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. The identification of specific genes that predispose to atherosclerosis will enable new strategies for preventing cardiovascular disease, which is the leading cause of death in the USA. The overall goal is to conduct a genome search in pedigreed baboons to identify individual genes that contribute to variation in lipoprotein-and adiposity-related phenotypes. We are determining the chromosomal locations of genes that modulate the cholesterolemic responses to dietary cholesterol and/or to dietary saturated fatty acids and of genes that modulate blood pressure or adiposity-related phenotypes. Because most baboon and human genes are arranged in the same linear order, the localization of a gene in baboons may implicate one or more defined human genes as candidates. The genome scan uses a baboon genetic linkage map consisting of 331 microsatellite markers distributed along the chromosomes at an average of internal of 7.2 centimorgans. Inbred progeny are being produced and subjected to dietary challenge to measure genetic interactions with dietary fat and cholesterol in determining plasma lipoprotein characteristics. Measures of blood pressure and adiposity related characteristics also are made on the progeny and their parents. The animals are being genotyped for microsatellite markers, and analyses will be conducted to localize pertinent genes. Efforts to identify these genes and their mechanisms of function will then be initiated.
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