CN107743524B - 前列腺癌预后的方法 - Google Patents

前列腺癌预后的方法 Download PDF

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CN107743524B
CN107743524B CN201680031601.6A CN201680031601A CN107743524B CN 107743524 B CN107743524 B CN 107743524B CN 201680031601 A CN201680031601 A CN 201680031601A CN 107743524 B CN107743524 B CN 107743524B
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R·霍夫曼
E·德恩比耶赞-蒂默曼斯
D·A·M·W·范斯特里普
A·G·C·范布鲁塞尔
M·阿尔维斯德因达
J·费罗贝尔
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Abstract

本发明涉及以下方法，其用于确定用于诊断患有前列腺癌的患者的基因表达签名例如以建立针对这样的患者的预后、用于确定例如在初级处置之后所述患者发展侵袭性或惰性疾病的倾向、和/或用于针对可用疗法对识患者进行识别和分级。本发明还涉及用于在这样的方法中使用的产品，例如，套件、软件等。本发明还涉及用于处置已经在本文中所公开的方法中的任何方法中被诊断、识别或分级的患者的治疗。

Description

前列腺癌预后的方法
技术领域
本发明涉及以下方法，其用于确定用于诊断患有前列腺癌的患者的基因表达签名例如以建立针对这样的患者的预后、用于例如在初级处置之后确定所述患者发展侵袭性或惰性疾病的倾向、和/或用于针对可用疗法对患者进行识别和分级。本发明也涉及在这样的方法中使用的产品，例如，试剂盒(kit)、软件等。本发明还涉及用于在对已经在本文中所公开的方法的任意方法中被诊断、识别或分级的患者的处置中使用的疗法。
背景技术
癌症是细胞群组表现出不受控制的生长、侵袭并且有时转移的一类疾病。癌症的这三种恶性属性将其与自限性的、不会侵入或转移的良性肿瘤区分开来。
前列腺癌(PCa)是男性中最常发生的非皮肤性恶性肿瘤，在2008年全球确诊估计900000例新发病例。由于人口老龄化，PCa的发病率在未来数年将会急剧增加。通过确定前列腺特异性抗原(PSA)的血液水平、直肠指检(DRE)和经直肠超声分析(TRUS)进行的常规诊断导致对非癌性、良性前列腺状况的显著的首要过度诊断：单在美国每年执行1百万例前列腺活检发现大约250000例新病例，其中大约75％是不必要进行的，这导致患者出现严重并发症(尿脓毒血症、出血、尿潴留)并且总费用>20亿美元(每个活检流程～2100美元)。活检为阴性的100位男性中至少有4位可能由于副作用而住院治疗，并且10000位活检患者中有9位存在由于当前使用的流程而死亡的风险。
在美国每年约250000例新检测出的PCa病例中，大约200000例最初被表征为局限性疾病，即，限于前列腺器官的癌症。这种状况在一定程度上能通过诸如放射治疗的初级处置方法来治愈或者具体地通过手术(前列腺移除术)对前列腺的部分或全部移除。然而，这些介入通常具有严重的副作用，特别是尿失禁和/或勃起功能障碍，这是前列腺移除术的非常常见的后果。高达50％的经受根治性前列腺移除术的男性会发展成尿失禁。研究已经表明，手术之后一年，15％至50％之间的男性仍然报告有这样的问题。勃起问题同样是根治性前列腺移除术(RP)的严重副作用。仅大约一半的经手术的男性能够恢复其一些勃起能力。此外，针对局部PCa的所有常规施加的处置都是昂贵的(通常在20-30000美元左右)，并且每年在美国发生50亿美元的总直接成本。
在美国，诊断具有临床局限性疾病的～200000位男性中，高达50％具有非常低或低的癌症风险。因此，NCCN(国家综合癌症网络)最近修订了其PCa处置指南，以扩展主动监管(AS)作为针对患有这样的低风险疾病的患者的温和并且方便的处置备选方案。通过将适当的患者转诊至AS，针对这样的患者的生活质量与经受初级处置的男性相比得到显著改善，并且据报导，针对AS的5年费用低于每位患者10000美元。
此外，在选择手术(相对于AS)作为针对给定患者的处置选择的情况下，根据患者的肿瘤的潜在侵袭性对手术程度进行分级是显著有利的。例如，保留神经的手术技术可以更一般性地应用于具有预测低风险疾病的男性，以使根治性前列腺移除术的效力相关的副作用最小化。类似地，根据欧洲泌尿学会(EAU)最新的前列腺癌指南，在预测高风险癌症的情况下推荐扩展的淋巴结清除，尽管该流程与更受限的流程相比是复杂、耗时并且与较高的并发症率相关联的。因此，尽管受限较少的淋巴结清除显示错过大约50％的淋巴结转移，但对局部前列腺癌患者的管理需要对个体肿瘤的侵袭性潜力的高度准确的手术前预测，以提供针对每位患者的最佳护理。
US 2013/196321 A1描述了分子测定，其包括测量来自前列腺癌患者的样本中的一个或多个基因的表达水平，以提供关于临床结果的可能性的信息、识别风险分类、并且促进处置决策制定。该参考文献公开了在这样的测定中待分析的许多基因，其被标准化为例如持家基因。此外，也公开了包括用于执行测定的基因特异性探针和/或引物的试剂盒，以及用于执行对表达水平的分析的基于计算机的系统、算法和计算机程序产品。
Mimoto Rei等人在Cancer Letters(2013)，第339卷，第2期，第214-225页上的文章“DYRK2 controls the epithelial-mesenchymal transition in breast cancer bydegrading Snail”中公开了DYRK2在人类乳腺癌组织中被下调并且具有低DYRK2表达肿瘤的患者比具有高SYRK2表达肿瘤的那些患者具有更差的结果。作者的结论是，DYRK2是乳腺癌的潜在预后指标，并且另外提到了，DYRK2也已经被发现在肺癌、结肠癌和前列腺癌中被下调。
WO 2010/131194 A1涉及PDE4D7作为恶性激素敏感性前列腺癌的指标，并且公开了用于诊断、检测、监测和预测恶性激素敏感性前列腺癌的方法，其包括确定PDE4D 7的水平的步骤。另外，描述了用于识别适合特定癌症疗法的个体的方法，以及用于执行该方法的复合物，包括针对PDE4D7表达产物特异性的寡核苷酸或探针。
WO 2014/153442 A2公开了用于对卵巢癌的诊断、预后和处置的方法，其涉及确定特定指标基因的表达水平。所述表达水平被转换成指数，其中，利用从上调基因中的一些上调基因中减去下调基因的表达水平对基因进行平均地加权。
发明内容
本发明涉及识别和使用与前列腺癌临床相关的感兴趣生物标记基因(也被称为标记基因)的基因表达谱、签名或模式。具体地，本发明基于对从生物学样本获得的核酸(优选为生物标记基因的转录物)的基因表达分析，以及对与侵袭性和惰性疾病、患者生存和前列腺癌复发相关的生物标记基因的识别。对这些标记基因的表达分析能够被用于提供前列腺癌进展指数(PCPI)，其能够被用于将患者分类为具有侵袭性和惰性疾病以及具有对应的不良或良好预后。
此外，PCPI也能够被用于预测在先前被临床诊断和处置的对象的疾病的进展，并且被用于根据其个体PCPI对患者进行分级。因此，PCPI为与前列腺癌患者的诊断、预后和处置有关的个性化医学提供非常有用的参数。PCPI可以单独使用或者可以与提供关于患者个人疾病状态或疾病阶段的信息的其他手段和方法结合使用。
医师和/或病理学家能够有利地使用PCPI来确认在用于对患者(例如，具有发展侵袭性与惰性前列腺癌形式的倾向的患者)进行诊断、识别、预后、分类和/或分级的其他方法中所获得的结果。因此，由本发明所提供的方法和手段帮助建立更好的诊断、预后等，从而找到针对患者的最佳处置，并且避免由于副作用而危险的不必要的手术或其他处置，其有时甚至是多余的并且导致巨大的公共卫生系统成本。
本发明的一方面涉及一种方法，包括：
确定针对以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，以获得针对对象的对象表达谱，并且
所述方法还包括：
基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；和/或
基于所述对象表达谱将所述对象分类为具有或者不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
在一个实施例中，所述方法还包括：
基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；或者
基于所述对象表达谱将对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
在一个实施例中，所述方法还包括：
基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；并且
基于所述对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
在一个实施例中，所述方法还包括：
基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；或者
基于所述对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
在一个实施例中，所述方法还包括：
基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；并且
基于所述对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
本发明的另一方面涉及一种方法，包括：
基于针对对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；和/或
基于针对对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
在一个实施例中，一种方法，包括：
基于针对对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；或者
基于针对对象的对象表达谱将对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2，本文任选地包括PDE4D5和/或PDE4D7的PDE4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
在一个实施例中，一种方法包括：
基于对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；并且
基于针对对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
在一个实施例中，一种方法，包括：
基于针对对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；或者
基于针对对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
在一个实施例中，一种方法，包括：
基于针对对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；并且
基于针对对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。
在本发明各方面的一些实施例中，所述对象是被诊断患有前列腺癌的患者。
在本发明各方面的一些实施例中，所述对象表达谱是从来自对象的样本获得的。
在本发明各方面的特定实施例中，样本是细胞系。
在本发明各方面的一些实施例中，患者是从包括(a)新诊断患有前列腺癌的患者、(b)已经经受针对前列腺癌的初级处置的患者的组中选择的。
在本发明各方面的一些实施例中，患者先前被诊断患有临床局部前列腺癌。
在本发明各方面的实施例中，所述初级处置是从包括前列腺手术、前列腺移除、放射疗法、化学疗法、有限或扩展淋巴结清除的组中选择的。
在本发明各方面的实施例中，组(a)中的患者进一步选自已经经受以下方法中的至少一种方法的新诊断患有前列腺癌的患者：确定前列腺特异性抗原(PSA)的血液水平、直肠指检(DRE)和经直肠超声分析(TRUS)、以及前列腺活组织检查。
在本发明各方面的一些实施例中，所述预定时段为至少6个月、至少1年、至少2年、至少3年、至少4年、至少5年、至少10年或至少15年。
在本发明各方面的一些实施例中，通过使用一个或多个探针和/或一个或多个探针集检测mRNA表达来确定基因表达水平。
在本发明各方面的一些实施例中，通过基于扩增的方法和/或微阵列分析来确定基因表达水平。
在本发明各方面的一些实施例中，通过RNA测序、PCR、qPCR或多路复用PCR来确定基因表达水平。
在本发明各方面的一些实施例中，所述患者表达谱被转换为前列腺癌进展指数(PCPI)。
在实施例中，所述前列腺癌进展指数是根据以下等式来计算的：
PCPI＝(GEV_av_GOI_up)-(GEV_av_GOI_down)，其中，GEV_av_GOI_up是上调基因的平均基因表达值，并且其中，GEV_av_GOI_down是下调基因的平均基因表达值，其中，所述值是基于每个对象样本的标准化基因表达数据来确定的。PCPI计算能够呈现对预后的良好预测或者如在本文中所描述的在其他临床应用中的良好性能。
在本发明各方面的一些实施例中，将一组签名基因的表达水平标准化为参考基因的表达，优选地，其中，所述参考基因是持家基因，并且更优选地，其中，所述持家基因是TBP、HPRT1、ACTB、RPLP0、PUM1、POLR2A或B2M。
在本文中也描述了以下方法，其中，当选自包括COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5、DYRK2的组中的任意一个或多个基因的表达与对照样本中的对应基因表达水平相比被上调时，并且其中，当选自包括AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2的组中的任意一个或多个基因的表达与对照样本中的对应基因表达水平相比被下调时，将所述对象分类为前列腺癌阳性；或者，当选自包括COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5、DYRK2的组中的任意一个或多个基因的表达与对照样本中的对应基因表达水平相比被下调时，并且其中，当选自包括AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2和任选的PDE4D5和/或PDE4D7的组中的任意一个或多个基因与对照样本中对应基因表达相比被上调时，所述对象被分类为前列腺癌阴性。所选择的基因能够呈现在分类中的良好性能。
在本发明各方面的一些实施例中，如果所述前列腺癌进展指数低于选定的阈值，则所述对象被分类为具有良好预后，或者如果所述前列腺癌进展指数高于选定的阈值，则所述对象被分类为具有不良预后；并且/或者，如果所述前列腺癌进展指数高于选定的阈值，则所述对象被分类为具有易遭受疾病进展影响的前列腺癌的倾向，或者如果所述前列腺癌进展指数低于选定的阈值，则所述对象被分类为不具有易遭受疾病进展影响的前列腺癌的倾向。
在本发明各方面的一些实施例中，所述方法还包括：根据所确定的预后或所确定的倾向，针对侵袭性疾病与非侵袭性疾病的风险来对对象进行分级；和/或根据所确定的预后或所确定的倾向，向有需要的对象提供合适的癌症处置。
在本发明各方面的一些实施例中，所述癌症处置选自：前列腺手术、前列腺移除、放射疗法、化学疗法、近距离放射疗法、有限或扩展的淋巴结移除、或者其组合，优选是激素疗法和放射疗法的组合。
在本发明各方面的一些实施例中，不良预后或易遭受疾病进展影响的前列腺癌的倾向指示要利用选自包括以下项的组的处置中的任何一种或多种来处置对象的适用性：前列腺手术、前列腺移除、化学疗法、放射疗法、近距离放射疗法、有限或扩展的淋巴结清除。
在本发明各方面的一些实施例中，针对侵袭性前列腺癌的倾向指示对选自包括以下项的组中的处置的适用性：重新活检、前列腺手术、前列腺移除、化学疗法、放射疗法、激素疗法、有限或扩展的淋巴结清除、或其其组合，优选是激素疗法与放射疗法的组合。
在本发明各方面的一些实施例中，所述方法还包括向用户接口设备、计算机可读存储介质、监视器或作为网络一部分的计算机显示或输出步骤之一的结果。
另一方面涉及一种产品的用途，包括：
用于确定针对以下签名基因的基因表达水平的引物和/或探针：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体；
任选地还包括用于确定除了上文所提到的基因之外的、在图1或图2中所列出的一组基因的表达水平的引物和/或探针；和/或
任选地还包括用于确定参考基因的基因表达水平的引物和/或探针，优选地，其中，所述参考基因是持家基因，并且更优选地，其中，所述持家基因是TBP、HPRT1、ACTB、RPLP0、PUM1、POLR2A或B2M；
用于建立针对被诊断有前列腺癌的患者的预后，用于将被诊断有前列腺癌的患者进行分级，用于确定在具有前列腺癌的患者中的侵袭性前列腺癌或惰性前列腺癌的倾向。
在一些实施例中，所述产品是试剂盒，例如包括PCR试剂盒、RNA测序试剂盒或微阵列试剂盒，优选是DNA微阵列试剂盒。在另一实施例中，所述产品是微阵列。所述产品能够提供用于确定如在本文中所描述的水平的有效方式，并且因此，能够呈现如在本文中所描述在临床应用中的良好性能。
在一些实施例中，所述产品是用于执行本发明方法的产品，或者所述产品是以下产品：用于诊断前列腺癌，用于建立诊断患有前列腺癌的患者的预后，用于将诊断患有前列腺癌的患者进行分级，用于确定在具有前列腺癌的患者中侵袭性或惰性前列腺癌的倾向。
在一些实施例中，所述产品是包括一组核酸分子的复合物，每个核酸分子包括至少一个多核苷酸探针序列，用于分析由图1或图2中的任意一个所包括的基因或者如在上文所描述的基因的基因表达。
在一些实施例中，所述产物是核酸阵列，其包括，针对一组基因中的每个基因，包括图1或2中所列出的基因的一组基因，或者上文所描述的基因，一个或多个多核苷酸探针互补物和能杂交到基因中的编码序列，用于确定如在上文所定义的前列腺表达谱和/或PCPI。
在一些实施例中，所述产品是试剂盒，根据在本文中所描述的方法中的任一种方法，其用于建立针对诊断患有前列腺癌的患者的预后，用于对诊断患有前列腺癌的患者进行分级，用于确定具有前列腺癌的患者中的侵袭性前列腺癌或惰性前列腺癌的倾向性，所述产品包括：a)如在本文中所定义的阵列，b)试剂盒对照；以及c)任选的使用指令。
在一些实施例中，所述产品是用于对从生物学样品获得的核酸进行表达分析的核酸阵列，其中，所述阵列包括基底，所述基底包括探针，所述探针适合于通过在图1或图2中所提及的基因或者如在上文所描述的基因而特异性结合核酸或者其片段。
在一些实施例中，所述产品是用于PCR的制品，包括用于特定地扩增和检测由图1或图2所述的基因或者如在上文所描述的基因编码的核酸或者其片段的成分。
本发明的另一方面涉及选自前列腺手术、前列腺移除、放射疗法、激素疗法、化学疗法、有限或扩展的淋巴结清除或者其组合的疗法，用于处置被识别为适合的患者，其中，所述患者被诊断患有本发明的方法所定义的针对侵袭性前列腺癌的倾向。
本发明的另一方面涉及一种计算机程序产品，其包括被存储在计算机可读介质上或者能从通信网络下载的计算机可读代码，所述计算机可读代码当在计算机上运行时实施如在本文中所描述的方法中的任意一种方法的一个或多个步骤或者所有步骤。
本发明的另一方面涉及在其上存储有可执行程序的非瞬态计算机可读存储介质，其中，所述程序指示微处理器执行本发明的方法中的任何方法的一个或多个步骤。
本发明的又一方面涉及一种设备，其用于由图1或图2中所提及的基因或者上文所描述的基因编码的核酸(或其片段)的基因表达分析，其中，所述设备优选包括：
a)数据库，其包括包含与临床结果相关联的参考基因表达值的记录，每个参考谱包括在图1或图2中所列出的一组基因或上述基因的表达水平，和/或
b)用户接口，其能够接收和/或输入对一组基因的基因表达值的选择，所述组包括在图1或图2中所列出的基因或者如在上文中所描述的基因，用于与数据库中的基因参考表达谱进行比较；
c)输出部，其根据该组基因的表达水平来显示临床预后预测。
本发明的又一方面涉及用于执行本发明的方法的设备。
本发明的另一方面涉及一种系统，其包括上文所描述的产品以及本发明的计算机程序产品或非瞬态计算机可读存储介质或者本发明的用于核酸的基因表达分析的设备或者执行本发明的方法的设备。
附图说明
图1示出了包括从公开可用的研究数据导出的经分析的基因候选的表格。
图2示出了包括被分析以构建PCPI的57个基因候选的表格。
图3示出了关于PCPI_18或PCPI_17预测在针对数据集GSE21032、GSE41408、GSE25136、GSE16560、GSE10645的初级处置(前列腺手术)之后的10-15年内的远处转移的发展的初级终点的性能的概述。
图4示出了PCPI_18预测在针对数据集GSE46691的初级处置之后的10-15年内的远处转移发展的初级终点的性能。
图5示出了，与标准临床参数(如处置前PSA、活检或病理学Gleason分数、或者临床/病理疾病阶段)相比较，PCPI_18或PCPI_17在多变量COX回归分析中预测针对数据集GSE21032、GSE41408、GSE16560、GSE10645的初级处置(一般是前列腺手术)之后的10-15年内的远处转移发展的初级终点的性能。针对每个个体数据集示出了针对PCPI和个体临床参数的卡方以及风险比。
图6示出了PCPI_18预测在针对数据集GSE21032、GSE41408、GSE25136的初级处置(一般为前列腺手术)之后的10-15年内的生化疾病复发(BCR)发展的初级终点的性能的概述。
图7示出了，与标准临床参数(如处置前PSA、活检或病理学Gleason分数、或临床/病理疾病阶段)相比较，PCPI_18在多变量COX回归中预测针对数据集GSE21032、GSE41408、GSE25136的初级处置(一般为前列腺手术)之后的10-15年内的生化疾病复发(BCR)发展的初级终点的性能。
图8示出了针对PCPI_18支持对例如针对主动监视(AS)或主动处置(例如，前列腺移除术、放射疗法和激素治疗)的患者分级做出临床决策的ROC曲线截断分析。
图9列出了在本申请中所提到的感兴趣基因，其具有转录物ID、蛋白质ID以及针对感兴趣基因特异性的引物和探针序列。
图10列出了在本申请中所提到的参考基因，其具有转录物ID、蛋白质ID以及针对参考基因特异性的引物和探针序列。
图11示出了针对根据PCPI_19以及能够从美国国家综合癌症网络(NCCN)网页指南(https://www.nccn.org/professionals/physician_gls/f_guidelines.asp)推断的NCCN临床风险特性而分组的422位患者在5至10年内的不同复发风险的分析。
图12示出了根据GPSu分数以及能够从美国国家综合癌症网络(NCCN)网页指南(https://www.nccn.org/professionals/physician_gls/f_guidelines.asp)推断出的NCCN临床风险特征而分组的407位患者在5至10年内的不同复发风险的分析。
图13示出了根据CCP分数以及能够从美国国家综合癌症网络(NCCN)网页指南(https://www.nccn.org/professionals/physician_gls/f_guidelines.asp)推断出的NCCN临床风险特性而分组的407位患者在5至10年内的不同复发风险的分析。
具体实施方式
尽管将针对具体实施例来描述本发明，但是该描述不应当被解释为限制性的意义。
在详细描述本发明的示范性实施例之前，给出了对于理解本发明重要的定义。
如在本说明书和随附的权利要求中所使用的，除非上下文另外明确指出，否则单数形式的“一”和“一个”也包括相应的复数形式。
在本发明的上下文中，术语“大约”和“近似”表示本领域技术人员将理解仍然确保所讨论特征的技术效果的准确性的区间。该术语通常指示与所指示的数值的±20％、优选±15％、更优选±10％、并且甚至更优选±5％的偏差。
应当理解，术语“包括”不是限制性的。为了本发明的目的，术语“由...组成”被认为是术语“包括”的优选实施例。如果在下文中将组定义为包括至少特定数量的实施例，则这意味着也涵盖优选仅由这些实施例组成的组。
此外，在说明书和权利要求中的术语“第一”、“第二”、“第三”或者“(a)”、“(b)”、“(c)”、“(d)”等被用于区分相似的元件，而不一定用于描述顺序或时间次序。应当理解，这样使用的术语在适当情况下是能互换的，并且在本文中所描述的本发明的实施例能够以不同于在本文中所描述或例示的其他顺序来操作。
在术语“第一”、“第二”、“第三”或者“(a)”、“(b)”、“(c)”、“(d)”等涉及方法或使用的步骤的情况下，则在这些步骤之间没有时间或时间间隔一致性，即，这些步骤可以同时被执行，或者在这样的步骤之间可以存在数秒、数分钟、数小时、数天、数周、数月或甚至数年的时间间隔，除非如在本申请上文或下文所阐述地在本申请中另外指出。应当理解，本发明不限于在本文中所描述的具体方法、协议、蛋白质、细菌、载体、试剂等，因为这些可以变化。也应当理解，在本文中所使用的术语仅仅是出于描述具体实施例的目的，而并非意图限制本发明的范围，该范围仅由随附的权利要求来限定。除非另外定义，否则在本文在所使用的所有技术和科学术语具有与本领域普通技术人员通常理解的相同的含义。
在本发明的上下文中，术语“(一个或多个)签名基因”、(一个或多个)标记基因、或者“感兴趣基因(GOI)”能够互换使用，并且指定在本发明的方法中确定其表达水平的生物标记。在本发明的优选实施例中，在本公开的图2中描绘了这些基因，并且在下文以及权利要求中被明确地提及。因此，本发明涉及(一个或多个)标记基因，当将在初级处置之后或者在初始前列腺癌诊断之后获得的前列腺癌组织中的表达与在初始前列腺癌诊断之前和/或在初始前列腺癌特异性处置之前获得的在前列腺癌组织中的表达进行比较时，所述标记基因的表达或者被上调或者被下调。在初级处置之后或者在初始前列腺癌诊断之后获得的组织中的标记基因表达可以与患者结果参数(例如，生化复发、转移的发展、骨癌和/或死亡)相关。
当在本发明的方法的上下文中确定表达值时，获得个体化的“基因表达谱”，其反映样本或对象中的GOI的基因表达值。在后一种情况下，所述表达值也被称为“对象表达谱”。应当注意，样本表达谱和/或对象表达谱可以随时间而变化。例如，在被诊断有前列腺癌的患者的治疗性处置之前或之后的基因表达谱可能是不同的。类似地，在包含前列腺癌细胞的样本中发现的基因表达谱将不同于在不包含前列腺癌细胞的样本中发现的那些基因表达谱。
因此，在本文中所使用的术语“(一个或多个)标记基因”或者“(一个或多个)感兴趣基因”涉及在本文中上文所定义的(一个或多个)基因、(一个或多个)基因单元、或(一个或多个)序列(核苷酸序列)的集合，当与对照水平进行比较时，优选当与在不同时间点处(例如，在初始诊断处，紧接在初级处置之后，或者稍后，即，在初始诊断或初级处置之后的数月或数年)获得的前列腺组织中的表达进行比较时，其表达水平在前列腺癌细胞或组织中或者在包括这样的细胞或组织或者其部分或片段的任何类型的样本中或者被上调或者被下调。该术语指代所述基因单元或序列的任何表达产物，特别指代mRNA转录物。当第一次检查标记基因或感兴趣基因时，即，当第一次怀疑患者患有前列腺癌时，也设想到了使用源自正常组织或良性前列腺癌组织的额外对照材料。
如在本文中所使用的术语“表达水平”指代能从限定数量的细胞或限定的组织部分导出的(一个或多个)标记基因转录物的量，优选指代在标准核酸(例如，RNA)提取流程中能获得的转录物的量。合适的提取方法对于本领域技术人员是已知的。
如在本文中所使用的，术语“对照水平”(或“对照状态”)涉及与测试样本同时地和/或在相似或相当的条件下通过使用从已知其状况或疾病状态(例如，非癌症、正常或良性前列腺癌、晚期前列腺癌等)的一位或多位患者先前收集和存储的(一个或多个)样本来确定表达水平。为了确定侵袭性癌症与惰性癌症的倾向性，优选在所获得的癌症组织中确定对照水平以确立初始诊断，然后将其与在稍后阶段(例如，在初级处置之后)确定的GOI的表达进行比较。术语“疾病状态”或“癌性疾病状态”涉及在非癌细胞状态与(包括)末期癌细胞状态之间的细胞或分子状态的任何状态或类型。优选地，该术语包括有机体内在(和排除)非癌细胞状态与(包括)末期癌细胞状态之间的不同癌变增殖/发展阶段或肿瘤发展水平。这样的发展阶段可以包括由UICC定义的恶性肿瘤的TNM(肿瘤、结节、转移)分类系统的所有阶段，例如，阶段0和I到IV。该术语也包括在TNM阶段0之前的阶段，例如，在其中本领域技术人员已知的癌症生物标记显示修改的表达或表达模式的发展阶段。
如上文所提到的表达水平优选可以是在本文中所定义的(一个或多个)标记基因或GOI的表达水平。
术语“癌性”在本发明的上下文中涉及如上文所定义的癌性疾病状态。
术语“非癌性”在本发明的上下文中涉及其中不能够检测到良性或恶性增殖的状况。用于所述检测的合适的手段在本领域中是已知的。
可以通过基于通过在来自已知其疾病状态的对象的样本中分析先前确定的本发明的(一个或多个)标记基因的(一个或多个)表达水平而获得的结果的统计学方法，来确定表达对照水平。此外，能够从来自先前测试的患者、组织或细胞的表达模式或表达水平的数据库中导出所述对照水平。能够根据来源于已经被诊断患有前列腺癌(例如，激素独立或激素抗性前列腺癌)的患者的参考样本来确定对照水平。此外，可以将待测试的生物学样本中的本发明的标记基因的表达水平与多个对照水平进行比较，所述对照水平是根据多个参考样本来确定的。设想到了，使用根据从类似于来源于对象的生物学样本的组织类型导出的参考样本而确定的对照水平。特别优选的是，使用源自如在本文中上文所定义的疾病状态为癌性的患者的(一个或多个)样本。
在使用在本文中所描述的标记基因对前列腺癌的一般诊断方法中，也能够确定呈现不能够检测到良性或恶性增殖的健康状况的对象组织中的对照水平。也设想到了，使用来源于患有在本文中上文所定义的良性前列腺癌的一个或多个患者的(一个或多个)样本，即，所述患者呈现能够检测到良性增殖的健康状况。
在本文中所使用的术语“良性前列腺癌”指代缺乏癌症的全部三种恶性属性(即，不以无限侵袭性方式生长、不侵入周围组织、并且不转移)的前列腺癌。通常，良性前列腺癌意味着缺乏癌症的侵袭属性的温和并且非进行性前列腺癌或肿胀疾病。此外，良性前列腺癌通常被封装，并且因此抑制其以恶性方式行为的能力。良性肿瘤或健康状况能够通过本领域技术人员已知的任何合适的、独立分子学、组织学或生理学方法来确定。
备选地，参考样本可以包括源自细胞系(例如，永生化的癌细胞系)的材料。优选地，源自前列腺癌细胞系的材料根据本发明可以被包括在参考样本中。优选的癌细胞系的范例包括细胞系PC346P、PC346B、LNCaP、VCaP、DuCaP、PC346C、PC3、DU145、PC346CDD、PC346Flu1、PC346Flu2。
在另一优选备选方案中，参考样本可以来源于在临床环境中获得的对象/患者组织或组织系列或组织集合。样本例如可以从正在进行手术的男性患者获得。样本可以来源于任何合适的组织类型，例如，来自前列腺组织或淋巴结。患者组织集合的优选范例来源于外科手术(例如，前列腺移除术)。
此外，设想到了使用具有已知疾病状态的群体中(例如，具有良性前列腺癌的群体或健康群体)的本发明的(一个或多个)标记基因的表达水平的标准值。所述标准值能够通过本领域已知的任何方法来获得。例如，可以使用平均值±2SD(标准偏差)或平均值±3SD的范围作为标准值。
此外，也能够通过使用先前从已知其疾病状态是癌性的一位或多位患者(即，已经被独立地诊断患有前列腺癌的患者，特别是患有侵袭性前列腺癌的患者)收集并存储的(一个或多个)样本，在与测试样本同时和/或相似或相当的条件下确定对照水平。
在本发明的上下文中，从已知不是癌性的生物学样本(例如，健康组织样本或良性前列腺癌样本)所确定的对照水平被称为“正常对照水平”。
如果从癌性生物学样本(特别是来自被独立诊断为前列腺癌的患者的样本)确定对照水平，则能将其指定为“癌性对照水平”。
术语“前列腺癌”涉及男性生殖系统中的前列腺的癌症，其发生于前列腺细胞突变且开始繁殖失控时。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例中，术语“前列腺癌”涉及示出PSA水平高于4.0的癌症。在另一实施例中，该术语涉及示出PSA水平高于2.0的癌症。术语“PSA水平”指代以ng/ml计的血液中的PSA的浓度。
术语“前列腺癌”也包括对男性性激素刺激敏感的前列腺癌或前列腺癌细胞系，只要涉及其生长或增殖。术语“敏感性”涉及前列腺癌或前列腺癌细胞系在男性性激素存在下显示生化或细胞反应模式，但确实需要男性性激素用于生长和/或增殖的情况。激素敏感性前列腺因此被理解为恶性前列腺癌，其从如PIN(前列腺上皮内瘤)的前恶变形式发展并且其特征在于其生长仍然依赖于男性性激素男性激素的存在。相反，一旦这样的肿瘤被激素损耗治疗所处置，那些癌症通常发展成激素抵抗形式，其生长独立于男性激素的存在。
术语“激素抗性前列腺癌”意指前列腺癌或前列腺癌细胞系的生长和增殖对男性性激素刺激具有抗性。该术语也涉及晚期前列腺癌发展阶段，其不再适于施予如在本文中上文所定义的抗激素(优选抗男性激素)给药。
在本文中所使用的术语“男性性激素”指代男性激素，优选是睾酮、雄烯二酮、二氢睾酮、脱氢表雄酮、雄烯二醇或雄酮。
在另一方面中，本发明涉及使用(一个或多个)标记基因或GOI作为诊断、检测、监测或预测恶性、激素敏感的前列腺癌或者朝向前列腺癌的进展的标记。
在本发明的上下文中，术语“上调的”或“上调的表达水平”或“表达水平的增加”(可以同义地使用)因此表示在待分析的情况(例如，能源自患者的样本的情况)与参考点之间的表达水平的提高，所述参考点可以是源自本领域技术人员已知的任何合适的前列腺癌或癌症阶段的正常对照水平或癌性对照水平。当例如在待分析的样本中的基因表达与对照水平相比相差(即，提高)例如5％、6％、7％、8％、9％、10％、15％、20％、25％、30％、40％、50％、或多于50％时，或者与对照水平相比相差至少0.1倍、至少0.2倍、至少1倍、至少2倍、至少5倍或至少10倍或更多倍时，将表达水平认为是“上调的”。所述对照水平可以是如在本文中上文所定义的正常对照水平或癌性对照水平。如果要进行与癌性对照水平的比较，则优选与正常对照水平的额外比较。这样的额外比较允许确定修改的趋势，例如，可以观测到表达水平增加的幅度和/或可以得出对应的结论。优选的是与良性前列腺癌或者与健康组织或者源于健康个体的样本进行比较。
在本发明的上下文中，术语“下调的”或“下调的表达水平”或“表达水平的下降”(其可以同义地使用)因此表示在待分析的情况(例如，源自患者样本的情况)与参考点之间的表达水平的下降，所述参考点可以是能源自本领域技术人员已知的任何合适的前列腺癌或癌症阶段的正常对照水平或优选癌性对照水平。当例如在待分析的样本中的基因表达与对照水平相比相差(即，下降)例如5％、6％、7％、8％、9％、10％、15％、20％、25％、30％、40％、50％、或多于50％时，或者与对照水平相比相差至少0.1倍、至少0.2倍、至少1倍、至少2倍、至少5倍或至少10倍或更多倍时，将表达水平认为是“下调的”。所述对照水平可以是如在本文中上文所定义的正常对照水平或癌性对照水平。如果要执行与癌性对照水平的比较，则能够与正常对照水平进行额外比较。这样的额外比较允许确定修改的趋势，例如，可以观测到表达水平减少的幅度和/或可以得出对应的结论。优选的是与良性前列腺癌或者与健康组织或源于健康个体的样本进行比较。
在本文中提到的(一个或多个)感兴趣基因的表达值能够被用于使用以下公式来建立“前列腺癌进展指数(PCPI)”：
PCPI＝(GEV_av_GOI_up)-(GEV_av_GOI_down)，
其中，GOI指代所选择的感兴趣基因，例如，(生物)标记基因，与在初级处置之后有进展和没有进展的患者组之间上调的组相比，其被分组到在初级处置之后有进展和没有进展的患者组之间被下调的那些组中。计算针对下调基因的平均基因表达值(GEV_av_GOI_down)以及针对上调基因的平均基因表达值(GEV_av_GOI_up)。
根据以下等式来计算对象样本特异性前列腺癌进展指数的具体实施例：
PCPI＝(GEV_av_GOI_up)-(GEV_av_GOI_down)，
其中GEV_av_GOI_up是上调基因的平均基因表达值，并且其中，GEV_av_GOI_down是下调基因的平均基因表达值，其中，所述值是基于每个患者样本的归一化基因表达数据来确定的，并且其中，“上调的基因”指代在初级处置之后在有进展或没有进展的患者组之间被上调的基因，而“下调的基因”指代在初级处置之后在有进展或没有进展的患者组之间被下调的基因。
例如在图2中提供了对基因的选择，所述基因潜在地涉及前列腺癌中的患者分级，或者涉及确定在初级处置之后发展侵袭性前列腺癌的倾向。图2提供了被发现显著(p<0.05)不同地表达并且在相同方向(即，上调或下调)上的患者组之间调节的57个选定基因的概述。根据本发明的一个方面，这57个基因可以被用作GOI。也能够使用从上述57个基因中选择的基因，例如，至少17个基因、至少18个基因、至少19个基因、至少20个基因、至少21个基因、至少22个基因、至少23个基因、至少24个基因、至少25个基因、至少26个基因、至少27个基因、至少28个基因、至少29个基因、至少30个基因、至少31个基因、至少32个基因、至少33个基因、至少34个基因、至少35个基因、至少36个基因、至少37个基因、至少38个基因、至少39个基因、至少40个基因、至少41个基因、至少42个基因、至少43个基因、至少44个基因、至少45个基因、至少46个基因、至少47个基因、至少48个基因、至少49个基因、至少50个基因、或者更多个基因。
在另一方面中，提供了包括个体基因的组合的基因表达预后签名，其中，这些GOI的表达水平能够使用例如以定量方式从人类前列腺癌组织样本中提取的RNA来进行测量。这些特征组合到单个数据模型(即，PCPI)中提供了预测前列腺癌的进展的显著改善的分类能力。
在一个优选实施例中，PCPI签名包括以下19个基因：PDE4D5、PDE4D7、AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2。
术语“磷酸二酯酶4D5”或“PDE4D5”涉及人类磷酸二酯酶PDE4D的剪接变体5，即，人类磷酸二酯酶PDE4D5基因，优选涉及在NCBI参考序列：NM_001197218.1中定义的序列，更优选涉及如在SEQ ID NO：1中阐述的核苷酸序列，其对应于上文所指示的PDE4D5转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：2中阐述的对应氨基酸序列，其对应于在对PDE4D5多肽进行编码的NCBI蛋白质加入参考序列NP_001184147.1中定义的蛋白质序列。术语“磷酸二酯酶4D5”或“PDE4D5”也涉及能够通过引物对PDE1D5_正向(SEQ ID NO：3)和PDE1D5_逆向(SEQ ID NO：4)生成的扩增子，并且能够通过探针SEQ ID NO：5来检测。
术语“磷酸二酯酶4D7”或“PDE4D7”涉及人类磷酸二酯酶PDE4D的剪接变体7，即，人类磷酸二酯酶PDE4D7基因，优选涉及在NCBI参考序列：NM_001165899.1中定义的序列，更优选涉及如在SEQ ID NO：6中阐述的核苷酸序列，其对应于上文所指示的PDE4D7转录物的NCBI参考序列的序列，并且也涉及与如在SEQ ID NO：7中阐述的对应氨基酸序列，其对应于在对PDE4D7多肽进行编码的NCBI蛋白质加入参考序列NP_001159371.1中定义的蛋白质序列。术语“磷酸二酯酶4D7”或“PDE4D7”也涉及能够通过引物对PDE1D7_正向(SEQ ID NO：8)和PDE1D7_反向(SEQ ID NO：9)生成的扩增子，并且能够通过探针SEQ ID NO：10来检测。
术语“AZGP1”涉及α-2-糖蛋白1-锌-结合基因，优选涉及如在NCBI参考序列：NM_001185.3中定义的序列，更优选涉及如在SEQ ID NO：11中阐述的核苷酸序列，其对应于上文所指示的AZGP1转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：12中阐述的对应氨基酸序列，其对应于对AZGP1多肽进行编码的NCBI蛋白质加入参考序列NP_001176.1。术语“AZGP1”也涉及能够通过引物对AZGP1_正向(SEQ ID NO：13)和AZGP1_逆向(SEQ ID NO：14)生成的扩增子，并且其能够通过探针SEQ ID NO：15来检测。
术语“FBLN1”涉及Fibulin1基因，优选涉及如在NCBI参考序列：NM_001996.3、NM_006485.3、NM_006486.2和NM_006487.2中定义的序列中的一个或多个，更优选分别涉及在SEQ ID NO：16、17、18和19中阐述的核苷酸序列，其对应于上文所指示的Fibulin1转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：20、21、22和23中阐述的对应氨基酸序列，其分别对应于在对Fibulin1多肽进行编码的NCBI蛋白质加入参考序列NP_001987.2、NP_006476.2、NP_006477.2和NP_006478.2中定义的蛋白质序列。术语“FBLN1”也涉及能够通过引物对FBLN1_正向(SEQ ID NO：24)和FBLN1_逆向(SEQ ID NO：250)生成的扩增子，并且能够通过探针SEQ ID NO：26来检测。
术语“ILK”涉及整合素链接激酶基因，优选涉及如在NCBI参考序列：NM_001014794.2、NM_001014795.2、NM_001278441.1、NM_001278442.1和NM_004517.3中定义的序列中的一个或多个，更优选分别涉及如在SEQ ID NO：27、28、29、30和31中阐述的核苷酸序列，其对应于上文所指示的整合素链接激酶转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：32、33、34、35和36中阐述的对应氨基酸序列，其分别对应于在对整合素链接激酶多肽进行编码的NCBI蛋白质加入参考序列NP_001014794.1、NP_001014795.1、NP_001265370.1、NP_001265371.1和NP_004508.1中定义的蛋白质序列。术语“ILK”也涉及能够通过引物对ILK_正向(SEQ ID NO：37)和ILK_逆向(SEQ ID NO：38)生成的(一个或多个)扩增子，并且能够通过探针SEQ ID NO：39来检测。
术语“KRT15”涉及角蛋白15基因，优选涉及如在NCBI参考序列：NM_002275.3中定义的序列，更优选涉及如在SEQ ID NO：40中阐述的核苷酸序列，其对应于上文所指示的KRT15转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：41中阐述的对应氨基酸序列，其对应于在对KRT15多肽进行编码的NCBI蛋白质加入参考序列NP_002266.2中定义的蛋白质序列。术语“KRT15”也涉及能够通过引物对KRT15_正向(SEQ ID NO：42)和KRT15_逆向(SEQ ID NO：43)生成的扩增子，并且能够通过探针SEQ ID NO：44来检测。
术语“MEIS2”涉及Meis同源异形体2，优选涉及如在NCBI参考序列：NM_001220482.1、NM_002399.3、NM_170674.4、NM_170675.4、NM_170676.4、NM_170677.4、NM_172315.2和NM_020149.2中定义的序列中的一个或多个，更优选分别涉及如在SEQ ID NO：45、46、47、48、49、50和/或51中阐述的核苷酸序列，其对应于上文所指示的MEIS2转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：53、54、55、56、57、58、59和/或60中阐述的对应氨基酸序列，其分别对应于在对MEIS2多肽进行编码的NCBI蛋白质加入参考序列NP_001207411.1、NP_002390.1、NP_733774.1、NP_733775.1、NP_733776.1、NP_733777.1、NP_758526.1和NP_758527.1中定义的蛋白质序列。术语“MEIS2”也涉及能够通过引物对MEIS2_正向(SEQ ID NO：61)和MEIS2_逆向(SEQ ID NO：62)生成的(一个或多个)扩增子，并且能够通过探针SEQ ID NO：63来检测。
术语“MYBPC1”涉及肌球蛋白结合蛋白C，慢型；优选涉及如在NCBI参考序列NM_001254718.1、NM_001254719.1、NM_001254720.1、NM_001254721.1、NM_001254722.1、NM_001254723.1、NM_002465.3、NM_206819.2、NM_206820.2和NM_206821.2中定义的序列中的一个或多个，更优选分别涉及在SEQ ID NO：64、65、66、67、68、69、70、71、72和/或73中阐述的核苷酸序列，其对应于上文所指示的MYBPC1转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：74、75、76、77、78、79、80、81、82和/或83中阐述的对应氨基酸序列，其分别对应于在对MYBPC1多肽进行编码的NCBI蛋白质加入参考序列NP_001241647.1、NP_001241648.1、NP_001241649.1、NP_001241650.1、NP_001241651.1、NP_001241652.1、NP_002456.2、NP_996555.1、NP_996556.1和NP_996557.1中定义的蛋白质序列。术语“MYBPC1”也涉及能够通过引物对MYBPC1_正向(SEQ ID NO：84)和MYBPC1_逆向(SEQ ID NO：85)生成的(一个或多个)扩增子，并且能够通过探针SEQ ID NO：86来检测。
术语“PAGE4”涉及P抗原家族、成员4基因，优选涉及如在NCBI参考序列：NM_007003.3中定义的序列，更优选涉及如在SEQ ID NO：87中阐述的核苷酸序列，其对应于上文所指示的PAGE4转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：88中阐述的对应氨基酸序列，其对应于在对PAGE4多肽进行编码的NCBI蛋白质加入参考序列NP_008934.1中定义的蛋白质序列。术语“PAGE4”也涉及能够由引物对PAGE4_正向(SEQ ID NO：89)和PAGE4_逆向(SEQ ID NO：90)生成的扩增子，并且能够通过探针SEQ ID NO：91来检测。
术语“SRD5A2”涉及类固醇5-α还原酶2基因，优选涉及如在NCBI参考序列：NM_000348.3中定义的序列，更优选涉及如在SEQ ID NO：92中阐述的核苷酸序列，其对应于上文所指示的SRD5A2转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：93中阐述的对应氨基酸序列，其对应于在对SRD5A2多肽进行编码的NCBI蛋白质加入参考序列NP_000339.2中定义的蛋白质序列。术语“SRD5A2”也涉及能够通过引物对SRD5A2_正向(SEQ IDNO：94)和SRD5A2_逆向(SEQ ID NO：95)生成的扩增子，并且能够通过探针SEQ ID NO：96来检测。
术语“COL1A1”涉及胶原，I型，α1基因，优选涉及如在NCBI参考序列：NM_000088.3中定义的序列，更优选涉及如在SEQ ID NO：97中阐述的核苷酸序列，其对应于上文所指示的COL1A1转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：98中阐述的对应氨基酸序列，其对应于在对COL1A1多肽进行编码的NCBI蛋白质加入参考序列NP_000079.2中定义的蛋白质序列。术语“COL1A1”也涉及能够通过引物对COL1A1_正向(SEQ ID NO：99)和COL1A1_逆向(SEQ ID NO：100)生成的扩增子，并且能够通过探针SEQ ID NO：101来检测。
术语“COL3A1”涉及胶原，III型，α1基因，优选涉及如在NCBI参考序列：NM_000090.3中定义的序列，更优选涉及如在SEQ ID NO：102中阐述的核苷酸序列，其对应于上文所指示的COL3A1转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：103中阐述的对应氨基酸序列，其对应于在对COL3A1多肽进行编码的NCBI蛋白质加入参考序列NP_000081.1中定义的蛋白质序列。术语“COL3A1”也涉及能够通过引物对COL3A1_正向(SEQ IDNO：104)和COL3A1_逆向(SEQ ID NO：105)生成的扩增子，并且能够通过探针SEQ ID NO：106来检测。
术语“COL5A2”涉及胶原，V型，α2基因，优选涉及如在NCBI参考序列：NM_000393.3中定义的序列，更优选涉及如在SEQ ID NO：107中阐述的核苷酸序列，其对应于上文所指示的COL5A2转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：108中阐述的对应氨基酸序列，其对应于在对SRD5A2多肽进行编码的NCBI蛋白质加入序列NP_000384.2中定义的蛋白质序列。术语“COL5A2”也涉及能够通过引物对COL5A2_正向(SEQ ID NO：109)和COL5A2_逆向(SEQ ID NO：110)生成的扩增子，并且能够通过探针SEQ ID NO：111来检测。
术语“INHBA”涉及抑制素，βA基因，优选涉及如在NCBI参考序列NM_002192.2中定义的序列，更优选涉及如在SEQ ID NO：112中阐述的核苷酸序列，其对应于上文所指示的INHBA转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：113中阐述的对应氨基酸序列，其对应于在对INHBA多肽进行编码的NCBI蛋白质加入参考序列NP_002183.1中定义的蛋白质序列。术语“INHBA”也涉及能够通过引物对INHBA_正向(SEQ ID NO：114)和INHBA_逆向(SEQ ID NO：115)生成的扩增器，并且能够通过探针SEQ ID NO：116来检测。
术语“THBS2”涉及血小板反应蛋白2基因，优选涉及如在NCBI参考序列：NM_003247.3中定义的序列，更优选涉及如在SEQ ID NO：117中阐述的核苷酸序列，其对应于上文所指示的THBS2转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：118中阐述的对应氨基酸序列，其对应于在对THBS2多肽进行编码的NCBI蛋白质加入参考序列NP_003238.2中定义的蛋白质序列。术语“THBS2”也涉及能够由引物对THBS2_正向(SEQ ID NO：119)和THBS2_逆向(SEQ ID NO：120)生成的扩增子，并且能够通过探针SEQ ID NO：121来检测。
术语“VCAN”涉及多功能蛋白聚糖基因，优选涉及如在NCBI参考序列：NM_001126336.2、NM_001164097.1、NM_001164098.1和NM_004385.4中定义的一个或多个序列，更优选分别涉及如在SEQ ID NO：122、123、124和125中阐述一个或多个核苷酸序列，其对应于上文所指示的VCAN转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：126、127、128和129中阐述的对应氨基酸序列，其分别对应于在对VCAN多肽进行编码的NCBI蛋白质加入参考序列NP_001119808.1、NP_001157569.1、NP_001157570.1和NP_004376.2中定义的蛋白质序列。术语“VCAN”也涉及能够通过引物对VCAN_正向(SEQ ID NO：130)和VCAN_逆向(SEQ ID NO：131)生成的(一个或多个)扩增子，并且能够通过探针SEQ ID NO：132来检测。
术语“BNG”涉及双糖链蛋白多糖基因，优选涉及如在NCBI参考序列：NM_001711.4中定义的序列，更优选涉及如在SEQ ID NO：133中阐述的核苷酸序列，其对应于上文所指示的BNG转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：134中阐述的对应氨基酸序列，其对应于在对BNG多肽进行编码的NCBI蛋白质加入参考序列NP_001702.1中定义的蛋白质序列。术语“BNG”也涉及能够由引物对BNG_正向(SEQ ID NO：135)和BNG_逆向(SEQ IDNO：136)生成的扩增器，并且能够通过探针SEQ ID NO：137来检测。
术语“BIRC5”涉及多功能蛋白聚糖基因，优选涉及如在NCBI参考序列：NM_001012270.1、NM_001012271.1和NM_001168.2中定义的一个或多个序列，更优选分别涉及如在SEQ ID NO：138、139和140中阐述的一个或多个核苷酸序列，其对应于上文所指示的BIRC5转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：141、142和143中阐述的对应氨基酸序列，其分别对应于在对BIRC5多肽进行编码的NCBI蛋白质加入参考序列NP_001012270.1、NP_001012271.1和NP_001159.2中定义的蛋白质序列。术语“BIRC5”也涉及能够通过引物对BIRC5_正向(SEQ ID NO：144)和BIRC5_逆向(SEQ ID NO：145)生成的(一个或多个)扩增子，并且能够通过探针SEQ ID NO：146来检测。
术语“DYRK2”涉及Versican基因，优选涉及如在NCBI参考序列：NM_003583.3和NM_006482.2中定义的一个或多个序列，更优选分别涉及如在SEQ ID NO：147和148中阐述的一个或多个核苷酸序列，其对应于上文所指示的DYRK2转录物的NCBI参考序列的序列，并且也涉及如在SEQ ID NO：149和150中阐述的对应氨基酸序列，其分别对应于在对DYRK2多肽进行编码的NCBI蛋白质加入参考序列NP_003574.1和NP_006473.2中定义的蛋白质序列。术语“DYRK2”也涉及能够通过引物对DYRK2_正向(SEQ ID NO：151)和DYRK2_逆向(SEQ ID NO：152)生成的(一个或多个)扩增子，并且能够通过探针SEQ ID NO：153来检测。
在其他实施例中，PCPI签名能够是包括PDE4D而非PDE4D5和PDE4D7的18-基因列表，或者其可以包括剩余的17个基因。因此，在优选实施例中，PCPI签名能够是包括上文所提到的17个基因并且既不包括PDE4D5也不包括PDE4D7的17基因列表。
在另一实施例中，本发明提供了基因表达预后签名，其包括19个个体基因的组合，所述个体基因能够以定量方式在来自人类前列腺癌组织样本的所提取的RNA上进行测量。将这些特征组合成单数据模型(＝PCPI->前列腺癌进展指数)提供了显著改善的分类能力以预测前列腺癌的进展。在使用这19个基因或者17、18或57的实施例中，在本发明中提及的PCPI被用在诊断样本中的前列腺癌的方法中，预测患者的个体疾病状态以及预期的疾病发展，并且其在适用时提供用于针对个体优选的处置或疗法对患者进行分级和/或识别的方法中的参数。基于PCPI参数，能够确定例如肿瘤发展成侵袭性前列腺癌的倾向或可能性。例如，如果在对肿瘤的分析中获得的PCPI高于定义的截止(或阈值)水平，则所述肿瘤进展为侵袭性形式的概率也更高，并且反之亦然。
根据在本文中所描述的方法而分析的肿瘤样本的分类步骤因此包括：在过去的特定时间点(例如，在初始诊断为前列腺癌之前)获得的样本以及在后续阶段处获得的样本之间的PCPI值的比较。当在所述后续阶段在对肿瘤样本的分析中获得的PCPI高于定义的阈值或截止值时，该参数能够被用作朝向侵袭性前列腺癌进展的指示。
截止值可以基于包括具有或不具有进展的患者组的参考数据集来定义。对于没有或具有进展的患者的分类，可以将截止值设定为例如70％、80％、85％、90％、93％、95％、96％、97％、98％或99％的敏感性。在优选实施例中，所述截止值可以被设定为90％的敏感性。
当然，PCPI也可以被用在建立患者预后的方法中，被用在用于将患者分级到组中以进行适当处置的方法中，借助于该方法，医师得出结论：特异性处置是不适当的，(尚且)不需要治疗，或者鉴于患者的总体身体状况而不再需要治疗。
因此，本发明的实施例涉及识别和使用与前列腺癌临床相关的标记基因(或序列)表达模式(或“谱”或“签名”)。无论是在核酸表达、蛋白质表达还是其他表达格式中体现的标记基因表达谱都可以被用于预测罹患前列腺癌的对象的前列腺癌复发率和/或生存率。具体地，所述标记基因被用于建立在本文中所描述的用于识别/分类具有侵袭性或惰性疾病的患者的前列腺癌进展谱(PCPI)。
在本申请的上下文中，表达“初始诊断”指代在执行根据本发明的方法之一的日期之前的第一次或随后的诊断，并且计算PCPI。例如，针对第一次并且优选在对前列腺癌的诊断之前分析其前列腺组织材料的患者，可以建立初始诊断。
在本申请的上下文中，术语“在初始诊断之后的预定时段”包括大约6个月、1年、2年、3年、4年、5年、6年、7年、8年、9年、10年、15年或20年或更多年。在本申请的上下文中，表达“新近诊断有前列腺癌的患者”指代已经被诊断为具有确认或引起怀疑在从该患者第一次取得的样本中存在前列腺癌细胞的生化值、临床值或PCPI值的个体。
在本申请的上下文中，表达“针对前列腺癌的初级处置”指代用于对前列腺癌的处置的任何已知方法，即，手术、化学疗法、利用生物制剂的处置、放射疗法等。
在本申请的上下文中，表达“利用生物制剂的处置”指代利用单克隆抗体或者其衍生物，或者其肽或片段对前列腺癌的处置，其尤其抑制或阻断或中和涉及生长、增殖、维持的体内和体外生物学分子，或者前列腺癌细胞使用的任何其他代谢路径。针对所建立的靶标的单克隆抗体包括准许用于实体肿瘤的那些，诸如抗人EGFR2单克隆抗体(诸如曲妥珠单抗)，抗EGFR抗体(诸如利妥昔单抗和帕尼单抗)、以及抗血管内皮生长因子(VEGF)单克隆抗体贝伐单抗。
在本申请的上下文中，表达“生化复发”例如指代增加的PSA的复发生物学值，其指示样本中的前列腺癌细胞的存在。然而，也能够使用能够被用于检测存在或引起怀疑这样的存在的其他标记。
在本申请的上下文中，术语“临床复发”指代例如使用Gleason分数测量的临床体征或临床值的存在。
在本申请的上下文中，表达“易遭受疾病进展影响的前列腺癌的倾向”指代能测量的并且显著的参数(例如PCPI)，其提供了调查其样本的患者将发展侵袭性前列腺癌的可能性的指示，即，在对经诊断的前列腺癌的初级处置(例如，通过前列腺移除术、化学疗法和/或放射疗法)之后，前列腺癌细胞再次出现，其具有侵袭性生长的潜力，诸如在淋巴结和骨骼中形成转移。
在本申请的上下文中，表达“用于确定患有前列腺癌的患者的预后的计算机实施的方法”指代以下方法，其中，软件算法计算PCPI并且基于此提供针对被分析的患者的预后，其中，该方法使用在测量在本文中所提及的基因的基因表达水平时获得的原始数据，并且使用上文所描述的方程将其转换成PCPI。
在本申请的上下文中，以下方法，其用于对侵袭性前列腺癌的发展或进展的倾向的诊断、预后、识别，对患有前列腺癌或者在初级处置之后经受前列腺癌复发的患者的识别，可以基于根据本发明的方法中的任意方法获得的结果利用合适的治疗方案来进行处置。因此，例如，如果预后是基于确定针对这种类型的癌症的倾向的结果患者将发展侵袭性前列腺癌，那么医师可以决定是否使用可用疗法中的任意疗法来处置前列腺癌，诸如手术、化学疗法、放射疗法、激素疗法或者其组合等。
根据本发明的方法也借助于PCPI来提供信息，基于PCPI能够决定患者是否应当进行手术、化学疗法、放射疗法，或者是否要执行进一步的活检。因此，PCPI表示建立个体化诊断、预后的重要参数，允许识别具有侵袭性前列腺癌倾向的患者，或者对其进行分级以用于最适合于该患者的疗法。PCPI也能够与其他手段和方法结合使用以建立诊断或预后，并且如在本文中所讨论地对患者进行识别或分级。因此，本发明也涉及如上文所指出的前列腺癌特异性疗法或处置，用于基于PCPI已经被识别为适合这样的疗法的患者的处置，任选地与其他诊断或预后方法相组合，以期为所述患者选择最合适的癌症处置。例如，当与对照样本相比PCPI较高时，对已经识别或诊断的患者或者已经使用本发明的方法建立预后的患者的处置中可以选择完全移除淋巴结。
在涉及在初始临床诊断后通过前列腺移除术处置的患者的本发明的实施例中，本发明包括预测前列腺癌复发、癌症转移、和/或升高的PSA水平的复发的可能性或倾向的方法。
本发明的另外的实施例涉及识别并且然后使用在样本中的提供与前列腺癌有关的预后信息的标记基因(或序列)表达谱的方法。所述表达谱与具有良好或不良癌症复发率、癌症转移和/或生存结果的患者相关(并且因此能够在其之间进行区分)。
在本发明的实施例中，提供了识别与患有前列腺癌患者的癌症复发和/或转移有关的标记基因表达谱的方法。
在本发明的另外的实施例中，提供了以下方法，所述方法用于将在包括来自患者的前列腺癌细胞中的基因表达分析的样本中的标记基因(或序列)表达与所识别的表达谱(PCPI)进行比较，以确定例如在前列腺移除术、化学疗法、放射疗法等之后患者的可能结果。在本发明的这些实施例的另外的方面中，所获得的信息可以有利地被用于预测患者是否将可能从例如处置前列腺癌的手术中获益或者患者利用另一类型的处置是否将更好，或者是否需要除了手术之外的辅助处置。如在本文中所公开的，能够基于患者的前列腺样本的表达谱来选择可能从手术(诸如根治性前列腺移除术)获益的患者，从而在手术后没有癌症复发和/或转移。在另外的实施例中，可能预期不从手术获益的患者是通过如在本文中所公开的患者的前列腺癌细胞的表达谱预测在手术后发展癌转移的患者。通过范例的方式，前列腺癌的复发可以处在相同的位置，而转移经常到达不同的位置或组织，例如淋巴结或骨骼。本发明的另外的实施例涉及一种方法，所述方法从具有前列腺癌细胞的患者群体中或者在前列腺移除术之后，将患者识别为属于相对于另一亚群具有更好的癌症复发和/或生存结果的患者的亚群(诸如较低的复发或转移风险)，或者属于相对于另一亚群具有较差的癌症复发和/或生存结果(诸如复发或转移风险升高)的亚群。因此，本发明的方法允许将患者分级成亚群或亚型。
本发明的方法涉及，任选在前列腺移除术后，通过针对在本文中所公开的PCPI进行测定而将具有前列腺癌的患者识别为可能具有更好或更差的癌症复发、癌症转移和/或生存结果的实施例。当对从患者获得的样本的先前主观解释(诸如基于免疫组织化学染色和主观分析)可能已经被用于确定侵袭性疾病相对于惰性疾病的倾向和/或处置前列腺癌患者，或者前列腺移除术前或术后的患者，或者已通过不同疗法处置的前列腺癌患者，本发明引入了反映表达模式的客观指标，其可以单独使用或者与其他(主观和/或客观)标准组合使用以提供对患者结果的更准确的评估，包括生存率以及癌症的复发或转移。因此，基于对本发明的标记基因表达模式的分析的方法包括用于检测/诊断前列腺癌或者前列腺癌移除术前或术后的预后的手段，或者更一般地，确定侵袭性或惰性疾病的初级处置前或初级处置后的倾向。
PCPI基于对多于一种标记基因或表达的序列的分析，其能够区分前列腺癌阶段，或者以显著的准确性来区分前列腺移除术前或术后的前列腺癌阶段。(一个或多个)标记基因或表达的(一个或多个)感兴趣序列的(一个或多个)表达水平被识别为与结果相关，使得(一个或多个)表达水平与确定患者的优选处置协议相关。因此，本发明包括涉及任选地在前列腺移除术之前或之后，通过根据在本文中所公开的方法针对与患者结果相关的表达水平测定怀疑包含来自所述患者的癌细胞的前列腺样本，以确定罹患前列腺癌的对象的结果的方法的实施例。在本发明的另一实施例中，公开了一种用于确定对象患者中的前列腺癌复发和/或转移的风险的方法。
在本发明的方法中，针对在本文中所公开的标记基因的表达水平，分析怀疑包括来自患者的前列腺癌细胞的样本。所述标记基因的合计表达水平能够与前列腺癌细胞群体中其(一个或多个)平均或中值表达水平进行比较。然后，该评估可以被用于确定在使用PCPI时从其获得样本的对象中前列腺癌复发和/或转移的风险。所公开的基因(或表达的序列)的表达水平与癌症复发和/或转移的低风险相关或者与癌症复发和/或转移的高风险相关。
换言之，在本文中所公开的个体标记基因(或表达的序列)以较高或较低的水平(与前列腺癌细胞群体中的标准化表达值相比)表达，使得偏差与在先前诊断为前列腺癌的患者(任选为已经被专门处置前列腺癌的患者，或重新诊断的患者)中发生侵袭性与惰性癌症的更高或更低的风险或者倾向相关。
在一些实施例中，针对表达水平进行测定可以通过使用选择的特别识别在本文中所公开的标记基因的核酸探针来执行。这些探针在合适的条件下杂交并检测如在本文中所公开的表达序列。在本发明的实施例中，探针能够被用于检测从表达的标记(基因)序列扩增的序列的区域。
对标记(基因)序列的表达水平的检测或确定可以被称为检测或确定表达谱或签名。如在本文中所描述地识别和使用包括所公开的标记基因序列的本发明的表达模式。针对其识别，通过对mRNA的表达水平进行量化来获得包含前列腺癌细胞的样本中基因表达水平的大采样。在一个实施例中，本发明包括通过分析来自单细胞或均质细胞群体的基因表达来检测标记基因(或序列)表达水平，所述单细胞或均质细胞群体已经此外可能通过简单的活检与污染细胞切离或者以其他方式被隔离或纯化。由于在来自不同患者的细胞之间以及在来自同一患者样本的细胞之间的众多基因的表达波动，因此将来自个体基因序列的表达的多个数据用作参考数据以生成模型，该模型继而允许识别个体基因和序列，所述个体基因和序列的表达与特定的前列腺癌、或者前列腺移除术前或术后的结果相关，或者其允许根据患者的侵袭性与惰性癌症的倾向对患者进行分类。在这些方法中，使用本申请的权利要求中和贯穿说明书中所提及的感兴趣标记基因，将基因表达水平优选转化为如上文所定义的PCPI。
根据本发明，然后分析这些模型中的各种基因的标记基因表达水平，以识别核苷酸序列，所述核苷酸序列的表达与前列腺癌或前列腺癌处置后的结果正相关或负相关。
本发明的优选实施例基于在细胞中对表达的标记基因序列的子集的识别，其被识别为与在本文中所描述的结果相关。本发明的表达模式或概况包括被转化成PCPI的这些识别的标记序列(或基因)的组合。使用多个样本用于识别表达的序列增加了基因被认为与前列腺癌复发、转移和/或生存结果相关的置信度。在没有足够的置信度的情况下，仍然不能预测特定基因是否实际上与结果相关，并且也不能预测基因的表达是否可以成功用于识别前列腺癌、或者前列腺移除术前或术后对象或患者的结果。可以选择与所公开的感兴趣的标记基因(或表达序列)相对应的所识别的核苷酸序列作为待检测或评估其预测属性的表达谱来进行评估。
与一个结果相对于另一个高度相关的表达水平谱或PCPI可以被用于测定包含来自对象或患者的样本的前列腺癌细胞，以预测从其获得样本的对象的结果。这样的测定可以被用作基于所识别的结果来确定针对所述对象的治疗性处置的方法的一部分。这种相关性提供了如在本文中所公开的对前列腺癌复发、癌症转移和/或生存结果的分子确定。在不受理论束缚的情况下，并且提供以改善对本发明的理解，所公开的分子确定比涉及前列腺癌的其他分子指示器(例如，对前列腺血清抗原(PSA)水平的确定)更有效。相关表达模式和谱的额外用途在于对细胞和组织的分类；对诊断和/或预后的确定；以及对疗法的确定和/或改变。
区分的能力是通过将个体标记基因序列的表达识别为相关、而不是通过被用于确定实际表达水平的测定形式来赋予的。本发明的方法定量地或定性地反映“转录物”(基因组中基因的转录部分)中的(一个或多个)标记基因序列的表达。包含前列腺癌细胞的样本的性质不是限制性的，因为在所公开的方法中可以使用新鲜组织、新鲜冷冻组织和固定组织，诸如福尔马林固定的石蜡包埋(FFPE)组织。在一些实施例中，所述样本可以是针(芯)活检或其他活检的样本。
为了检测所识别的表达模式或PCPI签名，本发明的实施例包括通过从已经与污染细胞切离或以其他方式被隔离或纯化(除此之外可能通过简单的活检)的单细胞或同质细胞群体中收集全局或接近全局的基因表达数据来检测基因(或序列)表达模式。然后，检测或者以其他方式测量模式或谱中标记基因(序列)的表达水平。在其他实施例中，一种方法可以仅检测或测量谱中的基因(序列)的表达水平，而不执行对其他基因或序列的表达的评估或其他确定。
在额外的方面中，对表达水平的分析可以与前列腺癌的其他评估或指示器组合执行或者替代其进行。在一些实施例中，与确定在包括来自对象的前列腺癌细胞的样本中的前列腺癌等级的方法组合地进行所述分析。在其他实施例中，是与确定样本中前列腺癌阶段的方法进行组合。第三种可能性是与检测或确定对象中的PSA水平进行组合，任选地在被用于隔离前列腺癌细胞的流程之前。当然，与这些代表性范例中的任何一个、两个或所有三个的组合是可能的。每当使用多于一种类型的评估时，结果都是多变量分析。本发明明确包括在本文中描述为多变量实施例的评估的所有可能的组合。
通常，可以使用本领域技术人员已知的任何接受的评估前列腺癌等级和/或阶段的方法。在一些情况下，确定前列腺癌等级的方法包括确定Gleason分数(或Gleason分级)。在其他情况下，确定前列腺癌等级的方法包括根据美国癌症联合委员会(AJCC)的肿瘤分期系统来估计前列腺癌阶段。并且如在本文中所描述的，可以替代或组合Gleason分数或AJCC肿瘤阶段确定来执行对基因(序列)表达水平的分析。在PSA水平的情况下，可以在被用于提供包括前列腺癌细胞的样本的前列腺移除术之前进行其评估，以用于在本文中所描述的任何方法中使用。
在其他实施例中，本发明包括用于检测在本文中所公开的基因(或序列)的表达的物理和方法学手段。这些手段可以涉及测定以下一个或多个方面：基于基因(或序列)的表达的DNA模板、用作表达基因(或序列)的中间体的RNA、或者由基因(或序列)表达的蛋白质产物。
尽管本发明主要在人类前列腺癌的上下文中进行了描述，但是可以在已知可能患有前列腺癌的任何动物的前列腺癌的上下文中实践。用于应用本发明的动物的非限制性范例是哺乳动物，特别是那些对农业应用(诸如，但不限于：牛、羊、马和其他“农场动物”)重要的哺乳动物、前列腺癌的动物模型、以及人类陪伴的动物(诸如但不限于狗和猫)。
基因表达“模式”或“谱”或“签名”以及对应的计算的PCPI指代在两种或更多种前列腺癌之间，或者前列腺移除术前或术后，癌症复发，转移和/或生存结果(其表达与能够区分结果相关)的感兴趣基因(表达序列)的相对表达。
“基因”或“表达的序列”是以能检测的方式来编码和表达离散产物的多核苷酸，无论本质是RNA还是蛋白质。应当领会到，多于一个的多核苷酸可以能够对离散产物进行编码。该项包括基因或表达序列的等位基因和多态性，其基于染色体位置以及在正常有丝分裂期间重组的能力对相同的产物、或者其功能相关的(包括功能的增益、减少或调制)类似物进行编码。
术语“相关”或“相关性”或者其等价物指代在两个或更多个基因的表达与前列腺细胞的生理状态之间的关联，以排除如通过使用在本文中所描述的方法而识别的一个或多个其他状态。基因可以以更高或更低的水平来表达，并且仍然与一种或多种前列腺癌、或者前列腺癌移除术前或术后、状态或结果相关。
如在本文中所使用的，在本发明的上下文中分析其表达的“标记基因”或“标记基因序列”也可以被描述为感兴趣基因(GOI)。
在本发明的实施例中，将给定的标记基因(或表达的序列)的表达强度标准化(例如，相对于以相对恒定水平表达的参考基因的表达，或者跨所有可用样本测量GOI的表达，并且表达值被标准化)，以提供用于对标记基因表达签名(例如，PCPI)和其他参数(例如临床数据)的相关性分析的标准化值或分数。在许多情况下，所述表达数据被标准化，以中值为中心，并且如本领域技术人员在进一步使用之前已知地进行对数转换，例如在聚类和判别分析中。在使用多于一个表达水平的情况下(如在基因表达谱或指数的情况下，例如PCPI)，可以将所述值或分数相加，并且然后进行分析作为用于评估相关性或基于相关性进行分类的合计值。
“多核苷酸”是任何长度的核苷酸(核糖核苷酸或脱氧核糖核苷酸)的聚合形式。该术语仅指代分子的初级结构。因此，该术语包括双链和单链DNA和RNA。其也包括已知类型的修饰，包括本领域已知的标签，甲基化，“帽”，利用类似物取代一个或多个天然存在的核苷酸，和核苷酸间修饰，诸如不带电荷的键(例如，硫代磷酸酯、二硫代磷酸酯等)，以及多核苷酸的未修饰形式。
术语“扩增”在广义上被用于意指创建扩增产物能够利用DNA或RNA聚合酶酶促地制备。如在本文中所使用，“扩增”通常指代产生期望序列(特别是样本)的多个副本的过程。“多个副本”意指至少2个副本。“副本”不一定意指与模板序列完美的序列互补性或同一性。还能够使用本领域已知的任何测序方法来识别GOI的序列。
术语“对应的”在适当的情况下可以指代核酸分子与另一核酸分子共享大量的序列同一性。大量意指至少95％，通常至少98％，并且更通常至少99％，并且使用BLAST算法来确定序列同一性，如Altschul等人在(1990)，J.Mol.Biol.215:403-410(使用公布的默认设置，即，参数w＝4，t＝17)所描述的。用于扩增mRNA的方法通常是在本领域中已知的，并且包括逆转录物PCR(RT-PCR)，以及在美国专利申请序列号No.10/062857(2001年10月25日提交)和美国临时专利申请60/298847(2001年6月15日提交的)和60/257801(2000年12月22日提交的)中描述的那些，其全部内容通过引用被合并入本文，如同完全进行了阐述一样。可以使用的另一种方法是定量PCR(或Q-PCR)。备选地，能够通过本领域已知的方法将RNA直接标记为对应的cDNA。
术语“Cq值”定义了在qRT-PCR(定量实时PCR)中的PCR循环，其中，所测量的荧光首次与背景荧光交叉。
“微阵列”是离散区域的线性或二维阵列，每个离散区域具有限定的面积，形成在通常为固体支撑体(诸如，但不限于玻璃、塑料或合成膜)的表面上。微阵列上的离散区域的密度是由要在单个固相支撑体的表面上检测的固定化的多核苷酸的总数来确定的，诸如至少约50/cm2，至少约100/cm2，至少约500/cm2，但在一些实施例中低于约1000/cm2。所述阵列总共可以包含小于约500、约1000、约1500、约2000、约2500或者约3000个固定化的多核苷酸。如在本文中所使用的，DNA微阵列是被放置在芯片或其他表面上的寡核苷酸或多核苷酸的阵列，所述芯片或其他表面被用于与来自样本的扩增或克隆的多核苷酸杂交。因为阵列中的多核苷酸的每个特定组的位置是已知的，所以样本多核苷酸的同一性能够基于它们与微阵列中的特定位置的结合来确定。
因为本发明依赖于对过表达或欠表达的基因(或表达序列)的识别，本发明的一个实施例涉及通过将样本细胞的mRNA或者其扩增或克隆的版本(诸如DNA或cDNA)与对特定基因序列唯一的多核苷酸进行杂交来确定表达。这种类型的多核苷酸可以包含未在其他基因序列中找到的基因序列的至少约20个、至少约22个、至少约24个、至少约26个、至少约28个、至少约30个或者至少约32个连续碱基对。如在前一句中所使用的术语“约”指代从所陈述的数值增加或减少1。其他实施例可以使用在其他基因序列中未发现的基因序列的至少或约50、至少或约100、至少约或150、至少或约200、至少或约250、至少或约300、至少或约350或者至少或约400个碱基对。在前面的句子中所使用的术语“约”指代从所陈述的数值增加或减少10％。这样的多核苷酸也可以被称为能够与在本文中所描述的基因序列或者其独特部分杂交的多核苷酸探针。在许多情况下，杂交条件是约30％v/v至约50％甲酰胺以及约0.01M至约0.15M杂交盐的严格条件，以及在约55℃至约65℃或更高的从约0.01M至约0.15M盐的洗涤条件，或者与其等同的条件。
在其他实施例中，用于在本发明中使用的多核苷酸探针可以与应当确定其表达的标记基因序列具有约或95％，约或96％，约或97％，约或98％，或者约或99％的同一性。如上所述，使用BLAST算法来确定同一性。也可以基于如上所述在严格条件或者与其等同条件下用于本发明的方法的杂交表达的标记基因的能力来描述这些探针。
在许多情况下，所述序列是由标记基因编码的mRNA，与这样的mRNA相对应的cDNA，和/或这样的序列的扩增版本。在本发明的一些实施例中，将多核苷酸探针在阵列、其他设备上或者固定在定位探针的个体斑点中。
能够根据本发明使用的合适的标签包括放射性同位素、核苷酸发色团、酶、底物、荧光分子、化学发光基团、磁性颗粒、生物发光基团等。这样，标签是通过光谱、光化学、生物化学、免疫化学、电学、光学或化学手段能检测的任何复合物。术语“支撑体”指代常规的支撑体，诸如珠粒、颗粒、浸渍棒、纤维、过滤器、膜和硅烷或硅酸盐支撑体(诸如玻璃载片)。
如在本文中所使用的，“前列腺组织样本”或“前列腺癌细胞样本”指代从个体(诸如患有前列腺癌的个体)隔离的前列腺组织的样本。所述样本可以来自经由前列腺移除术(诸如根治性前列腺移除术)移除的材料。备选地，能通过其他手段获得它们，诸如针状(芯)活检或其他活检技术，如侧向活检，常规的六分仪活检方法，作为扩展技术的六分仪和侧向活检的不同组合，经直肠超声引导的前列腺活检，以及其他如本领域技术人员已知的技术。这样的样本是初级隔离物(与培养的细胞相反)，并且可以通过本领域公认的任何合适的手段来收集。在一些实施例中，“样本”可以通过侵入性方法来收集，包括但不限于手术活检。样本可以包含前列腺癌细胞，通过已知方法或熟练从业者认为需要的其他适当方法对其进行隔离。在根据本发明使用之前，隔离方法包括但不限于显微切割、激光捕获显微切割(LCM)、或者激光显微切割(LMD)。“表达”和“基因表达”包括核酸材料的转录和/或翻译。如在本文中所使用的，术语“包括”及其同源词以其包括的含义使用；亦即，相当于术语“包括”以及其对应的同源词。
“允许”事件发生的条件或者“适合于”发生事件(诸如杂交、链延伸等)的条件或“适合的”条件是不妨碍这样的事件发生的条件。因此，这些条件允许、增强、促进和/或有利于所述事件。本领域已知并且如在本文中所描述的这样的条件取决于例如核苷酸序列的性质、温度和缓冲条件。这些条件也取决于期望的事件，诸如杂交、切割、链延伸或转录。
“检测”包括任何检测手段，包括对基因表达以及其中的改变的直接和间接检测。例如，可以直接或间接观测“可检测性较低”的产物，并且该术语指示任何减少(包括不存在能检测的信号)。类似地，“可检测性较高”产物意指任何增加，无论是直接还是间接地观测到。
“前列腺移除术”指代由熟练的临床医师(诸如外科医师)对前列腺组织的移除。非限制性范例包括根治性前列腺移除术；开放(常规)前列腺移除术(涉及通过会阴切口)；腹腔镜前列腺移除术；以及机器人(保留神经)前列腺移除术。
“Gleason分数”指代根据Gleason系统由经训练的病理学家对前列腺癌的样本进行分级，Gleason系统基于前列腺组织的样本的细胞中与癌组织或正常前列腺组织的相似性，使用1至5的数字来分配Gleason分数。对看起来非常像正常前列腺组织的组织给予分数或等级1，而对缺乏正常特征的组织以及似乎随意地通过前列腺散布的细胞给予分数或等级5。分数或等级2到4(包含)具有在这些可能性之间的特征。但是，因为前列腺癌可能包括具有不同分数或等级的区域，所以对组成大部分组织的两个区域给出单独的分数或等级。将所述两个分数或等级相加以产生在2至10之间的Gleason分数(或者Gleason之和)。
在本文中所提及的标记基因的表达水平与在本文中所描述的临床结果相关，并且因此可以被用作如在本文中所描述的预测子。已经报道了所识别的基因将参与如http://csbi.ltdk.Helsinki.fi/anduril/tcga-gbm/table4_2.html中概述的各种细胞功能。在本发明实施例下的方法中，如在WO2010131194和WO2010131195(其内容通过引用并入本文)中所描述的，这些数据与推定的预后基因标记PDE4D7相关。在本发明的背景下，选择显示出显著相关性的那些分子路径用于下游分析(图2)。
在本发明的实施例中，标记基因表达模式(或PCPI)可以与术前或术后PSA水平、Gleason分数和pT阶段相关。所述谱也能够将具有Gleason分数<＝6和7的样本分级为PSA失败的低风险和高风险。在具有已知预后因子的多变量分析中，谱是保持统计学显著性的仅有的预测子(p<0.05)。因此，在活检中或者在前列腺移除术期间移除的组织中对谱的检测允许区分惰性癌症和侵袭性癌症。
因此，本发明的实施例涉及识别和使用在对象中区分(或相关)前列腺癌生存和复发结果的基因表达模式(或谱或“签名”)。这样的模式可以通过本发明的方法通过使用许多参考细胞或组织样本来确定，诸如由前列腺癌的病理学中的普通病理学家回顾的那些，其反映前列腺癌细胞而不是正常的或其他非癌细胞。其样本可以与表达数据相关的对象经历的结果，以识别与结果相关的模式。因为总体基因表达谱因人、癌症以及癌症细胞而异，因此可以如在本文中所公开的那样进行在特定细胞与表达或欠表达的基因之间的相关性，以识别能够区分前列腺癌结果的基因。
在本发明的实施例中，使用与前列腺癌(或前列腺移除术前或术后)生存、转移或复发结果显著相关的基因来区分结果。模式或指数能够基于用于模型中进行区分的基因的表达来预测对未知样本的分类。
在本发明的实施例中，与前列腺癌、或者前列腺移除术前或术后/初级处置结果相关地表达的标记基因(序列)提供了将基因表达分析仅聚焦于有助于在不同结果中对对象进行分级的能力的那些基因。
如本领域技术人员将领会的，表达模式(和PCPI)对于区分前列腺癌、或者前列腺移除术前或术后中的不同结果是非常有用的，并且本领域技术人员可以容易地执行以允许生成如上文所描述的模型，从而基于这些基因的表达水平来预测未知样本的状态。
为了确定在本发明的实践中的基因(表达序列)的(上调的或下调的)表达水平，可以使用本领域已知的任何方法。在一些实施例中，使用基于对与在本文中识别并且公开的基因(或探针序列)杂交的RNA的检测的表达。这很容易通过本领域已知的或公认为等同的任何RNA检测或扩增+检测方法来执行，诸如但不限于RNA测序、逆转录-PCR(RT-PCR)、实时PCR，实时RT-PCR、在美国专利申请系列号NO.10/062857(2001年10月25日提交)以及美国临时专利申请60/298847(2001年6月15日提交)和60/257801(2000年12月22日提交)中公开的方法，以及用于检测存在或不存在RNA稳定化或去稳定化序列的方法。
备选地，可以使用基于对DNA状态的检测的表达。将所识别的基因的DNA检测为甲基化或删除的可以用于具有与特定前列腺癌、前列腺移除术前或术后、结果相关的表达降低的基因。这可以通过本领域已知的基于PCR的方法容易地执行，包括但不限于Q-PCR。
相反地，将所识别的基因的DNA检测为扩增的可以用于具有与特定的前列腺癌、前列腺移除术前或术后、结果相关的上调表达的基因。这可以通过本领域已知的基于PCR的荧光原位杂交(FISH)和染色体原位杂交(CISH)方法容易地执行。
例如，除了计算针对个体样本/患者的PCPI之外，也可以使用基于检测蛋白质水平或活性的存在、增加或减少的表达。可以通过本领域已知的基于任何免疫组织化学(IHC)、基于血液(特别是针对分泌的蛋白质)、基于抗体(包括抗蛋白质的自身抗体)、基于剥离细胞(来自癌症的)、基于质谱、以及基于图像(包括使用标记的配体)的方法，并且所述方法被认为适合于检测蛋白质。基于抗体和基于图像的方法额外地能用于通过使用通过非侵入性流程(诸如灌洗或针抽吸)获得的细胞来确定癌症之后的肿瘤的定位，其中，癌细胞的来源是未知的。标记的抗体或配体可以被用于定位患者体内的(一处或多处)癌变。
涉及使用基于核酸的测定来确定表达的本发明的实施例通过将在本文中所识别的标记基因的一个或多个序列固定为固体支撑体上的多核苷酸来完成，所述固体支撑体包括但不限于固体基质，如本领域已知的阵列或基于珠粒的技术。在一些实施例中，所述测定是能从Illumina获得的DASL(cDNA介导的退火、选择、延伸和结扎)测定。备选地，也可以使用本领域已知的基于溶液的表达测定法。固定的多核苷酸探针对于所公开的基因(或表达的序列)可以是独有的或者以其他方式特异性的，使得多核苷酸能够与对应于基因(或表达的序列)的DNA或RNA杂交。这些多核苷酸可以是基因(或表达的序列)的全长或者是较短长度的探针(通过从序列的5'或3'端删除，比本领域已知的全长序列短达一个核苷酸)，其任选地是最小地中断的(诸如通过错配或插入非互补碱基对)，从而其与对应于基因(或表达的序列)的同源DNA或RNA的杂交不受影响。在许多实施例中，多核苷酸探针包含来自所公开的基因或表达的序列的3'端的序列。也可以使用包含相对于所公开基因的序列的突变的多核苷酸探针，只要突变的存在仍然允许杂交以产生能检测的信号即可。固定化的多核苷酸可以被用于确定由(一个或多个)样本前列腺细胞制备的核酸样本的状态，针对所述样本前列腺细胞，样本的对象(例如，从其获得样本的患者)的结果是未知的，或者确认已经被分配到样本对象的结果。在不限制本发明的情况下，这样的细胞可以来自患有前列腺癌的患者，诸如通过前列腺移除术移除的材料。(一个或多个)固定化的多核苷酸只需要足以在合适的条件下与源自样本的对应核酸分子进行特定的杂交。尽管甚至单个相关的基因的表达可以能够在区分两种前列腺癌结果时提供足够的准确度，但是本发明包括使用来自多于一种基因或表达序列的表达水平。具体地，使用实施例部分(下文)中提到的17、18、19的组或57的组的基因(表达序列)。
在一些实施例中，可以通过使用适当的引物(诸如在PCR中使用的)来优先扩增源自(一个或多个)样本前列腺癌细胞的核酸，从而仅扩增待分析的基因以减少来自样本中的其他表达的基因或序列的污染背景信号。本发明的PCR扩增的大小可以是任意大小，包括至少或约50、至少或约100、至少约或150、至少或约200、至少或约250、至少或约300、至少或约350、或者至少或约400个连续的核苷酸，全都包括与所使用的PCR引物互补的部分。当然，PCR任选地可以是逆转录耦合PCR(或者在RNA起始材料的情况下是RT-PCR)或定量PCR，诸如实时PCR，或者其组合。当然，来自在本文中所描述的样本的RNA可以通过本领域技术人员容易知晓的手段来制备和使用。备选地，并且在要分析多个基因或者使用非常少的细胞(或一个细胞)的情况下，来自样本的核酸可以在与固定化的多核苷酸探针杂交之前被全局地扩增，诸如在阵列或微阵列上。当然，RNA或其cDNA对应物可以通过本领域中已知的方法直接标记和使用，而无需扩增。用于检测在本文中所描述的标记基因的方法的优选实施例是RNA测序。
本发明提供了一组更为客观的标准，以离散的一组标记基因的基因表达谱的形式，来区分(或描绘)前列腺癌、或者前列腺移除术前或术后、结果，并且允许预测针对侵袭性与惰性疾病的倾向。在一些实施例中，所述测定被用于在约6个月、1年、2年、3年、4年、5年、7年、10年、15年或甚至更晚的时间内区分更好和更差的结果。
尽管更好和更差的癌症复发、转移和/或生存结果可以相比于彼此进行相对地定义，但是可以将“更好”的结果或“良好预后”看作在手术介入以移除(一个或多个)前列腺癌症肿瘤后约60个月之后比50％癌症复发几率和/或50％生存几率更好的结果。“更好的”结果或者“良好的预后”也可以是在手术介入后约60个月的优于约60％、约70％、约80％或约90％的癌症复发和/或生存几率。“更差”的结果/预后可以被视为在手术介入以移除(一个或多个)前列腺癌肿瘤的约60个月之后的50％或更大癌症复发几率和/或低于50％的生存几率。PCPI和根据本发明的方法帮助将患者分类成具有上述预后的患者。
所公开的方法也可以与固体组织材料一起使用。例如，可以收集固体活检并进行制备以用于可视化，然后确定在本文中所识别的两个或更多个基因或表达的序列的表达以确定前列腺癌、或者前列腺移除术前或术后、结果。一种手段是通过使用与(一个或多个)多核苷酸识别探针进行原位杂交以用于测定(一个或多个)所述基因的表达。
在一些实施例中，为了方便和准确，对来自样本的基因表达的检测可以通过使用能够测定来自本文中所公开的一些或所有基因的基因表达的单个微阵列。
本发明的其他用途包括提供识别如与特定的前列腺癌生存或复发结果相关的前列腺癌细胞样本以用于进一步研究或学习的能力。这在需要基于客观的基因或分子标准来识别细胞的许多情况下提供了特别的优点。
用于在本发明的方法中使用的材料理想地适用于制备按照公知方法生产的试剂盒。本发明因此提供了包括用于对所公开的用于识别前列腺癌、或前列腺移除术前或术后、结果的基因的表达和序列的表达的检测的试剂的试剂盒。这样的试剂盒任选包括提供具有与其在本发明的方法中的用途相关的识别描述或标签或指令的试剂。这样的试剂盒可以包括容器，每个容器具有在所述方法中使用的各种试剂(通常为浓缩形式)中的一种或多种，例如包括预制微阵列、缓冲器、合适的三磷酸核苷酸(例如，dATP、dCTP、dGTP和dTTP；或rATP、rCTP、RGTP和UTP)、逆转录酶、DNA聚合酶、RNA聚合酶以及本发明的一种或多种引物复合物(例如，适合长度的多聚(T)或链接到与RNA聚合酶反应的启动子的随机引物)。通常也将包括一组指令。
本发明所提供的方法也可以全部或部分自动化。本发明的所有方面也可以被实践为使得其基本上包括所公开基因的子集，排除与经由包含细胞的样本对前列腺癌复发、转移和/或生存结果的识别无关的材料。
在本发明的方法的上下文中，PCPI被用于诊断患者的前列腺癌，识别患者的前列腺癌，并建立前列腺癌患者的预后，确定发展侵袭性与惰性疾病的倾向性，并且对前列腺癌患者进行分级，从而处置医师能够(如果发生的话)决定应当如何处置患者。PCPI能够被用作上述目的的唯一参数，或者其能够与其他已知的诊断、预后或分级方法组合使用从而为医师提供进一步的支持。
如在本文中所使用的，术语“诊断前列腺癌”意指，与在本文中上文所定义的对照水平相比，优选如果与在本文中上文所定义的正常对照水平相比，当本发明的GOI的表达水平被上调或下调，PCPI显著高于/不同于在对照组织中发现的水平时，则患者或个体可以被认为患有前列腺癌。术语“诊断”也指代通过所述比较过程得出的结论。
在本发明的另一实施例中，所述诊断可以与另外的癌症生物标记表达水平的阐述相结合，特别是前列腺癌生物标记。本领域技术人员将知道若干种特定的前列腺癌生物标记。例如，可以测试生物标记(如PSA)的表达。
当与在本文中上文所定义的正常对照水平相比本发明的GOI的表达水平被上调或下调时并且当PCPI显著高于利用对照材料获得的PCPI时，可以认为诊断出前列腺癌。
在另外的优选实施例中，如果在本文中所提到的GOI的表达水平被上调或下调的值在20％至80％之间，优选在与对照水平(优选为标准化对照水平)相比较时在测试样本中的30％、40％、50％、60％或70％的值，则可以认为诊断出前列腺癌或者确定了发展侵袭性与惰性疾病的倾向。如在本文中上文所定义的，所述对照水平可以是正常对照水平或癌性对照水平。在特别优选的实施例中，如果如在本文中上文所定义的表达水平被上调或下调了1.5至10倍的因子，优选与对照水平相比较在测试样本中2至5倍的因子，特别是在健康组织或良性前列腺癌中或者非常优选地与初始诊断时相同患者的前列腺癌组织中，则可以认为诊断出前列腺癌或发展侵袭性与惰性疾病的倾向。
如在本文所使用的术语“检测前列腺癌”意指可以确定有机体中前列腺癌疾病或失调的存在或者可以在有机体中识别出这样的疾病或失调。对前列腺癌疾病或失调的确定或识别可以通过比较本发明的GOI的表达水平与在上文定义的正常对照水平或者通过确定PCPI来完成。与在本文中上文所定义的正常对照水平相比较，当GOI的表达水平被上调或下调时，可以检测到前列腺癌。在本发明的优选实施例中，如果GOI的表达水平与已建立的(例如，独立建立的)前列腺癌细胞或细胞系(例如，前列腺奥细胞系或上述细胞系)的表达水平相似，则可以检测到前列腺癌。
如在本文中所使用的，术语“监视前列腺癌”和“识别具有易疾病进展的前列腺癌的倾向的对象”(即，识别侵袭性疾病与惰性疾病)涉及例如在处置流程期间或之后或者在特定时段期间或之后伴随所诊断或检测到的前列腺癌疾病或失调，通常在2个月、3个月、4个月、6个月、1年、2年、3年、5年、10年，或者在初级处置的开始和结束期间或之后的任何其他时段。术语“伴随”意指，如在本文中上文所定义的疾病状态或PCPI，并且特别是这些疾病状态或PCPI的变化，可以通过以下操作来检测：将样本中本发明的GOI的表达水平与在本文中上文所定义的正常对照水平(优选源自良性肿瘤对照或健康对照的对照表达水平)进行比较，或者与建立的(例如独立建立的)前列腺癌细胞或细胞系(例如，前列腺癌细胞系或任何类型的周期性时间分段中的细胞系)的表达水平进行比较，所述周期性时间分段例如是：每周，每2周，每月，每2、3、4、5、6、7、8、9、10、11或12个月，每1.5年，每2、3、4、5、6、7、8、9或10年，在任何时间段期间，例如，分别在2周，3周，1、2、3、4、5、6、7、8、9、10、11、12个月、1.5、2、3、4、5、6、7、8、9、10、15或20年。所建立的(例如，独立建立的)产生额外的对照水平的前列腺癌细胞或细胞系可以来源于与癌症发展的不同阶段相对应的样本，例如，TNM分类系统的阶段0和I至IV。在本发明的优选实施例中，该术语涉及对所诊断的前列腺癌的伴随，例如，恶性激素敏感的前列腺癌。所述监测也可以包括对额外基因或基因元素的表达的检测，例如，看家基因，如GAPDH或PBGD。本发明也涉及监测患者的方法，以使用整个说明书中公开的PCPI来识别在本文中所公开的签名基因中的变化，以便识别那些可能发展侵袭性前列腺癌的患者。然后，这些患者将按照整个说明书中所描述地进行治疗。
如在本文中所使用的，术语“预测(侵袭性)前列腺癌”指代例如在处置期间或者在治疗之后，在特定时间段期间，预测所诊断或检测到的侵袭性前列腺癌的过程或结果。该术语也指代确定从疾病生存或恢复的机会，以及指代预测患者的预期生存时间。预后具体可以涉及在未来的一段时间期间建立患者生存的可能性，诸如6个月、1年、2年、3年、5年、10年或任何其他时间段。
如在本文中所使用的，术语“朝向前列腺癌的进展”和“朝向侵袭性(与惰性)前列腺癌的进展”涉及在癌症发展的不同阶段之间的切换，例如，TNM分类的阶段0以及I至IV，或者任何其他阶段或亚阶段，从健康状况直至恶性激素敏感性或恶性激素抵抗性前列腺癌。通常，与来自同一个体的先前测试样本相比，例如，与来源于良性前列腺癌对照或健康组织对照的样本相比，在测试样本中，这样的切换伴随有对(一个或多个)标记基因或GOI的表达水平以及如在本文中所使用的不同PCPI的修改。如果如在本文中上文所定义的用于计算PCPI的GOI的表达水平不同，例如，在与来自同一个体的测试样本中从基因表达值计算的先前PCPI相比，在测试样本中，不同的值在3％至50％之间，优选不同的值为10％、15％、20％或25％，则可以认为检测到或诊断出朝向侵袭性前列腺癌的进展。可以在任何时间段检测修改，优选在1、2、3、4、5、6、7、8、9、10、11、12个月、1.5、2、3、4、5、6、7、8、9、10、15或20年期间，即，上文所指出的值可用通过对在上文所指示的时间段之后的第一时间点和第二时间点处的(一个或多个)标记基因或GOI的表达水平或者PCPI来计算。
在本发明的特别优选的实施例中，术语“朝向前列腺癌发展”涉及从健康状态或良性前列腺癌状态切换到恶性前列腺癌状态。与来自被诊断为健康的同一个体的先前测试样本相比，在测试样本中，如果如在本文中上文所定义的PCPI高出20％至50％之间的值，优选高出20％、25％、30％或35％的值，则可以认为检测到或诊断出从健康状态到前列腺癌状态的进展。备选地，为了比较，可以使用来自其他个体的测试样本，例如，健康个体的测试样本。也设想到了使用关于表达的可用数据库信息或采用癌细胞收集样本等。
与来自已经被诊断为患有良性前列腺癌的同一个体的先前测试样本相比，在测试样本中，如果如在本文中上文所定义的PCPI高出3％至30％之间的值，优选高出5％、10％、15％或20％的值，则认为检测到或诊断出从良性前列腺癌状态进展至恶性前列腺癌状态。备选地，为了进行比较，可以使用来自其他个体的测试样本，例如，被诊断为患有良性前列腺癌的个体的测试样本。也设想到了使用关于表达的可用数据库信息或采用癌细胞采集样本等。
可以在任何时间段检测修改，优选在1、2、3、4、5、6、7、8、9、10、11、12个月、1.5、2、3、4、5、6、7、8、9、10、15或20年，即，上述值能够通过比较在上述时段之后的第一时间点和第二时间点标记基因或GOI的表达水平来计算。
在本发明的另一实施例中，涉及诊断和检测发展前列腺癌的倾向。在本发明的上下文中，“发展(侵袭性)前列腺癌的倾向”是发展(侵袭性)前列腺癌的风险状态。优选地，在其中本文上述定义的GOI的表达水平或PCPI与本文定义的对照水平显著不同的情况下，可以存在发展侵袭性前列腺癌的倾向，所述对照水平即来源于明显健康的患者的组织或样本或者来源于在初始诊断前列腺癌之前获得的患者的样本或组织的参考表达水平或参考PCPI，从而基于癌组织中的基因表达计算出的PCPI也高于从对照样本获得的PCPI。因此，如果观测到上述情况，则认为诊断出或检测到侵袭性前列腺癌的倾向。
通常，并且也在建立PCPI时，能够将在测试生物学样本的表达水平与对照水平之间的差异标准化为另外的对照核酸的表达水平，所述另外的对照核酸例如是持家基因，其表达水平已知不会根据细胞的癌性或非癌性状态而不同。示范性对照基因尤其包括β-肌动蛋白、甘油醛-3-磷酸脱氢酶(GAPDH)、胆色素原脱氨酶(PBGD)等。
在本发明的上下文中，术语“诊断”和“预测”也意图涵盖预测和可能性分析。作为参数的PCPI因此可以在临床上用于作出关于治疗模式的决定，包括治疗性介入或诊断标准，诸如针对疾病的监管。根据本发明，可以提供用于检查患者状况的中间结果。这样的中间结果可以与额外信息相组合以辅助医生、护士或其他从业者诊断患者患有疾病。备选地，本发明可以被用于检测来源于患者的组织中的癌细胞，并且向医生提供有用的信息以诊断患者患有该疾病。
根据本发明要被诊断、监测或者在其中要检测或预测前列腺癌、朝向侵袭性与惰性前列腺癌的进展或者针对侵袭性与惰性前列腺癌的倾向的患者或个体是动物，优选是哺乳动物，更优选是人类。除了PCPI作为用于诊断、检测、监测或预测朝向侵袭性与惰性前列腺癌的进展的前列腺癌的标记之外，使用如本领域技术人员已知的分子成像工具，例如，磁共振成像(MRI)和/或磁光子共振成像(MPI)技术和/或多参数MRI(mpMRI)技术。
在另一方面中，本发明涉及用于在个体中诊断、检测、监测或预测前列腺癌或朝向前列腺癌的进展或前列腺癌的倾向的复合物。根据本发明的复合物可以包括(一种或多种)GOI表达产物的核酸亲和配体。
如在本文中所使用的，术语“用于GOI表达产物的核酸亲和配体”指代能够与GOI转录物特异性结合的核酸分子。所述核酸亲和配体也可以能够与至少90％、91％、92％、93％、94％、95％、96％、97％、98％或99％等同于GOI序列或所述序列的任何片段的核酸序列特异性结合。
如在本文中所使用的，术语“表达产物”指代由GOI的表达所生成的GOI或mRNA分子的转录物。更优选地，该术语涉及如上文所定义的经处理的转录物。
本发明的复合物例如可以包括针对GOI表达产物特异性的一组寡核苷酸和/或针对GOI表达产物特异性的探针。如在本文中所使用的，术语“针对GOI表达产物特异性的寡核苷酸”指代与GOI的有义链或反义链互补的核苷酸序列。
所述寡核苷酸可以具有本领域技术人员已知的任何合适的长度和序列，如能从GOI或其互补序列得到的。通常，所述寡核苷酸可以具有在8至60个核苷酸之间的长度，优选在10至35个核苷酸之间的长度，更优选是11、12、13、14、15、16、17、18、19、20、21，22、23、24、25、26、27、28、29、30、31、32或33个核苷酸的长度。寡核苷酸序列，例如，可用作针对GOI表达产物特异性的正向和反向引物的寡核苷酸，可以借助于本领域技术人员已知的软件工具来定义。
如在本文中所使用的，术语“针对GOI表达产物特异性的探针”意指与在本文中所描述的GOI的有义链或反义链互补的核苷酸序列。
所述探针可以具有本领域技术人员已知的任何合适的长度和序列，如能从在本文中所描述的GOI的序列得到的。通常，所述探针可以具有在6至300个核苷酸之间的长度，优选在15至60个核苷酸之间的长度，更优选是20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49或50个核苷酸的长度。可以在本领域技术人员已知的软件工具的帮助下来定义针对GOI表达产物特异性的探针序列。
如在本文中上文所描述的核酸亲和配体可以利用各种标记进行标记，或者可以通过利用各种标记进行标记的次级亲和配体来检测，以允许检测、可视化和/或量化。这能够通过使用任何合适的标签来实现，所述标签能够使用本领域技术人员已知的任何合适的技术或方法缀合(conjegate)至能够与表达产物交互的亲和配体或者缀合至任何次级亲和配体。术语“次级亲和配体”指代能够结合到如在本文中上文所定义的亲和配体的分子(即，如果在具有两个交互的亲和配体的系统中使用的情况下，则为“初级亲和配体”)。结合交互优选是特定结合。
能够缀合到初级和/或次级亲和配体的标签的范例包括荧光染料或金属(例如，荧光素、若丹明、藻红蛋白、荧光胺)，发色染料(例如，视紫红质)、化学发光化合物(例如，鲁米那、咪唑)以及生物发光蛋白质(例如，荧光素、萤光素酶)、半抗原(例如生物素)。
在本发明的实施例中，要被用作探针的核酸亲和配体，特别是在本文中上文所定义的针对GOI表达产物特异性的探针，可以利用荧光标签(如6-FAM、HEX、TET、ROX、Cy3、Cy5、德克萨斯红或罗丹明)和/或同时利用与淬灭标签(如TAMRA、Dabcyl、黑洞猝灭剂、BHQ-I或BHQ-2)进行标记。在Stryer，1968，Science，162:526-533中描述了各种其他有用的荧光剂和发色团。亲和配体也可以利用酶(例如，辣根过氧化物酶、碱性磷酸酶、β-内酰胺酶)、放射性同位素(例如，3H、14C、32P、33P、35S、125I)或颗粒(例如，金)进行标记。可以使用各种化学方法(例如，胺反应或硫醇反应)将不同类型的标签缀合至亲和配体。然而，也可以使用除胺和硫醇之外的其他反应性基，例如醛、羧酸和谷氨酰胺。
在本发明的特定实施例中，复合物可额外地包括辅助成分，如PCR缓冲剂、dNTP、聚合酶、离子(如二价阳离子或单价阳离子)、杂交溶液、检测染料以及任何其他适合的化合物或液体，其对于执行如本文上面所定义的检测是必需的，这对本领域技术人员是已知的。
在另一方面中，本发明涉及针对GOI表达产物使用核酸，如在本文中上文所定义的，用于制备用于诊断、检测、监测或预测在个体中的前列腺癌或朝向侵袭性与惰性前列腺癌的进展或侵袭性与惰性疾病的倾向的复合物，如在本文在上文所描述的。
在优选实施例中，本发明涉及使用针对GOI表达产物特异性的一组寡核苷酸和/或针对表达产物特异性的探针，如在本文中上文所定义的，用于制备用于在个体中诊断、检测、监测或预测前列腺癌或朝向侵袭性与惰性前列腺癌的进展或侵袭性与惰性疾病的倾向的复合物，如在本文在上文所描述的。
在本发明的优选实施例中，如在本文中上文所定义的复合物是诊断复合物。
在另一方面中，本发明涉及用于检测、诊断、监测或预测前列腺癌或朝向前列腺癌的进展或侵袭性前列腺癌的倾向的诊断试剂盒，其包括针对GOI表达产物特异性的一组寡核苷酸，针对GOI表达产物特异性的探针。
通常，本发明的诊断试剂盒包含一种或多种试剂，其允许对如在本文中上文所定义的(一个或多个)标记基因或GOI的特异性检测。根据本发明，诊断试剂盒的试剂或成分可以被包括在一个或多个容器或单独的实体中。试剂的性质由试剂盒意图针对的检测方法来确定。
此外，所述试剂盒可以包括一定量的已知核酸分子，其能够被用于对试剂盒的校准或者作为内部对照。通常，用于检测(一个或多个)标记基因或GOI表达产物的诊断试剂盒可以包括辅助成分，如PCR缓冲剂、dNTP、聚合酶、离子(如二价阳离子或单价阳离子)、杂交溶液等。这样的成分是本领域技术人员已知的，并且可以根据所执行的检测方法而变化。另外，所述试剂盒可以包括指令页，和/或可以提供关于所获得的结果的相关性的信息。
在其他方面中，本发明涉及用于例如在个体中检测、诊断、监测或预测前列腺癌或朝向侵袭性与惰性前列腺癌的进展的方法，其至少包括确定样本中(一个或多个)标记基因或GOI水平的步骤。术语“确定(一个或多个)标记基因或GOI的水平”指代确定(一个或多个)标记基因或GOI表达产物的存在或量。因此，术语“(一个或多个)标记基因或GOI的水平”意指(一个或多个)标记基因或GOI表达产物(例如，转录物)的存在或量，和/或对(一个或多个)标记基因或GOI的存在或量的确定。对(一个或多个)标记基因或GOI表达产物的存在或量的确定可以通过本领域已知的任何方式来完成。
在本发明的优选实施例中，通过对核酸的测量来完成对(一个或多个)标记基因或GOI表达产物的存在或量的确定。因此，(一个或多个)表达水平可以通过涉及对由基因编码的mRNA的检测的方法来确定。
例如，可以通过纯化从样本获得的核酸分子(例如，RNA或cDNA)，然后与如在本文中上文所定义的特异性寡核苷酸探针杂交，来估计(一个或多个)标记基因或GOI表达的核酸水平的测量。可以通过视觉或借助合适的设备来完成对表达水平的比较。用于检测mRNA或表达产物的方法是本领域技术人员已知的。
备选地，可以在DNA阵列或微阵列方法中检测标记基因或GOI表达的核酸水平。通常，来源于待测试患者的样本核酸被处理和标记，优选利用荧光标签。随后，这样的核酸分子可以在利用与本发明的标记基因相对应的固定化捕获探针的杂交方法中使用。用于执行微阵列分析的合适手段是本领域技术人员已知的。
在标准设置中，DNA阵列或微阵列包括固定化的高密度探针以检测基因的数量。阵列上的探针与标记基因序列的一个或多个部分互补。通常，cDNA、PCR产物和寡核苷酸用作探针。
基于DNA阵列或微阵列的检测方法通常包括以下步骤：(1)从样本中隔离mRNA，并且任选地将mRNA转化成cDNA，并且随后标记该RNA或cDNA。在针对微阵列技术手册中描述了用于隔离RNA、将其转化成cDNA并标记核酸的方法。(2)将来自步骤1的核酸与针对标记基因的探针杂交。来自样本的核酸能够利用染料来标记，诸如荧光染料Cy3(红色)或Cy5(蓝色)。通常，对照样本被利用不同的染料来标记。(3)检测来自样本的核酸与探针的杂交，并且至少定性地并且更具体地定量地确定样本中被调查标记基因的mRNA的量。能够基于信号强度的差异来估计在样本与对照之间表达水平的差异。这些能够通过适当的软件来测量和分析，所述软件诸如但不限于例如由Affymetrix所提供的软件。
与所使用的标记基因相对应的探针的数量没有限制，其被点在DNA阵列上。同样地，标记基因能够由两个或更多个探针来表示，所述探针与基因的不同部分杂交。探针是针对每个所选标记基因而设计的。这样的探针通常是包括5-50个核苷酸残基的寡核苷酸。更长的DNA能够通过PCR或化学地合成。用于合成这样的寡核苷酸并将其应用在基质上的方法在微阵列领域是周知的。除了标记基因外的基因也可以被点在DNA阵列上。例如，可以将表达水平没有显著改变的基因的探针点在DNA阵列上以使测定结果标准化，或者比较多个阵列或不同测定的测定结果。
备选地，(一个或多个)标记基因或GOI表达的核酸水平可以在定量RT-PCR方法中检测，优选在感兴趣的逆转录转录物之后以实时PCR方法来检测。通常，作为第一步，根据本领域技术人员已知的任何合适的方法将转录物逆转录成cDNA分子。随后可以基于如上文所描述获得的第一DNA链执行定量或实时PCR方法。
优选地，可以将作为该类型的基于FRET的主要探针的Taqman或分子信标探针用于定量PCR检测。在这两种情况下，所述探针用作内部探针，其与位于感兴趣靶区域侧面的一对相对引物结合使用，优选与如在本文中上文所定义的一组(一个或多个)标记基因特异性寡核苷酸结合使用。在扩增目标片段后，所述探针可以在引物位点之间的识别序列处被选择性地结合到产物，由此导致相对于目标频率增加的FRET信令的增加。
优选地，用于根据本发明的定量PCR方法的Taqman探针可以包括约22至30个碱基的如上文所定义的特异性寡核苷酸，所述碱基两端利用FRET对进行标记。通常，5'末端将具有较短波长的荧光团，诸如荧光素(例如，FAM)；并且3'末端通常利用较长波长的荧光猝灭剂(例如，TAMRA)或非荧光猝灭剂化合物(例如，黑洞猝灭剂)进行标记。优选地，被用于定量PCR的探针(特别是如在本文中上文所定义的探针)在报告染料附近的5'末端不具有鸟嘌呤(G)，以便避免在探针降级之后报告荧光的淬灭。
被用于根据本发明的定量PCR方法的分子信标探针优选使用FRET交互来检测和量化PCR产物，每个探针具有5'荧光标记的末端以及3'猝灭剂标记的末端。探针结构的该发夹或茎环配置优选包括具有两个短自我结合末端的茎以及具有约20至30个碱基的长内部目标特异性区域的环。
也可以在本发明的上下文中采用的备选检测机制涉及仅利用环结构制造并且不具有短的互补茎区域的探针。也可以被用于本发明的上下文的定量PCR的备选的基于FRET的方法基于使用两个杂交探针，所述探针结合到目标上的相邻位点，其中，第一探针在3'末端处具有荧光供体标签，并且第二探针在其5'末端处具有荧光受体标签。
在又一实施例中，作为另外的附加步骤，关于癌症的存在或阶段或者癌症的进展的决定可以基于比较步骤的结果。在根据在本文中上文在标记基因或GOI的上下文中所提供的对应定义的所述方法中，可以诊断或预测恶性、激素敏感的前列腺癌，或者这可以诊断或预测朝向(侵袭性)前列腺癌的进展，作为针对恶性前列腺癌的标记。
在另一实施例中，本发明涉及用于检测、诊断、监测或预测(侵袭性)前列腺癌或朝向(侵袭性)前列腺癌的进展的方法，其至少包括以下步骤：
(a)针对GOI表达产物的表达水平，对从怀疑患有前列腺癌的至少一个个体获得的至少一个样本中进行测试；
(b)针对GOI表达产物的表达水平，在至少一个对照样本中进行测试；
(c)确定步骤(a)和(b)的表达中的差异；并且
(d)基于步骤(c)中获得的结果，决定前列腺癌的存在或阶段或者朝向侵袭性前列腺癌的进展。
在一个实施例中，可以在人体或动物体外，例如在从患者或个体获得的样本中，来执行该诊断方法的步骤a)、b)、c)和/或d)。
在另一方面中，本发明涉及用于诊断、监测或预测例如侵袭性的前列腺癌或朝向侵袭性前列腺癌的进展的方法，其中，所述方法区分良性和侵袭性前列腺癌，所述方法包括以下步骤：
(a)确定(一个或多个)标记基因或GOI的水平，
(b)确定样本中的参考基因的表达水平；
(c)将测量到的(一个或多个)标记基因或GOI的表达水平标准化为参考基因的表达；并且
(d)将经标准化的表达水平与被选取用于排除良性前列腺癌的预定截止值进行比较，其中，高于所述截止值的标准化表达水平指示侵袭性前列腺癌，其中，所述截留值在-2和+2之间，优选大约为0。
表达结果可根据本领域技术人员已知的任何合适的方法来标准化。通常，将使用本领域技术人员已知的这种测试或对应的公式来将表达数据进行标准化，以使得能够区分基因表达水平的实际变化与由于测量过程而导致的变化。对于微阵列，可以将鲁棒多阵列平均值(RMA)用作标准化方法。
在特定实施例中，通过应用以下公式来生成标准化值：
N(Cq感兴趣基因)＝Mean(Cq参考基因)–(Cq感兴趣基因)
其中，N(Cq感兴趣基因)是针对所选的感兴趣基因的标准化基因表达值；其中，Mean(Cq参考基因)是参考基因的所选组合的PCR Cq值的算术平均值；其中，(Cq感兴趣基因)是感兴趣基因的PCR Cq值。
在特定实施例中，通过应用以下公式来生成标准化值：
N(Cq感兴趣基因)＝Mean(Cq参考基因)–(Cq感兴趣基因)
其中，N(Cq感兴趣基因)是针对所选感兴趣基因的标准化基因表达值；其中，Mean(Cq参考基因)是选自TBP、HPRT1、ACTB、RPLP0、POLR2A、B2M、PUM1、K-ALPHA-1和ALAS-1中的至少两个参考基因的PCR Cq值的算术平均值；其中，(Cq感兴趣基因)是感兴趣基因的PCR Cq值。
在特定实施例中，通过应用以下公式来生成标准值：
N(Cq感兴趣基因)＝Mean(Cq参考基因)–(Cq感兴趣基因)
其中，N(Cq感兴趣基因)是针对所选感兴趣基因的标准化基因表达值；其中，Mean(Cq参考基因)是参考基因TBP、HPRT1、ACTB和RPLP0的PCR Cq值的算术平均值；其中，(Cq感兴趣基因)是感兴趣基因的PCR Cq值。
在特定实施例中，通过应用以下公式来生成标准化值：
N(Cq感兴趣基因)＝Mean(Cq参考基因)–(Cq感兴趣基因)
其中，N(Cq感兴趣基因)是针对所选感兴趣基因的标准化基因表达值；其中，Mean(Cq参考基因)是参考基因TBP、HPRT1、PUM1、K-ALPHA-1和ALAS-1的PCR Cq值的算术平均值，其中，(Cq感兴趣基因)是感兴趣基因的PCR Cq值。
示例性参考基因尤其包括智人TATA盒结合蛋白(TBP)、智人次黄嘌呤磷酸核糖转移酶1(HPRT1)、智人肌动蛋白，β、mRNA(ACTB)、智人60S酸性核糖体磷蛋白P0 mRNA(RPLP0)、智人山松醇RNA结合组成员1(PUM1)、聚合酶(RNA)II(DNA定向的)多肽A、220kDa(POLR2A)，β-2-微球蛋白(B2M)、微管蛋白-α-1b(K-ALPHA-1)、氨基乙酰丙酸-Δ-合酶(ALAS-1)。
在优选实施例中，参考基因的组合选自TATA盒结合蛋白(TBP)、智人次黄嘌呤磷酸核糖基转移酶1(HPRT1)、智人肌动蛋白、β，mRNA(ACTB)、智人60S酸性核糖体磷蛋白P0 mRNA(RPLP0)、智人山松醇RNA结合族成员(PUM1)、聚合酶(RNA)II(DNA导向的)多肽A、220kDa(POLR2A)、β2-微球蛋白(B2M)、微管蛋白-α-1b(K-ALPHA-1)、氨基乙酰丙酸-Δ-合成酶(ALAS-1)。
在特定实施例中，签名基因的表达水平被标准化为参考基因的表达，其中，参考基因优选为持家基因，并且其中，持家基因优选为TBP、HPRT1、ACTB、RPLP0、PUM1、POLR2A或B2M。
在另一优选实施例中，参考基因的组合包括TBP、HPRT1一级从包括ACTB、RPLP0、PUM1、POLR2A、B2M、K-ALPHA-1(TUBA1B)或ALAS-1的组中选择的至少一个、至少两个或者至少三个额外的参考基因。
在另一优选实施例中，参考基因的组合包括TBP、HPRT1一级从包括ACTB、RPLP0、PUM1、K-ALPHA-1(TUBA1B)或ALAS-1的组中选择的至少两个额外的参考基因。
特别优选的组合是TBP、HPRT1、ACTB、RPLP0。另一特别优选的组合是TBP、HPRT1、PUM1、K-ALPHA-1、ALAS-1。
在图10中公开了对参考基因的详细描述，所述包括其对应的核苷酸序列的转录物ID(NCBI RefSeq)和SEQ ID NO、对应氨基酸序列的蛋白质ID(蛋白质加入)和SEQ ID NO。此外，图10公开了针对每个参考基因的用于生成针对参考基因特异性的扩增子的正向引物、反向引物以及特异性地结合扩增子的探针序列。如在本文中上文所描述的，可以在核苷酸上确定(一个或多个)标记基因或GOI的表达水平。优选的是确定(一个或多个)标记基因或GOI转录物的表达水平。另外，可以确定样本中的持家基因的水平。
如在本文中所使用的，术语“参考基因”指代任何合适的基因，例如，指代在选择的生物体中稳定表达和可连续检测的基因、基因产物、表达产物、蛋白质或蛋白质变体。
所述表达优选可以在相同的样本中执行，即，在相同的样本中确定(一个或多个)标记基因或GOI的水平以及参考基因的水平。如果在相同的样本中执行所述测试，则可以执行如在本文中所描述的单个检测或多路复用检测方法。为了执行多路复用检测，可以修改引物和/或探针寡核苷酸的浓度。此外，可以修改如缓冲剂、离子等的其他成分的浓度和存在，与制造商的指示相比被上调或下调或下降。
此外，表达结果可以与来自参考案例或数据库的已知结果进行比较。所述比较可以额外地包括标准化过程，以便提高结果的统计相关性。
可以根据本领域技术人员已知的任何合适的方法对表达结果进行标准化，例如，根据如标准分数、学生T测试、学生化残差测试、标准化时刻文本或系数变异测试等的标准化统计学方法。通常，将使用本领域技术人员已知的这种测试或对应的公式来将表达数据标准化，以使得能够在基因表达水平的实际变化与由于测量过程而导致的变化进行区分。
基于在步骤(a)和(b)中获得的表达结果和/或在步骤(c)中获得的标准化结果，可以执行与针对GOI表达水平的截止值的比较。(一个或多个)标记基因或GOI的表达水平在所述截止值之上表示侵袭性前列腺癌，由此排除良性前列腺癌形式或健康情况或健康组织形式，所述截止值在约-3和+3之间、-3和+2.75之间、-3和+2.5之间、-3和+2.25之间、-3和+2之间、-3和+1.75之间、-3和+1.5之间、-3和+1.25之间、-3和+1之间、-3和+0.75之间、-3和+0.5之间、-3和+0.25之间、-3和0之间、-2.75和+3之间、-2.5和+3之间、-2.25和+3之间、-2和+3之间、-1.75和+3之间、-1.5和+3之间、-1.25和+3之间、-1和+3之间、-0.75和+3之间、-0.5和+3之间、-0.25和+3之间、或者0和+3之间。更优选的是截止值大约为0，例如，0.9、0.8、0.7、0.6、0.5、0.4、0.3、0.2、0.1或者-0.9、-0.8、-0.7、-0.6、-0.5、-0.4、-0.3、-0.2或-0.1。
如果测量的和/或标准化的表达水平低于所指示的截止值，则这可以被看作是指示个体对于前列腺癌是健康的，或者仅患有良性前列腺癌，而不是侵袭性前列腺癌。
在另一方面中，本发明涉及一种数据采集方法，至少包括以下步骤：
(a)针对(一个或多个)标记基因或GOI的表达在个体中进行测试；并且
(b)将在步骤(a)中确定出的表达与对照水平进行比较。可以根据如在本文中上文所定义的步骤执行针对(一个或多个)标记基因或GOI的表达的测试。优选地，可以将测试作为对(一个或多个)标记基因或GOI的核酸的测量来执行。所述测试可以在个体中执行，即，在体内执行；或者在个体外部执行，即，离体或体外地执行。在数据采集的方法的上下文中所使用的术语“对照水平”指代如在本文中上文所定义的在本文中所提及的标记基因的表达或者在正常对照或癌性对照中的其他合适标记的表达。所述对照水平的状态、性质、数量和状况可以根据需要进行调整。优选地，可以使用正常、健康的对照水平。表达与对照水平的比较可以根据估计、计算、评估或处理数据的任何合适的方法来执行，并且特别旨在检测两个数据集之间的差异。可以进一步执行对差异的显著性的统计学评估。合适的统计学方法是本领域技术人员已知的。所获得的数据和信息可以通过本领域技术人员已知的合适的信息学或计算机方法或工具来存储、积累或处理，和/或以适当的方式来呈现，以允许从业者将数据用于一个或多个后续推论或结论步骤。
另外，可以确定样本中如在本文中上文所定义的参考基因的水平。备选地，可以利用任何其他合适的试剂来执行对参考基因的确定，或者所述确定可以与如在本文中所述的对核酸的存在或量的检测相组合地执行。
在另外的方面中，本发明涉及识别适合于前列腺癌治疗的个体的方法，包括：
(a)在从个体获得的样本中针对(一个或多个)标记基因或GOI表达进行测试；
(b)针对参考基因的表达在所述样本中进行测试和/或针对(一个或多个)标记基因或GOI的表达在对照样本中进行测试；
(c)将步骤(a)的表达的水平相对于步骤(b)的水平进行分类，并计算各自的PCPI；
(d)将所述个体识别为适合于接收前列腺癌疗法，其中，所述个体的样本被分类为具有上调或下调水平的(一个或多个)标记基因或GOI表达水平或者指示侵袭性疾病的PCPI。
如在本文中所使用的，术语“相对于步骤(b)的水平对步骤(a)的表达水平进行分类”意指将在测试样本中针对GOI的表达与在对照样本中针对GOI的表达进行比较，例如，在相对于适合的标准化参考进行标准化之后和/或在计算相应的PCPI之后。
根据对PCPI的计算，当基因表达水平与对照样本相比显著不同时，可认为个体适合于前列腺癌治疗。
如在本文中所使用的术语“将个体或个体的群组分级为前列腺癌疗法”意指个体被识别为属于一组相似的个体，其最佳疗法形式是前列腺癌疗法，例如，根据如在本文中上文所描述的对PCPI的计算的结果的疗法。
被认为适合于进行前列腺癌治疗或者被分级至如在本文中上文所描述的前列腺癌疗法的个体可以接收针对本领域技术人员已知的这种前列腺癌形式的任何合适的治疗性处置。具体地，如在本文中所使用的术语“前列腺癌疗法”指代本领域技术人员已知的任何适合的前列腺癌疗法，并且优选包括通过移除作为雄性性激素产物的主要器官的睾丸的手术去势，通过例如抑制雄性激素的生成或者通过禁止雄性激素受体活动的化学去势，细胞毒素，化学疗法，放射疗法(外部束放射疗法、近距离放射疗法)，冷冻疗法，局部疗法如HIFU消融(高频超声消融)，或热消融或者其组合，优选激素疗法和放射疗法的组合。
通常，被认为适合于进行前列腺癌治疗的个体可能被认为患有(侵袭性)前列腺癌，或者在将来易患这种疾病，例如在接下来的1至24个月内。对应地识别的或分级的个体可以利用抑制性药物复合物治疗。在另外的实施例中，对应地识别的个体可以利用抑制性药物复合物与额外的癌症疗法相组合来处置。术语“额外的癌症疗法”指代本领域技术人员已知的任何类型的癌症疗法。优选的是已知用于前列腺癌的癌症疗法形式。例如，该术语包括所有适合形式的化学疗法、放射疗法、手术、抗体疗法等。
备选地，对应地识别的或分级的个体也可以仅利用一种或多种癌症疗法进行治疗，诸如化学疗法、放射疗法、手术、抗体疗法等。优选的是通常用于前列腺癌的癌症疗法，更优选的是被用于侵袭性前列腺癌的癌症疗法。
在本发明的另外实施例中，如在本文中上文所描述的针对适用性或者针对分级的分类方法也可以被用于监测对个体的处置，例如，被分类为患有侵袭性前列腺癌的个体。所述监测过程可以在延长的时间段期间作为表达确定来执行，例如，在处置会话期间或之后，在1、2、3、4、5、6、7、8、9、10周，1、2、3、4、5、6、7、8、9、10个月，或者1、2、3年或更长期间。可以以适当的间隔来执行确定步骤，例如，每周、2周、3周、每个月、2个月、3个月、6个月、12个月等。在本发明的另外的实施例中，可以调整在本文中上文所提到的任何治疗方案，例如根据监测过程的结果以任何适当的方式强制或减弱或改变。
在本发明的另外的实施例中，基于如在本文中上文所描述的(一个或多个)标记基因或GOI的表达以及对应的PCPI来识别适合于进行侵袭性前列腺癌治疗个体的方法还可以基于一种或多种不同生物标记的表达而与一种或多种类似识别方法相组合。优选的是确定血液中前列腺特异性抗原(PSA)的水平。因此，如果血液中的PSA水平遇到约2至5或更多ng/ml的范围，优选约2.2至4.8ng/ml或更多的范围，2.4至4.4ng/ml或更多的范围，1.6至4.2ng/ml或更多的范围，或者2.8-4.0ng/ml或更多的范围，更优选约2.5-4ng/ml或更多的范围，则个体可被认为患有恶性前列腺癌，或者可能在不久的将来发展为恶性前列腺癌，即，在接下来的1、2、3、4、5、6、12、14、48个月之内。针对(一个或多个)标记基因或GOI表达的测试以及对PCPI的确定可以根据如在本文中上文所定义的步骤来执行。
在本发明的优选实施例中，如上文所提及的诊断、检测、监测或预测是在从个体获得的样本上执行的。如在本文中所使用的术语“从个体获得的样本”涉及经由本领域技术人员已知的适合的方法从个体获得的任何生物材料。在本发明的上下文中使用的样本应当优选以临床上可接受的方式收集，更优选以保留核酸(特别是RNA)或蛋白质的方式收集。
生物学样本可以包括身体组织和流体，例如血液、汗液和尿液。此外，生物学样本可以包含来源于上皮细胞或包括上皮细胞的细胞群体的细胞提取物，优选是癌性上皮细胞或来源于疑似为癌性的组织的上皮细胞。甚至更优选地，生物学样本可以包含来源于腺体组织的细胞群体，例如，样本可能来源于男性个体的前列腺。另外，如果需要，细胞可以从所获得的身体组织和流体中纯化，并且然后被用作生物学样本。
可以池化样本，尤其是在初始处理之后。然而，也可以使用非池化的样本。
在本发明的特定实施例中，生物学样本的内容也可以被提交至富集步骤。例如，样本可以与针对特定细胞类型的细胞膜或细胞器(例如，前列腺细胞)特异性的配体相接触，例如利用磁性颗粒进行功能化。随后，可以将由磁性颗粒浓缩的材料用于如在本文中上文或下文所描述的检测和分析的步骤。
在本发明的特定实施例中，可以获得和/或使用活组织检查或移除样本。这样的样本可以包括细胞或细胞裂解物。
此外，可以经由流体或液体样本(例如，血液、尿液等)的过滤过程来富集细胞(例如，肿瘤细胞)。这样的过滤过程也可以与基于如在本文中上文所描述的配体特异性交互的富集步骤相组合。
在本发明的特别优选的实施例中，样本可以是组织样本、活组织检查样本、尿液样本、尿液沉淀物样本、血液样本、唾液样本、精液样本、包括循环肿瘤细胞的样本、或者包含前列腺分泌的外泌体的样本。血液样本例如可以是血清样本或血浆样本。
在对前列腺癌的处置中，能够使用对癌细胞具有活性抵抗的化合物或药物复合物。所述药物复合物可以包括激素抑制剂，优选抗雄性激素或雄性激素拮抗剂，如螺内酯、醋酸环丙孕酮、氟他胺、尼鲁米特、比卡鲁胺、酮康唑、非那雄胺或度他雄胺。
在另外的特定实施例中，本发明设想了一种监测前列腺癌发展的方法，其涵盖确定(一个或多个)标记基因或GOI，优选与如在本文中上文所描述的确定参考基因相结合，在特定时间段内，即，在重复的确定步骤之后，例如，每4周、6周、两个月、4个月、6个月、8个月、12个月、1.5年、2年、2.5年、3年、4年或任何其他合适的时间段等。所述方法可以提供以下数据，所述数据示出了(一个或多个)标记基因或GOI的水平相较于对照(例如，非癌性对照、癌性对照或者从相同个体获得的早期数据)的增加或降低。借助于本领域技术人员已知的适合的统计学方法，可以确定所述曲线内的位置。根据所述曲线内的位置，即，在所述曲线的增大部分或下降部分中，可以诊断存在或将来发展的前列腺癌。相应地，设想到了使用药物复合物。优选地，任何这样的确定可以与次级生物标记的确定相结合，例如，针对前列腺癌的标记，特别是PSA。在低PSA水平(达2.0-4.0ng/ml)的情况下，可以相对于早期前列腺癌，即良性或激素依赖性/激素敏感的前列腺癌来分析GOI数据。在较高PSA水平(高于约20ng/ml，例如约30、40或50ng/ml)的情况下，可以相对于更晚期的前列腺癌(例如，激素抵抗的前列腺癌)来分析所述数据。
如在本文中所使用的“激素敏感的阶段I至IV前列腺癌”表示能够根据国际抗癌联盟(UICC)的TNM分类分为阶段I至IV的前列腺癌。
如在本文中所使用的“激素敏感的复发性前列腺癌”表示其生长和进展被调节并依赖于男性性激素的前列腺癌。这种男性性激素的优选范例是雄性激素。
如在本文中所使用的“激素敏感的转移性前列腺癌”表示其生长和进展被调节并依赖于男性性激素的前列腺癌。这种男性性激素的优选范例是雄性激素。
如在本文中所使用的“激素不敏感前列腺癌”表示其生长和进展不被调节并且独立于男性性激素的前列腺癌。这种男性性激素的优选范例是雄性激素。
本发明的另一方面涉及一种计算机程序产品，其包括被存储在计算机可读介质上或者能从通信网络下载的计算机可读代码，所述计算机可读代码在计算机上运行时实施在本文中上文所描述的任何一种方法的一个或多个步骤或所有步骤。
可以利用一个或多个计算机可读介质的任何组合。所述计算机可读介质可以是计算机可读信号介质或计算机可读存储介质。计算机可读存储介质例如可以是但不限于电子的、磁的、光学的、电磁的、红外的或半导体的系统、装置或设备，或者前述的任何合适的组合。计算机可读存储介质的更具体的范例(非穷举列表)包括以下项：具有一条或多条线的电连接、便携式计算机磁盘、硬盘、随机存取存储器(RAM)、只读存储器(ROM)、可擦除可编程只读存储器(EPROM或闪存)、光纤、、便携式压缩盘只读存储器(CD-ROM)、光学存储设备、磁存储设备、或者前述任何适当的组合。在本文档的上下文中，计算机可读存储介质可以是任何有形介质，其能够包含或存储由指令执行系统、装置或设备使用或者与其结合使用的程序。
计算机可读信号介质可以包括在其中体现计算机可读程序代码的传播的数据信号，例如，在基带中或者作为载波的一部分。这样的传播的信号可以采取多种形式中的任意形式，其包括但不限于：电磁、光学或者其任何适当的组合。计算机可读信号介质可以是计算机可读存储介质之外的任何计算机可读介质，并且其能够通信、传播或传输供指令执行系统、装置或设备使用或与其结合使用的程序。
体现在计算机可读介质上的程序代码可以使用任何适当的介质来传输，所述介质包括但不限于：无线、有线、光缆、RF等，或者前述的任何适当的组合。
用于执行针对本发明的各方面的操作的计算机程序代码可以以一种或多种编程语言的任何组合来编写，所述语言包括：面向对象编程语言，诸如Java、Smalltalk、C++等；以及常规程序编程语言，例如“C”编程语言或类似的编程语言。程序代码可以完全在用户的计算机上、部分在用户的计算机上作为独立的软件包、部分在用户的计算机上以及部分在远程计算机上、或者全部在远程计算机或服务器上执行。在后一种场景中，所述远程计算机可以通过任何类型的网络(包括局域网(LAN)或广域网(WAN))被连接到用户的计算机，或者可以被连接到外部计算机(例如，通过使用互联网服务提供商的互联网)。
这些计算机程序指令还可以被存储在计算机可读介质中，其能够指导计算机、其他可编程数据处理装置或其他设备以特定方式运行，使得被存储在计算机可读介质中的指令产生包括实施在本文中所指定的功能/动作的指令的制品。
所述计算机程序指令也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，以使得在计算机、其他可编程装置或其他设备上执行一系列操作步骤来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执行的指令提供用于实施在本文中所指定的功能/动作的过程。
除非另外地定义，否则在本文中所使用的所有技术和科学术语具有与本发明所属领域的普通技术人员通常理解的相同的含义。
下面的范例和附图是为了例示说明的目的而提供的。因此，应当理解，范例和附图不应当被解释为限制性的。本领域技术人员将能够清楚地设想到对在此阐述的原理的进一步修改。
范例
范例1-用于构建前列腺癌预后指数(PCPI)的基因选择
为了选择基因候选以构建PCPI，如在WO2010131194和WO2010131195中所描述的，针对推定的预后基因标记PDE4D7的相关性研究了各种分子路径，如在http://csbi.ltdk.helsinki.fi/anduril/tcga-gbm/table4_2.html中所概述的。示出了显著相关性的那些分子路径被选择用于下游分析(图1)。
此外，从以下文献中选择与转移性和/或激素难治性前列腺癌相关的基因候选：
-Gorlov IP等人，Candidate pathways and genes for prostate cancer:ameta-analysis of gene expression data；BMC Medical Genomics 2009，2:48
-Stanbrough M等人：Increased Expression of Genes Converting AdrenalAndrogens to Testosterone in Androgen-Independent Prostate Cancer；Cancer Res2006；66:2815-2825
-Tamura K等人，Molecular Features of Hormone-Refractory ProstateCancer Cells by Genome-Wide Gene Expression Profiles；Cancer Res 2007；67(11):5117-25
-Lapointe J等人，Gene expression profiling identifies clinicallyrelevant subtypes of prostate cancer；PNAS 2003；101(3):8110816
-Sun Y等人，Optimizing Molecular Signatures for Predicting ProstateCancer Recurrence。Prostate，69:1119-1127(2009)
总共选择了(参见图1)被报道可能与前列腺癌进展有关的967个基因以供将来的分析。
为了构建19-基因预后签名，即，一组感兴趣标记基因，使用以下数据集：
-Taylor BS等人，Integrative Genomic Profiling of Human ProstateCancer。Cancer Cell 18，11-22，2010(GEO数据集ID:GSE21032)
-Boormans JL等人，Identification of TDRD1 as a direct target gene ofERG in primary prostate cancer。Int J Cancer 2013年7月15日；133(2):335-45(GEO数据集ID:GSE41408)
-Sun Y等人，Optimizing Molecular Signatures for Predicting ProstateCancer Recurrence。The Prostate，69:1119-1127(2009)(GEO数据集ID：GSE25136)
-Sboner A等人，Molecular sampling of prostate cancer:a dilemma forpredicting disease progression。BMC Medical Genomics 2010，3:8(GEO数据集ID：GSE16560)
-Nagakawa等人，A Tissue Biomarker Panel Predicting SystemicProgression after PSA Recurrence Post-Definitive Prostate Cancer Therapy。PLoSONE 3(5)，e2318(2010)(GEO数据集ID：GSE10645)
为了进一步测试和验证所构建的前列腺癌预后指数(PCPI)，使用以下数据集：
Erho N等人，Discovery and Validation of a Prostate Cancer GenomicClassifier that Predicts Early Metastasis Following Radical Prostatectomy。PLoS One 8(6)，e66855(2013)(GEO数据集ID：GSE46691)
对GSE基因表达数据的处理
各自的CEL文件从GEO(基因表达综合数据库)下载：http://www.ncbi.nlm.nih.gov/geo/。CEL文件数据被上传到表达控制台(Affymetrix Inc；Build1.3.1.187)中，并且在适当的情况下使用由Affymetrix Inc.提供的适当的探针组注释文件(即，在Affymetrix Inc平台上运行的数据集：GSE21032、GSE41408、GSE25136)进行预处理。针对在DASL平台上运行的数据集(即，GSE16560、GSE10645)，使用如由GEO提供的数据序列矩阵文件进行下游数据分析。
参考基因被怀疑具有独立于被处理的样本的稳定表达，并且因此能够被用作内部标准以对PCR分析的输出Cq值进行标准化，从而使结果可比较地独立于所使用的输入样本的量。尽管这样的基因被认为是稳定的，但是在其表达中始终存在一些变异，并且该稳定性也能够取决于被分析的组织。出于这样的原因，建议在对PCR Cq值的标准化中使用多于一个的参考基因，并且使用在被分析的特定类型的组织/样本中呈现低变异性的一组基因(C.L.Andersen，JL Jensen和TF
Figure GDA0003695866600000651
“Normalization of Real-Time QuantitativeReverse Transcription-PCR Data:A model-based Variance Estimation Approach toIdentify Genes Suited for Normalization,Applied to Bladder and Colon CancerData Sets”，Cancer Res.，第64卷，第15期，第5245-5250页，2004年8月；J.Vandesompele，K.De Preter，F.Pattyn，B.Poppe，N.Van Roy，A.De Paepe和F.Speleman，“Accuratenormalization of real-time quantitative RT-PCR data by geometric averaging ofmultiple internal control genes”，Genome Biol.，第3卷，第7期，p.RESEARCH0034，2002年6月)。
执行在本研究中所使用的9个参考基因的初始选择。通过在所有经分析的临床样本上运行Biogazelle Software工具(qBase+with GeNorm analysis J.Hellemans,G.Mortier,A.D.Paepe,F.Speleman,and J.Vandesompele,“qBase relativequantification framework and software for management and automated analysisof real-time quantitative PCR data,”Genome Biol.，第8卷，第2期，p.R19，2007年2月)，进行对用于标准化的参考基因组的最终选择。
PCR测定的输出Cq值本质上是对数的(底数为2)，并且与样本中存在的mRNA的量成反比。我们使用下面的公式来标准化原始的Cq值：
N(Cq感兴趣基因)＝Mean(Cq参考基因)–(Cq感兴趣基因)
其中，N(Cq感兴趣基因)是针对所选感兴趣基因的标准化基因表达值；其中，Mean(Cq参考基因)是所选参考基因组合的PCR Cq值的算术平均值；其中，(Cq感兴趣基因)是感兴趣基因的PCR Cq值。
在使用除qRT-PCR之外的其他技术来测量参考基因或感兴趣基因的表达的情况下，PCR Cq值将被相应技术的标准化测量结果来替代(例如，针对DNA微阵列的RMA(鲁棒多阵列平均值)标准化基因表达值，或者针对RNA测序的FPKM(每映射的百万片段的外显子的每千碱基的片段)标准化基因表达值)。
前列腺癌进展指数(PCPI)的计算
与在初级处置之后具有或没有进展的患者组之间上调相比，选定的感兴趣基因(GOI)被分组为在初级处置之后具有或没有进展的患者组之间被下调。从每个分析的患者样本的标准化基因表达数据计算针对下调基因的平均基因表达值(GEV_av_GOI_down)以及针对上调基因的平均基因表达值(GEV_av_GOI_up)。每个患者样本的前列腺癌进展指数PCPI被确定为：
PCPI＝(GEV_av_GOI_up)-(GEV_av_GOI_down)
所计算的PCPI被用于任何进一步的统计学数据分析。
PCPI_17计算(基于定量实时PCR数据)
使用以下公式计算PCPI：
PCPI＝Mean(N(CqPCPI基因上调))–Mean(N(CqPCPI基因下调))
其中，
Mean(N(CqPCPI基因上调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：BGN、BIRC5、COL1A1、COL3A1、COL5A2、DYRK2、INHBA、THBS2和VCAN
并且其中，
Mean(N(CqPCPI基因下调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4和SRD5A2。
PCPI_18计算(基于定量实时PCR数据)
使用以下公式来计算PCPI：
PCPI＝Mean(N(CqPCPI基因上调))–Mean(N(CqPCPI基因下调))
其中，
Mean(N(CqPCPI基因上调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：BGN、BIRC5、COL1A1、COL3A1、COL5A2、DYRK2、INHBA、THBS2和VCAN
并且其中，
Mean(N(CqPCPI基因下调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：PDE4D、AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4和SRD5A2
PCPI_19计算(基于定量实时PCR数据)
使用以下公式来计算PCPI：
PCPI＝Mean(N(CqPCPI基因上调))–Mean(N(CqPCPI基因下调))
其中，
Mean(N(CqPCPI基因上调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：BGN、BIRC5、COL1A1、COL3A1、COL5A2、DYRK2、INHBA、THBS2和VCAN
并且其中，
Mean(N(CqPCPI基因下调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：PDE4D5、PDE4D7、AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4和SRD5A2。
前列腺癌进展指数(PCPI)与临床参数对患者结果的相关性分析
利用XLSTAT版本2014.1.03执行对PCPI的所有统计学分析(例如，逻辑回归分析、ROC分析、COX回归分析等)以及其和患者结果的相关性与临床参数(如PSA、pGleason、pT阶段)的比较。
结果
针对以上基因表达数据集中的不同表达，在初级处置之后没有显示其疾病的进展的前列腺癌患者与那些显示了下列临床终点中任一个的疾病进展的患者组之间，研究了967个选定基因候选，所述临床终点为：生化复发、通过检测局部或远处转移的临床复发、前列腺癌特异性死亡。
表2(参见图2)提供了57个选定基因的概述，所述基因被发现显著(p<0.05)差异地表达，并且五个测试数据集中的至少三个中的上文所提到的患者组之间在相同方向上(即，上调或下调)的患者组之间进行调节。随后，根据以下标准将基因分为三类：
Rank_3：在最大3个数据集中观测到的在相同方向上以显著的p值(p<0.05)差异地表达的所有基因，或者具有非独特注释的基因
Rank_2：在4个或5个数据集中观测到的在相同方向上以显著的p值(p<0.05)差异地表达的所有基因
Rank_1：在4或5个数据集中观测到的在相同方向上以显著p值(p<0.05)差异地表达的所有基因，但限于上调的9个基因和下调的10个基因。
优选的PCPI签名包括以下19个基因或者由其组成：PDE4D5、PDE4D7、AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2。
由于并非所有数据集都提供关于PDE4D异构体(即，PDE4D5和PDE4D7)的转录水平的信息，所以经证实的结果基于PDE4D基因的测量结果，因为在数据集GSE21032和GSE41408中PDE4D的表达与PDE4D7的表达非常相关(标准化为PDE4D5的表达)；因此，所确定的PCPI_18包括以下18个基因：PDE4D、AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、INHBA、THBS2、VCAN、BGN、BIRC5、DYRK2。
针对其中未测量PDE4D基因的这样的数据集(即，GSE16560、GSE10645)，所确定的PCPI_17包括以下17个基因：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、INHBA、THBS2、VCAN、BGN、BIRC5、DYRK2。
前列腺癌患者在初级处置之后PCPI与临床结果数据的相关性
表3(参见图3)示出了关于PCPI_18或PCPI_17的性能的概述，以针对数据集GSE21032、GSE41408、GSE25136、GSE16560、GSE10645来预测在初级处置(通常是前列腺疗法)之后10-15年内远处转移的发展的初级终点。针对在数据集GSE16560中研究的患者，在TURP(经尿道移除术)期间检测到前列腺癌，并且随后保守地管理患者(即，不移除前列腺)。针对在数据集GSE10645中研究的患者，针对终点对患者的监测仅在生化复发之后开始。这些数据集被用于构建PCPI签名(训练数据)。示出了每组患者的数量(无进展与进展至转移)以及来源于ROC分析的AUC(曲线下面积)。AUC指示不同数据集中PCPI的相对功率以预测群组内的初级终点。
表4(参见图4)示出了PCPI_18的性能，以针对数据集GSE46691来预测在初级处置之后10-15年内远处转移的发展的初级终点；该数据集不被用于训练PCPI，而是被用作独立的验证数据集(验证数据)。针对在数据集GSE10645中研究的患者，针对终点对患者的监测仅在生化复发之后开始。示出了每组患者的数量(无进展与进展至转移)以及来源于ROC分析的AUC(曲线下面积)。AUC指示不同数据集中PCPI的相对功率，以预测群组内的初级终点。
表5(参见图5)示出了PCPI_18或PCPI_17的性能，以针对数据集GSE21032、GSE41408、GSE16560、GSE10645，与标准临床参数(如治疗前PSA，活组织检查或病理学Gleason分数，或临床/病理学疾病阶段)相比，在多变量COX回归分析中预测在初级处置(通常是前列腺疗法)之后10-15年内发生远处转移的初级终点。针对每个个体数据集示出了卡方以及PCPI的危险比和个体临床参数。
表6(参见图6)示出了PCPI_18的性能的概况，以针对数据集GSE21032、GSE41408、GSE25136预测在初级处置(通常是前列腺疗法)后10-15年内生化疾病复发(BCR)发展的初级终点。示出了每组患者的数量(没有进展与进展至BCR)以及来源于ROC分析的AUC(曲线下面积)。AUC指示不同数据集中PCPI的相对功率以预测群组内的初级终点。
表7(参见图7)示出了PCPI_18的性能，以针对数据集GSE21032、GSE41408、GSE25136，与标准临床参数(如治疗前PSA，活组织检查或病理学Gleason分数，或临床/病理学疾病阶段)相比，在多变量COX回归分析中预测在初级处置(通常是前列腺疗法)之后10-15年内发生生化疾病复发(BCR)的发展的初级终点。针对每个个体数据集示出了卡方以及PCPI的危险比和个体临床参数。
表8(参见图8)示出了PCPI_18的ROC曲线截止分析，以支持针对主动监管(AS)或主动治疗(例如，前列腺移除术、放射疗法、激素疗法)的患者分级的临床决策。表中所示的截止值选自ROC曲线，从而具有侵袭性疾病的>90％男性被正确分类(对应于90％的敏感性)。该截止值允许将具有非常低风险谱的134的分级到例如主动监管而不是例如手术。该群组中无进展生存到超过约10年随访的转移性疾病的终点接近85％。将相同的方法应用于临床模型(病理学Gleason分数)，结果是Gleason分数<＝6的截止将导致仅有57名男性分级到例如主动监管而不是例如手术。在该患者群组中的无进展生存将接近90％，但代价是许多具有非进展疾病的男性将被分级至例如手术；与病理学Gleason分数相比，使用PCPI_18分级的人数是AS的两倍多，而风险谱非常相似(分别为85％和90％无进展生存)。通过PCPI_18和病理学Gleason的组合模型可以进一步增加分级的能力。使用该模型，146名男性(相比于134名)将被分级至AS，在超过10年内无进展生存概率约为87％。
针对所显示的患者群组的截止分析是针对总群组(545名患者)、病理学Gleason分数>＝7的子群组(482名患者)、以及病理学Gleason分数>＝8的另一子群组(211名患者)来执行的。
图11、12和13涉及根据研究获得的分析，该分析对约500位患者执行纵向随访，与PCPI_19(图11)的性能相比，来源于RNAseq数据的GPSu得分分析12种癌症相关基因和5种参考基因的表达，并且按照该方法进行计算，所述方法能够从Dejan Knezevic等人的文章“Analytical validation of the Oncotype DX prostate cancer assay-a clinicalRT-PCR assay optimized for prostate needle biopsies”，BMC Genomics(2013)，14:690(图12)中推断出，并且CCP分数来源于31个基因的表达水平，并且被计算，其能够从JackCuzick等人的文章“Prognostic value of an RNA expression signature derived fromcell cycle proliferation genes for recurrence and deathe from prostatecancer:A retrospective study in two cohorts”，Lancet Oncol.(2011)；12(3):245-255(图13)推断出。
为了更好地比较，GPSu和CCP得分已经被缩放到1到5之间的范围。
图11、12和13示出了根据不同的患者组的5年或10年的不同复发风险(参见以下描述)。在X轴上，通过NCCN风险组定义了患者组；VL&LR＝非常低和低风险；FIR＝有利的中间风险；UIR＝不利的中间风险；HR＝高风险。NCCN是美国常用的肿瘤学指南(https://www.nccn.org/professionals/physician_gls/f_guidelines.asp)。在y轴上，通过4类不同分数对患者组进行定义：1-2；2-3；3-4和4-5。在4x4网格中，根据其NCCN临床风险特性并且根据其针对PCPI、GPSu或CCP的分数，针对网络的任何细胞来选择患者。根据临床风险组(最下面一行)或者根据分数类别(表格右侧栏)来计算不同的风险。为了清楚起见，在细胞内仅描绘了5年的BCR复发风险。
风险描述是：
5年BCR-5年以上生化复发
10年CR-10年以上临床复发转移
10年PCSM-10年以上前列腺癌特异性死亡率
10年OM-10年以上总体死亡率(由于所有原因)
图11、12和13中下划线的数字表示与其他签名相比改善性能的PCPI的区域。与积极治疗的临床决策相比，属于这些类别的患者是积极监管的潜在患者，因此应当具有尽可能小的复发风险。PCPI在这些领域胜过其他签名。
序列表
<110> 皇家飞利浦有限公司
<120> 前列腺癌预后的方法
<130> P14144 2014PF00611
<160> 204
<170> PatentIn version 3.5
<210> 1
<211> 7979
<212> DNA
<213> Homo sapiens
<400> 1
cagcagcagg ctcagacctg cttccctgga catttccggg accgtgagcg agggaaccac 60
gttgccctgg attcttgcca gctgtacaaa gttgaccagg aaaatggctc agcagacaag 120
cccggacact ttaacagtac ctgaagtgga taatccgcat tgtccaaacc cgtggctgaa 180
cgaagacctt gtgaaatcct tgcgagaaaa cctgttgcag catgagaagt ccaagacagc 240
gaggaaatcg gtttctccca agctctctcc agtgatctct ccgagaaatt cccccaggct 300
tctgcgcaga atgcttctca gcagcaacat ccccaaacag cggcgtttca cggtggcaca 360
tacatgtttt gatgtggaca atggcacatc tgcgggacgg agtcccttgg atcccatgac 420
cagcccagga tccgggctaa ttctccaagc aaattttgtc cacagtcaac gacgggagtc 480
cttcctgtat cgatccgaca gcgattatga cctctctcca aagtctatgt cccggaactc 540
ctccattgcc agtgatatac acggagatga cttgattgtg actccatttg ctcaggtctt 600
ggccagtctg cgaactgtac gaaacaactt tgctgcatta actaatttgc aagatcgagc 660
acctagcaaa agatcaccca tgtgcaacca accatccatc aacaaagcca ccataacaga 720
ggaggcctac cagaaactgg ccagcgagac cctggaggag ctggactggt gtctggacca 780
gctagagacc ctacagacca ggcactccgt cagtgagatg gcctccaaca agtttaaaag 840
gatgcttaat cgggagctca cccatctctc tgaaatgagt cggtctggaa atcaagtgtc 900
agagtttata tcaaacacat tcttagataa gcaacatgaa gtggaaattc cttctccaac 960
tcagaaggaa aaggagaaaa agaaaagacc aatgtctcag atcagtggag tcaagaaatt 1020
gatgcacagc tctagtctga ctaattcaag tatcccaagg tttggagtta aaactgaaca 1080
agaagatgtc cttgccaagg aactagaaga tgtgaacaaa tggggtcttc atgttttcag 1140
aatagcagag ttgtctggta accggccctt gactgttatc atgcacacca tttttcagga 1200
acgggattta ttaaaaacat ttaaaattcc agtagatact ttaattacat atcttatgac 1260
tctcgaagac cattaccatg ctgatgtggc ctatcacaac aatatccatg ctgcagatgt 1320
tgtccagtct actcatgtgc tattatctac acctgctttg gaggctgtgt ttacagattt 1380
ggagattctt gcagcaattt ttgccagtgc aatacatgat gtagatcatc ctggtgtgtc 1440
caatcaattt ctgatcaata caaactctga acttgccttg atgtacaatg attcctcagt 1500
cttagagaac catcatttgg ctgtgggctt taaattgctt caggaagaaa actgtgacat 1560
tttccagaat ttgaccaaaa aacaaagaca atctttaagg aaaatggtca ttgacatcgt 1620
acttgcaaca gatatgtcaa aacacatgaa tctactggct gatttgaaga ctatggttga 1680
aactaagaaa gtgacaagct ctggagttct tcttcttgat aattattccg ataggattca 1740
ggttcttcag aatatggtgc actgtgcaga tctgagcaac ccaacaaagc ctctccagct 1800
gtaccgccag tggacggacc ggataatgga ggagttcttc cgccaaggag accgagagag 1860
ggaacgtggc atggagataa gccccatgtg tgacaagcac aatgcttccg tggaaaaatc 1920
acaggtgggc ttcatagact atattgttca tcccctctgg gagacatggg cagacctcgt 1980
ccaccctgac gcccaggata ttttggacac tttggaggac aatcgtgaat ggtaccagag 2040
cacaatccct cagagcccct ctcctgcacc tgatgaccca gaggagggcc ggcagggtca 2100
aactgagaaa ttccagtttg aactaacttt agaggaagat ggtgagtcag acacggaaaa 2160
ggacagtggc agtcaagtgg aagaagacac tagctgcagt gactccaaga ctctttgtac 2220
tcaagactca gagtctactg aaattcccct tgatgaacag gttgaagagg aggcagtagg 2280
