应用外显子组测序技术对维吾尔族早发糖尿病MODY家系致病或易感基因定位

MODY是特殊类型糖尿病，单基因显性遗传病。本研究首次对维族（维吾尔族）MODY家系进行深入的分子流行病学研究。现获3个四代健在新疆维族MODY家系。拟用外显子测序技术对该MODY家系易感和致病基因定位并对致病基因进行功能验证，重点阐述维族MODY发生分子机理中遗传因素及其作用强度和方式；从能量来源、膳食结构、维生素、矿物质、微量元素摄入量对该MODY家系、T2DM病人和正常维族的膳食摄入构成进行对比分析，得到这三组人群膳食摄入构成特点；结合遗传因素和前期维族MODY家系血、尿液代谢组学研究结果，运用遗传与环境因素交互作用分析方法，确定遗传、环境（膳食）和代谢因素在维族MODY发病中的作用。该领域的探索性研究应能加深对维族MODY病因和发病机制的认识，促进针对SNPs和致病基因病因学一级预防。国内外尚无报道。若MODY致病基因能确定，将是我国应用外显子组测序技术进行单基因病研究的一项突破。

Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous form of diabetes characterized by an autosomal-dominant mode of inheritance. We mainly aimed to use exome sequencing in 3 four-generations Uyghur MODY-X family to identify new susceptibility genes and/or disease cause genes of MODY and finally to validate genes function. We focus on exploring intensity of genetic factor in Uyghur MODY families. Meanwhile，to compare the diet survey of these MODY families, T2DM patients, and normal Uyghur populations in order to confirm the diet intake model of these three populations. Intake amount of energy sources, vitamin, minerals, trace elements and dietary pattern of these three populations will be investigated and concreatly calculated. Epidemiolgy methodology and statistics will be used to analyze the interaction of heredity, environment and metabolism combined with the former result of metabonomics study of Uyghur MODY families. This research may deepen the understanding of molecular pathogenetic of Uyghur MODY, may promote the primary prevention through nosazontology understanding of MODY. There is no any report about Uyghur MODY families in the field of exome sequencing and other molecular pathogenetic research. Determining of SNPs and disease cause genes of MODY will be a breakthrough in the field of monogenetic disease research using exome sequencing in China. These results will lay an important research basis for study of genetic susceptibility in MODY families and association study of MODY genes with T2DM.