CN114214398B - 突变的fbn1基因及马凡氏综合征检测试剂盒 - Google Patents
突变的fbn1基因及马凡氏综合征检测试剂盒 Download PDFInfo
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Abstract
本发明涉及人类遗传学和内科心血管技术领域，具体涉及了一种突变的FBN1基因，在基因组位置chr15:48717688处，碱基A突变为碱基T；参考基因组版本是GRCh37。本发明还涉及一种马凡氏综合征检测试剂盒，包括用于扩增突变的FBN1基因的引物。本发明提供的突变的FBN1基因可以作为临床辅助诊断的生物标志物；检测该变异的携带者，为受试者提供优生优育指导和遗传咨询，减少患儿出生，对马凡氏综合征的早期诊断，或者辅助临床判断具有重要意义。
Description
技术领域
本发明涉及人类遗传学和内科心血管技术领域，尤其涉及突变的FBN1基因及马凡氏综合征检测试剂盒。
背景技术
马凡氏综合征(MFS)为常染色体显性遗传的结缔组织病。1990年，Kainulainen等应用连锁分析的方法将马凡氏综合征的致病基因定位于15号染色体上；1991年，Dietz等进一步确定其基因定位于15q15-q21.3。同年，Dietz等首先在马凡氏综合征病人里发现了两种突变的FBN1基因，并提出FBN1基因突变是马凡氏综合征的致病原因。
FBN1基因转录产物为10kd的mRNA，其编码产物为原纤维蛋白1(FBN1)前体，为分泌性糖蛋白，向对方分子量为350000，有2871个氨基酸构成，其中14％为半胱氨酸。除去信号肽，原纤维蛋白前体还有4个不同的结构区域，这些重要的结构区域在维持微纤维正常形态和功能方面发挥着不可替代的作用。突变的FBN1基因所致的疾病，又称为FBN1病，具有高度临床异质性，疾病谱从严重的致死性新生儿马凡氏综合征至全身异常的晶状体异位。
FBN1基因的突变率高，几乎所有的突变在受累的个人和家庭中都是独特的，没有明显的热点位置。从分子水平揭示与FBN1基因相关的马凡氏综合征的发病机制，能够马凡氏综合征的临床治疗提供理论依据，但是目前仍存在大量未知的FBN1基因突变位点，进一步发现新的FBN1基因的突变位点将有助于进一步研究单基因高血压中的马凡氏综合征，对马凡氏综合征的早期诊断，或者辅助临床判断具有重要意义。
发明内容
本发明的目的是针对马凡氏综合征，提供一种突变的FBN1基因及马凡氏综合征检测试剂盒。
本发明提供的技术方案如下：
一、本发明提供一种突变的FBN1基因，在基因组位置chr15:48717688处，碱基A突变为碱基T；参考基因组版本是GRCh37。
优选地，在基因组位置chr15:48717667-chr15:48717716处，突变的FBN1基因的序列为SEQ ID NO:2。
二、本发明还提供了马凡氏综合征检测试剂盒，包括用于扩增突变的FBN1基因的引物。
优选地，引物的序列为SEQ ID NO:7和SEQ ID NO:8。
三、本发明的原理和有益效果在于：
本发明公开的突变的FBN1基因可以作为临床辅助诊断马凡氏综合征的生物标志物，对马凡氏综合征的早期诊断，或者辅助临床判断具有重要意义；基于突变的FBN1基因开发的检测试剂盒，可以检测出具有突变的FBN1基因的患者，为受试者提供优生优育指导和遗传咨询，减少患儿出生。
附图说明
图1为实施例1的家系图；
图2为实施例1中先证者的Sanger测序图；
图3为实施例1家系中未患病成员的Sanger测序图。
具体实施方式
下面通过具体实施方式进一步详细说明：
实施例1-先证者验证实验
样本来源：福建医科大学附属协和医院，在先证者(男，31岁)及其家属自愿签署知情同意书的前提下，寄送5-10mL全血样本，建立病历资料库，详细记录先证者病情、家系情况等资料。本研究已得到本单位伦理委员会批准。
先证者病史描述：
表1先证者病史描述
采用Sanger测序法对先证者及其家属的FBN1基因进行基因检测，具体步骤如下：
S1、提取基因组DNA；
采用江苏百世诺医疗科技有限公司的磁珠法全血基因组DNA提取试剂对先证者及其家属的人类全血EDTA抗凝样本进行全基因组DNA的提取，对DNA的浓度和纯度进行检测。
S2、准备PCR反应体系：
设计包含目的片段的特异性扩增引物:
上游引物(FBN1-E60F，SEQ ID NO:7)：5'GCACAGGACAATCATCAAAGTCT 3'；
下游引物(FBN1-E60R，SEQ ID NO:8)：5'GCTGCTTCCTCCACAATCTCC 3'；
长度：463bp。
扩增试剂使用江苏康为世纪生物科技有限公司生产的2×Taq Master Mix(Dye)。扩增体系：2×Taq Master Mix(Dye)25μL；上下游引物(10μM)各1μL；DNA模板<0.5μg；用ddH2O补至50μL。
PCR扩增条件：90℃预变性3min；94℃变性30s，63℃退火30s，72℃延伸30s，共30循环。75℃终延伸2min。
产物检测：取2μL的PCR产物，使用1.5％的琼脂糖凝胶电泳检测PCR产物，选用1000bp Marker作为参考，检测验证扩增产物为预期的大小。
S3、采用3730XL Genetic Analyzer全自动测序仪对PCR产物进行测序。从NCBI(https://www.ncbi.nlm.nih.gov/)数据库获得参考序列和测序结果进行比对。
实验结果：
(1)本实施例发现先证者携带突变的FBN1基因，具体检测结果如下表2所示：
表2突变的FBN1基因的具体检测结果
| 基因 | 基因组位置 | 转录本号 | 碱基改变 | 氨基酸改变 | 参考基因组版本 | 外显子号 |
| FBN1 | chr15:48717688 | NM_000138 | c.7331A>T | p.Asp2444Val | GRCh37/hg19 | exon60 |
在基因组位置chr15:48717667-chr15:48717716处，野生型FBN1基因的序列为SEQID NO:1：cagtcacgctgtatttctttgatcatagATCTGAACGAGTGCAACCAGGC，A为基因组位置chr15:48717688处突变前碱基；
在基因组位置chr15:48717667-chr15:48717716处，突变的FBN1基因的序列为SEQID NO:2：cagtcacgctgtatttctttgatcatagTTCTGAACGAGTGCAACCAGGC，T为基因组位置chr15:48717688处突变后碱基；
野生型FBN1基因编码DNA的参考序列为SEQ ID NO:3：
ATGCGTCGAGGGCGTCTGCTGGAGATCGCCCTGGGATTTACCGTGCTTTTAGCGTCCTACACGAGCCATGGGGCGGACGCCAATTTGGAGGCTGGGAACGTGAAGGAAACCAGAGCCAGTCGGGCCAAGAGAAGAGGCGGTGGAGGACACGACGCGCTTAAAGGACCCAATGTCTGTGGATCACGTTATAATGCTTACTGTTGCCCTGGATGGAAAACCTTACCTGGCGGAAATCAGTGTATTGTCCCCATTTGCCGGCATTCCTGTGGGGATGGATTTTGTTCGAGGCCAAATATGTGCACTTGCCCATCTGGTCAGATAGCTCCTTCCTGTGGCTCCAGATCCATACAACACTGCAATATTCGCTGTATGAATGGAGGTAGCTGCAGTGACGATCACTGTCTATGCCAGAAAGGATACATAGGGACTCACTGTGGACAACCTGTTTGTGAAAGTGGCTGTCTCAATGGAGGAAGGTGTGTGGCCCCAAATCGATGTGCATGCACTTACGGATTTACTGGACCCCAGTGTGAAAGAGATTACAGGACAGGCCCATGTTTTACTGTGATCAGCAACCAGATGTGCCAGGGACAACTCAGCGGGATTGTCTGCACAAAAACGCTCTGCTGTGCCACAGTCGGCCGAGCCTGGGGCCACCCCTGTGAGATGTGTCCTGCCCAGCCTCACCCCTGCCGCCGTGGCTTCATTCCAAATATCCGCACGGGAGCTTGTCAAGATGTGGATGAATGCCAGGCCATCCCCGGGCTCTGTCAGGGAGGAAATTGCATTAATACTGTTGGGTCTTTTGAGTGCAAATGCCCTGCTGGACACAAACTTAATGAAGTGTCACAAAAATGTGAAGATATTGATGAATGCAGCACCATTCCTGGAATCTGTGAAGGGGGTGAATGTACAAACACAGTCAGCAGTTACTTTTGCAAATGTCCCCCTGGTTTTTACACCTCTCCAGATGGTACCAGATGCATAGATGTTCGCCCAGGATACTGTTACACAGCTCTGACAAACGGGCGCTGCTCTAACCAGCTGCCACAGTCCATAACCAAAATGCAGTGCTGCTGTGATGCCGGCCGATGCTGGTCTCCAGGGGTCACTGTCGCCCCTGAGATGTGTCCCATCAGAGCAACCGAGGATTTCAACAAGCTGTGCTCTGTTCCTATGGTAATTCCTGGGAGACCAGAATATCCTCCCCCACCCCTTGGCCCCATTCCTCCAGTTCTCCCTGTTCCTCCTGGCTTTCCTCCTGGACCTCAAATTCCGGTCCCTCGACCACCAGTGGAATATCTGTATCCATCTCGGGAGCCACCAAGGGTGCTGCCAGTAAACGTTACTGATTACTGCCAGTTGGTCCGCTATCTCTGTCAAAATGGACGCTGCATTCCAACTCCTGGGAGTTACCGGTGTGAGTGCAACAAAGGGTTCCAGCTGGACCTCCGTGGGGAGTGTATTGATGTTGATGAATGTGAGAAAAACCCCTGTGCTGGTGGTGAGTGTATTAACAACCAGGGTTCGTACACCTGTCAGTGCCGAGCTGGATATCAGAGCACACTCACGCGGACAGAATGCCGAGACATTGATGAGTGTTTACAGAATGGCCGGATCTGCAATAATGGACGCTGCATCAACACAGATGGCAGTTTTCATTGCGTGTGTAATGCGGGCTTTCATGTTACACGAGATGGGAAGAACTGTGAAGATATGGATGAATGCAGCATAAGGAACATGTGCCTTAATGGAATGTGTATCAATGAAGATGGCAGTTTTAAATGTATTTGCAAACCTGGATTCCAGCTGGCATCAGATGGACGTTATTGCAAAGACATTAACGAGTGTGAAACCCCTGGGATCTGCATGAATGGGCGTTGCGTCAACACTGATGGCTCCTACAGATGTGAATGCTTCCCTGGACTGGCTGTGGGTCTGGATGGCCGTGTGTGTGTTGACACACACATGCGGAGCACATGCTATGGTGGATACAAGAGAGGCCAGTGTATCAAACCTTTGTTTGGTGCTGTCACTAAATCTGAATGCTGTTGCGCCAGCACTGAGTATGCATTTGGGGAACCTTGCCAGCCGTGTCCTGCACAGAATTCAGCGGAATATCAGGCACTCTGCAGCAGTGGGCCAGGAATGACGTCAGCAGGCAGTGATATAAATGAATGTGCACTAGATCCTGATATTTGCCCAAATGGAATCTGTGAAAACCTTCGTGGGACCTATAAATGTATATGCAATTCAGGATATGAAGTGGATTCAACTGGGAAAAACTGCGTTGATATTAATGAATGTGTACTGAACAGTCTCCTTTGTGACAATGGACAATGTAGAAATACTCCTGGAAGTTTTGTCTGTACCTGCCCCAAGGGATTTATCTACAAACCTGATCTAAAAACATGTGAAGACATTGATGAATGCGAATCAAGTCCTTGCATTAATGGAGTCTGCAAGAACAGCCCAGGCTCTTTTATTTGTGAATGTTCTTCTGAAAGTACTTTGGATCCAACAAAAACCATCTGCATAGAAACCATCAAGGGCACTTGCTGGCAGACTGTCATTGATGGGCGATGTGAGATCAACATCAATGGAGCCACCTTAAAGTCCCAGTGCTGCTCCTCCCTCGGTGCTGCGTGGGGAAGCCCGTGCACCCTATGCCAAGTTGATCCCATATGTGGTAAAGGGTACTCAAGAATTAAAGGAACACAATGTGAAGATATAGATGAATGTGAAGTGTTCCCAGGAGTGTGTAAAAATGGCCTGTGTGTTAACACTAGGGGGTCATTCAAGTGTCAGTGTCCCAGTGGAATGACTTTGGATGCCACAGGAAGGATCTGTCTTGATATCCGCCTGGAAACCTGCTTCCTGAGGTACGAGGACGAGGAGTGCACCCTGCCTATTGCTGGCCGCCACCGCATGGACGCCTGCTGCTGCTCCGTCGGGGCAGCCTGGGGTACTGAGGAATGCGAGGAGTGTCCCATGAGAAATACTCCTGAGTACGAGGAGCTGTGTCCGAGAGGACCCGGATTTGCCACAAAAGAAATTACAAATGGAAAGCCTTTCTTCAAAGATATCAATGAGTGCAAGATGATACCCAGCCTCTGCACCCACGGCAAGTGCAGAAACACCATTGGCAGCTTTAAGTGCAGGTGTGACAGCGGCTTTGCTCTTGATTCTGAAGAAAGGAACTGCACAGACATTGACGAATGCCGCATATCTCCTGACCTCTGTGGCAGAGGCCAGTGTGTGAACACCCCTGGGGACTTTGAATGCAAGTGTGACGAAGGCTATGAAAGTGGATTCATGATGATGAAGAACTGCATGGATATTGATGAGTGTCAGAGAGATCCTCTCCTATGCCGAGGTGGTGTTTGCCATAACACAGAGGGAAGTTACCGCTGTGAATGCCCGCCTGGCCATCAGCTGTCCCCCAACATCTCCGCGTGTATCGACATCAATGAATGTGAGCTGAGTGCACACCTGTGCCCCAATGGCCGTTGCGTGAACCTCATAGGGAAGTATCAGTGTGCCTGCAACCCTGGCTACCATTCAACTCCCGATAGGCTATTTTGTGTTGACATTGATGAATGCAGCATAATGAATGGTGGTTGTGAAACCTTCTGCACAAACTCTGAAGGCAGCTATGAATGTAGCTGTCAGCCGGGATTTGCACTAATGCCTGACCAGAGATCATGCACCGACATCGATGAGTGTGAAGATAATCCCAATATCTGTGATGGTGGTCAGTGCACAAATATCCCTGGAGAGTACAGGTGCTTGTGTTATGATGGATTCATGGCATCTGAAGACATGAAGACTTGTGTAGATGTCAATGAGTGTGACCTGAATCCAAATATCTGCCTAAGTGGGACCTGTGAAAACACGAAAGGCTCATTTATCTGCCACTGTGATATGGGCTACTCCGGCAAAAAAGGAAAAACTGGCTGTACAGACATCAATGAATGTGAAATTGGAGCACACAACTGTGGCAAACATGCTGTATGTACCAATACAGCAGGAAGCTTCAAATGTAGCTGCAGTCCCGGGTGGATTGGAGATGGCATTAAGTGCACTGATCTGGACGAATGTTCCAATGGAACCCATATGTGCAGCCAGCATGCAGACTGCAAGAATACCATGGGATCTTACCGCTGTCTGTGCAAGGAAGGATACACAGGTGATGGCTTCACTTGTACAGACCTTGATGAGTGCTCTGAGAACCTGAATCTCTGTGGCAATGGCCAGTGCCTCAATGCACCAGGAGGATACCGCTGTGAATGCGACATGGGCTTCGTGCCCAGTGCTGACGGGAAAGCCTGTGAAGATATTGATGAGTGCTCCCTTCCGAACATCTGTGTCTTTGGAACTTGCCACAACCTCCCTGGCCTGTTCCGCTGTGAGTGTGAGATAGGCTACGAACTGGACAGAAGCGGCGGGAACTGCACAGATGTGAATGAATGCCTGGATCCAACCACGTGCATCAGTGGGAACTGTGTCAACACTCCAGGCAGCTATATCTGTGACTGCCCACCTGATTTTGAACTGAACCCAACTCGAGTTGGCTGTGTTGATACCCGCTCTGGAAATTGCTATTTGGATATTCGACCTCGAGGAGACAATGGAGATACAGCCTGCAGCAATGAAATTGGAGTTGGTGTTTCCAAAGCTTCCTGCTGCTGTTCTCTGGGTAAAGCCTGGGGTACTCCTTGTGAGATGTGTCCTGCTGTGAACACATCCGAGTACAAAATTCTTTGTCCTGGAGGGGAAGGTTTCCGACCAAATCCTATCACCGTTATATTGGAAGATATTGATGAGTGCCAGGAGCTACCAGGGCTGTGCCAAGGAGGAAAATGTATCAACACCTTTGGGAGTTTCCAGTGCCGCTGTCCAACCGGCTACTACCTGAATGAAGATACACGAGTGTGTGATGATGTGAATGAATGTGAGACTCCTGGAATCTGTGGTCCAGGGACATGTTACAACACCGTTGGCAACTACACCTGTATCTGTCCTCCAGACTACATGCAAGTGAATGGGGGAAATAATTGCATGGATATGAGAAGAAGTTTGTGCTACAGAAACTACTATGCTGACAACCAGACCTGTGATGGAGAATTGTTATTCAACATGACCAAGAAGATGTGCTGCTGTTCCTACAACATTGGCCGGGCGTGGAACAAGCCCTGTGAACAGTGTCCCATCCCAAGTACAGATGAGTTTGCTACACTCTGTGGAAGTCAAAGGCCAGGCTTTGTCATCGACATTTATACCGGTTTACCCGTTGATATTGATGAGTGCCGGGAGATCCCAGGGGTCTGTGAAAATGGAGTGTGTATCAACATGGTTGGCAGCTTCCGATGTGAATGTCCAGTGGGATTCTTCTATAATGACAAGTTGTTGGTTTGTGAAGATATTGACGAGTGTCAGAACGGCCCAGTGTGCCAGCGCAACGCCGAATGCATCAACACTGCAGGCAGCTACCGCTGTGACTGTAAGCCCGGCTACCGCTTCACCTCCACAGGACAGTGCAATGATCGTAATGAATGTCAAGAAATCCCCAATATATGCAGTCATGGGCAGTGCATTGACACAGTTGGAAGCTTTTATTGCCTTTGCCACACTGGTTTTAAAACAAATGATGACCAAACCATGTGCTTGGACATAAATGAATGTGAAAGAGATGCCTGTGGGAATGGAACTTGCCGGAACACAATTGGTTCCTTCAACTGCCGCTGCAATCATGGTTTCATCCTTTCTCACAACAATGACTGTATAGATGTTGATGAATGTGCAAGTGGAAATGGGAATCTTTGCAGAAATGGCCAATGCATTAATACAGTGGGGTCTTTCCAGTGCCAGTGCAATGAAGGCTATGAGGTGGCTCCAGATGGGAGGACCTGTGTGGATATCAATGAATGTCTTCTAGAACCCAGAAAATGTGCACCAGGTACCTGTCAAAACTTGGATGGGTCCTACAGATGCATTTGCCCACCTGGATACAGTCTTCAAAATGAGAAGTGTGAAGATATTGATGAGTGTGTCGAAGAGCCAGAAATTTGTGCCCTGGGCACATGCAGTAACACTGAAGGCAGCTTCAAATGTCTGTGTCCAGAAGGGTTTTCCTTGTCCTCCAGTGGAAGAAGGTGCCAAGATTTGCGAATGAGCTACTGTTATGCGAAGTTTGAAGGAGGAAAGTGTTCATCACCCAAATCCAGAAATCACTCCAAGCAGGAATGCTGCTGTGCCTTGAAGGGAGAAGGCTGGGGAGACCCCTGCGAGCTCTGCCCCACGGAACCTGATGAGGCCTTCCGCCAGATATGTCCTTATGGAAGTGGGATCATCGTGGGACCTGATGATTCAGCAGTTGATATGGACGAATGCAAAGAACCCGATGTCTGTAAACATGGACAGTGCATCAATACAGATGGTTCCTATCGCTGCGAGTGTCCCTTTGGTTATATTCTAGCAGGGAATGAATGTGTAGATACTGATGAATGTTCTGTTGGCAATCCTTGTGGAAATGGAACCTGCAAGAATGTGATTGGAGGTTTTGAATGCACCTGCGAGGAGGGATTTGAGCCCGGTCCAATGATGACATGTGAAGATATAAATGAATGTGCCCAGAATCCTCTGCTCTGTGCCTTCCGATGTGTGAACACTTATGGGTCATATGAATGCAAATGTCCCGTGGGATATGTGCTCAGAGAAGACCGTAGGATGTGCAAAGATGAGGATGAGTGTGAAGAGGGAAAACATGACTGTACTGAAAAACAAATGGAATGCAAGAACCTCATTGGCACATATATGTGCATCTGTGGACCCGGGTATCAGCGGAGACCTGATGGAGAAGGCTGTGTAGATGAGAATGAATGTCAGACGAAGCCAGGGATCTGTGAGAATGGGCGCTGCCTCAACACCCGTGGGAGCTACACCTGTGAGTGTAATGATGGGTTTACCGCCAGCCCCAACCAGGACGAGTGCCTTGACAATCGGGAAGGGTACTGCTTCACAGAGGTGCTACAAAACATGTGTCAGATCGGCTCCAGCAACAGGAACCCCGTCACCAAATCGGAATGCTGCTGTGACGGAGGGAGAGGCTGGGGTCCCCACTGTGAGATCTGCCCTTTCCAGGGGACTGTGGCTTTCAAGAAACTCTGTCCCCATGGCCGAGGATTCATGACCAATGGAGCAGATATCGATGAATGCAAGGTTATTCACGATGTTTGCCGAAATGGGGAATGTGTCAATGACAGAGGATCATATCATTGCATTTGTAAAACTGGGTACACTCCAGATATAACTGGGACTTCCTGTGTAGATCTGAACGAGTGCAACCAGGCTCCCAAACCCTGCAATTTTATCTGCAAAAACACAGAAGGGAGTTACCAGTGTTCATGCCCGAAAGGCTACATTCTGCAAGAGGATGGAAGGAGCTGCAAAGATCTTGATGAGTGTGCAACCAAGCAACACAACTGCCAGTTCCTATGTGTTAACACCATTGGCGGCTTCACATGCAAATGTCCTCCCGGATTTACCCAACACCATACGTCCTGCATTGATAACAATGAATGCACCTCTGACATCAATCTGTGCGGGTCTAAGGGCATTTGCCAGAACACTCCTGGAAGCTTCACCTGTGAATGCCAGCGGGGATTCTCACTTGATCAGACCGGCTCCAGCTGTGAAGACGTGGACGAGTGTGAGGGTAACCACCGCTGCCAGCATGGCTGCCAGAACATCATTGGGGGCTACAGGTGCAGCTGCCCCCAGGGCTACCTCCAGCACTACCAGTGGAACCAGTGTGTTGATGAAAACGAATGCCTCAGCGCTCACATCTGCGGAGGAGCCTCCTGTCACAACACCCTGGGGAGCTACAAGTGCATGTGTCCCGCCGGCTTCCAGTATGAACAGTTCAGTGGAGGATGCCAAGACATCAATGAATGTGGCTCTGCGCAGGCCCCCTGCAGCTATGGCTGTTCCAATACCGAGGGCGGTTACCTGTGTGGCTGTCCACCTGGTTACTTCCGCATAGGCCAAGGGCACTGTGTTTCTGGAATGGGCATGGGCCGAGGAAACCCAGAGCCACCTGTCAGTGGTGAAATGGATGACAATTCACTCTCCCCAGAGGCTTGTTACGAGTGTAAGATCAATGGCTACCCCAAACGGGGCAGGAAACGGAGAAGCACAAACGAAACTGATGCCTCCAATATCGAGGATCAGTCTGAGACAGAAGCCAATGTGAGTCTTGCAAGTTGGGATGTTGAGAAGACAGCCATCTTTGCTTTCAATATTTCCCACGTCAGTAACAAGGTTCGAATCCTAGAACTCCTTCCAGCTCTTACAACTCTGACGAATCACAACAGATACTTGATCGAATCTGGAAATGAAGATGGCTTCTTTAAAATCAACCAAAAGGAAGGGATCAGCTACCTCCACTTCACAAAGAAGAAGCCAGTGGCTGGAACCTATTCATTACAAATCAGTAGTACTCCACTTTATAAAAAGAAAGAACTTAACCAACTAGAAGACAAATATGACAAAGACTACCTCAGTGGTGAACTGGGTGATAATCTGAAGATGAAAATCCAGGTTTTGCTTCATTAA，A为编码DNA的参考序列的第7331位突变前碱基。
突变的FBN1基因编码DNA的参考序列为SEQ ID NO4：
ATGCGTCGAGGGCGTCTGCTGGAGATCGCCCTGGGATTTACCGTGCTTTTAGCGTCCTACACGAGCCATGGGGCGGACGCCAATTTGGAGGCTGGGAACGTGAAGGAAACCAGAGCCAGTCGGGCCAAGAGAAGAGGCGGTGGAGGACACGACGCGCTTAAAGGACCCAATGTCTGTGGATCACGTTATAATGCTTACTGTTGCCCTGGATGGAAAACCTTACCTGGCGGAAATCAGTGTATTGTCCCCATTTGCCGGCATTCCTGTGGGGATGGATTTTGTTCGAGGCCAAATATGTGCACTTGCCCATCTGGTCAGATAGCTCCTTCCTGTGGCTCCAGATCCATACAACACTGCAATATTCGCTGTATGAATGGAGGTAGCTGCAGTGACGATCACTGTCTATGCCAGAAAGGATACATAGGGACTCACTGTGGACAACCTGTTTGTGAAAGTGGCTGTCTCAATGGAGGAAGGTGTGTGGCCCCAAATCGATGTGCATGCACTTACGGATTTACTGGACCCCAGTGTGAAAGAGATTACAGGACAGGCCCATGTTTTACTGTGATCAGCAACCAGATGTGCCAGGGACAACTCAGCGGGATTGTCTGCACAAAAACGCTCTGCTGTGCCACAGTCGGCCGAGCCTGGGGCCACCCCTGTGAGATGTGTCCTGCCCAGCCTCACCCCTGCCGCCGTGGCTTCATTCCAAATATCCGCACGGGAGCTTGTCAAGATGTGGATGAATGCCAGGCCATCCCCGGGCTCTGTCAGGGAGGAAATTGCATTAATACTGTTGGGTCTTTTGAGTGCAAATGCCCTGCTGGACACAAACTTAATGAAGTGTCACAAAAATGTGAAGATATTGATGAATGCAGCACCATTCCTGGAATCTGTGAAGGGGGTGAATGTACAAACACAGTCAGCAGTTACTTTTGCAAATGTCCCCCTGGTTTTTACACCTCTCCAGATGGTACCAGATGCATAGATGTTCGCCCAGGATACTGTTACACAGCTCTGACAAACGGGCGCTGCTCTAACCAGCTGCCACAGTCCATAACCAAAATGCAGTGCTGCTGTGATGCCGGCCGATGCTGGTCTCCAGGGGTCACTGTCGCCCCTGAGATGTGTCCCATCAGAGCAACCGAGGATTTCAACAAGCTGTGCTCTGTTCCTATGGTAATTCCTGGGAGACCAGAATATCCTCCCCCACCCCTTGGCCCCATTCCTCCAGTTCTCCCTGTTCCTCCTGGCTTTCCTCCTGGACCTCAAATTCCGGTCCCTCGACCACCAGTGGAATATCTGTATCCATCTCGGGAGCCACCAAGGGTGCTGCCAGTAAACGTTACTGATTACTGCCAGTTGGTCCGCTATCTCTGTCAAAATGGACGCTGCATTCCAACTCCTGGGAGTTACCGGTGTGAGTGCAACAAAGGGTTCCAGCTGGACCTCCGTGGGGAGTGTATTGATGTTGATGAATGTGAGAAAAACCCCTGTGCTGGTGGTGAGTGTATTAACAACCAGGGTTCGTACACCTGTCAGTGCCGAGCTGGATATCAGAGCACACTCACGCGGACAGAATGCCGAGACATTGATGAGTGTTTACAGAATGGCCGGATCTGCAATAATGGACGCTGCATCAACACAGATGGCAGTTTTCATTGCGTGTGTAATGCGGGCTTTCATGTTACACGAGATGGGAAGAACTGTGAAGATATGGATGAATGCAGCATAAGGAACATGTGCCTTAATGGAATGTGTATCAATGAAGATGGCAGTTTTAAATGTATTTGCAAACCTGGATTCCAGCTGGCATCAGATGGACGTTATTGCAAAGACATTAACGAGTGTGAAACCCCTGGGATCTGCATGAATGGGCGTTGCGTCAACACTGATGGCTCCTACAGATGTGAATGCTTCCCTGGACTGGCTGTGGGTCTGGATGGCCGTGTGTGTGTTGACACACACATGCGGAGCACATGCTATGGTGGATACAAGAGAGGCCAGTGTATCAAACCTTTGTTTGGTGCTGTCACTAAATCTGAATGCTGTTGCGCCAGCACTGAGTATGCATTTGGGGAACCTTGCCAGCCGTGTCCTGCACAGAATTCAGCGGAATATCAGGCACTCTGCAGCAGTGGGCCAGGAATGACGTCAGCAGGCAGTGATATAAATGAATGTGCACTAGATCCTGATATTTGCCCAAATGGAATCTGTGAAAACCTTCGTGGGACCTATAAATGTATATGCAATTCAGGATATGAAGTGGATTCAACTGGGAAAAACTGCGTTGATATTAATGAATGTGTACTGAACAGTCTCCTTTGTGACAATGGACAATGTAGAAATACTCCTGGAAGTTTTGTCTGTACCTGCCCCAAGGGATTTATCTACAAACCTGATCTAAAAACATGTGAAGACATTGATGAATGCGAATCAAGTCCTTGCATTAATGGAGTCTGCAAGAACAGCCCAGGCTCTTTTATTTGTGAATGTTCTTCTGAAAGTACTTTGGATCCAACAAAAACCATCTGCATAGAAACCATCAAGGGCACTTGCTGGCAGACTGTCATTGATGGGCGATGTGAGATCAACATCAATGGAGCCACCTTAAAGTCCCAGTGCTGCTCCTCCCTCGGTGCTGCGTGGGGAAGCCCGTGCACCCTATGCCAAGTTGATCCCATATGTGGTAAAGGGTACTCAAGAATTAAAGGAACACAATGTGAAGATATAGATGAATGTGAAGTGTTCCCAGGAGTGTGTAAAAATGGCCTGTGTGTTAACACTAGGGGGTCATTCAAGTGTCAGTGTCCCAGTGGAATGACTTTGGATGCCACAGGAAGGATCTGTCTTGATATCCGCCTGGAAACCTGCTTCCTGAGGTACGAGGACGAGGAGTGCACCCTGCCTATTGCTGGCCGCCACCGCATGGACGCCTGCTGCTGCTCCGTCGGGGCAGCCTGGGGTACTGAGGAATGCGAGGAGTGTCCCATGAGAAATACTCCTGAGTACGAGGAGCTGTGTCCGAGAGGACCCGGATTTGCCACAAAAGAAATTACAAATGGAAAGCCTTTCTTCAAAGATATCAATGAGTGCAAGATGATACCCAGCCTCTGCACCCACGGCAAGTGCAGAAACACCATTGGCAGCTTTAAGTGCAGGTGTGACAGCGGCTTTGCTCTTGATTCTGAAGAAAGGAACTGCACAGACATTGACGAATGCCGCATATCTCCTGACCTCTGTGGCAGAGGCCAGTGTGTGAACACCCCTGGGGACTTTGAATGCAAGTGTGACGAAGGCTATGAAAGTGGATTCATGATGATGAAGAACTGCATGGATATTGATGAGTGTCAGAGAGATCCTCTCCTATGCCGAGGTGGTGTTTGCCATAACACAGAGGGAAGTTACCGCTGTGAATGCCCGCCTGGCCATCAGCTGTCCCCCAACATCTCCGCGTGTATCGACATCAATGAATGTGAGCTGAGTGCACACCTGTGCCCCAATGGCCGTTGCGTGAACCTCATAGGGAAGTATCAGTGTGCCTGCAACCCTGGCTACCATTCAACTCCCGATAGGCTATTTTGTGTTGACATTGATGAATGCAGCATAATGAATGGTGGTTGTGAAACCTTCTGCACAAACTCTGAAGGCAGCTATGAATGTAGCTGTCAGCCGGGATTTGCACTAATGCCTGACCAGAGATCATGCACCGACATCGATGAGTGTGAAGATAATCCCAATATCTGTGATGGTGGTCAGTGCACAAATATCCCTGGAGAGTACAGGTGCTTGTGTTATGATGGATTCATGGCATCTGAAGACATGAAGACTTGTGTAGATGTCAATGAGTGTGACCTGAATCCAAATATCTGCCTAAGTGGGACCTGTGAAAACACGAAAGGCTCATTTATCTGCCACTGTGATATGGGCTACTCCGGCAAAAAAGGAAAAACTGGCTGTACAGACATCAATGAATGTGAAATTGGAGCACACAACTGTGGCAAACATGCTGTATGTACCAATACAGCAGGAAGCTTCAAATGTAGCTGCAGTCCCGGGTGGATTGGAGATGGCATTAAGTGCACTGATCTGGACGAATGTTCCAATGGAACCCATATGTGCAGCCAGCATGCAGACTGCAAGAATACCATGGGATCTTACCGCTGTCTGTGCAAGGAAGGATACACAGGTGATGGCTTCACTTGTACAGACCTTGATGAGTGCTCTGAGAACCTGAATCTCTGTGGCAATGGCCAGTGCCTCAATGCACCAGGAGGATACCGCTGTGAATGCGACATGGGCTTCGTGCCCAGTGCTGACGGGAAAGCCTGTGAAGATATTGATGAGTGCTCCCTTCCGAACATCTGTGTCTTTGGAACTTGCCACAACCTCCCTGGCCTGTTCCGCTGTGAGTGTGAGATAGGCTACGAACTGGACAGAAGCGGCGGGAACTGCACAGATGTGAATGAATGCCTGGATCCAACCACGTGCATCAGTGGGAACTGTGTCAACACTCCAGGCAGCTATATCTGTGACTGCCCACCTGATTTTGAACTGAACCCAACTCGAGTTGGCTGTGTTGATACCCGCTCTGGAAATTGCTATTTGGATATTCGACCTCGAGGAGACAATGGAGATACAGCCTGCAGCAATGAAATTGGAGTTGGTGTTTCCAAAGCTTCCTGCTGCTGTTCTCTGGGTAAAGCCTGGGGTACTCCTTGTGAGATGTGTCCTGCTGTGAACACATCCGAGTACAAAATTCTTTGTCCTGGAGGGGAAGGTTTCCGACCAAATCCTATCACCGTTATATTGGAAGATATTGATGAGTGCCAGGAGCTACCAGGGCTGTGCCAAGGAGGAAAATGTATCAACACCTTTGGGAGTTTCCAGTGCCGCTGTCCAACCGGCTACTACCTGAATGAAGATACACGAGTGTGTGATGATGTGAATGAATGTGAGACTCCTGGAATCTGTGGTCCAGGGACATGTTACAACACCGTTGGCAACTACACCTGTATCTGTCCTCCAGACTACATGCAAGTGAATGGGGGAAATAATTGCATGGATATGAGAAGAAGTTTGTGCTACAGAAACTACTATGCTGACAACCAGACCTGTGATGGAGAATTGTTATTCAACATGACCAAGAAGATGTGCTGCTGTTCCTACAACATTGGCCGGGCGTGGAACAAGCCCTGTGAACAGTGTCCCATCCCAAGTACAGATGAGTTTGCTACACTCTGTGGAAGTCAAAGGCCAGGCTTTGTCATCGACATTTATACCGGTTTACCCGTTGATATTGATGAGTGCCGGGAGATCCCAGGGGTCTGTGAAAATGGAGTGTGTATCAACATGGTTGGCAGCTTCCGATGTGAATGTCCAGTGGGATTCTTCTATAATGACAAGTTGTTGGTTTGTGAAGATATTGACGAGTGTCAGAACGGCCCAGTGTGCCAGCGCAACGCCGAATGCATCAACACTGCAGGCAGCTACCGCTGTGACTGTAAGCCCGGCTACCGCTTCACCTCCACAGGACAGTGCAATGATCGTAATGAATGTCAAGAAATCCCCAATATATGCAGTCATGGGCAGTGCATTGACACAGTTGGAAGCTTTTATTGCCTTTGCCACACTGGTTTTAAAACAAATGATGACCAAACCATGTGCTTGGACATAAATGAATGTGAAAGAGATGCCTGTGGGAATGGAACTTGCCGGAACACAATTGGTTCCTTCAACTGCCGCTGCAATCATGGTTTCATCCTTTCTCACAACAATGACTGTATAGATGTTGATGAATGTGCAAGTGGAAATGGGAATCTTTGCAGAAATGGCCAATGCATTAATACAGTGGGGTCTTTCCAGTGCCAGTGCAATGAAGGCTATGAGGTGGCTCCAGATGGGAGGACCTGTGTGGATATCAATGAATGTCTTCTAGAACCCAGAAAATGTGCACCAGGTACCTGTCAAAACTTGGATGGGTCCTACAGATGCATTTGCCCACCTGGATACAGTCTTCAAAATGAGAAGTGTGAAGATATTGATGAGTGTGTCGAAGAGCCAGAAATTTGTGCCCTGGGCACATGCAGTAACACTGAAGGCAGCTTCAAATGTCTGTGTCCAGAAGGGTTTTCCTTGTCCTCCAGTGGAAGAAGGTGCCAAGATTTGCGAATGAGCTACTGTTATGCGAAGTTTGAAGGAGGAAAGTGTTCATCACCCAAATCCAGAAATCACTCCAAGCAGGAATGCTGCTGTGCCTTGAAGGGAGAAGGCTGGGGAGACCCCTGCGAGCTCTGCCCCACGGAACCTGATGAGGCCTTCCGCCAGATATGTCCTTATGGAAGTGGGATCATCGTGGGACCTGATGATTCAGCAGTTGATATGGACGAATGCAAAGAACCCGATGTCTGTAAACATGGACAGTGCATCAATACAGATGGTTCCTATCGCTGCGAGTGTCCCTTTGGTTATATTCTAGCAGGGAATGAATGTGTAGATACTGATGAATGTTCTGTTGGCAATCCTTGTGGAAATGGAACCTGCAAGAATGTGATTGGAGGTTTTGAATGCACCTGCGAGGAGGGATTTGAGCCCGGTCCAATGATGACATGTGAAGATATAAATGAATGTGCCCAGAATCCTCTGCTCTGTGCCTTCCGATGTGTGAACACTTATGGGTCATATGAATGCAAATGTCCCGTGGGATATGTGCTCAGAGAAGACCGTAGGATGTGCAAAGATGAGGATGAGTGTGAAGAGGGAAAACATGACTGTACTGAAAAACAAATGGAATGCAAGAACCTCATTGGCACATATATGTGCATCTGTGGACCCGGGTATCAGCGGAGACCTGATGGAGAAGGCTGTGTAGATGAGAATGAATGTCAGACGAAGCCAGGGATCTGTGAGAATGGGCGCTGCCTCAACACCCGTGGGAGCTACACCTGTGAGTGTAATGATGGGTTTACCGCCAGCCCCAACCAGGACGAGTGCCTTGACAATCGGGAAGGGTACTGCTTCACAGAGGTGCTACAAAACATGTGTCAGATCGGCTCCAGCAACAGGAACCCCGTCACCAAATCGGAATGCTGCTGTGACGGAGGGAGAGGCTGGGGTCCCCACTGTGAGATCTGCCCTTTCCAGGGGACTGTGGCTTTCAAGAAACTCTGTCCCCATGGCCGAGGATTCATGACCAATGGAGCAGATATCGATGAATGCAAGGTTATTCACGATGTTTGCCGAAATGGGGAATGTGTCAATGACAGAGGATCATATCATTGCATTTGTAAAACTGGGTACACTCCAGATATAACTGGGACTTCCTGTGTAGTTCTGAACGAGTGCAACCAGGCTCCCAAACCCTGCAATTTTATCTGCAAAAACACAGAAGGGAGTTACCAGTGTTCATGCCCGAAAGGCTACATTCTGCAAGAGGATGGAAGGAGCTGCAAAGATCTTGATGAGTGTGCAACCAAGCAACACAACTGCCAGTTCCTATGTGTTAACACCATTGGCGGCTTCACATGCAAATGTCCTCCCGGATTTACCCAACACCATACGTCCTGCATTGATAACAATGAATGCACCTCTGACATCAATCTGTGCGGGTCTAAGGGCATTTGCCAGAACACTCCTGGAAGCTTCACCTGTGAATGCCAGCGGGGATTCTCACTTGATCAGACCGGCTCCAGCTGTGAAGACGTGGACGAGTGTGAGGGTAACCACCGCTGCCAGCATGGCTGCCAGAACATCATTGGGGGCTACAGGTGCAGCTGCCCCCAGGGCTACCTCCAGCACTACCAGTGGAACCAGTGTGTTGATGAAAACGAATGCCTCAGCGCTCACATCTGCGGAGGAGCCTCCTGTCACAACACCCTGGGGAGCTACAAGTGCATGTGTCCCGCCGGCTTCCAGTATGAACAGTTCAGTGGAGGATGCCAAGACATCAATGAATGTGGCTCTGCGCAGGCCCCCTGCAGCTATGGCTGTTCCAATACCGAGGGCGGTTACCTGTGTGGCTGTCCACCTGGTTACTTCCGCATAGGCCAAGGGCACTGTGTTTCTGGAATGGGCATGGGCCGAGGAAACCCAGAGCCACCTGTCAGTGGTGAAATGGATGACAATTCACTCTCCCCAGAGGCTTGTTACGAGTGTAAGATCAATGGCTACCCCAAACGGGGCAGGAAACGGAGAAGCACAAACGAAACTGATGCCTCCAATATCGAGGATCAGTCTGAGACAGAAGCCAATGTGAGTCTTGCAAGTTGGGATGTTGAGAAGACAGCCATCTTTGCTTTCAATATTTCCCACGTCAGTAACAAGGTTCGAATCCTAGAACTCCTTCCAGCTCTTACAACTCTGACGAATCACAACAGATACTTGATCGAATCTGGAAATGAAGATGGCTTCTTTAAAATCAACCAAAAGGAAGGGATCAGCTACCTCCACTTCACAAAGAAGAAGCCAGTGGCTGGAACCTATTCATTACAAATCAGTAGTACTCCACTTTATAAAAAGAAAGAACTTAACCAACTAGAAGACAAATATGACAAAGACTACCTCAGTGGTGAACTGGGTGATAATCTGAAGATGAAAATCCAGGTTTTGCTTCATTAA，与编码DNA的参考序列的第7331位相比，T为突变后碱基。
