Maintenance of the SPF Breeding Colonies at Yerkes National Primate Research Center: MHC Genetic Typing Core

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Project Summary/Abstract--MHC Genetic Typing Core Rhesus macaques are a critical animal model for AIDS research. To keep pace with the high demand of animals for AIDS-related studies, the Yerkes National Primate Research Center maintains a carefully monitored breeding program under the auspices of our Specific Pathogen Free (SPF) colony. Genetic characterization of rhesus macaques in the SPF colony is essential to: (1) ensure adequate genetic diversity and long-term health of the colony and (2) provide suitable experimental animals to AIDS studies that do not contain alleles known to affect SIV infection. The primary role of the Yerkes SPF MHC Genetic Typing Core is to (1) establish parentage of animals and design genetic strategies to avoid inbreeding and maximize genetic diversity of the colony and (2) determine the genotype of loci known to affect SIV infection (primarily the MHC class I and II genes) and provide this information to AIDS researchers. Since 2010, these services have been performed by the Yerkes SPF Genetic Typing Core, enabled by U24 support. In the last funding cycle, the Core has developed a novel high-throughput assay for parentage, which we used to complete parentage analysis of the Yerkes SPF colony, and this tool will be implemented throughout the upcoming funding period. Next-generation sequencing technology applied to the rhesus macaque has now enabled the creation of a high-resolution reference genome and acquistion of whole-genome data on hundreds of animals. These developments have profoundly broadened the opportunities to use high-resolution genotyping as part of colony management for rhesus macaque SPF colonies. In Aim 3, the secondary objective of this Core, we propose a novel strategy that combines the existing pedigree information of the Yerkes SPF colony with whole-genome sequencing and genetic imputation to establish genome-wide sequence data for a deep pedigree of animals at low cost. This approach will provide the groundwork for obtaining genome-wide information of the entire colony in future years and establish the rhesus macaque as an emerging and promising model for genetic studies. Aim 1: To apply advanced parentage testing and genetic breeding strategies to the SPF rhesus colony. Aim 2: To apply state-of-the-art MHC typing to inform colony management and provide well- characterized animals for AIDS-related investigations. Aim 3: To develop a cohort of pedigreed animals with genotypes defined at a genome-wide scale as a platform for allele discovery. Taken together, these proposed aims will ensure the genetic diversity and sustainability of the Yerkes SPF colony for years to come and provide NHP AIDS researchers with unprecedented genetic data on their study animals, thereby advancing preclinical research to prevent, treat and cure HIV infection. This model will contribute to identifying preventive strategies and treatments to reduce the burden of HIV.