Mapping Genes for NIDDM Nephropathy in African Americans

绘制非裔美国人 NIDDM 肾病基因图谱

基本信息

批准号：
7236165
负责人：
DONALD W BOWDEN
金额：
$ 46.86万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-30 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7236165
关键词：
10q 12p 16p 18q Accounting Affect African American Alleles Angiotensin-Converting Enzyme Inhibitors Blood Glucose Candidate Disease Gene Chromosome Mapping Chromosomes Chronic Kidney Failure Collection DNA DNA Sequence Data Data Analyses Databases Development Diabetes Mellitus Diabetic Nephropathy Dialysis procedure Disease susceptibility End stage renal failure Etiology Facility Construction Funding Category Family Genes Genetic Predisposition to Disease Genome Scan Genomics Genotype Haplotypes Hypertension Individual Inherited Kidney Diseases Kidney Failure Location Maps Medicare Methods Minority Molecular Genetics Native Americans Non-Insulin-Dependent Diabetes Mellitus Patients Phase Physical Dialysis Population Predisposition Recruitment Activity Risk SNP genotyping Sampling Sequence Analysis Single Nucleotide Polymorphism Map Staging United States blood pressure regulation case control density diabetic genetic analysis illness length member mortality positional cloning

项目摘要

DESCRIPTION (provided by applicant): Despite improvements in blood pressure control and the use of angiotensin converting enzyme inhibitors, type 2 diabetes mellitus (T2DM) associated end stage renal disease (ESRD) is the most common and rapidly increasing etiology of chronic renal failure in the United States. Diabetic nephropathy accounts for more than 34% of incident Medicare supported dialysis cases and patients with diabetic ESRD suffer 50% mortality in two years. It remains unclear why only a minority of diabetic patients will ultimately develop renal failure, while the majority of diabetics who have poorly controlled blood sugar and/or hypertension will not. We hypothesize that genes contributing to the development of diabetes-associated ESRD in African Americans exist and can be identified using modern molecular genetic methods. In the first phase of this study we recruited an extensive collection of African American families with T2DM- ESRD. Extensive candidate gene analysis was performed and a genome scan carried out. Analysis of the genome scan results has located several genomic regions inherited with T2DM-ESRD. The focus of this renewal application is to locate and identify one or more of these genes using modern molecular genetic methods. Specifically, targeted linkage studies, i.e. fine mapping, will be carried out for the 6 most likely locations for linkage on chromosomes 3q, 7p, 10q, 12p, 16p, and 18q. One linkage peak will be chosen for a focused, comprehensive search for the underlying T2DM-ESRD gene through construction of a framework haplotype block map of the region, followed by high density genotyping of SNPs across the linkage region, and assessment of association in case-control samples leading to the identification of a specific haplotype block containing the T2DM-ESRD gene. Detailed sequencing and analysis will be used to identify the T2DM-ESRD gene.

描述（由申请人提供）：尽管血压控制有所改善并使用血管紧张素转换酶抑制剂，但 2 型糖尿病 (T2DM) 相关的终末期肾病 (ESRD) 是慢性肾衰竭最常见且增长迅速的病因。美国。糖尿病肾病占 Medicare 支持的透析病例的 34% 以上，患有糖尿病 ESRD 的患者两年内死亡率高达 50%。目前尚不清楚为什么只有少数糖尿病患者最终会出现肾衰竭，而大多数血糖和/或高血压控制不佳的糖尿病患者却不会。我们假设非裔美国人中存在促进糖尿病相关 ESRD 发展的基因，并且可以使用现代分子遗传学方法进行鉴定。在本研究的第一阶段，我们招募了大量患有 T2DM-ESRD 的非裔美国家庭。进行了广泛的候选基因分析并进行了基因组扫描。基因组扫描结果分析定位了几个遗传 T2DM-ESRD 的基因组区域。这一更新应用的重点是使用现代分子遗传学方法来定位和识别这些基因中的一个或多个。具体来说，将对染色体3q、7p、10q、12p、16p和18q上6个最可能发生连锁的位置进行有针对性的连锁研究，即精细定位。将选择一个连锁峰，通过构建该区域的框架单倍型块图，对潜在的 T2DM-ESRD 基因进行集中、全面的搜索，然后对整个连锁区域的 SNP 进行高密度基因分型，并评估案例中的关联性对照样品导致含有 T2DM-ESRD 基因的特定单倍型块的鉴定。详细的测序和分析将用于鉴定 T2DM-ESRD 基因。