacaaa 11220
gttaggagcc agtaagaaag tgacagaagc aatgaatgtc ttaatgcagt atagttaaaa 11280
tggcttccca cagggtagat aattatccag gatccttcct tttccttctt cctccaggtt 11340
tttcaggggt cacttcacat ttctaaagaa agagtgaata ggctgggcat ggtggctcaa 11400
gcctctaatc tcaacgcttt gggaggctga ggcaggagga tcgcttgagg ccaggagttt 11460
gagaccacct tgggcaacat aacgagaccc cgtctctaca aaaaaaattt aaaaattagc 11520
tgagcatggt ggcatgtgcc agtagtccca gctactcgaa aggctaagac tggaggatcg 11580
cttgagccaa tgagttggag gctgcagtga gctataatca cgccactgca ctccagcctg 11640
ggctgcaggg tgaggtcctg tctctggaaa aaaaaaaaaa aaaaaaagga ataggtaaaa 11700
gggacagagg tgaaattttg agtgacttga gtctcttgca gtccctgatt acacagaacc 11760
tttctgggct acttggagca tcacgaatag tctttcctgt acttaccaga tttcaagtat 11820
tcataacttg actccctaag tgtacaagtt gggaatagta cagggccaag ttcaagtcgc 11880
atatgctgta ctgttcctcc tgcaaatgtg gggaaagaag agggagatac tagaggaact 11940
gaggctccac ccattcattc agttgctcta agcaccagag gacttgtttc agaaaagggg 12000
agtgggaacg ccctcgactt tgccctcctc cggagcatct ctgggacgca gggagtctgg 12060
ctagcgttaa taggaaaggt tgctcggcag agctgccctg gagtactgac ttgtctctcc 12120
ctcctttgtc aaggtccatg tttttctggc tcttcctgca cactcatccc tagattatga 12180
gcgttaatgt acgaaatgtg cagagcaaat tgaggccaac tgtggcatca atactgcaac 12240
ttaaacttga caatcatggt ttgctggtcc tcaaacaggc actgaaatct cagtatgggt 12300
atacgattta ataatcggcc cctcccttct atttgtcggt tttatgtttc tatccttcaa 12360
tagctgcact gttttctaat gtgctgtaga gtttttgaaa taatttatgc aagtatttgg 12420
tttccatgtt tacaatttat acagctttcc tagcatttta aatggaaatg tcaataaatg 12480
ctatgaattg gtgtcaaa 12498
<210> 9
<211> 1934
<212> PRT
<213> Homo sapiens
<400> 9
Met Pro Gly Ala Arg Arg Arg Arg Arg Gly Ala Ala Met Glu Gly Lys
1 5 10 15
Pro Arg Ala Gly Val Ala Leu Ala Pro Gly Pro Ser Gly Arg Arg Pro
20 25 30
Ser Ala Arg Cys Ala Arg Arg Arg Arg Pro Gly Leu Leu Leu Pro Gly
35 40 45
Leu Trp Leu Leu Leu Leu Ala Arg Pro Ala Ser Cys Ala Pro Asp Glu
50 55 60
Leu Ser Pro Glu Gln His Asn Leu Ser Leu Tyr Ser Met Glu Leu Val
65 70 75 80
Leu Lys Lys Ser Thr Gly His Ser Ala Ala Gln Val Ala Leu Thr Glu
85 90 95
Thr Ala Pro Gly Ser Gln His Ser Ser Pro Leu His Val Thr Ala Pro
100 105 110
Pro Ser Ala Thr Thr Phe Asp Thr Ala Phe Phe Asn Gln Gly Lys Gln
115 120 125
Thr Lys Ser Thr Ala Asp Pro Ser Ile Phe Val Ala Thr Tyr Val Ser
130 135 140
Val Thr Ser Lys Glu Val Ala Val Asn Asp Asp Glu Met Asp Asn Phe
145 150 155 160
Leu Pro Asp Thr His Trp Thr Thr Pro Arg Met Val Ser Pro Ile Gln
165 170 175
Tyr Ile Thr Val Ser Pro Pro Gly Leu Pro Arg Glu Ala Leu Glu Pro
180 185 190
Met Leu Thr Pro Ser Leu Pro Met Val Ser Leu Gln Asp Glu Glu Val
195 200 205
Thr Ser Gly Trp Gln Asn Thr Thr Arg Gln Pro Ala Ala Tyr Ala Glu
210 215 220
Ser Ala Ser His Phe His Thr Phe Arg Ser Ala Phe Arg Thr Ser Glu
225 230 235 240
Gly Ile Val Pro Thr Pro Gly Arg Asn Leu Val Leu Tyr Pro Thr Asp
245 250 255
Ala Tyr Ser His Leu Ser Ser Arg Thr Leu Pro Glu Ile Val Ala Ser
260 265 270
Leu Thr Glu Gly Val Glu Thr Thr Leu Phe Leu Ser Ser Arg Ser Leu
275 280 285
Met Pro Gln Pro Leu Gly Asp Gly Ile Thr Ile Pro Leu Pro Ser Leu
290 295 300
Gly Glu Val Ser Gln Pro Pro Glu Glu Val Trp Ala Thr Ser Ala Asp
305 310 315 320
Arg Tyr Thr Asp Val Thr Thr Val Leu Ser Gln Ser Leu Glu Glu Thr
325 330 335
Ile Ser Pro Arg Thr Tyr Pro Thr Val Thr Ala Ser His Ala Ala Leu
340 345 350
Ala Phe Ser Arg Thr His Ser Pro Leu Leu Ser Thr Pro Leu Ala Phe
355 360 365
Ala Ser Ser Ala Ser Pro Thr Asp Val Ser Ser Asn Pro Phe Leu Pro
370 375 380
Ser Asp Ser Ser Lys Thr Ser Glu Leu His Ser Asn Ser Ala Leu Pro
385 390 395 400
Gly Pro Val Asp Asn Thr His Ile Leu Ser Pro Val Ser Ser Phe Arg
405 410 415
Pro Tyr Thr Trp Cys Ala Ala Cys Thr Val Pro Ser Pro Gln Gln Val
420 425 430
Leu Ala Thr Ser Leu Met Glu Lys Asp Val Gly Ser Gly Asp Gly Ala
435 440 445
Glu Thr Leu Cys Met Thr Val Leu Glu Glu Ser Ser Ile Ser Leu Met
450 455 460
Ser Ser Val Val Ala Asp Phe Ser Glu Phe Glu Glu Asp Pro Gln Val
465 470 475 480
Phe Asn Thr Leu Phe Pro Ser Arg Pro Ile Val Pro Leu Ser Ser Arg
485 490 495
Ser Met Glu Ile Ser Glu Thr Ser Val Gly Ile Ser Ala Glu Val Asp
500 505 510
Met Ser Ser Val Thr Thr Thr Gln Val Pro Pro Ala His Gly Arg Leu
515 520 525
Ser Val Pro Ala Ser Leu Asp Pro Thr Ala Gly Ser Leu Ser Val Ala
530 535 540
Glu Thr Gln Val Thr Pro Ser Ser Val Thr Thr Ala Phe Phe Ser Val
545 550 555 560
Ile Thr Ser Ile Leu Leu Asp Ser Ser Phe Ser Val Ile Ala Asn Lys
565 570 575
Asn Thr Pro Ser Leu Ala Val Arg Asp Pro Ser Val Phe Thr Pro Tyr
580 585 590
Ser Leu Val Pro Ser Val Glu Ser Ser Leu Phe Ser Asp Gln Glu Arg
595 600 605
Ser Ser Phe Ser Glu His Lys Pro Arg Gly Ala Leu Asp Phe Ala Ser
610 615 620
Ser Phe Phe Ser Thr Pro Pro Leu Glu Leu Ser Gly Ser Ile Ser Ser
625 630 635 640
Pro Ser Glu Ala Pro Ala Ser Leu Ser Leu Met Pro Ser Asp Leu Ser
645 650 655
Pro Phe Thr Ser Gln Ser Phe Ser Pro Leu Val Glu Thr Phe Thr Leu
660 665 670
Phe Asp Ser Ser Asp Leu Gln Ser Ser Gln Leu Ser Leu Pro Ser Ser
675 680 685
Thr Asn Leu Glu Phe Ser Gln Leu Gln Pro Ser Ser Glu Leu Pro Leu
690 695 700
Asn Thr Ile Met Leu Leu Pro Ser Arg Ser Glu Val Ser Pro Trp Ser
705 710 715 720
Ser Phe Pro Ser Asp Ser Leu Glu Phe Val Glu Ala Ser Thr Val Ser
725 730 735
Leu Thr Asp Ser Glu Ala His Phe Thr Ser Ala Phe Ile Glu Thr Thr
740 745 750
Ser Tyr Leu Glu Ser Ser Leu Ile Ser His Glu Ser Ala Val Thr Ala
755 760 765
Leu Val Pro Pro Gly Ser Glu Ser Phe Asp Ile Leu Thr Ala Gly Ile
770 775 780
Gln Ala Thr Ser Pro Leu Thr Thr Val His Thr Thr Pro Ile Leu Thr
785 790 795 800
Glu Ser Ser Leu Phe Ser Thr Leu Thr Pro Pro Asp Asp Gln Ile Ser
805 810 815
Ala Leu Asp Gly His Val Ser Val Leu Ala Ser Phe Ser Lys Ala Ile
820 825 830
Pro Thr Gly Thr Val Leu Ile Thr Asp Ala Tyr Leu Pro Ser Gly Ser
835 840 845
Ser Phe Val Ser Glu Ala Thr Pro Phe Pro Leu Pro Thr Glu Leu Thr
850 855 860
Val Val Gly Pro Ser Leu Thr Pro Thr Glu Val Pro Leu Asn Thr Ser
865 870 875 880
Thr Glu Val Ser Thr Thr Ser Thr Gly Ala Ala Thr Gly Gly Pro Leu
885 890 895
Asp Ser Thr Leu Met Gly Asp Ala Ala Ser Gln Ser Pro Pro Glu Ser
900 905 910
Ser Ala Ala Pro Pro Leu Pro Ser Leu Arg Pro Val Thr Ala Phe Thr
915 920 925
Leu Glu Ala Thr Val Asp Thr Pro Thr Leu Ala Thr Ala Lys Pro Pro
930 935 940
Tyr Val Cys Asp Ile Thr Val Pro Asp Ala Tyr Leu Ile Thr Thr Val
945 950 955 960
Leu Ala Arg Arg Ala Val Gln Glu Tyr Ile Ile Thr Ala Ile Lys Glu
965 970 975
Val Leu Arg Ile His Phe Asn Arg Ala Val Glu Leu Lys Val Tyr Glu
980 985 990
Leu Phe Thr Asp Phe Thr Phe Leu Val Thr Ser Gly Pro Phe Val Tyr
995 1000 1005
Thr Ala Ile Ser Val Ile Asn Val Leu Ile Asn Ser Lys Leu Val
1010 1015 1020
Arg Asp Gln Thr Pro Leu Ile Leu Ser Val Lys Pro Ser Phe Leu
1025 1030 1035
Val Pro Glu Ser Arg Phe Gln Val Gln Thr Val Leu Gln Phe Val
1040 1045 1050
Pro Pro Ser Val Asp Thr Gly Phe Cys Asn Phe Thr Gln Arg Ile
1055 1060 1065
Glu Lys Gly Leu Met Thr Ala Leu Phe Glu Val Arg Lys His His
1070 1075 1080
Gln Gly Thr Tyr Asn Leu Thr Val Gln Ile Leu Asn Ile Thr Ile
1085 1090 1095
Ser Ser Ser Arg Val Thr Pro Arg Arg Gly Pro Val Asn Ile Ile
1100 1105 1110
Phe Ala Val Lys Ser Thr Gln Gly Phe Leu Asn Gly Ser Glu Val
1115 1120 1125
Ser Glu Leu Leu Arg Asn Leu Ser Val Val Glu Phe Ser Phe Tyr
1130 1135 1140
Leu Gly Tyr Pro Val Leu Gln Ile Ala Glu Pro Phe Gln Tyr Pro
1145 1150 1155
Gln Leu Asn Leu Ser Gln Leu Leu Lys Ser Ser Trp Val Arg Thr
1160 1165 1170
Val Leu Leu Gly Val Met Glu Lys Gln Leu Gln Asn Glu Val Phe
1175 1180 1185
Gln Ala Glu Met Glu Arg Lys Leu Ala Gln Leu Leu Ser Glu Val
1190 1195 1200
Ser Thr Arg Arg Arg Met Trp Arg Arg Ala Thr Val Ala Ala Gly
1205 1210 1215
Asn Ser Val Val Gln Val Val Asn Val Ser Arg Leu Glu Gly Asp
1220 1225 1230
Asp Asn Pro Val Gln Leu Ile Tyr Phe Val Glu Asp Gln Asp Gly
1235 1240 1245
Glu Arg Leu Ser Ala Val Lys Ser Ser Asp Leu Ile Asn Lys Met
1250 1255 1260
Asp Leu Gln Arg Ala Ala Ile Ile Leu Gly Tyr Arg Ile Gln Gly
1265 1270 1275
Val Ile Ala Gln Pro Val Asp Arg Val Lys Arg Pro Ser Pro Glu
1280 1285 1290
Ser Gln Ser Asn Asn Leu Trp Val Ile Val Gly Val Val Ile Pro
1295 1300 1305
Val Leu Val Val Met Val Ile Val Val Ile Leu Tyr Trp Lys Leu
1310 1315 1320
Cys Arg Thr Asp Lys Leu Asp Phe Gln Pro Asp Thr Val Ala Asn
1325 1330 1335
Ile Gln Gln Arg Gln Lys Leu Gln Ile Pro Ser Val Lys Gly Phe
1340 1345 1350
Asp Phe Ala Lys Gln His Leu Gly Gln His Asn Lys Asp Asp Ile
1355 1360 1365
Leu Ile Ile His Glu Pro Ala Pro Leu Pro Gly Pro Leu Lys Asp
1370 1375 1380
His Thr Thr Pro Ser Glu Asn Gly Asp Val Pro Ser Pro Lys Ser
1385 1390 1395
Lys Ile Pro Ser Lys Asn Val Arg His Arg Gly Arg Val Ser Pro
1400 1405 1410
Ser Asp Ala Asp Ser Thr Val Ser Glu Glu Ser Ser Glu Arg Asp
1415 1420 1425
Ala Gly Asp Lys Thr Pro Gly Ala Val Asn Asp Gly Arg Ser His
1430 1435 1440
Arg Ala Pro Gln Ser Gly Pro Pro Leu Pro Ser Ser Gly Asn Glu
1445 1450 1455
Gln His Ser Ser Ala Ser Ile Phe Glu His Val Asp Arg Ile Ser
1460 1465 1470
Arg Pro Pro Glu Ala Ser Arg Arg Val Pro Ser Lys Ile Gln Leu
1475 1480 1485
Ile Ala Met Gln Pro Ile Pro Ala Pro Pro Val Gln Arg Pro Ser
1490 1495 1500
Pro Ala Asp Arg Val Ala Glu Ser Asn Lys Ile Asn Lys Glu Ile
1505 1510 1515
Gln Thr Ala Leu Arg His Lys Ser Glu Ile Glu His His Arg Asn
1520 1525 1530
Lys Ile Arg Leu Arg Ala Lys Arg Arg Gly His Tyr Glu Phe Pro
1535 1540 1545
Val Val Asp Asp Leu Ser Ser Gly Asp Thr Lys Glu Arg His Arg
1550 1555 1560
Val Tyr Arg Arg Ala Gln Met Gln Ile Asp Lys Ile Leu Asp Pro
1565 1570 1575
Thr Ala Ser Val Pro Ser Val Phe Ile Glu Pro Arg Lys Ser Ser
1580 1585 1590
Arg Ile Lys Arg Ser Pro Lys Pro Arg Arg Lys His Gln Val Asn
1595 1600 1605
Gly Cys Pro Ala Asp Ala Glu Lys Asp Arg Leu Ile Thr Thr Asp
1610 1615 1620
Ser Asp Gly Thr Tyr Arg Arg Pro Pro Gly Val His Asn Ser Ala
1625 1630 1635
Tyr Ile Gly Cys Pro Ser Asp Pro Asp Leu Pro Ala Asp Val Gln
1640 1645 1650
Thr Pro Ser Ser Val Glu Leu Gly Arg Tyr Pro Ala Leu Pro Phe
1655 1660 1665
Pro Ala Ser Gln Tyr Ile Pro Pro Gln Pro Ser Ile Glu Glu Ala
1670 1675 1680
Arg Gln Thr Met His Ser Leu Leu Asp Asp Ala Phe Ala Leu Val
1685 1690 1695
Ala Pro Ser Ser Gln Pro Ala Ser Thr Ala Gly Val Gly Pro Gly
1700 1705 1710
Val Pro Pro Gly Leu Pro Ala Asn Ser Thr Pro Ser Gln Glu Glu
1715 1720 1725
Arg Arg Ala Thr Gln Trp Gly Ser Phe Tyr Ser Pro Ala Gln Thr
1730 1735 1740
Ala Asn Asn Pro Cys Ser Arg Tyr Glu Asp Tyr Gly Met Thr Pro
1745 1750 1755
Pro Thr Gly Pro Leu Pro Arg Pro Gly Phe Gly Pro Gly Leu Leu
1760 1765 1770
Gln Ser Thr Glu Leu Val Pro Pro Asp Pro Gln Gln Pro Gln Ala
1775 1780 1785
Ser Ala Glu Ala Pro Phe Ala Ala Arg Gly Ile Tyr Ser Glu Glu
1790 1795 1800
Met Pro Ser Val Ala Arg Pro Arg Pro Val Gly Gly Thr Thr Gly
1805 1810 1815
Ser Gln Ile Gln His Leu Thr Gln Val Gly Ile Ala Ser Arg Ile
1820 1825 1830
Gly Ala Gln Pro Val Glu Ile Pro Pro Ser Arg Gly Ser Gln Tyr
1835 1840 1845
Gly Gly Pro Gly Trp Pro Ser Tyr Gly Glu Asp Glu Ala Gly Arg
1850 1855 1860
Arg Glu Ala Val Pro Arg Thr Ser Gly Arg Glu Pro Ser Ala Pro
1865 1870 1875
Ser Gly Asn Leu Pro His Arg Gly Leu Gln Gly Pro Gly Leu Gly
1880 1885 1890
Tyr Pro Thr Ser Ser Thr Glu Asp Leu Gln Pro Gly His Ser Ser
1895 1900 1905
Ala Ser Leu Ile Lys Ala Ile Arg Glu Glu Leu Leu Arg Leu Ser
1910 1915 1920
Gln Lys Gln Ser Thr Val Gln Asn Phe His Ser
1925 1930
<210> 10
<211> 1950
<212> PRT
<213> Homo sapiens
<400> 10
Met Pro Gly Ala Arg Arg Arg Arg Arg Gly Ala Ala Met Glu Gly Lys
1 5 10 15
Pro Arg Ala Gly Val Ala Leu Ala Pro Gly Pro Ser Gly Arg Arg Pro
20 25 30
Ser Ala Arg Cys Ala Arg Arg Arg Arg Pro Gly Leu Leu Leu Pro Gly
35 40 45
Leu Trp Leu Leu Leu Leu Ala Arg Pro Ala Ser Cys Ala Pro Asp Glu
50 55 60
Leu Ser Pro Glu Gln His Asn Leu Ser Leu Tyr Ser Met Glu Leu Val
65 70 75 80
Leu Lys Lys Ser Thr Gly His Ser Ala Ala Gln Val Ala Leu Thr Glu
85 90 95
Thr Ala Pro Gly Ser Gln His Ser Ser Pro Leu His Val Thr Ala Pro
100 105 110
Pro Ser Ala Thr Thr Phe Asp Thr Ala Phe Phe Asn Gln Gly Lys Gln
115 120 125
Thr Lys Ser Thr Ala Asp Pro Ser Ile Phe Val Ala Thr Tyr Val Ser
130 135 140
Val Thr Ser Lys Glu Val Ala Val Asn Asp Asp Glu Met Asp Asn Phe
145 150 155 160
Leu Pro Asp Thr His Trp Thr Thr Pro Arg Met Val Ser Pro Ile Gln
165 170 175
Tyr Ile Thr Val Ser Pro Pro Gly Leu Pro Arg Glu Ala Leu Glu Pro
180 185 190
Met Leu Thr Pro Ser Leu Pro Met Val Ser Leu Gln Asp Glu Glu Val
195 200 205
Thr Ser Gly Trp Gln Asn Thr Thr Arg Gln Pro Ala Ala Tyr Ala Glu
210 215 220
Ser Ala Ser His Phe His Thr Phe Arg Ser Ala Phe Arg Thr Ser Glu
225 230 235 240
Gly Ile Val Pro Thr Pro Gly Arg Asn Leu Val Leu Tyr Pro Thr Asp
245 250 255
Ala Tyr Ser His Leu Ser Ser Arg Thr Leu Pro Glu Ile Val Ala Ser
260 265 270
Leu Thr Glu Gly Val Glu Thr Thr Leu Phe Leu Ser Ser Arg Ser Leu
275 280 285
Met Pro Gln Pro Leu Gly Asp Gly Ile Thr Ile Pro Leu Pro Ser Leu
290 295 300
Gly Glu Val Ser Gln Pro Pro Glu Glu Val Trp Ala Thr Ser Ala Asp
305 310 315 320
Arg Tyr Thr Asp Val Thr Thr Val Leu Ser Gln Ser Leu Glu Glu Thr
325 330 335
Ile Ser Pro Arg Thr Tyr Pro Thr Val Thr Ala Ser His Ala Ala Leu
340 345 350
Ala Phe Ser Arg Thr His Ser Pro Leu Leu Ser Thr Pro Leu Ala Phe
355 360 365
Ala Ser Ser Ala Ser Pro Thr Asp Val Ser Ser Asn Pro Phe Leu Pro
370 375 380
Ser Asp Ser Ser Lys Thr Ser Glu Leu His Ser Asn Ser Ala Leu Pro
385 390 395 400
Gly Pro Val Asp Asn Thr His Ile Leu Ser Pro Val Ser Ser Phe Arg
405 410 415
Pro Tyr Thr Trp Cys Ala Ala Cys Thr Val Pro Ser Pro Gln Gln Val
420 425 430
Leu Ala Thr Ser Leu Met Glu Lys Asp Val Gly Ser Gly Asp Gly Ala
435 440 445
Glu Thr Leu Cys Met Thr Val Leu Glu Glu Ser Ser Ile Ser Leu Met
450 455 460
Ser Ser Val Val Ala Asp Phe Ser Glu Phe Glu Glu Asp Pro Gln Val
465 470 475 480
Phe Asn Thr Leu Phe Pro Ser Arg Pro Ile Val Pro Leu Ser Ser Arg
485 490 495
Ser Met Glu Ile Ser Glu Thr Ser Val Gly Ile Ser Ala Glu Val Asp
500 505 510
Met Ser Ser Val Thr Thr Thr Gln Val Pro Pro Ala His Gly Arg Leu
515 520 525
Ser Val Pro Ala Ser Leu Asp Pro Thr Ala Gly Ser Leu Ser Val Ala
530 535 540
Glu Thr Gln Val Thr Pro Ser Ser Val Thr Thr Ala Phe Phe Ser Val
545 550 555 560
Ile Thr Ser Ile Leu Leu Asp Ser Ser Phe Ser Val Ile Ala Asn Lys
565 570 575
Asn Thr Pro Ser Leu Ala Val Arg Asp Pro Ser Val Phe Thr Pro Tyr
580 585 590
Ser Leu Val Pro Ser Val Glu Ser Ser Leu Phe Ser Asp Gln Glu Arg
595 600 605
Ser Ser Phe Ser Glu His Lys Pro Arg Gly Ala Leu Asp Phe Ala Ser
610 615 620
Ser Phe Phe Ser Thr Pro Pro Leu Glu Leu Ser Gly Ser Ile Ser Ser
625 630 635 640
Pro Ser Glu Ala Pro Ala Ser Leu Ser Leu Met Pro Ser Asp Leu Ser
645 650 655
Pro Phe Thr Ser Gln Ser Phe Ser Pro Leu Val Glu Thr Phe Thr Leu
660 665 670
Phe Asp Ser Ser Asp Leu Gln Ser Ser Gln Leu Ser Leu Pro Ser Ser
675 680 685
Thr Asn Leu Glu Phe Ser Gln Leu Gln Pro Ser Ser Glu Leu Pro Leu
690 695 700
Asn Thr Ile Met Leu Leu Pro Ser Arg Ser Glu Val Ser Pro Trp Ser
705 710 715 720
Ser Phe Pro Ser Asp Ser Leu Glu Phe Val Glu Ala Ser Thr Val Ser
725 730 735
Leu Thr Asp Ser Glu Ala His Phe Thr Ser Ala Phe Ile Glu Thr Thr
740 745 750
Ser Tyr Leu Glu Ser Ser Leu Ile Ser His Glu Ser Ala Val Thr Ala
755 760 765
Leu Val Pro Pro Gly Ser Glu Ser Phe Asp Ile Leu Thr Ala Gly Ile
770 775 780
Gln Ala Thr Ser Pro Leu Thr Thr Val His Thr Thr Pro Ile Leu Thr
785 790 795 800
Glu Ser Ser Leu Phe Ser Thr Leu Thr Pro Pro Asp Asp Gln Ile Ser
805 810 815
Ala Leu Asp Gly His Val Ser Val Leu Ala Ser Phe Ser Lys Ala Ile
820 825 830
Pro Thr Gly Thr Val Leu Ile Thr Asp Ala Tyr Leu Pro Ser Gly Ser
835 840 845
Ser Phe Val Ser Glu Ala Thr Pro Phe Pro Leu Pro Thr Glu Leu Thr
850 855 860
Val Val Gly Pro Ser Leu Thr Pro Thr Glu Val Pro Leu Asn Thr Ser
865 870 875 880
Thr Glu Val Ser Thr Thr Ser Thr Gly Ala Ala Thr Gly Gly Pro Leu
885 890 895
Asp Ser Thr Leu Met Gly Asp Ala Ala Ser Gln Ser Pro Pro Glu Ser
900 905 910
Ser Ala Ala Pro Pro Leu Pro Ser Leu Arg Pro Val Thr Ala Phe Thr
915 920 925
Leu Glu Ala Thr Val Asp Thr Pro Thr Leu Ala Thr Ala Lys Pro Pro
930 935 940
Tyr Val Cys Asp Ile Thr Val Pro Asp Ala Tyr Leu Ile Thr Thr Val
945 950 955 960
Leu Ala Arg Arg Ala Val Gln Glu Tyr Ile Ile Thr Ala Ile Lys Glu
965 970 975
Val Leu Arg Ile His Phe Asn Arg Ala Val Glu Leu Lys Val Tyr Glu
980 985 990
Leu Phe Thr Asp Phe Thr Phe Leu Val Thr Ser Gly Pro Phe Val Tyr
995 1000 1005
Thr Ala Ile Ser Val Ile Asn Val Leu Ile Asn Ser Lys Leu Val
1010 1015 1020
Arg Asp Gln Thr Pro Leu Ile Leu Ser Val Lys Pro Ser Phe Leu
1025 1030 1035
Val Pro Glu Ser Arg Phe Gln Val Gln Thr Val Leu Gln Phe Val
1040 1045 1050
Pro Pro Ser Val Asp Thr Gly Phe Cys Asn Phe Thr Gln Arg Ile
1055 1060 1065
Glu Lys Gly Leu Met Thr Ala Leu Phe Glu Val Arg Lys His His
1070 1075 1080
Gln Gly Thr Tyr Asn Leu Thr Val Gln Ile Leu Asn Ile Thr Ile
1085 1090 1095
Ser Ser Ser Arg Val Thr Pro Arg Arg Gly Pro Val Asn Ile Ile
1100 1105 1110
Phe Ala Val Lys Ser Thr Gln Gly Phe Leu Asn Gly Ser Glu Val
1115 1120 1125
Ser Glu Leu Leu Arg Asn Leu Ser Val Val Glu Phe Ser Phe Tyr
1130 1135 1140
Leu Gly Tyr Pro Val Leu Gln Ile Ala Glu Pro Phe Gln Tyr Pro
1145 1150 1155
Gln Leu Asn Leu Ser Gln Leu Leu Lys Ser Ser Trp Val Arg Thr
1160 1165 1170
Val Leu Leu Gly Val Met Glu Lys Gln Leu Gln Asn Glu Val Phe
1175 1180 1185
Gln Ala Glu Met Glu Arg Lys Leu Ala Gln Leu Leu Ser Glu Val
1190 1195 1200
Ser Thr Arg Arg Arg Met Trp Arg Arg Ala Thr Val Ala Ala Gly
1205 1210 1215
Asn Ser Val Val Gln Val Val Asn Val Ser Arg Leu Glu Gly Asp
1220 1225 1230
Asp Asn Pro Val Gln Leu Ile Tyr Phe Val Glu Asp Gln Asp Gly
1235 1240 1245
Glu Arg Leu Ser Ala Val Lys Ser Ser Asp Leu Ile Asn Lys Met
1250 1255 1260
Asp Leu Gln Arg Ala Ala Ile Ile Leu Gly Tyr Arg Ile Gln Gly
1265 1270 1275
Val Ile Ala Gln Pro Val Asp Arg Val Lys Arg Pro Ser Pro Glu
1280 1285 1290
Ser Gln Ser Asn Asn Leu Trp Val Ile Val Gly Val Val Ile Pro
1295 1300 1305
Val Leu Val Val Met Val Ile Val Val Ile Leu Tyr Trp Lys Leu
1310 1315 1320
Cys Arg Thr Asp Lys Leu Asp Phe Gln Pro Asp Thr Val Ala Asn
1325 1330 1335
Ile Gln Gln Arg Gln Lys Leu Gln Ile Pro Ser Val Lys Gly Phe
1340 1345 1350
Asp Phe Ala Lys Gln His Leu Gly Gln His Asn Lys Asp Asp Ile
1355 1360 1365
Leu Ile Ile His Glu Pro Ala Pro Leu Pro Gly Pro Leu Lys Asp
1370 1375 1380
His Thr Thr Pro Ser Glu Asn Gly Asp Val Pro Ser Pro Lys Ser
1385 1390 1395
Lys Ile Pro Ser Lys Asn Val Arg His Arg Gly Arg Val Ser Pro
1400 1405 1410
Ser Asp Ala Asp Ser Thr Val Ser Glu Glu Ser Ser Glu Arg Asp
1415 1420 1425
Ala Gly Asp Lys Thr Pro Gly Ala Val Asn Asp Gly Arg Ser His
1430 1435 1440
Arg Ala Pro Gln Ser Gly Pro Pro Leu Pro Ser Ser Gly Asn Glu
1445 1450 1455
Gln His Ser Ser Ala Ser Ile Phe Glu His Val Asp Arg Ile Ser
1460 1465 1470
Arg Pro Pro Glu Ala Ser Arg Arg Val Pro Ser Lys Ile Gln Leu
1475 1480 1485
Ile Ala Met Gln Pro Ile Pro Ala Pro Pro Val Gln Arg Pro Ser
1490 1495 1500
Pro Ala Asp Arg Val Ala Glu Ser Asn Lys Ile Asn Lys Glu Ile
1505 1510 1515
Gln Thr Ala Leu Arg His Lys Ser Glu Ile Glu His His Arg Asn
1520 1525 1530
Lys Ile Arg Leu Arg Ala Lys Arg Arg Gly His Tyr Glu Phe Pro
1535 1540 1545
Val Val Asp Asp Leu Ser Ser Gly Asp Thr Lys Glu Arg His Arg
1550 1555 1560
Val Tyr Arg Arg Ala Gln Met Gln Ile Asp Lys Ile Leu Asp Pro
1565 1570 1575
Thr Ala Ser Val Pro Ser Val Phe Ile Glu Pro Arg Lys Ser Ser
1580 1585 1590
Arg Ile Lys Arg Ser Pro Lys Pro Arg Arg Lys His Gln Val Asn
1595 1600 1605
Gly Cys Pro Ala Asp Ala Glu Lys Asp Arg Leu Ile Thr Thr Asp
1610 1615 1620
Ser Asp Gly Thr Tyr Arg Arg Pro Pro Gly Val His Asn Ser Ala
1625 1630 1635
Tyr Ile Gly Cys Pro Ser Asp Pro Asp Leu Pro Ala Asp Val Gln
1640 1645 1650
Thr Pro Ser Ser Val Glu Leu Gly Arg Tyr Pro Ala Leu Pro Phe
1655 1660 1665
Pro Ala Ser Gln Tyr Ile Pro Pro Gln Pro Ser Ile Glu Glu Ala
1670 1675 1680
Arg Gln Thr Met His Ser Leu Leu Asp Asp Ala Phe Ala Leu Val
1685 1690 1695
Ala Pro Ser Ser Gln Pro Ala Ser Thr Ala Gly Val Gly Pro Gly
1700 1705 1710
Val Pro Pro Gly Leu Pro Ala Asn Ser Thr Pro Ser Gln Glu Glu
1715 1720 1725
Arg Arg Ala Thr Gln Trp Gly Ser Phe Tyr Ser Pro Ala Gln Thr
1730 1735 1740
Ala Asn Asn Pro Cys Ser Arg Tyr Glu Asp Tyr Gly Met Thr Pro
1745 1750 1755
Pro Thr Gly Pro Leu Pro Arg Pro Gly Phe Gly Pro Gly Leu Leu
1760 1765 1770
Gln Ser Thr Glu Leu Val Pro Pro Asp Pro Gln Gln Pro Gln Ala
1775 1780 1785
Ser Ala Glu Ala Pro Phe Ala Ala Arg Gly Ile Tyr Ser Glu Glu
1790 1795 1800
Met Pro Ser Val Ala Arg Pro Arg Pro Val Gly Gly Thr Thr Gly
1805 1810 1815
Ser Gln Ile Gln His Leu Thr Gln Val Gly Ile Ala Ser Arg Ile
1820 1825 1830
Gly Ala Gln Pro Val Glu Ile Pro Pro Ser Arg Gly Ser Gln Tyr
1835 1840 1845
Gly Gly Pro Gly Trp Pro Ser Tyr Gly Glu Asp Glu Ala Gly Arg
1850 1855 1860
Arg Glu Ala Thr His Met Leu Gly His Gln Glu Tyr Ser Ser Ser
1865 1870 1875
Pro Leu Phe Gln Val Pro Arg Thr Ser Gly Arg Glu Pro Ser Ala
1880 1885 1890
Pro Ser Gly Asn Leu Pro His Arg Gly Leu Gln Gly Pro Gly Leu
1895 1900 1905
Gly Tyr Pro Thr Ser Ser Thr Glu Asp Leu Gln Pro Gly His Ser
1910 1915 1920
Ser Ala Ser Leu Ile Lys Ala Ile Arg Glu Glu Leu Leu Arg Leu
1925 1930 1935
Ser Gln Lys Gln Ser Thr Val Gln Asn Phe His Ser
1940 1945 1950
<210> 11
<211> 8240
<212> DNA
<213> Homo sapiens
<400> 11
cccctctcgg tagccctgag gctctggcgc cttcaagtga gaagctaagc accagcctct 60
gctgggctgc agaagcggcg gcggcggcag cagcagcagc agcatcagga aggcgctcgg 120
gccagcgcgg tgaacccggg ctgggcagca ggtcgcggag ccgcgagcca ggatggaggc 180
agagggcagc agcgcgccgg cccgggcggg cagcggagag ggcagcgaca gcgccggcgg 240
ggccacgctc aaagccccca agcatctctg gaggcacgag cagcaccacc agtacccgct 300
ccggcagccc cagttccgcc tcctgcatcc ccatcaccac ctgcccccgc cgccgccacc 360
ctcgccccag ccccagcccc agtgtccgct acagccgccg ccgccgcccc ccctgccgcc 420
gcccccgccg ccgcccgggg ctgcccgcgg ccgctacgcc tcgagcgggg ccaccggccg 480
cgtccggcat cgcggctact cggacaccga gcgctacctg tactgtcgcg ccatggaccg 540
cacctcctac gcggtggaga ccggccaccg gcccggcctg aagaaatcca ggatgtcctg 600
gccctcctcg ttccagggac tcaggcgttt tgatgtggac aatggcacat ctgcgggacg 660
gagtcccttg gatcccatga ccagcccagg atccgggcta attctccaag caaattttgt 720
ccacagtcaa cgacgggagt ccttcctgta tcgatccgac agcgattatg acctctctcc 780
aaagtctatg tcccggaact cctccattgc cagtgatata cacggagatg acttgattgt 840
gactccattt gctcaggtct tggccagtct gcgaactgta cgaaacaact ttgctgcatt 900
aactaatttg caagatcgag cacctagcaa aagatcaccc atgtgcaacc aaccatccat 960
caacaaagcc accataacag aggaggccta ccagaaactg gccagcgaga ccctggagga 1020
gctggactgg tgtctggacc agctagagac cctacagacc aggcactccg tcagtgagat 1080
ggcctccaac aagtttaaaa ggatgcttaa tcgggagctc acccatctct ctgaaatgag 1140
tcggtctgga aatcaagtgt cagagtttat atcaaacaca ttcttagata agcaacatga 1200
agtggaaatt ccttctccaa ctcagaagga aaaggagaaa aagaaaagac caatgtctca 1260
gatcagtgga gtcaagaaat tgatgcacag ctctagtctg actaattcaa gtatcccaag 1320
gtttggagtt aaaactgaac aagaagatgt ccttgccaag gaactagaag atgtgaacaa 1380
atggggtctt catgttttca gaatagcaga gttgtctggt aaccggccct tgactgttat 1440
catgcacacc atttttcagg aacgggattt attaaaaaca tttaaaattc cagtagatac 1500
tttaattaca tatcttatga ctctcgaaga ccattaccat gctgatgtgg cctatcacaa 1560
caatatccat gctgcagatg ttgtccagtc tactcatgtg ctattatcta cacctgcttt 1620
ggaggctgtg tttacagatt tggagattct tgcagcaatt tttgccagtg caatacatga 1680
tgtagatcat cctggtgtgt ccaatcaatt tctgatcaat acaaactctg aacttgcctt 1740
gatgtacaat gattcctcag tcttagagaa ccatcatttg gctgtgggct ttaaattgct 1800
tcaggaagaa aactgtgaca ttttccagaa tttgaccaaa aaacaaagac aatctttaag 1860
gaaaatggtc attgacatcg tacttgcaac agatatgtca aaacacatga atctactggc 1920
tgatttgaag actatggttg aaactaagaa agtgacaagc tctggagttc ttcttcttga 1980
taattattcc gataggattc aggttcttca gaatatggtg cactgtgcag atctgagcaa 2040
cccaacaaag cctctccagc tgtaccgcca gtggacggac cggataatgg aggagttctt 2100
ccgccaagga gaccgagaga gggaacgtgg catggagata agccccatgt gtgacaagca 2160
caatgcttcc gtggaaaaat cacaggtggg cttcatagac tatattgttc atcccctctg 2220
ggagacatgg gcagacctcg tccaccctga cgcccaggat attttggaca ctttggagga 2280
caatcgtgaa tggtaccaga gcacaatccc tcagagcccc tctcctgcac ctgatgaccc 2340
agaggagggc cggcagggtc aaactgagaa attccagttt gaactaactt tagaggaaga 2400
tggtgagtca gacacggaaa aggacagtgg cagtcaagtg gaagaagaca ctagctgcag 2460
tgactccaag actctttgta ctcaagactc agagtctact gaaattcccc ttgatgaaca 2520
ggttgaagag gaggcagtag gggaagaaga ggaaagccag cctgaagcct gtgtcataga 2580
tgatcgttct cctgacacgt aacagtgcaa aaactttcat gccttttttt tttttaagta 2640
gaaaaattgt ttccaaagtg catgtcacat gccacaacca cggtcacacc tcactgtcat 2700
ctgccaggac gtttgttgaa caaaactgac cttgactact cagtccagcg ctcaggaata 2760
tcgtaaccag ttttttcacc tccatgtcat ccgagcaagg tggacatctt cacgaacagc 2820
gtttttaaca agatttcagc ttggtagagc tgacaaagca gataaaatct actccaaatt 2880
attttcaaga gagtgtgact catcaggcag cccaaaagtt tattggactt ggggtttcta 2940
ttccttttta tttgtttgca atattttcag aagaaaggca ttgcacagag tgaacttaat 3000
ggacgaagca acaaatatgt caagaacagg acatagcacg aatctgttac cagtaggagg 3060
aggatgagcc acagaaattg cataattttc taatttcaag tcttcctgat acatgactga 3120
atagtgtggt tcagtgagct gcactgacct ctacattttg tatgatatgt aaaacagatt 3180
ttttgtagag cttactttta ttattaaatg tattgaggta ttatatttaa aaaaaactat 3240
gttcagaact tcatctgcca ctggttattt ttttctaagg agtaacttgc aagttttcag 3300
tacaaatctg tgctacactg gataaaaatc taatttatga attttacttg caccttatag 3360
ttcatagcaa ttaactgatt tgtagtgatt cattgtttgt tttatatacc aatgacttcc 3420
atattttaaa agagaaaaac aactttatgt tgcaggaaac cctttttgta agtctttatt 3480
atttactttg cattttgttt cactctttcc agataagcag agttgctctt caccagtgtt 3540
tttcttcatg tgcaaagtga ctatttgttc tataatactt ttatgtgtgt tatatcaaat 3600
gtgtcttaag cttcatgcaa actcagtcat cagttcgtgt tgtctgaagc aagtgggaga 3660
tatataaata cccagtagct aaaatggtca gtctttttta gatgttttcc tacttagtat 3720
ctcctaataa cgttttgctg tgtcactaga tgttcatttc acaagtgcat gtctttctaa 3780
taatccacac atttcatgct ctaataatcc acacatttca tgctcatttt tattgttttt 3840
acagccagtt atagtaagaa aaaggttttt ccccttgtgc tgctttataa tttagcgtgt 3900
gtctgaacct tatccatgtt tgctagatga ggtcttgtca aatatatcac taccattgtc 3960
accggtgaaa agaaacaggt agttaagtta gggttaacat tcatttcaac cacgaggttg 4020
tatatcatga ctagctttta ctcttggttt acagagaaaa gttaaacagc caactaggca 4080
gtttttaaga atattaacaa tatattaaca aacaccaata caactaatcc tatttggttt 4140
taatgatttc accatgggat taagaactat atcaggaaca tccctgagaa acggttttaa 4200