ggaagaagag gaaagccagc ctgaagcctg tgtcatagat gatcgttctc ctgacacgta 2340
acagtgcaaa aactttcatg cctttttttt ttttaagtag aaaaattgtt tccaaagtgc 2400
atgtcacatg ccacaaccac ggtcacacct cactgtcatc tgccaggacg tttgttgaac 2460
aaaactgacc ttgactactc agtccagcgc tcaggaatat cgtaaccagt tttttcacct 2520
ccatgtcatc cgagcaaggt ggacatcttc acgaacagcg tttttaacaa gatttcagct 2580
tggtagagct gacaaagcag ataaaatcta ctccaaatta ttttcaagag agtgtgactc 2640
atcaggcagc ccaaaagttt attggacttg gggtttctat tcctttttat ttgtttgcaa 2700
tattttcaga agaaaggcat tgcacagagt gaacttaatg gacgaagcaa caaatatgtc 2760
aagaacagga catagcacga atctgttacc agtaggagga ggatgagcca cagaaattgc 2820
ataattttct aatttcaagt cttcctgata catgactgaa tagtgtggtt cagtgagctg 2880
cactgacctc tacattttgt atgatatgta aaacagattt tttgtagagc ttacttttat 2940
tattaaatgt attgaggtat tatatttaaa aaaaactatg ttcagaactt catctgccac 3000
tggttatttt tttctaagga gtaacttgca agttttcagt acaaatctgt gctacactgg 3060
ataaaaatct aatttatgaa ttttacttgc accttatagt tcatagcaat taactgattt 3120
gtagtgattc attgtttgtt ttatatacca atgacttcca tattttaaaa gagaaaaaca 3180
actttatgtt gcaggaaacc ctttttgtaa gtctttatta tttactttgc attttgtttc 3240
actctttcca gataagcaga gttgctcttc accagtgttt ttcttcatgt gcaaagtgac 3300
tatttgttct ataatacttt tatgtgtgtt atatcaaatg tgtcttaagc ttcatgcaaa 3360
ctcagtcatc agttcgtgtt gtctgaagca agtgggagat atataaatac ccagtagcta 3420
aaatggtcag tcttttttag atgttttcct acttagtatc tcctaataac gttttgctgt 3480
gtcactagat gttcatttca caagtgcatg tctttctaat aatccacaca tttcatgctc 3540
taataatcca cacatttcat gctcattttt attgttttta cagccagtta tagtaagaaa 3600
aaggtttttc cccttgtgct gctttataat ttagcgtgtg tctgaacctt atccatgttt 3660
gctagatgag gtcttgtcaa atatatcact accattgtca ccggtgaaaa gaaacaggta 3720
gttaagttag ggttaacatt catttcaacc acgaggttgt atatcatgac tagcttttac 3780
tcttggttta cagagaaaag ttaaacagcc aactaggcag tttttaagaa tattaacaat 3840
atattaacaa acaccaatac aactaatcct atttggtttt aatgatttca ccatgggatt 3900
aagaactata tcaggaacat ccctgagaaa cggttttaag tgtagcaact actcttcctt 3960
aatggacagc cacataacgt gtaggaagtc ctttatcact tatcctcgat ccataagcat 4020
atcttgcaga ggggaactac ttctttaaac acatggaggg aaagaagatg atgccactgg 4080
caccagaggg ttagtactgt gatgcatcct aaaatattta ttatattggt aaaaattctg 4140
gttaaataaa aaattagaga tcactcttgg ctgatttcag caccaggaac tgtattacag 4200
ttttagagat taattcctag tgtttacctg attatagcag ttggcatcat ggggcattta 4260
attctgactt tatccccacg tcagccttaa taaagtcttc tttaccttct ctatgaagac 4320
tttaaagccc aaataatcat ttttcacatt gatattcaag aattgagata gatagaagcc 4380
aaagtgggta tctgacaagt ggaaaatcaa acgtttaaga agaattacaa ctctgaaaag 4440
catttatatg tggaacttct caaggagcct cctggggact ggaaagtaag tcatcagcca 4500
ggcaaatgac tcatgctgaa gagagtcccc atttcagtcc cctgagatct agctgatgct 4560
tagatccttt gaaataaaaa ttatgtcttt ataactctga tcttttacat aaagcagaag 4620
aggaatcaac tagttaattg caaggtttct actctgtttc ctctgtaaag atcagatggt 4680
aatctttcaa ataagaaaaa aataaagacg tatgtttgac caagtagttt cacaagaata 4740
tttgggaact tgtttctttt aattttattt gtccctgagt gaagtctaga aagaaaggta 4800
aagagtctag agtttattcc tctttccaaa acattctcat tcctctcctc cctacactta 4860
gtatttcccc cacagagtgc ctagaatctt aataatgaat aaaataaaaa gcagcaatat 4920
gtcattaaca aatccagacc tgaaagggta aagggtttat aactgcacta ataaagagag 4980
gctctttttt tttcttccag tttgttggtt tttaatggta ccgtgttgta aagataccca 5040
ctaatggaca atcaaattgc agaaaaggct caatatccaa gagacaggga ctaatgcact 5100
gtacaatctg cttatccttg cccttctctc ttgccaaagt gtgcttcaga aatatatact 5160
gctttaaaaa agaataaaag aatatccttt tacaagtggc tttacatttc ctaaaatgcc 5220
ataagaaaat gcaatatctg ggtactgtat ggggaaaaaa atgtccaagt ttgtgtaaaa 5280
ccagtgcatt tcagcttgca agttactgaa cacaataatg ctgttttaat tttgttttat 5340
atcagttaaa attcacaata atgtagatag aacaaattac agacaaggaa agaaaaaact 5400
tgaatgaaat ggattttaca gaaagcttta tgataatttt tgaatgcatt atttattttt 5460
tgtgccatgc attttttttc tcaccaaatg accttacctg taatacagtc ttgtttgtct 5520
gtttacaacc atgtatttat tgcaatgtac atactgtaat gttaattgta aattatctgt 5580
tcttattaaa acatcatccc atgatgggat ggtgttgata tatttggaaa ctcttggtga 5640
gagaatgaat ggtgtgtata catactctgt acatttttct tttctcctgt aatatagtct 5700
tgtcacctta gagcttgttt atggaagatt caagaaaact ataaaatact taaagatata 5760
taaatttaaa aaaacatagc tgcaggtctt tggtcccagg gctgtgcctt aactttaacc 5820
aatattttct tctgttttgc tgcatttgaa aggtaacagt ggagctaggg ctgggcattt 5880
tacatccagg cttttaattg attagaattc tgccaatagg tggattttac aaaaccacag 5940
acaacctctg aaagattctg agaccctttt gagacagaag ctcttaagta cttcttgcca 6000
gggagcagca ctgcatgtgt gatggttgtt tgccatctgt tgatcaggaa ctacttcagc 6060
tacttgcatt tgattatttc cttttttttt ttttttaact cggaaacaca actggggaaa 6120
tatattcttt cccagtgatt ataaacaatc tttttctttt ttttaagtcc ttttggcttc 6180
tagagctcat aggaaaatgg acttgatttg aaattggagc cagagtttac tcgtgttggt 6240
tatctattca tcagcttcct gacatgttaa gagaatacat taaagagaaa atactgtttt 6300
ttaatcctaa aatttttctt ccactaagat aaaccaaatg tccttacata tatgtaaacc 6360
catctattta aacgcaaagg tgggttgatg tcagtttaca tagcagaaag cattcactat 6420
cctctaagat ttgtttctgc aaaactttca ttgctttaga attttaaaat ttcaccttgt 6480
acaatggcca gcccctaaag caggaaacat ttataatgga ttatatggaa acatcctccc 6540
agtacttgcc cagcccttga atcatgtggc ttttcagtga aaggaaagat tctttttcta 6600
ggaaaaatga gcctatttta ttttatttta ttttattttt tgacacaaac tgtagatttt 6660
agcagccctg gcccaaagga atttgattac ttttgtttta aacagtacaa aggggacact 6720
ataattacaa aaacatcctt aactgatttg agttgttttt atttctttgg atatattttc 6780
agagtggtaa attgtgtgtg agaattacaa atgattattc ttttagtggt ttcttagcct 6840
ctcttacagc ccacggggat agtactgtac atcaatacct tcatatgaaa tttttatatg 6900
caatgaaaat aaaagcatgg gttgattctg cctatttatg actcaatctt ttacaaataa 6960
aagattattc attttaaatt atagttcaat cagcatgtct cttaggatac tgaacgtggt 7020
tgaaatgaaa ggatagtgac atcataagtt agtactgata ttcataacca aataaagcca 7080
acttgagtaa ttttgctaca ttaaaaatta ccaaaattac ttagatggcc tataagatta 7140
agcatggtgt tttctaagca agctttgaaa ggggccttcc atacttactt aattgaatat 7200
tctgggatat tgaaaattat tcagatactt gacaattatt tttggttacc tactccgcaa 7260
actacaaagt tttaaggact caacaataag ttaatgagac acagtgtttg ctttcatgga 7320
gcttacagtc tggaggggac aaaggcttaa acaatactca tataattata tatgtgatca 7380
gtacaatgaa ggagctcagt ggggtaaata agcaggaacc tgaacttgat ctgttccgga 7440
gggccacaga aggcttcctt gaggccttga gaaagtgatt tgcatctgag ttctgaagga 7500
ttgtaagagg taactaggga aaaagttgac aggaagagga aggggatcca gacaagaaac 7560
atttgcaaag atcttgaggc ataaatgagc ttgagacatc tggagaaact gaggaaaagt 7620
gagagagtag gcagggcctg gagccgcaga gccattgcta accatcctgt gtgagatatc 7680
ccccattctg tagctttatt ctcataaccc tgctcaattt tctttataac acttctcaca 7740
gatttatata cgtgtttgtt tttgttatct gtctctccca ccagaccaca gctccatgag 7800
agcaaggtct ttgcttacca atatatcact agcacttaaa actatgcctg gtacacagta 7860
ggttcttaat atgtgttgaa tatagccatc aaattgatat tggatataat tcaatctgat 7920
aagatatttt gagatattaa agagttttta acttgatacc ataaaaaaaa aaaaaaaaa 7979
<210> 2
<211> 745
<212> PRT
<213> Homo sapiens
<400> 2
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> 3
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> PDE4D5_forward primer
<400> 3
gcttctcagc agcaacatc 19
<210> 4
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> PDE4D5_reverse primer
<400> 4
tgccattgtc cacatcaaaa 20
<210> 5
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> PDE4D5 probe
<400> 5
acagcggcgt ttcacggtgg caca 24
<210> 6
<211> 8130
<212> DNA
<213> Homo sapiens
<400> 6
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> 7
<211> 748
<212> PRT
<213> Homo sapiens
<400> 7
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> 8
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> PDE4D7
<400> 8
gaacattcaa cgaccaacca 20
<210> 9
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> PDE4D7_reverse primer
<400> 9
tgccattgtc cacatcaaaa 20
<210> 10
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> PDE4D7 probe
<400> 10
ctgccgctga ttgctatcac ttctgca 27
<210> 11
<211> 1278
<212> DNA
<213> Homo sapiens
<400> 11
ccattggcct gtagattcac ctcccctggg cagggcccca ggacccagga taatatctgt 60
gcctcctgcc cagaaccctc caagcagaca caatggtaag aatggtgcct gtcctgctgt 120
ctctgctgct gcttctgggt cctgctgtcc cccaggagaa ccaagatggt cgttactctc 180
tgacctatat ctacactggg ctgtccaagc atgttgaaga cgtccccgcg tttcaggccc 240
ttggctcact caatgacctc cagttcttta gatacaacag taaagacagg aagtctcagc 300
ccatgggact ctggagacag gtggaaggaa tggaggattg gaagcaggac agccaacttc 360
agaaggccag ggaggacatc tttatggaga ccctgaaaga catcgtggag tattacaacg 420
acagtaacgg gtctcacgta ttgcagggaa ggtttggttg tgagatcgag aataacagaa 480
gcagcggagc attctggaaa tattactatg atggaaagga ctacattgaa ttcaacaaag 540
aaatcccagc ctgggtcccc ttcgacccag cagcccagat aaccaagcag aagtgggagg 600
cagaaccagt ctacgtgcag cgggccaagg cttacctgga ggaggagtgc cctgcgactc 660
tgcggaaata cctgaaatac agcaaaaata tcctggaccg gcaagatcct ccctctgtgg 720
tggtcaccag ccaccaggcc ccaggagaaa agaagaaact gaagtgcctg gcctacgact 780
tctacccagg gaaaattgat gtgcactgga ctcgggccgg cgaggtgcag gagcctgagt 840
tacggggaga tgttcttcac aatggaaatg gcacttacca gtcctgggtg gtggtggcag 900
tgcccccgca ggacacagcc ccctactcct gccacgtgca gcacagcagc ctggcccagc 960
ccctcgtggt gccctgggag gccagctagg aagcaagggt tggaggcaat gtgggatctc 1020
agacccagta gctgcccttc ctgcctgatg tgggagctga accacagaaa tcacagtcaa 1080
tggatccaca aggcctgagg agcagtgtgg ggggacagac aggaggtgga tttggagacc 1140
gaagactggg atgcctgtct tgagtagact tggacccaaa aaatcatctc accttgagcc 1200
cacccccacc ccattgtcta atctgtagaa gctaataaat aatcatccct ccttgcctag 1260
cataaaaaaa aaaaaaaa 1278
<210> 12
<211> 298
<212> PRT
<213> Homo sapiens
<400> 12
Met Val Arg Met Val Pro Val Leu Leu Ser Leu Leu Leu Leu Leu Gly
1 5 10 15
Pro Ala Val Pro Gln Glu Asn Gln Asp Gly Arg Tyr Ser Leu Thr Tyr
20 25 30
Ile Tyr Thr Gly Leu Ser Lys His Val Glu Asp Val Pro Ala Phe Gln
35 40 45
Ala Leu Gly Ser Leu Asn Asp Leu Gln Phe Phe Arg Tyr Asn Ser Lys
50 55 60
Asp Arg Lys Ser Gln Pro Met Gly Leu Trp Arg Gln Val Glu Gly Met
65 70 75 80
Glu Asp Trp Lys Gln Asp Ser Gln Leu Gln Lys Ala Arg Glu Asp Ile
85 90 95
Phe Met Glu Thr Leu Lys Asp Ile Val Glu Tyr Tyr Asn Asp Ser Asn
100 105 110
Gly Ser His Val Leu Gln Gly Arg Phe Gly Cys Glu Ile Glu Asn Asn
115 120 125
Arg Ser Ser Gly Ala Phe Trp Lys Tyr Tyr Tyr Asp Gly Lys Asp Tyr
130 135 140
Ile Glu Phe Asn Lys Glu Ile Pro Ala Trp Val Pro Phe Asp Pro Ala
145 150 155 160
Ala Gln Ile Thr Lys Gln Lys Trp Glu Ala Glu Pro Val Tyr Val Gln
165 170 175
Arg Ala Lys Ala Tyr Leu Glu Glu Glu Cys Pro Ala Thr Leu Arg Lys
180 185 190
Tyr Leu Lys Tyr Ser Lys Asn Ile Leu Asp Arg Gln Asp Pro Pro Ser
195 200 205
Val Val Val Thr Ser His Gln Ala Pro Gly Glu Lys Lys Lys Leu Lys
210 215 220
Cys Leu Ala Tyr Asp Phe Tyr Pro Gly Lys Ile Asp Val His Trp Thr
225 230 235 240
Arg Ala Gly Glu Val Gln Glu Pro Glu Leu Arg Gly Asp Val Leu His
245 250 255
Asn Gly Asn Gly Thr Tyr Gln Ser Trp Val Val Val Ala Val Pro Pro
260 265 270
Gln Asp Thr Ala Pro Tyr Ser Cys His Val Gln His Ser Ser Leu Ala
275 280 285
Gln Pro Leu Val Val Pro Trp Glu Ala Ser
290 295
<210> 13
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> AZGP1_forward primer
<400> 13
tggagaccct gaaagacatc 20
<210> 14
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> AZGP1_reverse primer
<400> 14
ctcgatctca caaccaaacc 20
<210> 15
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> AZGP1 probe
<400> 15
acgggtctca cgtattgcag gga 23
<210> 16
<211> 2312
<212> DNA
<213> Homo sapiens
<400> 16
ctcctcccgg gcgggataat tgaacggcgc ggccctggcc cagcgttggc tgccgaggct 60
cggccggagc gtggagcccg cgccgctgcc ccaggaccgc gcccgcgcct ttgtccgccg 120
ccgcccaccg cccgtcgccc gccgcccatg gagcgcgccg cgccgtcgcg ccgggtcccg 180
cttccgctgc tgctgctcgg cggccttgcg ctgctggcgg ccggagtgga cgcggatgtc 240
ctcctggagg cctgctgtgc ggacggacac cggatggcca ctcatcagaa ggactgctcg 300
ctgccatatg ctacggaatc caaagaatgc aggatggtgc aggagcagtg ctgccacagc 360
cagctggagg agctgcactg tgccacgggc atcagcctgg ccaacgagca ggaccgctgt 420
gccacgcccc acggtgacaa cgccagcctg gaggccacat ttgtgaagag gtgctgccat 480
tgctgtctgc tggggagggc ggcccaggcc cagggccaga gctgcgagta cagcctcatg 540
gttggctacc agtgtggaca ggtcttccgg gcatgctgtg tcaagagcca ggagaccgga 600
gatttggatg tcgggggcct ccaagaaacg gataagatca ttgaggttga ggaggaacaa 660
gaggacccat atctgaatga ccgctgccga ggaggcgggc cctgcaagca gcagtgccga 720
gacacgggtg acgaggtggt ctgctcctgc ttcgtgggct accagctgct gtctgatggt 780
gtctcctgtg aagatgtcaa tgaatgcatc acgggcagcc acagctgccg gcttggagaa 840
tcctgcatca acacagtggg ctctttccgc tgccagcggg acagcagctg cgggactggc 900
tatgagctca cagaggacaa tagctgcaaa gatattgacg agtgtgagag tggtattcat 960
aactgcctcc ccgattttat ctgtcagaat actctgggat ccttccgctg ccgacccaag 1020
ctacagtgca agagtggctt tatacaagat gctctaggca actgtattga tatcaatgag 1080
tgtttgagta tcagtgcccc gtgccctatc gggcatacat gcatcaacac agagggctcc 1140
tacacgtgcc agaagaacgt gcccaactgt ggccgtggct accatctcaa cgaggaggga 1200
acgcgctgtg ttgatgtgga cgagtgcgcg ccacctgctg agccctgtgg gaagggacat 1260
cgctgcgtga actctcccgg cagtttccgc tgcgaatgca agacgggtta ctattttgac 1320
ggcatcagca ggatgtgtgt cgatgtcaac gagtgccagc gctaccccgg gcgcctgtgt 1380
ggccacaagt gcgagaacac gctgggctcc tacctctgca gctgttccgt gggcttccgg 1440
ctctctgtgg atggcaggtc atgtgaagac atcaatgagt gcagcagcag cccctgtagc 1500
caggagtgtg ccaacgtcta cggctcctac cagtgttact gccggcgagg ctaccagctc 1560
agcgatgtgg atggagtcac ctgtgaagac atcgacgagt gcgccctgcc caccgggggc 1620
cacatctgct cctaccgctg catcaacatc cctggaagct tccagtgcag ctgcccctcg 1680
tctggctaca ggctggcccc caatggccgc aactgccaag acattgatga gtgtgtgact 1740
ggcatccaca actgctccat caacgagacc tgcttcaaca tccagggcgg cttccgctgc 1800
ctggccttcg agtgccctga gaactaccgc cgctccgcag ccacccgctg tgagcgcttg 1860
ccttgccatg agaatcggga gtgctccaag ctgcctctga gaataaccta ctaccacctc 1920
tctttcccca ccaacatcca agcgcccgcg gtggttttcc gcatgggccc ctccagtgct 1980
gtccccgggg acagcatgca gctggccatc accggcggca atgaggaggg ctttttcacc 2040
acccggaagg tgagccccca cagtggggtg gtggccctca ccaagcctgt ccccgagccc 2100
agggacttgc tcctgaccgt caagatggat ctctctcgcc acggcaccgt cagctccttt 2160
gtggccaagc ttttcatctt tgtgtctgca gagctctgag cactcgcttc gcgtcgcggg 2220
gtctccctcc tgttgctttc ctaaccctgc cctccggggc gttaataaag tcttagcaag 2280
cgtcccacac agtgaaaaaa aaaaaaaaaa aa 2312
<210> 17
<211> 2662
<212> DNA
<213> Homo sapiens
<400> 17
ctcctcccgg gcgggataat tgaacggcgc ggccctggcc cagcgttggc tgccgaggct 60
cggccggagc gtggagcccg cgccgctgcc ccaggaccgc gcccgcgcct ttgtccgccg 120
ccgcccaccg cccgtcgccc gccgcccatg gagcgcgccg cgccgtcgcg ccgggtcccg 180
cttccgctgc tgctgctcgg cggccttgcg ctgctggcgg ccggagtgga cgcggatgtc 240
ctcctggagg cctgctgtgc ggacggacac cggatggcca ctcatcagaa ggactgctcg 300
ctgccatatg ctacggaatc caaagaatgc aggatggtgc aggagcagtg ctgccacagc 360
cagctggagg agctgcactg tgccacgggc atcagcctgg ccaacgagca ggaccgctgt 420
gccacgcccc acggtgacaa cgccagcctg gaggccacat ttgtgaagag gtgctgccat 480
tgctgtctgc tggggagggc ggcccaggcc cagggccaga gctgcgagta cagcctcatg 540
gttggctacc agtgtggaca ggtcttccgg gcatgctgtg tcaagagcca ggagaccgga 600
gatttggatg tcgggggcct ccaagaaacg gataagatca ttgaggttga ggaggaacaa 660
gaggacccat atctgaatga ccgctgccga ggaggcgggc cctgcaagca gcagtgccga 720
gacacgggtg acgaggtggt ctgctcctgc ttcgtgggct accagctgct gtctgatggt 780
gtctcctgtg aagatgtcaa tgaatgcatc acgggcagcc acagctgccg gcttggagaa 840
tcctgcatca acacagtggg ctctttccgc tgccagcggg acagcagctg cgggactggc 900
tatgagctca cagaggacaa tagctgcaaa gatattgacg agtgtgagag tggtattcat 960
aactgcctcc ccgattttat ctgtcagaat actctgggat ccttccgctg ccgacccaag 1020
ctacagtgca agagtggctt tatacaagat gctctaggca actgtattga tatcaatgag 1080
tgtttgagta tcagtgcccc gtgccctatc gggcatacat gcatcaacac agagggctcc 1140
tacacgtgcc agaagaacgt gcccaactgt ggccgtggct accatctcaa cgaggaggga 1200
acgcgctgtg ttgatgtgga cgagtgcgcg ccacctgctg agccctgtgg gaagggacat 1260
cgctgcgtga actctcccgg cagtttccgc tgcgaatgca agacgggtta ctattttgac 1320
ggcatcagca ggatgtgtgt cgatgtcaac gagtgccagc gctaccccgg gcgcctgtgt 1380
ggccacaagt gcgagaacac gctgggctcc tacctctgca gctgttccgt gggcttccgg 1440
ctctctgtgg atggcaggtc atgtgaagac atcaatgagt gcagcagcag cccctgtagc 1500
caggagtgtg ccaacgtcta cggctcctac cagtgttact gccggcgagg ctaccagctc 1560
agcgatgtgg atggagtcac ctgtgaagac atcgacgagt gcgccctgcc caccgggggc 1620
cacatctgct cctaccgctg catcaacatc cctggaagct tccagtgcag ctgcccctcg 1680
tctggctaca ggctggcccc caatggccgc aactgccaag acattgatga gtgtgtgact 1740
ggcatccaca actgctccat caacgagacc tgcttcaaca tccagggcgg cttccgctgc 1800
ctggccttcg agtgccctga gaactaccgc cgctccgcag ccacgcagaa atccaagaag 1860
ggaaggcaga acaccccagc gggatcaagt aaagaggact gcagggttct tccatggaag 1920
caggggttgg aggataccca ccttgatgcc tagtgaggaa gatggacctg gacagacagt 1980
cagctccaca ccttgcgctg agcagctgtg attgtgccac gggagcatga gcccttttcc 2040
ccacggccct tgccactgtc tcctggccct ctctctgatc atgccaggtt tgcaccagcc 2100
tcgagtctcc catgttgtag tacattctcc aagatgcagc ccaggagcct ctctgaagga 2160
ccagtctggt tacgatggtc tgagcttcct tagaaccttc catggttgtc ttttcccagc 2220
agatgaagca tagcctcctt ggaatggcat gggaggcctg gcctgatctg gcctctgccc 2280
accctttgag ctgcacctgc cccaccccag ctcatccatg tgcttgtacc ctggccccac 2340
ggggaggctt gcccttccct gaatctgcct tcttgtggct ttagcatgtg ccatgctgtc 2400
cccctgcaga ctgccattct ccttgcagac ttggctcaga agtcacctcc tcagtgcagt 2460
tagcctgagc tcccctggcc ccaggtgcct ccatcagagc atttacccca ttgtgttgtg 2520
gctgttcctt aacgtcccca ctagccaggc tctttgaggg cagggattgt gtctggttaa 2580
tttctgtatt ctctgcaact ttgcaatgtt tggcttgaag aaggagctca gtaaacatct 2640
gaataaacat gcaggttgat gg 2662
<210> 18
<211> 2947
<212> DNA
<213> Homo sapiens
<400> 18
ctcctcccgg gcgggataat tgaacggcgc ggccctggcc cagcgttggc tgccgaggct 60
cggccggagc gtggagcccg cgccgctgcc ccaggaccgc gcccgcgcct ttgtccgccg 120
ccgcccaccg cccgtcgccc gccgcccatg gagcgcgccg cgccgtcgcg ccgggtcccg 180
cttccgctgc tgctgctcgg cggccttgcg ctgctggcgg ccggagtgga cgcggatgtc 240
ctcctggagg cctgctgtgc ggacggacac cggatggcca ctcatcagaa ggactgctcg 300
ctgccatatg ctacggaatc caaagaatgc aggatggtgc aggagcagtg ctgccacagc 360
cagctggagg agctgcactg tgccacgggc atcagcctgg ccaacgagca ggaccgctgt 420
gccacgcccc acggtgacaa cgccagcctg gaggccacat ttgtgaagag gtgctgccat 480
tgctgtctgc tggggagggc ggcccaggcc cagggccaga gctgcgagta cagcctcatg 540
gttggctacc agtgtggaca ggtcttccgg gcatgctgtg tcaagagcca ggagaccgga 600
gatttggatg tcgggggcct ccaagaaacg gataagatca ttgaggttga ggaggaacaa 660
gaggacccat atctgaatga ccgctgccga ggaggcgggc cctgcaagca gcagtgccga 720
gacacgggtg acgaggtggt ctgctcctgc ttcgtgggct accagctgct gtctgatggt 780
gtctcctgtg aagatgtcaa tgaatgcatc acgggcagcc acagctgccg gcttggagaa 840
tcctgcatca acacagtggg ctctttccgc tgccagcggg acagcagctg cgggactggc 900
tatgagctca cagaggacaa tagctgcaaa gatattgacg agtgtgagag tggtattcat 960
aactgcctcc ccgattttat ctgtcagaat actctgggat ccttccgctg ccgacccaag 1020
ctacagtgca agagtggctt tatacaagat gctctaggca actgtattga tatcaatgag 1080
tgtttgagta tcagtgcccc gtgccctatc gggcatacat gcatcaacac agagggctcc 1140
tacacgtgcc agaagaacgt gcccaactgt ggccgtggct accatctcaa cgaggaggga 1200
acgcgctgtg ttgatgtgga cgagtgcgcg ccacctgctg agccctgtgg gaagggacat 1260
cgctgcgtga actctcccgg cagtttccgc tgcgaatgca agacgggtta ctattttgac 1320
ggcatcagca ggatgtgtgt cgatgtcaac gagtgccagc gctaccccgg gcgcctgtgt 1380
ggccacaagt gcgagaacac gctgggctcc tacctctgca gctgttccgt gggcttccgg 1440
ctctctgtgg atggcaggtc atgtgaagac atcaatgagt gcagcagcag cccctgtagc 1500
caggagtgtg ccaacgtcta cggctcctac cagtgttact gccggcgagg ctaccagctc 1560
agcgatgtgg atggagtcac ctgtgaagac atcgacgagt gcgccctgcc caccgggggc 1620
cacatctgct cctaccgctg catcaacatc cctggaagct tccagtgcag ctgcccctcg 1680
tctggctaca ggctggcccc caatggccgc aactgccaag acattgatga gtgtgtgact 1740
ggcatccaca actgctccat caacgagacc tgcttcaaca tccagggcgg cttccgctgc 1800
ctggccttcg agtgccctga gaactaccgc cgctccgcag ccacgctcca gcaggagaag 1860
acagacacgg tccgctgcat caagtcctgc cgccccaacg atgtcacatg cgtgttcgac 1920
cccgtgcaca ccatctccca caccgtcatc tcgctgccta ccttccgcga gttcacccgc 1980
cctgaagaga tcatcttcct ccgggccatc acgccaccgc atcctgccag ccaggctaac 2040
atcatcttcg acatcacgga agggaacctg cgggactctt ttgacatcat caagcgttac 2100
atggacggca tgaccgtggg tgtcgtgcgc caggtgcggc ccatcgtggg cccatttcat 2160
gccgtcctga agctggagat gaactatgtg gtcgggggcg tggtctccca ccgaaatgtt 2220
gtcaacgtcc acatcttcgt ctctgagtac tggttctgag ggctggtctg ccgcacagcc 2280
gcaggtgcac ctccaggcca aatcattgct gccagtgact gtggtctgta cttgtttata 2340
ccctcagact tttttaatgt taggtatttg tagcattagg ccaacatgta ttaagctgag 2400
ccagatgaat aagtccatct gatgtatttt cggtgtttaa aaaatgagcc cagttgctca 2460
actgtttggt tgaaaacctt gctcattttt taatgcgaag gctaagtgtc accccctttc 2520
tctgcctctg gctgggcctt gctaagggcc aaggaaagaa agacattttt tagggggcag 2580
ccagtccaaa tgccaaaaga agaccagttc ttgccctgat tgtatgaaat ttgacatttt 2640
ggcacttttt tttttttttt ggccaatcag attttctatg ttctaaggac atggctgctg 2700
tagaatagca cagacgtgga tgataaatta tccccagaag cagcatgaca gaatgcctcg 2760
gggagcactt ggaagggaaa ttgcagttct gttgaaatag aggaaaatcc cttggtaaag 2820
acacagcctg ttaggctcgt gtgggcctcc agtatgttca ccaggggaat ggctgggatt 2880
tctcggcact ctgcatcatc catcttttct tataggtggg aaaataaaca actttgtgat 2940
cctcctg 2947
<210> 19
<211> 2485
<212> DNA
<213> Homo sapiens
<400> 19
ctcctcccgg gcgggataat tgaacggcgc ggccctggcc cagcgttggc tgccgaggct 60
cggccggagc gtggagcccg cgccgctgcc ccaggaccgc gcccgcgcct ttgtccgccg 120
ccgcccaccg cccgtcgccc gccgcccatg gagcgcgccg cgccgtcgcg ccgggtcccg 180
cttccgctgc tgctgctcgg cggccttgcg ctgctggcgg ccggagtgga cgcggatgtc 240
ctcctggagg cctgctgtgc ggacggacac cggatggcca ctcatcagaa ggactgctcg 300
ctgccatatg ctacggaatc caaagaatgc aggatggtgc aggagcagtg ctgccacagc 360
cagctggagg agctgcactg tgccacgggc atcagcctgg ccaacgagca ggaccgctgt 420
gccacgcccc acggtgacaa cgccagcctg gaggccacat ttgtgaagag gtgctgccat 480
tgctgtctgc tggggagggc ggcccaggcc cagggccaga gctgcgagta cagcctcatg 540
gttggctacc agtgtggaca ggtcttccgg gcatgctgtg tcaagagcca ggagaccgga 600
gatttggatg tcgggggcct ccaagaaacg gataagatca ttgaggttga ggaggaacaa 660
gaggacccat atctgaatga ccgctgccga ggaggcgggc cctgcaagca gcagtgccga 720
gacacgggtg acgaggtggt ctgctcctgc ttcgtgggct accagctgct gtctgatggt 780
gtctcctgtg aagatgtcaa tgaatgcatc acgggcagcc acagctgccg gcttggagaa 840
tcctgcatca acacagtggg ctctttccgc tgccagcggg acagcagctg cgggactggc 900
tatgagctca cagaggacaa tagctgcaaa gatattgacg agtgtgagag tggtattcat 960
aactgcctcc ccgattttat ctgtcagaat actctgggat ccttccgctg ccgacccaag 1020
ctacagtgca agagtggctt tatacaagat gctctaggca actgtattga tatcaatgag 1080
tgtttgagta tcagtgcccc gtgccctatc gggcatacat gcatcaacac agagggctcc 1140
tacacgtgcc agaagaacgt gcccaactgt ggccgtggct accatctcaa cgaggaggga 1200
acgcgctgtg ttgatgtgga cgagtgcgcg ccacctgctg agccctgtgg gaagggacat 1260
cgctgcgtga actctcccgg cagtttccgc tgcgaatgca agacgggtta ctattttgac 1320
ggcatcagca ggatgtgtgt cgatgtcaac gagtgccagc gctaccccgg gcgcctgtgt 1380
ggccacaagt gcgagaacac gctgggctcc tacctctgca gctgttccgt gggcttccgg 1440
ctctctgtgg atggcaggtc atgtgaagac atcaatgagt gcagcagcag cccctgtagc 1500
caggagtgtg ccaacgtcta cggctcctac cagtgttact gccggcgagg ctaccagctc 1560
agcgatgtgg atggagtcac ctgtgaagac atcgacgagt gcgccctgcc caccgggggc 1620
cacatctgct cctaccgctg catcaacatc cctggaagct tccagtgcag ctgcccctcg 1680
tctggctaca ggctggcccc caatggccgc aactgccaag acattgatga gtgtgtgact 1740
ggcatccaca actgctccat caacgagacc tgcttcaaca tccagggcgg cttccgctgc 1800
ctggccttcg agtgccctga gaactaccgc cgctccgcag ccacatgatc gtagggaact 1860
ctgcatgagg ccatcggtgc aggctggaga agagaaggca agttggcagg agtggagacc 1920
acgggcattt gagccacttc ctcatgtaac ttaacttgtg ccttcaggac ctgctcaagc 1980
ccgatcacgt atataccact tccatttgat gatggaatgc tgctgttcat gaccaacttt 2040
atggctagat gggtcagaaa gcacccagtt catgataggc agttcaggtc atatggtgac 2100
ttgatgaccc agagtcaaac attcagtttc caccaaagcc cagtaacagg ccaagagctg 2160
tctctcaaaa ggagagtagt tatctgcaga agatggcagg gccttgctcc gaaagcctag 2220
agaccgccac tgtgattcac ctatgggggc ctgccaaagg ctgcagccag catccttatc 2280
tgccactgac acctcaagca acattggatc tgctgggtca tatggcccaa gtggcagagc 2340
aacttgcaca acagcctgga cctgtcatag agctttctcc tgttctggac cccactcaaa 2400
actggcagcc tttcaggtca ctcgataaat gtgctggagt aacactcaaa cgaggaatgt 2460
gttgcctcca aaatccaata ggccc 2485
<210> 20
<211> 566
<212> PRT
<213> Homo sapiens
<400> 20
Met Glu Arg Ala Ala Pro Ser Arg Arg Val Pro Leu Pro Leu Leu Leu
1 5 10 15
Leu Gly Gly Leu Ala Leu Leu Ala Ala Gly Val Asp Ala Asp Val Leu
20 25 30
Leu Glu Ala Cys Cys Ala Asp Gly His Arg Met Ala Thr His Gln Lys
35 40 45
Asp Cys Ser Leu Pro Tyr Ala Thr Glu Ser Lys Glu Cys Arg Met Val
50 55 60
Gln Glu Gln Cys Cys His Ser Gln Leu Glu Glu Leu His Cys Ala Thr
65 70 75 80
Gly Ile Ser Leu Ala Asn Glu Gln Asp Arg Cys Ala Thr Pro His Gly
85 90 95
Asp Asn Ala Ser Leu Glu Ala Thr Phe Val Lys Arg Cys Cys His Cys
100 105 110
Cys Leu Leu Gly Arg Ala Ala Gln Ala Gln Gly Gln Ser Cys Glu Tyr
115 120 125
Ser Leu Met Val Gly Tyr Gln Cys Gly Gln Val Phe Arg Ala Cys Cys
130 135 140
Val Lys Ser Gln Glu Thr Gly Asp Leu Asp Val Gly Gly Leu Gln Glu
145 150 155 160
Thr Asp Lys Ile Ile Glu Val Glu Glu Glu Gln Glu Asp Pro Tyr Leu
165 170 175
Asn Asp Arg Cys Arg Gly Gly Gly Pro Cys Lys Gln Gln Cys Arg Asp
180 185 190
Thr Gly Asp Glu Val Val Cys Ser Cys Phe Val Gly Tyr Gln Leu Leu
195 200 205
Ser Asp Gly Val Ser Cys Glu Asp Val Asn Glu Cys Ile Thr Gly Ser
210 215 220
His Ser Cys Arg Leu Gly Glu Ser Cys Ile Asn Thr Val Gly Ser Phe
225 230 235 240
Arg Cys Gln Arg Asp Ser Ser Cys Gly Thr Gly Tyr Glu Leu Thr Glu
245 250 255
Asp Asn Ser Cys Lys Asp Ile Asp Glu Cys Glu Ser Gly Ile His Asn
260 265 270
Cys Leu Pro Asp Phe Ile Cys Gln Asn Thr Leu Gly Ser Phe Arg Cys
275 280 285
Arg Pro Lys Leu Gln Cys Lys Ser Gly Phe Ile Gln Asp Ala Leu Gly
290 295 300
Asn Cys Ile Asp Ile Asn Glu Cys Leu Ser Ile Ser Ala Pro Cys Pro
305 310 315 320
Ile Gly His Thr Cys Ile Asn Thr Glu Gly Ser Tyr Thr Cys Gln Lys
325 330 335
Asn Val Pro Asn Cys Gly Arg Gly Tyr His Leu Asn Glu Glu Gly Thr
340 345 350
Arg Cys Val Asp Val Asp Glu Cys Ala Pro Pro Ala Glu Pro Cys Gly
355 360 365
Lys Gly His Arg Cys Val Asn Ser Pro Gly Ser Phe Arg Cys Glu Cys
370 375 380
Lys Thr Gly Tyr Tyr Phe Asp Gly Ile Ser Arg Met Cys Val Asp Val
385 390 395 400
Asn Glu Cys Gln Arg Tyr Pro Gly Arg Leu Cys Gly His Lys Cys Glu
405 410 415
Asn Thr Leu Gly Ser Tyr Leu Cys Ser Cys Ser Val Gly Phe Arg Leu
420 425 430
Ser Val Asp Gly Arg Ser Cys Glu Asp Ile Asn Glu Cys Ser Ser Ser
435 440 445
Pro Cys Ser Gln Glu Cys Ala Asn Val Tyr Gly Ser Tyr Gln Cys Tyr
450 455 460
Cys Arg Arg Gly Tyr Gln Leu Ser Asp Val Asp Gly Val Thr Cys Glu
465 470 475 480
Asp Ile Asp Glu Cys Ala Leu Pro Thr Gly Gly His Ile Cys Ser Tyr
485 490 495
Arg Cys Ile Asn Ile Pro Gly Ser Phe Gln Cys Ser Cys Pro Ser Ser
500 505 510
Gly Tyr Arg Leu Ala Pro Asn Gly Arg Asn Cys Gln Asp Ile Asp Glu
515 520 525
Cys Val Thr Gly Ile His Asn Cys Ser Ile Asn Glu Thr Cys Phe Asn
530 535 540
Ile Gln Gly Gly Phe Arg Cys Leu Ala Phe Glu Cys Pro Glu Asn Tyr
545 550 555 560
Arg Arg Ser Ala Ala Thr
565
<210> 21
<211> 601
<212> PRT
<213> Homo sapiens
<400> 21
Met Glu Arg Ala Ala Pro Ser Arg Arg Val Pro Leu Pro Leu Leu Leu
1 5 10 15
Leu Gly Gly Leu Ala Leu Leu Ala Ala Gly Val Asp Ala Asp Val Leu
20 25 30
Leu Glu Ala Cys Cys Ala Asp Gly His Arg Met Ala Thr His Gln Lys
35 40 45
Asp Cys Ser Leu Pro Tyr Ala Thr Glu Ser Lys Glu Cys Arg Met Val
50 55 60
Gln Glu Gln Cys Cys His Ser Gln Leu Glu Glu Leu His Cys Ala Thr
65 70 75 80
Gly Ile Ser Leu Ala Asn Glu Gln Asp Arg Cys Ala Thr Pro His Gly
85 90 95
Asp Asn Ala Ser Leu Glu Ala Thr Phe Val Lys Arg Cys Cys His Cys
100 105 110
Cys Leu Leu Gly Arg Ala Ala Gln Ala Gln Gly Gln Ser Cys Glu Tyr
115 120 125
Ser Leu Met Val Gly Tyr Gln Cys Gly Gln Val Phe Arg Ala Cys Cys
130 135 140
Val Lys Ser Gln Glu Thr Gly Asp Leu Asp Val Gly Gly Leu Gln Glu
145 150 155 160
Thr Asp Lys Ile Ile Glu Val Glu Glu Glu Gln Glu Asp Pro Tyr Leu
165 170 175
Asn Asp Arg Cys Arg Gly Gly Gly Pro Cys Lys Gln Gln Cys Arg Asp
180 185 190
Thr Gly Asp Glu Val Val Cys Ser Cys Phe Val Gly Tyr Gln Leu Leu
195 200 205
Ser Asp Gly Val Ser Cys Glu Asp Val Asn Glu Cys Ile Thr Gly Ser
210 215 220
His Ser Cys Arg Leu Gly Glu Ser Cys Ile Asn Thr Val Gly Ser Phe
225 230 235 240
Arg Cys Gln Arg Asp Ser Ser Cys Gly Thr Gly Tyr Glu Leu Thr Glu
245 250 255
Asp Asn Ser Cys Lys Asp Ile Asp Glu Cys Glu Ser Gly Ile His Asn
260 265 270
Cys Leu Pro Asp Phe Ile Cys Gln Asn Thr Leu Gly Ser Phe Arg Cys
275 280 285
Arg Pro Lys Leu Gln Cys Lys Ser Gly Phe Ile Gln Asp Ala Leu Gly
290 295 300
Asn Cys Ile Asp Ile Asn Glu Cys Leu Ser Ile Ser Ala Pro Cys Pro
305 310 315 320
Ile Gly His Thr Cys Ile Asn Thr Glu Gly Ser Tyr Thr Cys Gln Lys
325 330 335
Asn Val Pro Asn Cys Gly Arg Gly Tyr His Leu Asn Glu Glu Gly Thr
340 345 350
Arg Cys Val Asp Val Asp Glu Cys Ala Pro Pro Ala Glu Pro Cys Gly
355 360 365
Lys Gly His Arg Cys Val Asn Ser Pro Gly Ser Phe Arg Cys Glu Cys
370 375 380
Lys Thr Gly Tyr Tyr Phe Asp Gly Ile Ser Arg Met Cys Val Asp Val
385 390 395 400
Asn Glu Cys Gln Arg Tyr Pro Gly Arg Leu Cys Gly His Lys Cys Glu
405 410 415
Asn Thr Leu Gly Ser Tyr Leu Cys Ser Cys Ser Val Gly Phe Arg Leu
420 425 430
Ser Val Asp Gly Arg Ser Cys Glu Asp Ile Asn Glu Cys Ser Ser Ser
435 440 445
Pro Cys Ser Gln Glu Cys Ala Asn Val Tyr Gly Ser Tyr Gln Cys Tyr
450 455 460
Cys Arg Arg Gly Tyr Gln Leu Ser Asp Val Asp Gly Val Thr Cys Glu
465 470 475 480
Asp Ile Asp Glu Cys Ala Leu Pro Thr Gly Gly His Ile Cys Ser Tyr
485 490 495
Arg Cys Ile Asn Ile Pro Gly Ser Phe Gln Cys Ser Cys Pro Ser Ser
500 505 510
Gly Tyr Arg Leu Ala Pro Asn Gly Arg Asn Cys Gln Asp Ile Asp Glu
515 520 525
Cys Val Thr Gly Ile His Asn Cys Ser Ile Asn Glu Thr Cys Phe Asn
530 535 540
Ile Gln Gly Gly Phe Arg Cys Leu Ala Phe Glu Cys Pro Glu Asn Tyr
545 550 555 560
Arg Arg Ser Ala Ala Thr Gln Lys Ser Lys Lys Gly Arg Gln Asn Thr
565 570 575
Pro Ala Gly Ser Ser Lys Glu Asp Cys Arg Val Leu Pro Trp Lys Gln
580 585 590
Gly Leu Glu Asp Thr His Leu Asp Ala
595 600
<210> 22
<211> 703
<212> PRT
<213> Homo sapiens
<400> 22
Met Glu Arg Ala Ala Pro Ser Arg Arg Val Pro Leu Pro Leu Leu Leu
1 5 10 15
Leu Gly Gly Leu Ala Leu Leu Ala Ala Gly Val Asp Ala Asp Val Leu
20 25 30
Leu Glu Ala Cys Cys Ala Asp Gly His Arg Met Ala Thr His Gln Lys
35 40 45
Asp Cys Ser Leu Pro Tyr Ala Thr Glu Ser Lys Glu Cys Arg Met Val
50 55 60
Gln Glu Gln Cys Cys His Ser Gln Leu Glu Glu Leu His Cys Ala Thr
65 70 75 80
Gly Ile Ser Leu Ala Asn Glu Gln Asp Arg Cys Ala Thr Pro His Gly
85 90 95
Asp Asn Ala Ser Leu Glu Ala Thr Phe Val Lys Arg Cys Cys His Cys
100 105 110
Cys Leu Leu Gly Arg Ala Ala Gln Ala Gln Gly Gln Ser Cys Glu Tyr
115 120 125
Ser Leu Met Val Gly Tyr Gln Cys Gly Gln Val Phe Arg Ala Cys Cys
130 135 140
Val Lys Ser Gln Glu Thr Gly Asp Leu Asp Val Gly Gly Leu Gln Glu
145 150 155 160
Thr Asp Lys Ile Ile Glu Val Glu Glu Glu Gln Glu Asp Pro Tyr Leu
165 170 175
Asn Asp Arg Cys Arg Gly Gly Gly Pro Cys Lys Gln Gln Cys Arg Asp
180 185 190
Thr Gly Asp Glu Val Val Cys Ser Cys Phe Val Gly Tyr Gln Leu Leu
195 200 205
Ser Asp Gly Val Ser Cys Glu Asp Val Asn Glu Cys Ile Thr Gly Ser
210 215 220
His Ser Cys Arg Leu Gly Glu Ser Cys Ile Asn Thr Val Gly Ser Phe
225 230 235 240
Arg Cys Gln Arg Asp Ser Ser Cys Gly Thr Gly Tyr Glu Leu Thr Glu
245 250 255
Asp Asn Ser Cys Lys Asp Ile Asp Glu Cys Glu Ser Gly Ile His Asn
260 265 270
Cys Leu Pro Asp Phe Ile Cys Gln Asn Thr Leu Gly Ser Phe Arg Cys
275 280 285
Arg Pro Lys Leu Gln Cys Lys Ser Gly Phe Ile Gln Asp Ala Leu Gly
290 295 300
Asn Cys Ile Asp Ile Asn Glu Cys Leu Ser Ile Ser Ala Pro Cys Pro
305 310 315 320
Ile Gly His Thr Cys Ile Asn Thr Glu Gly Ser Tyr Thr Cys Gln Lys
325 330 335
Asn Val Pro Asn Cys Gly Arg Gly Tyr His Leu Asn Glu Glu Gly Thr
340 345 350
Arg Cys Val Asp Val Asp Glu Cys Ala Pro Pro Ala Glu Pro Cys Gly
355 360 365
Lys Gly His Arg Cys Val Asn Ser Pro Gly Ser Phe Arg Cys Glu Cys
370 375 380
Lys Thr Gly Tyr Tyr Phe Asp Gly Ile Ser Arg Met Cys Val Asp Val
385 390 395 400
Asn Glu Cys Gln Arg Tyr Pro Gly Arg Leu Cys Gly His Lys Cys Glu
405 410 415
Asn Thr Leu Gly Ser Tyr Leu Cys Ser Cys Ser Val Gly Phe Arg Leu
420 425 430
Ser Val Asp Gly Arg Ser Cys Glu Asp Ile Asn Glu Cys Ser Ser Ser
435 440 445
Pro Cys Ser Gln Glu Cys Ala Asn Val Tyr Gly Ser Tyr Gln Cys Tyr
450 455 460
Cys Arg Arg Gly Tyr Gln Leu Ser Asp Val Asp Gly Val Thr Cys Glu
465 470 475 480
Asp Ile Asp Glu Cys Ala Leu Pro Thr Gly Gly His Ile Cys Ser Tyr
485 490 495
Arg Cys Ile Asn Ile Pro Gly Ser Phe Gln Cys Ser Cys Pro Ser Ser
500 505 510
Gly Tyr Arg Leu Ala Pro Asn Gly Arg Asn Cys Gln Asp Ile Asp Glu
515 520 525
Cys Val Thr Gly Ile His Asn Cys Ser Ile Asn Glu Thr Cys Phe Asn
530 535 540
Ile Gln Gly Gly Phe Arg Cys Leu Ala Phe Glu Cys Pro Glu Asn Tyr
545 550 555 560
Arg Arg Ser Ala Ala Thr Leu Gln Gln Glu Lys Thr Asp Thr Val Arg
565 570 575
Cys Ile Lys Ser Cys Arg Pro Asn Asp Val Thr Cys Val Phe Asp Pro
580 585 590
Val His Thr Ile Ser His Thr Val Ile Ser Leu Pro Thr Phe Arg Glu
595 600 605
Phe Thr Arg Pro Glu Glu Ile Ile Phe Leu Arg Ala Ile Thr Pro Pro
610 615 620
His Pro Ala Ser Gln Ala Asn Ile Ile Phe Asp Ile Thr Glu Gly Asn
625 630 635 640
Leu Arg Asp Ser Phe Asp Ile Ile Lys Arg Tyr Met Asp Gly Met Thr
645 650 655
Val Gly Val Val Arg Gln Val Arg Pro Ile Val Gly Pro Phe His Ala
660 665 670
Val Leu Lys Leu Glu Met Asn Tyr Val Val Gly Gly Val Val Ser His
675 680 685
Arg Asn Val Val Asn Val His Ile Phe Val Ser Glu Tyr Trp Phe
690 695 700
<210> 23
<211> 566
<212> PRT
<213> Homo sapiens
<400> 23
Met Glu Arg Ala Ala Pro Ser Arg Arg Val Pro Leu Pro Leu Leu Leu
1 5 10 15
Leu Gly Gly Leu Ala Leu Leu Ala Ala Gly Val Asp Ala Asp Val Leu
20 25 30
Leu Glu Ala Cys Cys Ala Asp Gly His Arg Met Ala Thr His Gln Lys
35 40 45
Asp Cys Ser Leu Pro Tyr Ala Thr Glu Ser Lys Glu Cys Arg Met Val
50 55 60
Gln Glu Gln Cys Cys His Ser Gln Leu Glu Glu Leu His Cys Ala Thr
65 70 75 80
Gly Ile Ser Leu Ala Asn Glu Gln Asp Arg Cys Ala Thr Pro His Gly
85 90 95
Asp Asn Ala Ser Leu Glu Ala Thr Phe Val Lys Arg Cys Cys His Cys
100 105 110
Cys Leu Leu Gly Arg Ala Ala Gln Ala Gln Gly Gln Ser Cys Glu Tyr
115 120 125
Ser Leu Met Val Gly Tyr Gln Cys Gly Gln Val Phe Arg Ala Cys Cys
130 135 140
Val Lys Ser Gln Glu Thr Gly Asp Leu Asp Val Gly Gly Leu Gln Glu
145 150 155 160
Thr Asp Lys Ile Ile Glu Val Glu Glu Glu Gln Glu Asp Pro Tyr Leu
165 170 175
Asn Asp Arg Cys Arg Gly Gly Gly Pro Cys Lys Gln Gln Cys Arg Asp
180 185 190
Thr Gly Asp Glu Val Val Cys Ser Cys Phe Val Gly Tyr Gln Leu Leu
195 200 205
Ser Asp Gly Val Ser Cys Glu Asp Val Asn Glu Cys Ile Thr Gly Ser
210 215 220
His Ser Cys Arg Leu Gly Glu Ser Cys Ile Asn Thr Val Gly Ser Phe
225 230 235 240
Arg Cys Gln Arg Asp Ser Ser Cys Gly Thr Gly Tyr Glu Leu Thr Glu
245 250 255
Asp Asn Ser Cys Lys Asp Ile Asp Glu Cys Glu Ser Gly Ile His Asn
260 265 270
Cys Leu Pro Asp Phe Ile Cys Gln Asn Thr Leu Gly Ser Phe Arg Cys
275 280 285
Arg Pro Lys Leu Gln Cys Lys Ser Gly Phe Ile Gln Asp Ala Leu Gly
290 295 300
Asn Cys Ile Asp Ile Asn Glu Cys Leu Ser Ile Ser Ala Pro Cys Pro
305 310 315 320
Ile Gly His Thr Cys Ile Asn Thr Glu Gly Ser Tyr Thr Cys Gln Lys
325 330 335
Asn Val Pro Asn Cys Gly Arg Gly Tyr His Leu Asn Glu Glu Gly Thr
340 345 350
Arg Cys Val Asp Val Asp Glu Cys Ala Pro Pro Ala Glu Pro Cys Gly
355 360 365
Lys Gly His Arg Cys Val Asn Ser Pro Gly Ser Phe Arg Cys Glu Cys
370 375 380
Lys Thr Gly Tyr Tyr Phe Asp Gly Ile Ser Arg Met Cys Val Asp Val
385 390 395 400
Asn Glu Cys Gln Arg Tyr Pro Gly Arg Leu Cys Gly His Lys Cys Glu
405 410 415
Asn Thr Leu Gly Ser Tyr Leu Cys Ser Cys Ser Val Gly Phe Arg Leu
420 425 430
Ser Val Asp Gly Arg Ser Cys Glu Asp Ile Asn Glu Cys Ser Ser Ser
435 440 445
Pro Cys Ser Gln Glu Cys Ala Asn Val Tyr Gly Ser Tyr Gln Cys Tyr
450 455 460
Cys Arg Arg Gly Tyr Gln Leu Ser Asp Val Asp Gly Val Thr Cys Glu
465 470 475 480
Asp Ile Asp Glu Cys Ala Leu Pro Thr Gly Gly His Ile Cys Ser Tyr
485 490 495
Arg Cys Ile Asn Ile Pro Gly Ser Phe Gln Cys Ser Cys Pro Ser Ser
500 505 510
Gly Tyr Arg Leu Ala Pro Asn Gly Arg Asn Cys Gln Asp Ile Asp Glu
515 520 525
Cys Val Thr Gly Ile His Asn Cys Ser Ile Asn Glu Thr Cys Phe Asn
530 535 540
Ile Gln Gly Gly Phe Arg Cys Leu Ala Phe Glu Cys Pro Glu Asn Tyr
545 550 555 560
Arg Arg Ser Ala Ala Thr
565
<210> 24
<211> 17
<212> DNA
<213> Artificial Sequence
<220>
<223> FBLN1_forward primer
<400> 24
gcctggaggc cacattt 17
<210> 25
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> FBLN1_reverse primer
<400> 25
ccaaccatga ggctgtactc 20
<210> 26
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> FBLN1 probe
<400> 26
tgctgccatt gctgtctgct g 21
<210> 27
<211> 1797
<212> DNA
<213> Homo sapiens
<400> 27
agggacggag gcccgcgctg cccaagagcg ccacgggcgg ggcggggccg gcggcgggct 60
gcgggcgcgg ccggacggga gttccccgga gaaggatcct gcagcccgag tcccgtcctc 120
aggcttcccc aatccagggg actcggcgcc gggacgctgc tatggacgac attttcactc 180
agtgccggga gggcaacgca gtcgccgttc gcctgtggct ggacaacacg gagaacgacc 240
tcaaccaggg ggacgatcat ggcttctccc ccttgcactg ggcctgccga gagggccgct 300
ctgctgtggt tgagatgttg atcatgcggg gggcacggat caatgtaatg aaccgtgggg 360
atgacacccc cctgcatctg gcagccagtc atggacaccg tgatattgta cagaagctat 420
tgcagtacaa ggcagacatc aatgcagtga atgaacacgg gaatgtgccc ctgcactatg 480
cctgtttttg gggccaagat caagtggcag aggacctggt ggcaaatggg gcccttgtca 540
gcatctgtaa caagtatgga gagatgcctg tggacaaagc caaggcaccc ctgagagagc 600
ttctccgaga gcgggcagag aagatgggcc agaatctcaa ccgtattcca tacaaggaca 660
cattctggaa ggggaccacc cgcactcggc cccgaaatgg aaccctgaac aaacactctg 720
gcattgactt caaacagctt aacttcctga cgaagctcaa cgagaatcac tctggagagc 780
tatggaaggg ccgctggcag ggcaatgaca ttgtcgtgaa ggtgctgaag gttcgagact 840
ggagtacaag gaagagcagg gacttcaatg aagagtgtcc ccggctcagg attttctcgc 900
atccaaatgt gctcccagtg ctaggtgcct gccagtctcc acctgctcct catcctactc 960
tcatcacaca ctggatgccg tatggatccc tctacaatgt actacatgaa ggcaccaatt 1020
tcgtcgtgga ccagagccag gctgtgaagt ttgctttgga catggcaagg ggcatggcct 1080
tcctacacac actagagccc ctcatcccac gacatgcact caatagccgt agtgtaatga 1140
ttgatgagga catgactgcc cgaattagca tggctgatgt caagttctct ttccaatgtc 1200
ctggtcgcat gtatgcacct gcctgggtag cccccgaagc tctgcagaag aagcctgaag 1260
acacaaacag acgctcagca gacatgtgga gttttgcagt gcttctgtgg gaactggtga 1320
cacgggaggt accctttgct gacctctcca atatggagat tggaatgaag gtggcattgg 1380
aaggccttcg gcctaccatc ccaccaggta tttcccctca tgtgtgtaag ctcatgaaga 1440
tctgcatgaa tgaagaccct gcaaagcgac ccaaatttga catgattgtg cctatccttg 1500
agaagatgca ggacaagtag gactggaagg tccttgcctg aactccagag gtgtcgggac 1560
atggttgggg gaatgcacct ccccaaagca gcaggcctct ggttgcctcc cccgcctcca 1620
gtcatggtac taccccagcc atggggtcca tccccttccc ccatccctac cactgtggcc 1680
ccaagagggg cgggctcaga gctttgtcac ttgccacatg gtgtctccca acatgggagg 1740
gatcagcccc gcctgtcaca ataaagttta ttatgaaaac aggaaaaaaa aaaaaaa 1797
<210> 28
<211> 2098
<212> DNA
<213> Homo sapiens
<400> 28
agcccgagtc ccggtgagtg cgagaggacc cgcgccccct gtcacccctc acttctcctg 60
agtcccaagt aaggaacgga gccaaccctg gggaggaccc ccggtcccct ctcccagagt 120
atacggagcc tgaacctccc cacttccccc aactctgttc gcggataggg tctagttgcc 180
tgctctcgga catccgttca gcagacacta cctcttcgtc accccctgcc caccctgacc 240
cgcctttacc tcgcgtctag aggacacagc cagggatcat cccgcagccc cgaactcctt 300
cacagacccc cactagccgg ggacgcagct caggccccct acccccaaca caaacacttc 360
tctcctgtag aggataaagc ttggggttca tcctccttcc ctggatcact ccacagtcct 420
caggcttccc caatccaggg gactcggcgc cgggacgctg ctatggacga cattttcact 480
cagtgccggg agggcaacgc agtcgccgtt cgcctgtggc tggacaacac ggagaacgac 540
ctcaaccagg gggacgatca tggcttctcc cccttgcact gggcctgccg agagggccgc 600
tctgctgtgg ttgagatgtt gatcatgcgg ggggcacgga tcaatgtaat gaaccgtggg 660
gatgacaccc ccctgcatct ggcagccagt catggacacc gtgatattgt acagaagcta 720
ttgcagtaca aggcagacat caatgcagtg aatgaacacg ggaatgtgcc cctgcactat 780
gcctgttttt ggggccaaga tcaagtggca gaggacctgg tggcaaatgg ggcccttgtc 840
agcatctgta acaagtatgg agagatgcct gtggacaaag ccaaggcacc cctgagagag 900
cttctccgag agcgggcaga gaagatgggc cagaatctca accgtattcc atacaaggac 960
acattctgga aggggaccac ccgcactcgg ccccgaaatg gaaccctgaa caaacactct 1020
ggcattgact tcaaacagct taacttcctg acgaagctca acgagaatca ctctggagag 1080
ctatggaagg gccgctggca gggcaatgac attgtcgtga aggtgctgaa ggttcgagac 1140
tggagtacaa ggaagagcag ggacttcaat gaagagtgtc cccggctcag gattttctcg 1200
catccaaatg tgctcccagt gctaggtgcc tgccagtctc cacctgctcc tcatcctact 1260
ctcatcacac actggatgcc gtatggatcc ctctacaatg tactacatga aggcaccaat 1320
ttcgtcgtgg accagagcca ggctgtgaag tttgctttgg acatggcaag gggcatggcc 1380
ttcctacaca cactagagcc cctcatccca cgacatgcac tcaatagccg tagtgtaatg 1440
attgatgagg acatgactgc ccgaattagc atggctgatg tcaagttctc tttccaatgt 1500
cctggtcgca tgtatgcacc tgcctgggta gcccccgaag ctctgcagaa gaagcctgaa 1560
gacacaaaca gacgctcagc agacatgtgg agttttgcag tgcttctgtg ggaactggtg 1620
acacgggagg taccctttgc tgacctctcc aatatggaga ttggaatgaa ggtggcattg 1680
gaaggccttc ggcctaccat cccaccaggt atttcccctc atgtgtgtaa gctcatgaag 1740
atctgcatga atgaagaccc tgcaaagcga cccaaatttg acatgattgt gcctatcctt 1800
gagaagatgc aggacaagta ggactggaag gtccttgcct gaactccaga ggtgtcggga 1860
catggttggg ggaatgcacc tccccaaagc agcaggcctc tggttgcctc ccccgcctcc 1920
agtcatggta ctaccccagc catggggtcc atccccttcc cccatcccta ccactgtggc 1980
cccaagaggg gcgggctcag agctttgtca cttgccacat ggtgtctccc aacatgggag 2040
ggatcagccc cgcctgtcac aataaagttt attatgaaaa caggaaaaaa aaaaaaaa 2098
<210> 29
<211> 1660
<212> DNA
<213> Homo sapiens
<400> 29
agggacggag gcccgcgctg cccaagagcg ccacgggcgg ggcggggccg gcggcgggct 60
gcgggcgcgg ccggacggga gttccccgga gaaggatcct gcagcccgag tcccgaggat 120
aaagcttggg gttcatcctc cttccctgga tcactccaca gtcctcaggc ttccccaatc 180
caggggactc ggcgccggga cgctgctatg gacgacattt tcactcagtg ccgggagggc 240
aacgcagtcg ccgttcgcct gtggctggac aacacggaga acgacctcaa ccagggggac 300
gatcatggct tctccccctt gcactgggcc tgccgagagg gccgctctgc tgtggttgag 360
atgttgatca tgcggggggc acggatcaat gtaatgaacc gtggggatga cacccccctg 420
catctggcag ccagtcatgg acaccgtgat attgtacaga agctattgca gtacaaggca 480
gacatcaatg cagtgaatga acacgggaat gtgcccctgc actatgcctg tttttggggc 540
caagatcaag tggcagagag cgggcagaga agatgggcca gaatctcaac cgtattccat 600
acaaggacac attctggaag gggaccaccc gcactcggcc ccctatggaa gggccgctgg 660
cagggcaatg acattgtcgt gaaggtgctg aaggttcgag actggagtac aaggaagagc 720
agggacttca atgaagagtg tccccggctc aggattttct cgcatccaaa tgtgctccca 780
gtgctaggtg cctgccagtc tccacctgct cctcatccta ctctcatcac acactggatg 840
ccgtatggat ccctctacaa tgtactacat gaaggcacca atttcgtcgt ggaccagagc 900
caggctgtga agtttgcttt ggacatggca aggggcatgg ccttcctaca cacactagag 960
cccctcatcc cacgacatgc actcaatagc cgtagtgtaa tgattgatga ggacatgact 1020
gcccgaatta gcatggctga tgtcaagttc tctttccaat gtcctggtcg catgtatgca 1080
cctgcctggg tagcccccga agctctgcag aagaagcctg aagacacaaa cagacgctca 1140
gcagacatgt ggagttttgc agtgcttctg tgggaactgg tgacacggga ggtacccttt 1200
gctgacctct ccaatatgga gattggaatg aaggtggcat tggaaggcct tcggcctacc 1260
atcccaccag gtatttcccc tcatgtgtgt aagctcatga agatctgcat gaatgaagac 1320
cctgcaaagc gacccaaatt tgacatgatt gtgcctatcc ttgagaagat gcaggacaag 1380
taggactgga aggtccttgc ctgaactcca gaggtgtcgg gacatggttg ggggaatgca 1440
cctccccaaa gcagcaggcc tctggttgcc tcccccgcct ccagtcatgg tactacccca 1500
gccatggggt ccatcccctt cccccatccc taccactgtg gccccaagag gggcgggctc 1560
agagctttgt cacttgccac atggtgtctc ccaacatggg agggatcagc cccgcctgtc 1620
acaataaagt ttattatgaa aacaggaaaa aaaaaaaaaa 1660
<210> 30
<211> 1631
<212> DNA
<213> Homo sapiens
<400> 30
agggacggag gcccgcgctg cccaagagcg ccacgggcgg ggcggggccg gcggcgggct 60
gcgggcgcgg ccggacggga gttccccgga gaaggatcct gcagcccgag tcccgtcctc 120
aggcttcccc aatccagggg actcggcgcc gggacgctgc tatggacgac attttcactc 180
agtgccggga gggcaacgca gtcgccgttc gcctgtggct ggacaacacg gagaacgacc 240
tcaaccaggg ctattgcagt acaaggcaga catcaatgca gtgaatgaac acgggaatgt 300
gcccctgcac tatgcctgtt tttggggcca agatcaagtg gcagaggacc tggtggcaaa 360
tggggccctt gtcagcatct gtaacaagta tggagagatg cctgtggaca aagccaaggc 420
acccctgaga gagcttctcc gagagcgggc agagaagatg ggccagaatc tcaaccgtat 480
tccatacaag gacacattct ggaaggggac cacccgcact cggccccgaa atggaaccct 540
gaacaaacac tctggcattg acttcaaaca gcttaacttc ctgacgaagc tcaacgagaa 600
tcactctgga gagctatgga agggccgctg gcagggcaat gacattgtcg tgaaggtgct 660
gaaggttcga gactggagta caaggaagag cagggacttc aatgaagagt gtccccggct 720
caggattttc tcgcatccaa atgtgctccc agtgctaggt gcctgccagt ctccacctgc 780
tcctcatcct actctcatca cacactggat gccgtatgga tccctctaca atgtactaca 840
tgaaggcacc aatttcgtcg tggaccagag ccaggctgtg aagtttgctt tggacatggc 900
aaggggcatg gccttcctac acacactaga gcccctcatc ccacgacatg cactcaatag 960
ccgtagtgta atgattgatg aggacatgac tgcccgaatt agcatggctg atgtcaagtt 1020
ctctttccaa tgtcctggtc gcatgtatgc acctgcctgg gtagcccccg aagctctgca 1080
gaagaagcct gaagacacaa acagacgctc agcagacatg tggagttttg cagtgcttct 1140
gtgggaactg gtgacacggg aggtaccctt tgctgacctc tccaatatgg agattggaat 1200
gaaggtggca ttggaaggcc ttcggcctac catcccacca ggtatttccc ctcatgtgtg 1260
taagctcatg aagatctgca tgaatgaaga ccctgcaaag cgacccaaat ttgacatgat 1320
tgtgcctatc cttgagaaga tgcaggacaa gtaggactgg aaggtccttg cctgaactcc 1380
agaggtgtcg ggacatggtt gggggaatgc acctccccaa agcagcaggc ctctggttgc 1440
ctcccccgcc tccagtcatg gtactacccc agccatgggg tccatcccct tcccccatcc 1500
ctaccactgt ggccccaaga ggggcgggct cagagctttg tcacttgcca catggtgtct 1560
cccaacatgg gagggatcag ccccgcctgt cacaataaag tttattatga aaacaggaaa 1620
aaaaaaaaaa a 1631
<210> 31
<211> 1843
<212> DNA
<213> Homo sapiens
<400> 31
agggacggag gcccgcgctg cccaagagcg ccacgggcgg ggcggggccg gcggcgggct 60
gcgggcgcgg ccggacggga gttccccgga gaaggatcct gcagcccgag tcccgaggat 120
aaagcttggg gttcatcctc cttccctgga tcactccaca gtcctcaggc ttccccaatc 180
caggggactc ggcgccggga cgctgctatg gacgacattt tcactcagtg ccgggagggc 240
aacgcagtcg ccgttcgcct gtggctggac aacacggaga acgacctcaa ccagggggac 300
gatcatggct tctccccctt gcactgggcc tgccgagagg gccgctctgc tgtggttgag 360
atgttgatca tgcggggggc acggatcaat gtaatgaacc gtggggatga cacccccctg 420
catctggcag ccagtcatgg acaccgtgat attgtacaga agctattgca gtacaaggca 480
gacatcaatg cagtgaatga acacgggaat gtgcccctgc actatgcctg tttttggggc 540
caagatcaag tggcagagga cctggtggca aatggggccc ttgtcagcat ctgtaacaag 600
tatggagaga tgcctgtgga caaagccaag gcacccctga gagagcttct ccgagagcgg 660
gcagagaaga tgggccagaa tctcaaccgt attccataca aggacacatt ctggaagggg 720
accacccgca ctcggccccg aaatggaacc ctgaacaaac actctggcat tgacttcaaa 780
cagcttaact tcctgacgaa gctcaacgag aatcactctg gagagctatg gaagggccgc 840
tggcagggca atgacattgt cgtgaaggtg ctgaaggttc gagactggag tacaaggaag 900
agcagggact tcaatgaaga gtgtccccgg ctcaggattt tctcgcatcc aaatgtgctc 960
ccagtgctag gtgcctgcca gtctccacct gctcctcatc ctactctcat cacacactgg 1020
atgccgtatg gatccctcta caatgtacta catgaaggca ccaatttcgt cgtggaccag 1080
agccaggctg tgaagtttgc tttggacatg gcaaggggca tggccttcct acacacacta 1140
gagcccctca tcccacgaca tgcactcaat agccgtagtg taatgattga tgaggacatg 1200
actgcccgaa ttagcatggc tgatgtcaag ttctctttcc aatgtcctgg tcgcatgtat 1260
gcacctgcct gggtagcccc cgaagctctg cagaagaagc ctgaagacac aaacagacgc 1320
tcagcagaca tgtggagttt tgcagtgctt ctgtgggaac tggtgacacg ggaggtaccc 1380
tttgctgacc tctccaatat ggagattgga atgaaggtgg cattggaagg ccttcggcct 1440
accatcccac caggtatttc ccctcatgtg tgtaagctca tgaagatctg catgaatgaa 1500
gaccctgcaa agcgacccaa atttgacatg attgtgccta tccttgagaa gatgcaggac 1560
aagtaggact ggaaggtcct tgcctgaact ccagaggtgt cgggacatgg ttgggggaat 1620
gcacctcccc aaagcagcag gcctctggtt gcctcccccg cctccagtca tggtactacc 1680
ccagccatgg ggtccatccc cttcccccat ccctaccact gtggccccaa gaggggcggg 1740
ctcagagctt tgtcacttgc cacatggtgt ctcccaacat gggagggatc agccccgcct 1800
gtcacaataa agtttattat gaaaacagga aaaaaaaaaa aaa 1843
<210> 32
<211> 452
<212> PRT
<213> Homo sapiens
<400> 32
Met Asp Asp Ile Phe Thr Gln Cys Arg Glu Gly Asn Ala Val Ala Val
1 5 10 15
Arg Leu Trp Leu Asp Asn Thr Glu Asn Asp Leu Asn Gln Gly Asp Asp
20 25 30
His Gly Phe Ser Pro Leu His Trp Ala Cys Arg Glu Gly Arg Ser Ala
35 40 45
Val Val Glu Met Leu Ile Met Arg Gly Ala Arg Ile Asn Val Met Asn
50 55 60
Arg Gly Asp Asp Thr Pro Leu His Leu Ala Ala Ser His Gly His Arg
65 70 75 80
Asp Ile Val Gln Lys Leu Leu Gln Tyr Lys Ala Asp Ile Asn Ala Val
85 90 95
Asn Glu His Gly Asn Val Pro Leu His Tyr Ala Cys Phe Trp Gly Gln
100 105 110
Asp Gln Val Ala Glu Asp Leu Val Ala Asn Gly Ala Leu Val Ser Ile
115 120 125
Cys Asn Lys Tyr Gly Glu Met Pro Val Asp Lys Ala Lys Ala Pro Leu
130 135 140
Arg Glu Leu Leu Arg Glu Arg Ala Glu Lys Met Gly Gln Asn Leu Asn
145 150 155 160
Arg Ile Pro Tyr Lys Asp Thr Phe Trp Lys Gly Thr Thr Arg Thr Arg
165 170 175
Pro Arg Asn Gly Thr Leu Asn Lys His Ser Gly Ile Asp Phe Lys Gln
180 185 190
Leu Asn Phe Leu Thr Lys Leu Asn Glu Asn His Ser Gly Glu Leu Trp
195 200 205
Lys Gly Arg Trp Gln Gly Asn Asp Ile Val Val Lys Val Leu Lys Val
210 215 220
Arg Asp Trp Ser Thr Arg Lys Ser Arg Asp Phe Asn Glu Glu Cys Pro
225 230 235 240
Arg Leu Arg Ile Phe Ser His Pro Asn Val Leu Pro Val Leu Gly Ala
245 250 255
Cys Gln Ser Pro Pro Ala Pro His Pro Thr Leu Ile Thr His Trp Met
260 265 270
Pro Tyr Gly Ser Leu Tyr Asn Val Leu His Glu Gly Thr Asn Phe Val
275 280 285
Val Asp Gln Ser Gln Ala Val Lys Phe Ala Leu Asp Met Ala Arg Gly
290 295 300
Met Ala Phe Leu His Thr Leu Glu Pro Leu Ile Pro Arg His Ala Leu
305 310 315 320
Asn Ser Arg Ser Val Met Ile Asp Glu Asp Met Thr Ala Arg Ile Ser
325 330 335
Met Ala Asp Val Lys Phe Ser Phe Gln Cys Pro Gly Arg Met Tyr Ala
340 345 350
Pro Ala Trp Val Ala Pro Glu Ala Leu Gln Lys Lys Pro Glu Asp Thr
355 360 365
Asn Arg Arg Ser Ala Asp Met Trp Ser Phe Ala Val Leu Leu Trp Glu
370 375 380
Leu Val Thr Arg Glu Val Pro Phe Ala Asp Leu Ser Asn Met Glu Ile
385 390 395 400
Gly Met Lys Val Ala Leu Glu Gly Leu Arg Pro Thr Ile Pro Pro Gly
405 410 415
Ile Ser Pro His Val Cys Lys Leu Met Lys Ile Cys Met Asn Glu Asp
420 425 430
Pro Ala Lys Arg Pro Lys Phe Asp Met Ile Val Pro Ile Leu Glu Lys
435 440 445
Met Gln Asp Lys
450
<210> 33
<211> 452
<212> PRT
<213> Homo sapiens
<400> 33
Met Asp Asp Ile Phe Thr Gln Cys Arg Glu Gly Asn Ala Val Ala Val
1 5 10 15
Arg Leu Trp Leu Asp Asn Thr Glu Asn Asp Leu Asn Gln Gly Asp Asp
20 25 30
His Gly Phe Ser Pro Leu His Trp Ala Cys Arg Glu Gly Arg Ser Ala
35 40 45
Val Val Glu Met Leu Ile Met Arg Gly Ala Arg Ile Asn Val Met Asn
50 55 60
Arg Gly Asp Asp Thr Pro Leu His Leu Ala Ala Ser His Gly His Arg
65 70 75 80
Asp Ile Val Gln Lys Leu Leu Gln Tyr Lys Ala Asp Ile Asn Ala Val
85 90 95
Asn Glu His Gly Asn Val Pro Leu His Tyr Ala Cys Phe Trp Gly Gln
100 105 110
Asp Gln Val Ala Glu Asp Leu Val Ala Asn Gly Ala Leu Val Ser Ile
115 120 125
Cys Asn Lys Tyr Gly Glu Met Pro Val Asp Lys Ala Lys Ala Pro Leu
130 135 140
Arg Glu Leu Leu Arg Glu Arg Ala Glu Lys Met Gly Gln Asn Leu Asn
145 150 155 160
Arg Ile Pro Tyr Lys Asp Thr Phe Trp Lys Gly Thr Thr Arg Thr Arg
165 170 175
Pro Arg Asn Gly Thr Leu Asn Lys His Ser Gly Ile Asp Phe Lys Gln
180 185 190
Leu Asn Phe Leu Thr Lys Leu Asn Glu Asn His Ser Gly Glu Leu Trp
195 200 205
Lys Gly Arg Trp Gln Gly Asn Asp Ile Val Val Lys Val Leu Lys Val
210 215 220
Arg Asp Trp Ser Thr Arg Lys Ser Arg Asp Phe Asn Glu Glu Cys Pro
225 230 235 240
Arg Leu Arg Ile Phe Ser His Pro Asn Val Leu Pro Val Leu Gly Ala
245 250 255
Cys Gln Ser Pro Pro Ala Pro His Pro Thr Leu Ile Thr His Trp Met
260 265 270
Pro Tyr Gly Ser Leu Tyr Asn Val Leu His Glu Gly Thr Asn Phe Val
275 280 285
Val Asp Gln Ser Gln Ala Val Lys Phe Ala Leu Asp Met Ala Arg Gly
290 295 300
Met Ala Phe Leu His Thr Leu Glu Pro Leu Ile Pro Arg His Ala Leu
305 310 315 320
Asn Ser Arg Ser Val Met Ile Asp Glu Asp Met Thr Ala Arg Ile Ser
325 330 335
Met Ala Asp Val Lys Phe Ser Phe Gln Cys Pro Gly Arg Met Tyr Ala
340 345 350
Pro Ala Trp Val Ala Pro Glu Ala Leu Gln Lys Lys Pro Glu Asp Thr
355 360 365
Asn Arg Arg Ser Ala Asp Met Trp Ser Phe Ala Val Leu Leu Trp Glu
370 375 380
Leu Val Thr Arg Glu Val Pro Phe Ala Asp Leu Ser Asn Met Glu Ile
385 390 395 400
Gly Met Lys Val Ala Leu Glu Gly Leu Arg Pro Thr Ile Pro Pro Gly
405 410 415
Ile Ser Pro His Val Cys Lys Leu Met Lys Ile Cys Met Asn Glu Asp
420 425 430
Pro Ala Lys Arg Pro Lys Phe Asp Met Ile Val Pro Ile Leu Glu Lys
435 440 445
Met Gln Asp Lys
450
<210> 34
<211> 391
<212> PRT
<213> Homo sapiens
<400> 34
Met Asp Asp Ile Phe Thr Gln Cys Arg Glu Gly Asn Ala Val Ala Val
1 5 10 15
Arg Leu Trp Leu Asp Asn Thr Glu Asn Asp Leu Asn Gln Gly Asp Asp
20 25 30
His Gly Phe Ser Pro Leu His Trp Ala Cys Arg Glu Gly Arg Ser Ala
35 40 45
Val Val Glu Met Leu Ile Met Arg Gly Ala Arg Ile Asn Val Met Asn
50 55 60
Arg Gly Asp Asp Thr Pro Leu His Leu Ala Ala Ser His Gly His Arg
65 70 75 80
Asp Ile Val Gln Lys Leu Leu Gln Tyr Lys Ala Asp Ile Asn Ala Val
85 90 95
Asn Glu His Gly Asn Val Pro Leu His Tyr Ala Cys Phe Trp Gly Gln
100 105 110
Asp Gln Val Ala Glu Ser Gly Gln Arg Arg Trp Ala Arg Ile Ser Thr
115 120 125
Val Phe His Thr Arg Thr His Ser Gly Arg Gly Pro Pro Ala Leu Gly
130 135 140
Pro Leu Trp Lys Gly Arg Trp Gln Gly Asn Asp Ile Val Val Lys Val
145 150 155 160
Leu Lys Val Arg Asp Trp Ser Thr Arg Lys Ser Arg Asp Phe Asn Glu
165 170 175
Glu Cys Pro Arg Leu Arg Ile Phe Ser His Pro Asn Val Leu Pro Val
180 185 190
Leu Gly Ala Cys Gln Ser Pro Pro Ala Pro His Pro Thr Leu Ile Thr
195 200 205
His Trp Met Pro Tyr Gly Ser Leu Tyr Asn Val Leu His Glu Gly Thr
210 215 220
Asn Phe Val Val Asp Gln Ser Gln Ala Val Lys Phe Ala Leu Asp Met
225 230 235 240
Ala Arg Gly Met Ala Phe Leu His Thr Leu Glu Pro Leu Ile Pro Arg
245 250 255
His Ala Leu Asn Ser Arg Ser Val Met Ile Asp Glu Asp Met Thr Ala
260 265 270
Arg Ile Ser Met Ala Asp Val Lys Phe Ser Phe Gln Cys Pro Gly Arg
275 280 285
Met Tyr Ala Pro Ala Trp Val Ala Pro Glu Ala Leu Gln Lys Lys Pro
290 295 300
Glu Asp Thr Asn Arg Arg Ser Ala Asp Met Trp Ser Phe Ala Val Leu
305 310 315 320
Leu Trp Glu Leu Val Thr Arg Glu Val Pro Phe Ala Asp Leu Ser Asn
325 330 335
Met Glu Ile Gly Met Lys Val Ala Leu Glu Gly Leu Arg Pro Thr Ile
340 345 350
Pro Pro Gly Ile Ser Pro His Val Cys Lys Leu Met Lys Ile Cys Met
355 360 365
Asn Glu Asp Pro Ala Lys Arg Pro Lys Phe Asp Met Ile Val Pro Ile
370 375 380
Leu Glu Lys Met Gln Asp Lys
385 390
<210> 35
<211> 318
<212> PRT
<213> Homo sapiens
<400> 35
Met Pro Val Asp Lys Ala Lys Ala Pro Leu Arg Glu Leu Leu Arg Glu
1 5 10 15
Arg Ala Glu Lys Met Gly Gln Asn Leu Asn Arg Ile Pro Tyr Lys Asp
20 25 30
Thr Phe Trp Lys Gly Thr Thr Arg Thr Arg Pro Arg Asn Gly Thr Leu
35 40 45
Asn Lys His Ser Gly Ile Asp Phe Lys Gln Leu Asn Phe Leu Thr Lys
50 55 60
Leu Asn Glu Asn His Ser Gly Glu Leu Trp Lys Gly Arg Trp Gln Gly
65 70 75 80
Asn Asp Ile Val Val Lys Val Leu Lys Val Arg Asp Trp Ser Thr Arg
85 90 95
Lys Ser Arg Asp Phe Asn Glu Glu Cys Pro Arg Leu Arg Ile Phe Ser
100 105 110
His Pro Asn Val Leu Pro Val Leu Gly Ala Cys Gln Ser Pro Pro Ala
115 120 125
Pro His Pro Thr Leu Ile Thr His Trp Met Pro Tyr Gly Ser Leu Tyr
130 135 140
Asn Val Leu His Glu Gly Thr Asn Phe Val Val Asp Gln Ser Gln Ala
145 150 155 160
Val Lys Phe Ala Leu Asp Met Ala Arg Gly Met Ala Phe Leu His Thr
165 170 175
Leu Glu Pro Leu Ile Pro Arg His Ala Leu Asn Ser Arg Ser Val Met
180 185 190
Ile Asp Glu Asp Met Thr Ala Arg Ile Ser Met Ala Asp Val Lys Phe
195 200 205
Ser Phe Gln Cys Pro Gly Arg Met Tyr Ala Pro Ala Trp Val Ala Pro
210 215 220
Glu Ala Leu Gln Lys Lys Pro Glu Asp Thr Asn Arg Arg Ser Ala Asp
225 230 235 240
Met Trp Ser Phe Ala Val Leu Leu Trp Glu Leu Val Thr Arg Glu Val
245 250 255
Pro Phe Ala Asp Leu Ser Asn Met Glu Ile Gly Met Lys Val Ala Leu
260 265 270
Glu Gly Leu Arg Pro Thr Ile Pro Pro Gly Ile Ser Pro His Val Cys
275 280 285
Lys Leu Met Lys Ile Cys Met Asn Glu Asp Pro Ala Lys Arg Pro Lys
290 295 300
Phe Asp Met Ile Val Pro Ile Leu Glu Lys Met Gln Asp Lys
305 310 315
<210> 36
<211> 452
<212> PRT
<213> Homo sapiens
<400> 36
Met Asp Asp Ile Phe Thr Gln Cys Arg Glu Gly Asn Ala Val Ala Val
1 5 10 15
Arg Leu Trp Leu Asp Asn Thr Glu Asn Asp Leu Asn Gln Gly Asp Asp
20 25 30
His Gly Phe Ser Pro Leu His Trp Ala Cys Arg Glu Gly Arg Ser Ala
35 40 45
Val Val Glu Met Leu Ile Met Arg Gly Ala Arg Ile Asn Val Met Asn
50 55 60
Arg Gly Asp Asp Thr Pro Leu His Leu Ala Ala Ser His Gly His Arg
65 70 75 80
Asp Ile Val Gln Lys Leu Leu Gln Tyr Lys Ala Asp Ile Asn Ala Val
85 90 95
Asn Glu His Gly Asn Val Pro Leu His Tyr Ala Cys Phe Trp Gly Gln
100 105 110
Asp Gln Val Ala Glu Asp Leu Val Ala Asn Gly Ala Leu Val Ser Ile
115 120 125
Cys Asn Lys Tyr Gly Glu Met Pro Val Asp Lys Ala Lys Ala Pro Leu
130 135 140
Arg Glu Leu Leu Arg Glu Arg Ala Glu Lys Met Gly Gln Asn Leu Asn
145 150 155 160
Arg Ile Pro Tyr Lys Asp Thr Phe Trp Lys Gly Thr Thr Arg Thr Arg
165 170 175
Pro Arg Asn Gly Thr Leu Asn Lys His Ser Gly Ile Asp Phe Lys Gln
180 185 190
Leu Asn Phe Leu Thr Lys Leu Asn Glu Asn His Ser Gly Glu Leu Trp
195 200 205
Lys Gly Arg Trp Gln Gly Asn Asp Ile Val Val Lys Val Leu Lys Val
210 215 220
Arg Asp Trp Ser Thr Arg Lys Ser Arg Asp Phe Asn Glu Glu Cys Pro
225 230 235 240
Arg Leu Arg Ile Phe Ser His Pro Asn Val Leu Pro Val Leu Gly Ala
245 250 255
Cys Gln Ser Pro Pro Ala Pro His Pro Thr Leu Ile Thr His Trp Met
260 265 270
Pro Tyr Gly Ser Leu Tyr Asn Val Leu His Glu Gly Thr Asn Phe Val
275 280 285
Val Asp Gln Ser Gln Ala Val Lys Phe Ala Leu Asp Met Ala Arg Gly
290 295 300
Met Ala Phe Leu His Thr Leu Glu Pro Leu Ile Pro Arg His Ala Leu
305 310 315 320
Asn Ser Arg Ser Val Met Ile Asp Glu Asp Met Thr Ala Arg Ile Ser
325 330 335
Met Ala Asp Val Lys Phe Ser Phe Gln Cys Pro Gly Arg Met Tyr Ala
340 345 350
Pro Ala Trp Val Ala Pro Glu Ala Leu Gln Lys Lys Pro Glu Asp Thr
355 360 365
Asn Arg Arg Ser Ala Asp Met Trp Ser Phe Ala Val Leu Leu Trp Glu
370 375 380
Leu Val Thr Arg Glu Val Pro Phe Ala Asp Leu Ser Asn Met Glu Ile
385 390 395 400
Gly Met Lys Val Ala Leu Glu Gly Leu Arg Pro Thr Ile Pro Pro Gly
405 410 415
Ile Ser Pro His Val Cys Lys Leu Met Lys Ile Cys Met Asn Glu Asp
420 425 430
Pro Ala Lys Arg Pro Lys Phe Asp Met Ile Val Pro Ile Leu Glu Lys
435 440 445
Met Gln Asp Lys
450
<210> 37
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> ILK_forward primer
<400> 37
catccaaatg tgctcccagt g 21
<210> 38
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> ILK_reverse primer
<400> 38
tggctctggt ccacgacgaa 20
<210> 39
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> ILK probe
<400> 39
tgcctgccag tctccacctg ct 22
<210> 40
<211> 1861
<212> DNA
<213> Homo sapiens
<400> 40
cactcaaggt gtgcaggcag ctgtgtttgt caggaaggca gaaggagttg gctttgcttt 60
aggggaggag acgaggtccc acaacaccct ctgaagggta tataaggagc cccagcgtgc 120
agcctggcct ggtacctcct gccagcatct cttgggtttg ctgagaactc acgggctcca 180
gctacctggc catgaccacc acatttctgc aaacttcttc ctccaccttt gggggtggct 240
caacccgagg gggttccctc ctggctgggg gaggtggctt tggtgggggg agtctctctg 300
ggggaggtgg aagccgaagt atctcagctt cttctgctag gtttgtctct tcagggtcag 360
gaggaggata tgggggtggc atgagggtct gtggctttgg tggaggggct ggtagtgttt 420
tcggtggagg ctttggaggg ggcgttggtg ggggttttgg tggtggcttt ggtggtggcg 480
atggtggtct cctctctggc aatgagaaaa ttaccatgca gaacctcaat gaccgcctgg 540
cctcctacct ggacaaggta cgtgccctgg aggaggccaa tgctgacctg gaggtgaaga 600
tccatgactg gtaccagaag cagaccccaa ccagcccaga atgcgactac agccaatact 660
tcaagaccat tgaagagctc cgggacaaga tcatggccac caccatcgac aactcccggg 720
tcatcctgga gatcgacaat gccaggctgg ctgcggacga cttcaggctc aagtatgaga 780
atgagctggc cctgcgccag ggcgttgagg ctgacatcaa cggcttgcgc cgagtcctgg 840
atgagctgac cctggccagg actgacctgg agatgcagat cgagggcctg aatgaggagc 900
tagcctacct gaagaagaac cacgaagagg agatgaagga gttcagcagc cagctggccg 960
gccaggtcaa tgtggagatg gacgcagcac cgggtgtgga cctgacccgt gtgctggcag 1020
agatgaggga gcagtacgag gccatggcgg agaagaaccg ccgggatgtc gaggcctggt 1080
tcttcagcaa gactgaggag ctgaacaaag aggtggcctc caacacagaa atgatccaga 1140
ccagcaagac ggagatcaca gacctgagac gcacgatgca ggagctggag atcgagctgc 1200
agtcccagct cagcatgaaa gctgggctgg agaactcact ggccgagaca gagtgccgct 1260
atgccacgca gctgcagcag atccaggggc tcattggtgg cctggaggcc cagctgagtg 1320
agctccgatg cgagatggag gctcagaacc aggagtacaa gatgctgctt gacataaaga 1380
cacggctgga gcaggagatc gctacttacc gcagcctgct cgagggccag gatgccaaga 1440
tggctggcat tggcatcagg gaagcctctt caggaggtgg tggtagcagc agcaatttcc 1500
acatcaatgt agaagagtca gtggatggac aggtggtttc ttcccacaag agagaaatct 1560
aagtgtctat tgcaggagaa acgtcccttg ccactcccca ctctcatcag gccaagtgga 1620
ggactggcca gagggcctgc acatgcaaac tccagtccct gccttcagag agctgaaaag 1680
ggtccctcgg tcttttattt cagggctttg catgcgctct attccccctc tgcctctccc 1740
caccttcttt ggagcaagga gatgcagctg tattgtgtaa caagctcatt tgtacagtgt 1800
ctgttcatgt aataaagaat tacttttcct tttgcaaata aaaaaaaaaa aaaaaaaaaa 1860
a 1861
<210> 41
<211> 456
<212> PRT
<213> Homo sapiens
<400> 41
Met Thr Thr Thr Phe Leu Gln Thr Ser Ser Ser Thr Phe Gly Gly Gly
1 5 10 15
Ser Thr Arg Gly Gly Ser Leu Leu Ala Gly Gly Gly Gly Phe Gly Gly
20 25 30
Gly Ser Leu Ser Gly Gly Gly Gly Ser Arg Ser Ile Ser Ala Ser Ser
35 40 45
Ala Arg Phe Val Ser Ser Gly Ser Gly Gly Gly Tyr Gly Gly Gly Met
50 55 60
Arg Val Cys Gly Phe Gly Gly Gly Ala Gly Ser Val Phe Gly Gly Gly
65 70 75 80
Phe Gly Gly Gly Val Gly Gly Gly Phe Gly Gly Gly Phe Gly Gly Gly
85 90 95
Asp Gly Gly Leu Leu Ser Gly Asn Glu Lys Ile Thr Met Gln Asn Leu
100 105 110
Asn Asp Arg Leu Ala Ser Tyr Leu Asp Lys Val Arg Ala Leu Glu Glu
115 120 125
Ala Asn Ala Asp Leu Glu Val Lys Ile His Asp Trp Tyr Gln Lys Gln
130 135 140
Thr Pro Thr Ser Pro Glu Cys Asp Tyr Ser Gln Tyr Phe Lys Thr Ile
145 150 155 160
Glu Glu Leu Arg Asp Lys Ile Met Ala Thr Thr Ile Asp Asn Ser Arg
165 170 175
Val Ile Leu Glu Ile Asp Asn Ala Arg Leu Ala Ala Asp Asp Phe Arg
180 185 190
Leu Lys Tyr Glu Asn Glu Leu Ala Leu Arg Gln Gly Val Glu Ala Asp
195 200 205
Ile Asn Gly Leu Arg Arg Val Leu Asp Glu Leu Thr Leu Ala Arg Thr
210 215 220
Asp Leu Glu Met Gln Ile Glu Gly Leu Asn Glu Glu Leu Ala Tyr Leu
225 230 235 240
Lys Lys Asn His Glu Glu Glu Met Lys Glu Phe Ser Ser Gln Leu Ala
245 250 255
Gly Gln Val Asn Val Glu Met Asp Ala Ala Pro Gly Val Asp Leu Thr
260 265 270
Arg Val Leu Ala Glu Met Arg Glu Gln Tyr Glu Ala Met Ala Glu Lys
275 280 285
Asn Arg Arg Asp Val Glu Ala Trp Phe Phe Ser Lys Thr Glu Glu Leu
290 295 300
Asn Lys Glu Val Ala Ser Asn Thr Glu Met Ile Gln Thr Ser Lys Thr
305 310 315 320
Glu Ile Thr Asp Leu Arg Arg Thr Met Gln Glu Leu Glu Ile Glu Leu
325 330 335
Gln Ser Gln Leu Ser Met Lys Ala Gly Leu Glu Asn Ser Leu Ala Glu
340 345 350
Thr Glu Cys Arg Tyr Ala Thr Gln Leu Gln Gln Ile Gln Gly Leu Ile
355 360 365
Gly Gly Leu Glu Ala Gln Leu Ser Glu Leu Arg Cys Glu Met Glu Ala
370 375 380
Gln Asn Gln Glu Tyr Lys Met Leu Leu Asp Ile Lys Thr Arg Leu Glu
385 390 395 400
Gln Glu Ile Ala Thr Tyr Arg Ser Leu Leu Glu Gly Gln Asp Ala Lys
405 410 415
Met Ala Gly Ile Gly Ile Arg Glu Ala Ser Ser Gly Gly Gly Gly Ser
420 425 430
Ser Ser Asn Phe His Ile Asn Val Glu Glu Ser Val Asp Gly Gln Val
435 440 445
Val Ser Ser His Lys Arg Glu Ile
450 455
<210> 42
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> KRT15_forward primer
<400> 42
gctagcctac ctgaagaaga a 21
<210> 43
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> KRT15_reverse primer
<400> 43
ccagctggct gctgaact 18
<210> 44
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> KRT15 probe
<400> 44
ccacgaagag gagatgaagg 20
<210> 45
<211> 3123
<212> DNA
<213> Homo sapiens
<400> 45
ttggctacat cggacccaga tgactgcctc ctcacttcct ccctcccgat tccgccgcgg 60
cccccaaaga ctctcggggt ggccccttgt ccgcaccgct tggagggagt gtgctctgag 120
ttaagctggt ctcttctggt cctggaaaaa aatgagtatt gacaaggttg ctggatctgc 180
gcagaaaaga aagtgccact taataaaaaa tttagcccgg cagtggtacc gtctgcagag 240
cttgctgccc ttggacgtta gcaggaagcc ttcggggtgc tgtaatcggc gggcagagga 300
gagggaggcc gcggaattaa aaggaacaaa agctagagcg ccatgccaaa cgtccccggc 360
aagacccagt taggcaggag ccgggagtga tgggaaaatg aactagaaca tattggagaa 420
ttgggagaag tctctttggt ttggaaaaaa aaaaaaggaa tcttcagcct agatcacttt 480
cttatccgga ctgggatatt aaatatacga cacatccagg agtttattgg agcgcagact 540
gatggcgcaa aggtacgatg agctgcccca ttacggcggg atggacggag taggggttcc 600
cgcttccatg tacggagacc ctcacgcgcc gcggccgatc cccccggttc accacctgaa 660
ccacgggccg ccgctccacg ccacacagca ctacggcgcg cacgccccgc accccaatgt 720
catgccggcc agtatgggat ccgctgtcaa cgacgccttg aagcgggaca aggacgcgat 780
ctatgggcac ccgttgtttc ctctgttagc tctggtcttt gagaagtgcg agctggcgac 840
ctgcactccc cgggaacctg gagtggctgg cggagacgtc tgctcctccg actccttcaa 900
cgaggacatc gcggtcttcg ccaagcaggt tcgcgccgaa aagccacttt tttcctcaaa 960
tccagagctg gacaatttga tgatacaagc aatacaagta ctaaggtttc atcttttgga 1020
gttagaaaag gtccacgaac tgtgcgataa cttctgccac cgatacatta gctgtttgaa 1080
ggggaaaatg cccatcgacc tcgtcattga tgaaagagac ggcagctcca agtcagatca 1140
tgaagaactt tcaggctcct ccacaaatct cgctgaccat aacccttctt cttggcgaga 1200
ccacgatgat gcaacctcaa cccactcagc aggcacccca gggccctcca gtgggggcca 1260
tgcttcccag agcggagaca acagcagtga gcaaggggat ggtttagaca acagtgtagc 1320
ttcacctggt acaggtgacg atgatgatcc ggataaggac aaaaaacgcc agaagaaaag 1380
aggcattttc cccaaagtag caacaaatat catgagagca tggctcttcc agcatctcac 1440
acatccgtac ccttccgaag agcagaagaa acagttagcg caagacacag gacttacaat 1500
tctccaagta aacaactggt ttattaatgc cagaagaaga atagtacagc ccatgattga 1560
ccagtcaaat cgagcagtga gccaaggagc agcatatagt ccagagggtc agcccatggg 1620
gagctttgtg ttggatggtc agcaacacat ggggatccgg cctgcaggtt tgcagagcat 1680
gccaggggac tacgtttctc agggtggtcc tatgggaatg agtatggcac agccaagtta 1740
cactcctccc cagatgaccc cacaccctac tcaattaaga catggacccc caatgcattc 1800
atatttgcca agccatcccc accacccagc catgatgatg cacggaggac cccctaccca 1860
ccctggaatg actatgtcag cacagagccc cacaatgtta aattctgtag atcccaatgt 1920
tggcggacag gttatggaca ttcatgccca atagtataag ggaactcaag ggaaaaggaa 1980
acacacgcaa aaactatttt aagactttct gaactttgac cagatgttga cacttaatat 2040
gaaattccag acagctgtga ttatttttta cttttgtcat ttttcatcaa gcaacagagg 2100
accaatgcaa caagaacaca aatgtgaaat catgggctga ctgagacaat tctgtccatg 2160
taaagatcct ctggaaaaag actccgagag ttataactac tgtagtataa atataggaac 2220
taagttaaac ttgtacattt ctgttgatca cgccgttatg ttgcctcaaa tagttttaga 2280
agagaaaaaa aaatatatcc ttgttttcca cactatgtgt gttgttccca aaagaatgac 2340
tgttttggtt catcagtgaa ttcaccatcc aggagagact gtggtatata ttttaaacct 2400
gttgggccaa tgagaaaaga accacactgg agatcatgat gaacttttgg ctgaacctca 2460
tcactcgaac tccagcttca agaatgtgtt ttcatgcccg gcctttgttc ctccataaat 2520
gtgtccttta gtttcaaaca gatctttata gttcgtgctt cataagccaa ttcttattat 2580
tatttttggg ggactcttct tcaaagagct tgccaatgaa gatttaaaga cagagcagga 2640
gcttcttcca ggagttctga gccttggttg tggacaaaac aatcttaagt tgggcagctt 2700
tcctcaacac aaaaaaaagt tattaatggt cattgaacca taactaggac tttatcagaa 2760
actcaaagct tgggggataa aaaggagcaa gagaatactg taacaaactt cgtacagagt 2820
tcggtctatt aattgtttca tgttagatat tctatgtgtt tacctcaatt gaaaaaaaaa 2880
agaatgtttt tgctagtatc agatctgctg tggaattggt attgtatgtc catgaattct 2940
tcttttctca gcacgtgttc ctcactagaa gaaaatgctg ttacctttaa gctttgtcaa 3000
atttacatta aaatacttgt atgaggactg tgacgttatg ttaaaaaaaa aaaggtgtta 3060
agtcacaaaa agcggtaata aatatttcat ttttgatttt ttgttaaaaa aaaaaaaaaa 3120
aaa 3123
<210> 46
<211> 3074
<212> DNA
<213> Homo sapiens
<400> 46
ttggctacat cggacccaga tgactgcctc ctcacttcct ccctcccgat tccgccgcgg 60
cccccaaaga ctctcggggt ggccccttgt ccgcaccgct tggagggagt gtgctctgag 120
ttaagctggt ctcttctggt cctggaaaaa aatgagtatt gacaaggttg ctggatctgc 180
gcagaaaaga aagtgccact taataaaaaa tttagcccgg cagtggtacc gtctgcagag 240
cttgctgccc ttggacgtta gcaggaagcc ttcggggtgc tgtaatcggc gggcagagga 300
gagggaggcc gcggaattaa aaggaacaaa agctagagcg ccatgccaaa cgtccccggc 360
aagacccagt taggcaggag ccgggagtga tgggaaaatg aactagaata cgatgagctg 420
ccccattacg gcgggatgga cggagtaggg gttcccgctt ccatgtacgg agaccctcac 480
gcgccgcggc cgatcccccc ggttcaccac ctgaaccacg ggccgccgct ccacgccaca 540
cagcactacg gcgcgcacgc cccgcacccc aatgtcatgc cggccagtat gggatccgct 600
gtcaacgacg ccttgaagcg ggacaaggac gcgatctatg ggcacccgtt gtttcctctg 660
ttagctctgg tctttgagaa gtgcgagctg gcgacctgca ctccccggga acctggagtg 720
gctggcggag acgtctgctc ctccgactcc ttcaacgagg acatcgcggt cttcgccaag 780
caggttcgcg ccgaaaagcc acttttttcc tcaaatccag agctggacaa tttgatgata 840
caagcaatac aagtactaag gtttcatctt ttggagttag aaaaggtcca cgaactgtgc 900
gataacttct gccaccgata cattagctgt ttgaagggga aaatgcccat cgacctcgtc 960
attgatgaaa gagacggcag ctccaagtca gatcatgaag aactttcagg ctcctccaca 1020
aatctcgctg accataaccc ttcttcttgg cgagaccacg atgatgcaac ctcaacccac 1080
tcagcaggca ccccagggcc ctccagtggg ggccatgctt cccagagcgg agacaacagc 1140
agtgagcaag gggatggttt agacaacagt gtagcttcac ctggtacagg tgacgatgat 1200
gatccggata aggacaaaaa acgccagaag aaaagaggca ttttccccaa agtagcaaca 1260
aatatcatga gagcatggct cttccagcat ctcacacatc cgtacccttc cgaagagcag 1320
aagaaacagt tagcgcaaga cacaggactt acaattctcc aagtaaacaa ctggtttatt 1380
aatgccagaa gaagaatagt acagcccatg attgaccagt caaatcgagc agtgagccaa 1440
ggagcagcat atagtccaga gggtcagccc atggggagct ttgtgttgga tggtcagcaa 1500
cacatgggga tccggcctgc aggacctatg agtggaatgg gcatgaatat gggcatggat 1560
gggcaatggc actacatgta accttcatca tgtaaagcaa tcgcaaagca agggggaagt 1620
ttgcagagca tgccagggga ctacgtttct cagggtggtc ctatgggaat gagtatggca 1680
cagccaagtt acactcctcc ccagatgacc ccacacccta ctcaattaag acatggaccc 1740
ccaatgcatt catatttgcc aagccatccc caccacccag ccatgatgat gcacggagga 1800
ccccctaccc accctggaat gactatgtca gcacagagcc ccacaatgtt aaattctgta 1860
gatcccaatg ttggcggaca ggttatggac attcatgccc aatagtataa gggaactcaa 1920
