CN107119055A - 分子标志物bub1b基因及其应用 - Google Patents

分子标志物bub1b基因及其应用 Download PDF

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CN107119055A
CN107119055A CN201710351995.XA CN201710351995A CN107119055A CN 107119055 A CN107119055 A CN 107119055A CN 201710351995 A CN201710351995 A CN 201710351995A CN 107119055 A CN107119055 A CN 107119055A
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杨烨
顾春艳
陆思丞
陈瑞妮
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Abstract

分子标志物BUB1B基因及其应用，是一种用于多发性骨髓瘤诊断的分子标志物，具体涉及骨髓瘤细胞中的分子标志物BUB1B基因在制备诊断多发性骨髓瘤的产品中的应用。本发明首次发现了BUB1B基因表达与多发性骨髓瘤的相关性。即可以通过检测受试者中BUB1B的表达情况，来判断受试者是否患有多发性骨髓瘤或者判断受试者是否存在患有多发性骨髓瘤的风险，为临床医师提供诊断的依据和个性化预防方案或治疗方案。本发明发现了一种新的生物标记物‑BUB1B基因，相比传统的检测手段，基因诊断具有特异性好、灵敏度高、针对性强、诊断快速等优点，能够实现多发性骨髓瘤的早期诊断，降低多发性骨髓瘤的死亡率。

Description

分子标志物BUB1B基因及其应用
技术领域
本发明属于分子诊断领域，涉及一种用于多发性骨髓瘤诊断的分子标志物，具体涉及骨髓瘤细胞中的分子标志物BUB1B基因在制备诊断多发性骨髓瘤的产品中的应用。
背景技术
多发性骨髓瘤(Multiple Myeloma,MM)是一种浆细胞异常增生的血液系统恶性肿瘤，约占所有血液系统恶性肿瘤的10％，随着我国人口的老龄化，MM的发病率都在上升。多发性骨髓瘤常伴有多发性溶骨性损害、高钙血症、贫血、肾脏损害等。由于正常免疫球蛋白的生成受抑制，因此容易出现各种细菌性感染。
目前多发性骨髓瘤的诊断主要依靠骨髓克隆性浆细胞比例和(或)活组织病理学检查作为MM诊断基础。2014年，国际骨髓瘤工作组(IMWG)对MM诊断标注进行了修订，定义骨髓克隆性浆细胞比例≥10％和/或活组织病理学检查证实为浆细胞瘤；同时伴有以下一种或多种情况：高钙血症、肾功能不全、贫血和溶骨性骨损害；将骨髓克隆性浆细胞比例≥60％、受累血清游离轻链与未受累血清游离轻链比值≥100、MRI检查发现局灶性病变部位>1处(每处检查的病灶直径≥5mm)作为极高危无症状MM生物学标志物纳入MM诊断标准。此外，MRI、低剂量全身CT、FDG/PET及PET/CT等现代影像学技术被纳入检查辅助方法。
到目前为止，很多生物标志物都不能很好的用来作为临床诊断标志。目前临床常用的诊断标志物是单克隆免疫球蛋白(M蛋白)，在MM患者血清中M蛋白所属免疫球蛋白显著增高而非M蛋白所属免疫球蛋白含量显著下降。但修订后的MM诊断标准强调单克隆蛋白水平并不是诊断活动性MM所必需。
综上，目前多发性骨髓瘤诊断的方法复杂、检查项目多，缺少一种可靠、方便的临床诊断方法。新的研究表明，在多发性骨髓瘤患者中，检出BUB1B基因的表达显著增高，BUB1B基因的表达水平与骨髓瘤细胞的生长或抑制有直接关系。表明BUB1B是一种高危的骨髓瘤基因，可为多发性骨髓瘤的临床诊断提供可靠的判断。
BUB1B是有丝分裂检验点蛋白之一，本课题组证实在多发性骨髓瘤患者中的表达异常增高。其在MM中的异常表达通过影响染色体的不稳定性以及有丝分裂的过程等促进肿瘤的发展、转移及预后。因此，BUB1B的表达水平为肿瘤诊断、评估、预后等提供一个重要指标。
发明内容
解决的技术问题：本发明提供了一种分子标志物BUB1B基因的应用,可用于多发性骨髓瘤的诊断。相比于目前的诊断方法，大大减少了检查项目，降低成本；配合辅助诊断方法，准确率高；具有及时性，特异性，灵敏性。
技术方案：骨髓瘤细胞中的分子标志物BUB1B基因，序列如SEQ ID NO.1所示。
骨髓瘤细胞中的分子标志物BUB1B蛋白，序列如SEQ ID NO.2所示。
骨髓瘤细胞中的分子标志物BUB1B基因在制备诊断多发性骨髓瘤的产品中的应用。
上述产品包括：通过RT-PCR、实时定量PCR、免疫检测、原位杂交、芯片或高通量测序平台检测BUB1B基因表达水平以诊断多发性骨髓瘤的产品。
上述用RT-PCR诊断多发性骨髓瘤的产品至少包括一对特异扩增BUB1B基因的引物；所述用实时定量PCR诊断多发性骨髓瘤的产品至少包括一对特异扩增BUB1B基因的引物；所述用免疫检测诊断多发性骨髓瘤的产品包括：与BUB1B蛋白特异性结合的抗体；所述用原位杂交诊断多发性骨髓瘤的产品包括：与BUB1B基因的核酸序列杂交的探针；所述用芯片诊断多发性骨髓瘤的产品包括：蛋白芯片和基因芯片，其中蛋白芯片包括与BUB1B蛋白特异性结合的抗体，基因芯片包括与BUB1B基因的核酸序列杂交的探针。
上述用实时定量PCR诊断多发性骨髓瘤的产品至少包括一对特异扩增BUB1B基因的引物，序列如：SEQ ID NO.3和SEQ ID NO.4所示。
一种用于诊断多发性骨髓瘤的工具，该工具能够检测样本中BUB1B基因的表达。
上述工具包括芯片、试剂盒、试纸或高通量测序平台。
上述芯片包括基因芯片或蛋白质芯片，所述基因芯片包括固相载体以及固定在固相载体的寡核苷酸探针，所述寡核苷酸探针包括用于检测BUB1B基因转录水平的针对BUB1B基因的寡核苷酸探针；所述蛋白质芯片包括固相载体以及固定在固相载体的BUB1B蛋白的特异性抗体；所述试剂盒包括基因检测试剂盒和蛋白免疫检测试剂盒；所述基因检测试剂盒包括用于检测BUB1B基因转录水平的试剂；所述蛋白免疫检测试剂盒包括BUB1B蛋白的特异性抗体；所述试纸包括用于检测BUB1B基因转录水平的试纸；所述高通量测序平台包括用于检测BUB1B基因转录水平的试剂。
上述检测BUB1B基因转录水平的试剂包括针对BUB1B基因的引物和/或探针。
有益效果：本发明首次发现了BUB1B基因表达与多发性骨髓瘤相关。通过受试者中BUB1B的表达，来判断受试者是否患有多发性骨髓瘤或者判断受试者是否存在患有多发性骨髓瘤的风险，为临床医师提供诊断的依据和个性化预防方案或治疗方案。本发明发现了一种新的生物标记物-BUB1B基因，相比传统的检测手段，基因诊断具有特异性好、灵敏度高、针对性强、诊断快速等优点，能够实现多发性骨髓瘤的早期诊断，降低多发性骨髓瘤的死亡率。
附图说明
图1显示利用基因芯片检测BUB1B基因在多发性骨髓瘤患者和正常人中的表达差异图。分析22例正常骨髓，44例意义未明的单克隆丙种球蛋白疾病(monoclonalgammopathy of undetermined significance，MGUS，MM前体疾病)，351例MM初诊样本，发现BUB1B基因的表达水平在MM患者中要明显高于正常以及MGUS样本。
图2显示利用QPCR检测BUB1B基因在多发性骨髓瘤患者和正常人中的表达差异图。
图3显示利用免疫组化染色分析BUB1B在多发性骨髓瘤患者中的表达水平图，与正常浆细胞相比，BUB1B在MM样本中显著增高。
具体实施方式
下面结合附图和实施例对本发明作进一步详细的说明。以下实施例仅用于说明本发明而不用于限制本发明的范围。实施例中未注明具体条件的试验方法，通常按照常规条件，例如Sambrook等人，分子克隆：实验室手册(New York：Cold Spring HarborLaboratory Press，1989)中所述的条件，或按照制造厂商所建议的条件。
本发明提供了检测BUB1B基因表达的产品在制备诊断多发性骨髓瘤的工具中的应用。
进一步，上面所提到的检测BUB1B基因表达的产品包括：通过RT-PCR，实时定量PCR、免疫检测、原位杂交、芯片或高通量测序平台等检测BUB1B基因表达水平以诊断多发性骨髓瘤的产品。
进一步，所述用RT-PCR诊断多发性骨髓瘤的产品至少包括一对特异扩增BUB1B基因的引物；所述用实时定量PCR诊断多发性骨髓瘤的产品至少包括一对特异扩增BUB1B基因的引物；所述用免疫检测诊断多发性骨髓瘤的产品包括：与BUB1B蛋白特异性结合的抗体；所述用原位杂交诊断多发性骨髓瘤的产品包括：与BUB1B基因的核酸序列杂交的探针；所述用芯片诊断多发性骨髓瘤的产品包括：蛋白芯片和基因芯片；其中，蛋白芯片包括与BUB1B蛋白特异性结合的抗体，基因芯片包括与BUB1B基因的核酸序列杂交的探针。
在本发明的具体实施方案中，所述用实时定量PCR诊断多发性骨髓瘤的产品至少包括一对特异扩增BUB1B基因的引物的序列如：SEQ ID NO.3和SEQ ID NO.4所示。
优选地，所述诊断工具包括芯片、试剂盒、试纸或高通量测序平台。其中，高通量测序平台是一种特殊的诊断工具，检测BUB1B基因表达的产品可以应用于该平台实现对BUB1B基因的表达情况的检测。随着高通量测序技术的发展，对一个人的基因表达谱的构建将成为十分便捷的工作。通过对比疾病患者和正常人群的基因表达谱，容易分析出哪个基因的异常与疾病相关。因此，在高通量测序中获知BUB1B基因的异常与多发性骨髓瘤相关也属于BUB1B基因的用途，同样在本发明的保护范围之内。
本发明还提供了一种多发性骨髓瘤的工具，所述产品包括芯片、试剂盒、试纸、或高通量测序平台。
其中，所述芯片包括基因芯片、蛋白质芯片；所述基因芯片包括固相载体以及固定在固相载体的寡核苷酸探针，所述寡核苷酸探针包括用于检测BUB1B基因转录水平的针对BUB1B基因的寡核苷酸探针；所述蛋白质芯片包括固相载体以及固定在固相载体的BUB1B蛋白的特异性抗体；所述基因芯片可用于检测包括BUB1B基因在内的多个基因(例如，与多发性骨髓瘤相关的多个基因)的表达水平。所述蛋白质芯片可用于检测包括BUB1B蛋白在内的多个蛋白质(例如与多发性骨髓瘤相关的多个蛋白质)的表达水平。通过将多个与多发性骨髓瘤相关的标志物同时检测，可大大提高多发性骨髓瘤诊断的准确率。
其中，所述试剂盒包括基因检测试剂盒和蛋白免疫检测试剂盒；所述基因检测试剂盒包括用于检测BUB1B基因转录水平的试剂；所述蛋白免疫检测试剂盒包括BUB1B蛋白的特异性抗体。进一步，所述试剂包括使用RT-PCR、实时定量PCR、免疫检测、原位杂交或芯片方法检测BUB1B基因表达水平过程中所需的试剂。优选地，所述试剂包括针对BUB1B基因的引物和/或探针。根据基因的核苷酸序列信息容易设计出可以用于检测BUB1B基因表达水平的引物和探针。
所述高通量测序平台包括检测BUB1B基因表达水平的试剂。
所述试纸包括试纸载体和固定在试纸载体上的寡核苷酸，所述寡核苷酸能够检测BUB1B基因的转录水平。
与BUB1B基因的核酸序列杂交的探针可以是DNA、RNA、DNA-RNA嵌合体、PNA或其他衍生物。所述探针的长度没有限制，只要完成特异性杂交、与目的核苷酸序列特异性结合，任何长度都可以。所述探针的长度可短至25、20、15、13或10个碱基长度。同样，所述探针的长度可长至60、80、100、150、300个碱基对或更长，甚至整个基因。由于不同的探针长度对杂交效率、信号特异性有不同的影响，所述探针的长度通常至少是14个碱基对，最长一般不超过30个碱基对，与目的核苷酸序列互补的长度以15-25个碱基对最佳。所述探针自身互补序列最好少于4碱基对，以免影响杂交效率。
进一步，所述BUB1B蛋白的特异性抗体包括单克隆抗体、多克隆抗体。所述BUB1B蛋白的特异性抗体包括完整的抗体分子、抗体的任何片段或修饰(例如：嵌合抗体，scFv、Fab、F(ab’)2、Fv等)。只要所述片段能够保留与BUB1B蛋白的结合能力即可。用于蛋白质水平的抗体的制备时本领域技术人员公知的，并且本发明可以使用任何方法来制备所述抗体。
本发明的具体实施方案中，所述针对BUB1B基因的引物序列如下：正向引物序列如SEQ ID NO.3所示，反向引物序列如SEQ ID NO.4所示。
用于诊断多发性骨髓瘤的BUB1B基因及其表达产物的来源包括但不限于骨髓、血液、组织液、尿液、唾液等可以获得基因组DNA的体液。在本发明的具体实施方案中，用于诊断多发性骨髓瘤的BUB1B基因及其表达产物的来源是骨髓。
本发明的上下文中，“BUB1B基因”包括BUB1B基因以及BUB1B基因的任何功能等同物的多核苷酸。BUB1B基因包括与目前国际公共核酸序列GeneBank中BUB1B基因(NC_000015.10)DNA序列具有70％以上同源性，且编码相同功能蛋白质的DNA序列；
优选地，BUB1B基因的编码序列包括以下任意一种：
(1)序列表中SEQ ID NO.1所示的DNA序列；
(2)在严格条件下与1)限定的DNA序列杂交且编码相同蛋白质的DNA序列；
(3)与(1)或(2)限定的DNA序列具有70％、优选地，90％以上同源性，且编码相同功能蛋白质的DNA分子。
在本发明的具体实施方案中，所述BUB1B基因的编码序列是SEQ ID NO.1所示的DNA序列。
在本发明的上下文中，BUB1B基因表达产物包括BUB1B蛋白以及BUB1B蛋白的部分肽。所述BUB1B蛋白的部分肽含有与多发性骨髓瘤相关的功能域。
“BUB1B蛋白”包括BUB1B蛋白以及BUB1B蛋白的任何功能等同物。所述功能等同物包括BUB1B蛋白保守性变异蛋白质、或其活性片段，或其活性衍生物，等位变异体、天然突变体、诱导突变体、在高或低的严谨条件下能与BUB1B的DNA杂交的DNA所编码的蛋白质。
优选地，BUB1B蛋白是具有下列氨基酸序列的蛋白质：
(1)由序列表中SEQ ID NO.2所示的氨基酸序列组成的蛋白质；
(2)将SEQ ID NO.2所示的氨基酸序列经过一个或几个氨基酸残基的取代和/或缺失和/或添加且与SEQ ID NO.2所示的氨基酸序列具有相同功能的由SEQ ID NO.2所示的氨基酸序列衍生物的蛋白质。取代、缺失或者添加的氨基酸的个数通常为1-50个，较佳地1-20个，最佳地1-10个。
(3)与SEQ ID NO.2所示的氨基酸序列至少具有80％同源性(又称为序列统一性)，更优选地，与SEQ ID NO.2所示的氨基酸序列至少约90％至95％的同源性，常为96％、97％、98％、99％同源性的氨基酸序列构成的多肽。
在本发明的具体实施方案中，所述BUB1B蛋白是具有SEQ ID NO.2所示的氨基酸序列的蛋白质。
通常，已知的是，一个蛋白质中一个或多个氨基酸的修饰不会影响蛋白质的功能。本领域技术人员会认可改变单个氨基酸或小百分比的氨基酸或对氨基酸序列的个别添加、缺失、插入、替换是保守修饰，其中蛋白质的改变产生具有相似功能的蛋白质。提供功能相似的氨基酸的保守替换表是本领域公知的。
通过添加一个氨基酸或多个氨基酸残基修饰的蛋白质的例子是BUB1B蛋白的融合蛋白。对于与BUB1B蛋白融合的肽或者蛋白质没有限制，只要所得的融合蛋白保留BUB1B蛋白的生物活性即可。
本发明的BUB1B蛋白也包括对SEQ ID NO.2所示的氨基酸序列的非保守修饰，只要经过修饰的蛋白质仍然能够保留BUB1B蛋白的生物学活性即可。在此类修饰蛋白质中突变的氨基酸数目通常是10个或者更少，例如6个或者更少，例如3个或者更少。
在本发明的上下文中，“多发性骨髓瘤”既包括判断受试者是否已经患有多发性骨髓瘤、也包括受试者是否存在患有多发性骨髓瘤的风险。
实施例1筛选多发性骨髓瘤患者和正常人中差异表达的基因
1、研究对象：
收集多发性骨髓瘤患者8例，正常人8例
多发性骨髓瘤患者的纳入标准：所有多发性骨髓瘤的诊断根据WHO诊断多发性骨髓瘤标准，所有初治多发性骨髓瘤患者骨髓单个核细胞标本获得病人的知情同意。
多发性骨髓瘤患者的排除标准：转移癌，反应性浆细胞增多症和未定性的单克隆免疫球蛋白病。
2、骨髓中总RNA的提取
(1)骨髓单个核细胞的分离：向收集到的骨髓标本中加入3倍体积的红细胞裂解液，用滴管反复吹打混匀后于冰上放置10～15min，使骨髓标本中的红细胞充分裂解；1200rpm/min离心5min，弃上清，PBS洗涤细胞1次。弃上清，加入1mL PBS吹打混匀后转移至1.5mL EP管中，1200rpm/min离心5min，弃上清。每个样本加1mL Trizol，吹打混匀。
(2)每1mL Trizol加入氯仿200μL，充分混匀剧烈震荡15秒，室温静置10min等待分层。
(3)于4℃12000rpm/min离心15min。离心后可见管中混合物液面分为3层，最上层为无色水相，含有RNA；中间层为白色絮状，含有蛋白层与DNA；最下层为红色的酚-氯仿有机相。
取上层水相约400μL至另一EP管中，注意避免吸入中间的蛋白层，每管加入等体积异丙醇，轻轻上下颠倒混匀，室温静置10min，于4℃12000rpm/min离心10min，可见管底白色沉淀。
弃上清，加入-20℃预冷的75％DEPC酒精1mL，悬起沉淀，4℃7500rpm/min离心5min。
弃上清，室温放置10-20min风干沉淀，依据沉淀量的多少酌情加入DEPC水溶解沉淀。-80℃冰箱保存。
3、RNA样品的质量分析
紫外分光光度计检测RNA样品，OD260/OD280为1.8-2.0。
4、基因芯片杂交及扫描
采用Affymetrix U133Plus 2.0microarrays检测RNA水平。多发性骨髓瘤患者组的数据可在NIH基因表达综合(GEO)下GSE2658检索号查得，正常组和未定性的单克隆免疫球蛋白病的基因芯片数据在GSE5900下。
5、芯片数据处理与分析
基因芯片的数据分析基于GCO1.1软件(Affymetrix)，包含对与疾病相关相关的生存的单变量的对数等级检测。对于两组比值的自然对数绝对值大于2.0或小于0.5的基因作为差异表达基因。
6、统计学处理
采用SPSS 13.0统计软件进行数据分析，组间差异比较采用单因素方差分析法，P＜0.05有显著意义。
7、结果
如图1所示，分析22例正常骨髓，44例意义未明的单克隆丙种球蛋白疾病(monoclonal gammopathy of undetermined significance，MGUS，MM前体疾病)，351例MM初诊病人浆细胞基因芯片数据库，发现BUB1B基因的表达水平在MM患者中要明显高于正常以及MGUS样本)，与正常人相比，多发性骨髓瘤患者BUB1B基因的MRNA水平显著升高，差异具有统计学意义(P＜0.05)。
实施例2QPCR实验验证多发性骨髓瘤患者和正常人中差异表达的基因
1、研究对象
筛选标准同实施例1，多发性骨髓瘤患者46例，正常人66例。
2、骨髓中总RNA的提取
步骤同实施例1。
3、逆转录
根据TAKARA逆转录试剂盒进行RNA逆转录。采用10μL反应体系，分别加入5×PrimeScript RT Master Mix 2μL，总RNA 0.5μg，加一定量RNase Free Water至10μL。37℃反应15min，85℃反应5s。产物cDNA置-20℃冰箱保存。
4、QPCR
采用10μL反应体系，每个样本设置3个复孔，加样过程避光。配制以下反应体系：2×SYBGREEN Master Mix 5μL，正向引物0.5μL，反向引物(5pm)0.5μL，反向引物(5pm)0.5μL，模板cDNA 1μL，ddH2O 3μL。扩增FOXM1基因的正向引物序列为5’-GCACCGACAATTCCAAGCTC-3’(SEQ ID NO.3)，反向引物序列为5’-TGTGCTTCGTTGTGGTACAGA-3’(SEQ ID NO.4)；扩增GAPDH基因的正向引物序列为5’-GCACCGTCAAGGCTGAGAAC-3’(SEQID NO.5)，反向引物序列为5’-TGGTGAAGACGCCAGTGGA-3’(SEQ ID NO.6)，各项操作均于冰上进行。扩增程序为：95℃1min，95℃15s，60℃15s，72℃30s；共40个循环。以SYBR Green作为荧光标记物，在Light Cycler荧光实时定量PCR仪上进行反应，通过融解曲线分析和电泳确定目的条带，△△CT法进行相对定量。
5、统计学方法
结果数据都是以平均值±标准差的方式来表示，采用SPSS13.0统计软件来进行统计分析，两者之间差异采用t检验，认为当P＜0.05时具有统计学意义。
6、结果
结果如图2所示，与正常人相比，多发性骨髓瘤患者的BUB1B基因的mRNA水平显著增高，差异具有统计学意义(P＜0.05)，结果同基因芯片实验。
上述实施例为本发明较佳的实施方式，但本发明的实施方式并不受上述实施例的限制，其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化，均应为等效的置换方式，都包含在本发明的保护范围之内。
SEQUENCE LISTING
<110> 南京中医药大学
<120> 分子标志物BUB1B基因的应用
<130>
<160> 6
<170> PatentIn version 3.3
<210> 1
<211> 60128
<212> DNA
<213> 人源
<400> 1
aggggcgtgg ccacgtcgac cgcgcgggac cgttaaattt gaaacttggc ggctaggggt 60
gtgggcttga ggtggccggt ttgttaggga gtcgtgtacg tgccttggtc gcttctgtag 120
ctccgagggc aggttgcgga agaaagccca ggcggtctgt ggcccagagg aaaggcctgc 180
agcaggacga ggacctgagc caggaatgca ggatggcggc ggtgaagaag gaagggggtg 240
ctctgaggta ggtacgggag aaagctgctg ggggctgggc ctgagaggac acggcctggt 300
aggtaataga aggctccgct cggagcagtc gagggggaga tcggcaccgt cagaacagac 360
cccaccggag cctccttcct tttggagtag aatgccggag gtggaggtga aaacgcagtg 420
gactgagggc acgtgcgaat cctgccgcat ccagcttcaa agcgaagaag gctgcgggac 480
cccagcggaa caaagagttt ggaagttgca atgttgtctg tttgtaactc agctcagcca 540
cctgctagtt gtttgacctt gggcaaatcg tttgtatgga aaatgctgat gttaatgctg 600
ccttacgtgg ttctggggga attcaaagta tttgttaagt aactgcttcc aaataagcgc 660
tcaacaaatg gcaggtgcta tgccaatagc acagagatct gaaagccttt agccaatatc 720
atagagatct aaattatgcc aataacatag agatctaaaa gcctttttct gcatgtttgc 780
ggcttttcct tgtattaaaa aaactatatt gcagttctag gttggaaatc tgtatgtgtt 840
ttcactgtgg tgcccgcaat acctagataa gtgctatgtc atgggctctt tcattcatgt 900
aacaagtatt tttttggcta agctctgagt gcagcaaata tacagacaca aaaatctcaa 960
ccctcatgaa gcttaagttc tggcatggga tgaaggtggg ggagtcagac aataaagaca 1020
aactgttagg tggagatgtg gtcagtacta aaaaaaataa taaagcaact gggtgtagtg 1080
aatattgggg gtggggattg gtgcaattta acttgaacac tggagtctca ctgaggagat 1140
gtcactttgg tcaagacttg aaggaatctc aaaagctaga ggttctatat ctgaggagag 1200
tacaaaggct gagggtgaga gctaggggag gaagttgcac ctggcatgtc caaggccatt 1260
gtcactggag cagaattaac tagaagagta aaaggatatt atgtaaaaat ggtgaagatg 1320
cagattgtaa ggacttagct tttactctag ttgtaatcaa aagtcattgg aaggttttga 1380
gcaaaggaaa gacataatct gacttgggtt taaatggggt cactttggct gtagtgttga 1440
atacactaaa ggcagcaaag gatggaagca agggacacca gttaagaggt tattgaaata 1500
attcagctca aaagtgagtt gagccaggtg gaaaacagtg gagatgatga taagtggttg 1560
atttctgtat atattttgaa ggtagaacca gtaggacttg ctgactgact gaggggtatg 1620