gtgtagcaac tactcttcct taatggacag ccacataacg tgtaggaagt cctttatcac 4260
ttatcctcga tccataagca tatcttgcag aggggaacta cttctttaaa cacatggagg 4320
gaaagaagat gatgccactg gcaccagagg gttagtactg tgatgcatcc taaaatattt 4380
attatattgg taaaaattct ggttaaataa aaaattagag atcactcttg gctgatttca 4440
gcaccaggaa ctgtattaca gttttagaga ttaattccta gtgtttacct gattatagca 4500
gttggcatca tggggcattt aattctgact ttatccccac gtcagcctta ataaagtctt 4560
ctttaccttc tctatgaaga ctttaaagcc caaataatca tttttcacat tgatattcaa 4620
gaattgagat agatagaagc caaagtgggt atctgacaag tggaaaatca aacgtttaag 4680
aagaattaca actctgaaaa gcatttatat gtggaacttc tcaaggagcc tcctggggac 4740
tggaaagtaa gtcatcagcc aggcaaatga ctcatgctga agagagtccc catttcagtc 4800
ccctgagatc tagctgatgc ttagatcctt tgaaataaaa attatgtctt tataactctg 4860
atcttttaca taaagcagaa gaggaatcaa ctagttaatt gcaaggtttc tactctgttt 4920
cctctgtaaa gatcagatgg taatctttca aataagaaaa aaataaagac gtatgtttga 4980
ccaagtagtt tcacaagaat atttgggaac ttgtttcttt taattttatt tgtccctgag 5040
tgaagtctag aaagaaaggt aaagagtcta gagtttattc ctctttccaa aacattctca 5100
ttcctctcct ccctacactt agtatttccc ccacagagtg cctagaatct taataatgaa 5160
taaaataaaa agcagcaata tgtcattaac aaatccagac ctgaaagggt aaagggttta 5220
taactgcact aataaagaga ggctcttttt ttttcttcca gtttgttggt ttttaatggt 5280
accgtgttgt aaagataccc actaatggac aatcaaattg cagaaaaggc tcaatatcca 5340
agagacaggg actaatgcac tgtacaatct gcttatcctt gcccttctct cttgccaaag 5400
tgtgcttcag aaatatatac tgctttaaaa aagaataaaa gaatatcctt ttacaagtgg 5460
ctttacattt cctaaaatgc cataagaaaa tgcaatatct gggtactgta tggggaaaaa 5520
aatgtccaag tttgtgtaaa accagtgcat ttcagcttgc aagttactga acacaataat 5580
gctgttttaa ttttgtttta tatcagttaa aattcacaat aatgtagata gaacaaatta 5640
cagacaagga aagaaaaaac ttgaatgaaa tggattttac agaaagcttt atgataattt 5700
ttgaatgcat tatttatttt ttgtgccatg catttttttt ctcaccaaat gaccttacct 5760
gtaatacagt cttgtttgtc tgtttacaac catgtattta ttgcaatgta catactgtaa 5820
tgttaattgt aaattatctg ttcttattaa aacatcatcc catgatggga tggtgttgat 5880
atatttggaa actcttggtg agagaatgaa tggtgtgtat acatactctg tacatttttc 5940
ttttctcctg taatatagtc ttgtcacctt agagcttgtt tatggaagat tcaagaaaac 6000
tataaaatac ttaaagatat ataaatttaa aaaaacatag ctgcaggtct ttggtcccag 6060
ggctgtgcct taactttaac caatattttc ttctgttttg ctgcatttga aaggtaacag 6120
tggagctagg gctgggcatt ttacatccag gcttttaatt gattagaatt ctgccaatag 6180
gtggatttta caaaaccaca gacaacctct gaaagattct gagacccttt tgagacagaa 6240
gctcttaagt acttcttgcc agggagcagc actgcatgtg tgatggttgt ttgccatctg 6300
ttgatcagga actacttcag ctacttgcat ttgattattt cctttttttt tttttttaac 6360
tcggaaacac aactggggaa atatattctt tcccagtgat tataaacaat ctttttcttt 6420
tttttaagtc cttttggctt ctagagctca taggaaaatg gacttgattt gaaattggag 6480
ccagagttta ctcgtgttgg ttatctattc atcagcttcc tgacatgtta agagaataca 6540
ttaaagagaa aatactgttt tttaatccta aaatttttct tccactaaga taaaccaaat 6600
gtccttacat atatgtaaac ccatctattt aaacgcaaag gtgggttgat gtcagtttac 6660
atagcagaaa gcattcacta tcctctaaga tttgtttctg caaaactttc attgctttag 6720
aattttaaaa tttcaccttg tacaatggcc agcccctaaa gcaggaaaca tttataatgg 6780
attatatgga aacatcctcc cagtacttgc ccagcccttg aatcatgtgg cttttcagtg 6840
aaaggaaaga ttctttttct aggaaaaatg agcctatttt attttatttt attttatttt 6900
ttgacacaaa ctgtagattt tagcagccct ggcccaaagg aatttgatta cttttgtttt 6960
aaacagtaca aaggggacac tataattaca aaaacatcct taactgattt gagttgtttt 7020
tatttctttg gatatatttt cagagtggta aattgtgtgt gagaattaca aatgattatt 7080
cttttagtgg tttcttagcc tctcttacag cccacgggga tagtactgta catcaatacc 7140
ttcatatgaa atttttatat gcaatgaaaa taaaagcatg ggttgattct gcctatttat 7200
gactcaatct tttacaaata aaagattatt cattttaaat tatagttcaa tcagcatgtc 7260
tcttaggata ctgaacgtgg ttgaaatgaa aggatagtga catcataagt tagtactgat 7320
attcataacc aaataaagcc aacttgagta attttgctac attaaaaatt accaaaatta 7380
cttagatggc ctataagatt aagcatggtg ttttctaagc aagctttgaa aggggccttc 7440
catacttact taattgaata ttctgggata ttgaaaatta ttcagatact tgacaattat 7500
ttttggttac ctactccgca aactacaaag ttttaaggac tcaacaataa gttaatgaga 7560
cacagtgttt gctttcatgg agcttacagt ctggagggga caaaggctta aacaatactc 7620
atataattat atatgtgatc agtacaatga aggagctcag tggggtaaat aagcaggaac 7680
ctgaacttga tctgttccgg agggccacag aaggcttcct tgaggccttg agaaagtgat 7740
ttgcatctga gttctgaagg attgtaagag gtaactaggg aaaaagttga caggaagagg 7800
aaggggatcc agacaagaaa catttgcaaa gatcttgagg cataaatgag cttgagacat 7860
ctggagaaac tgaggaaaag tgagagagta ggcagggcct ggagccgcag agccattgct 7920
aaccatcctg tgtgagatat cccccattct gtagctttat tctcataacc ctgctcaatt 7980
ttctttataa cacttctcac agatttatat acgtgtttgt ttttgttatc tgtctctccc 8040
accagaccac agctccatga gagcaaggtc tttgcttacc aatatatcac tagcacttaa 8100
aactatgcct ggtacacagt aggttcttaa tatgtgttga atatagccat caaattgata 8160
ttggatataa ttcaatctga taagatattt tgagatatta aagagttttt aacttgatac 8220
cataaaaaaa aaaaaaaaaa 8240
<210> 12
<211> 8153
<212> DNA
<213> Homo sapiens
<400> 12
aatacttgtt gcaataattg cccacgatag ctgctcaaac aagagagttg gaattcatct 60
gtaaaaatca ctacatgtaa cgtaggagac aagaaaaata ttaatgacag aagatctgcg 120
aacatgatgc acgtgaataa ttttcccttt agaaggcatt cctggatatg ctgatggtaa 180
cagcagaaaa atgtgaactc tgaataaaga ggtgggagtt tttcagcaca taaagaatat 240
ttaaagccaa ttcattggat gcattgacca gtaagtgtag agatcaaaat caagaacaac 300
tccaagaatt gagagcagat gcaaacccca atttttgtgg gtctccagtc cagccttccc 360
aggaatgctg gtctgactac tcagatttgc ttttacttct tgccttttgg atataatgag 420
tttgccaagc agctgtgagt acctgactct ggggaaggtg gctagattcc gaagcgctta 480
tgttcatgga tcaccatacg cgatcaacat gccaattgat attaagccac agaggagacg 540
ttttgatgtg gacaatggca catctgcggg acggagtccc ttggatccca tgaccagccc 600
aggatccggg ctaattctcc aagcaaattt tgtccacagt caacgacggg agtccttcct 660
gtatcgatcc gacagcgatt atgacctctc tccaaagtct atgtcccgga actcctccat 720
tgccagtgat atacacggag atgacttgat tgtgactcca tttgctcagg tcttggccag 780
tctgcgaact gtacgaaaca actttgctgc attaactaat ttgcaagatc gagcacctag 840
caaaagatca cccatgtgca accaaccatc catcaacaaa gccaccataa cagaggaggc 900
ctaccagaaa ctggccagcg agaccctgga ggagctggac tggtgtctgg accagctaga 960
gaccctacag accaggcact ccgtcagtga gatggcctcc aacaagttta aaaggatgct 1020
taatcgggag ctcacccatc tctctgaaat gagtcggtct ggaaatcaag tgtcagagtt 1080
tatatcaaac acattcttag ataagcaaca tgaagtggaa attccttctc caactcagaa 1140
ggaaaaggag aaaaagaaaa gaccaatgtc tcagatcagt ggagtcaaga aattgatgca 1200
cagctctagt ctgactaatt caagtatccc aaggtttgga gttaaaactg aacaagaaga 1260
tgtccttgcc aaggaactag aagatgtgaa caaatggggt cttcatgttt tcagaatagc 1320
agagttgtct ggtaaccggc ccttgactgt tatcatgcac accatttttc aggaacggga 1380
tttattaaaa acatttaaaa ttccagtaga tactttaatt acatatctta tgactctcga 1440
agaccattac catgctgatg tggcctatca caacaatatc catgctgcag atgttgtcca 1500
gtctactcat gtgctattat ctacacctgc tttggaggct gtgtttacag atttggagat 1560
tcttgcagca atttttgcca gtgcaataca tgatgtagat catcctggtg tgtccaatca 1620
atttctgatc aatacaaact ctgaacttgc cttgatgtac aatgattcct cagtcttaga 1680
gaaccatcat ttggctgtgg gctttaaatt gcttcaggaa gaaaactgtg acattttcca 1740
gaatttgacc aaaaaacaaa gacaatcttt aaggaaaatg gtcattgaca tcgtacttgc 1800
aacagatatg tcaaaacaca tgaatctact ggctgatttg aagactatgg ttgaaactaa 1860
gaaagtgaca agctctggag ttcttcttct tgataattat tccgatagga ttcaggttct 1920
tcagaatatg gtgcactgtg cagatctgag caacccaaca aagcctctcc agctgtaccg 1980
ccagtggacg gaccggataa tggaggagtt cttccgccaa ggagaccgag agagggaacg 2040
tggcatggag ataagcccca tgtgtgacaa gcacaatgct tccgtggaaa aatcacaggt 2100
gggcttcata gactatattg ttcatcccct ctgggagaca tgggcagacc tcgtccaccc 2160
tgacgcccag gatattttgg acactttgga ggacaatcgt gaatggtacc agagcacaat 2220
ccctcagagc ccctctcctg cacctgatga cccagaggag ggccggcagg gtcaaactga 2280
gaaattccag tttgaactaa ctttagagga agatggtgag tcagacacgg aaaaggacag 2340
tggcagtcaa gtggaagaag acactagctg cagtgactcc aagactcttt gtactcaaga 2400
ctcagagtct actgaaattc cccttgatga acaggttgaa gaggaggcag taggggaaga 2460
agaggaaagc cagcctgaag cctgtgtcat agatgatcgt tctcctgaca cgtaacagtg 2520
caaaaacttt catgcctttt ttttttttaa gtagaaaaat tgtttccaaa gtgcatgtca 2580
catgccacaa ccacggtcac acctcactgt catctgccag gacgtttgtt gaacaaaact 2640
gaccttgact actcagtcca gcgctcagga atatcgtaac cagttttttc acctccatgt 2700
catccgagca aggtggacat cttcacgaac agcgttttta acaagatttc agcttggtag 2760
agctgacaaa gcagataaaa tctactccaa attattttca agagagtgtg actcatcagg 2820
cagcccaaaa gtttattgga cttggggttt ctattccttt ttatttgttt gcaatatttt 2880
cagaagaaag gcattgcaca gagtgaactt aatggacgaa gcaacaaata tgtcaagaac 2940
aggacatagc acgaatctgt taccagtagg aggaggatga gccacagaaa ttgcataatt 3000
ttctaatttc aagtcttcct gatacatgac tgaatagtgt ggttcagtga gctgcactga 3060
cctctacatt ttgtatgata tgtaaaacag attttttgta gagcttactt ttattattaa 3120
atgtattgag gtattatatt taaaaaaaac tatgttcaga acttcatctg ccactggtta 3180
tttttttcta aggagtaact tgcaagtttt cagtacaaat ctgtgctaca ctggataaaa 3240
atctaattta tgaattttac ttgcacctta tagttcatag caattaactg atttgtagtg 3300
attcattgtt tgttttatat accaatgact tccatatttt aaaagagaaa aacaacttta 3360
tgttgcagga aacccttttt gtaagtcttt attatttact ttgcattttg tttcactctt 3420
tccagataag cagagttgct cttcaccagt gtttttcttc atgtgcaaag tgactatttg 3480
ttctataata cttttatgtg tgttatatca aatgtgtctt aagcttcatg caaactcagt 3540
catcagttcg tgttgtctga agcaagtggg agatatataa atacccagta gctaaaatgg 3600
tcagtctttt ttagatgttt tcctacttag tatctcctaa taacgttttg ctgtgtcact 3660
agatgttcat ttcacaagtg catgtctttc taataatcca cacatttcat gctctaataa 3720
tccacacatt tcatgctcat ttttattgtt tttacagcca gttatagtaa gaaaaaggtt 3780
tttccccttg tgctgcttta taatttagcg tgtgtctgaa ccttatccat gtttgctaga 3840
tgaggtcttg tcaaatatat cactaccatt gtcaccggtg aaaagaaaca ggtagttaag 3900
ttagggttaa cattcatttc aaccacgagg ttgtatatca tgactagctt ttactcttgg 3960
tttacagaga aaagttaaac agccaactag gcagttttta agaatattaa caatatatta 4020
acaaacacca atacaactaa tcctatttgg ttttaatgat ttcaccatgg gattaagaac 4080
tatatcagga acatccctga gaaacggttt taagtgtagc aactactctt ccttaatgga 4140
cagccacata acgtgtagga agtcctttat cacttatcct cgatccataa gcatatcttg 4200
cagaggggaa ctacttcttt aaacacatgg agggaaagaa gatgatgcca ctggcaccag 4260
agggttagta ctgtgatgca tcctaaaata tttattatat tggtaaaaat tctggttaaa 4320
taaaaaatta gagatcactc ttggctgatt tcagcaccag gaactgtatt acagttttag 4380
agattaattc ctagtgttta cctgattata gcagttggca tcatggggca tttaattctg 4440
actttatccc cacgtcagcc ttaataaagt cttctttacc ttctctatga agactttaaa 4500
gcccaaataa tcatttttca cattgatatt caagaattga gatagataga agccaaagtg 4560
ggtatctgac aagtggaaaa tcaaacgttt aagaagaatt acaactctga aaagcattta 4620
tatgtggaac ttctcaagga gcctcctggg gactggaaag taagtcatca gccaggcaaa 4680
tgactcatgc tgaagagagt ccccatttca gtcccctgag atctagctga tgcttagatc 4740
ctttgaaata aaaattatgt ctttataact ctgatctttt acataaagca gaagaggaat 4800
caactagtta attgcaaggt ttctactctg tttcctctgt aaagatcaga tggtaatctt 4860
tcaaataaga aaaaaataaa gacgtatgtt tgaccaagta gtttcacaag aatatttggg 4920
aacttgtttc ttttaatttt atttgtccct gagtgaagtc tagaaagaaa ggtaaagagt 4980
ctagagttta ttcctctttc caaaacattc tcattcctct cctccctaca cttagtattt 5040
cccccacaga gtgcctagaa tcttaataat gaataaaata aaaagcagca atatgtcatt 5100
aacaaatcca gacctgaaag ggtaaagggt ttataactgc actaataaag agaggctctt 5160
tttttttctt ccagtttgtt ggtttttaat ggtaccgtgt tgtaaagata cccactaatg 5220
gacaatcaaa ttgcagaaaa ggctcaatat ccaagagaca gggactaatg cactgtacaa 5280
tctgcttatc cttgcccttc tctcttgcca aagtgtgctt cagaaatata tactgcttta 5340
aaaaagaata aaagaatatc cttttacaag tggctttaca tttcctaaaa tgccataaga 5400
aaatgcaata tctgggtact gtatggggaa aaaaatgtcc aagtttgtgt aaaaccagtg 5460
catttcagct tgcaagttac tgaacacaat aatgctgttt taattttgtt ttatatcagt 5520
taaaattcac aataatgtag atagaacaaa ttacagacaa ggaaagaaaa aacttgaatg 5580
aaatggattt tacagaaagc tttatgataa tttttgaatg cattatttat tttttgtgcc 5640
atgcattttt tttctcacca aatgacctta cctgtaatac agtcttgttt gtctgtttac 5700
aaccatgtat ttattgcaat gtacatactg taatgttaat tgtaaattat ctgttcttat 5760
taaaacatca tcccatgatg ggatggtgtt gatatatttg gaaactcttg gtgagagaat 5820
gaatggtgtg tatacatact ctgtacattt ttcttttctc ctgtaatata gtcttgtcac 5880
cttagagctt gtttatggaa gattcaagaa aactataaaa tacttaaaga tatataaatt 5940
taaaaaaaca tagctgcagg tctttggtcc cagggctgtg ccttaacttt aaccaatatt 6000
ttcttctgtt ttgctgcatt tgaaaggtaa cagtggagct agggctgggc attttacatc 6060
caggctttta attgattaga attctgccaa taggtggatt ttacaaaacc acagacaacc 6120
tctgaaagat tctgagaccc ttttgagaca gaagctctta agtacttctt gccagggagc 6180
agcactgcat gtgtgatggt tgtttgccat ctgttgatca ggaactactt cagctacttg 6240
catttgatta tttccttttt tttttttttt aactcggaaa cacaactggg gaaatatatt 6300
ctttcccagt gattataaac aatctttttc ttttttttaa gtccttttgg cttctagagc 6360
tcataggaaa atggacttga tttgaaattg gagccagagt ttactcgtgt tggttatcta 6420
ttcatcagct tcctgacatg ttaagagaat acattaaaga gaaaatactg ttttttaatc 6480
ctaaaatttt tcttccacta agataaacca aatgtcctta catatatgta aacccatcta 6540
tttaaacgca aaggtgggtt gatgtcagtt tacatagcag aaagcattca ctatcctcta 6600
agatttgttt ctgcaaaact ttcattgctt tagaatttta aaatttcacc ttgtacaatg 6660
gccagcccct aaagcaggaa acatttataa tggattatat ggaaacatcc tcccagtact 6720
tgcccagccc ttgaatcatg tggcttttca gtgaaaggaa agattctttt tctaggaaaa 6780
atgagcctat tttattttat tttattttat tttttgacac aaactgtaga ttttagcagc 6840
cctggcccaa aggaatttga ttacttttgt tttaaacagt acaaagggga cactataatt 6900
acaaaaacat ccttaactga tttgagttgt ttttatttct ttggatatat tttcagagtg 6960
gtaaattgtg tgtgagaatt acaaatgatt attcttttag tggtttctta gcctctctta 7020
cagcccacgg ggatagtact gtacatcaat accttcatat gaaattttta tatgcaatga 7080
aaataaaagc atgggttgat tctgcctatt tatgactcaa tcttttacaa ataaaagatt 7140
attcatttta aattatagtt caatcagcat gtctcttagg atactgaacg tggttgaaat 7200
gaaaggatag tgacatcata agttagtact gatattcata accaaataaa gccaacttga 7260
gtaattttgc tacattaaaa attaccaaaa ttacttagat ggcctataag attaagcatg 7320
gtgttttcta agcaagcttt gaaaggggcc ttccatactt acttaattga atattctggg 7380
atattgaaaa ttattcagat acttgacaat tatttttggt tacctactcc gcaaactaca 7440
aagttttaag gactcaacaa taagttaatg agacacagtg tttgctttca tggagcttac 7500
agtctggagg ggacaaaggc ttaaacaata ctcatataat tatatatgtg atcagtacaa 7560
tgaaggagct cagtggggta aataagcagg aacctgaact tgatctgttc cggagggcca 7620
cagaaggctt ccttgaggcc ttgagaaagt gatttgcatc tgagttctga aggattgtaa 7680
gaggtaacta gggaaaaagt tgacaggaag aggaagggga tccagacaag aaacatttgc 7740
aaagatcttg aggcataaat gagcttgaga catctggaga aactgaggaa aagtgagaga 7800
gtaggcaggg cctggagccg cagagccatt gctaaccatc ctgtgtgaga tatcccccat 7860
tctgtagctt tattctcata accctgctca attttcttta taacacttct cacagattta 7920
tatacgtgtt tgtttttgtt atctgtctct cccaccagac cacagctcca tgagagcaag 7980
gtctttgctt accaatatat cactagcact taaaactatg cctggtacac agtaggttct 8040
taatatgtgt tgaatatagc catcaaattg atattggata taattcaatc tgataagata 8100
ttttgagata ttaaagagtt tttaacttga taccataaaa aaaaaaaaaa aaa 8153
<210> 13
<211> 8203
<212> DNA
<213> Homo sapiens
<400> 13
gcggcgcatt agttccaata gtttaacagg ctgctttgta gcacggacaa agccgtgcga 60
gcgcggtgct ttccctcctt gttcatttgc tatgcgagct tgtcagtgat ctttggcagg 120
ggcttgggag aggaggggtg acgtttaata cgcttccgcg gaggagtgcg ctcgcctcct 180
ctgcacccag ccccaggctc tacagagaga ctgaggcagg cgactgaatg cactaacagc 240
agcaggctca gacctgcttc cctggacatt tccgggaccg tgagcgaggg aaccacgttg 300
ccctggattc ttgccagctg tacaaagttg accaggaaaa tggctcagca gacaagcccg 360
gacactttaa cagtacctga agtggataat ccgcattgtc caaacccgtg gctgaacgaa 420
gaccttgtga aatccttgcg agaaaacctg ttgcagcatg agaagtccaa gacagcgagg 480
aaatcggttt ctcccaagct ctctccagtg atctctccga gaaattcccc caggcttctg 540
cgcagaatgc ttctcagcag caacatcccc aaacagcggc gtttcacggt ggcacataca 600
tgttttgatg tggacaatgg cacatctgcg ggacggagtc ccttggatcc catgaccagc 660
ccaggatccg ggctaattct ccaagcaaat tttgtccaca gtcaacgacg ggagtccttc 720
ctgtatcgat ccgacagcga ttatgacctc tctccaaagt ctatgtcccg gaactcctcc 780
attgccagtg atatacacgg agatgacttg attgtgactc catttgctca ggtcttggcc 840
agtctgcgaa ctgtacgaaa caactttgct gcattaacta atttgcaaga tcgagcacct 900
agcaaaagat cacccatgtg caaccaacca tccatcaaca aagccaccat aacagaggag 960
gcctaccaga aactggccag cgagaccctg gaggagctgg actggtgtct ggaccagcta 1020
gagaccctac agaccaggca ctccgtcagt gagatggcct ccaacaagtt taaaaggatg 1080
cttaatcggg agctcaccca tctctctgaa atgagtcggt ctggaaatca agtgtcagag 1140
tttatatcaa acacattctt agataagcaa catgaagtgg aaattccttc tccaactcag 1200
aaggaaaagg agaaaaagaa aagaccaatg tctcagatca gtggagtcaa gaaattgatg 1260
cacagctcta gtctgactaa ttcaagtatc ccaaggtttg gagttaaaac tgaacaagaa 1320
gatgtccttg ccaaggaact agaagatgtg aacaaatggg gtcttcatgt tttcagaata 1380
gcagagttgt ctggtaaccg gcccttgact gttatcatgc acaccatttt tcaggaacgg 1440
gatttattaa aaacatttaa aattccagta gatactttaa ttacatatct tatgactctc 1500
gaagaccatt accatgctga tgtggcctat cacaacaata tccatgctgc agatgttgtc 1560
cagtctactc atgtgctatt atctacacct gctttggagg ctgtgtttac agatttggag 1620
attcttgcag caatttttgc cagtgcaata catgatgtag atcatcctgg tgtgtccaat 1680
caatttctga tcaatacaaa ctctgaactt gccttgatgt acaatgattc ctcagtctta 1740
gagaaccatc atttggctgt gggctttaaa ttgcttcagg aagaaaactg tgacattttc 1800
cagaatttga ccaaaaaaca aagacaatct ttaaggaaaa tggtcattga catcgtactt 1860
gcaacagata tgtcaaaaca catgaatcta ctggctgatt tgaagactat ggttgaaact 1920
aagaaagtga caagctctgg agttcttctt cttgataatt attccgatag gattcaggtt 1980
cttcagaata tggtgcactg tgcagatctg agcaacccaa caaagcctct ccagctgtac 2040
cgccagtgga cggaccggat aatggaggag ttcttccgcc aaggagaccg agagagggaa 2100
cgtggcatgg agataagccc catgtgtgac aagcacaatg cttccgtgga aaaatcacag 2160
gtgggcttca tagactatat tgttcatccc ctctgggaga catgggcaga cctcgtccac 2220
cctgacgccc aggatatttt ggacactttg gaggacaatc gtgaatggta ccagagcaca 2280
atccctcaga gcccctctcc tgcacctgat gacccagagg agggccggca gggtcaaact 2340
gagaaattcc agtttgaact aactttagag gaagatggtg agtcagacac ggaaaaggac 2400
agtggcagtc aagtggaaga agacactagc tgcagtgact ccaagactct ttgtactcaa 2460
gactcagagt ctactgaaat tccccttgat gaacaggttg aagaggaggc agtaggggaa 2520
gaagaggaaa gccagcctga agcctgtgtc atagatgatc gttctcctga cacgtaacag 2580
tgcaaaaact ttcatgcctt tttttttttt aagtagaaaa attgtttcca aagtgcatgt 2640
cacatgccac aaccacggtc acacctcact gtcatctgcc aggacgtttg ttgaacaaaa 2700
ctgaccttga ctactcagtc cagcgctcag gaatatcgta accagttttt tcacctccat 2760
gtcatccgag caaggtggac atcttcacga acagcgtttt taacaagatt tcagcttggt 2820
agagctgaca aagcagataa aatctactcc aaattatttt caagagagtg tgactcatca 2880
ggcagcccaa aagtttattg gacttggggt ttctattcct ttttatttgt ttgcaatatt 2940
ttcagaagaa aggcattgca cagagtgaac ttaatggacg aagcaacaaa tatgtcaaga 3000
acaggacata gcacgaatct gttaccagta ggaggaggat gagccacaga aattgcataa 3060
ttttctaatt tcaagtcttc ctgatacatg actgaatagt gtggttcagt gagctgcact 3120
gacctctaca ttttgtatga tatgtaaaac agattttttg tagagcttac ttttattatt 3180
aaatgtattg aggtattata tttaaaaaaa actatgttca gaacttcatc tgccactggt 3240
tatttttttc taaggagtaa cttgcaagtt ttcagtacaa atctgtgcta cactggataa 3300
aaatctaatt tatgaatttt acttgcacct tatagttcat agcaattaac tgatttgtag 3360
tgattcattg tttgttttat ataccaatga cttccatatt ttaaaagaga aaaacaactt 3420
tatgttgcag gaaacccttt ttgtaagtct ttattattta ctttgcattt tgtttcactc 3480
tttccagata agcagagttg ctcttcacca gtgtttttct tcatgtgcaa agtgactatt 3540
tgttctataa tacttttatg tgtgttatat caaatgtgtc ttaagcttca tgcaaactca 3600
gtcatcagtt cgtgttgtct gaagcaagtg ggagatatat aaatacccag tagctaaaat 3660
ggtcagtctt ttttagatgt tttcctactt agtatctcct aataacgttt tgctgtgtca 3720
ctagatgttc atttcacaag tgcatgtctt tctaataatc cacacatttc atgctctaat 3780
aatccacaca tttcatgctc atttttattg tttttacagc cagttatagt aagaaaaagg 3840
tttttcccct tgtgctgctt tataatttag cgtgtgtctg aaccttatcc atgtttgcta 3900
gatgaggtct tgtcaaatat atcactacca ttgtcaccgg tgaaaagaaa caggtagtta 3960
agttagggtt aacattcatt tcaaccacga ggttgtatat catgactagc ttttactctt 4020
ggtttacaga gaaaagttaa acagccaact aggcagtttt taagaatatt aacaatatat 4080
taacaaacac caatacaact aatcctattt ggttttaatg atttcaccat gggattaaga 4140
actatatcag gaacatccct gagaaacggt tttaagtgta gcaactactc ttccttaatg 4200
gacagccaca taacgtgtag gaagtccttt atcacttatc ctcgatccat aagcatatct 4260
tgcagagggg aactacttct ttaaacacat ggagggaaag aagatgatgc cactggcacc 4320
agagggttag tactgtgatg catcctaaaa tatttattat attggtaaaa attctggtta 4380
aataaaaaat tagagatcac tcttggctga tttcagcacc aggaactgta ttacagtttt 4440
agagattaat tcctagtgtt tacctgatta tagcagttgg catcatgggg catttaattc 4500
tgactttatc cccacgtcag ccttaataaa gtcttcttta ccttctctat gaagacttta 4560
aagcccaaat aatcattttt cacattgata ttcaagaatt gagatagata gaagccaaag 4620
tgggtatctg acaagtggaa aatcaaacgt ttaagaagaa ttacaactct gaaaagcatt 4680
tatatgtgga acttctcaag gagcctcctg gggactggaa agtaagtcat cagccaggca 4740
aatgactcat gctgaagaga gtccccattt cagtcccctg agatctagct gatgcttaga 4800
tcctttgaaa taaaaattat gtctttataa ctctgatctt ttacataaag cagaagagga 4860
atcaactagt taattgcaag gtttctactc tgtttcctct gtaaagatca gatggtaatc 4920
tttcaaataa gaaaaaaata aagacgtatg tttgaccaag tagtttcaca agaatatttg 4980
ggaacttgtt tcttttaatt ttatttgtcc ctgagtgaag tctagaaaga aaggtaaaga 5040
gtctagagtt tattcctctt tccaaaacat tctcattcct ctcctcccta cacttagtat 5100
ttcccccaca gagtgcctag aatcttaata atgaataaaa taaaaagcag caatatgtca 5160
ttaacaaatc cagacctgaa agggtaaagg gtttataact gcactaataa agagaggctc 5220
tttttttttc ttccagtttg ttggttttta atggtaccgt gttgtaaaga tacccactaa 5280
tggacaatca aattgcagaa aaggctcaat atccaagaga cagggactaa tgcactgtac 5340
aatctgctta tccttgccct tctctcttgc caaagtgtgc ttcagaaata tatactgctt 5400
taaaaaagaa taaaagaata tccttttaca agtggcttta catttcctaa aatgccataa 5460
gaaaatgcaa tatctgggta ctgtatgggg aaaaaaatgt ccaagtttgt gtaaaaccag 5520
tgcatttcag cttgcaagtt actgaacaca ataatgctgt tttaattttg ttttatatca 5580
gttaaaattc acaataatgt agatagaaca aattacagac aaggaaagaa aaaacttgaa 5640
tgaaatggat tttacagaaa gctttatgat aatttttgaa tgcattattt attttttgtg 5700
ccatgcattt tttttctcac caaatgacct tacctgtaat acagtcttgt ttgtctgttt 5760
acaaccatgt atttattgca atgtacatac tgtaatgtta attgtaaatt atctgttctt 5820
attaaaacat catcccatga tgggatggtg ttgatatatt tggaaactct tggtgagaga 5880
atgaatggtg tgtatacata ctctgtacat ttttcttttc tcctgtaata tagtcttgtc 5940
accttagagc ttgtttatgg aagattcaag aaaactataa aatacttaaa gatatataaa 6000
tttaaaaaaa catagctgca ggtctttggt cccagggctg tgccttaact ttaaccaata 6060
ttttcttctg ttttgctgca tttgaaaggt aacagtggag ctagggctgg gcattttaca 6120
tccaggcttt taattgatta gaattctgcc aataggtgga ttttacaaaa ccacagacaa 6180
cctctgaaag attctgagac ccttttgaga cagaagctct taagtacttc ttgccaggga 6240
gcagcactgc atgtgtgatg gttgtttgcc atctgttgat caggaactac ttcagctact 6300
tgcatttgat tatttccttt tttttttttt ttaactcgga aacacaactg gggaaatata 6360
ttctttccca gtgattataa acaatctttt tctttttttt aagtcctttt ggcttctaga 6420
gctcatagga aaatggactt gatttgaaat tggagccaga gtttactcgt gttggttatc 6480
tattcatcag cttcctgaca tgttaagaga atacattaaa gagaaaatac tgttttttaa 6540
tcctaaaatt tttcttccac taagataaac caaatgtcct tacatatatg taaacccatc 6600
tatttaaacg caaaggtggg ttgatgtcag tttacatagc agaaagcatt cactatcctc 6660
taagatttgt ttctgcaaaa ctttcattgc tttagaattt taaaatttca ccttgtacaa 6720
tggccagccc ctaaagcagg aaacatttat aatggattat atggaaacat cctcccagta 6780
cttgcccagc ccttgaatca tgtggctttt cagtgaaagg aaagattctt tttctaggaa 6840
aaatgagcct attttatttt attttatttt attttttgac acaaactgta gattttagca 6900
gccctggccc aaaggaattt gattactttt gttttaaaca gtacaaaggg gacactataa 6960
ttacaaaaac atccttaact gatttgagtt gtttttattt ctttggatat attttcagag 7020
tggtaaattg tgtgtgagaa ttacaaatga ttattctttt agtggtttct tagcctctct 7080
tacagcccac ggggatagta ctgtacatca ataccttcat atgaaatttt tatatgcaat 7140
gaaaataaaa gcatgggttg attctgccta tttatgactc aatcttttac aaataaaaga 7200
ttattcattt taaattatag ttcaatcagc atgtctctta ggatactgaa cgtggttgaa 7260
atgaaaggat agtgacatca taagttagta ctgatattca taaccaaata aagccaactt 7320
gagtaatttt gctacattaa aaattaccaa aattacttag atggcctata agattaagca 7380
tggtgttttc taagcaagct ttgaaagggg ccttccatac ttacttaatt gaatattctg 7440
ggatattgaa aattattcag atacttgaca attatttttg gttacctact ccgcaaacta 7500
caaagtttta aggactcaac aataagttaa tgagacacag tgtttgcttt catggagctt 7560
acagtctgga ggggacaaag gcttaaacaa tactcatata attatatatg tgatcagtac 7620
aatgaaggag ctcagtgggg taaataagca ggaacctgaa cttgatctgt tccggagggc 7680
cacagaaggc ttccttgagg ccttgagaaa gtgatttgca tctgagttct gaaggattgt 7740
aagaggtaac tagggaaaaa gttgacagga agaggaaggg gatccagaca agaaacattt 7800
gcaaagatct tgaggcataa atgagcttga gacatctgga gaaactgagg aaaagtgaga 7860
gagtaggcag ggcctggagc cgcagagcca ttgctaacca tcctgtgtga gatatccccc 7920
attctgtagc tttattctca taaccctgct caattttctt tataacactt ctcacagatt 7980
tatatacgtg tttgtttttg ttatctgtct ctcccaccag accacagctc catgagagca 8040
aggtctttgc ttaccaatat atcactagca cttaaaacta tgcctggtac acagtaggtt 8100
cttaatatgt gttgaatata gccatcaaat tgatattgga tataattcaa tctgataaga 8160
tattttgaga tattaaagag tttttaactt gataccataa aaa 8203
<210> 14
<211> 7783
<212> DNA
<213> Homo sapiens
<400> 14
aatacttgtt gcaataattg cccacgatag ctgctcaaac aagagagttg gaattcatct 60
gtaaaaatca ctacatgtaa cgtaggagac aagaaaaata ttaatgacag aagatctgcg 120
aacatgatgc acgtgaataa ttttcccttt agaaggcatt cctggatatg ttttgatgtg 180
gacaatggca catctgcggg acggagtccc ttggatccca tgaccagccc aggatccggg 240
ctaattctcc aagcaaattt tgtccacagt caacgacggg agtccttcct gtatcgatcc 300
gacagcgatt atgacctctc tccaaagtct atgtcccgga actcctccat tgccagtgat 360
atacacggag atgacttgat tgtgactcca tttgctcagg tcttggccag tctgcgaact 420
gtacgaaaca actttgctgc attaactaat ttgcaagatc gagcacctag caaaagatca 480
cccatgtgca accaaccatc catcaacaaa gccaccataa cagaggaggc ctaccagaaa 540
ctggccagcg agaccctgga ggagctggac tggtgtctgg accagctaga gaccctacag 600
accaggcact ccgtcagtga gatggcctcc aacaagttta aaaggatgct taatcgggag 660
ctcacccatc tctctgaaat gagtcggtct ggaaatcaag tgtcagagtt tatatcaaac 720
acattcttag ataagcaaca tgaagtggaa attccttctc caactcagaa ggaaaaggag 780
aaaaagaaaa gaccaatgtc tcagatcagt ggagtcaaga aattgatgca cagctctagt 840
ctgactaatt caagtatccc aaggtttgga gttaaaactg aacaagaaga tgtccttgcc 900
aaggaactag aagatgtgaa caaatggggt cttcatgttt tcagaatagc agagttgtct 960
ggtaaccggc ccttgactgt tatcatgcac accatttttc aggaacggga tttattaaaa 1020
acatttaaaa ttccagtaga tactttaatt acatatctta tgactctcga agaccattac 1080
catgctgatg tggcctatca caacaatatc catgctgcag atgttgtcca gtctactcat 1140