c.7331A>T表示：与野生型FBN1基因编码DNA的参考序列相比，第7331位点的碱基A突变为碱基T。
野生型FBN1基因编码蛋白为SEQ ID NO:5：
MRRGRLLEIALGFTVLLASYTSHGADANLEAGNVKETRASRAKRRGGGGHDALKGPNVCGSRYNAYCCPGWKTLPGGNQCIVPICRHSCGDGFCSRPNMCTCPSGQIAPSCGSRSIQHCNIRCMNGGSCSDDHCLCQKGYIGTHCGQPVCESGCLNGGRCVAPNRCACTYGFTGPQCERDYRTGPCFTVISNQMCQGQLSGIVCTKTLCCATVGRAWGHPCEMCPAQPHPCRRGFIPNIRTGACQDVDECQAIPGLCQGGNCINTVGSFECKCPAGHKLNEVSQKCEDIDECSTIPGICEGGECTNTVSSYFCKCPPGFYTSPDGTRCIDVRPGYCYTALTNGRCSNQLPQSITKMQCCCDAGRCWSPGVTVAPEMCPIRATEDFNKLCSVPMVIPGRPEYPPPPLGPIPPVLPVPPGFPPGPQIPVPRPPVEYLYPSREPPRVLPVNVTDYCQLVRYLCQNGRCIPTPGSYRCECNKGFQLDLRGECIDVDECEKNPCAGGECINNQGSYTCQCRAGYQSTLTRTECRDIDECLQNGRICNNGRCINTDGSFHCVCNAGFHVTRDGKNCEDMDECSIRNMCLNGMCINEDGSFKCICKPGFQLASDGRYCKDINECETPGICMNGRCVNTDGSYRCECFPGLAVGLDGRVCVDTHMRSTCYGGYKRGQCIKPLFGAVTKSECCCASTEYAFGEPCQPCPAQNSAEYQALCSSGPGMTSAGSDINECALDPDICPNGICENLRGTYKCICNSGYEVDSTGKNCVDINECVLNSLLCDNGQCRNTPGSFVCTCPKGFIYKPDLKTCEDIDECESSPCINGVCKNSPGSFICECSSESTLDPTKTICIETIKGTCWQTVIDGRCEININGATLKSQCCSSLGAAWGSPCTLCQVDPICGKGYSRIKGTQCEDIDECEVFPGVCKNGLCVNTRGSFKCQCPSGMTLDATGRICLDIRLETCFLRYEDEECTLPIAGRHRMDACCCSVGAAWGTEECEECPMRNTPEYEELCPRGPGFATKEITNGKPFFKDINECKMIPSLCTHGKCRNTIGSFKCRCDSGFALDSEERNCTDIDECRISPDLCGRGQCVNTPGDFECKCDEGYESGFMMMKNCMDIDECQRDPLLCRGGVCHNTEGSYRCECPPGHQLSPNISACIDINECELSAHLCPNGRCVNLIGKYQCACNPGYHSTPDRLFCVDIDECSIMNGGCETFCTNSEGSYECSCQPGFALMPDQRSCTDIDECEDNPNICDGGQCTNIPGEYRCLCYDGFMASEDMKTCVDVNECDLNPNICLSGTCENTKGSFICHCDMGYSGKKGKTGCTDINECEIGAHNCGKHAVCTNTAGSFKCSCSPGWIGDGIKCTDLDECSNGTHMCSQHADCKNTMGSYRCLCKEGYTGDGFTCTDLDECSENLNLCGNGQCLNAPGGYRCECDMGFVPSADGKACEDIDECSLPNICVFGTCHNLPGLFRCECEIGYELDRSGGNCTDVNECLDPTTCISGNCVNTPGSYICDCPPDFELNPTRVGCVDTRSGNCYLDIRPRGDNGDTACSNEIGVGVSKASCCCSLGKAWGTPCEMCPAVNTSEYKILCPGGEGFRPNPITVILEDIDECQELPGLCQGGKCINTFGSFQCRCPTGYYLNEDTRVCDDVNECETPGICGPGTCYNTVGNYTCICPPDYMQVNGGNNCMDMRRSLCYRNYYADNQTCDGELLFNMTKKMCCCSYNIGRAWNKPCEQCPIPSTDEFATLCGSQRPGFVIDIYTGLPVDIDECREIPGVCENGVCINMVGSFRCECPVGFFYNDKLLVCEDIDECQNGPVCQRNAECINTAGSYRCDCKPGYRFTSTGQCNDRNECQEIPNICSHGQCIDTVGSFYCLCHTGFKTNDDQTMCLDINECERDACGNGTCRNTIGSFNCRCNHGFILSHNNDCIDVDECASGNGNLCRNGQCINTVGSFQCQCNEGYEVAPDGRTCVDINECLLEPRKCAPGTCQNLDGSYRCICPPGYSLQNEKCEDIDECVEEPEICALGTCSNTEGSFKCLCPEGFSLSSSGRRCQDLRMSYCYAKFEGGKCSSPKSRNHSKQECCCALKGEGWGDPCELCPTEPDEAFRQICPYGSGIIVGPDDSAVDMDECKEPDVCKHGQCINTDGSYRCECPFGYILAGNECVDTDECSVGNPCGNGTCKNVIGGFECTCEEGFEPGPMMTCEDINECAQNPLLCAFRCVNTYGSYECKCPVGYVLREDRRMCKDEDECEEGKHDCTEKQMECKNLIGTYMCICGPGYQRRPDGEGCVDENECQTKPGICENGRCLNTRGSYTCECNDGFTASPNQDECLDNREGYCFTEVLQNMCQIGSSNRNPVTKSECCCDGGRGWGPHCEICPFQGTVAFKKLCPHGRGFMTNGADIDECKVIHDVCRNGECVNDRGSYHCICKTGYTPDITGTSCVDLNECNQAPKPCNFICKNTEGSYQCSCPKGYILQEDGRSCKDLDECATKQHNCQFLCVNTIGGFTCKCPPGFTQHHTSCIDNNECTSDINLCGSKGICQNTPGSFTCECQRGFSLDQTGSSCEDVDECEGNHRCQHGCQNIIGGYRCSCPQGYLQHYQWNQCVDENECLSAHICGGASCHNTLGSYKCMCPAGFQYEQFSGGCQDINECGSAQAPCSYGCSNTEGGYLCGCPPGYFRIGQGHCVSGMGMGRGNPEPPVSGEMDDNSLSPEACYECKINGYPKRGRKRRSTNETDASNIEDQSETEANVSLASWDVEKTAIFAFNISHVSNKVRILELLPALTTLTNHNRYLIESGNEDGFFKINQKEGISYLHFTKKKPVAGTYSLQISSTPLYKKKELNQLEDKYDKDYLSGELGDNLKMKIQVLLH。D为第2444位天冬氨酸(Asp,D)。
突变的FBN1基因编码的173个蛋白为SEQ ID NO:6：
MRRGRLLEIALGFTVLLASYTSHGADANLEAGNVKETRASRAKRRGGGGHDALKGPNVCGSRYNAYCCPGWKTLPGGNQCIVPICRHSCGDGFCSRPNMCTCPSGQIAPSCGSRSIQHCNIRCMNGGSCSDDHCLCQKGYIGTHCGQPVCESGCLNGGRCVAPNRCACTYGFTGPQCERDYRTGPCFTVISNQMCQGQLSGIVCTKTLCCATVGRAWGHPCEMCPAQPHPCRRGFIPNIRTGACQDVDECQAIPGLCQGGNCINTVGSFECKCPAGHKLNEVSQKCEDIDECSTIPGICEGGECTNTVSSYFCKCPPGFYTSPDGTRCIDVRPGYCYTALTNGRCSNQLPQSITKMQCCCDAGRCWSPGVTVAPEMCPIRATEDFNKLCSVPMVIPGRPEYPPPPLGPIPPVLPVPPGFPPGPQIPVPRPPVEYLYPSREPPRVLPVNVTDYCQLVRYLCQNGRCIPTPGSYRCECNKGFQLDLRGECIDVDECEKNPCAGGECINNQGSYTCQCRAGYQSTLTRTECRDIDECLQNGRICNNGRCINTDGSFHCVCNAGFHVTRDGKNCEDMDECSIRNMCLNGMCINEDGSFKCICKPGFQLASDGRYCKDINECETPGICMNGRCVNTDGSYRCECFPGLAVGLDGRVCVDTHMRSTCYGGYKRGQCIKPLFGAVTKSECCCASTEYAFGEPCQPCPAQNSAEYQALCSSGPGMTSAGSDINECALDPDICPNGICENLRGTYKCICNSGYEVDSTGKNCVDINECVLNSLLCDNGQCRNTPGSFVCTCPKGFIYKPDLKTCEDIDECESSPCINGVCKNSPGSFICECSSESTLDPTKTICIETIKGTCWQTVIDGRCEININGATLKSQCCSSLGAAWGSPCTLCQVDPICGKGYSRIKGTQCEDIDECEVFPGVCKNGLCVNTRGSFKCQCPSGMTLDATGRICLDIRLETCFLRYEDEECTLPIAGRHRMDACCCSVGAAWGTEECEECPMRNTPEYEELCPRGPGFATKEITNGKPFFKDINECKMIPSLCTHGKCRNTIGSFKCRCDSGFALDSEERNCTDIDECRISPDLCGRGQCVNTPGDFECKCDEGYESGFMMMKNCMDIDECQRDPLLCRGGVCHNTEGSYRCECPPGHQLSPNISACIDINECELSAHLCPNGRCVNLIGKYQCACNPGYHSTPDRLFCVDIDECSIMNGGCETFCTNSEGSYECSCQPGFALMPDQRSCTDIDECEDNPNICDGGQCTNIPGEYRCLCYDGFMASEDMKTCVDVNECDLNPNICLSGTCENTKGSFICHCDMGYSGKKGKTGCTDINECEIGAHNCGKHAVCTNTAGSFKCSCSPGWIGDGIKCTDLDECSNGTHMCSQHADCKNTMGSYRCLCKEGYTGDGFTCTDLDECSENLNLCGNGQCLNAPGGYRCECDMGFVPSADGKACEDIDECSLPNICVFGTCHNLPGLFRCECEIGYELDRSGGNCTDVNECLDPTTCISGNCVNTPGSYICDCPPDFELNPTRVGCVDTRSGNCYLDIRPRGDNGDTACSNEIGVGVSKASCCCSLGKAWGTPCEMCPAVNTSEYKILCPGGEGFRPNPITVILEDIDECQELPGLCQGGKCINTFGSFQCRCPTGYYLNEDTRVCDDVNECETPGICGPGTCYNTVGNYTCICPPDYMQVNGGNNCMDMRRSLCYRNYYADNQTCDGELLFNMTKKMCCCSYNIGRAWNKPCEQCPIPSTDEFATLCGSQRPGFVIDIYTGLPVDIDECREIPGVCENGVCINMVGSFRCECPVGFFYNDKLLVCEDIDECQNGPVCQRNAECINTAGSYRCDCKPGYRFTSTGQCNDRNECQEIPNICSHGQCIDTVGSFYCLCHTGFKTNDDQTMCLDINECERDACGNGTCRNTIGSFNCRCNHGFILSHNNDCIDVDECASGNGNLCRNGQCINTVGSFQCQCNEGYEVAPDGRTCVDINECLLEPRKCAPGTCQNLDGSYRCICPPGYSLQNEKCEDIDECVEEPEICALGTCSNTEGSFKCLCPEGFSLSSSGRRCQDLRMSYCYAKFEGGKCSSPKSRNHSKQECCCALKGEGWGDPCELCPTEPDEAFRQICPYGSGIIVGPDDSAVDMDECKEPDVCKHGQCINTDGSYRCECPFGYILAGNECVDTDECSVGNPCGNGTCKNVIGGFECTCEEGFEPGPMMTCEDINECAQNPLLCAFRCVNTYGSYECKCPVGYVLREDRRMCKDEDECEEGKHDCTEKQMECKNLIGTYMCICGPGYQRRPDGEGCVDENECQTKPGICENGRCLNTRGSYTCECNDGFTASPNQDECLDNREGYCFTEVLQNMCQIGSSNRNPVTKSECCCDGGRGWGPHCEICPFQGTVAFKKLCPHGRGFMTNGADIDECKVIHDVCRNGECVNDRGSYHCICKTGYTPDITGTSCVVLNECNQAPKPCNFICKNTEGSYQCSCPKGYILQEDGRSCKDLDECATKQHNCQFLCVNTIGGFTCKCPPGFTQHHTSCIDNNECTSDINLCGSKGICQNTPGSFTCECQRGFSLDQTGSSCEDVDECEGNHRCQHGCQNIIGGYRCSCPQGYLQHYQWNQCVDENECLSAHICGGASCHNTLGSYKCMCPAGFQYEQFSGGCQDINECGSAQAPCSYGCSNTEGGYLCGCPPGYFRIGQGHCVSGMGMGRGNPEPPVSGEMDDNSLSPEACYECKINGYPKRGRKRRSTNETDASNIEDQSETEANVSLASWDVEKTAIFAFNISHVSNKVRILELLPALTTLTNHNRYLIESGNEDGFFKINQKEGISYLHFTKKKPVAGTYSLQISSTPLYKKKELNQLEDKYDKDYLSGELGDNLKMKIQVLLH，V为第2444位的缬氨酸(Val,V)。
p.Asp2444Val表示：第2444位的天冬氨酸(Asp,D)突变为缬氨酸(Val,V)。
查询人群频率数据库发现该变异为罕见变异(千人基因组：无，ESP6500：无，ExAC：无)。百世诺本地人群数据库中的马凡氏综合征患者和对照人群均未携带该变异。
本实施例还采用多个生物信息预测软件(包括SIFT和Polyphen-2等)进行交叉预测，结果均为有害(SIFT为“D”，Polyphen-2为“D”，MutationTaster_pred为“D”，VEST3评分为“0.893”，其他为“5个D/1个H”)，提示该变异所致的氨基酸改变可能会对蛋白功能产生影响。氨基酸由极性带负电荷的天冬氨酸变为非极性的缬氨酸。查询数据库发现该位置的氨基酸在脊椎动物中高度保守。查询ClinVar、HGMD数据库未发现该变异，该位置的其他错义变异p.Asp2444Gly被上报者评定为马凡氏综合征的致病突变(HGMD数据库，ClinVar数据库)；该位点附近的错义变异p.Cys2448Arg、p.Glu2447Lys均被上报者评定为马凡氏综合征的致病突变(ClinVar数据库)；文献检索未发现该变异与疾病相关的报导。根据现有证据：该变异为罕见变异、软件预测该变异可能会对蛋白功能产生影响、该位置氨基酸在脊椎动物中高度保守、附近位点多次被报导为致病突变，推测该变异为马凡氏综合征的高度可疑致病突变。
(2)图1为实施例1的家系图；图2为实施例1中先证者的Sanger测序图；图3为实施例1家系中未患病成员的Sanger测序图。
如图1-图3所示，先证者携带的突变的FBN1基因遗传自先证者父亲，先证者爷爷(80+岁)身高较高，无其他症状。先证者姐姐，身高较高，因主动脉夹层破裂猝死；先证者叔叔30+岁猝死，具体原因不详。先证者的姑姑也携带了突变的FBN1基因。
实施例2-马凡氏综合征检测试剂盒
本实施例提供用于检测人类FBN1基因c.7331A>T杂合错义变异的试剂盒，包括2×Taq MasterMix(Dye)、能够检测突变的FBN1基因的引物等，试剂盒的具体组成如下表3所示。
利用本试剂盒筛选具有c.7331A>T FBN1基因突变的患者的具体步骤为：按照实施例1的步骤提取待测者DNA，然后使用经设计的引物组合(SEQ ID NO:7和SEQ ID NO:8)对FBN1基因进行扩增，得到PCR产物，最后对PCR产物进行测序。从NCBI(https://www.ncbi.nlm.nih.gov/)数据库获得参考序列和测序结果进行比对，判断待测者FBN1基因是否携带c.7331A>T杂合错义变异，协助临床确诊待测者是否患有具有c.7331A>T FBN1基因突变的患者。
表3试剂盒组成
实施例3针对家系外的正常人的突变验证
参照实施例1的方法或采用实施例2的马凡氏综合征检测试剂盒，对793例同种族无关正常人(即家系外正常人)进行FBN1基因c.7331A>T突变位点检测，结果均未能检测到该突变。
结果显示，基于FBN1基因的c.7331A>T杂合错义变异会导致FBN1基因编码的蛋白质发生p.Ter173Gly的改变，而FBN1基因是已知致病基因，从而再次证明了FBN1基因的c.7331A>T杂合错义变异为致病突变。
以上详细描述了本发明的较佳具体实施例。应当理解，本领域的普通技术人员无需创造性劳动就可以根据本发明的构思作出诸多修改和变化。因此，凡本技术领域中技术人员依本发明的构思在现有技术的基础上通过逻辑分析、推理或者有限的实验可以得到的技术方案，皆应在由权利要求书所确定的保护范围内。
序列表
<110> 百世诺（北京）医学检验实验室有限公司
<120> 突变的FBN1基因及马凡氏综合征检测试剂盒
<160> 8
<170> SIPOSequenceListing 1.0
<210> 1
<211> 50
<212> DNA
<213> homo sapiens
<400> 1
cagtcacgct gtatttcttt gatcatagat ctgaacgagt gcaaccaggc 50
<210> 2
<211> 50
<212> DNA
<213> homo sapiens
<400> 2
cagtcacgct gtatttcttt gatcatagtt ctgaacgagt gcaaccaggc 50
<210> 3
<211> 8616
<212> DNA
<213> homo sapiens
<400> 3
atgcgtcgag ggcgtctgct ggagatcgcc ctgggattta ccgtgctttt agcgtcctac 60
acgagccatg gggcggacgc caatttggag gctgggaacg tgaaggaaac cagagccagt 120
cgggccaaga gaagaggcgg tggaggacac gacgcgctta aaggacccaa tgtctgtgga 180
tcacgttata atgcttactg ttgccctgga tggaaaacct tacctggcgg aaatcagtgt 240
attgtcccca tttgccggca ttcctgtggg gatggatttt gttcgaggcc aaatatgtgc 300
acttgcccat ctggtcagat agctccttcc tgtggctcca gatccataca acactgcaat 360
attcgctgta tgaatggagg tagctgcagt gacgatcact gtctatgcca gaaaggatac 420
atagggactc actgtggaca acctgtttgt gaaagtggct gtctcaatgg aggaaggtgt 480
gtggccccaa atcgatgtgc atgcacttac ggatttactg gaccccagtg tgaaagagat 540
tacaggacag gcccatgttt tactgtgatc agcaaccaga tgtgccaggg acaactcagc 600
gggattgtct gcacaaaaac gctctgctgt gccacagtcg gccgagcctg gggccacccc 660
tgtgagatgt gtcctgccca gcctcacccc tgccgccgtg gcttcattcc aaatatccgc 720
acgggagctt gtcaagatgt ggatgaatgc caggccatcc ccgggctctg tcagggagga 780
aattgcatta atactgttgg gtcttttgag tgcaaatgcc ctgctggaca caaacttaat 840
gaagtgtcac aaaaatgtga agatattgat gaatgcagca ccattcctgg aatctgtgaa 900
gggggtgaat gtacaaacac agtcagcagt tacttttgca aatgtccccc tggtttttac 960
acctctccag atggtaccag atgcatagat gttcgcccag gatactgtta cacagctctg 1020
acaaacgggc gctgctctaa ccagctgcca cagtccataa ccaaaatgca gtgctgctgt 1080