gggaaaagga aacacacgca aaaactattt taagactttc tgaactttga ccagatgttg 1980
acacttaata tgaaattcca gacagctgtg attatttttt acttttgtca tttttcatca 2040
agcaacagag gaccaatgca acaagaacac aaatgtgaaa tcatgggctg actgagacaa 2100
ttctgtccat gtaaagatcc tctggaaaaa gactccgaga gttataacta ctgtagtata 2160
aatataggaa ctaagttaaa cttgtacatt tctgttgatc acgccgttat gttgcctcaa 2220
atagttttag aagagaaaaa aaaatatatc cttgttttcc acactatgtg tgttgttccc 2280
aaaagaatga ctgttttggt tcatcagtga attcaccatc caggagagac tgtggtatat 2340
attttaaacc tgttgggcca atgagaaaag aaccacactg gagatcatga tgaacttttg 2400
gctgaacctc atcactcgaa ctccagcttc aagaatgtgt tttcatgccc ggcctttgtt 2460
cctccataaa tgtgtccttt agtttcaaac agatctttat agttcgtgct tcataagcca 2520
attcttatta ttatttttgg gggactcttc ttcaaagagc ttgccaatga agatttaaag 2580
acagagcagg agcttcttcc aggagttctg agccttggtt gtggacaaaa caatcttaag 2640
ttgggcagct ttcctcaaca caaaaaaaag ttattaatgg tcattgaacc ataactagga 2700
ctttatcaga aactcaaagc ttgggggata aaaaggagca agagaatact gtaacaaact 2760
tcgtacagag ttcggtctat taattgtttc atgttagata ttctatgtgt ttacctcaat 2820
tgaaaaaaaa aagaatgttt ttgctagtat cagatctgct gtggaattgg tattgtatgt 2880
ccatgaattc ttcttttctc agcacgtgtt cctcactaga agaaaatgct gttaccttta 2940
agctttgtca aatttacatt aaaatacttg tatgaggact gtgacgttat gttaaaaaaa 3000
aaaaggtgtt aagtcacaaa aagcggtaat aaatatttca tttttgattt tttgttaaaa 3060
aaaaaaaaaa aaaa 3074
<210> 47
<211> 3352
<212> DNA
<213> Homo sapiens
<400> 47
tttaaagaga gaggatcgta ttatagatac cgcgggggca aagctaaaaa aggggggagg 60
ggggaggaaa aaattcaaga agcagaaacc cctcgcggag ttttactgga agaaaaaaac 120
gggtctgaaa gattcctcct cttcatcatc atcaaccatc attcattcac taccttgaca 180
ttccgggctt tgattgacag ctggagtggc aaaaagccat gaaacacgac agttcggtta 240
catgtgggct gctgacgggc cgctcgtaac cttcagttcg ggggcttgac aatttttttc 300
ttctttttct tctttttctt ttctttcttt ttttttccaa ctgaggggaa gagaagagaa 360
agagggggaa aggaggaccg aagaggagga ggaggggagg ggggaggagg aggaggtgga 420
ggaggaggag gaagatcagg aggaggagga agaagaggaa aaaagagaaa aagaagaaat 480
atcacagaaa aaaaaattct tcgttgtcta gactgggctt tttttccccc ctaaaaaata 540
gcatattgga gaattgggag aagtctcttt ggtttggaaa aaaaaaaaag gaatcttcag 600
cctagatcac tttcttatcc ggactgggat attaaatata cgacacatcc aggagtttat 660
tggagcgcag actgatggcg caaaggtacg atgagctgcc ccattacggc gggatggacg 720
gagtaggggt tcccgcttcc atgtacggag accctcacgc gccgcggccg atccccccgg 780
ttcaccacct gaaccacggg ccgccgctcc acgccacaca gcactacggc gcgcacgccc 840
cgcaccccaa tgtcatgccg gccagtatgg gatccgctgt caacgacgcc ttgaagcggg 900
acaaggacgc gatctatggg cacccgttgt ttcctctgtt agctctggtc tttgagaagt 960
gcgagctggc gacctgcact ccccgggaac ctggagtggc tggcggagac gtctgctcct 1020
ccgactcctt caacgaggac atcgcggtct tcgccaagca ggttcgcgcc gaaaagccac 1080
ttttttcctc aaatccagag ctggacaatt tgatgataca agcaatacaa gtactaaggt 1140
ttcatctttt ggagttagaa aaggtccacg aactgtgcga taacttctgc caccgataca 1200
ttagctgttt gaaggggaaa atgcccatcg acctcgtcat tgatgaaaga gacggcagct 1260
ccaagtcaga tcatgaagaa ctttcaggct cctccacaaa tctcgctgac cataaccctt 1320
cttcttggcg agaccacgat gatgcaacct caacccactc agcaggcacc ccagggccct 1380
ccagtggggg ccatgcttcc cagagcggag acaacagcag tgagcaaggg gatggtttag 1440
acaacagtgt agcttcacct ggtacaggtg acgatgatga tccggataag gacaaaaaac 1500
gccagaagaa aagaggcatt ttccccaaag tagcaacaaa tatcatgaga gcatggctct 1560
tccagcatct cacacatccg tacccttccg aagagcagaa gaaacagtta gcgcaagaca 1620
caggacttac aattctccaa gtaaacaact ggtttattaa tgccagaaga agaatagtac 1680
agcccatgat tgaccagtca aatcgagcag tgagccaagg agcagcatat agtccagagg 1740
gtcagcccat ggggagcttt gtgttggatg gtcagcaaca catggggatc cggcctgcag 1800
gacctatgag tggaatgggc atgaatatgg gcatggatgg gcaatggcac tacatgtaac 1860
cttcatcatg taaagcaatc gcaaagcaag ggggaagttt gcagagcatg ccaggggact 1920
acgtttctca gggtggtcct atgggaatga gtatggcaca gccaagttac actcctcccc 1980
agatgacccc acaccctact caattaagac atggaccccc aatgcattca tatttgccaa 2040
gccatcccca ccacccagcc atgatgatgc acggaggacc ccctacccac cctggaatga 2100
ctatgtcagc acagagcccc acaatgttaa attctgtaga tcccaatgtt ggcggacagg 2160
ttatggacat tcatgcccaa tagtataagg gaactcaagg gaaaaggaaa cacacgcaaa 2220
aactatttta agactttctg aactttgacc agatgttgac acttaatatg aaattccaga 2280
cagctgtgat tattttttac ttttgtcatt tttcatcaag caacagagga ccaatgcaac 2340
aagaacacaa atgtgaaatc atgggctgac tgagacaatt ctgtccatgt aaagatcctc 2400
tggaaaaaga ctccgagagt tataactact gtagtataaa tataggaact aagttaaact 2460
tgtacatttc tgttgatcac gccgttatgt tgcctcaaat agttttagaa gagaaaaaaa 2520
aatatatcct tgttttccac actatgtgtg ttgttcccaa aagaatgact gttttggttc 2580
atcagtgaat tcaccatcca ggagagactg tggtatatat tttaaacctg ttgggccaat 2640
gagaaaagaa ccacactgga gatcatgatg aacttttggc tgaacctcat cactcgaact 2700
ccagcttcaa gaatgtgttt tcatgcccgg cctttgttcc tccataaatg tgtcctttag 2760
tttcaaacag atctttatag ttcgtgcttc ataagccaat tcttattatt atttttgggg 2820
gactcttctt caaagagctt gccaatgaag atttaaagac agagcaggag cttcttccag 2880
gagttctgag ccttggttgt ggacaaaaca atcttaagtt gggcagcttt cctcaacaca 2940
aaaaaaagtt attaatggtc attgaaccat aactaggact ttatcagaaa ctcaaagctt 3000
gggggataaa aaggagcaag agaatactgt aacaaacttc gtacagagtt cggtctatta 3060
attgtttcat gttagatatt ctatgtgttt acctcaattg aaaaaaaaaa gaatgttttt 3120
gctagtatca gatctgctgt ggaattggta ttgtatgtcc atgaattctt cttttctcag 3180
cacgtgttcc tcactagaag aaaatgctgt tacctttaag ctttgtcaaa tttacattaa 3240
aatacttgta tgaggactgt gacgttatgt taaaaaaaaa aaggtgttaa gtcacaaaaa 3300
gcggtaataa atatttcatt tttgattttt tgttaaaaaa aaaaaaaaaa aa 3352
<210> 48
<211> 3277
<212> DNA
<213> Homo sapiens
<400> 48
tttaaagaga gaggatcgta ttatagatac cgcgggggca aagctaaaaa aggggggagg 60
ggggaggaaa aaattcaaga agcagaaacc cctcgcggag ttttactgga agaaaaaaac 120
gggtctgaaa gattcctcct cttcatcatc atcaaccatc attcattcac taccttgaca 180
ttccgggctt tgattgacag ctggagtggc aaaaagccat gaaacacgac agttcggtta 240
catgtgggct gctgacgggc cgctcgtaac cttcagttcg ggggcttgac aatttttttc 300
ttctttttct tctttttctt ttctttcttt ttttttccaa ctgaggggaa gagaagagaa 360
agagggggaa aggaggaccg aagaggagga ggaggggagg ggggaggagg aggaggtgga 420
ggaggaggag gaagatcagg aggaggagga agaagaggaa aaaagagaaa aagaagaaat 480
atcacagaaa aaaaaattct tcgttgtcta gactgggctt tttttccccc ctaaaaaata 540
gcatattgga gaattgggag aagtctcttt ggtttggaaa aaaaaaaaag gaatcttcag 600
cctagatcac tttcttatcc ggactgggat attaaatata cgacacatcc aggagtttat 660
tggagcgcag actgatggcg caaaggtacg atgagctgcc ccattacggc gggatggacg 720
gagtaggggt tcccgcttcc atgtacggag accctcacgc gccgcggccg atccccccgg 780
ttcaccacct gaaccacggg ccgccgctcc acgccacaca gcactacggc gcgcacgccc 840
cgcaccccaa tgtcatgccg gccagtatgg gatccgctgt caacgacgcc ttgaagcggg 900
acaaggacgc gatctatggg cacccgttgt ttcctctgtt agctctggtc tttgagaagt 960
gcgagctggc gacctgcact ccccgggaac ctggagtggc tggcggagac gtctgctcct 1020
ccgactcctt caacgaggac atcgcggtct tcgccaagca ggttcgcgcc gaaaagccac 1080
ttttttcctc aaatccagag ctggacaatt tgatgataca agcaatacaa gtactaaggt 1140
ttcatctttt ggagttagaa aaggtccacg aactgtgcga taacttctgc caccgataca 1200
ttagctgttt gaaggggaaa atgcccatcg acctcgtcat tgatgaaaga gacggcagct 1260
ccaagtcaga tcatgaagaa ctttcaggct cctccacaaa tctcgctgac cataaccctt 1320
cttcttggcg agaccacgat gatgcaacct caacccactc agcaggcacc ccagggccct 1380
ccagtggggg ccatgcttcc cagagcggag acaacagcag tgagcaaggg gatggtttag 1440
acaacagtgt agcttcacct ggtacaggtg acgatgatga tccggataag gacaaaaaac 1500
gccagaagaa aagaggcatt ttccccaaag tagcaacaaa tatcatgaga gcatggctct 1560
tccagcatct cacacatccg tacccttccg aagagcagaa gaaacagtta gcgcaagaca 1620
caggacttac aattctccaa gtaaacaact ggtttattaa tgccagaaga agaatagtac 1680
agcccatgat tgaccagtca aatcgagcag gttttcttct tgatccttca gtgagccaag 1740
gagcagcata tagtccagag ggtcagccca tggggagctt tgtgttggat ggtcagcaac 1800
acatggggat ccggcctgca ggtttgcaga gcatgccagg ggactacgtt tctcagggtg 1860
gtcctatggg aatgagtatg gcacagccaa gttacactcc tccccagatg accccacacc 1920
ctactcaatt aagacatgga cccccaatgc attcatattt gccaagccat ccccaccacc 1980
cagccatgat gatgcacgga ggacccccta cccaccctgg aatgactatg tcagcacaga 2040
gccccacaat gttaaattct gtagatccca atgttggcgg acaggttatg gacattcatg 2100
cccaatagta taagggaact caagggaaaa ggaaacacac gcaaaaacta ttttaagact 2160
ttctgaactt tgaccagatg ttgacactta atatgaaatt ccagacagct gtgattattt 2220
tttacttttg tcatttttca tcaagcaaca gaggaccaat gcaacaagaa cacaaatgtg 2280
aaatcatggg ctgactgaga caattctgtc catgtaaaga tcctctggaa aaagactccg 2340
agagttataa ctactgtagt ataaatatag gaactaagtt aaacttgtac atttctgttg 2400
atcacgccgt tatgttgcct caaatagttt tagaagagaa aaaaaaatat atccttgttt 2460
tccacactat gtgtgttgtt cccaaaagaa tgactgtttt ggttcatcag tgaattcacc 2520
atccaggaga gactgtggta tatattttaa acctgttggg ccaatgagaa aagaaccaca 2580
ctggagatca tgatgaactt ttggctgaac ctcatcactc gaactccagc ttcaagaatg 2640
tgttttcatg cccggccttt gttcctccat aaatgtgtcc tttagtttca aacagatctt 2700
tatagttcgt gcttcataag ccaattctta ttattatttt tgggggactc ttcttcaaag 2760
agcttgccaa tgaagattta aagacagagc aggagcttct tccaggagtt ctgagccttg 2820
gttgtggaca aaacaatctt aagttgggca gctttcctca acacaaaaaa aagttattaa 2880
tggtcattga accataacta ggactttatc agaaactcaa agcttggggg ataaaaagga 2940
gcaagagaat actgtaacaa acttcgtaca gagttcggtc tattaattgt ttcatgttag 3000
atattctatg tgtttacctc aattgaaaaa aaaaagaatg tttttgctag tatcagatct 3060
gctgtggaat tggtattgta tgtccatgaa ttcttctttt ctcagcacgt gttcctcact 3120
agaagaaaat gctgttacct ttaagctttg tcaaatttac attaaaatac ttgtatgagg 3180
actgtgacgt tatgttaaaa aaaaaaaggt gttaagtcac aaaaagcggt aataaatatt 3240
tcatttttga ttttttgtta aaaaaaaaaa aaaaaaa 3277
<210> 49
<211> 3256
<212> DNA
<213> Homo sapiens
<400> 49
tttaaagaga gaggatcgta ttatagatac cgcgggggca aagctaaaaa aggggggagg 60
ggggaggaaa aaattcaaga agcagaaacc cctcgcggag ttttactgga agaaaaaaac 120
gggtctgaaa gattcctcct cttcatcatc atcaaccatc attcattcac taccttgaca 180
ttccgggctt tgattgacag ctggagtggc aaaaagccat gaaacacgac agttcggtta 240
catgtgggct gctgacgggc cgctcgtaac cttcagttcg ggggcttgac aatttttttc 300
ttctttttct tctttttctt ttctttcttt ttttttccaa ctgaggggaa gagaagagaa 360
agagggggaa aggaggaccg aagaggagga ggaggggagg ggggaggagg aggaggtgga 420
ggaggaggag gaagatcagg aggaggagga agaagaggaa aaaagagaaa aagaagaaat 480
atcacagaaa aaaaaattct tcgttgtcta gactgggctt tttttccccc ctaaaaaata 540
gcatattgga gaattgggag aagtctcttt ggtttggaaa aaaaaaaaag gaatcttcag 600
cctagatcac tttcttatcc ggactgggat attaaatata cgacacatcc aggagtttat 660
tggagcgcag actgatggcg caaaggtacg atgagctgcc ccattacggc gggatggacg 720
gagtaggggt tcccgcttcc atgtacggag accctcacgc gccgcggccg atccccccgg 780
ttcaccacct gaaccacggg ccgccgctcc acgccacaca gcactacggc gcgcacgccc 840
cgcaccccaa tgtcatgccg gccagtatgg gatccgctgt caacgacgcc ttgaagcggg 900
acaaggacgc gatctatggg cacccgttgt ttcctctgtt agctctggtc tttgagaagt 960
gcgagctggc gacctgcact ccccgggaac ctggagtggc tggcggagac gtctgctcct 1020
ccgactcctt caacgaggac atcgcggtct tcgccaagca ggttcgcgcc gaaaagccac 1080
ttttttcctc aaatccagag ctggacaatt tgatgataca agcaatacaa gtactaaggt 1140
ttcatctttt ggagttagaa aaggtccacg aactgtgcga taacttctgc caccgataca 1200
ttagctgttt gaaggggaaa atgcccatcg acctcgtcat tgatgaaaga gacggcagct 1260
ccaagtcaga tcatgaagaa ctttcaggct cctccacaaa tctcgctgac cataaccctt 1320
cttcttggcg agaccacgat gatgcaacct caacccactc agcaggcacc ccagggccct 1380
ccagtggggg ccatgcttcc cagagcggag acaacagcag tgagcaaggg gatggtttag 1440
acaacagtgt agcttcacct ggtacaggtg acgatgatga tccggataag gacaaaaaac 1500
gccagaagaa aagaggcatt ttccccaaag tagcaacaaa tatcatgaga gcatggctct 1560
tccagcatct cacacatccg tacccttccg aagagcagaa gaaacagtta gcgcaagaca 1620
caggacttac aattctccaa gtaaacaact ggtttattaa tgccagaaga agaatagtac 1680
agcccatgat tgaccagtca aatcgagcag tgagccaagg agcagcatat agtccagagg 1740
gtcagcccat ggggagcttt gtgttggatg gtcagcaaca catggggatc cggcctgcag 1800
gtttgcagag catgccaggg gactacgttt ctcagggtgg tcctatggga atgagtatgg 1860
cacagccaag ttacactcct ccccagatga ccccacaccc tactcaatta agacatggac 1920
ccccaatgca ttcatatttg ccaagccatc cccaccaccc agccatgatg atgcacggag 1980
gaccccctac ccaccctgga atgactatgt cagcacagag ccccacaatg ttaaattctg 2040
tagatcccaa tgttggcgga caggttatgg acattcatgc ccaatagtat aagggaactc 2100
aagggaaaag gaaacacacg caaaaactat tttaagactt tctgaacttt gaccagatgt 2160
tgacacttaa tatgaaattc cagacagctg tgattatttt ttacttttgt catttttcat 2220
caagcaacag aggaccaatg caacaagaac acaaatgtga aatcatgggc tgactgagac 2280
aattctgtcc atgtaaagat cctctggaaa aagactccga gagttataac tactgtagta 2340
taaatatagg aactaagtta aacttgtaca tttctgttga tcacgccgtt atgttgcctc 2400
aaatagtttt agaagagaaa aaaaaatata tccttgtttt ccacactatg tgtgttgttc 2460
ccaaaagaat gactgttttg gttcatcagt gaattcacca tccaggagag actgtggtat 2520
atattttaaa cctgttgggc caatgagaaa agaaccacac tggagatcat gatgaacttt 2580
tggctgaacc tcatcactcg aactccagct tcaagaatgt gttttcatgc ccggcctttg 2640
ttcctccata aatgtgtcct ttagtttcaa acagatcttt atagttcgtg cttcataagc 2700
caattcttat tattattttt gggggactct tcttcaaaga gcttgccaat gaagatttaa 2760
agacagagca ggagcttctt ccaggagttc tgagccttgg ttgtggacaa aacaatctta 2820
agttgggcag ctttcctcaa cacaaaaaaa agttattaat ggtcattgaa ccataactag 2880
gactttatca gaaactcaaa gcttggggga taaaaaggag caagagaata ctgtaacaaa 2940
cttcgtacag agttcggtct attaattgtt tcatgttaga tattctatgt gtttacctca 3000
attgaaaaaa aaaagaatgt ttttgctagt atcagatctg ctgtggaatt ggtattgtat 3060
gtccatgaat tcttcttttc tcagcacgtg ttcctcacta gaagaaaatg ctgttacctt 3120
taagctttgt caaatttaca ttaaaatact tgtatgagga ctgtgacgtt atgttaaaaa 3180
aaaaaaggtg ttaagtcaca aaaagcggta ataaatattt catttttgat tttttgttaa 3240
aaaaaaaaaa aaaaaa 3256
<210> 50
<211> 3373
<212> DNA
<213> Homo sapiens
<400> 50
tttaaagaga gaggatcgta ttatagatac cgcgggggca aagctaaaaa aggggggagg 60
ggggaggaaa aaattcaaga agcagaaacc cctcgcggag ttttactgga agaaaaaaac 120
gggtctgaaa gattcctcct cttcatcatc atcaaccatc attcattcac taccttgaca 180
ttccgggctt tgattgacag ctggagtggc aaaaagccat gaaacacgac agttcggtta 240
catgtgggct gctgacgggc cgctcgtaac cttcagttcg ggggcttgac aatttttttc 300
ttctttttct tctttttctt ttctttcttt ttttttccaa ctgaggggaa gagaagagaa 360
agagggggaa aggaggaccg aagaggagga ggaggggagg ggggaggagg aggaggtgga 420
ggaggaggag gaagatcagg aggaggagga agaagaggaa aaaagagaaa aagaagaaat 480
atcacagaaa aaaaaattct tcgttgtcta gactgggctt tttttccccc ctaaaaaata 540
gcatattgga gaattgggag aagtctcttt ggtttggaaa aaaaaaaaag gaatcttcag 600
cctagatcac tttcttatcc ggactgggat attaaatata cgacacatcc aggagtttat 660
tggagcgcag actgatggcg caaaggtacg atgagctgcc ccattacggc gggatggacg 720
gagtaggggt tcccgcttcc atgtacggag accctcacgc gccgcggccg atccccccgg 780
ttcaccacct gaaccacggg ccgccgctcc acgccacaca gcactacggc gcgcacgccc 840
cgcaccccaa tgtcatgccg gccagtatgg gatccgctgt caacgacgcc ttgaagcggg 900
acaaggacgc gatctatggg cacccgttgt ttcctctgtt agctctggtc tttgagaagt 960
gcgagctggc gacctgcact ccccgggaac ctggagtggc tggcggagac gtctgctcct 1020
ccgactcctt caacgaggac atcgcggtct tcgccaagca ggttcgcgcc gaaaagccac 1080
ttttttcctc aaatccagag ctggacaatt tgatgataca agcaatacaa gtactaaggt 1140
ttcatctttt ggagttagaa aaggtccacg aactgtgcga taacttctgc caccgataca 1200
ttagctgttt gaaggggaaa atgcccatcg acctcgtcat tgatgaaaga gacggcagct 1260
ccaagtcaga tcatgaagaa ctttcaggct cctccacaaa tctcgctgac cataaccctt 1320
cttcttggcg agaccacgat gatgcaacct caacccactc agcaggcacc ccagggccct 1380
ccagtggggg ccatgcttcc cagagcggag acaacagcag tgagcaaggg gatggtttag 1440
acaacagtgt agcttcacct ggtacaggtg acgatgatga tccggataag gacaaaaaac 1500
gccagaagaa aagaggcatt ttccccaaag tagcaacaaa tatcatgaga gcatggctct 1560
tccagcatct cacacatccg tacccttccg aagagcagaa gaaacagtta gcgcaagaca 1620
caggacttac aattctccaa gtaaacaact ggtttattaa tgccagaaga agaatagtac 1680
agcccatgat tgaccagtca aatcgagcag gttttcttct tgatccttca gtgagccaag 1740
gagcagcata tagtccagag ggtcagccca tggggagctt tgtgttggat ggtcagcaac 1800
acatggggat ccggcctgca ggacctatga gtggaatggg catgaatatg ggcatggatg 1860
ggcaatggca ctacatgtaa ccttcatcat gtaaagcaat cgcaaagcaa gggggaagtt 1920
tgcagagcat gccaggggac tacgtttctc agggtggtcc tatgggaatg agtatggcac 1980
agccaagtta cactcctccc cagatgaccc cacaccctac tcaattaaga catggacccc 2040
caatgcattc atatttgcca agccatcccc accacccagc catgatgatg cacggaggac 2100
cccctaccca ccctggaatg actatgtcag cacagagccc cacaatgtta aattctgtag 2160
atcccaatgt tggcggacag gttatggaca ttcatgccca atagtataag ggaactcaag 2220
ggaaaaggaa acacacgcaa aaactatttt aagactttct gaactttgac cagatgttga 2280
cacttaatat gaaattccag acagctgtga ttatttttta cttttgtcat ttttcatcaa 2340
gcaacagagg accaatgcaa caagaacaca aatgtgaaat catgggctga ctgagacaat 2400
tctgtccatg taaagatcct ctggaaaaag actccgagag ttataactac tgtagtataa 2460
atataggaac taagttaaac ttgtacattt ctgttgatca cgccgttatg ttgcctcaaa 2520
tagttttaga agagaaaaaa aaatatatcc ttgttttcca cactatgtgt gttgttccca 2580
aaagaatgac tgttttggtt catcagtgaa ttcaccatcc aggagagact gtggtatata 2640
ttttaaacct gttgggccaa tgagaaaaga accacactgg agatcatgat gaacttttgg 2700
ctgaacctca tcactcgaac tccagcttca agaatgtgtt ttcatgcccg gcctttgttc 2760
ctccataaat gtgtccttta gtttcaaaca gatctttata gttcgtgctt cataagccaa 2820
ttcttattat tatttttggg ggactcttct tcaaagagct tgccaatgaa gatttaaaga 2880
cagagcagga gcttcttcca ggagttctga gccttggttg tggacaaaac aatcttaagt 2940
tgggcagctt tcctcaacac aaaaaaaagt tattaatggt cattgaacca taactaggac 3000
tttatcagaa actcaaagct tgggggataa aaaggagcaa gagaatactg taacaaactt 3060
cgtacagagt tcggtctatt aattgtttca tgttagatat tctatgtgtt tacctcaatt 3120
gaaaaaaaaa agaatgtttt tgctagtatc agatctgctg tggaattggt attgtatgtc 3180
catgaattct tcttttctca gcacgtgttc ctcactagaa gaaaatgctg ttacctttaa 3240
gctttgtcaa atttacatta aaatacttgt atgaggactg tgacgttatg ttaaaaaaaa 3300
aaaggtgtta agtcacaaaa agcggtaata aatatttcat ttttgatttt ttgttaaaaa 3360
aaaaaaaaaa aaa 3373
<210> 51
<211> 2849
<212> DNA
<213> Homo sapiens
<400> 51
tcctcctcct ctcttctctc ttacctccct ccctctctct catctttatc ccttcctctc 60
ttttctgttc gccctcttct ccctgctctt tttccctttc cacccccctc ctctgttctc 120
cctcacctcc tgcgccccct cccccttccc gggttctgac agtacgatga gctgccccat 180
tacggcggga tggacggagt aggggttccc gcttccatgt acggagaccc tcacgcgccg 240
cggccgatcc ccccggttca ccacctgaac cacgggccgc cgctccacgc cacacagcac 300
tacggcgcgc acgccccgca ccccaatgtc atgccggcca gtatgggatc cgctgtcaac 360
gacgccttga agcgggacaa ggacgcgatc tatgggcacc cgttgtttcc tctgttagct 420
ctggtctttg agaagtgcga gctggcgacc tgcactcccc gggaacctgg agtggctggc 480
ggagacgtct gctcctccga ctccttcaac gaggacatcg cggtcttcgc caagcaggtt 540
cgcgccgaaa agccactttt ttcctcaaat ccagagctgg acaatttgat gatacaagca 600
atacaagtac taaggtttca tcttttggag ttagaaaagg tccacgaact gtgcgataac 660
ttctgccacc gatacattag ctgtttgaag gggaaaatgc ccatcgacct cgtcattgat 720
gaaagagacg gcagctccaa gtcagatcat gaagaacttt caggctcctc cacaaatctc 780
gctgaccata acccttcttc ttggcgagac cacgatgatg caacctcaac ccactcagca 840
ggcaccccag ggccctccag tgggggccat gcttcccaga gcggagacaa cagcagtgag 900
caaggggatg gtttagacaa cagtgtagct tcacctggta caggtgacga tgatgatccg 960
gataaggaca aaaaacgcca gaagaaaaga ggcattttcc ccaaagtagc aacaaatatc 1020
atgagagcat ggctcttcca gcatctcaca catccgtacc cttccgaaga gcagaagaaa 1080
cagttagcgc aagacacagg acttacaatt ctccaagtaa acaactggtt tattaatgcc 1140
agaagaagaa tagtacagcc catgattgac cagtcaaatc gagcaggttt tcttcttgat 1200
ccttcagtga gccaaggagc agcatatagt ccagagggtc agcccatggg gagctttgtg 1260
ttggatggtc agcaacacat ggggatccgg cctgcaggac ctatgagtgg aatgggcatg 1320
aatatgggca tggatgggca atggcactac atgtaacctt catcatgtaa agcaatcgca 1380
aagcaagggg gaagtttgca gagcatgcca ggggactacg tttctcaggg tggtcctatg 1440
ggaatgagta tggcacagcc aagttacact cctccccaga tgaccccaca ccctactcaa 1500
ttaagacatg gacccccaat gcattcatat ttgccaagcc atccccacca cccagccatg 1560
atgatgcacg gaggaccccc tacccaccct ggaatgacta tgtcagcaca gagccccaca 1620
atgttaaatt ctgtagatcc caatgttggc ggacaggtta tggacattca tgcccaatag 1680
tataagggaa ctcaagggaa aaggaaacac acgcaaaaac tattttaaga ctttctgaac 1740
tttgaccaga tgttgacact taatatgaaa ttccagacag ctgtgattat tttttacttt 1800
tgtcattttt catcaagcaa cagaggacca atgcaacaag aacacaaatg tgaaatcatg 1860
ggctgactga gacaattctg tccatgtaaa gatcctctgg aaaaagactc cgagagttat 1920
aactactgta gtataaatat aggaactaag ttaaacttgt acatttctgt tgatcacgcc 1980
gttatgttgc ctcaaatagt tttagaagag aaaaaaaaat atatccttgt tttccacact 2040
atgtgtgttg ttcccaaaag aatgactgtt ttggttcatc agtgaattca ccatccagga 2100
gagactgtgg tatatatttt aaacctgttg ggccaatgag aaaagaacca cactggagat 2160
catgatgaac ttttggctga acctcatcac tcgaactcca gcttcaagaa tgtgttttca 2220
tgcccggcct ttgttcctcc ataaatgtgt cctttagttt caaacagatc tttatagttc 2280
gtgcttcata agccaattct tattattatt tttgggggac tcttcttcaa agagcttgcc 2340
aatgaagatt taaagacaga gcaggagctt cttccaggag ttctgagcct tggttgtgga 2400
caaaacaatc ttaagttggg cagctttcct caacacaaaa aaaagttatt aatggtcatt 2460
gaaccataac taggacttta tcagaaactc aaagcttggg ggataaaaag gagcaagaga 2520
atactgtaac aaacttcgta cagagttcgg tctattaatt gtttcatgtt agatattcta 2580
tgtgtttacc tcaattgaaa aaaaaaagaa tgtttttgct agtatcagat ctgctgtgga 2640
attggtattg tatgtccatg aattcttctt ttctcagcac gtgttcctca ctagaagaaa 2700
atgctgttac ctttaagctt tgtcaaattt acattaaaat acttgtatga ggactgtgac 2760
gttatgttaa aaaaaaaaag gtgttaagtc acaaaaagcg gtaataaata tttcattttt 2820
gattttttgt taaaaaaaaa aaaaaaaaa 2849
<210> 52
<211> 0
<212> DNA
<213> Homo sapiens
<400> 52
000
<210> 53
<211> 470
<212> PRT
<213> Homo sapiens
<400> 53
Met Ala Gln Arg Tyr Asp Glu Leu Pro His Tyr Gly Gly Met Asp Gly
1 5 10 15
Val Gly Val Pro Ala Ser Met Tyr Gly Asp Pro His Ala Pro Arg Pro
20 25 30
Ile Pro Pro Val His His Leu Asn His Gly Pro Pro Leu His Ala Thr
35 40 45
Gln His Tyr Gly Ala His Ala Pro His Pro Asn Val Met Pro Ala Ser
50 55 60
Met Gly Ser Ala Val Asn Asp Ala Leu Lys Arg Asp Lys Asp Ala Ile
65 70 75 80
Tyr Gly His Pro Leu Phe Pro Leu Leu Ala Leu Val Phe Glu Lys Cys
85 90 95
Glu Leu Ala Thr Cys Thr Pro Arg Glu Pro Gly Val Ala Gly Gly Asp
100 105 110
Val Cys Ser Ser Asp Ser Phe Asn Glu Asp Ile Ala Val Phe Ala Lys
115 120 125
Gln Val Arg Ala Glu Lys Pro Leu Phe Ser Ser Asn Pro Glu Leu Asp
130 135 140
Asn Leu Met Ile Gln Ala Ile Gln Val Leu Arg Phe His Leu Leu Glu
145 150 155 160
Leu Glu Lys Val His Glu Leu Cys Asp Asn Phe Cys His Arg Tyr Ile
165 170 175
Ser Cys Leu Lys Gly Lys Met Pro Ile Asp Leu Val Ile Asp Glu Arg
180 185 190
Asp Gly Ser Ser Lys Ser Asp His Glu Glu Leu Ser Gly Ser Ser Thr
195 200 205
Asn Leu Ala Asp His Asn Pro Ser Ser Trp Arg Asp His Asp Asp Ala
210 215 220
Thr Ser Thr His Ser Ala Gly Thr Pro Gly Pro Ser Ser Gly Gly His
225 230 235 240
Ala Ser Gln Ser Gly Asp Asn Ser Ser Glu Gln Gly Asp Gly Leu Asp
245 250 255
Asn Ser Val Ala Ser Pro Gly Thr Gly Asp Asp Asp Asp Pro Asp Lys
260 265 270
Asp Lys Lys Arg Gln Lys Lys Arg Gly Ile Phe Pro Lys Val Ala Thr
275 280 285
Asn Ile Met Arg Ala Trp Leu Phe Gln His Leu Thr His Pro Tyr Pro
290 295 300
Ser Glu Glu Gln Lys Lys Gln Leu Ala Gln Asp Thr Gly Leu Thr Ile
305 310 315 320
Leu Gln Val Asn Asn Trp Phe Ile Asn Ala Arg Arg Arg Ile Val Gln
325 330 335
Pro Met Ile Asp Gln Ser Asn Arg Ala Val Ser Gln Gly Ala Ala Tyr
340 345 350
Ser Pro Glu Gly Gln Pro Met Gly Ser Phe Val Leu Asp Gly Gln Gln
355 360 365
His Met Gly Ile Arg Pro Ala Gly Leu Gln Ser Met Pro Gly Asp Tyr
370 375 380
Val Ser Gln Gly Gly Pro Met Gly Met Ser Met Ala Gln Pro Ser Tyr
385 390 395 400
Thr Pro Pro Gln Met Thr Pro His Pro Thr Gln Leu Arg His Gly Pro
405 410 415
Pro Met His Ser Tyr Leu Pro Ser His Pro His His Pro Ala Met Met
420 425 430
Met His Gly Gly Pro Pro Thr His Pro Gly Met Thr Met Ser Ala Gln
435 440 445
Ser Pro Thr Met Leu Asn Ser Val Asp Pro Asn Val Gly Gly Gln Val
450 455 460
Met Asp Ile His Ala Gln
465 470
<210> 54
<211> 381
<212> PRT
<213> Homo sapiens
<400> 54
Met Asp Gly Val Gly Val Pro Ala Ser Met Tyr Gly Asp Pro His Ala
1 5 10 15
Pro Arg Pro Ile Pro Pro Val His His Leu Asn His Gly Pro Pro Leu
20 25 30
His Ala Thr Gln His Tyr Gly Ala His Ala Pro His Pro Asn Val Met
35 40 45
Pro Ala Ser Met Gly Ser Ala Val Asn Asp Ala Leu Lys Arg Asp Lys
50 55 60
Asp Ala Ile Tyr Gly His Pro Leu Phe Pro Leu Leu Ala Leu Val Phe
65 70 75 80
Glu Lys Cys Glu Leu Ala Thr Cys Thr Pro Arg Glu Pro Gly Val Ala
85 90 95
Gly Gly Asp Val Cys Ser Ser Asp Ser Phe Asn Glu Asp Ile Ala Val
100 105 110
Phe Ala Lys Gln Val Arg Ala Glu Lys Pro Leu Phe Ser Ser Asn Pro
115 120 125
Glu Leu Asp Asn Leu Met Ile Gln Ala Ile Gln Val Leu Arg Phe His
130 135 140
Leu Leu Glu Leu Glu Lys Val His Glu Leu Cys Asp Asn Phe Cys His
145 150 155 160
Arg Tyr Ile Ser Cys Leu Lys Gly Lys Met Pro Ile Asp Leu Val Ile
165 170 175
Asp Glu Arg Asp Gly Ser Ser Lys Ser Asp His Glu Glu Leu Ser Gly
180 185 190
Ser Ser Thr Asn Leu Ala Asp His Asn Pro Ser Ser Trp Arg Asp His
195 200 205
Asp Asp Ala Thr Ser Thr His Ser Ala Gly Thr Pro Gly Pro Ser Ser
210 215 220
Gly Gly His Ala Ser Gln Ser Gly Asp Asn Ser Ser Glu Gln Gly Asp
225 230 235 240
Gly Leu Asp Asn Ser Val Ala Ser Pro Gly Thr Gly Asp Asp Asp Asp
245 250 255
Pro Asp Lys Asp Lys Lys Arg Gln Lys Lys Arg Gly Ile Phe Pro Lys
260 265 270
Val Ala Thr Asn Ile Met Arg Ala Trp Leu Phe Gln His Leu Thr His
275 280 285
Pro Tyr Pro Ser Glu Glu Gln Lys Lys Gln Leu Ala Gln Asp Thr Gly
290 295 300
Leu Thr Ile Leu Gln Val Asn Asn Trp Phe Ile Asn Ala Arg Arg Arg
305 310 315 320
Ile Val Gln Pro Met Ile Asp Gln Ser Asn Arg Ala Val Ser Gln Gly
325 330 335
Ala Ala Tyr Ser Pro Glu Gly Gln Pro Met Gly Ser Phe Val Leu Asp
340 345 350
Gly Gln Gln His Met Gly Ile Arg Pro Ala Gly Pro Met Ser Gly Met
355 360 365
Gly Met Asn Met Gly Met Asp Gly Gln Trp His Tyr Met
370 375 380
<210> 55
<211> 394
<212> PRT
<213> Homo sapiens
<400> 55
Met Ala Gln Arg Tyr Asp Glu Leu Pro His Tyr Gly Gly Met Asp Gly
1 5 10 15
Val Gly Val Pro Ala Ser Met Tyr Gly Asp Pro His Ala Pro Arg Pro
20 25 30
Ile Pro Pro Val His His Leu Asn His Gly Pro Pro Leu His Ala Thr
35 40 45
Gln His Tyr Gly Ala His Ala Pro His Pro Asn Val Met Pro Ala Ser
50 55 60
Met Gly Ser Ala Val Asn Asp Ala Leu Lys Arg Asp Lys Asp Ala Ile
65 70 75 80
Tyr Gly His Pro Leu Phe Pro Leu Leu Ala Leu Val Phe Glu Lys Cys
85 90 95
Glu Leu Ala Thr Cys Thr Pro Arg Glu Pro Gly Val Ala Gly Gly Asp
100 105 110
Val Cys Ser Ser Asp Ser Phe Asn Glu Asp Ile Ala Val Phe Ala Lys
115 120 125
Gln Val Arg Ala Glu Lys Pro Leu Phe Ser Ser Asn Pro Glu Leu Asp
130 135 140
Asn Leu Met Ile Gln Ala Ile Gln Val Leu Arg Phe His Leu Leu Glu
145 150 155 160
Leu Glu Lys Val His Glu Leu Cys Asp Asn Phe Cys His Arg Tyr Ile
165 170 175
Ser Cys Leu Lys Gly Lys Met Pro Ile Asp Leu Val Ile Asp Glu Arg
180 185 190
Asp Gly Ser Ser Lys Ser Asp His Glu Glu Leu Ser Gly Ser Ser Thr
195 200 205
Asn Leu Ala Asp His Asn Pro Ser Ser Trp Arg Asp His Asp Asp Ala
210 215 220
Thr Ser Thr His Ser Ala Gly Thr Pro Gly Pro Ser Ser Gly Gly His
225 230 235 240
Ala Ser Gln Ser Gly Asp Asn Ser Ser Glu Gln Gly Asp Gly Leu Asp
245 250 255
Asn Ser Val Ala Ser Pro Gly Thr Gly Asp Asp Asp Asp Pro Asp Lys
260 265 270
Asp Lys Lys Arg Gln Lys Lys Arg Gly Ile Phe Pro Lys Val Ala Thr
275 280 285
Asn Ile Met Arg Ala Trp Leu Phe Gln His Leu Thr His Pro Tyr Pro
290 295 300
Ser Glu Glu Gln Lys Lys Gln Leu Ala Gln Asp Thr Gly Leu Thr Ile
305 310 315 320
Leu Gln Val Asn Asn Trp Phe Ile Asn Ala Arg Arg Arg Ile Val Gln
325 330 335
Pro Met Ile Asp Gln Ser Asn Arg Ala Val Ser Gln Gly Ala Ala Tyr
340 345 350
Ser Pro Glu Gly Gln Pro Met Gly Ser Phe Val Leu Asp Gly Gln Gln
355 360 365
His Met Gly Ile Arg Pro Ala Gly Pro Met Ser Gly Met Gly Met Asn
370 375 380
Met Gly Met Asp Gly Gln Trp His Tyr Met
385 390
<210> 56
<211> 477
<212> PRT
<213> Homo sapiens
<400> 56
Met Ala Gln Arg Tyr Asp Glu Leu Pro His Tyr Gly Gly Met Asp Gly
1 5 10 15
Val Gly Val Pro Ala Ser Met Tyr Gly Asp Pro His Ala Pro Arg Pro
20 25 30
Ile Pro Pro Val His His Leu Asn His Gly Pro Pro Leu His Ala Thr
35 40 45
Gln His Tyr Gly Ala His Ala Pro His Pro Asn Val Met Pro Ala Ser
50 55 60
Met Gly Ser Ala Val Asn Asp Ala Leu Lys Arg Asp Lys Asp Ala Ile
65 70 75 80
Tyr Gly His Pro Leu Phe Pro Leu Leu Ala Leu Val Phe Glu Lys Cys
85 90 95
Glu Leu Ala Thr Cys Thr Pro Arg Glu Pro Gly Val Ala Gly Gly Asp
100 105 110
Val Cys Ser Ser Asp Ser Phe Asn Glu Asp Ile Ala Val Phe Ala Lys
115 120 125
Gln Val Arg Ala Glu Lys Pro Leu Phe Ser Ser Asn Pro Glu Leu Asp
130 135 140
Asn Leu Met Ile Gln Ala Ile Gln Val Leu Arg Phe His Leu Leu Glu
145 150 155 160
Leu Glu Lys Val His Glu Leu Cys Asp Asn Phe Cys His Arg Tyr Ile
165 170 175
Ser Cys Leu Lys Gly Lys Met Pro Ile Asp Leu Val Ile Asp Glu Arg
180 185 190
Asp Gly Ser Ser Lys Ser Asp His Glu Glu Leu Ser Gly Ser Ser Thr
195 200 205
Asn Leu Ala Asp His Asn Pro Ser Ser Trp Arg Asp His Asp Asp Ala
210 215 220
Thr Ser Thr His Ser Ala Gly Thr Pro Gly Pro Ser Ser Gly Gly His
225 230 235 240
Ala Ser Gln Ser Gly Asp Asn Ser Ser Glu Gln Gly Asp Gly Leu Asp
245 250 255
Asn Ser Val Ala Ser Pro Gly Thr Gly Asp Asp Asp Asp Pro Asp Lys
260 265 270
Asp Lys Lys Arg Gln Lys Lys Arg Gly Ile Phe Pro Lys Val Ala Thr
275 280 285
Asn Ile Met Arg Ala Trp Leu Phe Gln His Leu Thr His Pro Tyr Pro
290 295 300
Ser Glu Glu Gln Lys Lys Gln Leu Ala Gln Asp Thr Gly Leu Thr Ile
305 310 315 320
Leu Gln Val Asn Asn Trp Phe Ile Asn Ala Arg Arg Arg Ile Val Gln
325 330 335
Pro Met Ile Asp Gln Ser Asn Arg Ala Gly Phe Leu Leu Asp Pro Ser
340 345 350
Val Ser Gln Gly Ala Ala Tyr Ser Pro Glu Gly Gln Pro Met Gly Ser
355 360 365
Phe Val Leu Asp Gly Gln Gln His Met Gly Ile Arg Pro Ala Gly Leu
370 375 380
Gln Ser Met Pro Gly Asp Tyr Val Ser Gln Gly Gly Pro Met Gly Met
385 390 395 400
Ser Met Ala Gln Pro Ser Tyr Thr Pro Pro Gln Met Thr Pro His Pro
405 410 415
Thr Gln Leu Arg His Gly Pro Pro Met His Ser Tyr Leu Pro Ser His
420 425 430
Pro His His Pro Ala Met Met Met His Gly Gly Pro Pro Thr His Pro
435 440 445
Gly Met Thr Met Ser Ala Gln Ser Pro Thr Met Leu Asn Ser Val Asp
450 455 460
Pro Asn Val Gly Gly Gln Val Met Asp Ile His Ala Gln
465 470 475
<210> 57
<211> 470
<212> PRT
<213> Homo sapiens
<400> 57
Met Ala Gln Arg Tyr Asp Glu Leu Pro His Tyr Gly Gly Met Asp Gly
1 5 10 15
Val Gly Val Pro Ala Ser Met Tyr Gly Asp Pro His Ala Pro Arg Pro
20 25 30
Ile Pro Pro Val His His Leu Asn His Gly Pro Pro Leu His Ala Thr
35 40 45
Gln His Tyr Gly Ala His Ala Pro His Pro Asn Val Met Pro Ala Ser
50 55 60
Met Gly Ser Ala Val Asn Asp Ala Leu Lys Arg Asp Lys Asp Ala Ile
65 70 75 80
Tyr Gly His Pro Leu Phe Pro Leu Leu Ala Leu Val Phe Glu Lys Cys
85 90 95
Glu Leu Ala Thr Cys Thr Pro Arg Glu Pro Gly Val Ala Gly Gly Asp
100 105 110
Val Cys Ser Ser Asp Ser Phe Asn Glu Asp Ile Ala Val Phe Ala Lys
115 120 125
Gln Val Arg Ala Glu Lys Pro Leu Phe Ser Ser Asn Pro Glu Leu Asp
130 135 140
Asn Leu Met Ile Gln Ala Ile Gln Val Leu Arg Phe His Leu Leu Glu
145 150 155 160
Leu Glu Lys Val His Glu Leu Cys Asp Asn Phe Cys His Arg Tyr Ile
165 170 175
Ser Cys Leu Lys Gly Lys Met Pro Ile Asp Leu Val Ile Asp Glu Arg
180 185 190
Asp Gly Ser Ser Lys Ser Asp His Glu Glu Leu Ser Gly Ser Ser Thr
195 200 205
Asn Leu Ala Asp His Asn Pro Ser Ser Trp Arg Asp His Asp Asp Ala
210 215 220
Thr Ser Thr His Ser Ala Gly Thr Pro Gly Pro Ser Ser Gly Gly His
225 230 235 240
Ala Ser Gln Ser Gly Asp Asn Ser Ser Glu Gln Gly Asp Gly Leu Asp
245 250 255
Asn Ser Val Ala Ser Pro Gly Thr Gly Asp Asp Asp Asp Pro Asp Lys
260 265 270
Asp Lys Lys Arg Gln Lys Lys Arg Gly Ile Phe Pro Lys Val Ala Thr
275 280 285
Asn Ile Met Arg Ala Trp Leu Phe Gln His Leu Thr His Pro Tyr Pro
290 295 300
Ser Glu Glu Gln Lys Lys Gln Leu Ala Gln Asp Thr Gly Leu Thr Ile
305 310 315 320
Leu Gln Val Asn Asn Trp Phe Ile Asn Ala Arg Arg Arg Ile Val Gln
325 330 335
Pro Met Ile Asp Gln Ser Asn Arg Ala Val Ser Gln Gly Ala Ala Tyr
340 345 350
Ser Pro Glu Gly Gln Pro Met Gly Ser Phe Val Leu Asp Gly Gln Gln
355 360 365
His Met Gly Ile Arg Pro Ala Gly Leu Gln Ser Met Pro Gly Asp Tyr
370 375 380
Val Ser Gln Gly Gly Pro Met Gly Met Ser Met Ala Gln Pro Ser Tyr
385 390 395 400
Thr Pro Pro Gln Met Thr Pro His Pro Thr Gln Leu Arg His Gly Pro
405 410 415
Pro Met His Ser Tyr Leu Pro Ser His Pro His His Pro Ala Met Met
420 425 430
Met His Gly Gly Pro Pro Thr His Pro Gly Met Thr Met Ser Ala Gln
435 440 445
Ser Pro Thr Met Leu Asn Ser Val Asp Pro Asn Val Gly Gly Gln Val
450 455 460
Met Asp Ile His Ala Gln
465 470
<210> 58
<211> 401
<212> PRT
<213> Homo sapiens
<400> 58
Met Ala Gln Arg Tyr Asp Glu Leu Pro His Tyr Gly Gly Met Asp Gly
1 5 10 15
Val Gly Val Pro Ala Ser Met Tyr Gly Asp Pro His Ala Pro Arg Pro
20 25 30
Ile Pro Pro Val His His Leu Asn His Gly Pro Pro Leu His Ala Thr
35 40 45
Gln His Tyr Gly Ala His Ala Pro His Pro Asn Val Met Pro Ala Ser
50 55 60
Met Gly Ser Ala Val Asn Asp Ala Leu Lys Arg Asp Lys Asp Ala Ile
65 70 75 80
Tyr Gly His Pro Leu Phe Pro Leu Leu Ala Leu Val Phe Glu Lys Cys
85 90 95
Glu Leu Ala Thr Cys Thr Pro Arg Glu Pro Gly Val Ala Gly Gly Asp
100 105 110
Val Cys Ser Ser Asp Ser Phe Asn Glu Asp Ile Ala Val Phe Ala Lys
115 120 125
Gln Val Arg Ala Glu Lys Pro Leu Phe Ser Ser Asn Pro Glu Leu Asp
130 135 140
Asn Leu Met Ile Gln Ala Ile Gln Val Leu Arg Phe His Leu Leu Glu
145 150 155 160
Leu Glu Lys Val His Glu Leu Cys Asp Asn Phe Cys His Arg Tyr Ile
165 170 175
Ser Cys Leu Lys Gly Lys Met Pro Ile Asp Leu Val Ile Asp Glu Arg
180 185 190
Asp Gly Ser Ser Lys Ser Asp His Glu Glu Leu Ser Gly Ser Ser Thr
195 200 205
Asn Leu Ala Asp His Asn Pro Ser Ser Trp Arg Asp His Asp Asp Ala
210 215 220
Thr Ser Thr His Ser Ala Gly Thr Pro Gly Pro Ser Ser Gly Gly His
225 230 235 240
Ala Ser Gln Ser Gly Asp Asn Ser Ser Glu Gln Gly Asp Gly Leu Asp
245 250 255
Asn Ser Val Ala Ser Pro Gly Thr Gly Asp Asp Asp Asp Pro Asp Lys
260 265 270
Asp Lys Lys Arg Gln Lys Lys Arg Gly Ile Phe Pro Lys Val Ala Thr
275 280 285
Asn Ile Met Arg Ala Trp Leu Phe Gln His Leu Thr His Pro Tyr Pro
290 295 300
Ser Glu Glu Gln Lys Lys Gln Leu Ala Gln Asp Thr Gly Leu Thr Ile
305 310 315 320
Leu Gln Val Asn Asn Trp Phe Ile Asn Ala Arg Arg Arg Ile Val Gln
325 330 335
Pro Met Ile Asp Gln Ser Asn Arg Ala Gly Phe Leu Leu Asp Pro Ser
340 345 350
Val Ser Gln Gly Ala Ala Tyr Ser Pro Glu Gly Gln Pro Met Gly Ser
355 360 365
Phe Val Leu Asp Gly Gln Gln His Met Gly Ile Arg Pro Ala Gly Pro
370 375 380
Met Ser Gly Met Gly Met Asn Met Gly Met Asp Gly Gln Trp His Tyr
385 390 395 400
Met
<210> 59
<211> 388
<212> PRT
<213> Homo sapiens
<400> 59
Met Asp Gly Val Gly Val Pro Ala Ser Met Tyr Gly Asp Pro His Ala
1 5 10 15
Pro Arg Pro Ile Pro Pro Val His His Leu Asn His Gly Pro Pro Leu
20 25 30
His Ala Thr Gln His Tyr Gly Ala His Ala Pro His Pro Asn Val Met
35 40 45
Pro Ala Ser Met Gly Ser Ala Val Asn Asp Ala Leu Lys Arg Asp Lys
50 55 60
Asp Ala Ile Tyr Gly His Pro Leu Phe Pro Leu Leu Ala Leu Val Phe
65 70 75 80
Glu Lys Cys Glu Leu Ala Thr Cys Thr Pro Arg Glu Pro Gly Val Ala
85 90 95
Gly Gly Asp Val Cys Ser Ser Asp Ser Phe Asn Glu Asp Ile Ala Val
100 105 110
Phe Ala Lys Gln Val Arg Ala Glu Lys Pro Leu Phe Ser Ser Asn Pro
115 120 125
Glu Leu Asp Asn Leu Met Ile Gln Ala Ile Gln Val Leu Arg Phe His
130 135 140
Leu Leu Glu Leu Glu Lys Val His Glu Leu Cys Asp Asn Phe Cys His
145 150 155 160
Arg Tyr Ile Ser Cys Leu Lys Gly Lys Met Pro Ile Asp Leu Val Ile
165 170 175
Asp Glu Arg Asp Gly Ser Ser Lys Ser Asp His Glu Glu Leu Ser Gly
180 185 190
Ser Ser Thr Asn Leu Ala Asp His Asn Pro Ser Ser Trp Arg Asp His
195 200 205
Asp Asp Ala Thr Ser Thr His Ser Ala Gly Thr Pro Gly Pro Ser Ser
210 215 220
Gly Gly His Ala Ser Gln Ser Gly Asp Asn Ser Ser Glu Gln Gly Asp
225 230 235 240
Gly Leu Asp Asn Ser Val Ala Ser Pro Gly Thr Gly Asp Asp Asp Asp
245 250 255
Pro Asp Lys Asp Lys Lys Arg Gln Lys Lys Arg Gly Ile Phe Pro Lys
260 265 270
Val Ala Thr Asn Ile Met Arg Ala Trp Leu Phe Gln His Leu Thr His
275 280 285
Pro Tyr Pro Ser Glu Glu Gln Lys Lys Gln Leu Ala Gln Asp Thr Gly
290 295 300
Leu Thr Ile Leu Gln Val Asn Asn Trp Phe Ile Asn Ala Arg Arg Arg
305 310 315 320
Ile Val Gln Pro Met Ile Asp Gln Ser Asn Arg Ala Gly Phe Leu Leu
325 330 335
Asp Pro Ser Val Ser Gln Gly Ala Ala Tyr Ser Pro Glu Gly Gln Pro
340 345 350
Met Gly Ser Phe Val Leu Asp Gly Gln Gln His Met Gly Ile Arg Pro
355 360 365
Ala Gly Pro Met Ser Gly Met Gly Met Asn Met Gly Met Asp Gly Gln
370 375 380
Trp His Tyr Met
385
<210> 60
<211> 306
<212> PRT
<213> Homo sapiens
<400> 60
Met Ala Leu Val Phe Glu Lys Cys Glu Leu Ala Thr Cys Thr Pro Arg
1 5 10 15
Glu Pro Gly Val Ala Gly Gly Asp Val Cys Ser Ser Asp Ser Phe Asn
20 25 30
Glu Asp Ile Ala Val Phe Ala Lys Gln Val Arg Ala Glu Lys Pro Leu
35 40 45
Phe Ser Ser Asn Pro Glu Leu Asp Asn Leu Met Ile Gln Ala Ile Gln
50 55 60
Val Leu Arg Phe His Leu Leu Glu Leu Glu Lys Val His Glu Leu Cys
65 70 75 80
Asp Asn Phe Cys His Arg Tyr Ile Ser Cys Leu Lys Gly Lys Met Pro
85 90 95
Ile Asp Leu Val Ile Asp Glu Arg Asp Gly Ser Ser Lys Ser Asp His
100 105 110
Glu Glu Leu Ser Gly Ser Ser Thr Asn Leu Ala Asp His Asn Pro Ser
115 120 125
Ser Trp Arg Asp His Asp Asp Ala Thr Ser Thr His Ser Ala Gly Thr
130 135 140
Pro Gly Pro Ser Ser Gly Gly His Ala Ser Gln Ser Gly Asp Asn Ser
145 150 155 160
Ser Glu Gln Gly Asp Gly Leu Asp Asn Ser Val Ala Ser Pro Gly Thr
165 170 175
Gly Asp Asp Asp Asp Pro Asp Lys Asp Lys Lys Arg Gln Lys Lys Arg
180 185 190
Gly Ile Phe Pro Lys Val Ala Thr Asn Ile Met Arg Ala Trp Leu Phe
195 200 205
Gln His Leu Thr His Pro Tyr Pro Ser Glu Glu Gln Lys Lys Gln Leu
210 215 220
Ala Gln Asp Thr Gly Leu Thr Ile Leu Gln Val Asn Asn Trp Phe Ile
225 230 235 240
Asn Ala Arg Arg Arg Ile Val Gln Pro Met Ile Asp Gln Ser Asn Arg
245 250 255
Ala Val Ser Gln Gly Ala Ala Tyr Ser Pro Glu Gly Gln Pro Met Gly
260 265 270
Ser Phe Val Leu Asp Gly Gln Gln His Met Gly Ile Arg Pro Ala Gly
275 280 285
Pro Met Ser Gly Met Gly Met Asn Met Gly Met Asp Gly Gln Trp His
290 295 300
Tyr Met
305
<210> 61
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> MEIS2_forward primer
<400> 61
tcaaatccag agctggacaa 20
<210> 62
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> MEIS2_reverse primer
<400> 62
cccttcaaac agctaatgta tcg 23
<210> 63
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> MEIS2 probe
<400> 63
aaaggtccac gaactgtgcg at 22
<210> 64
<211> 3930
<212> DNA
<213> Homo sapiens
<400> 64
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggaaaat gaagtgccag 180
ccccagcccc acccccggaa gaaccaagta aagagaagga ggccggaact acaccagcaa 240
aagactggac ccttgtcgaa actcctcctg gggaggaaca agccaagcag aatgccaact 300
cccagctgtc catcttgttc attgaaaaac ctcaaggagg aacagtgaaa gttggtgaag 360
atatcacctt catagccaaa gtcaaggctg aagatcttct gagaaaaccc actatcaaat 420
ggttcaaagg aaaatggatg gacctggcca gcaaagccgg gaagcacctt cagctgaagg 480
aaacctttga gaggcacagt cgggtgtaca catttgagat gcagatcatc aaggccaaag 540
ataactttgc aggaaattac agatgcgagg tcacctataa ggataagttt gacagctgtt 600
catttgatct tgaagtgcac gaatctactg ggactactcc aaacattgac atcagatctg 660
ctttcaagag aagtggagaa ggtcaagagg atgcaggaga acttgacttt agtggtctcc 720
tgaaacgtag ggaggtgaag cagcaggagg aagaacccca ggtggacgta tgggagttgc 780
tgaagaacgc gaaacccagt gagtacgaga agatcgcctt ccagtatgga atcaccgacc 840
tgcgcggcat gctcaagcga ctcaagcgca tgcgcagaga ggagaagaag agcgcagctt 900
ttgcaaaaat tcttgatcct gcatatcagg ttgacaaagg aggcagagtg aggtttgttg 960
tggagctggc agatccaaag ttggaggtga aatggtataa aaatggtcaa gaaattcgac 1020
ccagtaccaa atacatcttt gaacacaaag gatgccagag aatcctgttt atcaataact 1080
gtcagatgac agatgattca gagtattatg tgacagccgg tgatgagaaa tgttccactg 1140
agctcttcgt aagagagcct ccaattatgg tgaccaaaca gctggaagat acaactgctt 1200
attgtgggga gagagtggaa ttagaatgtg aggtgtctga agatgatgcc aatgtaaaat 1260
ggtttaagaa tggtgaagag attatccctg gtccaaaatc aagataccga attagagttg 1320
agggtaaaaa acacatcttg atcatagagg gagcaacaaa ggctgatgct gcagaatatt 1380
cagtaatgac aacaggagga caatcatctg ctaaacttag tgttgacttg aaacctctga 1440
agattttgac acctctgact gatcagactg taaatcttgg aaaagaaatc tgcctgaagt 1500
gtgaaatctc tgaaaacata ccaggaaaat ggactaaaaa tggcctacct gttcaggaga 1560
gtgaccgtct aaaggtggtt cacaagggaa ggatccacaa gttagtgata gccaatgccc 1620
tcactgaaga tgaaggtgat tatgtatttg cacctgatgc ctacaatgtt actctgcctg 1680
ccaaagttca tgttattgat cctcctaaga tcatcctgga tggtcttgat gctgacaaca 1740
cagtgacagt gattgcagga aacaagcttc gtcttgagat ccccatcagc ggagaaccac 1800
ctcctaaagc catgtggagc cggggagata aggctattat ggaaggcagt ggccggataa 1860
gaacagaatc ttaccctgat agcagcactc tggtcattga tatagctgaa agagatgact 1920
ctggtgttta ccacatcaat ctgaaaaacg aagctggaga ggcacatgca agcatcaagg 1980
ttaaagttgt ggacttccct gatcctccag tggcaccgac tgtgacagag gtgggagatg 2040
actggtgtat catgaactgg gagcctcctg cctacgacgg aggctctcca atcctaggat 2100
attttattga gaggaagaag aaacaaagct ccaggtggat gaggctgaat tttgatctct 2160
gcaaagaaac aacttttgag cccaagaaga tgattgaagg tgtggcctat gaggtccgca 2220
tctttgcagt caatgccatt ggcatctcca agcccagtat gccctccagg ccttttgttc 2280
ctttggctgt aacaagccct cctactcttc tgactgtgga ctctgtcact gacacgactg 2340
tcacgatgag gtggcgcccc ccagaccaca ttggtgcagc aggtttagat ggctatgtgc 2400
tagagtattg ctttgaagga agtacatcag caaaacagtc tgatgaaaat ggggaggctg 2460
cctatgatct gccagctgag gactggatag ttgcaaacaa agatctgatt gacaagacga 2520
agttcaccat cacaggtctg ccaacagatg caaagatctt tgtgcgtgtg aaggctgtta 2580
atgcagctgg tgccagcgag cccaagtact attctcagcc cattctcgtg aaggaaatca 2640
tagaacctcc aaagattcgc attccaagac acctgaagca aacctatatc cgcagagttg 2700
gagaagctgt caatctggtt atacctttcc agggaaaacc aagaccagaa ttaacttgga 2760
agaaggatgg tgcagaaatt gataagaatc aaataaacat tcgcaactct gagactgata 2820
caatcatatt tattagaaaa gcagagagga gccactctgg gaaatatgat ctgcaagtca 2880
aagtggacaa attcgtggag accgcatcaa ttgacatcca gatcattgac cgtccaggtc 2940
caccccaaat tgtgaagatt gaggatgtct ggggagaaaa tgtcgctctc acatggactc 3000
caccaaagga tgatggaaat gctgctatca caggctatac cattcagaag gctgacaaga 3060
agagcatgga atggtttact gtcattgagc attatcatcg aaccagtgcc accattactg 3120
aattggtcat agggaatgaa tattacttcc gggtcttttc tgaaaacatg tgtggcctca 3180
gtgaggatgc caccatgact aaagagagtg cagtgatcgc cagggatggt aaaatctaca 3240
aaaatccagt gtatgaagac tttgatttct cagaggcacc catgtttact cagcctttgg 3300
ttaacaccta tgccatagct ggttacaatg ccaccctaaa ctgcagtgtg agaggaaatc 3360
ctaagcctaa aataacctgg atgaaaaaca aagttgctat tgtggatgat ccaagataca 3420
ggatgttcag caaccaggga gtctgtaccc tggaaattcg caagcccagc ccctatgatg 3480
gaggcactta ctgctgcaaa gcagtcaatg accttgggac agtggagatt gaatgcaaac 3540
tggaggtgaa agtgatatat caaggagtaa atacccctgg acaaccagtc ttcctggagg 3600
ggcagcaaca ggtgggctct ccttctgcag actcctcttg caaggcgtac ctccaaacat 3660
aattgattcg tatctgcgag acttacactc aagcaatcct gaggaatact gagggagggc 3720
ctggctactg tctctctgca ctctgctgct ttgaaatctg gttgaaatga gaaaaagcat 3780
tttctgtttt cccaccaggc ccccaagtgt ggtctttttc tttcctccta atgttgaaga 3840
gaaaaaaaaa aaaaaaagtt tgcccagatt gcttaattaa aaattgcaaa caaaatctca 3900
tttgaagtca aaaaaaaaaa aaaaaaaaaa 3930
<210> 65
<211> 3919
<212> DNA
<213> Homo sapiens
<400> 65
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggaaaat gaagtgccag 180
ccccagcccc acccccggaa gaaccaagta aagagaagga ggccggaact acaccagcaa 240
aagactggac ccttgtcgaa actcctcctg gggaggaaca agccaagcag aatgccaact 300
cccagctgtc catcttgttc attgaaaaac ctcaaggagg aacagtgaaa gttggtgaag 360
atatcacctt catagccaaa gtcaaggctg aagatcttct gagaaaaccc actatcaaat 420
ggttcaaagg aaaatggatg gacctggcca gcaaagccgg gaagcacctt cagctgaagg 480
aaacctttga gaggcacagt cgggtgtaca catttgagat gcagatcatc aaggccaaag 540
ataactttgc aggaaattac agatgcgagg tcacctataa ggataagttt gacagctgtt 600
catttgatct tgaagtgcac gaatctactg ggactactcc aaacattgac atcagatctg 660
ctttcaagag aagtggagaa ggtcaagagg atgcaggaga acttgacttt agtggtctcc 720
tgaaacgtag ggaggtgaag cagcaggagg aagaacccca ggtggacgta tgggagttgc 780
tgaagaacgc gaaacccagt gagtacgaga agatcgcctt ccagtatgga atcaccgacc 840
tgcgcggcat gctcaagcga ctcaagcgca tgcgcagaga ggagaagaag agcgcagctt 900
ttgcaaaaat tcttgatcct gcatatcagg ttgacaaagg aggcagagtg aggtttgttg 960
tggagctggc agatccaaag ttggaggtga aatggtataa aaatggtcaa gaaattcgac 1020
ccagtaccaa atacatcttt gaacacaaag gatgccagag aatcctgttt atcaataact 1080
gtcagatgac agatgattca gagtattatg tgacagccgg tgatgagaaa tgttccactg 1140
agctcttcgt aagagagcct ccaattatgg tgaccaaaca gctggaagat acaactgctt 1200
attgtgggga gagagtggaa ttagaatgtg aggtgtctga agatgatgcc aatgtaaaat 1260
ggtttaagaa tggtgaagag attatccctg gtccaaaatc aagataccga attagagttg 1320
agggtaaaaa acacatcttg atcatagagg gagcaacaaa ggctgatgct gcagaatatt 1380
cagtaatgac aacaggagga caatcatctg ctaaacttag tgttgacttg aaacctctga 1440
agattttgac acctctgact gatcagactg taaatcttgg aaaagaaatc tgcctgaagt 1500
gtgaaatctc tgaaaacata ccaggaaaat ggactaaaaa tggcctacct gttcaggaga 1560
gtgaccgtct aaaggtggtt cacaagggaa ggatccacaa gttagtgata gccaatgccc 1620
tcactgaaga tgaaggtgat tatgtatttg cacctgatgc ctacaatgtt actctgcctg 1680
ccaaagttca tgttattgat cctcctaaga tcatcctgga tggtcttgat gctgacaaca 1740
cagtgacagt gattgcagga aacaagcttc gtcttgagat ccccatcagc ggagaaccac 1800
ctcctaaagc catgtggagc cggggagata aggctattat ggaaggcagt ggccggataa 1860
gaacagaatc ttaccctgat agcagcactc tggtcattga tatagctgaa agagatgact 1920
ctggtgttta ccacatcaat ctgaaaaacg aagctggaga ggcacatgca agcatcaagg 1980
ttaaagttgt ggacttccct gatcctccag tggcaccgac tgtgacagag gtgggagatg 2040
actggtgtat catgaactgg gagcctcctg cctacgacgg aggctctcca atcctaggat 2100
attttattga gaggaagaag aaacaaagct ccaggtggat gaggctgaat tttgatctct 2160
gcaaagaaac aacttttgag cccaagaaga tgattgaagg tgtggcctat gaggtccgca 2220
tctttgcagt caatgccatt ggcatctcca agcccagtat gccctccagg ccttttgttc 2280
ctttggctgt aacaagccct cctactcttc tgactgtgga ctctgtcact gacacgactg 2340
tcacgatgag gtggcgcccc ccagaccaca ttggtgcagc aggtttagat ggctatgtgc 2400
tagagtattg ctttgaagga actgaggact ggatagttgc aaacaaagat ctgattgaca 2460
agacgaagtt caccatcaca ggtctgccaa cagatgcaaa gatctttgtg cgtgtgaagg 2520
ctgttaatgc agctggtgcc agcgagccca agtactattc tcagcccatt ctcgtgaagg 2580
aaatcataga acctccaaag attcgcattc caagacacct gaagcaaacc tatatccgca 2640
gagttggaga agctgtcaat ctggttatac ctttccaggg aaaaccaaga ccagaattaa 2700
cttggaagaa ggatggtgca gaaattgata agaatcaaat aaacattcgc aactctgaga 2760
ctgatacaat catatttatt agaaaagcag agaggagcca ctctgggaaa tatgatctgc 2820
aagtcaaagt ggacaaattc gtggagaccg catcaattga catccagatc attgaccgtc 2880
caggtccacc ccaaattgtg aagattgagg atgtctgggg agaaaatgtc gctctcacat 2940
ggactccacc aaaggatgat ggaaatgctg ctatcacagg ctataccatt cagaaggctg 3000
acaagaagag catggaatgg tttactgtca ttgagcatta tcatcgaacc agtgccacca 3060
ttactgaatt ggtcataggg aatgaatatt acttccgggt cttttctgaa aacatgtgtg 3120
gcctcagtga ggatgccacc atgactaaag agagtgcagt gatcgccagg gatggtaaaa 3180
tctacaaaaa tccagtgtat gaagactttg atttctcaga ggcacccatg tttactcagc 3240
ctttggttaa cacctatgcc atagctggtt acaatgccac cctaaactgc agtgtgagag 3300
gaaatcctaa gcctaaaata acctggatga aaaacaaagt tgctattgtg gatgatccaa 3360
gatacaggat gttcagcaac cagggagtct gtaccctgga aattcgcaag cccagcccct 3420
atgatggagg cacttactgc tgcaaagcag tcaatgacct tgggacagtg gagattgaat 3480
gcaaactgga ggtgaaagtg atatatcaag gagtaaatac ccctggacaa ccagtcttcc 3540
tggaggggca gcaacagtca ttgcacaata aggatttttg aatgtataat atcatctaag 3600
gtgggctctc cttctgcaga ctcctcttgc aaggcgtacc tccaaacata attgattcgt 3660
atctgcgaga cttacactca agcaatcctg aggaatactg agggagggcc tggctactgt 3720
ctctctgcac tctgctgctt tgaaatctgg ttgaaatgag aaaaagcatt ttctgttttc 3780
ccaccaggcc cccaagtgtg gtctttttct ttcctcctaa tgttgaagag aaaaaaaaaa 3840
aaaaaagttt gcccagattg cttaattaaa aattgcaaac aaaatctcat ttgaagtcaa 3900
aaaaaaaaaa aaaaaaaaa 3919
<210> 66
<211> 3883
<212> DNA
<213> Homo sapiens
<400> 66
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggaacca agtaaagaga 180
aggaggccgg aactacacca gcaaaagact ggacccttgt cgaaactcct cctggggagg 240
aacaagccaa gcagaatgcc aactcccagc tgtccatctt gttcattgaa aaacctcaag 300
gaggaacagt gaaagttggt gaagatatca ccttcatagc caaagtcaag gctgaagatc 360
ttctgagaaa acccactatc aaatggttca aaggaaaatg gatggacctg gccagcaaag 420
ccgggaagca ccttcagctg aaggaaacct ttgagaggca cagtcgggtg tacacatttg 480
agatgcagat catcaaggcc aaagataact ttgcaggaaa ttacagatgc gaggtcacct 540
ataaggataa gtttgacagc tgttcatttg atcttgaagt gcacgaatct actgggacta 600
ctccaaacat tgacatcaga tctgctttca agagaagtgg agaaggtcaa gaggatgcag 660
gagaacttga ctttagtggt ctcctgaaac gtagggaggt gaagcagcag gaggaagaac 720
cccaggtgga cgtatgggag ttgctgaaga acgcgaaacc cagtgagtac gagaagatcg 780
ccttccagta tggaatcacc gacctgcgcg gcatgctcaa gcgactcaag cgcatgcgca 840
gagaggagaa gaagagcgca gcttttgcaa aaattcttga tcctgcatat caggttgaca 900
aaggaggcag agtgaggttt gttgtggagc tggcagatcc aaagttggag gtgaaatggt 960
ataaaaatgg tcaagaaatt cgacccagta ccaaatacat ctttgaacac aaaggatgcc 1020
agagaatcct gtttatcaat aactgtcaga tgacagatga ttcagagtat tatgtgacag 1080
ccggtgatga gaaatgttcc actgagctct tcgtaagaga gcctccaatt atggtgacca 1140
aacagctgga agatacaact gcttattgtg gggagagagt ggaattagaa tgtgaggtgt 1200
ctgaagatga tgccaatgta aaatggttta agaatggtga agagattatc cctggtccaa 1260
aatcaagata ccgaattaga gttgagggta aaaaacacat cttgatcata gagggagcaa 1320
caaaggctga tgctgcagaa tattcagtaa tgacaacagg aggacaatca tctgctaaac 1380
ttagtgttga cttgaaacct ctgaagattt tgacacctct gactgatcag actgtaaatc 1440
ttggaaaaga aatctgcctg aagtgtgaaa tctctgaaaa cataccagga aaatggacta 1500
aaaatggcct acctgttcag gagagtgacc gtctaaaggt ggttcacaag ggaaggatcc 1560
acaagttagt gatagccaat gccctcactg aagatgaagg tgattatgta tttgcacctg 1620
atgcctacaa tgttactctg cctgccaaag ttcatgttat tgatcctcct aagatcatcc 1680
tggatggtct tgatgctgac aacacagtga cagtgattgc aggaaacaag cttcgtcttg 1740
agatccccat cagcggagaa ccacctccta aagccatgtg gagccgggga gataaggcta 1800
ttatggaagg cagtggccgg ataagaacag aatcttaccc tgatagcagc actctggtca 1860
ttgatatagc tgaaagagat gactctggtg tttaccacat caatctgaaa aacgaagctg 1920
gagaggcaca tgcaagcatc aaggttaaag ttgtggactt ccctgatcct ccagtggcac 1980
cgactgtgac agaggtggga gatgactggt gtatcatgaa ctgggagcct cctgcctacg 2040
acggaggctc tccaatccta ggatatttta ttgagaggaa gaagaaacaa agctccaggt 2100
ggatgaggct gaattttgat ctctgcaaag aaacaacttt tgagcccaag aagatgattg 2160
aaggtgtggc ctatgaggtc cgcatctttg cagtcaatgc cattggcatc tccaagccca 2220
gtatgccctc caggcctttt gttcctttgg ctgtaacaag ccctcctact cttctgactg 2280
tggactctgt cactgacacg actgtcacga tgaggtggcg ccccccagac cacattggtg 2340
cagcaggttt agatggctat gtgctagagt attgctttga aggaactgag gactggatag 2400
ttgcaaacaa agatctgatt gacaagacga agttcaccat cacaggtctg ccaacagatg 2460
caaagatctt tgtgcgtgtg aaggctgtta atgcagctgg tgccagcgag cccaagtact 2520
attctcagcc cattctcgtg aaggaaatca tagaacctcc aaagattcgc attccaagac 2580
acctgaagca aacctatatc cgcagagttg gagaagctgt caatctggtt atacctttcc 2640
agggaaaacc aagaccagaa ttaacttgga agaaggatgg tgcagaaatt gataagaatc 2700
aaataaacat tcgcaactct gagactgata caatcatatt tattagaaaa gcagagagga 2760
gccactctgg gaaatatgat ctgcaagtca aagtggacaa attcgtggag accgcatcaa 2820
ttgacatcca gatcattgac cgtccaggtc caccccaaat tgtgaagatt gaggatgtct 2880
ggggagaaaa tgtcgctctc acatggactc caccaaagga tgatggaaat gctgctatca 2940
caggctatac cattcagaag gctgacaaga agagcatgga atggtttact gtcattgagc 3000
attatcatcg aaccagtgcc accattactg aattggtcat agggaatgaa tattacttcc 3060
gggtcttttc tgaaaacatg tgtggcctca gtgaggatgc caccatgact aaagagagtg 3120
cagtgatcgc cagggatggt aaaatctaca aaaatccagt gtatgaagac tttgatttct 3180
cagaggcacc catgtttact cagcctttgg ttaacaccta tgccatagct ggttacaatg 3240
ccaccctaaa ctgcagtgtg agaggaaatc ctaagcctaa aataacctgg atgaaaaaca 3300
aagttgctat tgtggatgat ccaagataca ggatgttcag caaccaggga gtctgtaccc 3360
tggaaattcg caagcccagc ccctatgatg gaggcactta ctgctgcaaa gcagtcaatg 3420
accttgggac agtggagatt gaatgcaaac tggaggtgaa agtgatatat caaggagtaa 3480
atacccctgg acaaccagtc ttcctggagg ggcagcaaca gtcattgcac aataaggatt 3540
tttgaatgta taatatcatc taaggtgggc tctccttctg cagactcctc ttgcaaggcg 3600
tacctccaaa cataattgat tcgtatctgc gagacttaca ctcaagcaat cctgaggaat 3660
actgagggag ggcctggcta ctgtctctct gcactctgct gctttgaaat ctggttgaaa 3720
tgagaaaaag cattttctgt tttcccacca ggcccccaag tgtggtcttt ttctttcctc 3780
ctaatgttga agagaaaaaa aaaaaaaaaa gtttgcccag attgcttaat taaaaattgc 3840
aaacaaaatc tcatttgaag tcaaaaaaaa aaaaaaaaaa aaa 3883
<210> 67
<211> 3862
<212> DNA
<213> Homo sapiens
<400> 67
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggaaaat gaagtgccag 180
ccccagcccc acccccggaa gaaccaagta aagagaagga ggccggaact acaccagcaa 240
aagactggac ccttgtcgaa actcctcctg gggaggaaca agccaagcag aatgccaact 300
cccagctgtc catcttgttc attgaaaaac ctcaaggagg aacagtgaaa gttggtgaag 360
atatcacctt catagccaaa gtcaaggctg aagatcttct gagaaaaccc actatcaaat 420
ggttcaaagg aaaatggatg gacctggcca gcaaagccgg gaagcacctt cagctgaagg 480
aaacctttga gaggcacagt cgggtgtaca catttgagat gcagatcatc aaggccaaag 540
ataactttgc aggaaattac agatgcgagg tcacctataa ggataagttt gacagctgtt 600
catttgatct tgaagtgcac gaatctactg ggactactcc aaacattgac atcagatctg 660
ctttcaagag aagggaggtg aagcagcagg aggaagaacc ccaggtggac gtatgggagt 720
tgctgaagaa cgcgaaaccc agtgagtacg agaagatcgc cttccagtat ggaatcaccg 780
acctgcgcgg catgctcaag cgactcaagc gcatgcgcag agaggagaag aagagcgcag 840
cttttgcaaa aattcttgat cctgcatatc aggttgacaa aggaggcaga gtgaggtttg 900
ttgtggagct ggcagatcca aagttggagg tgaaatggta taaaaatggt caagaaattc 960
gacccagtac caaatacatc tttgaacaca aaggatgcca gagaatcctg tttatcaata 1020
actgtcagat gacagatgat tcagagtatt atgtgacagc cggtgatgag aaatgttcca 1080
ctgagctctt cgtaagagag cctccaatta tggtgaccaa acagctggaa gatacaactg 1140
cttattgtgg ggagagagtg gaattagaat gtgaggtgtc tgaagatgat gccaatgtaa 1200
aatggtttaa gaatggtgaa gagattatcc ctggtccaaa atcaagatac cgaattagag 1260
ttgagggtaa aaaacacatc ttgatcatag agggagcaac aaaggctgat gctgcagaat 1320
attcagtaat gacaacagga ggacaatcat ctgctaaact tagtgttgac ttgaaacctc 1380
tgaagatttt gacacctctg actgatcaga ctgtaaatct tggaaaagaa atctgcctga 1440
agtgtgaaat ctctgaaaac ataccaggaa aatggactaa aaatggccta cctgttcagg 1500
agagtgaccg tctaaaggtg gttcacaagg gaaggatcca caagttagtg atagccaatg 1560
ccctcactga agatgaaggt gattatgtat ttgcacctga tgcctacaat gttactctgc 1620
ctgccaaagt tcatgttatt gatcctccta agatcatcct ggatggtctt gatgctgaca 1680
acacagtgac agtgattgca ggaaacaagc ttcgtcttga gatccccatc agcggagaac 1740
cacctcctaa agccatgtgg agccggggag ataaggctat tatggaaggc agtggccgga 1800
taagaacaga atcttaccct gatagcagca ctctggtcat tgatatagct gaaagagatg 1860
actctggtgt ttaccacatc aatctgaaaa acgaagctgg agaggcacat gcaagcatca 1920
aggttaaagt tgtggacttc cctgatcctc cagtggcacc gactgtgaca gaggtgggag 1980
atgactggtg tatcatgaac tgggagcctc ctgcctacga cggaggctct ccaatcctag 2040
gatattttat tgagaggaag aagaaacaaa gctccaggtg gatgaggctg aattttgatc 2100
tctgcaaaga aacaactttt gagcccaaga agatgattga aggtgtggcc tatgaggtcc 2160
gcatctttgc agtcaatgcc attggcatct ccaagcccag tatgccctcc aggccttttg 2220
ttcctttggc tgtaacaagc cctcctactc ttctgactgt ggactctgtc actgacacga 2280
ctgtcacgat gaggtggcgc cccccagacc acattggtgc agcaggttta gatggctatg 2340
tgctagagta ttgctttgaa ggaactgagg actggatagt tgcaaacaaa gatctgattg 2400
acaagacgaa gttcaccatc acaggtctgc caacagatgc aaagatcttt gtgcgtgtga 2460
aggctgttaa tgcagctggt gccagcgagc ccaagtacta ttctcagccc attctcgtga 2520
aggaaatcat agaacctcca aagattcgca ttccaagaca cctgaagcaa acctatatcc 2580
gcagagttgg agaagctgtc aatctggtta tacctttcca gggaaaacca agaccagaat 2640
taacttggaa gaaggatggt gcagaaattg ataagaatca aataaacatt cgcaactctg 2700
agactgatac aatcatattt attagaaaag cagagaggag ccactctggg aaatatgatc 2760
tgcaagtcaa agtggacaaa ttcgtggaga ccgcatcaat tgacatccag atcattgacc 2820
gtccaggtcc accccaaatt gtgaagattg aggatgtctg gggagaaaat gtcgctctca 2880
catggactcc accaaaggat gatggaaatg ctgctatcac aggctatacc attcagaagg 2940
ctgacaagaa gagcatggaa tggtttactg tcattgagca ttatcatcga accagtgcca 3000
ccattactga attggtcata gggaatgaat attacttccg ggtcttttct gaaaacatgt 3060
gtggcctcag tgaggatgcc accatgacta aagagagtgc agtgatcgcc agggatggta 3120
aaatctacaa aaatccagtg tatgaagact ttgatttctc agaggcaccc atgtttactc 3180
agcctttggt taacacctat gccatagctg gttacaatgc caccctaaac tgcagtgtga 3240
gaggaaatcc taagcctaaa ataacctgga tgaaaaacaa agttgctatt gtggatgatc 3300
caagatacag gatgttcagc aaccagggag tctgtaccct ggaaattcgc aagcccagcc 3360
cctatgatgg aggcacttac tgctgcaaag cagtcaatga ccttgggaca gtggagattg 3420
aatgcaaact ggaggtgaaa gtgatatatc aaggagtaaa tacccctgga caaccagtct 3480
tcctggaggg gcagcaacag tcattgcaca ataaggattt ttgaatgtat aatatcatct 3540
aaggtgggct ctccttctgc agactcctct tgcaaggcgt acctccaaac ataattgatt 3600
cgtatctgcg agacttacac tcaagcaatc ctgaggaata ctgagggagg gcctggctac 3660
tgtctctctg cactctgctg ctttgaaatc tggttgaaat gagaaaaagc attttctgtt 3720
ttcccaccag gcccccaagt gtggtctttt tctttcctcc taatgttgaa gagaaaaaaa 3780
aaaaaaaaag tttgcccaga ttgcttaatt aaaaattgca aacaaaatct catttgaagt 3840
caaaaaaaaa aaaaaaaaaa aa 3862
<210> 68
<211> 3841
<212> DNA
<213> Homo sapiens
<400> 68
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggactgg acccttgtcg 180
aaactcctcc tggggaggaa caagccaagc agaatgccaa ctcccagctg tccatcttgt 240
tcattgaaaa acctcaagga ggaacagtga aagttggtga agatatcacc ttcatagcca 300
aagtcaaggc tgaagatctt ctgagaaaac ccactatcaa atggttcaaa ggaaaatgga 360
tggacctggc cagcaaagcc gggaagcacc ttcagctgaa ggaaaccttt gagaggcaca 420
gtcgggtgta cacatttgag atgcagatca tcaaggccaa agataacttt gcaggaaatt 480
acagatgcga ggtcacctat aaggataagt ttgacagctg ttcatttgat cttgaagtgc 540
acgaatctac tgggactact ccaaacattg acatcagatc tgctttcaag agaagtggag 600
aaggtcaaga ggatgcagga gaacttgact ttagtggtct cctgaaacgt agggaggtga 660
agcagcagga ggaagaaccc caggtggacg tatgggagtt gctgaagaac gcgaaaccca 720
gtgagtacga gaagatcgcc ttccagtatg gaatcaccga cctgcgcggc atgctcaagc 780
gactcaagcg catgcgcaga gaggagaaga agagcgcagc ttttgcaaaa attcttgatc 840
ctgcatatca ggttgacaaa ggaggcagag tgaggtttgt tgtggagctg gcagatccaa 900
agttggaggt gaaatggtat aaaaatggtc aagaaattcg acccagtacc aaatacatct 960
ttgaacacaa aggatgccag agaatcctgt ttatcaataa ctgtcagatg acagatgatt 1020
cagagtatta tgtgacagcc ggtgatgaga aatgttccac tgagctcttc gtaagagagc 1080
ctccaattat ggtgaccaaa cagctggaag atacaactgc ttattgtggg gagagagtgg 1140
aattagaatg tgaggtgtct gaagatgatg ccaatgtaaa atggtttaag aatggtgaag 1200
agattatccc tggtccaaaa tcaagatacc gaattagagt tgagggtaaa aaacacatct 1260
tgatcataga gggagcaaca aaggctgatg ctgcagaata ttcagtaatg acaacaggag 1320
gacaatcatc tgctaaactt agtgttgact tgaaacctct gaagattttg acacctctga 1380
ctgatcagac tgtaaatctt ggaaaagaaa tctgcctgaa gtgtgaaatc tctgaaaaca 1440
taccaggaaa atggactaaa aatggcctac ctgttcagga gagtgaccgt ctaaaggtgg 1500
ttcacaaggg aaggatccac aagttagtga tagccaatgc cctcactgaa gatgaaggtg 1560
attatgtatt tgcacctgat gcctacaatg ttactctgcc tgccaaagtt catgttattg 1620
atcctcctaa gatcatcctg gatggtcttg atgctgacaa cacagtgaca gtgattgcag 1680
gaaacaagct tcgtcttgag atccccatca gcggagaacc acctcctaaa gccatgtgga 1740
gccggggaga taaggctatt atggaaggca gtggccggat aagaacagaa tcttaccctg 1800
atagcagcac tctggtcatt gatatagctg aaagagatga ctctggtgtt taccacatca 1860
atctgaaaaa cgaagctgga gaggcacatg caagcatcaa ggttaaagtt gtggacttcc 1920
ctgatcctcc agtggcaccg actgtgacag aggtgggaga tgactggtgt atcatgaact 1980
gggagcctcc tgcctacgac ggaggctctc caatcctagg atattttatt gagaggaaga 2040
agaaacaaag ctccaggtgg atgaggctga attttgatct ctgcaaagaa acaacttttg 2100
agcccaagaa gatgattgaa ggtgtggcct atgaggtccg catctttgca gtcaatgcca 2160
ttggcatctc caagcccagt atgccctcca ggccttttgt tcctttggct gtaacaagcc 2220
ctcctactct tctgactgtg gactctgtca ctgacacgac tgtcacgatg aggtggcgcc 2280
ccccagacca cattggtgca gcaggtttag atggctatgt gctagagtat tgctttgaag 2340
gaactgagga ctggatagtt gcaaacaaag atctgattga caagacgaag ttcaccatca 2400
caggtctgcc aacagatgca aagatctttg tgcgtgtgaa ggctgttaat gcagctggtg 2460
ccagcgagcc caagtactat tctcagccca ttctcgtgaa ggaaatcata gaacctccaa 2520
agattcgcat tccaagacac ctgaagcaaa cctatatccg cagagttgga gaagctgtca 2580
atctggttat acctttccag ggaaaaccaa gaccagaatt aacttggaag aaggatggtg 2640
cagaaattga taagaatcaa ataaacattc gcaactctga gactgataca atcatattta 2700
ttagaaaagc agagaggagc cactctggga aatatgatct gcaagtcaaa gtggacaaat 2760
tcgtggagac cgcatcaatt gacatccaga tcattgaccg tccaggtcca ccccaaattg 2820
tgaagattga ggatgtctgg ggagaaaatg tcgctctcac atggactcca ccaaaggatg 2880
atggaaatgc tgctatcaca ggctatacca ttcagaaggc tgacaagaag agcatggaat 2940
ggtttactgt cattgagcat tatcatcgaa ccagtgccac cattactgaa ttggtcatag 3000
ggaatgaata ttacttccgg gtcttttctg aaaacatgtg tggcctcagt gaggatgcca 3060
ccatgactaa agagagtgca gtgatcgcca gggatggtaa aatctacaaa aatccagtgt 3120
atgaagactt tgatttctca gaggcaccca tgtttactca gcctttggtt aacacctatg 3180
ccatagctgg ttacaatgcc accctaaact gcagtgtgag aggaaatcct aagcctaaaa 3240
taacctggat gaaaaacaaa gttgctattg tggatgatcc aagatacagg atgttcagca 3300
accagggagt ctgtaccctg gaaattcgca agcccagccc ctatgatgga ggcacttact 3360
gctgcaaagc agtcaatgac cttgggacag tggagattga atgcaaactg gaggtgaaag 3420
tgatatatca aggagtaaat acccctggac aaccagtctt cctggagggg cagcaacagt 3480
cattgcacaa taaggatttt tgaatgtata atatcatcta aggtgggctc tccttctgca 3540
gactcctctt gcaaggcgta cctccaaaca taattgattc gtatctgcga gacttacact 3600
caagcaatcc tgaggaatac tgagggaggg cctggctact gtctctctgc actctgctgc 3660
tttgaaatct ggttgaaatg agaaaaagca ttttctgttt tcccaccagg cccccaagtg 3720
tggtcttttt ctttcctcct aatgttgaag agaaaaaaaa aaaaaaaagt ttgcccagat 3780
tgcttaatta aaaattgcaa acaaaatctc atttgaagtc aaaaaaaaaa aaaaaaaaaa 3840
a 3841
<210> 69
<211> 3778
<212> DNA
<213> Homo sapiens
<400> 69
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggatgaa gaggaagtct 180
ccccgcctag cgccttgcct ccagactgga cccttgtcga aactcctcct ggggaggaac 240
aagccaagca gaatgccaac tcccagctgt ccatcttgtt cattgaaaaa cctcaaggag 300
gaacagtgaa agttggtgaa gatatcacct tcatagccaa agtcaaggct gaagatcttc 360
tgagaaaacc cactatcaaa tggttcaaag gaaaatggat ggacctggcc agcaaagccg 420
ggaagcacct tcagctgaag gaaacctttg agaggcacag tcgggtgtac acatttgaga 480
tgcagatcat caaggccaaa gataactttg caggaaatta cagatgcgag gtcacctata 540
aggataagtt tgacagctgt tcatttgatc ttgaagtgca cgaatctact gggactactc 600
caaacattga catcagatct gctttcaaga gaagtggaga aggtcaagag gatgcaggag 660
aacttgactt tagtggtctc ctgaaacgta gggaggtgaa gcagcaggag gaagaacccc 720
aggtggacgt atgggagttg ctgaagaacg cgaaacccag tgagtacgag aagatcgcct 780
tccagtatgg aatcaccgac ctgcgcggca tgctcaagcg actcaagcgc atgcgcagag 840
aggagaagaa gagcgcagct tttgcaaaaa ttcttgatcc tgcatatcag gttgacaaag 900
gaggcagagt gaggtttgtt gtggagctgg cagatccaaa gttggaggtg aaatggtata 960
aaaatggtca agaaattcga cccagtacca aatacatctt tgaacacaaa ggatgccaga 1020
gaatcctgtt tatcaataac tgtcagatga cagatgattc agagtattat gtgacagccg 1080
gtgatgagaa atgttccact gagctcttcg taagagagcc tccaattatg gtgaccaaac 1140
agctggaaga tacaactgct tattgtgggg agagagtgga attagaatgt gaggtgtctg 1200
aagatgatgc caatgtaaaa tggtttaaga atggtgaaga gattatccct ggtccaaaat 1260
caagataccg aattagagtt gagggtaaaa aacacatctt gatcatagag ggagcaacaa 1320
aggctgatgc tgcagaatat tcagtaatga caacaggagg acaatcatct gctaaactta 1380
gtgttgactt gaaacctctg aagattttga cacctctgac tgatcagact gtaaatcttg 1440
gaaaagaaat ctgcctgaag tgtgaaatct ctgaaaacat accaggaaaa tggactaaaa 1500
atggcctacc tgttcaggag agtgaccgtc taaaggtggt tcacaaggga aggatccaca 1560
agttagtgat agccaatgcc ctcactgaag atgaaggtga ttatgtattt gcacctgatg 1620
cctacaatgt tactctgcct gccaaagttc atgttattga tcctcctaag atcatcctgg 1680
atggtcttga tgctgacaac acagtgacag tgattgcagg aaacaagctt cgtcttgaga 1740
tccccatcag cggagaacca cctcctaaag ccatgtggag ccggggagat aaggctatta 1800
tggaaggcag tggccggata agaacagaat cttaccctga tagcagcact ctggtcattg 1860
atatagctga aagagatgac tctggtgttt accacatcaa tctgaaaaac gaagctggag 1920
aggcacatgc aagcatcaag gttaaagttg tggacttccc tgatcctcca gtggcaccga 1980
ctgtgacaga ggtgggagat gactggtgta tcatgaactg ggagcctcct gcctacgacg 2040
gaggctctcc aatcctagga tattttattg agaggaagaa gaaacaaagc tccaggtgga 2100
tgaggctgaa ttttgatctc tgcaaagaaa caacttttga gcccaagaag atgattgaag 2160
gtgtggccta tgaggtccgc atctttgcag tcaatgccat tggcatctcc aagcccagta 2220
tgccctccag gccttttgtt cctttggctg taacaagccc tcctactctt ctgactgtgg 2280
actctgtcac tgacacgact gtcacgatga ggtggcgccc cccagaccac attggtgcag 2340
caggtttaga tggctatgtg ctagagtatt gctttgaagg aactgaggac tggatagttg 2400
caaacaaaga tctgattgac aagacgaagt tcaccatcac aggtctgcca acagatgcaa 2460
agatctttgt gcgtgtgaag gctgttaatg cagctggtgc cagcgagccc aagtactatt 2520
ctcagcccat tctcgtgaag gaaatcatag aacctccaaa gattcgcatt ccaagacacc 2580
tgaagcaaac ctatatccgc agagttggag aagctgtcaa tctggttata cctttccagg 2640
gaaaaccaag accagaatta acttggaaga aggatggtgc agaaattgat aagaatcaaa 2700
taaacattcg caactctgag actgatacaa tcatatttat tagaaaagca gagaggagcc 2760
actctgggaa atatgatctg caagtcaaag tggacaaatt cgtggagacc gcatcaattg 2820
acatccagat cattgaccgt ccaggtccac cccaaattgt gaagattgag gatgtctggg 2880
gagaaaatgt cgctctcaca tggactccac caaaggatga tggaaatgct gctatcacag 2940
gctataccat tcagaaggct gacaagaaga gcatggaatg gtttactgtc attgagcatt 3000
atcatcgaac cagtgccacc attactgaat tggtcatagg gaatgaatat tacttccggg 3060
tcttttctga aaacatgtgt ggcctcagtg aggatgccac catgactaaa gagagtgcag 3120
tgatcgccag ggatggtaaa atctacaaaa atccagtgta tgaagacttt gatttctcag 3180
aggcacccat gtttactcag cctttggtta acacctatgc catagctggt tacaatgcca 3240
ccctaaactg cagtgtgaga ggaaatccta agcctaaaat aacctggatg aaaaacaaag 3300
ttgctattgt ggatgatcca agatacagga tgttcagcaa ccagggagtc tgtaccctgg 3360
aaattcgcaa gcccagcccc tatgatggag gcacttactg ctgcaaagca gtcaatgacc 3420
ttgggacagt ggagattgaa tgcaaactgg aggtgaaagg tgggctctcc ttctgcagac 3480
tcctcttgca aggcgtacct ccaaacataa ttgattcgta tctgcgagac ttacactcaa 3540
gcaatcctga ggaatactga gggagggcct ggctactgtc tctctgcact ctgctgcttt 3600
gaaatctggt tgaaatgaga aaaagcattt tctgttttcc caccaggccc ccaagtgtgg 3660
tctttttctt tcctcctaat gttgaagaga aaaaaaaaaa aaaaagtttg cccagattgc 3720
ttaattaaaa attgcaaaca aaatctcatt tgaagtcaaa aaaaaaaaaa aaaaaaaa 3778
<210> 70
<211> 3994
<212> DNA
<213> Homo sapiens
<400> 70
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggaaaat gaagtgccag 180
ccccagcccc acccccggaa gaaccaagta aagagaagga ggccggaact acaccagcaa 240
aagatgaaga ggaagtctcc ccgcctagcg ccttgcctcc aggtttgggt agtcgggccc 300
tggagagaaa agattcagac tggacccttg tcgaaactcc tcctggggag gaacaagcca 360
agcagaatgc caactcccag ctgtccatct tgttcattga aaaacctcaa ggaggaacag 420
tgaaagttgg tgaagatatc accttcatag ccaaagtcaa ggctgaagat cttctgagaa 480
aacccactat caaatggttc aaaggaaaat ggatggacct ggccagcaaa gccgggaagc 540
accttcagct gaaggaaacc tttgagaggc acagtcgggt gtacacattt gagatgcaga 600
tcatcaaggc caaagataac tttgcaggaa attacagatg cgaggtcacc tataaggata 660
agtttgacag ctgttcattt gatcttgaag tgcacgaatc tactgggact actccaaaca 720
ttgacatcag atctgctttc aagagaagtg gagaaggtca agaggatgca ggagaacttg 780
actttagtgg tctcctgaaa cgtagggagg tgaagcagca ggaggaagaa ccccaggtgg 840
acgtatggga gttgctgaag aacgcgaaac ccagtgagta cgagaagatc gccttccagt 900
atggaatcac cgacctgcgc ggcatgctca agcgactcaa gcgcatgcgc agagaggaga 960
agaagagcgc agcttttgca aaaattcttg atcctgcata tcaggttgac aaaggaggca 1020
gagtgaggtt tgttgtggag ctggcagatc caaagttgga ggtgaaatgg tataaaaatg 1080
gtcaagaaat tcgacccagt accaaataca tctttgaaca caaaggatgc cagagaatcc 1140
tgtttatcaa taactgtcag atgacagatg attcagagta ttatgtgaca gccggtgatg 1200
agaaatgttc cactgagctc ttcgtaagag agcctccaat tatggtgacc aaacagctgg 1260
aagatacaac tgcttattgt ggggagagag tggaattaga atgtgaggtg tctgaagatg 1320
atgccaatgt aaaatggttt aagaatggtg aagagattat ccctggtcca aaatcaagat 1380
accgaattag agttgagggt aaaaaacaca tcttgatcat agagggagca acaaaggctg 1440
atgctgcaga atattcagta atgacaacag gaggacaatc atctgctaaa cttagtgttg 1500
acttgaaacc tctgaagatt ttgacacctc tgactgatca gactgtaaat cttggaaaag 1560
aaatctgcct gaagtgtgaa atctctgaaa acataccagg aaaatggact aaaaatggcc 1620
tacctgttca ggagagtgac cgtctaaagg tggttcacaa gggaaggatc cacaagttag 1680
tgatagccaa tgccctcact gaagatgaag gtgattatgt atttgcacct gatgcctaca 1740
atgttactct gcctgccaaa gttcatgtta ttgatcctcc taagatcatc ctggatggtc 1800
ttgatgctga caacacagtg acagtgattg caggaaacaa gcttcgtctt gagatcccca 1860
tcagcggaga accacctcct aaagccatgt ggagccgggg agataaggct attatggaag 1920
gcagtggccg gataagaaca gaatcttacc ctgatagcag cactctggtc attgatatag 1980
ctgaaagaga tgactctggt gtttaccaca tcaatctgaa aaacgaagct ggagaggcac 2040
atgcaagcat caaggttaaa gttgtggact tccctgatcc tccagtggca ccgactgtga 2100
cagaggtggg agatgactgg tgtatcatga actgggagcc tcctgcctac gacggaggct 2160
ctccaatcct aggatatttt attgagagga agaagaaaca aagctccagg tggatgaggc 2220
tgaattttga tctctgcaaa gaaacaactt ttgagcccaa gaagatgatt gaaggtgtgg 2280
cctatgaggt ccgcatcttt gcagtcaatg ccattggcat ctccaagccc agtatgccct 2340
ccaggccttt tgttcctttg gctgtaacaa gccctcctac tcttctgact gtggactctg 2400
tcactgacac gactgtcacg atgaggtggc gccccccaga ccacattggt gcagcaggtt 2460
tagatggcta tgtgctagag tattgctttg aaggaactga ggactggata gttgcaaaca 2520
aagatctgat tgacaagacg aagttcacca tcacaggtct gccaacagat gcaaagatct 2580
ttgtgcgtgt gaaggctgtt aatgcagctg gtgccagcga gcccaagtac tattctcagc 2640
ccattctcgt gaaggaaatc atagaacctc caaagattcg cattccaaga cacctgaagc 2700
aaacctatat ccgcagagtt ggagaagctg tcaatctggt tatacctttc cagggaaaac 2760
caagaccaga attaacttgg aagaaggatg gtgcagaaat tgataagaat caaataaaca 2820
ttcgcaactc tgagactgat acaatcatat ttattagaaa agcagagagg agccactctg 2880
ggaaatatga tctgcaagtc aaagtggaca aattcgtgga gaccgcatca attgacatcc 2940
agatcattga ccgtccaggt ccaccccaaa ttgtgaagat tgaggatgtc tggggagaaa 3000
atgtcgctct cacatggact ccaccaaagg atgatggaaa tgctgctatc acaggctata 3060
ccattcagaa ggctgacaag aagagcatgg aatggtttac tgtcattgag cattatcatc 3120
gaaccagtgc caccattact gaattggtca tagggaatga atattacttc cgggtctttt 3180
ctgaaaacat gtgtggcctc agtgaggatg ccaccatgac taaagagagt gcagtgatcg 3240
ccagggatgg taaaatctac aaaaatccag tgtatgaaga ctttgatttc tcagaggcac 3300
ccatgtttac tcagcctttg gttaacacct atgccatagc tggttacaat gccaccctaa 3360
actgcagtgt gagaggaaat cctaagccta aaataacctg gatgaaaaac aaagttgcta 3420
