This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have recently discovered that cynomolgus macaques from different geographical locations have distinct major histocompatibility complex (MHC) genetics. Since cynomolgus macaques are increasingly used for biodefense and AIDS research, it is important to understand differences in MHC genetics. In this project, we are defining the MHC genetics of cynomolgus macaques from five geographic origins, developing genetic tests, and defining peptide-binding motifs from common MHC alleles. This new subproject initiated in September 2005. Since the inception of this project, we have collected samples from Mauritian, Indonesian, Vietnamese, and Chinese cynomolgus macaques. Additionally, we are seeking regulatory approval to collect samples from a cohort of Filipino cynomolgus macaques. We are using a combination of approaches to identify the MHC genes present in each population of monkeys. High-throughput DNA sequencing of selected animals identified the first MHC class I alleles in Indonesian cynomolgus macaques, as well as extending the length of previously identified allele sequences from Mauritian cynomolgus macaques. Full-length MHC class II DP, -DQ, and DR sequencing is currently being performed on a select groups of animals from each geographic location. We have also recently developed a microsatellite map of the MHC in cynomolgus macaques and have used this map to identify common MHC haplotypes in Mauritian monkeys. This work has led to the identification of MHC pseudo-twins animals with identical MHC genetics on both chromosomes. We are currently evaluating the suitability of this technology to assay MHC genetics of other cynomolgus macaque populations. We have also modified a second MHC genetic assay, termed reference-strand mediated conformational analysis (RSCA), to study the MHC genetics of cynomolgus monkeys. RSCA successfully identified genetically matched animals for a WNPRC AIDS research study and intentionally genetically mismatched animals for a WNPRC solid organ transplant study.
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