Whole genome sequencing analysis identifies variations between “Wellderly” & “Illderly”

At the American Society of Human Genetics 60th annual meeting, Nov. 2 to 6, 2010, Sarah S. Murray, Ph.D., Director of Genetics at STSI, presented a poster titled, “Sequence Variants in Translation Regulator EIF4EBP3 Gene Region Associate with Disease Susceptibility,” about ongoing research to understand the genes and pathways related to health span.

Dr. Murray and her colleagues genotyped over one million SNPs in the DNA samples of 397 participants in the Wellderly study and 386 individuals (illderly control group) who had died from various chronic illnesses and were matched for birth year, gender and ancestry with the Wellderly participants.

In a GWAS of the whole-genome genotyping data on these two groups, the researchers found that multiple SNPs in the translator regulator EIF4EBP3 were associated where the allele frequency was higher in the illderly control group versus the Wellderly participants. EIF4EBP3 with EIF4EBP1 and EIF4EBP2 produce proteins that bind to eIF4E. The binding of these proteins to eIF4G inhibits translation and affects cell proliferation.

Dr. Murray’s collaborators include Bradley Patay, M.D., of Scripps Health and STSI; Erin Smith, Ph.D., Cinnamon Bloss, Ph.D., Ali Torkamani, Ph.D., Nikki Villarasa, Nicholas J. Schork, Ph.D., Samuel Levy, Ph.D., and Eric J. Topol, M.D., of STSI; Kai Wang, Ph.D., of Children’s Hospital of Philadelphia; Eric Orwoll, M.D., of Oregon Health Sciences University; and Steven Cummings, M.D., of California Pacific Medical Center.