ttgtggatga tccaagatac aggatgttca gcaaccaggg agtctgtacc ctggaaattc 3480
gcaagcccag cccctatgat ggaggcactt actgctgcaa agcagtcaat gaccttggga 3540
cagtggagat tgaatgcaaa ctggaggtga aagtgatata tcaaggagta aatacccctg 3600
gacaaccagt cttcctggag gggcagcaac agtcattgca caataaggat ttttgaatgt 3660
ataatatcat ctaaggtggg ctctccttct gcagactcct cttgcaaggc gtacctccaa 3720
acataattga ttcgtatctg cgagacttac actcaagcaa tcctgaggaa tactgaggga 3780
gggcctggct actgtctctc tgcactctgc tgctttgaaa tctggttgaa atgagaaaaa 3840
gcattttctg ttttcccacc aggcccccaa gtgtggtctt tttctttcct cctaatgttg 3900
aagagaaaaa aaaaaaaaaa agtttgccca gattgcttaa ttaaaaattg caaacaaaat 3960
ctcatttgaa gtcaaaaaaa aaaaaaaaaa aaaa 3994
<210> 71
<211> 3935
<212> DNA
<213> Homo sapiens
<400> 71
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggaaaat gaagtgccag 180
ccccagcccc acccccggaa gaaccaagta aagagaagga ggccggaact acaccagcaa 240
aagatgaaga ggaagtctcc ccgcctagcg ccttgcctcc aggtttgggt agtcgggccc 300
tggagagaaa agattcagac tggacccttg tcgaaactcc tcctggggag gaacaagcca 360
agcagaatgc caactcccag ctgtccatct tgttcattga aaaacctcaa ggaggaacag 420
tgaaagttgg tgaagatatc accttcatag ccaaagtcaa ggctgaagat cttctgagaa 480
aacccactat caaatggttc aaaggaaaat ggatggacct ggccagcaaa gccgggaagc 540
accttcagct gaaggaaacc tttgagaggc acagtcgggt gtacacattt gagatgcaga 600
tcatcaaggc caaagataac tttgcaggaa attacagatg cgaggtcacc tataaggata 660
agtttgacag ctgttcattt gatcttgaag tgcacgaatc tactgggact actccaaaca 720
ttgacatcag atctgctttc aagagaagtg gagaaggtca agaggatgca ggagaacttg 780
actttagtgg tctcctgaaa cgtagggagg tgaagcagca ggaggaagaa ccccaggtgg 840
acgtatggga gttgctgaag aacgcgaaac ccagtgagta cgagaagatc gccttccagt 900
atggaatcac cgacctgcgc ggcatgctca agcgactcaa gcgcatgcgc agagaggaga 960
agaagagcgc agcttttgca aaaattcttg atcctgcata tcaggttgac aaaggaggca 1020
gagtgaggtt tgttgtggag ctggcagatc caaagttgga ggtgaaatgg tataaaaatg 1080
gtcaagaaat tcgacccagt accaaataca tctttgaaca caaaggatgc cagagaatcc 1140
tgtttatcaa taactgtcag atgacagatg attcagagta ttatgtgaca gccggtgatg 1200
agaaatgttc cactgagctc ttcgtaagag agcctccaat tatggtgacc aaacagctgg 1260
aagatacaac tgcttattgt ggggagagag tggaattaga atgtgaggtg tctgaagatg 1320
atgccaatgt aaaatggttt aagaatggtg aagagattat ccctggtcca aaatcaagat 1380
accgaattag agttgagggt aaaaaacaca tcttgatcat agagggagca acaaaggctg 1440
atgctgcaga atattcagta atgacaacag gaggacaatc atctgctaaa cttagtgttg 1500
acttgaaacc tctgaagatt ttgacacctc tgactgatca gactgtaaat cttggaaaag 1560
aaatctgcct gaagtgtgaa atctctgaaa acataccagg aaaatggact aaaaatggcc 1620
tacctgttca ggagagtgac cgtctaaagg tggttcacaa gggaaggatc cacaagttag 1680
tgatagccaa tgccctcact gaagatgaag gtgattatgt atttgcacct gatgcctaca 1740
atgttactct gcctgccaaa gttcatgtta ttgatcctcc taagatcatc ctggatggtc 1800
ttgatgctga caacacagtg acagtgattg caggaaacaa gcttcgtctt gagatcccca 1860
tcagcggaga accacctcct aaagccatgt ggagccgggg agataaggct attatggaag 1920
gcagtggccg gataagaaca gaatcttacc ctgatagcag cactctggtc attgatatag 1980
ctgaaagaga tgactctggt gtttaccaca tcaatctgaa aaacgaagct ggagaggcac 2040
atgcaagcat caaggttaaa gttgtggact tccctgatcc tccagtggca ccgactgtga 2100
cagaggtggg agatgactgg tgtatcatga actgggagcc tcctgcctac gacggaggct 2160
ctccaatcct aggatatttt attgagagga agaagaaaca aagctccagg tggatgaggc 2220
tgaattttga tctctgcaaa gaaacaactt ttgagcccaa gaagatgatt gaaggtgtgg 2280
cctatgaggt ccgcatcttt gcagtcaatg ccattggcat ctccaagccc agtatgccct 2340
ccaggccttt tgttcctttg gctgtaacaa gccctcctac tcttctgact gtggactctg 2400
tcactgacac gactgtcacg atgaggtggc gccccccaga ccacattggt gcagcaggtt 2460
tagatggcta tgtgctagag tattgctttg aaggaactga ggactggata gttgcaaaca 2520
aagatctgat tgacaagacg aagttcacca tcacaggtct gccaacagat gcaaagatct 2580
ttgtgcgtgt gaaggctgtt aatgcagctg gtgccagcga gcccaagtac tattctcagc 2640
ccattctcgt gaaggaaatc atagaacctc caaagattcg cattccaaga cacctgaagc 2700
aaacctatat ccgcagagtt ggagaagctg tcaatctggt tatacctttc cagggaaaac 2760
caagaccaga attaacttgg aagaaggatg gtgcagaaat tgataagaat caaataaaca 2820
ttcgcaactc tgagactgat acaatcatat ttattagaaa agcagagagg agccactctg 2880
ggaaatatga tctgcaagtc aaagtggaca aattcgtgga gaccgcatca attgacatcc 2940
agatcattga ccgtccaggt ccaccccaaa ttgtgaagat tgaggatgtc tggggagaaa 3000
atgtcgctct cacatggact ccaccaaagg atgatggaaa tgctgctatc acaggctata 3060
ccattcagaa ggctgacaag aagagcatgg aatggtttac tgtcattgag cattatcatc 3120
gaaccagtgc caccattact gaattggtca tagggaatga atattacttc cgggtctttt 3180
ctgaaaacat gtgtggcctc agtgaggatg ccaccatgac taaagagagt gcagtgatcg 3240
ccagggatgg taaaatctac aaaaatccag tgtatgaaga ctttgatttc tcagaggcac 3300
ccatgtttac tcagcctttg gttaacacct atgccatagc tggttacaat gccaccctaa 3360
actgcagtgt gagaggaaat cctaagccta aaataacctg gatgaaaaac aaagttgcta 3420
ttgtggatga tccaagatac aggatgttca gcaaccaggg agtctgtacc ctggaaattc 3480
gcaagcccag cccctatgat ggaggcactt actgctgcaa agcagtcaat gaccttggga 3540
cagtggagat tgaatgcaaa ctggaggtga aagtcattgc acaataagga tttttgaatg 3600
tataatatca tctaaggtgg gctctccttc tgcagactcc tcttgcaagg cgtacctcca 3660
aacataattg attcgtatct gcgagactta cactcaagca atcctgagga atactgaggg 3720
agggcctggc tactgtctct ctgcactctg ctgctttgaa atctggttga aatgagaaaa 3780
agcattttct gttttcccac caggccccca agtgtggtct ttttctttcc tcctaatgtt 3840
gaagagaaaa aaaaaaaaaa aagtttgccc agattgctta attaaaaatt gcaaacaaaa 3900
tctcatttga agtcaaaaaa aaaaaaaaaa aaaaa 3935
<210> 72
<211> 3914
<212> DNA
<213> Homo sapiens
<400> 72
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggaaaat gaagtgccag 180
ccccagcccc acccccggaa gaaccaagta aagagaagga ggccggaact acaccagcaa 240
aagactggac ccttgtcgaa actcctcctg gggaggaaca agccaagcag aatgccaact 300
cccagctgtc catcttgttc attgaaaaac ctcaaggagg aacagtgaaa gttggtgaag 360
atatcacctt catagccaaa gtcaaggctg aagatcttct gagaaaaccc actatcaaat 420
ggttcaaagg aaaatggatg gacctggcca gcaaagccgg gaagcacctt cagctgaagg 480
aaacctttga gaggcacagt cgggtgtaca catttgagat gcagatcatc aaggccaaag 540
ataactttgc aggaaattac agatgcgagg tcacctataa ggataagttt gacagctgtt 600
catttgatct tgaagtgcac gaatctactg ggactactcc aaacattgac atcagatctg 660
ctttcaagag aagtggagaa ggtcaagagg atgcaggaga acttgacttt agtggtctcc 720
tgaaacgtag ggaggtgaag cagcaggagg aagaacccca ggtggacgta tgggagttgc 780
tgaagaacgc gaaacccagt gagtacgaga agatcgcctt ccagtatgga atcaccgacc 840
tgcgcggcat gctcaagcga ctcaagcgca tgcgcagaga ggagaagaag agcgcagctt 900
ttgcaaaaat tcttgatcct gcatatcagg ttgacaaagg aggcagagtg aggtttgttg 960
tggagctggc agatccaaag ttggaggtga aatggtataa aaatggtcaa gaaattcgac 1020
ccagtaccaa atacatcttt gaacacaaag gatgccagag aatcctgttt atcaataact 1080
gtcagatgac agatgattca gagtattatg tgacagccgg tgatgagaaa tgttccactg 1140
agctcttcgt aagagagcct ccaattatgg tgaccaaaca gctggaagat acaactgctt 1200
attgtgggga gagagtggaa ttagaatgtg aggtgtctga agatgatgcc aatgtaaaat 1260
ggtttaagaa tggtgaagag attatccctg gtccaaaatc aagataccga attagagttg 1320
agggtaaaaa acacatcttg atcatagagg gagcaacaaa ggctgatgct gcagaatatt 1380
cagtaatgac aacaggagga caatcatctg ctaaacttag tgttgacttg aaacctctga 1440
agattttgac acctctgact gatcagactg taaatcttgg aaaagaaatc tgcctgaagt 1500
gtgaaatctc tgaaaacata ccaggaaaat ggactaaaaa tggcctacct gttcaggaga 1560
gtgaccgtct aaaggtggtt cacaagggaa ggatccacaa gttagtgata gccaatgccc 1620
tcactgaaga tgaaggtgat tatgtatttg cacctgatgc ctacaatgtt actctgcctg 1680
ccaaagttca tgttattgat cctcctaaga tcatcctgga tggtcttgat gctgacaaca 1740
cagtgacagt gattgcagga aacaagcttc gtcttgagat ccccatcagc ggagaaccac 1800
ctcctaaagc catgtggagc cggggagata aggctattat ggaaggcagt ggccggataa 1860
gaacagaatc ttaccctgat agcagcactc tggtcattga tatagctgaa agagatgact 1920
ctggtgttta ccacatcaat ctgaaaaacg aagctggaga ggcacatgca agcatcaagg 1980
ttaaagttgt ggacttccct gatcctccag tggcaccgac tgtgacagag gtgggagatg 2040
actggtgtat catgaactgg gagcctcctg cctacgacgg aggctctcca atcctaggat 2100
attttattga gaggaagaag aaacaaagct ccaggtggat gaggctgaat tttgatctct 2160
gcaaagaaac aacttttgag cccaagaaga tgattgaagg tgtggcctat gaggtccgca 2220
tctttgcagt caatgccatt ggcatctcca agcccagtat gccctccagg ccttttgttc 2280
ctttggctgt aacaagccct cctactcttc tgactgtgga ctctgtcact gacacgactg 2340
tcacgatgag gtggcgcccc ccagaccaca ttggtgcagc aggtttagat ggctatgtgc 2400
tagagtattg ctttgaagga agtacatcag caaaacagtc tgatgaaaat ggggaggctg 2460
cctatgatct gccagctgag gactggatag ttgcaaacaa agatctgatt gacaagacga 2520
agttcaccat cacaggtctg ccaacagatg caaagatctt tgtgcgtgtg aaggctgtta 2580
atgcagctgg tgccagcgag cccaagtact attctcagcc cattctcgtg aaggaaatca 2640
tagaacctcc aaagattcgc attccaagac acctgaagca aacctatatc cgcagagttg 2700
gagaagctgt caatctggtt atacctttcc agggaaaacc aagaccagaa ttaacttgga 2760
agaaggatgg tgcagaaatt gataagaatc aaataaacat tcgcaactct gagactgata 2820
caatcatatt tattagaaaa gcagagagga gccactctgg gaaatatgat ctgcaagtca 2880
aagtggacaa attcgtggag accgcatcaa ttgacatcca gatcattgac cgtccaggtc 2940
caccccaaat tgtgaagatt gaggatgtct ggggagaaaa tgtcgctctc acatggactc 3000
caccaaagga tgatggaaat gctgctatca caggctatac cattcagaag gctgacaaga 3060
agagcatgga atggtttact gtcattgagc attatcatcg aaccagtgcc accattactg 3120
aattggtcat agggaatgaa tattacttcc gggtcttttc tgaaaacatg tgtggcctca 3180
gtgaggatgc caccatgact aaagagagtg cagtgatcgc cagggatggt aaaatctaca 3240
aaaatccagt gtatgaagac tttgatttct cagaggcacc catgtttact cagcctttgg 3300
ttaacaccta tgccatagct ggttacaatg ccaccctaaa ctgcagtgtg agaggaaatc 3360
ctaagcctaa aataacctgg atgaaaaaca aagttgctat tgtggatgat ccaagataca 3420
ggatgttcag caaccaggga gtctgtaccc tggaaattcg caagcccagc ccctatgatg 3480
gaggcactta ctgctgcaaa gcagtcaatg accttgggac agtggagatt gaatgcaaac 3540
tggaggtgaa agtcattgca caataaggat ttttgaatgt ataatatcat ctaaggtggg 3600
ctctccttct gcagactcct cttgcaaggc gtacctccaa acataattga ttcgtatctg 3660
cgagacttac actcaagcaa tcctgaggaa tactgaggga gggcctggct actgtctctc 3720
tgcactctgc tgctttgaaa tctggttgaa atgagaaaaa gcattttctg ttttcccacc 3780
aggcccccaa gtgtggtctt tttctttcct cctaatgttg aagagaaaaa aaaaaaaaaa 3840
agtttgccca gattgcttaa ttaaaaattg caaacaaaat ctcatttgaa gtcaaaaaaa 3900
aaaaaaaaaa aaaa 3914
<210> 73
<211> 3860
<212> DNA
<213> Homo sapiens
<400> 73
agaggcagta taaaagcact gggtttctcc ccaactgctt gtcacaccga cctgcaccat 60
ctctcgcctg cctgtggggt ttctgtcaac tagtcgtgga gggaaggaga ctctttaaag 120
aataacatct tattgtggcc atgccagaac ccactaagaa agaggaaaat gaagtgccag 180
ccccagcccc acccccggaa gaaccaagta aagagaagga ggccggaact acaccagcaa 240
aagactggac ccttgtcgaa actcctcctg gggaggaaca agccaagcag aatgccaact 300
cccagctgtc catcttgttc attgaaaaac ctcaaggagg aacagtgaaa gttggtgaag 360
atatcacctt catagccaaa gtcaaggctg aagatcttct gagaaaaccc actatcaaat 420
ggttcaaagg aaaatggatg gacctggcca gcaaagccgg gaagcacctt cagctgaagg 480
aaacctttga gaggcacagt cgggtgtaca catttgagat gcagatcatc aaggccaaag 540
ataactttgc aggaaattac agatgcgagg tcacctataa ggataagttt gacagctgtt 600
catttgatct tgaagtgcac gaatctactg ggactactcc aaacattgac atcagatctg 660
ctttcaagag aagtggagaa ggtcaagagg atgcaggaga acttgacttt agtggtctcc 720
tgaaacgtag ggaggtgaag cagcaggagg aagaacccca ggtggacgta tgggagttgc 780
tgaagaacgc gaaacccagt gagtacgaga agatcgcctt ccagtatgga atcaccgacc 840
tgcgcggcat gctcaagcga ctcaagcgca tgcgcagaga ggagaagaag agcgcagctt 900
ttgcaaaaat tcttgatcct gcatatcagg ttgacaaagg aggcagagtg aggtttgttg 960
tggagctggc agatccaaag ttggaggtga aatggtataa aaatggtcaa gaaattcgac 1020
ccagtaccaa atacatcttt gaacacaaag gatgccagag aatcctgttt atcaataact 1080
gtcagatgac agatgattca gagtattatg tgacagccgg tgatgagaaa tgttccactg 1140
agctcttcgt aagagagcct ccaattatgg tgaccaaaca gctggaagat acaactgctt 1200
attgtgggga gagagtggaa ttagaatgtg aggtgtctga agatgatgcc aatgtaaaat 1260
ggtttaagaa tggtgaagag attatccctg gtccaaaatc aagataccga attagagttg 1320
agggtaaaaa acacatcttg atcatagagg gagcaacaaa ggctgatgct gcagaatatt 1380
cagtaatgac aacaggagga caatcatctg ctaaacttag tgttgacttg aaacctctga 1440
agattttgac acctctgact gatcagactg taaatcttgg aaaagaaatc tgcctgaagt 1500
gtgaaatctc tgaaaacata ccaggaaaat ggactaaaaa tggcctacct gttcaggaga 1560
gtgaccgtct aaaggtggtt cacaagggaa ggatccacaa gttagtgata gccaatgccc 1620
tcactgaaga tgaaggtgat tatgtatttg cacctgatgc ctacaatgtt actctgcctg 1680
ccaaagttca tgttattgat cctcctaaga tcatcctgga tggtcttgat gctgacaaca 1740
cagtgacagt gattgcagga aacaagcttc gtcttgagat ccccatcagc ggagaaccac 1800
ctcctaaagc catgtggagc cggggagata aggctattat ggaaggcagt ggccggataa 1860
gaacagaatc ttaccctgat agcagcactc tggtcattga tatagctgaa agagatgact 1920
ctggtgttta ccacatcaat ctgaaaaacg aagctggaga ggcacatgca agcatcaagg 1980
ttaaagttgt ggacttccct gatcctccag tggcaccgac tgtgacagag gtgggagatg 2040
actggtgtat catgaactgg gagcctcctg cctacgacgg aggctctcca atcctaggat 2100
attttattga gaggaagaag aaacaaagct ccaggtggat gaggctgaat tttgatctct 2160
gcaaagaaac aacttttgag cccaagaaga tgattgaagg tgtggcctat gaggtccgca 2220
tctttgcagt caatgccatt ggcatctcca agcccagtat gccctccagg ccttttgttc 2280
ctttggctgt aacaagccct cctactcttc tgactgtgga ctctgtcact gacacgactg 2340
tcacgatgag gtggcgcccc ccagaccaca ttggtgcagc aggtttagat ggctatgtgc 2400
tagagtattg ctttgaagga actgaggact ggatagttgc aaacaaagat ctgattgaca 2460
agacgaagtt caccatcaca ggtctgccaa cagatgcaaa gatctttgtg cgtgtgaagg 2520
ctgttaatgc agctggtgcc agcgagccca agtactattc tcagcccatt ctcgtgaagg 2580
aaatcataga acctccaaag attcgcattc caagacacct gaagcaaacc tatatccgca 2640
gagttggaga agctgtcaat ctggttatac ctttccaggg aaaaccaaga ccagaattaa 2700
cttggaagaa ggatggtgca gaaattgata agaatcaaat aaacattcgc aactctgaga 2760
ctgatacaat catatttatt agaaaagcag agaggagcca ctctgggaaa tatgatctgc 2820
aagtcaaagt ggacaaattc gtggagaccg catcaattga catccagatc attgaccgtc 2880
caggtccacc ccaaattgtg aagattgagg atgtctgggg agaaaatgtc gctctcacat 2940
ggactccacc aaaggatgat ggaaatgctg ctatcacagg ctataccatt cagaaggctg 3000
acaagaagag catggaatgg tttactgtca ttgagcatta tcatcgaacc agtgccacca 3060
ttactgaatt ggtcataggg aatgaatatt acttccgggt cttttctgaa aacatgtgtg 3120
gcctcagtga ggatgccacc atgactaaag agagtgcagt gatcgccagg gatggtaaaa 3180
tctacaaaaa tccagtgtat gaagactttg atttctcaga ggcacccatg tttactcagc 3240
ctttggttaa cacctatgcc atagctggtt acaatgccac cctaaactgc agtgtgagag 3300
gaaatcctaa gcctaaaata acctggatga aaaacaaagt tgctattgtg gatgatccaa 3360
gatacaggat gttcagcaac cagggagtct gtaccctgga aattcgcaag cccagcccct 3420
atgatggagg cacttactgc tgcaaagcag tcaatgacct tgggacagtg gagattgaat 3480
gcaaactgga ggtgaaagtc attgcacaat aaggattttt gaatgtataa tatcatctaa 3540
ggtgggctct ccttctgcag actcctcttg caaggcgtac ctccaaacat aattgattcg 3600
tatctgcgag acttacactc aagcaatcct gaggaatact gagggagggc ctggctactg 3660
tctctctgca ctctgctgct ttgaaatctg gttgaaatga gaaaaagcat tttctgtttt 3720
cccaccaggc ccccaagtgt ggtctttttc tttcctccta atgttgaaga gaaaaaaaaa 3780
aaaaaaagtt tgcccagatt gcttaattaa aaattgcaaa caaaatctca tttgaagtca 3840
aaaaaaaaaa aaaaaaaaaa 3860
<210> 74
<211> 1173
<212> PRT
<213> Homo sapiens
<400> 74
Met Pro Glu Pro Thr Lys Lys Glu Glu Asn Glu Val Pro Ala Pro Ala
1 5 10 15
Pro Pro Pro Glu Glu Pro Ser Lys Glu Lys Glu Ala Gly Thr Thr Pro
20 25 30
Ala Lys Asp Trp Thr Leu Val Glu Thr Pro Pro Gly Glu Glu Gln Ala
35 40 45
Lys Gln Asn Ala Asn Ser Gln Leu Ser Ile Leu Phe Ile Glu Lys Pro
50 55 60
Gln Gly Gly Thr Val Lys Val Gly Glu Asp Ile Thr Phe Ile Ala Lys
65 70 75 80
Val Lys Ala Glu Asp Leu Leu Arg Lys Pro Thr Ile Lys Trp Phe Lys
85 90 95
Gly Lys Trp Met Asp Leu Ala Ser Lys Ala Gly Lys His Leu Gln Leu
100 105 110
Lys Glu Thr Phe Glu Arg His Ser Arg Val Tyr Thr Phe Glu Met Gln
115 120 125
Ile Ile Lys Ala Lys Asp Asn Phe Ala Gly Asn Tyr Arg Cys Glu Val
130 135 140
Thr Tyr Lys Asp Lys Phe Asp Ser Cys Ser Phe Asp Leu Glu Val His
145 150 155 160
Glu Ser Thr Gly Thr Thr Pro Asn Ile Asp Ile Arg Ser Ala Phe Lys
165 170 175
Arg Ser Gly Glu Gly Gln Glu Asp Ala Gly Glu Leu Asp Phe Ser Gly
180 185 190
Leu Leu Lys Arg Arg Glu Val Lys Gln Gln Glu Glu Glu Pro Gln Val
195 200 205
Asp Val Trp Glu Leu Leu Lys Asn Ala Lys Pro Ser Glu Tyr Glu Lys
210 215 220
Ile Ala Phe Gln Tyr Gly Ile Thr Asp Leu Arg Gly Met Leu Lys Arg
225 230 235 240
Leu Lys Arg Met Arg Arg Glu Glu Lys Lys Ser Ala Ala Phe Ala Lys
245 250 255
Ile Leu Asp Pro Ala Tyr Gln Val Asp Lys Gly Gly Arg Val Arg Phe
260 265 270
Val Val Glu Leu Ala Asp Pro Lys Leu Glu Val Lys Trp Tyr Lys Asn
275 280 285
Gly Gln Glu Ile Arg Pro Ser Thr Lys Tyr Ile Phe Glu His Lys Gly
290 295 300
Cys Gln Arg Ile Leu Phe Ile Asn Asn Cys Gln Met Thr Asp Asp Ser
305 310 315 320
Glu Tyr Tyr Val Thr Ala Gly Asp Glu Lys Cys Ser Thr Glu Leu Phe
325 330 335
Val Arg Glu Pro Pro Ile Met Val Thr Lys Gln Leu Glu Asp Thr Thr
340 345 350
Ala Tyr Cys Gly Glu Arg Val Glu Leu Glu Cys Glu Val Ser Glu Asp
355 360 365
Asp Ala Asn Val Lys Trp Phe Lys Asn Gly Glu Glu Ile Ile Pro Gly
370 375 380
Pro Lys Ser Arg Tyr Arg Ile Arg Val Glu Gly Lys Lys His Ile Leu
385 390 395 400
Ile Ile Glu Gly Ala Thr Lys Ala Asp Ala Ala Glu Tyr Ser Val Met
405 410 415
Thr Thr Gly Gly Gln Ser Ser Ala Lys Leu Ser Val Asp Leu Lys Pro
420 425 430
Leu Lys Ile Leu Thr Pro Leu Thr Asp Gln Thr Val Asn Leu Gly Lys
435 440 445
Glu Ile Cys Leu Lys Cys Glu Ile Ser Glu Asn Ile Pro Gly Lys Trp
450 455 460
Thr Lys Asn Gly Leu Pro Val Gln Glu Ser Asp Arg Leu Lys Val Val
465 470 475 480
His Lys Gly Arg Ile His Lys Leu Val Ile Ala Asn Ala Leu Thr Glu
485 490 495
Asp Glu Gly Asp Tyr Val Phe Ala Pro Asp Ala Tyr Asn Val Thr Leu
500 505 510
Pro Ala Lys Val His Val Ile Asp Pro Pro Lys Ile Ile Leu Asp Gly
515 520 525
Leu Asp Ala Asp Asn Thr Val Thr Val Ile Ala Gly Asn Lys Leu Arg
530 535 540
Leu Glu Ile Pro Ile Ser Gly Glu Pro Pro Pro Lys Ala Met Trp Ser
545 550 555 560
Arg Gly Asp Lys Ala Ile Met Glu Gly Ser Gly Arg Ile Arg Thr Glu
565 570 575
Ser Tyr Pro Asp Ser Ser Thr Leu Val Ile Asp Ile Ala Glu Arg Asp
580 585 590
Asp Ser Gly Val Tyr His Ile Asn Leu Lys Asn Glu Ala Gly Glu Ala
595 600 605
His Ala Ser Ile Lys Val Lys Val Val Asp Phe Pro Asp Pro Pro Val
610 615 620
Ala Pro Thr Val Thr Glu Val Gly Asp Asp Trp Cys Ile Met Asn Trp
625 630 635 640
Glu Pro Pro Ala Tyr Asp Gly Gly Ser Pro Ile Leu Gly Tyr Phe Ile
645 650 655
Glu Arg Lys Lys Lys Gln Ser Ser Arg Trp Met Arg Leu Asn Phe Asp
660 665 670
Leu Cys Lys Glu Thr Thr Phe Glu Pro Lys Lys Met Ile Glu Gly Val
675 680 685
Ala Tyr Glu Val Arg Ile Phe Ala Val Asn Ala Ile Gly Ile Ser Lys
690 695 700
Pro Ser Met Pro Ser Arg Pro Phe Val Pro Leu Ala Val Thr Ser Pro
705 710 715 720
Pro Thr Leu Leu Thr Val Asp Ser Val Thr Asp Thr Thr Val Thr Met
725 730 735
Arg Trp Arg Pro Pro Asp His Ile Gly Ala Ala Gly Leu Asp Gly Tyr
740 745 750
Val Leu Glu Tyr Cys Phe Glu Gly Ser Thr Ser Ala Lys Gln Ser Asp
755 760 765
Glu Asn Gly Glu Ala Ala Tyr Asp Leu Pro Ala Glu Asp Trp Ile Val
770 775 780
Ala Asn Lys Asp Leu Ile Asp Lys Thr Lys Phe Thr Ile Thr Gly Leu
785 790 795 800
Pro Thr Asp Ala Lys Ile Phe Val Arg Val Lys Ala Val Asn Ala Ala
805 810 815
Gly Ala Ser Glu Pro Lys Tyr Tyr Ser Gln Pro Ile Leu Val Lys Glu
820 825 830
Ile Ile Glu Pro Pro Lys Ile Arg Ile Pro Arg His Leu Lys Gln Thr
835 840 845
Tyr Ile Arg Arg Val Gly Glu Ala Val Asn Leu Val Ile Pro Phe Gln
850 855 860
Gly Lys Pro Arg Pro Glu Leu Thr Trp Lys Lys Asp Gly Ala Glu Ile
865 870 875 880
Asp Lys Asn Gln Ile Asn Ile Arg Asn Ser Glu Thr Asp Thr Ile Ile
885 890 895
Phe Ile Arg Lys Ala Glu Arg Ser His Ser Gly Lys Tyr Asp Leu Gln
900 905 910
Val Lys Val Asp Lys Phe Val Glu Thr Ala Ser Ile Asp Ile Gln Ile
915 920 925
Ile Asp Arg Pro Gly Pro Pro Gln Ile Val Lys Ile Glu Asp Val Trp
930 935 940
Gly Glu Asn Val Ala Leu Thr Trp Thr Pro Pro Lys Asp Asp Gly Asn
945 950 955 960
Ala Ala Ile Thr Gly Tyr Thr Ile Gln Lys Ala Asp Lys Lys Ser Met
965 970 975
Glu Trp Phe Thr Val Ile Glu His Tyr His Arg Thr Ser Ala Thr Ile
980 985 990
Thr Glu Leu Val Ile Gly Asn Glu Tyr Tyr Phe Arg Val Phe Ser Glu
995 1000 1005
Asn Met Cys Gly Leu Ser Glu Asp Ala Thr Met Thr Lys Glu Ser
1010 1015 1020
Ala Val Ile Ala Arg Asp Gly Lys Ile Tyr Lys Asn Pro Val Tyr
1025 1030 1035
Glu Asp Phe Asp Phe Ser Glu Ala Pro Met Phe Thr Gln Pro Leu
1040 1045 1050
Val Asn Thr Tyr Ala Ile Ala Gly Tyr Asn Ala Thr Leu Asn Cys
1055 1060 1065
Ser Val Arg Gly Asn Pro Lys Pro Lys Ile Thr Trp Met Lys Asn
1070 1075 1080
Lys Val Ala Ile Val Asp Asp Pro Arg Tyr Arg Met Phe Ser Asn
1085 1090 1095
Gln Gly Val Cys Thr Leu Glu Ile Arg Lys Pro Ser Pro Tyr Asp
1100 1105 1110
Gly Gly Thr Tyr Cys Cys Lys Ala Val Asn Asp Leu Gly Thr Val
1115 1120 1125
Glu Ile Glu Cys Lys Leu Glu Val Lys Val Ile Tyr Gln Gly Val
1130 1135 1140
Asn Thr Pro Gly Gln Pro Val Phe Leu Glu Gly Gln Gln Gln Val
1145 1150 1155
Gly Ser Pro Ser Ala Asp Ser Ser Cys Lys Ala Tyr Leu Gln Thr
1160 1165 1170
<210> 75
<211> 1146
<212> PRT
<213> Homo sapiens
<400> 75
Met Pro Glu Pro Thr Lys Lys Glu Glu Asn Glu Val Pro Ala Pro Ala
1 5 10 15
Pro Pro Pro Glu Glu Pro Ser Lys Glu Lys Glu Ala Gly Thr Thr Pro
20 25 30
Ala Lys Asp Trp Thr Leu Val Glu Thr Pro Pro Gly Glu Glu Gln Ala
35 40 45
Lys Gln Asn Ala Asn Ser Gln Leu Ser Ile Leu Phe Ile Glu Lys Pro
50 55 60
Gln Gly Gly Thr Val Lys Val Gly Glu Asp Ile Thr Phe Ile Ala Lys
65 70 75 80
Val Lys Ala Glu Asp Leu Leu Arg Lys Pro Thr Ile Lys Trp Phe Lys
85 90 95
Gly Lys Trp Met Asp Leu Ala Ser Lys Ala Gly Lys His Leu Gln Leu
100 105 110
Lys Glu Thr Phe Glu Arg His Ser Arg Val Tyr Thr Phe Glu Met Gln
115 120 125
Ile Ile Lys Ala Lys Asp Asn Phe Ala Gly Asn Tyr Arg Cys Glu Val
130 135 140
Thr Tyr Lys Asp Lys Phe Asp Ser Cys Ser Phe Asp Leu Glu Val His
145 150 155 160
Glu Ser Thr Gly Thr Thr Pro Asn Ile Asp Ile Arg Ser Ala Phe Lys
165 170 175
Arg Ser Gly Glu Gly Gln Glu Asp Ala Gly Glu Leu Asp Phe Ser Gly
180 185 190
Leu Leu Lys Arg Arg Glu Val Lys Gln Gln Glu Glu Glu Pro Gln Val
195 200 205
Asp Val Trp Glu Leu Leu Lys Asn Ala Lys Pro Ser Glu Tyr Glu Lys
210 215 220
Ile Ala Phe Gln Tyr Gly Ile Thr Asp Leu Arg Gly Met Leu Lys Arg
225 230 235 240
Leu Lys Arg Met Arg Arg Glu Glu Lys Lys Ser Ala Ala Phe Ala Lys
245 250 255
Ile Leu Asp Pro Ala Tyr Gln Val Asp Lys Gly Gly Arg Val Arg Phe
260 265 270
Val Val Glu Leu Ala Asp Pro Lys Leu Glu Val Lys Trp Tyr Lys Asn
275 280 285
Gly Gln Glu Ile Arg Pro Ser Thr Lys Tyr Ile Phe Glu His Lys Gly
290 295 300
Cys Gln Arg Ile Leu Phe Ile Asn Asn Cys Gln Met Thr Asp Asp Ser
305 310 315 320
Glu Tyr Tyr Val Thr Ala Gly Asp Glu Lys Cys Ser Thr Glu Leu Phe
325 330 335
Val Arg Glu Pro Pro Ile Met Val Thr Lys Gln Leu Glu Asp Thr Thr
340 345 350
Ala Tyr Cys Gly Glu Arg Val Glu Leu Glu Cys Glu Val Ser Glu Asp
355 360 365
Asp Ala Asn Val Lys Trp Phe Lys Asn Gly Glu Glu Ile Ile Pro Gly
370 375 380
Pro Lys Ser Arg Tyr Arg Ile Arg Val Glu Gly Lys Lys His Ile Leu
385 390 395 400
Ile Ile Glu Gly Ala Thr Lys Ala Asp Ala Ala Glu Tyr Ser Val Met
405 410 415
Thr Thr Gly Gly Gln Ser Ser Ala Lys Leu Ser Val Asp Leu Lys Pro
420 425 430
Leu Lys Ile Leu Thr Pro Leu Thr Asp Gln Thr Val Asn Leu Gly Lys
435 440 445
Glu Ile Cys Leu Lys Cys Glu Ile Ser Glu Asn Ile Pro Gly Lys Trp
450 455 460
Thr Lys Asn Gly Leu Pro Val Gln Glu Ser Asp Arg Leu Lys Val Val
465 470 475 480
His Lys Gly Arg Ile His Lys Leu Val Ile Ala Asn Ala Leu Thr Glu
485 490 495
Asp Glu Gly Asp Tyr Val Phe Ala Pro Asp Ala Tyr Asn Val Thr Leu
500 505 510
Pro Ala Lys Val His Val Ile Asp Pro Pro Lys Ile Ile Leu Asp Gly
515 520 525
Leu Asp Ala Asp Asn Thr Val Thr Val Ile Ala Gly Asn Lys Leu Arg
530 535 540
Leu Glu Ile Pro Ile Ser Gly Glu Pro Pro Pro Lys Ala Met Trp Ser
545 550 555 560
Arg Gly Asp Lys Ala Ile Met Glu Gly Ser Gly Arg Ile Arg Thr Glu
565 570 575
Ser Tyr Pro Asp Ser Ser Thr Leu Val Ile Asp Ile Ala Glu Arg Asp
580 585 590
Asp Ser Gly Val Tyr His Ile Asn Leu Lys Asn Glu Ala Gly Glu Ala
595 600 605
His Ala Ser Ile Lys Val Lys Val Val Asp Phe Pro Asp Pro Pro Val
610 615 620
Ala Pro Thr Val Thr Glu Val Gly Asp Asp Trp Cys Ile Met Asn Trp
625 630 635 640
Glu Pro Pro Ala Tyr Asp Gly Gly Ser Pro Ile Leu Gly Tyr Phe Ile
645 650 655
Glu Arg Lys Lys Lys Gln Ser Ser Arg Trp Met Arg Leu Asn Phe Asp
660 665 670
Leu Cys Lys Glu Thr Thr Phe Glu Pro Lys Lys Met Ile Glu Gly Val
675 680 685
Ala Tyr Glu Val Arg Ile Phe Ala Val Asn Ala Ile Gly Ile Ser Lys
690 695 700
Pro Ser Met Pro Ser Arg Pro Phe Val Pro Leu Ala Val Thr Ser Pro
705 710 715 720
Pro Thr Leu Leu Thr Val Asp Ser Val Thr Asp Thr Thr Val Thr Met
725 730 735
Arg Trp Arg Pro Pro Asp His Ile Gly Ala Ala Gly Leu Asp Gly Tyr
740 745 750
Val Leu Glu Tyr Cys Phe Glu Gly Thr Glu Asp Trp Ile Val Ala Asn
755 760 765
Lys Asp Leu Ile Asp Lys Thr Lys Phe Thr Ile Thr Gly Leu Pro Thr
770 775 780
Asp Ala Lys Ile Phe Val Arg Val Lys Ala Val Asn Ala Ala Gly Ala
785 790 795 800
Ser Glu Pro Lys Tyr Tyr Ser Gln Pro Ile Leu Val Lys Glu Ile Ile
805 810 815
Glu Pro Pro Lys Ile Arg Ile Pro Arg His Leu Lys Gln Thr Tyr Ile
820 825 830
Arg Arg Val Gly Glu Ala Val Asn Leu Val Ile Pro Phe Gln Gly Lys
835 840 845
Pro Arg Pro Glu Leu Thr Trp Lys Lys Asp Gly Ala Glu Ile Asp Lys
850 855 860
Asn Gln Ile Asn Ile Arg Asn Ser Glu Thr Asp Thr Ile Ile Phe Ile
865 870 875 880
Arg Lys Ala Glu Arg Ser His Ser Gly Lys Tyr Asp Leu Gln Val Lys
885 890 895
Val Asp Lys Phe Val Glu Thr Ala Ser Ile Asp Ile Gln Ile Ile Asp
900 905 910
Arg Pro Gly Pro Pro Gln Ile Val Lys Ile Glu Asp Val Trp Gly Glu
915 920 925
Asn Val Ala Leu Thr Trp Thr Pro Pro Lys Asp Asp Gly Asn Ala Ala
930 935 940
Ile Thr Gly Tyr Thr Ile Gln Lys Ala Asp Lys Lys Ser Met Glu Trp
945 950 955 960
Phe Thr Val Ile Glu His Tyr His Arg Thr Ser Ala Thr Ile Thr Glu
965 970 975
Leu Val Ile Gly Asn Glu Tyr Tyr Phe Arg Val Phe Ser Glu Asn Met
980 985 990
Cys Gly Leu Ser Glu Asp Ala Thr Met Thr Lys Glu Ser Ala Val Ile
995 1000 1005
Ala Arg Asp Gly Lys Ile Tyr Lys Asn Pro Val Tyr Glu Asp Phe
1010 1015 1020
Asp Phe Ser Glu Ala Pro Met Phe Thr Gln Pro Leu Val Asn Thr
1025 1030 1035
Tyr Ala Ile Ala Gly Tyr Asn Ala Thr Leu Asn Cys Ser Val Arg
1040 1045 1050
Gly Asn Pro Lys Pro Lys Ile Thr Trp Met Lys Asn Lys Val Ala
1055 1060 1065
Ile Val Asp Asp Pro Arg Tyr Arg Met Phe Ser Asn Gln Gly Val
1070 1075 1080
Cys Thr Leu Glu Ile Arg Lys Pro Ser Pro Tyr Asp Gly Gly Thr
1085 1090 1095
Tyr Cys Cys Lys Ala Val Asn Asp Leu Gly Thr Val Glu Ile Glu
1100 1105 1110
Cys Lys Leu Glu Val Lys Val Ile Tyr Gln Gly Val Asn Thr Pro
1115 1120 1125
Gly Gln Pro Val Phe Leu Glu Gly Gln Gln Gln Ser Leu His Asn
1130 1135 1140
Lys Asp Phe
1145
<210> 76
<211> 1134
<212> PRT
<213> Homo sapiens
<400> 76
Met Pro Glu Pro Thr Lys Lys Glu Glu Pro Ser Lys Glu Lys Glu Ala
1 5 10 15
Gly Thr Thr Pro Ala Lys Asp Trp Thr Leu Val Glu Thr Pro Pro Gly
20 25 30
Glu Glu Gln Ala Lys Gln Asn Ala Asn Ser Gln Leu Ser Ile Leu Phe
35 40 45
Ile Glu Lys Pro Gln Gly Gly Thr Val Lys Val Gly Glu Asp Ile Thr
50 55 60
Phe Ile Ala Lys Val Lys Ala Glu Asp Leu Leu Arg Lys Pro Thr Ile
65 70 75 80
Lys Trp Phe Lys Gly Lys Trp Met Asp Leu Ala Ser Lys Ala Gly Lys
85 90 95
His Leu Gln Leu Lys Glu Thr Phe Glu Arg His Ser Arg Val Tyr Thr
100 105 110
Phe Glu Met Gln Ile Ile Lys Ala Lys Asp Asn Phe Ala Gly Asn Tyr
115 120 125
Arg Cys Glu Val Thr Tyr Lys Asp Lys Phe Asp Ser Cys Ser Phe Asp
130 135 140
Leu Glu Val His Glu Ser Thr Gly Thr Thr Pro Asn Ile Asp Ile Arg
145 150 155 160
Ser Ala Phe Lys Arg Ser Gly Glu Gly Gln Glu Asp Ala Gly Glu Leu
165 170 175
Asp Phe Ser Gly Leu Leu Lys Arg Arg Glu Val Lys Gln Gln Glu Glu
180 185 190
Glu Pro Gln Val Asp Val Trp Glu Leu Leu Lys Asn Ala Lys Pro Ser
195 200 205
Glu Tyr Glu Lys Ile Ala Phe Gln Tyr Gly Ile Thr Asp Leu Arg Gly
210 215 220
Met Leu Lys Arg Leu Lys Arg Met Arg Arg Glu Glu Lys Lys Ser Ala
225 230 235 240
Ala Phe Ala Lys Ile Leu Asp Pro Ala Tyr Gln Val Asp Lys Gly Gly
245 250 255
Arg Val Arg Phe Val Val Glu Leu Ala Asp Pro Lys Leu Glu Val Lys
260 265 270
Trp Tyr Lys Asn Gly Gln Glu Ile Arg Pro Ser Thr Lys Tyr Ile Phe
275 280 285
Glu His Lys Gly Cys Gln Arg Ile Leu Phe Ile Asn Asn Cys Gln Met
290 295 300
Thr Asp Asp Ser Glu Tyr Tyr Val Thr Ala Gly Asp Glu Lys Cys Ser
305 310 315 320
Thr Glu Leu Phe Val Arg Glu Pro Pro Ile Met Val Thr Lys Gln Leu
325 330 335
Glu Asp Thr Thr Ala Tyr Cys Gly Glu Arg Val Glu Leu Glu Cys Glu
340 345 350
Val Ser Glu Asp Asp Ala Asn Val Lys Trp Phe Lys Asn Gly Glu Glu
355 360 365
Ile Ile Pro Gly Pro Lys Ser Arg Tyr Arg Ile Arg Val Glu Gly Lys
370 375 380
Lys His Ile Leu Ile Ile Glu Gly Ala Thr Lys Ala Asp Ala Ala Glu
385 390 395 400
Tyr Ser Val Met Thr Thr Gly Gly Gln Ser Ser Ala Lys Leu Ser Val
405 410 415
Asp Leu Lys Pro Leu Lys Ile Leu Thr Pro Leu Thr Asp Gln Thr Val
420 425 430
Asn Leu Gly Lys Glu Ile Cys Leu Lys Cys Glu Ile Ser Glu Asn Ile
435 440 445
Pro Gly Lys Trp Thr Lys Asn Gly Leu Pro Val Gln Glu Ser Asp Arg
450 455 460
Leu Lys Val Val His Lys Gly Arg Ile His Lys Leu Val Ile Ala Asn
465 470 475 480
Ala Leu Thr Glu Asp Glu Gly Asp Tyr Val Phe Ala Pro Asp Ala Tyr
485 490 495
Asn Val Thr Leu Pro Ala Lys Val His Val Ile Asp Pro Pro Lys Ile
500 505 510
Ile Leu Asp Gly Leu Asp Ala Asp Asn Thr Val Thr Val Ile Ala Gly
515 520 525
Asn Lys Leu Arg Leu Glu Ile Pro Ile Ser Gly Glu Pro Pro Pro Lys
530 535 540
Ala Met Trp Ser Arg Gly Asp Lys Ala Ile Met Glu Gly Ser Gly Arg
545 550 555 560
Ile Arg Thr Glu Ser Tyr Pro Asp Ser Ser Thr Leu Val Ile Asp Ile
565 570 575
Ala Glu Arg Asp Asp Ser Gly Val Tyr His Ile Asn Leu Lys Asn Glu
580 585 590
Ala Gly Glu Ala His Ala Ser Ile Lys Val Lys Val Val Asp Phe Pro
595 600 605
Asp Pro Pro Val Ala Pro Thr Val Thr Glu Val Gly Asp Asp Trp Cys
610 615 620
Ile Met Asn Trp Glu Pro Pro Ala Tyr Asp Gly Gly Ser Pro Ile Leu
625 630 635 640
Gly Tyr Phe Ile Glu Arg Lys Lys Lys Gln Ser Ser Arg Trp Met Arg
645 650 655
Leu Asn Phe Asp Leu Cys Lys Glu Thr Thr Phe Glu Pro Lys Lys Met
660 665 670
Ile Glu Gly Val Ala Tyr Glu Val Arg Ile Phe Ala Val Asn Ala Ile
675 680 685
Gly Ile Ser Lys Pro Ser Met Pro Ser Arg Pro Phe Val Pro Leu Ala
690 695 700
Val Thr Ser Pro Pro Thr Leu Leu Thr Val Asp Ser Val Thr Asp Thr
705 710 715 720
Thr Val Thr Met Arg Trp Arg Pro Pro Asp His Ile Gly Ala Ala Gly
725 730 735
Leu Asp Gly Tyr Val Leu Glu Tyr Cys Phe Glu Gly Thr Glu Asp Trp
740 745 750
Ile Val Ala Asn Lys Asp Leu Ile Asp Lys Thr Lys Phe Thr Ile Thr
755 760 765
Gly Leu Pro Thr Asp Ala Lys Ile Phe Val Arg Val Lys Ala Val Asn
770 775 780
Ala Ala Gly Ala Ser Glu Pro Lys Tyr Tyr Ser Gln Pro Ile Leu Val
785 790 795 800
Lys Glu Ile Ile Glu Pro Pro Lys Ile Arg Ile Pro Arg His Leu Lys
805 810 815
Gln Thr Tyr Ile Arg Arg Val Gly Glu Ala Val Asn Leu Val Ile Pro
820 825 830
Phe Gln Gly Lys Pro Arg Pro Glu Leu Thr Trp Lys Lys Asp Gly Ala
835 840 845
Glu Ile Asp Lys Asn Gln Ile Asn Ile Arg Asn Ser Glu Thr Asp Thr
850 855 860
Ile Ile Phe Ile Arg Lys Ala Glu Arg Ser His Ser Gly Lys Tyr Asp
865 870 875 880
Leu Gln Val Lys Val Asp Lys Phe Val Glu Thr Ala Ser Ile Asp Ile
885 890 895
Gln Ile Ile Asp Arg Pro Gly Pro Pro Gln Ile Val Lys Ile Glu Asp
900 905 910
Val Trp Gly Glu Asn Val Ala Leu Thr Trp Thr Pro Pro Lys Asp Asp
915 920 925
Gly Asn Ala Ala Ile Thr Gly Tyr Thr Ile Gln Lys Ala Asp Lys Lys
930 935 940
Ser Met Glu Trp Phe Thr Val Ile Glu His Tyr His Arg Thr Ser Ala
945 950 955 960
Thr Ile Thr Glu Leu Val Ile Gly Asn Glu Tyr Tyr Phe Arg Val Phe
965 970 975
Ser Glu Asn Met Cys Gly Leu Ser Glu Asp Ala Thr Met Thr Lys Glu
980 985 990
Ser Ala Val Ile Ala Arg Asp Gly Lys Ile Tyr Lys Asn Pro Val Tyr
995 1000 1005
Glu Asp Phe Asp Phe Ser Glu Ala Pro Met Phe Thr Gln Pro Leu
1010 1015 1020
Val Asn Thr Tyr Ala Ile Ala Gly Tyr Asn Ala Thr Leu Asn Cys
1025 1030 1035
Ser Val Arg Gly Asn Pro Lys Pro Lys Ile Thr Trp Met Lys Asn
1040 1045 1050
Lys Val Ala Ile Val Asp Asp Pro Arg Tyr Arg Met Phe Ser Asn
1055 1060 1065
Gln Gly Val Cys Thr Leu Glu Ile Arg Lys Pro Ser Pro Tyr Asp
1070 1075 1080
Gly Gly Thr Tyr Cys Cys Lys Ala Val Asn Asp Leu Gly Thr Val
1085 1090 1095
Glu Ile Glu Cys Lys Leu Glu Val Lys Val Ile Tyr Gln Gly Val
1100 1105 1110
Asn Thr Pro Gly Gln Pro Val Phe Leu Glu Gly Gln Gln Gln Ser
1115 1120 1125
Leu His Asn Lys Asp Phe
1130
<210> 77
<211> 1127
<212> PRT
<213> Homo sapiens
<400> 77
Met Pro Glu Pro Thr Lys Lys Glu Glu Asn Glu Val Pro Ala Pro Ala
1 5 10 15
Pro Pro Pro Glu Glu Pro Ser Lys Glu Lys Glu Ala Gly Thr Thr Pro
20 25 30
Ala Lys Asp Trp Thr Leu Val Glu Thr Pro Pro Gly Glu Glu Gln Ala
35 40 45
Lys Gln Asn Ala Asn Ser Gln Leu Ser Ile Leu Phe Ile Glu Lys Pro
50 55 60
Gln Gly Gly Thr Val Lys Val Gly Glu Asp Ile Thr Phe Ile Ala Lys
65 70 75 80
Val Lys Ala Glu Asp Leu Leu Arg Lys Pro Thr Ile Lys Trp Phe Lys
85 90 95
Gly Lys Trp Met Asp Leu Ala Ser Lys Ala Gly Lys His Leu Gln Leu
100 105 110
Lys Glu Thr Phe Glu Arg His Ser Arg Val Tyr Thr Phe Glu Met Gln
115 120 125
Ile Ile Lys Ala Lys Asp Asn Phe Ala Gly Asn Tyr Arg Cys Glu Val
130 135 140
Thr Tyr Lys Asp Lys Phe Asp Ser Cys Ser Phe Asp Leu Glu Val His
145 150 155 160
Glu Ser Thr Gly Thr Thr Pro Asn Ile Asp Ile Arg Ser Ala Phe Lys
165 170 175
Arg Arg Glu Val Lys Gln Gln Glu Glu Glu Pro Gln Val Asp Val Trp
180 185 190
Glu Leu Leu Lys Asn Ala Lys Pro Ser Glu Tyr Glu Lys Ile Ala Phe
195 200 205
Gln Tyr Gly Ile Thr Asp Leu Arg Gly Met Leu Lys Arg Leu Lys Arg
210 215 220
Met Arg Arg Glu Glu Lys Lys Ser Ala Ala Phe Ala Lys Ile Leu Asp
225 230 235 240
Pro Ala Tyr Gln Val Asp Lys Gly Gly Arg Val Arg Phe Val Val Glu
245 250 255
Leu Ala Asp Pro Lys Leu Glu Val Lys Trp Tyr Lys Asn Gly Gln Glu
260 265 270
Ile Arg Pro Ser Thr Lys Tyr Ile Phe Glu His Lys Gly Cys Gln Arg
275 280 285
Ile Leu Phe Ile Asn Asn Cys Gln Met Thr Asp Asp Ser Glu Tyr Tyr
290 295 300
Val Thr Ala Gly Asp Glu Lys Cys Ser Thr Glu Leu Phe Val Arg Glu
305 310 315 320
Pro Pro Ile Met Val Thr Lys Gln Leu Glu Asp Thr Thr Ala Tyr Cys
325 330 335
Gly Glu Arg Val Glu Leu Glu Cys Glu Val Ser Glu Asp Asp Ala Asn
340 345 350
Val Lys Trp Phe Lys Asn Gly Glu Glu Ile Ile Pro Gly Pro Lys Ser
355 360 365
Arg Tyr Arg Ile Arg Val Glu Gly Lys Lys His Ile Leu Ile Ile Glu
370 375 380
Gly Ala Thr Lys Ala Asp Ala Ala Glu Tyr Ser Val Met Thr Thr Gly
385 390 395 400
Gly Gln Ser Ser Ala Lys Leu Ser Val Asp Leu Lys Pro Leu Lys Ile
405 410 415
Leu Thr Pro Leu Thr Asp Gln Thr Val Asn Leu Gly Lys Glu Ile Cys
420 425 430
Leu Lys Cys Glu Ile Ser Glu Asn Ile Pro Gly Lys Trp Thr Lys Asn
435 440 445
Gly Leu Pro Val Gln Glu Ser Asp Arg Leu Lys Val Val His Lys Gly
450 455 460
Arg Ile His Lys Leu Val Ile Ala Asn Ala Leu Thr Glu Asp Glu Gly
465 470 475 480
Asp Tyr Val Phe Ala Pro Asp Ala Tyr Asn Val Thr Leu Pro Ala Lys
485 490 495
Val His Val Ile Asp Pro Pro Lys Ile Ile Leu Asp Gly Leu Asp Ala
500 505 510
Asp Asn Thr Val Thr Val Ile Ala Gly Asn Lys Leu Arg Leu Glu Ile
515 520 525
Pro Ile Ser Gly Glu Pro Pro Pro Lys Ala Met Trp Ser Arg Gly Asp
530 535 540
Lys Ala Ile Met Glu Gly Ser Gly Arg Ile Arg Thr Glu Ser Tyr Pro
545 550 555 560
Asp Ser Ser Thr Leu Val Ile Asp Ile Ala Glu Arg Asp Asp Ser Gly
565 570 575
Val Tyr His Ile Asn Leu Lys Asn Glu Ala Gly Glu Ala His Ala Ser
580 585 590
Ile Lys Val Lys Val Val Asp Phe Pro Asp Pro Pro Val Ala Pro Thr
595 600 605
Val Thr Glu Val Gly Asp Asp Trp Cys Ile Met Asn Trp Glu Pro Pro
610 615 620
Ala Tyr Asp Gly Gly Ser Pro Ile Leu Gly Tyr Phe Ile Glu Arg Lys
625 630 635 640
Lys Lys Gln Ser Ser Arg Trp Met Arg Leu Asn Phe Asp Leu Cys Lys
645 650 655
Glu Thr Thr Phe Glu Pro Lys Lys Met Ile Glu Gly Val Ala Tyr Glu
660 665 670
Val Arg Ile Phe Ala Val Asn Ala Ile Gly Ile Ser Lys Pro Ser Met
675 680 685
Pro Ser Arg Pro Phe Val Pro Leu Ala Val Thr Ser Pro Pro Thr Leu
690 695 700
Leu Thr Val Asp Ser Val Thr Asp Thr Thr Val Thr Met Arg Trp Arg
705 710 715 720
Pro Pro Asp His Ile Gly Ala Ala Gly Leu Asp Gly Tyr Val Leu Glu
725 730 735
Tyr Cys Phe Glu Gly Thr Glu Asp Trp Ile Val Ala Asn Lys Asp Leu
740 745 750
Ile Asp Lys Thr Lys Phe Thr Ile Thr Gly Leu Pro Thr Asp Ala Lys
755 760 765
Ile Phe Val Arg Val Lys Ala Val Asn Ala Ala Gly Ala Ser Glu Pro
770 775 780
Lys Tyr Tyr Ser Gln Pro Ile Leu Val Lys Glu Ile Ile Glu Pro Pro
785 790 795 800
Lys Ile Arg Ile Pro Arg His Leu Lys Gln Thr Tyr Ile Arg Arg Val
805 810 815
Gly Glu Ala Val Asn Leu Val Ile Pro Phe Gln Gly Lys Pro Arg Pro
820 825 830
Glu Leu Thr Trp Lys Lys Asp Gly Ala Glu Ile Asp Lys Asn Gln Ile
835 840 845
Asn Ile Arg Asn Ser Glu Thr Asp Thr Ile Ile Phe Ile Arg Lys Ala
850 855 860
Glu Arg Ser His Ser Gly Lys Tyr Asp Leu Gln Val Lys Val Asp Lys
865 870 875 880
Phe Val Glu Thr Ala Ser Ile Asp Ile Gln Ile Ile Asp Arg Pro Gly
885 890 895
Pro Pro Gln Ile Val Lys Ile Glu Asp Val Trp Gly Glu Asn Val Ala
900 905 910
Leu Thr Trp Thr Pro Pro Lys Asp Asp Gly Asn Ala Ala Ile Thr Gly
915 920 925
Tyr Thr Ile Gln Lys Ala Asp Lys Lys Ser Met Glu Trp Phe Thr Val
930 935 940
Ile Glu His Tyr His Arg Thr Ser Ala Thr Ile Thr Glu Leu Val Ile
945 950 955 960
Gly Asn Glu Tyr Tyr Phe Arg Val Phe Ser Glu Asn Met Cys Gly Leu
965 970 975
Ser Glu Asp Ala Thr Met Thr Lys Glu Ser Ala Val Ile Ala Arg Asp
980 985 990
Gly Lys Ile Tyr Lys Asn Pro Val Tyr Glu Asp Phe Asp Phe Ser Glu
995 1000 1005
Ala Pro Met Phe Thr Gln Pro Leu Val Asn Thr Tyr Ala Ile Ala
1010 1015 1020
Gly Tyr Asn Ala Thr Leu Asn Cys Ser Val Arg Gly Asn Pro Lys
1025 1030 1035
Pro Lys Ile Thr Trp Met Lys Asn Lys Val Ala Ile Val Asp Asp
1040 1045 1050
Pro Arg Tyr Arg Met Phe Ser Asn Gln Gly Val Cys Thr Leu Glu
1055 1060 1065
Ile Arg Lys Pro Ser Pro Tyr Asp Gly Gly Thr Tyr Cys Cys Lys
1070 1075 1080
Ala Val Asn Asp Leu Gly Thr Val Glu Ile Glu Cys Lys Leu Glu
1085 1090 1095
Val Lys Val Ile Tyr Gln Gly Val Asn Thr Pro Gly Gln Pro Val
1100 1105 1110
Phe Leu Glu Gly Gln Gln Gln Ser Leu His Asn Lys Asp Phe
1115 1120 1125
<210> 78
<211> 1120
<212> PRT
<213> Homo sapiens
<400> 78
Met Pro Glu Pro Thr Lys Lys Glu Asp Trp Thr Leu Val Glu Thr Pro
1 5 10 15
Pro Gly Glu Glu Gln Ala Lys Gln Asn Ala Asn Ser Gln Leu Ser Ile
20 25 30
Leu Phe Ile Glu Lys Pro Gln Gly Gly Thr Val Lys Val Gly Glu Asp
35 40 45
Ile Thr Phe Ile Ala Lys Val Lys Ala Glu Asp Leu Leu Arg Lys Pro
50 55 60
Thr Ile Lys Trp Phe Lys Gly Lys Trp Met Asp Leu Ala Ser Lys Ala
65 70 75 80
Gly Lys His Leu Gln Leu Lys Glu Thr Phe Glu Arg His Ser Arg Val
85 90 95
Tyr Thr Phe Glu Met Gln Ile Ile Lys Ala Lys Asp Asn Phe Ala Gly
100 105 110
Asn Tyr Arg Cys Glu Val Thr Tyr Lys Asp Lys Phe Asp Ser Cys Ser
115 120 125
Phe Asp Leu Glu Val His Glu Ser Thr Gly Thr Thr Pro Asn Ile Asp
130 135 140
Ile Arg Ser Ala Phe Lys Arg Ser Gly Glu Gly Gln Glu Asp Ala Gly
145 150 155 160
Glu Leu Asp Phe Ser Gly Leu Leu Lys Arg Arg Glu Val Lys Gln Gln
165 170 175
Glu Glu Glu Pro Gln Val Asp Val Trp Glu Leu Leu Lys Asn Ala Lys
180 185 190
Pro Ser Glu Tyr Glu Lys Ile Ala Phe Gln Tyr Gly Ile Thr Asp Leu
195 200 205
Arg Gly Met Leu Lys Arg Leu Lys Arg Met Arg Arg Glu Glu Lys Lys
210 215 220
Ser Ala Ala Phe Ala Lys Ile Leu Asp Pro Ala Tyr Gln Val Asp Lys
225 230 235 240
Gly Gly Arg Val Arg Phe Val Val Glu Leu Ala Asp Pro Lys Leu Glu
245 250 255
Val Lys Trp Tyr Lys Asn Gly Gln Glu Ile Arg Pro Ser Thr Lys Tyr
260 265 270
Ile Phe Glu His Lys Gly Cys Gln Arg Ile Leu Phe Ile Asn Asn Cys
275 280 285
Gln Met Thr Asp Asp Ser Glu Tyr Tyr Val Thr Ala Gly Asp Glu Lys
290 295 300
Cys Ser Thr Glu Leu Phe Val Arg Glu Pro Pro Ile Met Val Thr Lys
305 310 315 320
Gln Leu Glu Asp Thr Thr Ala Tyr Cys Gly Glu Arg Val Glu Leu Glu
325 330 335
Cys Glu Val Ser Glu Asp Asp Ala Asn Val Lys Trp Phe Lys Asn Gly
340 345 350
Glu Glu Ile Ile Pro Gly Pro Lys Ser Arg Tyr Arg Ile Arg Val Glu
355 360 365
Gly Lys Lys His Ile Leu Ile Ile Glu Gly Ala Thr Lys Ala Asp Ala
370 375 380
Ala Glu Tyr Ser Val Met Thr Thr Gly Gly Gln Ser Ser Ala Lys Leu
385 390 395 400
Ser Val Asp Leu Lys Pro Leu Lys Ile Leu Thr Pro Leu Thr Asp Gln
405 410 415
Thr Val Asn Leu Gly Lys Glu Ile Cys Leu Lys Cys Glu Ile Ser Glu
420 425 430
Asn Ile Pro Gly Lys Trp Thr Lys Asn Gly Leu Pro Val Gln Glu Ser
435 440 445
Asp Arg Leu Lys Val Val His Lys Gly Arg Ile His Lys Leu Val Ile
450 455 460
Ala Asn Ala Leu Thr Glu Asp Glu Gly Asp Tyr Val Phe Ala Pro Asp
465 470 475 480
Ala Tyr Asn Val Thr Leu Pro Ala Lys Val His Val Ile Asp Pro Pro
485 490 495
Lys Ile Ile Leu Asp Gly Leu Asp Ala Asp Asn Thr Val Thr Val Ile
500 505 510
Ala Gly Asn Lys Leu Arg Leu Glu Ile Pro Ile Ser Gly Glu Pro Pro
515 520 525
Pro Lys Ala Met Trp Ser Arg Gly Asp Lys Ala Ile Met Glu Gly Ser
530 535 540
Gly Arg Ile Arg Thr Glu Ser Tyr Pro Asp Ser Ser Thr Leu Val Ile
545 550 555 560
Asp Ile Ala Glu Arg Asp Asp Ser Gly Val Tyr His Ile Asn Leu Lys
565 570 575
Asn Glu Ala Gly Glu Ala His Ala Ser Ile Lys Val Lys Val Val Asp
580 585 590
Phe Pro Asp Pro Pro Val Ala Pro Thr Val Thr Glu Val Gly Asp Asp
595 600 605
Trp Cys Ile Met Asn Trp Glu Pro Pro Ala Tyr Asp Gly Gly Ser Pro
610 615 620
Ile Leu Gly Tyr Phe Ile Glu Arg Lys Lys Lys Gln Ser Ser Arg Trp
625 630 635 640
Met Arg Leu Asn Phe Asp Leu Cys Lys Glu Thr Thr Phe Glu Pro Lys
645 650 655
Lys Met Ile Glu Gly Val Ala Tyr Glu Val Arg Ile Phe Ala Val Asn
660 665 670
Ala Ile Gly Ile Ser Lys Pro Ser Met Pro Ser Arg Pro Phe Val Pro
675 680 685
Leu Ala Val Thr Ser Pro Pro Thr Leu Leu Thr Val Asp Ser Val Thr
690 695 700
Asp Thr Thr Val Thr Met Arg Trp Arg Pro Pro Asp His Ile Gly Ala
705 710 715 720
Ala Gly Leu Asp Gly Tyr Val Leu Glu Tyr Cys Phe Glu Gly Thr Glu
725 730 735
Asp Trp Ile Val Ala Asn Lys Asp Leu Ile Asp Lys Thr Lys Phe Thr
740 745 750
Ile Thr Gly Leu Pro Thr Asp Ala Lys Ile Phe Val Arg Val Lys Ala
755 760 765
Val Asn Ala Ala Gly Ala Ser Glu Pro Lys Tyr Tyr Ser Gln Pro Ile
770 775 780
Leu Val Lys Glu Ile Ile Glu Pro Pro Lys Ile Arg Ile Pro Arg His
785 790 795 800
Leu Lys Gln Thr Tyr Ile Arg Arg Val Gly Glu Ala Val Asn Leu Val
805 810 815
Ile Pro Phe Gln Gly Lys Pro Arg Pro Glu Leu Thr Trp Lys Lys Asp
820 825 830
Gly Ala Glu Ile Asp Lys Asn Gln Ile Asn Ile Arg Asn Ser Glu Thr
835 840 845
Asp Thr Ile Ile Phe Ile Arg Lys Ala Glu Arg Ser His Ser Gly Lys
850 855 860
Tyr Asp Leu Gln Val Lys Val Asp Lys Phe Val Glu Thr Ala Ser Ile
865 870 875 880
Asp Ile Gln Ile Ile Asp Arg Pro Gly Pro Pro Gln Ile Val Lys Ile
885 890 895
Glu Asp Val Trp Gly Glu Asn Val Ala Leu Thr Trp Thr Pro Pro Lys
900 905 910
Asp Asp Gly Asn Ala Ala Ile Thr Gly Tyr Thr Ile Gln Lys Ala Asp
915 920 925
Lys Lys Ser Met Glu Trp Phe Thr Val Ile Glu His Tyr His Arg Thr
930 935 940
Ser Ala Thr Ile Thr Glu Leu Val Ile Gly Asn Glu Tyr Tyr Phe Arg
945 950 955 960
Val Phe Ser Glu Asn Met Cys Gly Leu Ser Glu Asp Ala Thr Met Thr
965 970 975
Lys Glu Ser Ala Val Ile Ala Arg Asp Gly Lys Ile Tyr Lys Asn Pro
980 985 990
Val Tyr Glu Asp Phe Asp Phe Ser Glu Ala Pro Met Phe Thr Gln Pro
995 1000 1005
Leu Val Asn Thr Tyr Ala Ile Ala Gly Tyr Asn Ala Thr Leu Asn
1010 1015 1020
Cys Ser Val Arg Gly Asn Pro Lys Pro Lys Ile Thr Trp Met Lys
1025 1030 1035
Asn Lys Val Ala Ile Val Asp Asp Pro Arg Tyr Arg Met Phe Ser
1040 1045 1050
Asn Gln Gly Val Cys Thr Leu Glu Ile Arg Lys Pro Ser Pro Tyr
1055 1060 1065
Asp Gly Gly Thr Tyr Cys Cys Lys Ala Val Asn Asp Leu Gly Thr
1070 1075 1080
Val Glu Ile Glu Cys Lys Leu Glu Val Lys Val Ile Tyr Gln Gly
1085 1090 1095
Val Asn Thr Pro Gly Gln Pro Val Phe Leu Glu Gly Gln Gln Gln
1100 1105 1110
Ser Leu His Asn Lys Asp Phe
1115 1120
<210> 79
<211> 1139
<212> PRT
<213> Homo sapiens
<400> 79
Met Pro Glu Pro Thr Lys Lys Glu Asp Glu Glu Glu Val Ser Pro Pro
1 5 10 15
Ser Ala Leu Pro Pro Asp Trp Thr Leu Val Glu Thr Pro Pro Gly Glu
20 25 30
Glu Gln Ala Lys Gln Asn Ala Asn Ser Gln Leu Ser Ile Leu Phe Ile
35 40 45
Glu Lys Pro Gln Gly Gly Thr Val Lys Val Gly Glu Asp Ile Thr Phe
50 55 60
Ile Ala Lys Val Lys Ala Glu Asp Leu Leu Arg Lys Pro Thr Ile Lys
65 70 75 80
Trp Phe Lys Gly Lys Trp Met Asp Leu Ala Ser Lys Ala Gly Lys His
85 90 95
Leu Gln Leu Lys Glu Thr Phe Glu Arg His Ser Arg Val Tyr Thr Phe
100 105 110
Glu Met Gln Ile Ile Lys Ala Lys Asp Asn Phe Ala Gly Asn Tyr Arg
115 120 125
Cys Glu Val Thr Tyr Lys Asp Lys Phe Asp Ser Cys Ser Phe Asp Leu
130 135 140
Glu Val His Glu Ser Thr Gly Thr Thr Pro Asn Ile Asp Ile Arg Ser
145 150 155 160
Ala Phe Lys Arg Ser Gly Glu Gly Gln Glu Asp Ala Gly Glu Leu Asp
165 170 175
Phe Ser Gly Leu Leu Lys Arg Arg Glu Val Lys Gln Gln Glu Glu Glu
180 185 190
Pro Gln Val Asp Val Trp Glu Leu Leu Lys Asn Ala Lys Pro Ser Glu
195 200 205
Tyr Glu Lys Ile Ala Phe Gln Tyr Gly Ile Thr Asp Leu Arg Gly Met
210 215 220
Leu Lys Arg Leu Lys Arg Met Arg Arg Glu Glu Lys Lys Ser Ala Ala
225 230 235 240
Phe Ala Lys Ile Leu Asp Pro Ala Tyr Gln Val Asp Lys Gly Gly Arg
245 250 255
Val Arg Phe Val Val Glu Leu Ala Asp Pro Lys Leu Glu Val Lys Trp
260 265 270
Tyr Lys Asn Gly Gln Glu Ile Arg Pro Ser Thr Lys Tyr Ile Phe Glu
275 280 285
His Lys Gly Cys Gln Arg Ile Leu Phe Ile Asn Asn Cys Gln Met Thr
290 295 300
Asp Asp Ser Glu Tyr Tyr Val Thr Ala Gly Asp Glu Lys Cys Ser Thr
305 310 315 320
Glu Leu Phe Val Arg Glu Pro Pro Ile Met Val Thr Lys Gln Leu Glu
325 330 335
Asp Thr Thr Ala Tyr Cys Gly Glu Arg Val Glu Leu Glu Cys Glu Val
340 345 350
Ser Glu Asp Asp Ala Asn Val Lys Trp Phe Lys Asn Gly Glu Glu Ile
355 360 365
Ile Pro Gly Pro Lys Ser Arg Tyr Arg Ile Arg Val Glu Gly Lys Lys
370 375 380
His Ile Leu Ile Ile Glu Gly Ala Thr Lys Ala Asp Ala Ala Glu Tyr
385 390 395 400
Ser Val Met Thr Thr Gly Gly Gln Ser Ser Ala Lys Leu Ser Val Asp
405 410 415
Leu Lys Pro Leu Lys Ile Leu Thr Pro Leu Thr Asp Gln Thr Val Asn
420 425 430
Leu Gly Lys Glu Ile Cys Leu Lys Cys Glu Ile Ser Glu Asn Ile Pro
435 440 445
Gly Lys Trp Thr Lys Asn Gly Leu Pro Val Gln Glu Ser Asp Arg Leu
450 455 460
Lys Val Val His Lys Gly Arg Ile His Lys Leu Val Ile Ala Asn Ala
465 470 475 480
Leu Thr Glu Asp Glu Gly Asp Tyr Val Phe Ala Pro Asp Ala Tyr Asn
485 490 495
Val Thr Leu Pro Ala Lys Val His Val Ile Asp Pro Pro Lys Ile Ile
500 505 510
Leu Asp Gly Leu Asp Ala Asp Asn Thr Val Thr Val Ile Ala Gly Asn
515 520 525
Lys Leu Arg Leu Glu Ile Pro Ile Ser Gly Glu Pro Pro Pro Lys Ala
530 535 540
Met Trp Ser Arg Gly Asp Lys Ala Ile Met Glu Gly Ser Gly Arg Ile
545 550 555 560
Arg Thr Glu Ser Tyr Pro Asp Ser Ser Thr Leu Val Ile Asp Ile Ala
565 570 575
Glu Arg Asp Asp Ser Gly Val Tyr His Ile Asn Leu Lys Asn Glu Ala
580 585 590
Gly Glu Ala His Ala Ser Ile Lys Val Lys Val Val Asp Phe Pro Asp
595 600 605
Pro Pro Val Ala Pro Thr Val Thr Glu Val Gly Asp Asp Trp Cys Ile
610 615 620
Met Asn Trp Glu Pro Pro Ala Tyr Asp Gly Gly Ser Pro Ile Leu Gly
625 630 635 640
Tyr Phe Ile Glu Arg Lys Lys Lys Gln Ser Ser Arg Trp Met Arg Leu
645 650 655
Asn Phe Asp Leu Cys Lys Glu Thr Thr Phe Glu Pro Lys Lys Met Ile
660 665 670
Glu Gly Val Ala Tyr Glu Val Arg Ile Phe Ala Val Asn Ala Ile Gly
675 680 685
Ile Ser Lys Pro Ser Met Pro Ser Arg Pro Phe Val Pro Leu Ala Val
690 695 700
Thr Ser Pro Pro Thr Leu Leu Thr Val Asp Ser Val Thr Asp Thr Thr
705 710 715 720
Val Thr Met Arg Trp Arg Pro Pro Asp His Ile Gly Ala Ala Gly Leu
725 730 735
Asp Gly Tyr Val Leu Glu Tyr Cys Phe Glu Gly Thr Glu Asp Trp Ile
740 745 750
Val Ala Asn Lys Asp Leu Ile Asp Lys Thr Lys Phe Thr Ile Thr Gly
755 760 765
Leu Pro Thr Asp Ala Lys Ile Phe Val Arg Val Lys Ala Val Asn Ala
770 775 780
Ala Gly Ala Ser Glu Pro Lys Tyr Tyr Ser Gln Pro Ile Leu Val Lys
785 790 795 800
Glu Ile Ile Glu Pro Pro Lys Ile Arg Ile Pro Arg His Leu Lys Gln
805 810 815
Thr Tyr Ile Arg Arg Val Gly Glu Ala Val Asn Leu Val Ile Pro Phe
820 825 830
Gln Gly Lys Pro Arg Pro Glu Leu Thr Trp Lys Lys Asp Gly Ala Glu
835 840 845
Ile Asp Lys Asn Gln Ile Asn Ile Arg Asn Ser Glu Thr Asp Thr Ile
850 855 860
Ile Phe Ile Arg Lys Ala Glu Arg Ser His Ser Gly Lys Tyr Asp Leu
865 870 875 880
Gln Val Lys Val Asp Lys Phe Val Glu Thr Ala Ser Ile Asp Ile Gln
885 890 895
Ile Ile Asp Arg Pro Gly Pro Pro Gln Ile Val Lys Ile Glu Asp Val
900 905 910
Trp Gly Glu Asn Val Ala Leu Thr Trp Thr Pro Pro Lys Asp Asp Gly
915 920 925
Asn Ala Ala Ile Thr Gly Tyr Thr Ile Gln Lys Ala Asp Lys Lys Ser
930 935 940
Met Glu Trp Phe Thr Val Ile Glu His Tyr His Arg Thr Ser Ala Thr
945 950 955 960
Ile Thr Glu Leu Val Ile Gly Asn Glu Tyr Tyr Phe Arg Val Phe Ser
965 970 975
Glu Asn Met Cys Gly Leu Ser Glu Asp Ala Thr Met Thr Lys Glu Ser
980 985 990
Ala Val Ile Ala Arg Asp Gly Lys Ile Tyr Lys Asn Pro Val Tyr Glu
995 1000 1005
Asp Phe Asp Phe Ser Glu Ala Pro Met Phe Thr Gln Pro Leu Val
1010 1015 1020
Asn Thr Tyr Ala Ile Ala Gly Tyr Asn Ala Thr Leu Asn Cys Ser
1025 1030 1035
Val Arg Gly Asn Pro Lys Pro Lys Ile Thr Trp Met Lys Asn Lys
1040 1045 1050
Val Ala Ile Val Asp Asp Pro Arg Tyr Arg Met Phe Ser Asn Gln
1055 1060 1065
Gly Val Cys Thr Leu Glu Ile Arg Lys Pro Ser Pro Tyr Asp Gly
1070 1075 1080
Gly Thr Tyr Cys Cys Lys Ala Val Asn Asp Leu Gly Thr Val Glu
1085 1090 1095
Ile Glu Cys Lys Leu Glu Val Lys Gly Gly Leu Ser Phe Cys Arg
1100 1105 1110
Leu Leu Leu Gln Gly Val Pro Pro Asn Ile Ile Asp Ser Tyr Leu
1115 1120 1125
Arg Asp Leu His Ser Ser Asn Pro Glu Glu Tyr
1130 1135
<210> 80
<211> 1171
<212> PRT
<213> Homo sapiens
<400> 80
Met Pro Glu Pro Thr Lys Lys Glu Glu Asn Glu Val Pro Ala Pro Ala
1 5 10 15
Pro Pro Pro Glu Glu Pro Ser Lys Glu Lys Glu Ala Gly Thr Thr Pro
20 25 30
Ala Lys Asp Glu Glu Glu Val Ser Pro Pro Ser Ala Leu Pro Pro Gly
35 40 45
Leu Gly Ser Arg Ala Leu Glu Arg Lys Asp Ser Asp Trp Thr Leu Val
50 55 60
Glu Thr Pro Pro Gly Glu Glu Gln Ala Lys Gln Asn Ala Asn Ser Gln
65 70 75 80
Leu Ser Ile Leu Phe Ile Glu Lys Pro Gln Gly Gly Thr Val Lys Val
85 90 95
Gly Glu Asp Ile Thr Phe Ile Ala Lys Val Lys Ala Glu Asp Leu Leu
100 105 110
Arg Lys Pro Thr Ile Lys Trp Phe Lys Gly Lys Trp Met Asp Leu Ala
115 120 125
Ser Lys Ala Gly Lys His Leu Gln Leu Lys Glu Thr Phe Glu Arg His
130 135 140
Ser Arg Val Tyr Thr Phe Glu Met Gln Ile Ile Lys Ala Lys Asp Asn
145 150 155 160
Phe Ala Gly Asn Tyr Arg Cys Glu Val Thr Tyr Lys Asp Lys Phe Asp
165 170 175
Ser Cys Ser Phe Asp Leu Glu Val His Glu Ser Thr Gly Thr Thr Pro
180 185 190
Asn Ile Asp Ile Arg Ser Ala Phe Lys Arg Ser Gly Glu Gly Gln Glu
195 200 205
Asp Ala Gly Glu Leu Asp Phe Ser Gly Leu Leu Lys Arg Arg Glu Val
210 215 220
Lys Gln Gln Glu Glu Glu Pro Gln Val Asp Val Trp Glu Leu Leu Lys
225 230 235 240
Asn Ala Lys Pro Ser Glu Tyr Glu Lys Ile Ala Phe Gln Tyr Gly Ile
245 250 255
Thr Asp Leu Arg Gly Met Leu Lys Arg Leu Lys Arg Met Arg Arg Glu
260 265 270
Glu Lys Lys Ser Ala Ala Phe Ala Lys Ile Leu Asp Pro Ala Tyr Gln
275 280 285
Val Asp Lys Gly Gly Arg Val Arg Phe Val Val Glu Leu Ala Asp Pro
290 295 300
Lys Leu Glu Val Lys Trp Tyr Lys Asn Gly Gln Glu Ile Arg Pro Ser
305 310 315 320
Thr Lys Tyr Ile Phe Glu His Lys Gly Cys Gln Arg Ile Leu Phe Ile
325 330 335
Asn Asn Cys Gln Met Thr Asp Asp Ser Glu Tyr Tyr Val Thr Ala Gly
340 345 350
Asp Glu Lys Cys Ser Thr Glu Leu Phe Val Arg Glu Pro Pro Ile Met
355 360 365
Val Thr Lys Gln Leu Glu Asp Thr Thr Ala Tyr Cys Gly Glu Arg Val
370 375 380
Glu Leu Glu Cys Glu Val Ser Glu Asp Asp Ala Asn Val Lys Trp Phe
385 390 395 400
Lys Asn Gly Glu Glu Ile Ile Pro Gly Pro Lys Ser Arg Tyr Arg Ile
405 410 415
Arg Val Glu Gly Lys Lys His Ile Leu Ile Ile Glu Gly Ala Thr Lys
420 425 430
Ala Asp Ala Ala Glu Tyr Ser Val Met Thr Thr Gly Gly Gln Ser Ser
435 440 445
Ala Lys Leu Ser Val Asp Leu Lys Pro Leu Lys Ile Leu Thr Pro Leu
450 455 460
Thr Asp Gln Thr Val Asn Leu Gly Lys Glu Ile Cys Leu Lys Cys Glu
465 470 475 480
Ile Ser Glu Asn Ile Pro Gly Lys Trp Thr Lys Asn Gly Leu Pro Val
485 490 495
Gln Glu Ser Asp Arg Leu Lys Val Val His Lys Gly Arg Ile His Lys
500 505 510
Leu Val Ile Ala Asn Ala Leu Thr Glu Asp Glu Gly Asp Tyr Val Phe
515 520 525
Ala Pro Asp Ala Tyr Asn Val Thr Leu Pro Ala Lys Val His Val Ile
530 535 540
Asp Pro Pro Lys Ile Ile Leu Asp Gly Leu Asp Ala Asp Asn Thr Val
545 550 555 560
Thr Val Ile Ala Gly Asn Lys Leu Arg Leu Glu Ile Pro Ile Ser Gly
565 570 575
Glu Pro Pro Pro Lys Ala Met Trp Ser Arg Gly Asp Lys Ala Ile Met
580 585 590
Glu Gly Ser Gly Arg Ile Arg Thr Glu Ser Tyr Pro Asp Ser Ser Thr
595 600 605
Leu Val Ile Asp Ile Ala Glu Arg Asp Asp Ser Gly Val Tyr His Ile
610 615 620
Asn Leu Lys Asn Glu Ala Gly Glu Ala His Ala Ser Ile Lys Val Lys
625 630 635 640
Val Val Asp Phe Pro Asp Pro Pro Val Ala Pro Thr Val Thr Glu Val
645 650 655
Gly Asp Asp Trp Cys Ile Met Asn Trp Glu Pro Pro Ala Tyr Asp Gly
660 665 670
Gly Ser Pro Ile Leu Gly Tyr Phe Ile Glu Arg Lys Lys Lys Gln Ser
675 680 685
Ser Arg Trp Met Arg Leu Asn Phe Asp Leu Cys Lys Glu Thr Thr Phe
690 695 700
Glu Pro Lys Lys Met Ile Glu Gly Val Ala Tyr Glu Val Arg Ile Phe
705 710 715 720
Ala Val Asn Ala Ile Gly Ile Ser Lys Pro Ser Met Pro Ser Arg Pro
725 730 735
Phe Val Pro Leu Ala Val Thr Ser Pro Pro Thr Leu Leu Thr Val Asp
740 745 750
Ser Val Thr Asp Thr Thr Val Thr Met Arg Trp Arg Pro Pro Asp His
755 760 765
Ile Gly Ala Ala Gly Leu Asp Gly Tyr Val Leu Glu Tyr Cys Phe Glu
770 775 780
Gly Thr Glu Asp Trp Ile Val Ala Asn Lys Asp Leu Ile Asp Lys Thr
785 790 795 800
Lys Phe Thr Ile Thr Gly Leu Pro Thr Asp Ala Lys Ile Phe Val Arg
805 810 815
Val Lys Ala Val Asn Ala Ala Gly Ala Ser Glu Pro Lys Tyr Tyr Ser
820 825 830
Gln Pro Ile Leu Val Lys Glu Ile Ile Glu Pro Pro Lys Ile Arg Ile
835 840 845
Pro Arg His Leu Lys Gln Thr Tyr Ile Arg Arg Val Gly Glu Ala Val
850 855 860
Asn Leu Val Ile Pro Phe Gln Gly Lys Pro Arg Pro Glu Leu Thr Trp
865 870 875 880
Lys Lys Asp Gly Ala Glu Ile Asp Lys Asn Gln Ile Asn Ile Arg Asn
885 890 895
Ser Glu Thr Asp Thr Ile Ile Phe Ile Arg Lys Ala Glu Arg Ser His
900 905 910
Ser Gly Lys Tyr Asp Leu Gln Val Lys Val Asp Lys Phe Val Glu Thr
915 920 925
Ala Ser Ile Asp Ile Gln Ile Ile Asp Arg Pro Gly Pro Pro Gln Ile
930 935 940
Val Lys Ile Glu Asp Val Trp Gly Glu Asn Val Ala Leu Thr Trp Thr
945 950 955 960
Pro Pro Lys Asp Asp Gly Asn Ala Ala Ile Thr Gly Tyr Thr Ile Gln
965 970 975
Lys Ala Asp Lys Lys Ser Met Glu Trp Phe Thr Val Ile Glu His Tyr
980 985 990
His Arg Thr Ser Ala Thr Ile Thr Glu Leu Val Ile Gly Asn Glu Tyr
995 1000 1005
Tyr Phe Arg Val Phe Ser Glu Asn Met Cys Gly Leu Ser Glu Asp
1010 1015 1020
Ala Thr Met Thr Lys Glu Ser Ala Val Ile Ala Arg Asp Gly Lys
1025 1030 1035
Ile Tyr Lys Asn Pro Val Tyr Glu Asp Phe Asp Phe Ser Glu Ala
1040 1045 1050
Pro Met Phe Thr Gln Pro Leu Val Asn Thr Tyr Ala Ile Ala Gly
1055 1060 1065
Tyr Asn Ala Thr Leu Asn Cys Ser Val Arg Gly Asn Pro Lys Pro
1070 1075 1080
Lys Ile Thr Trp Met Lys Asn Lys Val Ala Ile Val Asp Asp Pro
1085 1090 1095
Arg Tyr Arg Met Phe Ser Asn Gln Gly Val Cys Thr Leu Glu Ile
1100 1105 1110
Arg Lys Pro Ser Pro Tyr Asp Gly Gly Thr Tyr Cys Cys Lys Ala
1115 1120 1125
Val Asn Asp Leu Gly Thr Val Glu Ile Glu Cys Lys Leu Glu Val
1130 1135 1140
Lys Val Ile Tyr Gln Gly Val Asn Thr Pro Gly Gln Pro Val Phe
1145 1150 1155
Leu Glu Gly Gln Gln Gln Ser Leu His Asn Lys Asp Phe
1160 1165 1170
<210> 81
<211> 1148
<212> PRT
<213> Homo sapiens
<400> 81
Met Pro Glu Pro Thr Lys Lys Glu Glu Asn Glu Val Pro Ala Pro Ala
1 5 10 15
Pro Pro Pro Glu Glu Pro Ser Lys Glu Lys Glu Ala Gly Thr Thr Pro
20 25 30
Ala Lys Asp Glu Glu Glu Val Ser Pro Pro Ser Ala Leu Pro Pro Gly
35 40 45
Leu Gly Ser Arg Ala Leu Glu Arg Lys Asp Ser Asp Trp Thr Leu Val
50 55 60
Glu Thr Pro Pro Gly Glu Glu Gln Ala Lys Gln Asn Ala Asn Ser Gln
65 70 75 80
Leu Ser Ile Leu Phe Ile Glu Lys Pro Gln Gly Gly Thr Val Lys Val
85 90 95
Gly Glu Asp Ile Thr Phe Ile Ala Lys Val Lys Ala Glu Asp Leu Leu
100 105 110
Arg Lys Pro Thr Ile Lys Trp Phe Lys Gly Lys Trp Met Asp Leu Ala
115 120 125
Ser Lys Ala Gly Lys His Leu Gln Leu Lys Glu Thr Phe Glu Arg His
130 135 140
Ser Arg Val Tyr Thr Phe Glu Met Gln Ile Ile Lys Ala Lys Asp Asn
145 150 155 160
Phe Ala Gly Asn Tyr Arg Cys Glu Val Thr Tyr Lys Asp Lys Phe Asp
165 170 175
Ser Cys Ser Phe Asp Leu Glu Val His Glu Ser Thr Gly Thr Thr Pro
180 185 190
Asn Ile Asp Ile Arg Ser Ala Phe Lys Arg Ser Gly Glu Gly Gln Glu
195 200 205
Asp Ala Gly Glu Leu Asp Phe Ser Gly Leu Leu Lys Arg Arg Glu Val
210 215 220
Lys Gln Gln Glu Glu Glu Pro Gln Val Asp Val Trp Glu Leu Leu Lys
225 230 235 240
Asn Ala Lys Pro Ser Glu Tyr Glu Lys Ile Ala Phe Gln Tyr Gly Ile
245 250 255
Thr Asp Leu Arg Gly Met Leu Lys Arg Leu Lys Arg Met Arg Arg Glu
260 265 270
Glu Lys Lys Ser Ala Ala Phe Ala Lys Ile Leu Asp Pro Ala Tyr Gln
275 280 285
Val Asp Lys Gly Gly Arg Val Arg Phe Val Val Glu Leu Ala Asp Pro
290 295 300
Lys Leu Glu Val Lys Trp Tyr Lys Asn Gly Gln Glu Ile Arg Pro Ser
305 310 315 320
Thr Lys Tyr Ile Phe Glu His Lys Gly Cys Gln Arg Ile Leu Phe Ile
325 330 335
Asn Asn Cys Gln Met Thr Asp Asp Ser Glu Tyr Tyr Val Thr Ala Gly
340 345 350
Asp Glu Lys Cys Ser Thr Glu Leu Phe Val Arg Glu Pro Pro Ile Met
355 360 365
Val Thr Lys Gln Leu Glu Asp Thr Thr Ala Tyr Cys Gly Glu Arg Val
370 375 380
Glu Leu Glu Cys Glu Val Ser Glu Asp Asp Ala Asn Val Lys Trp Phe
385 390 395 400
Lys Asn Gly Glu Glu Ile Ile Pro Gly Pro Lys Ser Arg Tyr Arg Ile
405 410 415
Arg Val Glu Gly Lys Lys His Ile Leu Ile Ile Glu Gly Ala Thr Lys
420 425 430
Ala Asp Ala Ala Glu Tyr Ser Val Met Thr Thr Gly Gly Gln Ser Ser
435 440 445
Ala Lys Leu Ser Val Asp Leu Lys Pro Leu Lys Ile Leu Thr Pro Leu
450 455 460
Thr Asp Gln Thr Val Asn Leu Gly Lys Glu Ile Cys Leu Lys Cys Glu
465 470 475 480
Ile Ser Glu Asn Ile Pro Gly Lys Trp Thr Lys Asn Gly Leu Pro Val
485 490 495
Gln Glu Ser Asp Arg Leu Lys Val Val His Lys Gly Arg Ile His Lys
500 505 510
Leu Val Ile Ala Asn Ala Leu Thr Glu Asp Glu Gly Asp Tyr Val Phe
515 520 525
Ala Pro Asp Ala Tyr Asn Val Thr Leu Pro Ala Lys Val His Val Ile
530 535 540
Asp Pro Pro Lys Ile Ile Leu Asp Gly Leu Asp Ala Asp Asn Thr Val
545 550 555 560
Thr Val Ile Ala Gly Asn Lys Leu Arg Leu Glu Ile Pro Ile Ser Gly
565 570 575
Glu Pro Pro Pro Lys Ala Met Trp Ser Arg Gly Asp Lys Ala Ile Met
580 585 590
Glu Gly Ser Gly Arg Ile Arg Thr Glu Ser Tyr Pro Asp Ser Ser Thr
595 600 605
Leu Val Ile Asp Ile Ala Glu Arg Asp Asp Ser Gly Val Tyr His Ile
610 615 620
Asn Leu Lys Asn Glu Ala Gly Glu Ala His Ala Ser Ile Lys Val Lys
625 630 635 640
Val Val Asp Phe Pro Asp Pro Pro Val Ala Pro Thr Val Thr Glu Val
645 650 655
Gly Asp Asp Trp Cys Ile Met Asn Trp Glu Pro Pro Ala Tyr Asp Gly
660 665 670
Gly Ser Pro Ile Leu Gly Tyr Phe Ile Glu Arg Lys Lys Lys Gln Ser
675 680 685
Ser Arg Trp Met Arg Leu Asn Phe Asp Leu Cys Lys Glu Thr Thr Phe
690 695 700
Glu Pro Lys Lys Met Ile Glu Gly Val Ala Tyr Glu Val Arg Ile Phe
705 710 715 720
Ala Val Asn Ala Ile Gly Ile Ser Lys Pro Ser Met Pro Ser Arg Pro
725 730 735
Phe Val Pro Leu Ala Val Thr Ser Pro Pro Thr Leu Leu Thr Val Asp
740 745 750
Ser Val Thr Asp Thr Thr Val Thr Met Arg Trp Arg Pro Pro Asp His
755 760 765
Ile Gly Ala Ala Gly Leu Asp Gly Tyr Val Leu Glu Tyr Cys Phe Glu
770 775 780
Gly Thr Glu Asp Trp Ile Val Ala Asn Lys Asp Leu Ile Asp Lys Thr
785 790 795 800
Lys Phe Thr Ile Thr Gly Leu Pro Thr Asp Ala Lys Ile Phe Val Arg
805 810 815
Val Lys Ala Val Asn Ala Ala Gly Ala Ser Glu Pro Lys Tyr Tyr Ser
820 825 830
Gln Pro Ile Leu Val Lys Glu Ile Ile Glu Pro Pro Lys Ile Arg Ile
835 840 845
Pro Arg His Leu Lys Gln Thr Tyr Ile Arg Arg Val Gly Glu Ala Val
850 855 860
Asn Leu Val Ile Pro Phe Gln Gly Lys Pro Arg Pro Glu Leu Thr Trp
865 870 875 880
Lys Lys Asp Gly Ala Glu Ile Asp Lys Asn Gln Ile Asn Ile Arg Asn
885 890 895
Ser Glu Thr Asp Thr Ile Ile Phe Ile Arg Lys Ala Glu Arg Ser His
900 905 910
Ser Gly Lys Tyr Asp Leu Gln Val Lys Val Asp Lys Phe Val Glu Thr
915 920 925
Ala Ser Ile Asp Ile Gln Ile Ile Asp Arg Pro Gly Pro Pro Gln Ile
930 935 940
Val Lys Ile Glu Asp Val Trp Gly Glu Asn Val Ala Leu Thr Trp Thr
945 950 955 960
Pro Pro Lys Asp Asp Gly Asn Ala Ala Ile Thr Gly Tyr Thr Ile Gln
965 970 975
Lys Ala Asp Lys Lys Ser Met Glu Trp Phe Thr Val Ile Glu His Tyr
980 985 990
His Arg Thr Ser Ala Thr Ile Thr Glu Leu Val Ile Gly Asn Glu Tyr
995 1000 1005
Tyr Phe Arg Val Phe Ser Glu Asn Met Cys Gly Leu Ser Glu Asp
1010 1015 1020
Ala Thr Met Thr Lys Glu Ser Ala Val Ile Ala Arg Asp Gly Lys
1025 1030 1035
Ile Tyr Lys Asn Pro Val Tyr Glu Asp Phe Asp Phe Ser Glu Ala
1040 1045 1050
Pro Met Phe Thr Gln Pro Leu Val Asn Thr Tyr Ala Ile Ala Gly
1055 1060 1065
Tyr Asn Ala Thr Leu Asn Cys Ser Val Arg Gly Asn Pro Lys Pro
1070 1075 1080
Lys Ile Thr Trp Met Lys Asn Lys Val Ala Ile Val Asp Asp Pro
1085 1090 1095
Arg Tyr Arg Met Phe Ser Asn Gln Gly Val Cys Thr Leu Glu Ile
1100 1105 1110
Arg Lys Pro Ser Pro Tyr Asp Gly Gly Thr Tyr Cys Cys Lys Ala
1115 1120 1125
Val Asn Asp Leu Gly Thr Val Glu Ile Glu Cys Lys Leu Glu Val
1130 1135 1140
Lys Val Ile Ala Gln
1145
<210> 82
<211> 1141
<212> PRT
<213> Homo sapiens
<400> 82
Met Pro Glu Pro Thr Lys Lys Glu Glu Asn Glu Val Pro Ala Pro Ala
1 5 10 15
Pro Pro Pro Glu Glu Pro Ser Lys Glu Lys Glu Ala Gly Thr Thr Pro
20 25 30
Ala Lys Asp Trp Thr Leu Val Glu Thr Pro Pro Gly Glu Glu Gln Ala
35 40 45
Lys Gln Asn Ala Asn Ser Gln Leu Ser Ile Leu Phe Ile Glu Lys Pro
50 55 60
Gln Gly Gly Thr Val Lys Val Gly Glu Asp Ile Thr Phe Ile Ala Lys
65 70 75 80
Val Lys Ala Glu Asp Leu Leu Arg Lys Pro Thr Ile Lys Trp Phe Lys
85 90 95
Gly Lys Trp Met Asp Leu Ala Ser Lys Ala Gly Lys His Leu Gln Leu
100 105 110
Lys Glu Thr Phe Glu Arg His Ser Arg Val Tyr Thr Phe Glu Met Gln
115 120 125
Ile Ile Lys Ala Lys Asp Asn Phe Ala Gly Asn Tyr Arg Cys Glu Val
130 135 140
Thr Tyr Lys Asp Lys Phe Asp Ser Cys Ser Phe Asp Leu Glu Val His
145 150 155 160
Glu Ser Thr Gly Thr Thr Pro Asn Ile Asp Ile Arg Ser Ala Phe Lys
165 170 175
Arg Ser Gly Glu Gly Gln Glu Asp Ala Gly Glu Leu Asp Phe Ser Gly
180 185 190
Leu Leu Lys Arg Arg Glu Val Lys Gln Gln Glu Glu Glu Pro Gln Val
195 200 205
Asp Val Trp Glu Leu Leu Lys Asn Ala Lys Pro Ser Glu Tyr Glu Lys
210 215 220
Ile Ala Phe Gln Tyr Gly Ile Thr Asp Leu Arg Gly Met Leu Lys Arg
225 230 235 240
Leu Lys Arg Met Arg Arg Glu Glu Lys Lys Ser Ala Ala Phe Ala Lys
245 250 255
Ile Leu Asp Pro Ala Tyr Gln Val Asp Lys Gly Gly Arg Val Arg Phe
260 265 270
Val Val Glu Leu Ala Asp Pro Lys Leu Glu Val Lys Trp Tyr Lys Asn
275 280 285
Gly Gln Glu Ile Arg Pro Ser Thr Lys Tyr Ile Phe Glu His Lys Gly
290 295 300
Cys Gln Arg Ile Leu Phe Ile Asn Asn Cys Gln Met Thr Asp Asp Ser
305 310 315 320
Glu Tyr Tyr Val Thr Ala Gly Asp Glu Lys Cys Ser Thr Glu Leu Phe
325 330 335
Val Arg Glu Pro Pro Ile Met Val Thr Lys Gln Leu Glu Asp Thr Thr
340 345 350
Ala Tyr Cys Gly Glu Arg Val Glu Leu Glu Cys Glu Val Ser Glu Asp
355 360 365
Asp Ala Asn Val Lys Trp Phe Lys Asn Gly Glu Glu Ile Ile Pro Gly
370 375 380
Pro Lys Ser Arg Tyr Arg Ile Arg Val Glu Gly Lys Lys His Ile Leu
385 390 395 400
Ile Ile Glu Gly Ala Thr Lys Ala Asp Ala Ala Glu Tyr Ser Val Met
405 410 415
Thr Thr Gly Gly Gln Ser Ser Ala Lys Leu Ser Val Asp Leu Lys Pro
420 425 430
Leu Lys Ile Leu Thr Pro Leu Thr Asp Gln Thr Val Asn Leu Gly Lys
435 440 445
Glu Ile Cys Leu Lys Cys Glu Ile Ser Glu Asn Ile Pro Gly Lys Trp
450 455 460
Thr Lys Asn Gly Leu Pro Val Gln Glu Ser Asp Arg Leu Lys Val Val
465 470 475 480
His Lys Gly Arg Ile His Lys Leu Val Ile Ala Asn Ala Leu Thr Glu
485 490 495
Asp Glu Gly Asp Tyr Val Phe Ala Pro Asp Ala Tyr Asn Val Thr Leu
500 505 510
Pro Ala Lys Val His Val Ile Asp Pro Pro Lys Ile Ile Leu Asp Gly
515 520 525
Leu Asp Ala Asp Asn Thr Val Thr Val Ile Ala Gly Asn Lys Leu Arg
530 535 540
Leu Glu Ile Pro Ile Ser Gly Glu Pro Pro Pro Lys Ala Met Trp Ser
545 550 555 560
Arg Gly Asp Lys Ala Ile Met Glu Gly Ser Gly Arg Ile Arg Thr Glu
565 570 575
Ser Tyr Pro Asp Ser Ser Thr Leu Val Ile Asp Ile Ala Glu Arg Asp
580 585 590
Asp Ser Gly Val Tyr His Ile Asn Leu Lys Asn Glu Ala Gly Glu Ala
595 600 605
His Ala Ser Ile Lys Val Lys Val Val Asp Phe Pro Asp Pro Pro Val
610 615 620
Ala Pro Thr Val Thr Glu Val Gly Asp Asp Trp Cys Ile Met Asn Trp
625 630 635 640
Glu Pro Pro Ala Tyr Asp Gly Gly Ser Pro Ile Leu Gly Tyr Phe Ile
645 650 655
Glu Arg Lys Lys Lys Gln Ser Ser Arg Trp Met Arg Leu Asn Phe Asp
660 665 670
Leu Cys Lys Glu Thr Thr Phe Glu Pro Lys Lys Met Ile Glu Gly Val
675 680 685
Ala Tyr Glu Val Arg Ile Phe Ala Val Asn Ala Ile Gly Ile Ser Lys
690 695 700
Pro Ser Met Pro Ser Arg Pro Phe Val Pro Leu Ala Val Thr Ser Pro
705 710 715 720
Pro Thr Leu Leu Thr Val Asp Ser Val Thr Asp Thr Thr Val Thr Met
725 730 735
Arg Trp Arg Pro Pro Asp His Ile Gly Ala Ala Gly Leu Asp Gly Tyr
740 745 750
Val Leu Glu Tyr Cys Phe Glu Gly Ser Thr Ser Ala Lys Gln Ser Asp
755 760 765
Glu Asn Gly Glu Ala Ala Tyr Asp Leu Pro Ala Glu Asp Trp Ile Val
770 775 780
Ala Asn Lys Asp Leu Ile Asp Lys Thr Lys Phe Thr Ile Thr Gly Leu
785 790 795 800
Pro Thr Asp Ala Lys Ile Phe Val Arg Val Lys Ala Val Asn Ala Ala
805 810 815
Gly Ala Ser Glu Pro Lys Tyr Tyr Ser Gln Pro Ile Leu Val Lys Glu
820 825 830
Ile Ile Glu Pro Pro Lys Ile Arg Ile Pro Arg His Leu Lys Gln Thr
835 840 845
Tyr Ile Arg Arg Val Gly Glu Ala Val Asn Leu Val Ile Pro Phe Gln
850 855 860
Gly Lys Pro Arg Pro Glu Leu Thr Trp Lys Lys Asp Gly Ala Glu Ile
865 870 875 880
Asp Lys Asn Gln Ile Asn Ile Arg Asn Ser Glu Thr Asp Thr Ile Ile
885 890 895
Phe Ile Arg Lys Ala Glu Arg Ser His Ser Gly Lys Tyr Asp Leu Gln
900 905 910
Val Lys Val Asp Lys Phe Val Glu Thr Ala Ser Ile Asp Ile Gln Ile
915 920 925
Ile Asp Arg Pro Gly Pro Pro Gln Ile Val Lys Ile Glu Asp Val Trp
930 935 940
Gly Glu Asn Val Ala Leu Thr Trp Thr Pro Pro Lys Asp Asp Gly Asn
945 950 955 960
Ala Ala Ile Thr Gly Tyr Thr Ile Gln Lys Ala Asp Lys Lys Ser Met
965 970 975
Glu Trp Phe Thr Val Ile Glu His Tyr His Arg Thr Ser Ala Thr Ile
980 985 990
Thr Glu Leu Val Ile Gly Asn Glu Tyr Tyr Phe Arg Val Phe Ser Glu
995 1000 1005
Asn Met Cys Gly Leu Ser Glu Asp Ala Thr Met Thr Lys Glu Ser
1010 1015 1020
Ala Val Ile Ala Arg Asp Gly Lys Ile Tyr Lys Asn Pro Val Tyr
1025 1030 1035
Glu Asp Phe Asp Phe Ser Glu Ala Pro Met Phe Thr Gln Pro Leu
1040 1045 1050
Val Asn Thr Tyr Ala Ile Ala Gly Tyr Asn Ala Thr Leu Asn Cys
1055 1060 1065
Ser Val Arg Gly Asn Pro Lys Pro Lys Ile Thr Trp Met Lys Asn
1070 1075 1080
Lys Val Ala Ile Val Asp Asp Pro Arg Tyr Arg Met Phe Ser Asn
1085 1090 1095
Gln Gly Val Cys Thr Leu Glu Ile Arg Lys Pro Ser Pro Tyr Asp
1100 1105 1110
Gly Gly Thr Tyr Cys Cys Lys Ala Val Asn Asp Leu Gly Thr Val
1115 1120 1125
Glu Ile Glu Cys Lys Leu Glu Val Lys Val Ile Ala Gln
1130 1135 1140
<210> 83
<211> 1123
<212> PRT
<213> Homo sapiens
<400> 83
Met Pro Glu Pro Thr Lys Lys Glu Glu Asn Glu Val Pro Ala Pro Ala
1 5 10 15
Pro Pro Pro Glu Glu Pro Ser Lys Glu Lys Glu Ala Gly Thr Thr Pro
20 25 30
Ala Lys Asp Trp Thr Leu Val Glu Thr Pro Pro Gly Glu Glu Gln Ala
35 40 45
Lys Gln Asn Ala Asn Ser Gln Leu Ser Ile Leu Phe Ile Glu Lys Pro
50 55 60
Gln Gly Gly Thr Val Lys Val Gly Glu Asp Ile Thr Phe Ile Ala Lys
65 70 75 80
Val Lys Ala Glu Asp Leu Leu Arg Lys Pro Thr Ile Lys Trp Phe Lys
85 90 95
Gly Lys Trp Met Asp Leu Ala Ser Lys Ala Gly Lys His Leu Gln Leu
100 105 110
Lys Glu Thr Phe Glu Arg His Ser Arg Val Tyr Thr Phe Glu Met Gln
115 120 125
Ile Ile Lys Ala Lys Asp Asn Phe Ala Gly Asn Tyr Arg Cys Glu Val
130 135 140
Thr Tyr Lys Asp Lys Phe Asp Ser Cys Ser Phe Asp Leu Glu Val His
145 150 155 160
Glu Ser Thr Gly Thr Thr Pro Asn Ile Asp Ile Arg Ser Ala Phe Lys
165 170 175
Arg Ser Gly Glu Gly Gln Glu Asp Ala Gly Glu Leu Asp Phe Ser Gly
180 185 190
Leu Leu Lys Arg Arg Glu Val Lys Gln Gln Glu Glu Glu Pro Gln Val
195 200 205
Asp Val Trp Glu Leu Leu Lys Asn Ala Lys Pro Ser Glu Tyr Glu Lys
210 215 220
Ile Ala Phe Gln Tyr Gly Ile Thr Asp Leu Arg Gly Met Leu Lys Arg
225 230 235 240
Leu Lys Arg Met Arg Arg Glu Glu Lys Lys Ser Ala Ala Phe Ala Lys
245 250 255
Ile Leu Asp Pro Ala Tyr Gln Val Asp Lys Gly Gly Arg Val Arg Phe
260 265 270
Val Val Glu Leu Ala Asp Pro Lys Leu Glu Val Lys Trp Tyr Lys Asn
275 280 285
Gly Gln Glu Ile Arg Pro Ser Thr Lys Tyr Ile Phe Glu His Lys Gly
290 295 300
Cys Gln Arg Ile Leu Phe Ile Asn Asn Cys Gln Met Thr Asp Asp Ser
305 310 315 320
Glu Tyr Tyr Val Thr Ala Gly Asp Glu Lys Cys Ser Thr Glu Leu Phe
325 330 335
Val Arg Glu Pro Pro Ile Met Val Thr Lys Gln Leu Glu Asp Thr Thr
340 345 350
Ala Tyr Cys Gly Glu Arg Val Glu Leu Glu Cys Glu Val Ser Glu Asp
355 360 365
Asp Ala Asn Val Lys Trp Phe Lys Asn Gly Glu Glu Ile Ile Pro Gly
370 375 380
Pro Lys Ser Arg Tyr Arg Ile Arg Val Glu Gly Lys Lys His Ile Leu
385 390 395 400
Ile Ile Glu Gly Ala Thr Lys Ala Asp Ala Ala Glu Tyr Ser Val Met
405 410 415
Thr Thr Gly Gly Gln Ser Ser Ala Lys Leu Ser Val Asp Leu Lys Pro
420 425 430
Leu Lys Ile Leu Thr Pro Leu Thr Asp Gln Thr Val Asn Leu Gly Lys
435 440 445
Glu Ile Cys Leu Lys Cys Glu Ile Ser Glu Asn Ile Pro Gly Lys Trp
450 455 460
Thr Lys Asn Gly Leu Pro Val Gln Glu Ser Asp Arg Leu Lys Val Val
465 470 475 480
His Lys Gly Arg Ile His Lys Leu Val Ile Ala Asn Ala Leu Thr Glu
485 490 495
Asp Glu Gly Asp Tyr Val Phe Ala Pro Asp Ala Tyr Asn Val Thr Leu
500 505 510
Pro Ala Lys Val His Val Ile Asp Pro Pro Lys Ile Ile Leu Asp Gly
515 520 525
Leu Asp Ala Asp Asn Thr Val Thr Val Ile Ala Gly Asn Lys Leu Arg
530 535 540
Leu Glu Ile Pro Ile Ser Gly Glu Pro Pro Pro Lys Ala Met Trp Ser
545 550 555 560
Arg Gly Asp Lys Ala Ile Met Glu Gly Ser Gly Arg Ile Arg Thr Glu
565 570 575
Ser Tyr Pro Asp Ser Ser Thr Leu Val Ile Asp Ile Ala Glu Arg Asp
580 585 590
Asp Ser Gly Val Tyr His Ile Asn Leu Lys Asn Glu Ala Gly Glu Ala
595 600 605
His Ala Ser Ile Lys Val Lys Val Val Asp Phe Pro Asp Pro Pro Val
610 615 620
Ala Pro Thr Val Thr Glu Val Gly Asp Asp Trp Cys Ile Met Asn Trp
625 630 635 640
Glu Pro Pro Ala Tyr Asp Gly Gly Ser Pro Ile Leu Gly Tyr Phe Ile
645 650 655
Glu Arg Lys Lys Lys Gln Ser Ser Arg Trp Met Arg Leu Asn Phe Asp
660 665 670
Leu Cys Lys Glu Thr Thr Phe Glu Pro Lys Lys Met Ile Glu Gly Val
675 680 685
Ala Tyr Glu Val Arg Ile Phe Ala Val Asn Ala Ile Gly Ile Ser Lys
690 695 700
Pro Ser Met Pro Ser Arg Pro Phe Val Pro Leu Ala Val Thr Ser Pro
705 710 715 720
Pro Thr Leu Leu Thr Val Asp Ser Val Thr Asp Thr Thr Val Thr Met
725 730 735
Arg Trp Arg Pro Pro Asp His Ile Gly Ala Ala Gly Leu Asp Gly Tyr