agaagggcat caaagttggc actaagattt ttggcttggg taactgaaga atgggattgc 1680
catttatttg agaaagagga agactgtggg aggagcaggt ctgggaggaa gtgggggcag 1740
tcttagctca atttgggata tttaactgag atagtgtaat tcactatttt taagagcaag 1800
agaagaaagt tcagatgaat tcaacaaaca gggcataata gtgttatatc tcgtattaga 1860
tcatgggcat acaaaaataa atggcatagc ccttaccttt acagagttca cacaatatag 1920
agcaggtcct ggtataacat cgtttcgtta taatgttgat gagaaaaaaa atcaattcat 1980
tgcggggctg ctgtgtatgt ggagttttca tgttttccgc atgtctgcat gggtttcctt 2040
aggtactcca gtttccttct acatcccaaa gatgtgcctg ttaattggcg tgtctaaatg 2100
atcccagtct gaatgggtgt gaatgtgatg ctccctgtga tggagtggtg tcctgtccag 2160
ggttggttcc tctctgagtt gctgagatgg gctctggcca ccctcaaccc cgaactagaa 2220
taagtgagtt ggaaaatgaa tgaaggaatg aatacaaatt actgtaaaat aaaaatctgt 2280
aaaggctggg agcggtggct cacacctgta atcccagcac ttcgggaggc tgaggcaaca 2340
ggattgctta agctcagcgg ttcaagacca gcctgggcaa catagtaagg cctgtctcta 2400
tttaaaaagt ttatataaag tgtgtatgat aatcatataa atgcatgaca ataaacaatg 2460
ccttatgaaa gtgcccagca tgcccactat agtgttacta tttgtttttt gaactttgtg 2520
gtggtaggag gtacttcttg aaattttcac tctcaaacat ttattccttg agttaaccca 2580
ccaacactat gactgcagtc attcactgat tcgccaaaaa ttgggtaaat gattattttt 2640
tgttttcatt aaatgttctt aagtgtacgg atagctcaca tttatttcaa tatttagtat 2700
taaaaatgtt tgtttcgagt ctttattcag aagtttggtg acgtttttgt gaccagaaat 2760
atgccatagg aacttaactt ttgtttatgt cgatcagcct gtggtaaaat tggttttgtt 2820
acatgtcatt ttgattaaag tcatagtttc caagaagctg tctccaacga gttttcagtg 2880
ctcatctaga ctgaagtcac atataacttt cactctattt caaagattag tgccaatgtg 2940
tctctctttt tgttttaagt ccagaggtaa tgtctcttag aaatagtctt ctatctaacc 3000
attgcagggc tctgaattgc agaatacgta atgggaatta cctccaaaac gtttcggggg 3060
ttttctcagt aggcttgcta gaattgggtg tgaggatgca gggaattgtg actagtaaac 3120
tgtgtttgtt tgcttctgct tttagctact tatatgtaca aacttcagtt ttgaatcatc 3180
attgaaacat gggacattag tctcacccac actttgctaa ttttaatgtt ttttttttga 3240
gacagggtct tgctctgttg cccaggctgc agtgcagtgg tgtgatcatg gctcactgca 3300
gcttcgaccc ctgaacccaa gcaatgctcc cacctcagtc ttctaagtag ccacgaccat 3360
gggcgtgtac caccacgcct ggctaatttt tcactttttg tagagatggg ggtcttccta 3420
tgttgcccag ggtggtgttg aactcctggg ctcaagcact tctcctgact cagcctccca 3480
aagtggtagg attacaggca tgagctacca catccggcac taattttaaa ttaaactaga 3540
tgatgcattc aatggtaggc atagaattac ttgttgcctt tttgtctact ttgccaaatt 3600
tataacactt ttgttccctt cttttctttc tgccttaagc cctattcatt tttctttttt 3660
tttttttttt taaagaaaga ggcagggtct tgctatgttg cccaggctgg tatcaaactc 3720
ctggctcaag aaatcctccc acttcggcct cacaaagtgg tgggattaca ggtgtgagcc 3780
accgcacata gccatgccct attcttatag tactgtctac gatatccttg ccaagttgtc 3840
ttctatcagg caatactgta gccataaact tgaaaaacag ctaacaaaga agcttaggca 3900
tataataata ataataatta tgtgtcagtc cactatattc aacccaagac catgaataat 3960
cacctttcgg aagacattta caataatcta gtgctataat agtcaatgtt ggtatgagat 4020
ttacatttgt ttccttcttc acagtgaagc catgtccctg gagggagatg aatgggaact 4080
gagtaaagaa aatgtacaac ctttaaggca agggcggatc atgtccacgc ttcagggagc 4140
actggcacaa gaatctgcct gtaacaatac tcttcagcag cagaaacggt gtgtagaatg 4200
gctgagtctc aacctgtcgt cattcatcct aaatgttgta gataacgtgg gtgtggatcc 4260
atgagagatg gcataatgag tacttttcaa aaattggtag tatgagaatc tgttctctac 4320
ctgctttcgt atcacatgac agctatctga agatgtcctc aggtataatt aagaacaagg 4380
gctataggat ttcatttcac tgtggtgcag cgaaactctt tttatcaata gaaatacatt 4440
ttatacaggg ggcagtgata agcatagtaa agcaagtatt atattgcaat gcttcccaaa 4500
agtattatgt taggaactta tttttgagag tatgacaaaa aaagaagtgg tctccaaaga 4560
catgtaaacc tcagaacaat tgaatttata ccagaaagtt ctcaataatt ttaacaaact 4620
ctggataaat aaaagctgaa aaatactctt atgttattca aatggacctg tggatctcct 4680
ttaactaata catgttttga taaatatgct ttttaaaaaa aaaggtaaat cagagtatca 4740
gtttctacct tcaatctctg acaaaaagaa atactgccat tactggcaaa atatcataat 4800
ttgggattat aatgcaatga ctattcttat tcatctcttt ggattttttt ttttttttta 4860
atatgacagg gtctccctct atcacccagg ttggagtaca gtggcctgat ttcagctcac 4920
tgcaacctct gcctcccggt tttaagtgat tctcccacct cagcctccca aatagctggg 4980
attacaggcg tgcgccgcca cgcctgggta atttttgtat ttttagtaga gatgggtcct 5040
tgccatgttg gctgtgctgg tcttgaactc ctgagctcaa gtgatccgcc caccttggca 5100
tcccaaagtg ctgggattac aggcgtaagc taccgcactc agcctcattc atcatatttt 5160
ttcatgttac atgcatcagt agattgctct ttttattgct gaataggatt tcatttattt 5220
attcaccaat tgatgaatat ttagattctt ccagttttgt gctttataaa taatgttgct 5280
atggacattc ttgaacaagg ctttttgtag acataatttt ctctctctct cttttttttt 5340
tttcttttag agacggagtc tcgctctttc ggccaggctg gagtgcagtg gcacgatctt 5400
ggctcactgg aagctctgcc tcctgggttc acgccaatct cctgcctcag cctcctgagt 5460
agctgggact acaggtgcct gccaccacgc ccagctaatt ttttctattt tttagtagag 5520
acggggtttc accgtgttag ccaggatggt ctcgatctcc tgaccttgtg atccacccgc 5580
ctcagcctcc caaagtgctg ggattacagg cgtgagccac cgcgcccagc agtagacata 5640
attttcattt cccttggagt ggaattgttg gaccatagaa tagatgtatg tttaactgtt 5700
gaagaaactg gtttaccaag gaggttgtga cattttacat ttctaccagc aactcatgag 5760
agttcatttg taccaaatcc actccagtat ttggtgttgt cgatcttttt cgttttagcc 5820
attctagttt tgtggagttg tgtctcatta ctttgcattt ccctggtgac taataatggt 5880
gaacgttttt tcacatgctt tttggccttt tgtatatctt cttttgtggt gtatctgttt 5940
agatattttg cccagttttc aaattgtgtt gtaggggttc tttatttact tttcccagga 6000
gtatagattc aagtttccct gattcaagtt tcaggagcat agattcaaga ttccctgaat 6060
ctatgctcct cagtaggggt tctttataaa gtctctatac tagtctttta tcaaatatat 6120
gtgttgcaaa ttttttttcc ctcacccatg gctgtttatt ttctgggtgt tttttttttt 6180
ttaaactgct tagttttaaa ttttgatgaa gttcaattaa ttagtatttt tcttttatgg 6240
ttagcatttt ttgtgtcctc ttcaggagac ttttgcctac cccaaagtga caaagttact 6300
ctcttatgtt ttcttttact agcttcattt tagctttttt tttttttttt tttttttttg 6360
agacggagtg ttgctcttgt tgcccaggct ggagcgcaat ctcagctcac tgcaacctcc 6420
gcctcccggg ttcaagtgat tctcctgcct cagcctcctg agtagctggg attacaggca 6480
cgcaccacca cgcctggcta attttttgta tttttagtag agatggggtt tccccatggc 6540
caggctggtc ttgaacttct gacctcaggt gatccgcccg cctcggcctc ccagagtgct 6600
gggattacgg gcatgagcca ctgcgtccag ccaagcatta ttttagcttt tatgtttagg 6660
tgtatgattt ttcttaaatt tttccttgta tatggtgtgg ggttggagta aacaagtttt 6720
tttcctctca tatgggttat ctttctagtt gttctgcctc atttgttaga tttttttttt 6780
tcctttcctc actgaattgc gttggggccc ttttcaaaaa tcatttgacc acatatgtgt 6840
gggttatttc tggactctat attctgttcc attgatcaaa ttgtctgtcc tttcaccaat 6900
aaaatacact gttttgatta gttttacata gcaagtccag cagagtgagt tctacagctt 6960
ttgttctttt caaaattgct ttagttattc ttggtccttt gcctttgcaa acaaagtttg 7020
aaatcatctt gtcaatttct agaaaagagc ctactgaaaa agaaaaaaaa aaaaaaaggc 7080
tgggcacggt ggctcaagcc tgtaatccca gcactttagg aggccgaggc aggcggatca 7140
cctgaggtga ggagtttaag accagcctga ccaacatgga gaaaccctgt ctcaactaaa 7200
aatacaaaat tagccgggcg tggtggcgca tgcctgtaat cccagctact cgggaggctg 7260
aggtaggaga atcacttgaa cctaggaggt ggaggttgca gtgagccgag attgtgccat 7320
tgcactctag cctgggtagc aacagcgaaa ttccgtctca aaaaaaaaag aaaaggaaaa 7380
agagaaaaga aaagagccta ctgggatttt gattacattg gtttgaatct atagatcaat 7440
tggtaggatt gctgattttt atcagtagtg ccttagattt tattgtttta ccatttctgc 7500
agataatctc attatttcac actttaattg ccatattagc ctcataactg tggtcccttc 7560
ttctaatgcc tggctatcct tataaagttg cttgattaat ctttctgaaa tcttatattt 7620
aagatgccct ccaattaaag aaccaatagt ggctggagta gatggaatcc aaagtcttta 7680
aatttacatt taaagcatgt gcttcttact tctccagggg tctccatttg ctctcggtac 7740
tgactttatg ttatagctta gggttcactc accttccttt ggatgagctc ttccaccttc 7800
gtaattttat tcaatattag tttccctctg tcttgaaaaa actgtttttc tttcaaattc 7860
catggttctt tcagagtctc accttctgag gctgcttctg tgatacctcc ttttgactta 7920
aagcctttac tatccattct tggcaactgt aatttagtat cctgctttgt attactagtt 7980
catttttcat ttgtgtactt tgtttttctt attagagtat aaattcccat gtgtcaggga 8040
ctaattattt ttagatcaaa cataactgct tatccaattt ttattaatca ttatccaaat 8100
tctggcttat tacctaattc ttcccctcta ttctaactgg tcagtcttaa tttggtctta 8160
gccctctgcc tttcccagct ttttatagtc atattttacc ctttttttga ggtattctcc 8220
aaattattta tagtattatt cttctctgac caatgttacc catggaagtt ttttttgaac 8280
tttaaaattc ttatttatat atttgttcat gtgtgtaaac cctttacatt taagactagt 8340
caacctaata agaaagtact attattatcc ccattttaca aatgaggaaa ctgaaaacag 8400
agttttaagt agcttgtccg tgttactcag cttgtgattg gtggagctga atttgaatct 8460
aggttgtctt gttccagagt tcttaactgc tgtgtagtat taatactact tttctgtatg 8520
ttgtcttgaa atttgtttct ctaatttcta tatattttct ctctcttctt atgttaagta 8580
gaatcttaat tatttctatt cttttttttt tttttttttt tttgagacag agtcttgctt 8640
tgttgcccag gctggagtgc agtgctgcaa tctctgctca ctgcagcctc tacttccagg 8700
ttcaagtgct cttcccacct cagcctcccg agtagctggg attacaggtg cttggcacca 8760
cacccagcta atttttgtgt ttttagtaga gatgaggttt caccatgttg cccaggctgg 8820
tctcaaactt ctaacctcaa gtgatccacc ccacttggcc tcccaaagtg tcgggattac 8880
aggcatcagc caccatgcct ggcctttttc tattctataa caaacccata aactctagtg 8940
caataattta gatcaatatt acctacttat tacatgaata aaaatggaag tgatacttgt 9000
tcattggctg ttgtcactat tgcatatgct aactttttct gtttacattt cagggcattt 9060
gaatatgaaa ttcgatttta cactggaaat gaccctctgg atgtttggga taggtgggtc 9120
tttttatttc acaaggacaa tagaaacatt aacagataag tccttatggc catgtttctc 9180
aaattggggt atatggagtg tgtgtcagag tagacagtgg tgtcctgggg gcacagagat 9240
ccagaataat cataatatat cttcctgagg tgtttaagat tcaagaaatt tcaagtttat 9300
gatgtacaac tttgaactac acccttctat ccctatcctc agttttcccc agaagcatgt 9360
actagagata ctttggagaa gtttgaggga tacaggctta gggtatgtca ttgaggacct 9420
caaaagaaac atactttact tctgctaaaa tccagaatgg gtcttggagc aagaacaaaa 9480
gtacatgttc aatttaaaat gtgttcttat ctttttcctc ccatttaggt atatcagctg 9540
gacagagcag aactatcctc aaggtgggaa ggagagtaat atgtcaacgt tattagaaag 9600
agctgtagaa gcactacaag gagaaaaacg atattatagt gatcctcgat ttctcaatct 9660
ctggcttaaa ttagtaagtc tttctcaagt gccatctgag ttttaaatat taaactaaga 9720
gattttctct agaggtatct ggtataccaa aaaaaaagta aaacagccat tttgaaccat 9780
ttagtagatt ggaaacattt aataaatatg caatacttct taaattggtt ctacttaaag 9840
gtggacttaa atatagtata ataaggtatt ttcgcccttt taagattgat cgcaaagtct 9900
gtagatctct cagtgagtat ggattaataa tttattttat attttgaaac aaggtctcac 9960
tctgtcaccc aggctggagt gcagtggctc catcatggct cactgcagtc taaacctcct 10020
gggctcaagc aatcctctcg cctcagcctc gtgagtagct gggactacag gtgctgtgcc 10080
attacgtcca gctaattttt taatttttaa tagagatgac ttctctctct gttacccagg 10140
ctggtcttga actcctgagc tcaagccatc ctcccacctt ggcctcccaa agtgctggga 10200
ttataggcgt gagccaacac ccctagtccg gattacttat ttatttattc taaacataac 10260
tgggtgcagt gtttcatgtc tgtagtccca acactttgag aggctgaggt gggctgatcg 10320
cttcagccca ggagttcaag actagtcagg gcaaaattgg tgagacccca tctcataaag 10380
tacagaaatt aaccaggtgt ggtggcacag cacctgtagt cccagctact caggaggctg 10440
aggtgggagg gtcgcttgag cccgggacgt ccagactaca gtgagctgag attgcaccac 10500
tgtccgccag cccaagtgac agagcaagat cctgtctcaa aaaaacaacc aaaacagaaa 10560
aacataattg ggccattcaa ctgtactgga ggaggaggtg caggagctaa catttggcag 10620
cagtgtggtt gtttggggaa aaacttccct ctgtgattct ggtatccctt tcactccttt 10680
atgaaagtca tcaacacaaa gaagtgatat tttagttttt tattggtctt tggacttttt 10740
tcacctagta tattgctaca gccaaaaatg tctgcctcag ctgggcatgg tggctcatgc 10800
ctgtaatccc agcactactt tgtactgtct tacttgacat gtaggaaaaa catatttttt 10860
