中国男性非梗阻性无精子症的全转录组关联研究

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1、：Ｒ１８分类号单位代码：１０３１２：密级学号：２０１５１２００響＊京Ｓ种犬ｆ硕士学位论文题目：中国男性非梗阻性无精子症的全转录组关联研究研究生：姜婷婷指导教师：胡志斌教授学科专业：流行病与卫生统计学学院名称：公共卫生学院二一完成时间：〇八年五月目录一、中文摘要···················································································1二、英文摘要··················

2、·································································4三、论文正文前言··························································································7材料与方法···············································································10结果·······

3、·················································································17讨论························································································36总结···················································································

4、·····39参考文献··················································································40四、综述及参考文献········································································47五、附录附录一、论文缩略词表································································61附录

5、二、发表论文······································································63六、致谢·······················································································64南京医科大学硕士学位论文中国男性非梗阻性无精子症的全转录组关联研究中文摘要背景：不孕不育是全世界关注的人类生殖健康问题。世界范围内不孕不育发生率高达10-15%，不孕不育已成为继

6、癌症和心脑血管疾病外的第三大疾病。其中由于男性问题导致的不育将近50%，主要表现为严重少精、弱精、畸精和无精子症。临床上将三次精液检查均未发现精子者定义为无精子症，约占男性不育症的15-20%，根据输精管道是否通畅又可将其分为梗阻性无精子症（obstructiveazoospermia,OA）和非梗阻性无精子症（non-obstructiveazoospermia,NOA）。与OA相比，NOA是由于先天性生精障碍所致，其病因更为复杂，流行病学研究表明，成年男性NOA患病率将近1%，对于男性生殖健康有严重影响。因此，

7、寻找NOA的易感位点和致病基因，探讨NOA的分子机制，对于NOA的早期筛查、早期诊断具有重大意义。NOA是一种高度异质性的复杂疾病，其发生发展是遗传因素和环境因素单独或者共同作用的结果。宏观流行病学研究表明，高温、放射、有毒气体、长期服用损害性腺药物/粗制棉籽油等环境暴露是NOA的危险因素。而在相同暴露因素下，遗传背景的差异也可能影响个体对NOA的易感性。目前已报道的与NOA有关的遗传因素包括：染色体数目和结构异常，Y染色体微缺失，表观遗传改变，常染色体基因多态性和突变等。近年来，全基因组关联研究（Genome-w

8、ideAssociationStudies,GWASs）作为研究复杂疾病和遗传易感性关系的有效工具，被应用到了NOA病因的研究之中。该技术应用基因组中数以百万计的单核苷酸多态性（singlenucleotidepolymorphisms,SNPs）为标记进行病例对照关联分析，在全基因组范围内筛查与疾病关联的SNPs，从而确定与疾病相关的易感位点和区域。但是，