740 745 750
Val Leu Glu Tyr Cys Phe Glu Gly Thr Glu Asp Trp Ile Val Ala Asn
755 760 765
Lys Asp Leu Ile Asp Lys Thr Lys Phe Thr Ile Thr Gly Leu Pro Thr
770 775 780
Asp Ala Lys Ile Phe Val Arg Val Lys Ala Val Asn Ala Ala Gly Ala
785 790 795 800
Ser Glu Pro Lys Tyr Tyr Ser Gln Pro Ile Leu Val Lys Glu Ile Ile
805 810 815
Glu Pro Pro Lys Ile Arg Ile Pro Arg His Leu Lys Gln Thr Tyr Ile
820 825 830
Arg Arg Val Gly Glu Ala Val Asn Leu Val Ile Pro Phe Gln Gly Lys
835 840 845
Pro Arg Pro Glu Leu Thr Trp Lys Lys Asp Gly Ala Glu Ile Asp Lys
850 855 860
Asn Gln Ile Asn Ile Arg Asn Ser Glu Thr Asp Thr Ile Ile Phe Ile
865 870 875 880
Arg Lys Ala Glu Arg Ser His Ser Gly Lys Tyr Asp Leu Gln Val Lys
885 890 895
Val Asp Lys Phe Val Glu Thr Ala Ser Ile Asp Ile Gln Ile Ile Asp
900 905 910
Arg Pro Gly Pro Pro Gln Ile Val Lys Ile Glu Asp Val Trp Gly Glu
915 920 925
Asn Val Ala Leu Thr Trp Thr Pro Pro Lys Asp Asp Gly Asn Ala Ala
930 935 940
Ile Thr Gly Tyr Thr Ile Gln Lys Ala Asp Lys Lys Ser Met Glu Trp
945 950 955 960
Phe Thr Val Ile Glu His Tyr His Arg Thr Ser Ala Thr Ile Thr Glu
965 970 975
Leu Val Ile Gly Asn Glu Tyr Tyr Phe Arg Val Phe Ser Glu Asn Met
980 985 990
Cys Gly Leu Ser Glu Asp Ala Thr Met Thr Lys Glu Ser Ala Val Ile
995 1000 1005
Ala Arg Asp Gly Lys Ile Tyr Lys Asn Pro Val Tyr Glu Asp Phe
1010 1015 1020
Asp Phe Ser Glu Ala Pro Met Phe Thr Gln Pro Leu Val Asn Thr
1025 1030 1035
Tyr Ala Ile Ala Gly Tyr Asn Ala Thr Leu Asn Cys Ser Val Arg
1040 1045 1050
Gly Asn Pro Lys Pro Lys Ile Thr Trp Met Lys Asn Lys Val Ala
1055 1060 1065
Ile Val Asp Asp Pro Arg Tyr Arg Met Phe Ser Asn Gln Gly Val
1070 1075 1080
Cys Thr Leu Glu Ile Arg Lys Pro Ser Pro Tyr Asp Gly Gly Thr
1085 1090 1095
Tyr Cys Cys Lys Ala Val Asn Asp Leu Gly Thr Val Glu Ile Glu
1100 1105 1110
Cys Lys Leu Glu Val Lys Val Ile Ala Gln
1115 1120
<210> 84
<211> 17
<212> DNA
<213> Artificial Sequence
<220>
<223> MYBPC1_forward primer
<400> 84
tcccagctgt ccatctt 17
<210> 85
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> MYCBPC1
<400> 85
cagccttgac tttggctatg 20
<210> 86
<211> 26
<212> DNA
<213> Artificial Sequence
<220>
<223> MYCBPC1_reverse primer
<400> 86
caaggaggaa cagtgaaagt tggtga 26
<210> 87
<211> 563
<212> DNA
<213> Homo sapiens
<400> 87
gccacttctc ttcccttcat tcttcgccag gctctctgct gactcaagtt cttcagttca 60
cgatcttcta gttgcagcga tgagtgcacg agtgagatca agatccagag gaagaggaga 120
tggtcaggag gctcccgatg tggttgcatt cgtggctccc ggtgaatctc agcaagagga 180
accaccaact gacaatcagg atattgaacc tggacaagag agagaaggaa cacctccgat 240
cgaagaacgt aaagtagaag gtgattgcca ggaaatggat ctggaaaaga ctcggagtga 300
gcgtggagat ggctctgatg taaaagagaa gactccacct aatcctaagc atgctaagac 360
taaagaagca ggagatgggc agccataagt taaaaagaag acaagctgaa gctacacaca 420
tggctgatgt cacattgaaa atgtgactga aaatttgaaa attctctcaa taaagtttga 480
gttttctctg aagaagtcat gcgtgtcttt tgtaaaattt attcctagga aattgacact 540
attgtaaatg gtatctttaa aaa 563
<210> 88
<211> 102
<212> PRT
<213> Homo sapiens
<400> 88
Met Ser Ala Arg Val Arg Ser Arg Ser Arg Gly Arg Gly Asp Gly Gln
1 5 10 15
Glu Ala Pro Asp Val Val Ala Phe Val Ala Pro Gly Glu Ser Gln Gln
20 25 30
Glu Glu Pro Pro Thr Asp Asn Gln Asp Ile Glu Pro Gly Gln Glu Arg
35 40 45
Glu Gly Thr Pro Pro Ile Glu Glu Arg Lys Val Glu Gly Asp Cys Gln
50 55 60
Glu Met Asp Leu Glu Lys Thr Arg Ser Glu Arg Gly Asp Gly Ser Asp
65 70 75 80
Val Lys Glu Lys Thr Pro Pro Asn Pro Lys His Ala Lys Thr Lys Glu
85 90 95
Ala Gly Asp Gly Gln Pro
100
<210> 89
<211> 17
<212> DNA
<213> Artificial Sequence
<220>
<223> PAGE4_forward primer
<400> 89
gaaggaacac ctccgat 17
<210> 90
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> PAG1_reverse primer
<400> 90
catctccacg ctcactccga 20
<210> 91
<211> 25
<212> DNA
<213> Artificial Sequence
<220>
<223> PAGE1 probe
<400> 91
aggtgattgc caggaaatgg atctg 25
<210> 92
<211> 2446
<212> DNA
<213> Homo sapiens
<400> 92
tccataaagg ggttgcgggg gccgcgctct cttctgggag ggcagcggcc accggcgagg 60
aacacggcgc gatgcaggtt cagtgccagc agagcccagt gctggcaggc agcgccactt 120
tggtcgccct tggggcactg gccttgtacg tcgcgaagcc ctccggctac gggaagcaca 180
cggagagcct gaagccggcg gctacccgcc tgccagcccg cgccgcctgg ttcctgcagg 240
agctgccttc cttcgcggtg cccgcgggga tcctcgcccg gcagcccctc tccctcttcg 300
ggccacctgg gacggtactt ctgggcctct tctgcctaca ttacttccac aggacatttg 360
tgtactcact gctcaatcga gggaggcctt atccagctat actcattctc agaggcactg 420
ccttctgcac tggaaatgga gtccttcaag gctactatct gatttactgt gctgaatacc 480
ctgatgggtg gtacacagac atacggttta gcttgggtgt cttcttattt attttgggaa 540
tgggaataaa cattcatagt gactatatat tgcgccagct caggaagcct ggagaaatca 600
gctacaggat tccacaaggt ggcttgttta cgtatgtttc tggagccaat ttcctcggtg 660
agatcattga atggatcggc tatgccctgg ccacttggtc cctcccagca cttgcatttg 720
catttttctc actttgtttc cttgggctgc gagcttttca ccaccatagg ttctacctca 780
agatgtttga ggactacccc aaatctcgga aagcccttat tccattcatc ttttaaagga 840
accaaattaa aaaggagcag agctcccaca atgctgatga aaactgtcaa gctgctgaaa 900
ctgtaatttt catgatataa tagtcccgta tatatgtaat agtaggtctc ctggcgttct 960
gccagctggc ctggggattc tgagtggtgt ctgcttagag tttactccta cccttccagg 1020
gacccctatc ctgatcccca actgaagctt caaaaagcca cttttccaaa tggcgacagt 1080
tgcttcttag ctattgctct gagaaagtac aaacttctcc tatgtctttc accgggcaat 1140
ccaagtacat gtggcttcat acccactccc tgtcaatgca ggacaactct gtaatcaaga 1200
attttttgac ttgaaggcag tacttataga ccttattaaa ggtatgcatt ttatacatgt 1260
aacagagtag cagaaattta aactctgaag ccacaaagac ccagagcaaa cccactccca 1320
aatgaaaacc ccagtcatgg cttccttttt cttggttaat taggaaagat gagaaattat 1380
taggtagacc ttgaatacag gagccctctc ctcatagtgc tgaaaagata ctgatgcatt 1440
gacctcattt caaatttgtg cagtgtctta gttgatgagt gcctctgttt tccagaagat 1500
ttcacaatcc ccggaaaact ggtatggcta ttcttgaagg ccaggtttta ataaccacaa 1560
acaaaaaggc atgaacctgg gtggcttatg agagagtaga gaacaacatg accctggatg 1620
gctactaaga ggatagagaa cagttttaca atagacattg caaactctca tgtttttgga 1680
aactagtggc aatatccaaa taatgagtag tgtaaaacaa agagaattaa tgatgaggtt 1740
acatgctgct tgcctccacc agatgtccac aacaatatga agtacagcag aagccccaag 1800
caactttcct ttcctggagc ttcttccttg tagttctcag gacctgttca agaaggtgtc 1860
tcctaggggc agcctgaatg cctccctcaa aggacctgca ggcagagact gaaaattgca 1920
gacagagggg cacgtctggg cagaaaacct gttttgtttg gctcagacat atagtttttt 1980
ttttttttac aaagtttcaa aaacttaaaa atcaggagat tccttcataa aactctagca 2040
ttctagtttc atttaaaaag ttggaggatc tgaacataca gagcccacat ttccacacca 2100
gaactggaac tacgtagcta gtaagcattt gagtttgcaa actcttgtga aggggtcacc 2160
ccagcatgag tgctgagata tggactctct aaggaagggg ccgaacgctt gtaattggaa 2220
tacatggaaa tatttgtctt ctcaggccta tgtttgcgga atgcattgtc aatatttagc 2280
aaactgtttt gacaaatgag caccagtggt actaagcaca gaaactcact atataagtca 2340
cataggaaac ttgaaaggtc tgaggatgat gtagattact gaaaaatgca aattgcaatc 2400
atataaataa gtgtttttgt tgttcattaa atacctttaa atcatg 2446
<210> 93
<211> 254
<212> PRT
<213> Homo sapiens
<400> 93
Met Gln Val Gln Cys Gln Gln Ser Pro Val Leu Ala Gly Ser Ala Thr
1 5 10 15
Leu Val Ala Leu Gly Ala Leu Ala Leu Tyr Val Ala Lys Pro Ser Gly
20 25 30
Tyr Gly Lys His Thr Glu Ser Leu Lys Pro Ala Ala Thr Arg Leu Pro
35 40 45
Ala Arg Ala Ala Trp Phe Leu Gln Glu Leu Pro Ser Phe Ala Val Pro
50 55 60
Ala Gly Ile Leu Ala Arg Gln Pro Leu Ser Leu Phe Gly Pro Pro Gly
65 70 75 80
Thr Val Leu Leu Gly Leu Phe Cys Leu His Tyr Phe His Arg Thr Phe
85 90 95
Val Tyr Ser Leu Leu Asn Arg Gly Arg Pro Tyr Pro Ala Ile Leu Ile
100 105 110
Leu Arg Gly Thr Ala Phe Cys Thr Gly Asn Gly Val Leu Gln Gly Tyr
115 120 125
Tyr Leu Ile Tyr Cys Ala Glu Tyr Pro Asp Gly Trp Tyr Thr Asp Ile
130 135 140
Arg Phe Ser Leu Gly Val Phe Leu Phe Ile Leu Gly Met Gly Ile Asn
145 150 155 160
Ile His Ser Asp Tyr Ile Leu Arg Gln Leu Arg Lys Pro Gly Glu Ile
165 170 175
Ser Tyr Arg Ile Pro Gln Gly Gly Leu Phe Thr Tyr Val Ser Gly Ala
180 185 190
Asn Phe Leu Gly Glu Ile Ile Glu Trp Ile Gly Tyr Ala Leu Ala Thr
195 200 205
Trp Ser Leu Pro Ala Leu Ala Phe Ala Phe Phe Ser Leu Cys Phe Leu
210 215 220
Gly Leu Arg Ala Phe His His His Arg Phe Tyr Leu Lys Met Phe Glu
225 230 235 240
Asp Tyr Pro Lys Ser Arg Lys Ala Leu Ile Pro Phe Ile Phe
245 250
<210> 94
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> SRD5A2_forward primer
<400> 94
ggcctcttct gcctacatta c 21
<210> 95
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> SRD5A2_reverse primer
<400> 95
cagtgcctct gagaatgagt atag 24
<210> 96
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> SRD5A2
<400> 96
ctcactgctc aatcgaggga gg 22
<210> 97
<211> 5927
<212> DNA
<213> Homo sapiens
<400> 97
tcgtcggagc agacgggagt ttctcctcgg ggtcggagca ggaggcacgc ggagtgtgag 60
gccacgcatg agcggacgct aaccccctcc ccagccacaa agagtctaca tgtctagggt 120
ctagacatgt tcagctttgt ggacctccgg ctcctgctcc tcttagcggc caccgccctc 180
ctgacgcacg gccaagagga aggccaagtc gagggccaag acgaagacat cccaccaatc 240
acctgcgtac agaacggcct caggtaccat gaccgagacg tgtggaaacc cgagccctgc 300
cggatctgcg tctgcgacaa cggcaaggtg ttgtgcgatg acgtgatctg tgacgagacc 360
aagaactgcc ccggcgccga agtccccgag ggcgagtgct gtcccgtctg ccccgacggc 420
tcagagtcac ccaccgacca agaaaccacc ggcgtcgagg gacccaaggg agacactggc 480
ccccgaggcc caaggggacc cgcaggcccc cctggccgag atggcatccc tggacagcct 540
ggacttcccg gaccccccgg accccccgga cctcccggac cccctggcct cggaggaaac 600
tttgctcccc agctgtctta tggctatgat gagaaatcaa ccggaggaat ttccgtgcct 660
ggccccatgg gtccctctgg tcctcgtggt ctccctggcc cccctggtgc acctggtccc 720
caaggcttcc aaggtccccc tggtgagcct ggcgagcctg gagcttcagg tcccatgggt 780
ccccgaggtc ccccaggtcc ccctggaaag aatggagatg atggggaagc tggaaaacct 840
ggtcgtcctg gtgagcgtgg gcctcctggg cctcagggtg ctcgaggatt gcccggaaca 900
gctggcctcc ctggaatgaa gggacacaga ggtttcagtg gtttggatgg tgccaaggga 960
gatgctggtc ctgctggtcc taagggtgag cctggcagcc ctggtgaaaa tggagctcct 1020
ggtcagatgg gcccccgtgg cctgcctggt gagagaggtc gccctggagc ccctggccct 1080
gctggtgctc gtggaaatga tggtgctact ggtgctgccg ggccccctgg tcccaccggc 1140
cccgctggtc ctcctggctt ccctggtgct gttggtgcta agggtgaagc tggtccccaa 1200
gggccccgag gctctgaagg tccccagggt gtgcgtggtg agcctggccc ccctggccct 1260
gctggtgctg ctggccctgc tggaaaccct ggtgctgatg gacagcctgg tgctaaaggt 1320
gccaatggtg ctcctggtat tgctggtgct cctggcttcc ctggtgcccg aggcccctct 1380
ggaccccagg gccccggcgg ccctcctggt cccaagggta acagcggtga acctggtgct 1440
cctggcagca aaggagacac tggtgctaag ggagagcctg gccctgttgg tgttcaagga 1500
ccccctggcc ctgctggaga ggaaggaaag cgaggagctc gaggtgaacc cggacccact 1560
ggcctgcccg gaccccctgg cgagcgtggt ggacctggta gccgtggttt ccctggcgca 1620
gatggtgttg ctggtcccaa gggtcccgct ggtgaacgtg gttctcctgg ccctgctggc 1680
cccaaaggat ctcctggtga agctggtcgt cccggtgaag ctggtctgcc tggtgccaag 1740
ggtctgactg gaagccctgg cagccctggt cctgatggca aaactggccc ccctggtccc 1800
gccggtcaag atggtcgccc cggaccccca ggcccacctg gtgcccgtgg tcaggctggt 1860
gtgatgggat tccctggacc taaaggtgct gctggagagc ccggcaaggc tggagagcga 1920
ggtgttcccg gaccccctgg cgctgtcggt cctgctggca aagatggaga ggctggagct 1980
cagggacccc ctggccctgc tggtcccgct ggcgagagag gtgaacaagg ccctgctggc 2040
tcccccggat tccagggtct ccctggtcct gctggtcctc caggtgaagc aggcaaacct 2100
ggtgaacagg gtgttcctgg agaccttggc gcccctggcc cctctggagc aagaggcgag 2160
agaggtttcc ctggcgagcg tggtgtgcaa ggtccccctg gtcctgctgg tccccgaggg 2220
gccaacggtg ctcccggcaa cgatggtgct aagggtgatg ctggtgcccc tggagctccc 2280
ggtagccagg gcgcccctgg ccttcaggga atgcctggtg aacgtggtgc agctggtctt 2340
ccagggccta agggtgacag aggtgatgct ggtcccaaag gtgctgatgg ctctcctggc 2400
aaagatggcg tccgtggtct gactggcccc attggtcctc ctggccctgc tggtgcccct 2460
ggtgacaagg gtgaaagtgg tcccagcggc cctgctggtc ccactggagc tcgtggtgcc 2520
cccggagacc gtggtgagcc tggtcccccc ggccctgctg gctttgctgg cccccctggt 2580
gctgacggcc aacctggtgc taaaggcgaa cctggtgatg ctggtgctaa aggcgatgct 2640
ggtccccctg gccctgccgg acccgctgga ccccctggcc ccattggtaa tgttggtgct 2700
cctggagcca aaggtgctcg cggcagcgct ggtccccctg gtgctactgg tttccctggt 2760
gctgctggcc gagtcggtcc tcctggcccc tctggaaatg ctggaccccc tggccctcct 2820
ggtcctgctg gcaaagaagg cggcaaaggt ccccgtggtg agactggccc tgctggacgt 2880
cctggtgaag ttggtccccc tggtccccct ggccctgctg gcgagaaagg atcccctggt 2940
gctgatggtc ctgctggtgc tcctggtact cccgggcctc aaggtattgc tggacagcgt 3000
ggtgtggtcg gcctgcctgg tcagagagga gagagaggct tccctggtct tcctggcccc 3060
tctggtgaac ctggcaaaca aggtccctct ggagcaagtg gtgaacgtgg tccccctggt 3120
cccatgggcc cccctggatt ggctggaccc cctggtgaat ctggacgtga gggggctcct 3180
ggtgccgaag gttcccctgg acgagacggt tctcctggcg ccaagggtga ccgtggtgag 3240
accggccccg ctggaccccc tggtgctcct ggtgctcctg gtgcccctgg ccccgttggc 3300
cctgctggca agagtggtga tcgtggtgag actggtcctg ctggtcccgc cggtcctgtc 3360
ggccctgttg gcgcccgtgg ccccgccgga ccccaaggcc cccgtggtga caagggtgag 3420
acaggcgaac agggcgacag aggcataaag ggtcaccgtg gcttctctgg cctccagggt 3480
ccccctggcc ctcctggctc tcctggtgaa caaggtccct ctggagcctc tggtcctgct 3540
ggtccccgag gtccccctgg ctctgctggt gctcctggca aagatggact caacggtctc 3600
cctggcccca ttgggccccc tggtcctcgc ggtcgcactg gtgatgctgg tcctgttggt 3660
ccccccggcc ctcctggacc tcctggtccc cctggtcctc ccagcgctgg tttcgacttc 3720
agcttcctgc cccagccacc tcaagagaag gctcacgatg gtggccgcta ctaccgggct 3780
gatgatgcca atgtggttcg tgaccgtgac ctcgaggtgg acaccaccct caagagcctg 3840
agccagcaga tcgagaacat ccggagccca gagggcagcc gcaagaaccc cgcccgcacc 3900
tgccgtgacc tcaagatgtg ccactctgac tggaagagtg gagagtactg gattgacccc 3960
aaccaaggct gcaacctgga tgccatcaaa gtcttctgca acatggagac tggtgagacc 4020
tgcgtgtacc ccactcagcc cagtgtggcc cagaagaact ggtacatcag caagaacccc 4080
aaggacaaga ggcatgtctg gttcggcgag agcatgaccg atggattcca gttcgagtat 4140
ggcggccagg gctccgaccc tgccgatgtg gccatccagc tgaccttcct gcgcctgatg 4200
tccaccgagg cctcccagaa catcacctac cactgcaaga acagcgtggc ctacatggac 4260
cagcagactg gcaacctcaa gaaggccctg ctcctccagg gctccaacga gatcgagatc 4320
cgcgccgagg gcaacagccg cttcacctac agcgtcactg tcgatggctg cacgagtcac 4380
accggagcct ggggcaagac agtgattgaa tacaaaacca ccaagacctc ccgcctgccc 4440
atcatcgatg tggccccctt ggacgttggt gccccagacc aggaattcgg cttcgacgtt 4500
ggccctgtct gcttcctgta aactccctcc atcccaacct ggctccctcc cacccaacca 4560
actttccccc caacccggaa acagacaagc aacccaaact gaaccccctc aaaagccaaa 4620
aaatgggaga caatttcaca tggactttgg aaaatatttt tttcctttgc attcatctct 4680
caaacttagt ttttatcttt gaccaaccga acatgaccaa aaaccaaaag tgcattcaac 4740
cttaccaaaa aaaaaaaaaa aaaaagaata aataaataac tttttaaaaa aggaagcttg 4800
gtccacttgc ttgaagaccc atgcgggggt aagtcccttt ctgcccgttg ggcttatgaa 4860
accccaatgc tgccctttct gctcctttct ccacaccccc cttggggcct cccctccact 4920
ccttcccaaa tctgtctccc cagaagacac aggaaacaat gtattgtctg cccagcaatc 4980
aaaggcaatg ctcaaacacc caagtggccc ccaccctcag cccgctcctg cccgcccagc 5040
acccccaggc cctgggggac ctggggttct cagactgcca aagaagcctt gccatctggc 5100
gctcccatgg ctcttgcaac atctcccctt cgtttttgag ggggtcatgc cgggggagcc 5160
accagcccct cactgggttc ggaggagagt caggaagggc cacgacaaag cagaaacatc 5220
ggatttgggg aacgcgtgtc aatcccttgt gccgcagggc tgggcgggag agactgttct 5280
gttccttgtg taactgtgtt gctgaaagac tacctcgttc ttgtcttgat gtgtcaccgg 5340
ggcaactgcc tgggggcggg gatgggggca gggtggaagc ggctccccat tttataccaa 5400
aggtgctaca tctatgtgat gggtggggtg gggagggaat cactggtgct atagaaattg 5460
agatgccccc ccaggccagc aaatgttcct ttttgttcaa agtctatttt tattccttga 5520
tatttttctt tttttttttt tttttttgtg gatggggact tgtgaatttt tctaaaggtg 5580
ctatttaaca tgggaggaga gcgtgtgcgg ctccagccca gcccgctgct cactttccac 5640
cctctctcca cctgcctctg gcttctcagg cctctgctct ccgacctctc tcctctgaaa 5700
ccctcctcca cagctgcagc ccatcctccc ggctccctcc tagtctgtcc tgcgtcctct 5760
gtccccgggt ttcagagaca acttcccaaa gcacaaagca gtttttcccc ctaggggtgg 5820
gaggaagcaa aagactctgt acctattttg tatgtgtata ataatttgag atgtttttaa 5880
ttattttgat tgctggaata aagcatgtgg aaatgaccca aacataa 5927
<210> 98
<211> 1464
<212> PRT
<213> Homo sapiens
<400> 98
Met Phe Ser Phe Val Asp Leu Arg Leu Leu Leu Leu Leu Ala Ala Thr
1 5 10 15
Ala Leu Leu Thr His Gly Gln Glu Glu Gly Gln Val Glu Gly Gln Asp
20 25 30
Glu Asp Ile Pro Pro Ile Thr Cys Val Gln Asn Gly Leu Arg Tyr His
35 40 45
Asp Arg Asp Val Trp Lys Pro Glu Pro Cys Arg Ile Cys Val Cys Asp
50 55 60
Asn Gly Lys Val Leu Cys Asp Asp Val Ile Cys Asp Glu Thr Lys Asn
65 70 75 80
Cys Pro Gly Ala Glu Val Pro Glu Gly Glu Cys Cys Pro Val Cys Pro
85 90 95
Asp Gly Ser Glu Ser Pro Thr Asp Gln Glu Thr Thr Gly Val Glu Gly
100 105 110
Pro Lys Gly Asp Thr Gly Pro Arg Gly Pro Arg Gly Pro Ala Gly Pro
115 120 125
Pro Gly Arg Asp Gly Ile Pro Gly Gln Pro Gly Leu Pro Gly Pro Pro
130 135 140
Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Leu Gly Gly Asn Phe Ala
145 150 155 160
Pro Gln Leu Ser Tyr Gly Tyr Asp Glu Lys Ser Thr Gly Gly Ile Ser
165 170 175
Val Pro Gly Pro Met Gly Pro Ser Gly Pro Arg Gly Leu Pro Gly Pro
180 185 190
Pro Gly Ala Pro Gly Pro Gln Gly Phe Gln Gly Pro Pro Gly Glu Pro
195 200 205
Gly Glu Pro Gly Ala Ser Gly Pro Met Gly Pro Arg Gly Pro Pro Gly
210 215 220
Pro Pro Gly Lys Asn Gly Asp Asp Gly Glu Ala Gly Lys Pro Gly Arg
225 230 235 240
Pro Gly Glu Arg Gly Pro Pro Gly Pro Gln Gly Ala Arg Gly Leu Pro
245 250 255
Gly Thr Ala Gly Leu Pro Gly Met Lys Gly His Arg Gly Phe Ser Gly
260 265 270
Leu Asp Gly Ala Lys Gly Asp Ala Gly Pro Ala Gly Pro Lys Gly Glu
275 280 285
Pro Gly Ser Pro Gly Glu Asn Gly Ala Pro Gly Gln Met Gly Pro Arg
290 295 300
Gly Leu Pro Gly Glu Arg Gly Arg Pro Gly Ala Pro Gly Pro Ala Gly
305 310 315 320
Ala Arg Gly Asn Asp Gly Ala Thr Gly Ala Ala Gly Pro Pro Gly Pro
325 330 335
Thr Gly Pro Ala Gly Pro Pro Gly Phe Pro Gly Ala Val Gly Ala Lys
340 345 350
Gly Glu Ala Gly Pro Gln Gly Pro Arg Gly Ser Glu Gly Pro Gln Gly
355 360 365
Val Arg Gly Glu Pro Gly Pro Pro Gly Pro Ala Gly Ala Ala Gly Pro
370 375 380
Ala Gly Asn Pro Gly Ala Asp Gly Gln Pro Gly Ala Lys Gly Ala Asn
385 390 395 400
Gly Ala Pro Gly Ile Ala Gly Ala Pro Gly Phe Pro Gly Ala Arg Gly
405 410 415
Pro Ser Gly Pro Gln Gly Pro Gly Gly Pro Pro Gly Pro Lys Gly Asn
420 425 430
Ser Gly Glu Pro Gly Ala Pro Gly Ser Lys Gly Asp Thr Gly Ala Lys
435 440 445
Gly Glu Pro Gly Pro Val Gly Val Gln Gly Pro Pro Gly Pro Ala Gly
450 455 460
Glu Glu Gly Lys Arg Gly Ala Arg Gly Glu Pro Gly Pro Thr Gly Leu
465 470 475 480
Pro Gly Pro Pro Gly Glu Arg Gly Gly Pro Gly Ser Arg Gly Phe Pro
485 490 495
Gly Ala Asp Gly Val Ala Gly Pro Lys Gly Pro Ala Gly Glu Arg Gly
500 505 510
Ser Pro Gly Pro Ala Gly Pro Lys Gly Ser Pro Gly Glu Ala Gly Arg
515 520 525
Pro Gly Glu Ala Gly Leu Pro Gly Ala Lys Gly Leu Thr Gly Ser Pro
530 535 540
Gly Ser Pro Gly Pro Asp Gly Lys Thr Gly Pro Pro Gly Pro Ala Gly
545 550 555 560
Gln Asp Gly Arg Pro Gly Pro Pro Gly Pro Pro Gly Ala Arg Gly Gln
565 570 575
Ala Gly Val Met Gly Phe Pro Gly Pro Lys Gly Ala Ala Gly Glu Pro
580 585 590
Gly Lys Ala Gly Glu Arg Gly Val Pro Gly Pro Pro Gly Ala Val Gly
595 600 605
Pro Ala Gly Lys Asp Gly Glu Ala Gly Ala Gln Gly Pro Pro Gly Pro
610 615 620
Ala Gly Pro Ala Gly Glu Arg Gly Glu Gln Gly Pro Ala Gly Ser Pro
625 630 635 640
Gly Phe Gln Gly Leu Pro Gly Pro Ala Gly Pro Pro Gly Glu Ala Gly
645 650 655
Lys Pro Gly Glu Gln Gly Val Pro Gly Asp Leu Gly Ala Pro Gly Pro
660 665 670
Ser Gly Ala Arg Gly Glu Arg Gly Phe Pro Gly Glu Arg Gly Val Gln
675 680 685
Gly Pro Pro Gly Pro Ala Gly Pro Arg Gly Ala Asn Gly Ala Pro Gly
690 695 700
Asn Asp Gly Ala Lys Gly Asp Ala Gly Ala Pro Gly Ala Pro Gly Ser
705 710 715 720
Gln Gly Ala Pro Gly Leu Gln Gly Met Pro Gly Glu Arg Gly Ala Ala
725 730 735
Gly Leu Pro Gly Pro Lys Gly Asp Arg Gly Asp Ala Gly Pro Lys Gly
740 745 750
Ala Asp Gly Ser Pro Gly Lys Asp Gly Val Arg Gly Leu Thr Gly Pro
755 760 765
Ile Gly Pro Pro Gly Pro Ala Gly Ala Pro Gly Asp Lys Gly Glu Ser
770 775 780
Gly Pro Ser Gly Pro Ala Gly Pro Thr Gly Ala Arg Gly Ala Pro Gly
785 790 795 800
Asp Arg Gly Glu Pro Gly Pro Pro Gly Pro Ala Gly Phe Ala Gly Pro
805 810 815
Pro Gly Ala Asp Gly Gln Pro Gly Ala Lys Gly Glu Pro Gly Asp Ala
820 825 830
Gly Ala Lys Gly Asp Ala Gly Pro Pro Gly Pro Ala Gly Pro Ala Gly
835 840 845
Pro Pro Gly Pro Ile Gly Asn Val Gly Ala Pro Gly Ala Lys Gly Ala
850 855 860
Arg Gly Ser Ala Gly Pro Pro Gly Ala Thr Gly Phe Pro Gly Ala Ala
865 870 875 880
Gly Arg Val Gly Pro Pro Gly Pro Ser Gly Asn Ala Gly Pro Pro Gly
885 890 895
Pro Pro Gly Pro Ala Gly Lys Glu Gly Gly Lys Gly Pro Arg Gly Glu
900 905 910
Thr Gly Pro Ala Gly Arg Pro Gly Glu Val Gly Pro Pro Gly Pro Pro
915 920 925
Gly Pro Ala Gly Glu Lys Gly Ser Pro Gly Ala Asp Gly Pro Ala Gly
930 935 940
Ala Pro Gly Thr Pro Gly Pro Gln Gly Ile Ala Gly Gln Arg Gly Val
945 950 955 960
Val Gly Leu Pro Gly Gln Arg Gly Glu Arg Gly Phe Pro Gly Leu Pro
965 970 975
Gly Pro Ser Gly Glu Pro Gly Lys Gln Gly Pro Ser Gly Ala Ser Gly
980 985 990
Glu Arg Gly Pro Pro Gly Pro Met Gly Pro Pro Gly Leu Ala Gly Pro
995 1000 1005
Pro Gly Glu Ser Gly Arg Glu Gly Ala Pro Gly Ala Glu Gly Ser
1010 1015 1020
Pro Gly Arg Asp Gly Ser Pro Gly Ala Lys Gly Asp Arg Gly Glu
1025 1030 1035
Thr Gly Pro Ala Gly Pro Pro Gly Ala Pro Gly Ala Pro Gly Ala
1040 1045 1050
Pro Gly Pro Val Gly Pro Ala Gly Lys Ser Gly Asp Arg Gly Glu
1055 1060 1065
Thr Gly Pro Ala Gly Pro Ala Gly Pro Val Gly Pro Val Gly Ala
1070 1075 1080
Arg Gly Pro Ala Gly Pro Gln Gly Pro Arg Gly Asp Lys Gly Glu
1085 1090 1095
Thr Gly Glu Gln Gly Asp Arg Gly Ile Lys Gly His Arg Gly Phe
1100 1105 1110
Ser Gly Leu Gln Gly Pro Pro Gly Pro Pro Gly Ser Pro Gly Glu
1115 1120 1125
Gln Gly Pro Ser Gly Ala Ser Gly Pro Ala Gly Pro Arg Gly Pro
1130 1135 1140
Pro Gly Ser Ala Gly Ala Pro Gly Lys Asp Gly Leu Asn Gly Leu
1145 1150 1155
Pro Gly Pro Ile Gly Pro Pro Gly Pro Arg Gly Arg Thr Gly Asp
1160 1165 1170
Ala Gly Pro Val Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro
1175 1180 1185
Pro Gly Pro Pro Ser Ala Gly Phe Asp Phe Ser Phe Leu Pro Gln
1190 1195 1200
Pro Pro Gln Glu Lys Ala His Asp Gly Gly Arg Tyr Tyr Arg Ala
1205 1210 1215
Asp Asp Ala Asn Val Val Arg Asp Arg Asp Leu Glu Val Asp Thr
1220 1225 1230
Thr Leu Lys Ser Leu Ser Gln Gln Ile Glu Asn Ile Arg Ser Pro
1235 1240 1245
Glu Gly Ser Arg Lys Asn Pro Ala Arg Thr Cys Arg Asp Leu Lys
1250 1255 1260
Met Cys His Ser Asp Trp Lys Ser Gly Glu Tyr Trp Ile Asp Pro
1265 1270 1275
Asn Gln Gly Cys Asn Leu Asp Ala Ile Lys Val Phe Cys Asn Met
1280 1285 1290
Glu Thr Gly Glu Thr Cys Val Tyr Pro Thr Gln Pro Ser Val Ala
1295 1300 1305
Gln Lys Asn Trp Tyr Ile Ser Lys Asn Pro Lys Asp Lys Arg His
1310 1315 1320
Val Trp Phe Gly Glu Ser Met Thr Asp Gly Phe Gln Phe Glu Tyr
1325 1330 1335
Gly Gly Gln Gly Ser Asp Pro Ala Asp Val Ala Ile Gln Leu Thr
1340 1345 1350
Phe Leu Arg Leu Met Ser Thr Glu Ala Ser Gln Asn Ile Thr Tyr
1355 1360 1365
His Cys Lys Asn Ser Val Ala Tyr Met Asp Gln Gln Thr Gly Asn
1370 1375 1380
Leu Lys Lys Ala Leu Leu Leu Gln Gly Ser Asn Glu Ile Glu Ile
1385 1390 1395
Arg Ala Glu Gly Asn Ser Arg Phe Thr Tyr Ser Val Thr Val Asp
1400 1405 1410
Gly Cys Thr Ser His Thr Gly Ala Trp Gly Lys Thr Val Ile Glu
1415 1420 1425
Tyr Lys Thr Thr Lys Thr Ser Arg Leu Pro Ile Ile Asp Val Ala
1430 1435 1440
Pro Leu Asp Val Gly Ala Pro Asp Gln Glu Phe Gly Phe Asp Val
1445 1450 1455
Gly Pro Val Cys Phe Leu
1460
<210> 99
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> COL1A1_forward primer
<400> 99
gaagacatcc caccaatcac 20
<210> 100
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> COL1A1_reverse primer
<400> 100
cgggtttcca cacgtctc 18
<210> 101
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> COL1A1 probe
<400> 101
ctgcgtacag aacggcctca ggta 24
<210> 102
<211> 5490
<212> DNA
<213> Homo sapiens
<400> 102
ggctgagttt tatgacgggc ccggtgctga agggcaggga acaacttgat ggtgctactt 60
tgaactgctt ttcttttctc ctttttgcac aaagagtctc atgtctgata tttagacatg 120
atgagctttg tgcaaaaggg gagctggcta cttctcgctc tgcttcatcc cactattatt 180
ttggcacaac aggaagctgt tgaaggagga tgttcccatc ttggtcagtc ctatgcggat 240
agagatgtct ggaagccaga accatgccaa atatgtgtct gtgactcagg atccgttctc 300
tgcgatgaca taatatgtga cgatcaagaa ttagactgcc ccaacccaga aattccattt 360
ggagaatgtt gtgcagtttg cccacagcct ccaactgctc ctactcgccc tcctaatggt 420
caaggacctc aaggccccaa gggagatcca ggccctcctg gtattcctgg gagaaatggt 480
gaccctggta ttccaggaca accagggtcc cctggttctc ctggcccccc tggaatctgt 540
gaatcatgcc ctactggtcc tcagaactat tctccccagt atgattcata tgatgtcaag 600
tctggagtag cagtaggagg actcgcaggc tatcctggac cagctggccc cccaggccct 660
cccggtcccc ctggtacatc tggtcatcct ggttcccctg gatctccagg ataccaagga 720
ccccctggtg aacctgggca agctggtcct tcaggccctc caggacctcc tggtgctata 780
ggtccatctg gtcctgctgg aaaagatgga gaatcaggta gacccggacg acctggagag 840
cgaggattgc ctggacctcc aggtatcaaa ggtccagctg ggatacctgg attccctggt 900
atgaaaggac acagaggctt cgatggacga aatggagaaa agggtgaaac aggtgctcct 960
ggattaaagg gtgaaaatgg tcttccaggc gaaaatggag ctcctggacc catgggtcca 1020
agaggggctc ctggtgagcg aggacggcca ggacttcctg gggctgcagg tgctcggggt 1080
aatgacggtg ctcgaggcag tgatggtcaa ccaggccctc ctggtcctcc tggaactgcc 1140
ggattccctg gatcccctgg tgctaagggt gaagttggac ctgcagggtc tcctggttca 1200
aatggtgccc ctggacaaag aggagaacct ggacctcagg gacacgctgg tgctcaaggt 1260
cctcctggcc ctcctgggat taatggtagt cctggtggta aaggcgaaat gggtcccgct 1320
ggcattcctg gagctcctgg actgatggga gcccggggtc ctccaggacc agccggtgct 1380
aatggtgctc ctggactgcg aggtggtgca ggtgagcctg gtaagaatgg tgccaaagga 1440
gagcccggac cacgtggtga acgcggtgag gctggtattc caggtgttcc aggagctaaa 1500
ggcgaagatg gcaaggatgg atcacctgga gaacctggtg caaatgggct tccaggagct 1560
gcaggagaaa ggggtgcccc tgggttccga ggacctgctg gaccaaatgg catcccagga 1620
gaaaagggtc ctgctggaga gcgtggtgct ccaggccctg cagggcccag aggagctgct 1680
ggagaacctg gcagagatgg cgtccctgga ggtccaggaa tgaggggcat gcccggaagt 1740
ccaggaggac caggaagtga tgggaaacca gggcctcccg gaagtcaagg agaaagtggt 1800
cgaccaggtc ctcctgggcc atctggtccc cgaggtcagc ctggtgtcat gggcttcccc 1860
ggtcctaaag gaaatgatgg tgctcctggt aagaatggag aacgaggtgg ccctggagga 1920
cctggccctc agggtcctcc tggaaagaat ggtgaaactg gacctcaggg acccccaggg 1980
cctactgggc ctggtggtga caaaggagac acaggacccc ctggtccaca aggattacaa 2040
ggcttgcctg gtacaggtgg tcctccagga gaaaatggaa aacctgggga accaggtcca 2100
aagggtgatg ccggtgcacc tggagctcca ggaggcaagg gtgatgctgg tgcccctggt 2160
gaacgtggac ctcctggatt ggcaggggcc ccaggactta gaggtggagc tggtccccct 2220
ggtcccgaag gaggaaaggg tgctgctggt cctcctgggc cacctggtgc tgctggtact 2280
cctggtctgc aaggaatgcc tggagaaaga ggaggtcttg gaagtcctgg tccaaagggt 2340
gacaagggtg aaccaggcgg tccaggtgct gatggtgtcc cagggaaaga tggcccaagg 2400
ggtcctactg gtcctattgg tcctcctggc ccagctggcc agcctggaga taagggtgaa 2460
ggtggtgccc ccggacttcc aggtatagct ggacctcgtg gtagccctgg tgagagaggt 2520
gaaactggcc ctccaggacc tgctggtttc cctggtgctc ctggacagaa tggtgaacct 2580
ggtggtaaag gagaaagagg ggctccgggt gagaaaggtg aaggaggccc tcctggagtt 2640
gcaggacccc ctggaggttc tggacctgct ggtcctcctg gtccccaagg tgtcaaaggt 2700
gaacgtggca gtcctggtgg acctggtgct gctggcttcc ctggtgctcg tggtcttcct 2760
ggtcctcctg gtagtaatgg taacccagga cccccaggtc ccagcggttc tccaggcaag 2820
gatgggcccc caggtcctgc gggtaacact ggtgctcctg gcagccctgg agtgtctgga 2880
ccaaaaggtg atgctggcca accaggagag aagggatcgc ctggtgccca gggcccacca 2940
ggagctccag gcccacttgg gattgctggg atcactggag cacggggtct tgcaggacca 3000
ccaggcatgc caggtcctag gggaagccct ggccctcagg gtgtcaaggg tgaaagtggg 3060
aaaccaggag ctaacggtct cagtggagaa cgtggtcccc ctggacccca gggtcttcct 3120
ggtctggctg gtacagctgg tgaacctgga agagatggaa accctggatc agatggtctt 3180
ccaggccgag atggatctcc tggtggcaag ggtgatcgtg gtgaaaatgg ctctcctggt 3240
gcccctggcg ctcctggtca tccaggccca cctggtcctg tcggtccagc tggaaagagt 3300
ggtgacagag gagaaagtgg ccctgctggc cctgctggtg ctcccggtcc tgctggttcc 3360
cgaggtgctc ctggtcctca aggcccacgt ggtgacaaag gtgaaacagg tgaacgtgga 3420
gctgctggca tcaaaggaca tcgaggattc cctggtaatc caggtgcccc aggttctcca 3480
ggccctgctg gtcagcaggg tgcaatcggc agtccaggac ctgcaggccc cagaggacct 3540
gttggaccca gtggacctcc tggcaaagat ggaaccagtg gacatccagg tcccattgga 3600
ccaccagggc ctcgaggtaa cagaggtgaa agaggatctg agggctcccc aggccaccca 3660
gggcaaccag gccctcctgg acctcctggt gcccctggtc cttgctgtgg tggtgttgga 3720
gccgctgcca ttgctgggat tggaggtgaa aaagctggcg gttttgcccc gtattatgga 3780
gatgaaccaa tggatttcaa aatcaacacc gatgagatta tgacttcact caagtctgtt 3840
aatggacaaa tagaaagcct cattagtcct gatggttctc gtaaaaaccc cgctagaaac 3900
tgcagagacc tgaaattctg ccatcctgaa ctcaagagtg gagaatactg ggttgaccct 3960
aaccaaggat gcaaattgga tgctatcaag gtattctgta atatggaaac tggggaaaca 4020
tgcataagtg ccaatccttt gaatgttcca cggaaacact ggtggacaga ttctagtgct 4080
gagaagaaac acgtttggtt tggagagtcc atggatggtg gttttcagtt tagctacggc 4140
aatcctgaac ttcctgaaga tgtccttgat gtgcagctgg cattccttcg acttctctcc 4200
agccgagctt cccagaacat cacatatcac tgcaaaaata gcattgcata catggatcag 4260
gccagtggaa atgtaaagaa ggccctgaag ctgatggggt caaatgaagg tgaattcaag 4320
gctgaaggaa atagcaaatt cacctacaca gttctggagg atggttgcac gaaacacact 4380
ggggaatgga gcaaaacagt ctttgaatat cgaacacgca aggctgtgag actacctatt 4440
gtagatattg caccctatga cattggtggt cctgatcaag aatttggtgt ggacgttggc 4500
cctgtttgct ttttataaac caaactctat ctgaaatccc aacaaaaaaa atttaactcc 4560
atatgtgttc ctcttgttct aatcttgtca accagtgcaa gtgaccgaca aaattccagt 4620
tatttatttc caaaatgttt ggaaacagta taatttgaca aagaaaaatg atacttctct 4680
ttttttgctg ttccaccaaa tacaattcaa atgctttttg ttttattttt ttaccaattc 4740
caatttcaaa atgtctcaat ggtgctataa taaataaact tcaacactct ttatgataac 4800
aacactgtgt tatattcttt gaatcctagc ccatctgcag agcaatgact gtgctcacca 4860
gtaaaagata acctttcttt ctgaaatagt caaatacgaa attagaaaag ccctccctat 4920
tttaactacc tcaactggtc agaaacacag attgtattct atgagtccca gaagatgaaa 4980
aaaattttat acgttgataa aacttataaa tttcattgat taatctcctg gaagattggt 5040
ttaaaaagaa aagtgtaatg caagaattta aagaaatatt tttaaagcca caattatttt 5100
aatattggat atcaactgct tgtaaaggtg ctcctctttt ttcttgtcat tgctggtcaa 5160
gattactaat atttgggaag gctttaaaga cgcatgttat ggtgctaatg tactttcact 5220
tttaaactct agatcagaat tgttgacttg cattcagaac ataaatgcac aaaatctgta 5280
catgtctccc atcagaaaga ttcattggca tgccacaggg gattctcctc cttcatcctg 5340
taaaggtcaa caataaaaac caaattatgg ggctgctttt gtcacactag catagagaat 5400
gtgttgaaat ttaactttgt aagcttgtat gtggttgttg atcttttttt tccttacaga 5460
cacccataat aaaatatcat attaaaattc 5490
<210> 103
<211> 1466
<212> PRT
<213> Homo sapiens
<400> 103
Met Met Ser Phe Val Gln Lys Gly Ser Trp Leu Leu Leu Ala Leu Leu
1 5 10 15
His Pro Thr Ile Ile Leu Ala Gln Gln Glu Ala Val Glu Gly Gly Cys
20 25 30
Ser His Leu Gly Gln Ser Tyr Ala Asp Arg Asp Val Trp Lys Pro Glu
35 40 45
Pro Cys Gln Ile Cys Val Cys Asp Ser Gly Ser Val Leu Cys Asp Asp
50 55 60
Ile Ile Cys Asp Asp Gln Glu Leu Asp Cys Pro Asn Pro Glu Ile Pro
65 70 75 80
Phe Gly Glu Cys Cys Ala Val Cys Pro Gln Pro Pro Thr Ala Pro Thr
85 90 95
Arg Pro Pro Asn Gly Gln Gly Pro Gln Gly Pro Lys Gly Asp Pro Gly
100 105 110
Pro Pro Gly Ile Pro Gly Arg Asn Gly Asp Pro Gly Ile Pro Gly Gln
115 120 125
Pro Gly Ser Pro Gly Ser Pro Gly Pro Pro Gly Ile Cys Glu Ser Cys
130 135 140
Pro Thr Gly Pro Gln Asn Tyr Ser Pro Gln Tyr Asp Ser Tyr Asp Val
145 150 155 160
Lys Ser Gly Val Ala Val Gly Gly Leu Ala Gly Tyr Pro Gly Pro Ala
165 170 175
Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Thr Ser Gly His Pro Gly
180 185 190
Ser Pro Gly Ser Pro Gly Tyr Gln Gly Pro Pro Gly Glu Pro Gly Gln
195 200 205
Ala Gly Pro Ser Gly Pro Pro Gly Pro Pro Gly Ala Ile Gly Pro Ser
210 215 220
Gly Pro Ala Gly Lys Asp Gly Glu Ser Gly Arg Pro Gly Arg Pro Gly
225 230 235 240
Glu Arg Gly Leu Pro Gly Pro Pro Gly Ile Lys Gly Pro Ala Gly Ile
245 250 255
Pro Gly Phe Pro Gly Met Lys Gly His Arg Gly Phe Asp Gly Arg Asn
260 265 270
Gly Glu Lys Gly Glu Thr Gly Ala Pro Gly Leu Lys Gly Glu Asn Gly
275 280 285
Leu Pro Gly Glu Asn Gly Ala Pro Gly Pro Met Gly Pro Arg Gly Ala
290 295 300
Pro Gly Glu Arg Gly Arg Pro Gly Leu Pro Gly Ala Ala Gly Ala Arg
305 310 315 320
Gly Asn Asp Gly Ala Arg Gly Ser Asp Gly Gln Pro Gly Pro Pro Gly
325 330 335
Pro Pro Gly Thr Ala Gly Phe Pro Gly Ser Pro Gly Ala Lys Gly Glu
340 345 350
Val Gly Pro Ala Gly Ser Pro Gly Ser Asn Gly Ala Pro Gly Gln Arg
355 360 365
Gly Glu Pro Gly Pro Gln Gly His Ala Gly Ala Gln Gly Pro Pro Gly
370 375 380
Pro Pro Gly Ile Asn Gly Ser Pro Gly Gly Lys Gly Glu Met Gly Pro
385 390 395 400
Ala Gly Ile Pro Gly Ala Pro Gly Leu Met Gly Ala Arg Gly Pro Pro
405 410 415
Gly Pro Ala Gly Ala Asn Gly Ala Pro Gly Leu Arg Gly Gly Ala Gly
420 425 430
Glu Pro Gly Lys Asn Gly Ala Lys Gly Glu Pro Gly Pro Arg Gly Glu
435 440 445
Arg Gly Glu Ala Gly Ile Pro Gly Val Pro Gly Ala Lys Gly Glu Asp
450 455 460
Gly Lys Asp Gly Ser Pro Gly Glu Pro Gly Ala Asn Gly Leu Pro Gly
465 470 475 480
Ala Ala Gly Glu Arg Gly Ala Pro Gly Phe Arg Gly Pro Ala Gly Pro
485 490 495
Asn Gly Ile Pro Gly Glu Lys Gly Pro Ala Gly Glu Arg Gly Ala Pro
500 505 510
Gly Pro Ala Gly Pro Arg Gly Ala Ala Gly Glu Pro Gly Arg Asp Gly
515 520 525
Val Pro Gly Gly Pro Gly Met Arg Gly Met Pro Gly Ser Pro Gly Gly
530 535 540
Pro Gly Ser Asp Gly Lys Pro Gly Pro Pro Gly Ser Gln Gly Glu Ser
545 550 555 560
Gly Arg Pro Gly Pro Pro Gly Pro Ser Gly Pro Arg Gly Gln Pro Gly
565 570 575
Val Met Gly Phe Pro Gly Pro Lys Gly Asn Asp Gly Ala Pro Gly Lys
580 585 590
Asn Gly Glu Arg Gly Gly Pro Gly Gly Pro Gly Pro Gln Gly Pro Pro
595 600 605
Gly Lys Asn Gly Glu Thr Gly Pro Gln Gly Pro Pro Gly Pro Thr Gly
610 615 620
Pro Gly Gly Asp Lys Gly Asp Thr Gly Pro Pro Gly Pro Gln Gly Leu
625 630 635 640
Gln Gly Leu Pro Gly Thr Gly Gly Pro Pro Gly Glu Asn Gly Lys Pro
645 650 655
Gly Glu Pro Gly Pro Lys Gly Asp Ala Gly Ala Pro Gly Ala Pro Gly
660 665 670
Gly Lys Gly Asp Ala Gly Ala Pro Gly Glu Arg Gly Pro Pro Gly Leu
675 680 685
Ala Gly Ala Pro Gly Leu Arg Gly Gly Ala Gly Pro Pro Gly Pro Glu
690 695 700
Gly Gly Lys Gly Ala Ala Gly Pro Pro Gly Pro Pro Gly Ala Ala Gly
705 710 715 720
Thr Pro Gly Leu Gln Gly Met Pro Gly Glu Arg Gly Gly Leu Gly Ser
725 730 735
Pro Gly Pro Lys Gly Asp Lys Gly Glu Pro Gly Gly Pro Gly Ala Asp
740 745 750
Gly Val Pro Gly Lys Asp Gly Pro Arg Gly Pro Thr Gly Pro Ile Gly
755 760 765
Pro Pro Gly Pro Ala Gly Gln Pro Gly Asp Lys Gly Glu Gly Gly Ala
770 775 780
Pro Gly Leu Pro Gly Ile Ala Gly Pro Arg Gly Ser Pro Gly Glu Arg
785 790 795 800
Gly Glu Thr Gly Pro Pro Gly Pro Ala Gly Phe Pro Gly Ala Pro Gly
805 810 815
Gln Asn Gly Glu Pro Gly Gly Lys Gly Glu Arg Gly Ala Pro Gly Glu
820 825 830
Lys Gly Glu Gly Gly Pro Pro Gly Val Ala Gly Pro Pro Gly Gly Ser
835 840 845
Gly Pro Ala Gly Pro Pro Gly Pro Gln Gly Val Lys Gly Glu Arg Gly
850 855 860
Ser Pro Gly Gly Pro Gly Ala Ala Gly Phe Pro Gly Ala Arg Gly Leu
865 870 875 880
Pro Gly Pro Pro Gly Ser Asn Gly Asn Pro Gly Pro Pro Gly Pro Ser
885 890 895
Gly Ser Pro Gly Lys Asp Gly Pro Pro Gly Pro Ala Gly Asn Thr Gly
900 905 910
Ala Pro Gly Ser Pro Gly Val Ser Gly Pro Lys Gly Asp Ala Gly Gln
915 920 925
Pro Gly Glu Lys Gly Ser Pro Gly Ala Gln Gly Pro Pro Gly Ala Pro
930 935 940
Gly Pro Leu Gly Ile Ala Gly Ile Thr Gly Ala Arg Gly Leu Ala Gly
945 950 955 960
Pro Pro Gly Met Pro Gly Pro Arg Gly Ser Pro Gly Pro Gln Gly Val
965 970 975
Lys Gly Glu Ser Gly Lys Pro Gly Ala Asn Gly Leu Ser Gly Glu Arg
980 985 990
Gly Pro Pro Gly Pro Gln Gly Leu Pro Gly Leu Ala Gly Thr Ala Gly
995 1000 1005
Glu Pro Gly Arg Asp Gly Asn Pro Gly Ser Asp Gly Leu Pro Gly
1010 1015 1020
Arg Asp Gly Ser Pro Gly Gly Lys Gly Asp Arg Gly Glu Asn Gly
1025 1030 1035
Ser Pro Gly Ala Pro Gly Ala Pro Gly His Pro Gly Pro Pro Gly
1040 1045 1050
Pro Val Gly Pro Ala Gly Lys Ser Gly Asp Arg Gly Glu Ser Gly
1055 1060 1065
Pro Ala Gly Pro Ala Gly Ala Pro Gly Pro Ala Gly Ser Arg Gly
1070 1075 1080
Ala Pro Gly Pro Gln Gly Pro Arg Gly Asp Lys Gly Glu Thr Gly
1085 1090 1095
Glu Arg Gly Ala Ala Gly Ile Lys Gly His Arg Gly Phe Pro Gly
1100 1105 1110
Asn Pro Gly Ala Pro Gly Ser Pro Gly Pro Ala Gly Gln Gln Gly
1115 1120 1125
Ala Ile Gly Ser Pro Gly Pro Ala Gly Pro Arg Gly Pro Val Gly
1130 1135 1140
Pro Ser Gly Pro Pro Gly Lys Asp Gly Thr Ser Gly His Pro Gly
1145 1150 1155
Pro Ile Gly Pro Pro Gly Pro Arg Gly Asn Arg Gly Glu Arg Gly
1160 1165 1170
Ser Glu Gly Ser Pro Gly His Pro Gly Gln Pro Gly Pro Pro Gly
1175 1180 1185
Pro Pro Gly Ala Pro Gly Pro Cys Cys Gly Gly Val Gly Ala Ala
1190 1195 1200
Ala Ile Ala Gly Ile Gly Gly Glu Lys Ala Gly Gly Phe Ala Pro
1205 1210 1215
Tyr Tyr Gly Asp Glu Pro Met Asp Phe Lys Ile Asn Thr Asp Glu
1220 1225 1230
Ile Met Thr Ser Leu Lys Ser Val Asn Gly Gln Ile Glu Ser Leu
1235 1240 1245
Ile Ser Pro Asp Gly Ser Arg Lys Asn Pro Ala Arg Asn Cys Arg
1250 1255 1260
Asp Leu Lys Phe Cys His Pro Glu Leu Lys Ser Gly Glu Tyr Trp
1265 1270 1275
Val Asp Pro Asn Gln Gly Cys Lys Leu Asp Ala Ile Lys Val Phe
1280 1285 1290
Cys Asn Met Glu Thr Gly Glu Thr Cys Ile Ser Ala Asn Pro Leu
1295 1300 1305
Asn Val Pro Arg Lys His Trp Trp Thr Asp Ser Ser Ala Glu Lys
1310 1315 1320
Lys His Val Trp Phe Gly Glu Ser Met Asp Gly Gly Phe Gln Phe
1325 1330 1335
Ser Tyr Gly Asn Pro Glu Leu Pro Glu Asp Val Leu Asp Val Gln
1340 1345 1350
Leu Ala Phe Leu Arg Leu Leu Ser Ser Arg Ala Ser Gln Asn Ile
1355 1360 1365
Thr Tyr His Cys Lys Asn Ser Ile Ala Tyr Met Asp Gln Ala Ser
1370 1375 1380
Gly Asn Val Lys Lys Ala Leu Lys Leu Met Gly Ser Asn Glu Gly
1385 1390 1395
Glu Phe Lys Ala Glu Gly Asn Ser Lys Phe Thr Tyr Thr Val Leu
1400 1405 1410
Glu Asp Gly Cys Thr Lys His Thr Gly Glu Trp Ser Lys Thr Val
1415 1420 1425
Phe Glu Tyr Arg Thr Arg Lys Ala Val Arg Leu Pro Ile Val Asp
1430 1435 1440
Ile Ala Pro Tyr Asp Ile Gly Gly Pro Asp Gln Glu Phe Gly Val
1445 1450 1455
Asp Val Gly Pro Val Cys Phe Leu
1460 1465
<210> 104
<211> 17
<212> DNA
<213> Artificial Sequence
<220>
<223> COL3A1
<400> 104
gaggacggcc aggactt 17
<210> 105
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> COL3A1
<400> 105
ggtccaactt cacccttag 19
<210> 106
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> COL3A1 probe
<400> 106
agtgatggtc aaccaggccc t 21
<210> 107
<211> 6930
<212> DNA
<213> Homo sapiens
<400> 107
gaccgttgct tggcagacac tggatggtta tgagcctgaa caagctgaaa aggggcagga 60
aaagaagtgg aggcagcatt cttcctattt aaagctgcat cgcttgaaaa aagttttcgc 120
agactgtgct ggagctggtg ctgaaaaagg gggtttgcag aggctgccct ggggctggtg 180
ctgaaagaag agcccacagc tgacttcatg gtgctacaat aacctcagaa tctacttttc 240
actctcagga gaacccacat gtctaatatt tagacatgat ggcaaactgg gcggaagcaa 300
gacctctcct cattcttatt gttttattag ggcaatttgt ctcaataaaa gcccaggaag 360
aagacgagga tgaaggatat ggtgaagaaa tagcctgcac tcagaatggc cagatgtact 420
taaacaggga catttggaaa cctgcccctt gtcagatctg tgtctgtgac aatggagcca 480
ttctctgtga caagatagaa tgccaggatg tgctggactg tgccgaccct gtaacgcccc 540
ctggggaatg ctgtcctgtc tgttcacaaa cacctggagg tggcaataca aattttggta 600
gaggaagaaa gggacaaaag ggagaaccag gattagtgcc tgttgtaaca ggcatacgtg 660
gtcgtccagg accggcagga cctccaggat cacagggacc aagaggagag cgagggccaa 720
aaggaagacc tggccctcgt ggacctcagg gaattgatgg agaaccaggt gttcctggtc 780
aacctggtgc tccaggacct cctggacatc cgtcccaccc aggacccgat ggcttgagca 840
ggccgttttc agctcaaatg gctgggttgg atgaaaaatc tggacttggg agtcaagtag 900
gactaatgcc tggctctgtg ggtcctgttg gcccaagggg accacagggt ttacaaggac 960
agcaaggtgg tgcaggacct acaggacctc ctggtgaacc tggtgatcct ggaccaatgg 1020
gtccgattgg ttcacgtgga ccagagggcc ctcctggtaa acctggggaa gatggtgaac 1080
ctggcagaaa tggaaatcct ggtgaagtgg gatttgcagg atctccggga gctcgtggat 1140
ttcctggggc tcctggtctt ccaggtctga agggtcaccg aggacacaaa ggtcttgaag 1200
gccctaaagg tgaagttgga gcacctggtt ccaagggtga agctggcccc actggtccaa 1260
tgggtgccat gggtcctctg ggtccgaggg gaatgccagg agagagaggg agacttgggc 1320
cacagggtgc tcctggacaa cgaggtgcac atggtatgcc tggaaaacct ggaccaatgg 1380
gtcctcttgg gataccaggc tcttctggtt ttccaggaaa tcctggaatg aagggagaag 1440
caggtcctac aggggcgcga ggccctgaag gtcctcaggg gcagagaggt gaaactgggc 1500
ccccaggtcc agttggctct ccaggtcttc ctggtgcaat aggaactgat ggtactcctg 1560
gtgccaaagg cccaacgggc tctccgggta cctctggtcc tcctggctca gcagggcctc 1620
ctggatctcc aggacctcag ggtagcactg gtcctcaggg aattcgaggc caaccgggtg 1680
atccaggagt tccaggtttc aaaggagaag ctggcccaaa aggggaacca gggccacatg 1740
gtattcaggg tccgataggc ccacccggtg aagaaggcaa aagaggtccc agaggtgacc 1800
caggaacagt tggtcctcca gggccagtgg gagaaagggg tgctcctggc aatcgtggtt 1860
ttccaggctc tgatggttta cctgggccaa agggtgctca aggagaacgg ggtcctgtag 1920
gttcttcagg acccaaagga agccaggggg atccaggacg tccaggggaa cctgggcttc 1980
caggtgctcg gggtttgaca ggaaatcctg gtgttcaagg tcctgaagga aaacttggac 2040
ctttgggtgc gccaggggaa gatggccgtc caggtcctcc aggctccata ggaatcagag 2100
ggcagcccgg gagcatgggc cttccaggcc ccaaaggtag cagtggtgac cctgggaaac 2160
ctggagaagc aggaaatgct ggagttcctg ggcagagggg agctcctgga aaagatggtg 2220
aagttggtcc ttctggtcct gtgggcccgc cgggtctagc tggtgaaaga ggagaacaag 2280
gacctccagg ccccacaggt tttcaggggc ttcctggtcc tccagggcct cctggagaag 2340
gtggaaaacc aggtgatcaa ggtgttcctg gagatcccgg agcagttggc ccgttaggac 2400
ctagaggaga acgaggaaat cctggggaaa gaggagaacc tgggataact ggactccctg 2460
gtgagaaggg aatggctgga ggacatggtc ctgatggccc aaaaggcagt ccaggtccat 2520
ctgggacccc tggagataca ggcccaccag gtcttcaagg tatgccggga gaaagaggaa 2580
ttgcaggaac tcctggcccc aagggtgaca gaggtggcat aggagaaaaa ggtgctgaag 2640
gcacagctgg aaatgatggt gcaagaggtc ttccaggtcc tttgggccct ccaggtccgg 2700
caggtcctac tggagaaaag ggtgaacctg gtcctcgagg tttagttggc cctcctggct 2760
cccggggcaa tcctggttct cgaggtgaaa atgggccaac tggagctgtt ggttttgccg 2820
gaccccaggg tcctgacgga cagcctggag taaaaggtga acctggagag ccaggacaga 2880
agggagatgc tggttctcct ggaccacaag gtttagcagg atcccctggc cctcatggtc 2940
ctaatggtgt tcctggacta aaaggtggtc gaggaaccca aggtccgcct ggtgctacag 3000
gatttcctgg ttctgcgggc agagttggac ctccaggccc tgctggagct ccaggacctg 3060
cgggacccct aggggaaccc gggaaggagg gacctccagg tcttcgtggg gaccctggct 3120
ctcatgggcg tgtgggagat cgaggaccag ctggcccccc tggtggccca ggagacaaag 3180
gggacccagg agaagatggg caacctggtc cagatggccc ccctggtcca gctggaacga 3240
ccgggcagag aggaattgtt ggcatgcctg ggcaacgtgg agagagaggc atgcccggcc 3300
taccaggccc agcgggaaca ccaggaaaag taggaccaac tggtgcaaca ggagataaag 3360
gtccacctgg acctgtgggg cccccaggct ccaatggtcc tgtaggggaa cctggaccag 3420
aaggtccagc tggcaatgat ggtaccccag gacgggatgg tgctgttgga gaacgtggtg 3480
atcgtggaga ccctgggcct gcaggtctgc caggctctca gggtgcccct ggaactcctg 3540
gccctgtggg tgctccagga gatgcaggac aaagaggaga tccgggttct cggggtccta 3600
taggaccacc tggtcgagct gggaaacgtg gattacctgg accccaagga cctcgtggtg 3660
acaaaggtga tcatggagac cgaggcgaca gaggtcagaa gggccacaga ggctttactg 3720
gtcttcaggg tcttcctggc cctcctggtc caaatggtga acaaggaagt gctggaatcc 3780
ctggaccatt tggcccaaga ggtcctccag gcccagttgg tccttcaggt aaagaaggaa 3840
accctgggcc acttgggcca attggacctc caggtgtacg aggcagtgta ggagaagcag 3900
gacctgaggg ccctcctggt gagcctggcc cacctggccc tccgggtccc cctggccacc 3960
ttacagctgc tcttggggat atcatggggc actatgatga aagcatgcca gatccacttc 4020
ctgagtttac tgaagatcag gcggctcctg atgacaaaaa caaaacggac ccaggggttc 4080
atgctaccct gaagtcactc agtagtcaga ttgaaaccat gcgcagcccc gatggctcga 4140
aaaagcaccc agcccgcacg tgtgatgacc taaagctttg ccattccgca aagcagagtg 4200
gtgaatactg gattgatcct aaccaaggat ctgttgaaga tgcaatcaaa gtttactgca 4260
acatggaaac aggagaaaca tgtatttcag caaacccatc cagtgtacca cgtaaaacct 4320
ggtgggccag taaatctcct gacaataaac ctgtttggta tggtcttgat atgaacagag 4380
ggtctcagtt cgcttatgga gaccaccaat cacctaatac agccattact cagatgactt 4440
ttttgcgcct tttatcaaaa gaagcctccc agaacatcac ttacatctgt aaaaacagtg 4500
taggatacat ggacgatcaa gctaagaacc tcaaaaaagc tgtggttctc aaaggggcaa 4560
atgacttaga tatcaaagca gagggaaata ttagattccg gtatatcgtt cttcaagaca 4620
cttgctctaa gcggaatgga aatgtgggca agactgtctt tgaatataga acacagaatg 4680
tggcacgctt gcccatcata gatcttgctc ctgtggatgt tggcggcaca gaccaggaat 4740
tcggcgttga aattgggcca gtttgttttg tgtaaagtaa gccaagacac atcgacaatg 4800
agcaccacca tcaatgacca ccgccattca caagaacttt gactgtttga agttgatcct 4860
gagactcttg aagtaatggc tgatcctgca tcagcattgt atatatggtc ttaagtgcct 4920
ggcctcctta tccttcagaa tatttatttt acttacaatc ctcaagtttt aattgatttt 4980
aaatattttt caatacaaca gtttaggttt aagatgacca atgacaatga ccacctttgc 5040
agaaagtaaa ctgattgaat aaataaatct ccgttttctt caatttattt cagtgtaatg 5100
aaaaagttgc ttagtattta tgaggaaatt cttcttcctg gcaggtagct taaagagtgg 5160
ggtatataga gccacaacac atgtttattt tgcttggctg cagttgaaaa atagaaatta 5220
gtgccctttt gtgacctctc attccaagat tgtcaattaa aaatgagttt aaaatgttta 5280
acttgtgatc gagacctaca tgcatgtctt gatattgtgt aactataata gagactcttt 5340
aaggagaatc ttaaaaaaaa aaaaacgttt ctcactgtct taaatagaat ttttaaatag 5400
tatatattca gtggcatttt ggagaacaaa gtgaatttac ttcgacttct taaatttttg 5460
taaaagacta taagtttaga catctttctc attcaaattt aaagatatct ttctcctctt 5520
gatcaatcta tcaatattga tagaagtcac actagtatat accatttaat acatttacac 5580
tttcttattt aagaagatat tgaatgcaaa ataattgaca tatagaactt tacaaacata 5640
tgtccaagga ctctaaattg agactcttcc acatgtacaa tctcatcatc ctgaagccta 5700
taatgaagaa aaagatctag aaactgagtt gtggagctga ctctaatcaa atgtgatgat 5760
tggaattaga ccatttggcc tttgaacttt cataggaaaa atgacccaac atttcttagc 5820
atgagctacc tcatctctag aagctgggat ggacttacta ttcttgttta tattttagat 5880
actgaaaggt gctatgcttc tgttattatt ccaagactgg agataggcag ggctaaaaag 5940
gtattattat ttttccttta atgatggtgc taaaattctt cctataaaat tccttaaaaa 6000
taaagatggt ttaatcacta ccattgtgaa aacataactg ttagacttcc cgtttctgaa 6060
agaaagagca tcgttccaat gcttgttcac tgttcctctg tcatactgta tctggaatgc 6120
tttgtaatac ttgcatgctt cttagaccag aacatgtagg tccccttgtg tctcaatact 6180
ttttttttct taattgcatt tgttggctct attttaattt ttttctttta aaataaacag 6240
ctgggaccat cccaaaagac aagccatgca tacaactttg gtcatgtatc tctgcaaagc 6300
atcaaattaa atgcacgctt ttgtcatgtc agtggttttt gttttgtgaa attcctttga 6360
ccatattaga tctatttcat ttccaatagt gaaaaggaga tgtggtggta tactttgttt 6420
gccatttgtt taaaagatac aacggatacc ttctatcatg tatgtactgg cttataaatg 6480
aaaatctatc tacaacatta cccacaaagg caacatgaca ccaattatca ctgcctctgc 6540
ccttaaaaat gtcagagtag tattattgat aaaaagggca agcaatagat ttttcatgac 6600
tgaataaact gtaataataa aacatatgtc tcaaagtgta tcacatatga atttagccta 6660
attgttttca gtttcattct caatatttag tttacaacat cattttcccc taaactggtt 6720
atattttgac ctgtatatct taaatttgag tatttatatg cctaaataca tgtgtgagtt 6780
ttgtttgact tccaagtcca aactataaga ttatataagt tcatatagat gaatcagaaa 6840
tatgtggtaa tactattaag tcacaaacac taacaatttc caactataga aataacagtt 6900
cttatttgga ttttgggaat gctaccaata 6930
<210> 108
<211> 1499
<212> PRT
<213> Homo sapiens
<400> 108
Met Met Ala Asn Trp Ala Glu Ala Arg Pro Leu Leu Ile Leu Ile Val
1 5 10 15
Leu Leu Gly Gln Phe Val Ser Ile Lys Ala Gln Glu Glu Asp Glu Asp
20 25 30
Glu Gly Tyr Gly Glu Glu Ile Ala Cys Thr Gln Asn Gly Gln Met Tyr
35 40 45
Leu Asn Arg Asp Ile Trp Lys Pro Ala Pro Cys Gln Ile Cys Val Cys
50 55 60
Asp Asn Gly Ala Ile Leu Cys Asp Lys Ile Glu Cys Gln Asp Val Leu
65 70 75 80
Asp Cys Ala Asp Pro Val Thr Pro Pro Gly Glu Cys Cys Pro Val Cys
85 90 95
Ser Gln Thr Pro Gly Gly Gly Asn Thr Asn Phe Gly Arg Gly Arg Lys
100 105 110
Gly Gln Lys Gly Glu Pro Gly Leu Val Pro Val Val Thr Gly Ile Arg
115 120 125
Gly Arg Pro Gly Pro Ala Gly Pro Pro Gly Ser Gln Gly Pro Arg Gly
130 135 140
Glu Arg Gly Pro Lys Gly Arg Pro Gly Pro Arg Gly Pro Gln Gly Ile
145 150 155 160
Asp Gly Glu Pro Gly Val Pro Gly Gln Pro Gly Ala Pro Gly Pro Pro
165 170 175
Gly His Pro Ser His Pro Gly Pro Asp Gly Leu Ser Arg Pro Phe Ser
180 185 190
Ala Gln Met Ala Gly Leu Asp Glu Lys Ser Gly Leu Gly Ser Gln Val
195 200 205
Gly Leu Met Pro Gly Ser Val Gly Pro Val Gly Pro Arg Gly Pro Gln
210 215 220
Gly Leu Gln Gly Gln Gln Gly Gly Ala Gly Pro Thr Gly Pro Pro Gly
225 230 235 240
Glu Pro Gly Asp Pro Gly Pro Met Gly Pro Ile Gly Ser Arg Gly Pro
245 250 255
Glu Gly Pro Pro Gly Lys Pro Gly Glu Asp Gly Glu Pro Gly Arg Asn
260 265 270
Gly Asn Pro Gly Glu Val Gly Phe Ala Gly Ser Pro Gly Ala Arg Gly
275 280 285
Phe Pro Gly Ala Pro Gly Leu Pro Gly Leu Lys Gly His Arg Gly His
290 295 300
Lys Gly Leu Glu Gly Pro Lys Gly Glu Val Gly Ala Pro Gly Ser Lys
305 310 315 320
Gly Glu Ala Gly Pro Thr Gly Pro Met Gly Ala Met Gly Pro Leu Gly
325 330 335
Pro Arg Gly Met Pro Gly Glu Arg Gly Arg Leu Gly Pro Gln Gly Ala
340 345 350
Pro Gly Gln Arg Gly Ala His Gly Met Pro Gly Lys Pro Gly Pro Met
355 360 365
Gly Pro Leu Gly Ile Pro Gly Ser Ser Gly Phe Pro Gly Asn Pro Gly
370 375 380
Met Lys Gly Glu Ala Gly Pro Thr Gly Ala Arg Gly Pro Glu Gly Pro
385 390 395 400
Gln Gly Gln Arg Gly Glu Thr Gly Pro Pro Gly Pro Val Gly Ser Pro
405 410 415
Gly Leu Pro Gly Ala Ile Gly Thr Asp Gly Thr Pro Gly Ala Lys Gly
420 425 430
Pro Thr Gly Ser Pro Gly Thr Ser Gly Pro Pro Gly Ser Ala Gly Pro
435 440 445
Pro Gly Ser Pro Gly Pro Gln Gly Ser Thr Gly Pro Gln Gly Ile Arg
450 455 460
Gly Gln Pro Gly Asp Pro Gly Val Pro Gly Phe Lys Gly Glu Ala Gly
465 470 475 480
Pro Lys Gly Glu Pro Gly Pro His Gly Ile Gln Gly Pro Ile Gly Pro
485 490 495
Pro Gly Glu Glu Gly Lys Arg Gly Pro Arg Gly Asp Pro Gly Thr Val
500 505 510
Gly Pro Pro Gly Pro Val Gly Glu Arg Gly Ala Pro Gly Asn Arg Gly
515 520 525
Phe Pro Gly Ser Asp Gly Leu Pro Gly Pro Lys Gly Ala Gln Gly Glu
530 535 540
Arg Gly Pro Val Gly Ser Ser Gly Pro Lys Gly Ser Gln Gly Asp Pro
545 550 555 560
Gly Arg Pro Gly Glu Pro Gly Leu Pro Gly Ala Arg Gly Leu Thr Gly
565 570 575
Asn Pro Gly Val Gln Gly Pro Glu Gly Lys Leu Gly Pro Leu Gly Ala
580 585 590
Pro Gly Glu Asp Gly Arg Pro Gly Pro Pro Gly Ser Ile Gly Ile Arg
595 600 605
Gly Gln Pro Gly Ser Met Gly Leu Pro Gly Pro Lys Gly Ser Ser Gly
610 615 620
Asp Pro Gly Lys Pro Gly Glu Ala Gly Asn Ala Gly Val Pro Gly Gln
625 630 635 640
Arg Gly Ala Pro Gly Lys Asp Gly Glu Val Gly Pro Ser Gly Pro Val
645 650 655
Gly Pro Pro Gly Leu Ala Gly Glu Arg Gly Glu Gln Gly Pro Pro Gly
660 665 670
Pro Thr Gly Phe Gln Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly Glu
675 680 685
Gly Gly Lys Pro Gly Asp Gln Gly Val Pro Gly Asp Pro Gly Ala Val
690 695 700
Gly Pro Leu Gly Pro Arg Gly Glu Arg Gly Asn Pro Gly Glu Arg Gly
705 710 715 720
Glu Pro Gly Ile Thr Gly Leu Pro Gly Glu Lys Gly Met Ala Gly Gly
725 730 735
His Gly Pro Asp Gly Pro Lys Gly Ser Pro Gly Pro Ser Gly Thr Pro
740 745 750
Gly Asp Thr Gly Pro Pro Gly Leu Gln Gly Met Pro Gly Glu Arg Gly
755 760 765
Ile Ala Gly Thr Pro Gly Pro Lys Gly Asp Arg Gly Gly Ile Gly Glu
770 775 780
Lys Gly Ala Glu Gly Thr Ala Gly Asn Asp Gly Ala Arg Gly Leu Pro
785 790 795 800
Gly Pro Leu Gly Pro Pro Gly Pro Ala Gly Pro Thr Gly Glu Lys Gly
805 810 815
Glu Pro Gly Pro Arg Gly Leu Val Gly Pro Pro Gly Ser Arg Gly Asn
820 825 830
Pro Gly Ser Arg Gly Glu Asn Gly Pro Thr Gly Ala Val Gly Phe Ala
835 840 845
Gly Pro Gln Gly Pro Asp Gly Gln Pro Gly Val Lys Gly Glu Pro Gly
850 855 860
Glu Pro Gly Gln Lys Gly Asp Ala Gly Ser Pro Gly Pro Gln Gly Leu
865 870 875 880
Ala Gly Ser Pro Gly Pro His Gly Pro Asn Gly Val Pro Gly Leu Lys
885 890 895
Gly Gly Arg Gly Thr Gln Gly Pro Pro Gly Ala Thr Gly Phe Pro Gly
900 905 910
Ser Ala Gly Arg Val Gly Pro Pro Gly Pro Ala Gly Ala Pro Gly Pro
915 920 925
Ala Gly Pro Leu Gly Glu Pro Gly Lys Glu Gly Pro Pro Gly Leu Arg
930 935 940
Gly Asp Pro Gly Ser His Gly Arg Val Gly Asp Arg Gly Pro Ala Gly
945 950 955 960
Pro Pro Gly Gly Pro Gly Asp Lys Gly Asp Pro Gly Glu Asp Gly Gln
965 970 975
Pro Gly Pro Asp Gly Pro Pro Gly Pro Ala Gly Thr Thr Gly Gln Arg
980 985 990
Gly Ile Val Gly Met Pro Gly Gln Arg Gly Glu Arg Gly Met Pro Gly
995 1000 1005
Leu Pro Gly Pro Ala Gly Thr Pro Gly Lys Val Gly Pro Thr Gly
1010 1015 1020
Ala Thr Gly Asp Lys Gly Pro Pro Gly Pro Val Gly Pro Pro Gly
1025 1030 1035
Ser Asn Gly Pro Val Gly Glu Pro Gly Pro Glu Gly Pro Ala Gly
1040 1045 1050
Asn Asp Gly Thr Pro Gly Arg Asp Gly Ala Val Gly Glu Arg Gly
1055 1060 1065
Asp Arg Gly Asp Pro Gly Pro Ala Gly Leu Pro Gly Ser Gln Gly
1070 1075 1080
Ala Pro Gly Thr Pro Gly Pro Val Gly Ala Pro Gly Asp Ala Gly
1085 1090 1095
Gln Arg Gly Asp Pro Gly Ser Arg Gly Pro Ile Gly Pro Pro Gly
1100 1105 1110
Arg Ala Gly Lys Arg Gly Leu Pro Gly Pro Gln Gly Pro Arg Gly
1115 1120 1125
Asp Lys Gly Asp His Gly Asp Arg Gly Asp Arg Gly Gln Lys Gly
1130 1135 1140
His Arg Gly Phe Thr Gly Leu Gln Gly Leu Pro Gly Pro Pro Gly
1145 1150 1155
Pro Asn Gly Glu Gln Gly Ser Ala Gly Ile Pro Gly Pro Phe Gly
1160 1165 1170
Pro Arg Gly Pro Pro Gly Pro Val Gly Pro Ser Gly Lys Glu Gly
1175 1180 1185
Asn Pro Gly Pro Leu Gly Pro Ile Gly Pro Pro Gly Val Arg Gly
1190 1195 1200
Ser Val Gly Glu Ala Gly Pro Glu Gly Pro Pro Gly Glu Pro Gly
1205 1210 1215
Pro Pro Gly Pro Pro Gly Pro Pro Gly His Leu Thr Ala Ala Leu
1220 1225 1230
Gly Asp Ile Met Gly His Tyr Asp Glu Ser Met Pro Asp Pro Leu
1235 1240 1245
Pro Glu Phe Thr Glu Asp Gln Ala Ala Pro Asp Asp Lys Asn Lys
1250 1255 1260
Thr Asp Pro Gly Val His Ala Thr Leu Lys Ser Leu Ser Ser Gln
1265 1270 1275
Ile Glu Thr Met Arg Ser Pro Asp Gly Ser Lys Lys His Pro Ala
1280 1285 1290
Arg Thr Cys Asp Asp Leu Lys Leu Cys His Ser Ala Lys Gln Ser
1295 1300 1305
Gly Glu Tyr Trp Ile Asp Pro Asn Gln Gly Ser Val Glu Asp Ala
1310 1315 1320
Ile Lys Val Tyr Cys Asn Met Glu Thr Gly Glu Thr Cys Ile Ser
1325 1330 1335
Ala Asn Pro Ser Ser Val Pro Arg Lys Thr Trp Trp Ala Ser Lys
1340 1345 1350
Ser Pro Asp Asn Lys Pro Val Trp Tyr Gly Leu Asp Met Asn Arg
1355 1360 1365
Gly Ser Gln Phe Ala Tyr Gly Asp His Gln Ser Pro Asn Thr Ala
1370 1375 1380
Ile Thr Gln Met Thr Phe Leu Arg Leu Leu Ser Lys Glu Ala Ser
1385 1390 1395
Gln Asn Ile Thr Tyr Ile Cys Lys Asn Ser Val Gly Tyr Met Asp
1400 1405 1410
Asp Gln Ala Lys Asn Leu Lys Lys Ala Val Val Leu Lys Gly Ala
1415 1420 1425
Asn Asp Leu Asp Ile Lys Ala Glu Gly Asn Ile Arg Phe Arg Tyr
1430 1435 1440
Ile Val Leu Gln Asp Thr Cys Ser Lys Arg Asn Gly Asn Val Gly
1445 1450 1455
Lys Thr Val Phe Glu Tyr Arg Thr Gln Asn Val Ala Arg Leu Pro
1460 1465 1470
Ile Ile Asp Leu Ala Pro Val Asp Val Gly Gly Thr Asp Gln Glu
1475 1480 1485
Phe Gly Val Glu Ile Gly Pro Val Cys Phe Val
1490 1495
<210> 109
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> COL5A2
<400> 109
aagaggagaa caaggacctc 20
<210> 110
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> COL5A2_reverse primer
<400> 110
atctccagga acaccttgat 20
<210> 111
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> COL5A2_probe
<400> 111
tttccacctt ctccaggagg cc 22
<210> 112
<211> 2175
<212> DNA
<213> Homo sapiens
<400> 112
agtacagtat aaaacttcac agtgccaata ccatgaagag gagctcagac agctcttacc 60
acatgataca agagccggct ggtggaagag tggggaccag aaagagaatt tgctgaagag 120
gagaaggaaa aaaaaaacac caaaaaaaaa aataaaaaaa tccacacaca caaaaaaacc 180
tgcgcgtgag gggggaggaa aagcagggcc ttttaaaaag gcaatcacaa caacttttgc 240
tgccaggatg cccttgcttt ggctgagagg atttctgttg gcaagttgct ggattatagt 300
gaggagttcc cccaccccag gatccgaggg gcacagcgcg gcccccgact gtccgtcctg 360
tgcgctggcc gccctcccaa aggatgtacc caactctcag ccagagatgg tggaggccgt 420
caagaagcac attttaaaca tgctgcactt gaagaagaga cccgatgtca cccagccggt 480
acccaaggcg gcgcttctga acgcgatcag aaagcttcat gtgggcaaag tcggggagaa 540
cgggtatgtg gagatagagg atgacattgg aaggagggca gaaatgaatg aacttatgga 600
gcagacctcg gagatcatca cgtttgccga gtcaggaaca gccaggaaga cgctgcactt 660
cgagatttcc aaggaaggca gtgacctgtc agtggtggag cgtgcagaag tctggctctt 720
cctaaaagtc cccaaggcca acaggaccag gaccaaagtc accatccgcc tcttccagca 780
gcagaagcac ccgcagggca gcttggacac aggggaagag gccgaggaag tgggcttaaa 840
gggggagagg agtgaactgt tgctctctga aaaagtagta gacgctcgga agagcacctg 900
gcatgtcttc cctgtctcca gcagcatcca gcggttgctg gaccagggca agagctccct 960
ggacgttcgg attgcctgtg agcagtgcca ggagagtggc gccagcttgg ttctcctggg 1020
caagaagaag aagaaagaag aggaggggga agggaaaaag aagggcggag gtgaaggtgg 1080
ggcaggagca gatgaggaaa aggagcagtc gcacagacct ttcctcatgc tgcaggcccg 1140
gcagtctgaa gaccaccctc atcgccggcg tcggcggggc ttggagtgtg atggcaaggt 1200
caacatctgc tgtaagaaac agttctttgt cagtttcaag gacatcggct ggaatgactg 1260
gatcattgct ccctctggct atcatgccaa ctactgcgag ggtgagtgcc cgagccatat 1320
agcaggcacg tccgggtcct cactgtcctt ccactcaaca gtcatcaacc actaccgcat 1380
gcggggccat agcccctttg ccaacctcaa atcgtgctgt gtgcccacca agctgagacc 1440
catgtccatg ttgtactatg atgatggtca aaacatcatc aaaaaggaca ttcagaacat 1500
gatcgtggag gagtgtgggt gctcatagag ttgcccagcc cagggggaaa gggagcaaga 1560
gttgtccaga gaagacagtg gcaaaatgaa gaaattttta aggtttctga gttaaccaga 1620
aaaatagaaa ttaaaaacaa aacaaaaaaa aaaacaaaaa aaaacaaaag taaattaaaa 1680
acaaaacctg atgaaacaga tgaaggaaga tgtggaaaaa atccttagcc agggctcaga 1740
gatgaagcag tgaaagagac aggaattggg agggaaaggg agaatggtgt accctttatt 1800
tcttctgaaa tcacactgat gacatcagtt gtttaaacgg ggtattgtcc tttcccccct 1860
tgaggttccc ttgtgagcct tgaatcaacc aatctagtct gcagtagtgt ggactagaac 1920
aacccaaata gcatctagaa agccatgagt ttgaaagggc ccatcacagg cactttccta 1980
cccaattacc caggtcataa ggtatgtctg tgtgacactt atctctgtgt atatcagcat 2040
acacacacac acacacacac acacacacac acacaggcat ttccacacat tacatatata 2100
cacatactgg taaaagaaca atcgtgtgca ggtggtcaca cttccttttt ctgtaccact 2160
tttgcaacaa aacaa 2175
<210> 113
<211> 426
<212> PRT
<213> Homo sapiens
<400> 113
Met Pro Leu Leu Trp Leu Arg Gly Phe Leu Leu Ala Ser Cys Trp Ile
1 5 10 15
Ile Val Arg Ser Ser Pro Thr Pro Gly Ser Glu Gly His Ser Ala Ala
20 25 30
Pro Asp Cys Pro Ser Cys Ala Leu Ala Ala Leu Pro Lys Asp Val Pro
35 40 45
Asn Ser Gln Pro Glu Met Val Glu Ala Val Lys Lys His Ile Leu Asn
50 55 60
Met Leu His Leu Lys Lys Arg Pro Asp Val Thr Gln Pro Val Pro Lys
65 70 75 80
Ala Ala Leu Leu Asn Ala Ile Arg Lys Leu His Val Gly Lys Val Gly
85 90 95
Glu Asn Gly Tyr Val Glu Ile Glu Asp Asp Ile Gly Arg Arg Ala Glu
100 105 110
Met Asn Glu Leu Met Glu Gln Thr Ser Glu Ile Ile Thr Phe Ala Glu
115 120 125
Ser Gly Thr Ala Arg Lys Thr Leu His Phe Glu Ile Ser Lys Glu Gly
130 135 140
Ser Asp Leu Ser Val Val Glu Arg Ala Glu Val Trp Leu Phe Leu Lys
145 150 155 160
Val Pro Lys Ala Asn Arg Thr Arg Thr Lys Val Thr Ile Arg Leu Phe
165 170 175
Gln Gln Gln Lys His Pro Gln Gly Ser Leu Asp Thr Gly Glu Glu Ala
180 185 190
Glu Glu Val Gly Leu Lys Gly Glu Arg Ser Glu Leu Leu Leu Ser Glu
195 200 205
Lys Val Val Asp Ala Arg Lys Ser Thr Trp His Val Phe Pro Val Ser
210 215 220
Ser Ser Ile Gln Arg Leu Leu Asp Gln Gly Lys Ser Ser Leu Asp Val
225 230 235 240
Arg Ile Ala Cys Glu Gln Cys Gln Glu Ser Gly Ala Ser Leu Val Leu
245 250 255
Leu Gly Lys Lys Lys Lys Lys Glu Glu Glu Gly Glu Gly Lys Lys Lys
260 265 270
Gly Gly Gly Glu Gly Gly Ala Gly Ala Asp Glu Glu Lys Glu Gln Ser
275 280 285
His Arg Pro Phe Leu Met Leu Gln Ala Arg Gln Ser Glu Asp His Pro
290 295 300
His Arg Arg Arg Arg Arg Gly Leu Glu Cys Asp Gly Lys Val Asn Ile
305 310 315 320
Cys Cys Lys Lys Gln Phe Phe Val Ser Phe Lys Asp Ile Gly Trp Asn
325 330 335
Asp Trp Ile Ile Ala Pro Ser Gly Tyr His Ala Asn Tyr Cys Glu Gly
340 345 350
Glu Cys Pro Ser His Ile Ala Gly Thr Ser Gly Ser Ser Leu Ser Phe
355 360 365
His Ser Thr Val Ile Asn His Tyr Arg Met Arg Gly His Ser Pro Phe
370 375 380
Ala Asn Leu Lys Ser Cys Cys Val Pro Thr Lys Leu Arg Pro Met Ser
385 390 395 400
Met Leu Tyr Tyr Asp Asp Gly Gln Asn Ile Ile Lys Lys Asp Ile Gln
405 410 415
Asn Met Ile Val Glu Glu Cys Gly Cys Ser
420 425
<210> 114
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> INHBA_forward primer
<400> 114
cctcggagat catcacgttt 20
<210> 115
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> INHBA_reverse primer
<400> 115
cactgccttc cttggaaatc t 21
<210> 116
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> INHBA probe
<400> 116
cagccaggaa gacgctgcac tt 22
<210> 117
<211> 5898
<212> DNA
<213> Homo sapiens
<400> 117
aaaagtgagt ccctgccttc cctctctccg tctggctcct cccaggcctg tctggcaggg 60
gccggggtgc aggaggagga gacggcatcc agtacagagg ggctggactt ggacccctgc 120
agcagccctg cacaggagaa gcggcatata aagccgcgct gcccgggagc cgctcggcca 180
cgtccaccgg agcatcctgc actgcagggc cggtctctcg ctccagcaga gcctgcgcct 240
ttctgactcg gtccggaaca ctgaaaccag tcatcactgc atctttttgg caaaccagga 300
gctcagctgc aggaggcagg atggtctgga ggctggtcct gctggctctg tgggtgtggc 360
ccagcacgca agctggtcac caggacaaag acacgacctt cgaccttttc agtatcagca 420
acatcaaccg caagaccatt ggcgccaagc agttccgcgg gcccgacccc ggcgtgccgg 480
cttaccgctt cgtgcgcttt gactacatcc caccggtgaa cgcagatgac ctcagcaaga 540
tcaccaagat catgcggcag aaggagggct tcttcctcac ggcccagctc aagcaggacg 600
gcaagtccag gggcacgctg ttggctctgg agggccccgg tctctcccag aggcagttcg 660
agatcgtctc caacggcccc gcggacacgc tggatctcac ctactggatt gacggcaccc 720
ggcatgtggt ctccctggag gacgtcggcc tggctgactc gcagtggaag aacgtcaccg 780
tgcaggtggc tggcgagacc tacagcttgc acgtgggctg cgacctcata gacagcttcg 840
ctctggacga gcccttctac gagcacctgc aggcggaaaa gagccggatg tacgtggcca 900
aaggctctgc cagagagagt cacttcaggg gtttgcttca gaacgtccac ctagtgtttg 960
aaaactctgt ggaagatatt ctaagcaaga agggttgcca gcaaggccag ggagctgaga 1020
tcaacgccat cagtgagaac acagagacgc tgcgcctggg tccgcatgtc accaccgagt 1080
acgtgggccc cagctcggag aggaggcccg aggtgtgcga acgctcgtgc gaggagctgg 1140
gaaacatggt ccaggagctc tcggggctcc acgtcctcgt gaaccagctc agcgagaacc 1200
tcaagagagt gtcgaatgat aaccagtttc tctgggagct cattggtggc cctcctaaga 1260
caaggaacat gtcagcttgc tggcaggatg gccggttctt tgcggaaaat gaaacgtggg 1320
tggtggacag ctgcaccacg tgtacctgca agaaatttaa aaccatttgc caccaaatca 1380
cctgcccgcc tgcaacctgc gccagtccat cctttgtgga aggcgaatgc tgcccttcct 1440
gcctccactc ggtggacggt gaggagggct ggtctccgtg ggcagagtgg acccagtgct 1500
ccgtgacgtg tggctctggg acccagcaga gaggccggtc ctgtgacgtc accagcaaca 1560
cctgcttggg gccctccatc cagacacggg cttgcagtct gagcaagtgt gacacccgca 1620
tccggcagga cggcggctgg agccactggt caccttggtc ttcatgctct gtgacctgtg 1680
gagttggcaa tatcacacgc atccgtctct gcaactcccc agtgccccag atggggggca 1740
agaattgcaa agggagtggc cgggagacca aagcctgcca gggcgcccca tgcccaatcg 1800
atggccgctg gagcccctgg tccccgtggt cggcctgcac tgtcacctgt gccggtggga 1860
tccgggagcg cacccgggtc tgcaacagcc ctgagcctca gtacggaggg aaggcctgcg 1920
tgggggatgt gcaggagcgt cagatgtgca acaagaggag ctgccccgtg gatggctgtt 1980
tatccaaccc ctgcttcccg ggagcccagt gcagcagctt ccccgatggg tcctggtcat 2040
gcggctcctg ccctgtgggc ttcttgggca atggcaccca ctgtgaggac ctggacgagt 2100
gtgccctggt ccccgacatc tgcttctcca ccagcaaggt gcctcgctgt gtcaacactc 2160
agcctggctt ccactgcctg ccctgcccgc cccgatacag agggaaccag cccgtcgggg 2220
tcggcctgga agcagccaag acggaaaagc aagtgtgtga gcccgaaaac ccatgcaagg 2280
acaagacaca caactgccac aagcacgcgg agtgcatcta cctgggccac ttcagcgacc 2340
ccatgtacaa gtgcgagtgc cagacaggct acgcgggcga cgggctcatc tgcggggagg 2400
actcggacct ggacggctgg cccaacctca atctggtctg cgccaccaac gccacctacc 2460
actgcatcaa ggataactgc ccccatctgc caaattctgg gcaggaagac tttgacaagg 2520
acgggattgg cgatgcctgt gatgatgacg atgacaatga cggtgtgacc gatgagaagg 2580
acaactgcca gctcctcttc aatccccgcc aggctgacta tgacaaggat gaggttgggg 2640
accgctgtga caactgccct tacgtgcaca accctgccca gatcgacaca gacaacaatg 2700
gagagggtga cgcctgctcc gtggacattg atggggacga tgtcttcaat gaacgagaca 2760
attgtcccta cgtctacaac actgaccaga gggacacgga tggtgacggt gtgggggatc 2820
actgtgacaa ctgccccctg gtgcacaacc ctgaccagac cgacgtggac aatgaccttg 2880
ttggggacca gtgtgacaac aacgaggaca tagatgacga cggccaccag aacaaccagg 2940
acaactgccc ctacatctcc aacgccaacc aggctgacca tgacagagac ggccagggcg 3000
acgcctgtga ccctgatgat gacaacgatg gcgtccccga tgacagggac aactgccggc 3060
ttgtgttcaa cccagaccag gaggacttgg acggtgatgg acggggtgat atttgtaaag 3120
atgattttga caatgacaac atcccagata ttgatgatgt gtgtcctgaa aacaatgcca 3180
tcagtgagac agacttcagg aacttccaga tggtcccctt ggatcccaaa gggaccaccc 3240
aaattgatcc caactgggtc attcgccatc aaggcaagga gctggttcag acagccaact 3300
cggaccccgg catcgctgta ggttttgacg agtttgggtc tgtggacttc agtggcacat 3360
tctacgtaaa cactgaccgg gacgacgact atgccggctt cgtctttggt taccagtcaa 3420
gcagccgctt ctatgtggtg atgtggaagc aggtgacgca gacctactgg gaggaccagc 3480
ccacgcgggc ctatggctac tccggcgtgt ccctcaaggt ggtgaactcc accacgggga 3540
cgggcgagca cctgaggaac gcgctgtggc acacggggaa cacgccgggg caggtgcgaa 3600
ccttatggca cgaccccagg aacattggct ggaaggacta cacggcctat aggtggcacc 3660
tgactcacag gcccaagact ggctacatca gagtcttagt gcatgaagga aaacaggtca 3720
tggcagactc aggacctatc tatgaccaaa cctacgctgg cgggcggctg ggtctatttg 3780
tcttctctca agaaatggtc tatttctcag acctcaagta cgaatgcaga gatatttaaa 3840
caagatttgc tgcatttccg gcaatgccct gtgcatgcca tggtccctag acacctcagt 3900
tcattgtggt ccttgtggct tctctctcta gcagcacctc ctgtcccttg accttaactc 3960
tgatggttct tcacctcctg ccagcaaccc caaacccaag tgccttcaga ggataaatat 4020
caatggaact cagagatgaa catctaaccc actagaggaa accagtttgg tgatatatga 4080
gactttatgt ggagtgaaaa ttgggcatgc cattacattg ctttttcttg tttgtttaaa 4140
aagaatgacg tttacatata aaatgtaatt acttattgta tttatgtgta tatggagttg 4200
aagggaatac tgtgcataag ccattatgat aaattaagca tgaaaaatat tgctgaacta 4260
cttttggtgc ttaaagttgt cactattctt gaattagagt tgctctacaa tgacacacaa 4320
atcccattaa ataaattata aacaagggtc aattcaaatt tgaagtaatg ttttagtaag 4380
gagagattag aagacaacag gcatagcaaa tgacataagc taccgattaa ctaatcggaa 4440
catgtaaaac agttacaaaa ataaacgaac tctcctcttg tcctacaatg aaagccctca 4500
tgtgcagtag agatgcagtt tcatcaaaga acaaacatcc ttgcaaatgg gtgtgacgcg 4560
gttccagatg tggatttggc aaaacctcat ttaagtaaaa ggttagcaga gcaaagtgcg 4620
gtgctttagc tgctgcttgt gccgctgtgg cgtcggggag gctcctgcct gagcttcctt 4680
ccccagcttt gctgcctgag aggaaccaga gcagacgcac aggccggaaa aggcgcatct 4740
aacgcgtatc taggctttgg taactgcgga caagttgctt ttacctgatt tgatgataca 4800
tttcattaag gttccagtta taaatatttt gttaatattt attaagtgac tatagaatgc 4860
aactccattt accagtaact tattttaaat atgcctagta acacatatgt agtataattt 4920
ctagaaacaa acatctaata agtatataat cctgtgaaaa tatgaggctt gataatatta 4980
ggttgtcacg atgaagcatg ctagaagctg taacagaata catagagaat aatgaggagt 5040
ttatgatgga accttaaata tataatgttg ccagcgattt tagttcaata tttgttactg 5100
ttatctatct gctgtatatg gaattctttt aattcaaacg ctgaaaagaa tcagcattta 5160
gtcttgccag gcacacccaa taatcagtca tgtgtaatat gcacaagttt gtttttgttt 5220
ttgttttttt tgttggttgg tttgtttttt tgctttaagt tgcatgatct ttctgcagga 5280
aatagtcact catcccactc cacataaggg gtttagtaag agaagtctgt ctgtctgatg 5340
atggataggg ggcaaatctt tttccccttt ctgttaatag tcatcacatt tctatgccaa 5400
acaggaacaa tccataactt tagtcttaat gtacacattg cattttgata aaattaattt 5460
tgttgtttcc tttgaggttg atcgttgtgt tgttgttttg ctgcactttt tacttttttg 5520
cgtgtggagc tgtattcccg agaccaacga agcgttggga tacttcatta aatgtagcga 5580
ctgtcaacag cgtgcaggtt ttctgtttct gtgttgtggg gtcaaccgta caatggtgtg 5640
ggagtgacga tgatgtgaat atttagaatg taccatattt tttgtaaatt atttatgttt 5700
ttctaaacaa atttatcgta taggttgatg aaacgtcatg tgttttgcca aagactgtaa 5760
atatttattt atgtgttcac atggtcaaaa tttcaccact gaaaccctgc acttagctag 5820
aacctcattt ttaaagatta acaacaggaa ataaattgta aaaaaggttt tctatacatg 5880
aaaaaaaaaa aaaaaaaa 5898
<210> 118
<211> 1172
<212> PRT
<213> Homo sapiens
<400> 118
Met Val Trp Arg Leu Val Leu Leu Ala Leu Trp Val Trp Pro Ser Thr
1 5 10 15
Gln Ala Gly His Gln Asp Lys Asp Thr Thr Phe Asp Leu Phe Ser Ile
20 25 30
Ser Asn Ile Asn Arg Lys Thr Ile Gly Ala Lys Gln Phe Arg Gly Pro
35 40 45
Asp Pro Gly Val Pro Ala Tyr Arg Phe Val Arg Phe Asp Tyr Ile Pro
50 55 60
Pro Val Asn Ala Asp Asp Leu Ser Lys Ile Thr Lys Ile Met Arg Gln
65 70 75 80
Lys Glu Gly Phe Phe Leu Thr Ala Gln Leu Lys Gln Asp Gly Lys Ser
85 90 95
Arg Gly Thr Leu Leu Ala Leu Glu Gly Pro Gly Leu Ser Gln Arg Gln
100 105 110
Phe Glu Ile Val Ser Asn Gly Pro Ala Asp Thr Leu Asp Leu Thr Tyr
115 120 125
Trp Ile Asp Gly Thr Arg His Val Val Ser Leu Glu Asp Val Gly Leu
130 135 140
Ala Asp Ser Gln Trp Lys Asn Val Thr Val Gln Val Ala Gly Glu Thr
145 150 155 160
Tyr Ser Leu His Val Gly Cys Asp Leu Ile Asp Ser Phe Ala Leu Asp
165 170 175
Glu Pro Phe Tyr Glu His Leu Gln Ala Glu Lys Ser Arg Met Tyr Val
180 185 190
Ala Lys Gly Ser Ala Arg Glu Ser His Phe Arg Gly Leu Leu Gln Asn
195 200 205
Val His Leu Val Phe Glu Asn Ser Val Glu Asp Ile Leu Ser Lys Lys
210 215 220
Gly Cys Gln Gln Gly Gln Gly Ala Glu Ile Asn Ala Ile Ser Glu Asn
225 230 235 240
Thr Glu Thr Leu Arg Leu Gly Pro His Val Thr Thr Glu Tyr Val Gly
245 250 255
Pro Ser Ser Glu Arg Arg Pro Glu Val Cys Glu Arg Ser Cys Glu Glu
260 265 270
Leu Gly Asn Met Val Gln Glu Leu Ser Gly Leu His Val Leu Val Asn
275 280 285
Gln Leu Ser Glu Asn Leu Lys Arg Val Ser Asn Asp Asn Gln Phe Leu
290 295 300
Trp Glu Leu Ile Gly Gly Pro Pro Lys Thr Arg Asn Met Ser Ala Cys
305 310 315 320
Trp Gln Asp Gly Arg Phe Phe Ala Glu Asn Glu Thr Trp Val Val Asp
325 330 335
Ser Cys Thr Thr Cys Thr Cys Lys Lys Phe Lys Thr Ile Cys His Gln
340 345 350
Ile Thr Cys Pro Pro Ala Thr Cys Ala Ser Pro Ser Phe Val Glu Gly
355 360 365
Glu Cys Cys Pro Ser Cys Leu His Ser Val Asp Gly Glu Glu Gly Trp
370 375 380
Ser Pro Trp Ala Glu Trp Thr Gln Cys Ser Val Thr Cys Gly Ser Gly
385 390 395 400
Thr Gln Gln Arg Gly Arg Ser Cys Asp Val Thr Ser Asn Thr Cys Leu
405 410 415
Gly Pro Ser Ile Gln Thr Arg Ala Cys Ser Leu Ser Lys Cys Asp Thr
420 425 430
Arg Ile Arg Gln Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser
435 440 445
Cys Ser Val Thr Cys Gly Val Gly Asn Ile Thr Arg Ile Arg Leu Cys
450 455 460
Asn Ser Pro Val Pro Gln Met Gly Gly Lys Asn Cys Lys Gly Ser Gly
465 470 475 480
Arg Glu Thr Lys Ala Cys Gln Gly Ala Pro Cys Pro Ile Asp Gly Arg
485 490 495
Trp Ser Pro Trp Ser Pro Trp Ser Ala Cys Thr Val Thr Cys Ala Gly
500 505 510
Gly Ile Arg Glu Arg Thr Arg Val Cys Asn Ser Pro Glu Pro Gln Tyr
515 520 525
Gly Gly Lys Ala Cys Val Gly Asp Val Gln Glu Arg Gln Met Cys Asn
530 535 540
Lys Arg Ser Cys Pro Val Asp Gly Cys Leu Ser Asn Pro Cys Phe Pro
545 550 555 560
Gly Ala Gln Cys Ser Ser Phe Pro Asp Gly Ser Trp Ser Cys Gly Ser
565 570 575
Cys Pro Val Gly Phe Leu Gly Asn Gly Thr His Cys Glu Asp Leu Asp
580 585 590
Glu Cys Ala Leu Val Pro Asp Ile Cys Phe Ser Thr Ser Lys Val Pro
595 600 605
Arg Cys Val Asn Thr Gln Pro Gly Phe His Cys Leu Pro Cys Pro Pro
610 615 620
