In vitro whole-genome analysis identifies a susceptibility locus for HIV-1 |
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| Authors: | Loeuillet Corinne Deutsch Samuel Ciuffi Angela Robyr Daniel Taffé Patrick Muñoz Miguel Beckmann Jacques S Antonarakis Stylianos E Telenti Amalio |
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| Affiliation: | 1, Institute of Microbiology, University Hospital, University of Lausanne, Lausanne, Switzerland;2, Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospital of Geneva, Geneva, Switzerland;3, Swiss HIV Cohort Study, Lausanne, Switzerland;4, Department of Medical Genetics, University Hospital and University of Lausanne, Lausanne, Switzerland;University of Alabama, United States of America |
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| Abstract: | 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. |
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