attaaaaaaa tgaccaccgt ttgttagaca ttaatattac tgcttttatt ctaaaataaa 10920
tttaaaaaaa taaacaataa atatttggaa ttatttacaa ccaccacaat atgatgaaat 10980
attgacatta aaactgataa gatttcttac taaaataaat ctcttggcat taaaactgat 11040
aagatttctt aataaaataa agtaagaaat aaatttctta ctaaaataaa gaaataaatt 11100
tcttactaaa ataaagtaat aaagtaagaa ataaatttct tactaaaagt aataaagtaa 11160
gaaataaatt tcttactaaa ataaagtaat aaagtaagaa ataaatttct tactaaaata 11220
aagtaataaa gtaagaaata aatttcttac taaagtctta aggaggactg attttaaact 11280
tccaatacag ttgacccttg aacaacacag ggcttaggtg tgcccacccc tcacccagtt 11340
gaaagtctgc atataacttt tggcccccaa aattattaat agcctactgt tgaccagacg 11400
ccttaccaat aacataaagt tgatgaacac atagtttgta tgccatatgt attatatctt 11460
tttttttaca acaatcttag ctagagaaaa gaaaatgtta ttaagaaaat tataaggaag 11520
agaatgtata tttaatagtc attaagtgga tgattgtaaa gatcttcatc ctcgtcttca 11580
cattgagtag gctgcggagg aagaaaacgg gttcgtcttg ctgtctcacg ggtggcagag 11640
atggaagaaa atctgtatat gtgaacctat gcagttcaga cctgtgttgt tcaagggtca 11700
actgtagtta caagtataga aaattaggta aatcctgaag ccatgaggta tcttgatttc 11760
ctcaggacat tcgacaaata tttttacatc cttagtgaaa ggttggagaa attaccctat 11820
ggatattagt tacagaaact tataatgaag aatggcaccc aaagaatgct aaacagattt 11880
gttagcctgg agtctgtgga ccctggtggt gtaacaatgg attttgtcct tcatttgtca 11940
ctagcctaaa taatatcttt acatgtaatt tattataaga ttggagactg ggtgtggtgg 12000
ctcccacctg taatcccagc actttgggag gccaaggtaa gtgtatcatc tgaggttagg 12060
agttcgagac caacctggcc aacatggtga aacctcatct ctactaaaaa tacaaaaaat 12120
gcaaaaatta gccgcacgtg gtggtgcgca catgtaatcc cagttactcg ggaggctgag 12180
gcaggagaat cgcttgaacc caggagacag aggttgcatg aactgagatc atgccactgt 12240
actccagcct gggcgacaga gcgagactca gtctcagaaa aaaagataaa aaaaaaaaaa 12300
aaaaaaaaag attggactag ctgcacctct aaagtgactt ttaatcccag gattctatga 12360
ttatatttaa ttggagttgt taaaagtaac aattaattag aataatttat ctgtttattt 12420
ttgataacct ggtgcttgta ctgaagaaga ataatatcat gaagtaaaaa gcataatcta 12480
gatcagtgct actgaaagaa gggtttgcat actgtttgag ataagttcaa aaattgaaag 12540
tgagcttttg gaaactttgg taacaatttg atattgccgg gacatccaag cacatcatca 12600
ttctttgagt aacttctgtt tttattgtac tttatatcag tccataatgg aacacacaca 12660
tacacacaat aaaactggcc ccttcgccac agattttttg agaagcacgg gtatagacaa 12720
ccatcaaatt caaatgatca gcactagaat gatcagcaat aatctgaact ttgtatgtgg 12780
ctaacgaggt acatattaaa ctattgcttt ttctttgtgg gtctggtcaa gaggagtaac 12840
agatgaattc ttcacactac tttctttcgc tttgcagaag gatttctcca gtcagttatt 12900
ttatgtgact cctacagtct agctaaggaa aaaattgttt ctggaaaact tctggtattt 12960
ttatttaaag gtataaaatt attttagttt ggcaatttaa gggttaccaa aaaaaaggtt 13020
tatttaactt ttagatctat taatctaacc atatagtcct tttatttatg ttatttctta 13080
agtgatctta ttcagcactc tgaataacct gatctttact ggctgtccca cgcacaagaa 13140
caccagaacc attcagaaag ctctcaaaat agtgaaatca atgttaagct atatttatgt 13200
agtgacagat atcaaagact ggatcttatg ctggtagcac attcagagtt ataacttttc 13260
ttgaaacacc accacatatg agaaaacatc actaatttaa ataagcaaga aaaatccatt 13320
tactgaatta ctgcaaaatt aaactataaa atactaatta tttttgttaa agatataaat 13380
aaaacattcc atttatttag catttgttgt actagaccat gattaagggc tggcatatca 13440
tagcaatgtc ttctgagttt gtagagctta gtttatctga aagacaaata tgaagccatt 13500
aattgtaact gtaacagaga gaaaattacg agttctatag gaacaaatac aagacggact 13560
taacctgggc tagacaatta ggaacagata aataggagat atttggtaaa gtaacaaatg 13620
gtagcttctc tagtagtaac agaactccta actagaacat tgaaatgcta tttttgacca 13680
ggcatggtgg ctcacacctg taatcccagc actttgggag gccgaggtgg gtggatcacc 13740
aggtcaagag atggagacca tcctggccaa tatggtgaaa ccccatctct actaaaaata 13800
caaaaattag ccagccgtgg tggcgggcgc ctatagtccc agctactcgg gaggctgagg 13860
caggaggatc acttgaacct gggaggcgga agttgcagtg aggcgagatc gcgccgctgc 13920
actccagcct gggcgacaga gtgagactct gtctcaaaaa aaaggaaaaa aaatgctatt 13980
tttatgtgaa tttagggatt gtttttaata gcttctaatg ctgattagag tctggtggaa 14040
tgagtatttt tgcgaattat taaattttag cattaacaat ttttacaacc ttctcagaaa 14100
gcaatttgtt accttttaac atagttctag gaatttctct taagggaata atgtaaaatg 14160
tgaaaggttg tatgcatgaa gttatttttt atagaattat ttataattgg gcaaaattag 14220
aagttgttta aatatccaga agtagatgaa caattaaatt atggaagctc tattagatga 14280
aacatgatgc attcatttaa aaataatagt gaaaagaatt cgaggttgca gtgagctatg 14340
attgcgtcac tgcagtccag cctgggcaac agagcaagac cttgtctgta gaaataaaaa 14400
aaaattaaaa ataatggtta agtgtaagca gcagcgtgga aaagtgaatg atgcagtatt 14460
atagtggaat aaaagcaaat tttattatga tcaaaacttt ataagataat acatatcctt 14520
tcatccttaa gggaaaaaag actgaaaaaa tttatcaaaa tgtttgtgat gtgaggtttt 14580
tagtgatatt ttcctccctc ttgctaatag aattatctac attgtatatg gtctcataat 14640
gtcccttcta aaacacagat ttgactatgt cattcctttg cttatcgctc acccacccta 14700
acacatacaa caattactat taggcagatt caaaattgat tagcttgata ttcaagacct 14760
atcacagcct ttttctccag acaactatct agcctggacc cctacataac ttttaatttt 14820
ctgtatcttt gcttatgcta ttttctctgg ctgaaatacc cttcccttcc cattttccac 14880
ctgataaaag tccatttctc cttcagggct aagctcaaat gttaacccct tcctcccccc 14940
tttttttaat tttctttaga gacagggtct cactctgtca cccaggctag aatgcagtgg 15000
caccatcata gttcactgca gcctcaaact cttgggctca agtgattctc ctgccccagc 15060
ctcctgggta gctaggacta caggcgcctt ccaccatgcc cagctaaagt tttaaatttt 15120
gttgtagaga cagggtcttg ttatgttgcc caggcttgtc tcaaactcct aacctcaagc 15180
gatcctccta ctcctacctc ggcctcacaa agtgctgtaa ttacaggcag aagcgactgc 15240
acctggctta ttactccttc ttgaagcctt tactctccaa ctcttcttac aaatcgctca 15300
gttttgcctc ttttttaggt cctcccagta tggtccttat cacattgtaa taatagattt 15360
ttttttcaat acaggaattg catgtagtat ctccagtgat tgtttggcaa ctaataggca 15420
ttcaatacgt gagtagaaat tggttaactg ttaacacttc tgttacaggg gcgtttatgc 15480
aatgagcctt tggatatgta cagttacttg cacaaccaag ggattggtgt ttcacttgct 15540
cagttctata tctcatgggc agaagaatat gaagctagag aaaactttag gaaagcagat 15600
gcgatatttc aggaagggat tcaacagaag gctgaaccac tagaaagact acagtcccag 15660
caccggtaaa ctttctttgg agcttgtctt aactctaaaa ataatagaaa taaattatct 15720
cttttttgca tctgaataaa gtgctttctg gtggattggc atgttaagtt tacttagtta 15780
ctattcaatt tttttaaaga tatattttaa aaattttatt tatcatagag taaaatccac 15840
tctttggtat atggtactag gagtaaaaag acttgtgatc atcatcatta acaagataca 15900
gaataatttc acacccccca aaagaattcc ctttgtaatt agtacctatg ctgaacccaa 15960
acccctggca aacactgatt tattctccag cctgtggttt tgccttttcc agactgccat 16020
ataaatggaa tcgtataata tatagccttt tgagtttggc ctgtttgatt tagcataatg 16080
catttgagtt gtaaaagttc tttatagatt gtaagtataa gcctttgtca gatatgtgat 16140
ttgaaaatat tttctctcag cttaagcctg gtctgttcat tttcttaact gtctttttta 16200
gaacagaagt ttttaatttt aaagaagtct aatttacaag tttttcttgt atggatcgtg 16260
cttttgatgt tgtgtctgag aattttttgt ctagccaaag attgttacag agattttcat 16320
cttcaagttt tcatcttcaa gttttataat ttcacttttt acatttagat ccctgatcca 16380
ttttgagtta atttttgtag aggatagagg ttaaggttct tttttagcat attaatgttc 16440
atttgttcca atgccaattg ttgaaaagac taacctttct ccattgaatt gcctttatac 16500
cttgattttt aaaaaatcag ttgatcatat tcatgtaggt ttatttctat tattctattt 16560
tttctaccga tgtacgtgtc tatccattag tgtttaccat gctatctaga ttactatacc 16620
ttttatagta agtctagaaa tcagataaaa tgagtcctct aactttattc ttatatttaa 16680
ctctggtagt tcatttgact ttctatataa gttttagaat cagctttctg ggattttgat 16740
taggattata caggaatatg gtataattct ccatttattt aggctttttt ttttttaagt 16800
aaactttggt agatttttgt ctttcaagga attgatccat tcatccaagt taatgagttt 16860
gtgggcatag agttgttcat aatattccct tattatgctt ttaatgtctg taggttatat 16920
agtgattctc cctttctcct gatactggta atttatgtct tctcagtctg gcttggatat 16980
caattttact gattgtttta gaaaaccagc ttttgggttc atttcattga tttttttttt 17040
ttttctctta atgattttct gttcttaatt ttatttctgc actttatttc ttcccgcttg 17100
ctttggatat aacttgctct tctttttgta gtttaaggtg aaagcctaga tcactgattc 17160
tagacctttc tctttttcta atataagcat ttaatgctct aaattccctt ctaagcactg 17220
ctttagttgt atcccacaag ttgtgatata ctgtattttc attttaattt agttcaaaat 17280
attttctagc ttaccccgtg tcttcctttt gacccatgag ttacttagaa gtgtattact 17340
tcagttagga agtgtttttg gatttttcag atatctctgt tattgatatc tagtttaatt 17400
ccatagtggt cagagaacat aaggtatatg gtttcaagtc ttaaatttgt taaggtttgt 17460
tttatcaccc agattatggt ttatcttggt gaatgcttca tgtacacttg aaaaatatgt 17520
gtattctgtt ttttagagtg taatattctg taaatataat ttagggcaag ttgactggta 17580
gtctgttctg gtcttctgta tcattgatga ctttctgtct acttgttata tcaattacta 17640
agaagggttt tgaagcctct ttgtgatttt gtctatttct tttagtccca tcagttttgc 17700
ctaatatatt ttgaagttct tttagatgca taaacattta gaattgaccc ctgtatcatt 17760
atataatgtc tccctttatc cctgataata ctccttattc agaagtctac ctggtctgat 17820
attagtacag ctattccagc ttcctttttg tttgcatgat acatcttttc cctttcttta 17880
ctttttaaaa accacattaa aaaaaaacca ctcttagagt tgtataatca tcattacaat 17940
ctaattttag aacattttta acaccctaaa atgaacccca tgcccattag cagtcactct 18000
ccattcctac ttacctcgct cctaggcaac cactactctg ctttttgtct ctatggattt 18060
gcttattctg gacattttag ttaaatggaa tcctacaata catggtcttt tgtgattggc 18120
ttcttttact tagcatacta tttccttttt ttttttccag ggagggaagg gtggaacagg 18180
gattttcagc atactgtttt caaggttcat cataaatgaa catagttgtg acatgtatca 18240
gtactttatt cctgtttatt gccgaatgat attccatcat atgaatatta tttatccatt 18300
catcagttag tgaacattta ggttgtttgc accttctggc tattacaaaa taatactgtt 18360
atatttgcgt aacaggtttt tgtgtcattt tctttttacc cttttgttaa gctagttgaa 18420
tttagcagtg gagggttata taccaacttt agtgacactt atgttaatta gcttctttaa 18480
cttttaacct atgtctttat attttttaag tgggtttctt atacacagca aatagttggg 18540
tcttgttttt tctgtgaact ctaacaatat cttttttgtt atgttgagac catttaatag 18600
aatttttaat attgttgggt ttaggtctac tattttatta tttgttccat gccttttgtt 18660
cctcttcagc ctctttccta ccttcttttg gattatctga gtgtttttta gtatttcatt 18720
ttaatttgtg ttattggctt tttgcctctt acaactttaa gtggttgcta taaggtatat 18780
aatataccta aactttcaca ttctacttaa tgttttacca tttaaagtaa aatacagaag 18840
ctttataacc ataaaagttc ctttatattc cctacccttt tggtatactt gtcataggta 18900
ttacatctat atgcattgaa aaccccacca gacaatattt tgttttgctt tcaaaagcca 18960
tatatatata tatatatata tctcttaaat aacttaggaa aatagtctgt tgtgtttacc 19020
cttttttttg ttgttgtttt ttcttcattc ctgaagctcc aagttccctt ctagtatcat 19080
ttcccttcag tctgaagaac ttcttttagc cactttcttt tagagcaggt ccgttgtcaa 19140
ttaattctcc tagtttttct tcatctgaga atgtcttcat ttcatcttct ttcctgaaaa 19200
atatttttac tggatataga attctgggtc aacgtttcgt ttcttttttt tttttttttt 19260
tttgagatgg agtcttgctc tgtcacccag gctggagtgc aatggatggc acgatttcag 19320
ctcactgcaa cccccacctc ccaggctcaa gtgattctct tgcctcagcc tcccgagtag 19380
ctgagtagct gggactatag gcatgcgcca ccacacccgg ctaatttttg tagttttaga 19440
agagatgggg tttcatcaca ttggccaggc tggtctcaaa ctcctgacct caaatggtct 19500
gcccaccttg gcctcccaaa gtgctgggat tacaggcatg agccactgta cccagccaac 19560
atttcttttc tttcaccact ttaatgatgt tatcccactg tcttctggcc tccttggttt 19620
cttttttctt tttctttttt tttttttttt tttttttttg agacggagtc tcgctctgtc 19680
gtccgggcta cagtgcagtg gcgcaatctc ggctcactgc aagctccgcc tcctgggatt 19740
acgccattct cctgcctcag cctcccgagt agctgggact acaggtgcct gccaccacgg 19800
ctggctaatt tttgtatttt tagtagagat ggggtttcac catgttagcc aggatggtct 19860
caatctcctg atctcgtgat gagcctgctt cggcctccca aagtgctggg attgcaggca 19920
tgagccactg cgcccggccc tctctggttt ctaataagaa atctgtagtc atttagtagt 19980
