Genetic Analysis of African American Hypertensive End-Stage Renal Disease

非裔美国人高血压终末期肾病的基因分析

基本信息

批准号：
7623476
负责人：
BARRY Ira FREEDMAN
金额：
$ 41.13万
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：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2011-09-21
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7623476
关键词：
6p23 9p21.3 Accounting Affect African American Alleles American Candidate Disease Gene Caring Chromosome Mapping Collection DNA Sequence Data Databases Development Diabetes Mellitus Dialysis patients Disease End stage renal failure European Family Genes Genetic Polymorphism Genetic Predisposition to Disease Genome Scan Genomics Genotype Haplotypes Hypertension Hypotension Incidence Individual Kidney Diseases Kidney Failure Lead Linkage Disequilibrium Maps Medical Methods Microsatellite Repeats Minority Molecular Genetics Pathway interactions Patients Pharmaceutical Preparations Phase Polymorphism Analysis Population Predisposition Process Publishing Recruitment Activity Relative (related person)Renal Hypertension Research Personnel Resources Risk Sampling Siblings Signal Transduction Single Nucleotide Polymorphism Single Nucleotide Polymorphism Map Socioeconomic Status Staging Structure Surveys Susceptibility Gene Testing United States United States Centers for Medicare and Medicaid Services base case control density design genetic analysis genetic linkage analysis genetic pedigree hypertension control indexing member novel positional cloning prevent

项目摘要

DESCRIPTION (provided by investigator): The focus of this application is to locate and identify one or more genes that cause hypertension-associated end-stage renal (H-ESRD) disease in the African American population. Hypertensive end-stage renal disease is one of the leading causes of kidney failure in the United States and it disproportionately affects African Americans. This application builds upon a genome scan in 264 African American families containing index cases with H-ESRD and their siblings with end-stage kidney failure. We will perform fine mapping of the regions with the strongest evidence of linkage in the genome scan analysis. Linkage support intervals defined by the fine mapping process will be prioritized based on the evidence for linkage in our sample and other published data. High priority regions will be surveyed for candidate genes that could contribute to hypertension and H-ESRD. These genes will be subjected to a focused high density single nucleotide polymorphism (SNP) mapping effort, block identification and tested for association (e.g., single locus and haplotype) under a case-control design. The case-control sample is independent of the genome scan sample. The signal locus and haplotype analyses should help identify individual polymorphisms and haplotypes that are in linkage disequilibrium with H-ESRD. We anticipate that an intensive genetic analysis for the identification of haplotype blocks will facilitate the search for polymorphisms. Mapping the genes that predispose to hypertensive kidney disease will provide a framework for identifying the pathways that initiate or promote renal failure and could ultimately lead to the development of novel medications to prevent or slow progression of hypertensive kidney failure in African Americans.

描述（研究人员提供）：该应用的重点是在非裔美国人人群中定位和确定一个或多个引起与高血压相关的终末期肾脏（H-ESRD）疾病的基因。高血压末期肾脏疾病是美国肾衰竭的主要原因之一，它对非裔美国人产生了不成比例的影响。该应用基于264个非裔美国家庭的基因组扫描，其中包含H-ESRD及其终点肾衰竭的兄弟姐妹的指数案例。在基因组扫描分析中，我们将对区域进行精细映射。通过精细映射过程定义的链接支持间隔将根据我们的样本和其他已发布数据的链接的证据来优先考虑。将对可能有助于高血压和H-ESRD的候选基因进行高优先级区域。在病例对照设计下，这些基因将受到聚焦的高密度单核苷酸多态性（SNP）映射工作，块鉴定和对关联的测试（例如，单位基因座和单倍型）。病例对照样品与基因组扫描样品无关。信号基因座和单倍型分析应有助于确定与H-ESRD连锁不平衡的单个多态性和单倍型。我们预计，用于鉴定单倍型块的密集遗传分析将有助于寻找多态性。绘制易感高血压肾脏疾病的基因将提供一个框架，以识别引发或促进肾衰竭的途径，并最终可能导致新型药物的发展，以防止或缓慢地进展非裔美国人高血压肾衰竭。