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About the P.I.

Dr. James M. Cheverud

My major teaching effort is in Human Gross Anatomy at the Washington University School of Medicine. I also periodically teach a course in quantitative genetics and evolution.

My research centers on evolutionary quantitative genetics and morphology. The research in quantitative genetics concerns the development and genetic constraints imposed on the rate and direction of evolution by heritable variation patterns and the evolution of genetic variation patterns themselves. Current and planned future projects in this area involve both empirical and theoretical studies of the evolution of genetic correlations, maternal effects and kin selection, the genetics of somatic growth, the inheritance of brain surface morphology, and the heritability, genetic correlation and evolution of primate craniofacial morphology. We are currently studying the morphological genetics and systematics of New World Monkey species, specifically tamarins and marmosets. This study involves the reconstruction of selection acting on craniofacial morphology. The tamarins and marmosets include several endangered species and we are developing a quantitative genetic approach to captive population genetic surveys and management.

Projects

• Genetic Architecture and Evolution
• Primate Systematics and Morphological Integration
• Mouse Gene Mapping: Bone, Obesity, and Leptin
• Developmental Genetics of Long Bone Growth
• Dietary Obesity and Diabetes
• Genetic Correlates of Schizophrenia in the Mouse
• Genetics of Growth
• Genetics of t-AML Cancer in the Mouse
• Craniofacial Genes and Human Evolution
• LG/J by SM/J Mouse Intercross Populations
• Parent of Origin Effects: Maternal Effects and Genomic Imprinting
• Genetics of Wound Healing

Dietary Obesity and Diabetes

This project is designed to identify the genetic basis for variation in obesity and diabetes-associated traits and the development of obesity and diabetes in response to a high fat diet. Obesity has reached very high levels in the US and other developed countries and is beginning to increase in frequency even in countries with less developed economies. There are a variety of causes of obesity, including genes, environments, and their interactions but the dramatic secular trend towards obesity is most likely due to dietary and life-style changes associated with a developed economy, not to genetic changes in the population at large. The ‘obesity epidemic’ is of environmental origin. Even so, some individuals respond to the high fat “Western” diet by becoming obese while others exposed to the same diet do not. This individual variation in response to dietary fat is, in part, due to genetic differences. We are examining the genetic basis for variation in response to a high fat diet in mice by following up on our discovery of several dietary-obesity quantitative trait loci (QTLs) in the LGXSM Recombinant Inbred (RI) mice. We are fine-mapping these QTLs down to a sub-cM interval in an Advanced Intercross (AI) Line to identify a set of 5-20 positional candidate loci for each QTL and evaluating the positional candidate genes for sequence and expression polymorphism between the LG/J and SM/J mouse strains. These studies will enhance our understanding of the physiological bases of dietary obesity and diabetes and identify genes affecting response to a high fat diet.

Collaborators

Dr. Clay Semenkovich, Washington University

Grant Funding

Supported by a grant from NIDDK DK055736

Publications on the Topic

Fawcett, G, Roseman, C, Jarvis, J, Wang, B, Wolf, J & Cheverud, J. (2008) 'Genetic architecture of adiposity and organ weight using combined generation QTL analysis', Obesity, vol. 16, no. 8, pp. 1861-1868. doi:10.1038/oby.2008.300 [pdf]

Kraja, A, Province, M, Huang, P, Jarvis, J, Rice, T, Cheverud, J & Rao, D. (2008) 'Trends in Metabolic Syndrome and gene networks in human and rodent models', Endocrine, Metabolic & Immune Disorders - Drug Targets 8:198-207. doi:10.2174/187153008785700145 [pdf]

Schmitt, A, Al-Hasani, H, Cheverud, J, Pomp, D, Bünger, L & Brockmann, G. (2007) 'Fine mapping of mouse QTLs for fatness using SNP data', OMICS: A Journal of Integrative Biology, vol. 11, no. 4, pp. 341-350. doi:10.1089/omi.2007.0015 [pdf]

Kenney-Hunt, J, Vaughn, T, Pletscher, L, Peripato, A, Routman, E, Cothran, K, Durand, D, Norgard, E, Perel, C, & Cheverud, J. (2006) 'Quantitative trait loci for body size components in mice', Mammalian Genome, vol. 17, pp. 526-537. doi:10.1007/s00335-005-0160-6 [pdf]