gatgccggcc gatgctggtc tccaggggtc actgtcgccc ctgagatgtg tcccatcaga 1140
gcaaccgagg atttcaacaa gctgtgctct gttcctatgg taattcctgg gagaccagaa 1200
tatcctcccc caccccttgg ccccattcct ccagttctcc ctgttcctcc tggctttcct 1260
cctggacctc aaattccggt ccctcgacca ccagtggaat atctgtatcc atctcgggag 1320
ccaccaaggg tgctgccagt aaacgttact gattactgcc agttggtccg ctatctctgt 1380
caaaatggac gctgcattcc aactcctggg agttaccggt gtgagtgcaa caaagggttc 1440
cagctggacc tccgtgggga gtgtattgat gttgatgaat gtgagaaaaa cccctgtgct 1500
ggtggtgagt gtattaacaa ccagggttcg tacacctgtc agtgccgagc tggatatcag 1560
agcacactca cgcggacaga atgccgagac attgatgagt gtttacagaa tggccggatc 1620
tgcaataatg gacgctgcat caacacagat ggcagttttc attgcgtgtg taatgcgggc 1680
tttcatgtta cacgagatgg gaagaactgt gaagatatgg atgaatgcag cataaggaac 1740
atgtgcctta atggaatgtg tatcaatgaa gatggcagtt ttaaatgtat ttgcaaacct 1800
ggattccagc tggcatcaga tggacgttat tgcaaagaca ttaacgagtg tgaaacccct 1860
gggatctgca tgaatgggcg ttgcgtcaac actgatggct cctacagatg tgaatgcttc 1920
cctggactgg ctgtgggtct ggatggccgt gtgtgtgttg acacacacat gcggagcaca 1980
tgctatggtg gatacaagag aggccagtgt atcaaacctt tgtttggtgc tgtcactaaa 2040
tctgaatgct gttgcgccag cactgagtat gcatttgggg aaccttgcca gccgtgtcct 2100
gcacagaatt cagcggaata tcaggcactc tgcagcagtg ggccaggaat gacgtcagca 2160
ggcagtgata taaatgaatg tgcactagat cctgatattt gcccaaatgg aatctgtgaa 2220
aaccttcgtg ggacctataa atgtatatgc aattcaggat atgaagtgga ttcaactggg 2280
aaaaactgcg ttgatattaa tgaatgtgta ctgaacagtc tcctttgtga caatggacaa 2340
tgtagaaata ctcctggaag ttttgtctgt acctgcccca agggatttat ctacaaacct 2400
gatctaaaaa catgtgaaga cattgatgaa tgcgaatcaa gtccttgcat taatggagtc 2460
tgcaagaaca gcccaggctc ttttatttgt gaatgttctt ctgaaagtac tttggatcca 2520
acaaaaacca tctgcataga aaccatcaag ggcacttgct ggcagactgt cattgatggg 2580
cgatgtgaga tcaacatcaa tggagccacc ttaaagtccc agtgctgctc ctccctcggt 2640
gctgcgtggg gaagcccgtg caccctatgc caagttgatc ccatatgtgg taaagggtac 2700
tcaagaatta aaggaacaca atgtgaagat atagatgaat gtgaagtgtt cccaggagtg 2760
tgtaaaaatg gcctgtgtgt taacactagg gggtcattca agtgtcagtg tcccagtgga 2820
atgactttgg atgccacagg aaggatctgt cttgatatcc gcctggaaac ctgcttcctg 2880
aggtacgagg acgaggagtg caccctgcct attgctggcc gccaccgcat ggacgcctgc 2940
tgctgctccg tcggggcagc ctggggtact gaggaatgcg aggagtgtcc catgagaaat 3000
actcctgagt acgaggagct gtgtccgaga ggacccggat ttgccacaaa agaaattaca 3060
aatggaaagc ctttcttcaa agatatcaat gagtgcaaga tgatacccag cctctgcacc 3120
cacggcaagt gcagaaacac cattggcagc tttaagtgca ggtgtgacag cggctttgct 3180
cttgattctg aagaaaggaa ctgcacagac attgacgaat gccgcatatc tcctgacctc 3240
tgtggcagag gccagtgtgt gaacacccct ggggactttg aatgcaagtg tgacgaaggc 3300
tatgaaagtg gattcatgat gatgaagaac tgcatggata ttgatgagtg tcagagagat 3360
cctctcctat gccgaggtgg tgtttgccat aacacagagg gaagttaccg ctgtgaatgc 3420
ccgcctggcc atcagctgtc ccccaacatc tccgcgtgta tcgacatcaa tgaatgtgag 3480
ctgagtgcac acctgtgccc caatggccgt tgcgtgaacc tcatagggaa gtatcagtgt 3540
gcctgcaacc ctggctacca ttcaactccc gataggctat tttgtgttga cattgatgaa 3600
tgcagcataa tgaatggtgg ttgtgaaacc ttctgcacaa actctgaagg cagctatgaa 3660
tgtagctgtc agccgggatt tgcactaatg cctgaccaga gatcatgcac cgacatcgat 3720
gagtgtgaag ataatcccaa tatctgtgat ggtggtcagt gcacaaatat ccctggagag 3780
tacaggtgct tgtgttatga tggattcatg gcatctgaag acatgaagac ttgtgtagat 3840
gtcaatgagt gtgacctgaa tccaaatatc tgcctaagtg ggacctgtga aaacacgaaa 3900
ggctcattta tctgccactg tgatatgggc tactccggca aaaaaggaaa aactggctgt 3960
acagacatca atgaatgtga aattggagca cacaactgtg gcaaacatgc tgtatgtacc 4020
aatacagcag gaagcttcaa atgtagctgc agtcccgggt ggattggaga tggcattaag 4080
tgcactgatc tggacgaatg ttccaatgga acccatatgt gcagccagca tgcagactgc 4140
aagaatacca tgggatctta ccgctgtctg tgcaaggaag gatacacagg tgatggcttc 4200
acttgtacag accttgatga gtgctctgag aacctgaatc tctgtggcaa tggccagtgc 4260
ctcaatgcac caggaggata ccgctgtgaa tgcgacatgg gcttcgtgcc cagtgctgac 4320
gggaaagcct gtgaagatat tgatgagtgc tcccttccga acatctgtgt ctttggaact 4380
tgccacaacc tccctggcct gttccgctgt gagtgtgaga taggctacga actggacaga 4440
agcggcggga actgcacaga tgtgaatgaa tgcctggatc caaccacgtg catcagtggg 4500
aactgtgtca acactccagg cagctatatc tgtgactgcc cacctgattt tgaactgaac 4560
ccaactcgag ttggctgtgt tgatacccgc tctggaaatt gctatttgga tattcgacct 4620
cgaggagaca atggagatac agcctgcagc aatgaaattg gagttggtgt ttccaaagct 4680
tcctgctgct gttctctggg taaagcctgg ggtactcctt gtgagatgtg tcctgctgtg 4740
aacacatccg agtacaaaat tctttgtcct ggaggggaag gtttccgacc aaatcctatc 4800
accgttatat tggaagatat tgatgagtgc caggagctac cagggctgtg ccaaggagga 4860
aaatgtatca acacctttgg gagtttccag tgccgctgtc caaccggcta ctacctgaat 4920
gaagatacac gagtgtgtga tgatgtgaat gaatgtgaga ctcctggaat ctgtggtcca 4980
gggacatgtt acaacaccgt tggcaactac acctgtatct gtcctccaga ctacatgcaa 5040
gtgaatgggg gaaataattg catggatatg agaagaagtt tgtgctacag aaactactat 5100
gctgacaacc agacctgtga tggagaattg ttattcaaca tgaccaagaa gatgtgctgc 5160
tgttcctaca acattggccg ggcgtggaac aagccctgtg aacagtgtcc catcccaagt 5220
acagatgagt ttgctacact ctgtggaagt caaaggccag gctttgtcat cgacatttat 5280
accggtttac ccgttgatat tgatgagtgc cgggagatcc caggggtctg tgaaaatgga 5340
gtgtgtatca acatggttgg cagcttccga tgtgaatgtc cagtgggatt cttctataat 5400
gacaagttgt tggtttgtga agatattgac gagtgtcaga acggcccagt gtgccagcgc 5460
aacgccgaat gcatcaacac tgcaggcagc taccgctgtg actgtaagcc cggctaccgc 5520
ttcacctcca caggacagtg caatgatcgt aatgaatgtc aagaaatccc caatatatgc 5580
agtcatgggc agtgcattga cacagttgga agcttttatt gcctttgcca cactggtttt 5640
aaaacaaatg atgaccaaac catgtgcttg gacataaatg aatgtgaaag agatgcctgt 5700
gggaatggaa cttgccggaa cacaattggt tccttcaact gccgctgcaa tcatggtttc 5760
atcctttctc acaacaatga ctgtatagat gttgatgaat gtgcaagtgg aaatgggaat 5820
ctttgcagaa atggccaatg cattaataca gtggggtctt tccagtgcca gtgcaatgaa 5880
ggctatgagg tggctccaga tgggaggacc tgtgtggata tcaatgaatg tcttctagaa 5940
cccagaaaat gtgcaccagg tacctgtcaa aacttggatg ggtcctacag atgcatttgc 6000
ccacctggat acagtcttca aaatgagaag tgtgaagata ttgatgagtg tgtcgaagag 6060
ccagaaattt gtgccctggg cacatgcagt aacactgaag gcagcttcaa atgtctgtgt 6120
ccagaagggt tttccttgtc ctccagtgga agaaggtgcc aagatttgcg aatgagctac 6180
tgttatgcga agtttgaagg aggaaagtgt tcatcaccca aatccagaaa tcactccaag 6240
caggaatgct gctgtgcctt gaagggagaa ggctggggag acccctgcga gctctgcccc 6300
acggaacctg atgaggcctt ccgccagata tgtccttatg gaagtgggat catcgtggga 6360
cctgatgatt cagcagttga tatggacgaa tgcaaagaac ccgatgtctg taaacatgga 6420
cagtgcatca atacagatgg ttcctatcgc tgcgagtgtc cctttggtta tattctagca 6480
gggaatgaat gtgtagatac tgatgaatgt tctgttggca atccttgtgg aaatggaacc 6540
tgcaagaatg tgattggagg ttttgaatgc acctgcgagg agggatttga gcccggtcca 6600
atgatgacat gtgaagatat aaatgaatgt gcccagaatc ctctgctctg tgccttccga 6660
tgtgtgaaca cttatgggtc atatgaatgc aaatgtcccg tgggatatgt gctcagagaa 6720
gaccgtagga tgtgcaaaga tgaggatgag tgtgaagagg gaaaacatga ctgtactgaa 6780
aaacaaatgg aatgcaagaa cctcattggc acatatatgt gcatctgtgg acccgggtat 6840
cagcggagac ctgatggaga aggctgtgta gatgagaatg aatgtcagac gaagccaggg 6900
atctgtgaga atgggcgctg cctcaacacc cgtgggagct acacctgtga gtgtaatgat 6960
gggtttaccg ccagccccaa ccaggacgag tgccttgaca atcgggaagg gtactgcttc 7020
acagaggtgc tacaaaacat gtgtcagatc ggctccagca acaggaaccc cgtcaccaaa 7080
tcggaatgct gctgtgacgg agggagaggc tggggtcccc actgtgagat ctgccctttc 7140
caggggactg tggctttcaa gaaactctgt ccccatggcc gaggattcat gaccaatgga 7200
gcagatatcg atgaatgcaa ggttattcac gatgtttgcc gaaatgggga atgtgtcaat 7260
gacagaggat catatcattg catttgtaaa actgggtaca ctccagatat aactgggact 7320
tcctgtgtag atctgaacga gtgcaaccag gctcccaaac cctgcaattt tatctgcaaa 7380
aacacagaag ggagttacca gtgttcatgc ccgaaaggct acattctgca agaggatgga 7440
aggagctgca aagatcttga tgagtgtgca accaagcaac acaactgcca gttcctatgt 7500
gttaacacca ttggcggctt cacatgcaaa tgtcctcccg gatttaccca acaccatacg 7560
tcctgcattg ataacaatga atgcacctct gacatcaatc tgtgcgggtc taagggcatt 7620
tgccagaaca ctcctggaag cttcacctgt gaatgccagc ggggattctc acttgatcag 7680
accggctcca gctgtgaaga cgtggacgag tgtgagggta accaccgctg ccagcatggc 7740
tgccagaaca tcattggggg ctacaggtgc agctgccccc agggctacct ccagcactac 7800
cagtggaacc agtgtgttga tgaaaacgaa tgcctcagcg ctcacatctg cggaggagcc 7860
tcctgtcaca acaccctggg gagctacaag tgcatgtgtc ccgccggctt ccagtatgaa 7920
cagttcagtg gaggatgcca agacatcaat gaatgtggct ctgcgcaggc cccctgcagc 7980
tatggctgtt ccaataccga gggcggttac ctgtgtggct gtccacctgg ttacttccgc 8040
ataggccaag ggcactgtgt ttctggaatg ggcatgggcc gaggaaaccc agagccacct 8100
gtcagtggtg aaatggatga caattcactc tccccagagg cttgttacga gtgtaagatc 8160
aatggctacc ccaaacgggg caggaaacgg agaagcacaa acgaaactga tgcctccaat 8220
atcgaggatc agtctgagac agaagccaat gtgagtcttg caagttggga tgttgagaag 8280
acagccatct ttgctttcaa tatttcccac gtcagtaaca aggttcgaat cctagaactc 8340
cttccagctc ttacaactct gacgaatcac aacagatact tgatcgaatc tggaaatgaa 8400
gatggcttct ttaaaatcaa ccaaaaggaa gggatcagct acctccactt cacaaagaag 8460
aagccagtgg ctggaaccta ttcattacaa atcagtagta ctccacttta taaaaagaaa 8520
gaacttaacc aactagaaga caaatatgac aaagactacc tcagtggtga actgggtgat 8580
aatctgaaga tgaaaatcca ggttttgctt cattaa 8616
<210> 4
<211> 8616
<212> DNA
<213> homo sapiens
<400> 4
atgcgtcgag ggcgtctgct ggagatcgcc ctgggattta ccgtgctttt agcgtcctac 60
acgagccatg gggcggacgc caatttggag gctgggaacg tgaaggaaac cagagccagt 120
cgggccaaga gaagaggcgg tggaggacac gacgcgctta aaggacccaa tgtctgtgga 180
tcacgttata atgcttactg ttgccctgga tggaaaacct tacctggcgg aaatcagtgt 240
attgtcccca tttgccggca ttcctgtggg gatggatttt gttcgaggcc aaatatgtgc 300
acttgcccat ctggtcagat agctccttcc tgtggctcca gatccataca acactgcaat 360
attcgctgta tgaatggagg tagctgcagt gacgatcact gtctatgcca gaaaggatac 420
atagggactc actgtggaca acctgtttgt gaaagtggct gtctcaatgg aggaaggtgt 480
gtggccccaa atcgatgtgc atgcacttac ggatttactg gaccccagtg tgaaagagat 540
tacaggacag gcccatgttt tactgtgatc agcaaccaga tgtgccaggg acaactcagc 600
gggattgtct gcacaaaaac gctctgctgt gccacagtcg gccgagcctg gggccacccc 660