tcctgaccta tacataatgt gttgattttc ctctggcctt gtccaagatt ttttcttgtt 20040
tagttttggt tttcagaagt ttgattgtga tgtgtctaga tgtgattttt tttttttttt 20100
ttagacagag tctagctctg ttgcctaggc tggagtgcag tggcacgatc tcagctcaca 20160
gcaacctcca cctcccgggt tcaagtgatc ctcctgcctc agcctcctga gtagctggga 20220
ttacaggcat gcgccaccat acccagctaa ttttctattt ttagtagaga tggggtttct 20280
ccatgttggt caggctggtc tccaactccc aatctcaggt gatccacccg cctcggcctc 20340
ccaaagtgct gggattacag gcgtgaacca ccacgcctgg cctagatgtg gttttcttta 20400
catttaatct gggcttcact gggccttttg aatttgtaaa tgtatgcctt tcacaaaatt 20460
tgacaagttt tcagccgtta tttttaaaat gattttttat acctattatc tctttcttct 20520
ttctctctct gagacttcag ttgcacaaat tttagaccat ttcccccgac tctgctacca 20580
ataatctgtc caaattaaac cttttgatat cattccatag gtccctgaag ctctgtttaa 20640
ccatttttct ttttgttttt cagattggcc catttttatt gctctgtctt caggttcact 20700
tattcttttc tcttccatct ccatcctgct attgaaacca ttcaacataa attttttatt 20760
tcagatactg tatttttcaa ttctaaaatt tctgtttcat tcttttttat aatttctgtt 20820
tctctgttga gaatttctgt ctctccattc atttcaaatg tttttacctt catctcatgg 20880
aacatagtta tattaggtac tttaaaatct ccaggctggg cacagtggct cacgcctgta 20940
atcccaacac gctgggaggc caaggcgggg gaatcacttg aggtcagcag tttgagacca 21000
gcctggccaa tatggtgaaa ctctgtctct actaaaaatg caaaaattag ctgtgcatgg 21060
ttgtgggtgc ctgcaatctc agctactcgg gaggctgaag caggagaatc gcttgaaccc 21120
aggaggcaga ggttgtagtg agccgagatt gtgccactgt actccagctt gggtgacaga 21180
atgagactcc atctcaaaaa acaaaataaa atctccatct gaaaactata ccatctgggt 21240
cattttatgt ttgcatttgc ttattgtttt ttcctttgaa agttggtcac atttttctag 21300
ttctttgtgt gtcaagtaat tcttgtaccc tggacattta tcctgaccat atgttataag 21360
actctgatcc tgttggccaa tattccctgg agaatatcta tgtttttgtc ttagtagaca 21420
accacacttc agatattaca agttctttgt catcttgtgt ggctgttggt tccactgtca 21480
gttcagtttt caagaccttt gctgtgttgc tttgggtctg tcccatgcat gtcctgctta 21540
agggttaatc tggggcttgg gcagtggttt atatcattgt tcagttctca aagccttttc 21600
tgtgctgctt tgaatctacc ctgtgcatgc atagctcaag agggaaccta agatgtatgc 21660
caattcacat acagaattag gagatcctct tgttcagctc attcctttgc agttctcctc 21720
ccatattctt tggccttcag agtcctcttt tcccagtcct caggccagaa agatggggtt 21780
tctctgagtt ttacattcac ataccaccac tgcaacagtt caaaaccaca agagaaaata 21840
gaagaataaa aaaacaggaa acaatcctgc gtgggttgtt tcttcaagtt ttgacccctc 21900
tccacagtct gcttgctttt gttgactttt cagagccctc agttagttgc tttttttgta 21960
tatggtctat agtttttaat tcctatcagt gagagaaaga gaaaaggtac agtgggcata 22020
ctccatcttg gccaacacct gcaatttatt ctgggttttt tggggttttt tttaccctta 22080
tgataatact ttttaaggct agttaaatga agcagtggta ggaatggaga atctcttctg 22140
ataatactta aaactgtggc agcagcatag gaagtttact tttcaaactt ctgccagctt 22200
tgctaaagta caatgtcatg tcatatgcaa cttcatttca tataggtcag gagaaaccgt 22260
atatgtgtgt gcgtgcacgt gcgcgcatgc atgtgtatag aaaaagagac acagtgataa 22320
aatagatgtg gcacagtgtt aacaattggt gggtcaagtt ttctaataaa aagttagtgg 22380
gaaaactcta atcttaataa actctgtgat cttagtctta ataaccctaa cctgatcctc 22440
agatcaactt aatggtgatt ttcagaataa tttaaattgg tcaaacttgg gcatttaaag 22500
ggagagttaa ataattctag ccaaaacttt tcatgatctt aaggtgactc tctttacttc 22560
tgagagaata aacatgttct ttgggatatt tctgcattct tcccccagcc tgctcttcta 22620
atttgtttac tttaacaaat tggaaatttt gagtctggta aaatagtggt cacctcacta 22680
aaagttgtgc attctgctac tttagacaat tccaagctcg agtgtctcgg caaactctgt 22740
tggcacttga gaaagaagaa gaggaggaag tttttgagtc ttctgtacca caacgaagca 22800
cactagctga actaaagagc aaagggaaaa agacagcaag agctccaatc atccgtgtag 22860
gaggtgctct caagggtaag tttgttaaac gttatttcgg aaaactgtta gtttctagtg 22920
gtaaaatcat gtaagaagat aatacataaa tatacctgtg gacacttcta gtttgctgaa 22980
tactgagtag caaaaagaag gaagtcaaag gagagctaat attacagtgt gcagtaaaat 23040
caaaatgcat cagtaatttt gtgtcttaat taagaaagac ctaacattta ggaagcatca 23100
agattttctg agtttgaatt gttagttgaa agaagatatg tagtaacata gcaggtgttg 23160
ttaaagtgaa gcttacatat accaaagcct cagagaatga tactaatatg gttaagaacc 23220
ctgccttcag agccctttgg gaccagaaat tagactctct atatacccaa agatcagcaa 23280
taattttttt taattaacat ggactttttt tttttttgag agataggttc tcgctctgtt 23340
gcctgaaacg tggtagtgca atcatagctc accgcagctt caaactccta ggctcaagca 23400
gttcttttgc ctcagcctcc caagtagcta ggattatagg tgtgagccac tgcatctgga 23460
caacactgac tattttttag agtagtttta ggttcatagc aaaattgagc agaaggtaca 23520
gagaataata agcttttatt tactaaattt atagcagtta gacatgtaaa ccaggctgtt 23580
tttttaatct cttatttctt tcctggtatc aatttatcaa taatcagaat gttacttggt 23640
ggttctagaa ttaggatata gggagtgtat ggtcccaaag gctatttcat ccagatcatg 23700
atgaagcttg gttaataacc agccccacaa cagagaaaac ccctaataaa tgggttaatt 23760
ttgtattctc tagttccagt atatctctgc tgatttccat tgagagaaaa tttaaaactg 23820
aagaataaaa cttaggttag tttctgataa aactagataa tgttataatg atgactgaag 23880
gaagatgcag aatgtctttt ttggaaattt gtgaataaaa gatgtggggt gactggagga 23940
gggaaaagaa ggcagaatat aagtaacaaa gaatggataa aacgattcta tttttgattt 24000
attaattttt ttaaagatta tttttaaaat ttcttttttt ttttctgttg tagtggaaat 24060
actgtccttg agttgaggaa gaataggtat actttatctg gcatctaagt taataatgaa 24120
acattttaca tgaggtttta atatttttgc tcctagctcc aagccagaac agaggactcc 24180
aaaatccatt tcctcaacag atgcaaaata atagtagaat tactgttttt gatgaaaatg 24240
ctgatgaggc ttctacagca gagttgtcta agcctacagt ccagccatgg atagcacccc 24300
ccatgcccag ggccaaagag aatgagctgc aagcaggccc ttggaacaca ggcaggtcct 24360
tggaacacag ggtaaggact cttagatcca gtgctttgct gacacaacaa agacttcaca 24420
tttagggtag agaagtattt ttaccatctc ttttaattcc tcttgaatat ttagccatgg 24480
tctatatatg ctgtctgaga acataaaact atggtaattt tagttttctt cttcatctcc 24540
agcctcgtgg caatacagct tcactgatag ctgtacccgc tgtgcttccc agtttcactc 24600
catatgtgga agagactgca caacagccag ttatgtgagt gtggtttttg gatattttga 24660
agtgggaatt attaagggtg ggcagaggca cctattctac ttcccaaagg cagtttcttc 24720
tttatgaaga tgaaagtaac caggccaggc gcagtagctc acacctgtaa tcccagcaca 24780
ggctgaggca ggaggatccc ttgagcctag gtgttcaaga ccagcctggg cagcctagtg 24840
agaccctgtc tctatttatt aaaaaaaaaa gtaaccagac aaaattttgt atatccttta 24900
tgtttgtatt cctttgagta tgttagggtt aaaagaccat ttgttaatat tttattaagg 24960
aataaacatt aattaggttt atattttcat tactgaacat tgctttagga aaatcaatgg 25020
tggctattct ggaagatgga ttgaacatac ataaataagc tattggaata gttcaggcaa 25080
ggatattaag gggcggtatt tgggcagggt agtggtaatg aaaggagaag ggagcttgga 25140
tgggagaggc ttcagcagta gagttagaag atttgtctga tgggataatg gggatgtagg 25200
gaaaagataa tgtgatttaa atgagacgtt ctcattttgt cattgatagt aatgagaaat 25260
tatgatagtt ttccctctta tcctgctttt tccttctgga catatttttc ctctttcttc 25320
ctaatcctta gcatttctgt ttttaagaaa aagtatagta gctggtggtt aaataaacaa 25380
gccagcctga gatttagtct aatgcttaac attgcctagt tctttttttt tttttttttt 25440
tttttttgag atggagtctc gctgtgtcgc ccaggctgga gtgtggagtg cagtggtgcg 25500
atctgggctc actggaagct ctgcctccca ggttcacgcc attctcctgc cttagcctcc 25560
caagtagctg gaactacagg catctgccac cacgcccagc taattttttt ttttttttag 25620
tggacacggg gtttcaccgt gttagccagg atggtctcga tctcctgacc tagtgatccg 25680
cccgccttgg cctcccaaag tgctggaatt acaggcgtga gccactgcgc ccagccctag 25740
tcctaatact aggttgaatt ctgtcccagt gcaagagtta cctcataact aatttataac 25800
tcccactaca tgctaggaat gcaaaaataa taattaagat tttgagcaaa aattctgcct 25860
aagtgctcag gacaagggga aggctatttt ttttcttttt ttttttttct ttttaaacag 25920
agtcttgctc tgttgcccag caggctgaag tgcagtggca ccatctcagc tcaccgcaac 25980
ctcgacctcc tggttcaacg ggcatggcag cccacgtttg ccatcccagc actttgggag 26040
gccaaggtag gagaatcact ccaggccagg agttcgagac cagcctgggc aacatagcaa 26100
aaacctgacc ctacaaaaca aatttttttt tttttgagac ggagtcttgc tctgttgccc 26160
aggctggagt gcagtggcat gatctcagct cactgcaagc tctacctccc aggttcacgc 26220
cattctcctg cctcagcctc ctgagtatct gggactacag gcgcctgcca ccacgcctgg 26280
ctaatttttt ctatttttta gtagagacgg gatttcaccg tgttagccag gatggtctcg 26340
atctcctgac ctcatgatcc gcccacctca gcctcccaaa gtgctgggat tacagatgtg 26400
agccaccgca cccggtcaac aatttttttt taattagctg ggtatggtgg tgggtgcctg 26460
tagtcctaac tactcgagtg gctgaagcag gaggatcact tgagcccaag aatttgaagc 26520
tacagtaagc tatgatcatg ccacagcact ccagcctggg caacagggca agaacctatc 26580
tctaaaaaat aaatcaatta taataataaa gaaaaatcag cttggcatcg tggctcatgc 26640
ctgtaatttc agcactttgg gaggctgagg tgaaaggatc gcttgagccc aggagttcaa 26700
gaccagcctg ggcaacacag ggagaccctg tctccacaaa aaatttaaaa attagccaag 26760
tgcagtggct tgcacctgtg gtcccagcta cttgggaggc tagggatcac ttgagcccag 26820
gagtttgtgg ctacggtgag ctgtgactgc accactgcac tctagcctga gtacagagtg 26880
agaccttgtc tcaaaaataa ataacgaaaa taaaaaagaa aatcctatga gcctttatag 26940
aaatggataa catacatttg tagatgtctg gtttttctaa tgtttcaagt cattttgtag 27000
aaacatgact tatgttaaaa ttaatatggt acaggaaata ttaaacttat tatttttgag 27060
acggagtctc actctgttgc ccaggctgga gtgcagtggt gcaatcttgg ctcactgcaa 27120
cctccacctc ctaagttcaa gcaattctcc tgcctcagcc tcctgagtag ctgggattac 27180
aggttcgggc caccacgccc ggctgatttt tgtattttta gtagagacag ggtttcacca 27240
tgttggtcag gctggtctcg aactgacctc gtgatctgcc tgtctcggcc tcccaaagtg 27300
ctgggattac aggcatgagc caccatgccc gacctaaact tatttttatt ttaaattctt 27360
ttccatggat gttttatttg acctctccac acatttttct ttaggttgcg ttttgcttag 27420
tgatgtatag aagctcttca tagatgaaga aaatcagcta aaaatctata atacgagttg 27480
caaatatttt ccccctactt tgtccttgtc ttttggcttc atgtagcagt aaccattatg 27540
cttttaatta tcatacagtc aaatttaagt tttctttttt tttttttttt tcgagacaga 27600
gtcttgctct gttacccagg ctggagtgca gtggcgccgt ctcagctcac tgtaacctcc 27660
gcctcccggg ttcaagcaat tctcctgcct cagccacccg agtagctggc attatagacg 27720
cccgccacga cgcccagcta atttttgtat ttttagtaga gccatggttt caccatattg 27780
gccaggctgg tctcgaactc ctgacctcga gatctgcccg ccttagcctc ccaaagtgcc 27840
gggattacag gcatgagcca ctgcactcag ccttttaaag cttttttttc tttttttttc 27900
taaacttcat cgaaatataa ttccgtggct tttagtatgt tcacagagtt gtgcaaccct 27960
taccacaatc aattttagag catttttatc actccagaaa gaaccttgta cccatacctg 28020
taagactcga ttccccacca ttaccccaat ccccacccta gcaaccaact gtttttttct 28080
ctatagataa tttaccaatt ctagacatct cgtgtaaata atataatatg tggtctttgt 28140
ttttttttgt ttgtttgttt tttgtgtttt agacagagtc ttgctctgtc gcccaggctg 28200
gagtacattg gtgcaatctc tgctcactgc aaccttcgcc tctccagttc aagcatttct 28260
cctgtctcag ccttctgagt atctgggact acaggcatgt gccaccactc ctggctaact 28320
tttgtatttt cagtaaagac aggctttcac cacgttggcc aggctggtct caaactcctg 28380
acctcaagtg gtccgcccac ctcggcttcc cagaccgctg ggattatagg cgtgagccac 28440
tgcgtccagg cagtgtatgg tcttttctaa ctggtttctt tcacttaggg tagtgttttc 28500
aaggttcatc cacgttgtga catgtatcag tacttcatta ttttttattg ccaagtagta 28560
ttccgttgtg tggcttcaca acattttatt taaccattca tcagttgata caaattttaa 28620
ttgttttcat tttttggcta ttatggataa tgctgctgtg aataccgtgt atacattttt 28680
gtgtggacat gtgttttcgt ttttcttggc tgtataccta ggagaggaat tgctggatcg 28740
tgtgattaac tccatgttta atattttgag gaactgtcaa attgttttcc aaaaaagctg 28800
taccatttta ccttctcaca ttcccctaat gtacgagtac tccaattcct tcccaacact 28860
tgttattatg cttttttggt tattgtcatt ctaacagaga tgtgaagtgg tatttcgctg 28920
gttttgattt gcattttcct ggtgactaat gatgttgagc ctattttcat aggtttattg 28980
gccttttgta tatcttcttt ggagaaatga ctgtttaaat ccttggccta tttttccttt 29040
ggattacagt agtccctcct tatctgtagg ggatacgttc caagactcca gtggatgccc 29100
gaaacttgat agtaccaaac catttatata ctatgtttta tcttatacat gcactgtggc 29160
