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：
7436092
负责人：
DONALD W BOWDEN
金额：
$ 39.66万
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/7436092
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）：尽管血压控制的改善和血管紧张素转化酶抑制剂的使用，但2型糖尿病（T2DM）相关的终阶段肾病（ESRD）是美国最常见且迅速增长的慢性肾衰竭病因。糖尿病性肾病占透析病例的34％以上，糖尿病ESRD患者在两年内遭受50％的死亡率。尚不清楚为什么只有少数糖尿病患者最终会导致肾衰竭，而大多数控制血糖和/或高血压的糖尿病患者都不会。我们假设有助于使用现代分子遗传学方法来鉴定有助于糖尿病相关的ESRD发展的基因。在这项研究的第一阶段，我们招募了大量具有T2DM-ESRD的非裔美国人家庭。进行了广泛的候选基因分析，并进行了基因组扫描。基因组扫描结果的分析已找到了用T2DM-ESRD遗传的几个基因组区域。这种更新应用的重点是使用现代分子遗传学方法定位和识别其中一个或多个这些基因。具体而言，将针对6个最有可能的位置进行有针对性的连锁研究，即精细的映射，以3q，7p，10q，10q，12p，16p和18q进行连锁。 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.详细的测序和分析将用于识别T2DM-ESRD基因。