gtgctattat ctacacctgc tttggaggct gtgtttacag atttggagat tcttgcagca 1200
atttttgcca gtgcaataca tgatgtagat catcctggtg tgtccaatca atttctgatc 1260
aatacaaact ctgaacttgc cttgatgtac aatgattcct cagtcttaga gaaccatcat 1320
ttggctgtgg gctttaaatt gcttcaggaa gaaaactgtg acattttcca gaatttgacc 1380
aaaaaacaaa gacaatcttt aaggaaaatg gtcattgaca tcgtacttgc aacagatatg 1440
tcaaaacaca tgaatctact ggctgatttg aagactatgg ttgaaactaa gaaagtgaca 1500
agctctggag ttcttcttct tgataattat tccgatagga ttcaggttct tcagaatatg 1560
gtgcactgtg cagatctgag caacccaaca aagcctctcc agctgtaccg ccagtggacg 1620
gaccggataa tggaggagtt cttccgccaa ggagaccgag agagggaacg tggcatggag 1680
ataagcccca tgtgtgacaa gcacaatgct tccgtggaaa aatcacaggt gggcttcata 1740
gactatattg ttcatcccct ctgggagaca tgggcagacc tcgtccaccc tgacgcccag 1800
gatattttgg acactttgga ggacaatcgt gaatggtacc agagcacaat ccctcagagc 1860
ccctctcctg cacctgatga cccagaggag ggccggcagg gtcaaactga gaaattccag 1920
tttgaactaa ctttagagga agatggtgag tcagacacgg aaaaggacag tggcagtcaa 1980
gtggaagaag acactagctg cagtgactcc aagactcttt gtactcaaga ctcagagtct 2040
actgaaattc cccttgatga acaggttgaa gaggaggcag taggggaaga agaggaaagc 2100
cagcctgaag cctgtgtcat agatgatcgt tctcctgaca cgtaacagtg caaaaacttt 2160
catgcctttt ttttttttaa gtagaaaaat tgtttccaaa gtgcatgtca catgccacaa 2220
ccacggtcac acctcactgt catctgccag gacgtttgtt gaacaaaact gaccttgact 2280
actcagtcca gcgctcagga atatcgtaac cagttttttc acctccatgt catccgagca 2340
aggtggacat cttcacgaac agcgttttta acaagatttc agcttggtag agctgacaaa 2400
gcagataaaa tctactccaa attattttca agagagtgtg actcatcagg cagcccaaaa 2460
gtttattgga cttggggttt ctattccttt ttatttgttt gcaatatttt cagaagaaag 2520
gcattgcaca gagtgaactt aatggacgaa gcaacaaata tgtcaagaac aggacatagc 2580
acgaatctgt taccagtagg aggaggatga gccacagaaa ttgcataatt ttctaatttc 2640
aagtcttcct gatacatgac tgaatagtgt ggttcagtga gctgcactga cctctacatt 2700
ttgtatgata tgtaaaacag attttttgta gagcttactt ttattattaa atgtattgag 2760
gtattatatt taaaaaaaac tatgttcaga acttcatctg ccactggtta tttttttcta 2820
aggagtaact tgcaagtttt cagtacaaat ctgtgctaca ctggataaaa atctaattta 2880
tgaattttac ttgcacctta tagttcatag caattaactg atttgtagtg attcattgtt 2940
tgttttatat accaatgact tccatatttt aaaagagaaa aacaacttta tgttgcagga 3000
aacccttttt gtaagtcttt attatttact ttgcattttg tttcactctt tccagataag 3060
cagagttgct cttcaccagt gtttttcttc atgtgcaaag tgactatttg ttctataata 3120
cttttatgtg tgttatatca aatgtgtctt aagcttcatg caaactcagt catcagttcg 3180
tgttgtctga agcaagtggg agatatataa atacccagta gctaaaatgg tcagtctttt 3240
ttagatgttt tcctacttag tatctcctaa taacgttttg ctgtgtcact agatgttcat 3300
ttcacaagtg catgtctttc taataatcca cacatttcat gctctaataa tccacacatt 3360
tcatgctcat ttttattgtt tttacagcca gttatagtaa gaaaaaggtt tttccccttg 3420
tgctgcttta taatttagcg tgtgtctgaa ccttatccat gtttgctaga tgaggtcttg 3480
tcaaatatat cactaccatt gtcaccggtg aaaagaaaca ggtagttaag ttagggttaa 3540
cattcatttc aaccacgagg ttgtatatca tgactagctt ttactcttgg tttacagaga 3600
aaagttaaac agccaactag gcagttttta agaatattaa caatatatta acaaacacca 3660
atacaactaa tcctatttgg ttttaatgat ttcaccatgg gattaagaac tatatcagga 3720
acatccctga gaaacggttt taagtgtagc aactactctt ccttaatgga cagccacata 3780
acgtgtagga agtcctttat cacttatcct cgatccataa gcatatcttg cagaggggaa 3840
ctacttcttt aaacacatgg agggaaagaa gatgatgcca ctggcaccag agggttagta 3900
ctgtgatgca tcctaaaata tttattatat tggtaaaaat tctggttaaa taaaaaatta 3960
gagatcactc ttggctgatt tcagcaccag gaactgtatt acagttttag agattaattc 4020
ctagtgttta cctgattata gcagttggca tcatggggca tttaattctg actttatccc 4080
cacgtcagcc ttaataaagt cttctttacc ttctctatga agactttaaa gcccaaataa 4140
tcatttttca cattgatatt caagaattga gatagataga agccaaagtg ggtatctgac 4200
aagtggaaaa tcaaacgttt aagaagaatt acaactctga aaagcattta tatgtggaac 4260
ttctcaagga gcctcctggg gactggaaag taagtcatca gccaggcaaa tgactcatgc 4320
tgaagagagt ccccatttca gtcccctgag atctagctga tgcttagatc ctttgaaata 4380
aaaattatgt ctttataact ctgatctttt acataaagca gaagaggaat caactagtta 4440
attgcaaggt ttctactctg tttcctctgt aaagatcaga tggtaatctt tcaaataaga 4500
aaaaaataaa gacgtatgtt tgaccaagta gtttcacaag aatatttggg aacttgtttc 4560
ttttaatttt atttgtccct gagtgaagtc tagaaagaaa ggtaaagagt ctagagttta 4620
ttcctctttc caaaacattc tcattcctct cctccctaca cttagtattt cccccacaga 4680
gtgcctagaa tcttaataat gaataaaata aaaagcagca atatgtcatt aacaaatcca 4740
gacctgaaag ggtaaagggt ttataactgc actaataaag agaggctctt tttttttctt 4800
ccagtttgtt ggtttttaat ggtaccgtgt tgtaaagata cccactaatg gacaatcaaa 4860
ttgcagaaaa ggctcaatat ccaagagaca gggactaatg cactgtacaa tctgcttatc 4920
cttgcccttc tctcttgcca aagtgtgctt cagaaatata tactgcttta aaaaagaata 4980
aaagaatatc cttttacaag tggctttaca tttcctaaaa tgccataaga aaatgcaata 5040
tctgggtact gtatggggaa aaaaatgtcc aagtttgtgt aaaaccagtg catttcagct 5100
tgcaagttac tgaacacaat aatgctgttt taattttgtt ttatatcagt taaaattcac 5160
aataatgtag atagaacaaa ttacagacaa ggaaagaaaa aacttgaatg aaatggattt 5220
tacagaaagc tttatgataa tttttgaatg cattatttat tttttgtgcc atgcattttt 5280
tttctcacca aatgacctta cctgtaatac agtcttgttt gtctgtttac aaccatgtat 5340
ttattgcaat gtacatactg taatgttaat tgtaaattat ctgttcttat taaaacatca 5400
tcccatgatg ggatggtgtt gatatatttg gaaactcttg gtgagagaat gaatggtgtg 5460
tatacatact ctgtacattt ttcttttctc ctgtaatata gtcttgtcac cttagagctt 5520
gtttatggaa gattcaagaa aactataaaa tacttaaaga tatataaatt taaaaaaaca 5580
tagctgcagg tctttggtcc cagggctgtg ccttaacttt aaccaatatt ttcttctgtt 5640
ttgctgcatt tgaaaggtaa cagtggagct agggctgggc attttacatc caggctttta 5700
attgattaga attctgccaa taggtggatt ttacaaaacc acagacaacc tctgaaagat 5760
tctgagaccc ttttgagaca gaagctctta agtacttctt gccagggagc agcactgcat 5820
gtgtgatggt tgtttgccat ctgttgatca ggaactactt cagctacttg catttgatta 5880
tttccttttt tttttttttt aactcggaaa cacaactggg gaaatatatt ctttcccagt 5940
gattataaac aatctttttc ttttttttaa gtccttttgg cttctagagc tcataggaaa 6000
atggacttga tttgaaattg gagccagagt ttactcgtgt tggttatcta ttcatcagct 6060
tcctgacatg ttaagagaat acattaaaga gaaaatactg ttttttaatc ctaaaatttt 6120
tcttccacta agataaacca aatgtcctta catatatgta aacccatcta tttaaacgca 6180
aaggtgggtt gatgtcagtt tacatagcag aaagcattca ctatcctcta agatttgttt 6240
ctgcaaaact ttcattgctt tagaatttta aaatttcacc ttgtacaatg gccagcccct 6300
aaagcaggaa acatttataa tggattatat ggaaacatcc tcccagtact tgcccagccc 6360
ttgaatcatg tggcttttca gtgaaaggaa agattctttt tctaggaaaa atgagcctat 6420
tttattttat tttattttat tttttgacac aaactgtaga ttttagcagc cctggcccaa 6480
aggaatttga ttacttttgt tttaaacagt acaaagggga cactataatt acaaaaacat 6540
ccttaactga tttgagttgt ttttatttct ttggatatat tttcagagtg gtaaattgtg 6600
tgtgagaatt acaaatgatt attcttttag tggtttctta gcctctctta cagcccacgg 6660
ggatagtact gtacatcaat accttcatat gaaattttta tatgcaatga aaataaaagc 6720
atgggttgat tctgcctatt tatgactcaa tcttttacaa ataaaagatt attcatttta 6780
aattatagtt caatcagcat gtctcttagg atactgaacg tggttgaaat gaaaggatag 6840
tgacatcata agttagtact gatattcata accaaataaa gccaacttga gtaattttgc 6900
tacattaaaa attaccaaaa ttacttagat ggcctataag attaagcatg gtgttttcta 6960
agcaagcttt gaaaggggcc ttccatactt acttaattga atattctggg atattgaaaa 7020
ttattcagat acttgacaat tatttttggt tacctactcc gcaaactaca aagttttaag 7080
gactcaacaa taagttaatg agacacagtg tttgctttca tggagcttac agtctggagg 7140
ggacaaaggc ttaaacaata ctcatataat tatatatgtg atcagtacaa tgaaggagct 7200
cagtggggta aataagcagg aacctgaact tgatctgttc cggagggcca cagaaggctt 7260
ccttgaggcc ttgagaaagt gatttgcatc tgagttctga aggattgtaa gaggtaacta 7320
gggaaaaagt tgacaggaag aggaagggga tccagacaag aaacatttgc aaagatcttg 7380
aggcataaat gagcttgaga catctggaga aactgaggaa aagtgagaga gtaggcaggg 7440
cctggagccg cagagccatt gctaaccatc ctgtgtgaga tatcccccat tctgtagctt 7500
tattctcata accctgctca attttcttta taacacttct cacagattta tatacgtgtt 7560
tgtttttgtt atctgtctct cccaccagac cacagctcca tgagagcaag gtctttgctt 7620
accaatatat cactagcact taaaactatg cctggtacac agtaggttct taatatgtgt 7680
tgaatatagc catcaaattg atattggata taattcaatc tgataagata ttttgagata 7740
ttaaagagtt tttaacttga taccataaaa aaaaaaaaaa aaa 7783
<210> 15
<211> 7667
<212> DNA
<213> Homo sapiens
<400> 15
acttcaagtg ccgtgcagaa ggctcggcag gcggggcggg cgtggggccg cggctccggg 60
ttggggaccg aggagatccg gctgtggacc agacgctcct ctgcggggcg ggcacccaag 120
cgcgctcgcc accccctcgc catccgctag agccgggctc ctggactggg actcgggccc 180
gccgcacagt tgaaaagtcg catagtggtt tttccgctcg cgtcgctgtg tgaaagttgg 240
ctcgccgctc tttgcacgcc ctccctggag gccgacccga gacgccaagc tggagagacc 300
gtgcctcccc gaggccggcc gccccgcgag cacagcctcc gcccccgttg cactgccggg 360
ctgggcaata tgaaggagca gccctcatgt gccggcaccg ggcatccgag catggcggga 420
ggaggcctac cagaaactgg ccagcgagac cctggaggag ctggactggt gtctggacca 480
gctagagacc ctacagacca ggcactccgt cagtgagatg gcctccaaca agtttaaaag 540
gatgcttaat cgggagctca cccatctctc tgaaatgagt cggtctggaa atcaagtgtc 600
agagtttata tcaaacacat tcttagataa gcaacatgaa gtggaaattc cttctccaac 660
tcagaaggaa aaggagaaaa agaaaagacc aatgtctcag atcagtggag tcaagaaatt 720
gatgcacagc tctagtctga ctaattcaag tatcccaagg tttggagtta aaactgaaca 780
agaagatgtc cttgccaagg aactagaaga tgtgaacaaa tggggtcttc atgttttcag 840
aatagcagag ttgtctggta accggccctt gactgttatc atgcacacca tttttcagga 900
acgggattta ttaaaaacat ttaaaattcc agtagatact ttaattacat atcttatgac 960
tctcgaagac cattaccatg ctgatgtggc ctatcacaac aatatccatg ctgcagatgt 1020
tgtccagtct actcatgtgc tattatctac acctgctttg gaggctgtgt ttacagattt 1080
ggagattctt gcagcaattt ttgccagtgc aatacatgat gtagatcatc ctggtgtgtc 1140
caatcaattt ctgatcaata caaactctga acttgccttg atgtacaatg attcctcagt 1200
cttagagaac catcatttgg ctgtgggctt taaattgctt caggaagaaa actgtgacat 1260
tttccagaat ttgaccaaaa aacaaagaca atctttaagg aaaatggtca ttgacatcgt 1320
acttgcaaca gatatgtcaa aacacatgaa tctactggct gatttgaaga ctatggttga 1380
aactaagaaa gtgacaagct ctggagttct tcttcttgat aattattccg ataggattca 1440
ggttcttcag aatatggtgc actgtgcaga tctgagcaac ccaacaaagc ctctccagct 1500
gtaccgccag tggacggacc ggataatgga ggagttcttc cgccaaggag accgagagag 1560
ggaacgtggc atggagataa gccccatgtg tgacaagcac aatgcttccg tggaaaaatc 1620
acaggtgggc ttcatagact atattgttca tcccctctgg gagacatggg cagacctcgt 1680
ccaccctgac gcccaggata ttttggacac tttggaggac aatcgtgaat ggtaccagag 1740
cacaatccct cagagcccct ctcctgcacc tgatgaccca gaggagggcc ggcagggtca 1800
aactgagaaa ttccagtttg aactaacttt agaggaagat ggtgagtcag acacggaaaa 1860
ggacagtggc agtcaagtgg aagaagacac tagctgcagt gactccaaga ctctttgtac 1920
tcaagactca gagtctactg aaattcccct tgatgaacag gttgaagagg aggcagtagg 1980
ggaagaagag gaaagccagc ctgaagcctg tgtcatagat gatcgttctc ctgacacgta 2040
acagtgcaaa aactttcatg cctttttttt ttttaagtag aaaaattgtt tccaaagtgc 2100
atgtcacatg ccacaaccac ggtcacacct cactgtcatc tgccaggacg tttgttgaac 2160
aaaactgacc ttgactactc agtccagcgc tcaggaatat cgtaaccagt tttttcacct 2220
ccatgtcatc cgagcaaggt ggacatcttc acgaacagcg tttttaacaa gatttcagct 2280
tggtagagct gacaaagcag ataaaatcta ctccaaatta ttttcaagag agtgtgactc 2340
atcaggcagc ccaaaagttt attggacttg gggtttctat tcctttttat ttgtttgcaa 2400
tattttcaga agaaaggcat tgcacagagt gaacttaatg gacgaagcaa caaatatgtc 2460
aagaacagga catagcacga atctgttacc agtaggagga ggatgagcca cagaaattgc 2520
ataattttct aatttcaagt cttcctgata catgactgaa tagtgtggtt cagtgagctg 2580
cactgacctc tacattttgt atgatatgta aaacagattt tttgtagagc ttacttttat 2640
tattaaatgt attgaggtat tatatttaaa aaaaactatg ttcagaactt catctgccac 2700
tggttatttt tttctaagga gtaacttgca agttttcagt acaaatctgt gctacactgg 2760
ataaaaatct aatttatgaa ttttacttgc accttatagt tcatagcaat taactgattt 2820
gtagtgattc attgtttgtt ttatatacca atgacttcca tattttaaaa gagaaaaaca 2880
actttatgtt gcaggaaacc ctttttgtaa gtctttatta tttactttgc attttgtttc 2940
actctttcca gataagcaga gttgctcttc accagtgttt ttcttcatgt gcaaagtgac 3000
tatttgttct ataatacttt tatgtgtgtt atatcaaatg tgtcttaagc ttcatgcaaa 3060
ctcagtcatc agttcgtgtt gtctgaagca agtgggagat atataaatac ccagtagcta 3120
aaatggtcag tcttttttag atgttttcct acttagtatc tcctaataac gttttgctgt 3180
gtcactagat gttcatttca caagtgcatg tctttctaat aatccacaca tttcatgctc 3240
taataatcca cacatttcat gctcattttt attgttttta cagccagtta tagtaagaaa 3300
aaggtttttc cccttgtgct gctttataat ttagcgtgtg tctgaacctt atccatgttt 3360
gctagatgag gtcttgtcaa atatatcact accattgtca ccggtgaaaa gaaacaggta 3420
gttaagttag ggttaacatt catttcaacc acgaggttgt atatcatgac tagcttttac 3480
tcttggttta cagagaaaag ttaaacagcc aactaggcag tttttaagaa tattaacaat 3540
atattaacaa acaccaatac aactaatcct atttggtttt aatgatttca ccatgggatt 3600
aagaactata tcaggaacat ccctgagaaa cggttttaag tgtagcaact actcttcctt 3660
aatggacagc cacataacgt gtaggaagtc ctttatcact tatcctcgat ccataagcat 3720
atcttgcaga ggggaactac ttctttaaac acatggaggg aaagaagatg atgccactgg 3780
caccagaggg ttagtactgt gatgcatcct aaaatattta ttatattggt aaaaattctg 3840
gttaaataaa aaattagaga tcactcttgg ctgatttcag caccaggaac tgtattacag 3900
ttttagagat taattcctag tgtttacctg attatagcag ttggcatcat ggggcattta 3960
attctgactt tatccccacg tcagccttaa taaagtcttc tttaccttct ctatgaagac 4020
tttaaagccc aaataatcat ttttcacatt gatattcaag aattgagata gatagaagcc 4080
aaagtgggta tctgacaagt ggaaaatcaa acgtttaaga agaattacaa ctctgaaaag 4140
catttatatg tggaacttct caaggagcct cctggggact ggaaagtaag tcatcagcca 4200
ggcaaatgac tcatgctgaa gagagtcccc atttcagtcc cctgagatct agctgatgct 4260
tagatccttt gaaataaaaa ttatgtcttt ataactctga tcttttacat aaagcagaag 4320
aggaatcaac tagttaattg caaggtttct actctgtttc ctctgtaaag atcagatggt 4380
aatctttcaa ataagaaaaa aataaagacg tatgtttgac caagtagttt cacaagaata 4440
tttgggaact tgtttctttt aattttattt gtccctgagt gaagtctaga aagaaaggta 4500
aagagtctag agtttattcc tctttccaaa acattctcat tcctctcctc cctacactta 4560
gtatttcccc cacagagtgc ctagaatctt aataatgaat aaaataaaaa gcagcaatat 4620
gtcattaaca aatccagacc tgaaagggta aagggtttat aactgcacta ataaagagag 4680
gctctttttt tttcttccag tttgttggtt tttaatggta ccgtgttgta aagataccca 4740
ctaatggaca atcaaattgc agaaaaggct caatatccaa gagacaggga ctaatgcact 4800
gtacaatctg cttatccttg cccttctctc ttgccaaagt gtgcttcaga aatatatact 4860
gctttaaaaa agaataaaag aatatccttt tacaagtggc tttacatttc ctaaaatgcc 4920
ataagaaaat gcaatatctg ggtactgtat ggggaaaaaa atgtccaagt ttgtgtaaaa 4980
ccagtgcatt tcagcttgca agttactgaa cacaataatg ctgttttaat tttgttttat 5040
atcagttaaa attcacaata atgtagatag aacaaattac agacaaggaa agaaaaaact 5100
tgaatgaaat ggattttaca gaaagcttta tgataatttt tgaatgcatt atttattttt 5160
tgtgccatgc attttttttc tcaccaaatg accttacctg taatacagtc ttgtttgtct 5220
gtttacaacc atgtatttat tgcaatgtac atactgtaat gttaattgta aattatctgt 5280
tcttattaaa acatcatccc atgatgggat ggtgttgata tatttggaaa ctcttggtga 5340
gagaatgaat ggtgtgtata catactctgt acatttttct tttctcctgt aatatagtct 5400
tgtcacctta gagcttgttt atggaagatt caagaaaact ataaaatact taaagatata 5460
taaatttaaa aaaacatagc tgcaggtctt tggtcccagg gctgtgcctt aactttaacc 5520
aatattttct tctgttttgc tgcatttgaa aggtaacagt ggagctaggg ctgggcattt 5580
tacatccagg cttttaattg attagaattc tgccaatagg tggattttac aaaaccacag 5640
acaacctctg aaagattctg agaccctttt gagacagaag ctcttaagta cttcttgcca 5700
gggagcagca ctgcatgtgt gatggttgtt tgccatctgt tgatcaggaa ctacttcagc 5760
tacttgcatt tgattatttc cttttttttt ttttttaact cggaaacaca actggggaaa 5820
tatattcttt cccagtgatt ataaacaatc tttttctttt ttttaagtcc ttttggcttc 5880
tagagctcat aggaaaatgg acttgatttg aaattggagc cagagtttac tcgtgttggt 5940
tatctattca tcagcttcct gacatgttaa gagaatacat taaagagaaa atactgtttt 6000
ttaatcctaa aatttttctt ccactaagat aaaccaaatg tccttacata tatgtaaacc 6060
catctattta aacgcaaagg tgggttgatg tcagtttaca tagcagaaag cattcactat 6120
cctctaagat ttgtttctgc aaaactttca ttgctttaga attttaaaat ttcaccttgt 6180
acaatggcca gcccctaaag caggaaacat ttataatgga ttatatggaa acatcctccc 6240
agtacttgcc cagcccttga atcatgtggc ttttcagtga aaggaaagat tctttttcta 6300
ggaaaaatga gcctatttta ttttatttta ttttattttt tgacacaaac tgtagatttt 6360
agcagccctg gcccaaagga atttgattac ttttgtttta aacagtacaa aggggacact 6420
ataattacaa aaacatcctt aactgatttg agttgttttt atttctttgg atatattttc 6480
agagtggtaa attgtgtgtg agaattacaa atgattattc ttttagtggt ttcttagcct 6540
ctcttacagc ccacggggat agtactgtac atcaatacct tcatatgaaa tttttatatg 6600
caatgaaaat aaaagcatgg gttgattctg cctatttatg actcaatctt ttacaaataa 6660
aagattattc attttaaatt atagttcaat cagcatgtct cttaggatac tgaacgtggt 6720
tgaaatgaaa ggatagtgac atcataagtt agtactgata ttcataacca aataaagcca 6780
acttgagtaa ttttgctaca ttaaaaatta ccaaaattac ttagatggcc tataagatta 6840
agcatggtgt tttctaagca agctttgaaa ggggccttcc atacttactt aattgaatat 6900
tctgggatat tgaaaattat tcagatactt gacaattatt tttggttacc tactccgcaa 6960
actacaaagt tttaaggact caacaataag ttaatgagac acagtgtttg ctttcatgga 7020
gcttacagtc tggaggggac aaaggcttaa acaatactca tataattata tatgtgatca 7080
gtacaatgaa ggagctcagt ggggtaaata agcaggaacc tgaacttgat ctgttccgga 7140
gggccacaga aggcttcctt gaggccttga gaaagtgatt tgcatctgag ttctgaagga 7200
ttgtaagagg taactaggga aaaagttgac aggaagagga aggggatcca gacaagaaac 7260
atttgcaaag atcttgaggc ataaatgagc ttgagacatc tggagaaact gaggaaaagt 7320
gagagagtag gcagggcctg gagccgcaga gccattgcta accatcctgt gtgagatatc 7380
ccccattctg tagctttatt ctcataaccc tgctcaattt tctttataac acttctcaca 7440
gatttatata cgtgtttgtt tttgttatct gtctctccca ccagaccaca gctccatgag 7500
agcaaggtct ttgcttacca atatatcact agcacttaaa actatgcctg gtacacagta 7560
ggttcttaat atgtgttgaa tatagccatc aaattgatat tggatataat tcaatctgat 7620
aagatatttt gagatattaa agagttttta acttgatacc ataaaaa 7667
<210> 16
<211> 8379
<212> DNA
<213> Homo sapiens
<400> 16
cactgccctg cggtgttttg aactgccttc ttacagacgt catacagccc ttgaggaata 60
gtttctgcct ggtgagattg aatgatagtt ctcattcaca aaaccctgga ttctaagcag 120
ggacacacag aaattacttt cgcaggtaaa tcagcccacc cagccaaagt gtggagagat 180
ttgttccttg gctgacttct ttgctccacg gagaggagtg ttttcctgtg cttgccctga 240
aatggaactt ccttgacagc tctcccgtgt tacagtacct cccggtcatt ttctttttct 300
ctctctctac ctgcgctctt cgagtgtcag aaacctttaa agctgttact atggaattgc 360
aaaaaagaga tcaagtgact ctttcactat gctggtttcc cttgtgaccc agatgaagaa 420
tcaattcaga attcagttcc tcccttggca ttgcaagaca cagaagaaac tgtcacttcc 480
taacagccta gtactggagt aaattcagta tgaaggaaga aagcgctcct gcgtgttaga 540
accttgccca tgagctggac cgaggacagg agatggactc caggaaaatt ggatttcttc 600
aagcagcctc ccttggaaat ggaatatctt taaaatcttc tttgcagaaa gacagttaga 660
atgtattaat cagaatagtt gaagacttat tttccttttt attttttttc aaaatgagca 720
ttattatgaa gccaagatcc cgatctacaa gttccctaag gactgcagag gcagtttgtt 780
ttgatgtgga caatggcaca tctgcgggac ggagtccctt ggatcccatg accagcccag 840
gatccgggct aattctccaa gcaaattttg tccacagtca acgacgggag tccttcctgt 900
atcgatccga cagcgattat gacctctctc caaagtctat gtcccggaac tcctccattg 960
ccagtgatat acacggagat gacttgattg tgactccatt tgctcaggtc ttggccagtc 1020
tgcgaactgt acgaaacaac tttgctgcat taactaattt gcaagatcga gcacctagca 1080
aaagatcacc catgtgcaac caaccatcca tcaacaaagc caccataaca gaggaggcct 1140
accagaaact ggccagcgag accctggagg agctggactg gtgtctggac cagctagaga 1200
ccctacagac caggcactcc gtcagtgaga tggcctccaa caagtttaaa aggatgctta 1260
atcgggagct cacccatctc tctgaaatga gtcggtctgg aaatcaagtg tcagagttta 1320
tatcaaacac attcttagat aagcaacatg aagtggaaat tccttctcca actcagaagg 1380
aaaaggagaa aaagaaaaga ccaatgtctc agatcagtgg agtcaagaaa ttgatgcaca 1440
gctctagtct gactaattca agtatcccaa ggtttggagt taaaactgaa caagaagatg 1500
tccttgccaa ggaactagaa gatgtgaaca aatggggtct tcatgttttc agaatagcag 1560
agttgtctgg taaccggccc ttgactgtta tcatgcacac catttttcag gaacgggatt 1620
tattaaaaac atttaaaatt ccagtagata ctttaattac atatcttatg actctcgaag 1680
accattacca tgctgatgtg gcctatcaca acaatatcca tgctgcagat gttgtccagt 1740
ctactcatgt gctattatct acacctgctt tggaggctgt gtttacagat ttggagattc 1800
ttgcagcaat ttttgccagt gcaatacatg atgtagatca tcctggtgtg tccaatcaat 1860
ttctgatcaa tacaaactct gaacttgcct tgatgtacaa tgattcctca gtcttagaga 1920
accatcattt ggctgtgggc tttaaattgc ttcaggaaga aaactgtgac attttccaga 1980
atttgaccaa aaaacaaaga caatctttaa ggaaaatggt cattgacatc gtacttgcaa 2040
cagatatgtc aaaacacatg aatctactgg ctgatttgaa gactatggtt gaaactaaga 2100
aagtgacaag ctctggagtt cttcttcttg ataattattc cgataggatt caggttcttc 2160
agaatatggt gcactgtgca gatctgagca acccaacaaa gcctctccag ctgtaccgcc 2220
agtggacgga ccggataatg gaggagttct tccgccaagg agaccgagag agggaacgtg 2280
gcatggagat aagccccatg tgtgacaagc acaatgcttc cgtggaaaaa tcacaggtgg 2340
gcttcataga ctatattgtt catcccctct gggagacatg ggcagacctc gtccaccctg 2400
acgcccagga tattttggac actttggagg acaatcgtga atggtaccag agcacaatcc 2460
ctcagagccc ctctcctgca cctgatgacc cagaggaggg ccggcagggt caaactgaga 2520
aattccagtt tgaactaact ttagaggaag atggtgagtc agacacggaa aaggacagtg 2580
gcagtcaagt ggaagaagac actagctgca gtgactccaa gactctttgt actcaagact 2640
cagagtctac tgaaattccc cttgatgaac aggttgaaga ggaggcagta ggggaagaag 2700
aggaaagcca gcctgaagcc tgtgtcatag atgatcgttc tcctgacacg taacagtgca 2760
aaaactttca tgcctttttt ttttttaagt agaaaaattg tttccaaagt gcatgtcaca 2820
tgccacaacc acggtcacac ctcactgtca tctgccagga cgtttgttga acaaaactga 2880
ccttgactac tcagtccagc gctcaggaat atcgtaacca gttttttcac ctccatgtca 2940
tccgagcaag gtggacatct tcacgaacag cgtttttaac aagatttcag cttggtagag 3000
ctgacaaagc agataaaatc tactccaaat tattttcaag agagtgtgac tcatcaggca 3060
gcccaaaagt ttattggact tggggtttct attccttttt atttgtttgc aatattttca 3120
gaagaaaggc attgcacaga gtgaacttaa tggacgaagc aacaaatatg tcaagaacag 3180
gacatagcac gaatctgtta ccagtaggag gaggatgagc cacagaaatt gcataatttt 3240
ctaatttcaa gtcttcctga tacatgactg aatagtgtgg ttcagtgagc tgcactgacc 3300
tctacatttt gtatgatatg taaaacagat tttttgtaga gcttactttt attattaaat 3360
gtattgaggt attatattta aaaaaaacta tgttcagaac ttcatctgcc actggttatt 3420
tttttctaag gagtaacttg caagttttca gtacaaatct gtgctacact ggataaaaat 3480
ctaatttatg aattttactt gcaccttata gttcatagca attaactgat ttgtagtgat 3540
tcattgtttg ttttatatac caatgacttc catattttaa aagagaaaaa caactttatg 3600
ttgcaggaaa ccctttttgt aagtctttat tatttacttt gcattttgtt tcactctttc 3660
cagataagca gagttgctct tcaccagtgt ttttcttcat gtgcaaagtg actatttgtt 3720
ctataatact tttatgtgtg ttatatcaaa tgtgtcttaa gcttcatgca aactcagtca 3780
tcagttcgtg ttgtctgaag caagtgggag atatataaat acccagtagc taaaatggtc 3840
agtctttttt agatgttttc ctacttagta tctcctaata acgttttgct gtgtcactag 3900
atgttcattt cacaagtgca tgtctttcta ataatccaca catttcatgc tctaataatc 3960
cacacatttc atgctcattt ttattgtttt tacagccagt tatagtaaga aaaaggtttt 4020
tccccttgtg ctgctttata atttagcgtg tgtctgaacc ttatccatgt ttgctagatg 4080
aggtcttgtc aaatatatca ctaccattgt caccggtgaa aagaaacagg tagttaagtt 4140
agggttaaca ttcatttcaa ccacgaggtt gtatatcatg actagctttt actcttggtt 4200
tacagagaaa agttaaacag ccaactaggc agtttttaag aatattaaca atatattaac 4260
aaacaccaat acaactaatc ctatttggtt ttaatgattt caccatggga ttaagaacta 4320
tatcaggaac atccctgaga aacggtttta agtgtagcaa ctactcttcc ttaatggaca 4380
gccacataac gtgtaggaag tcctttatca cttatcctcg atccataagc atatcttgca 4440
gaggggaact acttctttaa acacatggag ggaaagaaga tgatgccact ggcaccagag 4500
ggttagtact gtgatgcatc ctaaaatatt tattatattg gtaaaaattc tggttaaata 4560
aaaaattaga gatcactctt ggctgatttc agcaccagga actgtattac agttttagag 4620
attaattcct agtgtttacc tgattatagc agttggcatc atggggcatt taattctgac 4680
tttatcccca cgtcagcctt aataaagtct tctttacctt ctctatgaag actttaaagc 4740
ccaaataatc atttttcaca ttgatattca agaattgaga tagatagaag ccaaagtggg 4800
tatctgacaa gtggaaaatc aaacgtttaa gaagaattac aactctgaaa agcatttata 4860
tgtggaactt ctcaaggagc ctcctgggga ctggaaagta agtcatcagc caggcaaatg 4920
actcatgctg aagagagtcc ccatttcagt cccctgagat ctagctgatg cttagatcct 4980
ttgaaataaa aattatgtct ttataactct gatcttttac ataaagcaga agaggaatca 5040
actagttaat tgcaaggttt ctactctgtt tcctctgtaa agatcagatg gtaatctttc 5100
aaataagaaa aaaataaaga cgtatgtttg accaagtagt ttcacaagaa tatttgggaa 5160
cttgtttctt ttaattttat ttgtccctga gtgaagtcta gaaagaaagg taaagagtct 5220
agagtttatt cctctttcca aaacattctc attcctctcc tccctacact tagtatttcc 5280
cccacagagt gcctagaatc ttaataatga ataaaataaa aagcagcaat atgtcattaa 5340
caaatccaga cctgaaaggg taaagggttt ataactgcac taataaagag aggctctttt 5400
tttttcttcc agtttgttgg tttttaatgg taccgtgttg taaagatacc cactaatgga 5460
caatcaaatt gcagaaaagg ctcaatatcc aagagacagg gactaatgca ctgtacaatc 5520
tgcttatcct tgcccttctc tcttgccaaa gtgtgcttca gaaatatata ctgctttaaa 5580
aaagaataaa agaatatcct tttacaagtg gctttacatt tcctaaaatg ccataagaaa 5640
atgcaatatc tgggtactgt atggggaaaa aaatgtccaa gtttgtgtaa aaccagtgca 5700
tttcagcttg caagttactg aacacaataa tgctgtttta attttgtttt atatcagtta 5760
aaattcacaa taatgtagat agaacaaatt acagacaagg aaagaaaaaa cttgaatgaa 5820
atggatttta cagaaagctt tatgataatt tttgaatgca ttatttattt tttgtgccat 5880
gcattttttt tctcaccaaa tgaccttacc tgtaatacag tcttgtttgt ctgtttacaa 5940
ccatgtattt attgcaatgt acatactgta atgttaattg taaattatct gttcttatta 6000
aaacatcatc ccatgatggg atggtgttga tatatttgga aactcttggt gagagaatga 6060
atggtgtgta tacatactct gtacattttt cttttctcct gtaatatagt cttgtcacct 6120
tagagcttgt ttatggaaga ttcaagaaaa ctataaaata cttaaagata tataaattta 6180
aaaaaacata gctgcaggtc tttggtccca gggctgtgcc ttaactttaa ccaatatttt 6240
cttctgtttt gctgcatttg aaaggtaaca gtggagctag ggctgggcat tttacatcca 6300
ggcttttaat tgattagaat tctgccaata ggtggatttt acaaaaccac agacaacctc 6360
tgaaagattc tgagaccctt ttgagacaga agctcttaag tacttcttgc cagggagcag 6420
cactgcatgt gtgatggttg tttgccatct gttgatcagg aactacttca gctacttgca 6480
tttgattatt tccttttttt ttttttttaa ctcggaaaca caactgggga aatatattct 6540
ttcccagtga ttataaacaa tctttttctt ttttttaagt ccttttggct tctagagctc 6600
ataggaaaat ggacttgatt tgaaattgga gccagagttt actcgtgttg gttatctatt 6660
catcagcttc ctgacatgtt aagagaatac attaaagaga aaatactgtt ttttaatcct 6720
aaaatttttc ttccactaag ataaaccaaa tgtccttaca tatatgtaaa cccatctatt 6780
taaacgcaaa ggtgggttga tgtcagttta catagcagaa agcattcact atcctctaag 6840
atttgtttct gcaaaacttt cattgcttta gaattttaaa atttcacctt gtacaatggc 6900
cagcccctaa agcaggaaac atttataatg gattatatgg aaacatcctc ccagtacttg 6960
cccagccctt gaatcatgtg gcttttcagt gaaaggaaag attctttttc taggaaaaat 7020
gagcctattt tattttattt tattttattt tttgacacaa actgtagatt ttagcagccc 7080
tggcccaaag gaatttgatt acttttgttt taaacagtac aaaggggaca ctataattac 7140
aaaaacatcc ttaactgatt tgagttgttt ttatttcttt ggatatattt tcagagtggt 7200
aaattgtgtg tgagaattac aaatgattat tcttttagtg gtttcttagc ctctcttaca 7260