cataactttt gcagtttgag gtatgacagc aaaactaact ttttttcctt cttcacaatt 29220
tcactgatag aagattcatt cttactgtaa atcttatcaa cttcagcatg tgatttattt 29280
tttattttta ttttattttt tttagtgaaa gttgaggctg ggcatggtgg ctgatgcctt 29340
taatctcagc actttggctc tgggaggctg gggcaggagg attgcttgag accaggagtt 29400
caagaccagc ctgagcaata tagtgagacc ccatctctac taaaaataaa aatacactgg 29460
ctgggcatag tggcacatgc ctatggtttc cgttactatg gaggatgagg tgggaggatt 29520
gtttgtgccc aggagtctac ggctgcagtg agccagggtc acgccactgt actccaccct 29580
aggcaacaga ttcagatcct gtctctaaaa ataaaataaa acaataaaat aaaagttaag 29640
aactttcacc tttggcatat ccaaatcatc agcatcgcta ctcttgtgct ttggggccat 29700
tattaagtat aataagggtt acttgaacac aagaactgca atgctgggac agctgatctg 29760
atacgagtca gctgctaagt gactaatatg tggatgctga acaaaaggat gattcacatc 29820
ctaggtggaa caaaatggga atatatggga tttcatcagg atagtcagaa cgccttgtaa 29880
tttttttttt tttttttgag accgagtctc actctgttgc ccattctgga gtgcagtagt 29940
gccatcgtgg ctcactgcaa cctcagcttc ccgggttcaa ccgattcttg tacctcagcc 30000
tcccaagtag ctgagattac aggcttgtgc catcacaccc aggtaatttt tgtgttttta 30060
gtagagacgg ggtttcgcca tattgcccag gctggtctcg aactcttggg ctcaagtgat 30120
ccacccgact cagcatccca aaatgctggg attacaggca tgagccactg cgcctggcca 30180
gaatgacttg taatttaaaa ctgatgaatt atttctggaa tttttcactt aatatttttg 30240
gaccaccatt gaccatagat aactgaaact gctgaaaatg aaaccatgag taaggggaaa 30300
ctactctatt tggtttttta ttgttgagtt taagagtctt ttatgtattc tagatacaac 30360
ttcttttcgg atacatgatt tgcaaatatt ttctcccatt ctgggttgtc attttatttt 30420
ctcaatgatc tcttttgaag accaaaagtt atttaaaatt ttgatgaaat gcaatttatc 30480
tgttttttaa aattttgtcc ctgagctttc actgtcatat ctaagaaggc tctgactaat 30540
ccaaagtcat gaagatttgc ttttatacat tttcttctag gagttttata gttttagctc 30600
ttatatttag gtctgtgatc cattcttagc taatttttgt gtatggtata aggaaggagt 30660
ccaaattcat ttttcttcat gtggatatcc agtggtccca gcaccacttg ttgaagacta 30720
ctcttttgct attgaatggt cttggcactc ttgttgaaat atcagttgac caaaatgtat 30780
gaatttattt ctagactctt aattctattc cattgatctt tttgtctatc cttatgtcaa 30840
taccacacag tctttttttt ttcccctaca cgatctcgat tactgcagat ttgtagtaac 30900
ttttgaaatt gagaaggatg aatccaactt tgttcctctt tttaaagatt gttttgacta 30960
ttctgattct cttgtaattc cttatacatt ttaagattag cctgtcaatt tctgcagaaa 31020
agccagctgg aattttgata gtgattctgt tgaatctgta ggttaattta atgatattga 31080
catcttaaaa atattaagtc ttctggtcca tgaacatagg atgtctttcc agttatgtat 31140
gtctttgaat tctttcagtg ttttgtaggt ttcagaatac aagttttgca cttctttttc 31200
tttaattaat agactttatt ttttagggca gtgttagctt tgcagaaaaa tggagtagaa 31260
agtacagaga gttcccacat actccatccc cacccctcaa ccctgtacac agtttttcct 31320
attactaaca tcatgcatga gtgtggtaca tttgttataa ttgatgaacc aatattgata 31380
cattattatt ggttaaagtt ctttgtttac attaggattc actctaatgt gttttacagt 31440
tctgtgtgtt ttaacaaata cataatatta tctatccatc attacggtgt cattcagaat 31500
tgtttcattg tcccagaaat cccctttgct ccatttgttc atccctttct ctctctcccc 31560
aaatcccctg taactattga tcttttcatt gtctttatag ttctgccctt tccagaaaat 31620
catgtagctg gaatcatagt atatgtagcc ttttcaatct ggctccttcc acttaacaat 31680
aaggttcctc tgcatcttct tctgacacaa tacctcattt atagtgctga atgatattcc 31740
attgtataga tgtgccacga tttgtttatc cattcgccca caggaggtca ttttggtgac 31800
ttacaagttt tagcaattat gaataaggtt gcggtagaca ttcatgtgca ggtttgtttg 31860
ttttaaatag tcttgttctt tcacctacgc tggagtacag tagcatgatc ctggctcact 31920
gcagtcctga ctcctggact caagtgatcc tcccacctca tcctccctag tagctgggac 31980
tacaggtgca tgccaccatg gctggcttat tatttttttt ttttaaagat ggggtctcac 32040
tgtgttgccc agcctggtct tgaactcctg ggatcaagtg atcttcctgc gtcagcctcc 32100
cagagcactg ggattacaag catgagtcac cacacccagc caggttttgg tgcagacata 32160
agttttcaac tcatttggct ggattgtata ataagactaa ttttagcctt gtaggaaagt 32220
gccaagttat ttttcaaagt agctatactg ttttgcattc ctaccaccca tcaatgagag 32280
cttctattgt tccacatcct tggcagcatt cagtgttgtc aatattttag attttaacca 32340
ctctaatagg tgtgcagcag tatcttattg ttttaatttg caattcctta atgacatctg 32400
ggaagcatct tttcatatgc ttactatcat cttttttttt ttttatatgc ttattaccac 32460
tttttttttt tttttttttt ttttccctta gagacagtgt ctcactctgt tgcccaggct 32520
gggctcaagc aatcctcctg ccttatccat cctggtagtt gggactatag gtgcatgaca 32580
ccatgcctgg ctaatttttt ttttgaagac agggtctcag ccgggcgtgg tggctcatgc 32640
ttgtaatccc agtactttgg aaggtgaggc aggtggatca tgaggtcagg agttcgccaa 32700
catggcaaaa ccccatctct actaaaaata caaaaattag ctgggcgtgg tggcaggtgc 32760
ctgtaatccc agctactcgg gaggcggagg caggagaatc gcttgaacct gagaggcgga 32820
ggttgcagtg aactgcgatc atgccattgc actccagcct gggtgacaag agcaagattc 32880
tgtctaaaaa aaaaaaaaaa aacagggtct cactgtattg cccaggctgg tcttgaactc 32940
ctggcctcaa gtgatcctcc tgcctcagcc tcccaaagtg ctggaattac aggccactgt 33000
gtccaacttc catctatatg tcttctctca cttccttatt ttaaatttat tgtgaagtat 33060
tttactattt ttgaagctat agtaaataga attgttttct taatttcatt ttcttttttc 33120
ccctttttta catgctgcct tgagatgtga tttaatttta ttttcagatt gttcattgca 33180
aatgggtaaa ataggttgat tttgtatact gatcttgtat tctttgactt tgatgaactc 33240
gtttgttatc taagaccata tcttctgcaa aaagagatag ttttgcttct tcctttccca 33300
tctggactcc ttttctttgt ttctcttgcc taatagcctt gactagaact tctagtacag 33360
tgttgtatag aagtgacaag aatggacatc cttgtcttgt tcctgatctt agggggaaag 33420
catctagcct tttaccatga agtatgatgt tagtgtgggt ttttcataga tgtcctctag 33480
caggttgagc aagttgggga aactttttaa gcatgtaaat gcttggaccc taccattaca 33540
gtttttgatt cactgagtct gggaaggacc ggtatcttta gttgtacaaa ggtatataag 33600
aaaataaaag gtatataagt tattctgatc cacagggttg aaaatacctg ctatatcatg 33660
gttgaggtat cttatacttc attcttttaa aagctatgct gccactctga ttcttccccc 33720
tcagctgagc accttggact taatattatt aggttcctaa tgctatattc ttaactctaa 33780
ttcttttgga tactaaacca tgaaaaatgg attgtattgc ataggttaat ttctttttat 33840
atactggtta tgatgaggat atggtattaa gatttgcttt cacctataag taatataagc 33900
tacttgatta tcccacttat ggctaatttc cttccttatc atagcagagg tggtactcag 33960
aacataattt tattttcctt ttttttacat ttcaataggt tttggggaac aggtggtgtt 34020
tggttacaca aataagttac ttagcggtta tttctgaaat tttggtgcac ccgtcacctg 34080
agcagtgtac actgtacccg atgtgtagtc ttttaaccct tactcccccc atcctttccc 34140
ccaaatcccc aaagtccatt gtatcatttt tatggctttg tgtccttata gcttagctcc 34200
cacttataag tgagaacata tgatgtttgg ttttccattc ctcagttacg tcacttagaa 34260
taatggtctc caattccatc caggttgctt caaatgccat ttttttgttc ctttttgtgg 34320
ctgagtagta tttcatggta gatatatacc acattttctt tatccatgca ttgattgatg 34380
ggcatttggg ctggttccat atttttgcag ttgtgaatta tgctgctaaa atatgcatgt 34440
gcaagtatct ttttcatata atgacttctt ttcctctggg tagataccca ggagtgggat 34500
tgctggatca aatggtggat ctacttttag ttccttaagg aatctccgta ctgttttcca 34560
tagtggttgt acgagtttac attcccccca acagtgtaaa cgtgttcccg tttcaccaca 34620
tccatgccag tgtctattat tttttgattt ctttattatg gccattctca caggagtaag 34680
gggttattgc gttgtggttt tgatttgcat ttccctgata attagtgatg ctgaacattt 34740
tttcatatgc tcgttggcca tttgtttatc ttttgaaaat tgtctattca tgtccttagc 34800
ccactttttg ataggattgt ttgttttttt cttgctgatt tgtttgagtt cctggtagat 34860
tctggatatt agtcctttgt cggatgcata gatcgtgaag attttctccc actctgtggg 34920
ttgtctgttt actctgctga ttattccttt tgctgtgcag aagcttttta gtttagttta 34980
gccccatcta attatctttg tttttgttgc gtttgctttt gggttcttgg tcatgaagtc 35040
tttaccgaag ccaatgtcta ggagggtttt tccagtgtta tcgtctagaa tttttatggt 35100
ttcagatctt agatttaatt aagtctttga tccaccttga gttgattttt tgtataaggt 35160
gagagaggag gatctagttt cattctccta cttgtgactt gccaattatc ccagcaccat 35220
ttgttgaata gagtatcttt ccccacttta cgcttttgtt tgctttgtca aagatcagtt 35280
gactgtgagt atttggcttt atttctgggc tctctattct gttccattga tctatatgcc 35340
tgtttttata ccagtattat gctgttttgg tgactatggc cttacagcat agtttgaagt 35400
caggtaatgt aaggcctcca gatttgcaga acataattat tgatggccct tgtaaattat 35460
ttttagcttc ttttatcaat cttattgatt ttttttattt tgacccatat gaataatagt 35520
aattttgctt ctttaggaca ccatgtaaaa ttgaacctag tataaaccac atcctaagca 35580
ccagaaagcc tggaaaggaa gaaggagatc ctctacaaag ggttcagagc catcagcaag 35640
cgtctgagga gaagaaagag aagatgatgt attgtaagga gaagatttat gcaggagtag 35700
gggaattctc ctttgaagaa attcgggctg aagttttccg gaagaaatta aaagagcaaa 35760
gggaaggtgt gtgtaattca agtttgtgaa gaggacttaa cttagttgtg tgaaggttga 35820
gctgacctat taagtctgaa gaaaactaac cttatagttt gtacctttgt atgatgtttc 35880
tatggtagta ctgtttcttt ctgtgtatca gccaaaatcc cactgctgcc ttctatggtt 35940
gtactgtttc tgtgtatcag ccaaactccc attgctgcct tccatgaaaa ctccttgggg 36000
tgtgggggca ctgagtatgt ttagaagtaa aggaagaagt tctgaactgt atgaacaatt 36060
tatattcccc aatacaataa gcaagcagct atgatccctg acatgcatat atgtacattc 36120
catgcatccc tattaagtac ttttcctaat gttattgctt gaaatatttc actttacctt 36180
tgatactttg tctgaaattt ctccaagggc ttatttagat taacatagta ggtcatactg 36240
cagtgattta gattatagat attcgtattg ttttttaaag acattatatt tctaaattaa 36300
aggaaaaggt ttaaaaattg agatatgggg aatttttggg aaacaggaag cagttctgat 36360
tctggagcct ggagtacttg aaggcaagag gtagggcaga atgggctgga aagtagggaa 36420
gtaaggcata tggggcttaa ggcatgagaa ggtgaaggag aataaagaag ggtacagaaa 36480
atgaggtagg ggagggtcca cttccattta gacatttttt attaggatct gtaaggagaa 36540
agtaatgttt cttttataca tccgtatcca gaataaccta ctaatatagc tcagctctct 36600
taacaggatg tggtgtttgt ggggttagct gggaaactta accatcactt atactttgag 36660
gagcaatctt ttctgagttc caggtgacaa cctggaagca aactttggta aagcagactg 36720
ttagtaagtt tgaaattgcc ttcatttgtt acactaatta gtgtcatcca agattgtcaa 36780
aagtgctctg ggttcaaatg gaacttgtgt gtctaggtag aagagaggga tggttgcaaa 36840
gcaaggtgtt gagtaaggct tttaaaaaag gagaaccact ccagcaaaga aataggctag 36900
gagggtggcc aaatatgaac cagaaaagga actaggtatc tagataaaaa ctgtttccta 36960
agggaaaagc ttagtctgta ccagatatat agaaggaaaa tgaaagtcca ttttagggcc 37020
aggcacagtg gctcacacct gtaatcccag cactttggga aaaaaagacc agcctgggca 37080
acatggtgaa ttctcatctc tgtgggaaaa agaaaaggta cattttgttt tcaactagcc 37140
aaagaaggac ctactctaga ttacatggga tttaattagg aataagaagg cattgacctc 37200
tgagaatttt ttaatactca tttctattgt gttttttttt tttttaaata gagagatggg 37260
atctccctgt gttgcccagg ctggtctcaa actcctgggc tcaagctatc cttcccacct 37320
tggcctttca aagtgctggg attataggca tgagccacca tgcagacctt aatgcttatt 37380
tctaagctgg tctctgaatc tatttcatga acttgtataa attcccatct gtgtataagt 37440
ttgtaccctt acataaatcc tcatttcaat aaatgtggtt tctagttact gtcaaaaact 37500
gacttcaaag acttgccaac tacttactct cagggaaaaa tacaagaaaa gaggaagcca 37560
caatcagggc ctacacaaag gttgtttttt ctttgcgttg cacttccaaa tcattttttc 37620
cctcttcttt caaaaacttt agcttctttc agatttctgt cctctaattc ttttctatct 37680
cctgagcctc cttagtgtac tcacctcaga cttttcagtc acactccatc attcattaat 37740
tgactaataa gcacatggct tactatctat gcctctttac cctaacctgc aaaaccctgc 37800
atggccaagc atggtagcat gtgcctgtag tcccagctac tcaggagagt gaggcagaag 37860
gattgagccc acaagtttga gaccagcctg ggcaatatag caagacccca tctccaaaaa 37920
caaacaaaac tccatgtggc ttagccttta cctacctctc caaccccatc tttttctatt 37980
caccctctta ctatgctgca actacactgg acttcctttg gattcttaga cacagtggtc 38040
ttttcctgca ttggggcctt tgtgccacct agtttgttag cctagaatct ttccccagaa 38100
ctttggcccc ttatcattta aattacagct taatactgtc actttatcag aatgatcttc 38160
cctgatcact ggtcttaagt agccctccct tggcctccat ctccctaccc agtcaaacat 38220
tctcacgtca cctattttat tctttttcct aaactgattt tcttgtgtgt gtgttgcccc 38280
