Abstract # 65:

Scheduled for Thursday, June 21, 2007 05:00 PM-07:00 PM: Session 7 (South Main Hall) Poster Presentation

Single nucleotide polymorphisms of the TNF-alpha gene in captive vervet monkeys (Chlorocebus aethiops)

S. B. Gray1, T. D. Howard1, G. A. Hawkins1, A. F. Diallo1, C. D. Langefeld2 and J. D. Wagner1
1Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA, 2Section on Statistical Genetics and Bioinformatics, Wake Forest University School of Medicine
     Several single nucleotide polymorphisms (SNPs) in the human TNFa gene have been associated with differential TNFa expression and susceptibility to a variety of complex diseases. Vervet monkeys are becoming an important animal model for such complex diseases as obesity, Type 2 diabetes and atherosclerosis. However, compared to other non-human primates which serve as models of human disease, there is a relative paucity of genetic information for the vervet. Towards further defining the vervet as a model of human diseases, we have sequenced the promoter, coding, and intronic regions of the TNFa gene in 24 presumably unrelated vervets producing a contiguous sequence of ~4 kb to evaluate conservation with other primates and identify SNPs for future studies. The use of 24 individuals yields a 91.5% chance of detecting polymorphisms with a minor allele frequency of 5% or greater in the population. Sequencing revealed a total of 9 SNPs with 5 in the promoter region, 4 in intronic regions and frequencies between 0.15 and 0.40. This yielded 7 total haplotypes with frequencies between 0.021 and 0.25. An intronic tetranucleotide repeat polymorphism was also discovered but was not used in determination of haplotypes. This genetic characterization is a valuable initial step towards further developing the vervet as a model of complex, polygenic disease and will allow future association studies as well as facilitate phylogenetic analysis.