Arg Tyr Arg Gly Asn Gln Pro Val Gly Val Gly Leu Glu Ala Ala Lys
625 630 635 640
Thr Glu Lys Gln Val Cys Glu Pro Glu Asn Pro Cys Lys Asp Lys Thr
645 650 655
His Asn Cys His Lys His Ala Glu Cys Ile Tyr Leu Gly His Phe Ser
660 665 670
Asp Pro Met Tyr Lys Cys Glu Cys Gln Thr Gly Tyr Ala Gly Asp Gly
675 680 685
Leu Ile Cys Gly Glu Asp Ser Asp Leu Asp Gly Trp Pro Asn Leu Asn
690 695 700
Leu Val Cys Ala Thr Asn Ala Thr Tyr His Cys Ile Lys Asp Asn Cys
705 710 715 720
Pro His Leu Pro Asn Ser Gly Gln Glu Asp Phe Asp Lys Asp Gly Ile
725 730 735
Gly Asp Ala Cys Asp Asp Asp Asp Asp Asn Asp Gly Val Thr Asp Glu
740 745 750
Lys Asp Asn Cys Gln Leu Leu Phe Asn Pro Arg Gln Ala Asp Tyr Asp
755 760 765
Lys Asp Glu Val Gly Asp Arg Cys Asp Asn Cys Pro Tyr Val His Asn
770 775 780
Pro Ala Gln Ile Asp Thr Asp Asn Asn Gly Glu Gly Asp Ala Cys Ser
785 790 795 800
Val Asp Ile Asp Gly Asp Asp Val Phe Asn Glu Arg Asp Asn Cys Pro
805 810 815
Tyr Val Tyr Asn Thr Asp Gln Arg Asp Thr Asp Gly Asp Gly Val Gly
820 825 830
Asp His Cys Asp Asn Cys Pro Leu Val His Asn Pro Asp Gln Thr Asp
835 840 845
Val Asp Asn Asp Leu Val Gly Asp Gln Cys Asp Asn Asn Glu Asp Ile
850 855 860
Asp Asp Asp Gly His Gln Asn Asn Gln Asp Asn Cys Pro Tyr Ile Ser
865 870 875 880
Asn Ala Asn Gln Ala Asp His Asp Arg Asp Gly Gln Gly Asp Ala Cys
885 890 895
Asp Pro Asp Asp Asp Asn Asp Gly Val Pro Asp Asp Arg Asp Asn Cys
900 905 910
Arg Leu Val Phe Asn Pro Asp Gln Glu Asp Leu Asp Gly Asp Gly Arg
915 920 925
Gly Asp Ile Cys Lys Asp Asp Phe Asp Asn Asp Asn Ile Pro Asp Ile
930 935 940
Asp Asp Val Cys Pro Glu Asn Asn Ala Ile Ser Glu Thr Asp Phe Arg
945 950 955 960
Asn Phe Gln Met Val Pro Leu Asp Pro Lys Gly Thr Thr Gln Ile Asp
965 970 975
Pro Asn Trp Val Ile Arg His Gln Gly Lys Glu Leu Val Gln Thr Ala
980 985 990
Asn Ser Asp Pro Gly Ile Ala Val Gly Phe Asp Glu Phe Gly Ser Val
995 1000 1005
Asp Phe Ser Gly Thr Phe Tyr Val Asn Thr Asp Arg Asp Asp Asp
1010 1015 1020
Tyr Ala Gly Phe Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr
1025 1030 1035
Val Val Met Trp Lys Gln Val Thr Gln Thr Tyr Trp Glu Asp Gln
1040 1045 1050
Pro Thr Arg Ala Tyr Gly Tyr Ser Gly Val Ser Leu Lys Val Val
1055 1060 1065
Asn Ser Thr Thr Gly Thr Gly Glu His Leu Arg Asn Ala Leu Trp
1070 1075 1080
His Thr Gly Asn Thr Pro Gly Gln Val Arg Thr Leu Trp His Asp
1085 1090 1095
Pro Arg Asn Ile Gly Trp Lys Asp Tyr Thr Ala Tyr Arg Trp His
1100 1105 1110
Leu Thr His Arg Pro Lys Thr Gly Tyr Ile Arg Val Leu Val His
1115 1120 1125
Glu Gly Lys Gln Val Met Ala Asp Ser Gly Pro Ile Tyr Asp Gln
1130 1135 1140
Thr Tyr Ala Gly Gly Arg Leu Gly Leu Phe Val Phe Ser Gln Glu
1145 1150 1155
Met Val Tyr Phe Ser Asp Leu Lys Tyr Glu Cys Arg Asp Ile
1160 1165 1170
<210> 119
<211> 17
<212> DNA
<213> Artificial Sequence
<220>
<223> THBS2_forward primer
<400> 119
cagcacgcaa gctggtc 17
<210> 120
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> THBS2_reverse primer
<400> 120
tgcggttgat gttgctgata 20
<210> 121
<211> 25
<212> DNA
<213> Artificial Sequence
<220>
<223> THBS2 probe
<400> 121
accaggacaa agacacgacc ttcga 25
<210> 122
<211> 4193
<212> DNA
<213> Homo sapiens
<400> 122
cttcttctcg ctgagtctcc tcctcggctc tgacggtaca gtgatataat gatgatgggt 60
gtcacaaccc gcatttgaac ttgcaggcga gctgccccga gcctttctgg ggaagaactc 120
caggcgtgcg gacgcaacag ccgagaacat taggtgttgt ggacaggagc tgggaccaag 180
atcttcggcc agccccgcat cctcccgcat cttccagcac cgtcccgcac cctccgcatc 240
cttccccggg ccaccacgct tcctatgtga cccgcctggg caacgccgaa cccagtcgcg 300
cagcgctgca gtgaattttc cccccaaact gcaataagcc gccttccaag gccaagatgt 360
tcataaatat aaagagcatc ttatggatgt gttcaacctt aatagtaacc catgcgctac 420
ataaagtcaa agtgggaaaa agcccaccgg tgaggggctc cctctctgga aaagtcagcc 480
taccttgtca tttttcaacg atgcctactt tgccacccag ttacaacacc agtgaatttc 540
tccgcatcaa atggtctaag attgaagtgg acaaaaatgg aaaagatttg aaagagacta 600
ctgtccttgt ggcccaaaat ggaaatatca agattggtca ggactacaaa gggagagtgt 660
ctgtgcccac acatcccgag gctgtgggcg atgcctccct cactgtggtc aagctgctgg 720
caagtgatgc gggtctttac cgctgtgacg tcatgtacgg gattgaagac acacaagaca 780
cggtgtcact gactgtggat ggggttgtgt ttcactacag ggcggcaacc agcaggtaca 840
cactgaattt tgaggctgct cagaaggctt gtttggacgt tggggcagtc atagcaactc 900
cagagcagct ctttgctgcc tatgaagatg gatttgagca gtgtgacgca ggctggctgg 960
ctgatcagac tgtcagatat cccatccggg ctcccagagt aggctgttat ggagataaga 1020
tgggaaaggc aggagtcagg acttatggat tccgttctcc ccaggaaact tacgatgtgt 1080
attgttatgt ggatcatctg gatggtgatg tgttccacct cactgtcccc agtaaattca 1140
ccttcgagga ggctgcaaaa gagtgtgaaa accaggatgc caggctggca acagtggggg 1200
aactccaggc ggcatggagg aacggctttg accagtgcga ttacgggtgg ctgtcggatg 1260
ccagcgtgcg ccaccctgtg actgtggcca gggcccagtg tggaggtggt ctacttgggg 1320
tgagaaccct gtatcgtttt gagaaccaga caggcttccc tccccctgat agcagatttg 1380
atgcctactg ctttaaacga cctgatcgct gcaaaatgaa cccgtgcctt aacggaggca 1440
cctgttatcc tactgaaact tcctacgtat gcacctgtgt gccaggatac agcggagacc 1500
agtgtgaact tgattttgat gaatgtcact ctaatccctg tcgtaatgga gccacttgtg 1560
ttgatggttt taacacattc aggtgcctct gccttccaag ttatgttggt gcactttgtg 1620
agcaagatac cgagacatgt gactatggct ggcacaaatt ccaagggcag tgctacaaat 1680
actttgccca tcgacgcaca tgggatgcag ctgaacggga atgccgtctg cagggtgccc 1740
atctcacaag catcctgtct cacgaagaac aaatgtttgt taatcgtgtg ggccatgatt 1800
atcagtggat aggcctcaat gacaagatgt ttgagcatga cttccgttgg actgatggca 1860
gcacactgca atacgagaat tggagaccca accagccaga cagcttcttt tctgctggag 1920
aagactgtgt tgtaatcatt tggcatgaga atggccagtg gaatgatgtt ccctgcaatt 1980
accatctcac ctatacgtgc aagaaaggaa cagtcgcttg cggccagccc cctgttgtag 2040
aaaatgccaa gacctttgga aagatgaaac ctcgttatga aatcaactcc ctgattagat 2100
accactgcaa agatggtttc attcaacgtc accttccaac tatccggtgc ttaggaaatg 2160
gaagatgggc tatacctaaa attacctgca tgaacccatc tgcataccaa aggacttatt 2220
ctatgaaata ctttaaaaat tcctcatcag caaaggacaa ttcaataaat acatccaaac 2280
atgatcatcg ttggagccgg aggtggcagg agtcgaggcg ctgatcccta aaatggcgaa 2340
catgtgtttt catcatttca gccaaagtcc taacttcctg tgcctttcct atcacctcga 2400
gaagtaatta tcagttggtt tggatttttg gaccaccgtt cagtcatttt gggttgccgt 2460
gctcccaaaa cattttaaat gaaagtattg gcattcaaaa agacagcaga caaaatgaaa 2520
gaaaatgaga gcagaaagta agcatttcca gcctatctaa tttctttagt tttctatttg 2580
cctccagtgc agtccatttc ctaatgtata ccagcctact gtactattta aaatgctcaa 2640
tttcagcacc gatggccatg taaataagat gatttaatgt tgattttaat cctgtatata 2700
aaataaaaag tcacaatgag tttgggcata tttaatgatg attatggagc cttagaggtc 2760
tttaatcatt ggttcggctg cttttatgta gtttaggctg gaaatggttt cacttgctct 2820
ttgactgtca gcaagactga agatggcttt tcctggacag ctagaaaaca caaaatcttg 2880
taggtcattg cacctatctc agccataggt gcagtttgct tctacatgat gctaaaggct 2940
gcgaatggga tcctgatgga actaaggact ccaatgtcga actcttcttt gctgcattcc 3000
tttttcttca cttacaagaa aggcctgaat ggaggacttt tctgtaacca ggaacatttt 3060
ttaggggtca aagtgctaat aattaactca accaggtcta ctttttaatg gctttcataa 3120
cactaactca taaggttacc gatcaatgca tttcatacgg atatagacct agggctctgg 3180
agggtggggg attgttaaaa cacatgcaaa aaaaaaaaaa aaaaaaaaaa aagaaatttt 3240
gtatatataa ccattttaat cttttataaa gttttgaatg ttcatgtatg aatgctgcag 3300
ctgtgaagca tacataaata aatgaagtaa gccatactga tttaatttat tggatgttat 3360
tttccctaag acctgaaaat gaacatagta tgctagttat ttttcagtgt tagcctttta 3420
ctttcctcac acaatttgga atcatataat ataggtactt tgtccctgat taaataatgt 3480
gacggataga atgcatcaag tgtttattat gaaaagagtg gaaaagtata tagcttttag 3540
caaaaggtgt ttgcccattc taagaaatga gcgaatatat agaaatagtg tgggcatttc 3600
ttcctgttag gtggagtgta tgtgttgaca tttctcccca tctcttccca ctctgttttc 3660
tccccattat ttgaataaag tgactgctga agatgacttt gaatccttat ccacttaatt 3720
taatgtttaa agaaaaacct gtaatggaaa gtaagactcc ttccctaatt tcagtttaga 3780
gcaacttgaa gaagagtaga caaaaaataa aatgcacata gaaaaagaga aaaagggcac 3840
aaagggattg gcccaatatt gattcttttt ttataaaacc tcctttggct tagaaggaat 3900
gactctagct acaataatac acagtatgtt taagcaggtt cccttggttg ttgcattaaa 3960
tgtaatccac ctttaggtat tttagagcac agaacaacac tgtgttgatc tagtaggttt 4020
ctatttttcc tttctcttta caatgcacat aatactttcc tgtatttata tcataacgtg 4080
tatagtgtaa aatgtgaatg actttttttg tgaatgaaaa tctaaaatct ttgtaacttt 4140
ttatatctgc ttttgtttca ccaaagaaac ctaaaatcct tcttttacta cac 4193
<210> 123
<211> 9455
<212> DNA
<213> Homo sapiens
<400> 123
cttcttctcg ctgagtctcc tcctcggctc tgacggtaca gtgatataat gatgatgggt 60
gtcacaaccc gcatttgaac ttgcaggcga gctgccccga gcctttctgg ggaagaactc 120
caggcgtgcg gacgcaacag ccgagaacat taggtgttgt ggacaggagc tgggaccaag 180
atcttcggcc agccccgcat cctcccgcat cttccagcac cgtcccgcac cctccgcatc 240
cttccccggg ccaccacgct tcctatgtga cccgcctggg caacgccgaa cccagtcgcg 300
cagcgctgca gtgaattttc cccccaaact gcaataagcc gccttccaag gccaagatgt 360
tcataaatat aaagagcatc ttatggatgt gttcaacctt aatagtaacc catgcgctac 420
ataaagtcaa agtgggaaaa agcccaccgg tgaggggctc cctctctgga aaagtcagcc 480
taccttgtca tttttcaacg atgcctactt tgccacccag ttacaacacc agtgaatttc 540
tccgcatcaa atggtctaag attgaagtgg acaaaaatgg aaaagatttg aaagagacta 600
ctgtccttgt ggcccaaaat ggaaatatca agattggtca ggactacaaa gggagagtgt 660
ctgtgcccac acatcccgag gctgtgggcg atgcctccct cactgtggtc aagctgctgg 720
caagtgatgc gggtctttac cgctgtgacg tcatgtacgg gattgaagac acacaagaca 780
cggtgtcact gactgtggat ggggttgtgt ttcactacag ggcggcaacc agcaggtaca 840
cactgaattt tgaggctgct cagaaggctt gtttggacgt tggggcagtc atagcaactc 900
cagagcagct ctttgctgcc tatgaagatg gatttgagca gtgtgacgca ggctggctgg 960
ctgatcagac tgtcagatat cccatccggg ctcccagagt aggctgttat ggagataaga 1020
tgggaaaggc aggagtcagg acttatggat tccgttctcc ccaggaaact tacgatgtgt 1080
attgttatgt ggatcatctg gatggtgatg tgttccacct cactgtcccc agtaaattca 1140
ccttcgagga ggctgcaaaa gagtgtgaaa accaggatgc caggctggca acagtggggg 1200
aactccaggc ggcatggagg aacggctttg accagtgcga ttacgggtgg ctgtcggatg 1260
ccagcgtgcg ccaccctgtg actgtggcca gggcccagtg tggaggtggt ctacttgggg 1320
tgagaaccct gtatcgtttt gagaaccaga caggcttccc tccccctgat agcagatttg 1380
atgcctactg ctttaaacgt cgaatgagtg atttgagtgt aattggtcat ccaatagatt 1440
cagaatctaa agaagatgaa ccttgtagtg aagaaacaga tccagtgcat gatctaatgg 1500
ctgaaatttt acctgaattc cctgacataa ttgaaataga cctataccac agtgaagaaa 1560
atgaagaaga agaagaagag tgtgcaaatg ctactgatgt gacaaccacc ccatctgtgc 1620
agtacataaa tgggaagcat ctcgttacca ctgtgcccaa ggacccagaa gctgcagaag 1680
ctaggcgtgg ccagtttgaa agtgttgcac cttctcagaa tttctcggac agctctgaaa 1740
gtgatactca tccatttgta atagccaaaa cggaattgtc tactgctgtg caacctaatg 1800
aatctacaga aacaactgag tctcttgaag ttacatggaa gcctgagact taccctgaaa 1860
catcagaaca tttttcaggt ggtgagcctg atgttttccc cacagtccca ttccatgagg 1920
aatttgaaag tggaacagcc aaaaaagggg cagaatcagt cacagagaga gatactgaag 1980
ttggtcatca ggcacatgaa catactgaac ctgtatctct gtttcctgaa gagtcttcag 2040
gagagattgc cattgaccaa gaatctcaga aaatagcctt tgcaagggct acagaagtaa 2100
catttggtga agaggtagaa aaaagtactt ctgtcacata cactcccact atagttccaa 2160
gttctgcatc agcatatgtt tcagaggaag aagcagttac cctaatagga aatccttggc 2220
cagatgacct gttgtctacc aaagaaagct gggtagaagc aactcctaga caagttgtag 2280
agctctcagg gagttcttcg attccaatta cagaaggctc tggagaagca gaagaagatg 2340
aagatacaat gttcaccatg gtaactgatt tatcacagag aaatactact gatacactca 2400
ttactttaga cactagcagg ataatcacag aaagcttttt tgaggttcct gcaaccacca 2460
tttatccagt ttctgaacaa ccttctgcaa aagtggtgcc taccaagttt gtaagtgaaa 2520
cagacacttc tgagtggatt tccagtacca ctgttgagga aaagaaaagg aaggaggagg 2580
agggaactac aggtacggct tctacatttg aggtatattc atctacacag agatcggatc 2640
aattaatttt accctttgaa ttagaaagtc caaatgtagc tacatctagt gattcaggta 2700
ccaggaaaag ttttatgtcc ttgacaacac caacacagtc tgaaagggaa atgacagatt 2760
ctactcctgt ctttacagaa acaaatacat tagaaaattt gggggcacag accactgagc 2820
acagcagtat ccatcaacct ggggttcagg aagggctgac cactctccca cgtagtcctg 2880
cctctgtctt tatggagcag ggctctggag aagctgctgc cgacccagaa accaccactg 2940
tttcttcatt ttcattaaac gtagagtatg caattcaagc cgaaaaggaa gtagctggca 3000
ctttgtctcc gcatgtggaa actacattct ccactgagcc aacaggactg gttttgagta 3060
cagtaatgga cagagtagtt gctgaaaata taacccaaac atccagggaa atagtgattt 3120
cagagcgatt aggagaacca aattatgggg cagaaataag gggcttttcc acaggttttc 3180
ctttggagga agatttcagt ggtgacttta gagaatactc aacagtgtct catcccatag 3240
caaaagaaga aacggtaatg atggaaggct ctggagatgc agcatttagg gacacccaga 3300
cttcaccatc tacagtacct acttcagttc acatcagtca catatctgac tcagaaggac 3360
ccagtagcac catggtcagc acttcagcct tcccctggga agagtttaca tcctcagctg 3420
agggctcagg tgagcaactg gtcacagtca gcagctctgt tgttccagtg cttcccagtg 3480
ctgtgcaaaa gttttctggt acagcttcct ccattatcga cgaaggattg ggagaagtgg 3540
gtactgtcaa tgaaattgat agaagatcca ccattttacc aacagcagaa gtggaaggta 3600
cgaaagctcc agtagagaag gaggaagtaa aggtcagtgg cacagtttca acaaactttc 3660
cccaaactat agagccagcc aaattatggt ctaggcaaga agtcaaccct gtaagacaag 3720
aaattgaaag tgaaacaaca tcagaggaac aaattcaaga agaaaagtca tttgaatccc 3780
ctcaaaactc tcctgcaaca gaacaaacaa tctttgattc acagacattt actgaaactg 3840
aactcaaaac cacagattat tctgtactaa caacaaagaa aacttacagt gatgataaag 3900
aaatgaagga ggaagacact tctttagtta acatgtctac tccagatcca gatgcaaatg 3960
gcttggaatc ttacacaact ctccctgaag ctactgaaaa gtcacatttt ttcttagcta 4020
ctgcattagt aactgaatct ataccagctg aacatgtagt cacagattca ccaatcaaaa 4080
aggaagaaag tacaaaacat tttccgaaag gcatgagacc aacaattcaa gagtcagata 4140
ctgagctctt attctctgga ctgggatcag gagaagaagt tttacctact ctaccaacag 4200
agtcagtgaa ttttactgaa gtggaacaaa tcaataacac attatatccc cacacttctc 4260
aagtggaaag tacctcaagt gacaaaattg aagactttaa cagaatggaa aatgtggcaa 4320
aagaagttgg accactcgta tctcaaacag acatctttga aggtagtggg tcagtaacca 4380
gcacaacatt aatagaaatt ttaagtgaca ctggagcaga aggacccacg gtggcacctc 4440
tccctttctc cacggacatc ggacatcctc aaaatcagac tgtcaggtgg gcagaagaaa 4500
tccagactag tagaccacaa accataactg aacaagactc taacaagaat tcttcaacag 4560
cagaaattaa cgaaacaaca acctcatcta ctgattttct ggctagagct tatggttttg 4620
aaatggccaa agaatttgtt acatcagcac caaaaccatc tgacttgtat tatgaacctt 4680
ctggagaagg atctggagaa gtggatattg ttgattcatt tcacacttct gcaactactc 4740
aggcaaccag acaagaaagc agcaccacat ttgtttctga tgggtccctg gaaaaacatc 4800
ctgaggtgcc aagcgctaaa gctgttactg ctgatggatt cccaacagtt tcagtgatgc 4860
tgcctcttca ttcagagcag aacaaaagct cccctgatcc aactagcaca ctgtcaaata 4920
cagtgtcata tgagaggtcc acagacggta gtttccaaga ccgtttcagg gaattcgagg 4980
attccacctt aaaacctaac agaaaaaaac ccactgaaaa tattatcata gacctggaca 5040
aagaggacaa ggatttaata ttgacaatta cagagagtac catccttgaa attctacctg 5100
agctgacatc ggataaaaat actatcatag atattgatca tactaaacct gtgtatgaag 5160
acattcttgg aatgcaaaca gatatagata cagaggtacc atcagaacca catgacagta 5220
atgatgaaag taatgatgac agcactcaag ttcaagagat ctatgaggca gctgtcaacc 5280
tttctttaac tgaggaaaca tttgagggct ctgctgatgt tctggctagc tacactcagg 5340
caacacatga tgaatcaatg acttatgaag atagaagcca actagatcac atgggctttc 5400
acttcacaac tgggatccct gctcctagca cagaaacaga attagacgtt ttacttccca 5460
cggcaacatc cctgccaatt cctcgtaagt ctgccacagt tattccagag attgaaggaa 5520
taaaagctga agcaaaagcc ctggatgaca tgtttgaatc aagcactttg tctgatggtc 5580
aagctattgc agaccaaagt gaaataatac caacattggg ccaatttgaa aggactcagg 5640
aggagtatga agacaaaaaa catgctggtc cttcttttca gccagaattc tcttcaggag 5700
ctgaggaggc attagtagac catactccct atctaagtat tgctactacc caccttatgg 5760
atcagagtgt aacagaggtg cctgatgtga tggaaggatc caatccccca tattacactg 5820
atacaacatt agcagtttca acatttgcga agttgtcttc tcagacacca tcatctcccc 5880
tcactatcta ctcaggcagt gaagcctctg gacacacaga gatcccccag cccagtgctc 5940
tgccaggaat agacgtcggc tcatctgtaa tgtccccaca ggattctttt aaggaaattc 6000
atgtaaatat tgaagcgact ttcaaaccat caagtgagga ataccttcac ataactgagc 6060
ctccctcttt atctcctgac acaaaattag aaccttcaga agatgatggt aaacctgagt 6120
tattagaaga aatggaagct tctcccacag aacttattgc tgtggaagga actgagattc 6180
tccaagattt ccaaaacaaa accgatggtc aagtttctgg agaagcaatc aagatgtttc 6240
ccaccattaa aacacctgag gctggaactg ttattacaac tgccgatgaa attgaattag 6300
aaggtgctac acagtggcca cactctactt ctgcttctgc cacctatggg gtcgaggcag 6360
gtgtggtgcc ttggctaagt ccacagactt ctgagaggcc cacgctttct tcttctccag 6420
aaataaaccc tgaaactcaa gcagctttaa tcagagggca ggattccacg atagcagcat 6480
cagaacagca agtggcagcg agaattcttg attccaatga tcaggcaaca gtaaaccctg 6540
tggaatttaa tactgaggtt gcaacaccac cattttccct tctggagact tctaatgaaa 6600
cagatttcct gattggcatt aatgaagagt cagtggaagg cacggcaatc tatttaccag 6660
gacctgatcg ctgcaaaatg aacccgtgcc ttaacggagg cacctgttat cctactgaaa 6720
cttcctacgt atgcacctgt gtgccaggat acagcggaga ccagtgtgaa cttgattttg 6780
atgaatgtca ctctaatccc tgtcgtaatg gagccacttg tgttgatggt tttaacacat 6840
tcaggtgcct ctgccttcca agttatgttg gtgcactttg tgagcaagat accgagacat 6900
gtgactatgg ctggcacaaa ttccaagggc agtgctacaa atactttgcc catcgacgca 6960
catgggatgc agctgaacgg gaatgccgtc tgcagggtgc ccatctcaca agcatcctgt 7020
ctcacgaaga acaaatgttt gttaatcgtg tgggccatga ttatcagtgg ataggcctca 7080
atgacaagat gtttgagcat gacttccgtt ggactgatgg cagcacactg caatacgaga 7140
attggagacc caaccagcca gacagcttct tttctgctgg agaagactgt gttgtaatca 7200
tttggcatga gaatggccag tggaatgatg ttccctgcaa ttaccatctc acctatacgt 7260
gcaagaaagg aacagtcgct tgcggccagc cccctgttgt agaaaatgcc aagacctttg 7320
gaaagatgaa acctcgttat gaaatcaact ccctgattag ataccactgc aaagatggtt 7380
tcattcaacg tcaccttcca actatccggt gcttaggaaa tggaagatgg gctataccta 7440
aaattacctg catgaaccca tctgcatacc aaaggactta ttctatgaaa tactttaaaa 7500
attcctcatc agcaaaggac aattcaataa atacatccaa acatgatcat cgttggagcc 7560
ggaggtggca ggagtcgagg cgctgatccc taaaatggcg aacatgtgtt ttcatcattt 7620
cagccaaagt cctaacttcc tgtgcctttc ctatcacctc gagaagtaat tatcagttgg 7680
tttggatttt tggaccaccg ttcagtcatt ttgggttgcc gtgctcccaa aacattttaa 7740
atgaaagtat tggcattcaa aaagacagca gacaaaatga aagaaaatga gagcagaaag 7800
taagcatttc cagcctatct aatttcttta gttttctatt tgcctccagt gcagtccatt 7860
tcctaatgta taccagccta ctgtactatt taaaatgctc aatttcagca ccgatggcca 7920
tgtaaataag atgatttaat gttgatttta atcctgtata taaaataaaa agtcacaatg 7980
agtttgggca tatttaatga tgattatgga gccttagagg tctttaatca ttggttcggc 8040
tgcttttatg tagtttaggc tggaaatggt ttcacttgct ctttgactgt cagcaagact 8100
gaagatggct tttcctggac agctagaaaa cacaaaatct tgtaggtcat tgcacctatc 8160
tcagccatag gtgcagtttg cttctacatg atgctaaagg ctgcgaatgg gatcctgatg 8220
gaactaagga ctccaatgtc gaactcttct ttgctgcatt cctttttctt cacttacaag 8280
aaaggcctga atggaggact tttctgtaac caggaacatt ttttaggggt caaagtgcta 8340
ataattaact caaccaggtc tactttttaa tggctttcat aacactaact cataaggtta 8400
ccgatcaatg catttcatac ggatatagac ctagggctct ggagggtggg ggattgttaa 8460
aacacatgca aaaaaaaaaa aaaaaaaaaa aaaagaaatt ttgtatatat aaccatttta 8520
atcttttata aagttttgaa tgttcatgta tgaatgctgc agctgtgaag catacataaa 8580
taaatgaagt aagccatact gatttaattt attggatgtt attttcccta agacctgaaa 8640
atgaacatag tatgctagtt atttttcagt gttagccttt tactttcctc acacaatttg 8700
gaatcatata atataggtac tttgtccctg attaaataat gtgacggata gaatgcatca 8760
agtgtttatt atgaaaagag tggaaaagta tatagctttt agcaaaaggt gtttgcccat 8820
tctaagaaat gagcgaatat atagaaatag tgtgggcatt tcttcctgtt aggtggagtg 8880
tatgtgttga catttctccc catctcttcc cactctgttt tctccccatt atttgaataa 8940
agtgactgct gaagatgact ttgaatcctt atccacttaa tttaatgttt aaagaaaaac 9000
ctgtaatgga aagtaagact ccttccctaa tttcagttta gagcaacttg aagaagagta 9060
gacaaaaaat aaaatgcaca tagaaaaaga gaaaaagggc acaaagggat tggcccaata 9120
ttgattcttt ttttataaaa cctcctttgg cttagaagga atgactctag ctacaataat 9180
acacagtatg tttaagcagg ttcccttggt tgttgcatta aatgtaatcc acctttaggt 9240
attttagagc acagaacaac actgtgttga tctagtaggt ttctattttt cctttctctt 9300
tacaatgcac ataatacttt cctgtattta tatcataacg tgtatagtgt aaaatgtgaa 9360
tgactttttt tgtgaatgaa aatctaaaat ctttgtaact ttttatatct gcttttgttt 9420
caccaaagaa acctaaaatc cttcttttac tacac 9455
<210> 124
<211> 7154
<212> DNA
<213> Homo sapiens
<400> 124
cttcttctcg ctgagtctcc tcctcggctc tgacggtaca gtgatataat gatgatgggt 60
gtcacaaccc gcatttgaac ttgcaggcga gctgccccga gcctttctgg ggaagaactc 120
caggcgtgcg gacgcaacag ccgagaacat taggtgttgt ggacaggagc tgggaccaag 180
atcttcggcc agccccgcat cctcccgcat cttccagcac cgtcccgcac cctccgcatc 240
cttccccggg ccaccacgct tcctatgtga cccgcctggg caacgccgaa cccagtcgcg 300
cagcgctgca gtgaattttc cccccaaact gcaataagcc gccttccaag gccaagatgt 360
tcataaatat aaagagcatc ttatggatgt gttcaacctt aatagtaacc catgcgctac 420
ataaagtcaa agtgggaaaa agcccaccgg tgaggggctc cctctctgga aaagtcagcc 480
taccttgtca tttttcaacg atgcctactt tgccacccag ttacaacacc agtgaatttc 540
tccgcatcaa atggtctaag attgaagtgg acaaaaatgg aaaagatttg aaagagacta 600
ctgtccttgt ggcccaaaat ggaaatatca agattggtca ggactacaaa gggagagtgt 660
ctgtgcccac acatcccgag gctgtgggcg atgcctccct cactgtggtc aagctgctgg 720
caagtgatgc gggtctttac cgctgtgacg tcatgtacgg gattgaagac acacaagaca 780
cggtgtcact gactgtggat ggggttgtgt ttcactacag ggcggcaacc agcaggtaca 840
cactgaattt tgaggctgct cagaaggctt gtttggacgt tggggcagtc atagcaactc 900
cagagcagct ctttgctgcc tatgaagatg gatttgagca gtgtgacgca ggctggctgg 960
ctgatcagac tgtcagatat cccatccggg ctcccagagt aggctgttat ggagataaga 1020
tgggaaaggc aggagtcagg acttatggat tccgttctcc ccaggaaact tacgatgtgt 1080
attgttatgt ggatcatctg gatggtgatg tgttccacct cactgtcccc agtaaattca 1140
ccttcgagga ggctgcaaaa gagtgtgaaa accaggatgc caggctggca acagtggggg 1200
aactccaggc ggcatggagg aacggctttg accagtgcga ttacgggtgg ctgtcggatg 1260
ccagcgtgcg ccaccctgtg actgtggcca gggcccagtg tggaggtggt ctacttgggg 1320
tgagaaccct gtatcgtttt gagaaccaga caggcttccc tccccctgat agcagatttg 1380
atgcctactg ctttaaacct aaagaggcta caaccatcga tttgagtatc ctcgcagaaa 1440
ctgcatcacc cagtttatcc aaagaaccac aaatggtttc tgatagaact acaccaatca 1500
tccctttagt tgatgaatta cctgtcattc caacagagtt ccctcccgtg ggaaatattg 1560
tcagttttga acagaaagcc acagtccaac ctcaggctat cacagatagt ttagccacca 1620
aattacccac acctactggc agtaccaaga agccctggga tatggatgac tactcacctt 1680
ctgcttcagg acctcttgga aagctagaca tatcagaaat taaggaagaa gtgctccaga 1740
gtacaactgg cgtctctcat tatgctacgg attcatggga tggtgtcgtg gaagataaac 1800
aaacacaaga atcggttaca cagattgaac aaatagaagt gggtcctttg gtaacatcta 1860
tggaaatctt aaagcacatt ccttccaagg aattccctgt aactgaaaca ccattggtaa 1920
ctgcaagaat gatcctggaa tccaaaactg aaaagaaaat ggtaagcact gtttctgaat 1980
tggtaaccac aggtcactat ggattcacct tgggagaaga ggatgatgaa gacagaacac 2040
ttacagttgg atctgatgag agcaccttga tctttgacca aattcctgaa gtcattacgg 2100
tgtcaaagac ttcagaagac accatccaca ctcatttaga agacttggag tcagtctcag 2160
catccacaac tgtttcccct ttaattatgc ctgataataa tggatcatcc atggatgact 2220
gggaagagag acaaactagt ggtaggataa cggaagagtt tcttggcaaa tatctgtcta 2280
ctacaccttt tccatcacag catcgtacag aaatagaatt gtttccttat tctggtgata 2340
aaatattagt agagggaatt tccacagtta tttatccttc tctacaaaca gaaatgacac 2400
atagaagaga aagaacagaa acactaatac cagagatgag aacagatact tatacagatg 2460
aaatacaaga agagatcact aaaagtccat ttatgggaaa aacagaagaa gaagtcttct 2520
ctgggatgaa actctctaca tctctctcag agccaattca tgttacagag tcttctgtgg 2580
aaatgaccaa gtcttttgat ttcccaacat tgataacaaa gttaagtgca gagccaacag 2640
aagtaagaga tatggaggaa gactttacag caactccagg tactacaaaa tatgatgaaa 2700
atattacaac agtgcttttg gcccatggta ctttaagtgt tgaagcagcc actgtatcaa 2760
aatggtcatg ggatgaagat aatacaacat ccaagccttt agagtctaca gaaccttcag 2820
cctcttcaaa attgccccct gccttactca caactgtggg gatgaatgga aaggataaag 2880
acatcccaag tttcactgaa gatggagcag atgaatttac tcttattcca gatagtactc 2940
aaaagcagtt agaggaggtt actgatgaag acatagcagc ccatggaaaa ttcacaatta 3000
gatttcagcc aactacatca actggtattg cagaaaagtc aactttgaga gattctacaa 3060
ctgaagaaaa agttccacct atcacaagca ctgaaggcca agtttatgca accatggaag 3120
gaagtgcttt gggtgaagta gaagatgtgg acctctctaa gccagtatct actgttcccc 3180
aatttgcaca cacttcagag gtggaaggat tagcatttgt tagttatagt agcacccaag 3240
agcctactac ttatgtagac tcttcccata ccattcctct ttctgtaatt cccaagacag 3300
actggggagt gttagtacct tctgttccat cagaagatga agttctaggt gaaccctctc 3360
aagacatact tgtcattgat cagactcgcc ttgaagcgac tatttctcca gaaactatga 3420
gaacaacaaa aatcacagag ggaacaactc aggaagaatt cccttggaaa gaacagactg 3480
cagagaaacc agttcctgct ctcagttcta cagcttggac tcccaaggag gcagtaacac 3540
cactggatga acaagagggc gatggatcag catatacagt ctctgaagat gaattgttga 3600
caggttctga gagggtccca gttttagaaa caactccagt tggaaaaatt gatcacagtg 3660
tgtcttatcc accaggtgct gtaactgagc acaaagtgaa aacagatgaa gtggtaacac 3720
taacaccacg cattgggcca aaagtatctt taagtccagg gcctgaacaa aaatatgaaa 3780
cagaaggtag tagtacaaca ggatttacat catctttgag tccttttagt acccacatta 3840
cccagcttat ggaagaaacc actactgaga aaacatccct agaggatatt gatttaggct 3900
caggattatt tgaaaagccc aaagccacag aactcataga attttcaaca atcaaagtca 3960
cagttccaag tgatattacc actgccttca gttcagtaga cagacttcac acaacttcag 4020
cattcaagcc atcttccgcg atcactaaga aaccacctct catcgacagg gaacctggtg 4080
aagaaacaac cagtgacatg gtaatcattg gagaatcaac atctcatgtt cctcccacta 4140
cccttgaaga tattgtagcc aaggaaacag aaaccgatat tgatagagag tatttcacga 4200
cttcaagtcc tcctgctaca cagccaacaa gaccacccac tgtggaagac aaagaggcct 4260
ttggacctca ggcgctttct acgccacagc ccccagcaag cacaaaattt caccctgaca 4320
ttaatgttta tattattgag gtcagagaaa ataagacagg acctgatcgc tgcaaaatga 4380
acccgtgcct taacggaggc acctgttatc ctactgaaac ttcctacgta tgcacctgtg 4440
tgccaggata cagcggagac cagtgtgaac ttgattttga tgaatgtcac tctaatccct 4500
gtcgtaatgg agccacttgt gttgatggtt ttaacacatt caggtgcctc tgccttccaa 4560
gttatgttgg tgcactttgt gagcaagata ccgagacatg tgactatggc tggcacaaat 4620
tccaagggca gtgctacaaa tactttgccc atcgacgcac atgggatgca gctgaacggg 4680
aatgccgtct gcagggtgcc catctcacaa gcatcctgtc tcacgaagaa caaatgtttg 4740
ttaatcgtgt gggccatgat tatcagtgga taggcctcaa tgacaagatg tttgagcatg 4800
acttccgttg gactgatggc agcacactgc aatacgagaa ttggagaccc aaccagccag 4860
acagcttctt ttctgctgga gaagactgtg ttgtaatcat ttggcatgag aatggccagt 4920
ggaatgatgt tccctgcaat taccatctca cctatacgtg caagaaagga acagtcgctt 4980
gcggccagcc ccctgttgta gaaaatgcca agacctttgg aaagatgaaa cctcgttatg 5040
aaatcaactc cctgattaga taccactgca aagatggttt cattcaacgt caccttccaa 5100
ctatccggtg cttaggaaat ggaagatggg ctatacctaa aattacctgc atgaacccat 5160
ctgcatacca aaggacttat tctatgaaat actttaaaaa ttcctcatca gcaaaggaca 5220
attcaataaa tacatccaaa catgatcatc gttggagccg gaggtggcag gagtcgaggc 5280
gctgatccct aaaatggcga acatgtgttt tcatcatttc agccaaagtc ctaacttcct 5340
gtgcctttcc tatcacctcg agaagtaatt atcagttggt ttggattttt ggaccaccgt 5400
tcagtcattt tgggttgccg tgctcccaaa acattttaaa tgaaagtatt ggcattcaaa 5460
aagacagcag acaaaatgaa agaaaatgag agcagaaagt aagcatttcc agcctatcta 5520
atttctttag ttttctattt gcctccagtg cagtccattt cctaatgtat accagcctac 5580
tgtactattt aaaatgctca atttcagcac cgatggccat gtaaataaga tgatttaatg 5640
ttgattttaa tcctgtatat aaaataaaaa gtcacaatga gtttgggcat atttaatgat 5700
gattatggag ccttagaggt ctttaatcat tggttcggct gcttttatgt agtttaggct 5760
ggaaatggtt tcacttgctc tttgactgtc agcaagactg aagatggctt ttcctggaca 5820
gctagaaaac acaaaatctt gtaggtcatt gcacctatct cagccatagg tgcagtttgc 5880
ttctacatga tgctaaaggc tgcgaatggg atcctgatgg aactaaggac tccaatgtcg 5940
aactcttctt tgctgcattc ctttttcttc acttacaaga aaggcctgaa tggaggactt 6000
ttctgtaacc aggaacattt tttaggggtc aaagtgctaa taattaactc aaccaggtct 6060
actttttaat ggctttcata acactaactc ataaggttac cgatcaatgc atttcatacg 6120
gatatagacc tagggctctg gagggtgggg gattgttaaa acacatgcaa aaaaaaaaaa 6180
aaaaaaaaaa aaagaaattt tgtatatata accattttaa tcttttataa agttttgaat 6240
gttcatgtat gaatgctgca gctgtgaagc atacataaat aaatgaagta agccatactg 6300
atttaattta ttggatgtta ttttccctaa gacctgaaaa tgaacatagt atgctagtta 6360
tttttcagtg ttagcctttt actttcctca cacaatttgg aatcatataa tataggtact 6420
ttgtccctga ttaaataatg tgacggatag aatgcatcaa gtgtttatta tgaaaagagt 6480
ggaaaagtat atagctttta gcaaaaggtg tttgcccatt ctaagaaatg agcgaatata 6540
tagaaatagt gtgggcattt cttcctgtta ggtggagtgt atgtgttgac atttctcccc 6600
atctcttccc actctgtttt ctccccatta tttgaataaa gtgactgctg aagatgactt 6660
tgaatcctta tccacttaat ttaatgttta aagaaaaacc tgtaatggaa agtaagactc 6720
cttccctaat ttcagtttag agcaacttga agaagagtag acaaaaaata aaatgcacat 6780
agaaaaagag aaaaagggca caaagggatt ggcccaatat tgattctttt tttataaaac 6840
ctcctttggc ttagaaggaa tgactctagc tacaataata cacagtatgt ttaagcaggt 6900
tcccttggtt gttgcattaa atgtaatcca cctttaggta ttttagagca cagaacaaca 6960
ctgtgttgat ctagtaggtt tctatttttc ctttctcttt acaatgcaca taatactttc 7020
ctgtatttat atcataacgt gtatagtgta aaatgtgaat gacttttttt gtgaatgaaa 7080
atctaaaatc tttgtaactt tttatatctg cttttgtttc accaaagaaa cctaaaatcc 7140
ttcttttact acac 7154
<210> 125
<211> 12416
<212> DNA
<213> Homo sapiens
<400> 125
cttcttctcg ctgagtctcc tcctcggctc tgacggtaca gtgatataat gatgatgggt 60
gtcacaaccc gcatttgaac ttgcaggcga gctgccccga gcctttctgg ggaagaactc 120
caggcgtgcg gacgcaacag ccgagaacat taggtgttgt ggacaggagc tgggaccaag 180
atcttcggcc agccccgcat cctcccgcat cttccagcac cgtcccgcac cctccgcatc 240
cttccccggg ccaccacgct tcctatgtga cccgcctggg caacgccgaa cccagtcgcg 300
cagcgctgca gtgaattttc cccccaaact gcaataagcc gccttccaag gccaagatgt 360
tcataaatat aaagagcatc ttatggatgt gttcaacctt aatagtaacc catgcgctac 420
ataaagtcaa agtgggaaaa agcccaccgg tgaggggctc cctctctgga aaagtcagcc 480
taccttgtca tttttcaacg atgcctactt tgccacccag ttacaacacc agtgaatttc 540
tccgcatcaa atggtctaag attgaagtgg acaaaaatgg aaaagatttg aaagagacta 600
ctgtccttgt ggcccaaaat ggaaatatca agattggtca ggactacaaa gggagagtgt 660
ctgtgcccac acatcccgag gctgtgggcg atgcctccct cactgtggtc aagctgctgg 720
caagtgatgc gggtctttac cgctgtgacg tcatgtacgg gattgaagac acacaagaca 780
cggtgtcact gactgtggat ggggttgtgt ttcactacag ggcggcaacc agcaggtaca 840
cactgaattt tgaggctgct cagaaggctt gtttggacgt tggggcagtc atagcaactc 900
cagagcagct ctttgctgcc tatgaagatg gatttgagca gtgtgacgca ggctggctgg 960
ctgatcagac tgtcagatat cccatccggg ctcccagagt aggctgttat ggagataaga 1020
tgggaaaggc aggagtcagg acttatggat tccgttctcc ccaggaaact tacgatgtgt 1080
attgttatgt ggatcatctg gatggtgatg tgttccacct cactgtcccc agtaaattca 1140
ccttcgagga ggctgcaaaa gagtgtgaaa accaggatgc caggctggca acagtggggg 1200
aactccaggc ggcatggagg aacggctttg accagtgcga ttacgggtgg ctgtcggatg 1260
ccagcgtgcg ccaccctgtg actgtggcca gggcccagtg tggaggtggt ctacttgggg 1320
tgagaaccct gtatcgtttt gagaaccaga caggcttccc tccccctgat agcagatttg 1380
atgcctactg ctttaaacct aaagaggcta caaccatcga tttgagtatc ctcgcagaaa 1440
ctgcatcacc cagtttatcc aaagaaccac aaatggtttc tgatagaact acaccaatca 1500
tccctttagt tgatgaatta cctgtcattc caacagagtt ccctcccgtg ggaaatattg 1560
tcagttttga acagaaagcc acagtccaac ctcaggctat cacagatagt ttagccacca 1620
aattacccac acctactggc agtaccaaga agccctggga tatggatgac tactcacctt 1680
ctgcttcagg acctcttgga aagctagaca tatcagaaat taaggaagaa gtgctccaga 1740
gtacaactgg cgtctctcat tatgctacgg attcatggga tggtgtcgtg gaagataaac 1800
aaacacaaga atcggttaca cagattgaac aaatagaagt gggtcctttg gtaacatcta 1860
tggaaatctt aaagcacatt ccttccaagg aattccctgt aactgaaaca ccattggtaa 1920
ctgcaagaat gatcctggaa tccaaaactg aaaagaaaat ggtaagcact gtttctgaat 1980
tggtaaccac aggtcactat ggattcacct tgggagaaga ggatgatgaa gacagaacac 2040
ttacagttgg atctgatgag agcaccttga tctttgacca aattcctgaa gtcattacgg 2100
tgtcaaagac ttcagaagac accatccaca ctcatttaga agacttggag tcagtctcag 2160
catccacaac tgtttcccct ttaattatgc ctgataataa tggatcatcc atggatgact 2220
gggaagagag acaaactagt ggtaggataa cggaagagtt tcttggcaaa tatctgtcta 2280
ctacaccttt tccatcacag catcgtacag aaatagaatt gtttccttat tctggtgata 2340
aaatattagt agagggaatt tccacagtta tttatccttc tctacaaaca gaaatgacac 2400
atagaagaga aagaacagaa acactaatac cagagatgag aacagatact tatacagatg 2460
aaatacaaga agagatcact aaaagtccat ttatgggaaa aacagaagaa gaagtcttct 2520
ctgggatgaa actctctaca tctctctcag agccaattca tgttacagag tcttctgtgg 2580
aaatgaccaa gtcttttgat ttcccaacat tgataacaaa gttaagtgca gagccaacag 2640
aagtaagaga tatggaggaa gactttacag caactccagg tactacaaaa tatgatgaaa 2700
atattacaac agtgcttttg gcccatggta ctttaagtgt tgaagcagcc actgtatcaa 2760
aatggtcatg ggatgaagat aatacaacat ccaagccttt agagtctaca gaaccttcag 2820
cctcttcaaa attgccccct gccttactca caactgtggg gatgaatgga aaggataaag 2880
acatcccaag tttcactgaa gatggagcag atgaatttac tcttattcca gatagtactc 2940
aaaagcagtt agaggaggtt actgatgaag acatagcagc ccatggaaaa ttcacaatta 3000
gatttcagcc aactacatca actggtattg cagaaaagtc aactttgaga gattctacaa 3060
ctgaagaaaa agttccacct atcacaagca ctgaaggcca agtttatgca accatggaag 3120
gaagtgcttt gggtgaagta gaagatgtgg acctctctaa gccagtatct actgttcccc 3180
aatttgcaca cacttcagag gtggaaggat tagcatttgt tagttatagt agcacccaag 3240
agcctactac ttatgtagac tcttcccata ccattcctct ttctgtaatt cccaagacag 3300
actggggagt gttagtacct tctgttccat cagaagatga agttctaggt gaaccctctc 3360
aagacatact tgtcattgat cagactcgcc ttgaagcgac tatttctcca gaaactatga 3420
gaacaacaaa aatcacagag ggaacaactc aggaagaatt cccttggaaa gaacagactg 3480
cagagaaacc agttcctgct ctcagttcta cagcttggac tcccaaggag gcagtaacac 3540
cactggatga acaagagggc gatggatcag catatacagt ctctgaagat gaattgttga 3600
caggttctga gagggtccca gttttagaaa caactccagt tggaaaaatt gatcacagtg 3660
tgtcttatcc accaggtgct gtaactgagc acaaagtgaa aacagatgaa gtggtaacac 3720
taacaccacg cattgggcca aaagtatctt taagtccagg gcctgaacaa aaatatgaaa 3780
cagaaggtag tagtacaaca ggatttacat catctttgag tccttttagt acccacatta 3840
cccagcttat ggaagaaacc actactgaga aaacatccct agaggatatt gatttaggct 3900
caggattatt tgaaaagccc aaagccacag aactcataga attttcaaca atcaaagtca 3960
cagttccaag tgatattacc actgccttca gttcagtaga cagacttcac acaacttcag 4020
cattcaagcc atcttccgcg atcactaaga aaccacctct catcgacagg gaacctggtg 4080
aagaaacaac cagtgacatg gtaatcattg gagaatcaac atctcatgtt cctcccacta 4140
cccttgaaga tattgtagcc aaggaaacag aaaccgatat tgatagagag tatttcacga 4200
cttcaagtcc tcctgctaca cagccaacaa gaccacccac tgtggaagac aaagaggcct 4260
ttggacctca ggcgctttct acgccacagc ccccagcaag cacaaaattt caccctgaca 4320
ttaatgttta tattattgag gtcagagaaa ataagacagg tcgaatgagt gatttgagtg 4380
taattggtca tccaatagat tcagaatcta aagaagatga accttgtagt gaagaaacag 4440
atccagtgca tgatctaatg gctgaaattt tacctgaatt ccctgacata attgaaatag 4500
acctatacca cagtgaagaa aatgaagaag aagaagaaga gtgtgcaaat gctactgatg 4560
tgacaaccac cccatctgtg cagtacataa atgggaagca tctcgttacc actgtgccca 4620
aggacccaga agctgcagaa gctaggcgtg gccagtttga aagtgttgca ccttctcaga 4680
atttctcgga cagctctgaa agtgatactc atccatttgt aatagccaaa acggaattgt 4740
ctactgctgt gcaacctaat gaatctacag aaacaactga gtctcttgaa gttacatgga 4800
agcctgagac ttaccctgaa acatcagaac atttttcagg tggtgagcct gatgttttcc 4860
ccacagtccc attccatgag gaatttgaaa gtggaacagc caaaaaaggg gcagaatcag 4920
tcacagagag agatactgaa gttggtcatc aggcacatga acatactgaa cctgtatctc 4980
tgtttcctga agagtcttca ggagagattg ccattgacca agaatctcag aaaatagcct 5040
ttgcaagggc tacagaagta acatttggtg aagaggtaga aaaaagtact tctgtcacat 5100
acactcccac tatagttcca agttctgcat cagcatatgt ttcagaggaa gaagcagtta 5160
ccctaatagg aaatccttgg ccagatgacc tgttgtctac caaagaaagc tgggtagaag 5220
caactcctag acaagttgta gagctctcag ggagttcttc gattccaatt acagaaggct 5280
ctggagaagc agaagaagat gaagatacaa tgttcaccat ggtaactgat ttatcacaga 5340
gaaatactac tgatacactc attactttag acactagcag gataatcaca gaaagctttt 5400
ttgaggttcc tgcaaccacc atttatccag tttctgaaca accttctgca aaagtggtgc 5460
ctaccaagtt tgtaagtgaa acagacactt ctgagtggat ttccagtacc actgttgagg 5520
aaaagaaaag gaaggaggag gagggaacta caggtacggc ttctacattt gaggtatatt 5580
catctacaca gagatcggat caattaattt taccctttga attagaaagt ccaaatgtag 5640
ctacatctag tgattcaggt accaggaaaa gttttatgtc cttgacaaca ccaacacagt 5700
ctgaaaggga aatgacagat tctactcctg tctttacaga aacaaataca ttagaaaatt 5760
tgggggcaca gaccactgag cacagcagta tccatcaacc tggggttcag gaagggctga 5820
ccactctccc acgtagtcct gcctctgtct ttatggagca gggctctgga gaagctgctg 5880
ccgacccaga aaccaccact gtttcttcat tttcattaaa cgtagagtat gcaattcaag 5940
ccgaaaagga agtagctggc actttgtctc cgcatgtgga aactacattc tccactgagc 6000
caacaggact ggttttgagt acagtaatgg acagagtagt tgctgaaaat ataacccaaa 6060
catccaggga aatagtgatt tcagagcgat taggagaacc aaattatggg gcagaaataa 6120
ggggcttttc cacaggtttt cctttggagg aagatttcag tggtgacttt agagaatact 6180
caacagtgtc tcatcccata gcaaaagaag aaacggtaat gatggaaggc tctggagatg 6240
cagcatttag ggacacccag acttcaccat ctacagtacc tacttcagtt cacatcagtc 6300
acatatctga ctcagaagga cccagtagca ccatggtcag cacttcagcc ttcccctggg 6360
aagagtttac atcctcagct gagggctcag gtgagcaact ggtcacagtc agcagctctg 6420
ttgttccagt gcttcccagt gctgtgcaaa agttttctgg tacagcttcc tccattatcg 6480
acgaaggatt gggagaagtg ggtactgtca atgaaattga tagaagatcc accattttac 6540
caacagcaga agtggaaggt acgaaagctc cagtagagaa ggaggaagta aaggtcagtg 6600
gcacagtttc aacaaacttt ccccaaacta tagagccagc caaattatgg tctaggcaag 6660
aagtcaaccc tgtaagacaa gaaattgaaa gtgaaacaac atcagaggaa caaattcaag 6720
aagaaaagtc atttgaatcc cctcaaaact ctcctgcaac agaacaaaca atctttgatt 6780
cacagacatt tactgaaact gaactcaaaa ccacagatta ttctgtacta acaacaaaga 6840
aaacttacag tgatgataaa gaaatgaagg aggaagacac ttctttagtt aacatgtcta 6900
ctccagatcc agatgcaaat ggcttggaat cttacacaac tctccctgaa gctactgaaa 6960
agtcacattt tttcttagct actgcattag taactgaatc tataccagct gaacatgtag 7020
tcacagattc accaatcaaa aaggaagaaa gtacaaaaca ttttccgaaa ggcatgagac 7080
caacaattca agagtcagat actgagctct tattctctgg actgggatca ggagaagaag 7140
ttttacctac tctaccaaca gagtcagtga attttactga agtggaacaa atcaataaca 7200
cattatatcc ccacacttct caagtggaaa gtacctcaag tgacaaaatt gaagacttta 7260
acagaatgga aaatgtggca aaagaagttg gaccactcgt atctcaaaca gacatctttg 7320
aaggtagtgg gtcagtaacc agcacaacat taatagaaat tttaagtgac actggagcag 7380
aaggacccac ggtggcacct ctccctttct ccacggacat cggacatcct caaaatcaga 7440
ctgtcaggtg ggcagaagaa atccagacta gtagaccaca aaccataact gaacaagact 7500
ctaacaagaa ttcttcaaca gcagaaatta acgaaacaac aacctcatct actgattttc 7560
tggctagagc ttatggtttt gaaatggcca aagaatttgt tacatcagca ccaaaaccat 7620
ctgacttgta ttatgaacct tctggagaag gatctggaga agtggatatt gttgattcat 7680
ttcacacttc tgcaactact caggcaacca gacaagaaag cagcaccaca tttgtttctg 7740
atgggtccct ggaaaaacat cctgaggtgc caagcgctaa agctgttact gctgatggat 7800
tcccaacagt ttcagtgatg ctgcctcttc attcagagca gaacaaaagc tcccctgatc 7860
caactagcac actgtcaaat acagtgtcat atgagaggtc cacagacggt agtttccaag 7920
accgtttcag ggaattcgag gattccacct taaaacctaa cagaaaaaaa cccactgaaa 7980
atattatcat agacctggac aaagaggaca aggatttaat attgacaatt acagagagta 8040
ccatccttga aattctacct gagctgacat cggataaaaa tactatcata gatattgatc 8100
atactaaacc tgtgtatgaa gacattcttg gaatgcaaac agatatagat acagaggtac 8160
catcagaacc acatgacagt aatgatgaaa gtaatgatga cagcactcaa gttcaagaga 8220
tctatgaggc agctgtcaac ctttctttaa ctgaggaaac atttgagggc tctgctgatg 8280
ttctggctag ctacactcag gcaacacatg atgaatcaat gacttatgaa gatagaagcc 8340
aactagatca catgggcttt cacttcacaa ctgggatccc tgctcctagc acagaaacag 8400
aattagacgt tttacttccc acggcaacat ccctgccaat tcctcgtaag tctgccacag 8460
ttattccaga gattgaagga ataaaagctg aagcaaaagc cctggatgac atgtttgaat 8520
caagcacttt gtctgatggt caagctattg cagaccaaag tgaaataata ccaacattgg 8580
gccaatttga aaggactcag gaggagtatg aagacaaaaa acatgctggt ccttcttttc 8640
agccagaatt ctcttcagga gctgaggagg cattagtaga ccatactccc tatctaagta 8700
ttgctactac ccaccttatg gatcagagtg taacagaggt gcctgatgtg atggaaggat 8760
ccaatccccc atattacact gatacaacat tagcagtttc aacatttgcg aagttgtctt 8820
ctcagacacc atcatctccc ctcactatct actcaggcag tgaagcctct ggacacacag 8880
agatccccca gcccagtgct ctgccaggaa tagacgtcgg ctcatctgta atgtccccac 8940
aggattcttt taaggaaatt catgtaaata ttgaagcgac tttcaaacca tcaagtgagg 9000
aataccttca cataactgag cctccctctt tatctcctga cacaaaatta gaaccttcag 9060
aagatgatgg taaacctgag ttattagaag aaatggaagc ttctcccaca gaacttattg 9120
ctgtggaagg aactgagatt ctccaagatt tccaaaacaa aaccgatggt caagtttctg 9180
gagaagcaat caagatgttt cccaccatta aaacacctga ggctggaact gttattacaa 9240
ctgccgatga aattgaatta gaaggtgcta cacagtggcc acactctact tctgcttctg 9300
ccacctatgg ggtcgaggca ggtgtggtgc cttggctaag tccacagact tctgagaggc 9360
ccacgctttc ttcttctcca gaaataaacc ctgaaactca agcagcttta atcagagggc 9420
aggattccac gatagcagca tcagaacagc aagtggcagc gagaattctt gattccaatg 9480
atcaggcaac agtaaaccct gtggaattta atactgaggt tgcaacacca ccattttccc 9540
ttctggagac ttctaatgaa acagatttcc tgattggcat taatgaagag tcagtggaag 9600
gcacggcaat ctatttacca ggacctgatc gctgcaaaat gaacccgtgc cttaacggag 9660
gcacctgtta tcctactgaa acttcctacg tatgcacctg tgtgccagga tacagcggag 9720
accagtgtga acttgatttt gatgaatgtc actctaatcc ctgtcgtaat ggagccactt 9780
gtgttgatgg ttttaacaca ttcaggtgcc tctgccttcc aagttatgtt ggtgcacttt 9840
gtgagcaaga taccgagaca tgtgactatg gctggcacaa attccaaggg cagtgctaca 9900
aatactttgc ccatcgacgc acatgggatg cagctgaacg ggaatgccgt ctgcagggtg 9960
cccatctcac aagcatcctg tctcacgaag aacaaatgtt tgttaatcgt gtgggccatg 10020
attatcagtg gataggcctc aatgacaaga tgtttgagca tgacttccgt tggactgatg 10080
gcagcacact gcaatacgag aattggagac ccaaccagcc agacagcttc ttttctgctg 10140
gagaagactg tgttgtaatc atttggcatg agaatggcca gtggaatgat gttccctgca 10200
attaccatct cacctatacg tgcaagaaag gaacagtcgc ttgcggccag ccccctgttg 10260
tagaaaatgc caagaccttt ggaaagatga aacctcgtta tgaaatcaac tccctgatta 10320
gataccactg caaagatggt ttcattcaac gtcaccttcc aactatccgg tgcttaggaa 10380
atggaagatg ggctatacct aaaattacct gcatgaaccc atctgcatac caaaggactt 10440
attctatgaa atactttaaa aattcctcat cagcaaagga caattcaata aatacatcca 10500
aacatgatca tcgttggagc cggaggtggc aggagtcgag gcgctgatcc ctaaaatggc 10560
gaacatgtgt tttcatcatt tcagccaaag tcctaacttc ctgtgccttt cctatcacct 10620
cgagaagtaa ttatcagttg gtttggattt ttggaccacc gttcagtcat tttgggttgc 10680
cgtgctccca aaacatttta aatgaaagta ttggcattca aaaagacagc agacaaaatg 10740
aaagaaaatg agagcagaaa gtaagcattt ccagcctatc taatttcttt agttttctat 10800
ttgcctccag tgcagtccat ttcctaatgt ataccagcct actgtactat ttaaaatgct 10860
caatttcagc accgatggcc atgtaaataa gatgatttaa tgttgatttt aatcctgtat 10920
ataaaataaa aagtcacaat gagtttgggc atatttaatg atgattatgg agccttagag 10980
gtctttaatc attggttcgg ctgcttttat gtagtttagg ctggaaatgg tttcacttgc 11040
tctttgactg tcagcaagac tgaagatggc ttttcctgga cagctagaaa acacaaaatc 11100
ttgtaggtca ttgcacctat ctcagccata ggtgcagttt gcttctacat gatgctaaag 11160
gctgcgaatg ggatcctgat ggaactaagg actccaatgt cgaactcttc tttgctgcat 11220
tcctttttct tcacttacaa gaaaggcctg aatggaggac ttttctgtaa ccaggaacat 11280
tttttagggg tcaaagtgct aataattaac tcaaccaggt ctacttttta atggctttca 11340
taacactaac tcataaggtt accgatcaat gcatttcata cggatataga cctagggctc 11400
tggagggtgg gggattgtta aaacacatgc aaaaaaaaaa aaaaaaaaaa aaaaagaaat 11460
tttgtatata taaccatttt aatcttttat aaagttttga atgttcatgt atgaatgctg 11520
cagctgtgaa gcatacataa ataaatgaag taagccatac tgatttaatt tattggatgt 11580
tattttccct aagacctgaa aatgaacata gtatgctagt tatttttcag tgttagcctt 11640
ttactttcct cacacaattt ggaatcatat aatataggta ctttgtccct gattaaataa 11700
tgtgacggat agaatgcatc aagtgtttat tatgaaaaga gtggaaaagt atatagcttt 11760
tagcaaaagg tgtttgccca ttctaagaaa tgagcgaata tatagaaata gtgtgggcat 11820
ttcttcctgt taggtggagt gtatgtgttg acatttctcc ccatctcttc ccactctgtt 11880
ttctccccat tatttgaata aagtgactgc tgaagatgac tttgaatcct tatccactta 11940
atttaatgtt taaagaaaaa cctgtaatgg aaagtaagac tccttcccta atttcagttt 12000
agagcaactt gaagaagagt agacaaaaaa taaaatgcac atagaaaaag agaaaaaggg 12060
cacaaaggga ttggcccaat attgattctt tttttataaa acctcctttg gcttagaagg 12120
aatgactcta gctacaataa tacacagtat gtttaagcag gttcccttgg ttgttgcatt 12180
aaatgtaatc cacctttagg tattttagag cacagaacaa cactgtgttg atctagtagg 12240
tttctatttt tcctttctct ttacaatgca cataatactt tcctgtattt atatcataac 12300
gtgtatagtg taaaatgtga atgacttttt ttgtgaatga aaatctaaaa tctttgtaac 12360
tttttatatc tgcttttgtt tcaccaaaga aacctaaaat ccttctttta ctacac 12416
<210> 126
<211> 655
<212> PRT
<213> Homo sapiens
<400> 126
Met Phe Ile Asn Ile Lys Ser Ile Leu Trp Met Cys Ser Thr Leu Ile
1 5 10 15
Val Thr His Ala Leu His Lys Val Lys Val Gly Lys Ser Pro Pro Val
20 25 30
Arg Gly Ser Leu Ser Gly Lys Val Ser Leu Pro Cys His Phe Ser Thr
35 40 45
Met Pro Thr Leu Pro Pro Ser Tyr Asn Thr Ser Glu Phe Leu Arg Ile
50 55 60
Lys Trp Ser Lys Ile Glu Val Asp Lys Asn Gly Lys Asp Leu Lys Glu
65 70 75 80
Thr Thr Val Leu Val Ala Gln Asn Gly Asn Ile Lys Ile Gly Gln Asp
85 90 95
Tyr Lys Gly Arg Val Ser Val Pro Thr His Pro Glu Ala Val Gly Asp
100 105 110
Ala Ser Leu Thr Val Val Lys Leu Leu Ala Ser Asp Ala Gly Leu Tyr
115 120 125
Arg Cys Asp Val Met Tyr Gly Ile Glu Asp Thr Gln Asp Thr Val Ser
130 135 140
Leu Thr Val Asp Gly Val Val Phe His Tyr Arg Ala Ala Thr Ser Arg
145 150 155 160
Tyr Thr Leu Asn Phe Glu Ala Ala Gln Lys Ala Cys Leu Asp Val Gly
165 170 175
Ala Val Ile Ala Thr Pro Glu Gln Leu Phe Ala Ala Tyr Glu Asp Gly
180 185 190
Phe Glu Gln Cys Asp Ala Gly Trp Leu Ala Asp Gln Thr Val Arg Tyr
195 200 205
Pro Ile Arg Ala Pro Arg Val Gly Cys Tyr Gly Asp Lys Met Gly Lys
210 215 220
Ala Gly Val Arg Thr Tyr Gly Phe Arg Ser Pro Gln Glu Thr Tyr Asp
225 230 235 240
Val Tyr Cys Tyr Val Asp His Leu Asp Gly Asp Val Phe His Leu Thr
245 250 255
Val Pro Ser Lys Phe Thr Phe Glu Glu Ala Ala Lys Glu Cys Glu Asn
260 265 270
Gln Asp Ala Arg Leu Ala Thr Val Gly Glu Leu Gln Ala Ala Trp Arg
275 280 285
Asn Gly Phe Asp Gln Cys Asp Tyr Gly Trp Leu Ser Asp Ala Ser Val
290 295 300
Arg His Pro Val Thr Val Ala Arg Ala Gln Cys Gly Gly Gly Leu Leu
305 310 315 320
Gly Val Arg Thr Leu Tyr Arg Phe Glu Asn Gln Thr Gly Phe Pro Pro
325 330 335
Pro Asp Ser Arg Phe Asp Ala Tyr Cys Phe Lys Arg Pro Asp Arg Cys
340 345 350
Lys Met Asn Pro Cys Leu Asn Gly Gly Thr Cys Tyr Pro Thr Glu Thr
355 360 365
Ser Tyr Val Cys Thr Cys Val Pro Gly Tyr Ser Gly Asp Gln Cys Glu
370 375 380
Leu Asp Phe Asp Glu Cys His Ser Asn Pro Cys Arg Asn Gly Ala Thr
385 390 395 400
Cys Val Asp Gly Phe Asn Thr Phe Arg Cys Leu Cys Leu Pro Ser Tyr
405 410 415
Val Gly Ala Leu Cys Glu Gln Asp Thr Glu Thr Cys Asp Tyr Gly Trp
420 425 430
His Lys Phe Gln Gly Gln Cys Tyr Lys Tyr Phe Ala His Arg Arg Thr
435 440 445
Trp Asp Ala Ala Glu Arg Glu Cys Arg Leu Gln Gly Ala His Leu Thr
450 455 460
Ser Ile Leu Ser His Glu Glu Gln Met Phe Val Asn Arg Val Gly His
465 470 475 480
Asp Tyr Gln Trp Ile Gly Leu Asn Asp Lys Met Phe Glu His Asp Phe
485 490 495
Arg Trp Thr Asp Gly Ser Thr Leu Gln Tyr Glu Asn Trp Arg Pro Asn
500 505 510
Gln Pro Asp Ser Phe Phe Ser Ala Gly Glu Asp Cys Val Val Ile Ile
515 520 525
Trp His Glu Asn Gly Gln Trp Asn Asp Val Pro Cys Asn Tyr His Leu
530 535 540
Thr Tyr Thr Cys Lys Lys Gly Thr Val Ala Cys Gly Gln Pro Pro Val
545 550 555 560
Val Glu Asn Ala Lys Thr Phe Gly Lys Met Lys Pro Arg Tyr Glu Ile
565 570 575
Asn Ser Leu Ile Arg Tyr His Cys Lys Asp Gly Phe Ile Gln Arg His
580 585 590
Leu Pro Thr Ile Arg Cys Leu Gly Asn Gly Arg Trp Ala Ile Pro Lys
595 600 605
Ile Thr Cys Met Asn Pro Ser Ala Tyr Gln Arg Thr Tyr Ser Met Lys
610 615 620
Tyr Phe Lys Asn Ser Ser Ser Ala Lys Asp Asn Ser Ile Asn Thr Ser
625 630 635 640
Lys His Asp His Arg Trp Ser Arg Arg Trp Gln Glu Ser Arg Arg
645 650 655
<210> 127
<211> 2409
<212> PRT
<213> Homo sapiens
<400> 127
Met Phe Ile Asn Ile Lys Ser Ile Leu Trp Met Cys Ser Thr Leu Ile
1 5 10 15
Val Thr His Ala Leu His Lys Val Lys Val Gly Lys Ser Pro Pro Val
20 25 30
Arg Gly Ser Leu Ser Gly Lys Val Ser Leu Pro Cys His Phe Ser Thr
35 40 45
Met Pro Thr Leu Pro Pro Ser Tyr Asn Thr Ser Glu Phe Leu Arg Ile
50 55 60
Lys Trp Ser Lys Ile Glu Val Asp Lys Asn Gly Lys Asp Leu Lys Glu
65 70 75 80
Thr Thr Val Leu Val Ala Gln Asn Gly Asn Ile Lys Ile Gly Gln Asp
85 90 95
Tyr Lys Gly Arg Val Ser Val Pro Thr His Pro Glu Ala Val Gly Asp
100 105 110
Ala Ser Leu Thr Val Val Lys Leu Leu Ala Ser Asp Ala Gly Leu Tyr
115 120 125
Arg Cys Asp Val Met Tyr Gly Ile Glu Asp Thr Gln Asp Thr Val Ser
130 135 140
Leu Thr Val Asp Gly Val Val Phe His Tyr Arg Ala Ala Thr Ser Arg
145 150 155 160
Tyr Thr Leu Asn Phe Glu Ala Ala Gln Lys Ala Cys Leu Asp Val Gly
165 170 175
Ala Val Ile Ala Thr Pro Glu Gln Leu Phe Ala Ala Tyr Glu Asp Gly
180 185 190
Phe Glu Gln Cys Asp Ala Gly Trp Leu Ala Asp Gln Thr Val Arg Tyr
195 200 205
Pro Ile Arg Ala Pro Arg Val Gly Cys Tyr Gly Asp Lys Met Gly Lys
210 215 220
Ala Gly Val Arg Thr Tyr Gly Phe Arg Ser Pro Gln Glu Thr Tyr Asp
225 230 235 240
Val Tyr Cys Tyr Val Asp His Leu Asp Gly Asp Val Phe His Leu Thr
245 250 255
Val Pro Ser Lys Phe Thr Phe Glu Glu Ala Ala Lys Glu Cys Glu Asn
260 265 270
Gln Asp Ala Arg Leu Ala Thr Val Gly Glu Leu Gln Ala Ala Trp Arg
275 280 285
Asn Gly Phe Asp Gln Cys Asp Tyr Gly Trp Leu Ser Asp Ala Ser Val
290 295 300
Arg His Pro Val Thr Val Ala Arg Ala Gln Cys Gly Gly Gly Leu Leu
305 310 315 320
Gly Val Arg Thr Leu Tyr Arg Phe Glu Asn Gln Thr Gly Phe Pro Pro
325 330 335
Pro Asp Ser Arg Phe Asp Ala Tyr Cys Phe Lys Arg Arg Met Ser Asp
340 345 350
Leu Ser Val Ile Gly His Pro Ile Asp Ser Glu Ser Lys Glu Asp Glu
355 360 365
Pro Cys Ser Glu Glu Thr Asp Pro Val His Asp Leu Met Ala Glu Ile
370 375 380
Leu Pro Glu Phe Pro Asp Ile Ile Glu Ile Asp Leu Tyr His Ser Glu
385 390 395 400
Glu Asn Glu Glu Glu Glu Glu Glu Cys Ala Asn Ala Thr Asp Val Thr
405 410 415
Thr Thr Pro Ser Val Gln Tyr Ile Asn Gly Lys His Leu Val Thr Thr
420 425 430
Val Pro Lys Asp Pro Glu Ala Ala Glu Ala Arg Arg Gly Gln Phe Glu
435 440 445
Ser Val Ala Pro Ser Gln Asn Phe Ser Asp Ser Ser Glu Ser Asp Thr
450 455 460
His Pro Phe Val Ile Ala Lys Thr Glu Leu Ser Thr Ala Val Gln Pro
465 470 475 480
Asn Glu Ser Thr Glu Thr Thr Glu Ser Leu Glu Val Thr Trp Lys Pro
485 490 495
Glu Thr Tyr Pro Glu Thr Ser Glu His Phe Ser Gly Gly Glu Pro Asp
500 505 510
Val Phe Pro Thr Val Pro Phe His Glu Glu Phe Glu Ser Gly Thr Ala
515 520 525
Lys Lys Gly Ala Glu Ser Val Thr Glu Arg Asp Thr Glu Val Gly His
530 535 540
Gln Ala His Glu His Thr Glu Pro Val Ser Leu Phe Pro Glu Glu Ser
545 550 555 560
Ser Gly Glu Ile Ala Ile Asp Gln Glu Ser Gln Lys Ile Ala Phe Ala
565 570 575
Arg Ala Thr Glu Val Thr Phe Gly Glu Glu Val Glu Lys Ser Thr Ser
580 585 590
Val Thr Tyr Thr Pro Thr Ile Val Pro Ser Ser Ala Ser Ala Tyr Val
595 600 605
Ser Glu Glu Glu Ala Val Thr Leu Ile Gly Asn Pro Trp Pro Asp Asp
610 615 620
Leu Leu Ser Thr Lys Glu Ser Trp Val Glu Ala Thr Pro Arg Gln Val
625 630 635 640
Val Glu Leu Ser Gly Ser Ser Ser Ile Pro Ile Thr Glu Gly Ser Gly
645 650 655
Glu Ala Glu Glu Asp Glu Asp Thr Met Phe Thr Met Val Thr Asp Leu
660 665 670
Ser Gln Arg Asn Thr Thr Asp Thr Leu Ile Thr Leu Asp Thr Ser Arg
675 680 685
Ile Ile Thr Glu Ser Phe Phe Glu Val Pro Ala Thr Thr Ile Tyr Pro
690 695 700
Val Ser Glu Gln Pro Ser Ala Lys Val Val Pro Thr Lys Phe Val Ser
705 710 715 720
Glu Thr Asp Thr Ser Glu Trp Ile Ser Ser Thr Thr Val Glu Glu Lys
725 730 735
Lys Arg Lys Glu Glu Glu Gly Thr Thr Gly Thr Ala Ser Thr Phe Glu
740 745 750
Val Tyr Ser Ser Thr Gln Arg Ser Asp Gln Leu Ile Leu Pro Phe Glu
755 760 765
Leu Glu Ser Pro Asn Val Ala Thr Ser Ser Asp Ser Gly Thr Arg Lys
770 775 780
Ser Phe Met Ser Leu Thr Thr Pro Thr Gln Ser Glu Arg Glu Met Thr
785 790 795 800
Asp Ser Thr Pro Val Phe Thr Glu Thr Asn Thr Leu Glu Asn Leu Gly
805 810 815
Ala Gln Thr Thr Glu His Ser Ser Ile His Gln Pro Gly Val Gln Glu
820 825 830
Gly Leu Thr Thr Leu Pro Arg Ser Pro Ala Ser Val Phe Met Glu Gln
835 840 845
Gly Ser Gly Glu Ala Ala Ala Asp Pro Glu Thr Thr Thr Val Ser Ser
850 855 860
Phe Ser Leu Asn Val Glu Tyr Ala Ile Gln Ala Glu Lys Glu Val Ala
865 870 875 880
Gly Thr Leu Ser Pro His Val Glu Thr Thr Phe Ser Thr Glu Pro Thr
885 890 895
Gly Leu Val Leu Ser Thr Val Met Asp Arg Val Val Ala Glu Asn Ile
900 905 910
Thr Gln Thr Ser Arg Glu Ile Val Ile Ser Glu Arg Leu Gly Glu Pro
915 920 925
Asn Tyr Gly Ala Glu Ile Arg Gly Phe Ser Thr Gly Phe Pro Leu Glu
930 935 940
Glu Asp Phe Ser Gly Asp Phe Arg Glu Tyr Ser Thr Val Ser His Pro
945 950 955 960
Ile Ala Lys Glu Glu Thr Val Met Met Glu Gly Ser Gly Asp Ala Ala
965 970 975
Phe Arg Asp Thr Gln Thr Ser Pro Ser Thr Val Pro Thr Ser Val His
980 985 990
Ile Ser His Ile Ser Asp Ser Glu Gly Pro Ser Ser Thr Met Val Ser
995 1000 1005
Thr Ser Ala Phe Pro Trp Glu Glu Phe Thr Ser Ser Ala Glu Gly
1010 1015 1020
Ser Gly Glu Gln Leu Val Thr Val Ser Ser Ser Val Val Pro Val
1025 1030 1035
Leu Pro Ser Ala Val Gln Lys Phe Ser Gly Thr Ala Ser Ser Ile
1040 1045 1050
Ile Asp Glu Gly Leu Gly Glu Val Gly Thr Val Asn Glu Ile Asp
1055 1060 1065
Arg Arg Ser Thr Ile Leu Pro Thr Ala Glu Val Glu Gly Thr Lys
1070 1075 1080
Ala Pro Val Glu Lys Glu Glu Val Lys Val Ser Gly Thr Val Ser
1085 1090 1095
Thr Asn Phe Pro Gln Thr Ile Glu Pro Ala Lys Leu Trp Ser Arg
1100 1105 1110
Gln Glu Val Asn Pro Val Arg Gln Glu Ile Glu Ser Glu Thr Thr
1115 1120 1125
Ser Glu Glu Gln Ile Gln Glu Glu Lys Ser Phe Glu Ser Pro Gln
1130 1135 1140
Asn Ser Pro Ala Thr Glu Gln Thr Ile Phe Asp Ser Gln Thr Phe
1145 1150 1155
Thr Glu Thr Glu Leu Lys Thr Thr Asp Tyr Ser Val Leu Thr Thr
1160 1165 1170
Lys Lys Thr Tyr Ser Asp Asp Lys Glu Met Lys Glu Glu Asp Thr
1175 1180 1185
Ser Leu Val Asn Met Ser Thr Pro Asp Pro Asp Ala Asn Gly Leu
1190 1195 1200
Glu Ser Tyr Thr Thr Leu Pro Glu Ala Thr Glu Lys Ser His Phe
1205 1210 1215
Phe Leu Ala Thr Ala Leu Val Thr Glu Ser Ile Pro Ala Glu His
1220 1225 1230
Val Val Thr Asp Ser Pro Ile Lys Lys Glu Glu Ser Thr Lys His
1235 1240 1245
Phe Pro Lys Gly Met Arg Pro Thr Ile Gln Glu Ser Asp Thr Glu
1250 1255 1260
Leu Leu Phe Ser Gly Leu Gly Ser Gly Glu Glu Val Leu Pro Thr
1265 1270 1275
Leu Pro Thr Glu Ser Val Asn Phe Thr Glu Val Glu Gln Ile Asn
1280 1285 1290
Asn Thr Leu Tyr Pro His Thr Ser Gln Val Glu Ser Thr Ser Ser
1295 1300 1305
Asp Lys Ile Glu Asp Phe Asn Arg Met Glu Asn Val Ala Lys Glu
1310 1315 1320
Val Gly Pro Leu Val Ser Gln Thr Asp Ile Phe Glu Gly Ser Gly
1325 1330 1335
Ser Val Thr Ser Thr Thr Leu Ile Glu Ile Leu Ser Asp Thr Gly
1340 1345 1350
Ala Glu Gly Pro Thr Val Ala Pro Leu Pro Phe Ser Thr Asp Ile
1355 1360 1365
Gly His Pro Gln Asn Gln Thr Val Arg Trp Ala Glu Glu Ile Gln
1370 1375 1380
Thr Ser Arg Pro Gln Thr Ile Thr Glu Gln Asp Ser Asn Lys Asn
1385 1390 1395
Ser Ser Thr Ala Glu Ile Asn Glu Thr Thr Thr Ser Ser Thr Asp
1400 1405 1410
Phe Leu Ala Arg Ala Tyr Gly Phe Glu Met Ala Lys Glu Phe Val
1415 1420 1425
Thr Ser Ala Pro Lys Pro Ser Asp Leu Tyr Tyr Glu Pro Ser Gly
1430 1435 1440
Glu Gly Ser Gly Glu Val Asp Ile Val Asp Ser Phe His Thr Ser
1445 1450 1455
Ala Thr Thr Gln Ala Thr Arg Gln Glu Ser Ser Thr Thr Phe Val
1460 1465 1470
Ser Asp Gly Ser Leu Glu Lys His Pro Glu Val Pro Ser Ala Lys
1475 1480 1485
Ala Val Thr Ala Asp Gly Phe Pro Thr Val Ser Val Met Leu Pro
1490 1495 1500
Leu His Ser Glu Gln Asn Lys Ser Ser Pro Asp Pro Thr Ser Thr
1505 1510 1515
Leu Ser Asn Thr Val Ser Tyr Glu Arg Ser Thr Asp Gly Ser Phe
1520 1525 1530
Gln Asp Arg Phe Arg Glu Phe Glu Asp Ser Thr Leu Lys Pro Asn
1535 1540 1545
Arg Lys Lys Pro Thr Glu Asn Ile Ile Ile Asp Leu Asp Lys Glu
1550 1555 1560
Asp Lys Asp Leu Ile Leu Thr Ile Thr Glu Ser Thr Ile Leu Glu
1565 1570 1575
Ile Leu Pro Glu Leu Thr Ser Asp Lys Asn Thr Ile Ile Asp Ile
1580 1585 1590
Asp His Thr Lys Pro Val Tyr Glu Asp Ile Leu Gly Met Gln Thr
1595 1600 1605
Asp Ile Asp Thr Glu Val Pro Ser Glu Pro His Asp Ser Asn Asp
1610 1615 1620
Glu Ser Asn Asp Asp Ser Thr Gln Val Gln Glu Ile Tyr Glu Ala
1625 1630 1635
Ala Val Asn Leu Ser Leu Thr Glu Glu Thr Phe Glu Gly Ser Ala
1640 1645 1650
Asp Val Leu Ala Ser Tyr Thr Gln Ala Thr His Asp Glu Ser Met
1655 1660 1665
Thr Tyr Glu Asp Arg Ser Gln Leu Asp His Met Gly Phe His Phe
1670 1675 1680
Thr Thr Gly Ile Pro Ala Pro Ser Thr Glu Thr Glu Leu Asp Val
1685 1690 1695
Leu Leu Pro Thr Ala Thr Ser Leu Pro Ile Pro Arg Lys Ser Ala
1700 1705 1710
Thr Val Ile Pro Glu Ile Glu Gly Ile Lys Ala Glu Ala Lys Ala
1715 1720 1725
Leu Asp Asp Met Phe Glu Ser Ser Thr Leu Ser Asp Gly Gln Ala
1730 1735 1740
Ile Ala Asp Gln Ser Glu Ile Ile Pro Thr Leu Gly Gln Phe Glu
1745 1750 1755
Arg Thr Gln Glu Glu Tyr Glu Asp Lys Lys His Ala Gly Pro Ser
1760 1765 1770
Phe Gln Pro Glu Phe Ser Ser Gly Ala Glu Glu Ala Leu Val Asp
1775 1780 1785
His Thr Pro Tyr Leu Ser Ile Ala Thr Thr His Leu Met Asp Gln
1790 1795 1800
Ser Val Thr Glu Val Pro Asp Val Met Glu Gly Ser Asn Pro Pro
1805 1810 1815
Tyr Tyr Thr Asp Thr Thr Leu Ala Val Ser Thr Phe Ala Lys Leu
1820 1825 1830
Ser Ser Gln Thr Pro Ser Ser Pro Leu Thr Ile Tyr Ser Gly Ser
1835 1840 1845
Glu Ala Ser Gly His Thr Glu Ile Pro Gln Pro Ser Ala Leu Pro
1850 1855 1860
Gly Ile Asp Val Gly Ser Ser Val Met Ser Pro Gln Asp Ser Phe
1865 1870 1875
Lys Glu Ile His Val Asn Ile Glu Ala Thr Phe Lys Pro Ser Ser
1880 1885 1890
Glu Glu Tyr Leu His Ile Thr Glu Pro Pro Ser Leu Ser Pro Asp
1895 1900 1905
Thr Lys Leu Glu Pro Ser Glu Asp Asp Gly Lys Pro Glu Leu Leu
1910 1915 1920
Glu Glu Met Glu Ala Ser Pro Thr Glu Leu Ile Ala Val Glu Gly
1925 1930 1935
Thr Glu Ile Leu Gln Asp Phe Gln Asn Lys Thr Asp Gly Gln Val
1940 1945 1950
Ser Gly Glu Ala Ile Lys Met Phe Pro Thr Ile Lys Thr Pro Glu
1955 1960 1965
Ala Gly Thr Val Ile Thr Thr Ala Asp Glu Ile Glu Leu Glu Gly
1970 1975 1980
Ala Thr Gln Trp Pro His Ser Thr Ser Ala Ser Ala Thr Tyr Gly
1985 1990 1995
Val Glu Ala Gly Val Val Pro Trp Leu Ser Pro Gln Thr Ser Glu
2000 2005 2010
Arg Pro Thr Leu Ser Ser Ser Pro Glu Ile Asn Pro Glu Thr Gln
2015 2020 2025
Ala Ala Leu Ile Arg Gly Gln Asp Ser Thr Ile Ala Ala Ser Glu
2030 2035 2040
Gln Gln Val Ala Ala Arg Ile Leu Asp Ser Asn Asp Gln Ala Thr
2045 2050 2055
Val Asn Pro Val Glu Phe Asn Thr Glu Val Ala Thr Pro Pro Phe
2060 2065 2070
Ser Leu Leu Glu Thr Ser Asn Glu Thr Asp Phe Leu Ile Gly Ile
2075 2080 2085
Asn Glu Glu Ser Val Glu Gly Thr Ala Ile Tyr Leu Pro Gly Pro
2090 2095 2100
Asp Arg Cys Lys Met Asn Pro Cys Leu Asn Gly Gly Thr Cys Tyr
2105 2110 2115
Pro Thr Glu Thr Ser Tyr Val Cys Thr Cys Val Pro Gly Tyr Ser
2120 2125 2130
Gly Asp Gln Cys Glu Leu Asp Phe Asp Glu Cys His Ser Asn Pro
2135 2140 2145
Cys Arg Asn Gly Ala Thr Cys Val Asp Gly Phe Asn Thr Phe Arg
2150 2155 2160
Cys Leu Cys Leu Pro Ser Tyr Val Gly Ala Leu Cys Glu Gln Asp
2165 2170 2175
Thr Glu Thr Cys Asp Tyr Gly Trp His Lys Phe Gln Gly Gln Cys
2180 2185 2190
Tyr Lys Tyr Phe Ala His Arg Arg Thr Trp Asp Ala Ala Glu Arg
2195 2200 2205
Glu Cys Arg Leu Gln Gly Ala His Leu Thr Ser Ile Leu Ser His
2210 2215 2220
Glu Glu Gln Met Phe Val Asn Arg Val Gly His Asp Tyr Gln Trp
2225 2230 2235
Ile Gly Leu Asn Asp Lys Met Phe Glu His Asp Phe Arg Trp Thr
2240 2245 2250
Asp Gly Ser Thr Leu Gln Tyr Glu Asn Trp Arg Pro Asn Gln Pro
2255 2260 2265
Asp Ser Phe Phe Ser Ala Gly Glu Asp Cys Val Val Ile Ile Trp
2270 2275 2280
His Glu Asn Gly Gln Trp Asn Asp Val Pro Cys Asn Tyr His Leu
2285 2290 2295
Thr Tyr Thr Cys Lys Lys Gly Thr Val Ala Cys Gly Gln Pro Pro
2300 2305 2310
Val Val Glu Asn Ala Lys Thr Phe Gly Lys Met Lys Pro Arg Tyr
2315 2320 2325
Glu Ile Asn Ser Leu Ile Arg Tyr His Cys Lys Asp Gly Phe Ile
2330 2335 2340
Gln Arg His Leu Pro Thr Ile Arg Cys Leu Gly Asn Gly Arg Trp
2345 2350 2355
Ala Ile Pro Lys Ile Thr Cys Met Asn Pro Ser Ala Tyr Gln Arg
2360 2365 2370
Thr Tyr Ser Met Lys Tyr Phe Lys Asn Ser Ser Ser Ala Lys Asp
2375 2380 2385
Asn Ser Ile Asn Thr Ser Lys His Asp His Arg Trp Ser Arg Arg
2390 2395 2400
Trp Gln Glu Ser Arg Arg
2405
<210> 128
<211> 1642
<212> PRT
<213> Homo sapiens
<400> 128
Met Phe Ile Asn Ile Lys Ser Ile Leu Trp Met Cys Ser Thr Leu Ile
1 5 10 15
Val Thr His Ala Leu His Lys Val Lys Val Gly Lys Ser Pro Pro Val
20 25 30
Arg Gly Ser Leu Ser Gly Lys Val Ser Leu Pro Cys His Phe Ser Thr
35 40 45
Met Pro Thr Leu Pro Pro Ser Tyr Asn Thr Ser Glu Phe Leu Arg Ile
50 55 60
Lys Trp Ser Lys Ile Glu Val Asp Lys Asn Gly Lys Asp Leu Lys Glu
65 70 75 80
Thr Thr Val Leu Val Ala Gln Asn Gly Asn Ile Lys Ile Gly Gln Asp
85 90 95
Tyr Lys Gly Arg Val Ser Val Pro Thr His Pro Glu Ala Val Gly Asp
100 105 110
Ala Ser Leu Thr Val Val Lys Leu Leu Ala Ser Asp Ala Gly Leu Tyr
115 120 125
Arg Cys Asp Val Met Tyr Gly Ile Glu Asp Thr Gln Asp Thr Val Ser
130 135 140
Leu Thr Val Asp Gly Val Val Phe His Tyr Arg Ala Ala Thr Ser Arg
145 150 155 160
Tyr Thr Leu Asn Phe Glu Ala Ala Gln Lys Ala Cys Leu Asp Val Gly
165 170 175
Ala Val Ile Ala Thr Pro Glu Gln Leu Phe Ala Ala Tyr Glu Asp Gly
180 185 190
Phe Glu Gln Cys Asp Ala Gly Trp Leu Ala Asp Gln Thr Val Arg Tyr
195 200 205
Pro Ile Arg Ala Pro Arg Val Gly Cys Tyr Gly Asp Lys Met Gly Lys
210 215 220
Ala Gly Val Arg Thr Tyr Gly Phe Arg Ser Pro Gln Glu Thr Tyr Asp
225 230 235 240
Val Tyr Cys Tyr Val Asp His Leu Asp Gly Asp Val Phe His Leu Thr
245 250 255
Val Pro Ser Lys Phe Thr Phe Glu Glu Ala Ala Lys Glu Cys Glu Asn
260 265 270
Gln Asp Ala Arg Leu Ala Thr Val Gly Glu Leu Gln Ala Ala Trp Arg
275 280 285
Asn Gly Phe Asp Gln Cys Asp Tyr Gly Trp Leu Ser Asp Ala Ser Val
290 295 300
Arg His Pro Val Thr Val Ala Arg Ala Gln Cys Gly Gly Gly Leu Leu
305 310 315 320
Gly Val Arg Thr Leu Tyr Arg Phe Glu Asn Gln Thr Gly Phe Pro Pro
325 330 335
Pro Asp Ser Arg Phe Asp Ala Tyr Cys Phe Lys Pro Lys Glu Ala Thr
340 345 350
Thr Ile Asp Leu Ser Ile Leu Ala Glu Thr Ala Ser Pro Ser Leu Ser
355 360 365
Lys Glu Pro Gln Met Val Ser Asp Arg Thr Thr Pro Ile Ile Pro Leu
370 375 380
Val Asp Glu Leu Pro Val Ile Pro Thr Glu Phe Pro Pro Val Gly Asn
385 390 395 400
Ile Val Ser Phe Glu Gln Lys Ala Thr Val Gln Pro Gln Ala Ile Thr
405 410 415
Asp Ser Leu Ala Thr Lys Leu Pro Thr Pro Thr Gly Ser Thr Lys Lys
420 425 430
Pro Trp Asp Met Asp Asp Tyr Ser Pro Ser Ala Ser Gly Pro Leu Gly
435 440 445
Lys Leu Asp Ile Ser Glu Ile Lys Glu Glu Val Leu Gln Ser Thr Thr
450 455 460
Gly Val Ser His Tyr Ala Thr Asp Ser Trp Asp Gly Val Val Glu Asp
465 470 475 480
Lys Gln Thr Gln Glu Ser Val Thr Gln Ile Glu Gln Ile Glu Val Gly
485 490 495
Pro Leu Val Thr Ser Met Glu Ile Leu Lys His Ile Pro Ser Lys Glu
500 505 510
Phe Pro Val Thr Glu Thr Pro Leu Val Thr Ala Arg Met Ile Leu Glu
515 520 525
Ser Lys Thr Glu Lys Lys Met Val Ser Thr Val Ser Glu Leu Val Thr
530 535 540
Thr Gly His Tyr Gly Phe Thr Leu Gly Glu Glu Asp Asp Glu Asp Arg
545 550 555 560
Thr Leu Thr Val Gly Ser Asp Glu Ser Thr Leu Ile Phe Asp Gln Ile
565 570 575
Pro Glu Val Ile Thr Val Ser Lys Thr Ser Glu Asp Thr Ile His Thr
580 585 590
His Leu Glu Asp Leu Glu Ser Val Ser Ala Ser Thr Thr Val Ser Pro
595 600 605
Leu Ile Met Pro Asp Asn Asn Gly Ser Ser Met Asp Asp Trp Glu Glu
610 615 620
Arg Gln Thr Ser Gly Arg Ile Thr Glu Glu Phe Leu Gly Lys Tyr Leu
625 630 635 640
Ser Thr Thr Pro Phe Pro Ser Gln His Arg Thr Glu Ile Glu Leu Phe
645 650 655
Pro Tyr Ser Gly Asp Lys Ile Leu Val Glu Gly Ile Ser Thr Val Ile
660 665 670
Tyr Pro Ser Leu Gln Thr Glu Met Thr His Arg Arg Glu Arg Thr Glu
675 680 685
Thr Leu Ile Pro Glu Met Arg Thr Asp Thr Tyr Thr Asp Glu Ile Gln
690 695 700
Glu Glu Ile Thr Lys Ser Pro Phe Met Gly Lys Thr Glu Glu Glu Val
705 710 715 720
Phe Ser Gly Met Lys Leu Ser Thr Ser Leu Ser Glu Pro Ile His Val
725 730 735
Thr Glu Ser Ser Val Glu Met Thr Lys Ser Phe Asp Phe Pro Thr Leu
740 745 750
Ile Thr Lys Leu Ser Ala Glu Pro Thr Glu Val Arg Asp Met Glu Glu
755 760 765
Asp Phe Thr Ala Thr Pro Gly Thr Thr Lys Tyr Asp Glu Asn Ile Thr
770 775 780
Thr Val Leu Leu Ala His Gly Thr Leu Ser Val Glu Ala Ala Thr Val
785 790 795 800
Ser Lys Trp Ser Trp Asp Glu Asp Asn Thr Thr Ser Lys Pro Leu Glu
805 810 815
Ser Thr Glu Pro Ser Ala Ser Ser Lys Leu Pro Pro Ala Leu Leu Thr
820 825 830
Thr Val Gly Met Asn Gly Lys Asp Lys Asp Ile Pro Ser Phe Thr Glu
835 840 845
Asp Gly Ala Asp Glu Phe Thr Leu Ile Pro Asp Ser Thr Gln Lys Gln
850 855 860
Leu Glu Glu Val Thr Asp Glu Asp Ile Ala Ala His Gly Lys Phe Thr
865 870 875 880
Ile Arg Phe Gln Pro Thr Thr Ser Thr Gly Ile Ala Glu Lys Ser Thr
885 890 895
Leu Arg Asp Ser Thr Thr Glu Glu Lys Val Pro Pro Ile Thr Ser Thr
900 905 910
Glu Gly Gln Val Tyr Ala Thr Met Glu Gly Ser Ala Leu Gly Glu Val
915 920 925
Glu Asp Val Asp Leu Ser Lys Pro Val Ser Thr Val Pro Gln Phe Ala
930 935 940
His Thr Ser Glu Val Glu Gly Leu Ala Phe Val Ser Tyr Ser Ser Thr
945 950 955 960
Gln Glu Pro Thr Thr Tyr Val Asp Ser Ser His Thr Ile Pro Leu Ser
965 970 975
Val Ile Pro Lys Thr Asp Trp Gly Val Leu Val Pro Ser Val Pro Ser
980 985 990
Glu Asp Glu Val Leu Gly Glu Pro Ser Gln Asp Ile Leu Val Ile Asp
995 1000 1005
Gln Thr Arg Leu Glu Ala Thr Ile Ser Pro Glu Thr Met Arg Thr
1010 1015 1020
Thr Lys Ile Thr Glu Gly Thr Thr Gln Glu Glu Phe Pro Trp Lys
1025 1030 1035
Glu Gln Thr Ala Glu Lys Pro Val Pro Ala Leu Ser Ser Thr Ala
1040 1045 1050
Trp Thr Pro Lys Glu Ala Val Thr Pro Leu Asp Glu Gln Glu Gly
1055 1060 1065
Asp Gly Ser Ala Tyr Thr Val Ser Glu Asp Glu Leu Leu Thr Gly
1070 1075 1080
Ser Glu Arg Val Pro Val Leu Glu Thr Thr Pro Val Gly Lys Ile
1085 1090 1095
Asp His Ser Val Ser Tyr Pro Pro Gly Ala Val Thr Glu His Lys
1100 1105 1110
Val Lys Thr Asp Glu Val Val Thr Leu Thr Pro Arg Ile Gly Pro
1115 1120 1125
Lys Val Ser Leu Ser Pro Gly Pro Glu Gln Lys Tyr Glu Thr Glu
1130 1135 1140
Gly Ser Ser Thr Thr Gly Phe Thr Ser Ser Leu Ser Pro Phe Ser
1145 1150 1155
Thr His Ile Thr Gln Leu Met Glu Glu Thr Thr Thr Glu Lys Thr
1160 1165 1170
Ser Leu Glu Asp Ile Asp Leu Gly Ser Gly Leu Phe Glu Lys Pro
1175 1180 1185
Lys Ala Thr Glu Leu Ile Glu Phe Ser Thr Ile Lys Val Thr Val
1190 1195 1200
Pro Ser Asp Ile Thr Thr Ala Phe Ser Ser Val Asp Arg Leu His
1205 1210 1215
Thr Thr Ser Ala Phe Lys Pro Ser Ser Ala Ile Thr Lys Lys Pro
1220 1225 1230
Pro Leu Ile Asp Arg Glu Pro Gly Glu Glu Thr Thr Ser Asp Met
1235 1240 1245
Val Ile Ile Gly Glu Ser Thr Ser His Val Pro Pro Thr Thr Leu
1250 1255 1260
Glu Asp Ile Val Ala Lys Glu Thr Glu Thr Asp Ile Asp Arg Glu
1265 1270 1275
Tyr Phe Thr Thr Ser Ser Pro Pro Ala Thr Gln Pro Thr Arg Pro
1280 1285 1290
Pro Thr Val Glu Asp Lys Glu Ala Phe Gly Pro Gln Ala Leu Ser
1295 1300 1305
Thr Pro Gln Pro Pro Ala Ser Thr Lys Phe His Pro Asp Ile Asn
1310 1315 1320
Val Tyr Ile Ile Glu Val Arg Glu Asn Lys Thr Gly Pro Asp Arg
1325 1330 1335
Cys Lys Met Asn Pro Cys Leu Asn Gly Gly Thr Cys Tyr Pro Thr
1340 1345 1350
Glu Thr Ser Tyr Val Cys Thr Cys Val Pro Gly Tyr Ser Gly Asp
1355 1360 1365
Gln Cys Glu Leu Asp Phe Asp Glu Cys His Ser Asn Pro Cys Arg
1370 1375 1380
Asn Gly Ala Thr Cys Val Asp Gly Phe Asn Thr Phe Arg Cys Leu
1385 1390 1395
Cys Leu Pro Ser Tyr Val Gly Ala Leu Cys Glu Gln Asp Thr Glu
1400 1405 1410
Thr Cys Asp Tyr Gly Trp His Lys Phe Gln Gly Gln Cys Tyr Lys
1415 1420 1425
Tyr Phe Ala His Arg Arg Thr Trp Asp Ala Ala Glu Arg Glu Cys
1430 1435 1440
Arg Leu Gln Gly Ala His Leu Thr Ser Ile Leu Ser His Glu Glu
1445 1450 1455
Gln Met Phe Val Asn Arg Val Gly His Asp Tyr Gln Trp Ile Gly
1460 1465 1470
Leu Asn Asp Lys Met Phe Glu His Asp Phe Arg Trp Thr Asp Gly
1475 1480 1485
Ser Thr Leu Gln Tyr Glu Asn Trp Arg Pro Asn Gln Pro Asp Ser
1490 1495 1500
Phe Phe Ser Ala Gly Glu Asp Cys Val Val Ile Ile Trp His Glu
1505 1510 1515
Asn Gly Gln Trp Asn Asp Val Pro Cys Asn Tyr His Leu Thr Tyr
1520 1525 1530
Thr Cys Lys Lys Gly Thr Val Ala Cys Gly Gln Pro Pro Val Val
1535 1540 1545
Glu Asn Ala Lys Thr Phe Gly Lys Met Lys Pro Arg Tyr Glu Ile
1550 1555 1560
Asn Ser Leu Ile Arg Tyr His Cys Lys Asp Gly Phe Ile Gln Arg
1565 1570 1575
His Leu Pro Thr Ile Arg Cys Leu Gly Asn Gly Arg Trp Ala Ile
1580 1585 1590
Pro Lys Ile Thr Cys Met Asn Pro Ser Ala Tyr Gln Arg Thr Tyr
1595 1600 1605
Ser Met Lys Tyr Phe Lys Asn Ser Ser Ser Ala Lys Asp Asn Ser
1610 1615 1620
Ile Asn Thr Ser Lys His Asp His Arg Trp Ser Arg Arg Trp Gln
1625 1630 1635
Glu Ser Arg Arg
1640
<210> 129
<211> 3396
<212> PRT
<213> Homo sapiens
<400> 129
Met Phe Ile Asn Ile Lys Ser Ile Leu Trp Met Cys Ser Thr Leu Ile
1 5 10 15
Val Thr His Ala Leu His Lys Val Lys Val Gly Lys Ser Pro Pro Val
20 25 30
Arg Gly Ser Leu Ser Gly Lys Val Ser Leu Pro Cys His Phe Ser Thr
35 40 45
Met Pro Thr Leu Pro Pro Ser Tyr Asn Thr Ser Glu Phe Leu Arg Ile
50 55 60
Lys Trp Ser Lys Ile Glu Val Asp Lys Asn Gly Lys Asp Leu Lys Glu
65 70 75 80
Thr Thr Val Leu Val Ala Gln Asn Gly Asn Ile Lys Ile Gly Gln Asp
85 90 95
Tyr Lys Gly Arg Val Ser Val Pro Thr His Pro Glu Ala Val Gly Asp
100 105 110
Ala Ser Leu Thr Val Val Lys Leu Leu Ala Ser Asp Ala Gly Leu Tyr
115 120 125
Arg Cys Asp Val Met Tyr Gly Ile Glu Asp Thr Gln Asp Thr Val Ser
130 135 140
Leu Thr Val Asp Gly Val Val Phe His Tyr Arg Ala Ala Thr Ser Arg
145 150 155 160
Tyr Thr Leu Asn Phe Glu Ala Ala Gln Lys Ala Cys Leu Asp Val Gly
165 170 175
Ala Val Ile Ala Thr Pro Glu Gln Leu Phe Ala Ala Tyr Glu Asp Gly
180 185 190
Phe Glu Gln Cys Asp Ala Gly Trp Leu Ala Asp Gln Thr Val Arg Tyr
195 200 205
Pro Ile Arg Ala Pro Arg Val Gly Cys Tyr Gly Asp Lys Met Gly Lys
210 215 220
Ala Gly Val Arg Thr Tyr Gly Phe Arg Ser Pro Gln Glu Thr Tyr Asp
225 230 235 240
Val Tyr Cys Tyr Val Asp His Leu Asp Gly Asp Val Phe His Leu Thr
245 250 255
Val Pro Ser Lys Phe Thr Phe Glu Glu Ala Ala Lys Glu Cys Glu Asn
260 265 270
Gln Asp Ala Arg Leu Ala Thr Val Gly Glu Leu Gln Ala Ala Trp Arg
275 280 285
Asn Gly Phe Asp Gln Cys Asp Tyr Gly Trp Leu Ser Asp Ala Ser Val
290 295 300
Arg His Pro Val Thr Val Ala Arg Ala Gln Cys Gly Gly Gly Leu Leu
305 310 315 320
Gly Val Arg Thr Leu Tyr Arg Phe Glu Asn Gln Thr Gly Phe Pro Pro
325 330 335
Pro Asp Ser Arg Phe Asp Ala Tyr Cys Phe Lys Pro Lys Glu Ala Thr
340 345 350
Thr Ile Asp Leu Ser Ile Leu Ala Glu Thr Ala Ser Pro Ser Leu Ser
355 360 365
Lys Glu Pro Gln Met Val Ser Asp Arg Thr Thr Pro Ile Ile Pro Leu
370 375 380
Val Asp Glu Leu Pro Val Ile Pro Thr Glu Phe Pro Pro Val Gly Asn
385 390 395 400
Ile Val Ser Phe Glu Gln Lys Ala Thr Val Gln Pro Gln Ala Ile Thr
405 410 415
Asp Ser Leu Ala Thr Lys Leu Pro Thr Pro Thr Gly Ser Thr Lys Lys
420 425 430
Pro Trp Asp Met Asp Asp Tyr Ser Pro Ser Ala Ser Gly Pro Leu Gly
435 440 445
Lys Leu Asp Ile Ser Glu Ile Lys Glu Glu Val Leu Gln Ser Thr Thr
450 455 460
Gly Val Ser His Tyr Ala Thr Asp Ser Trp Asp Gly Val Val Glu Asp
465 470 475 480
