麻风致残基因的搜寻及功能分析

项目名称： 麻风致残基因的搜寻及功能分析

项目编号： No.81472868

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘殿昌

作者单位： 山东省医学科学院

项目金额： 75万元

中文摘要： 麻风是由麻风分支杆菌感染易感个体后，选择性侵犯皮肤和外周神经可致残的慢性传染病。麻风反应是导致畸残的主要原因，有学者认为麻风反应的发生与宿主的遗传素质相关，但麻风反应/致残相关基因尚未确定。课题组前期在国家自然科学基金项目（30771943、81071288）等支持下，开展了麻风的GWAS，建立了包括3000例麻风病例和4000例正常对照分型结果的GWAS数据库。依托数据库先后开展了麻风的发病易感基因和型别易感基因研究，已定位了16个易感基因位点。本研究拟在前期研究的基础上，从数据库中直接提取800例畸残患者与1000例无畸残患者的数据进行关联分析，筛选与麻风畸残相关的位点，并进一步在2000例畸残患者、2000例无畸残患者和3000例正常对照中进行验证，通过连锁不平衡分析、基因表达性状座位分析和基因功能分析等，鉴定麻风致残基因，为阐明麻风畸残的发生机理、风险预测及干预措施的制定累积基础。

中文关键词： 麻风；致残基因；关联分析；功能分析

英文摘要： Leprosy is a human infectious disease caused by Mycobacterium leprae. Skin and peripheral nerve can be selectively disabled.Leprosy could lead to irreversible disability, it has been proven that host susceptibility plays a critical role in the development of disability .The disabled-related susceptibility genes remains not identified. We have performed several genome wide association studies (GWAS) and established a GWAS dataset including the data of 3000 leprosy cases and 4000 healthy controls supported by National Natural Science Foundation of China（30771943、81071288）. And based on our GWAS dataset, we conducted the association analysis to identify disabled-related susceptibility genes and clinical subtype-related susceptibility genes and totally 16 susceptibility loci have been found. Next we plan to extract the data of 800 leprosy cases with disabilities and 1000 leprosy cases without disabilities and perform a new association analysis. The promising SNPs will be validated in another series of samples including 2000 leprosy cases with disabilities, 2000 leprosy cases without disabilities and 3000 healthy controls. By further linkage disequilibrium, eQTL and functional analysis, the susceptibility genes related to the disability of leprosy will be identified, which would be greatly helpful to the clarification of the pathogenesis of the disabilities in leprosy and the prediction of risk.

英文关键词： leprosy;disabled-related susceptibility genes;association analysis;functional analysis