Outcomes to both exposure to and infection by many viruses are highly variable in human populations. While the differential response may result from genetic differences in the virus, a possible interpretation of the epidemiological data is that there are genetic differences in the host population which influence both susceptibility to infection and disease outcomes following viral infection. The primary objective of this study is to identify those host genetic factors that regulate virus infection, disease progression, immune response and reactivity to therapeutics. We have established collaborations with well-defined epidemiologic disease cohorts at risk for AIDS and for Hepatitis B. Immortal B-cell lines from all members of the cohort were established and genomic DNA is screened using restriction fragment length polymorphism (RFLP) methodology (See Project #ZOICPO5678-01 LVC). Distortion of allelic, genotypic or linkage equilibrium of linked human loci in clinically defined disease categories provides the signal to discover disease susceptibility/resistance loci in human populations. Approxi- mately 250 RFLPs in both """"""""candidate"""""""" genes and equivalently spaced anonymous RFLP markers are used in the screenings. A networked data base to monitor cell and DNA inventory, molecular reagents, accumulated data and genetic analysis has been established. Putative genetic disequilibrium in the two cohorts of homosexual men are being affirmed.
