Genetic Analysis of African American Hypertensive End-Stage Renal Disease

描述(由研究人员提供)：这项应用的重点是定位和识别在非裔美国人群体中导致高血压相关终末期肾脏(H-ESRD)疾病的一个或多个基因。高血压终末期肾病是美国肾衰竭的主要原因之一，它对非裔美国人的影响不成比例。这一应用程序建立在264个非裔美国家庭的基因组扫描基础上，这些家庭包含H-ESRD及其兄弟姐妹患有终末期肾功能衰竭的索引病例。我们将在基因组扫描分析中对具有最强连锁证据的区域进行精细绘制。将根据我们样本中的链接证据和其他公布的数据来确定精细绘图过程中定义的链接支持间隔的优先顺序。将对高优先级区域进行调查，以寻找可能导致高血压和H-ESRD的候选基因。这些基因将在病例对照设计下进行集中的高密度单核苷酸多态(SNP)定位、区块鉴定和关联测试(例如，单基因座和单倍型)。病例对照样本独立于基因组扫描样本。信号位点和单倍型分析有助于识别与H-ESRD连锁不平衡的个体多态和单倍型。我们预计，对单倍型区块进行密集的遗传分析将有助于寻找多态。绘制高血压肾病易感基因的图谱将为识别引发或促进肾功能衰竭的途径提供一个框架，并最终可能导致开发新的药物来预防或减缓非裔美国人高血压肾功能衰竭的进展。

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.