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The overall focus of the lab is to understand the role of gene regulatory sequences in human biology and disease. Through a combination of comparative genomic strategies, regulatory element analysis, human patient samples, and mouse and fish genetic engineering technologies, we are working to elucidate mechanisms whereby genetic variation within these sequences lead to changes in human phenotypes. The research focuses on three clinically relevant phenotypic categories. The first is monogenic disease, using limb abnormalities, one of the most common forms of human congenital abnormalities (prevalence of 1 in every 500 births), as a model. The second is complex disease, analyzing how nucleotide changes in regulatory sequences contribute to obesity. The third is pharmacogenomics, characterizing how genetic differences in regulatory sequences lead to clinical variation in response to drugs.

Selected Publications

Ahituv N, Zhu Y, Visel A, Holt A, Afzal V, Pennacchio LA, Rubin EM “Deletion of ultraconserved elements yields viable mice”, PLOS Biology , 2007, 5: e234.

Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Martin A, Hébert S, Doelle H, Ersoy B, Kryukov G, Schmidt S, Yosef N, Ruppin E, Sharan R, Vaisse C, Sunyaev S, Dent R, Cohen J, McPherson R, Pennacchio LA “Medical sequencing at the extremes of human body mass”, American Journal of Human Genetics , 2007, 80: 779-791.

Pennacchio LA, Ahituv N , Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, De Val S, Afzal V, Black BL, Couronne O, Eisen MB, Visel A, Rubin EM “In vivo enhancer analysis of human conserved noncoding sequences”, Nature , 2006, 444:499-502.

Bejerano G, Lowe C, Ahituv N, King B, Siepel A, Salama S, Rubin EM, Kent WJ, Haussler D “A distal enhancer and an ultraconserved exon are derived from a novel retroposon.” Nature , 2006, 441:87-90.

Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Collier JM, Hébert S, Doelle H, Dent R, Pennacchio LA, McPherson R “A PYY Q62P variant linked to human obesity.” Human Molecular Genetics , 2006, 15: 387-391.

Ahituv N , Prabhakar S, Poulin F, Rubin EM, Couronne O “Mapping cis-regulatory domains in the human genome using multi-species conservation of synteny.” Human Molecular Genetics , 2005 14: 3057-3063.