The Cheverud Lab

We are interested in defining the genetic architecture of complex traits in order to gain a better understanding of trait variation in evolution, health, and disease. By genetic architecture we refer to the number of genes affecting trait variation, the relative size of gene effects, the role of dominance interactions between alleles, the epistatic interactions between genes, epigenetic and maternal effects, and the range of multiple trait pleiotropic effects. Our findings in this regard are that there are many genes, each of relatively small effect (< 10% of variance), with variable dominance, common small epistatic interactions, and modular pleiotropic effects responsible for complex trait variation. Maternal and epigenetic imprinting effects also occur during growth and persist at a significant level into adulthood.

 

Publications on the Topic

Wagner, G. P., J. P. Kenney-Hunt, M. Pavlicev, J. R. Peck, D. Waxman and J. M. Cheverud. 2008. Pleiotropic scaling of gene effects and the “Cost of Complexity”. Nature: 452: 470-473.

Funk, R. K., T. J. Maxwell, M. Izumi, D. Edwin, F. Kreisel, T. J. Ley, J. M. Cheverud and T. A. Graubert. 2008. Quantitative trait loci associated with susceptibility to therapy-related acute murine promyelocytic leukemia in hCG-PML/RARA transgenic mice. Blood (in press).

Kraja A. T., M. A. Province, P. Huang, J. P. Jarvis, T. Rice, J. M. Cheverud and D. C. Rao. 2008. Trends in Metabolic Syndrome and gene networks in human and rodent models. Endocrine, Metabolic & Immune Disorders - Drug Targets (in press).

Kenney-Hunt, J. P., B. Wang, E. A Norgard, G. Fawcett, D. Falk, L. S. Pletscher, J. P. Jarvis, C. Roseman, J. Wolf, J. M. Cheverud. 2008. Pleiotropic patterns of quantitative trait loci for seventy murine skeletal traits. Genetics 178: 2275-2288.

Norgard E. A., C. C. Roseman, G. L. Fawcett, M. Pavličev, C. D. Morgan, L. S. Pletscher, B. Wang, J. M. Cheverud. 2008. Identification of quantitative trait loci affecting murine long bone length in a two-generation intercross of LG/J and SM/J mice. Journal of Bone and Mineral Research 23: 887-895.

Pavlicev, M., J. P. Kenney-Hunt, E. A. Norgard, C. C. Roseman, J. B. Wolf, and J. M. Cheverud. 2008. Genetic variation in pleiotropy: Differential epistasis as a source of variation in the allometric relationship between long bone lengths and body weight. Evolution 62: 199-213.

Wagner, G. P., M. Pavlicev, and J. M. Cheverud. 2007. The road to modularity. Nature Reviews Genetics, 8: 921-931.

Scarelli, N., J. M. Cheverud, B. A. Schaal, and P. X. Kover. 2007. Antagonistic pleiotropic effects reduce the potential adaptive value of the FRIGIDA locus. Proceedings of the National Academy of Sciences, 104:16986-16991.

Hou W, J. S. F. Yap, S. Wu, T. Liu, J. M. Cheverud and R. Wu. 2007. Haplotyping a quantitative trait with a high-density map in experimental crosses. PLoS ONE 2:e732.

Kover, P. and J. M. Cheverud. 2007. The genetic basis of quantitative variation in susceptibility of Arabidopsis thaliana to Pseudomonas syringae (Pst DC3000): evidence for a new genetic factor of large effect. New Phytologist 174: 172-181.

Cheverud, J. M. 2007. The relationship between development and evolution through heritable variation. In: Tinkering: The microevolution of development, No. 284, Novartis Foundation (ed.), Wiley & Sons, Ltd., Chichester, UK, p. 55-70.

Cheverud, J. M. 2006. Genetic architecture of quantitative variation. In: Evolutionary Genetics: Concepts and Case Studies, C. W. Fox and J. B. Wolf (eds.), Oxford University Press, Oxford, pp. 288-309.

Kenney-Hunt, J. P., T. T. Vaughn, L. S. Pletscher, A. Peripato, E. Routman, K. Cothran, D. Durand, E. Norgard, C. Perel, and J. M. Cheverud. 2006. Quantitative trait loci for body size components in mice. Mammalian Genome 17: 526-537.

Long, F., Y. Q. Chen, J. M. Cheverud and R. Wong. 2006. Genetic mapping of allometric scaling laws. Genetical Research, Cambridge 87: 207-216.

Wolf, J.B., D. Pomp, E. J. Eisen, J. M. Cheverud and L. J. Leamy. 2006. The contribution of epistatic pleiotropy to the genetic architecture of covariation among organ weights and limb bone lengths in mice. Evolution & Development 8: 468-476.

de Brito, R. A., L. L. Pletscher, and J. M. Cheverud. 2005. The evolution of genetic architecture. I. Diversification of genetic backgrounds by genetic drift. Evolution 59(11): 2333-2342.

