IDENTIFICATION OF GENES INVOLVED IN HIV 1 INFECTION AND PROGRESSION TO AIDS

R5-delta32、CCR2-V64I和第三个基因已被鉴定。 通过对患者170多个候选基因的检测 测试HIV-1和HIV-1易感性假说的队列 进展为艾滋病。从长远来看，我们一直在开发一种 一种在患者队列中识别疾病基因的新方法 “混合体链接不平衡测绘”(MALD；见项目#Z01 公元前10261-01LGD)。遗传多态的候选基因筛选 基因依赖于人类体内存在的细微尺度连锁不平衡 人口。用目前已有的候选基因进行筛选 已知的多态和其他可用的基因座正在进行中 通过对其余基因座的多态进行鉴定。在……里面 本工作，单链构象多态性/异源双链 文献中的分析和多态之后是序列 分析这些多态并将其转换为PCR格式的分析。 数千名艾滋病毒携带者和感染者的DNA已经被 整理并等分成96孔格式的聚合酶链式反应模板，以实现准确和 37板Mega面板的可靠高通量基因分型。 基因分型允许执行生存和分类分析 确定基因类型和表型之间的关系，从而使 基因多态的相对风险和危害的估计 影响HIV-1感染和疾病进展的因素。“ 该项目的目的是识别新的宿主基因和 与HIV-1感染和艾滋病进展有关的基因多态性 通过对候选基因的检查以及通过 混合连锁不平衡(MALD)基因组扫描。美国大学的实验室 基因组多样性(LGD)拥有来自近4,000个个体的样本 有HIV-1接触史或感染史。一种高通量的聚合酶 基于链式反应(PCR)的基因分型实验室已经检测出 数千名HIV感染者中存在大量候选基因多态 暴露的患者已经被开发出来。

R5-delta32, CCR2-V64I and a third gene.<P/ These have been identified by pursuing an approach of examining over 170 candidate genes in patient cohorts for testing hypotheses of susceptibility to HIV-1 and progression to AIDS. For the longer term, we have been developing a novel method for disease gene identification in patient cohorts called "Mapping by Admixture Linkage Disequilibrium" (MALD; See Project #Z01 BC 10261-01 LGD). Candidate gene screening of polymorphisms in or near a gene depends on fine scale linkage disequilbrium that exists in human populations. Screening with the candidate genes that currently have known polymorphisms and additional loci that become available is ongoing through the identification of polymorphisms for the remaining loci. In this work, single strand conformation polymorphism /heteroduplex analysis and polymorphisms from the literature are followed by sequence analysis and conversion of these polymorphisms to PCR formatted assays. Several thousand DNAs of HIV-exposed and -infected individuals have been organized and aliquoted into 96-well format PCR plates for accurate and reliable high-throughput genotyping of the 37-plate Mega panel. Genotyping allows performance of survival and categorical analysis to determine relationships between genotypes and phenotypes making possible estimates of the relative risks and hazards of genetic polymorphisms that influence HIV-1 infection and disease progression. " The aim of this project is to identify novel host genes and polymorphisms involved in HIV-1 infection and progression to AIDS through an examination of candidate genes along with a mapping by admixture linkage disequilibrium (MALD) genome scan. The Laboratory of Genomic Diversity (LGD) has samples from almost 4,000 individuals with a history of HIV-1 exposure or infection. A high-throughput, polymerase chain reaction (PCR)-based genotyping laboratory that has assayed numerous candidate gene polymorphisms in thousands of HIV-infected and - exposed patients has been developed.