Abstract # 50:

Scheduled for Saturday, September 17, 2011 03:55 PM-04:15 PM: Session 10 (Salon F (Sixth Floor)) Oral Presentation


J. Rogers1,2
1Baylor College of Medicine, Human Genome Sequencing Center, Houston, Texas 77030, USA, 2Southwest National Primate Research Center, San Antonio, Texas
     Nonhuman primates are central to translational research because they provide research models that so closely mimic the physiological processes of human disease. Recent studies document naturally occurring genetic variation in macaques, baboons and other species that provide valuable parallels to human genetic polymorphisms known or suspected to influence disease risk. Remarkable recent advances in DNA sequencing technology now make it practical to sequence the whole genome or exome from hundreds of individuals in multiple primate species. As illustration, we have cataloged functionally significant DNA polymorphisms across 15 unrelated rhesus macaques (Macaca mulatta). This survey identified >3 million previously unknown SNPs, with >4000 non-synonymous variants that change protein sequences and 600 splice site variants. More than 700 non-synonymous changes are predicted by Polyphen-2 to negatively impact protein function, including genes that influence metabolic syndrome and cancer. Similar large-scale sequencing studies in marmosets (Callithrix jacchus) and other species are also identifying large amounts of functionally significant genetic variation. This strategy of “forward genetics” in which rapid inexpensive DNA sequencing is used to discover variation in primate genes that are important for understanding human health and disease will transform and accelerate translational medicine by providing comprehensive catalogs of natural functionally significant genetic variants in primate models, and thus open new avenues of physiological and pharmacological studies with direct relevance to disease risk and new therapies.