The goal of this competitive renewal is to increase the value of rhesus macaques (Macaca mulatto) for genetic and genomic research by continuing development of a highly informative genetic linkage map for this species. Rhesus monkeys are the most widely used nonhuman primate in biomedical research. This species is already an important model organism for studies of neurobiology, immunology, HIV infection and AIDS, pharmacology, diabetes and obesity, bone biology, alcoholism, developmental psychology and other significant human health problems. Improved research tools and information related to genetics and genomics will make this species even more valuable for analyses of the genetic basis of various human diseases. During the first four years of this project, an initial genetic linkage map was produced that consists of 241 human microsatellite loci genotyped and analyzed in more than 800 pedigreed rhesus monkeys. This initial map covers all 20 rhesus autosomes, and the average spacing between markers is approximately 9.3 centiMorgans. However, the value of this map is limited by the lack of genetic markers in some chromo- somal regions, and the low heterozygosity of loci in others. In this renewal application, support is requested to add 300 additional microsatellite polymorphisms to this initial rhesus linkage map. This will improve the density, coverage and scientific value of the rhesus linkage map. Support is also requested to establish a collaboration with the Baylor Human Genome Sequencing Center in order to integrate the growing genetic linkage map with the whole genome DNA sequence that BHGSC is generating for this species. Integration of genetic linkage data with physical mapping and sequence data will benefit both projects and make these resources and this species more useful for many different genetic analyses. Finally, this project will establish a website designed to give the research community easy access to up-to-date rhesus linkage mapping data, including detailed information about the microsatellite polymorphisms discovered through this study. A more informative linkage map for this species will significantly increase the opportunity for and statistical power of whole genome linkage screens (i.e. QTL mapping analyses) intended to locate functional genes that influence significant traits related to human health and disease.