Wolf, J, Pomp, D, Eisen, E, Cheverud, J & Leamy, L. (2006) 'The contribution of epistatic pleiotropy to the genetic architecture of covariation among organ weights and limb bone lengths in mice', Evolution & Development, vol. 8, pp. 468-476. doi:10.1017/S0016672306008172 [pdf]

Kardia, S, Bielak, L, Langer, L, Cheverud, J, Boerwinkle, E, Turner, S, Sheedy II, P & Peyser, P. (2006) 'Epistatic effects between two genes in the renin-angiotensis system and systolic blood pressure and coronary artery calcification', Medical Science Monitor, vol. 12, pp. CR150-158. pmid:16572049 [pdf]

Jarvis, J, Kenney-Hunt, J, Ehrich, T, Pletscher, L, Semenkovich, C & Cheverud, J. (2005) 'Maternal genotype affects adult offspring lipid, obesity, and diabetes phenotypes in LGXSM recombinant inbred strains', Journal of Lipid Research, vol. 46, pp. 1692-1702. doi:10.1194/jlr.M500073-JLR200 [pdf]

Ehrich, T, Kenney-Hunt, J, Pletscher, L & Cheverud, J. (2005) 'Genetic variation and correlation of dietary response in an advanced intercross mouse line produced from two divergent growth lines', Genetical Research, vol. 85, pp. 211-222. doi:10.1017/S0016672305007603 [pdf]

Ehrich, T, Hrbek, T, Kenney-Hunt, J, Pletscher, L Wang, B, Semenkovich, C & Cheverud, J. (2005) 'Fine-mapping gene by diet interactions on chromosome 13 in a LG/J´SM/J murine model of obesity', Diabetes, vol. 54, pp. 1863-1872. doi:10.2337/diabetes.54.6.1863 [pdf]

Cheverud, J, Ehrich, T, Kenney, J, Pletscher, L & Semenkovich, C. (2004) 'Quantitative trait loci for obesity and diabetes-related traits and their dietary responses to high fat feeding in the LGXSM recombinant inbred mouse strains', Diabetes, vol. 53, pp. 3328-3336. doi:10.2337/diabetes.53.12.3328 [pdf] [Appendix A] [Appendix B]

Ehrich, T, Kenney, J, Vaughn, T, Pletscher, L & Cheverud, J. (2003) 'Diet, obesity, and hyperglycemia in LG/J and SM/J Mice', Obesity Research, vol. 11, pp. 1400-1410. doi:10.1038/oby.2003.189 [pdf]

Leamy, L, Pomp, D, Eisen, E & Cheverud, J. (2002) 'Pleiotropy of uantitative trait loci for organ weights and limb bone lengths in mice', Physiological Genomics, vol. 10, pp. 21-29. doi:10.1152/physiolgenomics.00018.2002 [pdf]

Cheverud, J, Vaughn, T, Pletscher, L, Peripato, A, Adams, E, Erickson, C & King-Ellison, K. (2001) 'Genetic architecture of adiposity in the cross of Large (LG/J) and Small (SM/J) inbred mice', Mammalian Genome, vol. 12, pp. 3-12. doi:10.1007/s003350010218 [pdf]

Cheverud, J, Pletscher, L, Vaughn, T & Marshall, B. (1999) 'Differential response to dietary fat in Large (LG/J) and Small (SM/J) inbred mouse strains', Physiological Genomics, vol. 1, pp. 33-39. pmid:11015559 [pdf]

Vaughn, T, Pletscher, L, Peripato, A, King-Ellison, K, Adams, E, Erikson, C & Cheverud, J. (1999) 'Mapping quantitative trait loci for murine growth - A closer look at genetic architecture', Genetical Research, Cambridge, vol. 74, pp. 313-322. doi:10.1017/S0016672399004103 [pdf]

Kramer, M, Vaughn, T, Pletscher, L, King-Ellison, K, Adams, E, Erickson, C & Cheverud, J. (1998) 'Genetic variation in body weight growth and composition in the intercross of Large (LG/J) and Small (SM/J) inbred strains of mice', Genetics and Molecular Biology, vol. 21, pp. 211-218.

Cheverud, J, Routman, E, Duarte, F, van Swinderen, B, Cothran, K & Perel, C. (1996) 'Quantitative trait loci for murine growth', Genetics, vol. 142, pp. 1305-1319. pmid:8846907 [pdf]