gcccacgggg atagtactgt acatcaatac cttcatatga aatttttata tgcaatgaaa 7320
ataaaagcat gggttgattc tgcctattta tgactcaatc ttttacaaat aaaagattat 7380
tcattttaaa ttatagttca atcagcatgt ctcttaggat actgaacgtg gttgaaatga 7440
aaggatagtg acatcataag ttagtactga tattcataac caaataaagc caacttgagt 7500
aattttgcta cattaaaaat taccaaaatt acttagatgg cctataagat taagcatggt 7560
gttttctaag caagctttga aaggggcctt ccatacttac ttaattgaat attctgggat 7620
attgaaaatt attcagatac ttgacaatta tttttggtta cctactccgc aaactacaaa 7680
gttttaagga ctcaacaata agttaatgag acacagtgtt tgctttcatg gagcttacag 7740
tctggagggg acaaaggctt aaacaatact catataatta tatatgtgat cagtacaatg 7800
aaggagctca gtggggtaaa taagcaggaa cctgaacttg atctgttccg gagggccaca 7860
gaaggcttcc ttgaggcctt gagaaagtga tttgcatctg agttctgaag gattgtaaga 7920
ggtaactagg gaaaaagttg acaggaagag gaaggggatc cagacaagaa acatttgcaa 7980
agatcttgag gcataaatga gcttgagaca tctggagaaa ctgaggaaaa gtgagagagt 8040
aggcagggcc tggagccgca gagccattgc taaccatcct gtgtgagata tcccccattc 8100
tgtagcttta ttctcataac cctgctcaat tttctttata acacttctca cagatttata 8160
tacgtgtttg tttttgttat ctgtctctcc caccagacca cagctccatg agagcaaggt 8220
ctttgcttac caatatatca ctagcactta aaactatgcc tggtacacag taggttctta 8280
atatgtgttg aatatagcca tcaaattgat attggatata attcaatctg ataagatatt 8340
ttgagatatt aaagagtttt taacttgata ccataaaaa 8379
<210> 17
<211> 7545
<212> DNA
<213> Homo sapiens
<400> 17
ctttcttgca actaagcatc ttgacataca ttattcatta agccctggag ctcgggagag 60
aaagatgcag acccttagat ctttagatat tcctttatca cgtggatttt ctttattcag 120
aatagttgct gaattttgtg ccattctgga gtcttacaaa tggcatgtat tcgatgggaa 180
gacggctgga tgggatttaa tgcgaggctt tcttatgtat acttaattac caaaaatctt 240
taaaaactca tactctgcgt ggcttgtgga ggttgttaaa gtgtcgagat tttgaagcta 300
aatacatttt agagcttact atatatatac atatatatat atatacatat aatcaatcaa 360
aaatgcctga agcaaactat ttactgtcag tgtcttgggg ctacataaag tttaaaagga 420
tgcttaatcg ggagctcacc catctctctg aaatgagtcg gtctggaaat caagtgtcag 480
agtttatatc aaacacattc ttagataagc aacatgaagt ggaaattcct tctccaactc 540
agaaggaaaa ggagaaaaag aaaagaccaa tgtctcagat cagtggagtc aagaaattga 600
tgcacagctc tagtctgact aattcaagta tcccaaggtt tggagttaaa actgaacaag 660
aagatgtcct tgccaaggaa ctagaagatg tgaacaaatg gggtcttcat gttttcagaa 720
tagcagagtt gtctggtaac cggcccttga ctgttatcat gcacaccatt tttcaggaac 780
gggatttatt aaaaacattt aaaattccag tagatacttt aattacatat cttatgactc 840
tcgaagacca ttaccatgct gatgtggcct atcacaacaa tatccatgct gcagatgttg 900
tccagtctac tcatgtgcta ttatctacac ctgctttgga ggctgtgttt acagatttgg 960
agattcttgc agcaattttt gccagtgcaa tacatgatgt agatcatcct ggtgtgtcca 1020
atcaatttct gatcaataca aactctgaac ttgccttgat gtacaatgat tcctcagtct 1080
tagagaacca tcatttggct gtgggcttta aattgcttca ggaagaaaac tgtgacattt 1140
tccagaattt gaccaaaaaa caaagacaat ctttaaggaa aatggtcatt gacatcgtac 1200
ttgcaacaga tatgtcaaaa cacatgaatc tactggctga tttgaagact atggttgaaa 1260
ctaagaaagt gacaagctct ggagttcttc ttcttgataa ttattccgat aggattcagg 1320
ttcttcagaa tatggtgcac tgtgcagatc tgagcaaccc aacaaagcct ctccagctgt 1380
accgccagtg gacggaccgg ataatggagg agttcttccg ccaaggagac cgagagaggg 1440
aacgtggcat ggagataagc cccatgtgtg acaagcacaa tgcttccgtg gaaaaatcac 1500
aggtgggctt catagactat attgttcatc ccctctggga gacatgggca gacctcgtcc 1560
accctgacgc ccaggatatt ttggacactt tggaggacaa tcgtgaatgg taccagagca 1620
caatccctca gagcccctct cctgcacctg atgacccaga ggagggccgg cagggtcaaa 1680
ctgagaaatt ccagtttgaa ctaactttag aggaagatgg tgagtcagac acggaaaagg 1740
acagtggcag tcaagtggaa gaagacacta gctgcagtga ctccaagact ctttgtactc 1800
aagactcaga gtctactgaa attccccttg atgaacaggt tgaagaggag gcagtagggg 1860
aagaagagga aagccagcct gaagcctgtg tcatagatga tcgttctcct gacacgtaac 1920
agtgcaaaaa ctttcatgcc tttttttttt ttaagtagaa aaattgtttc caaagtgcat 1980
gtcacatgcc acaaccacgg tcacacctca ctgtcatctg ccaggacgtt tgttgaacaa 2040
aactgacctt gactactcag tccagcgctc aggaatatcg taaccagttt tttcacctcc 2100
atgtcatccg agcaaggtgg acatcttcac gaacagcgtt tttaacaaga tttcagcttg 2160
gtagagctga caaagcagat aaaatctact ccaaattatt ttcaagagag tgtgactcat 2220
caggcagccc aaaagtttat tggacttggg gtttctattc ctttttattt gtttgcaata 2280
ttttcagaag aaaggcattg cacagagtga acttaatgga cgaagcaaca aatatgtcaa 2340
gaacaggaca tagcacgaat ctgttaccag taggaggagg atgagccaca gaaattgcat 2400
aattttctaa tttcaagtct tcctgataca tgactgaata gtgtggttca gtgagctgca 2460
ctgacctcta cattttgtat gatatgtaaa acagattttt tgtagagctt acttttatta 2520
ttaaatgtat tgaggtatta tatttaaaaa aaactatgtt cagaacttca tctgccactg 2580
gttatttttt tctaaggagt aacttgcaag ttttcagtac aaatctgtgc tacactggat 2640
aaaaatctaa tttatgaatt ttacttgcac cttatagttc atagcaatta actgatttgt 2700
agtgattcat tgtttgtttt atataccaat gacttccata ttttaaaaga gaaaaacaac 2760
tttatgttgc aggaaaccct ttttgtaagt ctttattatt tactttgcat tttgtttcac 2820
tctttccaga taagcagagt tgctcttcac cagtgttttt cttcatgtgc aaagtgacta 2880
tttgttctat aatactttta tgtgtgttat atcaaatgtg tcttaagctt catgcaaact 2940
cagtcatcag ttcgtgttgt ctgaagcaag tgggagatat ataaataccc agtagctaaa 3000
atggtcagtc ttttttagat gttttcctac ttagtatctc ctaataacgt tttgctgtgt 3060
cactagatgt tcatttcaca agtgcatgtc tttctaataa tccacacatt tcatgctcta 3120
ataatccaca catttcatgc tcatttttat tgtttttaca gccagttata gtaagaaaaa 3180
ggtttttccc cttgtgctgc tttataattt agcgtgtgtc tgaaccttat ccatgtttgc 3240
tagatgaggt cttgtcaaat atatcactac cattgtcacc ggtgaaaaga aacaggtagt 3300
taagttaggg ttaacattca tttcaaccac gaggttgtat atcatgacta gcttttactc 3360
ttggtttaca gagaaaagtt aaacagccaa ctaggcagtt tttaagaata ttaacaatat 3420
attaacaaac accaatacaa ctaatcctat ttggttttaa tgatttcacc atgggattaa 3480
gaactatatc aggaacatcc ctgagaaacg gttttaagtg tagcaactac tcttccttaa 3540
tggacagcca cataacgtgt aggaagtcct ttatcactta tcctcgatcc ataagcatat 3600
cttgcagagg ggaactactt ctttaaacac atggagggaa agaagatgat gccactggca 3660
ccagagggtt agtactgtga tgcatcctaa aatatttatt atattggtaa aaattctggt 3720
taaataaaaa attagagatc actcttggct gatttcagca ccaggaactg tattacagtt 3780
ttagagatta attcctagtg tttacctgat tatagcagtt ggcatcatgg ggcatttaat 3840
tctgacttta tccccacgtc agccttaata aagtcttctt taccttctct atgaagactt 3900
taaagcccaa ataatcattt ttcacattga tattcaagaa ttgagataga tagaagccaa 3960
agtgggtatc tgacaagtgg aaaatcaaac gtttaagaag aattacaact ctgaaaagca 4020
tttatatgtg gaacttctca aggagcctcc tggggactgg aaagtaagtc atcagccagg 4080
caaatgactc atgctgaaga gagtccccat ttcagtcccc tgagatctag ctgatgctta 4140
gatcctttga aataaaaatt atgtctttat aactctgatc ttttacataa agcagaagag 4200
gaatcaacta gttaattgca aggtttctac tctgtttcct ctgtaaagat cagatggtaa 4260
tctttcaaat aagaaaaaaa taaagacgta tgtttgacca agtagtttca caagaatatt 4320
tgggaacttg tttcttttaa ttttatttgt ccctgagtga agtctagaaa gaaaggtaaa 4380
gagtctagag tttattcctc tttccaaaac attctcattc ctctcctccc tacacttagt 4440
atttccccca cagagtgcct agaatcttaa taatgaataa aataaaaagc agcaatatgt 4500
cattaacaaa tccagacctg aaagggtaaa gggtttataa ctgcactaat aaagagaggc 4560
tctttttttt tcttccagtt tgttggtttt taatggtacc gtgttgtaaa gatacccact 4620
aatggacaat caaattgcag aaaaggctca atatccaaga gacagggact aatgcactgt 4680
acaatctgct tatccttgcc cttctctctt gccaaagtgt gcttcagaaa tatatactgc 4740
tttaaaaaag aataaaagaa tatcctttta caagtggctt tacatttcct aaaatgccat 4800
aagaaaatgc aatatctggg tactgtatgg ggaaaaaaat gtccaagttt gtgtaaaacc 4860
agtgcatttc agcttgcaag ttactgaaca caataatgct gttttaattt tgttttatat 4920
cagttaaaat tcacaataat gtagatagaa caaattacag acaaggaaag aaaaaacttg 4980
aatgaaatgg attttacaga aagctttatg ataatttttg aatgcattat ttattttttg 5040
tgccatgcat tttttttctc accaaatgac cttacctgta atacagtctt gtttgtctgt 5100
ttacaaccat gtatttattg caatgtacat actgtaatgt taattgtaaa ttatctgttc 5160
ttattaaaac atcatcccat gatgggatgg tgttgatata tttggaaact cttggtgaga 5220
gaatgaatgg tgtgtataca tactctgtac atttttcttt tctcctgtaa tatagtcttg 5280
tcaccttaga gcttgtttat ggaagattca agaaaactat aaaatactta aagatatata 5340
aatttaaaaa aacatagctg caggtctttg gtcccagggc tgtgccttaa ctttaaccaa 5400
tattttcttc tgttttgctg catttgaaag gtaacagtgg agctagggct gggcatttta 5460
catccaggct tttaattgat tagaattctg ccaataggtg gattttacaa aaccacagac 5520
aacctctgaa agattctgag acccttttga gacagaagct cttaagtact tcttgccagg 5580
gagcagcact gcatgtgtga tggttgtttg ccatctgttg atcaggaact acttcagcta 5640
cttgcatttg attatttcct tttttttttt ttttaactcg gaaacacaac tggggaaata 5700
tattctttcc cagtgattat aaacaatctt tttctttttt ttaagtcctt ttggcttcta 5760
gagctcatag gaaaatggac ttgatttgaa attggagcca gagtttactc gtgttggtta 5820
tctattcatc agcttcctga catgttaaga gaatacatta aagagaaaat actgtttttt 5880
aatcctaaaa tttttcttcc actaagataa accaaatgtc cttacatata tgtaaaccca 5940
tctatttaaa cgcaaaggtg ggttgatgtc agtttacata gcagaaagca ttcactatcc 6000
tctaagattt gtttctgcaa aactttcatt gctttagaat tttaaaattt caccttgtac 6060
aatggccagc ccctaaagca ggaaacattt ataatggatt atatggaaac atcctcccag 6120
tacttgccca gcccttgaat catgtggctt ttcagtgaaa ggaaagattc tttttctagg 6180
aaaaatgagc ctattttatt ttattttatt ttattttttg acacaaactg tagattttag 6240
cagccctggc ccaaaggaat ttgattactt ttgttttaaa cagtacaaag gggacactat 6300
aattacaaaa acatccttaa ctgatttgag ttgtttttat ttctttggat atattttcag 6360
agtggtaaat tgtgtgtgag aattacaaat gattattctt ttagtggttt cttagcctct 6420
cttacagccc acggggatag tactgtacat caataccttc atatgaaatt tttatatgca 6480
atgaaaataa aagcatgggt tgattctgcc tatttatgac tcaatctttt acaaataaaa 6540
gattattcat tttaaattat agttcaatca gcatgtctct taggatactg aacgtggttg 6600
aaatgaaagg atagtgacat cataagttag tactgatatt cataaccaaa taaagccaac 6660
ttgagtaatt ttgctacatt aaaaattacc aaaattactt agatggccta taagattaag 6720
catggtgttt tctaagcaag ctttgaaagg ggccttccat acttacttaa ttgaatattc 6780
tgggatattg aaaattattc agatacttga caattatttt tggttaccta ctccgcaaac 6840
tacaaagttt taaggactca acaataagtt aatgagacac agtgtttgct ttcatggagc 6900
ttacagtctg gaggggacaa aggcttaaac aatactcata taattatata tgtgatcagt 6960
acaatgaagg agctcagtgg ggtaaataag caggaacctg aacttgatct gttccggagg 7020
gccacagaag gcttccttga ggccttgaga aagtgatttg catctgagtt ctgaaggatt 7080
gtaagaggta actagggaaa aagttgacag gaagaggaag gggatccaga caagaaacat 7140
ttgcaaagat cttgaggcat aaatgagctt gagacatctg gagaaactga ggaaaagtga 7200
gagagtaggc agggcctgga gccgcagagc cattgctaac catcctgtgt gagatatccc 7260
ccattctgta gctttattct cataaccctg ctcaattttc tttataacac ttctcacaga 7320
tttatatacg tgtttgtttt tgttatctgt ctctcccacc agaccacagc tccatgagag 7380
caaggtcttt gcttaccaat atatcactag cacttaaaac tatgcctggt acacagtagg 7440
ttcttaatat gtgttgaata tagccatcaa attgatattg gatataattc aatctgataa 7500
gatattttga gatattaaag agtttttaac ttgataccat aaaaa 7545
<210> 18
<211> 8130
<212> DNA
<213> Homo sapiens
<400> 18
agattatagc ccagcgtacg agaagcacga gtcctatagt tggcgtaccc tgaggcctgc 60
cagttcctgc cttaatgcat atgtagtcgt aattgagttc tgacacggcc ttggatgttt 120
ctgtcctaaa tagctgacat tgcatcttca agactgtcat tccagttggc ttttgagtgg 180
atacgtgcag tgagatcatt gacactggaa acactagttc ccattttaat tacttaaaac 240
accacgatga aaagaaatac ctgtgatttg ctttctcgga gcaaaagtgc ctctgaggaa 300
acactacatt ccagtaatga agaggaagac cctttccgcg gaatggaacc ctatcttgtc 360
cggagacttt catgtcgcaa tattcagctt ccccctctcg ccttcagaca gttggaacaa 420
gctgacttga aaagtgaatc agagaacatt caacgaccaa ccagcctccc cctgaagatt 480
ctgccgctga ttgctatcac ttctgcagaa tccagtggtt ttgatgtgga caatggcaca 540
tctgcgggac ggagtccctt ggatcccatg accagcccag gatccgggct aattctccaa 600
gcaaattttg tccacagtca acgacgggag tccttcctgt atcgatccga cagcgattat 660
gacctctctc caaagtctat gtcccggaac tcctccattg ccagtgatat acacggagat 720
gacttgattg tgactccatt tgctcaggtc ttggccagtc tgcgaactgt acgaaacaac 780
tttgctgcat taactaattt gcaagatcga gcacctagca aaagatcacc catgtgcaac 840
caaccatcca tcaacaaagc caccataaca gaggaggcct accagaaact ggccagcgag 900
accctggagg agctggactg gtgtctggac cagctagaga ccctacagac caggcactcc 960
gtcagtgaga tggcctccaa caagtttaaa aggatgctta atcgggagct cacccatctc 1020
tctgaaatga gtcggtctgg aaatcaagtg tcagagttta tatcaaacac attcttagat 1080
aagcaacatg aagtggaaat tccttctcca actcagaagg aaaaggagaa aaagaaaaga 1140
ccaatgtctc agatcagtgg agtcaagaaa ttgatgcaca gctctagtct gactaattca 1200
agtatcccaa ggtttggagt taaaactgaa caagaagatg tccttgccaa ggaactagaa 1260
gatgtgaaca aatggggtct tcatgttttc agaatagcag agttgtctgg taaccggccc 1320
ttgactgtta tcatgcacac catttttcag gaacgggatt tattaaaaac atttaaaatt 1380
ccagtagata ctttaattac atatcttatg actctcgaag accattacca tgctgatgtg 1440
gcctatcaca acaatatcca tgctgcagat gttgtccagt ctactcatgt gctattatct 1500
acacctgctt tggaggctgt gtttacagat ttggagattc ttgcagcaat ttttgccagt 1560
gcaatacatg atgtagatca tcctggtgtg tccaatcaat ttctgatcaa tacaaactct 1620
gaacttgcct tgatgtacaa tgattcctca gtcttagaga accatcattt ggctgtgggc 1680
tttaaattgc ttcaggaaga aaactgtgac attttccaga atttgaccaa aaaacaaaga 1740
caatctttaa ggaaaatggt cattgacatc gtacttgcaa cagatatgtc aaaacacatg 1800
aatctactgg ctgatttgaa gactatggtt gaaactaaga aagtgacaag ctctggagtt 1860
cttcttcttg ataattattc cgataggatt caggttcttc agaatatggt gcactgtgca 1920
gatctgagca acccaacaaa gcctctccag ctgtaccgcc agtggacgga ccggataatg 1980
gaggagttct tccgccaagg agaccgagag agggaacgtg gcatggagat aagccccatg 2040
tgtgacaagc acaatgcttc cgtggaaaaa tcacaggtgg gcttcataga ctatattgtt 2100
catcccctct gggagacatg ggcagacctc gtccaccctg acgcccagga tattttggac 2160
actttggagg acaatcgtga atggtaccag agcacaatcc ctcagagccc ctctcctgca 2220
cctgatgacc cagaggaggg ccggcagggt caaactgaga aattccagtt tgaactaact 2280
ttagaggaag atggtgagtc agacacggaa aaggacagtg gcagtcaagt ggaagaagac 2340
actagctgca gtgactccaa gactctttgt actcaagact cagagtctac tgaaattccc 2400
cttgatgaac aggttgaaga ggaggcagta ggggaagaag aggaaagcca gcctgaagcc 2460
tgtgtcatag atgatcgttc tcctgacacg taacagtgca aaaactttca tgcctttttt 2520
ttttttaagt agaaaaattg tttccaaagt gcatgtcaca tgccacaacc acggtcacac 2580
ctcactgtca tctgccagga cgtttgttga acaaaactga ccttgactac tcagtccagc 2640
gctcaggaat atcgtaacca gttttttcac ctccatgtca tccgagcaag gtggacatct 2700
tcacgaacag cgtttttaac aagatttcag cttggtagag ctgacaaagc agataaaatc 2760
tactccaaat tattttcaag agagtgtgac tcatcaggca gcccaaaagt ttattggact 2820
tggggtttct attccttttt atttgtttgc aatattttca gaagaaaggc attgcacaga 2880
gtgaacttaa tggacgaagc aacaaatatg tcaagaacag gacatagcac gaatctgtta 2940
ccagtaggag gaggatgagc cacagaaatt gcataatttt ctaatttcaa gtcttcctga 3000
tacatgactg aatagtgtgg ttcagtgagc tgcactgacc tctacatttt gtatgatatg 3060
taaaacagat tttttgtaga gcttactttt attattaaat gtattgaggt attatattta 3120
aaaaaaacta tgttcagaac ttcatctgcc actggttatt tttttctaag gagtaacttg 3180
caagttttca gtacaaatct gtgctacact ggataaaaat ctaatttatg aattttactt 3240
gcaccttata gttcatagca attaactgat ttgtagtgat tcattgtttg ttttatatac 3300
caatgacttc catattttaa aagagaaaaa caactttatg ttgcaggaaa ccctttttgt 3360
aagtctttat tatttacttt gcattttgtt tcactctttc cagataagca gagttgctct 3420
tcaccagtgt ttttcttcat gtgcaaagtg actatttgtt ctataatact tttatgtgtg 3480
ttatatcaaa tgtgtcttaa gcttcatgca aactcagtca tcagttcgtg ttgtctgaag 3540
caagtgggag atatataaat acccagtagc taaaatggtc agtctttttt agatgttttc 3600
ctacttagta tctcctaata acgttttgct gtgtcactag atgttcattt cacaagtgca 3660
tgtctttcta ataatccaca catttcatgc tctaataatc cacacatttc atgctcattt 3720
ttattgtttt tacagccagt tatagtaaga aaaaggtttt tccccttgtg ctgctttata 3780
atttagcgtg tgtctgaacc ttatccatgt ttgctagatg aggtcttgtc aaatatatca 3840
ctaccattgt caccggtgaa aagaaacagg tagttaagtt agggttaaca ttcatttcaa 3900
ccacgaggtt gtatatcatg actagctttt actcttggtt tacagagaaa agttaaacag 3960
ccaactaggc agtttttaag aatattaaca atatattaac aaacaccaat acaactaatc 4020
ctatttggtt ttaatgattt caccatggga ttaagaacta tatcaggaac atccctgaga 4080
aacggtttta agtgtagcaa ctactcttcc ttaatggaca gccacataac gtgtaggaag 4140
tcctttatca cttatcctcg atccataagc atatcttgca gaggggaact acttctttaa 4200
acacatggag ggaaagaaga tgatgccact ggcaccagag ggttagtact gtgatgcatc 4260
ctaaaatatt tattatattg gtaaaaattc tggttaaata aaaaattaga gatcactctt 4320
ggctgatttc agcaccagga actgtattac agttttagag attaattcct agtgtttacc 4380
tgattatagc agttggcatc atggggcatt taattctgac tttatcccca cgtcagcctt 4440
aataaagtct tctttacctt ctctatgaag actttaaagc ccaaataatc atttttcaca 4500
ttgatattca agaattgaga tagatagaag ccaaagtggg tatctgacaa gtggaaaatc 4560
aaacgtttaa gaagaattac aactctgaaa agcatttata tgtggaactt ctcaaggagc 4620
ctcctgggga ctggaaagta agtcatcagc caggcaaatg actcatgctg aagagagtcc 4680
ccatttcagt cccctgagat ctagctgatg cttagatcct ttgaaataaa aattatgtct 4740
ttataactct gatcttttac ataaagcaga agaggaatca actagttaat tgcaaggttt 4800
ctactctgtt tcctctgtaa agatcagatg gtaatctttc aaataagaaa aaaataaaga 4860
cgtatgtttg accaagtagt ttcacaagaa tatttgggaa cttgtttctt ttaattttat 4920
ttgtccctga gtgaagtcta gaaagaaagg taaagagtct agagtttatt cctctttcca 4980
aaacattctc attcctctcc tccctacact tagtatttcc cccacagagt gcctagaatc 5040
ttaataatga ataaaataaa aagcagcaat atgtcattaa caaatccaga cctgaaaggg 5100
taaagggttt ataactgcac taataaagag aggctctttt tttttcttcc agtttgttgg 5160
tttttaatgg taccgtgttg taaagatacc cactaatgga caatcaaatt gcagaaaagg 5220
ctcaatatcc aagagacagg gactaatgca ctgtacaatc tgcttatcct tgcccttctc 5280
tcttgccaaa gtgtgcttca gaaatatata ctgctttaaa aaagaataaa agaatatcct 5340
tttacaagtg gctttacatt tcctaaaatg ccataagaaa atgcaatatc tgggtactgt 5400
atggggaaaa aaatgtccaa gtttgtgtaa aaccagtgca tttcagcttg caagttactg 5460
aacacaataa tgctgtttta attttgtttt atatcagtta aaattcacaa taatgtagat 5520
agaacaaatt acagacaagg aaagaaaaaa cttgaatgaa atggatttta cagaaagctt 5580
tatgataatt tttgaatgca ttatttattt tttgtgccat gcattttttt tctcaccaaa 5640
tgaccttacc tgtaatacag tcttgtttgt ctgtttacaa ccatgtattt attgcaatgt 5700
acatactgta atgttaattg taaattatct gttcttatta aaacatcatc ccatgatggg 5760
atggtgttga tatatttgga aactcttggt gagagaatga atggtgtgta tacatactct 5820
gtacattttt cttttctcct gtaatatagt cttgtcacct tagagcttgt ttatggaaga 5880
ttcaagaaaa ctataaaata cttaaagata tataaattta aaaaaacata gctgcaggtc 5940
tttggtccca gggctgtgcc ttaactttaa ccaatatttt cttctgtttt gctgcatttg 6000
aaaggtaaca gtggagctag ggctgggcat tttacatcca ggcttttaat tgattagaat 6060
tctgccaata ggtggatttt acaaaaccac agacaacctc tgaaagattc tgagaccctt 6120
ttgagacaga agctcttaag tacttcttgc cagggagcag cactgcatgt gtgatggttg 6180
tttgccatct gttgatcagg aactacttca gctacttgca tttgattatt tccttttttt 6240
ttttttttaa ctcggaaaca caactgggga aatatattct ttcccagtga ttataaacaa 6300
tctttttctt ttttttaagt ccttttggct tctagagctc ataggaaaat ggacttgatt 6360
tgaaattgga gccagagttt actcgtgttg gttatctatt catcagcttc ctgacatgtt 6420
aagagaatac attaaagaga aaatactgtt ttttaatcct aaaatttttc ttccactaag 6480
ataaaccaaa tgtccttaca tatatgtaaa cccatctatt taaacgcaaa ggtgggttga 6540
tgtcagttta catagcagaa agcattcact atcctctaag atttgtttct gcaaaacttt 6600
cattgcttta gaattttaaa atttcacctt gtacaatggc cagcccctaa agcaggaaac 6660
atttataatg gattatatgg aaacatcctc ccagtacttg cccagccctt gaatcatgtg 6720
gcttttcagt gaaaggaaag attctttttc taggaaaaat gagcctattt tattttattt 6780
tattttattt tttgacacaa actgtagatt ttagcagccc tggcccaaag gaatttgatt 6840
acttttgttt taaacagtac aaaggggaca ctataattac aaaaacatcc ttaactgatt 6900
tgagttgttt ttatttcttt ggatatattt tcagagtggt aaattgtgtg tgagaattac 6960
aaatgattat tcttttagtg gtttcttagc ctctcttaca gcccacgggg atagtactgt 7020
acatcaatac cttcatatga aatttttata tgcaatgaaa ataaaagcat gggttgattc 7080
tgcctattta tgactcaatc ttttacaaat aaaagattat tcattttaaa ttatagttca 7140
atcagcatgt ctcttaggat actgaacgtg gttgaaatga aaggatagtg acatcataag 7200
ttagtactga tattcataac caaataaagc caacttgagt aattttgcta cattaaaaat 7260
taccaaaatt acttagatgg cctataagat taagcatggt gttttctaag caagctttga 7320
aaggggcctt ccatacttac ttaattgaat attctgggat attgaaaatt attcagatac 7380
ttgacaatta tttttggtta cctactccgc aaactacaaa gttttaagga ctcaacaata 7440
agttaatgag acacagtgtt tgctttcatg gagcttacag tctggagggg acaaaggctt 7500
aaacaatact catataatta tatatgtgat cagtacaatg aaggagctca gtggggtaaa 7560
taagcaggaa cctgaacttg atctgttccg gagggccaca gaaggcttcc ttgaggcctt 7620
gagaaagtga tttgcatctg agttctgaag gattgtaaga ggtaactagg gaaaaagttg 7680
acaggaagag gaaggggatc cagacaagaa acatttgcaa agatcttgag gcataaatga 7740
gcttgagaca tctggagaaa ctgaggaaaa gtgagagagt aggcagggcc tggagccgca 7800
gagccattgc taaccatcct gtgtgagata tcccccattc tgtagcttta ttctcataac 7860
cctgctcaat tttctttata acacttctca cagatttata tacgtgtttg tttttgttat 7920
ctgtctctcc caccagacca cagctccatg agagcaaggt ctttgcttac caatatatca 7980
ctagcactta aaactatgcc tggtacacag taggttctta atatgtgttg aatatagcca 8040
tcaaattgat attggatata attcaatctg ataagatatt ttgagatatt aaagagtttt 8100
taacttgata ccataaaaaa aaaaaaaaaa 8130
<210> 19
<211> 7814
<212> DNA
<213> Homo sapiens
<400> 19
acaaaggaaa tgccctcact cagctacaag tgcctcctgc tccgtgcggg gcctcagggc 60
cccagagccc cgcaccagct ctgacttctc gtggttcctg gggatcttgg catcgtcctt 120
aaaaatggct tttgtttggg atcctctggg agccacggtg ccaggaccat ctacaagagc 180
caaatcaaga ttgcgtttct caaagtccta cagttttgat gtggacaatg gcacatctgc 240
gggacggagt cccttggatc ccatgaccag cccaggatcc gggctaattc tccaagcaaa 300
ttttgtccac agtcaacgac gggagtcctt cctgtatcga tccgacagcg attatgacct 360
ctctccaaag tctatgtccc ggaactcctc cattgccagt gatatacacg gagatgactt 420
gattgtgact ccatttgctc aggtcttggc cagtctgcga actgtacgaa acaactttgc 480
tgcattaact aatttgcaag atcgagcacc tagcaaaaga tcacccatgt gcaaccaacc 540
atccatcaac aaagccacca taacagagga ggcctaccag aaactggcca gcgagaccct 600
ggaggagctg gactggtgtc tggaccagct agagacccta cagaccaggc actccgtcag 660
tgagatggcc tccaacaagt ttaaaaggat gcttaatcgg gagctcaccc atctctctga 720
aatgagtcgg tctggaaatc aagtgtcaga gtttatatca aacacattct tagataagca 780
acatgaagtg gaaattcctt ctccaactca gaaggaaaag gagaaaaaga aaagaccaat 840
gtctcagatc agtggagtca agaaattgat gcacagctct agtctgacta attcaagtat 900
cccaaggttt ggagttaaaa ctgaacaaga agatgtcctt gccaaggaac tagaagatgt 960
gaacaaatgg ggtcttcatg ttttcagaat agcagagttg tctggtaacc ggcccttgac 1020
tgttatcatg cacaccattt ttcaggaacg ggatttatta aaaacattta aaattccagt 1080
agatacttta attacatatc ttatgactct cgaagaccat taccatgctg atgtggccta 1140
tcacaacaat atccatgctg cagatgttgt ccagtctact catgtgctat tatctacacc 1200
tgctttggag gctgtgttta cagatttgga gattcttgca gcaatttttg ccagtgcaat 1260
acatgatgta gatcatcctg gtgtgtccaa tcaatttctg atcaatacaa actctgaact 1320
tgccttgatg tacaatgatt cctcagtctt agagaaccat catttggctg tgggctttaa 1380
attgcttcag gaagaaaact gtgacatttt ccagaatttg accaaaaaac aaagacaatc 1440
tttaaggaaa atggtcattg acatcgtact tgcaacagat atgtcaaaac acatgaatct 1500
actggctgat ttgaagacta tggttgaaac taagaaagtg acaagctctg gagttcttct 1560
tcttgataat tattccgata ggattcaggt tcttcagaat atggtgcact gtgcagatct 1620
gagcaaccca acaaagcctc tccagctgta ccgccagtgg acggaccgga taatggagga 1680
gttcttccgc caaggagacc gagagaggga acgtggcatg gagataagcc ccatgtgtga 1740
caagcacaat gcttccgtgg aaaaatcaca ggtgggcttc atagactata ttgttcatcc 1800
cctctgggag acatgggcag acctcgtcca ccctgacgcc caggatattt tggacacttt 1860
ggaggacaat cgtgaatggt accagagcac aatccctcag agcccctctc ctgcacctga 1920
tgacccagag gagggccggc agggtcaaac tgagaaattc cagtttgaac taactttaga 1980
ggaagatggt gagtcagaca cggaaaagga cagtggcagt caagtggaag aagacactag 2040
ctgcagtgac tccaagactc tttgtactca agactcagag tctactgaaa ttccccttga 2100
tgaacaggtt gaagaggagg cagtagggga agaagaggaa agccagcctg aagcctgtgt 2160
catagatgat cgttctcctg acacgtaaca gtgcaaaaac tttcatgcct tttttttttt 2220
taagtagaaa aattgtttcc aaagtgcatg tcacatgcca caaccacggt cacacctcac 2280
tgtcatctgc caggacgttt gttgaacaaa actgaccttg actactcagt ccagcgctca 2340
ggaatatcgt aaccagtttt ttcacctcca tgtcatccga gcaaggtgga catcttcacg 2400
aacagcgttt ttaacaagat ttcagcttgg tagagctgac aaagcagata aaatctactc 2460
caaattattt tcaagagagt gtgactcatc aggcagccca aaagtttatt ggacttgggg 2520
tttctattcc tttttatttg tttgcaatat tttcagaaga aaggcattgc acagagtgaa 2580
cttaatggac gaagcaacaa atatgtcaag aacaggacat agcacgaatc tgttaccagt 2640
aggaggagga tgagccacag aaattgcata attttctaat ttcaagtctt cctgatacat 2700
gactgaatag tgtggttcag tgagctgcac tgacctctac attttgtatg atatgtaaaa 2760
cagatttttt gtagagctta cttttattat taaatgtatt gaggtattat atttaaaaaa 2820
aactatgttc agaacttcat ctgccactgg ttattttttt ctaaggagta acttgcaagt 2880
tttcagtaca aatctgtgct acactggata aaaatctaat ttatgaattt tacttgcacc 2940
ttatagttca tagcaattaa ctgatttgta gtgattcatt gtttgtttta tataccaatg 3000
acttccatat tttaaaagag aaaaacaact ttatgttgca ggaaaccctt tttgtaagtc 3060
tttattattt actttgcatt ttgtttcact ctttccagat aagcagagtt gctcttcacc 3120
agtgtttttc ttcatgtgca aagtgactat ttgttctata atacttttat gtgtgttata 3180
tcaaatgtgt cttaagcttc atgcaaactc agtcatcagt tcgtgttgtc tgaagcaagt 3240
gggagatata taaataccca gtagctaaaa tggtcagtct tttttagatg ttttcctact 3300
tagtatctcc taataacgtt ttgctgtgtc actagatgtt catttcacaa gtgcatgtct 3360
ttctaataat ccacacattt catgctctaa taatccacac atttcatgct catttttatt 3420
gtttttacag ccagttatag taagaaaaag gtttttcccc ttgtgctgct ttataattta 3480
gcgtgtgtct gaaccttatc catgtttgct agatgaggtc ttgtcaaata tatcactacc 3540
attgtcaccg gtgaaaagaa acaggtagtt aagttagggt taacattcat ttcaaccacg 3600
aggttgtata tcatgactag cttttactct tggtttacag agaaaagtta aacagccaac 3660
taggcagttt ttaagaatat taacaatata ttaacaaaca ccaatacaac taatcctatt 3720
tggttttaat gatttcacca tgggattaag aactatatca ggaacatccc tgagaaacgg 3780
ttttaagtgt agcaactact cttccttaat ggacagccac ataacgtgta ggaagtcctt 3840
tatcacttat cctcgatcca taagcatatc ttgcagaggg gaactacttc tttaaacaca 3900
tggagggaaa gaagatgatg ccactggcac cagagggtta gtactgtgat gcatcctaaa 3960
atatttatta tattggtaaa aattctggtt aaataaaaaa ttagagatca ctcttggctg 4020
atttcagcac caggaactgt attacagttt tagagattaa ttcctagtgt ttacctgatt 4080
atagcagttg gcatcatggg gcatttaatt ctgactttat ccccacgtca gccttaataa 4140
agtcttcttt accttctcta tgaagacttt aaagcccaaa taatcatttt tcacattgat 4200
attcaagaat tgagatagat agaagccaaa gtgggtatct gacaagtgga aaatcaaacg 4260
tttaagaaga attacaactc tgaaaagcat ttatatgtgg aacttctcaa ggagcctcct 4320
ggggactgga aagtaagtca tcagccaggc aaatgactca tgctgaagag agtccccatt 4380
tcagtcccct gagatctagc tgatgcttag atcctttgaa ataaaaatta tgtctttata 4440
actctgatct tttacataaa gcagaagagg aatcaactag ttaattgcaa ggtttctact 4500
ctgtttcctc tgtaaagatc agatggtaat ctttcaaata agaaaaaaat aaagacgtat 4560
gtttgaccaa gtagtttcac aagaatattt gggaacttgt ttcttttaat tttatttgtc 4620
cctgagtgaa gtctagaaag aaaggtaaag agtctagagt ttattcctct ttccaaaaca 4680
ttctcattcc tctcctccct acacttagta tttcccccac agagtgccta gaatcttaat 4740