Wolf, J., L. J. Leamy, E. J. Routman and J. M. Cheverud 2005. Epistatic pleiotropy and the genetic architecture of covariation within early- and late-developing skull trait complexes in mice. Genetics 171(2): 683-694.

Kover P. X., J. B. Wolf, B. N. Kunkel and J. M. Cheverud 2005. The genetic architecture of Arabidopsis thaliana response to infection by Pseudomonas syringae. Heredity 94: 507-517.

Leamy, L. J., M. S. Workman, E. J. Routman and J. M. Cheverud 2005. An epistatic genetic basis for fluctuating asymmetry of tooth size and shape in mice. Heredity 94: 316-325.

Cheverud, J., T. H. Ehrich, T. T. Vaughn, S. F. Koreishi, R. B. Linsey, L. S. Pletscher 2004. Pleiotropic effects on mandibular morphology II. Differential epistasis and genetic variation in morphological integration. Journal of Experimental Zoology (Molecular and Developmental Evolution), 302B: 424-435.

Lewis, M., J. M. Cheverud, C. Pikaard 2004. Evidence for NORs as the units of regulation in nucleolar dominance in Arabidopsis thaliana inter-ecotype hybrids. Genetics 167: 931-939.

Klingenberg, C. P., L. J. Leamy and J. M. Cheverud 2004. Integration and modularity of quantitative trait locus effects on geometric shape in the mouse mandible. Genetics 166: 1909-1921 .

Peripato, A. C., R. A. de Brito, S. R. Matioli, L. S. Pletscher, T. T. Vaughn and J. M. Cheverud 2004. Epistasis among quantitative trait loci affecting litter size in mice. Journal of Evolutionary Biology 17:593-602.

Cheverud, J. M. 2004. Modular pleiotropic effects of quantitative trait loci on morphological traits. In: Modularity in Development and Evolution, G. Schlosser and G. Wagner, eds., University of Chicago Press, Chicago, pp. 132-153.

Flaherty, L. O. … J. Cheverud, …et al. 2003. The nature and identification of quantitative trait loci: a community’s view. Nature Reviews: Genetics 4: 911-916.

de Visser, J. A. G.M…. J. M. Cheverud…et al. 2003. Perspective: Evolution and detection of robustness. Evolution 57: 1959-1972.

Ehrich, T., T. T. Vaughn, S. F. Koreishi, R. B. Linsey, L. S. Pletscher, J. M. Cheverud 2003. Pleiotropic effects on mandibular morphology I. Developmental morphological integration and differential dominance. Journal of Experimental Zoology (Molecular and Developmental Evolution) 296B: 58-79.

Leamy, L. J., D. Pomp, E. J. Eisen and J. M. Cheverud 2002. Quantitative trait loci for organ weights and limb bone lengths in mice. Physiological Genomics 10: 21-29.

Workman, M. S., L. J. Leamy, E. J. Routman and J. M. Cheverud 2002. Analysis of QTL effects on the size and shape of mandibular molars in mice. Genetics 160:1573-1586.

Leamy, L., E. Routman and J. Cheverud 2002. An epistatic genetic basis for fluctuating asymmetry of mandible size in mice. Evolution 56: 642-653.

Cheverud, J. 2001. A simple correction for multiple comparisons in interval mapping genome scans. Heredity 87: 52-58.

Klingenberg, C. P., L. J. Leamy, E. J. Routman and J. M. Cheverud 2001. Genetic architecture of mandible shape in mice: Effects of quantitative trait loci analyzed by geometric morphometrics. Genetics 157: 785-802.

Cheverud, J. 2001. The genetic architecture of pleiotropic relations and differential epistasis. In: The Character Concept in Evolutionary Biology, G. Wagner, ed., Academic Press, New York, pp. 411-434.

Cheverud, J. 2000. Detecting epistasis among quantitative trait loci. In: Epistasis and the Evolutionary Process, Wolf, J., E. Brodie III and M. Wade, eds., Oxford University Press, New York, pp. 58-81.

Mezey, J., J. Cheverud and G. Wagner 2000. Is the genotype-phenotype map modular? A statistical approach using mouse QTL data. Genetics 156: 305-311.

Leamy, L. J., D. Pomp, E. J. Eisen and J. M. Cheverud 2000. Quantitative trait loci for directional but not fluctuating asymmetry of mandible characters in mice. Genetical Research, Camb., 76: 27-40.

Routman, E. and J. Cheverud 1998 Quantitative trait loci – A new approach to old evolutionary problems. In: Molecular Approaches to Ecology and Evolution, Vol. 2, B. Schierwater, B. Streit, G. Wagner, R. DeSalle (eds.), Birkhauser Verlag, Basel, Switzerland, pp. 211-220.

Routman, E. and J. Cheverud 1994 Individual genes underlying quantitative traits: Molecular and analytical methods. In: Molecular Approaches to Ecology and Evolution, B. Schierwater, B. Streit, G. Wagner, R. DeSalle (eds.), Birkhauser Verlag, Basel, Switzerland, pp. 593-606.