巴马小型猪2型糖尿病关联遗传变异分析

项目名称： 巴马小型猪2型糖尿病关联遗传变异分析

项目编号： No.31472057

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 动物学

项目作者： 陈华

作者单位： 中国人民解放军总医院

项目金额： 87万元

中文摘要： 全基因组关联研究（GWAS）给复杂性状/疾病的遗传学研究带来了全新的信息。至2012年末，已报道了超过30个大规模人群的糖尿病病例-对照GWAS分析，发现了近70个2型糖尿病关联SNP。然而，这些发现在糖尿病的预测、预防和治疗上还未取得明显进展。猪的基因组测序工作现已完成，分析表明远比小鼠和犬的基因组更近似于人类，是深入开展人类复杂性状/疾病遗传学分析的理想模型。本项目拟利用2型糖尿病易感小型猪选育过程中不同世代的动物为材料，充分利用小型猪遗传背景均一，可按需选择繁育，可实验性诱发糖尿病的优势，通过易感病例-对照分析和连锁不平衡分析，获得小型猪2型糖尿病关联SNP，并与人类的研究成果比对，探讨2型糖尿病关联基因的遗传连锁关系、易感性与关联基因聚集的关系，以及在2型糖尿病发生发展过程中的表达变化。与此同时，将2型糖尿病易感小型猪的培育推进到第5世代。

中文关键词： 2型糖尿病；人类疾病动物模型；小型猪；遗传变异

英文摘要： Recent application of genome-wide association studies (GWAS) to complex human phenotypes/diseases produce many novel findings. More than 30 large-scale GWAS have been conducted in populations of diabetes cases and controls until the end of 2012, and nearly 70 individual SNPs have been reported linked with type 2 diabetes risk. Overall, prospective studies showed limited value of these genetic markers on the prediction, prevention and treatment of type 2 diabetes. For several decades swine have been a valuable model for human health and disease. The pig genome has been sequenced and is found more similar to humans than mice and dogs. Using comparative genomics, the swine will be an ideal model for the further researches on these novel findings. Our aim is to make use of the minipigs during the breeding process for type 2 diabetes susceptible strains, and to rely on the superiority of their homologous, selective breeding and diabetes can be induced, so as to get further understanding of the GWAS findings on humans, to investigate the genetic mechanisms of type 2 diabetes. Meanwhile, to put forth the select breeding to the 5th generation.

英文关键词： type 2 diabetes mellitus;animal model for human disease;minipig;genetic variant