GENETIC FACTORS FOR PROGRESSION OF HIV ASSOCIATED NEPHROPATHY

与许多全身性疾病类似，HIV-1感染在确定的人群亚群（主要是非裔美国人）中导致终末期肾脏疾病（ESRD），因此表明遗传风险因素在肾衰竭的发展中起关键作用。该项目的目的是通过关注HIV-1相关肾病（HIVAN）的小鼠模型来绘制与ESRD发展相关的数量性状位点（QTL）。为了实现这一目标，Core B将在HIV-1转基因小鼠系（Tg26）和M. cataneus （MCAST）菌株之间提供一个仔细表型的B2杂交。这个项目将执行QTL的映射。这一努力将构成鉴定导致肾功能衰竭的潜在性状位点的关键一步。这个项目的功能将解决以下目标：1。鉴定了160个简单序列长度多态性的筛选集，这些多态性间隔约为10 cM，在Tg26 x MCAST杂交中具有信息性。2. 对B2队列动物进行基因型分析，然后进行连锁分析，比较每个性状与跨越小鼠基因组的标记位点的分离。3. 捕获目标2中qtl的同源菌株的遗传特性。4. 通过对同源菌株进行减数分裂定位，对QTL进行精细定位，然后通过候选基因分析和定位克隆鉴定对肾功能衰竭发展的基因反应。人们认为，将大部分分子遗传学项目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任务中使用的人员和设备，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.