tgtgagatgt gtcctgccca gcctcacccc tgccgccgtg gcttcattcc aaatatccgc 720
acgggagctt gtcaagatgt ggatgaatgc caggccatcc ccgggctctg tcagggagga 780
aattgcatta atactgttgg gtcttttgag tgcaaatgcc ctgctggaca caaacttaat 840
gaagtgtcac aaaaatgtga agatattgat gaatgcagca ccattcctgg aatctgtgaa 900
gggggtgaat gtacaaacac agtcagcagt tacttttgca aatgtccccc tggtttttac 960
acctctccag atggtaccag atgcatagat gttcgcccag gatactgtta cacagctctg 1020
acaaacgggc gctgctctaa ccagctgcca cagtccataa ccaaaatgca gtgctgctgt 1080
gatgccggcc gatgctggtc tccaggggtc actgtcgccc ctgagatgtg tcccatcaga 1140
gcaaccgagg atttcaacaa gctgtgctct gttcctatgg taattcctgg gagaccagaa 1200
tatcctcccc caccccttgg ccccattcct ccagttctcc ctgttcctcc tggctttcct 1260
cctggacctc aaattccggt ccctcgacca ccagtggaat atctgtatcc atctcgggag 1320
ccaccaaggg tgctgccagt aaacgttact gattactgcc agttggtccg ctatctctgt 1380
caaaatggac gctgcattcc aactcctggg agttaccggt gtgagtgcaa caaagggttc 1440
cagctggacc tccgtgggga gtgtattgat gttgatgaat gtgagaaaaa cccctgtgct 1500
ggtggtgagt gtattaacaa ccagggttcg tacacctgtc agtgccgagc tggatatcag 1560
agcacactca cgcggacaga atgccgagac attgatgagt gtttacagaa tggccggatc 1620
tgcaataatg gacgctgcat caacacagat ggcagttttc attgcgtgtg taatgcgggc 1680
tttcatgtta cacgagatgg gaagaactgt gaagatatgg atgaatgcag cataaggaac 1740
atgtgcctta atggaatgtg tatcaatgaa gatggcagtt ttaaatgtat ttgcaaacct 1800
ggattccagc tggcatcaga tggacgttat tgcaaagaca ttaacgagtg tgaaacccct 1860
gggatctgca tgaatgggcg ttgcgtcaac actgatggct cctacagatg tgaatgcttc 1920
cctggactgg ctgtgggtct ggatggccgt gtgtgtgttg acacacacat gcggagcaca 1980
tgctatggtg gatacaagag aggccagtgt atcaaacctt tgtttggtgc tgtcactaaa 2040
tctgaatgct gttgcgccag cactgagtat gcatttgggg aaccttgcca gccgtgtcct 2100
gcacagaatt cagcggaata tcaggcactc tgcagcagtg ggccaggaat gacgtcagca 2160
ggcagtgata taaatgaatg tgcactagat cctgatattt gcccaaatgg aatctgtgaa 2220
aaccttcgtg ggacctataa atgtatatgc aattcaggat atgaagtgga ttcaactggg 2280
aaaaactgcg ttgatattaa tgaatgtgta ctgaacagtc tcctttgtga caatggacaa 2340
tgtagaaata ctcctggaag ttttgtctgt acctgcccca agggatttat ctacaaacct 2400
gatctaaaaa catgtgaaga cattgatgaa tgcgaatcaa gtccttgcat taatggagtc 2460
tgcaagaaca gcccaggctc ttttatttgt gaatgttctt ctgaaagtac tttggatcca 2520
acaaaaacca tctgcataga aaccatcaag ggcacttgct ggcagactgt cattgatggg 2580
cgatgtgaga tcaacatcaa tggagccacc ttaaagtccc agtgctgctc ctccctcggt 2640
gctgcgtggg gaagcccgtg caccctatgc caagttgatc ccatatgtgg taaagggtac 2700
tcaagaatta aaggaacaca atgtgaagat atagatgaat gtgaagtgtt cccaggagtg 2760
tgtaaaaatg gcctgtgtgt taacactagg gggtcattca agtgtcagtg tcccagtgga 2820
atgactttgg atgccacagg aaggatctgt cttgatatcc gcctggaaac ctgcttcctg 2880
aggtacgagg acgaggagtg caccctgcct attgctggcc gccaccgcat ggacgcctgc 2940
tgctgctccg tcggggcagc ctggggtact gaggaatgcg aggagtgtcc catgagaaat 3000
actcctgagt acgaggagct gtgtccgaga ggacccggat ttgccacaaa agaaattaca 3060
aatggaaagc ctttcttcaa agatatcaat gagtgcaaga tgatacccag cctctgcacc 3120
cacggcaagt gcagaaacac cattggcagc tttaagtgca ggtgtgacag cggctttgct 3180
cttgattctg aagaaaggaa ctgcacagac attgacgaat gccgcatatc tcctgacctc 3240
tgtggcagag gccagtgtgt gaacacccct ggggactttg aatgcaagtg tgacgaaggc 3300
tatgaaagtg gattcatgat gatgaagaac tgcatggata ttgatgagtg tcagagagat 3360
cctctcctat gccgaggtgg tgtttgccat aacacagagg gaagttaccg ctgtgaatgc 3420
ccgcctggcc atcagctgtc ccccaacatc tccgcgtgta tcgacatcaa tgaatgtgag 3480
ctgagtgcac acctgtgccc caatggccgt tgcgtgaacc tcatagggaa gtatcagtgt 3540
gcctgcaacc ctggctacca ttcaactccc gataggctat tttgtgttga cattgatgaa 3600
tgcagcataa tgaatggtgg ttgtgaaacc ttctgcacaa actctgaagg cagctatgaa 3660
tgtagctgtc agccgggatt tgcactaatg cctgaccaga gatcatgcac cgacatcgat 3720
gagtgtgaag ataatcccaa tatctgtgat ggtggtcagt gcacaaatat ccctggagag 3780
tacaggtgct tgtgttatga tggattcatg gcatctgaag acatgaagac ttgtgtagat 3840
gtcaatgagt gtgacctgaa tccaaatatc tgcctaagtg ggacctgtga aaacacgaaa 3900
ggctcattta tctgccactg tgatatgggc tactccggca aaaaaggaaa aactggctgt 3960
acagacatca atgaatgtga aattggagca cacaactgtg gcaaacatgc tgtatgtacc 4020
aatacagcag gaagcttcaa atgtagctgc agtcccgggt ggattggaga tggcattaag 4080
tgcactgatc tggacgaatg ttccaatgga acccatatgt gcagccagca tgcagactgc 4140
aagaatacca tgggatctta ccgctgtctg tgcaaggaag gatacacagg tgatggcttc 4200
acttgtacag accttgatga gtgctctgag aacctgaatc tctgtggcaa tggccagtgc 4260
ctcaatgcac caggaggata ccgctgtgaa tgcgacatgg gcttcgtgcc cagtgctgac 4320
gggaaagcct gtgaagatat tgatgagtgc tcccttccga acatctgtgt ctttggaact 4380
tgccacaacc tccctggcct gttccgctgt gagtgtgaga taggctacga actggacaga 4440
agcggcggga actgcacaga tgtgaatgaa tgcctggatc caaccacgtg catcagtggg 4500
aactgtgtca acactccagg cagctatatc tgtgactgcc cacctgattt tgaactgaac 4560
ccaactcgag ttggctgtgt tgatacccgc tctggaaatt gctatttgga tattcgacct 4620
cgaggagaca atggagatac agcctgcagc aatgaaattg gagttggtgt ttccaaagct 4680
tcctgctgct gttctctggg taaagcctgg ggtactcctt gtgagatgtg tcctgctgtg 4740
aacacatccg agtacaaaat tctttgtcct ggaggggaag gtttccgacc aaatcctatc 4800
accgttatat tggaagatat tgatgagtgc caggagctac cagggctgtg ccaaggagga 4860
aaatgtatca acacctttgg gagtttccag tgccgctgtc caaccggcta ctacctgaat 4920
gaagatacac gagtgtgtga tgatgtgaat gaatgtgaga ctcctggaat ctgtggtcca 4980
gggacatgtt acaacaccgt tggcaactac acctgtatct gtcctccaga ctacatgcaa 5040
gtgaatgggg gaaataattg catggatatg agaagaagtt tgtgctacag aaactactat 5100
gctgacaacc agacctgtga tggagaattg ttattcaaca tgaccaagaa gatgtgctgc 5160
tgttcctaca acattggccg ggcgtggaac aagccctgtg aacagtgtcc catcccaagt 5220
acagatgagt ttgctacact ctgtggaagt caaaggccag gctttgtcat cgacatttat 5280
accggtttac ccgttgatat tgatgagtgc cgggagatcc caggggtctg tgaaaatgga 5340
gtgtgtatca acatggttgg cagcttccga tgtgaatgtc cagtgggatt cttctataat 5400
gacaagttgt tggtttgtga agatattgac gagtgtcaga acggcccagt gtgccagcgc 5460
aacgccgaat gcatcaacac tgcaggcagc taccgctgtg actgtaagcc cggctaccgc 5520
ttcacctcca caggacagtg caatgatcgt aatgaatgtc aagaaatccc caatatatgc 5580
agtcatgggc agtgcattga cacagttgga agcttttatt gcctttgcca cactggtttt 5640
aaaacaaatg atgaccaaac catgtgcttg gacataaatg aatgtgaaag agatgcctgt 5700
gggaatggaa cttgccggaa cacaattggt tccttcaact gccgctgcaa tcatggtttc 5760
atcctttctc acaacaatga ctgtatagat gttgatgaat gtgcaagtgg aaatgggaat 5820
ctttgcagaa atggccaatg cattaataca gtggggtctt tccagtgcca gtgcaatgaa 5880
ggctatgagg tggctccaga tgggaggacc tgtgtggata tcaatgaatg tcttctagaa 5940
cccagaaaat gtgcaccagg tacctgtcaa aacttggatg ggtcctacag atgcatttgc 6000
ccacctggat acagtcttca aaatgagaag tgtgaagata ttgatgagtg tgtcgaagag 6060
ccagaaattt gtgccctggg cacatgcagt aacactgaag gcagcttcaa atgtctgtgt 6120
ccagaagggt tttccttgtc ctccagtgga agaaggtgcc aagatttgcg aatgagctac 6180
tgttatgcga agtttgaagg aggaaagtgt tcatcaccca aatccagaaa tcactccaag 6240
caggaatgct gctgtgcctt gaagggagaa ggctggggag acccctgcga gctctgcccc 6300
acggaacctg atgaggcctt ccgccagata tgtccttatg gaagtgggat catcgtggga 6360
cctgatgatt cagcagttga tatggacgaa tgcaaagaac ccgatgtctg taaacatgga 6420
cagtgcatca atacagatgg ttcctatcgc tgcgagtgtc cctttggtta tattctagca 6480
gggaatgaat gtgtagatac tgatgaatgt tctgttggca atccttgtgg aaatggaacc 6540
tgcaagaatg tgattggagg ttttgaatgc acctgcgagg agggatttga gcccggtcca 6600
atgatgacat gtgaagatat aaatgaatgt gcccagaatc ctctgctctg tgccttccga 6660
tgtgtgaaca cttatgggtc atatgaatgc aaatgtcccg tgggatatgt gctcagagaa 6720
gaccgtagga tgtgcaaaga tgaggatgag tgtgaagagg gaaaacatga ctgtactgaa 6780
aaacaaatgg aatgcaagaa cctcattggc acatatatgt gcatctgtgg acccgggtat 6840
cagcggagac ctgatggaga aggctgtgta gatgagaatg aatgtcagac gaagccaggg 6900
atctgtgaga atgggcgctg cctcaacacc cgtgggagct acacctgtga gtgtaatgat 6960
gggtttaccg ccagccccaa ccaggacgag tgccttgaca atcgggaagg gtactgcttc 7020
acagaggtgc tacaaaacat gtgtcagatc ggctccagca acaggaaccc cgtcaccaaa 7080
tcggaatgct gctgtgacgg agggagaggc tggggtcccc actgtgagat ctgccctttc 7140
caggggactg tggctttcaa gaaactctgt ccccatggcc gaggattcat gaccaatgga 7200
gcagatatcg atgaatgcaa ggttattcac gatgtttgcc gaaatgggga atgtgtcaat 7260
gacagaggat catatcattg catttgtaaa actgggtaca ctccagatat aactgggact 7320
tcctgtgtag ttctgaacga gtgcaaccag gctcccaaac cctgcaattt tatctgcaaa 7380
aacacagaag ggagttacca gtgttcatgc ccgaaaggct acattctgca agaggatgga 7440
aggagctgca aagatcttga tgagtgtgca accaagcaac acaactgcca gttcctatgt 7500
gttaacacca ttggcggctt cacatgcaaa tgtcctcccg gatttaccca acaccatacg 7560
tcctgcattg ataacaatga atgcacctct gacatcaatc tgtgcgggtc taagggcatt 7620
tgccagaaca ctcctggaag cttcacctgt gaatgccagc ggggattctc acttgatcag 7680
accggctcca gctgtgaaga cgtggacgag tgtgagggta accaccgctg ccagcatggc 7740
tgccagaaca tcattggggg ctacaggtgc agctgccccc agggctacct ccagcactac 7800
cagtggaacc agtgtgttga tgaaaacgaa tgcctcagcg ctcacatctg cggaggagcc 7860
tcctgtcaca acaccctggg gagctacaag tgcatgtgtc ccgccggctt ccagtatgaa 7920
cagttcagtg gaggatgcca agacatcaat gaatgtggct ctgcgcaggc cccctgcagc 7980
tatggctgtt ccaataccga gggcggttac ctgtgtggct gtccacctgg ttacttccgc 8040
ataggccaag ggcactgtgt ttctggaatg ggcatgggcc gaggaaaccc agagccacct 8100
gtcagtggtg aaatggatga caattcactc tccccagagg cttgttacga gtgtaagatc 8160
aatggctacc ccaaacgggg caggaaacgg agaagcacaa acgaaactga tgcctccaat 8220
atcgaggatc agtctgagac agaagccaat gtgagtcttg caagttggga tgttgagaag 8280
acagccatct ttgctttcaa tatttcccac gtcagtaaca aggttcgaat cctagaactc 8340
cttccagctc ttacaactct gacgaatcac aacagatact tgatcgaatc tggaaatgaa 8400
gatggcttct ttaaaatcaa ccaaaaggaa gggatcagct acctccactt cacaaagaag 8460
aagccagtgg ctggaaccta ttcattacaa atcagtagta ctccacttta taaaaagaaa 8520
gaacttaacc aactagaaga caaatatgac aaagactacc tcagtggtga actgggtgat 8580
aatctgaaga tgaaaatcca ggttttgctt cattaa 8616
<210> 5
<211> 2871
<212> PRT
<213> homo sapiens
<400> 5
Met Arg Arg Gly Arg Leu Leu Glu Ile Ala Leu Gly Phe Thr Val Leu
1 5 10 15
Leu Ala Ser Tyr Thr Ser His Gly Ala Asp Ala Asn Leu Glu Ala Gly
20 25 30
Asn Val Lys Glu Thr Arg Ala Ser Arg Ala Lys Arg Arg Gly Gly Gly
35 40 45