aatgaataaa ataaaaagca gcaatatgtc attaacaaat ccagacctga aagggtaaag 4800
ggtttataac tgcactaata aagagaggct cttttttttt cttccagttt gttggttttt 4860
aatggtaccg tgttgtaaag atacccacta atggacaatc aaattgcaga aaaggctcaa 4920
tatccaagag acagggacta atgcactgta caatctgctt atccttgccc ttctctcttg 4980
ccaaagtgtg cttcagaaat atatactgct ttaaaaaaga ataaaagaat atccttttac 5040
aagtggcttt acatttccta aaatgccata agaaaatgca atatctgggt actgtatggg 5100
gaaaaaaatg tccaagtttg tgtaaaacca gtgcatttca gcttgcaagt tactgaacac 5160
aataatgctg ttttaatttt gttttatatc agttaaaatt cacaataatg tagatagaac 5220
aaattacaga caaggaaaga aaaaacttga atgaaatgga ttttacagaa agctttatga 5280
taatttttga atgcattatt tattttttgt gccatgcatt ttttttctca ccaaatgacc 5340
ttacctgtaa tacagtcttg tttgtctgtt tacaaccatg tatttattgc aatgtacata 5400
ctgtaatgtt aattgtaaat tatctgttct tattaaaaca tcatcccatg atgggatggt 5460
gttgatatat ttggaaactc ttggtgagag aatgaatggt gtgtatacat actctgtaca 5520
tttttctttt ctcctgtaat atagtcttgt caccttagag cttgtttatg gaagattcaa 5580
gaaaactata aaatacttaa agatatataa atttaaaaaa acatagctgc aggtctttgg 5640
tcccagggct gtgccttaac tttaaccaat attttcttct gttttgctgc atttgaaagg 5700
taacagtgga gctagggctg ggcattttac atccaggctt ttaattgatt agaattctgc 5760
caataggtgg attttacaaa accacagaca acctctgaaa gattctgaga cccttttgag 5820
acagaagctc ttaagtactt cttgccaggg agcagcactg catgtgtgat ggttgtttgc 5880
catctgttga tcaggaacta cttcagctac ttgcatttga ttatttcctt tttttttttt 5940
tttaactcgg aaacacaact ggggaaatat attctttccc agtgattata aacaatcttt 6000
ttcttttttt taagtccttt tggcttctag agctcatagg aaaatggact tgatttgaaa 6060
ttggagccag agtttactcg tgttggttat ctattcatca gcttcctgac atgttaagag 6120
aatacattaa agagaaaata ctgtttttta atcctaaaat ttttcttcca ctaagataaa 6180
ccaaatgtcc ttacatatat gtaaacccat ctatttaaac gcaaaggtgg gttgatgtca 6240
gtttacatag cagaaagcat tcactatcct ctaagatttg tttctgcaaa actttcattg 6300
ctttagaatt ttaaaatttc accttgtaca atggccagcc cctaaagcag gaaacattta 6360
taatggatta tatggaaaca tcctcccagt acttgcccag cccttgaatc atgtggcttt 6420
tcagtgaaag gaaagattct ttttctagga aaaatgagcc tattttattt tattttattt 6480
tattttttga cacaaactgt agattttagc agccctggcc caaaggaatt tgattacttt 6540
tgttttaaac agtacaaagg ggacactata attacaaaaa catccttaac tgatttgagt 6600
tgtttttatt tctttggata tattttcaga gtggtaaatt gtgtgtgaga attacaaatg 6660
attattcttt tagtggtttc ttagcctctc ttacagccca cggggatagt actgtacatc 6720
aataccttca tatgaaattt ttatatgcaa tgaaaataaa agcatgggtt gattctgcct 6780
atttatgact caatctttta caaataaaag attattcatt ttaaattata gttcaatcag 6840
catgtctctt aggatactga acgtggttga aatgaaagga tagtgacatc ataagttagt 6900
actgatattc ataaccaaat aaagccaact tgagtaattt tgctacatta aaaattacca 6960
aaattactta gatggcctat aagattaagc atggtgtttt ctaagcaagc tttgaaaggg 7020
gccttccata cttacttaat tgaatattct gggatattga aaattattca gatacttgac 7080
aattattttt ggttacctac tccgcaaact acaaagtttt aaggactcaa caataagtta 7140
atgagacaca gtgtttgctt tcatggagct tacagtctgg aggggacaaa ggcttaaaca 7200
atactcatat aattatatat gtgatcagta caatgaagga gctcagtggg gtaaataagc 7260
aggaacctga acttgatctg ttccggaggg ccacagaagg cttccttgag gccttgagaa 7320
agtgatttgc atctgagttc tgaaggattg taagaggtaa ctagggaaaa agttgacagg 7380
aagaggaagg ggatccagac aagaaacatt tgcaaagatc ttgaggcata aatgagcttg 7440
agacatctgg agaaactgag gaaaagtgag agagtaggca gggcctggag ccgcagagcc 7500
attgctaacc atcctgtgtg agatatcccc cattctgtag ctttattctc ataaccctgc 7560
tcaattttct ttataacact tctcacagat ttatatacgt gtttgttttt gttatctgtc 7620
tctcccacca gaccacagct ccatgagagc aaggtctttg cttaccaata tatcactagc 7680
acttaaaact atgcctggta cacagtaggt tcttaatatg tgttgaatat agccatcaaa 7740
ttgatattgg atataattca atctgataag atattttgag atattaaaga gtttttaact 7800
tgataccata aaaa 7814
<210> 20
<211> 809
<212> PRT
<213> Homo sapiens
<400> 20
Met Glu Ala Glu Gly Ser Ser Ala Pro Ala Arg Ala Gly Ser Gly Glu
1 5 10 15
Gly Ser Asp Ser Ala Gly Gly Ala Thr Leu Lys Ala Pro Lys His Leu
20 25 30
Trp Arg His Glu Gln His His Gln Tyr Pro Leu Arg Gln Pro Gln Phe
35 40 45
Arg Leu Leu His Pro His His His Leu Pro Pro Pro Pro Pro Pro Ser
50 55 60
Pro Gln Pro Gln Pro Gln Cys Pro Leu Gln Pro Pro Pro Pro Pro Pro
65 70 75 80
Leu Pro Pro Pro Pro Pro Pro Pro Gly Ala Ala Arg Gly Arg Tyr Ala
85 90 95
Ser Ser Gly Ala Thr Gly Arg Val Arg His Arg Gly Tyr Ser Asp Thr
100 105 110
Glu Arg Tyr Leu Tyr Cys Arg Ala Met Asp Arg Thr Ser Tyr Ala Val
115 120 125
Glu Thr Gly His Arg Pro Gly Leu Lys Lys Ser Arg Met Ser Trp Pro
130 135 140
Ser Ser Phe Gln Gly Leu Arg Arg Phe Asp Val Asp Asn Gly Thr Ser
145 150 155 160
Ala Gly Arg Ser Pro Leu Asp Pro Met Thr Ser Pro Gly Ser Gly Leu
165 170 175
Ile Leu Gln Ala Asn Phe Val His Ser Gln Arg Arg Glu Ser Phe Leu
180 185 190
Tyr Arg Ser Asp Ser Asp Tyr Asp Leu Ser Pro Lys Ser Met Ser Arg
195 200 205
Asn Ser Ser Ile Ala Ser Asp Ile His Gly Asp Asp Leu Ile Val Thr
210 215 220
Pro Phe Ala Gln Val Leu Ala Ser Leu Arg Thr Val Arg Asn Asn Phe
225 230 235 240
Ala Ala Leu Thr Asn Leu Gln Asp Arg Ala Pro Ser Lys Arg Ser Pro
245 250 255
Met Cys Asn Gln Pro Ser Ile Asn Lys Ala Thr Ile Thr Glu Glu Ala
260 265 270
Tyr Gln Lys Leu Ala Ser Glu Thr Leu Glu Glu Leu Asp Trp Cys Leu
275 280 285
Asp Gln Leu Glu Thr Leu Gln Thr Arg His Ser Val Ser Glu Met Ala
290 295 300
Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His Leu Ser
305 310 315 320
Glu Met Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser Asn Thr
325 330 335
Phe Leu Asp Lys Gln His Glu Val Glu Ile Pro Ser Pro Thr Gln Lys
340 345 350
Glu Lys Glu Lys Lys Lys Arg Pro Met Ser Gln Ile Ser Gly Val Lys
355 360 365
Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro Arg Phe
370 375 380
Gly Val Lys Thr Glu Gln Glu Asp Val Leu Ala Lys Glu Leu Glu Asp
385 390 395 400
Val Asn Lys Trp Gly Leu His Val Phe Arg Ile Ala Glu Leu Ser Gly
405 410 415
Asn Arg Pro Leu Thr Val Ile Met His Thr Ile Phe Gln Glu Arg Asp
420 425 430
Leu Leu Lys Thr Phe Lys Ile Pro Val Asp Thr Leu Ile Thr Tyr Leu
435 440 445
Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His Asn Asn
450 455 460
Ile His Ala Ala Asp Val Val Gln Ser Thr His Val Leu Leu Ser Thr
465 470 475 480
Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile
485 490 495
Phe Ala Ser Ala Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln
500 505 510
Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Ser
515 520 525
Ser Val Leu Glu Asn His His Leu Ala Val Gly Phe Lys Leu Leu Gln
530 535 540
Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln Arg Gln
545 550 555 560
Ser Leu Arg Lys Met Val Ile Asp Ile Val Leu Ala Thr Asp Met Ser
565 570 575
Lys His Met Asn Leu Leu Ala Asp Leu Lys Thr Met Val Glu Thr Lys
580 585 590
Lys Val Thr Ser Ser Gly Val Leu Leu Leu Asp Asn Tyr Ser Asp Arg
595 600 605
Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser Asn Pro
610 615 620
Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu
625 630 635 640
Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met Glu Ile
645 650 655
Ser Pro Met Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser Gln Val
660 665 670
Gly Phe Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp
675 680 685
Leu Val His Pro Asp Ala Gln Asp Ile Leu Asp Thr Leu Glu Asp Asn
690 695 700
Arg Glu Trp Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser Pro Ala Pro
705 710 715 720
Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe Gln Phe
725 730 735
Glu Leu Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys Asp Ser
740 745 750
Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys Thr Leu
755 760 765
Cys Thr Gln Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp Glu Gln Val
770 775 780
Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu Ala Cys
785 790 795 800
Val Ile Asp Asp Arg Ser Pro Asp Thr
805
<210> 21
<211> 699
<212> PRT
<213> Homo sapiens
<400> 21
Met Ser Leu Pro Ser Ser Cys Glu Tyr Leu Thr Leu Gly Lys Val Ala
1 5 10 15
Arg Phe Arg Ser Ala Tyr Val His Gly Ser Pro Tyr Ala Ile Asn Met
20 25 30
Pro Ile Asp Ile Lys Pro Gln Arg Arg Arg Phe Asp Val Asp Asn Gly
35 40 45
Thr Ser Ala Gly Arg Ser Pro Leu Asp Pro Met Thr Ser Pro Gly Ser
50 55 60
Gly Leu Ile Leu Gln Ala Asn Phe Val His Ser Gln Arg Arg Glu Ser
65 70 75 80
Phe Leu Tyr Arg Ser Asp Ser Asp Tyr Asp Leu Ser Pro Lys Ser Met
85 90 95
Ser Arg Asn Ser Ser Ile Ala Ser Asp Ile His Gly Asp Asp Leu Ile
100 105 110
Val Thr Pro Phe Ala Gln Val Leu Ala Ser Leu Arg Thr Val Arg Asn
115 120 125
Asn Phe Ala Ala Leu Thr Asn Leu Gln Asp Arg Ala Pro Ser Lys Arg
130 135 140
Ser Pro Met Cys Asn Gln Pro Ser Ile Asn Lys Ala Thr Ile Thr Glu
145 150 155 160
Glu Ala Tyr Gln Lys Leu Ala Ser Glu Thr Leu Glu Glu Leu Asp Trp
165 170 175
Cys Leu Asp Gln Leu Glu Thr Leu Gln Thr Arg His Ser Val Ser Glu
180 185 190
Met Ala Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His
195 200 205
Leu Ser Glu Met Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser
210 215 220
Asn Thr Phe Leu Asp Lys Gln His Glu Val Glu Ile Pro Ser Pro Thr
225 230 235 240
Gln Lys Glu Lys Glu Lys Lys Lys Arg Pro Met Ser Gln Ile Ser Gly
245 250 255
Val Lys Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro
260 265 270
Arg Phe Gly Val Lys Thr Glu Gln Glu Asp Val Leu Ala Lys Glu Leu
275 280 285
Glu Asp Val Asn Lys Trp Gly Leu His Val Phe Arg Ile Ala Glu Leu
290 295 300
Ser Gly Asn Arg Pro Leu Thr Val Ile Met His Thr Ile Phe Gln Glu
305 310 315 320
Arg Asp Leu Leu Lys Thr Phe Lys Ile Pro Val Asp Thr Leu Ile Thr
325 330 335
Tyr Leu Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His
340 345 350
Asn Asn Ile His Ala Ala Asp Val Val Gln Ser Thr His Val Leu Leu
355 360 365
Ser Thr Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala
370 375 380
Ala Ile Phe Ala Ser Ala Ile His Asp Val Asp His Pro Gly Val Ser
385 390 395 400
Asn Gln Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn
405 410 415
Asp Ser Ser Val Leu Glu Asn His His Leu Ala Val Gly Phe Lys Leu
420 425 430
Leu Gln Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln
435 440 445
Arg Gln Ser Leu Arg Lys Met Val Ile Asp Ile Val Leu Ala Thr Asp
450 455 460
Met Ser Lys His Met Asn Leu Leu Ala Asp Leu Lys Thr Met Val Glu
465 470 475 480
Thr Lys Lys Val Thr Ser Ser Gly Val Leu Leu Leu Asp Asn Tyr Ser
485 490 495
Asp Arg Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser
500 505 510
Asn Pro Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile
515 520 525
Met Glu Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met
530 535 540
Glu Ile Ser Pro Met Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser
545 550 555 560
Gln Val Gly Phe Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp
565 570 575
Ala Asp Leu Val His Pro Asp Ala Gln Asp Ile Leu Asp Thr Leu Glu
580 585 590
Asp Asn Arg Glu Trp Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser Pro
595 600 605
Ala Pro Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe
610 615 620
Gln Phe Glu Leu Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys
625 630 635 640
Asp Ser Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys
645 650 655
Thr Leu Cys Thr Gln Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp Glu
660 665 670
Gln Val Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu
675 680 685
Ala Cys Val Ile Asp Asp Arg Ser Pro Asp Thr
690 695
<210> 22
<211> 745
<212> PRT
<213> Homo sapiens
<400> 22
Met Ala Gln Gln Thr Ser Pro Asp Thr Leu Thr Val Pro Glu Val Asp
1 5 10 15
Asn Pro His Cys Pro Asn Pro Trp Leu Asn Glu Asp Leu Val Lys Ser
20 25 30
Leu Arg Glu Asn Leu Leu Gln His Glu Lys Ser Lys Thr Ala Arg Lys
35 40 45
Ser Val Ser Pro Lys Leu Ser Pro Val Ile Ser Pro Arg Asn Ser Pro
50 55 60
Arg Leu Leu Arg Arg Met Leu Leu Ser Ser Asn Ile Pro Lys Gln Arg
65 70 75 80
Arg Phe Thr Val Ala His Thr Cys Phe Asp Val Asp Asn Gly Thr Ser
85 90 95
Ala Gly Arg Ser Pro Leu Asp Pro Met Thr Ser Pro Gly Ser Gly Leu
100 105 110
Ile Leu Gln Ala Asn Phe Val His Ser Gln Arg Arg Glu Ser Phe Leu
115 120 125
Tyr Arg Ser Asp Ser Asp Tyr Asp Leu Ser Pro Lys Ser Met Ser Arg
130 135 140
Asn Ser Ser Ile Ala Ser Asp Ile His Gly Asp Asp Leu Ile Val Thr
145 150 155 160
Pro Phe Ala Gln Val Leu Ala Ser Leu Arg Thr Val Arg Asn Asn Phe
165 170 175
Ala Ala Leu Thr Asn Leu Gln Asp Arg Ala Pro Ser Lys Arg Ser Pro
180 185 190
Met Cys Asn Gln Pro Ser Ile Asn Lys Ala Thr Ile Thr Glu Glu Ala
195 200 205
Tyr Gln Lys Leu Ala Ser Glu Thr Leu Glu Glu Leu Asp Trp Cys Leu
210 215 220
Asp Gln Leu Glu Thr Leu Gln Thr Arg His Ser Val Ser Glu Met Ala
225 230 235 240
Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His Leu Ser
245 250 255
Glu Met Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser Asn Thr
260 265 270
Phe Leu Asp Lys Gln His Glu Val Glu Ile Pro Ser Pro Thr Gln Lys
275 280 285
Glu Lys Glu Lys Lys Lys Arg Pro Met Ser Gln Ile Ser Gly Val Lys
290 295 300
Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro Arg Phe
305 310 315 320
Gly Val Lys Thr Glu Gln Glu Asp Val Leu Ala Lys Glu Leu Glu Asp
325 330 335
Val Asn Lys Trp Gly Leu His Val Phe Arg Ile Ala Glu Leu Ser Gly
340 345 350
Asn Arg Pro Leu Thr Val Ile Met His Thr Ile Phe Gln Glu Arg Asp
355 360 365
Leu Leu Lys Thr Phe Lys Ile Pro Val Asp Thr Leu Ile Thr Tyr Leu
370 375 380
Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His Asn Asn
385 390 395 400
Ile His Ala Ala Asp Val Val Gln Ser Thr His Val Leu Leu Ser Thr
405 410 415
Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile
420 425 430
Phe Ala Ser Ala Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln
435 440 445
Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Ser
450 455 460
Ser Val Leu Glu Asn His His Leu Ala Val Gly Phe Lys Leu Leu Gln
465 470 475 480
Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln Arg Gln
485 490 495
Ser Leu Arg Lys Met Val Ile Asp Ile Val Leu Ala Thr Asp Met Ser
500 505 510
Lys His Met Asn Leu Leu Ala Asp Leu Lys Thr Met Val Glu Thr Lys
515 520 525
Lys Val Thr Ser Ser Gly Val Leu Leu Leu Asp Asn Tyr Ser Asp Arg
530 535 540
Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser Asn Pro
545 550 555 560
Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu
565 570 575
Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met Glu Ile
580 585 590
Ser Pro Met Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser Gln Val
595 600 605
Gly Phe Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp
610 615 620
Leu Val His Pro Asp Ala Gln Asp Ile Leu Asp Thr Leu Glu Asp Asn
625 630 635 640
Arg Glu Trp Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser Pro Ala Pro
645 650 655
Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe Gln Phe
660 665 670
Glu Leu Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys Asp Ser
675 680 685
Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys Thr Leu
690 695 700
Cys Thr Gln Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp Glu Gln Val
705 710 715 720
Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu Ala Cys
725 730 735
Val Ile Asp Asp Arg Ser Pro Asp Thr
740 745
<210> 23
<211> 673
<212> PRT
<213> Homo sapiens
<400> 23
Met Met His Val Asn Asn Phe Pro Phe Arg Arg His Ser Trp Ile Cys
1 5 10 15
Phe Asp Val Asp Asn Gly Thr Ser Ala Gly Arg Ser Pro Leu Asp Pro
20 25 30
Met Thr Ser Pro Gly Ser Gly Leu Ile Leu Gln Ala Asn Phe Val His
35 40 45
Ser Gln Arg Arg Glu Ser Phe Leu Tyr Arg Ser Asp Ser Asp Tyr Asp
50 55 60
Leu Ser Pro Lys Ser Met Ser Arg Asn Ser Ser Ile Ala Ser Asp Ile
65 70 75 80
His Gly Asp Asp Leu Ile Val Thr Pro Phe Ala Gln Val Leu Ala Ser
85 90 95
Leu Arg Thr Val Arg Asn Asn Phe Ala Ala Leu Thr Asn Leu Gln Asp
100 105 110
Arg Ala Pro Ser Lys Arg Ser Pro Met Cys Asn Gln Pro Ser Ile Asn
115 120 125
Lys Ala Thr Ile Thr Glu Glu Ala Tyr Gln Lys Leu Ala Ser Glu Thr
130 135 140
Leu Glu Glu Leu Asp Trp Cys Leu Asp Gln Leu Glu Thr Leu Gln Thr
145 150 155 160
Arg His Ser Val Ser Glu Met Ala Ser Asn Lys Phe Lys Arg Met Leu
165 170 175
Asn Arg Glu Leu Thr His Leu Ser Glu Met Ser Arg Ser Gly Asn Gln
180 185 190
Val Ser Glu Phe Ile Ser Asn Thr Phe Leu Asp Lys Gln His Glu Val
195 200 205
Glu Ile Pro Ser Pro Thr Gln Lys Glu Lys Glu Lys Lys Lys Arg Pro
210 215 220
Met Ser Gln Ile Ser Gly Val Lys Lys Leu Met His Ser Ser Ser Leu
225 230 235 240
Thr Asn Ser Ser Ile Pro Arg Phe Gly Val Lys Thr Glu Gln Glu Asp
245 250 255
Val Leu Ala Lys Glu Leu Glu Asp Val Asn Lys Trp Gly Leu His Val
260 265 270
Phe Arg Ile Ala Glu Leu Ser Gly Asn Arg Pro Leu Thr Val Ile Met
275 280 285
His Thr Ile Phe Gln Glu Arg Asp Leu Leu Lys Thr Phe Lys Ile Pro
290 295 300
Val Asp Thr Leu Ile Thr Tyr Leu Met Thr Leu Glu Asp His Tyr His
305 310 315 320
Ala Asp Val Ala Tyr His Asn Asn Ile His Ala Ala Asp Val Val Gln
325 330 335
Ser Thr His Val Leu Leu Ser Thr Pro Ala Leu Glu Ala Val Phe Thr
340 345 350
Asp Leu Glu Ile Leu Ala Ala Ile Phe Ala Ser Ala Ile His Asp Val
355 360 365
Asp His Pro Gly Val Ser Asn Gln Phe Leu Ile Asn Thr Asn Ser Glu
370 375 380
Leu Ala Leu Met Tyr Asn Asp Ser Ser Val Leu Glu Asn His His Leu
385 390 395 400
Ala Val Gly Phe Lys Leu Leu Gln Glu Glu Asn Cys Asp Ile Phe Gln
405 410 415
Asn Leu Thr Lys Lys Gln Arg Gln Ser Leu Arg Lys Met Val Ile Asp
420 425 430
Ile Val Leu Ala Thr Asp Met Ser Lys His Met Asn Leu Leu Ala Asp
435 440 445
Leu Lys Thr Met Val Glu Thr Lys Lys Val Thr Ser Ser Gly Val Leu
450 455 460
Leu Leu Asp Asn Tyr Ser Asp Arg Ile Gln Val Leu Gln Asn Met Val
465 470 475 480
His Cys Ala Asp Leu Ser Asn Pro Thr Lys Pro Leu Gln Leu Tyr Arg
485 490 495
Gln Trp Thr Asp Arg Ile Met Glu Glu Phe Phe Arg Gln Gly Asp Arg
500 505 510
Glu Arg Glu Arg Gly Met Glu Ile Ser Pro Met Cys Asp Lys His Asn
515 520 525
Ala Ser Val Glu Lys Ser Gln Val Gly Phe Ile Asp Tyr Ile Val His
530 535 540
Pro Leu Trp Glu Thr Trp Ala Asp Leu Val His Pro Asp Ala Gln Asp
545 550 555 560
Ile Leu Asp Thr Leu Glu Asp Asn Arg Glu Trp Tyr Gln Ser Thr Ile
565 570 575
Pro Gln Ser Pro Ser Pro Ala Pro Asp Asp Pro Glu Glu Gly Arg Gln
580 585 590
Gly Gln Thr Glu Lys Phe Gln Phe Glu Leu Thr Leu Glu Glu Asp Gly
595 600 605
Glu Ser Asp Thr Glu Lys Asp Ser Gly Ser Gln Val Glu Glu Asp Thr
610 615 620
Ser Cys Ser Asp Ser Lys Thr Leu Cys Thr Gln Asp Ser Glu Ser Thr
625 630 635 640
Glu Ile Pro Leu Asp Glu Gln Val Glu Glu Glu Ala Val Gly Glu Glu
645 650 655
Glu Glu Ser Gln Pro Glu Ala Cys Val Ile Asp Asp Arg Ser Pro Asp
660 665 670
Thr
<210> 24
<211> 507
<212> PRT
<213> Homo sapiens
<400> 24
Met Ala Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His
1 5 10 15
Leu Ser Glu Met Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser
20 25 30
Asn Thr Phe Leu Asp Lys Gln His Glu Val Glu Ile Pro Ser Pro Thr
35 40 45
Gln Lys Glu Lys Glu Lys Lys Lys Arg Pro Met Ser Gln Ile Ser Gly
50 55 60
Val Lys Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro
65 70 75 80
Arg Phe Gly Val Lys Thr Glu Gln Glu Asp Val Leu Ala Lys Glu Leu
85 90 95
Glu Asp Val Asn Lys Trp Gly Leu His Val Phe Arg Ile Ala Glu Leu
100 105 110
Ser Gly Asn Arg Pro Leu Thr Val Ile Met His Thr Ile Phe Gln Glu
115 120 125
Arg Asp Leu Leu Lys Thr Phe Lys Ile Pro Val Asp Thr Leu Ile Thr
130 135 140
Tyr Leu Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His
145 150 155 160
Asn Asn Ile His Ala Ala Asp Val Val Gln Ser Thr His Val Leu Leu
165 170 175
Ser Thr Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala
180 185 190
Ala Ile Phe Ala Ser Ala Ile His Asp Val Asp His Pro Gly Val Ser
195 200 205
Asn Gln Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn
210 215 220
Asp Ser Ser Val Leu Glu Asn His His Leu Ala Val Gly Phe Lys Leu
225 230 235 240
Leu Gln Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln
245 250 255
Arg Gln Ser Leu Arg Lys Met Val Ile Asp Ile Val Leu Ala Thr Asp
260 265 270
Met Ser Lys His Met Asn Leu Leu Ala Asp Leu Lys Thr Met Val Glu
275 280 285
Thr Lys Lys Val Thr Ser Ser Gly Val Leu Leu Leu Asp Asn Tyr Ser
290 295 300
Asp Arg Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser
305 310 315 320
Asn Pro Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile
325 330 335
Met Glu Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met
340 345 350
Glu Ile Ser Pro Met Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser
355 360 365
Gln Val Gly Phe Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp
370 375 380
Ala Asp Leu Val His Pro Asp Ala Gln Asp Ile Leu Asp Thr Leu Glu
385 390 395 400
Asp Asn Arg Glu Trp Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser Pro
405 410 415
Ala Pro Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe
420 425 430
Gln Phe Glu Leu Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys
435 440 445
Asp Ser Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys
450 455 460
Thr Leu Cys Thr Gln Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp Glu
465 470 475 480
Gln Val Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu
485 490 495
Ala Cys Val Ile Asp Asp Arg Ser Pro Asp Thr
500 505
<210> 25
<211> 679
<212> PRT
<213> Homo sapiens
<400> 25
Met Ser Ile Ile Met Lys Pro Arg Ser Arg Ser Thr Ser Ser Leu Arg
1 5 10 15
Thr Ala Glu Ala Val Cys Phe Asp Val Asp Asn Gly Thr Ser Ala Gly
20 25 30
Arg Ser Pro Leu Asp Pro Met Thr Ser Pro Gly Ser Gly Leu Ile Leu
35 40 45
Gln Ala Asn Phe Val His Ser Gln Arg Arg Glu Ser Phe Leu Tyr Arg
50 55 60
Ser Asp Ser Asp Tyr Asp Leu Ser Pro Lys Ser Met Ser Arg Asn Ser
65 70 75 80
Ser Ile Ala Ser Asp Ile His Gly Asp Asp Leu Ile Val Thr Pro Phe
85 90 95
Ala Gln Val Leu Ala Ser Leu Arg Thr Val Arg Asn Asn Phe Ala Ala
100 105 110
Leu Thr Asn Leu Gln Asp Arg Ala Pro Ser Lys Arg Ser Pro Met Cys
115 120 125
Asn Gln Pro Ser Ile Asn Lys Ala Thr Ile Thr Glu Glu Ala Tyr Gln
130 135 140
Lys Leu Ala Ser Glu Thr Leu Glu Glu Leu Asp Trp Cys Leu Asp Gln
145 150 155 160
Leu Glu Thr Leu Gln Thr Arg His Ser Val Ser Glu Met Ala Ser Asn
165 170 175
Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His Leu Ser Glu Met
180 185 190
Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser Asn Thr Phe Leu
195 200 205
Asp Lys Gln His Glu Val Glu Ile Pro Ser Pro Thr Gln Lys Glu Lys
210 215 220
Glu Lys Lys Lys Arg Pro Met Ser Gln Ile Ser Gly Val Lys Lys Leu
225 230 235 240
Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro Arg Phe Gly Val
245 250 255
Lys Thr Glu Gln Glu Asp Val Leu Ala Lys Glu Leu Glu Asp Val Asn
260 265 270
Lys Trp Gly Leu His Val Phe Arg Ile Ala Glu Leu Ser Gly Asn Arg
275 280 285
Pro Leu Thr Val Ile Met His Thr Ile Phe Gln Glu Arg Asp Leu Leu
290 295 300
Lys Thr Phe Lys Ile Pro Val Asp Thr Leu Ile Thr Tyr Leu Met Thr
305 310 315 320
Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His Asn Asn Ile His
325 330 335
Ala Ala Asp Val Val Gln Ser Thr His Val Leu Leu Ser Thr Pro Ala
340 345 350
Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile Phe Ala
355 360 365
Ser Ala Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln Phe Leu
370 375 380
Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Ser Ser Val
385 390 395 400
Leu Glu Asn His His Leu Ala Val Gly Phe Lys Leu Leu Gln Glu Glu
405 410 415
Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln Arg Gln Ser Leu
420 425 430
Arg Lys Met Val Ile Asp Ile Val Leu Ala Thr Asp Met Ser Lys His
435 440 445
Met Asn Leu Leu Ala Asp Leu Lys Thr Met Val Glu Thr Lys Lys Val
450 455 460
Thr Ser Ser Gly Val Leu Leu Leu Asp Asn Tyr Ser Asp Arg Ile Gln
465 470 475 480
Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser Asn Pro Thr Lys
485 490 495
Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu Glu Phe
500 505 510
Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met Glu Ile Ser Pro
515 520 525
Met Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser Gln Val Gly Phe
530 535 540
Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp Leu Val
545 550 555 560
His Pro Asp Ala Gln Asp Ile Leu Asp Thr Leu Glu Asp Asn Arg Glu
565 570 575
Trp Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser Pro Ala Pro Asp Asp
580 585 590
Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe Gln Phe Glu Leu
595 600 605
Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys Asp Ser Gly Ser
610 615 620
Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys Thr Leu Cys Thr
625 630 635 640
Gln Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp Glu Gln Val Glu Glu
645 650 655
Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu Ala Cys Val Ile
660 665 670
Asp Asp Arg Ser Pro Asp Thr
675
<210> 26
<211> 518
<212> PRT
<213> Homo sapiens
<400> 26
Met Pro Glu Ala Asn Tyr Leu Leu Ser Val Ser Trp Gly Tyr Ile Lys
1 5 10 15
Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His Leu Ser Glu Met Ser
20 25 30
Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser Asn Thr Phe Leu Asp
35 40 45
Lys Gln His Glu Val Glu Ile Pro Ser Pro Thr Gln Lys Glu Lys Glu
50 55 60
Lys Lys Lys Arg Pro Met Ser Gln Ile Ser Gly Val Lys Lys Leu Met
65 70 75 80
His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro Arg Phe Gly Val Lys
85 90 95
Thr Glu Gln Glu Asp Val Leu Ala Lys Glu Leu Glu Asp Val Asn Lys
100 105 110
Trp Gly Leu His Val Phe Arg Ile Ala Glu Leu Ser Gly Asn Arg Pro
115 120 125
Leu Thr Val Ile Met His Thr Ile Phe Gln Glu Arg Asp Leu Leu Lys
130 135 140
Thr Phe Lys Ile Pro Val Asp Thr Leu Ile Thr Tyr Leu Met Thr Leu
145 150 155 160
Glu Asp His Tyr His Ala Asp Val Ala Tyr His Asn Asn Ile His Ala
165 170 175
Ala Asp Val Val Gln Ser Thr His Val Leu Leu Ser Thr Pro Ala Leu
180 185 190
Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile Phe Ala Ser
195 200 205
Ala Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln Phe Leu Ile
210 215 220
Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Ser Ser Val Leu
225 230 235 240
Glu Asn His His Leu Ala Val Gly Phe Lys Leu Leu Gln Glu Glu Asn
245 250 255
Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln Arg Gln Ser Leu Arg
260 265 270
Lys Met Val Ile Asp Ile Val Leu Ala Thr Asp Met Ser Lys His Met
275 280 285
Asn Leu Leu Ala Asp Leu Lys Thr Met Val Glu Thr Lys Lys Val Thr
290 295 300
Ser Ser Gly Val Leu Leu Leu Asp Asn Tyr Ser Asp Arg Ile Gln Val
305 310 315 320
Leu Gln Asn Met Val His Cys Ala Asp Leu Ser Asn Pro Thr Lys Pro
325 330 335
Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu Glu Phe Phe
340 345 350
Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met Glu Ile Ser Pro Met
355 360 365
Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser Gln Val Gly Phe Ile
370 375 380
Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp Leu Val His
385 390 395 400
Pro Asp Ala Gln Asp Ile Leu Asp Thr Leu Glu Asp Asn Arg Glu Trp
405 410 415
Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser Pro Ala Pro Asp Asp Pro
420 425 430
Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe Gln Phe Glu Leu Thr
435 440 445
Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys Asp Ser Gly Ser Gln
450 455 460
Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys Thr Leu Cys Thr Gln
465 470 475 480
Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp Glu Gln Val Glu Glu Glu
485 490 495
Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu Ala Cys Val Ile Asp
500 505 510
Asp Arg Ser Pro Asp Thr
515
<210> 27
<211> 748
<212> PRT
<213> Homo sapiens
<400> 27
Met Lys Arg Asn Thr Cys Asp Leu Leu Ser Arg Ser Lys Ser Ala Ser
1 5 10 15
Glu Glu Thr Leu His Ser Ser Asn Glu Glu Glu Asp Pro Phe Arg Gly
20 25 30
Met Glu Pro Tyr Leu Val Arg Arg Leu Ser Cys Arg Asn Ile Gln Leu
35 40 45
Pro Pro Leu Ala Phe Arg Gln Leu Glu Gln Ala Asp Leu Lys Ser Glu
50 55 60
Ser Glu Asn Ile Gln Arg Pro Thr Ser Leu Pro Leu Lys Ile Leu Pro
65 70 75 80
Leu Ile Ala Ile Thr Ser Ala Glu Ser Ser Gly Phe Asp Val Asp Asn
85 90 95
Gly Thr Ser Ala Gly Arg Ser Pro Leu Asp Pro Met Thr Ser Pro Gly
100 105 110
Ser Gly Leu Ile Leu Gln Ala Asn Phe Val His Ser Gln Arg Arg Glu
115 120 125
Ser Phe Leu Tyr Arg Ser Asp Ser Asp Tyr Asp Leu Ser Pro Lys Ser
130 135 140
Met Ser Arg Asn Ser Ser Ile Ala Ser Asp Ile His Gly Asp Asp Leu
145 150 155 160
Ile Val Thr Pro Phe Ala Gln Val Leu Ala Ser Leu Arg Thr Val Arg
165 170 175
Asn Asn Phe Ala Ala Leu Thr Asn Leu Gln Asp Arg Ala Pro Ser Lys
180 185 190
Arg Ser Pro Met Cys Asn Gln Pro Ser Ile Asn Lys Ala Thr Ile Thr
195 200 205
Glu Glu Ala Tyr Gln Lys Leu Ala Ser Glu Thr Leu Glu Glu Leu Asp
210 215 220
Trp Cys Leu Asp Gln Leu Glu Thr Leu Gln Thr Arg His Ser Val Ser
225 230 235 240
Glu Met Ala Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr
245 250 255
His Leu Ser Glu Met Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile
260 265 270
Ser Asn Thr Phe Leu Asp Lys Gln His Glu Val Glu Ile Pro Ser Pro
275 280 285
Thr Gln Lys Glu Lys Glu Lys Lys Lys Arg Pro Met Ser Gln Ile Ser
290 295 300
Gly Val Lys Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile
305 310 315 320
Pro Arg Phe Gly Val Lys Thr Glu Gln Glu Asp Val Leu Ala Lys Glu
325 330 335
Leu Glu Asp Val Asn Lys Trp Gly Leu His Val Phe Arg Ile Ala Glu
340 345 350
Leu Ser Gly Asn Arg Pro Leu Thr Val Ile Met His Thr Ile Phe Gln
355 360 365
Glu Arg Asp Leu Leu Lys Thr Phe Lys Ile Pro Val Asp Thr Leu Ile
370 375 380
Thr Tyr Leu Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr
385 390 395 400
His Asn Asn Ile His Ala Ala Asp Val Val Gln Ser Thr His Val Leu
405 410 415
Leu Ser Thr Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu
420 425 430
Ala Ala Ile Phe Ala Ser Ala Ile His Asp Val Asp His Pro Gly Val
435 440 445
Ser Asn Gln Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr
450 455 460
Asn Asp Ser Ser Val Leu Glu Asn His His Leu Ala Val Gly Phe Lys
465 470 475 480
Leu Leu Gln Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys
485 490 495
Gln Arg Gln Ser Leu Arg Lys Met Val Ile Asp Ile Val Leu Ala Thr
500 505 510
Asp Met Ser Lys His Met Asn Leu Leu Ala Asp Leu Lys Thr Met Val
515 520 525
Glu Thr Lys Lys Val Thr Ser Ser Gly Val Leu Leu Leu Asp Asn Tyr
530 535 540
Ser Asp Arg Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu
545 550 555 560
Ser Asn Pro Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg
565 570 575
Ile Met Glu Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly
580 585 590
Met Glu Ile Ser Pro Met Cys Asp Lys His Asn Ala Ser Val Glu Lys
595 600 605
Ser Gln Val Gly Phe Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr
610 615 620
Trp Ala Asp Leu Val His Pro Asp Ala Gln Asp Ile Leu Asp Thr Leu
625 630 635 640
Glu Asp Asn Arg Glu Trp Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser
645 650 655
Pro Ala Pro Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys
660 665 670
Phe Gln Phe Glu Leu Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu
675 680 685
Lys Asp Ser Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser
690 695 700
Lys Thr Leu Cys Thr Gln Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp
705 710 715 720
Glu Gln Val Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro
725 730 735
Glu Ala Cys Val Ile Asp Asp Arg Ser Pro Asp Thr
740 745
<210> 28
<211> 687
<212> PRT
<213> Homo sapiens
<400> 28
Met Ala Phe Val Trp Asp Pro Leu Gly Ala Thr Val Pro Gly Pro Ser
1 5 10 15
Thr Arg Ala Lys Ser Arg Leu Arg Phe Ser Lys Ser Tyr Ser Phe Asp
20 25 30
Val Asp Asn Gly Thr Ser Ala Gly Arg Ser Pro Leu Asp Pro Met Thr
35 40 45
Ser Pro Gly Ser Gly Leu Ile Leu Gln Ala Asn Phe Val His Ser Gln
50 55 60
Arg Arg Glu Ser Phe Leu Tyr Arg Ser Asp Ser Asp Tyr Asp Leu Ser
65 70 75 80
Pro Lys Ser Met Ser Arg Asn Ser Ser Ile Ala Ser Asp Ile His Gly
85 90 95
Asp Asp Leu Ile Val Thr Pro Phe Ala Gln Val Leu Ala Ser Leu Arg
100 105 110
Thr Val Arg Asn Asn Phe Ala Ala Leu Thr Asn Leu Gln Asp Arg Ala
115 120 125
Pro Ser Lys Arg Ser Pro Met Cys Asn Gln Pro Ser Ile Asn Lys Ala
130 135 140
Thr Ile Thr Glu Glu Ala Tyr Gln Lys Leu Ala Ser Glu Thr Leu Glu
145 150 155 160
Glu Leu Asp Trp Cys Leu Asp Gln Leu Glu Thr Leu Gln Thr Arg His
165 170 175
Ser Val Ser Glu Met Ala Ser Asn Lys Phe Lys Arg Met Leu Asn Arg
180 185 190
Glu Leu Thr His Leu Ser Glu Met Ser Arg Ser Gly Asn Gln Val Ser
195 200 205
Glu Phe Ile Ser Asn Thr Phe Leu Asp Lys Gln His Glu Val Glu Ile
210 215 220
Pro Ser Pro Thr Gln Lys Glu Lys Glu Lys Lys Lys Arg Pro Met Ser
225 230 235 240
Gln Ile Ser Gly Val Lys Lys Leu Met His Ser Ser Ser Leu Thr Asn
245 250 255
Ser Ser Ile Pro Arg Phe Gly Val Lys Thr Glu Gln Glu Asp Val Leu
260 265 270
Ala Lys Glu Leu Glu Asp Val Asn Lys Trp Gly Leu His Val Phe Arg
275 280 285
Ile Ala Glu Leu Ser Gly Asn Arg Pro Leu Thr Val Ile Met His Thr
290 295 300
Ile Phe Gln Glu Arg Asp Leu Leu Lys Thr Phe Lys Ile Pro Val Asp
305 310 315 320
Thr Leu Ile Thr Tyr Leu Met Thr Leu Glu Asp His Tyr His Ala Asp
325 330 335
Val Ala Tyr His Asn Asn Ile His Ala Ala Asp Val Val Gln Ser Thr
340 345 350
His Val Leu Leu Ser Thr Pro Ala Leu Glu Ala Val Phe Thr Asp Leu
355 360 365
Glu Ile Leu Ala Ala Ile Phe Ala Ser Ala Ile His Asp Val Asp His
370 375 380
Pro Gly Val Ser Asn Gln Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala
385 390 395 400
Leu Met Tyr Asn Asp Ser Ser Val Leu Glu Asn His His Leu Ala Val
405 410 415
Gly Phe Lys Leu Leu Gln Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu
420 425 430
Thr Lys Lys Gln Arg Gln Ser Leu Arg Lys Met Val Ile Asp Ile Val
435 440 445
Leu Ala Thr Asp Met Ser Lys His Met Asn Leu Leu Ala Asp Leu Lys
450 455 460
Thr Met Val Glu Thr Lys Lys Val Thr Ser Ser Gly Val Leu Leu Leu
465 470 475 480
Asp Asn Tyr Ser Asp Arg Ile Gln Val Leu Gln Asn Met Val His Cys
485 490 495
Ala Asp Leu Ser Asn Pro Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp
500 505 510
Thr Asp Arg Ile Met Glu Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg
515 520 525
Glu Arg Gly Met Glu Ile Ser Pro Met Cys Asp Lys His Asn Ala Ser
530 535 540
Val Glu Lys Ser Gln Val Gly Phe Ile Asp Tyr Ile Val His Pro Leu
545 550 555 560
Trp Glu Thr Trp Ala Asp Leu Val His Pro Asp Ala Gln Asp Ile Leu
565 570 575
Asp Thr Leu Glu Asp Asn Arg Glu Trp Tyr Gln Ser Thr Ile Pro Gln
580 585 590
Ser Pro Ser Pro Ala Pro Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln
595 600 605
Thr Glu Lys Phe Gln Phe Glu Leu Thr Leu Glu Glu Asp Gly Glu Ser
610 615 620
Asp Thr Glu Lys Asp Ser Gly Ser Gln Val Glu Glu Asp Thr Ser Cys
625 630 635 640
Ser Asp Ser Lys Thr Leu Cys Thr Gln Asp Ser Glu Ser Thr Glu Ile
645 650 655
Pro Leu Asp Glu Gln Val Glu Glu Glu Ala Val Gly Glu Glu Glu Glu
660 665 670
Ser Gln Pro Glu Ala Cys Val Ile Asp Asp Arg Ser Pro Asp Thr
675 680 685
<210> 29
<211> 6663
<212> DNA
<213> Homo sapiens
<400> 29
actgaccccg ctgtaccacg gccctcttgc ggacagcccc ggggacgtcg ttgggacatc 60
gctgggaccc cgggctctgc agccacaacc atgtttggcc ggaagcgcag tgtctccttt 120
gggggcttcg gatggatcga caagaccatg ctggcaagtc tgaaggtcaa gaagcaggag 180
ctggccaaca gctcggatgc gaccctccca gaccggccgc tctcccctcc tctcacggca 240
cctcccacca tgaagtcgtc ggagttcttt gagatgctgg agaaaatgca ggggatcaag 300
cttgaagagc agaagccggg accccagaag aacaaggacg actatatccc ataccccagc 360
atcgacgagg ttgtggagaa gggaggcccg taccctcagg tcatcctgcc acagtttggg 420
ggctattgga tcgaggaccc ggagaacgtg ggcaccccaa catcgctggg gagcagcatc 480
tgtgaggagg aggaagagga caacctcagc cccaacacat ttggctacaa gctcgagtgc 540
aagggtgaag ccagggccta ccggaggcac ttcctgggga aggatcatct aaacttttac 600
tgtaccggca gcagcctggg gaacttgatc ctgtccgtca agtgcgagga agcagagggg 660
atcgagtacc tccgggtcat ccttaggtcc aaactgaaga cggtacatga gcggatcccc 720
ttggctggac tgagcaagct tcccagtgtc cctcagattg caaaggcttt ctgtgatgat 780
gcagtgggac tgagattcaa tcctgtcctg taccccaagg cctcccaaat gattgtgtcc 840
tatgatgagc atgaagtcaa caacacattc aaattcggag tcatttatca aaaagccagg 900
cagaccctgg aggaggagct atttgggaac aatgaggaga gcccagcttt taaggagttc 960
ttggacctgc tgggggacac gatcacactg caggatttca aaggtttccg aggaggcctg 1020
gacgtgaccc acggacagac aggggtggaa tcagtgtaca caacattccg ggacagggag 1080
atcatgtttc acgtttccac aaagctgcca tttaccgacg gagacgccca gcagctccag 1140
agaaagagac acattggaaa tgacatcgtg gccatcatct tccaagagga aaacacgccg 1200
tttgtcccag acatgatagc ctccaatttc ttacatgcct acatcgtcgt gcaggtcgag 1260
accccaggca cagagacccc atcctacaag gtctctgtca ctgcgcggga agatgtgccc 1320
acctttggtc cacctctgcc cagtcccccc gttttccaga agggcccgga attcagggag 1380
tttctgctca ccaagctcac caatgccgag aacgcctgct gcaagtcgga caagtttgca 1440
aagctggagg accggaccag ggctgccctc ctggacaacc ttcacgatga gctccacgcc 1500
cacacacagg ccatgctggg actgggccca gaggaggaca agtttgagaa tggaggccac 1560
ggggggttcc tggagtcttt taagagggcc atccgcgtac gcagccactc catggagacc 1620
atggtgggcg gccagaagaa gtcgcacagt gggggcatcc ctggcagcct cagcgggggc 1680
atctcccaca acagcatgga ggtcaccaag accaccttct cgcctccagt ggtggcggca 1740
acggtgaaga accagtcacg gagtcccatc aagcgacgct cggggctctt cccccgcctg 1800
cacacgggct cagaaggcca gggcgacagc cgggcacgat gtgacagcac atccagcaca 1860
cccaagaccc cagatggtgg acactcctct caggagataa agtctgagac ctcatccaat 1920
cccagctctc cggaaatctg ccccaacaag gagaagccct tcatgaagtt gaaggaaaac 1980
ggccgtgcca tctcccgctc ctcctccagc accagcagcg tcagcagcac tgcaggggag 2040
ggcgaggcca tggaggaggg cgacagtggg ggcagccagc cgtccacgac ctcacccttc 2100
aagcaggagg tgtttgtcta cagcccgtcc ccgagcagcg agagccccag cctgggggca 2160
gctgccaccc cgatcatcat gagccggagt cccacagatg ccaaaagcag aaactccccg 2220
agatcgaacc tgaaattccg ctttgacaag ctcagccatg ccagctctgg tgcgggtcac 2280
taatgtgaaa gtggagtcct tcgcctgtcc aagggaatcc cctcttctgt cctggaaaag 2340
gctcctgtac cagcagtttg ggagtgccgt ccacgaccct gacagtccca gccctgctgc 2400
cccatggcca cgtgcccaca gatgtgctgt tggtccaggt gtcccagtct ggccacagcc 2460
ctgcctccgc cctcacctac atgccctccc agcccctccc atctctggac gaggcctcct 2520
tcctcaggtt cctcctgctc ctgacctccc agtgtgatgt ccgggtcctt tatcatccta 2580
ttcatcctgg agaggaaaag tgtcgggcaa agggggatct ggggggagct cagcagtgac 2640
tggggagctg gtctgcctca gagacagagt agggggtggg agcagagcct cggtgagggt 2700
cttggccaca gggcagtgcc ttcctgaacg tggcaggctt tactaccagg aacgcactcg 2760
gtggtggagg ccccatgttc ccaggagcca agattcgtag catccttgag gccatcctga 2820
taaaattcgg cgctattgcc cccgtagctc tggagctcta aaccgtctat ctgcttctgt 2880
gctgaacgcc tttcccatct gctgacgtag gcccagggct gccctgcccc tgctgccagt 2940
gtaccgtgag cggggctcca gccagttcaa gctcagagcc agagctggac gggccagaac 3000
tgcgctgcac acttcctgga ctgaggcggg gactttgggt cccacccggt ttctcctgat 3060
tatggctgct gtggggtgag gggagggagg ggcagccccg aggcagtctc ttccctttga 3120
gaagatattt tcccacaaag gggtgggaag ccaggagtga gaaggaattc agggagagca 3180
aaggagccag tgctgagatg ctgctgtgtt ggttgaggaa aacctcgggc ctgagggcca 3240
ggccggagcc caggtctctg ctgacaatgg gggttcaagg aagacgtcgt tatctcccct 3300
ccccacttac tcgaggagag aggtgagggg gggatgactt gcgggttctg atcaggcccc 3360
tgggtgggga aggggcacag tgtccctcag cagcttacgc ccctggagtc ttggggggcc 3420
cagcctggcc ctggggcctt ttccagctac tgtgcccttg ggcagctgcg tctggggctc 3480
aaccccccaa tcctgttccc ctctccagct gcgggtctgt aggcagctgt cacatctgaa 3540
gggtttctgc aacctggacc ccatctgggt gtgggtcaga ccctgtgacc cacatgccac 3600
ccccaccctc cacagagccc ccttgctggg acagccagct cacctccaag gacatcccct 3660
cctggcttct cccccttccg agtctgcagc gccgtgggct tctctgccga tgggcccggg 3720
ttggggttaa ggtgggcatc ctccaggtac aacgagcctg aagagcccct ttcagtgcag 3780
acggggctgc agagtgacac tggctgggca cctgccccac gaccaatgac aaggatttcc 3840
agctgaatgc tttattccca tagggatctg gacctgtgcc caagatataa atactacact 3900
tttttttttt ttttttaact gacattgtga aattctccct atagcttttg ccattcaagc 3960
aacattgtga tctttcttcc ccgccacgtg tgtgggaatg attgagtcct gtttgcaagc 4020
tggagaggag ctctcccttt gctagtactt tctctaaagt actagtctag taaaatttat 4080
tcttgttaga aggtcaacaa aatatctgtt tagcttttat gaagagtcac cgtagcagcc 4140
cccacggctg gaaagaggcc tgtacgttct ggacgcgttt tgttggctgg gcttctggag 4200
gcactggcaa ggtcaaactg catttcttta agaacagttg caggatctgg ctcgcctctg 4260
tgggaagccg gcattacagg tgcttggtgg atgggccgtg tcacattgcc atctggggtc 4320
ctttggggtt tccaggttgt caccatgctg tcccatttgg gaatcccata cctgcctgtc 4380
cccactgcgc tggctgaccc ttgctgcctg ctgcctcttg ggagggcttt gtccctgcct 4440
ctgagctggt gggcaggatg gctgggtggc ccccagagaa gcacagacct gagatggggt 4500
ctccatgccc ggtttgctgt tggaatgatc tgaacaggac cccaaatgcc tcttccctct 4560
ggtcatgcct cactatctct aggagctcca tcctgtggct tccagagtgt gcacttccag 4620
cccacccggg cagtgctgag agggaggagg agaacaagga tggcccagcc tcccctccct 4680
cccctagacc acggggcggg cagctcgggt tcctggaggg ctgtttcccc cacgctgtcc 4740
ctacatctgc tctgatctaa aatgtctttc cttttatgct gcgcccagtc ttggggctca 4800
aagatttgcc caaacctcat tggccctcgt gactaggctc atctagatgg tgctcacgct 4860
ggtgtttgag gcatttccac tgtgatctcc acgaggggat gttttccggg acacatctct 4920
ggctctggga actgcctgac tcactgaaga aactactttt caggcactgt agggtcaccc 4980
atatgcctcc agctcagttg acgcttaaaa acaggtgcag aaaagctcgc gatggaaggt 5040
cttaatgaga gtgtctgtct atgccaatca tgtaaaatga cgtttcttga aaaagattca 5100
gtggttcagc tttgtcagca tcatctcaac acaagcctgc tggctctttt tagcatctca 5160
tccaaccatg tcatcgtcca gatgagaaat cttagcccag gtgaggggag taacttgctt 5220
gaggtcacac agctggctgt tggcaaagct gggattagaa ccctcaaccc agggtccctt 5280
cctctgcagc gcctacatgg ttggttgaat aagtggctgc gtttcctggg gccctgggtt 5340
ttggggaagc cagttagctg ctgctttggc actggcatgg aggtgagcag tcaaggatgc 5400
tggtgaggct gcagtttctg ctctttttca tcagggggga tagtctctag gatttttcag 5460
tgaggaccct tgggctttgg atgcagcttg aaccaagaaa acgaggaggg aaagggattc 5520
agtgaactat tcctcagtgg gatcggttct tcagctcctg atgggggctg tgtaatgggg 5580
gcagaggcca gggaaaaaga tgctgttcac ccaccctcag cttccctttt cctaaattaa 5640
gaggaaaagt ggtcaaagaa aaactcttca tttctccctg attcttaaac gaaggtggtt 5700
aatagaaact caggctcccg tgacaaggca ggacaagagc ctgtttcgct ttcctccctg 5760
accctgccag gtgccaactc aaacactacc tttctcattg gtttctaagt cagtagagac 5820
agatctgttt taagcagttg ggggttcgag tagatctcat gggtacagga ggccagcagg 5880
gaccaggcca gtcagccatg ctcaggaccc ctcggctcct cccccagcct ctagctaccc 5940
tgtatcgagg caaggggagg ccagtaaagt ttgccaagcc tgatcctgca gcctggtggg 6000
gctggctggg gtattctttt accaaactct gttttaccgc cagccccttg tacaccccaa 6060
tcccatgtct ccctcccttc agctggaccg tgtgcccctt tgggaggaag aagacaagcc 6120
ccactagggc caagggcagc agagccctgc cgagtgagag gctgtggggc agcggctctg 6180
tcctgtgcct taccagccct ggggaggggg gcatttggct ggaagactgg aatttaattg 6240
ccatcgtctt tgattttgtg acatttctgc ttggaagtgt gaactacccc cccccccccg 6300
cttcctgctc cttagcatgc gtgcagctct ctcctgtttt gggtgttccc cttggacact 6360
ccagctcggg gactgctggc gtgtgaatgt gcagattccc ctgtgtggtc gaacctaaga 6420
actgtggctt ggaagtgatg ctccatgtga cgacgacttt gctttctttc ctcttagtga 6480
ggaggtgatt cgtagatccc aactgcctat gtaatgtaaa taatgtacat ttaatttatt 6540
gctatggtag cacattgtat ttgttaatgt acaaaacaaa ttctaaaagg ttgacaaatg 6600
tatattttgt tgcttaaatg tgtctttgca gaaattgaca ataaataaca tattttgtgt 6660
cca 6663
<210> 30
<211> 6618
<212> DNA
<213> Homo sapiens
<400> 30
actgaccccg ctgtaccacg gccctcttgc ggacagcccc ggggacgtcg ttgggacatc 60
gctgggaccc cgggctctgc agccacaacc atgtttggcc ggaagcgcag tgtctccttt 120
gggggcttcg gatggatcga caagaccatg ctggcaagtc tgaaggtcaa gaagcaggag 180
ctggccaaca gctcggatgc gaccctccca gaccggccgc tctcccctcc tctcacggca 240
cctcccacca tgaagtcgtc ggagttcttt gagatgctgg agaaaatgca ggacgactat 300
atcccatacc ccagcatcga cgaggttgtg gagaagggag gcccgtaccc tcaggtcatc 360
ctgccacagt ttgggggcta ttggatcgag gacccggaga acgtgggcac cccaacatcg 420
ctggggagca gcatctgtga ggaggaggaa gaggacaacc tcagccccaa cacatttggc 480
tacaagctcg agtgcaaggg tgaagccagg gcctaccgga ggcacttcct ggggaaggat 540
catctaaact tttactgtac cggcagcagc ctggggaact tgatcctgtc cgtcaagtgc 600
gaggaagcag aggggatcga gtacctccgg gtcatcctta ggtccaaact gaagacggta 660
catgagcgga tccccttggc tggactgagc aagcttccca gtgtccctca gattgcaaag 720
gctttctgtg atgatgcagt gggactgaga ttcaatcctg tcctgtaccc caaggcctcc 780
caaatgattg tgtcctatga tgagcatgaa gtcaacaaca cattcaaatt cggagtcatt 840
tatcaaaaag ccaggcagac cctggaggag gagctatttg ggaacaatga ggagagccca 900
gcttttaagg agttcttgga cctgctgggg gacacgatca cactgcagga tttcaaaggt 960
ttccgaggag gcctggacgt gacccacgga cagacagggg tggaatcagt gtacacaaca 1020
ttccgggaca gggagatcat gtttcacgtt tccacaaagc tgccatttac cgacggagac 1080
gcccagcagc tccagagaaa gagacacatt ggaaatgaca tcgtggccat catcttccaa 1140
gaggaaaaca cgccgtttgt cccagacatg atagcctcca atttcttaca tgcctacatc 1200
gtcgtgcagg tcgagacccc aggcacagag accccatcct acaaggtctc tgtcactgcg 1260
cgggaagatg tgcccacctt tggtccacct ctgcccagtc cccccgtttt ccagaagggc 1320
ccggaattca gggagtttct gctcaccaag ctcaccaatg ccgagaacgc ctgctgcaag 1380
tcggacaagt ttgcaaagct ggaggaccgg accagggctg ccctcctgga caaccttcac 1440
gatgagctcc acgcccacac acaggccatg ctgggactgg gcccagagga ggacaagttt 1500
gagaatggag gccacggggg gttcctggag tcttttaaga gggccatccg cgtacgcagc 1560
cactccatgg agaccatggt gggcggccag aagaagtcgc acagtggggg catccctggc 1620
agcctcagcg ggggcatctc ccacaacagc atggaggtca ccaagaccac cttctcgcct 1680
ccagtggtgg cggcaacggt gaagaaccag tcacggagtc ccatcaagcg acgctcgggg 1740
ctcttccccc gcctgcacac gggctcagaa ggccagggcg acagccgggc acgatgtgac 1800
agcacatcca gcacacccaa gaccccagat ggtggacact cctctcagga gataaagtct 1860
gagacctcat ccaatcccag ctctccggaa atctgcccca acaaggagaa gcccttcatg 1920
aagttgaagg aaaacggccg tgccatctcc cgctcctcct ccagcaccag cagcgtcagc 1980
agcactgcag gggagggcga ggccatggag gagggcgaca gtgggggcag ccagccgtcc 2040
acgacctcac ccttcaagca ggaggtgttt gtctacagcc cgtccccgag cagcgagagc 2100
cccagcctgg gggcagctgc caccccgatc atcatgagcc ggagtcccac agatgccaaa 2160
agcagaaact ccccgagatc gaacctgaaa ttccgctttg acaagctcag ccatgccagc 2220
tctggtgcgg gtcactaatg tgaaagtgga gtccttcgcc tgtccaaggg aatcccctct 2280
tctgtcctgg aaaaggctcc tgtaccagca gtttgggagt gccgtccacg accctgacag 2340
tcccagccct gctgccccat ggccacgtgc ccacagatgt gctgttggtc caggtgtccc 2400
agtctggcca cagccctgcc tccgccctca cctacatgcc ctcccagccc ctcccatctc 2460
tggacgaggc ctccttcctc aggttcctcc tgctcctgac ctcccagtgt gatgtccggg 2520
tcctttatca tcctattcat cctggagagg aaaagtgtcg ggcaaagggg gatctggggg 2580
gagctcagca gtgactgggg agctggtctg cctcagagac agagtagggg gtgggagcag 2640
agcctcggtg agggtcttgg ccacagggca gtgccttcct gaacgtggca ggctttacta 2700
ccaggaacgc actcggtggt ggaggcccca tgttcccagg agccaagatt cgtagcatcc 2760
ttgaggccat cctgataaaa ttcggcgcta ttgcccccgt agctctggag ctctaaaccg 2820
tctatctgct tctgtgctga acgcctttcc catctgctga cgtaggccca gggctgccct 2880
gcccctgctg ccagtgtacc gtgagcgggg ctccagccag ttcaagctca gagccagagc 2940
tggacgggcc agaactgcgc tgcacacttc ctggactgag gcggggactt tgggtcccac 3000
ccggtttctc ctgattatgg ctgctgtggg gtgaggggag ggaggggcag ccccgaggca 3060
gtctcttccc tttgagaaga tattttccca caaaggggtg ggaagccagg agtgagaagg 3120
aattcaggga gagcaaagga gccagtgctg agatgctgct gtgttggttg aggaaaacct 3180
cgggcctgag ggccaggccg gagcccaggt ctctgctgac aatgggggtt caaggaagac 3240
gtcgttatct cccctcccca cttactcgag gagagaggtg agggggggat gacttgcggg 3300
ttctgatcag gcccctgggt ggggaagggg cacagtgtcc ctcagcagct tacgcccctg 3360
gagtcttggg gggcccagcc tggccctggg gccttttcca gctactgtgc ccttgggcag 3420
ctgcgtctgg ggctcaaccc cccaatcctg ttcccctctc cagctgcggg tctgtaggca 3480
gctgtcacat ctgaagggtt tctgcaacct ggaccccatc tgggtgtggg tcagaccctg 3540
tgacccacat gccaccccca ccctccacag agcccccttg ctgggacagc cagctcacct 3600
ccaaggacat cccctcctgg cttctccccc ttccgagtct gcagcgccgt gggcttctct 3660
gccgatgggc ccgggttggg gttaaggtgg gcatcctcca ggtacaacga gcctgaagag 3720
cccctttcag tgcagacggg gctgcagagt gacactggct gggcacctgc cccacgacca 3780
atgacaagga tttccagctg aatgctttat tcccataggg atctggacct gtgcccaaga 3840
tataaatact acactttttt tttttttttt taactgacat tgtgaaattc tccctatagc 3900
ttttgccatt caagcaacat tgtgatcttt cttccccgcc acgtgtgtgg gaatgattga 3960
gtcctgtttg caagctggag aggagctctc cctttgctag tactttctct aaagtactag 4020
tctagtaaaa tttattcttg ttagaaggtc aacaaaatat ctgtttagct tttatgaaga 4080
gtcaccgtag cagcccccac ggctggaaag aggcctgtac gttctggacg cgttttgttg 4140
gctgggcttc tggaggcact ggcaaggtca aactgcattt ctttaagaac agttgcagga 4200
tctggctcgc ctctgtggga agccggcatt acaggtgctt ggtggatggg ccgtgtcaca 4260
ttgccatctg gggtcctttg gggtttccag gttgtcacca tgctgtccca tttgggaatc 4320
ccatacctgc ctgtccccac tgcgctggct gacccttgct gcctgctgcc tcttgggagg 4380
gctttgtccc tgcctctgag ctggtgggca ggatggctgg gtggccccca gagaagcaca 4440
gacctgagat ggggtctcca tgcccggttt gctgttggaa tgatctgaac aggaccccaa 4500
atgcctcttc cctctggtca tgcctcacta tctctaggag ctccatcctg tggcttccag 4560
agtgtgcact tccagcccac ccgggcagtg ctgagaggga ggaggagaac aaggatggcc 4620
cagcctcccc tccctcccct agaccacggg gcgggcagct cgggttcctg gagggctgtt 4680
tcccccacgc tgtccctaca tctgctctga tctaaaatgt ctttcctttt atgctgcgcc 4740
cagtcttggg gctcaaagat ttgcccaaac ctcattggcc ctcgtgacta ggctcatcta 4800
gatggtgctc acgctggtgt ttgaggcatt tccactgtga tctccacgag gggatgtttt 4860
ccgggacaca tctctggctc tgggaactgc ctgactcact gaagaaacta cttttcaggc 4920
actgtagggt cacccatatg cctccagctc agttgacgct taaaaacagg tgcagaaaag 4980
ctcgcgatgg aaggtcttaa tgagagtgtc tgtctatgcc aatcatgtaa aatgacgttt 5040
cttgaaaaag attcagtggt tcagctttgt cagcatcatc tcaacacaag cctgctggct 5100
ctttttagca tctcatccaa ccatgtcatc gtccagatga gaaatcttag cccaggtgag 5160
gggagtaact tgcttgaggt cacacagctg gctgttggca aagctgggat tagaaccctc 5220
aacccagggt cccttcctct gcagcgccta catggttggt tgaataagtg gctgcgtttc 5280
ctggggccct gggttttggg gaagccagtt agctgctgct ttggcactgg catggaggtg 5340
agcagtcaag gatgctggtg aggctgcagt ttctgctctt tttcatcagg ggggatagtc 5400
tctaggattt ttcagtgagg acccttgggc tttggatgca gcttgaacca agaaaacgag 5460
gagggaaagg gattcagtga actattcctc agtgggatcg gttcttcagc tcctgatggg 5520
ggctgtgtaa tgggggcaga ggccagggaa aaagatgctg ttcacccacc ctcagcttcc 5580
cttttcctaa attaagagga aaagtggtca aagaaaaact cttcatttct ccctgattct 5640
taaacgaagg tggttaatag aaactcaggc tcccgtgaca aggcaggaca agagcctgtt 5700
tcgctttcct ccctgaccct gccaggtgcc aactcaaaca ctacctttct cattggtttc 5760
taagtcagta gagacagatc tgttttaagc agttgggggt tcgagtagat ctcatgggta 5820
caggaggcca gcagggacca ggccagtcag ccatgctcag gacccctcgg ctcctccccc 5880
agcctctagc taccctgtat cgaggcaagg ggaggccagt aaagtttgcc aagcctgatc 5940
ctgcagcctg gtggggctgg ctggggtatt cttttaccaa actctgtttt accgccagcc 6000
ccttgtacac cccaatccca tgtctccctc ccttcagctg gaccgtgtgc ccctttggga 6060
ggaagaagac aagccccact agggccaagg gcagcagagc cctgccgagt gagaggctgt 6120
ggggcagcgg ctctgtcctg tgccttacca gccctgggga ggggggcatt tggctggaag 6180
actggaattt aattgccatc gtctttgatt ttgtgacatt tctgcttgga agtgtgaact 6240
accccccccc ccccgcttcc tgctccttag catgcgtgca gctctctcct gttttgggtg 6300
ttccccttgg acactccagc tcggggactg ctggcgtgtg aatgtgcaga ttcccctgtg 6360
tggtcgaacc taagaactgt ggcttggaag tgatgctcca tgtgacgacg actttgcttt 6420
ctttcctctt agtgaggagg tgattcgtag atcccaactg cctatgtaat gtaaataatg 6480
tacatttaat ttattgctat ggtagcacat tgtatttgtt aatgtacaaa acaaattcta 6540
aaaggttgac aaatgtatat tttgttgctt aaatgtgtct ttgcagaaat tgacaataaa 6600
taacatattt tgtgtcca 6618
<210> 31
<211> 6719
<212> DNA
<213> Homo sapiens
<400> 31
gtgcgctggg gccggccggg gtgcgcgcgt gcgcggcagg actgctgcga gggaccccgc 60
cgccccggag gaggaggagg aggaggagga ggaggaggag ggggctgggc cgagggaggg 120
ggcgaccgcg gggactgagg tgcccttcgc tccgggtcca gaggcagccg cgcgccaggc 180
ggcgcagaag gatcgacaag accatgctgg caagtctgaa ggtcaagaag caggagctgg 240
ccaacagctc ggatgcgacc ctcccagacc ggccgctctc ccctcctctc acggcacctc 300
ccaccatgaa gtcgtcggag ttctttgaga tgctggagaa aatgcagggg atcaagcttg 360
aagagcagaa gccgggaccc cagaagaaca aggacgacta tatcccatac cccagcatcg 420
acgaggttgt ggagaaggga ggcccgtacc ctcaggtcat cctgccacag tttgggggct 480
attggatcga ggacccggag aacgtgggca ccccaacatc gctggggagc agcatctgtg 540
aggaggagga agaggacaac ctcagcccca acacatttgg ctacaagctc gagtgcaagg 600
gtgaagccag ggcctaccgg aggcacttcc tggggaagga tcatctaaac ttttactgta 660
ccggcagcag cctggggaac ttgatcctgt ccgtcaagtg cgaggaagca gaggggatcg 720
agtacctccg ggtcatcctt aggtccaaac tgaagacggt acatgagcgg atccccttgg 780
ctggactgag caagcttccc agtgtccctc agattgcaaa ggctttctgt gatgatgcag 840
tgggactgag attcaatcct gtcctgtacc ccaaggcctc ccaaatgatt gtgtcctatg 900
atgagcatga agtcaacaac acattcaaat tcggagtcat ttatcaaaaa gccaggcaga 960
ccctggagga ggagctattt gggaacaatg aggagagccc agcttttaag gagttcttgg 1020
acctgctggg ggacacgatc acactgcagg atttcaaagg tttccgagga ggcctggacg 1080
tgacccacgg acagacaggg gtggaatcag tgtacacaac attccgggac agggagatca 1140
tgtttcacgt ttccacaaag ctgccattta ccgacggaga cgcccagcag ctccagagaa 1200
agagacacat tggaaatgac atcgtggcca tcatcttcca agaggaaaac acgccgtttg 1260
tcccagacat gatagcctcc aatttcttac atgcctacat cgtcgtgcag gtcgagaccc 1320
caggcacaga gaccccatcc tacaaggtct ctgtcactgc gcgggaagat gtgcccacct 1380