caaatttgaa tgttagtatc acataaccaa ggactttgta ttatgtacca ctgaaaccta 38340
agtactcaga gctgtgcttg gcacatagta ggtattcaat gtttttttcc ttttagtaga 38400
aacctgtgtt gttcaaaggt attctatttt tttattgaat ggataaagaa tagaggccta 38460
gaccacaagt tgaggacctt attccactta aatcattttc atctgtatta gtaacatata 38520
tgttgaggag atgagctcca aaggcagttt ttgacagaat gagttactat gaggaataat 38580
acctcaagca actttactgt ttctagccga gctattgacc agtgcagaga agagagcaga 38640
aatgcagaaa cagattgaag agatggagaa gaagctaaaa gaaatccaaa ctactcagca 38700
agaaagaaca ggtgatcagg taatttttct tttttcatac acaaaactag aatttattga 38760
aacaaattta aacattataa aaatatagaa ggttaaagtc ctcccaaccc ccatttagag 38820
tttctggtag tttcttagct gttagtagcc ggaaagttga gcgggaaagt aatttaacag 38880
gtgacttcaa atggaatttg tggcatgtga aataagtggt gcagtttatt gacttcttag 38940
ttatactcca aatcattatg ttattaattc tggcttaagc tttttattct agctatgttc 39000
cattaaaatg ggattgccta aagaaattta gtatatgcct ggcactgctc agttgagtac 39060
aacagtactg gtttagagta ggaataaaaa ttattggaaa tgacttttgt ggtacactca 39120
ttttgtactg ttagtggatg tctagggaaa gagtacagta aagctaatgt tagaactaga 39180
aaatagcatt ttctggatgg gagggacatt gattttgttt atttaatgca aacagcaaga 39240
agagacgatg cctacaaagg agacaactaa actgcaaatt gcttccgagt ctcagaaaat 39300
accaggaatg actctatcca gttctgtttg tcaagtaaac tgttgtgcca ggtaagacta 39360
cataggtgga agggacaatg catataggag ggcatttaga accaaccttt gactctctag 39420
tgccttgaag tctccttgac gtttacagta tcgagacatg gtttttgtaa gtctctgtca 39480
caacataagc tttgatgctg atgagggagg acagagcatt gactattttc cactgaagaa 39540
acatgtttct tatagaaaca aatacatata ctgtttttaa aaaacaaaat cacccatttc 39600
taccactaag agatgattac cattaacact gttctgtctc ttcttttgtg ttgtattttt 39660
gttttgtttt ataaaaatgg cagcttacca ttttgtaatc tgcttatact attaatgcaa 39720
cttgacatct attatcaaat atatttctgc aacatttttg ataaccaaag cttccatctt 39780
ctttaagaga atttgaattg acagtaataa tttatcttag agtaaatatt atatttaatg 39840
gaaaagcctc ttggactttt aaaaattaaa cagttctttc tgtgggtatt gagcacatga 39900
tttaaaacaa gtttctttac agagaaactt cacttgcgga gaacatttgg caggaacaac 39960
ctcattctaa aggtgagttg tatttgacag ccttgagaag aacttgctga taacaaatgt 40020
attatgtaat aaatggtaaa tatttttaat tatgataaag ggattgaaag acagggggac 40080
taggatacta ggaatttagt ataagcatat gctttatgat aggaaagaca tttgaaagag 40140
tattttttta aagattcctc agtgcttcaa aatatttggt ttaattgtaa ttttaaattt 40200
acactaacca ccaaatctta tactttagtt actgtacact aaacagcaaa gacactaagg 40260
gaagtgtttc ttttcaggga aaaaaaaatt taaagctatt ttatactcaa attggttttc 40320
ttttcttcaa aatgtgttaa aagtggtgaa acatgaatat ctacttgtaa atggtttggc 40380
aaaaataaaa ataaaaaaca ttaaaatcta attaaacctc tgtttctaac cgtcaattta 40440
ttggaaatat aaagcatgga ggaacgttgt taaacaacac agcgggatgg aattggcaaa 40500
atccagcatt atggggctag caacccagtt tgttcaacaa aaattccccc caaaactcta 40560
tagaataaaa gagatttaag aggcatttga acagtcacag tatacggatc ttaactctgc 40620
attcccaatt caaacaaact ttaaaaaaat ttttttttat ttattaatat ttttttgaga 40680
ctgagtctcg ctctgtcgcc caggctggag tgcggtggcg cgatctcagc tcactacaag 40740
ctctgcctcc tgggttcatg ccattctctt gcctcagcct cccgactagc tgggactaca 40800
ggcgcccacc accacgcccg gctaattttt ttttgtattt ttagtagaga cggggtttca 40860
tcatgttagc caggatggtc tcgatctcct gacctcgtga tccgcccacc atggcctccc 40920
aaagtgctgg gattacaggt gtgagccacc acacccggcc aaaacatttt tttaattggt 40980
aaaatatgaa acttctcact ggacatttga tattatatat atattcataa attgttcatt 41040
ttataggtag gtatcatgtt ttgggattgg gatttttaaa aagcctcttt tagaaatata 41100
tactgaaata tttgcagata aaatgacatg tctggaattt gctttaaaat aatcctgttg 41160
ggttgggttt ggggagtagt gacagtggta gagaatctaa atggaacaag atcatctaag 41220
tttaggtaat tggtaaattg tttaatgacc ttttatatgt ttgaagcttt ttgttattaa 41280
aaaaacaggt tgccttcctg ctttcaaaca acacaaaata ttgattaatt tatctggttg 41340
tcttgaagag taaagcattt actcctagag tatgtatcta gtctctcttt ctctaggtcc 41400
cagtgtacct ttctccattt ttgatgagtt tcttctttca gaaaagaaga ataaaaggta 41460
cgttgttttt ttgttttttt ggtttttttt tacttaagaa ttttctgtta ttataagtga 41520
ggataaatta ggggttactg ttatgaaaaa aattgctaag tgaggtatgt ctttttccag 41580
tcctcctgca gatcccccac gagttttagc tcaacgaaga ccccttgcag ttctcaaaac 41640
ctcagaaagc atcacctcaa atgaagatgt gtctccagat gtttgtgtaa ggagcagtat 41700
ccttaagtta atgtaaatgg gctagtggat tgtttattca aaaccacaaa agcttaaggt 41760
taaaattgaa accactgact tgaattaagc acatgaaaag atgctcagca ttactactca 41820
acagggaaat gcaaatcaaa accacagtga gatactactt tatatcctct aggatagcta 41880
taataaaaaa ttacgcacag taacaagtgt tggcaaaatt gtggagaaat tagaacatac 41940
attactggtg ggaatgtaaa atggtgtagc cactttggaa aacagtttgg cagctcttta 42000
aaatgttaaa cacagttacc atatgatcct gcagatctct gcccaggtat atactcaaaa 42060
taattgaaaa cacatgttca tacaaaaaat ttgtacacaa atgttcatag ccgtattact 42120
catgatagtg gaaacaaccc caaatgtcca tcaactgatg aatggataaa caaaatgtta 42180
tgtatccata ccatgaaata ttatttggca acaaaaagga atgaagtact aatacctgtc 42240
acaacataga tgaaccttga aaacgttatg tcaagtgaat gaagccagat acaaagacca 42300
catactatat gatctaattt tcatgaaata tccagaatag gcaaaagtgt catggattga 42360
ggttttccag gggattagag ggtggtggag agtgactgct aatgggtata gggtttcttt 42420
ttggagtgat gaaagtattc tggaattaga tagtgatgat ggttgtacaa ccttgtgaat 42480
ttactaaaaa ccactgaaat atactttaaa agggtcaatt ttatggtata tgaattatat 42540
ctcaattttt ataagtaggg aaaaatcact aattttaaag ccttttgtac ttttaatttt 42600
ttaaccaaca tagcaaaaga catttgttct tttttatata aaataccttt tttggcaatg 42660
caaaagttat gtgggccaat catttttctt cagtaatgtt ctatattaac cgctatagac 42720
taatgacata atacttaagg taaaaagacc ctgtgtagac atttaagtca aaataaataa 42780
cctgtatcat tggcatttta ttaaagtttt aaggaggaaa aatcattctc ttcaaaccag 42840
cctctggaag cttgtcatga gactgaaaag aattgagtat gtttaatctg aagactttta 42900
aggggtgatg tgagcagtag ctttagtaac ttaaagcagt gttttccaca tcctagggaa 42960
tcatttggag gaagtttttt aaaagcactt tttcatttta gtttcttctc tgttgatgta 43020
tattttatat ccagtaaact gcacaaatat tgtacagcta gatgaatttt tccatgcaat 43080
tttttcccat atcaagatac agaatatttc catcaactca gaagagacta gcgagtcttt 43140
tgtgactaac agtgcttaag ccccattcca tctaggtgcc attggaattt ccagggaaga 43200
agtccaagca tgtatttttg tctttttaaa aatactttct cagataattc tgctacagtt 43260
agtctactga ctgctatgaa aagacagtga tgtaagagta attaattaca tattgtgttc 43320
tggagtaaac caccagagaa catgatgaac aggctagatt tggatacagt ggttctagat 43380
tcagctgttc aaggatatgc ttaattgtta aaggagtcca acttcattta cctttttttt 43440
tttttaacca gtcttttact tgaattttgt taataagtac ctaccagaat tttcatcccc 43500
taaaaaaatc atatttaaaa tgtctaagct aatatggcca taagtagtat ttgcataaaa 43560
tgtatagatt ataaacatct attttacttt aatcacatat ataaatacat atatatgtat 43620
atatatattt ttttcttttt cttttttaga cagggcctcg ctctgtcacc caggctggag 43680
tacagtggca tgatctcagc tcactgcagc ctctgcctcc tgtactcaag cattcctccc 43740
acctcagcct cccaattagc tgggactaca ggtgtgagcc accatgcctg gctaattttt 43800
tattttttgg agagacaggg ttttgccatg ttgcccaagc tggtctcaaa ctcctgtgct 43860
caagtgatct tcccacctca gcctgcctcc caaagtgttg ggattacagg tgtgagcaaa 43920
tgtacctggc caaatctttt tttttttttt ttttttgaga ctgagtttca ctcttgcact 43980
caggctggag tgaagtggcg tgatctcggc tcactgcagc ctccgcctcc tgggttcaag 44040
caattctcct gcctcagcct cccgagtagc tgggattaca ggcgcccacc accacgccca 44100
gctaattttt gtatttttag tagggacggg gttttgccat gttggccagg ctggtctcga 44160
gcgcctgacc tcaggtgatc cacccaactc agcgtcccaa agtgctggga ttacaggcgt 44220
gagccactgc acccggccta taattttttt tttaactata ctttgtttct tccagatgta 44280
cctcccacct ttagttacta agtcagaaat tcaaagtatg tgtcaaattg gtaatgatct 44340
agaaaattaa tctctggtat ccatatgggt taaatcaaat aggcactatt tgtatactac 44400
aggtaaatat gtaaagtggt ataatctctc tgaggacagc taagtaatat agataaagaa 44460
ctttagtgtt tataaccttt tgaccttaca attctacttt taggaattaa tcctaagaaa 44520
attaaaggat ttataaagat ttatgtataa ggataaagta gttttaaact agtaaaaaac 44580
agaataacct gaaagttggt taatttctta tagacccaca atgtggccat tatgttttta 44640
aagaattttt aatagcatag gaaggaagaa atacaaaaag tatgagaaag agcaatacag 44700
agtatcatga atgctacagt ttcactggtt gtaaaactgc ttttcaaatg catagaatat 44760
gctatgcata tatcctacca gacatacatg aattgtcttt aagaaataaa taaaaattag 44820
gtatgtagca tagaggaaga agacctaaaa actaggagga tagcaaatca ttagaatatt 44880
tactaagtga aagcagaaga aaaatagtat ttgtgcttta gttcataggt gaaatttgtt 44940
gaggaacaaa accattgccc aatatttttc tttgtatgga gaatcttcct ggtacatttt 45000
ttggatgaag tatagtttac tgtgttcatg atataaaaac ctttttatat ttgcctagat 45060
attctgatat gctatttctg taccctgtgt cactgagcta atatgtctct ctcagtaaaa 45120
aagttcttca tgtattgaaa tattttagct aaactttata tggtctttat ttcaggatga 45180
atttacagga attgaaccct tgagcgagga tgccattatc acaggcttca gaaatgtaac 45240
aatttgtcct aacccagaag acacttgtga ctttgccaga gcagctcgtt ttgtatccac 45300
tccttttcat gagataatgt ccttgaagga tctcccttct gatcctgaga gactgttacc 45360
ggaagaagat ctagatgtaa agacctctga ggaccagcag acagcttgtg gcactatcta 45420
cagtcagact ctcagcatca agaagctgag gtgattgggg atttacaggt tttacaaacc 45480
agattgttta ctctcttatt ctgcatgtgc ttgtcagtta cagtaatcag ttatcaagtt 45540
cttactaact gccaggtact gtgctaagtg ctttacatga gagtagggct gccccagatg 45600
aagtgtcaat gggatttagt gattgatttg gatgtgaggg ttaaaagtaa attttgatgg 45660
tagagaaact aagtggtccg agaggagtat agtaccattg aggaaacttt gcaaagtgta 45720
catgactgac gaaaaggagg catttagttt ttctttaata ttgagtttaa aatagtggta 45780
ggatagcttt tgttaatttt atgtatttat ttatttattg aaatggagtc tcactctgtc 45840
gcccaggctg gagtgcagtg gcactatctt agctcactga aacctccgtc tcccgggttc 45900
aagcgattct cctgcctcag cctcccaagt agctgggact acaggtgcgc accatcatgc 45960
ctggcttatt tttatatttt tagtagagac ggggtttcgc catgttggcc aggctggtct 46020
caaactcctg acctcaggtg atccacccgc ctcggcctct caaagtgctg ggattacagg 46080
agtgagccac tgtgcctggc cagcttatgt gaattttaaa taggcaacta gagatgtgtt 46140
ttttaaaaaa ctatcttttg atagagaggt ggaaatgaac tatggaatag atatgaggga 46200
atggcttatg gccagggtct gacacttgtt ttaggtcagc taatttaact aattccagtt 46260
ttaggaattc tttgtaattg gcaaattttt gcttttaaag ctacattttg agaggccaga 46320
tgcagtggct cacctctgta atcctggcac tttgggaggc tgagggaggc ggatcatttc 46380
aggccaggag ttgaagacca gcctggtcaa catggctgta ctcaaaaaaa cttttttttg 46440
aaactttttc cctacaggct tttaagcaca tttgctagca tgtattcaca ttgcatgatt 46500
tgggtttctc ttttctttgc ctaacctttt cttcttgaag aaaaaaaagt ccagagaaag 46560
gataaagagg aagaaagtgt caatgttagt gtttctcaat attatggaat atagagtaga 46620
tatttactat aggtaaataa agcataaatc cagaaatgta tgctggacat ggcttattca 46680
ccaggtttag aggaggttac ctagattctg atttggggaa ataatggact tgaaaaatga 46740
gactattgct gagtgcattg gctcttgcct gtaatcccag cactttggga ggctaaggtg 46800
ggaggatcac ttgaggccag gagtttaaga ccagcctggg caacaaagtg atgccttgtg 46860
tctaataaaa ataaaaaaaa aaaatagcta ggcatggtag cactcaccca gctatcattt 46920
cctgggctca agtgattctc ccacctcagc ctcccaagta gtcccagata ttagcttttt 46980
tgttttacaa cctttcagct acttgggagg ctgaggtggg aggatcactt gagcccagga 47040
aatcaaggct gcagtgagcc atgatcgcac cactgccctc cagcctgggt gacggaatga 47100
gatcctgtct caaaaataaa atgaaaagta aaaaaaaaaa atgaggctat caaataaatt 47160
gataacaaat tataaattat ttaaacctaa attttattgt gttaaaaaat aaaagaataa 47220
cataaaatta taaaatgtgt acattaaggc caggtgcagt ggctcacgcc tataatccca 47280
gcactttagg aggctgagac gggtggacca tctgaagtca ggagttcaag accagtctgg 47340
ctaacatggt gaaaccctgt ctctactaaa aatacaaaaa tcagctgggc atggtggcag 47400
