DEVELOPMENT, MANAGEMENT AND USE OF A SNP MAP FOR RHESUS MACAQUES

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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. We will use the recently completed rhesus macaque genome map, to identify approximately 83,333 single nucleotide polymorphisms (SNPs) randomly distributed throughout the rhesus macaque (Macaca mulatta) genome. At least ten copies of each DNA fragments in reduced representation libraries (RRLs) constructed from pooled (n=25)DNA samples from 7 different regional populations will be sequenced, then filtered, parsed and compared to the rhesus macaque draft sequence and to each other using bioinformatics tools we previously developed to identify the locations, flanking sequences and minor allele frequencies (MAFs) of 83,333 SNPs. Genotyping assays on lliumina iSelect chips will be constructed for the 7,600 SNPs whose frequencies differ most between Indian and Chinese rhesus macaques and genotyped in geographically representative samples of 192 Indian rhesus macaques, and192 Chinese rhesus macaques and in 678 Indian/Chines rhesus macaques with varying proportions of Indian and Chinese ancestry. Genotypes for the 7,600 SNPs will be used to 1) confirm Mendelian segregation of SNPs in multigeneration families, 2) assess the ability of the SNPs to accurately estimate proportions of Indian and Chinese ancestry in Indian/Chinese hybrid, pedigreed animals and 3) identify ancestry informative markers for admixture mapping of QTLs and to conduct admixture mapping of a QTL for "temperament.". Our SNP map will be made publically available through several outlets including dbSNP. The 384 most potentially informative of the 83,333 SNPs for longtail macaques will be genotyped in 96 samples from six different longtail macaque populations to identify minimum panels of 96 SNPs each for identifying country of origin and for parentage analysis and estiinating parameters useful for genetic management. Assays will be constructed of these two panels and made available to NIH investigators, providing cost recovery. The genotypes of SNPs described above will be used for genomic and population structure analyses of regional populations of rhesus and longtail macaques. PUBLIC HEALTH RELEVANCE (provided by applicant): Rhesus and longtail macaques are the most and second most used models for the biomedical study of human diseases. Genetic resources developed for rhesus macaques are not available for longtail macaques. Mapping disease phenotypes and QTLs is possible with the recent sequencing of the rhesus genome but requires the identification of many known polymorphic loci (e.g., SNPs) throughout the macaque genome. The most practical method for conducting whole genome association studies is admixture mapping.