ttggtccacc tctgcccagt ccccccgttt tccagaaggg cccggaattc agggagtttc 1440
tgctcaccaa gctcaccaat gccgagaacg cctgctgcaa gtcggacaag tttgcaaagc 1500
tggaggaccg gaccagggct gccctcctgg acaaccttca cgatgagctc cacgcccaca 1560
cacaggccat gctgggactg ggcccagagg aggacaagtt tgagaatgga ggccacgggg 1620
ggttcctgga gtcttttaag agggccatcc gcgtacgcag ccactccatg gagaccatgg 1680
tgggcggcca gaagaagtcg cacagtgggg gcatccctgg cagcctcagc gggggcatct 1740
cccacaacag catggaggtc accaagacca ccttctcgcc tccagtggtg gcggcaacgg 1800
tgaagaacca gtcacggagt cccatcaagc gacgctcggg gctcttcccc cgcctgcaca 1860
cgggctcaga aggccagggc gacagccggg cacgatgtga cagcacatcc agcacaccca 1920
agaccccaga tggtggacac tcctctcagg agataaagtc tgagacctca tccaatccca 1980
gctctccgga aatctgcccc aacaaggaga agcccttcat gaagttgaag gaaaacggcc 2040
gtgccatctc ccgctcctcc tccagcacca gcagcgtcag cagcactgca ggggagggcg 2100
aggccatgga ggagggcgac agtgggggca gccagccgtc cacgacctca cccttcaagc 2160
aggaggtgtt tgtctacagc ccgtccccga gcagcgagag ccccagcctg ggggcagctg 2220
ccaccccgat catcatgagc cggagtccca cagatgccaa aagcagaaac tccccgagat 2280
cgaacctgaa attccgcttt gacaagctca gccatgccag ctctggtgcg ggtcactaat 2340
gtgaaagtgg agtccttcgc ctgtccaagg gaatcccctc ttctgtcctg gaaaaggctc 2400
ctgtaccagc agtttgggag tgccgtccac gaccctgaca gtcccagccc tgctgcccca 2460
tggccacgtg cccacagatg tgctgttggt ccaggtgtcc cagtctggcc acagccctgc 2520
ctccgccctc acctacatgc cctcccagcc cctcccatct ctggacgagg cctccttcct 2580
caggttcctc ctgctcctga cctcccagtg tgatgtccgg gtcctttatc atcctattca 2640
tcctggagag gaaaagtgtc gggcaaaggg ggatctgggg ggagctcagc agtgactggg 2700
gagctggtct gcctcagaga cagagtaggg ggtgggagca gagcctcggt gagggtcttg 2760
gccacagggc agtgccttcc tgaacgtggc aggctttact accaggaacg cactcggtgg 2820
tggaggcccc atgttcccag gagccaagat tcgtagcatc cttgaggcca tcctgataaa 2880
attcggcgct attgcccccg tagctctgga gctctaaacc gtctatctgc ttctgtgctg 2940
aacgcctttc ccatctgctg acgtaggccc agggctgccc tgcccctgct gccagtgtac 3000
cgtgagcggg gctccagcca gttcaagctc agagccagag ctggacgggc cagaactgcg 3060
ctgcacactt cctggactga ggcggggact ttgggtccca cccggtttct cctgattatg 3120
gctgctgtgg ggtgagggga gggaggggca gccccgaggc agtctcttcc ctttgagaag 3180
atattttccc acaaaggggt gggaagccag gagtgagaag gaattcaggg agagcaaagg 3240
agccagtgct gagatgctgc tgtgttggtt gaggaaaacc tcgggcctga gggccaggcc 3300
ggagcccagg tctctgctga caatgggggt tcaaggaaga cgtcgttatc tcccctcccc 3360
acttactcga ggagagaggt gaggggggga tgacttgcgg gttctgatca ggcccctggg 3420
tggggaaggg gcacagtgtc cctcagcagc ttacgcccct ggagtcttgg ggggcccagc 3480
ctggccctgg ggccttttcc agctactgtg cccttgggca gctgcgtctg gggctcaacc 3540
ccccaatcct gttcccctct ccagctgcgg gtctgtaggc agctgtcaca tctgaagggt 3600
ttctgcaacc tggaccccat ctgggtgtgg gtcagaccct gtgacccaca tgccaccccc 3660
accctccaca gagccccctt gctgggacag ccagctcacc tccaaggaca tcccctcctg 3720
gcttctcccc cttccgagtc tgcagcgccg tgggcttctc tgccgatggg cccgggttgg 3780
ggttaaggtg ggcatcctcc aggtacaacg agcctgaaga gcccctttca gtgcagacgg 3840
ggctgcagag tgacactggc tgggcacctg ccccacgacc aatgacaagg atttccagct 3900
gaatgcttta ttcccatagg gatctggacc tgtgcccaag atataaatac tacacttttt 3960
tttttttttt ttaactgaca ttgtgaaatt ctccctatag cttttgccat tcaagcaaca 4020
ttgtgatctt tcttccccgc cacgtgtgtg ggaatgattg agtcctgttt gcaagctgga 4080
gaggagctct ccctttgcta gtactttctc taaagtacta gtctagtaaa atttattctt 4140
gttagaaggt caacaaaata tctgtttagc ttttatgaag agtcaccgta gcagccccca 4200
cggctggaaa gaggcctgta cgttctggac gcgttttgtt ggctgggctt ctggaggcac 4260
tggcaaggtc aaactgcatt tctttaagaa cagttgcagg atctggctcg cctctgtggg 4320
aagccggcat tacaggtgct tggtggatgg gccgtgtcac attgccatct ggggtccttt 4380
ggggtttcca ggttgtcacc atgctgtccc atttgggaat cccatacctg cctgtcccca 4440
ctgcgctggc tgacccttgc tgcctgctgc ctcttgggag ggctttgtcc ctgcctctga 4500
gctggtgggc aggatggctg ggtggccccc agagaagcac agacctgaga tggggtctcc 4560
atgcccggtt tgctgttgga atgatctgaa caggacccca aatgcctctt ccctctggtc 4620
atgcctcact atctctagga gctccatcct gtggcttcca gagtgtgcac ttccagccca 4680
cccgggcagt gctgagaggg aggaggagaa caaggatggc ccagcctccc ctccctcccc 4740
tagaccacgg ggcgggcagc tcgggttcct ggagggctgt ttcccccacg ctgtccctac 4800
atctgctctg atctaaaatg tctttccttt tatgctgcgc ccagtcttgg ggctcaaaga 4860
tttgcccaaa cctcattggc cctcgtgact aggctcatct agatggtgct cacgctggtg 4920
tttgaggcat ttccactgtg atctccacga ggggatgttt tccgggacac atctctggct 4980
ctgggaactg cctgactcac tgaagaaact acttttcagg cactgtaggg tcacccatat 5040
gcctccagct cagttgacgc ttaaaaacag gtgcagaaaa gctcgcgatg gaaggtctta 5100
atgagagtgt ctgtctatgc caatcatgta aaatgacgtt tcttgaaaaa gattcagtgg 5160
ttcagctttg tcagcatcat ctcaacacaa gcctgctggc tctttttagc atctcatcca 5220
accatgtcat cgtccagatg agaaatctta gcccaggtga ggggagtaac ttgcttgagg 5280
tcacacagct ggctgttggc aaagctggga ttagaaccct caacccaggg tcccttcctc 5340
tgcagcgcct acatggttgg ttgaataagt ggctgcgttt cctggggccc tgggttttgg 5400
ggaagccagt tagctgctgc tttggcactg gcatggaggt gagcagtcaa ggatgctggt 5460
gaggctgcag tttctgctct ttttcatcag gggggatagt ctctaggatt tttcagtgag 5520
gacccttggg ctttggatgc agcttgaacc aagaaaacga ggagggaaag ggattcagtg 5580
aactattcct cagtgggatc ggttcttcag ctcctgatgg gggctgtgta atgggggcag 5640
aggccaggga aaaagatgct gttcacccac cctcagcttc ccttttccta aattaagagg 5700
aaaagtggtc aaagaaaaac tcttcatttc tccctgattc ttaaacgaag gtggttaata 5760
gaaactcagg ctcccgtgac aaggcaggac aagagcctgt ttcgctttcc tccctgaccc 5820
tgccaggtgc caactcaaac actacctttc tcattggttt ctaagtcagt agagacagat 5880
ctgttttaag cagttggggg ttcgagtaga tctcatgggt acaggaggcc agcagggacc 5940
aggccagtca gccatgctca ggacccctcg gctcctcccc cagcctctag ctaccctgta 6000
tcgaggcaag gggaggccag taaagtttgc caagcctgat cctgcagcct ggtggggctg 6060
gctggggtat tcttttacca aactctgttt taccgccagc cccttgtaca ccccaatccc 6120
atgtctccct cccttcagct ggaccgtgtg cccctttggg aggaagaaga caagccccac 6180
tagggccaag ggcagcagag ccctgccgag tgagaggctg tggggcagcg gctctgtcct 6240
gtgccttacc agccctgggg aggggggcat ttggctggaa gactggaatt taattgccat 6300
cgtctttgat tttgtgacat ttctgcttgg aagtgtgaac tacccccccc cccccgcttc 6360
ctgctcctta gcatgcgtgc agctctctcc tgttttgggt gttccccttg gacactccag 6420
ctcggggact gctggcgtgt gaatgtgcag attcccctgt gtggtcgaac ctaagaactg 6480
tggcttggaa gtgatgctcc atgtgacgac gactttgctt tctttcctct tagtgaggag 6540
gtgattcgta gatcccaact gcctatgtaa tgtaaataat gtacatttaa tttattgcta 6600
tggtagcaca ttgtatttgt taatgtacaa aacaaattct aaaaggttga caaatgtata 6660
ttttgttgct taaatgtgtc tttgcagaaa ttgacaataa ataacatatt ttgtgtcca 6719
<210> 32
<211> 730
<212> PRT
<213> Homo sapiens
<400> 32
Met Phe Gly Arg Lys Arg Ser Val Ser Phe Gly Gly Phe Gly Trp Ile
1 5 10 15
Asp Lys Thr Met Leu Ala Ser Leu Lys Val Lys Lys Gln Glu Leu Ala
20 25 30
Asn Ser Ser Asp Ala Thr Leu Pro Asp Arg Pro Leu Ser Pro Pro Leu
35 40 45
Thr Ala Pro Pro Thr Met Lys Ser Ser Glu Phe Phe Glu Met Leu Glu
50 55 60
Lys Met Gln Gly Ile Lys Leu Glu Glu Gln Lys Pro Gly Pro Gln Lys
65 70 75 80
Asn Lys Asp Asp Tyr Ile Pro Tyr Pro Ser Ile Asp Glu Val Val Glu
85 90 95
Lys Gly Gly Pro Tyr Pro Gln Val Ile Leu Pro Gln Phe Gly Gly Tyr
100 105 110
Trp Ile Glu Asp Pro Glu Asn Val Gly Thr Pro Thr Ser Leu Gly Ser
115 120 125
Ser Ile Cys Glu Glu Glu Glu Glu Asp Asn Leu Ser Pro Asn Thr Phe
130 135 140
Gly Tyr Lys Leu Glu Cys Lys Gly Glu Ala Arg Ala Tyr Arg Arg His
145 150 155 160
Phe Leu Gly Lys Asp His Leu Asn Phe Tyr Cys Thr Gly Ser Ser Leu
165 170 175
Gly Asn Leu Ile Leu Ser Val Lys Cys Glu Glu Ala Glu Gly Ile Glu
180 185 190
Tyr Leu Arg Val Ile Leu Arg Ser Lys Leu Lys Thr Val His Glu Arg
195 200 205
Ile Pro Leu Ala Gly Leu Ser Lys Leu Pro Ser Val Pro Gln Ile Ala
210 215 220
Lys Ala Phe Cys Asp Asp Ala Val Gly Leu Arg Phe Asn Pro Val Leu
225 230 235 240
Tyr Pro Lys Ala Ser Gln Met Ile Val Ser Tyr Asp Glu His Glu Val
245 250 255
Asn Asn Thr Phe Lys Phe Gly Val Ile Tyr Gln Lys Ala Arg Gln Thr
260 265 270
Leu Glu Glu Glu Leu Phe Gly Asn Asn Glu Glu Ser Pro Ala Phe Lys
275 280 285
Glu Phe Leu Asp Leu Leu Gly Asp Thr Ile Thr Leu Gln Asp Phe Lys
290 295 300
Gly Phe Arg Gly Gly Leu Asp Val Thr His Gly Gln Thr Gly Val Glu
305 310 315 320
Ser Val Tyr Thr Thr Phe Arg Asp Arg Glu Ile Met Phe His Val Ser
325 330 335
Thr Lys Leu Pro Phe Thr Asp Gly Asp Ala Gln Gln Leu Gln Arg Lys
340 345 350
Arg His Ile Gly Asn Asp Ile Val Ala Ile Ile Phe Gln Glu Glu Asn
355 360 365
Thr Pro Phe Val Pro Asp Met Ile Ala Ser Asn Phe Leu His Ala Tyr
370 375 380
Ile Val Val Gln Val Glu Thr Pro Gly Thr Glu Thr Pro Ser Tyr Lys
385 390 395 400
Val Ser Val Thr Ala Arg Glu Asp Val Pro Thr Phe Gly Pro Pro Leu
405 410 415
Pro Ser Pro Pro Val Phe Gln Lys Gly Pro Glu Phe Arg Glu Phe Leu
420 425 430
Leu Thr Lys Leu Thr Asn Ala Glu Asn Ala Cys Cys Lys Ser Asp Lys
435 440 445
Phe Ala Lys Leu Glu Asp Arg Thr Arg Ala Ala Leu Leu Asp Asn Leu
450 455 460
His Asp Glu Leu His Ala His Thr Gln Ala Met Leu Gly Leu Gly Pro
465 470 475 480
Glu Glu Asp Lys Phe Glu Asn Gly Gly His Gly Gly Phe Leu Glu Ser
485 490 495
Phe Lys Arg Ala Ile Arg Val Arg Ser His Ser Met Glu Thr Met Val
500 505 510
Gly Gly Gln Lys Lys Ser His Ser Gly Gly Ile Pro Gly Ser Leu Ser
515 520 525
Gly Gly Ile Ser His Asn Ser Met Glu Val Thr Lys Thr Thr Phe Ser
530 535 540
Pro Pro Val Val Ala Ala Thr Val Lys Asn Gln Ser Arg Ser Pro Ile
545 550 555 560
Lys Arg Arg Ser Gly Leu Phe Pro Arg Leu His Thr Gly Ser Glu Gly
565 570 575
Gln Gly Asp Ser Arg Ala Arg Cys Asp Ser Thr Ser Ser Thr Pro Lys
580 585 590
Thr Pro Asp Gly Gly His Ser Ser Gln Glu Ile Lys Ser Glu Thr Ser
595 600 605
Ser Asn Pro Ser Ser Pro Glu Ile Cys Pro Asn Lys Glu Lys Pro Phe
610 615 620
Met Lys Leu Lys Glu Asn Gly Arg Ala Ile Ser Arg Ser Ser Ser Ser
625 630 635 640
Thr Ser Ser Val Ser Ser Thr Ala Gly Glu Gly Glu Ala Met Glu Glu
645 650 655
Gly Asp Ser Gly Gly Ser Gln Pro Ser Thr Thr Ser Pro Phe Lys Gln
660 665 670
Glu Val Phe Val Tyr Ser Pro Ser Pro Ser Ser Glu Ser Pro Ser Leu
675 680 685
Gly Ala Ala Ala Thr Pro Ile Ile Met Ser Arg Ser Pro Thr Asp Ala
690 695 700
Lys Ser Arg Asn Ser Pro Arg Ser Asn Leu Lys Phe Arg Phe Asp Lys
705 710 715 720
Leu Ser His Ala Ser Ser Gly Ala Gly His
725 730
<210> 33
<211> 715
<212> PRT
<213> Homo sapiens
<400> 33
Met Phe Gly Arg Lys Arg Ser Val Ser Phe Gly Gly Phe Gly Trp Ile
1 5 10 15
Asp Lys Thr Met Leu Ala Ser Leu Lys Val Lys Lys Gln Glu Leu Ala
20 25 30
Asn Ser Ser Asp Ala Thr Leu Pro Asp Arg Pro Leu Ser Pro Pro Leu
35 40 45
Thr Ala Pro Pro Thr Met Lys Ser Ser Glu Phe Phe Glu Met Leu Glu
50 55 60
Lys Met Gln Asp Asp Tyr Ile Pro Tyr Pro Ser Ile Asp Glu Val Val
65 70 75 80
Glu Lys Gly Gly Pro Tyr Pro Gln Val Ile Leu Pro Gln Phe Gly Gly
85 90 95
Tyr Trp Ile Glu Asp Pro Glu Asn Val Gly Thr Pro Thr Ser Leu Gly
100 105 110
Ser Ser Ile Cys Glu Glu Glu Glu Glu Asp Asn Leu Ser Pro Asn Thr
115 120 125
Phe Gly Tyr Lys Leu Glu Cys Lys Gly Glu Ala Arg Ala Tyr Arg Arg
130 135 140
His Phe Leu Gly Lys Asp His Leu Asn Phe Tyr Cys Thr Gly Ser Ser
145 150 155 160
Leu Gly Asn Leu Ile Leu Ser Val Lys Cys Glu Glu Ala Glu Gly Ile
165 170 175
Glu Tyr Leu Arg Val Ile Leu Arg Ser Lys Leu Lys Thr Val His Glu
180 185 190
Arg Ile Pro Leu Ala Gly Leu Ser Lys Leu Pro Ser Val Pro Gln Ile
195 200 205
Ala Lys Ala Phe Cys Asp Asp Ala Val Gly Leu Arg Phe Asn Pro Val
210 215 220
Leu Tyr Pro Lys Ala Ser Gln Met Ile Val Ser Tyr Asp Glu His Glu
225 230 235 240
Val Asn Asn Thr Phe Lys Phe Gly Val Ile Tyr Gln Lys Ala Arg Gln
245 250 255
Thr Leu Glu Glu Glu Leu Phe Gly Asn Asn Glu Glu Ser Pro Ala Phe
260 265 270
Lys Glu Phe Leu Asp Leu Leu Gly Asp Thr Ile Thr Leu Gln Asp Phe
275 280 285
Lys Gly Phe Arg Gly Gly Leu Asp Val Thr His Gly Gln Thr Gly Val
290 295 300
Glu Ser Val Tyr Thr Thr Phe Arg Asp Arg Glu Ile Met Phe His Val
305 310 315 320
Ser Thr Lys Leu Pro Phe Thr Asp Gly Asp Ala Gln Gln Leu Gln Arg
325 330 335
Lys Arg His Ile Gly Asn Asp Ile Val Ala Ile Ile Phe Gln Glu Glu
340 345 350
Asn Thr Pro Phe Val Pro Asp Met Ile Ala Ser Asn Phe Leu His Ala
355 360 365
Tyr Ile Val Val Gln Val Glu Thr Pro Gly Thr Glu Thr Pro Ser Tyr
370 375 380
Lys Val Ser Val Thr Ala Arg Glu Asp Val Pro Thr Phe Gly Pro Pro
385 390 395 400
Leu Pro Ser Pro Pro Val Phe Gln Lys Gly Pro Glu Phe Arg Glu Phe
405 410 415
Leu Leu Thr Lys Leu Thr Asn Ala Glu Asn Ala Cys Cys Lys Ser Asp
420 425 430
Lys Phe Ala Lys Leu Glu Asp Arg Thr Arg Ala Ala Leu Leu Asp Asn
435 440 445
Leu His Asp Glu Leu His Ala His Thr Gln Ala Met Leu Gly Leu Gly
450 455 460
Pro Glu Glu Asp Lys Phe Glu Asn Gly Gly His Gly Gly Phe Leu Glu
465 470 475 480
Ser Phe Lys Arg Ala Ile Arg Val Arg Ser His Ser Met Glu Thr Met
485 490 495
Val Gly Gly Gln Lys Lys Ser His Ser Gly Gly Ile Pro Gly Ser Leu
500 505 510
Ser Gly Gly Ile Ser His Asn Ser Met Glu Val Thr Lys Thr Thr Phe
515 520 525
Ser Pro Pro Val Val Ala Ala Thr Val Lys Asn Gln Ser Arg Ser Pro
530 535 540
Ile Lys Arg Arg Ser Gly Leu Phe Pro Arg Leu His Thr Gly Ser Glu
545 550 555 560
Gly Gln Gly Asp Ser Arg Ala Arg Cys Asp Ser Thr Ser Ser Thr Pro
565 570 575
Lys Thr Pro Asp Gly Gly His Ser Ser Gln Glu Ile Lys Ser Glu Thr
580 585 590
Ser Ser Asn Pro Ser Ser Pro Glu Ile Cys Pro Asn Lys Glu Lys Pro
595 600 605
Phe Met Lys Leu Lys Glu Asn Gly Arg Ala Ile Ser Arg Ser Ser Ser
610 615 620
Ser Thr Ser Ser Val Ser Ser Thr Ala Gly Glu Gly Glu Ala Met Glu
625 630 635 640
Glu Gly Asp Ser Gly Gly Ser Gln Pro Ser Thr Thr Ser Pro Phe Lys
645 650 655
Gln Glu Val Phe Val Tyr Ser Pro Ser Pro Ser Ser Glu Ser Pro Ser
660 665 670
Leu Gly Ala Ala Ala Thr Pro Ile Ile Met Ser Arg Ser Pro Thr Asp
675 680 685
Ala Lys Ser Arg Asn Ser Pro Arg Ser Asn Leu Lys Phe Arg Phe Asp
690 695 700
Lys Leu Ser His Ala Ser Ser Gly Ala Gly His
705 710 715
<210> 34
<211> 711
<212> PRT
<213> Homo sapiens
<400> 34
Met Leu Ala Ser Leu Lys Val Lys Lys Gln Glu Leu Ala Asn Ser Ser
1 5 10 15
Asp Ala Thr Leu Pro Asp Arg Pro Leu Ser Pro Pro Leu Thr Ala Pro
20 25 30
Pro Thr Met Lys Ser Ser Glu Phe Phe Glu Met Leu Glu Lys Met Gln
35 40 45
Gly Ile Lys Leu Glu Glu Gln Lys Pro Gly Pro Gln Lys Asn Lys Asp
50 55 60
Asp Tyr Ile Pro Tyr Pro Ser Ile Asp Glu Val Val Glu Lys Gly Gly
65 70 75 80
Pro Tyr Pro Gln Val Ile Leu Pro Gln Phe Gly Gly Tyr Trp Ile Glu
85 90 95
Asp Pro Glu Asn Val Gly Thr Pro Thr Ser Leu Gly Ser Ser Ile Cys
100 105 110
Glu Glu Glu Glu Glu Asp Asn Leu Ser Pro Asn Thr Phe Gly Tyr Lys
115 120 125
Leu Glu Cys Lys Gly Glu Ala Arg Ala Tyr Arg Arg His Phe Leu Gly
130 135 140
Lys Asp His Leu Asn Phe Tyr Cys Thr Gly Ser Ser Leu Gly Asn Leu
145 150 155 160
Ile Leu Ser Val Lys Cys Glu Glu Ala Glu Gly Ile Glu Tyr Leu Arg
165 170 175
Val Ile Leu Arg Ser Lys Leu Lys Thr Val His Glu Arg Ile Pro Leu
180 185 190
Ala Gly Leu Ser Lys Leu Pro Ser Val Pro Gln Ile Ala Lys Ala Phe
195 200 205
Cys Asp Asp Ala Val Gly Leu Arg Phe Asn Pro Val Leu Tyr Pro Lys
210 215 220
Ala Ser Gln Met Ile Val Ser Tyr Asp Glu His Glu Val Asn Asn Thr
225 230 235 240
Phe Lys Phe Gly Val Ile Tyr Gln Lys Ala Arg Gln Thr Leu Glu Glu
245 250 255
Glu Leu Phe Gly Asn Asn Glu Glu Ser Pro Ala Phe Lys Glu Phe Leu
260 265 270
Asp Leu Leu Gly Asp Thr Ile Thr Leu Gln Asp Phe Lys Gly Phe Arg
275 280 285
Gly Gly Leu Asp Val Thr His Gly Gln Thr Gly Val Glu Ser Val Tyr
290 295 300
Thr Thr Phe Arg Asp Arg Glu Ile Met Phe His Val Ser Thr Lys Leu
305 310 315 320
Pro Phe Thr Asp Gly Asp Ala Gln Gln Leu Gln Arg Lys Arg His Ile
325 330 335
Gly Asn Asp Ile Val Ala Ile Ile Phe Gln Glu Glu Asn Thr Pro Phe
340 345 350
Val Pro Asp Met Ile Ala Ser Asn Phe Leu His Ala Tyr Ile Val Val
355 360 365
Gln Val Glu Thr Pro Gly Thr Glu Thr Pro Ser Tyr Lys Val Ser Val
370 375 380
Thr Ala Arg Glu Asp Val Pro Thr Phe Gly Pro Pro Leu Pro Ser Pro
385 390 395 400
Pro Val Phe Gln Lys Gly Pro Glu Phe Arg Glu Phe Leu Leu Thr Lys
405 410 415
Leu Thr Asn Ala Glu Asn Ala Cys Cys Lys Ser Asp Lys Phe Ala Lys
420 425 430
Leu Glu Asp Arg Thr Arg Ala Ala Leu Leu Asp Asn Leu His Asp Glu
435 440 445
Leu His Ala His Thr Gln Ala Met Leu Gly Leu Gly Pro Glu Glu Asp
450 455 460
Lys Phe Glu Asn Gly Gly His Gly Gly Phe Leu Glu Ser Phe Lys Arg
465 470 475 480
Ala Ile Arg Val Arg Ser His Ser Met Glu Thr Met Val Gly Gly Gln
485 490 495
Lys Lys Ser His Ser Gly Gly Ile Pro Gly Ser Leu Ser Gly Gly Ile
500 505 510
Ser His Asn Ser Met Glu Val Thr Lys Thr Thr Phe Ser Pro Pro Val
515 520 525
Val Ala Ala Thr Val Lys Asn Gln Ser Arg Ser Pro Ile Lys Arg Arg
530 535 540
Ser Gly Leu Phe Pro Arg Leu His Thr Gly Ser Glu Gly Gln Gly Asp
545 550 555 560
Ser Arg Ala Arg Cys Asp Ser Thr Ser Ser Thr Pro Lys Thr Pro Asp
565 570 575
Gly Gly His Ser Ser Gln Glu Ile Lys Ser Glu Thr Ser Ser Asn Pro
580 585 590
Ser Ser Pro Glu Ile Cys Pro Asn Lys Glu Lys Pro Phe Met Lys Leu
595 600 605
Lys Glu Asn Gly Arg Ala Ile Ser Arg Ser Ser Ser Ser Thr Ser Ser
610 615 620
Val Ser Ser Thr Ala Gly Glu Gly Glu Ala Met Glu Glu Gly Asp Ser
625 630 635 640
Gly Gly Ser Gln Pro Ser Thr Thr Ser Pro Phe Lys Gln Glu Val Phe
645 650 655
Val Tyr Ser Pro Ser Pro Ser Ser Glu Ser Pro Ser Leu Gly Ala Ala
660 665 670
Ala Thr Pro Ile Ile Met Ser Arg Ser Pro Thr Asp Ala Lys Ser Arg
675 680 685
Asn Ser Pro Arg Ser Asn Leu Lys Phe Arg Phe Asp Lys Leu Ser His
690 695 700
Ala Ser Ser Gly Ala Gly His
705 710
<210> 35
<211> 2732
<212> DNA
<213> Homo sapiens
<400> 35
gactgcggga gtggagccgg cgagagagtg gcagcggggg ctgatggaag tgcagtgggg 60
gctggagagg gcaccctact gtatccagca tgctccaagg ccacagctct gtgttccagg 120
ccttgctggg gaccttcttc acctggggga tgacagcagc tggggcagct ctcgtgttcg 180
tattctctag tggacagagg cggatcttag atggaagtct tggctttgct gcaggggtca 240
tgttggcagc ttcctattgg tctcttctgg ccccagcagt tgagatggcc acgtcctctg 300
ggggcttcgg tgcctttgcc ttcttccctg tggctgttgg cttcaccctt ggagcggctt 360
ttgtctactt ggctgacctc ctgatgcctc acttgggtgc agcagaagac ccccagacga 420
ccctggcact gaacttcggc tctacgttga tgaagaagaa gtctgatcct gagggtcccg 480
cgctgctctt ccctgagagt gaactttcca tccggataga caagagtgag aatggtgagg 540
catatcagag aaagaaggcg gcagccactg gccttccaga gggtcctgct gtccctgtgc 600
cttctcgagg gaatctggca cagcccggcg gcagcagctg gaggaggatc gcactgctca 660
tcttggccat cactatacac aacgttccag agggtctcgc tgttggagtt ggatttgggg 720
ctatagaaaa gacggcatct gctacctttg agagtgccag gaatttggcc attggaatcg 780
ggatccagaa tttccccgag ggcctggctg tcagccttcc cttgcgaggg gcaggcttct 840
ccacctggag agctttctgg tatgggcagc tgagcggcat ggtggagccc ctggccgggg 900
tctttggtgc ctttgccgtg gtgctggctg agcccatcct gccctacgct ctggcctttg 960
ctgccggtgc catggtctac gtggtcatgg acgacatcat ccccgaagcc cagatcagtg 1020
gtaatgggaa actggcatcc tgggcctcca tcctgggatt tgtagtgatg atgtcactgg 1080
acgttggcct gggctagggc tgagacgctt cggaccccgg gaaaggccat acgaagaaac 1140
agcagtggtt ggcttctatg ggacaacaag cttctttctt cacattaaaa cttttttcct 1200
tcctctcttc ttcatctcat tatcctgatt gactctgatt ataatagaac catttttact 1260
ttgctttgag ggagattttt gatttaatgg ggaattttaa ggtgtcatgg aaatacagat 1320
tctttgtttt ggccactgaa tggactctct cttcagtggg attatcaagg aacttcagat 1380
cagggaaatc tccacttcgg gaccttctat ctgcctccca actcctcaag gtcacctata 1440
gaagcgagct accaaaagac gtctcctaag cattttggtg gcctagtgac tcagggcaga 1500
gtggccagca cacctctcat ccgcccctcc tgctccatca ctgctgagcc tctccccatc 1560
tagaatgttg gaactggagc atcataaaga tagcaagcta ccttccaagg ccgagccagc 1620
ccagagagga gcatgtcttc ctttacctcc ccctaaggag atactacatg ggagggggac 1680
acagaaaaag ggaaggaaat tggctagtct ggcttttttt tttttttttt ttaaaggcaa 1740
agattgacat tattgaagga aaggggatga ggacaactgt gaactcacag tgagccctgt 1800
ggaaagaaga gacagacaga gtgtgggttt gttcggaggc ctctgctgtc aatggattcc 1860
aggagcaagg ccatttgtcg cgctttccaa atttcttagg catttatttt gataagttta 1920
tagccatcat gtttctaaga gacttggaga caccagcaaa ctgctagaac tcaaactctt 1980
caattactca aagaaggagc catttcagtt aactcaagtg aatgaaagag ttttggaatc 2040
tgctgtgggt ccttccctgt tgaccatttg gtaacttata atctgacaaa aactcttgag 2100
ctgcaacagg ccttgccaga gggctcagga tgggaaagga agaaggggat aggaaaagaa 2160
gaggtaattt tacatttccc ctttaaagta aattttagcc aactcatcat tctgaaatgt 2220
ccctataaag aatgagtcga actagaccag aagccagcct actccttctt acatagcttc 2280
tccaacaggg gtagcaatga cctgtccact tcaaacacag ataaggcctg ccatcctcat 2340
tggttaaagg cacacgtgag actttcagtg ggctctgctg agaaggaagg cagcccagga 2400
gtcaggtatg caggcattgc attgtcagtg tctgctctca gagtttacac attcaattgc 2460
ttccaagggt gaatctcctg ctctgtgaat gctatcagac cccaaaggcc aaccttgggc 2520
tgggtctatg tacgttcttc cgaagcactg atgatcaaaa ttgaagacac attcagaggt 2580
ttgattggtt gagattaact ggtgtggtgg ttggtgtatg tatgttttat ttttatgtct 2640
ttgtatgtag ttctacataa tgcaaattgt gctttctgat ggacaagacc tcataactgt 2700
gattaatatc aataaaaagg ggatgttgtg ga 2732
<210> 36
<211> 2869
<212> DNA
<213> Homo sapiens
<400> 36
gactgcggga gtggagccgg cgagagagtg gcagcggggg ctgatggaag tgcagtgggg 60
gctggagagg gcaccctagt gagttggctt ttctctcctt cggtgccttt ggttgggctc 120
gaggcccggg gtcggaggcc atcaggacaa gagtgtggga cttggaaggg cagccacctg 180
gagcttggaa ggggctgtat ccagcatgct ccaaggccac agctctgtgt tccaggcctt 240
gctggggacc ttcttcacct gggggatgac agcagctggg gcagctctcg tgttcgtatt 300
ctctagtgga cagaggcgga tcttagatgg aagtcttggc tttgctgcag gggtcatgtt 360
ggcagcttcc tattggtctc ttctggcccc agcagttgag atggccacgt cctctggggg 420
cttcggtgcc tttgccttct tccctgtggc tgttggcttc acccttggag cggcttttgt 480
ctacttggct gacctcctga tgcctcactt gggtgcagca gaagaccccc agacgaccct 540
ggcactgaac ttcggctcta cgttgatgaa gaagaagtct gatcctgagg gtcccgcgct 600
gctcttccct gagagtgaac tttccatccg gataggtaga gctgggcttc tttcagacaa 660
gagtgagaat ggtgaggcat atcagagaaa gaaggcggca gccactggcc ttccagaggg 720
tcctgctgtc cctgtgcctt ctcgagggaa tctggcacag cccggcggca gcagctggag 780
gaggatcgca ctgctcatct tggccatcac tatacacaac gttccagagg gtctcgctgt 840
tggagttgga tttggggcta tagaaaagac ggcatctgct acctttgaga gtgccaggaa 900
tttggccatt ggaatcggga tccagaattt ccccgagggc ctggctgtca gccttccctt 960
gcgaggggca ggcttctcca cctggagagc tttctggtat gggcagctga gcggcatggt 1020
ggagcccctg gccggggtct ttggtgcctt tgccgtggtg ctggctgagc ccatcctgcc 1080
ctacgctctg gcctttgctg ccggtgccat ggtctacgtg gtcatggacg acatcatccc 1140
cgaagcccag atcagtggta atgggaaact ggcatcctgg gcctccatcc tgggatttgt 1200
agtgatgatg tcactggacg ttggcctggg ctagggctga gacgcttcgg accccgggaa 1260
aggccatacg aagaaacagc agtggttggc ttctatggga caacaagctt ctttcttcac 1320
attaaaactt ttttccttcc tctcttcttc atctcattat cctgattgac tctgattata 1380
atagaaccat ttttactttg ctttgaggga gatttttgat ttaatgggga attttaaggt 1440
gtcatggaaa tacagattct ttgttttggc cactgaatgg actctctctt cagtgggatt 1500
atcaaggaac ttcagatcag ggaaatctcc acttcgggac cttctatctg cctcccaact 1560
cctcaaggtc acctatagaa gcgagctacc aaaagacgtc tcctaagcat tttggtggcc 1620
tagtgactca gggcagagtg gccagcacac ctctcatccg cccctcctgc tccatcactg 1680
ctgagcctct ccccatctag aatgttggaa ctggagcatc ataaagatag caagctacct 1740
tccaaggccg agccagccca gagaggagca tgtcttcctt tacctccccc taaggagata 1800
ctacatggga gggggacaca gaaaaaggga aggaaattgg ctagtctggc tttttttttt 1860
ttttttttta aaggcaaaga ttgacattat tgaaggaaag gggatgagga caactgtgaa 1920
ctcacagtga gccctgtgga aagaagagac agacagagtg tgggtttgtt cggaggcctc 1980
tgctgtcaat ggattccagg agcaaggcca tttgtcgcgc tttccaaatt tcttaggcat 2040
ttattttgat aagtttatag ccatcatgtt tctaagagac ttggagacac cagcaaactg 2100
ctagaactca aactcttcaa ttactcaaag aaggagccat ttcagttaac tcaagtgaat 2160
gaaagagttt tggaatctgc tgtgggtcct tccctgttga ccatttggta acttataatc 2220
tgacaaaaac tcttgagctg caacaggcct tgccagaggg ctcaggatgg gaaaggaaga 2280
aggggatagg aaaagaagag gtaattttac atttcccctt taaagtaaat tttagccaac 2340
tcatcattct gaaatgtccc tataaagaat gagtcgaact agaccagaag ccagcctact 2400
ccttcttaca tagcttctcc aacaggggta gcaatgacct gtccacttca aacacagata 2460
aggcctgcca tcctcattgg ttaaaggcac acgtgagact ttcagtgggc tctgctgaga 2520
aggaaggcag cccaggagtc aggtatgcag gcattgcatt gtcagtgtct gctctcagag 2580
tttacacatt caattgcttc caagggtgaa tctcctgctc tgtgaatgct atcagacccc 2640
aaaggccaac cttgggctgg gtctatgtac gttcttccga agcactgatg atcaaaattg 2700
aagacacatt cagaggtttg attggttgag attaactggt gtggtggttg gtgtatgtat 2760
gttttatttt tatgtctttg tatgtagttc tacataatgc aaattgtgct ttctgatgga 2820
caagacctca taactgtgat taatatcaat aaaaagggga tgttgtgga 2869
<210> 37
<211> 335
<212> PRT
<213> Homo sapiens
<400> 37
Met Leu Gln Gly His Ser Ser Val Phe Gln Ala Leu Leu Gly Thr Phe
1 5 10 15
Phe Thr Trp Gly Met Thr Ala Ala Gly Ala Ala Leu Val Phe Val Phe
20 25 30
Ser Ser Gly Gln Arg Arg Ile Leu Asp Gly Ser Leu Gly Phe Ala Ala
35 40 45
Gly Val Met Leu Ala Ala Ser Tyr Trp Ser Leu Leu Ala Pro Ala Val
50 55 60
Glu Met Ala Thr Ser Ser Gly Gly Phe Gly Ala Phe Ala Phe Phe Pro
65 70 75 80
Val Ala Val Gly Phe Thr Leu Gly Ala Ala Phe Val Tyr Leu Ala Asp
85 90 95
Leu Leu Met Pro His Leu Gly Ala Ala Glu Asp Pro Gln Thr Thr Leu
100 105 110
Ala Leu Asn Phe Gly Ser Thr Leu Met Lys Lys Lys Ser Asp Pro Glu
115 120 125
Gly Pro Ala Leu Leu Phe Pro Glu Ser Glu Leu Ser Ile Arg Ile Asp
130 135 140
Lys Ser Glu Asn Gly Glu Ala Tyr Gln Arg Lys Lys Ala Ala Ala Thr
145 150 155 160
Gly Leu Pro Glu Gly Pro Ala Val Pro Val Pro Ser Arg Gly Asn Leu
165 170 175
Ala Gln Pro Gly Gly Ser Ser Trp Arg Arg Ile Ala Leu Leu Ile Leu
180 185 190
Ala Ile Thr Ile His Asn Val Pro Glu Gly Leu Ala Val Gly Val Gly
195 200 205
Phe Gly Ala Ile Glu Lys Thr Ala Ser Ala Thr Phe Glu Ser Ala Arg
210 215 220
Asn Leu Ala Ile Gly Ile Gly Ile Gln Asn Phe Pro Glu Gly Leu Ala
225 230 235 240
Val Ser Leu Pro Leu Arg Gly Ala Gly Phe Ser Thr Trp Arg Ala Phe
245 250 255
Trp Tyr Gly Gln Leu Ser Gly Met Val Glu Pro Leu Ala Gly Val Phe
260 265 270
Gly Ala Phe Ala Val Val Leu Ala Glu Pro Ile Leu Pro Tyr Ala Leu
275 280 285
Ala Phe Ala Ala Gly Ala Met Val Tyr Val Val Met Asp Asp Ile Ile
290 295 300
Pro Glu Ala Gln Ile Ser Gly Asn Gly Lys Leu Ala Ser Trp Ala Ser
305 310 315 320
Ile Leu Gly Phe Val Val Met Met Ser Leu Asp Val Gly Leu Gly
325 330 335
<210> 38
<211> 342
<212> PRT
<213> Homo sapiens
<400> 38
Met Leu Gln Gly His Ser Ser Val Phe Gln Ala Leu Leu Gly Thr Phe
1 5 10 15
Phe Thr Trp Gly Met Thr Ala Ala Gly Ala Ala Leu Val Phe Val Phe
20 25 30
Ser Ser Gly Gln Arg Arg Ile Leu Asp Gly Ser Leu Gly Phe Ala Ala
35 40 45
Gly Val Met Leu Ala Ala Ser Tyr Trp Ser Leu Leu Ala Pro Ala Val
50 55 60
Glu Met Ala Thr Ser Ser Gly Gly Phe Gly Ala Phe Ala Phe Phe Pro
65 70 75 80
Val Ala Val Gly Phe Thr Leu Gly Ala Ala Phe Val Tyr Leu Ala Asp
85 90 95
