HIV study with OTHER, WGS data on dbGaP (20 participants)

phs000445 — HIV-Resistant People with Hemophilia

<p>Rare individuals are highly resistant to infection with human immunodeficiency virus (HIV). Studies of candidate genes resulted in the discovery of a 32bp deletion in the CC-chemokine receptor 5 gene (CCR5Δ32), which rendered this critical co-receptor for primary HIV infection to be non-functional. Pharmacologic and vaccine-induced blockade of CCR5 is being pursued to treat and prevent HIV infection and other conditions.</p> <p>The allele frequency of CCR5Δ32 among persons of European ancestry is approximately 10%. CCR5Δ32/Δ32 homozygotes are almost totally resistant to HIV infection. People with severe hemophilia A require frequent replacement with clotting Factor VIII (FVIII) to control hemorrhage. Prior to the discovery of HIV in 1984 and licensure of recombinant FVIII in the late 1980s, people with severe hemophilia A were treated with plasma-derived FVIII and thus were intensively exposed to HIV. Only 5% of such patients were not infected with HIV. Of these, approximately 1/3 were CCR5Δ32/Δ32 homozygotes. The remaining 2/3 of these people who were highly resistant to HIV remain unexplained. This project seeks to discover genome variations among people who are highly resistant to HIV infection. Such variation is likely to serve as a target for reducing the morbidity and incidence of HIV. </p>