Genetic Analysis of African American Hypertensive End-Stage Renal Disease

描述（由研究者提供）：本申请的重点是定位和鉴定非洲裔美国人人群中引起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，非裔美国人受其影响尤为严重。该应用程序建立在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的索引病例及其患有终末期肾衰竭的兄弟姐妹。我们将在基因组扫描分析中对具有最强关联证据的区域进行精细绘图。由精细映射过程定义的链接支持间隔将根据我们样本中的链接证据和其他已发表的数据进行优先排序。将对可能导致高血压和H-ESRD的候选基因进行高优先级区域调查。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性（SNP）定位工作，块鉴定和关联测试（例如，单位点和单倍型）。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性和单倍型。我们预计，对单倍型块进行密集的遗传分析将有助于寻找多态性。绘制易患高血压肾病的基因图谱将为确定引发或促进肾衰竭的途径提供一个框架，并可能最终导致开发新的药物来预防或减缓非裔美国人高血压肾衰竭的进展。

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.