Gly His Asp Ala Leu Lys Gly Pro Asn Val Cys Gly Ser Arg Tyr Asn
50 55 60
Ala Tyr Cys Cys Pro Gly Trp Lys Thr Leu Pro Gly Gly Asn Gln Cys
65 70 75 80
Ile Val Pro Ile Cys Arg His Ser Cys Gly Asp Gly Phe Cys Ser Arg
85 90 95
Pro Asn Met Cys Thr Cys Pro Ser Gly Gln Ile Ala Pro Ser Cys Gly
100 105 110
Ser Arg Ser Ile Gln His Cys Asn Ile Arg Cys Met Asn Gly Gly Ser
115 120 125
Cys Ser Asp Asp His Cys Leu Cys Gln Lys Gly Tyr Ile Gly Thr His
130 135 140
Cys Gly Gln Pro Val Cys Glu Ser Gly Cys Leu Asn Gly Gly Arg Cys
145 150 155 160
Val Ala Pro Asn Arg Cys Ala Cys Thr Tyr Gly Phe Thr Gly Pro Gln
165 170 175
Cys Glu Arg Asp Tyr Arg Thr Gly Pro Cys Phe Thr Val Ile Ser Asn
180 185 190
Gln Met Cys Gln Gly Gln Leu Ser Gly Ile Val Cys Thr Lys Thr Leu
195 200 205
Cys Cys Ala Thr Val Gly Arg Ala Trp Gly His Pro Cys Glu Met Cys
210 215 220
Pro Ala Gln Pro His Pro Cys Arg Arg Gly Phe Ile Pro Asn Ile Arg
225 230 235 240
Thr Gly Ala Cys Gln Asp Val Asp Glu Cys Gln Ala Ile Pro Gly Leu
245 250 255
Cys Gln Gly Gly Asn Cys Ile Asn Thr Val Gly Ser Phe Glu Cys Lys
260 265 270
Cys Pro Ala Gly His Lys Leu Asn Glu Val Ser Gln Lys Cys Glu Asp
275 280 285
Ile Asp Glu Cys Ser Thr Ile Pro Gly Ile Cys Glu Gly Gly Glu Cys
290 295 300
Thr Asn Thr Val Ser Ser Tyr Phe Cys Lys Cys Pro Pro Gly Phe Tyr
305 310 315 320
Thr Ser Pro Asp Gly Thr Arg Cys Ile Asp Val Arg Pro Gly Tyr Cys
325 330 335
Tyr Thr Ala Leu Thr Asn Gly Arg Cys Ser Asn Gln Leu Pro Gln Ser
340 345 350
Ile Thr Lys Met Gln Cys Cys Cys Asp Ala Gly Arg Cys Trp Ser Pro
355 360 365
Gly Val Thr Val Ala Pro Glu Met Cys Pro Ile Arg Ala Thr Glu Asp
370 375 380
Phe Asn Lys Leu Cys Ser Val Pro Met Val Ile Pro Gly Arg Pro Glu
385 390 395 400
Tyr Pro Pro Pro Pro Leu Gly Pro Ile Pro Pro Val Leu Pro Val Pro
405 410 415
Pro Gly Phe Pro Pro Gly Pro Gln Ile Pro Val Pro Arg Pro Pro Val
420 425 430
Glu Tyr Leu Tyr Pro Ser Arg Glu Pro Pro Arg Val Leu Pro Val Asn
435 440 445
Val Thr Asp Tyr Cys Gln Leu Val Arg Tyr Leu Cys Gln Asn Gly Arg
450 455 460
Cys Ile Pro Thr Pro Gly Ser Tyr Arg Cys Glu Cys Asn Lys Gly Phe
465 470 475 480
Gln Leu Asp Leu Arg Gly Glu Cys Ile Asp Val Asp Glu Cys Glu Lys
485 490 495
Asn Pro Cys Ala Gly Gly Glu Cys Ile Asn Asn Gln Gly Ser Tyr Thr
500 505 510
Cys Gln Cys Arg Ala Gly Tyr Gln Ser Thr Leu Thr Arg Thr Glu Cys
515 520 525
Arg Asp Ile Asp Glu Cys Leu Gln Asn Gly Arg Ile Cys Asn Asn Gly
530 535 540
Arg Cys Ile Asn Thr Asp Gly Ser Phe His Cys Val Cys Asn Ala Gly
545 550 555 560
Phe His Val Thr Arg Asp Gly Lys Asn Cys Glu Asp Met Asp Glu Cys
565 570 575
Ser Ile Arg Asn Met Cys Leu Asn Gly Met Cys Ile Asn Glu Asp Gly
580 585 590
Ser Phe Lys Cys Ile Cys Lys Pro Gly Phe Gln Leu Ala Ser Asp Gly
595 600 605
Arg Tyr Cys Lys Asp Ile Asn Glu Cys Glu Thr Pro Gly Ile Cys Met
610 615 620
Asn Gly Arg Cys Val Asn Thr Asp Gly Ser Tyr Arg Cys Glu Cys Phe
625 630 635 640
Pro Gly Leu Ala Val Gly Leu Asp Gly Arg Val Cys Val Asp Thr His
645 650 655
Met Arg Ser Thr Cys Tyr Gly Gly Tyr Lys Arg Gly Gln Cys Ile Lys
660 665 670
Pro Leu Phe Gly Ala Val Thr Lys Ser Glu Cys Cys Cys Ala Ser Thr
675 680 685
Glu Tyr Ala Phe Gly Glu Pro Cys Gln Pro Cys Pro Ala Gln Asn Ser
690 695 700
Ala Glu Tyr Gln Ala Leu Cys Ser Ser Gly Pro Gly Met Thr Ser Ala
705 710 715 720
Gly Ser Asp Ile Asn Glu Cys Ala Leu Asp Pro Asp Ile Cys Pro Asn
725 730 735
Gly Ile Cys Glu Asn Leu Arg Gly Thr Tyr Lys Cys Ile Cys Asn Ser
740 745 750
Gly Tyr Glu Val Asp Ser Thr Gly Lys Asn Cys Val Asp Ile Asn Glu
755 760 765
Cys Val Leu Asn Ser Leu Leu Cys Asp Asn Gly Gln Cys Arg Asn Thr
770 775 780
Pro Gly Ser Phe Val Cys Thr Cys Pro Lys Gly Phe Ile Tyr Lys Pro
785 790 795 800
Asp Leu Lys Thr Cys Glu Asp Ile Asp Glu Cys Glu Ser Ser Pro Cys
805 810 815
Ile Asn Gly Val Cys Lys Asn Ser Pro Gly Ser Phe Ile Cys Glu Cys
820 825 830
Ser Ser Glu Ser Thr Leu Asp Pro Thr Lys Thr Ile Cys Ile Glu Thr
835 840 845
Ile Lys Gly Thr Cys Trp Gln Thr Val Ile Asp Gly Arg Cys Glu Ile
850 855 860
Asn Ile Asn Gly Ala Thr Leu Lys Ser Gln Cys Cys Ser Ser Leu Gly
865 870 875 880
Ala Ala Trp Gly Ser Pro Cys Thr Leu Cys Gln Val Asp Pro Ile Cys
885 890 895
Gly Lys Gly Tyr Ser Arg Ile Lys Gly Thr Gln Cys Glu Asp Ile Asp
900 905 910
Glu Cys Glu Val Phe Pro Gly Val Cys Lys Asn Gly Leu Cys Val Asn
915 920 925
Thr Arg Gly Ser Phe Lys Cys Gln Cys Pro Ser Gly Met Thr Leu Asp
930 935 940
Ala Thr Gly Arg Ile Cys Leu Asp Ile Arg Leu Glu Thr Cys Phe Leu
945 950 955 960
Arg Tyr Glu Asp Glu Glu Cys Thr Leu Pro Ile Ala Gly Arg His Arg
965 970 975
Met Asp Ala Cys Cys Cys Ser Val Gly Ala Ala Trp Gly Thr Glu Glu
980 985 990
Cys Glu Glu Cys Pro Met Arg Asn Thr Pro Glu Tyr Glu Glu Leu Cys
995 1000 1005
Pro Arg Gly Pro Gly Phe Ala Thr Lys Glu Ile Thr Asn Gly Lys Pro
1010 1015 1020
Phe Phe Lys Asp Ile Asn Glu Cys Lys Met Ile Pro Ser Leu Cys Thr
1025 1030 1035 1040
His Gly Lys Cys Arg Asn Thr Ile Gly Ser Phe Lys Cys Arg Cys Asp
1045 1050 1055
Ser Gly Phe Ala Leu Asp Ser Glu Glu Arg Asn Cys Thr Asp Ile Asp
1060 1065 1070
Glu Cys Arg Ile Ser Pro Asp Leu Cys Gly Arg Gly Gln Cys Val Asn
1075 1080 1085
Thr Pro Gly Asp Phe Glu Cys Lys Cys Asp Glu Gly Tyr Glu Ser Gly
1090 1095 1100
Phe Met Met Met Lys Asn Cys Met Asp Ile Asp Glu Cys Gln Arg Asp
1105 1110 1115 1120
Pro Leu Leu Cys Arg Gly Gly Val Cys His Asn Thr Glu Gly Ser Tyr
1125 1130 1135
Arg Cys Glu Cys Pro Pro Gly His Gln Leu Ser Pro Asn Ile Ser Ala
1140 1145 1150
Cys Ile Asp Ile Asn Glu Cys Glu Leu Ser Ala His Leu Cys Pro Asn
1155 1160 1165
Gly Arg Cys Val Asn Leu Ile Gly Lys Tyr Gln Cys Ala Cys Asn Pro
1170 1175 1180
Gly Tyr His Ser Thr Pro Asp Arg Leu Phe Cys Val Asp Ile Asp Glu
1185 1190 1195 1200
Cys Ser Ile Met Asn Gly Gly Cys Glu Thr Phe Cys Thr Asn Ser Glu
1205 1210 1215
Gly Ser Tyr Glu Cys Ser Cys Gln Pro Gly Phe Ala Leu Met Pro Asp
1220 1225 1230
Gln Arg Ser Cys Thr Asp Ile Asp Glu Cys Glu Asp Asn Pro Asn Ile
1235 1240 1245
Cys Asp Gly Gly Gln Cys Thr Asn Ile Pro Gly Glu Tyr Arg Cys Leu
1250 1255 1260
Cys Tyr Asp Gly Phe Met Ala Ser Glu Asp Met Lys Thr Cys Val Asp
1265 1270 1275 1280
Val Asn Glu Cys Asp Leu Asn Pro Asn Ile Cys Leu Ser Gly Thr Cys
1285 1290 1295
Glu Asn Thr Lys Gly Ser Phe Ile Cys His Cys Asp Met Gly Tyr Ser
1300 1305 1310
Gly Lys Lys Gly Lys Thr Gly Cys Thr Asp Ile Asn Glu Cys Glu Ile
1315 1320 1325
Gly Ala His Asn Cys Gly Lys His Ala Val Cys Thr Asn Thr Ala Gly
1330 1335 1340
Ser Phe Lys Cys Ser Cys Ser Pro Gly Trp Ile Gly Asp Gly Ile Lys
1345 1350 1355 1360
Cys Thr Asp Leu Asp Glu Cys Ser Asn Gly Thr His Met Cys Ser Gln
1365 1370 1375
His Ala Asp Cys Lys Asn Thr Met Gly Ser Tyr Arg Cys Leu Cys Lys
1380 1385 1390
Glu Gly Tyr Thr Gly Asp Gly Phe Thr Cys Thr Asp Leu Asp Glu Cys
1395 1400 1405
Ser Glu Asn Leu Asn Leu Cys Gly Asn Gly Gln Cys Leu Asn Ala Pro
1410 1415 1420
Gly Gly Tyr Arg Cys Glu Cys Asp Met Gly Phe Val Pro Ser Ala Asp
1425 1430 1435 1440
Gly Lys Ala Cys Glu Asp Ile Asp Glu Cys Ser Leu Pro Asn Ile Cys
1445 1450 1455
Val Phe Gly Thr Cys His Asn Leu Pro Gly Leu Phe Arg Cys Glu Cys
1460 1465 1470
Glu Ile Gly Tyr Glu Leu Asp Arg Ser Gly Gly Asn Cys Thr Asp Val
1475 1480 1485
Asn Glu Cys Leu Asp Pro Thr Thr Cys Ile Ser Gly Asn Cys Val Asn
1490 1495 1500
Thr Pro Gly Ser Tyr Ile Cys Asp Cys Pro Pro Asp Phe Glu Leu Asn
1505 1510 1515 1520
Pro Thr Arg Val Gly Cys Val Asp Thr Arg Ser Gly Asn Cys Tyr Leu
1525 1530 1535
Asp Ile Arg Pro Arg Gly Asp Asn Gly Asp Thr Ala Cys Ser Asn Glu
1540 1545 1550
Ile Gly Val Gly Val Ser Lys Ala Ser Cys Cys Cys Ser Leu Gly Lys
1555 1560 1565
Ala Trp Gly Thr Pro Cys Glu Met Cys Pro Ala Val Asn Thr Ser Glu
1570 1575 1580
Tyr Lys Ile Leu Cys Pro Gly Gly Glu Gly Phe Arg Pro Asn Pro Ile
1585 1590 1595 1600
Thr Val Ile Leu Glu Asp Ile Asp Glu Cys Gln Glu Leu Pro Gly Leu
1605 1610 1615
Cys Gln Gly Gly Lys Cys Ile Asn Thr Phe Gly Ser Phe Gln Cys Arg
1620 1625 1630
Cys Pro Thr Gly Tyr Tyr Leu Asn Glu Asp Thr Arg Val Cys Asp Asp
1635 1640 1645
Val Asn Glu Cys Glu Thr Pro Gly Ile Cys Gly Pro Gly Thr Cys Tyr
1650 1655 1660
Asn Thr Val Gly Asn Tyr Thr Cys Ile Cys Pro Pro Asp Tyr Met Gln
1665 1670 1675 1680
Val Asn Gly Gly Asn Asn Cys Met Asp Met Arg Arg Ser Leu Cys Tyr
1685 1690 1695
Arg Asn Tyr Tyr Ala Asp Asn Gln Thr Cys Asp Gly Glu Leu Leu Phe
1700 1705 1710
Asn Met Thr Lys Lys Met Cys Cys Cys Ser Tyr Asn Ile Gly Arg Ala
1715 1720 1725
Trp Asn Lys Pro Cys Glu Gln Cys Pro Ile Pro Ser Thr Asp Glu Phe
1730 1735 1740
Ala Thr Leu Cys Gly Ser Gln Arg Pro Gly Phe Val Ile Asp Ile Tyr
1745 1750 1755 1760
Thr Gly Leu Pro Val Asp Ile Asp Glu Cys Arg Glu Ile Pro Gly Val
1765 1770 1775
Cys Glu Asn Gly Val Cys Ile Asn Met Val Gly Ser Phe Arg Cys Glu
1780 1785 1790
Cys Pro Val Gly Phe Phe Tyr Asn Asp Lys Leu Leu Val Cys Glu Asp
1795 1800 1805
Ile Asp Glu Cys Gln Asn Gly Pro Val Cys Gln Arg Asn Ala Glu Cys
1810 1815 1820
Ile Asn Thr Ala Gly Ser Tyr Arg Cys Asp Cys Lys Pro Gly Tyr Arg
1825 1830 1835 1840
Phe Thr Ser Thr Gly Gln Cys Asn Asp Arg Asn Glu Cys Gln Glu Ile
1845 1850 1855
Pro Asn Ile Cys Ser His Gly Gln Cys Ile Asp Thr Val Gly Ser Phe
1860 1865 1870
Tyr Cys Leu Cys His Thr Gly Phe Lys Thr Asn Asp Asp Gln Thr Met
1875 1880 1885
Cys Leu Asp Ile Asn Glu Cys Glu Arg Asp Ala Cys Gly Asn Gly Thr
1890 1895 1900
Cys Arg Asn Thr Ile Gly Ser Phe Asn Cys Arg Cys Asn His Gly Phe
1905 1910 1915 1920
Ile Leu Ser His Asn Asn Asp Cys Ile Asp Val Asp Glu Cys Ala Ser
1925 1930 1935
Gly Asn Gly Asn Leu Cys Arg Asn Gly Gln Cys Ile Asn Thr Val Gly
1940 1945 1950
Ser Phe Gln Cys Gln Cys Asn Glu Gly Tyr Glu Val Ala Pro Asp Gly
1955 1960 1965
Arg Thr Cys Val Asp Ile Asn Glu Cys Leu Leu Glu Pro Arg Lys Cys
1970 1975 1980
Ala Pro Gly Thr Cys Gln Asn Leu Asp Gly Ser Tyr Arg Cys Ile Cys
1985 1990 1995 2000
Pro Pro Gly Tyr Ser Leu Gln Asn Glu Lys Cys Glu Asp Ile Asp Glu
2005 2010 2015
Cys Val Glu Glu Pro Glu Ile Cys Ala Leu Gly Thr Cys Ser Asn Thr
2020 2025 2030
