GENETIC FACTORS FOR PROGRESSION OF HIV ASSOCIATED NEPHROPATHY

与许多系统性疾病相似，HIV-1感染在定义的人群亚组（主要是非洲裔美国人）中引起终末期肾病（ESRD），从而表明遗传风险因素在肾衰竭的发展中起关键作用。 本项目的目的是通过关注HIV-1相关性肾病（HIVAN）的小鼠模型来定位与ESRD发展相关的数量性状基因座（QTL）。 为了实现这一目标，核心B将在HIV-1转基因小鼠系（Tg 26）和M之间提供仔细分型的B2杂交。cataneus（MCAST）菌株。 这个项目将进行QTL的定位。 这一努力将构成确定潜在的性状基因座有助于肾功能衰竭的关键一步。该项目的功能将实现以下目标：1。鉴定160个简单序列长度多态性的筛选组，其间隔约为10 cM，在Tg 26 x MCAST杂交中提供信息。 2. 对B2组群中的动物进行基因型分析，然后进行连锁分析，将每个性状的分离与跨越小鼠基因组的标记基因座进行比较。 3. 捕获目标2中鉴定的QTL的同源菌株的遗传特征。4. 通过同源株的减数分裂作图精细定位QTL，然后通过候选基因分析和定位克隆鉴定肾衰竭发生的基因反应。人们认为，将该计划项目的大部分分子遗传学的性能放在一个具有既定专业知识的单一项目中是合乎逻辑的，因为它最大限度地利用了重复性任务中所使用的人员和设备，如标记开发，基因分型和连锁分析。

Similar to many systemic disorders, HIV-1 infection causes end-stage renal disease (ESRD) in defined population subgroups, primarily African Americans, thereby suggesting that genetic risk factors have a critical role in the development of renal failure. The aim of this project is to map the quantitative trait loci (QTL's) relevant to the development of ESRD by focusing on a murine model of HIV-1 associated nephropathy (HIVAN). To achieve this goal, Core B will provide a carefully phenotyped B2 cross between the HIV-1 transgenic mouse line (Tg26) and M. cataneus (MCAST) strains. This project will perform mapping of QTL's. This effort will constitute a critical step toward identification of underlying trait loci contributing to renal failure. The function of this project will address the following aims: 1. Identification of a screening set of 160 simple sequence length polymorphisms spaced at approximately 10 cM intervals that are informative in the Tg26 x MCAST cross. 2. Genotypic analysis of animals in the B2 cohort followed by analysis of linkage comparing the segregation of each trait to marker loci spanning the mouse genome. 3. Genetic characterization of congenic strains trapping the QTLs identified in aim 2. 4. Fine mapping of the QTL by meiotic mapping of the congenic strains followed by identification of the gene(s) response for the development of renal failure by candidate gene analysis and positional cloning. It is believed that placing performance of much of the molecular genetics of the program project in a single project with established expertise is logical, since it maximizes use of personnel and equipment employed in repetitive tasks such as marker development, genotyping and analysis of linkage.