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

与 HIV 1 感染和进展为艾滋病有关的基因的鉴定

• 批准号: 6101061
• 负责人: M W SMITH
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6101061
• 关键词: AIDS; HIV infections; disease /disorder proneness /risk; genetic polymorphism; human genetic material tag; human immunodeficiency virus 1; human population genetics; human tissue; immunogenetics; linkage disequilibriums; pathologic process; polymerase chain reaction

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.

R5-delta 32、CCR 2-V64 I和第三基因。<P/这些已经被确认 通过研究患者中超过170个候选基因， 用于检验HIV-1易感性假设的队列， 发展为艾滋病。从长远来看，我们一直在发展一个 一种新的方法，用于在患者队列中识别疾病基因， “通过混合物连锁不平衡作图”（MALD;参见项目#Z01 BC 10261-01 LGD）。多态性的候选基因筛选 一个基因依赖于存在于人类中的精细连锁不平衡， 人口。筛选候选基因， 已知的多态性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性的鉴定。在 这项工作，单链构象多态性/异源双链体 根据文献分析和多态性， 分析这些多态性并将其转化为PCR形式的测定。 数千名艾滋病毒暴露和感染者的DNA已经被 组织并等分到96孔格式的PCR板中，以进行准确和 37板Mega panel的可靠高通量基因分型。 基因分型允许进行生存和分类分析， 确定基因型和表型之间的关系， 遗传多态性的相对风险和危害的估计 影响HIV-1感染和疾病进展。" 该项目的目的是鉴定新的宿主基因， 与HIV-1感染和艾滋病进展有关的多态性 通过对候选基因的检查，沿着进行映射， 混合连锁不平衡（MALD）基因组扫描。实验室 基因组多样性（LGD）有来自近4,000个个体的样本， HIV-1暴露或感染史。一种高通量聚合酶 基于PCR的基因分型实验室， 在成千上万的艾滋病毒感染者和- 暴露的患者已经发展。