Glu Gly Ser Phe Lys Cys Leu Cys Pro Glu Gly Phe Ser Leu Ser Ser
2035 2040 2045
Ser Gly Arg Arg Cys Gln Asp Leu Arg Met Ser Tyr Cys Tyr Ala Lys
2050 2055 2060
Phe Glu Gly Gly Lys Cys Ser Ser Pro Lys Ser Arg Asn His Ser Lys
2065 2070 2075 2080
Gln Glu Cys Cys Cys Ala Leu Lys Gly Glu Gly Trp Gly Asp Pro Cys
2085 2090 2095
Glu Leu Cys Pro Thr Glu Pro Asp Glu Ala Phe Arg Gln Ile Cys Pro
2100 2105 2110
Tyr Gly Ser Gly Ile Ile Val Gly Pro Asp Asp Ser Ala Val Asp Met
2115 2120 2125
Asp Glu Cys Lys Glu Pro Asp Val Cys Lys His Gly Gln Cys Ile Asn
2130 2135 2140
Thr Asp Gly Ser Tyr Arg Cys Glu Cys Pro Phe Gly Tyr Ile Leu Ala
2145 2150 2155 2160
Gly Asn Glu Cys Val Asp Thr Asp Glu Cys Ser Val Gly Asn Pro Cys
2165 2170 2175
Gly Asn Gly Thr Cys Lys Asn Val Ile Gly Gly Phe Glu Cys Thr Cys
2180 2185 2190
Glu Glu Gly Phe Glu Pro Gly Pro Met Met Thr Cys Glu Asp Ile Asn
2195 2200 2205
Glu Cys Ala Gln Asn Pro Leu Leu Cys Ala Phe Arg Cys Val Asn Thr
2210 2215 2220
Tyr Gly Ser Tyr Glu Cys Lys Cys Pro Val Gly Tyr Val Leu Arg Glu
2225 2230 2235 2240
Asp Arg Arg Met Cys Lys Asp Glu Asp Glu Cys Glu Glu Gly Lys His
2245 2250 2255
Asp Cys Thr Glu Lys Gln Met Glu Cys Lys Asn Leu Ile Gly Thr Tyr
2260 2265 2270
Met Cys Ile Cys Gly Pro Gly Tyr Gln Arg Arg Pro Asp Gly Glu Gly
2275 2280 2285
Cys Val Asp Glu Asn Glu Cys Gln Thr Lys Pro Gly Ile Cys Glu Asn
2290 2295 2300
Gly Arg Cys Leu Asn Thr Arg Gly Ser Tyr Thr Cys Glu Cys Asn Asp
2305 2310 2315 2320
Gly Phe Thr Ala Ser Pro Asn Gln Asp Glu Cys Leu Asp Asn Arg Glu
2325 2330 2335
Gly Tyr Cys Phe Thr Glu Val Leu Gln Asn Met Cys Gln Ile Gly Ser
2340 2345 2350
Ser Asn Arg Asn Pro Val Thr Lys Ser Glu Cys Cys Cys Asp Gly Gly
2355 2360 2365
Arg Gly Trp Gly Pro His Cys Glu Ile Cys Pro Phe Gln Gly Thr Val
2370 2375 2380
Ala Phe Lys Lys Leu Cys Pro His Gly Arg Gly Phe Met Thr Asn Gly
2385 2390 2395 2400
Ala Asp Ile Asp Glu Cys Lys Val Ile His Asp Val Cys Arg Asn Gly
2405 2410 2415
Glu Cys Val Asn Asp Arg Gly Ser Tyr His Cys Ile Cys Lys Thr Gly
2420 2425 2430
Tyr Thr Pro Asp Ile Thr Gly Thr Ser Cys Val Asp Leu Asn Glu Cys
2435 2440 2445
Asn Gln Ala Pro Lys Pro Cys Asn Phe Ile Cys Lys Asn Thr Glu Gly
2450 2455 2460
Ser Tyr Gln Cys Ser Cys Pro Lys Gly Tyr Ile Leu Gln Glu Asp Gly
2465 2470 2475 2480
Arg Ser Cys Lys Asp Leu Asp Glu Cys Ala Thr Lys Gln His Asn Cys
2485 2490 2495
Gln Phe Leu Cys Val Asn Thr Ile Gly Gly Phe Thr Cys Lys Cys Pro
2500 2505 2510
Pro Gly Phe Thr Gln His His Thr Ser Cys Ile Asp Asn Asn Glu Cys
2515 2520 2525
Thr Ser Asp Ile Asn Leu Cys Gly Ser Lys Gly Ile Cys Gln Asn Thr
2530 2535 2540
Pro Gly Ser Phe Thr Cys Glu Cys Gln Arg Gly Phe Ser Leu Asp Gln
2545 2550 2555 2560
Thr Gly Ser Ser Cys Glu Asp Val Asp Glu Cys Glu Gly Asn His Arg
2565 2570 2575
Cys Gln His Gly Cys Gln Asn Ile Ile Gly Gly Tyr Arg Cys Ser Cys
2580 2585 2590
Pro Gln Gly Tyr Leu Gln His Tyr Gln Trp Asn Gln Cys Val Asp Glu
2595 2600 2605
Asn Glu Cys Leu Ser Ala His Ile Cys Gly Gly Ala Ser Cys His Asn
2610 2615 2620
Thr Leu Gly Ser Tyr Lys Cys Met Cys Pro Ala Gly Phe Gln Tyr Glu
2625 2630 2635 2640
Gln Phe Ser Gly Gly Cys Gln Asp Ile Asn Glu Cys Gly Ser Ala Gln
2645 2650 2655
Ala Pro Cys Ser Tyr Gly Cys Ser Asn Thr Glu Gly Gly Tyr Leu Cys
2660 2665 2670
Gly Cys Pro Pro Gly Tyr Phe Arg Ile Gly Gln Gly His Cys Val Ser
2675 2680 2685
Gly Met Gly Met Gly Arg Gly Asn Pro Glu Pro Pro Val Ser Gly Glu
2690 2695 2700
Met Asp Asp Asn Ser Leu Ser Pro Glu Ala Cys Tyr Glu Cys Lys Ile
2705 2710 2715 2720
Asn Gly Tyr Pro Lys Arg Gly Arg Lys Arg Arg Ser Thr Asn Glu Thr
2725 2730 2735
Asp Ala Ser Asn Ile Glu Asp Gln Ser Glu Thr Glu Ala Asn Val Ser
2740 2745 2750
Leu Ala Ser Trp Asp Val Glu Lys Thr Ala Ile Phe Ala Phe Asn Ile
2755 2760 2765
Ser His Val Ser Asn Lys Val Arg Ile Leu Glu Leu Leu Pro Ala Leu
2770 2775 2780
Thr Thr Leu Thr Asn His Asn Arg Tyr Leu Ile Glu Ser Gly Asn Glu
2785 2790 2795 2800
Asp Gly Phe Phe Lys Ile Asn Gln Lys Glu Gly Ile Ser Tyr Leu His
2805 2810 2815
Phe Thr Lys Lys Lys Pro Val Ala Gly Thr Tyr Ser Leu Gln Ile Ser
2820 2825 2830
Ser Thr Pro Leu Tyr Lys Lys Lys Glu Leu Asn Gln Leu Glu Asp Lys
2835 2840 2845
Tyr Asp Lys Asp Tyr Leu Ser Gly Glu Leu Gly Asp Asn Leu Lys Met
2850 2855 2860
Lys Ile Gln Val Leu Leu His
2865 2870
<210> 6
<211> 2871
<212> PRT
<213> homo sapiens
<400> 6
Met Arg Arg Gly Arg Leu Leu Glu Ile Ala Leu Gly Phe Thr Val Leu
1 5 10 15
Leu Ala Ser Tyr Thr Ser His Gly Ala Asp Ala Asn Leu Glu Ala Gly
20 25 30
Asn Val Lys Glu Thr Arg Ala Ser Arg Ala Lys Arg Arg Gly Gly Gly
35 40 45
Gly His Asp Ala Leu Lys Gly Pro Asn Val Cys Gly Ser Arg Tyr Asn
50 55 60
Ala Tyr Cys Cys Pro Gly Trp Lys Thr Leu Pro Gly Gly Asn Gln Cys
65 70 75 80
Ile Val Pro Ile Cys Arg His Ser Cys Gly Asp Gly Phe Cys Ser Arg
85 90 95
Pro Asn Met Cys Thr Cys Pro Ser Gly Gln Ile Ala Pro Ser Cys Gly
100 105 110
Ser Arg Ser Ile Gln His Cys Asn Ile Arg Cys Met Asn Gly Gly Ser
115 120 125
Cys Ser Asp Asp His Cys Leu Cys Gln Lys Gly Tyr Ile Gly Thr His
130 135 140
Cys Gly Gln Pro Val Cys Glu Ser Gly Cys Leu Asn Gly Gly Arg Cys
145 150 155 160
Val Ala Pro Asn Arg Cys Ala Cys Thr Tyr Gly Phe Thr Gly Pro Gln
165 170 175
Cys Glu Arg Asp Tyr Arg Thr Gly Pro Cys Phe Thr Val Ile Ser Asn
180 185 190
Gln Met Cys Gln Gly Gln Leu Ser Gly Ile Val Cys Thr Lys Thr Leu
195 200 205
Cys Cys Ala Thr Val Gly Arg Ala Trp Gly His Pro Cys Glu Met Cys
210 215 220
Pro Ala Gln Pro His Pro Cys Arg Arg Gly Phe Ile Pro Asn Ile Arg
225 230 235 240
Thr Gly Ala Cys Gln Asp Val Asp Glu Cys Gln Ala Ile Pro Gly Leu
245 250 255
Cys Gln Gly Gly Asn Cys Ile Asn Thr Val Gly Ser Phe Glu Cys Lys
260 265 270
Cys Pro Ala Gly His Lys Leu Asn Glu Val Ser Gln Lys Cys Glu Asp
275 280 285
Ile Asp Glu Cys Ser Thr Ile Pro Gly Ile Cys Glu Gly Gly Glu Cys
290 295 300
Thr Asn Thr Val Ser Ser Tyr Phe Cys Lys Cys Pro Pro Gly Phe Tyr
305 310 315 320
Thr Ser Pro Asp Gly Thr Arg Cys Ile Asp Val Arg Pro Gly Tyr Cys
325 330 335
Tyr Thr Ala Leu Thr Asn Gly Arg Cys Ser Asn Gln Leu Pro Gln Ser
340 345 350
Ile Thr Lys Met Gln Cys Cys Cys Asp Ala Gly Arg Cys Trp Ser Pro
355 360 365
Gly Val Thr Val Ala Pro Glu Met Cys Pro Ile Arg Ala Thr Glu Asp
370 375 380
Phe Asn Lys Leu Cys Ser Val Pro Met Val Ile Pro Gly Arg Pro Glu
385 390 395 400
Tyr Pro Pro Pro Pro Leu Gly Pro Ile Pro Pro Val Leu Pro Val Pro
405 410 415
Pro Gly Phe Pro Pro Gly Pro Gln Ile Pro Val Pro Arg Pro Pro Val
420 425 430
Glu Tyr Leu Tyr Pro Ser Arg Glu Pro Pro Arg Val Leu Pro Val Asn
435 440 445
Val Thr Asp Tyr Cys Gln Leu Val Arg Tyr Leu Cys Gln Asn Gly Arg
450 455 460
Cys Ile Pro Thr Pro Gly Ser Tyr Arg Cys Glu Cys Asn Lys Gly Phe
465 470 475 480
Gln Leu Asp Leu Arg Gly Glu Cys Ile Asp Val Asp Glu Cys Glu Lys
485 490 495
Asn Pro Cys Ala Gly Gly Glu Cys Ile Asn Asn Gln Gly Ser Tyr Thr
500 505 510
Cys Gln Cys Arg Ala Gly Tyr Gln Ser Thr Leu Thr Arg Thr Glu Cys
515 520 525
Arg Asp Ile Asp Glu Cys Leu Gln Asn Gly Arg Ile Cys Asn Asn Gly
530 535 540
Arg Cys Ile Asn Thr Asp Gly Ser Phe His Cys Val Cys Asn Ala Gly
545 550 555 560
Phe His Val Thr Arg Asp Gly Lys Asn Cys Glu Asp Met Asp Glu Cys
565 570 575
Ser Ile Arg Asn Met Cys Leu Asn Gly Met Cys Ile Asn Glu Asp Gly
580 585 590
Ser Phe Lys Cys Ile Cys Lys Pro Gly Phe Gln Leu Ala Ser Asp Gly
595 600 605
Arg Tyr Cys Lys Asp Ile Asn Glu Cys Glu Thr Pro Gly Ile Cys Met
610 615 620
Asn Gly Arg Cys Val Asn Thr Asp Gly Ser Tyr Arg Cys Glu Cys Phe
625 630 635 640
Pro Gly Leu Ala Val Gly Leu Asp Gly Arg Val Cys Val Asp Thr His
645 650 655
Met Arg Ser Thr Cys Tyr Gly Gly Tyr Lys Arg Gly Gln Cys Ile Lys
660 665 670
Pro Leu Phe Gly Ala Val Thr Lys Ser Glu Cys Cys Cys Ala Ser Thr
675 680 685
Glu Tyr Ala Phe Gly Glu Pro Cys Gln Pro Cys Pro Ala Gln Asn Ser
690 695 700
Ala Glu Tyr Gln Ala Leu Cys Ser Ser Gly Pro Gly Met Thr Ser Ala
705 710 715 720
Gly Ser Asp Ile Asn Glu Cys Ala Leu Asp Pro Asp Ile Cys Pro Asn
725 730 735
Gly Ile Cys Glu Asn Leu Arg Gly Thr Tyr Lys Cys Ile Cys Asn Ser
740 745 750
Gly Tyr Glu Val Asp Ser Thr Gly Lys Asn Cys Val Asp Ile Asn Glu
755 760 765
Cys Val Leu Asn Ser Leu Leu Cys Asp Asn Gly Gln Cys Arg Asn Thr
770 775 780
Pro Gly Ser Phe Val Cys Thr Cys Pro Lys Gly Phe Ile Tyr Lys Pro
785 790 795 800
Asp Leu Lys Thr Cys Glu Asp Ile Asp Glu Cys Glu Ser Ser Pro Cys
805 810 815
Ile Asn Gly Val Cys Lys Asn Ser Pro Gly Ser Phe Ile Cys Glu Cys
820 825 830
Ser Ser Glu Ser Thr Leu Asp Pro Thr Lys Thr Ile Cys Ile Glu Thr
835 840 845
Ile Lys Gly Thr Cys Trp Gln Thr Val Ile Asp Gly Arg Cys Glu Ile
850 855 860
Asn Ile Asn Gly Ala Thr Leu Lys Ser Gln Cys Cys Ser Ser Leu Gly
865 870 875 880
Ala Ala Trp Gly Ser Pro Cys Thr Leu Cys Gln Val Asp Pro Ile Cys
885 890 895
Gly Lys Gly Tyr Ser Arg Ile Lys Gly Thr Gln Cys Glu Asp Ile Asp
900 905 910
Glu Cys Glu Val Phe Pro Gly Val Cys Lys Asn Gly Leu Cys Val Asn
915 920 925
Thr Arg Gly Ser Phe Lys Cys Gln Cys Pro Ser Gly Met Thr Leu Asp
930 935 940
Ala Thr Gly Arg Ile Cys Leu Asp Ile Arg Leu Glu Thr Cys Phe Leu
945 950 955 960
Arg Tyr Glu Asp Glu Glu Cys Thr Leu Pro Ile Ala Gly Arg His Arg
965 970 975
Met Asp Ala Cys Cys Cys Ser Val Gly Ala Ala Trp Gly Thr Glu Glu
980 985 990
Cys Glu Glu Cys Pro Met Arg Asn Thr Pro Glu Tyr Glu Glu Leu Cys
995 1000 1005
Pro Arg Gly Pro Gly Phe Ala Thr Lys Glu Ile Thr Asn Gly Lys Pro
1010 1015 1020
Phe Phe Lys Asp Ile Asn Glu Cys Lys Met Ile Pro Ser Leu Cys Thr
1025 1030 1035 1040
His Gly Lys Cys Arg Asn Thr Ile Gly Ser Phe Lys Cys Arg Cys Asp
1045 1050 1055
Ser Gly Phe Ala Leu Asp Ser Glu Glu Arg Asn Cys Thr Asp Ile Asp
1060 1065 1070
Glu Cys Arg Ile Ser Pro Asp Leu Cys Gly Arg Gly Gln Cys Val Asn
1075 1080 1085
Thr Pro Gly Asp Phe Glu Cys Lys Cys Asp Glu Gly Tyr Glu Ser Gly
1090 1095 1100
Phe Met Met Met Lys Asn Cys Met Asp Ile Asp Glu Cys Gln Arg Asp
1105 1110 1115 1120
Pro Leu Leu Cys Arg Gly Gly Val Cys His Asn Thr Glu Gly Ser Tyr
1125 1130 1135