Lys Gln Thr Gln Glu Ser Val Thr Gln Ile Glu Gln Ile Glu Val Gly
485 490 495
Pro Leu Val Thr Ser Met Glu Ile Leu Lys His Ile Pro Ser Lys Glu
500 505 510
Phe Pro Val Thr Glu Thr Pro Leu Val Thr Ala Arg Met Ile Leu Glu
515 520 525
Ser Lys Thr Glu Lys Lys Met Val Ser Thr Val Ser Glu Leu Val Thr
530 535 540
Thr Gly His Tyr Gly Phe Thr Leu Gly Glu Glu Asp Asp Glu Asp Arg
545 550 555 560
Thr Leu Thr Val Gly Ser Asp Glu Ser Thr Leu Ile Phe Asp Gln Ile
565 570 575
Pro Glu Val Ile Thr Val Ser Lys Thr Ser Glu Asp Thr Ile His Thr
580 585 590
His Leu Glu Asp Leu Glu Ser Val Ser Ala Ser Thr Thr Val Ser Pro
595 600 605
Leu Ile Met Pro Asp Asn Asn Gly Ser Ser Met Asp Asp Trp Glu Glu
610 615 620
Arg Gln Thr Ser Gly Arg Ile Thr Glu Glu Phe Leu Gly Lys Tyr Leu
625 630 635 640
Ser Thr Thr Pro Phe Pro Ser Gln His Arg Thr Glu Ile Glu Leu Phe
645 650 655
Pro Tyr Ser Gly Asp Lys Ile Leu Val Glu Gly Ile Ser Thr Val Ile
660 665 670
Tyr Pro Ser Leu Gln Thr Glu Met Thr His Arg Arg Glu Arg Thr Glu
675 680 685
Thr Leu Ile Pro Glu Met Arg Thr Asp Thr Tyr Thr Asp Glu Ile Gln
690 695 700
Glu Glu Ile Thr Lys Ser Pro Phe Met Gly Lys Thr Glu Glu Glu Val
705 710 715 720
Phe Ser Gly Met Lys Leu Ser Thr Ser Leu Ser Glu Pro Ile His Val
725 730 735
Thr Glu Ser Ser Val Glu Met Thr Lys Ser Phe Asp Phe Pro Thr Leu
740 745 750
Ile Thr Lys Leu Ser Ala Glu Pro Thr Glu Val Arg Asp Met Glu Glu
755 760 765
Asp Phe Thr Ala Thr Pro Gly Thr Thr Lys Tyr Asp Glu Asn Ile Thr
770 775 780
Thr Val Leu Leu Ala His Gly Thr Leu Ser Val Glu Ala Ala Thr Val
785 790 795 800
Ser Lys Trp Ser Trp Asp Glu Asp Asn Thr Thr Ser Lys Pro Leu Glu
805 810 815
Ser Thr Glu Pro Ser Ala Ser Ser Lys Leu Pro Pro Ala Leu Leu Thr
820 825 830
Thr Val Gly Met Asn Gly Lys Asp Lys Asp Ile Pro Ser Phe Thr Glu
835 840 845
Asp Gly Ala Asp Glu Phe Thr Leu Ile Pro Asp Ser Thr Gln Lys Gln
850 855 860
Leu Glu Glu Val Thr Asp Glu Asp Ile Ala Ala His Gly Lys Phe Thr
865 870 875 880
Ile Arg Phe Gln Pro Thr Thr Ser Thr Gly Ile Ala Glu Lys Ser Thr
885 890 895
Leu Arg Asp Ser Thr Thr Glu Glu Lys Val Pro Pro Ile Thr Ser Thr
900 905 910
Glu Gly Gln Val Tyr Ala Thr Met Glu Gly Ser Ala Leu Gly Glu Val
915 920 925
Glu Asp Val Asp Leu Ser Lys Pro Val Ser Thr Val Pro Gln Phe Ala
930 935 940
His Thr Ser Glu Val Glu Gly Leu Ala Phe Val Ser Tyr Ser Ser Thr
945 950 955 960
Gln Glu Pro Thr Thr Tyr Val Asp Ser Ser His Thr Ile Pro Leu Ser
965 970 975
Val Ile Pro Lys Thr Asp Trp Gly Val Leu Val Pro Ser Val Pro Ser
980 985 990
Glu Asp Glu Val Leu Gly Glu Pro Ser Gln Asp Ile Leu Val Ile Asp
995 1000 1005
Gln Thr Arg Leu Glu Ala Thr Ile Ser Pro Glu Thr Met Arg Thr
1010 1015 1020
Thr Lys Ile Thr Glu Gly Thr Thr Gln Glu Glu Phe Pro Trp Lys
1025 1030 1035
Glu Gln Thr Ala Glu Lys Pro Val Pro Ala Leu Ser Ser Thr Ala
1040 1045 1050
Trp Thr Pro Lys Glu Ala Val Thr Pro Leu Asp Glu Gln Glu Gly
1055 1060 1065
Asp Gly Ser Ala Tyr Thr Val Ser Glu Asp Glu Leu Leu Thr Gly
1070 1075 1080
Ser Glu Arg Val Pro Val Leu Glu Thr Thr Pro Val Gly Lys Ile
1085 1090 1095
Asp His Ser Val Ser Tyr Pro Pro Gly Ala Val Thr Glu His Lys
1100 1105 1110
Val Lys Thr Asp Glu Val Val Thr Leu Thr Pro Arg Ile Gly Pro
1115 1120 1125
Lys Val Ser Leu Ser Pro Gly Pro Glu Gln Lys Tyr Glu Thr Glu
1130 1135 1140
Gly Ser Ser Thr Thr Gly Phe Thr Ser Ser Leu Ser Pro Phe Ser
1145 1150 1155
Thr His Ile Thr Gln Leu Met Glu Glu Thr Thr Thr Glu Lys Thr
1160 1165 1170
Ser Leu Glu Asp Ile Asp Leu Gly Ser Gly Leu Phe Glu Lys Pro
1175 1180 1185
Lys Ala Thr Glu Leu Ile Glu Phe Ser Thr Ile Lys Val Thr Val
1190 1195 1200
Pro Ser Asp Ile Thr Thr Ala Phe Ser Ser Val Asp Arg Leu His
1205 1210 1215
Thr Thr Ser Ala Phe Lys Pro Ser Ser Ala Ile Thr Lys Lys Pro
1220 1225 1230
Pro Leu Ile Asp Arg Glu Pro Gly Glu Glu Thr Thr Ser Asp Met
1235 1240 1245
Val Ile Ile Gly Glu Ser Thr Ser His Val Pro Pro Thr Thr Leu
1250 1255 1260
Glu Asp Ile Val Ala Lys Glu Thr Glu Thr Asp Ile Asp Arg Glu
1265 1270 1275
Tyr Phe Thr Thr Ser Ser Pro Pro Ala Thr Gln Pro Thr Arg Pro
1280 1285 1290
Pro Thr Val Glu Asp Lys Glu Ala Phe Gly Pro Gln Ala Leu Ser
1295 1300 1305
Thr Pro Gln Pro Pro Ala Ser Thr Lys Phe His Pro Asp Ile Asn
1310 1315 1320
Val Tyr Ile Ile Glu Val Arg Glu Asn Lys Thr Gly Arg Met Ser
1325 1330 1335
Asp Leu Ser Val Ile Gly His Pro Ile Asp Ser Glu Ser Lys Glu
1340 1345 1350
Asp Glu Pro Cys Ser Glu Glu Thr Asp Pro Val His Asp Leu Met
1355 1360 1365
Ala Glu Ile Leu Pro Glu Phe Pro Asp Ile Ile Glu Ile Asp Leu
1370 1375 1380
Tyr His Ser Glu Glu Asn Glu Glu Glu Glu Glu Glu Cys Ala Asn
1385 1390 1395
Ala Thr Asp Val Thr Thr Thr Pro Ser Val Gln Tyr Ile Asn Gly
1400 1405 1410
Lys His Leu Val Thr Thr Val Pro Lys Asp Pro Glu Ala Ala Glu
1415 1420 1425
Ala Arg Arg Gly Gln Phe Glu Ser Val Ala Pro Ser Gln Asn Phe
1430 1435 1440
Ser Asp Ser Ser Glu Ser Asp Thr His Pro Phe Val Ile Ala Lys
1445 1450 1455
Thr Glu Leu Ser Thr Ala Val Gln Pro Asn Glu Ser Thr Glu Thr
1460 1465 1470
Thr Glu Ser Leu Glu Val Thr Trp Lys Pro Glu Thr Tyr Pro Glu
1475 1480 1485
Thr Ser Glu His Phe Ser Gly Gly Glu Pro Asp Val Phe Pro Thr
1490 1495 1500
Val Pro Phe His Glu Glu Phe Glu Ser Gly Thr Ala Lys Lys Gly
1505 1510 1515
Ala Glu Ser Val Thr Glu Arg Asp Thr Glu Val Gly His Gln Ala
1520 1525 1530
His Glu His Thr Glu Pro Val Ser Leu Phe Pro Glu Glu Ser Ser
1535 1540 1545
Gly Glu Ile Ala Ile Asp Gln Glu Ser Gln Lys Ile Ala Phe Ala
1550 1555 1560
Arg Ala Thr Glu Val Thr Phe Gly Glu Glu Val Glu Lys Ser Thr
1565 1570 1575
Ser Val Thr Tyr Thr Pro Thr Ile Val Pro Ser Ser Ala Ser Ala
1580 1585 1590
Tyr Val Ser Glu Glu Glu Ala Val Thr Leu Ile Gly Asn Pro Trp
1595 1600 1605
Pro Asp Asp Leu Leu Ser Thr Lys Glu Ser Trp Val Glu Ala Thr
1610 1615 1620
Pro Arg Gln Val Val Glu Leu Ser Gly Ser Ser Ser Ile Pro Ile
1625 1630 1635
Thr Glu Gly Ser Gly Glu Ala Glu Glu Asp Glu Asp Thr Met Phe
1640 1645 1650
Thr Met Val Thr Asp Leu Ser Gln Arg Asn Thr Thr Asp Thr Leu
1655 1660 1665
Ile Thr Leu Asp Thr Ser Arg Ile Ile Thr Glu Ser Phe Phe Glu
1670 1675 1680
Val Pro Ala Thr Thr Ile Tyr Pro Val Ser Glu Gln Pro Ser Ala
1685 1690 1695
Lys Val Val Pro Thr Lys Phe Val Ser Glu Thr Asp Thr Ser Glu
1700 1705 1710
Trp Ile Ser Ser Thr Thr Val Glu Glu Lys Lys Arg Lys Glu Glu
1715 1720 1725
Glu Gly Thr Thr Gly Thr Ala Ser Thr Phe Glu Val Tyr Ser Ser
1730 1735 1740
Thr Gln Arg Ser Asp Gln Leu Ile Leu Pro Phe Glu Leu Glu Ser
1745 1750 1755
Pro Asn Val Ala Thr Ser Ser Asp Ser Gly Thr Arg Lys Ser Phe
1760 1765 1770
Met Ser Leu Thr Thr Pro Thr Gln Ser Glu Arg Glu Met Thr Asp
1775 1780 1785
Ser Thr Pro Val Phe Thr Glu Thr Asn Thr Leu Glu Asn Leu Gly
1790 1795 1800
Ala Gln Thr Thr Glu His Ser Ser Ile His Gln Pro Gly Val Gln
1805 1810 1815
Glu Gly Leu Thr Thr Leu Pro Arg Ser Pro Ala Ser Val Phe Met
1820 1825 1830
Glu Gln Gly Ser Gly Glu Ala Ala Ala Asp Pro Glu Thr Thr Thr
1835 1840 1845
Val Ser Ser Phe Ser Leu Asn Val Glu Tyr Ala Ile Gln Ala Glu
1850 1855 1860
Lys Glu Val Ala Gly Thr Leu Ser Pro His Val Glu Thr Thr Phe
1865 1870 1875
Ser Thr Glu Pro Thr Gly Leu Val Leu Ser Thr Val Met Asp Arg
1880 1885 1890
Val Val Ala Glu Asn Ile Thr Gln Thr Ser Arg Glu Ile Val Ile
1895 1900 1905
Ser Glu Arg Leu Gly Glu Pro Asn Tyr Gly Ala Glu Ile Arg Gly
1910 1915 1920
Phe Ser Thr Gly Phe Pro Leu Glu Glu Asp Phe Ser Gly Asp Phe
1925 1930 1935
Arg Glu Tyr Ser Thr Val Ser His Pro Ile Ala Lys Glu Glu Thr
1940 1945 1950
Val Met Met Glu Gly Ser Gly Asp Ala Ala Phe Arg Asp Thr Gln
1955 1960 1965
Thr Ser Pro Ser Thr Val Pro Thr Ser Val His Ile Ser His Ile
1970 1975 1980
Ser Asp Ser Glu Gly Pro Ser Ser Thr Met Val Ser Thr Ser Ala
1985 1990 1995
Phe Pro Trp Glu Glu Phe Thr Ser Ser Ala Glu Gly Ser Gly Glu
2000 2005 2010
Gln Leu Val Thr Val Ser Ser Ser Val Val Pro Val Leu Pro Ser
2015 2020 2025
Ala Val Gln Lys Phe Ser Gly Thr Ala Ser Ser Ile Ile Asp Glu
2030 2035 2040
Gly Leu Gly Glu Val Gly Thr Val Asn Glu Ile Asp Arg Arg Ser
2045 2050 2055
Thr Ile Leu Pro Thr Ala Glu Val Glu Gly Thr Lys Ala Pro Val
2060 2065 2070
Glu Lys Glu Glu Val Lys Val Ser Gly Thr Val Ser Thr Asn Phe
2075 2080 2085
Pro Gln Thr Ile Glu Pro Ala Lys Leu Trp Ser Arg Gln Glu Val
2090 2095 2100
Asn Pro Val Arg Gln Glu Ile Glu Ser Glu Thr Thr Ser Glu Glu
2105 2110 2115
Gln Ile Gln Glu Glu Lys Ser Phe Glu Ser Pro Gln Asn Ser Pro
2120 2125 2130
Ala Thr Glu Gln Thr Ile Phe Asp Ser Gln Thr Phe Thr Glu Thr
2135 2140 2145
Glu Leu Lys Thr Thr Asp Tyr Ser Val Leu Thr Thr Lys Lys Thr
2150 2155 2160
Tyr Ser Asp Asp Lys Glu Met Lys Glu Glu Asp Thr Ser Leu Val
2165 2170 2175
Asn Met Ser Thr Pro Asp Pro Asp Ala Asn Gly Leu Glu Ser Tyr
2180 2185 2190
Thr Thr Leu Pro Glu Ala Thr Glu Lys Ser His Phe Phe Leu Ala
2195 2200 2205
Thr Ala Leu Val Thr Glu Ser Ile Pro Ala Glu His Val Val Thr
2210 2215 2220
Asp Ser Pro Ile Lys Lys Glu Glu Ser Thr Lys His Phe Pro Lys
2225 2230 2235
Gly Met Arg Pro Thr Ile Gln Glu Ser Asp Thr Glu Leu Leu Phe
2240 2245 2250
Ser Gly Leu Gly Ser Gly Glu Glu Val Leu Pro Thr Leu Pro Thr
2255 2260 2265
Glu Ser Val Asn Phe Thr Glu Val Glu Gln Ile Asn Asn Thr Leu
2270 2275 2280
Tyr Pro His Thr Ser Gln Val Glu Ser Thr Ser Ser Asp Lys Ile
2285 2290 2295
Glu Asp Phe Asn Arg Met Glu Asn Val Ala Lys Glu Val Gly Pro
2300 2305 2310
Leu Val Ser Gln Thr Asp Ile Phe Glu Gly Ser Gly Ser Val Thr
2315 2320 2325
Ser Thr Thr Leu Ile Glu Ile Leu Ser Asp Thr Gly Ala Glu Gly
2330 2335 2340
Pro Thr Val Ala Pro Leu Pro Phe Ser Thr Asp Ile Gly His Pro
2345 2350 2355
Gln Asn Gln Thr Val Arg Trp Ala Glu Glu Ile Gln Thr Ser Arg
2360 2365 2370
Pro Gln Thr Ile Thr Glu Gln Asp Ser Asn Lys Asn Ser Ser Thr
2375 2380 2385
Ala Glu Ile Asn Glu Thr Thr Thr Ser Ser Thr Asp Phe Leu Ala
2390 2395 2400
Arg Ala Tyr Gly Phe Glu Met Ala Lys Glu Phe Val Thr Ser Ala
2405 2410 2415
Pro Lys Pro Ser Asp Leu Tyr Tyr Glu Pro Ser Gly Glu Gly Ser
2420 2425 2430
Gly Glu Val Asp Ile Val Asp Ser Phe His Thr Ser Ala Thr Thr
2435 2440 2445
Gln Ala Thr Arg Gln Glu Ser Ser Thr Thr Phe Val Ser Asp Gly
2450 2455 2460
Ser Leu Glu Lys His Pro Glu Val Pro Ser Ala Lys Ala Val Thr
2465 2470 2475
Ala Asp Gly Phe Pro Thr Val Ser Val Met Leu Pro Leu His Ser
2480 2485 2490
Glu Gln Asn Lys Ser Ser Pro Asp Pro Thr Ser Thr Leu Ser Asn
2495 2500 2505
Thr Val Ser Tyr Glu Arg Ser Thr Asp Gly Ser Phe Gln Asp Arg
2510 2515 2520
Phe Arg Glu Phe Glu Asp Ser Thr Leu Lys Pro Asn Arg Lys Lys
2525 2530 2535
Pro Thr Glu Asn Ile Ile Ile Asp Leu Asp Lys Glu Asp Lys Asp
2540 2545 2550
Leu Ile Leu Thr Ile Thr Glu Ser Thr Ile Leu Glu Ile Leu Pro
2555 2560 2565
Glu Leu Thr Ser Asp Lys Asn Thr Ile Ile Asp Ile Asp His Thr
2570 2575 2580
Lys Pro Val Tyr Glu Asp Ile Leu Gly Met Gln Thr Asp Ile Asp
2585 2590 2595
Thr Glu Val Pro Ser Glu Pro His Asp Ser Asn Asp Glu Ser Asn
2600 2605 2610
Asp Asp Ser Thr Gln Val Gln Glu Ile Tyr Glu Ala Ala Val Asn
2615 2620 2625
Leu Ser Leu Thr Glu Glu Thr Phe Glu Gly Ser Ala Asp Val Leu
2630 2635 2640
Ala Ser Tyr Thr Gln Ala Thr His Asp Glu Ser Met Thr Tyr Glu
2645 2650 2655
Asp Arg Ser Gln Leu Asp His Met Gly Phe His Phe Thr Thr Gly
2660 2665 2670
Ile Pro Ala Pro Ser Thr Glu Thr Glu Leu Asp Val Leu Leu Pro
2675 2680 2685
Thr Ala Thr Ser Leu Pro Ile Pro Arg Lys Ser Ala Thr Val Ile
2690 2695 2700
Pro Glu Ile Glu Gly Ile Lys Ala Glu Ala Lys Ala Leu Asp Asp
2705 2710 2715
Met Phe Glu Ser Ser Thr Leu Ser Asp Gly Gln Ala Ile Ala Asp
2720 2725 2730
Gln Ser Glu Ile Ile Pro Thr Leu Gly Gln Phe Glu Arg Thr Gln
2735 2740 2745
Glu Glu Tyr Glu Asp Lys Lys His Ala Gly Pro Ser Phe Gln Pro
2750 2755 2760
Glu Phe Ser Ser Gly Ala Glu Glu Ala Leu Val Asp His Thr Pro
2765 2770 2775
Tyr Leu Ser Ile Ala Thr Thr His Leu Met Asp Gln Ser Val Thr
2780 2785 2790
Glu Val Pro Asp Val Met Glu Gly Ser Asn Pro Pro Tyr Tyr Thr
2795 2800 2805
Asp Thr Thr Leu Ala Val Ser Thr Phe Ala Lys Leu Ser Ser Gln
2810 2815 2820
Thr Pro Ser Ser Pro Leu Thr Ile Tyr Ser Gly Ser Glu Ala Ser
2825 2830 2835
Gly His Thr Glu Ile Pro Gln Pro Ser Ala Leu Pro Gly Ile Asp
2840 2845 2850
Val Gly Ser Ser Val Met Ser Pro Gln Asp Ser Phe Lys Glu Ile
2855 2860 2865
His Val Asn Ile Glu Ala Thr Phe Lys Pro Ser Ser Glu Glu Tyr
2870 2875 2880
Leu His Ile Thr Glu Pro Pro Ser Leu Ser Pro Asp Thr Lys Leu
2885 2890 2895
Glu Pro Ser Glu Asp Asp Gly Lys Pro Glu Leu Leu Glu Glu Met
2900 2905 2910
Glu Ala Ser Pro Thr Glu Leu Ile Ala Val Glu Gly Thr Glu Ile
2915 2920 2925
Leu Gln Asp Phe Gln Asn Lys Thr Asp Gly Gln Val Ser Gly Glu
2930 2935 2940
Ala Ile Lys Met Phe Pro Thr Ile Lys Thr Pro Glu Ala Gly Thr
2945 2950 2955
Val Ile Thr Thr Ala Asp Glu Ile Glu Leu Glu Gly Ala Thr Gln
2960 2965 2970
Trp Pro His Ser Thr Ser Ala Ser Ala Thr Tyr Gly Val Glu Ala
2975 2980 2985
Gly Val Val Pro Trp Leu Ser Pro Gln Thr Ser Glu Arg Pro Thr
2990 2995 3000
Leu Ser Ser Ser Pro Glu Ile Asn Pro Glu Thr Gln Ala Ala Leu
3005 3010 3015
Ile Arg Gly Gln Asp Ser Thr Ile Ala Ala Ser Glu Gln Gln Val
3020 3025 3030
Ala Ala Arg Ile Leu Asp Ser Asn Asp Gln Ala Thr Val Asn Pro
3035 3040 3045
Val Glu Phe Asn Thr Glu Val Ala Thr Pro Pro Phe Ser Leu Leu
3050 3055 3060
Glu Thr Ser Asn Glu Thr Asp Phe Leu Ile Gly Ile Asn Glu Glu
3065 3070 3075
Ser Val Glu Gly Thr Ala Ile Tyr Leu Pro Gly Pro Asp Arg Cys
3080 3085 3090
Lys Met Asn Pro Cys Leu Asn Gly Gly Thr Cys Tyr Pro Thr Glu
3095 3100 3105
Thr Ser Tyr Val Cys Thr Cys Val Pro Gly Tyr Ser Gly Asp Gln
3110 3115 3120
Cys Glu Leu Asp Phe Asp Glu Cys His Ser Asn Pro Cys Arg Asn
3125 3130 3135
Gly Ala Thr Cys Val Asp Gly Phe Asn Thr Phe Arg Cys Leu Cys
3140 3145 3150
Leu Pro Ser Tyr Val Gly Ala Leu Cys Glu Gln Asp Thr Glu Thr
3155 3160 3165
Cys Asp Tyr Gly Trp His Lys Phe Gln Gly Gln Cys Tyr Lys Tyr
3170 3175 3180
Phe Ala His Arg Arg Thr Trp Asp Ala Ala Glu Arg Glu Cys Arg
3185 3190 3195
Leu Gln Gly Ala His Leu Thr Ser Ile Leu Ser His Glu Glu Gln
3200 3205 3210
Met Phe Val Asn Arg Val Gly His Asp Tyr Gln Trp Ile Gly Leu
3215 3220 3225
Asn Asp Lys Met Phe Glu His Asp Phe Arg Trp Thr Asp Gly Ser
3230 3235 3240
Thr Leu Gln Tyr Glu Asn Trp Arg Pro Asn Gln Pro Asp Ser Phe
3245 3250 3255
Phe Ser Ala Gly Glu Asp Cys Val Val Ile Ile Trp His Glu Asn
3260 3265 3270
Gly Gln Trp Asn Asp Val Pro Cys Asn Tyr His Leu Thr Tyr Thr
3275 3280 3285
Cys Lys Lys Gly Thr Val Ala Cys Gly Gln Pro Pro Val Val Glu
3290 3295 3300
Asn Ala Lys Thr Phe Gly Lys Met Lys Pro Arg Tyr Glu Ile Asn
3305 3310 3315
Ser Leu Ile Arg Tyr His Cys Lys Asp Gly Phe Ile Gln Arg His
3320 3325 3330
Leu Pro Thr Ile Arg Cys Leu Gly Asn Gly Arg Trp Ala Ile Pro
3335 3340 3345
Lys Ile Thr Cys Met Asn Pro Ser Ala Tyr Gln Arg Thr Tyr Ser
3350 3355 3360
Met Lys Tyr Phe Lys Asn Ser Ser Ser Ala Lys Asp Asn Ser Ile
3365 3370 3375
Asn Thr Ser Lys His Asp His Arg Trp Ser Arg Arg Trp Gln Glu
3380 3385 3390
Ser Arg Arg
3395
<210> 130
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> VCAN_forward primer
<400> 130
tcctgtctca cgaagaacaa 20
<210> 131
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> VCAN_reverse primer
<400> 131
atcagtccaa cggaagtcat 20
<210> 132
<211> 26
<212> DNA
<213> Artificial Sequence
<220>
<223> VCAN probe
<400> 132
tcgtgtgggc catgattatc agtgga 26
<210> 133
<211> 2465
<212> DNA
<213> Homo sapiens
<400> 133
cctttcctcc ctccccgccc tctccccgct gtcccctccc cgtcggcccg cctgcccagc 60
ctttagcctc ccgcccgccg cctctgtctc cctctctcca caaactgccc aggagtgagt 120
agctgctttc ggtccgccgg acacaccgga cagatagacg tgcggacggc ccaccacccc 180
agcccgccaa ctagtcagcc tgcgcctggc gcctcccctc tccaggtcca tccgccatgt 240
ggcccctgtg gcgcctcgtg tctctgctgg ccctgagcca ggccctgccc tttgagcaga 300
gaggcttctg ggacttcacc ctggacgatg ggccattcat gatgaacgat gaggaagctt 360
cgggcgctga cacctcgggc gtcctggacc cggactctgt cacacccacc tacagcgcca 420
tgtgtccttt cggctgccac tgccacctgc gggtggttca gtgctccgac ctgggtctga 480
agtctgtgcc caaagagatc tcccctgaca ccacgctgct ggacctgcag aacaacgaca 540
tctccgagct ccgcaaggat gacttcaagg gtctccagca cctctacgcc ctcgtcctgg 600
tgaacaacaa gatctccaag atccatgaga aggccttcag cccactgcgg aagctgcaga 660
agctctacat ctccaagaac cacctggtgg agatcccgcc caacctaccc agctccctgg 720
tggagctccg catccacgac aaccgcatcc gcaaggtgcc caagggagtg ttcagcgggc 780
tccggaacat gaactgcatc gagatgggcg ggaacccact ggagaacagt ggctttgaac 840
ctggagcctt cgatggcctg aagctcaact acctgcgcat ctcagaggcc aagctgactg 900
gcatccccaa agacctccct gagaccctga atgaactcca cctagaccac aacaaaatcc 960
aggccatcga actggaggac ctgcttcgct actccaagct gtacaggctg ggcctaggcc 1020
acaaccagat caggatgatc gagaacggga gcctgagctt cctgcccacc ctccgggagc 1080
tccacttgga caacaacaag ttggccaggg tgccctcagg gctcccagac ctcaagctcc 1140
tccaggtggt ctatctgcac tccaacaaca tcaccaaagt gggtgtcaac gacttctgtc 1200
ccatgggctt cggggtgaag cgggcctact acaacggcat cagcctcttc aacaaccccg 1260
tgccctactg ggaggtgcag ccggccactt tccgctgcgt cactgaccgc ctggccatcc 1320
agtttggcaa ctacaaaaag tagaggcagc tgcagccacc gcggggcctc agtgggggtc 1380
tctggggaac acagccagac atcctgatgg ggaggcagag ccaggaagct aagccagggc 1440
ccagctgcgt ccaacccagc cccccacctc gggtccctga ccccagctcg atgccccatc 1500
accgcctctc cctggctccc aagggtgcag gtgggcgcaa ggcccggccc ccatcacatg 1560
ttcccttggc ctcagagctg cccctgctct cccaccacag ccacccagag gcaccccatg 1620
aagctttttt ctcgttcact cccaaaccca agtgtccaag gctccagtcc taggagaaca 1680
gtccctgggt cagcagccag gaggcggtcc ataagaatgg ggacagtggg ctctgccagg 1740
gctgccgcac ctgtccagac acacatgttc tgttcctcct cctcatgcat ttccagcctt 1800
tcaaccctcc ccgactctgc ggctcccctc agcccccttg caagttcatg gcctgtccct 1860
cccagacccc tgctccactg gcccttcgac cagtcctccc ttctgttctc tctttccccg 1920
tccttcctct ctctctctct ctctctctct ctctctttct gtgtgtgtgt gtgtgtgtgt 1980
gtgtgtgtgt gtgtgtgtgt gtgtcttgtg cttcctcaga cctttctcgc ttctgagctt 2040
ggtggcctgt tccctccatc tctccgaacc tggcttcgcc tgtccctttc actccacacc 2100
ctctggcctt ctgccttgag ctgggactgc tttctgtctg tccggcctgc acccagcccc 2160
tgcccacaaa accccaggga cagcagtctc cccagcctgc cctgctcagg ccttgccccc 2220
aaacctgtac tgtcccggag gaggttggga ggtggaggcc cagcatcccg cgcagatgac 2280
accatcaacc gccagagtcc cagacaccgg ttttcctaga agcccctcac ccccactggc 2340
ccactggtgg ctaggtctcc ccttatcctt ctggtccagc gcaaggaggg gctgcttctg 2400
aggtcggtgg ctgtctttcc attaaagaaa caccgtgcaa cgtgaaaaaa aaaaaaaaaa 2460
aaaaa 2465
<210> 134
<211> 368
<212> PRT
<213> Homo sapiens
<400> 134
Met Trp Pro Leu Trp Arg Leu Val Ser Leu Leu Ala Leu Ser Gln Ala
1 5 10 15
Leu Pro Phe Glu Gln Arg Gly Phe Trp Asp Phe Thr Leu Asp Asp Gly
20 25 30
Pro Phe Met Met Asn Asp Glu Glu Ala Ser Gly Ala Asp Thr Ser Gly
35 40 45
Val Leu Asp Pro Asp Ser Val Thr Pro Thr Tyr Ser Ala Met Cys Pro
50 55 60
Phe Gly Cys His Cys His Leu Arg Val Val Gln Cys Ser Asp Leu Gly
65 70 75 80
Leu Lys Ser Val Pro Lys Glu Ile Ser Pro Asp Thr Thr Leu Leu Asp
85 90 95
Leu Gln Asn Asn Asp Ile Ser Glu Leu Arg Lys Asp Asp Phe Lys Gly
100 105 110
Leu Gln His Leu Tyr Ala Leu Val Leu Val Asn Asn Lys Ile Ser Lys
115 120 125
Ile His Glu Lys Ala Phe Ser Pro Leu Arg Lys Leu Gln Lys Leu Tyr
130 135 140
Ile Ser Lys Asn His Leu Val Glu Ile Pro Pro Asn Leu Pro Ser Ser
145 150 155 160
Leu Val Glu Leu Arg Ile His Asp Asn Arg Ile Arg Lys Val Pro Lys
165 170 175
Gly Val Phe Ser Gly Leu Arg Asn Met Asn Cys Ile Glu Met Gly Gly
180 185 190
Asn Pro Leu Glu Asn Ser Gly Phe Glu Pro Gly Ala Phe Asp Gly Leu
195 200 205
Lys Leu Asn Tyr Leu Arg Ile Ser Glu Ala Lys Leu Thr Gly Ile Pro
210 215 220
Lys Asp Leu Pro Glu Thr Leu Asn Glu Leu His Leu Asp His Asn Lys
225 230 235 240
Ile Gln Ala Ile Glu Leu Glu Asp Leu Leu Arg Tyr Ser Lys Leu Tyr
245 250 255
Arg Leu Gly Leu Gly His Asn Gln Ile Arg Met Ile Glu Asn Gly Ser
260 265 270
Leu Ser Phe Leu Pro Thr Leu Arg Glu Leu His Leu Asp Asn Asn Lys
275 280 285
Leu Ala Arg Val Pro Ser Gly Leu Pro Asp Leu Lys Leu Leu Gln Val
290 295 300
Val Tyr Leu His Ser Asn Asn Ile Thr Lys Val Gly Val Asn Asp Phe
305 310 315 320
Cys Pro Met Gly Phe Gly Val Lys Arg Ala Tyr Tyr Asn Gly Ile Ser
325 330 335
Leu Phe Asn Asn Pro Val Pro Tyr Trp Glu Val Gln Pro Ala Thr Phe
340 345 350
Arg Cys Val Thr Asp Arg Leu Ala Ile Gln Phe Gly Asn Tyr Lys Lys
355 360 365
<210> 135
<211> 17
<212> DNA
<213> Artificial Sequence
<220>
<223> BGN_forward primer
<400> 135
tgcccaaggg agtgttc 17
<210> 136
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> BGN_reverse primer
<400> 136
tagttgagct tcaggccatc 20
<210> 137
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> BGN probe
<400> 137
atgggcggga acccactgga 20
<210> 138
<211> 2537
<212> DNA
<213> Homo sapiens
<400> 138
cccagaaggc cgcggggggt ggaccgccta agagggcgtg cgctcccgac atgccccgcg 60
gcgcgccatt aaccgccaga tttgaatcgc gggacccgtt ggcagaggtg gcggcggcgg 120
catgggtgcc ccgacgttgc cccctgcctg gcagcccttt ctcaaggacc accgcatctc 180
tacattcaag aactggccct tcttggaggg ctgcgcctgc accccggagc ggatggccga 240
ggctggcttc atccactgcc ccactgagaa cgagccagac ttggcccagt gtttcttctg 300
cttcaaggag ctggaaggct gggagccaga tgacgacccc atgcaaagga aaccaacaat 360
aagaagaaag aatttgagga aactgcggag aaagtgcgcc gtgccatcga gcagctggct 420
gccatggatt gaggcctctg gccggagctg cctggtccca gagtggctgc accacttcca 480
gggtttattc cctggtgcca ccagccttcc tgtgggcccc ttagcaatgt cttaggaaag 540
gagatcaaca ttttcaaatt agatgtttca actgtgctct tgttttgtct tgaaagtggc 600
accagaggtg cttctgcctg tgcagcgggt gctgctggta acagtggctg cttctctctc 660
tctctctctt ttttgggggc tcatttttgc tgttttgatt cccgggctta ccaggtgaga 720
agtgagggag gaagaaggca gtgtcccttt tgctagagct gacagctttg ttcgcgtggg 780
cagagccttc cacagtgaat gtgtctggac ctcatgttgt tgaggctgtc acagtcctga 840
gtgtggactt ggcaggtgcc tgttgaatct gagctgcagg ttccttatct gtcacacctg 900
tgcctcctca gaggacagtt tttttgttgt tgtgtttttt tgtttttttt tttttggtag 960
atgcatgact tgtgtgtgat gagagaatgg agacagagtc cctggctcct ctactgttta 1020
acaacatggc tttcttattt tgtttgaatt gttaattcac agaatagcac aaactacaat 1080
taaaactaag cacaaagcca ttctaagtca ttggggaaac ggggtgaact tcaggtggat 1140
gaggagacag aatagagtga taggaagcgt ctggcagata ctccttttgc cactgctgtg 1200
tgattagaca ggcccagtga gccgcggggc acatgctggc cgctcctccc tcagaaaaag 1260
gcagtggcct aaatcctttt taaatgactt ggctcgatgc tgtgggggac tggctgggct 1320
gctgcaggcc gtgtgtctgt cagcccaacc ttcacatctg tcacgttctc cacacggggg 1380
agagacgcag tccgcccagg tccccgcttt ctttggaggc agcagctccc gcagggctga 1440
agtctggcgt aagatgatgg atttgattcg ccctcctccc tgtcatagag ctgcagggtg 1500
gattgttaca gcttcgctgg aaacctctgg aggtcatctc ggctgttcct gagaaataaa 1560
aagcctgtca tttcaaacac tgctgtggac cctactgggt ttttaaaata ttgtcagttt 1620
ttcatcgtcg tccctagcct gccaacagcc atctgcccag acagccgcag tgaggatgag 1680
cgtcctggca gagacgcagt tgtctctggg cgcttgccag agccacgaac cccagacctg 1740
tttgtatcat ccgggctcct tccgggcaga aacaactgaa aatgcacttc agacccactt 1800
atttctgcca catctgagtc ggcctgagat agacttttcc ctctaaactg ggagaatatc 1860
acagtggttt ttgttagcag aaaatgcact ccagcctctg tactcatcta agctgcttat 1920
ttttgatatt tgtgtcagtc tgtaaatgga tacttcactt taataactgt tgcttagtaa 1980
ttggctttgt agagaagctg gaaaaaaatg gttttgtctt caactccttt gcatgccagg 2040
cggtgatgtg gatctcggct tctgtgagcc tgtgctgtgg gcagggctga gctggagccg 2100
cccctctcag cccgcctgcc acggcctttc cttaaaggcc atccttaaaa ccagaccctc 2160
atggctacca gcacctgaaa gcttcctcga catctgttaa taaagccgta ggcccttgtc 2220
taagtgcaac cgcctagact ttctttcaga tacatgtcca catgtccatt tttcaggttc 2280
tctaagttgg agtggagtct gggaagggtt gtgaatgagg cttctgggct atgggtgagg 2340
ttccaatggc aggttagagc ccctcgggcc aactgccatc ctggaaagta gagacagcag 2400
tgcccgctgc ccagaagaga ccagcaagcc aaactggagc ccccattgca ggctgtcgcc 2460
atgtggaaag agtaactcac aattgccaat aaagtctcat gtggttttat ctaaaaaaaa 2520
aaaaaaaaaa aaaaaaa 2537
<210> 139
<211> 2724
<212> DNA
<213> Homo sapiens
<400> 139
cccagaaggc cgcggggggt ggaccgccta agagggcgtg cgctcccgac atgccccgcg 60
gcgcgccatt aaccgccaga tttgaatcgc gggacccgtt ggcagaggtg gcggcggcgg 120
catgggtgcc ccgacgttgc cccctgcctg gcagcccttt ctcaaggacc accgcatctc 180
tacattcaag aactggccct tcttggaggg ctgcgcctgc accccggagc ggatggccga 240
ggctggcttc atccactgcc ccactgagaa cgagccagac ttggcccagt gtttcttctg 300
cttcaaggag ctggaaggct gggagccaga tgacgacccc attgggccgg gcacggtggc 360
ttacgcctgt aataccagca ctttgggagg ccgaggcggg cggatcacga gagaggaaca 420
taaaaagcat tcgtccggtt gcgctttcct ttctgtcaag aagcagtttg aagaattaac 480
ccttggtgaa tttttgaaac tggacagaga aagagccaag aacaaaattg caaaggaaac 540
caacaataag aagaaagaat ttgaggaaac tgcggagaaa gtgcgccgtg ccatcgagca 600
gctggctgcc atggattgag gcctctggcc ggagctgcct ggtcccagag tggctgcacc 660
acttccaggg tttattccct ggtgccacca gccttcctgt gggcccctta gcaatgtctt 720
aggaaaggag atcaacattt tcaaattaga tgtttcaact gtgctcttgt tttgtcttga 780
aagtggcacc agaggtgctt ctgcctgtgc agcgggtgct gctggtaaca gtggctgctt 840
ctctctctct ctctcttttt tgggggctca tttttgctgt tttgattccc gggcttacca 900
ggtgagaagt gagggaggaa gaaggcagtg tcccttttgc tagagctgac agctttgttc 960
gcgtgggcag agccttccac agtgaatgtg tctggacctc atgttgttga ggctgtcaca 1020
gtcctgagtg tggacttggc aggtgcctgt tgaatctgag ctgcaggttc cttatctgtc 1080
acacctgtgc ctcctcagag gacagttttt ttgttgttgt gtttttttgt tttttttttt 1140
ttggtagatg catgacttgt gtgtgatgag agaatggaga cagagtccct ggctcctcta 1200
ctgtttaaca acatggcttt cttattttgt ttgaattgtt aattcacaga atagcacaaa 1260
ctacaattaa aactaagcac aaagccattc taagtcattg gggaaacggg gtgaacttca 1320
ggtggatgag gagacagaat agagtgatag gaagcgtctg gcagatactc cttttgccac 1380
tgctgtgtga ttagacaggc ccagtgagcc gcggggcaca tgctggccgc tcctccctca 1440
gaaaaaggca gtggcctaaa tcctttttaa atgacttggc tcgatgctgt gggggactgg 1500
ctgggctgct gcaggccgtg tgtctgtcag cccaaccttc acatctgtca cgttctccac 1560
acgggggaga gacgcagtcc gcccaggtcc ccgctttctt tggaggcagc agctcccgca 1620
gggctgaagt ctggcgtaag atgatggatt tgattcgccc tcctccctgt catagagctg 1680
cagggtggat tgttacagct tcgctggaaa cctctggagg tcatctcggc tgttcctgag 1740
aaataaaaag cctgtcattt caaacactgc tgtggaccct actgggtttt taaaatattg 1800
tcagtttttc atcgtcgtcc ctagcctgcc aacagccatc tgcccagaca gccgcagtga 1860
ggatgagcgt cctggcagag acgcagttgt ctctgggcgc ttgccagagc cacgaacccc 1920
agacctgttt gtatcatccg ggctccttcc gggcagaaac aactgaaaat gcacttcaga 1980
cccacttatt tctgccacat ctgagtcggc ctgagataga cttttccctc taaactggga 2040
gaatatcaca gtggtttttg ttagcagaaa atgcactcca gcctctgtac tcatctaagc 2100
tgcttatttt tgatatttgt gtcagtctgt aaatggatac ttcactttaa taactgttgc 2160
ttagtaattg gctttgtaga gaagctggaa aaaaatggtt ttgtcttcaa ctcctttgca 2220
tgccaggcgg tgatgtggat ctcggcttct gtgagcctgt gctgtgggca gggctgagct 2280
ggagccgccc ctctcagccc gcctgccacg gcctttcctt aaaggccatc cttaaaacca 2340
gaccctcatg gctaccagca cctgaaagct tcctcgacat ctgttaataa agccgtaggc 2400
ccttgtctaa gtgcaaccgc ctagactttc tttcagatac atgtccacat gtccattttt 2460
caggttctct aagttggagt ggagtctggg aagggttgtg aatgaggctt ctgggctatg 2520
ggtgaggttc caatggcagg ttagagcccc tcgggccaac tgccatcctg gaaagtagag 2580
acagcagtgc ccgctgccca gaagagacca gcaagccaaa ctggagcccc cattgcaggc 2640
tgtcgccatg tggaaagagt aactcacaat tgccaataaa gtctcatgtg gttttatcta 2700
aaaaaaaaaa aaaaaaaaaa aaaa 2724
<210> 140
<211> 2655
<212> DNA
<213> Homo sapiens
<400> 140
cccagaaggc cgcggggggt ggaccgccta agagggcgtg cgctcccgac atgccccgcg 60
gcgcgccatt aaccgccaga tttgaatcgc gggacccgtt ggcagaggtg gcggcggcgg 120
catgggtgcc ccgacgttgc cccctgcctg gcagcccttt ctcaaggacc accgcatctc 180
tacattcaag aactggccct tcttggaggg ctgcgcctgc accccggagc ggatggccga 240
ggctggcttc atccactgcc ccactgagaa cgagccagac ttggcccagt gtttcttctg 300
cttcaaggag ctggaaggct gggagccaga tgacgacccc atagaggaac ataaaaagca 360
ttcgtccggt tgcgctttcc tttctgtcaa gaagcagttt gaagaattaa cccttggtga 420
atttttgaaa ctggacagag aaagagccaa gaacaaaatt gcaaaggaaa ccaacaataa 480
gaagaaagaa tttgaggaaa ctgcggagaa agtgcgccgt gccatcgagc agctggctgc 540
catggattga ggcctctggc cggagctgcc tggtcccaga gtggctgcac cacttccagg 600
gtttattccc tggtgccacc agccttcctg tgggcccctt agcaatgtct taggaaagga 660
gatcaacatt ttcaaattag atgtttcaac tgtgctcttg ttttgtcttg aaagtggcac 720
cagaggtgct tctgcctgtg cagcgggtgc tgctggtaac agtggctgct tctctctctc 780
tctctctttt ttgggggctc atttttgctg ttttgattcc cgggcttacc aggtgagaag 840
tgagggagga agaaggcagt gtcccttttg ctagagctga cagctttgtt cgcgtgggca 900
gagccttcca cagtgaatgt gtctggacct catgttgttg aggctgtcac agtcctgagt 960
gtggacttgg caggtgcctg ttgaatctga gctgcaggtt ccttatctgt cacacctgtg 1020
cctcctcaga ggacagtttt tttgttgttg tgtttttttg tttttttttt tttggtagat 1080
gcatgacttg tgtgtgatga gagaatggag acagagtccc tggctcctct actgtttaac 1140
aacatggctt tcttattttg tttgaattgt taattcacag aatagcacaa actacaatta 1200
aaactaagca caaagccatt ctaagtcatt ggggaaacgg ggtgaacttc aggtggatga 1260
ggagacagaa tagagtgata ggaagcgtct ggcagatact ccttttgcca ctgctgtgtg 1320
attagacagg cccagtgagc cgcggggcac atgctggccg ctcctccctc agaaaaaggc 1380
agtggcctaa atccttttta aatgacttgg ctcgatgctg tgggggactg gctgggctgc 1440
tgcaggccgt gtgtctgtca gcccaacctt cacatctgtc acgttctcca cacgggggag 1500
agacgcagtc cgcccaggtc cccgctttct ttggaggcag cagctcccgc agggctgaag 1560
tctggcgtaa gatgatggat ttgattcgcc ctcctccctg tcatagagct gcagggtgga 1620
ttgttacagc ttcgctggaa acctctggag gtcatctcgg ctgttcctga gaaataaaaa 1680
gcctgtcatt tcaaacactg ctgtggaccc tactgggttt ttaaaatatt gtcagttttt 1740
catcgtcgtc cctagcctgc caacagccat ctgcccagac agccgcagtg aggatgagcg 1800
tcctggcaga gacgcagttg tctctgggcg cttgccagag ccacgaaccc cagacctgtt 1860
tgtatcatcc gggctccttc cgggcagaaa caactgaaaa tgcacttcag acccacttat 1920
ttctgccaca tctgagtcgg cctgagatag acttttccct ctaaactggg agaatatcac 1980
agtggttttt gttagcagaa aatgcactcc agcctctgta ctcatctaag ctgcttattt 2040
ttgatatttg tgtcagtctg taaatggata cttcacttta ataactgttg cttagtaatt 2100
ggctttgtag agaagctgga aaaaaatggt tttgtcttca actcctttgc atgccaggcg 2160
gtgatgtgga tctcggcttc tgtgagcctg tgctgtgggc agggctgagc tggagccgcc 2220
cctctcagcc cgcctgccac ggcctttcct taaaggccat ccttaaaacc agaccctcat 2280
ggctaccagc acctgaaagc ttcctcgaca tctgttaata aagccgtagg cccttgtcta 2340
agtgcaaccg cctagacttt ctttcagata catgtccaca tgtccatttt tcaggttctc 2400
taagttggag tggagtctgg gaagggttgt gaatgaggct tctgggctat gggtgaggtt 2460
ccaatggcag gttagagccc ctcgggccaa ctgccatcct ggaaagtaga gacagcagtg 2520
cccgctgccc agaagagacc agcaagccaa actggagccc ccattgcagg ctgtcgccat 2580
gtggaaagag taactcacaa ttgccaataa agtctcatgt ggttttatct aaaaaaaaaa 2640
aaaaaaaaaa aaaaa 2655
<210> 141
<211> 137
<212> PRT
<213> Homo sapiens
<400> 141
Met Gly Ala Pro Thr Leu Pro Pro Ala Trp Gln Pro Phe Leu Lys Asp
1 5 10 15
His Arg Ile Ser Thr Phe Lys Asn Trp Pro Phe Leu Glu Gly Cys Ala
20 25 30
Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr
35 40 45
Glu Asn Glu Pro Asp Leu Ala Gln Cys Phe Phe Cys Phe Lys Glu Leu
50 55 60
Glu Gly Trp Glu Pro Asp Asp Asp Pro Met Gln Arg Lys Pro Thr Ile
65 70 75 80
Arg Arg Lys Asn Leu Arg Lys Leu Arg Arg Lys Cys Ala Val Pro Ser
85 90 95
Ser Ser Trp Leu Pro Trp Ile Glu Ala Ser Gly Arg Ser Cys Leu Val
100 105 110
Pro Glu Trp Leu His His Phe Gln Gly Leu Phe Pro Gly Ala Thr Ser
115 120 125
Leu Pro Val Gly Pro Leu Ala Met Ser
130 135
<210> 142
<211> 165
<212> PRT
<213> Homo sapiens
<400> 142
Met Gly Ala Pro Thr Leu Pro Pro Ala Trp Gln Pro Phe Leu Lys Asp
1 5 10 15
His Arg Ile Ser Thr Phe Lys Asn Trp Pro Phe Leu Glu Gly Cys Ala
20 25 30
Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr
35 40 45
Glu Asn Glu Pro Asp Leu Ala Gln Cys Phe Phe Cys Phe Lys Glu Leu
50 55 60
Glu Gly Trp Glu Pro Asp Asp Asp Pro Ile Gly Pro Gly Thr Val Ala
65 70 75 80
Tyr Ala Cys Asn Thr Ser Thr Leu Gly Gly Arg Gly Gly Arg Ile Thr
85 90 95
Arg Glu Glu His Lys Lys His Ser Ser Gly Cys Ala Phe Leu Ser Val
100 105 110
Lys Lys Gln Phe Glu Glu Leu Thr Leu Gly Glu Phe Leu Lys Leu Asp
115 120 125
Arg Glu Arg Ala Lys Asn Lys Ile Ala Lys Glu Thr Asn Asn Lys Lys
130 135 140
Lys Glu Phe Glu Glu Thr Ala Glu Lys Val Arg Arg Ala Ile Glu Gln
145 150 155 160
Leu Ala Ala Met Asp
165
<210> 143
<211> 142
<212> PRT
<213> Homo sapiens
<400> 143
Met Gly Ala Pro Thr Leu Pro Pro Ala Trp Gln Pro Phe Leu Lys Asp
1 5 10 15
His Arg Ile Ser Thr Phe Lys Asn Trp Pro Phe Leu Glu Gly Cys Ala
20 25 30
Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr
35 40 45
Glu Asn Glu Pro Asp Leu Ala Gln Cys Phe Phe Cys Phe Lys Glu Leu
50 55 60
Glu Gly Trp Glu Pro Asp Asp Asp Pro Ile Glu Glu His Lys Lys His
65 70 75 80
Ser Ser Gly Cys Ala Phe Leu Ser Val Lys Lys Gln Phe Glu Glu Leu
85 90 95
Thr Leu Gly Glu Phe Leu Lys Leu Asp Arg Glu Arg Ala Lys Asn Lys
100 105 110
Ile Ala Lys Glu Thr Asn Asn Lys Lys Lys Glu Phe Glu Glu Thr Ala
115 120 125
Glu Lys Val Arg Arg Ala Ile Glu Gln Leu Ala Ala Met Asp
130 135 140
<210> 144
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> BIRC5_forward primer
<400> 144
cttggcccag tgtttctt 18
<210> 145
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> BIRC5_reverse primer
<400> 145
gttcctctat ggggtcgtca t 21
<210> 146
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> BIRC5 probe
<400> 146
agctggaagg ctgggagcca 20
<210> 147
<211> 6010
<212> DNA
<213> Homo sapiens
<400> 147
cgcgggggcg cgcgcgcgcg ggcccgggag aggctcccga gccaggcggt cttcggtcct 60
cgcagcgctt ccagctcccc gcgcccctat gtgagggaga cggggaggcc cgcggcgcgc 120
aggggagggc gaggcatgtg cacgggccgg agggtgctgc agccgcccga ggaagaggag 180
gacggcggcg aggaggagag cggggggctc gcggcggcgg gccccggccg aggggatgca 240
gtggactgtg tgtgtctggc tgtagcagac gcgaggcggc gacgaggcgc cggggacccg 300
cgcgaggggc ggccgggagg cggcggcggc ggccgccaga agtagcagca ggaccggcgg 360
cggcgacggc agccctgaaa tgcattttcc tctccagcgg ccatgttaac caggaaacct 420
tcggccgccg ctcccgccgc ctacccgacc gattggcggc agtaagcaca caatgaatga 480
tcacctgcat gtcggcagcc acgctcacgg acagatccag gttcaacagt tgtttgagga 540
taacagtaac aagcggacag tgctcacgac acaaccaaat gggcttacaa cagtgggcaa 600
aacgggcttg ccagtggtgc cagagcggca gctggacagc attcatagac ggcaggggag 660
ctccacctct ctaaagtcca tggaaggcat ggggaaggtg aaagccaccc ccatgacacc 720
tgaacaagca atgaagcaat acatgcaaaa actcacagcc ttcgaacacc atgagatttt 780
cagctaccct gaaatatatt tcttgggtct aaatgctaag aagcgccagg gcatgacagg 840
tgggcccaac aatggtggct atgatgatga ccagggatca tatgtgcagg tgccccacga 900
tcacgtggct tacaggtatg aggtcctcaa ggtcattggg aaggggagct ttgggcaggt 960
ggtcaaggcc tacgatcaca aagtccacca gcacgtggcc ctaaagatgg tgcggaatga 1020
gaagcgcttc caccggcaag cagcggagga gatccgaatc ctggaacacc tgcggaagca 1080
ggacaaggat aacacaatga atgtcatcca tatgctggag aatttcacct tccgcaacca 1140
catctgcatg acgtttgagc tgctgagcat gaacctctat gagctcatca agaagaataa 1200
attccagggc ttcagtctgc ctttggttcg caagtttgcc cactcgattc tgcagtgctt 1260
ggatgctttg cacaaaaaca gaataattca ctgtgacctt aagcccgaga acattttgtt 1320
aaagcagcag ggtagaagcg gtattaaagt aattgatttt ggctccagtt gttacgagca 1380
tcagcgtgtc tacacgtaca tccagtcgcg tttttaccgg gctccagaag tgatccttgg 1440
ggccaggtat ggcatgccca ttgatatgtg gagcctgggc tgcattttag cagagctcct 1500
gacgggttac cccctcttgc ctggggaaga tgaaggggac cagctggcct gtatgattga 1560
actgttgggc atgccctcac agaaactgct ggatgcatcc aaacgagcca aaaattttgt 1620
gagctccaag ggttatcccc gttactgcac tgtcacgact ctctcagatg gctctgtggt 1680
cctaaacgga ggccgttccc ggagggggaa actgaggggc ccaccggaga gcagagagtg 1740
ggggaacgcg ctgaaggggt gtgatgatcc ccttttcctt gacttcttaa aacagtgttt 1800
agagtgggat cctgcagtgc gcatgacccc aggccaggct ttgcggcacc cctggctgag 1860
gaggcggttg ccaaagcctc ccaccgggga gaaaacgtca gtgaaaagga taactgagag 1920
caccggtgct atcacatcta tatccaagtt acctccacct tctagctcag cttccaaact 1980
gaggactaat ttggcgcaga tgacagatgc caatgggaat attcagcaga ggacagtgtt 2040
gccaaaactt gttagctgag ctcacgtccc ctgatgctgg taacctgaaa gatacgacat 2100
tgctgagcct tactgggttg aaaaggagta gctcagacct gtttttattt gctcaataac 2160
tctactcatt tgtatctttt cagcacttaa ttttaatgta agaaagttgt tcattttgtt 2220
tttataaaat acatgaggac aatgctttaa gtttttatac tttcagaaac tttttgtgtt 2280
ctaaaagtac aatgagcctt actgtattta gtgtggcaga ataataacat cagtggcagg 2340
ccactgatta cttcatgact gccacgcatt tacagattgg tgtcaaagac attcactatg 2400
tttttatggt tcatgttata tcctccccag ggtgacagcc ccttaaggcc ctccttttcc 2460
ctccatgctc caggtccatg cacaggtgta gcatgtcctg cttccgtttt tcataaatta 2520
atctgggtgt tgggggtagt gggaggagaa cggtcagaat caaagtgaca ttctaagaaa 2580
aactgtacct tagagatttt cctctagtgc tcaaacaaat acaaaataag atccccaagg 2640
tttaaactgc ccagttagca ttctgacatt ctaaaagccg gcaaagcagc ttttagtgga 2700
taaatgggaa tggaaacgtg tgtgttcctc caaattttct agtatgatcg gtgagctgtt 2760
ttgtaaagaa gcctcatatt acagagttgc ttttgcacct aaatttagaa ttgtattcca 2820
tgaactgttc ctcccttttc tctgcttttc tcctctctgt tcctctttta ataccacacg 2880
tctgttgctt gcatttagtt tgtcttcttc cttcagctgt gtatcccaga ctgttaatac 2940
agaaaagaga catttcagct gtgattatga ccattgtttc atattccaat taaaaaaaga 3000
acagcagcct agctacttaa ggtggggatt tccatagttc caaagaagat ttagcagatt 3060
agagtgagtt cacacttttc aggtgccact gtaaggttct ctcagcctgg gaaactatca 3120
actctttctt taaaaagaaa gagggttgaa aatcctctgg acgaacagaa gtcactttgg 3180
ctgttcagta aggccaatgt taacaacacg tttagaggag gaaaagttca acctcaagtt 3240
aaatggtttg acttattctt cgtatcatta gaagaacccc agagatagca ttcctctatt 3300
ttattttact ttcttttgga ttgcactgat tgtttttgtg ggaatgacac tttatctggc 3360
aaagtaactg agagtttggt aaaagaatat tttcttctct gaataataat tattttcaca 3420
gtgaaaattt cagtatttta tcactaatgt atgagcaatg atctatatca atttcaaggc 3480
acgtgaaaaa aattttttag tatgtgcaat ttaatataga aagatttctg cctgtttgga 3540
caataggttt tgggtagtac agattaggat aagtaagctt atatatgcac agagattatt 3600
gtattacctg taaattgatt tacaagtact taaaagcgtg gtccccagtg aggccaagaa 3660
agtttccggt taagttcttt aataataatc ctacagttta tcttaagaaa aaaaaaaagg 3720
tttgaaaaaa acactttaat ttaggcttcg ttggttgatg gtggaaaaaa atgctcagga 3780
aatatttcag atatttgcca aaaaaccagt aataaggtta ccttattaaa atagtgatat 3840
ttgctttact atttaaggtg tcactgataa attaatttgt acttctgtgt ttagaaatta 3900
tagcttcttt tcccttagtc aaatttttta gcatattata cacatttctg tgtaatctgt 3960
ggaagtgcaa taatatgtta gtaagttaca ttttaaataa tgctcatgtg acaatactcc 4020
caatcaatgg cttatagaat ttaaagatct gtatattaga ttttggctta aaggcatgag 4080
aagtataaga cttggtttgg tggctttgta agaccaccag cctcttaatg atggttagct 4140
tctttaggtc attaaatcaa taaaaacata taatgctgtt ttgctcttct aatgctcctc 4200
ttccatttcc agttatcttc acatttacat ttaaatatac aaacctgagc ctgccattat 4260
taatttccct ataaaatgac gatacatgtg aacatttata aatggactaa tactgcttgt 4320
ctttccccca ccgcacaaaa ctggttctta agatgccagc aatgaatttg agactatctt 4380
tatttataaa tggaaaccgg aaacttttat accaaactat aataatgtgc agcactgtag 4440
ggcttttttt tttttccctc caaatacagt gaaatttttt tattcacaag agctgccaca 4500
tctcagcatt tagtaataga gctgctttaa taaaattcta gtttgattgt catgtcaaaa 4560
aaagaaaaat gttgcatctt tgtgatttta aaacataaat taatgaaggc tctgataggc 4620
tattaggagt tggcttggaa acagtttttg gtctcacagg ttaccattgt ttggggatgt 4680
ctgagctgtt ttcagatcta ggaatagcac agtgttgtct tgtctttggc agtctcattt 4740
ggctctgttt cttgcaccac cagcgtgttc attaccactt aaatatattg ctacagcagt 4800
ggaacaacag agtggtgcaa gacactgtag attaacggta gaggagaaat tgtgccctta 4860
gtgttaacaa tgtgcctttt gttctgaatg ccatgttgta gggcatgcat tttttggcct 4920
ctttaactct tcgaattcta gtcagtaaga atggaaccca tctctgcaaa gatacatctg 4980
tcttaaatat ctagttacag gccttaatag aaaccataag gcatgactca tcttcaggca 5040
ctgaaaaaag ataaccatca ggtagtgtta cacaaggact tcctatattt aaggggttaa 5100
agatggtctt tgttgtatct taacatcaga ctgattttta catttttttt ttgttatgct 5160
aacactagac aaaaatcaac tgtatttgta aaaatttacc tcaaaccatt taattttata 5220
gtgtgattaa tcccagggca tttggtatga accaaagtgc attcctttta tatgtgcctg 5280
gctctagtaa ggatggccag ggatttttac aatttgggtg caaggcactt aagccacttt 5340
taaacttaat gggtggtttg gggtcgtgtt aaatgactcc atcagaatgt tagaaaacac 5400
tttaggcatc agtagcattg ggccatattg gaatcctaaa gtgtgaatta ttttaaggag 5460
agcattcatt tttgtaattt ttttcatcaa aaatatttct ggtaagcaga agacttttta 5520
aaaaaactga tctggtctcg gtaaaggttt taatattgcc caacataatg ctgtaatagc 5580
attaaaaaaa gtatttgtga actctgtttc ttaggggctt gtacatctct ctgctatgga 5640
catacataaa attaattgta attatactca gctcaactgc tacagttctg tctaggcagt 5700
ggcttgggtt tttatcgagc aacaacttag acacgtgact gtaatatgct gcaactgtgt 5760
gtactgaaaa tatgtgaaaa tggttgaatg tggactgtgt atatatgtat gtaaaaattt 5820
ctgtgagatg ctgctgtcgc cacttaacat taaatatgtt ctagtggatt ttaatcctag 5880
tggccagttc tatgatactg tatgtattat acagctgatg acaggagtaa gactgtttag 5940
tgaatatctg ttaaatttta ttgttgtggc cagagataat ttcagaataa aattttaatg 6000
tcctacctta 6010
<210> 148
<211> 6159
<212> DNA
<213> Homo sapiens
<400> 148
cgcgggggcg cgcgcgcgcg ggcccgggag aggctcccga gccaggcggt cttcggtcct 60
cgcagcgctt ccagctcccc gcgcccctat gtgagggaga cggggaggcc cgcggcgcgc 120
aggggagggc gaggcatgtg cacgggccgg agggtgctgc agccgcccga ggaagaggag 180
gacggcggcg aggaggagag cggggggctc gcggcggcgg gccccggccg aggggatgca 240
gtggactgtg tgtgtctggc tgtagcagac gcgaggcggc gacgaggcgc cggggacccg 300
cgcgaggggc ggccgggagg cggcggcggc ggccgccaga agtagcagca ggaccggcgg 360
cggcgacggc agccctgaaa tgcattttcc tctccagcgg ccatgttaac caggaaacct 420
tcggccgccg ctcccgccgc ctacccgacc ggccgaggtg gggacagcgc cgttcgtcag 480
cttcaggctt ccccggggct cggtgcaggg gccacccgga gcggagtggg gactggcccg 540
ccctccccca tcgccctgcc gcctctccgg gccagcaacg ctgccgccgc agcccacacg 600
attggcggca gtaagcacac aatgaatgat cacctgcatg tcggcagcca cgctcacgga 660
cagatccagg ttcaacagtt gtttgaggat aacagtaaca agcggacagt gctcacgaca 720
caaccaaatg ggcttacaac agtgggcaaa acgggcttgc cagtggtgcc agagcggcag 780
ctggacagca ttcatagacg gcaggggagc tccacctctc taaagtccat ggaaggcatg 840
gggaaggtga aagccacccc catgacacct gaacaagcaa tgaagcaata catgcaaaaa 900
ctcacagcct tcgaacacca tgagattttc agctaccctg aaatatattt cttgggtcta 960
aatgctaaga agcgccaggg catgacaggt gggcccaaca atggtggcta tgatgatgac 1020
cagggatcat atgtgcaggt gccccacgat cacgtggctt acaggtatga ggtcctcaag 1080
gtcattggga aggggagctt tgggcaggtg gtcaaggcct acgatcacaa agtccaccag 1140
cacgtggccc taaagatggt gcggaatgag aagcgcttcc accggcaagc agcggaggag 1200
atccgaatcc tggaacacct gcggaagcag gacaaggata acacaatgaa tgtcatccat 1260
atgctggaga atttcacctt ccgcaaccac atctgcatga cgtttgagct gctgagcatg 1320
aacctctatg agctcatcaa gaagaataaa ttccagggct tcagtctgcc tttggttcgc 1380
aagtttgccc actcgattct gcagtgcttg gatgctttgc acaaaaacag aataattcac 1440
tgtgacctta agcccgagaa cattttgtta aagcagcagg gtagaagcgg tattaaagta 1500
attgattttg gctccagttg ttacgagcat cagcgtgtct acacgtacat ccagtcgcgt 1560
ttttaccggg ctccagaagt gatccttggg gccaggtatg gcatgcccat tgatatgtgg 1620
agcctgggct gcattttagc agagctcctg acgggttacc ccctcttgcc tggggaagat 1680
gaaggggacc agctggcctg tatgattgaa ctgttgggca tgccctcaca gaaactgctg 1740
gatgcatcca aacgagccaa aaattttgtg agctccaagg gttatccccg ttactgcact 1800
gtcacgactc tctcagatgg ctctgtggtc ctaaacggag gccgttcccg gagggggaaa 1860
ctgaggggcc caccggagag cagagagtgg gggaacgcgc tgaaggggtg tgatgatccc 1920
cttttccttg acttcttaaa acagtgttta gagtgggatc ctgcagtgcg catgacccca 1980
ggccaggctt tgcggcaccc ctggctgagg aggcggttgc caaagcctcc caccggggag 2040
aaaacgtcag tgaaaaggat aactgagagc accggtgcta tcacatctat atccaagtta 2100
cctccacctt ctagctcagc ttccaaactg aggactaatt tggcgcagat gacagatgcc 2160
aatgggaata ttcagcagag gacagtgttg ccaaaacttg ttagctgagc tcacgtcccc 2220
tgatgctggt aacctgaaag atacgacatt gctgagcctt actgggttga aaaggagtag 2280
ctcagacctg tttttatttg ctcaataact ctactcattt gtatcttttc agcacttaat 2340
tttaatgtaa gaaagttgtt cattttgttt ttataaaata catgaggaca atgctttaag 2400
tttttatact ttcagaaact ttttgtgttc taaaagtaca atgagcctta ctgtatttag 2460
tgtggcagaa taataacatc agtggcaggc cactgattac ttcatgactg ccacgcattt 2520
acagattggt gtcaaagaca ttcactatgt ttttatggtt catgttatat cctccccagg 2580
gtgacagccc cttaaggccc tccttttccc tccatgctcc aggtccatgc acaggtgtag 2640
catgtcctgc ttccgttttt cataaattaa tctgggtgtt gggggtagtg ggaggagaac 2700
ggtcagaatc aaagtgacat tctaagaaaa actgtacctt agagattttc ctctagtgct 2760
caaacaaata caaaataaga tccccaaggt ttaaactgcc cagttagcat tctgacattc 2820
taaaagccgg caaagcagct tttagtggat aaatgggaat ggaaacgtgt gtgttcctcc 2880
aaattttcta gtatgatcgg tgagctgttt tgtaaagaag cctcatatta cagagttgct 2940
tttgcaccta aatttagaat tgtattccat gaactgttcc tcccttttct ctgcttttct 3000
cctctctgtt cctcttttaa taccacacgt ctgttgcttg catttagttt gtcttcttcc 3060
ttcagctgtg tatcccagac tgttaataca gaaaagagac atttcagctg tgattatgac 3120
cattgtttca tattccaatt aaaaaaagaa cagcagccta gctacttaag gtggggattt 3180
ccatagttcc aaagaagatt tagcagatta gagtgagttc acacttttca ggtgccactg 3240
taaggttctc tcagcctggg aaactatcaa ctctttcttt aaaaagaaag agggttgaaa 3300
atcctctgga cgaacagaag tcactttggc tgttcagtaa ggccaatgtt aacaacacgt 3360
ttagaggagg aaaagttcaa cctcaagtta aatggtttga cttattcttc gtatcattag 3420
aagaacccca gagatagcat tcctctattt tattttactt tcttttggat tgcactgatt 3480
gtttttgtgg gaatgacact ttatctggca aagtaactga gagtttggta aaagaatatt 3540
ttcttctctg aataataatt attttcacag tgaaaatttc agtattttat cactaatgta 3600
tgagcaatga tctatatcaa tttcaaggca cgtgaaaaaa attttttagt atgtgcaatt 3660
taatatagaa agatttctgc ctgtttggac aataggtttt gggtagtaca gattaggata 3720
agtaagctta tatatgcaca gagattattg tattacctgt aaattgattt acaagtactt 3780
aaaagcgtgg tccccagtga ggccaagaaa gtttccggtt aagttcttta ataataatcc 3840
tacagtttat cttaagaaaa aaaaaaaggt ttgaaaaaaa cactttaatt taggcttcgt 3900
tggttgatgg tggaaaaaaa tgctcaggaa atatttcaga tatttgccaa aaaaccagta 3960
ataaggttac cttattaaaa tagtgatatt tgctttacta tttaaggtgt cactgataaa 4020
ttaatttgta cttctgtgtt tagaaattat agcttctttt cccttagtca aattttttag 4080
catattatac acatttctgt gtaatctgtg gaagtgcaat aatatgttag taagttacat 4140
tttaaataat gctcatgtga caatactccc aatcaatggc ttatagaatt taaagatctg 4200
tatattagat tttggcttaa aggcatgaga agtataagac ttggtttggt ggctttgtaa 4260
gaccaccagc ctcttaatga tggttagctt ctttaggtca ttaaatcaat aaaaacatat 4320
aatgctgttt tgctcttcta atgctcctct tccatttcca gttatcttca catttacatt 4380
taaatataca aacctgagcc tgccattatt aatttcccta taaaatgacg atacatgtga 4440
acatttataa atggactaat actgcttgtc tttcccccac cgcacaaaac tggttcttaa 4500
gatgccagca atgaatttga gactatcttt atttataaat ggaaaccgga aacttttata 4560
ccaaactata ataatgtgca gcactgtagg gctttttttt ttttccctcc aaatacagtg 4620
aaattttttt attcacaaga gctgccacat ctcagcattt agtaatagag ctgctttaat 4680
aaaattctag tttgattgtc atgtcaaaaa aagaaaaatg ttgcatcttt gtgattttaa 4740
aacataaatt aatgaaggct ctgataggct attaggagtt ggcttggaaa cagtttttgg 4800
tctcacaggt taccattgtt tggggatgtc tgagctgttt tcagatctag gaatagcaca 4860
gtgttgtctt gtctttggca gtctcatttg gctctgtttc ttgcaccacc agcgtgttca 4920
ttaccactta aatatattgc tacagcagtg gaacaacaga gtggtgcaag acactgtaga 4980
ttaacggtag aggagaaatt gtgcccttag tgttaacaat gtgccttttg ttctgaatgc 5040
catgttgtag ggcatgcatt ttttggcctc tttaactctt cgaattctag tcagtaagaa 5100
tggaacccat ctctgcaaag atacatctgt cttaaatatc tagttacagg ccttaataga 5160
aaccataagg catgactcat cttcaggcac tgaaaaaaga taaccatcag gtagtgttac 5220
acaaggactt cctatattta aggggttaaa gatggtcttt gttgtatctt aacatcagac 5280
tgatttttac attttttttt tgttatgcta acactagaca aaaatcaact gtatttgtaa 5340
aaatttacct caaaccattt aattttatag tgtgattaat cccagggcat ttggtatgaa 5400
ccaaagtgca ttccttttat atgtgcctgg ctctagtaag gatggccagg gatttttaca 5460
atttgggtgc aaggcactta agccactttt aaacttaatg ggtggtttgg ggtcgtgtta 5520
aatgactcca tcagaatgtt agaaaacact ttaggcatca gtagcattgg gccatattgg 5580
aatcctaaag tgtgaattat tttaaggaga gcattcattt ttgtaatttt tttcatcaaa 5640
aatatttctg gtaagcagaa gactttttaa aaaaactgat ctggtctcgg taaaggtttt 5700
aatattgccc aacataatgc tgtaatagca ttaaaaaaag tatttgtgaa ctctgtttct 5760
taggggcttg tacatctctc tgctatggac atacataaaa ttaattgtaa ttatactcag 5820
ctcaactgct acagttctgt ctaggcagtg gcttgggttt ttatcgagca acaacttaga 5880
cacgtgactg taatatgctg caactgtgtg tactgaaaat atgtgaaaat ggttgaatgt 5940
ggactgtgta tatatgtatg taaaaatttc tgtgagatgc tgctgtcgcc acttaacatt 6000
aaatatgttc tagtggattt taatcctagt ggccagttct atgatactgt atgtattata 6060
cagctgatga caggagtaag actgtttagt gaatatctgt taaattttat tgttgtggcc 6120
agagataatt tcagaataaa attttaatgt cctacctta 6159
<210> 149
<211> 528
<212> PRT
<213> Homo sapiens
<400> 149
Met Asn Asp His Leu His Val Gly Ser His Ala His Gly Gln Ile Gln
1 5 10 15
Val Gln Gln Leu Phe Glu Asp Asn Ser Asn Lys Arg Thr Val Leu Thr
20 25 30
Thr Gln Pro Asn Gly Leu Thr Thr Val Gly Lys Thr Gly Leu Pro Val
35 40 45
Val Pro Glu Arg Gln Leu Asp Ser Ile His Arg Arg Gln Gly Ser Ser
50 55 60
Thr Ser Leu Lys Ser Met Glu Gly Met Gly Lys Val Lys Ala Thr Pro
65 70 75 80
Met Thr Pro Glu Gln Ala Met Lys Gln Tyr Met Gln Lys Leu Thr Ala
85 90 95
Phe Glu His His Glu Ile Phe Ser Tyr Pro Glu Ile Tyr Phe Leu Gly
100 105 110
Leu Asn Ala Lys Lys Arg Gln Gly Met Thr Gly Gly Pro Asn Asn Gly
115 120 125
Gly Tyr Asp Asp Asp Gln Gly Ser Tyr Val Gln Val Pro His Asp His
130 135 140
Val Ala Tyr Arg Tyr Glu Val Leu Lys Val Ile Gly Lys Gly Ser Phe
145 150 155 160
Gly Gln Val Val Lys Ala Tyr Asp His Lys Val His Gln His Val Ala
165 170 175
Leu Lys Met Val Arg Asn Glu Lys Arg Phe His Arg Gln Ala Ala Glu
180 185 190
Glu Ile Arg Ile Leu Glu His Leu Arg Lys Gln Asp Lys Asp Asn Thr
195 200 205
Met Asn Val Ile His Met Leu Glu Asn Phe Thr Phe Arg Asn His Ile
210 215 220
Cys Met Thr Phe Glu Leu Leu Ser Met Asn Leu Tyr Glu Leu Ile Lys
225 230 235 240
Lys Asn Lys Phe Gln Gly Phe Ser Leu Pro Leu Val Arg Lys Phe Ala
245 250 255
His Ser Ile Leu Gln Cys Leu Asp Ala Leu His Lys Asn Arg Ile Ile
260 265 270
His Cys Asp Leu Lys Pro Glu Asn Ile Leu Leu Lys Gln Gln Gly Arg
275 280 285
Ser Gly Ile Lys Val Ile Asp Phe Gly Ser Ser Cys Tyr Glu His Gln
290 295 300
Arg Val Tyr Thr Tyr Ile Gln Ser Arg Phe Tyr Arg Ala Pro Glu Val
305 310 315 320
Ile Leu Gly Ala Arg Tyr Gly Met Pro Ile Asp Met Trp Ser Leu Gly
325 330 335
Cys Ile Leu Ala Glu Leu Leu Thr Gly Tyr Pro Leu Leu Pro Gly Glu
340 345 350
Asp Glu Gly Asp Gln Leu Ala Cys Met Ile Glu Leu Leu Gly Met Pro
355 360 365
Ser Gln Lys Leu Leu Asp Ala Ser Lys Arg Ala Lys Asn Phe Val Ser
370 375 380
Ser Lys Gly Tyr Pro Arg Tyr Cys Thr Val Thr Thr Leu Ser Asp Gly
385 390 395 400
Ser Val Val Leu Asn Gly Gly Arg Ser Arg Arg Gly Lys Leu Arg Gly
405 410 415
Pro Pro Glu Ser Arg Glu Trp Gly Asn Ala Leu Lys Gly Cys Asp Asp
420 425 430
Pro Leu Phe Leu Asp Phe Leu Lys Gln Cys Leu Glu Trp Asp Pro Ala
435 440 445
Val Arg Met Thr Pro Gly Gln Ala Leu Arg His Pro Trp Leu Arg Arg
450 455 460
Arg Leu Pro Lys Pro Pro Thr Gly Glu Lys Thr Ser Val Lys Arg Ile
465 470 475 480
Thr Glu Ser Thr Gly Ala Ile Thr Ser Ile Ser Lys Leu Pro Pro Pro
485 490 495
Ser Ser Ser Ala Ser Lys Leu Arg Thr Asn Leu Ala Gln Met Thr Asp
500 505 510
Ala Asn Gly Asn Ile Gln Gln Arg Thr Val Leu Pro Lys Leu Val Ser
515 520 525
<210> 150
<211> 601
<212> PRT
<213> Homo sapiens
<400> 150
Met Leu Thr Arg Lys Pro Ser Ala Ala Ala Pro Ala Ala Tyr Pro Thr
1 5 10 15
Gly Arg Gly Gly Asp Ser Ala Val Arg Gln Leu Gln Ala Ser Pro Gly
20 25 30
Leu Gly Ala Gly Ala Thr Arg Ser Gly Val Gly Thr Gly Pro Pro Ser
35 40 45
Pro Ile Ala Leu Pro Pro Leu Arg Ala Ser Asn Ala Ala Ala Ala Ala
50 55 60
His Thr Ile Gly Gly Ser Lys His Thr Met Asn Asp His Leu His Val
65 70 75 80
Gly Ser His Ala His Gly Gln Ile Gln Val Gln Gln Leu Phe Glu Asp
85 90 95
Asn Ser Asn Lys Arg Thr Val Leu Thr Thr Gln Pro Asn Gly Leu Thr
100 105 110
Thr Val Gly Lys Thr Gly Leu Pro Val Val Pro Glu Arg Gln Leu Asp
115 120 125
Ser Ile His Arg Arg Gln Gly Ser Ser Thr Ser Leu Lys Ser Met Glu
130 135 140
Gly Met Gly Lys Val Lys Ala Thr Pro Met Thr Pro Glu Gln Ala Met
145 150 155 160
Lys Gln Tyr Met Gln Lys Leu Thr Ala Phe Glu His His Glu Ile Phe
165 170 175
Ser Tyr Pro Glu Ile Tyr Phe Leu Gly Leu Asn Ala Lys Lys Arg Gln
180 185 190
Gly Met Thr Gly Gly Pro Asn Asn Gly Gly Tyr Asp Asp Asp Gln Gly
195 200 205
Ser Tyr Val Gln Val Pro His Asp His Val Ala Tyr Arg Tyr Glu Val
210 215 220
Leu Lys Val Ile Gly Lys Gly Ser Phe Gly Gln Val Val Lys Ala Tyr
225 230 235 240
Asp His Lys Val His Gln His Val Ala Leu Lys Met Val Arg Asn Glu
245 250 255
Lys Arg Phe His Arg Gln Ala Ala Glu Glu Ile Arg Ile Leu Glu His
260 265 270
Leu Arg Lys Gln Asp Lys Asp Asn Thr Met Asn Val Ile His Met Leu
275 280 285
Glu Asn Phe Thr Phe Arg Asn His Ile Cys Met Thr Phe Glu Leu Leu
290 295 300
Ser Met Asn Leu Tyr Glu Leu Ile Lys Lys Asn Lys Phe Gln Gly Phe
305 310 315 320
Ser Leu Pro Leu Val Arg Lys Phe Ala His Ser Ile Leu Gln Cys Leu
325 330 335
Asp Ala Leu His Lys Asn Arg Ile Ile His Cys Asp Leu Lys Pro Glu
340 345 350
Asn Ile Leu Leu Lys Gln Gln Gly Arg Ser Gly Ile Lys Val Ile Asp
355 360 365
Phe Gly Ser Ser Cys Tyr Glu His Gln Arg Val Tyr Thr Tyr Ile Gln
370 375 380
Ser Arg Phe Tyr Arg Ala Pro Glu Val Ile Leu Gly Ala Arg Tyr Gly
385 390 395 400
Met Pro Ile Asp Met Trp Ser Leu Gly Cys Ile Leu Ala Glu Leu Leu
405 410 415
Thr Gly Tyr Pro Leu Leu Pro Gly Glu Asp Glu Gly Asp Gln Leu Ala
420 425 430
Cys Met Ile Glu Leu Leu Gly Met Pro Ser Gln Lys Leu Leu Asp Ala
435 440 445
Ser Lys Arg Ala Lys Asn Phe Val Ser Ser Lys Gly Tyr Pro Arg Tyr
450 455 460
Cys Thr Val Thr Thr Leu Ser Asp Gly Ser Val Val Leu Asn Gly Gly
465 470 475 480
Arg Ser Arg Arg Gly Lys Leu Arg Gly Pro Pro Glu Ser Arg Glu Trp
485 490 495
Gly Asn Ala Leu Lys Gly Cys Asp Asp Pro Leu Phe Leu Asp Phe Leu
500 505 510
Lys Gln Cys Leu Glu Trp Asp Pro Ala Val Arg Met Thr Pro Gly Gln
515 520 525
Ala Leu Arg His Pro Trp Leu Arg Arg Arg Leu Pro Lys Pro Pro Thr
530 535 540
Gly Glu Lys Thr Ser Val Lys Arg Ile Thr Glu Ser Thr Gly Ala Ile
545 550 555 560
Thr Ser Ile Ser Lys Leu Pro Pro Pro Ser Ser Ser Ala Ser Lys Leu
565 570 575
Arg Thr Asn Leu Ala Gln Met Thr Asp Ala Asn Gly Asn Ile Gln Gln
580 585 590
Arg Thr Val Leu Pro Lys Leu Val Ser
595 600
<210> 151
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> DYRK2_forward primer
<400> 151
cggccatgtt aaccaggaaa c 21
<210> 152
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> DYRK2_reverse primer
<400> 152
cgacatgcag gtgatcattc 20
<210> 153
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> DYRK2 probe
<400> 153
cgattggcgg cagtaagcac acaa 24
<210> 154
<211> 1921
<212> DNA
<213> Homo sapiens
<400> 154
ggcggaagtg acattatcaa cgcgcgccag gggttcagtg aggtcgggca ggttcgctgt 60
ggcgggcgcc tgggccgccg gctgtttaac ttcgcttccg ctggcccata gtgatctttg 120
cagtgaccca gcatcactgt ttcttggcgt gtgaagataa cccaaggaat tgaggaagtt 180
gctgagaaga gtgtgctgga gatgctctag gaaaaaattg aatagtgaga cgagttccag 240
cgcaagggtt tctggtttgc caagaagaaa gtgaacatca tggatcagaa caacagcctg 300
ccaccttacg ctcagggctt ggcctcccct cagggtgcca tgactcccgg aatccctatc 360
tttagtccaa tgatgcctta tggcactgga ctgaccccac agcctattca gaacaccaat 420
agtctgtcta ttttggaaga gcaacaaagg cagcagcagc aacaacaaca gcagcagcag 480
cagcagcagc agcaacagca acagcagcag cagcagcagc agcagcagca gcagcagcag 540
cagcagcagc agcagcagca acaggcagtg gcagctgcag ccgttcagca gtcaacgtcc 600
cagcaggcaa cacagggaac ctcaggccag gcaccacagc tcttccactc acagactctc 660
acaactgcac ccttgccggg caccactcca ctgtatccct cccccatgac tcccatgacc 720
cccatcactc ctgccacgcc agcttcggag agttctggga ttgtaccgca gctgcaaaat 780
attgtatcca cagtgaatct tggttgtaaa cttgacctaa agaccattgc acttcgtgcc 840
cgaaacgccg aatataatcc caagcggttt gctgcggtaa tcatgaggat aagagagcca 900
cgaaccacgg cactgatttt cagttctggg aaaatggtgt gcacaggagc caagagtgaa 960
gaacagtcca gactggcagc aagaaaatat gctagagttg tacagaagtt gggttttcca 1020
gctaagttct tggacttcaa gattcagaat atggtgggga gctgtgatgt gaagtttcct 1080
ataaggttag aaggccttgt gctcacccac caacaattta gtagttatga gccagagtta 1140
tttcctggtt taatctacag aatgatcaaa cccagaattg ttctccttat ttttgtttct 1200
ggaaaagttg tattaacagg tgctaaagtc agagcagaaa tttatgaagc atttgaaaac 1260
atctacccta ttctaaaggg attcaggaag acgacgtaat ggctctcatg tacccttgcc 1320
tcccccaccc ccttcttttt ttttttttaa acaaatcagt ttgttttggt acctttaaat 1380
ggtggtgttg tgagaagatg gatgttgagt tgcagggtgt ggcaccaggt gatgcccttc 1440
tgtaagtgcc caccgcggga tgccgggaag gggcattatt tgtgcactga gaacaccgcg 1500
cagcgtgact gtgagttgct cataccgtgc tgctatctgg gcagcgctgc ccatttattt 1560
atatgtagat tttaaacact gctgttgaca agttggtttg agggagaaaa ctttaagtgt 1620
taaagccacc tctataattg attggacttt ttaattttaa tgtttttccc catgaaccac 1680
agtttttata tttctaccag aaaagtaaaa atctttttta aaagtgttgt ttttctaatt 1740
tataactcct aggggttatt tctgtgccag acacattcca cctctccagt attgcaggac 1800
agaatatatg tgttaatgaa aatgaatggc tgtacatatt tttttctttc ttcagagtac 1860
tctgtacaat aaatgcagtt tataaaagtg ttagattgtt gttaaaaaaa aaaaaaaaaa 1920
a 1921
<210> 155
<211> 1435
<212> DNA
<213> Homo sapiens
<400> 155
ggcggggcct gcttctcctc agcttcaggc ggctgcgacg agccctcagg cgaacctctc 60
ggctttcccg cgcggcgccg cctcttgctg cgcctccgcc tcctcctctg ctccgccacc 120
ggcttcctcc tcctgagcag tcagcccgcg cgccggccgg ctccgttatg gcgacccgca 180
gccctggcgt cgtgattagt gatgatgaac caggttatga ccttgattta ttttgcatac 240
ctaatcatta tgctgaggat ttggaaaggg tgtttattcc tcatggacta attatggaca 300
ggactgaacg tcttgctcga gatgtgatga aggagatggg aggccatcac attgtagccc 360
tctgtgtgct caaggggggc tataaattct ttgctgacct gctggattac atcaaagcac 420
tgaatagaaa tagtgataga tccattccta tgactgtaga ttttatcaga ctgaagagct 480
attgtaatga ccagtcaaca ggggacataa aagtaattgg tggagatgat ctctcaactt 540
taactggaaa gaatgtcttg attgtggaag atataattga cactggcaaa acaatgcaga 600
ctttgctttc cttggtcagg cagtataatc caaagatggt caaggtcgca agcttgctgg 660
tgaaaaggac cccacgaagt gttggatata agccagactt tgttggattt gaaattccag 720
acaagtttgt tgtaggatat gcccttgact ataatgaata cttcagggat ttgaatcatg 780
tttgtgtcat tagtgaaact ggaaaagcaa aatacaaagc ctaagatgag agttcaagtt 840
gagtttggaa acatctggag tcctattgac atcgccagta aaattatcaa tgttctagtt 900
ctgtggccat ctgcttagta gagctttttg catgtatctt ctaagaattt tatctgtttt 960
gtactttaga aatgtcagtt gctgcattcc taaactgttt atttgcacta tgagcctata 1020
gactatcagt tccctttggg cggattgttg tttaacttgt aaatgaaaaa attctcttaa 1080
accacagcac tattgagtga aacattgaac tcatatctgt aagaaataaa gagaagatat 1140
attagttttt taattggtat tttaattttt atatatgcag gaaagaatag aagtgattga 1200
atattgttaa ttataccacc gtgtgttaga aaagtaagaa gcagtcaatt ttcacatcaa 1260
agacagcatc taagaagttt tgttctgtcc tggaattatt ttagtagtgt ttcagtaatg 1320
ttgactgtat tttccaactt gttcaaatta ttaccagtga atctttgtca gcagttccct 1380
tttaaatgca aatcaataaa ttcccaaaaa tttaaaaaaa aaaaaaaaaa aaaaa 1435
<210> 156
<211> 1852
<212> DNA
<213> Homo sapiens
<400> 156
accgccgaga ccgcgtccgc cccgcgagca cagagcctcg cctttgccga tccgccgccc 60
gtccacaccc gccgccagct caccatggat gatgatatcg ccgcgctcgt cgtcgacaac 120
ggctccggca tgtgcaaggc cggcttcgcg ggcgacgatg ccccccgggc cgtcttcccc 180
tccatcgtgg ggcgccccag gcaccagggc gtgatggtgg gcatgggtca gaaggattcc 240
tatgtgggcg acgaggccca gagcaagaga ggcatcctca ccctgaagta ccccatcgag 300
cacggcatcg tcaccaactg ggacgacatg gagaaaatct ggcaccacac cttctacaat 360
gagctgcgtg tggctcccga ggagcacccc gtgctgctga ccgaggcccc cctgaacccc 420
aaggccaacc gcgagaagat gacccagatc atgtttgaga ccttcaacac cccagccatg 480
tacgttgcta tccaggctgt gctatccctg tacgcctctg gccgtaccac tggcatcgtg 540
atggactccg gtgacggggt cacccacact gtgcccatct acgaggggta tgccctcccc 600
catgccatcc tgcgtctgga cctggctggc cgggacctga ctgactacct catgaagatc 660
ctcaccgagc gcggctacag cttcaccacc acggccgagc gggaaatcgt gcgtgacatt 720
aaggagaagc tgtgctacgt cgccctggac ttcgagcaag agatggccac ggctgcttcc 780
agctcctccc tggagaagag ctacgagctg cctgacggcc aggtcatcac cattggcaat 840
gagcggttcc gctgccctga ggcactcttc cagccttcct tcctgggcat ggagtcctgt 900
ggcatccacg aaactacctt caactccatc atgaagtgtg acgtggacat ccgcaaagac 960
ctgtacgcca acacagtgct gtctggcggc accaccatgt accctggcat tgccgacagg 1020
atgcagaagg agatcactgc cctggcaccc agcacaatga agatcaagat cattgctcct 1080
cctgagcgca agtactccgt gtggatcggc ggctccatcc tggcctcgct gtccaccttc 1140
cagcagatgt ggatcagcaa gcaggagtat gacgagtccg gcccctccat cgtccaccgc 1200
aaatgcttct aggcggacta tgacttagtt gcgttacacc ctttcttgac aaaacctaac 1260
ttgcgcagaa aacaagatga gattggcatg gctttatttg ttttttttgt tttgttttgg 1320
tttttttttt ttttttggct tgactcagga tttaaaaact ggaacggtga aggtgacagc 1380
agtcggttgg agcgagcatc ccccaaagtt cacaatgtgg ccgaggactt tgattgcaca 1440
ttgttgtttt tttaatagtc attccaaata tgagatgcgt tgttacagga agtcccttgc 1500
catcctaaaa gccaccccac ttctctctaa ggagaatggc ccagtcctct cccaagtcca 1560
cacaggggag gtgatagcat tgctttcgtg taaattatgt aatgcaaaat ttttttaatc 1620
ttcgccttaa tactttttta ttttgtttta ttttgaatga tgagccttcg tgccccccct 1680
tccccctttt ttgtccccca acttgagatg tatgaaggct tttggtctcc ctgggagtgg 1740
gtggaggcag ccagggctta cctgtacact gacttgagac cagttgaata aaagtgcaca 1800
ccttaaaaat gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 1852
<210> 157
<211> 1229
<212> DNA
<213> Homo sapiens
<400> 157
gtctgacggg cgatggcgca gccaatagac aggagcgcta tccgcggttt ctgattggct 60
actttgttcg cattataaaa ggcacgcgcg ggcgcgaggc ccttctctcg ccaggcgtcc 120
tcgtggaagt gacatcgtct ttaaaccctg cgtggcaatc cctgacgcac cgccgtgatg 180
cccagggaag acagggcgac ctggaagtcc aactacttcc ttaagatcat ccaactattg 240
gatgattatc cgaaatgttt cattgtggga gcagacaatg tgggctccaa gcagatgcag 300
cagatccgca tgtcccttcg cgggaaggct gtggtgctga tgggcaagaa caccatgatg 360
cgcaaggcca tccgagggca cctggaaaac aacccagctc tggagaaact gctgcctcat 420
atccggggga atgtgggctt tgtgttcacc aaggaggacc tcactgagat cagggacatg 480
ttgctggcca ataaggtgcc agctgctgcc cgtgctggtg ccattgcccc atgtgaagtc 540
actgtgccag cccagaacac tggtctcggg cccgagaaga cctccttttt ccaggcttta 600
ggtatcacca ctaaaatctc caggggcacc attgaaatcc tgagtgatgt gcagctgatc 660
aagactggag acaaagtggg agccagcgaa gccacgctgc tgaacatgct caacatctcc 720
cccttctcct ttgggctggt catccagcag gtgttcgaca atggcagcat ctacaaccct 780
gaagtgcttg atatcacaga ggaaactctg cattctcgct tcctggaggg tgtccgcaat 840
gttgccagtg tctgtctgca gattggctac ccaactgttg catcagtacc ccattctatc 900
atcaacgggt acaaacgagt cctggccttg tctgtggaga cggattacac cttcccactt 960
gctgaaaagg tcaaggcctt cttggctgat ccatctgcct ttgtggctgc tgcccctgtg 1020
gctgctgcca ccacagctgc tcctgctgct gctgcagccc cagctaaggt tgaagccaag 1080
gaagagtcgg aggagtcgga cgaggatatg ggatttggtc tctttgacta atcaccaaaa 1140
agcaaccaac ttagccagtt ttatttgcaa aacaaggaaa taaaggctta cttctttaaa 1200
aagtaaaaaa aaaaaaaaaa aaaaaaaaa 1229
<210> 158
<211> 1229
<212> DNA
<213> Homo sapiens
<400> 158
gtctgacggg cgatggcgca gccaatagac aggagcgcta tccgcggttt ctgattggct 60
actttgttcg cattataaaa ggcacgcgcg ggcgcgaggc ccttctctcg ccaggcgtcc 120
tcgtggaagt gacatcgtct ttaaaccctg cgtggcaatc cctgacgcac cgccgtgatg 180
cccagggaag acagggcgac ctggaagtcc aactacttcc ttaagatcat ccaactattg 240
gatgattatc cgaaatgttt cattgtggga gcagacaatg tgggctccaa gcagatgcag 300
cagatccgca tgtcccttcg cgggaaggct gtggtgctga tgggcaagaa caccatgatg 360
cgcaaggcca tccgagggca cctggaaaac aacccagctc tggagaaact gctgcctcat 420
atccggggga atgtgggctt tgtgttcacc aaggaggacc tcactgagat cagggacatg 480
ttgctggcca ataaggtgcc agctgctgcc cgtgctggtg ccattgcccc atgtgaagtc 540
actgtgccag cccagaacac tggtctcggg cccgagaaga cctccttttt ccaggcttta 600
ggtatcacca ctaaaatctc caggggcacc attgaaatcc tgagtgatgt gcagctgatc 660
aagactggag acaaagtggg agccagcgaa gccacgctgc tgaacatgct caacatctcc 720
cccttctcct ttgggctggt catccagcag gtgttcgaca atggcagcat ctacaaccct 780
gaagtgcttg atatcacaga ggaaactctg cattctcgct tcctggaggg tgtccgcaat 840
gttgccagtg tctgtctgca gattggctac ccaactgttg catcagtacc ccattctatc 900
atcaacgggt acaaacgagt cctggccttg tctgtggaga cggattacac cttcccactt 960
gctgaaaagg tcaaggcctt cttggctgat ccatctgcct ttgtggctgc tgcccctgtg 1020
gctgctgcca ccacagctgc tcctgctgct gctgcagccc cagctaaggt tgaagccaag 1080
gaagagtcgg aggagtcgga cgaggatatg ggatttggtc tctttgacta atcaccaaaa 1140
agcaaccaac ttagccagtt ttatttgcaa aacaaggaaa taaaggctta cttctttaaa 1200
aagtaaaaaa aaaaaaaaaa aaaaaaaaa 1229
<210> 159
<211> 6738
<212> DNA
<213> Homo sapiens
<400> 159
gagagcgcgg ccgggacggt tggagaagaa ggcggctccc ggaaggggga gagacaaact 60
gccgtaacct ctgccgttca ggaacccggt tacttattta ttcgttaccc tttttcttct 120
tcctccccca aaaacctttt ccttttccct tctttttttt tcctttttgg gagctgaaaa 180
atttccggta agggaaagaa gggctccttt cgctccttat ttccccgcct ccttccctcc 240
cccaccttcc cctcctccgg ctttttcctc ccaactcggg gaggtccttc ccggtggccg 300
ccctgacgag gtctgagcac ctaggcggag gcggcgcagg ctttttgtag tgaggtttgc 360
gcctgcgcag cgcgcctgcc tccgccatgc acgggggtgg ccccccctcg ggggacagcg 420
catgcccgct gcgcaccatc aagagagtcc agttcggagt cctgagtccg gatgaactga 480
agcgaatgtc tgtgacggag ggtggcatca aatacccaga gacgactgag ggaggccgcc 540
ccaagcttgg ggggctgatg gacccgaggc agggggtgat tgagcggact ggccgctgcc 600
aaacatgtgc aggaaacatg acagagtgtc ctggccactt tggccacatt gaactggcca 660
agcctgtgtt tcacgtgggc ttcctggtga agacaatgaa agttttgcgc tgtgtctgct 720
tcttctgctc caaactgctt gtggactcta acaacccaaa gatcaaggat atcctggcta 780
agtccaaggg acagcccaag aagcggctca cacatgtcta cgacctttgc aagggcaaaa 840
acatatgcga gggtggggag gagatggaca acaagttcgg tgtggaacaa cctgagggtg 900
acgaggatct gaccaaagaa aagggccatg gtggctgtgg gcggtaccag cccaggatcc 960
ggcgttctgg cctagagctg tatgcggaat ggaagcacgt taatgaggac tctcaggaga 1020
agaagatcct gctgagtcca gagcgagtgc atgagatctt caaacgcatc tcagatgagg 1080
agtgttttgt gctgggcatg gagccccgct atgcacggcc agagtggatg attgtcacag 1140
tgctgcctgt gcccccgctc tccgtgcggc ctgctgttgt gatgcagggc tctgcccgta 1200
accaggatga cctgactcac aaactggctg acatcgtgaa gatcaacaat cagctgcggc 1260
gcaatgagca gaacggcgca gcggcccatg tcattgcaga ggatgtgaag ctcctccagt 1320
tccatgtggc caccatggtg gacaatgagc tgcctggctt gccccgtgcc atgcagaagt 1380
ctgggcgtcc cctcaagtcc ctgaagcagc ggttgaaggg caaggaaggc cgggtgcgag 1440
ggaacctgat gggcaaaaga gtggacttct cggcccgtac tgtcatcacc cccgacccca 1500
acctctccat tgaccaggtt ggcgtgcccc gctccattgc tgccaacatg acctttgcgg 1560
agattgtcac ccccttcaac attgacagac ttcaagaact agtgcgcagg gggaacagcc 1620
agtacccagg cgccaagtac atcatccgag acaatggtga tcgcattgac ttgcgtttcc 1680
accccaagcc cagtgacctt cacctgcaga ccggctataa ggtggaacgg cacatgtgtg 1740
atggggacat tgttatcttc aaccggcagc caactctgca caaaatgtcc atgatggggc 1800
atcgggtccg cattctccca tggtctacct ttcgcttgaa tcttagtgtg acaactccgt 1860
acaatgcaga ctttgacggg gatgagatga acttgcacct gccacagtct ctggagacgc 1920
gagcagagat ccaggagctg gccatggttc ctcgcatgat tgtcaccccc cagagcaatc 1980
ggcctgtcat gggtattgtg caggacacac tcacagcagt gcgcaaattc accaagagag 2040
acgtcttcct ggagcggggt gaagtgatga acctcctgat gttcctgtcg acgtgggatg 2100
ggaaggtccc acagccggcc atcctaaagc cccggcccct gtggacaggc aagcaaatct 2160
tctccctcat catacctggt cacatcaatt gtatccgtac ccacagcacc catcccgatg 2220
atgaagacag tggcccttac aagcacatct ctcctgggga caccaaggtg gtggtggaga 2280
atggggagct gatcatgggc atcctgtgta agaagtctct gggcacgtca gctggctccc 2340
tggtccacat ctcctaccta gagatgggtc atgacatcac tcgcctcttc tactccaaca 2400
ttcagactgt cattaacaac tggctcctca tcgagggtca tactattggc attggggact 2460
ccattgctga ttctaagact taccaggaca ttcagaacac tattaagaag gccaagcagg 2520
acgtaataga ggtcatcgag aaggcacaca acaatgagct ggagcccacc ccagggaaca 2580
ctctgcggca gacgtttgag aatcaggtga accgcattct taacgatgcc cgagacaaga 2640
ctggctcctc tgctcagaaa tccctgtctg aatacaacaa cttcaagtct atggtcgtgt 2700
ccggagctaa aggttccaag attaacatct cccaggtcat tgctgtcgtt ggacagcaga 2760
acgtcgaggg caagcggatt ccatttggct tcaagcaccg gactctgcct cacttcatca 2820
aggatgacta cgggcctgag agccgtggct ttgtggagaa ctcctaccta gccggcctca 2880
cacccactga gttctttttc cacgccatgg ggggtcgtga ggggctcatt gacacggctg 2940
tcaagactgc tgagactgga tacatccagc ggcggctgat caagtccatg gagtcagtga 3000
tggtgaagta cgacgcgact gtgcggaact ccatcaacca ggtggtgcag ctgcgctacg 3060
gcgaagacgg cctggcaggc gagagcgttg agttccagaa cctggctacg cttaagcctt 3120
ccaacaaggc ttttgagaag aagttccgct ttgattatac caatgagagg gccctgcggc 3180
gcactctgca ggaggacctg gtgaaggacg tgctgagcaa cgcacacatc cagaacgagt 3240
tggagcggga atttgagcgg atgcgggagg atcgggaggt gctcagggtc atcttcccaa 3300
ctggagacag caaggtcgtc ctcccctgta acctgctgcg gatgatctgg aatgctcaga 3360
aaatcttcca catcaaccca cgccttccct ccgacctgca ccccatcaaa gtggtggagg 3420
gagtcaagga attgagcaag aagctggtga ttgtgaatgg ggatgaccca ctaagtcgac 3480
aggcccagga aaatgccacg ctgctcttca acatccacct gcggtccacg ttgtgttccc 3540
gccgcatggc agaggagttt cggctcagtg gggaggcctt cgactggctg cttggggaga 3600
ttgagtccaa gttcaaccaa gccattgcgc atcccgggga aatggtgggg gctctggctg 3660
cgcagtccct tggagaacct gccacccaga tgaccttgaa taccttccac tatgctggtg 3720
tgtctgccaa gaatgtgacg ctgggtgtgc cccgacttaa ggagctcatc aacatttcca 3780
agaagccaaa gactccttcg cttactgtct tcctgttggg ccagtccgct cgagatgctg 3840
agagagccaa ggatattctg tgccgtctgg agcatacaac gttgaggaag gtgactgcca 3900
acacagccat ctactatgac cccaaccccc agagcacggt ggtggcagag gatcaggaat 3960
gggtgaatgt ctactatgaa atgcctgact ttgatgtggc ccgaatctcc ccctggctgt 4020
tgcgggtgga gctggatcgg aagcacatga ctgaccggaa gctcaccatg gagcagattg 4080
ctgaaaagat caatgctggt tttggtgacg acttgaactg catctttaat gatgacaatg 4140
cagagaagct ggtgctccgt attcgcatca tgaacagcga tgagaacaag atgcaagagg 4200
aggaagaggt ggtggacaag atggatgatg atgtcttcct gcgctgcatc gagtccaaca 4260
tgctgacaga tatgaccctg cagggcatcg agcagatcag caaggtgtac atgcacttgc 4320
cacagacaga caacaagaag aagatcatca tcacggagga tggggaattc aaggccctgc 4380
aggagtggat cctggagacg gacggcgtga gcttgatgcg ggtgctgagt gagaaggacg 4440
tggaccccgt acgcaccacg tccaatgaca ttgtggagat cttcacggtg ctgggcattg 4500
aagccgtgcg gaaggccctg gagcgggagc tgtaccacgt catctccttt gatggctcct 4560
atgtcaatta ccgacacttg gctctcttgt gtgataccat gacctgtcgt ggccacttga 4620
tggccatcac ccgacacgga gtcaaccgcc aggacacagg accactcatg aagtgttcct 4680
ttgaggaaac ggtggacgtg cttatggaag cagccgcaca cggtgagagt gaccccatga 4740
agggggtctc tgagaatatc atgctgggcc agctggctcc ggccggcact ggctgctttg 4800
acctcctgct tgatgcagag aagtgcaagt atggcatgga gatccccacc aatatccccg 4860
gcctgggggc tgctggaccc accggcatgt tctttggttc agcacccagt cccatgggtg 4920
gaatctctcc tgccatgaca ccttggaacc agggtgcaac ccctgcctat ggcgcctggt 4980
cccccagtgt tgggagtgga atgaccccag gggcagccgg cttctctccc agtgctgcgt 5040
cagatgccag cggcttcagc ccaggttact cccctgcctg gtctcccaca ccgggctccc 5100
cggggtcccc aggtccctca agcccctaca tcccttcacc aggtggtgcc atgtctccca 5160
gctactcgcc aacgtcacct gcctacgagc cccgctctcc tgggggctac acaccccaga 5220
gtccctctta ttcccccact tcaccctcct actcccctac ctctccatcc tattctccaa 5280
ccagtcccaa ctatagtccc acatcaccca gctattcgcc aacgtcaccc agctactcac 5340
