The major histocompatibility complex (MHC) is a cluster of genes critical to the immune response since it codes for antigen-presenting proteins in all vertebrates. It maintains a high level of polymorphism and has been linked to disease and parasite resistance and reproductive success. Studies of the MHC in wild animal populations in their natural environment are essential to understanding MHC function, selective pressures and evolutionary history. The long-term goal is to understand how the MHC influences health and reproduction in humans. The objective of this proposal is to examine the genetic variation and function of the MHC in the first study of wild chimpanzees. They are a valuable model system for humans because they are our closest living relative and have over 98% identical genomes and similar social patterns but less socioeconomic confounds. The study will 1) Characterize the MHC genetic variation in the chimpanzee population (Pan troglodytes schweinfurthii) at Gombe National Park, Tanzania;2) Examine the correlation between MHC genotype and health measures, including parasite load and disease susceptibility;3) Investigate the relationship between MHC genotype and reproductive success. Chimpanzees will be genotyped at MHC class I (A, B, C) and class II (DR, DQ, DP) classical loci using DNA isolated non-invasively from feces. Genetic variation will be characterized within chimpanzees and will also be compared to that of comparable human populations. Measures of health and reproductive success will be correlated with the presence or absence of particular alleles as well as the degree of heterozygosity of individuals. MHC-matched mating pairs will also be tested for evidence of decreased reproductive success compared to MHC-unmatched pairs. Immunogenetic study of MHC polymorphism and function is essential because MHC polymorphism, and its role in self and non-self recognition, is a key factor causing tissue transplant rejection. This study will also further the understanding of disease resistance as studies suggest MHC allelic composition and diversity are directly related to immunocompetence. Furthermore, it will contribute to the understanding of infertility and failed pregnancy due to particular deleterious alleles and the degree of heterozygosity of individuals, as well as parental MHC matching.

Public Health Relevance

Study of the genes that code for the core components of the immune system is essential to several aspects of human health. These genes determine the body's recognition of self versus non-self, and therefore play a key role in tissue transplant rejection. Additionally, differences in these genes affect the body's ability to fight disease as well as the ability of individuals and couples to successfully reproduce.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F07-C (20))
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Prograis, Lawrence J
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Stanford University
Schools of Medicine
United States
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