Arg Cys Glu Cys Pro Pro Gly His Gln Leu Ser Pro Asn Ile Ser Ala
1140 1145 1150
Cys Ile Asp Ile Asn Glu Cys Glu Leu Ser Ala His Leu Cys Pro Asn
1155 1160 1165
Gly Arg Cys Val Asn Leu Ile Gly Lys Tyr Gln Cys Ala Cys Asn Pro
1170 1175 1180
Gly Tyr His Ser Thr Pro Asp Arg Leu Phe Cys Val Asp Ile Asp Glu
1185 1190 1195 1200
Cys Ser Ile Met Asn Gly Gly Cys Glu Thr Phe Cys Thr Asn Ser Glu
1205 1210 1215
Gly Ser Tyr Glu Cys Ser Cys Gln Pro Gly Phe Ala Leu Met Pro Asp
1220 1225 1230
Gln Arg Ser Cys Thr Asp Ile Asp Glu Cys Glu Asp Asn Pro Asn Ile
1235 1240 1245
Cys Asp Gly Gly Gln Cys Thr Asn Ile Pro Gly Glu Tyr Arg Cys Leu
1250 1255 1260
Cys Tyr Asp Gly Phe Met Ala Ser Glu Asp Met Lys Thr Cys Val Asp
1265 1270 1275 1280
Val Asn Glu Cys Asp Leu Asn Pro Asn Ile Cys Leu Ser Gly Thr Cys
1285 1290 1295
Glu Asn Thr Lys Gly Ser Phe Ile Cys His Cys Asp Met Gly Tyr Ser
1300 1305 1310
Gly Lys Lys Gly Lys Thr Gly Cys Thr Asp Ile Asn Glu Cys Glu Ile
1315 1320 1325
Gly Ala His Asn Cys Gly Lys His Ala Val Cys Thr Asn Thr Ala Gly
1330 1335 1340
Ser Phe Lys Cys Ser Cys Ser Pro Gly Trp Ile Gly Asp Gly Ile Lys
1345 1350 1355 1360
Cys Thr Asp Leu Asp Glu Cys Ser Asn Gly Thr His Met Cys Ser Gln
1365 1370 1375
His Ala Asp Cys Lys Asn Thr Met Gly Ser Tyr Arg Cys Leu Cys Lys
1380 1385 1390
Glu Gly Tyr Thr Gly Asp Gly Phe Thr Cys Thr Asp Leu Asp Glu Cys
1395 1400 1405
Ser Glu Asn Leu Asn Leu Cys Gly Asn Gly Gln Cys Leu Asn Ala Pro
1410 1415 1420
Gly Gly Tyr Arg Cys Glu Cys Asp Met Gly Phe Val Pro Ser Ala Asp
1425 1430 1435 1440
Gly Lys Ala Cys Glu Asp Ile Asp Glu Cys Ser Leu Pro Asn Ile Cys
1445 1450 1455
Val Phe Gly Thr Cys His Asn Leu Pro Gly Leu Phe Arg Cys Glu Cys
1460 1465 1470
Glu Ile Gly Tyr Glu Leu Asp Arg Ser Gly Gly Asn Cys Thr Asp Val
1475 1480 1485
Asn Glu Cys Leu Asp Pro Thr Thr Cys Ile Ser Gly Asn Cys Val Asn
1490 1495 1500
Thr Pro Gly Ser Tyr Ile Cys Asp Cys Pro Pro Asp Phe Glu Leu Asn
1505 1510 1515 1520
Pro Thr Arg Val Gly Cys Val Asp Thr Arg Ser Gly Asn Cys Tyr Leu
1525 1530 1535
Asp Ile Arg Pro Arg Gly Asp Asn Gly Asp Thr Ala Cys Ser Asn Glu
1540 1545 1550
Ile Gly Val Gly Val Ser Lys Ala Ser Cys Cys Cys Ser Leu Gly Lys
1555 1560 1565
Ala Trp Gly Thr Pro Cys Glu Met Cys Pro Ala Val Asn Thr Ser Glu
1570 1575 1580
Tyr Lys Ile Leu Cys Pro Gly Gly Glu Gly Phe Arg Pro Asn Pro Ile
1585 1590 1595 1600
Thr Val Ile Leu Glu Asp Ile Asp Glu Cys Gln Glu Leu Pro Gly Leu
1605 1610 1615
Cys Gln Gly Gly Lys Cys Ile Asn Thr Phe Gly Ser Phe Gln Cys Arg
1620 1625 1630
Cys Pro Thr Gly Tyr Tyr Leu Asn Glu Asp Thr Arg Val Cys Asp Asp
1635 1640 1645
Val Asn Glu Cys Glu Thr Pro Gly Ile Cys Gly Pro Gly Thr Cys Tyr
1650 1655 1660
Asn Thr Val Gly Asn Tyr Thr Cys Ile Cys Pro Pro Asp Tyr Met Gln
1665 1670 1675 1680
Val Asn Gly Gly Asn Asn Cys Met Asp Met Arg Arg Ser Leu Cys Tyr
1685 1690 1695
Arg Asn Tyr Tyr Ala Asp Asn Gln Thr Cys Asp Gly Glu Leu Leu Phe
1700 1705 1710
Asn Met Thr Lys Lys Met Cys Cys Cys Ser Tyr Asn Ile Gly Arg Ala
1715 1720 1725
Trp Asn Lys Pro Cys Glu Gln Cys Pro Ile Pro Ser Thr Asp Glu Phe
1730 1735 1740
Ala Thr Leu Cys Gly Ser Gln Arg Pro Gly Phe Val Ile Asp Ile Tyr
1745 1750 1755 1760
Thr Gly Leu Pro Val Asp Ile Asp Glu Cys Arg Glu Ile Pro Gly Val
1765 1770 1775
Cys Glu Asn Gly Val Cys Ile Asn Met Val Gly Ser Phe Arg Cys Glu
1780 1785 1790
Cys Pro Val Gly Phe Phe Tyr Asn Asp Lys Leu Leu Val Cys Glu Asp
1795 1800 1805
Ile Asp Glu Cys Gln Asn Gly Pro Val Cys Gln Arg Asn Ala Glu Cys
1810 1815 1820
Ile Asn Thr Ala Gly Ser Tyr Arg Cys Asp Cys Lys Pro Gly Tyr Arg
1825 1830 1835 1840
Phe Thr Ser Thr Gly Gln Cys Asn Asp Arg Asn Glu Cys Gln Glu Ile
1845 1850 1855
Pro Asn Ile Cys Ser His Gly Gln Cys Ile Asp Thr Val Gly Ser Phe
1860 1865 1870
Tyr Cys Leu Cys His Thr Gly Phe Lys Thr Asn Asp Asp Gln Thr Met
1875 1880 1885
Cys Leu Asp Ile Asn Glu Cys Glu Arg Asp Ala Cys Gly Asn Gly Thr
1890 1895 1900
Cys Arg Asn Thr Ile Gly Ser Phe Asn Cys Arg Cys Asn His Gly Phe
1905 1910 1915 1920
Ile Leu Ser His Asn Asn Asp Cys Ile Asp Val Asp Glu Cys Ala Ser
1925 1930 1935
Gly Asn Gly Asn Leu Cys Arg Asn Gly Gln Cys Ile Asn Thr Val Gly
1940 1945 1950
Ser Phe Gln Cys Gln Cys Asn Glu Gly Tyr Glu Val Ala Pro Asp Gly
1955 1960 1965
Arg Thr Cys Val Asp Ile Asn Glu Cys Leu Leu Glu Pro Arg Lys Cys
1970 1975 1980
Ala Pro Gly Thr Cys Gln Asn Leu Asp Gly Ser Tyr Arg Cys Ile Cys
1985 1990 1995 2000
Pro Pro Gly Tyr Ser Leu Gln Asn Glu Lys Cys Glu Asp Ile Asp Glu
2005 2010 2015
Cys Val Glu Glu Pro Glu Ile Cys Ala Leu Gly Thr Cys Ser Asn Thr
2020 2025 2030
Glu Gly Ser Phe Lys Cys Leu Cys Pro Glu Gly Phe Ser Leu Ser Ser
2035 2040 2045
Ser Gly Arg Arg Cys Gln Asp Leu Arg Met Ser Tyr Cys Tyr Ala Lys
2050 2055 2060
Phe Glu Gly Gly Lys Cys Ser Ser Pro Lys Ser Arg Asn His Ser Lys
2065 2070 2075 2080
Gln Glu Cys Cys Cys Ala Leu Lys Gly Glu Gly Trp Gly Asp Pro Cys
2085 2090 2095
Glu Leu Cys Pro Thr Glu Pro Asp Glu Ala Phe Arg Gln Ile Cys Pro
2100 2105 2110
Tyr Gly Ser Gly Ile Ile Val Gly Pro Asp Asp Ser Ala Val Asp Met
2115 2120 2125
Asp Glu Cys Lys Glu Pro Asp Val Cys Lys His Gly Gln Cys Ile Asn
2130 2135 2140
Thr Asp Gly Ser Tyr Arg Cys Glu Cys Pro Phe Gly Tyr Ile Leu Ala
2145 2150 2155 2160
Gly Asn Glu Cys Val Asp Thr Asp Glu Cys Ser Val Gly Asn Pro Cys
2165 2170 2175
Gly Asn Gly Thr Cys Lys Asn Val Ile Gly Gly Phe Glu Cys Thr Cys
2180 2185 2190
Glu Glu Gly Phe Glu Pro Gly Pro Met Met Thr Cys Glu Asp Ile Asn
2195 2200 2205
Glu Cys Ala Gln Asn Pro Leu Leu Cys Ala Phe Arg Cys Val Asn Thr
2210 2215 2220
Tyr Gly Ser Tyr Glu Cys Lys Cys Pro Val Gly Tyr Val Leu Arg Glu
2225 2230 2235 2240
Asp Arg Arg Met Cys Lys Asp Glu Asp Glu Cys Glu Glu Gly Lys His
2245 2250 2255
Asp Cys Thr Glu Lys Gln Met Glu Cys Lys Asn Leu Ile Gly Thr Tyr
2260 2265 2270
Met Cys Ile Cys Gly Pro Gly Tyr Gln Arg Arg Pro Asp Gly Glu Gly
2275 2280 2285
Cys Val Asp Glu Asn Glu Cys Gln Thr Lys Pro Gly Ile Cys Glu Asn
2290 2295 2300
Gly Arg Cys Leu Asn Thr Arg Gly Ser Tyr Thr Cys Glu Cys Asn Asp
2305 2310 2315 2320
Gly Phe Thr Ala Ser Pro Asn Gln Asp Glu Cys Leu Asp Asn Arg Glu
2325 2330 2335
Gly Tyr Cys Phe Thr Glu Val Leu Gln Asn Met Cys Gln Ile Gly Ser
2340 2345 2350
Ser Asn Arg Asn Pro Val Thr Lys Ser Glu Cys Cys Cys Asp Gly Gly
2355 2360 2365
Arg Gly Trp Gly Pro His Cys Glu Ile Cys Pro Phe Gln Gly Thr Val
2370 2375 2380
Ala Phe Lys Lys Leu Cys Pro His Gly Arg Gly Phe Met Thr Asn Gly
2385 2390 2395 2400
Ala Asp Ile Asp Glu Cys Lys Val Ile His Asp Val Cys Arg Asn Gly
2405 2410 2415
Glu Cys Val Asn Asp Arg Gly Ser Tyr His Cys Ile Cys Lys Thr Gly
2420 2425 2430
Tyr Thr Pro Asp Ile Thr Gly Thr Ser Cys Val Val Leu Asn Glu Cys
2435 2440 2445
Asn Gln Ala Pro Lys Pro Cys Asn Phe Ile Cys Lys Asn Thr Glu Gly
2450 2455 2460
Ser Tyr Gln Cys Ser Cys Pro Lys Gly Tyr Ile Leu Gln Glu Asp Gly
2465 2470 2475 2480
Arg Ser Cys Lys Asp Leu Asp Glu Cys Ala Thr Lys Gln His Asn Cys
2485 2490 2495
Gln Phe Leu Cys Val Asn Thr Ile Gly Gly Phe Thr Cys Lys Cys Pro
2500 2505 2510
Pro Gly Phe Thr Gln His His Thr Ser Cys Ile Asp Asn Asn Glu Cys
2515 2520 2525
Thr Ser Asp Ile Asn Leu Cys Gly Ser Lys Gly Ile Cys Gln Asn Thr
2530 2535 2540
Pro Gly Ser Phe Thr Cys Glu Cys Gln Arg Gly Phe Ser Leu Asp Gln
2545 2550 2555 2560
Thr Gly Ser Ser Cys Glu Asp Val Asp Glu Cys Glu Gly Asn His Arg
2565 2570 2575
Cys Gln His Gly Cys Gln Asn Ile Ile Gly Gly Tyr Arg Cys Ser Cys
2580 2585 2590
Pro Gln Gly Tyr Leu Gln His Tyr Gln Trp Asn Gln Cys Val Asp Glu
2595 2600 2605
Asn Glu Cys Leu Ser Ala His Ile Cys Gly Gly Ala Ser Cys His Asn
2610 2615 2620
Thr Leu Gly Ser Tyr Lys Cys Met Cys Pro Ala Gly Phe Gln Tyr Glu
2625 2630 2635 2640
Gln Phe Ser Gly Gly Cys Gln Asp Ile Asn Glu Cys Gly Ser Ala Gln
2645 2650 2655
Ala Pro Cys Ser Tyr Gly Cys Ser Asn Thr Glu Gly Gly Tyr Leu Cys
2660 2665 2670
Gly Cys Pro Pro Gly Tyr Phe Arg Ile Gly Gln Gly His Cys Val Ser
2675 2680 2685
Gly Met Gly Met Gly Arg Gly Asn Pro Glu Pro Pro Val Ser Gly Glu
2690 2695 2700
Met Asp Asp Asn Ser Leu Ser Pro Glu Ala Cys Tyr Glu Cys Lys Ile
2705 2710 2715 2720
Asn Gly Tyr Pro Lys Arg Gly Arg Lys Arg Arg Ser Thr Asn Glu Thr
2725 2730 2735
Asp Ala Ser Asn Ile Glu Asp Gln Ser Glu Thr Glu Ala Asn Val Ser
2740 2745 2750
Leu Ala Ser Trp Asp Val Glu Lys Thr Ala Ile Phe Ala Phe Asn Ile
2755 2760 2765
Ser His Val Ser Asn Lys Val Arg Ile Leu Glu Leu Leu Pro Ala Leu
2770 2775 2780
Thr Thr Leu Thr Asn His Asn Arg Tyr Leu Ile Glu Ser Gly Asn Glu
2785 2790 2795 2800
Asp Gly Phe Phe Lys Ile Asn Gln Lys Glu Gly Ile Ser Tyr Leu His
2805 2810 2815
Phe Thr Lys Lys Lys Pro Val Ala Gly Thr Tyr Ser Leu Gln Ile Ser
2820 2825 2830
Ser Thr Pro Leu Tyr Lys Lys Lys Glu Leu Asn Gln Leu Glu Asp Lys
2835 2840 2845
Tyr Asp Lys Asp Tyr Leu Ser Gly Glu Leu Gly Asp Asn Leu Lys Met
2850 2855 2860
Lys Ile Gln Val Leu Leu His
2865 2870
<210> 7
<211> 23
<212> DNA
<213> homo sapiens
<400> 7
gcacaggaca atcatcaaag tct 23
<210> 8
<211> 21
<212> DNA
<213> homo sapiens
<400> 8
gctgcttcct ccacaatctc c 21
Claims (1)
1.突变的马凡氏综合征致病基因FBN1，其特征在于，与野生型FBN1基因编码DNA的参考序列相比，第7331位点的碱基A突变为碱基T，突变的FBN1基因编码DNA的序列为SEQ ID NO:4。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005116253A1 (ja) * | 2004-05-27 | 2005-12-08 | Nagasaki University | マルファン症候群診断用プローブ、及び当該プローブを用いたスクリーニング法 |
| CN104120132A (zh) * | 2013-04-28 | 2014-10-29 | 福建省立医院 | Fbn1基因突变体及其应用 |
| CN110423809A (zh) * | 2019-09-03 | 2019-11-08 | 郑州大学第一附属医院 | 一种影响人马凡综合征诊治的fbn1 g2125a突变及其应用 |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005116253A1 (ja) * | 2004-05-27 | 2005-12-08 | Nagasaki University | マルファン症候群診断用プローブ、及び当該プローブを用いたスクリーニング法 |
| CN104120132A (zh) * | 2013-04-28 | 2014-10-29 | 福建省立医院 | Fbn1基因突变体及其应用 |
| CN110423809A (zh) * | 2019-09-03 | 2019-11-08 | 郑州大学第一附属医院 | 一种影响人马凡综合征诊治的fbn1 g2125a突变及其应用 |
Non-Patent Citations (1)
| Title |
|---|
| rs1060501093;NCBI dbSNP;《NCBI dbSNP》;20210409;第1页 * |
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