In vitro whole-genome analysis identifies a susceptibility locus for HIV-1.
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.
Loeuillet
Corinne
C
Institute of Microbiology, University Hospital, University of Lausanne, Lausanne, Switzerland.
Deutsch
Samuel
S
Ciuffi
Angela
A
Robyr
Daniel
D
Taffé
Patrick
P
Muñoz
Miguel
M
Beckmann
Jacques S
JS
Antonarakis
Stylianos E
SE
Telenti
Amalio
A
D002874:Chromosome Mapping; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D017261:Glycosylphosphatidylinositols / Q000235:genetics; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans
D017261:Glycosylphosphatidylinositols