SEQUENCE AND POLYMORPHISM OF RHESUS MACAQUE MHC

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The increased utility of the rhesus macaque animal model in both HIV vaccine development and pathogenesis studies necessitates the development of a solid genetics and immunogeneticsdata infrastructure for this species. Relative to human data, there is a paucity of information about the larger-scale gene content of the macaqueMHC and very littlepolymorphism data from outsideof the macaque class I and I1 genes. As a pointed example, indirect evidence exists that there may be as many as 3 class I B loci and 2 class I A loci on certain macaque haplotypes, but this has not been confirmed through direct genomic analysis. Thus the number of actively expressed class I genes in an individual experimental macaque may be unknown. An essentially similar story underlies some class I1 loci, and very little structural data exists about the hundreds of other genes present in the macaque MHC, more than a third of which are also directly involved in the immuneresponse. These deficiencies provide substantial immediate motivation to better understand the genetics and immunogenetics of rhesus macaques that could be useful in the design and conduct of AIDS vaccine experiments in the simian immunodeficiency(SIV) and chimeric SIV-HIV(SHIV) animal models using this nonhuman primate species. Towards this end, we propose to develop a DNA sequenceof a macaque major histocompatibility complex (MHC)of finished high quality data. We further propose to annotatethis data string with extensivepolymorphism data (SNP) and larger-scale haplotypic variation, and with respect to the complete gene content of the region. One fundamental priority will be to effectively organize and disseminate this data to the interested scientific community. Todevelop this resource, we propose to accomplish the following specific aims: 1) To derive a complete and high quality genomic sequence of a major histocompatibility complex (MHC)from the rhesus macaque. 2) To develop and define a set of SNPs and larger scale haplotype structures useful as mapping tools in the association with MHC- linked phenotypes. 3) To identify and annotate genes and polymorphims in the macaque MHC and make this resource available in a useful and palatable form tothe scientific community. We will accomplish these aims in part by combining resources and expertise in macaque genetics,genomics, and function from three accomplished laboratories.