GENETIC MANAGEMENT OF ANIMAL COLONIES

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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. Objective: The genotypes or phenotypes of geographically representative samples of rhesus macaques, Macaca mulatta, of different subspecies of Chinese, Indian, and southeast Asian origin will be compared in phylogenetic context (i.e., together with those of six other species of macaques) using approximately 75 DNA loci, amplified using the polymerase chain reaction (PCR), to genetically characterize these taxa. These genetic differences will be compared among various hierarchical levels (e.g. regional populations, subspecies, countries of origin, species) of macaques to assess their biological significance using gene diversity and phylogenetic methods and each taxa will be genetically characterized with specific marker alleles relative to each other. The loci to be studied include neutral short tandem repeat (STR) loci widely dispersed over all chromosomes, mt DNA, a Y-chromosome haplotype,and both class I and class II major histocompatibility complex (MHC) loci which influence immune responsiveness. A program to assign samples of unknown provenience to their correct subspecies, geographic region or country of origin, now in use, will be substantially improved using the new population samples and genetic data generated by this grant application. Services provided to all NHP breeding facilities by this grant application include typing rhesus macaques using 15 most informative STR loci to establish pedigrees, the use of these data to estimate genetic parameters such as effective population size, inbreeding and average kinship coefficients, gene diversity, generate a genetic profile of individual animals, conduct paternity exclusion analysis for estimating relative reproductive success of male breeders and specific founding lineages, and the use of the aforementioned assignment program and taxa-specific genetic markers identified during the course of this study to identify the country of origin and subspecies of samples of unknown origin. In addition, specific recommendations tailored to the unique facilities at each specific pathogen free (SPF) breeding colony supported by the National Institutes of Health will be prepared and provided to each colony to facilitate maintenance of genetic heterogeneity