A Whole Genome Association Search for Type 2 Diabetes Genes in African Americans

这项雄心勃勃的计划的培训目标是逐步为研究员提供越来越多的 在复杂疾病的跨学科研究中的独立性和责任水平。研究 这项计划的目的是确定遗传变异，赋予2型糖尿病的易感性 （T2DM）在非洲裔美国人，并深入了解其作用机制。这个目标一定会实现的 通过1）复制从基因组全关联（GWA）分析鉴定的重要发现， > 650，000个与T2DM相关的SNP，2）验证T2DM相关性并探索T2DM的相关性。 这些变体通过额外的生理机制调节T2DM易感性， 3）基因组区域的精细作图一致显示与T2DM相关， 鉴定性状易感变异体，并最终4）利用分子生物学技术来确定 确定的T2DM易感性变体在体内发挥作用的生物学机制。这些 实验将提供参与疾病进展的确认，并确定这些因素的作用。 体内基因座。总的来说，这项建议整合了现代基因组方法，临床方法， 和生物化学测定，以增加鉴定导致T2DM的基因的可能性 可接受性。通过这种方法，研究员将得到支持，通过 流行病学、统计学、生物化学、 physiology.这将提供独立指导跨学科研究的技能和经验， 常见疾病的遗传学

The training goal for this ambitious proposal is to provide the fellow, in a stepwise fashion, with increasing levels of independence and responsibility in an interdisciplinary study of complex disease. The research goal of this proposal is to identify the genetic variants which confer susceptibility to type 2 diabetes mellitus (T2DM) in African Americans and gain insight into their mechanism of action. This goal will be attained through 1) Replication of significant findings identified from the genome wide association (GWA) analysis of >650,000 SNPs for association with T2DM, 2) Validation of T2DM associations and exploration of the physiological mechanism through which these variants modulate T2DM susceptibility in additional populations, 3) Fine mapping of the genomic regions consistently showing association with T2DM and identifying trait predisposing variants and ultimately 4) Utilize molecular biology techniques to determine the biological mechanism through which identified T2DM-susceptibility variants exert their effects in vivo. These experiments will provide confirmation of involvement in disease progression and determine the role of these loci in vivo. Taken together, this proposal integrates modern genomic approaches, clinical methodologies and biochemical assays to increase the likelihood of identifying genes which contribute to T2DM susceptibilty. With this approach, the fellow will be supported to develop independence through a comprehensive network of interactive researchers in the fields of epidemiology, statistics, biochemistry, physiology. This will provide the skills and experience to independently direct an interdisciplinary study of the genetics of common disease.