gtgcctgtaa tcccagctac tcaggaggct gagacaggag aatcacttga acccgggagg 47460
cagaggttgc agtgagccaa gatcatgcag ttgtgctcca gcctgggtga caagagcaaa 47520
actccatctc aaaaaaaaga aaaatgtata cattaagaat ttatgaaatt ataacaaagt 47580
tgatatatat tattcctata agaattaact tatttttgat tcttttagcc caattattga 47640
agacagtcgt gaagccacac actcctctgg cttctctggt tcttctgcct cggttgcaag 47700
cacctcctcc atcaaatgtc ttcaaattcc tgagaaacta gaacttacta atgagacttc 47760
aggtaggata tacataccac tatatccatg cctagtgaac acttgtttat ctcagcaaac 47820
tgagctgtat gtttttcttt ttttgagaca gggtctcact ctgtcaccca ggatggagtg 47880
cagtggcaca atcaaactca ctgggctcag gtgatcctcc tacctcagcc tcccgagtag 47940
ctgggaccac aactgtgcca ccaccaattt ttgtattttt tgtagaggtg gggtttcgcc 48000
atgttgccca ggctggtctc aaactcctgg cctcaaagga tcctcccgcc tcagcctccc 48060
actccctggg attataggtg tgagccacca tgcccagtct atgtgttttt ccttcttaaa 48120
gaagttgccg gccgggtgcg gtggctcacg cctgtaatcc cagcactttg ggaggccgag 48180
gcgggtggat cacgagggtc aggagatcga gaccatcctg gctaacatgg ggaaacccca 48240
actctactaa aaatacaaaa aaattagccg ggcatggtgg cgggtgtctg tagtcccagc 48300
tactctggag gctgaggcag gagaatggcg tgaacccggg aggcggagct tgcagcagtg 48360
agccgagatg gcgccactgc actccagcct gggcaacaga gcgagactcc gtctcaaaga 48420
agttgccata aattgtgaaa tttctagagt agattagtac gaagtgaaca cagtttcata 48480
aacacctgag acaggtgagt gtagttaaat taacagtgct gactgtgtaa tcttgatttt 48540
ttttttcttc tactctgtta taatatccat tttaagcatt agggtttttt tggtgatata 48600
ttttcacctt tccctcccac tggcagaaaa ccctactcag tcaccatggt gttcacagta 48660
tcgcagacag ctactgaagt ccctaccaga gttaagtgcc tctgcagagt tgtgtataga 48720
agacagacca atgcctaagt tggaaattga gaaggaaatt gaattaggta agtaccattg 48780
aactcatgtc ctctggttca tgacagtata caaataagtg attatttgta cttaagcttg 48840
atgcttgagc actgtaaata ttcctagatt gtatttttta aaaaagcaat atagaggatg 48900
acacatcagt aacttcatgt cctaataata ggaattatgt cttctcctct tgcaatcttt 48960
aacaaattat ttttaaaagt attctagata ctactaactg gcaaatacac cagtgcctct 49020
atcccttaaa ccaggaggta aaagctacag ggctgtatat gttcacagtg atttttaaat 49080
ggaatcaaac tttctcaaca ggtaatgagg attactgcat taaacgagaa tacctaatat 49140
gtgaagatta caagttattc tgggtggcgc caagaaactc tgcagaatta acagtaataa 49200
aggtgggact gattctttat aatttcagtt actttgtaaa taatacggat tggagcaata 49260
actgtcctca tgttaccatc aaatctttct aataatctct ttcaatatgt ccaaatatat 49320
taagtatcct ttcagtttca ttttttttag gaaatctctg ctgatacttt ctggcctgct 49380
ccaatctgga caagttatac attagctttc acacaatcac cacacacaat caccttggaa 49440
tttccattta ttatcatcct aggtattcac attacctttg tcttatattg gatacctagt 49500
ttctttttat ctttgttttt taaaggacac ggtctctgtc atccaggctg gagtacagta 49560
gcatgatcac ggctcactgc agcctcaacc tcttgagctc aagcaatcct cccacctcag 49620
cctctggaat agctgggacc gtaggtgcac gccaccactc ccagctaatt attttttgta 49680
gagacggggg cctctctgtg ttgcctaggc tggtcttgaa ttcatggctc aagcagtcct 49740
cccaccttgg cctcccaaag aactggatta caggcatcta actttgcttt tgaatttttt 49800
tgccattctg agtctcaaag ctttgtgtga agttattttt ccttctttct ggatccttat 49860
aggatcttat tcttgtcccc actattctga aatgtcacaa ttacatgcct tttcataagt 49920
ttgttgtcac ttatgtgcta ggtactcaat ggccatttca atctgttaat tccctcagtt 49980
ctgagaaatt ttcttcaatg ggaaaattat ttttcccctc agttttctct gttctcttat 50040
tctctaattc cttttattag aggtgtatat ggcatctttg gacagaacct ctaaaaattt 50100
aacttttttt ctcctatatt ctctctttgt ctttttactt tactttctga gtatattatc 50160
agcttaatat ttttggtctt tttactaggt ttttatttct atatttaatt ttcaagagct 50220
ctttttaaaa ttttttaccc ctttgtcatc tgtttcttct tgttttcttt tttgtctgtt 50280
ttgatctctc tcacactaca ggctttcttc aagtctttgg ctctctattc gtatttaagt 50340
atgggacatt gaaagctctg tgtatatgga aagaccttga cagctgtgga cctcaatgta 50400
ggatgatcta gtttggccat tttattggaa aaccctccaa tctttagatc ctttctcttg 50460
acctgatcat agaagtcttc tccctcagag aagacttcta attttctgcc tggagcatat 50520
aagcctggct gctagctttc tgaaatctga gtgaggaaat tggtctgaag aatagaagag 50580
cagggaggtg catcttaact gctgcatata taacatctga tatatatact ttttcctgtt 50640
ttctatgtta tttctacccc cctcagtggt gcctagtgcc ctctagtcca gagcccttct 50700
gttttatact cactaggtaa taaacttctg gacttcgaga ataggggaga ggtagttgct 50760
gggctgggct atgggagcag aggagggaag ctggggtcta ccttcctgtt tttttgtttt 50820
tttttttctt cgagacggag ttttgctctt gtcaccctgg ctggagtgca atggcatgat 50880
tttggctcac tgcaacctct gcctcccagg gtcaagcgat tctcctgtct cagcctcccg 50940
cgtagctggg attacaggca cccgccacca aaagcctagc taattttttg tatttttagc 51000
agagacgggg tttcacccct tcataatcat tggtcaggct ggtcttgaac ccctgatgtc 51060
aggtaatcca cacgcctcag cctcccagag tgctgggatt acaggcatga gccactgcac 51120
taggcctacc ttcctcttaa atgggattca atcactcctg tcttagctcc accctcagcc 51180
tcacttccat gggtaattgg tgctgccagt tatatagtat aggaaaatag ccttgtagtg 51240
taaatgtagc tcagctttct cctctgccaa aatcagtttt tattctaatt ggattgttac 51300
ctcctgttct ctttccagct tatcctcttt ccagaatttg ttgttattgt gtcttttata 51360
gtagatttat gcctttaaaa atatctcttt attatttctc tatcagaagg gctggaagga 51420
atgtgtttca acctgccagc cataaccata gacttaactg aacttatttt taaaatacaa 51480
tgtcttacag gtatcttctc aacctgtccc atgggacttt tatatcaacc tcaagttaaa 51540
ggaacgttta aatgaagatt ttgatcattt ttgcagctgt tatcaatatc aagatggctg 51600
tattgtttgg caccaatata taaactgctt cacccttcag gtctgtaata ctaaaaacat 51660
aatttaaagt cctgaagtag agagatttgt gctccattta gcaaaggaat ttagtacaaa 51720
attcctgtca atcttctaga aatagaccaa ttcaagtata agttagaagc attgataatt 51780
ttctcgttat tttgaccaaa gatctctttg gtattttttt aacttttttt ggtccgttgt 51840
caagcataaa taaaagtaga attgtacaat gaactcccat gaactagtca tctatgataa 51900
tcttagctca tggtcactct tgttttagct atactacccc cactggatag tttttaaaac 51960
ccagacacaa tatgtcattt tactcttcgg tttgttctta agaaggtttg ctatggattt 52020
tgatgataat atgaattctc aaaaatggtt ggaatgaggg tattttaaat ccatttatta 52080
agtacctatt ttgggccagg ctcatgcttg atgcccttca tcattatgtc attaaatcct 52140
tacaaacaat cttatgggag atggcagtgt tattaaaact gggacataga ctcagtctac 52200
agaggtgcct acgttccagt agagaacaag gaagactaca aaccatcagt tttcaaggta 52260
ttgagtataa ctacgatctg ccaaacttga gaaatagtga gttttctgtc cttcaatttc 52320
caggatcttc tccaacacag tgaatatatt acccatgaaa taacagtgtt gattatttat 52380
aaccttttga caatagtgga gatgctacac aaagcagaaa tagtccatgg tgacttgagt 52440
ccaaggtgtc tgattctcag aaacaggttg gtccttttca ttcttataat tctgccagct 52500
gtctcttaaa acatggatag ttgccacttt tttttttctt ttttgaggcg agggtctcac 52560
tctgtcacct aggttggagt acagtggcat gatcttggct cactgcagcc tccatctccc 52620
aggttcaaac gattctccca tcttaacctt gctagtagct gggaccacag gcgcgcacca 52680
ccacacctgg ctaatttttt gtattttttg gtagagatga ggtttcacca tgttgcccag 52740
gctggtctca aactcctggc ctcaagtgat ctgcccacct cagcctccca aagtgctggg 52800
attataggcg tgagccactg cacccggcca agttgccaat ttttaaagcc ttttgataaa 52860
tgccatatcg aggaacatat tatgttaaga gagtatttac ctaaaagtca aaaatcatta 52920
agaatagttt aaaataattc aaagaaataa acacattgag gaaatagatt aaatcagata 52980
aaagaattaa tcactgagta ttgtgatgat atatgtcaag atgagatata aaatatgaat 53040
attttgagga atataaagtg gattgtttag tcattctttg agtgggacca gtgccactct 53100
agcgaggatg ccagcaaaat caaggcacta ctcagtttca tagaccaaag cttaagtcag 53160
gcctaactga cctgttagcc aagagaagtg ggtaaaacca gagttcaaat acaaactatg 53220
ccaaggaatg gggtttagtg ttcaaattaa acccagtgtg tccatcaggt tcaaggggtg 53280
agcacagagc aggaaataat aaatgaatac taaggactga gaaaatatag atcacgttca 53340
ggcattaact aggcaaaaac agtccaacat ttttgctttg tgaaaagtac tagaggacta 53400
ctatattctt ttagtgatca ttggtgttat agtatttgag taaaagcagc ctggtttaaa 53460
gatgctgtgt ctgcccaacc ctgtgtcttg ggtgaggtgt taactttgtt tctgaggcca 53520
ctggtataca ctaatagctg gacttactct ttacatttct tctgaatact taatctatca 53580
gaagagattg aattagactc taaattatag ttaacgtgga aattaaaaga accctcaatg 53640
tgttcctgtg attgtaacca aaagaaccag agaatcccac cttctcccct gagatagcag 53700
agtcaaaggc tttcccagac ataatgtagc agcatttctc atccagggca ccataggtat 53760
tttgggtgag acaattcttt gtgcaggtgt gttccaagca atgcaggatg ttttatattc 53820
ctattccccc ccacccaccc aattaagtgc aagtaacaat cccctaagcc gttgtgacca 53880
ccaaaaatcc ccccaaattt ccaagtatga gaacccctgg tatattttca ctctacttaa 53940
cattaaaatg acagtgctga aattcccagg gctatggaaa ttggaagcag aggttttttc 54000
taagcctttt agaattggcc atttgtggtc taatgaagta cgataaccct tctctcagcc 54060
actagaggct ctaggaaagt ccatagtatt aaagaggcat tgctttttac tttgtcactg 54120
cttatcaaat ttaatcagaa atttcacata gattcataag gaattaaaag ccagaaaggg 54180
gccgagcaca gtggctcatg cctataatca atcccagcac ttttggaggc tgaggcgggc 54240
agatcacctg aggttgggag ttcaagacca gcctgaccaa catggagaaa ccccatccta 54300
ctaaaaatac aaaattagcc aggtatggtg gtgcatgcct gtaatcccag ctacttggga 54360
ggctgaggaa ggagaattgc ttgaactcag gaggcagagg ttgtggtgaa ctgagatcgc 54420
accattgtac tccagtctgg gcaacaagag caaaattctg tctcaaaaaa aaagccagag 54480
gccgggcgca gtagctcacg cctgtaatcc cagcattttg ggaggccgag gcgggcggat 54540
cacgaggtca ggagatcaag accatcctgg ctaacacagt gaaaccctgt ctctactaaa 54600
aatacaacaa gatagccagc cgtggtggca ggtgcctgta gtcccagcta ctcaggaggc 54660
tgaggcagga gaatggcgtg aacccgggag gcagagcttg cagtgagcca agatcatgcc 54720
actgcactcc agcctgggtg acagagcgag actccatctc aaaacaaaac aacaacaaaa 54780
gccagaaagg gctggatgca gtggttcaca tctgcaatcc cagcactttg ggaggcagag 54840
gcaggaggat ctcttgaggc caggagttca agaccagcct ggtcaacata gcaagaccct 54900
gtctctacaa aaataaaata aaagccagaa agaacctttt gaaattgctt agtttagttg 54960
cttactttag tttctgcata ttttttgtga ggaaaatgag atccaaaaaa atggaatgtc 55020
ctacccaaag taacagtgag tgagtagctg attagagggc taggacacct tcatgcatgc 55080
ttctttttat taatctatga gacatttttt ccctatgcct ccaaagttat ataaatattt 55140
tacaattaca ctgggcatgg tgactcacat ctgtaatccc agcactttgg gagaccaagg 55200
cagaggatca cttgagccta ggagttcaag accagtctgg gcaatataat gagacctcat 55260
ctctacaaaa aattaagaaa ttagccaggc atggtggcac acaccagtag tcccagctac 55320
tcgggaggct gagatgggag gatcgcttga acctaggagg cagagactgc actgagctga 55380
gatcgcacca ctgtactcca gcctcagtga caagagtgta gaccttgtct aagaaaccaa 55440
acaaaacaca cacatgcaca cactttacat atatatataa aatacatatg tatattttat 55500
atatatcaga atccacgatc cctataacta tatatatact atatatatat atatatatat 55560
atattttttt ttttttttaa ttatagtata gttttatggt ggccaaaaaa ggttggctct 55620
tgtgccaagg aaaaatgaga gcaattatca attttaaagt aaaatacata gatcattctg 55680
tgccgtggag gtatgtaatt ggagtagtta aagactgtat ttaggaatat tgcaccaata 55740
tcaggagttt gagggaatta attgagaaaa acagacaaaa ggaacacatg aaaacccact 55800
cttttcattt ataaacagtt cctatgtccc cttggagaat agcattattg cataggatag 55860
ataaacccaa ggaaaacaaa attaattgat aattaattag tattataaag atttttttag 55920
taaataactg gaattacaag taagagtaag ataaaatatg gtgttttaca agaaatttta 55980
caatacagat aggactttat aaaacagact tgcattgttt tccattaaac tctggaagga 56040
agaatctaaa caatacttgg aaagcctatc tggaatagta aacaagaaag gctatgacac 56100
ctataaaatt ttaatttcct ccatcataat tcctgtcagt gtataaatca ttgcaattgt 56160
atgtgttaat gtgtacagta cagggaagaa gcctgtgctc tgcttccata cttactttat 56220
ataatatgga agcttgataa atgtttaatg gtggccatgc accgtgattg aaatatactt 56280
tgtgtcacca aagtggtgac attccttccg cattgggtgg acactgccac tgctctgtct 56340
tacaggtgca ttttcaaaat taaccactgg agggagttgt tggcatagct aagatgtacc 56400
caaggtacct ttttttttta aagaccagct atgcagcttc tttcatggcc tatttttatt 56460
atctccttct cttaaatctg ggctcagaat ccacgatccc tatgattgta acaagaacaa 56520
