In vitro whole-genome analysis identifies a susceptibility locus for HIV-1
In vitro whole-genome analysis identifies a susceptibility locus for HIV-1
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DOI：
10.1371/journal.pbio.0060032
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发表时间：
2008-02-01
期刊：
影响因子：
9.8
通讯作者：
Telenti, Amalio
中科院分区：
文献类型：
--
作者：
Loeuillet, Corinne;Deutsch, Samuel;Telenti, Amalio
人类基因组变异性大规模分析的进展为研究传染性病原体易感性的遗传基础提供了前所未有的机会。我们在此报告使用体外系统鉴定HSA8q24.3上与细胞对HIV-1易感性相关的位点。该基因座是通过使用来自多代家族的细胞系进行定量连锁分析绘制的，并在体外验证，随后在hiv阳性个体中进行了两项独立的关联研究。单核苷酸多态性rs2572886与淋巴母细胞样B细胞和原代T细胞对HIV-1的细胞易感性相关，也与两组HIV-1感染患者中的一组的疾病加速进展相关。生物学分析表明rs2572886区域在调节glyyl -phosphatidyl- inositol （GPI）锚定蛋白LY6家族中的作用。体外细胞表型的遗传分析为发现感染因子的易感性位点提供了一种有吸引力的方法。
Advances in large-scale analysis of human genomic variability provide unprecedented opportunities to study the genetic basis of susceptibility to infectious agents. We report here the use of an in vitro system for the identification of a locus on HSA8q24.3 associated with cellular susceptibility to HIV-1. This locus was mapped through quantitative linkage analysis using cell lines from multigeneration families, validated in vitro, and followed up by two independent association studies in HIV-positive individuals. Single nucleotide polymorphism rs2572886, which is associated with cellular susceptibility to HIV-1 in lymphoblastoid B cells and in primary T cells, was also associated with accelerated disease progression in one of two cohorts of HIV-1-infected patients. Biological analysis suggests a role of the rs2572886 region in the regulation of the LY6 family of glycosyl-phosphatidyl- inositol ( GPI)-anchored proteins. Genetic analysis of in vitro cellular phenotypes provides an attractive approach for the discovery of susceptibility loci to infectious agents.