IDENTIFICATION OF HUMAN GENETIC LOCI WHICH INFLUENCE SUSCEPTIBILITY TO HIV

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Considerable variability has been observed in susceptibility to infection by HIV-1 and, following infection, length of "latency" and disease outcome. There are three primary reasons suggested for the observed heterogeneity in HIV-1 infections: (1) genetic variation among the HIV-1 "quasispecies" affects replication rates and pathogenesis; (2) there is a requirement for a cofactor for disease progression; and (3) genetic polymorphisms of the host population affect outcomes of exposure. Epidemiological studies have suggested that there is a strong genetic component to the outcome of infectious diseases. The major focus of this study is to identify host genetic factors that affect susceptibility or resistance to HIV-1 infections and progression by taking advantage of the rapid progress in the development of the human genetic map and several well-characterized, prospective, longitudinal cohort studies. A panel of 320 polymorphic loci (120 candidate loci thought to participate in retroviral activities and 200 anonymous DNA segments) spaced at approximately 10 centiMorgan intervals throughout the human genome have been typed in both hemophiliac and homosexual male cohorts in search of distortions of genetic equilibria (allelic, genotypic, and linkage equilibria) among different risk groups.