cgacctctcc cagctactca cccacctctc ccagctactc gcccacctct cccagctact 5400
cgcccacctc tcccagctac tcacccactt cccctagcta ctcgcccact tcccctagct 5460
actcgccaac gtctcccagc tactcgccga catctcccag ctactcgcca acttcaccca 5520
gctattctcc cacttctccc agctactcac ctacctctcc aagctattca cccacctccc 5580
ccagctactc acccacttcc ccaagttact cacccaccag cccgaactat tctccaacca 5640
gtcccaatta caccccaaca tcacccagct acagcccgac atcacccagc tattcaccta 5700
ctagtcccaa ctacacacct accagcccta actacagccc aacctctcca agctactctc 5760
caacatcacc cagctattcc ccgacctcac caagttactc cccttccagc ccacgataca 5820
caccacagtc tccaacctat accccaagct cacccagcta cagccccagc tcgcccagct 5880
acagcccaac ctcacccaag tacaccccaa ccagtccttc ttacagtccc agctccccag 5940
agtatacccc aacctctccc aagtactcac ctaccagtcc caaatattca cccacctctc 6000
ccaagtactc gcctaccagt cccacctatt cacccaccac cccaaaatac tccccaacat 6060
ctcctactta ttccccaacc tctccagtct acaccccaac ctctcccaag tactcaccta 6120
ctagccccac ttactcgccc acttccccca agtactcgcc caccagcccc acctactcgc 6180
ccacctcccc caaaggctca acctactctc ccacttcccc tggttactcg cccaccagcc 6240
ccacctacag tctcacaagc ccggctatca gcccggatga cagtgacgag gagaactgag 6300
ggcacgtggg gtgcggcagc gggctagggc ccagggcagc ttgcccgtgc tgctgtgcag 6360
ttcttgcctc cctcacgggg cgtcaccccc agcccagctc cgttgtacat aaatgccttg 6420
tggcagagct cccggtgaac ttctggatcc cgtttctgat gcagactctt gtcttgttct 6480
ccacttgtgc tgttagaact cactggccca gtggtgttct cactcctacc ccacccaccc 6540
cctgcctgtc cccaaattga agatccttcc ttgcctgtgg cttgatgcgg ggcgggtaaa 6600
gggtatttta acttaggggt agttcctgct gtgagtggtt acagctgatc ctcgggaaga 6660
acaaagctaa agctgccttt tgtctgttat tttatttttt tgaagtttaa ataaagttta 6720
ctaattttga ccaaaagt 6738
<210> 160
<211> 987
<212> DNA
<213> Homo sapiens
<400> 160
aatataagtg gaggcgtcgc gctggcgggc attcctgaag ctgacagcat tcgggccgag 60
atgtctcgct ccgtggcctt agctgtgctc gcgctactct ctctttctgg cctggaggct 120
atccagcgta ctccaaagat tcaggtttac tcacgtcatc cagcagagaa tggaaagtca 180
aatttcctga attgctatgt gtctgggttt catccatccg acattgaagt tgacttactg 240
aagaatggag agagaattga aaaagtggag cattcagact tgtctttcag caaggactgg 300
tctttctatc tcttgtacta cactgaattc acccccactg aaaaagatga gtatgcctgc 360
cgtgtgaacc atgtgacttt gtcacagccc aagatagtta agtgggatcg agacatgtaa 420
gcagcatcat ggaggtttga agatgccgca tttggattgg atgaattcca aattctgctt 480
gcttgctttt taatattgat atgcttatac acttacactt tatgcacaaa atgtagggtt 540
ataataatgt taacatggac atgatcttct ttataattct actttgagtg ctgtctccat 600
gtttgatgta tctgagcagg ttgctccaca ggtagctcta ggagggctgg caacttagag 660
gtggggagca gagaattctc ttatccaaca tcaacatctt ggtcagattt gaactcttca 720
atctcttgca ctcaaagctt gttaagatag ttaagcgtgc ataagttaac ttccaattta 780
catactctgc ttagaatttg ggggaaaatt tagaaatata attgacagga ttattggaaa 840
tttgttataa tgaatgaaac attttgtcat ataagattca tatttacttc ttatacattt 900
gataaagtaa ggcatggttg tggttaatct ggtttatttt tgttccacaa gttaaataaa 960
tcataaaact tgatgtgtta tctctta 987
<210> 161
<211> 5416
<212> DNA
<213> Homo sapiens
<400> 161
agtgggccgc catgttgtcg gagtgaaagg taagggggag cgagagcgcc agagagagaa 60
gatcgggggg ctgaaatcca tcttcatcct accgctccgc ccgtgttggt ggaatgagcg 120
ttgcatgtgt cttgaagaga aaagcagtgc tttggcagga ctctttcagc ccccacctga 180
aacatcaccc tcaagaacca gctaatccca acatgcctgt tgttttgaca tctggaacag 240
ggtcgcaagc gcagccacaa ccagctgcaa atcaggctct tgcagctggg actcactcca 300
gccctgtccc aggatctata ggagttgcag gccgttccca ggacgacgct atggtggact 360
acttctttca gaggcagcat ggtgagcagc ttgggggagg aggaagtgga ggaggcggct 420
ataataatag caaacatcga tggcctactg gggataacat tcatgcagaa catcaggtgc 480
gttccatgga tgaactgaat catgattttc aagcacttgc tctggaggga agagcgatgg 540
gagagcagct cttgccaggt aaaaagtttt gggaaacaga tgaatccagc aaagatggac 600
caaaaggaat attcctgggt gatcaatggc gagacagtgc ctggggaaca tcagatcatt 660
cagtttccca gccaatcatg gtgcagagaa gacctggtca gagtttccat gtgaacagtg 720
aggtcaattc tgtactgtcc ccacgatcgg agagtggggg actaggcgtt agcatggtgg 780
agtatgtgtt gagctcatcc ccgggcgatt cctgtctaag aaaaggagga tttggcccaa 840
gggatgcaga cagtgatgaa aacgacaaag gtgaaaagaa gaacaagggt acgtttgatg 900
gagataagct aggagatttg aaggaggagg gtgatgtgat ggacaagacc aatggtttac 960
cagtgcagaa tgggattgat gcagacgtca aagattttag ccgtacccct ggtaattgcc 1020
agaactctgc taatgaagtg gatcttctgg gtccaaacca gaatggttct gagggcttag 1080
cccagctgac cagcaccaat ggtgccaagc ctgtggagga tttctccaac atggagtccc 1140
agagtgtccc cttggacccc atggaacatg tgggcatgga gcctcttcag tttgattatt 1200
caggcacgca ggtacctgtg gactcagcag cagcaactgt gggacttttt gactacaatt 1260
ctcaacaaca gctgttccaa agacctaatg cgcttgctgt ccagcagttg acagctgctc 1320
agcagcagca gtatgcactg gcagctgctc atcagccgca catcggttta gctcccgctg 1380
cgtttgtccc caatccatac atcatcagcg ctgctccccc agggacggac ccctacacag 1440
ctggattggc tgcagcagcg acactaggcc cagctgtggt ccctcaccag tattatggag 1500
ttactccctg gggagtctac cctgccagtc ttttccagca gcaagctgcc gctgccgctg 1560
cagcaactaa ttcagctaat caacagacca ccccacaggc tcagcaagga cagcagcagg 1620
ttctccgtgg aggagccagc caacgtcctt tgaccccaaa ccagaaccag cagggacagc 1680
aaacggatcc ccttgtggca gctgcagcag tgaattctgc ccttgcattt ggacaaggtc 1740
tggcagcagg catgccaggt tatccggtgt tggctcctgc tgcttactat gaccaaactg 1800
gtgcccttgt agtgaatgca ggcgcgagaa atggtcttgg agctcctgtt cgacttgtag 1860
ctcctgcccc agtcatcatt agttcctcag ctgcacaagc agctgttgca gcagccgcag 1920
cttcagcaaa tggagcagct ggtggtcttg ctggaacaac aaatggacca tttcgccctt 1980
taggaacaca gcagcctcag ccccagcccc agcagcagcc caataacaac ctggcatcca 2040
gttctttcta cggcaacaac tctctgaaca gcaattcaca gagcagctcc ctcttctccc 2100
agggctctgc ccagcctgcc aacacatcct tgggattcgg aagtagcagt tctctcggcg 2160
ccaccctggg atccgccctt ggagggtttg gaacagcagt tgcaaactcc aacactggca 2220
gtggctcccg ccgtgactcc ctgactggca gcagtgacct ttataagagg acatcgagca 2280
gcttgacccc cattggacac agtttttata acggccttag cttttcctcc tctcctggac 2340
ccgtgggcat gcctctccct agtcagggac caggacattc acagacacca cctccttccc 2400
tctcttcaca tggatcctct tcaagcttaa acctgggagg actcacgaat ggcagtggaa 2460
gatacatctc tgctgctcca ggcgctgaag ccaagtaccg cagtgcaagc agcgcctcca 2520
gcctcttcag cccgagcagc actcttttct cttcctctcg tttgcgatat ggaatgtctg 2580
atgtcatgcc ttctggcagg agcaggcttt tggaagattt tcgaaacaac cggtacccca 2640
atttacaact gcgggagatt gctggacata taatggaatt ttcccaagac cagcatgggt 2700
ccagattcat tcagctgaaa ctggagcgtg ccacaccagc tgagcgccag cttgtcttca 2760
atgaaatcct ccaggctgcc taccaactca tggtggatgt gtttggtaat tacgtcattc 2820
agaagttctt tgaatttggc agtcttgaac agaagctggc tttggcagaa cggattcgag 2880
gccacgtcct gtcattggca ctacagatgt atggctgccg tgttatccag aaagctcttg 2940
agtttattcc ttcagaccag caggtaatta atgagatggt tcgggaacta gatggccatg 3000
tcttgaagtg tgtgaaagat cagaatggca atcacgtggt tcagaaatgc attgaatgtg 3060
tacagcccca gtctttgcaa tttatcatcg atgcgtttaa gggacaggta tttgccttat 3120
ccacacatcc ttatggctgc cgagtgattc agagaatcct ggagcactgt ctccctgacc 3180
agacactccc tattttagag gagcttcacc agcacacaga gcagcttgta caggatcaat 3240
atggaaatta tgtaatccaa catgtactgg agcacggtcg tcctgaggat aaaagcaaaa 3300
ttgtagcaga aatccgaggc aatgtacttg tattgagtca gcacaaattt gcaagcaatg 3360
ttgtggagaa gtgtgttact cacgcctcac gtacggagcg cgctgtgctc atcgatgagg 3420
tgtgcaccat gaacgacggt ccccacagtg ccttatacac catgatgaag gaccagtatg 3480
ccaactacgt ggtccagaag atgattgacg tggcggagcc aggccagcgg aagatcgtca 3540
tgcataagat ccggccccac atcgcaactc ttcgtaagta cacctatggc aagcacattc 3600
tggccaagct ggagaagtac tacatgaaga acggtgttga cttagggccc atctgtggcc 3660
cccctaatgg tatcatctga ggcagtgtca cccgctgttc cctcattccc gctgacctca 3720
ctggcccact ggcaaatcca accagcaacc agaaatgttc tagtgtagag tctgagacgg 3780
gcaagtggtt gctccaggat tactccctcc tccaaaaaag gaatcaaatc cacgagtgga 3840
aaagcctttg taaatttaat tttattacac ataacatgta ctattttttt taattgacta 3900
attgccctgc tgttttactg gtgtatagga tacttgtaca taggtaacca atgtacatgg 3960
gaggccacat attttgttca ctgttgtatc tatatttcac atgtggaaac tttcagggtg 4020
gttggtttaa caaaaaaaaa aagctttaaa aaaaaaagaa aaaaaggaaa aggtttttag 4080
ctcatttgcc tggccggcaa gttttgcaaa tagctcttcc ccacctcctc attttagtaa 4140
aaaacaaaca aaaacaaaaa aacctgagaa gtttgaattg tagttaaatg accccaaact 4200
ggcatttaac actgtttata aaaaatatat atatatatat atatatatat aatgaaaaag 4260
gtttcagagt tgctaaagct tcagtttgtg acattaagtt tatgaaattc taaaaaatgc 4320
cttttttgga gactatatta tgctgaagaa ggctgttcgt gaggaggaga tgcgagcacc 4380
cagaacgtct tttgaggctg ggcgggtgtg attgtttact gcctactgga tttttttcta 4440
ttaacattga aaggtaaaat ctgattattt agcatgagaa aaaaaaatcc aactctgctt 4500
ttggtcttgc ttctataaat atatagtgta tacttggtgt agactttgca tatatacaaa 4560
tttgtagtat tttcttgttt tgatgtctaa tctgtatcta taatgtaccc tagtagtcga 4620
acatactttt gattgtacaa ttgtacattt gtatacctgt aatgtaaatg tggagaagtt 4680
tgaatcaaca taaacacgtt ttttggtaag aaaagagaat tagccagccc tgtgcattca 4740
gtgtatattc tcacctttta tggtcgtagc atatagtgtt gtatattgta aattgtaatt 4800
tcaaccagaa gtaaattttt ttcttttgaa ggaataaatg ttctttatac agcctagtta 4860
atgtttaaaa agaaaaaaat agcttggttt tatttgtcat ctagtctcaa gtatagcgag 4920
attctttcta aatgttattc aagattgagt tctcactagt gtttttttaa tcctaaaaaa 4980
gtaatgtttt gattttgtga cagtcaaaag gacgtgcaaa agtctagcct tgcccgagct 5040
ttccttacaa tcagagcccc tctcaccttg taaagtgtga atcgcccttc ccttttgtac 5100
agaagatgaa ctgtattttg cattttgtct acttgtaagt gaatgtaaca tactgtcaat 5160
tttccttgtt tgaatataga attgtaacac tacacggtgt acatttccag agccttgtgt 5220
atatttccaa tgaacttttt tgcaagcaca cttgtaacca tatgtgtata attaacaaac 5280
ctgtgtatgc ttatgcctgg gcaactattt tttgtaactc ttgtgtagat tgtctctaaa 5340
caatgtgtga tctttatttt gaaaaataca gaactttgga atctgaaaaa aaaaaaaaaa 5400
aaaaaaaaaa aaaaaa 5416
<210> 162
<211> 5410
<212> DNA
<213> Homo sapiens
<400> 162
agtgggccgc catgttgtcg gagtgaaagg taagggggag cgagagcgcc agagagagaa 60
gatcgggggg ctgaaatcca tcttcatcct accgctccgc ccgtgttggt ggaatgagcg 120
ttgcatgtgt cttgaagaga aaagcagtgc tttggcagga ctctttcagc ccccacctga 180
aacatcaccc tcaagaacca gctaatccca acatgcctgt tgttttgaca tctggaacag 240
ggtcgcaagc gcagccacaa ccagctgcaa atcaggctct tgcagctggg actcactcca 300
gccctgtccc aggatctata ggagttgcag gccgttccca ggacgacgct atggtggact 360
acttctttca gaggcagcat ggtgagcagc ttgggggagg aggaagtgga ggaggcggct 420
ataataatag caaacatcga tggcctactg gggataacat tcatgcagaa catcaggtgc 480
gttccatgga tgaactgaat catgattttc aagcacttgc tctggaggga agagcgatgg 540
gagagcagct cttgccaggt aaaaagtttt gggaaacaga tgaatccagc aaagatggac 600
caaaaggaat attcctgggt gatcaatggc gagacagtgc ctggggaaca tcagatcatt 660
cagtttccca gccaatcatg gtgcagagaa gacctggtca gagtttccat gtgaacagtg 720
aggtcaattc tgtactgtcc ccacgatcgg agagtggggg actaggcgtt agcatggtgg 780
agtatgtgtt gagctcatcc ccgggcgatt cctgtctaag aaaaggagga tttggcccaa 840
gggatgcaga cagtgatgaa aacgacaaag gtgaaaagaa gaacaagggt acgtttgatg 900
gagataagct aggagatttg aaggaggagg gtgatgtgat ggacaagacc aatggtttac 960
cagtgcagaa tgggattgat gcagacgtca aagattttag ccgtacccct ggtaattgcc 1020
agaactctgc taatgaagtg gatcttctgg gtccaaacca gaatggttct gagggcttag 1080
cccagctgac cagcaccaat ggtgccaagc ctgtggagga tttctccaac atggagtccc 1140
agagtgtccc cttggacccc atggaacatg tgggcatgga gcctcttcag tttgattatt 1200
caggcacgca ggtacctgtg gactcagcag cagcaactgt gggacttttt gactacaatt 1260
ctcaacaaca gctgttccaa agacctaatg cgcttgctgt ccagcagttg acagctgctc 1320
agcagcagca gtatgcactg gcagctgctc atcagccgca catcggttta gctcccgctg 1380
cgtttgtccc caatccatac atcatcagcg ctgctccccc agggacggac ccctacacag 1440
ctggattggc tgcagcagcg acactaggcc cagctgtggt ccctcaccag tattatggag 1500
ttactccctg gggagtctac cctgccagtc ttttccagca gcaagctgcc gctgccgctg 1560
cagcaactaa ttcagctaat caacagacca ccccacaggc tcagcaagga cagcagcagg 1620
ttctccgtgg aggagccagc caacgtcctt tgaccccaaa ccagaaccag cagggacagc 1680
aaacggatcc ccttgtggca gctgcagcag tgaattctgc ccttgcattt ggacaaggtc 1740
tggcagcagg catgccaggt tatccggtgt tggctcctgc tgcttactat gaccaaactg 1800
gtgcccttgt agtgaatgca ggcgcgagaa atggtcttgg agctcctgtt cgacttgtag 1860
ctcctgcccc agtcatcatt agttcctcag ctgcacaagc agctgttgca gcagccgcag 1920
cttcagcaaa tggagcagct ggtggtcttg ctggaacaac aaatggacca tttcgccctt 1980
taggaacaca gcagcctcag ccccagcccc agcagcagcc caataacaac ctggcatcca 2040
gttctttcta cggcaacaac tctctgaaca gcaattcaca gagcagctcc ctcttctccc 2100
agggctctgc ccagcctgcc aacacatcct tgggattcgg aagtagcagt tctctcggcg 2160
ccaccctggg atccgccctt ggagggtttg gaacagcagt tgcaaactcc aacactggca 2220
gtggctcccg ccgtgactcc ctgactggca gcagtgacct ttataagagg acatcgagca 2280
gcttgacccc cattggacac agtttttata acggccttag cttttcctcc tctcctggac 2340
ccgtgggcat gcctctccct agtcagggac caggacattc acagacacca cctccttccc 2400
tctcttcaca tggatcctct tcaagcttaa acctgggagg actcacgaat ggcagtggaa 2460
gatacatctc tgctgctcca ggcgctgaag ccaagtaccg cagtgcaagc agcgcctcca 2520
gcctcttcag cccgagcagc actcttttct cttcctctcg tttgcgatat ggaatgtctg 2580
atgtcatgcc ttctggcagg agcaggcttt tggaagattt tcgaaacaac cggtacccca 2640
atttacaact gcgggagatt gctggacata taatggaatt ttcccaagac cagcatgggt 2700
ccagattcat tcagctgaaa ctggagcgtg ccacaccagc tgagcgccag cttgtcttca 2760
atgaaatcct ccaggctgcc taccaactca tggtggatgt gtttggtaat tacgtcattc 2820
agaagttctt tgaatttggc agtcttgaac agaagctggc tttggcagaa cggattcgag 2880
gccacgtcct gtcattggca ctacagatgt atggctgccg tgttatccag aaagctcttg 2940
agtttattcc ttcagaccag cagaatgaga tggttcggga actagatggc catgtcttga 3000
agtgtgtgaa agatcagaat ggcaatcacg tggttcagaa atgcattgaa tgtgtacagc 3060
cccagtcttt gcaatttatc atcgatgcgt ttaagggaca ggtatttgcc ttatccacac 3120
atccttatgg ctgccgagtg attcagagaa tcctggagca ctgtctccct gaccagacac 3180
tccctatttt agaggagctt caccagcaca cagagcagct tgtacaggat caatatggaa 3240
attatgtaat ccaacatgta ctggagcacg gtcgtcctga ggataaaagc aaaattgtag 3300
cagaaatccg aggcaatgta cttgtattga gtcagcacaa atttgcaagc aatgttgtgg 3360
agaagtgtgt tactcacgcc tcacgtacgg agcgcgctgt gctcatcgat gaggtgtgca 3420
ccatgaacga cggtccccac agtgccttat acaccatgat gaaggaccag tatgccaact 3480
acgtggtcca gaagatgatt gacgtggcgg agccaggcca gcggaagatc gtcatgcata 3540
agatccggcc ccacatcgca actcttcgta agtacaccta tggcaagcac attctggcca 3600
agctggagaa gtactacatg aagaacggtg ttgacttagg gcccatctgt ggccccccta 3660
atggtatcat ctgaggcagt gtcacccgct gttccctcat tcccgctgac ctcactggcc 3720
cactggcaaa tccaaccagc aaccagaaat gttctagtgt agagtctgag acgggcaagt 3780
ggttgctcca ggattactcc ctcctccaaa aaaggaatca aatccacgag tggaaaagcc 3840
tttgtaaatt taattttatt acacataaca tgtactattt tttttaattg actaattgcc 3900
ctgctgtttt actggtgtat aggatacttg tacataggta accaatgtac atgggaggcc 3960
acatattttg ttcactgttg tatctatatt tcacatgtgg aaactttcag ggtggttggt 4020
ttaacaaaaa aaaaaagctt taaaaaaaaa agaaaaaaag gaaaaggttt ttagctcatt 4080
tgcctggccg gcaagttttg caaatagctc ttccccacct cctcatttta gtaaaaaaca 4140
aacaaaaaca aaaaaacctg agaagtttga attgtagtta aatgacccca aactggcatt 4200
taacactgtt tataaaaaat atatatatat atatatatat atataatgaa aaaggtttca 4260
gagttgctaa agcttcagtt tgtgacatta agtttatgaa attctaaaaa atgccttttt 4320
tggagactat attatgctga agaaggctgt tcgtgaggag gagatgcgag cacccagaac 4380
gtcttttgag gctgggcggg tgtgattgtt tactgcctac tggatttttt tctattaaca 4440
ttgaaaggta aaatctgatt atttagcatg agaaaaaaaa atccaactct gcttttggtc 4500
ttgcttctat aaatatatag tgtatacttg gtgtagactt tgcatatata caaatttgta 4560
gtattttctt gttttgatgt ctaatctgta tctataatgt accctagtag tcgaacatac 4620
ttttgattgt acaattgtac atttgtatac ctgtaatgta aatgtggaga agtttgaatc 4680
aacataaaca cgttttttgg taagaaaaga gaattagcca gccctgtgca ttcagtgtat 4740
attctcacct tttatggtcg tagcatatag tgttgtatat tgtaaattgt aatttcaacc 4800
agaagtaaat ttttttcttt tgaaggaata aatgttcttt atacagccta gttaatgttt 4860
aaaaagaaaa aaatagcttg gttttatttg tcatctagtc tcaagtatag cgagattctt 4920
tctaaatgtt attcaagatt gagttctcac tagtgttttt ttaatcctaa aaaagtaatg 4980
ttttgatttt gtgacagtca aaaggacgtg caaaagtcta gccttgcccg agctttcctt 5040
acaatcagag cccctctcac cttgtaaagt gtgaatcgcc cttccctttt gtacagaaga 5100
tgaactgtat tttgcatttt gtctacttgt aagtgaatgt aacatactgt caattttcct 5160
tgtttgaata tagaattgta acactacacg gtgtacattt ccagagcctt gtgtatattt 5220
ccaatgaact tttttgcaag cacacttgta accatatgtg tataattaac aaacctgtgt 5280
atgcttatgc ctgggcaact attttttgta actcttgtgt agattgtctc taaacaatgt 5340
gtgatcttta ttttgaaaaa tacagaactt tggaatctga aaaaaaaaaa aaaaaaaaaa 5400
aaaaaaaaaa 5410
<210> 163
<211> 1771
<212> DNA
<213> Homo sapiens
<400> 163
ggcggccagg ccgggcgcgg agtgggcgcg cggggccgga ggaggggcca gcgaccgcgg 60
caccgcctgt gcccgcccgc ccctccgcag ccgctactta agaggctcca gcgccggccc 120
cgccctagtg cgttacttac ctcgactctt agcttgtcgg ggacggtaac cgggacccgg 180
tgtctgctcc tgtcgccttc gcctcctaat ccctagccac tatgcgtgag tgcatctcca 240
tccacgttgg ccaggctggt gtccagattg gcaatgcctg ctgggagctc tactgcctgg 300
aacacggcat ccagcccgat ggccagatgc caagtgacaa gaccattggg ggaggagatg 360
actccttcaa caccttcttc agtgagacgg gcgctggcaa gcacgtgccc cgggctgtgt 420
ttgtagactt ggaacccaca gtcattgatg aagttcgcac tggcacctac cgccagctct 480
tccaccctga gcagctcatc acaggcaagg aagatgctgc caataactat gcccgagggc 540
actacaccat tggcaaggag atcattgacc ttgtgttgga ccgaattcgc aagctggctg 600
accagtgcac cggtcttcag ggcttcttgg ttttccacag ctttggtggg ggaactggtt 660
ctgggttcac ctccctgctc atggaacgtc tctcagttga ttatggcaag aagtccaagc 720
tggagttctc catttaccca gcaccccagg tttccacagc tgtagttgag ccctacaact 780
ccatcctcac cacccacacc accctggagc actctgattg tgccttcatg gtagacaatg 840
aggccatcta tgacatctgt cgtagaaacc tcgatatcga gcgcccaacc tacactaacc 900
ttaaccgcct tattagccag attgtgtcct ccatcactgc ttccctgaga tttgatggag 960
ccctgaatgt tgacctgaca gaattccaga ccaacctggt gccctacccc cgcatccact 1020
tccctctggc cacatatgcc cctgtcatct ctgctgagaa agcctaccat gaacagcttt 1080
ctgtagcaga gatcaccaat gcttgctttg agccagccaa ccagatggtg aaatgtgacc 1140
ctcgccatgg taaatacatg gcttgctgcc tgttgtaccg tggtgacgtg gttcccaaag 1200
atgtcaatgc tgccattgcc accatcaaaa ccaagcgcag catccagttt gtggattggt 1260
gccccactgg cttcaaggtt ggcatcaact accagcctcc cactgtggtg cctggtggag 1320
acctggccaa ggtacagaga gctgtgtgca tgctgagcaa caccacagcc attgctgagg 1380
cctgggctcg cctggaccac aagtttgacc tgatgtatgc caagcgtgcc tttgttcact 1440
ggtacgtggg tgaggggatg gaggaaggcg agttttcaga ggcccgtgaa gatatggctg 1500
cccttgagaa ggattatgag gaggttggtg tggattctgt tgaaggagag ggtgaggaag 1560
aaggagagga atactaatta tccattcctt ttggccctgc agcatgtcat gctcccagaa 1620
tttcagcttc agcttaactg acagacgtta aagctttctg gttagattgt tttcacttgg 1680
tgatcatgtc ttttccatgt gtacctgtaa tatttttcca tcatatctca aagtaaagtc 1740
attaacatca aaaaaaaaaa aaaaaaaaaa a 1771
<210> 164
<211> 2458
<212> DNA
<213> Homo sapiens
<400> 164
cagaagaagg cagcgcccaa ggcgcatgcg cagcggtcac tcccgctgta tattaaggcg 60
ccggcgatcg cggcctgagg ctgctcccgg acaagggcaa cgagcgtttc gtttggactt 120
ctcgacttga gtgcccgcct ccttcgccgc cgcctctgca gtcctcagcg cagttatgcc 180
cagttcttcc cgctgtgggg acacgaccac ggaggaatcc ttgcttcagg gactcgggac 240
cctgctggac cccttcctcg ggtttagggg atgtggggac caggagaaag tcaggatccc 300
taagagtctt ccctgcctgg atggatgagt ggcttcttct ccacctagat tctttccaca 360
ggagccagca tacttcctga acatggagag tgttgttcgc cgctgcccat tcttatcccg 420
agtcccccag gcctttctgc agaaagcagg caaatctctg ttgttctatg cccaaaactg 480
ccccaagatg atggaagttg gggccaagcc agcccctcgg gcattgtcca ctgcagcagt 540
acactaccaa cagatcaaag aaacccctcc ggccagtgag aaagacaaaa ctgctaaggc 600
caaggtccaa cagactcctg atggatccca gcagagtcca gatggcacac agcttccgtc 660
tggacacccc ttgcctgcca caagccaggg cactgcaagc aaatgccctt tcctggcagc 720
acagatgaat cagagaggca gcagtgtctt ctgcaaagcc agtcttgagc ttcaggagga 780
tgtgcaggaa atgaatgccg tgaggaaaga ggttgctgaa acctcagcag gccccagtgt 840
ggttagtgtg aaaaccgatg gaggggatcc cagtggactg ctgaagaact tccaggacat 900
catgcaaaag caaagaccag aaagagtgtc tcatcttctt caagataact tgccaaaatc 960
tgtttccact tttcagtatg atcgtttctt tgagaaaaaa attgatgaga aaaagaatga 1020
ccacacctat cgagttttta aaactgtgaa ccggcgagca cacatcttcc ccatggcaga 1080
tgactattca gactccctca tcaccaaaaa gcaagtgtca gtctggtgca gtaatgacta 1140
cctaggaatg agtcgccacc cacgggtgtg tggggcagtt atggacactt tgaaacaaca 1200
tggtgctggg gcaggtggta ctagaaatat ttctggaact agtaaattcc atgtggactt 1260
agagcgggag ctggcagacc tccatgggaa agatgccgca ctcttgtttt cctcgtgctt 1320
tgtggccaat gactcaaccc tcttcaccct ggctaagatg atgccaggct gtgagattta 1380
ctctgattct gggaaccatg cctccatgat ccaagggatt cgaaacagcc gagtgccaaa 1440
gtacatcttc cgccacaatg atgtcagcca cctcagagaa ctgctgcaaa gatctgaccc 1500
ctcagtcccc aagattgtgg catttgaaac tgtccattca atggatgggg cggtgtgccc 1560
actggaagag ctgtgtgatg tggcccatga gtttggagca atcaccttcg tggatgaggt 1620
ccacgcagtg gggctttatg gggctcgagg cggagggatt ggggatcggg atggagtcat 1680
gccaaaaatg gacatcattt ctggaacact tggcaaagcc tttggttgtg ttggagggta 1740
catcgccagc acgagttctc tgattgacac cgtacggtcc tatgctgctg gcttcatctt 1800
caccacctct ctgccaccca tgctgctggc tggagccctg gagtctgtgc ggatcctgaa 1860
gagcgctgag ggacgggtgc ttcgccgcca gcaccagcgc aacgtcaaac tcatgagaca 1920
gatgctaatg gatgccggcc tccctgttgt ccactgcccc agccacatca tccctgtgcg 1980
ggttgcagat gctgctaaaa acacagaagt ctgtgatgaa ctaatgagca gacataacat 2040
ctacgtgcaa gcaatcaatt accctacggt gccccgggga gaagagctcc tacggattgc 2100
ccccacccct caccacacac cccagatgat gaactacttc cttgagaatc tgctagtcac 2160
atggaagcaa gtggggctgg aactgaagcc tcattcctca gctgagtgca acttctgcag 2220
gaggccactg cattttgaag tgatgagtga aagagagaag tcctatttct caggcttgag 2280
caagttggta tctgctcagg cctgagcatg acctcaatta tttcacttaa ccccaggcca 2340
ttatcatatc cagatggtct tcagagttgt ctttatatgt gaattaagtt atattaaatt 2400
ttaatctata gtaaaaacat agtcctggaa ataaattctt gcttaaatgg tgaaaaaa 2458
<210> 165
<211> 2281
<212> DNA
<213> Homo sapiens
<400> 165
cagaagaagg cagcgcccaa ggcgcatgcg cagcggtcac tcccgctgta tattaaggcg 60
ccggcgatcg cggcctgagg ctgctcccgg acaagggcaa cgagcgtttc gtttggactt 120
ctcgacttga gtgcccgcct ccttcgccgc cgcctctgca gtcctcagcg cagtctttcc 180
acaggagcca gcatacttcc tgaacatgga gagtgttgtt cgccgctgcc cattcttatc 240
ccgagtcccc caggcctttc tgcagaaagc aggcaaatct ctgttgttct atgcccaaaa 300
ctgccccaag atgatggaag ttggggccaa gccagcccct cgggcattgt ccactgcagc 360
agtacactac caacagatca aagaaacccc tccggccagt gagaaagaca aaactgctaa 420
ggccaaggtc caacagactc ctgatggatc ccagcagagt ccagatggca cacagcttcc 480
gtctggacac cccttgcctg ccacaagcca gggcactgca agcaaatgcc ctttcctggc 540
agcacagatg aatcagagag gcagcagtgt cttctgcaaa gccagtcttg agcttcagga 600
ggatgtgcag gaaatgaatg ccgtgaggaa agaggttgct gaaacctcag caggccccag 660
tgtggttagt gtgaaaaccg atggagggga tcccagtgga ctgctgaaga acttccagga 720
catcatgcaa aagcaaagac cagaaagagt gtctcatctt cttcaagata acttgccaaa 780
atctgtttcc acttttcagt atgatcgttt ctttgagaaa aaaattgatg agaaaaagaa 840
tgaccacacc tatcgagttt ttaaaactgt gaaccggcga gcacacatct tccccatggc 900
agatgactat tcagactccc tcatcaccaa aaagcaagtg tcagtctggt gcagtaatga 960
ctacctagga atgagtcgcc acccacgggt gtgtggggca gttatggaca ctttgaaaca 1020
acatggtgct ggggcaggtg gtactagaaa tatttctgga actagtaaat tccatgtgga 1080
cttagagcgg gagctggcag acctccatgg gaaagatgcc gcactcttgt tttcctcgtg 1140
ctttgtggcc aatgactcaa ccctcttcac cctggctaag atgatgccag gctgtgagat 1200
ttactctgat tctgggaacc atgcctccat gatccaaggg attcgaaaca gccgagtgcc 1260
aaagtacatc ttccgccaca atgatgtcag ccacctcaga gaactgctgc aaagatctga 1320
cccctcagtc cccaagattg tggcatttga aactgtccat tcaatggatg gggcggtgtg 1380
cccactggaa gagctgtgtg atgtggccca tgagtttgga gcaatcacct tcgtggatga 1440
ggtccacgca gtggggcttt atggggctcg aggcggaggg attggggatc gggatggagt 1500
catgccaaaa atggacatca tttctggaac acttggcaaa gcctttggtt gtgttggagg 1560
gtacatcgcc agcacgagtt ctctgattga caccgtacgg tcctatgctg ctggcttcat 1620
cttcaccacc tctctgccac ccatgctgct ggctggagcc ctggagtctg tgcggatcct 1680
gaagagcgct gagggacggg tgcttcgccg ccagcaccag cgcaacgtca aactcatgag 1740
acagatgcta atggatgccg gcctccctgt tgtccactgc cccagccaca tcatccctgt 1800
gcgggttgca gatgctgcta aaaacacaga agtctgtgat gaactaatga gcagacataa 1860
catctacgtg caagcaatca attaccctac ggtgccccgg ggagaagagc tcctacggat 1920
tgcccccacc cctcaccaca caccccagat gatgaactac ttccttgaga atctgctagt 1980
cacatggaag caagtggggc tggaactgaa gcctcattcc tcagctgagt gcaacttctg 2040
caggaggcca ctgcattttg aagtgatgag tgaaagagag aagtcctatt tctcaggctt 2100
gagcaagttg gtatctgctc aggcctgagc atgacctcaa ttatttcact taaccccagg 2160
ccattatcat atccagatgg tcttcagagt tgtctttata tgtgaattaa gttatattaa 2220
attttaatct atagtaaaaa catagtcctg gaaataaatt cttgcttaaa tggtgaaaaa 2280
a 2281
<210> 166
<211> 339
<212> PRT
<213> Homo sapiens
<400> 166
Met Asp Gln Asn Asn Ser Leu Pro Pro Tyr Ala Gln Gly Leu Ala Ser
1 5 10 15
Pro Gln Gly Ala Met Thr Pro Gly Ile Pro Ile Phe Ser Pro Met Met
20 25 30
Pro Tyr Gly Thr Gly Leu Thr Pro Gln Pro Ile Gln Asn Thr Asn Ser
35 40 45
Leu Ser Ile Leu Glu Glu Gln Gln Arg Gln Gln Gln Gln Gln Gln Gln
50 55 60
Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln
65 70 75 80
Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Ala
85 90 95
Val Ala Ala Ala Ala Val Gln Gln Ser Thr Ser Gln Gln Ala Thr Gln
100 105 110
Gly Thr Ser Gly Gln Ala Pro Gln Leu Phe His Ser Gln Thr Leu Thr
115 120 125
Thr Ala Pro Leu Pro Gly Thr Thr Pro Leu Tyr Pro Ser Pro Met Thr
130 135 140
Pro Met Thr Pro Ile Thr Pro Ala Thr Pro Ala Ser Glu Ser Ser Gly
145 150 155 160
Ile Val Pro Gln Leu Gln Asn Ile Val Ser Thr Val Asn Leu Gly Cys
165 170 175
Lys Leu Asp Leu Lys Thr Ile Ala Leu Arg Ala Arg Asn Ala Glu Tyr
180 185 190
Asn Pro Lys Arg Phe Ala Ala Val Ile Met Arg Ile Arg Glu Pro Arg
195 200 205
Thr Thr Ala Leu Ile Phe Ser Ser Gly Lys Met Val Cys Thr Gly Ala
210 215 220
Lys Ser Glu Glu Gln Ser Arg Leu Ala Ala Arg Lys Tyr Ala Arg Val
225 230 235 240
Val Gln Lys Leu Gly Phe Pro Ala Lys Phe Leu Asp Phe Lys Ile Gln
245 250 255
Asn Met Val Gly Ser Cys Asp Val Lys Phe Pro Ile Arg Leu Glu Gly
260 265 270
Leu Val Leu Thr His Gln Gln Phe Ser Ser Tyr Glu Pro Glu Leu Phe
275 280 285
Pro Gly Leu Ile Tyr Arg Met Ile Lys Pro Arg Ile Val Leu Leu Ile
290 295 300
Phe Val Ser Gly Lys Val Val Leu Thr Gly Ala Lys Val Arg Ala Glu
305 310 315 320
Ile Tyr Glu Ala Phe Glu Asn Ile Tyr Pro Ile Leu Lys Gly Phe Arg
325 330 335
Lys Thr Thr
<210> 167
<211> 218
<212> PRT
<213> Homo sapiens
<400> 167
Met Ala Thr Arg Ser Pro Gly Val Val Ile Ser Asp Asp Glu Pro Gly
1 5 10 15
Tyr Asp Leu Asp Leu Phe Cys Ile Pro Asn His Tyr Ala Glu Asp Leu
20 25 30
Glu Arg Val Phe Ile Pro His Gly Leu Ile Met Asp Arg Thr Glu Arg
35 40 45
Leu Ala Arg Asp Val Met Lys Glu Met Gly Gly His His Ile Val Ala
50 55 60
Leu Cys Val Leu Lys Gly Gly Tyr Lys Phe Phe Ala Asp Leu Leu Asp
65 70 75 80
Tyr Ile Lys Ala Leu Asn Arg Asn Ser Asp Arg Ser Ile Pro Met Thr
85 90 95
Val Asp Phe Ile Arg Leu Lys Ser Tyr Cys Asn Asp Gln Ser Thr Gly
100 105 110
Asp Ile Lys Val Ile Gly Gly Asp Asp Leu Ser Thr Leu Thr Gly Lys
115 120 125
Asn Val Leu Ile Val Glu Asp Ile Ile Asp Thr Gly Lys Thr Met Gln
130 135 140
Thr Leu Leu Ser Leu Val Arg Gln Tyr Asn Pro Lys Met Val Lys Val
145 150 155 160
Ala Ser Leu Leu Val Lys Arg Thr Pro Arg Ser Val Gly Tyr Lys Pro
165 170 175
Asp Phe Val Gly Phe Glu Ile Pro Asp Lys Phe Val Val Gly Tyr Ala
180 185 190
Leu Asp Tyr Asn Glu Tyr Phe Arg Asp Leu Asn His Val Cys Val Ile
195 200 205
Ser Glu Thr Gly Lys Ala Lys Tyr Lys Ala
210 215
<210> 168
<211> 375
<212> PRT
<213> Homo sapiens
<400> 168
Met Asp Asp Asp Ile Ala Ala Leu Val Val Asp Asn Gly Ser Gly Met
1 5 10 15
Cys Lys Ala Gly Phe Ala Gly Asp Asp Ala Pro Arg Ala Val Phe Pro
20 25 30
Ser Ile Val Gly Arg Pro Arg His Gln Gly Val Met Val Gly Met Gly
35 40 45
Gln Lys Asp Ser Tyr Val Gly Asp Glu Ala Gln Ser Lys Arg Gly Ile
50 55 60
Leu Thr Leu Lys Tyr Pro Ile Glu His Gly Ile Val Thr Asn Trp Asp
65 70 75 80
Asp Met Glu Lys Ile Trp His His Thr Phe Tyr Asn Glu Leu Arg Val
85 90 95
Ala Pro Glu Glu His Pro Val Leu Leu Thr Glu Ala Pro Leu Asn Pro
100 105 110
Lys Ala Asn Arg Glu Lys Met Thr Gln Ile Met Phe Glu Thr Phe Asn
115 120 125
Thr Pro Ala Met Tyr Val Ala Ile Gln Ala Val Leu Ser Leu Tyr Ala
130 135 140
Ser Gly Arg Thr Thr Gly Ile Val Met Asp Ser Gly Asp Gly Val Thr
145 150 155 160
His Thr Val Pro Ile Tyr Glu Gly Tyr Ala Leu Pro His Ala Ile Leu
165 170 175
Arg Leu Asp Leu Ala Gly Arg Asp Leu Thr Asp Tyr Leu Met Lys Ile
180 185 190
Leu Thr Glu Arg Gly Tyr Ser Phe Thr Thr Thr Ala Glu Arg Glu Ile
195 200 205
Val Arg Asp Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu Asp Phe Glu
210 215 220
Gln Glu Met Ala Thr Ala Ala Ser Ser Ser Ser Leu Glu Lys Ser Tyr
225 230 235 240
Glu Leu Pro Asp Gly Gln Val Ile Thr Ile Gly Asn Glu Arg Phe Arg
245 250 255
Cys Pro Glu Ala Leu Phe Gln Pro Ser Phe Leu Gly Met Glu Ser Cys
260 265 270
Gly Ile His Glu Thr Thr Phe Asn Ser Ile Met Lys Cys Asp Val Asp
275 280 285
Ile Arg Lys Asp Leu Tyr Ala Asn Thr Val Leu Ser Gly Gly Thr Thr
290 295 300
Met Tyr Pro Gly Ile Ala Asp Arg Met Gln Lys Glu Ile Thr Ala Leu
305 310 315 320
Ala Pro Ser Thr Met Lys Ile Lys Ile Ile Ala Pro Pro Glu Arg Lys
325 330 335
Tyr Ser Val Trp Ile Gly Gly Ser Ile Leu Ala Ser Leu Ser Thr Phe
340 345 350
Gln Gln Met Trp Ile Ser Lys Gln Glu Tyr Asp Glu Ser Gly Pro Ser
355 360 365
Ile Val His Arg Lys Cys Phe
370 375
<210> 169
<211> 317
<212> PRT
<213> Homo sapiens
<400> 169
Met Pro Arg Glu Asp Arg Ala Thr Trp Lys Ser Asn Tyr Phe Leu Lys
1 5 10 15
Ile Ile Gln Leu Leu Asp Asp Tyr Pro Lys Cys Phe Ile Val Gly Ala
20 25 30
Asp Asn Val Gly Ser Lys Gln Met Gln Gln Ile Arg Met Ser Leu Arg
35 40 45
Gly Lys Ala Val Val Leu Met Gly Lys Asn Thr Met Met Arg Lys Ala
50 55 60
Ile Arg Gly His Leu Glu Asn Asn Pro Ala Leu Glu Lys Leu Leu Pro
65 70 75 80
His Ile Arg Gly Asn Val Gly Phe Val Phe Thr Lys Glu Asp Leu Thr
85 90 95
Glu Ile Arg Asp Met Leu Leu Ala Asn Lys Val Pro Ala Ala Ala Arg
100 105 110
Ala Gly Ala Ile Ala Pro Cys Glu Val Thr Val Pro Ala Gln Asn Thr
115 120 125
Gly Leu Gly Pro Glu Lys Thr Ser Phe Phe Gln Ala Leu Gly Ile Thr
130 135 140
Thr Lys Ile Ser Arg Gly Thr Ile Glu Ile Leu Ser Asp Val Gln Leu
145 150 155 160
Ile Lys Thr Gly Asp Lys Val Gly Ala Ser Glu Ala Thr Leu Leu Asn
165 170 175
Met Leu Asn Ile Ser Pro Phe Ser Phe Gly Leu Val Ile Gln Gln Val
180 185 190
Phe Asp Asn Gly Ser Ile Tyr Asn Pro Glu Val Leu Asp Ile Thr Glu
195 200 205
Glu Thr Leu His Ser Arg Phe Leu Glu Gly Val Arg Asn Val Ala Ser
210 215 220
Val Cys Leu Gln Ile Gly Tyr Pro Thr Val Ala Ser Val Pro His Ser
225 230 235 240
Ile Ile Asn Gly Tyr Lys Arg Val Leu Ala Leu Ser Val Glu Thr Asp
245 250 255
Tyr Thr Phe Pro Leu Ala Glu Lys Val Lys Ala Phe Leu Ala Asp Pro
260 265 270
Ser Ala Phe Val Ala Ala Ala Pro Val Ala Ala Ala Thr Thr Ala Ala
275 280 285
Pro Ala Ala Ala Ala Ala Pro Ala Lys Val Glu Ala Lys Glu Glu Ser
290 295 300
Glu Glu Ser Asp Glu Asp Met Gly Phe Gly Leu Phe Asp
305 310 315
<210> 170
<211> 317
<212> PRT
<213> Homo sapiens
<400> 170
Met Pro Arg Glu Asp Arg Ala Thr Trp Lys Ser Asn Tyr Phe Leu Lys
1 5 10 15
Ile Ile Gln Leu Leu Asp Asp Tyr Pro Lys Cys Phe Ile Val Gly Ala
20 25 30
Asp Asn Val Gly Ser Lys Gln Met Gln Gln Ile Arg Met Ser Leu Arg
35 40 45
Gly Lys Ala Val Val Leu Met Gly Lys Asn Thr Met Met Arg Lys Ala
50 55 60
Ile Arg Gly His Leu Glu Asn Asn Pro Ala Leu Glu Lys Leu Leu Pro
65 70 75 80
His Ile Arg Gly Asn Val Gly Phe Val Phe Thr Lys Glu Asp Leu Thr
85 90 95
Glu Ile Arg Asp Met Leu Leu Ala Asn Lys Val Pro Ala Ala Ala Arg
100 105 110
Ala Gly Ala Ile Ala Pro Cys Glu Val Thr Val Pro Ala Gln Asn Thr
115 120 125
Gly Leu Gly Pro Glu Lys Thr Ser Phe Phe Gln Ala Leu Gly Ile Thr
130 135 140
Thr Lys Ile Ser Arg Gly Thr Ile Glu Ile Leu Ser Asp Val Gln Leu
145 150 155 160
Ile Lys Thr Gly Asp Lys Val Gly Ala Ser Glu Ala Thr Leu Leu Asn
165 170 175
Met Leu Asn Ile Ser Pro Phe Ser Phe Gly Leu Val Ile Gln Gln Val
180 185 190
Phe Asp Asn Gly Ser Ile Tyr Asn Pro Glu Val Leu Asp Ile Thr Glu
195 200 205
Glu Thr Leu His Ser Arg Phe Leu Glu Gly Val Arg Asn Val Ala Ser
210 215 220
Val Cys Leu Gln Ile Gly Tyr Pro Thr Val Ala Ser Val Pro His Ser
225 230 235 240
Ile Ile Asn Gly Tyr Lys Arg Val Leu Ala Leu Ser Val Glu Thr Asp
245 250 255
Tyr Thr Phe Pro Leu Ala Glu Lys Val Lys Ala Phe Leu Ala Asp Pro
260 265 270
Ser Ala Phe Val Ala Ala Ala Pro Val Ala Ala Ala Thr Thr Ala Ala
275 280 285
Pro Ala Ala Ala Ala Ala Pro Ala Lys Val Glu Ala Lys Glu Glu Ser
290 295 300
Glu Glu Ser Asp Glu Asp Met Gly Phe Gly Leu Phe Asp
305 310 315
<210> 171
<211> 1970
<212> PRT
<213> Homo sapiens
<400> 171
Met His Gly Gly Gly Pro Pro Ser Gly Asp Ser Ala Cys Pro Leu Arg
1 5 10 15
Thr Ile Lys Arg Val Gln Phe Gly Val Leu Ser Pro Asp Glu Leu Lys
20 25 30
Arg Met Ser Val Thr Glu Gly Gly Ile Lys Tyr Pro Glu Thr Thr Glu
35 40 45
Gly Gly Arg Pro Lys Leu Gly Gly Leu Met Asp Pro Arg Gln Gly Val
50 55 60
Ile Glu Arg Thr Gly Arg Cys Gln Thr Cys Ala Gly Asn Met Thr Glu
65 70 75 80
Cys Pro Gly His Phe Gly His Ile Glu Leu Ala Lys Pro Val Phe His
85 90 95
Val Gly Phe Leu Val Lys Thr Met Lys Val Leu Arg Cys Val Cys Phe
100 105 110
Phe Cys Ser Lys Leu Leu Val Asp Ser Asn Asn Pro Lys Ile Lys Asp
115 120 125
Ile Leu Ala Lys Ser Lys Gly Gln Pro Lys Lys Arg Leu Thr His Val
130 135 140
Tyr Asp Leu Cys Lys Gly Lys Asn Ile Cys Glu Gly Gly Glu Glu Met
145 150 155 160
Asp Asn Lys Phe Gly Val Glu Gln Pro Glu Gly Asp Glu Asp Leu Thr
165 170 175
Lys Glu Lys Gly His Gly Gly Cys Gly Arg Tyr Gln Pro Arg Ile Arg
180 185 190
Arg Ser Gly Leu Glu Leu Tyr Ala Glu Trp Lys His Val Asn Glu Asp
195 200 205
Ser Gln Glu Lys Lys Ile Leu Leu Ser Pro Glu Arg Val His Glu Ile
210 215 220
Phe Lys Arg Ile Ser Asp Glu Glu Cys Phe Val Leu Gly Met Glu Pro
225 230 235 240
Arg Tyr Ala Arg Pro Glu Trp Met Ile Val Thr Val Leu Pro Val Pro
245 250 255
Pro Leu Ser Val Arg Pro Ala Val Val Met Gln Gly Ser Ala Arg Asn
260 265 270
Gln Asp Asp Leu Thr His Lys Leu Ala Asp Ile Val Lys Ile Asn Asn
275 280 285
Gln Leu Arg Arg Asn Glu Gln Asn Gly Ala Ala Ala His Val Ile Ala
290 295 300
Glu Asp Val Lys Leu Leu Gln Phe His Val Ala Thr Met Val Asp Asn
305 310 315 320
Glu Leu Pro Gly Leu Pro Arg Ala Met Gln Lys Ser Gly Arg Pro Leu
325 330 335
Lys Ser Leu Lys Gln Arg Leu Lys Gly Lys Glu Gly Arg Val Arg Gly
340 345 350
Asn Leu Met Gly Lys Arg Val Asp Phe Ser Ala Arg Thr Val Ile Thr
355 360 365
Pro Asp Pro Asn Leu Ser Ile Asp Gln Val Gly Val Pro Arg Ser Ile
370 375 380
Ala Ala Asn Met Thr Phe Ala Glu Ile Val Thr Pro Phe Asn Ile Asp
385 390 395 400
Arg Leu Gln Glu Leu Val Arg Arg Gly Asn Ser Gln Tyr Pro Gly Ala
405 410 415
Lys Tyr Ile Ile Arg Asp Asn Gly Asp Arg Ile Asp Leu Arg Phe His
420 425 430
Pro Lys Pro Ser Asp Leu His Leu Gln Thr Gly Tyr Lys Val Glu Arg
435 440 445
His Met Cys Asp Gly Asp Ile Val Ile Phe Asn Arg Gln Pro Thr Leu
450 455 460
His Lys Met Ser Met Met Gly His Arg Val Arg Ile Leu Pro Trp Ser
465 470 475 480
Thr Phe Arg Leu Asn Leu Ser Val Thr Thr Pro Tyr Asn Ala Asp Phe
485 490 495
Asp Gly Asp Glu Met Asn Leu His Leu Pro Gln Ser Leu Glu Thr Arg
500 505 510
Ala Glu Ile Gln Glu Leu Ala Met Val Pro Arg Met Ile Val Thr Pro
515 520 525
Gln Ser Asn Arg Pro Val Met Gly Ile Val Gln Asp Thr Leu Thr Ala
530 535 540
Val Arg Lys Phe Thr Lys Arg Asp Val Phe Leu Glu Arg Gly Glu Val
545 550 555 560
Met Asn Leu Leu Met Phe Leu Ser Thr Trp Asp Gly Lys Val Pro Gln
565 570 575
Pro Ala Ile Leu Lys Pro Arg Pro Leu Trp Thr Gly Lys Gln Ile Phe
580 585 590
Ser Leu Ile Ile Pro Gly His Ile Asn Cys Ile Arg Thr His Ser Thr
595 600 605
His Pro Asp Asp Glu Asp Ser Gly Pro Tyr Lys His Ile Ser Pro Gly
610 615 620
Asp Thr Lys Val Val Val Glu Asn Gly Glu Leu Ile Met Gly Ile Leu
625 630 635 640
Cys Lys Lys Ser Leu Gly Thr Ser Ala Gly Ser Leu Val His Ile Ser
645 650 655
Tyr Leu Glu Met Gly His Asp Ile Thr Arg Leu Phe Tyr Ser Asn Ile
660 665 670
Gln Thr Val Ile Asn Asn Trp Leu Leu Ile Glu Gly His Thr Ile Gly
675 680 685
Ile Gly Asp Ser Ile Ala Asp Ser Lys Thr Tyr Gln Asp Ile Gln Asn
690 695 700
Thr Ile Lys Lys Ala Lys Gln Asp Val Ile Glu Val Ile Glu Lys Ala
705 710 715 720
His Asn Asn Glu Leu Glu Pro Thr Pro Gly Asn Thr Leu Arg Gln Thr
725 730 735
Phe Glu Asn Gln Val Asn Arg Ile Leu Asn Asp Ala Arg Asp Lys Thr
740 745 750
Gly Ser Ser Ala Gln Lys Ser Leu Ser Glu Tyr Asn Asn Phe Lys Ser
755 760 765
Met Val Val Ser Gly Ala Lys Gly Ser Lys Ile Asn Ile Ser Gln Val
770 775 780
Ile Ala Val Val Gly Gln Gln Asn Val Glu Gly Lys Arg Ile Pro Phe
785 790 795 800
Gly Phe Lys His Arg Thr Leu Pro His Phe Ile Lys Asp Asp Tyr Gly
805 810 815
Pro Glu Ser Arg Gly Phe Val Glu Asn Ser Tyr Leu Ala Gly Leu Thr
820 825 830
Pro Thr Glu Phe Phe Phe His Ala Met Gly Gly Arg Glu Gly Leu Ile
835 840 845
Asp Thr Ala Val Lys Thr Ala Glu Thr Gly Tyr Ile Gln Arg Arg Leu
850 855 860
Ile Lys Ser Met Glu Ser Val Met Val Lys Tyr Asp Ala Thr Val Arg
865 870 875 880
Asn Ser Ile Asn Gln Val Val Gln Leu Arg Tyr Gly Glu Asp Gly Leu
885 890 895
Ala Gly Glu Ser Val Glu Phe Gln Asn Leu Ala Thr Leu Lys Pro Ser
900 905 910
Asn Lys Ala Phe Glu Lys Lys Phe Arg Phe Asp Tyr Thr Asn Glu Arg
915 920 925
Ala Leu Arg Arg Thr Leu Gln Glu Asp Leu Val Lys Asp Val Leu Ser
930 935 940
Asn Ala His Ile Gln Asn Glu Leu Glu Arg Glu Phe Glu Arg Met Arg
945 950 955 960
Glu Asp Arg Glu Val Leu Arg Val Ile Phe Pro Thr Gly Asp Ser Lys
965 970 975
Val Val Leu Pro Cys Asn Leu Leu Arg Met Ile Trp Asn Ala Gln Lys
980 985 990
Ile Phe His Ile Asn Pro Arg Leu Pro Ser Asp Leu His Pro Ile Lys
995 1000 1005
Val Val Glu Gly Val Lys Glu Leu Ser Lys Lys Leu Val Ile Val
1010 1015 1020
Asn Gly Asp Asp Pro Leu Ser Arg Gln Ala Gln Glu Asn Ala Thr
1025 1030 1035
Leu Leu Phe Asn Ile His Leu Arg Ser Thr Leu Cys Ser Arg Arg
1040 1045 1050
Met Ala Glu Glu Phe Arg Leu Ser Gly Glu Ala Phe Asp Trp Leu
1055 1060 1065
Leu Gly Glu Ile Glu Ser Lys Phe Asn Gln Ala Ile Ala His Pro
1070 1075 1080
Gly Glu Met Val Gly Ala Leu Ala Ala Gln Ser Leu Gly Glu Pro
1085 1090 1095
Ala Thr Gln Met Thr Leu Asn Thr Phe His Tyr Ala Gly Val Ser
1100 1105 1110
Ala Lys Asn Val Thr Leu Gly Val Pro Arg Leu Lys Glu Leu Ile
1115 1120 1125
Asn Ile Ser Lys Lys Pro Lys Thr Pro Ser Leu Thr Val Phe Leu
1130 1135 1140
Leu Gly Gln Ser Ala Arg Asp Ala Glu Arg Ala Lys Asp Ile Leu
1145 1150 1155
Cys Arg Leu Glu His Thr Thr Leu Arg Lys Val Thr Ala Asn Thr
1160 1165 1170
Ala Ile Tyr Tyr Asp Pro Asn Pro Gln Ser Thr Val Val Ala Glu
1175 1180 1185
Asp Gln Glu Trp Val Asn Val Tyr Tyr Glu Met Pro Asp Phe Asp
1190 1195 1200
Val Ala Arg Ile Ser Pro Trp Leu Leu Arg Val Glu Leu Asp Arg
1205 1210 1215
Lys His Met Thr Asp Arg Lys Leu Thr Met Glu Gln Ile Ala Glu
1220 1225 1230
Lys Ile Asn Ala Gly Phe Gly Asp Asp Leu Asn Cys Ile Phe Asn
1235 1240 1245
Asp Asp Asn Ala Glu Lys Leu Val Leu Arg Ile Arg Ile Met Asn
1250 1255 1260
Ser Asp Glu Asn Lys Met Gln Glu Glu Glu Glu Val Val Asp Lys
1265 1270 1275
Met Asp Asp Asp Val Phe Leu Arg Cys Ile Glu Ser Asn Met Leu
1280 1285 1290
Thr Asp Met Thr Leu Gln Gly Ile Glu Gln Ile Ser Lys Val Tyr
1295 1300 1305
Met His Leu Pro Gln Thr Asp Asn Lys Lys Lys Ile Ile Ile Thr
1310 1315 1320
Glu Asp Gly Glu Phe Lys Ala Leu Gln Glu Trp Ile Leu Glu Thr
1325 1330 1335
Asp Gly Val Ser Leu Met Arg Val Leu Ser Glu Lys Asp Val Asp
1340 1345 1350
Pro Val Arg Thr Thr Ser Asn Asp Ile Val Glu Ile Phe Thr Val
1355 1360 1365
Leu Gly Ile Glu Ala Val Arg Lys Ala Leu Glu Arg Glu Leu Tyr
1370 1375 1380
His Val Ile Ser Phe Asp Gly Ser Tyr Val Asn Tyr Arg His Leu
1385 1390 1395
Ala Leu Leu Cys Asp Thr Met Thr Cys Arg Gly His Leu Met Ala
1400 1405 1410
Ile Thr Arg His Gly Val Asn Arg Gln Asp Thr Gly Pro Leu Met
1415 1420 1425
Lys Cys Ser Phe Glu Glu Thr Val Asp Val Leu Met Glu Ala Ala
1430 1435 1440
Ala His Gly Glu Ser Asp Pro Met Lys Gly Val Ser Glu Asn Ile
1445 1450 1455
Met Leu Gly Gln Leu Ala Pro Ala Gly Thr Gly Cys Phe Asp Leu
1460 1465 1470
Leu Leu Asp Ala Glu Lys Cys Lys Tyr Gly Met Glu Ile Pro Thr
1475 1480 1485
Asn Ile Pro Gly Leu Gly Ala Ala Gly Pro Thr Gly Met Phe Phe
1490 1495 1500
Gly Ser Ala Pro Ser Pro Met Gly Gly Ile Ser Pro Ala Met Thr
1505 1510 1515
Pro Trp Asn Gln Gly Ala Thr Pro Ala Tyr Gly Ala Trp Ser Pro
1520 1525 1530
Ser Val Gly Ser Gly Met Thr Pro Gly Ala Ala Gly Phe Ser Pro
1535 1540 1545
Ser Ala Ala Ser Asp Ala Ser Gly Phe Ser Pro Gly Tyr Ser Pro
1550 1555 1560
Ala Trp Ser Pro Thr Pro Gly Ser Pro Gly Ser Pro Gly Pro Ser
1565 1570 1575
Ser Pro Tyr Ile Pro Ser Pro Gly Gly Ala Met Ser Pro Ser Tyr
1580 1585 1590
Ser Pro Thr Ser Pro Ala Tyr Glu Pro Arg Ser Pro Gly Gly Tyr
1595 1600 1605
Thr Pro Gln Ser Pro Ser Tyr Ser Pro Thr Ser Pro Ser Tyr Ser
1610 1615 1620
Pro Thr Ser Pro Ser Tyr Ser Pro Thr Ser Pro Asn Tyr Ser Pro
1625 1630 1635
Thr Ser Pro Ser Tyr Ser Pro Thr Ser Pro Ser Tyr Ser Pro Thr
1640 1645 1650
Ser Pro Ser Tyr Ser Pro Thr Ser Pro Ser Tyr Ser Pro Thr Ser
1655 1660 1665
Pro Ser Tyr Ser Pro Thr Ser Pro Ser Tyr Ser Pro Thr Ser Pro
1670 1675 1680
Ser Tyr Ser Pro Thr Ser Pro Ser Tyr Ser Pro Thr Ser Pro Ser
1685 1690 1695
Tyr Ser Pro Thr Ser Pro Ser Tyr Ser Pro Thr Ser Pro Ser Tyr
1700 1705 1710
Ser Pro Thr Ser Pro Ser Tyr Ser Pro Thr Ser Pro Ser Tyr Ser
1715 1720 1725
Pro Thr Ser Pro Ser Tyr Ser Pro Thr Ser Pro Ser Tyr Ser Pro
1730 1735 1740
Thr Ser Pro Asn Tyr Ser Pro Thr Ser Pro Asn Tyr Thr Pro Thr
1745 1750 1755
Ser Pro Ser Tyr Ser Pro Thr Ser Pro Ser Tyr Ser Pro Thr Ser
1760 1765 1770
Pro Asn Tyr Thr Pro Thr Ser Pro Asn Tyr Ser Pro Thr Ser Pro
1775 1780 1785
Ser Tyr Ser Pro Thr Ser Pro Ser Tyr Ser Pro Thr Ser Pro Ser
1790 1795 1800
Tyr Ser Pro Ser Ser Pro Arg Tyr Thr Pro Gln Ser Pro Thr Tyr
1805 1810 1815
Thr Pro Ser Ser Pro Ser Tyr Ser Pro Ser Ser Pro Ser Tyr Ser
1820 1825 1830
Pro Thr Ser Pro Lys Tyr Thr Pro Thr Ser Pro Ser Tyr Ser Pro
1835 1840 1845
Ser Ser Pro Glu Tyr Thr Pro Thr Ser Pro Lys Tyr Ser Pro Thr
1850 1855 1860
Ser Pro Lys Tyr Ser Pro Thr Ser Pro Lys Tyr Ser Pro Thr Ser
1865 1870 1875
Pro Thr Tyr Ser Pro Thr Thr Pro Lys Tyr Ser Pro Thr Ser Pro
1880 1885 1890
Thr Tyr Ser Pro Thr Ser Pro Val Tyr Thr Pro Thr Ser Pro Lys
1895 1900 1905
Tyr Ser Pro Thr Ser Pro Thr Tyr Ser Pro Thr Ser Pro Lys Tyr
1910 1915 1920
Ser Pro Thr Ser Pro Thr Tyr Ser Pro Thr Ser Pro Lys Gly Ser
1925 1930 1935
Thr Tyr Ser Pro Thr Ser Pro Gly Tyr Ser Pro Thr Ser Pro Thr
1940 1945 1950
Tyr Ser Leu Thr Ser Pro Ala Ile Ser Pro Asp Asp Ser Asp Glu
1955 1960 1965
Glu Asn
1970
<210> 172
<211> 119
<212> PRT
<213> Homo sapiens
<400> 172
Met Ser Arg Ser Val Ala Leu Ala Val Leu Ala Leu Leu Ser Leu Ser
1 5 10 15
Gly Leu Glu Ala Ile Gln Arg Thr Pro Lys Ile Gln Val Tyr Ser Arg
20 25 30
His Pro Ala Glu Asn Gly Lys Ser Asn Phe Leu Asn Cys Tyr Val Ser
35 40 45
Gly Phe His Pro Ser Asp Ile Glu Val Asp Leu Leu Lys Asn Gly Glu
50 55 60
Arg Ile Glu Lys Val Glu His Ser Asp Leu Ser Phe Ser Lys Asp Trp
65 70 75 80
Ser Phe Tyr Leu Leu Tyr Tyr Thr Glu Phe Thr Pro Thr Glu Lys Asp
85 90 95
Glu Tyr Ala Cys Arg Val Asn His Val Thr Leu Ser Gln Pro Lys Ile
100 105 110
Val Lys Trp Asp Arg Asp Met
115
<210> 173
<211> 1188
<212> PRT
<213> Homo sapiens
<400> 173
Met Ser Val Ala Cys Val Leu Lys Arg Lys Ala Val Leu Trp Gln Asp
1 5 10 15
Ser Phe Ser Pro His Leu Lys His His Pro Gln Glu Pro Ala Asn Pro
20 25 30
Asn Met Pro Val Val Leu Thr Ser Gly Thr Gly Ser Gln Ala Gln Pro
35 40 45
Gln Pro Ala Ala Asn Gln Ala Leu Ala Ala Gly Thr His Ser Ser Pro
50 55 60
Val Pro Gly Ser Ile Gly Val Ala Gly Arg Ser Gln Asp Asp Ala Met
65 70 75 80
Val Asp Tyr Phe Phe Gln Arg Gln His Gly Glu Gln Leu Gly Gly Gly
85 90 95
Gly Ser Gly Gly Gly Gly Tyr Asn Asn Ser Lys His Arg Trp Pro Thr
100 105 110
Gly Asp Asn Ile His Ala Glu His Gln Val Arg Ser Met Asp Glu Leu
115 120 125
Asn His Asp Phe Gln Ala Leu Ala Leu Glu Gly Arg Ala Met Gly Glu
130 135 140
Gln Leu Leu Pro Gly Lys Lys Phe Trp Glu Thr Asp Glu Ser Ser Lys
145 150 155 160
Asp Gly Pro Lys Gly Ile Phe Leu Gly Asp Gln Trp Arg Asp Ser Ala
165 170 175
Trp Gly Thr Ser Asp His Ser Val Ser Gln Pro Ile Met Val Gln Arg
180 185 190
Arg Pro Gly Gln Ser Phe His Val Asn Ser Glu Val Asn Ser Val Leu
195 200 205
Ser Pro Arg Ser Glu Ser Gly Gly Leu Gly Val Ser Met Val Glu Tyr
210 215 220
Val Leu Ser Ser Ser Pro Gly Asp Ser Cys Leu Arg Lys Gly Gly Phe
225 230 235 240
Gly Pro Arg Asp Ala Asp Ser Asp Glu Asn Asp Lys Gly Glu Lys Lys
245 250 255
Asn Lys Gly Thr Phe Asp Gly Asp Lys Leu Gly Asp Leu Lys Glu Glu
260 265 270
Gly Asp Val Met Asp Lys Thr Asn Gly Leu Pro Val Gln Asn Gly Ile
275 280 285
Asp Ala Asp Val Lys Asp Phe Ser Arg Thr Pro Gly Asn Cys Gln Asn
290 295 300
Ser Ala Asn Glu Val Asp Leu Leu Gly Pro Asn Gln Asn Gly Ser Glu
305 310 315 320
Gly Leu Ala Gln Leu Thr Ser Thr Asn Gly Ala Lys Pro Val Glu Asp
325 330 335
Phe Ser Asn Met Glu Ser Gln Ser Val Pro Leu Asp Pro Met Glu His
340 345 350
Val Gly Met Glu Pro Leu Gln Phe Asp Tyr Ser Gly Thr Gln Val Pro
355 360 365
Val Asp Ser Ala Ala Ala Thr Val Gly Leu Phe Asp Tyr Asn Ser Gln
370 375 380
Gln Gln Leu Phe Gln Arg Pro Asn Ala Leu Ala Val Gln Gln Leu Thr
385 390 395 400
Ala Ala Gln Gln Gln Gln Tyr Ala Leu Ala Ala Ala His Gln Pro His
405 410 415
Ile Gly Leu Ala Pro Ala Ala Phe Val Pro Asn Pro Tyr Ile Ile Ser
420 425 430
Ala Ala Pro Pro Gly Thr Asp Pro Tyr Thr Ala Gly Leu Ala Ala Ala
435 440 445
Ala Thr Leu Gly Pro Ala Val Val Pro His Gln Tyr Tyr Gly Val Thr
450 455 460
Pro Trp Gly Val Tyr Pro Ala Ser Leu Phe Gln Gln Gln Ala Ala Ala
465 470 475 480
Ala Ala Ala Ala Thr Asn Ser Ala Asn Gln Gln Thr Thr Pro Gln Ala
485 490 495
Gln Gln Gly Gln Gln Gln Val Leu Arg Gly Gly Ala Ser Gln Arg Pro
500 505 510
Leu Thr Pro Asn Gln Asn Gln Gln Gly Gln Gln Thr Asp Pro Leu Val
515 520 525
Ala Ala Ala Ala Val Asn Ser Ala Leu Ala Phe Gly Gln Gly Leu Ala
530 535 540
Ala Gly Met Pro Gly Tyr Pro Val Leu Ala Pro Ala Ala Tyr Tyr Asp
545 550 555 560
Gln Thr Gly Ala Leu Val Val Asn Ala Gly Ala Arg Asn Gly Leu Gly
565 570 575
Ala Pro Val Arg Leu Val Ala Pro Ala Pro Val Ile Ile Ser Ser Ser
580 585 590
Ala Ala Gln Ala Ala Val Ala Ala Ala Ala Ala Ser Ala Asn Gly Ala
595 600 605
Ala Gly Gly Leu Ala Gly Thr Thr Asn Gly Pro Phe Arg Pro Leu Gly
610 615 620
Thr Gln Gln Pro Gln Pro Gln Pro Gln Gln Gln Pro Asn Asn Asn Leu
625 630 635 640
Ala Ser Ser Ser Phe Tyr Gly Asn Asn Ser Leu Asn Ser Asn Ser Gln
645 650 655
Ser Ser Ser Leu Phe Ser Gln Gly Ser Ala Gln Pro Ala Asn Thr Ser
660 665 670
Leu Gly Phe Gly Ser Ser Ser Ser Leu Gly Ala Thr Leu Gly Ser Ala
675 680 685
Leu Gly Gly Phe Gly Thr Ala Val Ala Asn Ser Asn Thr Gly Ser Gly
690 695 700
Ser Arg Arg Asp Ser Leu Thr Gly Ser Ser Asp Leu Tyr Lys Arg Thr
705 710 715 720
Ser Ser Ser Leu Thr Pro Ile Gly His Ser Phe Tyr Asn Gly Leu Ser
725 730 735
Phe Ser Ser Ser Pro Gly Pro Val Gly Met Pro Leu Pro Ser Gln Gly
740 745 750
Pro Gly His Ser Gln Thr Pro Pro Pro Ser Leu Ser Ser His Gly Ser
755 760 765
Ser Ser Ser Leu Asn Leu Gly Gly Leu Thr Asn Gly Ser Gly Arg Tyr
770 775 780
Ile Ser Ala Ala Pro Gly Ala Glu Ala Lys Tyr Arg Ser Ala Ser Ser
785 790 795 800
Ala Ser Ser Leu Phe Ser Pro Ser Ser Thr Leu Phe Ser Ser Ser Arg
805 810 815
Leu Arg Tyr Gly Met Ser Asp Val Met Pro Ser Gly Arg Ser Arg Leu
820 825 830
Leu Glu Asp Phe Arg Asn Asn Arg Tyr Pro Asn Leu Gln Leu Arg Glu
835 840 845
Ile Ala Gly His Ile Met Glu Phe Ser Gln Asp Gln His Gly Ser Arg
850 855 860
Phe Ile Gln Leu Lys Leu Glu Arg Ala Thr Pro Ala Glu Arg Gln Leu
865 870 875 880
Val Phe Asn Glu Ile Leu Gln Ala Ala Tyr Gln Leu Met Val Asp Val
885 890 895
Phe Gly Asn Tyr Val Ile Gln Lys Phe Phe Glu Phe Gly Ser Leu Glu
900 905 910
Gln Lys Leu Ala Leu Ala Glu Arg Ile Arg Gly His Val Leu Ser Leu
915 920 925
Ala Leu Gln Met Tyr Gly Cys Arg Val Ile Gln Lys Ala Leu Glu Phe
930 935 940
Ile Pro Ser Asp Gln Gln Val Ile Asn Glu Met Val Arg Glu Leu Asp
945 950 955 960
Gly His Val Leu Lys Cys Val Lys Asp Gln Asn Gly Asn His Val Val
965 970 975
Gln Lys Cys Ile Glu Cys Val Gln Pro Gln Ser Leu Gln Phe Ile Ile
980 985 990
Asp Ala Phe Lys Gly Gln Val Phe Ala Leu Ser Thr His Pro Tyr Gly
995 1000 1005
Cys Arg Val Ile Gln Arg Ile Leu Glu His Cys Leu Pro Asp Gln
1010 1015 1020
Thr Leu Pro Ile Leu Glu Glu Leu His Gln His Thr Glu Gln Leu
1025 1030 1035
Val Gln Asp Gln Tyr Gly Asn Tyr Val Ile Gln His Val Leu Glu
1040 1045 1050
His Gly Arg Pro Glu Asp Lys Ser Lys Ile Val Ala Glu Ile Arg
1055 1060 1065
Gly Asn Val Leu Val Leu Ser Gln His Lys Phe Ala Ser Asn Val
1070 1075 1080
Val Glu Lys Cys Val Thr His Ala Ser Arg Thr Glu Arg Ala Val
1085 1090 1095
Leu Ile Asp Glu Val Cys Thr Met Asn Asp Gly Pro His Ser Ala
1100 1105 1110
Leu Tyr Thr Met Met Lys Asp Gln Tyr Ala Asn Tyr Val Val Gln
1115 1120 1125
Lys Met Ile Asp Val Ala Glu Pro Gly Gln Arg Lys Ile Val Met
1130 1135 1140
His Lys Ile Arg Pro His Ile Ala Thr Leu Arg Lys Tyr Thr Tyr
1145 1150 1155
Gly Lys His Ile Leu Ala Lys Leu Glu Lys Tyr Tyr Met Lys Asn
1160 1165 1170
Gly Val Asp Leu Gly Pro Ile Cys Gly Pro Pro Asn Gly Ile Ile
1175 1180 1185
<210> 174
<211> 1186
<212> PRT
<213> Homo sapiens
<400> 174
Met Ser Val Ala Cys Val Leu Lys Arg Lys Ala Val Leu Trp Gln Asp
1 5 10 15
Ser Phe Ser Pro His Leu Lys His His Pro Gln Glu Pro Ala Asn Pro
20 25 30
Asn Met Pro Val Val Leu Thr Ser Gly Thr Gly Ser Gln Ala Gln Pro
35 40 45
Gln Pro Ala Ala Asn Gln Ala Leu Ala Ala Gly Thr His Ser Ser Pro
50 55 60
Val Pro Gly Ser Ile Gly Val Ala Gly Arg Ser Gln Asp Asp Ala Met
65 70 75 80
Val Asp Tyr Phe Phe Gln Arg Gln His Gly Glu Gln Leu Gly Gly Gly
85 90 95
Gly Ser Gly Gly Gly Gly Tyr Asn Asn Ser Lys His Arg Trp Pro Thr
100 105 110
Gly Asp Asn Ile His Ala Glu His Gln Val Arg Ser Met Asp Glu Leu
115 120 125
Asn His Asp Phe Gln Ala Leu Ala Leu Glu Gly Arg Ala Met Gly Glu
130 135 140
Gln Leu Leu Pro Gly Lys Lys Phe Trp Glu Thr Asp Glu Ser Ser Lys
145 150 155 160
Asp Gly Pro Lys Gly Ile Phe Leu Gly Asp Gln Trp Arg Asp Ser Ala
165 170 175
Trp Gly Thr Ser Asp His Ser Val Ser Gln Pro Ile Met Val Gln Arg
180 185 190
Arg Pro Gly Gln Ser Phe His Val Asn Ser Glu Val Asn Ser Val Leu
195 200 205
Ser Pro Arg Ser Glu Ser Gly Gly Leu Gly Val Ser Met Val Glu Tyr
210 215 220
Val Leu Ser Ser Ser Pro Gly Asp Ser Cys Leu Arg Lys Gly Gly Phe
225 230 235 240
Gly Pro Arg Asp Ala Asp Ser Asp Glu Asn Asp Lys Gly Glu Lys Lys
245 250 255
Asn Lys Gly Thr Phe Asp Gly Asp Lys Leu Gly Asp Leu Lys Glu Glu
260 265 270
Gly Asp Val Met Asp Lys Thr Asn Gly Leu Pro Val Gln Asn Gly Ile
275 280 285
Asp Ala Asp Val Lys Asp Phe Ser Arg Thr Pro Gly Asn Cys Gln Asn
290 295 300
Ser Ala Asn Glu Val Asp Leu Leu Gly Pro Asn Gln Asn Gly Ser Glu
305 310 315 320
Gly Leu Ala Gln Leu Thr Ser Thr Asn Gly Ala Lys Pro Val Glu Asp
325 330 335
Phe Ser Asn Met Glu Ser Gln Ser Val Pro Leu Asp Pro Met Glu His
340 345 350
Val Gly Met Glu Pro Leu Gln Phe Asp Tyr Ser Gly Thr Gln Val Pro
355 360 365
Val Asp Ser Ala Ala Ala Thr Val Gly Leu Phe Asp Tyr Asn Ser Gln
370 375 380
Gln Gln Leu Phe Gln Arg Pro Asn Ala Leu Ala Val Gln Gln Leu Thr
385 390 395 400
Ala Ala Gln Gln Gln Gln Tyr Ala Leu Ala Ala Ala His Gln Pro His
405 410 415
Ile Gly Leu Ala Pro Ala Ala Phe Val Pro Asn Pro Tyr Ile Ile Ser
420 425 430
Ala Ala Pro Pro Gly Thr Asp Pro Tyr Thr Ala Gly Leu Ala Ala Ala
435 440 445
Ala Thr Leu Gly Pro Ala Val Val Pro His Gln Tyr Tyr Gly Val Thr
450 455 460
Pro Trp Gly Val Tyr Pro Ala Ser Leu Phe Gln Gln Gln Ala Ala Ala
465 470 475 480
Ala Ala Ala Ala Thr Asn Ser Ala Asn Gln Gln Thr Thr Pro Gln Ala
485 490 495
Gln Gln Gly Gln Gln Gln Val Leu Arg Gly Gly Ala Ser Gln Arg Pro
500 505 510
Leu Thr Pro Asn Gln Asn Gln Gln Gly Gln Gln Thr Asp Pro Leu Val
515 520 525
Ala Ala Ala Ala Val Asn Ser Ala Leu Ala Phe Gly Gln Gly Leu Ala
530 535 540
Ala Gly Met Pro Gly Tyr Pro Val Leu Ala Pro Ala Ala Tyr Tyr Asp
545 550 555 560
Gln Thr Gly Ala Leu Val Val Asn Ala Gly Ala Arg Asn Gly Leu Gly
565 570 575
Ala Pro Val Arg Leu Val Ala Pro Ala Pro Val Ile Ile Ser Ser Ser
580 585 590
Ala Ala Gln Ala Ala Val Ala Ala Ala Ala Ala Ser Ala Asn Gly Ala
595 600 605
Ala Gly Gly Leu Ala Gly Thr Thr Asn Gly Pro Phe Arg Pro Leu Gly
610 615 620
Thr Gln Gln Pro Gln Pro Gln Pro Gln Gln Gln Pro Asn Asn Asn Leu
625 630 635 640
Ala Ser Ser Ser Phe Tyr Gly Asn Asn Ser Leu Asn Ser Asn Ser Gln
645 650 655
Ser Ser Ser Leu Phe Ser Gln Gly Ser Ala Gln Pro Ala Asn Thr Ser
660 665 670
Leu Gly Phe Gly Ser Ser Ser Ser Leu Gly Ala Thr Leu Gly Ser Ala
675 680 685
Leu Gly Gly Phe Gly Thr Ala Val Ala Asn Ser Asn Thr Gly Ser Gly
690 695 700
Ser Arg Arg Asp Ser Leu Thr Gly Ser Ser Asp Leu Tyr Lys Arg Thr
705 710 715 720
Ser Ser Ser Leu Thr Pro Ile Gly His Ser Phe Tyr Asn Gly Leu Ser
725 730 735
Phe Ser Ser Ser Pro Gly Pro Val Gly Met Pro Leu Pro Ser Gln Gly
740 745 750
Pro Gly His Ser Gln Thr Pro Pro Pro Ser Leu Ser Ser His Gly Ser
755 760 765
Ser Ser Ser Leu Asn Leu Gly Gly Leu Thr Asn Gly Ser Gly Arg Tyr
770 775 780
Ile Ser Ala Ala Pro Gly Ala Glu Ala Lys Tyr Arg Ser Ala Ser Ser
785 790 795 800
Ala Ser Ser Leu Phe Ser Pro Ser Ser Thr Leu Phe Ser Ser Ser Arg
805 810 815
Leu Arg Tyr Gly Met Ser Asp Val Met Pro Ser Gly Arg Ser Arg Leu
820 825 830
Leu Glu Asp Phe Arg Asn Asn Arg Tyr Pro Asn Leu Gln Leu Arg Glu
835 840 845
Ile Ala Gly His Ile Met Glu Phe Ser Gln Asp Gln His Gly Ser Arg
850 855 860
Phe Ile Gln Leu Lys Leu Glu Arg Ala Thr Pro Ala Glu Arg Gln Leu
865 870 875 880
Val Phe Asn Glu Ile Leu Gln Ala Ala Tyr Gln Leu Met Val Asp Val
885 890 895
Phe Gly Asn Tyr Val Ile Gln Lys Phe Phe Glu Phe Gly Ser Leu Glu
900 905 910
Gln Lys Leu Ala Leu Ala Glu Arg Ile Arg Gly His Val Leu Ser Leu
915 920 925
Ala Leu Gln Met Tyr Gly Cys Arg Val Ile Gln Lys Ala Leu Glu Phe
930 935 940
Ile Pro Ser Asp Gln Gln Asn Glu Met Val Arg Glu Leu Asp Gly His
945 950 955 960
Val Leu Lys Cys Val Lys Asp Gln Asn Gly Asn His Val Val Gln Lys
965 970 975
Cys Ile Glu Cys Val Gln Pro Gln Ser Leu Gln Phe Ile Ile Asp Ala
980 985 990
Phe Lys Gly Gln Val Phe Ala Leu Ser Thr His Pro Tyr Gly Cys Arg
995 1000 1005
Val Ile Gln Arg Ile Leu Glu His Cys Leu Pro Asp Gln Thr Leu
1010 1015 1020
Pro Ile Leu Glu Glu Leu His Gln His Thr Glu Gln Leu Val Gln
1025 1030 1035
Asp Gln Tyr Gly Asn Tyr Val Ile Gln His Val Leu Glu His Gly
1040 1045 1050
Arg Pro Glu Asp Lys Ser Lys Ile Val Ala Glu Ile Arg Gly Asn
1055 1060 1065
Val Leu Val Leu Ser Gln His Lys Phe Ala Ser Asn Val Val Glu
1070 1075 1080
Lys Cys Val Thr His Ala Ser Arg Thr Glu Arg Ala Val Leu Ile
1085 1090 1095
Asp Glu Val Cys Thr Met Asn Asp Gly Pro His Ser Ala Leu Tyr
1100 1105 1110
Thr Met Met Lys Asp Gln Tyr Ala Asn Tyr Val Val Gln Lys Met
1115 1120 1125
Ile Asp Val Ala Glu Pro Gly Gln Arg Lys Ile Val Met His Lys
1130 1135 1140
Ile Arg Pro His Ile Ala Thr Leu Arg Lys Tyr Thr Tyr Gly Lys
1145 1150 1155
His Ile Leu Ala Lys Leu Glu Lys Tyr Tyr Met Lys Asn Gly Val
1160 1165 1170
Asp Leu Gly Pro Ile Cys Gly Pro Pro Asn Gly Ile Ile
1175 1180 1185
<210> 175
<211> 451
<212> PRT
<213> Homo sapiens
<400> 175
Met Arg Glu Cys Ile Ser Ile His Val Gly Gln Ala Gly Val Gln Ile
1 5 10 15
Gly Asn Ala Cys Trp Glu Leu Tyr Cys Leu Glu His Gly Ile Gln Pro
20 25 30
Asp Gly Gln Met Pro Ser Asp Lys Thr Ile Gly Gly Gly Asp Asp Ser
35 40 45
Phe Asn Thr Phe Phe Ser Glu Thr Gly Ala Gly Lys His Val Pro Arg
50 55 60
Ala Val Phe Val Asp Leu Glu Pro Thr Val Ile Asp Glu Val Arg Thr
65 70 75 80
Gly Thr Tyr Arg Gln Leu Phe His Pro Glu Gln Leu Ile Thr Gly Lys
85 90 95
Glu Asp Ala Ala Asn Asn Tyr Ala Arg Gly His Tyr Thr Ile Gly Lys
100 105 110
Glu Ile Ile Asp Leu Val Leu Asp Arg Ile Arg Lys Leu Ala Asp Gln
115 120 125
Cys Thr Gly Leu Gln Gly Phe Leu Val Phe His Ser Phe Gly Gly Gly
130 135 140
Thr Gly Ser Gly Phe Thr Ser Leu Leu Met Glu Arg Leu Ser Val Asp
145 150 155 160
Tyr Gly Lys Lys Ser Lys Leu Glu Phe Ser Ile Tyr Pro Ala Pro Gln
165 170 175
Val Ser Thr Ala Val Val Glu Pro Tyr Asn Ser Ile Leu Thr Thr His
180 185 190
Thr Thr Leu Glu His Ser Asp Cys Ala Phe Met Val Asp Asn Glu Ala
195 200 205
Ile Tyr Asp Ile Cys Arg Arg Asn Leu Asp Ile Glu Arg Pro Thr Tyr
210 215 220
Thr Asn Leu Asn Arg Leu Ile Ser Gln Ile Val Ser Ser Ile Thr Ala
225 230 235 240
Ser Leu Arg Phe Asp Gly Ala Leu Asn Val Asp Leu Thr Glu Phe Gln
245 250 255
Thr Asn Leu Val Pro Tyr Pro Arg Ile His Phe Pro Leu Ala Thr Tyr
260 265 270
Ala Pro Val Ile Ser Ala Glu Lys Ala Tyr His Glu Gln Leu Ser Val
275 280 285
Ala Glu Ile Thr Asn Ala Cys Phe Glu Pro Ala Asn Gln Met Val Lys
290 295 300
Cys Asp Pro Arg His Gly Lys Tyr Met Ala Cys Cys Leu Leu Tyr Arg
305 310 315 320
Gly Asp Val Val Pro Lys Asp Val Asn Ala Ala Ile Ala Thr Ile Lys
325 330 335
Thr Lys Arg Ser Ile Gln Phe Val Asp Trp Cys Pro Thr Gly Phe Lys
340 345 350
Val Gly Ile Asn Tyr Gln Pro Pro Thr Val Val Pro Gly Gly Asp Leu
355 360 365
Ala Lys Val Gln Arg Ala Val Cys Met Leu Ser Asn Thr Thr Ala Ile
370 375 380
Ala Glu Ala Trp Ala Arg Leu Asp His Lys Phe Asp Leu Met Tyr Ala
385 390 395 400
Lys Arg Ala Phe Val His Trp Tyr Val Gly Glu Gly Met Glu Glu Gly
405 410 415
Glu Phe Ser Glu Ala Arg Glu Asp Met Ala Ala Leu Glu Lys Asp Tyr
420 425 430
Glu Glu Val Gly Val Asp Ser Val Glu Gly Glu Gly Glu Glu Glu Gly
435 440 445
Glu Glu Tyr
450
<210> 176
<211> 640
<212> PRT
<213> Homo sapiens
<400> 176
Met Glu Ser Val Val Arg Arg Cys Pro Phe Leu Ser Arg Val Pro Gln
1 5 10 15
Ala Phe Leu Gln Lys Ala Gly Lys Ser Leu Leu Phe Tyr Ala Gln Asn
20 25 30
Cys Pro Lys Met Met Glu Val Gly Ala Lys Pro Ala Pro Arg Ala Leu
35 40 45
Ser Thr Ala Ala Val His Tyr Gln Gln Ile Lys Glu Thr Pro Pro Ala
50 55 60
Ser Glu Lys Asp Lys Thr Ala Lys Ala Lys Val Gln Gln Thr Pro Asp
65 70 75 80
Gly Ser Gln Gln Ser Pro Asp Gly Thr Gln Leu Pro Ser Gly His Pro
85 90 95
Leu Pro Ala Thr Ser Gln Gly Thr Ala Ser Lys Cys Pro Phe Leu Ala
100 105 110
Ala Gln Met Asn Gln Arg Gly Ser Ser Val Phe Cys Lys Ala Ser Leu
115 120 125
Glu Leu Gln Glu Asp Val Gln Glu Met Asn Ala Val Arg Lys Glu Val
130 135 140
Ala Glu Thr Ser Ala Gly Pro Ser Val Val Ser Val Lys Thr Asp Gly
145 150 155 160
Gly Asp Pro Ser Gly Leu Leu Lys Asn Phe Gln Asp Ile Met Gln Lys
165 170 175
Gln Arg Pro Glu Arg Val Ser His Leu Leu Gln Asp Asn Leu Pro Lys
180 185 190
Ser Val Ser Thr Phe Gln Tyr Asp Arg Phe Phe Glu Lys Lys Ile Asp
195 200 205
Glu Lys Lys Asn Asp His Thr Tyr Arg Val Phe Lys Thr Val Asn Arg
210 215 220
Arg Ala His Ile Phe Pro Met Ala Asp Asp Tyr Ser Asp Ser Leu Ile
225 230 235 240
Thr Lys Lys Gln Val Ser Val Trp Cys Ser Asn Asp Tyr Leu Gly Met
245 250 255
Ser Arg His Pro Arg Val Cys Gly Ala Val Met Asp Thr Leu Lys Gln
260 265 270
His Gly Ala Gly Ala Gly Gly Thr Arg Asn Ile Ser Gly Thr Ser Lys
275 280 285
Phe His Val Asp Leu Glu Arg Glu Leu Ala Asp Leu His Gly Lys Asp
290 295 300
Ala Ala Leu Leu Phe Ser Ser Cys Phe Val Ala Asn Asp Ser Thr Leu
305 310 315 320
Phe Thr Leu Ala Lys Met Met Pro Gly Cys Glu Ile Tyr Ser Asp Ser
325 330 335
Gly Asn His Ala Ser Met Ile Gln Gly Ile Arg Asn Ser Arg Val Pro
340 345 350
Lys Tyr Ile Phe Arg His Asn Asp Val Ser His Leu Arg Glu Leu Leu
355 360 365
Gln Arg Ser Asp Pro Ser Val Pro Lys Ile Val Ala Phe Glu Thr Val
370 375 380
His Ser Met Asp Gly Ala Val Cys Pro Leu Glu Glu Leu Cys Asp Val
385 390 395 400
Ala His Glu Phe Gly Ala Ile Thr Phe Val Asp Glu Val His Ala Val
405 410 415
Gly Leu Tyr Gly Ala Arg Gly Gly Gly Ile Gly Asp Arg Asp Gly Val
420 425 430
Met Pro Lys Met Asp Ile Ile Ser Gly Thr Leu Gly Lys Ala Phe Gly
435 440 445
Cys Val Gly Gly Tyr Ile Ala Ser Thr Ser Ser Leu Ile Asp Thr Val
450 455 460
Arg Ser Tyr Ala Ala Gly Phe Ile Phe Thr Thr Ser Leu Pro Pro Met
465 470 475 480
Leu Leu Ala Gly Ala Leu Glu Ser Val Arg Ile Leu Lys Ser Ala Glu
485 490 495
Gly Arg Val Leu Arg Arg Gln His Gln Arg Asn Val Lys Leu Met Arg
500 505 510
Gln Met Leu Met Asp Ala Gly Leu Pro Val Val His Cys Pro Ser His
515 520 525
Ile Ile Pro Val Arg Val Ala Asp Ala Ala Lys Asn Thr Glu Val Cys
530 535 540
Asp Glu Leu Met Ser Arg His Asn Ile Tyr Val Gln Ala Ile Asn Tyr
545 550 555 560
Pro Thr Val Pro Arg Gly Glu Glu Leu Leu Arg Ile Ala Pro Thr Pro
565 570 575
His His Thr Pro Gln Met Met Asn Tyr Phe Leu Glu Asn Leu Leu Val
580 585 590
Thr Trp Lys Gln Val Gly Leu Glu Leu Lys Pro His Ser Ser Ala Glu
595 600 605
Cys Asn Phe Cys Arg Arg Pro Leu His Phe Glu Val Met Ser Glu Arg
610 615 620
Glu Lys Ser Tyr Phe Ser Gly Leu Ser Lys Leu Val Ser Ala Gln Ala
625 630 635 640
<210> 177
<211> 640
<212> PRT
<213> Homo sapiens
<400> 177
Met Glu Ser Val Val Arg Arg Cys Pro Phe Leu Ser Arg Val Pro Gln
1 5 10 15
Ala Phe Leu Gln Lys Ala Gly Lys Ser Leu Leu Phe Tyr Ala Gln Asn
20 25 30
Cys Pro Lys Met Met Glu Val Gly Ala Lys Pro Ala Pro Arg Ala Leu
35 40 45
Ser Thr Ala Ala Val His Tyr Gln Gln Ile Lys Glu Thr Pro Pro Ala
50 55 60
Ser Glu Lys Asp Lys Thr Ala Lys Ala Lys Val Gln Gln Thr Pro Asp
65 70 75 80
Gly Ser Gln Gln Ser Pro Asp Gly Thr Gln Leu Pro Ser Gly His Pro
85 90 95
Leu Pro Ala Thr Ser Gln Gly Thr Ala Ser Lys Cys Pro Phe Leu Ala
100 105 110
Ala Gln Met Asn Gln Arg Gly Ser Ser Val Phe Cys Lys Ala Ser Leu
115 120 125
Glu Leu Gln Glu Asp Val Gln Glu Met Asn Ala Val Arg Lys Glu Val
130 135 140
Ala Glu Thr Ser Ala Gly Pro Ser Val Val Ser Val Lys Thr Asp Gly
145 150 155 160
Gly Asp Pro Ser Gly Leu Leu Lys Asn Phe Gln Asp Ile Met Gln Lys
165 170 175
Gln Arg Pro Glu Arg Val Ser His Leu Leu Gln Asp Asn Leu Pro Lys
180 185 190
Ser Val Ser Thr Phe Gln Tyr Asp Arg Phe Phe Glu Lys Lys Ile Asp
195 200 205
Glu Lys Lys Asn Asp His Thr Tyr Arg Val Phe Lys Thr Val Asn Arg
210 215 220
Arg Ala His Ile Phe Pro Met Ala Asp Asp Tyr Ser Asp Ser Leu Ile
225 230 235 240
Thr Lys Lys Gln Val Ser Val Trp Cys Ser Asn Asp Tyr Leu Gly Met
245 250 255
Ser Arg His Pro Arg Val Cys Gly Ala Val Met Asp Thr Leu Lys Gln
260 265 270
His Gly Ala Gly Ala Gly Gly Thr Arg Asn Ile Ser Gly Thr Ser Lys
275 280 285
Phe His Val Asp Leu Glu Arg Glu Leu Ala Asp Leu His Gly Lys Asp
290 295 300
Ala Ala Leu Leu Phe Ser Ser Cys Phe Val Ala Asn Asp Ser Thr Leu
305 310 315 320
Phe Thr Leu Ala Lys Met Met Pro Gly Cys Glu Ile Tyr Ser Asp Ser
325 330 335
Gly Asn His Ala Ser Met Ile Gln Gly Ile Arg Asn Ser Arg Val Pro
340 345 350
Lys Tyr Ile Phe Arg His Asn Asp Val Ser His Leu Arg Glu Leu Leu
355 360 365
Gln Arg Ser Asp Pro Ser Val Pro Lys Ile Val Ala Phe Glu Thr Val
370 375 380
His Ser Met Asp Gly Ala Val Cys Pro Leu Glu Glu Leu Cys Asp Val
385 390 395 400
Ala His Glu Phe Gly Ala Ile Thr Phe Val Asp Glu Val His Ala Val
405 410 415
Gly Leu Tyr Gly Ala Arg Gly Gly Gly Ile Gly Asp Arg Asp Gly Val
420 425 430
Met Pro Lys Met Asp Ile Ile Ser Gly Thr Leu Gly Lys Ala Phe Gly
435 440 445
Cys Val Gly Gly Tyr Ile Ala Ser Thr Ser Ser Leu Ile Asp Thr Val
450 455 460
Arg Ser Tyr Ala Ala Gly Phe Ile Phe Thr Thr Ser Leu Pro Pro Met
465 470 475 480
Leu Leu Ala Gly Ala Leu Glu Ser Val Arg Ile Leu Lys Ser Ala Glu
485 490 495
Gly Arg Val Leu Arg Arg Gln His Gln Arg Asn Val Lys Leu Met Arg
500 505 510
Gln Met Leu Met Asp Ala Gly Leu Pro Val Val His Cys Pro Ser His
515 520 525
Ile Ile Pro Val Arg Val Ala Asp Ala Ala Lys Asn Thr Glu Val Cys
530 535 540
Asp Glu Leu Met Ser Arg His Asn Ile Tyr Val Gln Ala Ile Asn Tyr
545 550 555 560
Pro Thr Val Pro Arg Gly Glu Glu Leu Leu Arg Ile Ala Pro Thr Pro
565 570 575
His His Thr Pro Gln Met Met Asn Tyr Phe Leu Glu Asn Leu Leu Val
580 585 590
Thr Trp Lys Gln Val Gly Leu Glu Leu Lys Pro His Ser Ser Ala Glu
595 600 605
Cys Asn Phe Cys Arg Arg Pro Leu His Phe Glu Val Met Ser Glu Arg
610 615 620
Glu Lys Ser Tyr Phe Ser Gly Leu Ser Lys Leu Val Ser Ala Gln Ala
625 630 635 640
<210> 178
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> TBP_forward primer
<400> 178
gccaagaaga aagtgaacat cat 23
<210> 179
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> TBP_reverse primer
<400> 179
atagggattc cgggagtcat 20
<210> 180
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> TBP probe
<400> 180
tcagaacaac agcctgccac ctta 24
<210> 181
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> HPRT1_forward primer
<400> 181
gaggatttgg aaagggtgtt tatt 24
<210> 182
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> HPRT1_reverse primer
<400> 182
acagagggct acaatgtgat g 21
<210> 183
<211> 26
<212> DNA
<213> Artificial Sequence
<220>
<223> HPRT1 probe
<400> 183
acgtcttgct cgagatgtga tgaagg 26
<210> 184
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> ACTB_forward primer
<400> 184
ccaaccgcga gaagatga 18
<210> 185
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> ACTB_reverse primer
<400> 185
ccagaggcgt acagggatag 20
<210> 186
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> ACTB probe
<400> 186
ccatgtacgt tgctatccag gct 23
<210> 187
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> RPLP0_forward primer
<400> 187
taaaccctgc gtggcaat 18
<210> 188
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> RPLP0_reverse primer
<400> 188
acatttcgga taatcatcca atagttg 27
<210> 189
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> RPLP0 probe
<400> 189
aagtagttgg acttccaggt cgcc 24
<210> 190
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> POLR2A_forward primer
<400> 190
agtcctgagt ccggatgaa 19
<210> 191
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> POLR2A_reverse primer
<400> 191
cctccctcag tcgtctct 18
<210> 192
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> POLR2A probe
<400> 192
tgacggaggg tggcatcaaa tacc 24
<210> 193
<211> 17
<212> DNA
<213> Artificial Sequence
<220>
<223> B2M_forward primer
<400> 193
ccgtggcctt agctgtg 17
<210> 194
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> B2M_reverse primer
<400> 194
ctgctggatg acgtgagtaa a 21
<210> 195
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> B2M probe
<400> 195
tctctctttc tggcctggag gcta 24
<210> 196
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> PUM1_forward primer
<400> 196
gccagcttgt cttcaatgaa at 22
<210> 197
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> PUM1_reverse primer
<400> 197
caaagccagc ttctgttcaa g 21
<210> 198
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> PUM1 probe
<400> 198
atccaccatg agttggtagg cagc 24
<210> 199
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> K-ALPHA-1_forward primer
<400> 199
tgactccttc aacaccttct tc 22
<210> 200
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> K-ALPHA-1_reverse primer
<400> 200
tgccagtgcg aacttcat 18
<210> 201
<211> 24
<212> DNA
<213> Artificial Sequence
<220>
<223> K-ALPHA-1 probe
<400> 201
ccgggctgtg tttgtagact tgga 24
<210> 202
<211> 17
<212> DNA
<213> Artificial Sequence
<220>
<223> ALAS-1_forward primer
<400> 202
agccacatca tccctgt 17
<210> 203
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> ALAS-1_reverse primer
<400> 203
cgtagatgtt atgtctgctc at 22
<210> 204
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> ALAS-1 probe
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Claims (18)

1.一种用于对对象进行分类的装置，包括：
-用于基于针对所述对象的对象表达谱将所述对象分类为具有良好预后或不良预后的单元，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、以及生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；和/或
-用于基于针对所述对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向的单元，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加，
其中，所述对象表达谱被转换为前列腺癌进展指数，所述前列腺癌进展指数是根据以下等式来计算的：
PCPI＝(GEV_av_GOI_up)-(GEV_av_GOI_down)，其中GEV_av_GOI_up是上调基因的平均基因表达值并且GEV_av_GOI_down是下调基因的平均基因表达值，其中所述值是基于每个对象样本的标准化基因表达数据来确定的，
其中，所述表达水平是基因转录物水平并且所述签名基因的基因表达水平标准化为持家基因的表达，
其中，如果所述前列腺癌进展指数低于选定的阈值，则所述对象被分类为具有良好预后，或者如果所述前列腺癌进展指数高于所述选定的阈值，则所述对象被分类为具有不良预后；和/或
其中，如果所述前列腺癌进展指数高于选定的阈值，则所述对象被分类为具有易遭受疾病进展影响的前列腺癌的倾向，或者如果所述前列腺癌进展指数低于所述选定的阈值，则所述对象被分类为不具有易遭受疾病进展影响的前列腺癌的倾向。
2.根据权利要求1所述的装置，还包括用于确定或接收针对以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，以获得针对所述对象的对象表达谱的单元。
3.根据权利要求1所述的装置，其中，所述持家基因是TBP、HPRT1、ACTB、RPLP0、PUM1、POLR2A或B2M。
4.根据权利要求1或2所述的装置，还包括：
用于根据所确定的预后或所确定的倾向，针对侵袭性疾病与非侵袭性疾病的风险对所述对象进行分级的单元；和/或
用于根据所确定的预后或所确定的倾向，向有需要的所述对象提供适合的癌症处置的单元。
5.根据权利要求1或2所述的装置，其中，所述不良预后或者易遭受疾病进展影响的前列腺癌的所述倾向指示要利用选自包括以下项的组的处置中的任何一种或多种处置来处置所述对象的适用性：前列腺手术、前列腺移除、化学疗法、放射疗法、近距离放射疗法、有限或扩展的淋巴结清除、激素治疗。
6.一种用于建立针对被诊断有前列腺癌的患者的预后，用于将被诊断有前列腺癌的患者进行分级，或者用于确定在具有前列腺癌的患者中的侵袭性前列腺癌或惰性前列腺癌的倾向的产品，包括：
用于确定针对以下签名基因的基因表达水平的引物和/或探针：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体；
任选地还包括用于确定除了上文所提到的基因之外的在图1或图2中列出的一组基因的表达水平的引物和/或探针；和/或
任选地还包括用于确定持家基因的基因表达水平的引物和/或探针，
其中，所述表达水平是基因转录物水平。
7.根据权利要求6所述的产品，其中，所述持家基因是TBP、HPRT1、ACTB、RPLP0、PUM1、POLR2A或B2M。
8.根据权利要求6所述的产品，其中，所述产品是PCR试剂盒、RNA测序试剂盒、或者微阵列。
9.根据权利要求6所述的产品，其中，所述产品是微阵列试剂盒。
10.一种计算机可读介质，其存储计算机可读代码，所述计算机可读代码当在计算机上运行时被配置为：
-基于针对对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、以及生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；和/或
-基于针对所述对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加，
其中，所述对象表达谱被转换为前列腺癌进展指数，所述前列腺癌进展指数是根据以下等式来计算的：
PCPI＝(GEV_av_GOI_up)-(GEV_av_GOI_down)，
其中，GEV_av_GOI_up是上调基因的平均基因表达值，并且其中，GEV_av_GOI_down是下调基因的平均基因表达值，其中，所述值是基于每个对象样本的标准化基因表达数据来确定的，
其中，所述表达水平是基因转录物水平并且所述签名基因的基因表达水平标准化为持家基因的表达，
其中，如果所述前列腺癌进展指数低于选定的阈值，则所述对象被分类为具有良好预后，或者如果所述前列腺癌进展指数高于所述选定的阈值，则所述对象被分类为具有不良预后；和/或
其中，如果所述前列腺癌进展指数高于选定的阈值，则所述对象被分类为具有易遭受疾病进展影响的前列腺癌的倾向，或者如果所述前列腺癌进展指数低于所述选定的阈值，则所述对象被分类为不具有易遭受疾病进展影响的前列腺癌的倾向。
11.根据权利要求10所述的计算机可读介质，其中，所述计算机可读代码当在计算机上运行时被配置为：
确定针对以下签名基因的基因表达水平：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体，以获得针对所述对象的对象表达谱。
12.根据权利要求10所述的计算机可读介质，其中，所述持家基因是TBP、HPRT1、ACTB、RPLP0、PUM1、POLR2A或B2M。
13.根据权利要求10或11所述的计算机可读介质，所述计算机可读代码还被配置为：
根据所确定的预后或所确定的倾向，针对侵袭性疾病与非侵袭性疾病的风险对所述对象进行分级；和/或
根据所确定的预后或所确定的倾向，向有需要的所述对象提供适合的癌症处置。
14.根据权利要求10或11所述的计算机可读介质，其中，所述不良预后或者易遭受疾病进展影响的前列腺癌的所述倾向指示要利用选自包括以下项的组的处置中的任何一种或多种处置来处置所述对象的适用性：前列腺手术、前列腺移除、化学疗法、放射疗法、近距离放射疗法、有限或扩展的淋巴结清除、激素治疗。
15.一种包括根据权利要求10-14中的任一项所述的计算机可读介质以及包括以下项的产品的系统：
用于确定针对以下签名基因的基因表达水平的引物和/或探针：AZGP1、FBLN1、ILK、KRT15、MEIS2、MYBPC1、PAGE4、SRD5A2、COL1A1、COL3A1、COL5A2、INHBA、THBS2、VCAN、BGN、BIRC5和DYRK2、以及任选地包括PDE4D5和/或PDE4D7的PDE4异构体；
任选地还包括用于确定除了上文所提到的基因之外的在图1或图2中列出的一组基因的表达水平的引物和/或探针；和/或
任选地还包括用于确定持家基因的基因表达水平的引物和/或探针，
其中所述表达水平是基因转录物水平。
16.根据权利要求15所述的系统，其中，所述产品是PCR试剂盒、RNA测序试剂盒，或者微阵列。
17.根据权利要求15所述的系统，其中，所述产品是微阵列试剂盒。
18.根据权利要求15所述的系统，其中，所述持家基因是TBP、HPRT1、ACTB、RPLP0、PUM1、POLR2A或B2M。
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