tcaagctttg aagatagtgg acttttccta cagtgttgac cttagggtgc agctggatgt 56580
ttttaccctc agcggctttc ggactgtaca gatcctggaa ggacaaaaga tcctggctaa 56640
ctgttcttct ccctaccagg taagtgtaaa acaagcctga gcaaatatgg agagggtttc 56700
ttaatctctt tattatctag ataagctata aaagctactg tttactgata ccgactccta 56760
gaatagatga cctagttttc aaatatcacc aagtcaagta aaatgtaaca tttttgtgtt 56820
acagcattga agaatataca catacatgtg caaacacatg actaactctg taaccgagtg 56880
ccagggccac tcctactgcc taccacccat gtaatctttt ataagtcatt ttctgtgatc 56940
ttctctgtaa aatagggata acagtctctg ctatgtgttt atcagaattg ttatgaggag 57000
taaatgaagt aatgtatata aaaagaacat tagcacaaat gtaaagtctt ttgtatggtg 57060
gcattatatg cagaaattcc ttctaactca gctttagaca taagacattt gctgattgaa 57120
tatgtagcac aaacctgaac taatcatgtg gaccccattt agatcacagc tggagttcat 57180
gcaaactcag taggtctaca aatttgaatg tgatagtcca aatatttcat cttttgttct 57240
taaggataat tcctagaatt ggctctattg atcacttctt tggagagctt ctccctttac 57300
tgtaagggtg aggaacagtc tactaaaatg tatgtcataa aataaactta gttaagcact 57360
gtaatacctt tcaacttcct accgaaataa gctgccatgg tagaggcaga gaattatttt 57420
agctgatggt gctttttgtg atttcaggta gacctgtttg gtatagcaga tttagcacat 57480
ttactattgt tcaaggaaca cctacaggtc ttctgggatg ggtccttctg gaaacttagc 57540
caaaatattt ctgagtaagt attgatgaat gtcagggtct ctgcctgtcc caataatttt 57600
ctgtttctct tgggtgctat ctctgctttg gcagccttag ttttttaatc caaatgccat 57660
ggttccagta gtttcagcca gttttcatta gagtatcagc agagcagcta gtgcaggaaa 57720
aaggaactgc ttactaaaaa taagattcaa aactattcag acttcaggac atcattctga 57780
atctagctgt atcttccaga ctacagctat agtatggaag cttccctgtt tagatatgtg 57840
aaaagaagca tttcatgaga ataattttct aactaattgg tgttagcctt aaattccttt 57900
ttctttattt atttattttt tgagacggag tctcgctctg ttgcccaggc tggagtgcag 57960
tggcatgatc tcggctcact gcaacctctg cctcccaggt tcaagtgatt ctcctgcttc 58020
agcctcctga gtagctggga ttacaggcgt gcgccaccat gcctggctca tttttgtatt 58080
tttagtagag atgcggtttc actacgttgg ccaggctgat ctcgaactcc tgaccttgtg 58140
atccgcccgc ctcggcctcc caaagtgcta ggattacagg tgtgagccac cgtgtctggc 58200
ctaaattcct ttttaatagc aattattacc aaaagttaat aagcatcctt tgaaaagact 58260
tacatttcta aactatatgc taattttagg ctatttttta tttaataagt ggatagaacc 58320
aaaccagata actgactctc ctggagaaga agtaagtggt ctcttaataa gcactgcttg 58380
gtctcagaac cttagtactc cctcaagcct gctcataaaa cttactaagt cagccgggca 58440
tggtggctca cacctgtaat cacagcactt tgggaggccg aggcagatta cctgaggtca 58500
ggagtttgag agcagcctgg gcaacatggc gaaaccttgt ctctactcaa aatacaagaa 58560
aattagctgg gtgtggtggc acatgcctgt aatcctagct acttgggaag ctgaggcacg 58620
ggaatcactt gaacctggga ggcagaggtt gcagtgagct gagatcgcgc cactgcactc 58680
cacccagggc aacagagtga gactccgtct caaaaaaaac taagtatcta cgttccactt 58740
tagcttatct tagcaaataa gttcccagcc tgtcacctat tgttatattc tttggttaaa 58800
aaaaaaaatg agtgttgaag atttaatgcc ccttctctat tttcatcttt gaataattga 58860
attgtacttt tctcttcatt taattcagaa cttggccagt gttgtctctt acatgaactt 58920
ttaaaaatag gcttgaaata caatgtaaga catataggat ggatataggc atgtccactt 58980
ggctatggtc caggcaggtc tggctaacac aagcagaaac aagtggggtc agttggggtt 59040
tcctaacagc cctgccttat ctaataaggg aagtttctct gatcaaaaga aaataataag 59100
aagcaaaggt acaaacatat taagcagtag ttagtttagt caagcttacg attatcagag 59160
aattgtaaag aagatccact actggggtag gagaaaggag ctgtagcctt tttaatgacc 59220
tagactctag gaaagttaga ggaaataaaa ttcctttttc ttctatttgt agaagaaaag 59280
tgctatgtct tagtacacag aggaaattta tagatttaga tgagagatct tctttccctt 59340
tatgtgcatt gtatcttggc ttttcccact atggtagccc ttttttgtag ttcttccctg 59400
ggctttcaaa ggactatttg aatgatctct aaccctagag ttctaggtat taccttacac 59460
cattttggtg cataaatgta ccactgagtt aaactaaaag gaattataat tttcatatgc 59520
ctaatcttga tggaaatggt tttatatatt tttaggctaa aagatggtga attgtggaat 59580
aaattctttg tgcggattct gaatgccaat gatgaggcca cagtgtctgt tcttggggag 59640
cttgcagcag aaatgaatgg ggtttttgac actacattcc aaagtcacct gaacaaagcc 59700
ttatggaagg tagggaagtt aactagtcct ggggctttgc tctttcagtg agctaggcaa 59760
tcaagtctca cagattgctg cctcagagca atggttgtat tgtggaacac tgaaactgta 59820
tgtgctgtaa tttaatttag gacacattta gatgcactac cattgctgtt ctactttttg 59880
gtacaggtat attttgacgt cactgatatt ttttatacag tgatatactt actcatggcc 59940
ttgtctaact tttgtgaaga actattttat tctaaacaga ctcattacaa atggttacct 60000
tgttatttaa cccatttgtc tctacttttc cctgtacttt tcccatttgt aatttgtaaa 60060
atgttctctt atgatcacca tgtattttgt aaataataaa atagtatctg ttaaatttgt 60120
gcttctaa 60128
<210> 2
<211> 1050
<212> PRT
<213> 人源
<400> 2
Met Ala Ala Val Lys Lys Glu Gly Gly Ala Leu Ser Glu Ala Met Ser
1 5 10 15
Leu Glu Gly Asp Glu Trp Glu Leu Ser Lys Glu Asn Val Gln Pro Leu
20 25 30
Arg Gln Gly Arg Ile Met Ser Thr Leu Gln Gly Ala Leu Ala Gln Glu
35 40 45
Ser Ala Cys Asn Asn Thr Leu Gln Gln Gln Lys Arg Ala Phe Glu Tyr
50 55 60
Glu Ile Arg Phe Tyr Thr Gly Asn Asp Pro Leu Asp Val Trp Asp Arg
65 70 75 80
Tyr Ile Ser Trp Thr Glu Gln Asn Tyr Pro Gln Gly Gly Lys Glu Ser
85 90 95
Asn Met Ser Thr Leu Leu Glu Arg Ala Val Glu Ala Leu Gln Gly Glu
100 105 110
Lys Arg Tyr Tyr Ser Asp Pro Arg Phe Leu Asn Leu Trp Leu Lys Leu
115 120 125
Gly Arg Leu Cys Asn Glu Pro Leu Asp Met Tyr Ser Tyr Leu His Asn
130 135 140
Gln Gly Ile Gly Val Ser Leu Ala Gln Phe Tyr Ile Ser Trp Ala Glu
145 150 155 160
Glu Tyr Glu Ala Arg Glu Asn Phe Arg Lys Ala Asp Ala Ile Phe Gln
165 170 175
Glu Gly Ile Gln Gln Lys Ala Glu Pro Leu Glu Arg Leu Gln Ser Gln
180 185 190
His Arg Gln Phe Gln Ala Arg Val Ser Arg Gln Thr Leu Leu Ala Leu
195 200 205
Glu Lys Glu Glu Glu Glu Glu Val Phe Glu Ser Ser Val Pro Gln Arg
210 215 220
Ser Thr Leu Ala Glu Leu Lys Ser Lys Gly Lys Lys Thr Ala Arg Ala
225 230 235 240
Pro Ile Ile Arg Val Gly Gly Ala Leu Lys Ala Pro Ser Gln Asn Arg
245 250 255
Gly Leu Gln Asn Pro Phe Pro Gln Gln Met Gln Asn Asn Ser Arg Ile
260 265 270
Thr Val Phe Asp Glu Asn Ala Asp Glu Ala Ser Thr Ala Glu Leu Ser
275 280 285
Lys Pro Thr Val Gln Pro Trp Ile Ala Pro Pro Met Pro Arg Ala Lys
290 295 300
Glu Asn Glu Leu Gln Ala Gly Pro Trp Asn Thr Gly Arg Ser Leu Glu
305 310 315 320
His Arg Pro Arg Gly Asn Thr Ala Ser Leu Ile Ala Val Pro Ala Val
325 330 335
Leu Pro Ser Phe Thr Pro Tyr Val Glu Glu Thr Ala Gln Gln Pro Val
340 345 350
Met Thr Pro Cys Lys Ile Glu Pro Ser Ile Asn His Ile Leu Ser Thr
355 360 365
Arg Lys Pro Gly Lys Glu Glu Gly Asp Pro Leu Gln Arg Val Gln Ser
370 375 380
His Gln Gln Ala Ser Glu Glu Lys Lys Glu Lys Met Met Tyr Cys Lys
385 390 395 400
Glu Lys Ile Tyr Ala Gly Val Gly Glu Phe Ser Phe Glu Glu Ile Arg
405 410 415
Ala Glu Val Phe Arg Lys Lys Leu Lys Glu Gln Arg Glu Ala Glu Leu
420 425 430
Leu Thr Ser Ala Glu Lys Arg Ala Glu Met Gln Lys Gln Ile Glu Glu
435 440 445
Met Glu Lys Lys Leu Lys Glu Ile Gln Thr Thr Gln Gln Glu Arg Thr
450 455 460
Gly Asp Gln Gln Glu Glu Thr Met Pro Thr Lys Glu Thr Thr Lys Leu
465 470 475 480
Gln Ile Ala Ser Glu Ser Gln Lys Ile Pro Gly Met Thr Leu Ser Ser
485 490 495
Ser Val Cys Gln Val Asn Cys Cys Ala Arg Glu Thr Ser Leu Ala Glu
500 505 510
Asn Ile Trp Gln Glu Gln Pro His Ser Lys Gly Pro Ser Val Pro Phe
515 520 525
Ser Ile Phe Asp Glu Phe Leu Leu Ser Glu Lys Lys Asn Lys Ser Pro
530 535 540
Pro Ala Asp Pro Pro Arg Val Leu Ala Gln Arg Arg Pro Leu Ala Val
545 550 555 560
Leu Lys Thr Ser Glu Ser Ile Thr Ser Asn Glu Asp Val Ser Pro Asp
565 570 575
Val Cys Asp Glu Phe Thr Gly Ile Glu Pro Leu Ser Glu Asp Ala Ile
580 585 590
Ile Thr Gly Phe Arg Asn Val Thr Ile Cys Pro Asn Pro Glu Asp Thr
595 600 605
Cys Asp Phe Ala Arg Ala Ala Arg Phe Val Ser Thr Pro Phe His Glu
610 615 620
Ile Met Ser Leu Lys Asp Leu Pro Ser Asp Pro Glu Arg Leu Leu Pro
625 630 635 640
Glu Glu Asp Leu Asp Val Lys Thr Ser Glu Asp Gln Gln Thr Ala Cys
645 650 655
Gly Thr Ile Tyr Ser Gln Thr Leu Ser Ile Lys Lys Leu Ser Pro Ile
660 665 670
Ile Glu Asp Ser Arg Glu Ala Thr His Ser Ser Gly Phe Ser Gly Ser
675 680 685
Ser Ala Ser Val Ala Ser Thr Ser Ser Ile Lys Cys Leu Gln Ile Pro
690 695 700
Glu Lys Leu Glu Leu Thr Asn Glu Thr Ser Glu Asn Pro Thr Gln Ser
705 710 715 720
Pro Trp Cys Ser Gln Tyr Arg Arg Gln Leu Leu Lys Ser Leu Pro Glu
725 730 735
Leu Ser Ala Ser Ala Glu Leu Cys Ile Glu Asp Arg Pro Met Pro Lys
740 745 750
Leu Glu Ile Glu Lys Glu Ile Glu Leu Gly Asn Glu Asp Tyr Cys Ile
755 760 765
Lys Arg Glu Tyr Leu Ile Cys Glu Asp Tyr Lys Leu Phe Trp Val Ala
770 775 780
Pro Arg Asn Ser Ala Glu Leu Thr Val Ile Lys Val Ser Ser Gln Pro
785 790 795 800
Val Pro Trp Asp Phe Tyr Ile Asn Leu Lys Leu Lys Glu Arg Leu Asn
805 810 815
Glu Asp Phe Asp His Phe Cys Ser Cys Tyr Gln Tyr Gln Asp Gly Cys
820 825 830
Ile Val Trp His Gln Tyr Ile Asn Cys Phe Thr Leu Gln Asp Leu Leu
835 840 845
Gln His Ser Glu Tyr Ile Thr His Glu Ile Thr Val Leu Ile Ile Tyr
850 855 860
Asn Leu Leu Thr Ile Val Glu Met Leu His Lys Ala Glu Ile Val His
865 870 875 880
Gly Asp Leu Ser Pro Arg Cys Leu Ile Leu Arg Asn Arg Ile His Asp
885 890 895
Pro Tyr Asp Cys Asn Lys Asn Asn Gln Ala Leu Lys Ile Val Asp Phe
900 905 910
Ser Tyr Ser Val Asp Leu Arg Val Gln Leu Asp Val Phe Thr Leu Ser
915 920 925
Gly Phe Arg Thr Val Gln Ile Leu Glu Gly Gln Lys Ile Leu Ala Asn
930 935 940
Cys Ser Ser Pro Tyr Gln Val Asp Leu Phe Gly Ile Ala Asp Leu Ala
945 950 955 960
His Leu Leu Leu Phe Lys Glu His Leu Gln Val Phe Trp Asp Gly Ser
965 970 975
Phe Trp Lys Leu Ser Gln Asn Ile Ser Glu Leu Lys Asp Gly Glu Leu
980 985 990
Trp Asn Lys Phe Phe Val Arg Ile Leu Asn Ala Asn Asp Glu Ala Thr
995 1000 1005
Val Ser Val Leu Gly Glu Leu Ala Ala Glu Met Asn Gly Val Phe
1010 1015 1020
Asp Thr Thr Phe Gln Ser His Leu Asn Lys Ala Leu Trp Lys Val
1025 1030 1035
Gly Lys Leu Thr Ser Pro Gly Ala Leu Leu Phe Gln
1040 1045 1050
<210> 3
<211> 20
<212> DNA
<213> 人工序列
<400> 3
gcaccgacaa ttccaagctc 20
<210> 4
<211> 21
<212> DNA
<213> 人工序列
<400> 4
tgtgcttcgt tgtggtacag a 21
<210> 5
<211> 20
<212> DNA
<213> 人工序列
<400> 5
gcaccgtcaa ggctgagaac 20
<210> 6
<211> 19
<212> DNA
<213> 人工序列
<400> 6
tggtgaagac gccagtgga 19

Claims (10)

1.骨髓瘤细胞中的分子标志物BUB1B基因，其特征在于序列如SEQ ID NO.1所示。
2.骨髓瘤细胞中的分子标志物BUB1B蛋白，其特征在于序列如SEQ ID NO.2所示。
3.骨髓瘤细胞中的分子标志物BUB1B基因在制备诊断多发性骨髓瘤的产品中的应用。
4.根据权利要求3所述的应用，其特征在于所述产品包括：通过RT-PCR、实时定量PCR、免疫检测、原位杂交、芯片或高通量测序平台检测BUB1B基因表达水平以诊断多发性骨髓瘤的产品。
5.根据权利要求4所述的应用，其特征在于所述用RT-PCR诊断多发性骨髓瘤的产品至少包括一对特异扩增BUB1B基因的引物；所述用实时定量PCR诊断多发性骨髓瘤的产品至少包括一对特异扩增BUB1B基因的引物；所述用免疫检测诊断多发性骨髓瘤的产品包括：与BUB1B蛋白特异性结合的抗体；所述用原位杂交诊断多发性骨髓瘤的产品包括：与BUB1B基因的核酸序列杂交的探针；所述用芯片诊断多发性骨髓瘤的产品包括：蛋白芯片和基因芯片，其中蛋白芯片包括与BUB1B蛋白特异性结合的抗体，基因芯片包括与BUB1B基因的核酸序列杂交的探针。
6.根据权利要求5所述的应用，其特征在于所述用实时定量PCR诊断多发性骨髓瘤的产品至少包括一对特异扩增BUB1B基因的引物，序列如：SEQ ID NO.3和SEQ ID NO.4所示。
7.一种用于诊断多发性骨髓瘤的工具，其特征在于所述工具能够检测样本中BUB1B基因的表达。
8.根据权利要求7所述的工具，其特征在于所述工具包括芯片、试剂盒、试纸或高通量测序平台。
9.根据权利要求8所述的工具，其特征在于所述芯片包括基因芯片或蛋白质芯片，所述基因芯片包括固相载体以及固定在固相载体的寡核苷酸探针，所述寡核苷酸探针包括用于检测BUB1B基因转录水平的针对BUB1B基因的寡核苷酸探针；所述蛋白质芯片包括固相载体以及固定在固相载体的BUB1B蛋白的特异性抗体；所述试剂盒包括基因检测试剂盒和蛋白免疫检测试剂盒；所述基因检测试剂盒包括用于检测BUB1B基因转录水平的试剂；所述蛋白免疫检测试剂盒包括BUB1B蛋白的特异性抗体；所述试纸包括用于检测BUB1B基因转录水平的试纸；所述高通量测序平台包括用于检测BUB1B基因转录水平的试剂。
10.根据权利要求9所述的工具，其特征在于所述检测BUB1B基因转录水平的试剂包括针对BUB1B基因的引物和/或探针。
CN201710351995.XA 2017-05-18 2017-05-18 分子标志物bub1b基因及其应用 Pending CN107119055A (zh)

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CN109735612A (zh) * 2018-12-26 2019-05-10 暨南大学 川崎病冠状动脉瘤并发症的生物分子标志物及其试剂盒
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