Genetics of African American type 2 diabetes

非裔美国人 2 型糖尿病的遗传学

• 批准号: 7006930
• 负责人: MICHELE M SALE
• 金额: $ 2.92万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7006930
• 关键词: African American; biotechnology; case history; clinical research; diabetes mellitus genetics; disease /disorder etiology; family genetics; genetic susceptibility; genotype; human population genetics; human subject; linkage mapping; molecular biology information system; molecular cloning; noninsulin dependent diabetes mellitus; nucleic acid quantitation /detection; patient oriented research; phlebotomy; single nucleotide polymorphism; telomere

DESCRIPTION (provided by applicant): African Americans are twice as likely to develop type 2 diabetes (T2DM) as Caucasian Americans, and have 1.2-5 times the rate of diabetic complications. We have carried out the first large-scale genome-wide scan for African American T2DM using 636 affected sibling pairs from 251 families. We detected a linkage peak on chromosome 6q23-q27, LOD 2.08 163.5cM from the p telomere. Under models of heterogeneity, this linkage peak rises to 3.00. This region has provided modest evidence for linkage to T2DM and related phenotypes in other populations. Our goal is to use a positional cloning approach to identify variants in genes that contribute to T2DM susceptibility in the African American population. We will conduct comprehensive analyses of existing data, including adjustments for BMI, age at diagnosis, duration of disease, gender, and exploration of interactions using epistasis models and a genome x genome approach. The region of linkage will be refined by genotyping additional microsatellites, and an evaluation of a limited number of candidate genes initiated. We will embark upon construction of a dense SNP map to facilitate the identification of minimal haplotypes associated with African American T2DM, followed by a focused search for genes contributing to diabetes.

描述（由申请人提供）：非裔美国人患2型糖尿病（T2DM）的可能性是高加索美国人的两倍，并且具有糖尿病并发症发生率的1.2-5倍。我们使用来自251个家庭的636对兄弟姐妹对进行了第一次对非裔美国人T2DM的大规模基因组扫描。 我们在6q23-Q27染色体上检测到了一个连锁峰，距P端粒的LOD 2.08 163.5cm。在异质性模型下，这种连锁峰上升到3.00。该地区为其他人群中的T2DM和相关表型提供了适度的证据。我们的目标是使用一种位置克隆方法来识别在非洲裔美国人群中有助于T2DM敏感性的基因中的变异。我们将对现有数据进行全面的分析，包括对BMI的调整，诊断年龄，疾病持续时间，性别以及使用上学模型和基因组X基因组方法对相互作用的探索。连锁区域将通过基因分型来完善其他微卫星，并评估启动的有限候选基因。我们将启动建造密集的SNP图，以促进与非裔美国人T2DM相关的最小单倍型的鉴定，然后重点搜索促成糖尿病的基因。