线粒体相关基因遗传变异与麻风易感性关联分析

项目名称： 线粒体相关基因遗传变异与麻风易感性关联分析

项目编号： No.31271346

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 姚永刚

作者单位： 中国科学院昆明动物研究所

项目金额： 100万元

中文摘要： 麻风是由麻风杆菌引起的一种慢性传染病，对病人的皮肤、外周神经伤害极大，严重可致残和致盲。麻风防治工作在我国（尤其是云南）仍相当紧迫。麻风易感性和临床表型受到宿主遗传因素影响，但其中起关键作用的基因及相应机理尚未完全清楚。在进化过程中麻风杆菌大量基因功能丢失，对宿主的能量代谢系统产生严重依赖，宿主能量代谢方面的差异可能影响其易感。本项目将集中对9个线粒体相关基因（LRRK2、PINK1、PARL、POLG、TFAM、PEO1、MFN2、MAVS和MITA）遗传变异进行高通量基因分型，分析基因型、单倍型与临床表型间的关联性，以期确定易感遗传变异，并从分子和细胞水平上对易感基因开展功能验证实验，探讨其调控机制及在麻风杆菌感染过程中可能发挥的作用。结果有望阐明线粒体相关基因遗传变异与麻风遗传易感性之间的关系，提供该病防治的新思路，同时为其它细菌感染性疾病和神经退行性疾病的研究提供参考和启示。

中文关键词： 麻风；遗传易感性；线粒体基因；整合分析；功能验证

英文摘要： Leprosy is a chronic, systemic disease caused by Mycobacterium leprae. It affects human skin and the peripheral nerve system, as well as eyes and other systems, resulting in a variety of disabilities associated with leprosy. Leprosy control in China, particularly Yunnan Province, is still urgent, despite the fact that we had successfully achieved the eliminate goal at country level during the past decades. As an ancient disease, leprosy can be used as a good model to study the innate immune response to pathogen and to uncover the interaction between immune system and nerves system during the onset of leprosy. Genetic factors confer susceptibility to this disease. During the long evolution, more than half of the functional genes in the genome of M. leprae are inactivated or have became pseudogenes, and this bacterium has developed a dependence on host energy production and nutritional products. As a result, the parasitic life and adaptation might have shaped host genetic susceptibility to leprosy. In this study, we analyze genetic polymorphisms of 9 genes (LRRK2、PINK1、PARL、POLG、TFAM、PEO1、MFN2、MAVS and MITA) that are actively involved in mitochondrial function. We choose a sufficient number of tag SNPs to cover each gene and use a high throughput genotyping technology to genotype each SNP. Associations of alleles,

英文关键词： Leprosy；Genetic susceptibility；Mitochondrial genes；Integrative analysis；Functional assay