Leu Leu Met Pro His Leu Gly Ala Ala Glu Asp Pro Gln Thr Thr Leu
100 105 110
Ala Leu Asn Phe Gly Ser Thr Leu Met Lys Lys Lys Ser Asp Pro Glu
115 120 125
Gly Pro Ala Leu Leu Phe Pro Glu Ser Glu Leu Ser Ile Arg Ile Gly
130 135 140
Arg Ala Gly Leu Leu Ser Asp Lys Ser Glu Asn Gly Glu Ala Tyr Gln
145 150 155 160
Arg Lys Lys Ala Ala Ala Thr Gly Leu Pro Glu Gly Pro Ala Val Pro
165 170 175
Val Pro Ser Arg Gly Asn Leu Ala Gln Pro Gly Gly Ser Ser Trp Arg
180 185 190
Arg Ile Ala Leu Leu Ile Leu Ala Ile Thr Ile His Asn Val Pro Glu
195 200 205
Gly Leu Ala Val Gly Val Gly Phe Gly Ala Ile Glu Lys Thr Ala Ser
210 215 220
Ala Thr Phe Glu Ser Ala Arg Asn Leu Ala Ile Gly Ile Gly Ile Gln
225 230 235 240
Asn Phe Pro Glu Gly Leu Ala Val Ser Leu Pro Leu Arg Gly Ala Gly
245 250 255
Phe Ser Thr Trp Arg Ala Phe Trp Tyr Gly Gln Leu Ser Gly Met Val
260 265 270
Glu Pro Leu Ala Gly Val Phe Gly Ala Phe Ala Val Val Leu Ala Glu
275 280 285
Pro Ile Leu Pro Tyr Ala Leu Ala Phe Ala Ala Gly Ala Met Val Tyr
290 295 300
Val Val Met Asp Asp Ile Ile Pro Glu Ala Gln Ile Ser Gly Asn Gly
305 310 315 320
Lys Leu Ala Ser Trp Ala Ser Ile Leu Gly Phe Val Val Met Met Ser
325 330 335
Leu Asp Val Gly Leu Gly
340
<210> 39
<211> 4510
<212> DNA
<213> Homo sapiens
<400> 39
gctgaggcca ggagggcgca ctggggattg gaggcgaggg aagtgcaggg cgcatcccag 60
gcggcagggc tcccagcatc ggcagtcgcc atcaccgcca gaccgcagag acaggttcgg 120
atccgcggtc ctcttgcctc tttccaggcc tcgatgagtg ttaaatcgcc atttaatgtg 180
atgtcaagaa ataatttgga agcacctcct tgtaagatga cagagccatt taattttgag 240
aaaaatgaaa acaagcttcc accacatgag tctttaagaa gtcctggaac acttcctaac 300
caccctaatt tcaggctgaa aagctcagag aatggaaata aaaagaacaa ttttttgctt 360
tgtgagcaaa ccaaacaata tttggctagt caggaagaca attcagtttc ttcaaacccg 420
aatggcatca acggagaagt agttggctcc aaaggagaca ggaaaaaatt gccagcagga 480
aactcagtgt caccaccaag tgctgaaagt aattcaccac ccaaagaagt gaatattaag 540
cctggaaata atgtacgtcc tgcaaaatca aaaaaactaa acaagttggt cgagaattcc 600
ttgtccataa gtaatccagg gctcttcacc tccttaggac ctcctcttcg gtccacaact 660
tgccatcgct gtggcctatt tggatcgctg aggtgctctc agtgcaagca gacctactat 720
tgctccacag catgtcaaag aagagactgg tctgcacaca gcatcgtgtg caggcctgtt 780
cagccaaatt tccacaaact tgaaaataaa tcatctattg aaacaaagga tgtggaggta 840
aacaataaga gtgactgtcc acttggagtt actaaggaaa tagccatttg ggctgagaga 900
ataatgtttt ctgatttgag aagtctacaa ctcaagaaaa ccatggaaat aaagggtacg 960
gttaccgaat tcaaacaccc aggggacttc tacgtgcagt tatattcttc agaagtttta 1020
gaatacatga accaactctc tgccagctta aaagaaacat atgcaaatgt gcatgaaaaa 1080
gactatattc ctgttaaggg ggaagtttgt attgccaagt acactgttga tcagacctgg 1140
aacagagcaa tcatacaaaa cgttgatgtg cagcaaaaga aggcacatgt cttatatatt 1200
gattatggaa atgaagaaat aattccatta aacagaattt accacctcaa caggaacatt 1260
gacttgtttc ctccttgtgc cataaagtgc tttgtagcca atgttatccc agcagaaggg 1320
aattggagca gtgattgtat caaagctact aaaccactgt taatggagca gtactgctcc 1380
ataaagattg tcgacatctt ggaagaggaa gtggttacct ttgctgtaga agttgagctg 1440
ccaaattcag gaaaactttt agaccatgtg cttatagaaa tgggatatgg cttgaaaccc 1500
agtggacaag attctaagaa ggaaaatgca gatcaaagtg atcctgaaga tgttggaaaa 1560
atgacaactg aaaacaacat tgtcgtagac aaaagtgacc taatcccaaa agtgttaact 1620
ttgaatgtag gtgatgagtt ttgtggtgtg gttgcccaca ttcaaacacc agaagacttc 1680
ttttgtcaac aactgcaaag tggccgaaag cttgctgaac ttcaggcatc ccttagcaag 1740
tactgtgatc agttgcctcc acgctctgat ttttatccag ccattggtga tatatgttgt 1800
gctcagttct cagaggatga tcagtggtac cgtgcctctg ttttggctta cgcttctgaa 1860
gaatctgtac tggtcggata tgtagattat ggaaactttg aaatccttag tttgatgaga 1920
ctttgtccca taatcccaaa gttgttggaa ttgccaatgc aagctataaa gtgtgtacta 1980
gcaggagtaa agccatcatt aggaatttgg actccagaag ctatttgtct catgaaaaaa 2040
cttgtacaga acaaaataat cacagtgaaa gtggtggaca agttggaaaa cagttccctg 2100
gtggagctta ttgataaatc cgagacgcct catgtcagtg ttagcaaagt tctcctagat 2160
gcaggctttg ctgtgggaga acagagtatg gtgacagata aacccagtga cgtgaaagaa 2220
accagtgttc ccttgggtgt ggaaggaaaa gtaaatccat tggagtggac atgggttgaa 2280
cttggtgttg accaaacagt agatgttgtg gtctgtgtga tatatagtcc tggagaattt 2340
tattgccatg tgcttaaaga ggatgcttta aagaaactca atgatttgaa caagtcatta 2400
gcagaacact gccagcagaa gttacctaat ggtttcaagg cagagatagg acaaccttgt 2460
tgtgcttttt ttgcaggtga tggtagttgg tatcgtgctt tagtcaagga aatcttacca 2520
aatggacatg ttaaagtaca ttttgtggat tatggaaaca tcgaagaagt tactgcagat 2580
gaactccgaa tgatatcatc aacattttta aaccttccct ttcagggaat acggtgccag 2640
ttagcagata tacagtctag aaacaaacat tggtctgaag aagccataac aagattccag 2700
atgtgtgttg ctgggataaa attgcaagcc agagtggttg aagtcactga aaatgggata 2760
ggagttgaac tcaccgatct ctccacttgt tatcccagaa taattagtga tgttctgatt 2820
gatgaacatc tggttttaaa atctgcttca ccacataaag acttaccaaa tgacagactt 2880
gttaataaac atgagcttca agttcatgta cagggacttc aagctacctc ttcagctgag 2940
caatggaaga cgatagaatt gccagtggat aaaactatac aagcaaatgt attagaaatc 3000
ataagcccaa acttgtttta tgctctacca aaagggatgc cagaaaatca ggaaaagctg 3060
tgcatgttga cagctgaatt attagaatac tgcaatgctc cgaaaagtcg accaccctat 3120
agaccaagaa ttggagacgc atgctgtgcc aaatacacaa gtgatgattt ttggtatcgt 3180
gcagttgttc tggggacatc agacactgat gtggaagtgc tctatgcaga ctatggaaac 3240
attgaaaccc tgcctctttg cagagtgcaa ccaatcacct ctagccacct ggcgcttcct 3300
ttccaaatta ttagatgttc acttgaagga ttaatggaat tgaatggaag ctcttctcaa 3360
ttaataataa tgctattaaa aaatttcatg ttgaatcaga atgtaatgct ttctgtgaaa 3420
ggaattacaa agaatgtcca tacagtgtca gttgagaaat gttctgagaa tgggactgtc 3480
gatgtagctg ataagctagt gacatttggt ctggcaaaaa acatcacacc tcaaaggcag 3540
agtgctttaa atacagaaaa gatgtatagg atgaattgct gctgcacaga gttacagaaa 3600
caagttgaaa aacatgaaca tattcttctc ttcctcttaa acaattcaac caatcaaaat 3660
aaatttattg aaatgaaaaa actgttaaaa aaaacagcat ctcttggagg taaaccctta 3720
tgagacagga aacagcaaag gctagcttta ggagagaaag tacagcacct ggtgttttta 3780
tttatgagaa ccttttcttt gtccactttc tctgtaatga ccttctatcc ctccgttttt 3840
gcctgcctgc cattctccta ttaggttggt ggtttttatt ttcctctaag ttccttccac 3900
caaataaata ttacgtaaaa aattcatacc aaatcaatga gaatactggc aaggaataca 3960
tagggacttt ctgctatata tgtaactttt tattacttaa aggtaccgaa ggaaggccag 4020
gtgcagtggc tcacgcccag cactttggga ggctgaggtg ggaggatccc ttgaggccag 4080
gagttcaagg ttacagtgag ctatgatagt gccactgcac tccagcctgg gtgacagatt 4140
ttgtcttaaa aaaaaaaaaa aaaaagttga tatgagtttt attttctgtc cgtttgaaat 4200
attttgtaat attccctgca ttctctgtcg tctgcctctt ccacataatg tcctttgctt 4260
tcatgtttgt tatcttcttt ttctgttcac tcagaggtca tcaatttctt tctctccgtc 4320
cttaattgga ttatttttct tttggccttt gggcacagag tctgacctct ggaccactct 4380
aactggagaa ggaactttat gttccctctc ctgctgtgtc cacaacctta gaaatctgta 4440
gctagatttt tgttgttata gatagaattt actgtttctg aaacccaaat acagttatca 4500
gtttaaggtt 4510
<210> 40
<211> 1189
<212> PRT
<213> Homo sapiens
<400> 40
Met Ser Val Lys Ser Pro Phe Asn Val Met Ser Arg Asn Asn Leu Glu
1 5 10 15
Ala Pro Pro Cys Lys Met Thr Glu Pro Phe Asn Phe Glu Lys Asn Glu
20 25 30
Asn Lys Leu Pro Pro His Glu Ser Leu Arg Ser Pro Gly Thr Leu Pro
35 40 45
Asn His Pro Asn Phe Arg Leu Lys Ser Ser Glu Asn Gly Asn Lys Lys
50 55 60
Asn Asn Phe Leu Leu Cys Glu Gln Thr Lys Gln Tyr Leu Ala Ser Gln
65 70 75 80
Glu Asp Asn Ser Val Ser Ser Asn Pro Asn Gly Ile Asn Gly Glu Val
85 90 95
Val Gly Ser Lys Gly Asp Arg Lys Lys Leu Pro Ala Gly Asn Ser Val
100 105 110
Ser Pro Pro Ser Ala Glu Ser Asn Ser Pro Pro Lys Glu Val Asn Ile
115 120 125
Lys Pro Gly Asn Asn Val Arg Pro Ala Lys Ser Lys Lys Leu Asn Lys
130 135 140
Leu Val Glu Asn Ser Leu Ser Ile Ser Asn Pro Gly Leu Phe Thr Ser
145 150 155 160
Leu Gly Pro Pro Leu Arg Ser Thr Thr Cys His Arg Cys Gly Leu Phe
165 170 175
Gly Ser Leu Arg Cys Ser Gln Cys Lys Gln Thr Tyr Tyr Cys Ser Thr
180 185 190
Ala Cys Gln Arg Arg Asp Trp Ser Ala His Ser Ile Val Cys Arg Pro
195 200 205
Val Gln Pro Asn Phe His Lys Leu Glu Asn Lys Ser Ser Ile Glu Thr
210 215 220
Lys Asp Val Glu Val Asn Asn Lys Ser Asp Cys Pro Leu Gly Val Thr
225 230 235 240
Lys Glu Ile Ala Ile Trp Ala Glu Arg Ile Met Phe Ser Asp Leu Arg
245 250 255
Ser Leu Gln Leu Lys Lys Thr Met Glu Ile Lys Gly Thr Val Thr Glu
260 265 270
Phe Lys His Pro Gly Asp Phe Tyr Val Gln Leu Tyr Ser Ser Glu Val
275 280 285
Leu Glu Tyr Met Asn Gln Leu Ser Ala Ser Leu Lys Glu Thr Tyr Ala
290 295 300
Asn Val His Glu Lys Asp Tyr Ile Pro Val Lys Gly Glu Val Cys Ile
305 310 315 320
Ala Lys Tyr Thr Val Asp Gln Thr Trp Asn Arg Ala Ile Ile Gln Asn
325 330 335
Val Asp Val Gln Gln Lys Lys Ala His Val Leu Tyr Ile Asp Tyr Gly
340 345 350
Asn Glu Glu Ile Ile Pro Leu Asn Arg Ile Tyr His Leu Asn Arg Asn
355 360 365
Ile Asp Leu Phe Pro Pro Cys Ala Ile Lys Cys Phe Val Ala Asn Val
370 375 380
Ile Pro Ala Glu Gly Asn Trp Ser Ser Asp Cys Ile Lys Ala Thr Lys
385 390 395 400
Pro Leu Leu Met Glu Gln Tyr Cys Ser Ile Lys Ile Val Asp Ile Leu
405 410 415
Glu Glu Glu Val Val Thr Phe Ala Val Glu Val Glu Leu Pro Asn Ser
420 425 430
Gly Lys Leu Leu Asp His Val Leu Ile Glu Met Gly Tyr Gly Leu Lys
435 440 445
Pro Ser Gly Gln Asp Ser Lys Lys Glu Asn Ala Asp Gln Ser Asp Pro
450 455 460
Glu Asp Val Gly Lys Met Thr Thr Glu Asn Asn Ile Val Val Asp Lys
465 470 475 480
Ser Asp Leu Ile Pro Lys Val Leu Thr Leu Asn Val Gly Asp Glu Phe
485 490 495
Cys Gly Val Val Ala His Ile Gln Thr Pro Glu Asp Phe Phe Cys Gln
500 505 510
Gln Leu Gln Ser Gly Arg Lys Leu Ala Glu Leu Gln Ala Ser Leu Ser
515 520 525
Lys Tyr Cys Asp Gln Leu Pro Pro Arg Ser Asp Phe Tyr Pro Ala Ile
530 535 540
Gly Asp Ile Cys Cys Ala Gln Phe Ser Glu Asp Asp Gln Trp Tyr Arg
545 550 555 560
Ala Ser Val Leu Ala Tyr Ala Ser Glu Glu Ser Val Leu Val Gly Tyr
565 570 575
Val Asp Tyr Gly Asn Phe Glu Ile Leu Ser Leu Met Arg Leu Cys Pro
580 585 590
Ile Ile Pro Lys Leu Leu Glu Leu Pro Met Gln Ala Ile Lys Cys Val
595 600 605
Leu Ala Gly Val Lys Pro Ser Leu Gly Ile Trp Thr Pro Glu Ala Ile
610 615 620
Cys Leu Met Lys Lys Leu Val Gln Asn Lys Ile Ile Thr Val Lys Val
625 630 635 640
Val Asp Lys Leu Glu Asn Ser Ser Leu Val Glu Leu Ile Asp Lys Ser
645 650 655
Glu Thr Pro His Val Ser Val Ser Lys Val Leu Leu Asp Ala Gly Phe
660 665 670
Ala Val Gly Glu Gln Ser Met Val Thr Asp Lys Pro Ser Asp Val Lys
675 680 685
Glu Thr Ser Val Pro Leu Gly Val Glu Gly Lys Val Asn Pro Leu Glu
690 695 700
Trp Thr Trp Val Glu Leu Gly Val Asp Gln Thr Val Asp Val Val Val
705 710 715 720
Cys Val Ile Tyr Ser Pro Gly Glu Phe Tyr Cys His Val Leu Lys Glu
725 730 735
Asp Ala Leu Lys Lys Leu Asn Asp Leu Asn Lys Ser Leu Ala Glu His
740 745 750
Cys Gln Gln Lys Leu Pro Asn Gly Phe Lys Ala Glu Ile Gly Gln Pro
755 760 765
Cys Cys Ala Phe Phe Ala Gly Asp Gly Ser Trp Tyr Arg Ala Leu Val
770 775 780
Lys Glu Ile Leu Pro Asn Gly His Val Lys Val His Phe Val Asp Tyr
785 790 795 800
Gly Asn Ile Glu Glu Val Thr Ala Asp Glu Leu Arg Met Ile Ser Ser
805 810 815
Thr Phe Leu Asn Leu Pro Phe Gln Gly Ile Arg Cys Gln Leu Ala Asp
820 825 830
Ile Gln Ser Arg Asn Lys His Trp Ser Glu Glu Ala Ile Thr Arg Phe
835 840 845
Gln Met Cys Val Ala Gly Ile Lys Leu Gln Ala Arg Val Val Glu Val
850 855 860
Thr Glu Asn Gly Ile Gly Val Glu Leu Thr Asp Leu Ser Thr Cys Tyr
865 870 875 880
Pro Arg Ile Ile Ser Asp Val Leu Ile Asp Glu His Leu Val Leu Lys
885 890 895
Ser Ala Ser Pro His Lys Asp Leu Pro Asn Asp Arg Leu Val Asn Lys
900 905 910
His Glu Leu Gln Val His Val Gln Gly Leu Gln Ala Thr Ser Ser Ala
915 920 925
Glu Gln Trp Lys Thr Ile Glu Leu Pro Val Asp Lys Thr Ile Gln Ala
930 935 940
Asn Val Leu Glu Ile Ile Ser Pro Asn Leu Phe Tyr Ala Leu Pro Lys
945 950 955 960
Gly Met Pro Glu Asn Gln Glu Lys Leu Cys Met Leu Thr Ala Glu Leu
965 970 975
Leu Glu Tyr Cys Asn Ala Pro Lys Ser Arg Pro Pro Tyr Arg Pro Arg
980 985 990
Ile Gly Asp Ala Cys Cys Ala Lys Tyr Thr Ser Asp Asp Phe Trp Tyr
995 1000 1005
Arg Ala Val Val Leu Gly Thr Ser Asp Thr Asp Val Glu Val Leu
1010 1015 1020
Tyr Ala Asp Tyr Gly Asn Ile Glu Thr Leu Pro Leu Cys Arg Val
1025 1030 1035
Gln Pro Ile Thr Ser Ser His Leu Ala Leu Pro Phe Gln Ile Ile
1040 1045 1050
Arg Cys Ser Leu Glu Gly Leu Met Glu Leu Asn Gly Ser Ser Ser
1055 1060 1065
Gln Leu Ile Ile Met Leu Leu Lys Asn Phe Met Leu Asn Gln Asn
1070 1075 1080
Val Met Leu Ser Val Lys Gly Ile Thr Lys Asn Val His Thr Val
1085 1090 1095
Ser Val Glu Lys Cys Ser Glu Asn Gly Thr Val Asp Val Ala Asp
1100 1105 1110
Lys Leu Val Thr Phe Gly Leu Ala Lys Asn Ile Thr Pro Gln Arg
1115 1120 1125
Gln Ser Ala Leu Asn Thr Glu Lys Met Tyr Arg Met Asn Cys Cys
1130 1135 1140
Cys Thr Glu Leu Gln Lys Gln Val Glu Lys His Glu His Ile Leu
1145 1150 1155
Leu Phe Leu Leu Asn Asn Ser Thr Asn Gln Asn Lys Phe Ile Glu
1160 1165 1170
Met Lys Lys Leu Leu Lys Lys Thr Ala Ser Leu Gly Gly Lys Pro
1175 1180 1185
Leu
<210> 41
<211> 5799
<212> DNA
<213> Homo sapiens
<400> 41
agtgccggct gccgatgacc gattcacgct cccggtactg gggccccctc tgcccagcca 60
cccctaccca gagcacccgg gctgcgcggc cccgccgagg gtgcgggctt tgttcgcatt 120
gtctgcgcgc acctgagcgc ggccttcctg gcacggcggc gtcgggggaa gagcgcacct 180
ggcgcgcgcc tccctcgtgg ccactcgcgg tccgtcccgg gcgagctggc ggggttttgg 240
gaggggtgcg gtcagcagtt atatcaacat gccccctttc ctgttgctgg aagccgtctg 300
tgttttcctg ttttccagag tgcccccatc tctccctctc caggaagtcc atgtaagcaa 360
agaaaccatc gggaagattt cagctgccag caaaatgatg tggtgctcgg ctgcagtgga 420
catcatgttt ctgttagatg ggtctaacag cgtcgggaaa gggagctttg aaaggtccaa 480
gcactttgcc atcacagtct gtgacggtct ggacatcagc cccgagaggg tcagagtggg 540
agcattccag ttcagttcca ctcctcatct ggaattcccc ttggattcat tttcaaccca 600
acaggaagtg aaggcaagaa tcaagaggat ggttttcaaa ggagggcgca cggagacgga 660
acttgctctg aaataccttc tgcacagagg gttgcctgga ggcagaaatg cttctgtgcc 720
ccagatcctc atcatcgtca ctgatgggaa gtcccagggg gatgtggcac tgccatccaa 780
gcagctgaag gaaaggggtg tcactgtgtt tgctgtgggg gtcaggtttc ccaggtggga 840
ggagctgcat gcactggcca gcgagcctag agggcagcac gtgctgttgg ctgagcaggt 900
ggaggatgcc accaacggcc tcttcagcac cctcagcagc tcggccatct gctccagcgc 960
cacgccagac tgcagggtcg aggctcaccc ctgtgagcac aggacgctgg agatggtccg 1020
ggagttcgct ggcaatgccc catgctggag aggatcgcgg cggacccttg cggtgctggc 1080
tgcacactgt cccttctaca gctggaagag agtgttccta acccaccctg ccacctgcta 1140
caggaccacc tgcccaggcc cctgtgactc gcagccctgc cagaatggag gcacatgtgt 1200
tccagaagga ctggacggct accagtgcct ctgcccgctg gcctttggag gggaggctaa 1260
ctgtgccctg aagctgagcc tggaatgcag ggtcgacctc ctcttcctgc tggacagctc 1320
tgcgggcacc actctggacg gcttcctgcg ggccaaagtc ttcgtgaagc ggtttgtgcg 1380
ggccgtgctg agcgaggact ctcgggcccg agtgggtgtg gccacataca gcagggagct 1440
gctggtggcg gtgcctgtgg gggagtacca ggatgtgcct gacctggtct ggagcctcga 1500
tggcattccc ttccgtggtg gccccaccct gacgggcagt gccttgcggc aggcggcaga 1560
gcgtggcttc gggagcgcca ccaggacagg ccaggaccgg ccacgtagag tggtggtttt 1620
gctcactgag tcacactccg aggatgaggt tgcgggccca gcgcgtcacg caagggcgcg 1680
agagctgctc ctgctgggtg taggcagtga ggccgtgcgg gcagagctgg aggagatcac 1740
aggcagccca aagcatgtga tggtctactc ggatcctcag gatctgttca accaaatccc 1800
tgagctgcag gggaagctgt gcagccggca gcggccaggg tgccggacac aagccctgga 1860
cctcgtcttc atgttggaca cctctgcctc agtagggccc gagaattttg ctcagatgca 1920
gagctttgtg agaagctgtg ccctccagtt tgaggtgaac cctgacgtga cacaggtcgg 1980
cctggtggtg tatggcagcc aggtgcagac tgccttcggg ctggacacca aacccacccg 2040
ggctgcgatg ctgcgggcca ttagccaggc cccctaccta ggtggggtgg gctcagccgg 2100
caccgccctg ctgcacatct atgacaaagt gatgaccgtc cagaggggtg cccggcctgg 2160
tgtccccaaa gctgtggtgg tgctcacagg cgggagaggc gcagaggatg cagccgttcc 2220
tgcccagaag ctgaggaaca atggcatctc tgtcttggtc gtgggcgtgg ggcctgtcct 2280
aagtgagggt ctgcggaggc ttgcaggtcc ccgggattcc ctgatccacg tggcagctta 2340
cgccgacctg cggtaccacc aggacgtgct cattgagtgg ctgtgtggag aagccaagca 2400
gccagtcaac ctctgcaaac ccagcccgtg catgaatgag ggcagctgcg tcctgcagaa 2460
tgggagctac cgctgcaagt gtcgggatgg ctgggagggc ccccactgcg agaaccgatt 2520
cttgagacgc ccctgaggca catggctccc gtgcaggagg gcagcagccg tacccctccc 2580
agcaactaca gagaaggcct gggcactgaa atggtgccta ccttctggaa tgtctgtgcc 2640
ccaggtcctt agaatgtctg cttcccgccg tggccaggac cactattctc actgagggag 2700
gaggatgtcc caactgcagc catgctgctt agagacaaga aagcagctga tgtcacccac 2760
aaacgatgtt gttgaaaagt tttgatgtgt aagtaaatac ccactttctg tacctgctgt 2820
gccttgttga ggctatgtca tctgccacct ttcccttgag gataaacaag gggtcctgaa 2880
gacttaaatt tagcggcctg acgttccttt gcacacaatc aatgctcgcc agaatgttgt 2940
tgacacagta atgcccagca gaggccttta ctagagcatc ctttggacgg cgaaggccac 3000
ggcctttcaa gatggaaagc agcagctttt ccacttcccc agagacattc tggatgcatt 3060
tgcattgagt ctgaaagggg gcttgaggga cgtttgtgac ttctggcgac tgccttttgt 3120
gtgtggaaga gacttggaaa ggtctcagac tgaaatgtga ccaattaacc agcttgtttg 3180
atgatggggg aggggctgag tgtgcaatgg gcccaggtct ggaggggcca cgtaaaatcg 3240
ttctgagtcg tgagcagtgt ccacctgaag ggtcttcctt tcaaaagagg ctgcggccag 3300
agactgtggc tcatgcctgt aatcccagca ctttggaggc tgaggcaggt ggatcacccg 3360
aggtcaggag tttgagacca gcctggccaa cgtggtgaaa gtttgtcttt actaaaaata 3420
caaaaggtag ccgggggtgg tggtggatgc ctataatccc agctactcgg gaggctgaga 3480
caggagaatg gcttgaacct gggaggcgga agttacagtg agccgagatc tcaccactgc 3540
actccagcct gggcaacaag agtaaaaatc tgtctcaaaa agaaaaaaat gtacttagga 3600
ggggttaatt gtggcgtgtt tatggaattc tttccttatt ctccttttag tggggcaaag 3660
agaagtaaga ttcttaaact caaaaatata ggataaagaa acttacagag attttgcttt 3720
ttaaagcatt gatcttacgc tgtctaggtt ttaattttgt tttgctttgc ttttctacac 3780
agtttttaaa gaaatatttc aagaaatgtt ggttatttat taaacaggga tatttgtacc 3840
tatgtggcaa agaggcatat ttggaatatt ctctggcaaa ctagatactt acttccctat 3900
cgctgcagta tttaggaatt acttcttctc cttggttgtg ttgtttagag ttggattttc 3960
tgtagaaatc tttctagagc tctgatgtga ctccagacac tttatcgttt ttcttttttt 4020
tgagacggag ttttgctctt gttgcccagg ctagagtgca gtggtacaat cttggctcac 4080
tgcaaccttt gcctcccagg ttgaagtgat tctcatgcct cagcctcttg agtagctggg 4140
attagaggca ggtgccacca tgcctagcta atttttgtat ttttagttag agacagggtt 4200
tcaccatgtt ggccaggcta gtctcgaact tctgacctca ggtgatcccc ctgccttggc 4260
ctcccaaagt tctgggatta caggggtgaa ccactgtgcc tggcccattt ttctttataa 4320
atattgtaac ataatgtttt atagacaaac attcaagggt actttggctt taagaacttc 4380
aggatttctg gtgctagaaa agcgcttgaa gcagtatcac caagatttta gatattaaaa 4440
agtctggtgt accagacatt gagtcataat catctatatt caagggatac tttcattgat 4500
aactttgtta ttatgctgcc cttcacagaa gacaacgtcc ggggcaggat cacatgctcc 4560
ctagcagatg ctgatcagtg atgtcataga aattacatga atgcattgtc tttaaatagc 4620
agtttaacca tgttataatg taggcttttt gtcttgttcc gggctggtat ttgggtgccc 4680
tgattgaatt acttggattt aaacagcaaa ctgtgggctc tcgacttaca tagtaagggc 4740
ctttactgtt tctttgtagg aaatgggttt ctcgcctttg aaacattttt tccccttttg 4800
tagtgacagt gccactaaat agttcagctt ttgtcagtcc cccaggaaag tgctatccta 4860
tggcctaact agccaagcct tttttctttc atttaaaaga aattagcttt aatttttacc 4920
tttaattact tattcaaata agacagaaat atattttcct tgcaataatt aaaacattgc 4980
atataggcca taaatttcct tattttctct gaacgatcct gattccagtc atcttgttga 5040
ataccctagt tctaataatt gactcttgct tttctagaga aatatttcca aatgatgcta 5100
gttttgtctc ttcctttcaa agttgtatac cacttctttt tcttgtcatt ttgcattgcc 5160
tgggacctcc agaataatgt ttcatgaagt agcatgtatc catatctggt tcttgacttt 5220
ttcatcataa taattgtttt ctatgggtta cttatcagtt taagaatgct taattcctag 5280
atgaactaag agtgtttatt acatgttgag atttatggta tgctttttct tcctcaagat 5340
aatgcatttt ttgtattatc tgttaatgtg ataggttatc catttgtgta ttttcaatca 5400
ttgaacaacc cttgattttt ttggataaac tctatttggt cattatgcat cattctataa 5460
accctgctga atttttcatt tgccaacatc ttatttcaga ttcttttaat ctgtgtccaa 5520
caatgagatt tgttttcttt tgcaatttgt tttgaatttt tggtatcaga gctatactaa 5580
ccttataatg gaaaatacat atttctcaaa cttttacact gatatattca tagtattttt 5640
ttataatttg aaaaatcttg tcagtatctg tattaaggcc tccatttcag ttctgctatt 5700
tcatattgcc ttaggttgtc tatttgtctc tttaatgaac ccgattttga ttttgtcatt 5760
tttaaaataa acacatttat gctataaact tccttaatt 5799
<210> 42
<211> 755
<212> PRT
<213> Homo sapiens
<400> 42
Met Pro Pro Phe Leu Leu Leu Glu Ala Val Cys Val Phe Leu Phe Ser
1 5 10 15
Arg Val Pro Pro Ser Leu Pro Leu Gln Glu Val His Val Ser Lys Glu
20 25 30
Thr Ile Gly Lys Ile Ser Ala Ala Ser Lys Met Met Trp Cys Ser Ala
35 40 45
Ala Val Asp Ile Met Phe Leu Leu Asp Gly Ser Asn Ser Val Gly Lys
50 55 60
Gly Ser Phe Glu Arg Ser Lys His Phe Ala Ile Thr Val Cys Asp Gly
65 70 75 80
Leu Asp Ile Ser Pro Glu Arg Val Arg Val Gly Ala Phe Gln Phe Ser
85 90 95
Ser Thr Pro His Leu Glu Phe Pro Leu Asp Ser Phe Ser Thr Gln Gln
100 105 110
Glu Val Lys Ala Arg Ile Lys Arg Met Val Phe Lys Gly Gly Arg Thr
115 120 125
Glu Thr Glu Leu Ala Leu Lys Tyr Leu Leu His Arg Gly Leu Pro Gly
130 135 140
Gly Arg Asn Ala Ser Val Pro Gln Ile Leu Ile Ile Val Thr Asp Gly
145 150 155 160
Lys Ser Gln Gly Asp Val Ala Leu Pro Ser Lys Gln Leu Lys Glu Arg
165 170 175
Gly Val Thr Val Phe Ala Val Gly Val Arg Phe Pro Arg Trp Glu Glu
180 185 190
Leu His Ala Leu Ala Ser Glu Pro Arg Gly Gln His Val Leu Leu Ala
195 200 205
Glu Gln Val Glu Asp Ala Thr Asn Gly Leu Phe Ser Thr Leu Ser Ser
210 215 220
Ser Ala Ile Cys Ser Ser Ala Thr Pro Asp Cys Arg Val Glu Ala His
225 230 235 240
Pro Cys Glu His Arg Thr Leu Glu Met Val Arg Glu Phe Ala Gly Asn
245 250 255
Ala Pro Cys Trp Arg Gly Ser Arg Arg Thr Leu Ala Val Leu Ala Ala
260 265 270
His Cys Pro Phe Tyr Ser Trp Lys Arg Val Phe Leu Thr His Pro Ala
275 280 285
Thr Cys Tyr Arg Thr Thr Cys Pro Gly Pro Cys Asp Ser Gln Pro Cys
290 295 300
Gln Asn Gly Gly Thr Cys Val Pro Glu Gly Leu Asp Gly Tyr Gln Cys
305 310 315 320
Leu Cys Pro Leu Ala Phe Gly Gly Glu Ala Asn Cys Ala Leu Lys Leu
325 330 335
Ser Leu Glu Cys Arg Val Asp Leu Leu Phe Leu Leu Asp Ser Ser Ala
340 345 350
Gly Thr Thr Leu Asp Gly Phe Leu Arg Ala Lys Val Phe Val Lys Arg
355 360 365
Phe Val Arg Ala Val Leu Ser Glu Asp Ser Arg Ala Arg Val Gly Val
370 375 380
Ala Thr Tyr Ser Arg Glu Leu Leu Val Ala Val Pro Val Gly Glu Tyr
385 390 395 400
Gln Asp Val Pro Asp Leu Val Trp Ser Leu Asp Gly Ile Pro Phe Arg
405 410 415
Gly Gly Pro Thr Leu Thr Gly Ser Ala Leu Arg Gln Ala Ala Glu Arg
420 425 430
Gly Phe Gly Ser Ala Thr Arg Thr Gly Gln Asp Arg Pro Arg Arg Val
435 440 445
Val Val Leu Leu Thr Glu Ser His Ser Glu Asp Glu Val Ala Gly Pro
450 455 460
Ala Arg His Ala Arg Ala Arg Glu Leu Leu Leu Leu Gly Val Gly Ser
465 470 475 480
Glu Ala Val Arg Ala Glu Leu Glu Glu Ile Thr Gly Ser Pro Lys His
485 490 495
Val Met Val Tyr Ser Asp Pro Gln Asp Leu Phe Asn Gln Ile Pro Glu
500 505 510
Leu Gln Gly Lys Leu Cys Ser Arg Gln Arg Pro Gly Cys Arg Thr Gln
515 520 525
Ala Leu Asp Leu Val Phe Met Leu Asp Thr Ser Ala Ser Val Gly Pro
530 535 540
Glu Asn Phe Ala Gln Met Gln Ser Phe Val Arg Ser Cys Ala Leu Gln
545 550 555 560
Phe Glu Val Asn Pro Asp Val Thr Gln Val Gly Leu Val Val Tyr Gly
565 570 575
Ser Gln Val Gln Thr Ala Phe Gly Leu Asp Thr Lys Pro Thr Arg Ala
580 585 590
Ala Met Leu Arg Ala Ile Ser Gln Ala Pro Tyr Leu Gly Gly Val Gly
595 600 605
Ser Ala Gly Thr Ala Leu Leu His Ile Tyr Asp Lys Val Met Thr Val
610 615 620
Gln Arg Gly Ala Arg Pro Gly Val Pro Lys Ala Val Val Val Leu Thr
625 630 635 640
Gly Gly Arg Gly Ala Glu Asp Ala Ala Val Pro Ala Gln Lys Leu Arg
645 650 655
Asn Asn Gly Ile Ser Val Leu Val Val Gly Val Gly Pro Val Leu Ser
660 665 670
Glu Gly Leu Arg Arg Leu Ala Gly Pro Arg Asp Ser Leu Ile His Val
675 680 685
Ala Ala Tyr Ala Asp Leu Arg Tyr His Gln Asp Val Leu Ile Glu Trp
690 695 700
Leu Cys Gly Glu Ala Lys Gln Pro Val Asn Leu Cys Lys Pro Ser Pro
705 710 715 720
Cys Met Asn Glu Gly Ser Cys Val Leu Gln Asn Gly Ser Tyr Arg Cys
725 730 735
Lys Cys Arg Asp Gly Trp Glu Gly Pro His Cys Glu Asn Arg Phe Leu
740 745 750
Arg Arg Pro
755

Claims (16)

1.一种预测前列腺癌对象对放疗的反应的方法，包括：
确定接收对针对从包括以下各项的组中选择的两个或更多个，例如，2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱的确定的结果：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述(一个或多个)基因表达谱是在从所述对象获得的生物样本中确定的；
基于针对所述两个或更多个PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对放疗反应的所述预测，并且
任选地，将所述预测或基于所述预测的治疗推荐提供给医疗护理人员或所述对象。
2.根据权利要求1所述的方法，其中，所述两个或更多个PDE4D7相关基因包括：所述PDE4D7相关基因中的三个或更多个，优选地，六个或更多个，最优选地，所有。
3.根据权利要求1或2所述的方法，其中，对治疗反应的所述预测的所述确定包括利用已经根据前列腺癌对象的群体导出的回归函数来将针对所述PDE4D7相关基因中的两个或更多个，例如，2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因的所述基因表达谱进行组合。
4.根据权利要求1至3中的任一项所述的方法，其中，确定对所述放疗反应的所述预测还基于从所述对象获得的一个或多个临床参数。
5.根据权利要求4所述的方法，其中，所述临床参数包括以下中的一项或多项：(i)前列腺特异性抗原(PSA)水平；(ii)病理格里森评分(pGS)；iii)临床肿瘤阶段；iv)病理格里森分级组(pGGG)；v)病理阶段；vi)一个或多个病理变量，例如，手术切缘和/或淋巴结浸润和/或前列腺外生长和/或精囊浸润的状态；vii)CAPRA-S；以及viii)另一临床风险评分。
6.根据权利要求4或5所述的方法，其中，确定对所述放疗反应的所述预测包括利用已经根据前列腺癌对象的群体导出的回归函数来将针对所述两个或更多个PDE4D7相关基因的所述(一个或多个)基因表达谱和从所述对象获得的所述一个或多个临床参数进行组合。
7.根据权利要求1至6中的任一项所述的方法，其中，所述生物样本是在所述放疗开始之前从所述对象获得的。
8.根据权利要求1至7中的任一项所述的方法，其中，所述放疗是根治性放疗或挽救性放疗。
9.根据权利要求1至8中的任一项所述的方法，其中，对所述放疗反应的所述预测为针对所述放疗的有效性是负面的还是正面的，其中，治疗是基于所述预测来推荐的，并且如果所述预测是负面的，则所推荐的治疗包括以下中的一项或多项：(i)比标准更早提供的放疗；(ii)具有增加的辐射剂量的放疗；(iii)辅助治疗，例如，雄激素阻断治疗；iv)不是辐射治疗的替代治疗。
10.一种包括指令的计算机程序产品，当所述程序由计算机运行时，所述指令使所述计算机执行包括以下操作的方法：
接收指示针对从包括以下各项的组中选择的两个或更多个，例如，2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱的数据：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述(一个或多个)基因表达谱是在从前列腺癌对象获得的生物样本中确定的，
基于针对所述两个或更多个PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对前列腺癌对象对治疗的反应的预测，并且
任选地，将所述预测或基于所述预测的治疗推荐提供给医疗护理人员或所述对象。
11.一种用于预测前列腺癌对象对放疗的反应的装置，包括：
输入部，其适于接收指示针对从包括以下各项的组中选择的两个或更多个，例如，2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱的数据：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述(一个或多个)基因表达谱是在从所述对象获得的生物样本中确定的，
处理器，其适于基于针对所述两个或更多个PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对所述放疗反应的所述预测，
根据权利要求10所述的计算机程序产品，以及
任选地，提供单元，其适于将所述预测或基于所述预测的治疗推荐提供给医疗护理人员或所述对象。
12.一种诊断套件，包括：
至少一个引物和/或探针，其用于在从对象获得的生物样本中确定针对从包括以下各项的组中选择的两个或更多个，例如，1个、2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，以及
任选地，根据权利要求11所述的装置或跟权利要求10所述的计算机程序产品。
13.一种根据权利要求12所述的套件的使用。
14.一种根据权利要求13所述的套件在预测前列腺癌对象对放疗的反应的方法中的使用。
15.一种方法，包括：
接收从前列腺癌对象获得的生物样本，
使用根据权利要求12所述套件来在从所述对象获得的所述生物样本中确定针对从包括以下项的组中选择的两个或更多个，例如，2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2。
16.一种根据权利要求10所述计算机程序或根据权利要求11所述的装置的使用，其用于在预测前列腺癌对象对放疗的反应的方法中使用针对从包括以下项的组中选择的两项或更多项，例如，2个、3个、4个、5个、6个、7个或者所有，PDE4D7相关基因中的每个的基因表达谱：ABCC5、CUX2、KIAA1549、PDE4D、RAP1GAP2、SLC39A11、TDRD1和VWA2，所述使用包括：
基于针对所述两个或更多个PDE4D7相关基因的所述(一个或多个)基因表达谱来确定对所述放疗反应的所述预测，并且
任选地，将所述预测或基于所述预测的治疗推荐提供给医疗护理人员或所述对象。
CN202180053564.XA 2020-08-31 2021-08-17 基于pde4d7相关基因来预测前列腺癌对象对放疗的反应 Pending CN116802312A (zh)

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