Daniel Pomp

Most traits displaying continuous variation are exceptionally complex, with varying contributions of genetic susceptibility and interacting environmental factors. Genetic predisposition to a phenotypic range for complex traits such as body weight and body fat results from combinations of relatively small effects of DNA variations within a large number of unidentified polygenes, known as quantitative trait loci (QTL). While scientists have made great progress in understanding the proteins, pathways, and networks that functionally control a complex phenotype such as obesity, we know very little about the underlying genetic variation that an individual is born with to predispose it to a particular phenotypic range. This large gap between our extensive knowledge of the physiological mechanisms and our embryonic understanding of how genetic predisposition is manifested, impairs gene-based discovery and development of diagnostic and therapeutic tools. The paradigm of “quantitative genomics” is based on large-scale endo-phenotyping at the transcriptional, proteomic, and/or metabolomic levels that is performed within the context of a QTL mapping population. This can be a powerful force in dissecting the genetic architecture of complex traits by synergistically integrating the powers of recombination and functional analyses. Using polygenic mouse models and high-throughput approaches integrating genomics and physiology, the Pomp lab identifies genes underlying predisposition to obesity, and studies how these genes interact with each other and with nutritional interventions. They have also begun to apply their research populations and methods to investigate polygenic and dietary obesity risk factors for mammary and colon cancer susceptibility.

Selected Publications:
Ideraabdullah FY, Kim K, Pomp D, Moran JL, Beier D, Villena FP. (2007) Rescue of the Mouse DDK Syndrome by Parent-of-Origin-Dependent Modifiers. Biol Reprod. 76:286-293.

Yi N, Zinniel DK, Kim K, Eisen EJ, Bartolucci A, Allison DB, Pomp D. (2006) Bayesian analyses of multiple epistatic QTL models for body weight and body composition in mice. Genet Res. 87:45-60.

Allan MF, Eisen EJ, and Pomp D. (2005) Genomic mapping of direct and correlated responses to long-term selection for rapid weight gain in mice. Genetics 170:1863-77.

Jerez-Timaure NC, Eisen EJ, and Pomp D. (2005) Fine mapping of QTL with major effect on weight and fat on distal mouse chromosome 2. Physiol Genomics 21(3):411-22.

Yi N, Yandell B, Churchill GA, Allison DB, Eisen EJ, and Pomp D. (2005) Bayesian model selection for genome-wide interacting QTL analysis. Genetics 170:1333-44.

Allan MF, Eisen EJ, and Pomp D. (2004) The M16 Mouse: An outbred animal model of polygenic obesity and obesity-induced diabetes (diabesity). Obes Res 12:1397-1407.

Pomp D, Allan MF, and Wesolowski S. (2004) Quantitative Genomics: Exploring the genetic architecture of complex and Pomp D. (2004) A large sample QTL study in mice. I: Growth. Mamm Genome 15:83-99.