Chromosome 6q and Diabetes In African Americans

描述(申请人提供)：本申请建议鉴定在患有2型糖尿病(T2 DM)的非裔美国人家庭中发现的导致6q连锁高峰的基因(S)。将使用位置克隆的方法来评估和确定该区域的潜在候选基因。我们相信我们已经在这个区域发现了一个新的糖尿病基因，雌激素受体α(ESR1)，这将是第一个利用非裔美国人的数据确定的糖尿病基因。我们的目标是进一步探索ESR1中与T2 DM相关的单核苷酸多态和单倍型，以及分析其他候选基因的SNPs，以确定这些基因是否也存在关联。然后将通过功能分析对关联发现进行分析，以确定是否存在相关的SNPs/单倍型发挥生物学功能。了解ESR1或位于6q连锁峰下的任何其他候选基因的多态将提供关键信息，有助于理解T2 DM的病理生理机制，以及这些变异如何在不同人群中导致疾病。

DESCRIPTION (provided by applicant): This application proposes to identify the gene(s) contributing to the 6q linkage peak that has been identified in African American families that have type 2 diabetes mellitus (T2DM). The positional cloning method will be used to evaluate and determine potential candidate genes in this region. We believe we have identified a novel diabetes gene in this region, Estrogen Receptor alpha (ESR1), which would represent the first diabetes gene positionally identified using data from an African American population. We aim to further explore single nucleotide polymorphisms and haplotypes that show association with T2DM in ESR1, as well as analyze SNPs in additional candidate genes, in order to determine if there is any association in those genes as well. Association findings will then be analyzed through functional assays to determine if there is the associated SNPs/haplotypes serve a biological function. Understanding how polymorphisms in ESR1, or any other candidate genes located under the 6q linkage peak, will provide critical information that will aid in understanding the pathophysiology of T2DM and how these variations contribute to the disease across different populations.