, Core C: MHC Genetic Typing Core Genetically well-characterized animal models are critical for the success of S/HIV research, including characterization for MHC genotype, known ancestry, and pedigree relationships. In particular, informative and accurate MHC genotyping is essential, due to the complexity of the MHC class I loci in macaques, and the influence of allele type on disease progression. The need for genetically well-characterized animal models for research must also be balanced against the need to preserve genetic diversity in animal colonies dedicated to supporting biomedical research. This is a requirement not only to ensure long-term colony health, but to ensure the relevance of experimental findings to human disease. The ONPRC is a leader in the development of many of the current recommended approaches and technologies used in genetic typing and management of NHP colonies. Thus, the aims of the Genetics Core for this project are to, 1) use state-of-the-art genetic testing to characterize all ONPRC Indian-origin rhesus macaques for MHC genotype, and 2) to maximize the genetic diversity of the ONPRC breeding colony while producing sufficient numbers of MHC-genotyped Indian-origin rhesus macaques to meet research needs. To achieve these aims, we will conduct MHC Class I genotyping of an additional 1,760 SPF4 Indian-origin rhesus macaques to support continued research, and will additionally develop new or improved approaches to the genetic management of these macaques. These innovations include the use of cost-effective genome-wide sparse sequencing to assess pedigree relationships, genetic diversity, and ancestry in a single, combined assay; the implementation of automated, periodic reporting aimed at summarizing genetic diversity for every breeding group in the colony; and improved algorithms for estimating the genetic value of individual animals by adding information on demographics, genotypes or phenotypes of interest, and animal assignment history.
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