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 effects (< 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

Maxwell, T. J., C. M. Ballantyne, J. M. Cheverud, C. S. Guild, C. E. Ndumele and E. Boerwinkle. 2013. APOE modulates the correlation between triglycerides, cholesterol, and CHD through pleiotropy and gene-by-gene interactions. Genetics 195:1397-1405.

Pavlicev, M., G. P. Wagner, J. P. Noonan, B. Hallgrimsson, and J. M. Cheverud. 2013. Genomic correlates of relationship-QTL involved in fore- vs. hind limb divergence in mice. Genome Biology and Evolution, 5:1926-1936.

Lawson, H. A., J. E. Cady, C. Partridge, J.B. Wolf, C. F. Semenkovich, and J. M. Cheverud. 2011. Genetic effects at pleiotropic loci are context-dependent with consequences for the maintenance of genetic variation in populations. PLoS Genetics 7(9): e1002256.

Jarvis, J. P., S. N. Cropp, T. T. Vaughn, L. S. Pletscher, K. King-Ellison, E. Adams-Hunt, C. Erickson and J. M. Cheverud. 2011. The effect of a population bottleneck on the evolution of genetic variance/covariance structure. Journal of Evolutionary Biology, 24: 2139-2152. doi: 10.1111/j.1420-9101.2011.02347.x

Pavlicev, M., E. A. Norgard, G. L. Fawcett and J. M. Cheverud. 2011. Evolution of pleiotropy: Epistatic interaction pattern supports a mechanistic model underlying variation in genotype-phenotype map. Journal of Experimental Zoology (Molecular and Developmental Evolution), 316: 371-385.

Pavlicev, M., J. M. Cheverud, and G. P. Wagner. 2011. Evolution of adaptive phenotypic variation patterns by direct selection for evolvability. Proceedings of the Royal Society, B 278: 1903-1912, doi: 10.1098/rspb.2010.2113.

Jarvis, J. P. and J. M. Cheverud. 2011.  Mapping the epistatic network underlying murine reproductive fatpad variation, Genetics 187: 597-610.

Pavlicev, M., A. Le Rouzic, J. M. Cheverud, G. P. Wagner, T. F. Hansen. 2010. Directionality of epistasis in a murine intercross population. Genetics 185: 1489-1505.

Jarvis, J. P. and J. M. Cheverud. 2009. Epistasis and the evolutionary dynamics of measured genotypic values during simulated serial bottlenecks. Journal of Evolutionary Biology, 22: 1658-1668.

Kenney-Hunt, J. P. and J. M. Cheverud. 2009. Differential dominance of pleiotropic loci for mouse skeletal traits. Evolution 63: 1845-1851.

Wagner, G, Kenney-Hunt, J, Pavličev, M, Peck, J, Waxman, D & Cheverud, J. (2008) 'Pleiotropic scaling of gene effects and the 'cost of complexity'', Nature, vol. 452, no. 7186, pp. 470-472. doi:10.1038/nature06756 [pdf]

Funk, R, Maxwell, T, Izumi, M, Edwin, D, Kreisel, F, Ley, T, Cheverud, J & Graubert, T. (2008) 'Quantitative trait loci associated with susceptibility to therapy-related acute murine promyelocytic leukemia in hCG-PML/RARA transgenic mice', Blood, vol. 112, no. 4, pp. 1434-1442. doi:10.1182/blood-2008-01-132084 [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]

Kenney-Hunt, J, Wang, B, Norgard, E, Fawcett, G, Falk, D, Pletscher, L, Jarvis, J, Roseman, C, Wolf, J & Cheverud, J. (2008) 'Pleiotropic patterns of quantitative trait loci for 70 murine skeletal traits', Genetics, vol. 178, no. 4, pp. 2275-2288. doi:10.1534/genetics.107.084434 [pdf]

Norgard, E, Roseman, C, L Fawcett, G, Pavličev, M, D Morgan, C, Pletscher, L, Wang, B & Cheverud, J. (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, vol. 23, no. 6, pp. 887-895. doi:10.1359/jbmr.080210 [pdf] [Supplement]

Pavličev, M, Kenney-Hunt, J, Norgard, E, Roseman, C, Wolf, J & Cheverud, J. (2008) 'Genetic variation in pleiotropy: Differential epistasis as a source of variation in the allometric relationship between long bone lengths and body weight', Evolution, vol. 62, no. 2, pp. 199-213. doi:10.1111/j.1558-5646.2007.00255.x [pdf]

Wagner, G, Pavličev, M & Cheverud, J. (2007) 'The road to modularity', Nature Reviews Genetics, vol. 8, no. 12, pp. 921-931. doi:10.1038/nrg2267 [pdf]

Scarcelli, N, Cheverud, J, Schaal, B & Kover, P. (2007) 'Antagonistic pleiotropic effects reduce the potential adaptive value of the FRIGIDA locus', Proceedings of the National Academy of Sciences, vol. 104, no. 43, pp. 16986-16991. doi:10.1073/pnas.0708209104 [pdf]

Hou, W, Yap, J, Wu, S, Liu, T, Cheverud, J, Wu, R. (2007) 'Haplotyping a quantitative trait with a high-density map in experimental crosses', PLoS ONE, iss. 8. doi:10.1371/journal.pone.0000732 [pdf]

Kover, P & Cheverud, J. (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, vol. 174, no. 1, pp. 172-181. doi:10.1111/j.1469-8137.2007.01985.x [pdf]

Cheverud, J. (2007) 'The relationship between development and evolution through heritable variation', Tinkering: The Microevolution of Development: Novartis Foundation Symposium 285, vol. 285. pp. 55-70. doi:10.1002/9780470319390.ch4 [pdf]

Cheverud, J. (2006) 'Genetic architecture of quantitative variation', In: Evolutionary genetics: Concepts and case studies, Fox, C & Wolf, J (eds.), Oxford University Press, Oxford, pp. 288-309.

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]

Long, F, Chen, Y, Cheverud, J & Wong, R. (2006) 'Genetic mapping of allometric scaling laws', Genetical Research, Cambridge, vol 87, pp. 207-216. doi:10.1017/S0016672306008172 [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]

de Brito, R, Pletscher, L & Cheverud, J. (2005) 'The evolution of genetic architecture: I. Diversification of genetic backgrounds by genetic drift', Evolution, vol. 59, no. 11, pp. 2333-2342. doi:10.1111/j.0014-3820.2005.tb00943.x [pdf]

Wolf, J, Leamy, L, Routman, E & Cheverud, J. (2005) 'Epistatic pleiotropy and the genetic architecture of covariation within early- and late-developing skull trait complexes in mice', Genetics, vol. 171, no. 2, pp. 683-694. doi:10.1111/j.1525-142X.2006.00120.x [pdf]

Kover P, Wolf, J, Kunkel, B & Cheverud, J. (2005) 'The genetic architecture of Arabidopsis thaliana response to infection by Pseudomonas syringae', Heredity, vol. 94, pp. 507-517. doi:10.1038/sj.hdy.6800651 [pdf]

Leamy, L, Workman, M, Routman, E & Cheverud, J. (2005) 'An epistatic genetic basis for fluctuating asymmetry of tooth size and shape in mice', Heredity, vol. 94, pp. 316-325. doi:10.1038/sj.hdy.6800637 [pdf]

Cheverud, J, Ehrich, T, Vaughn, T, Koreishi, S, Linsey, R & Pletscher, L. (2004) 'Pleiotropic effects on mandibular morphology II. Differential epistasis and genetic variation in morphological integration', Journal of Experimental Zoology (Molecular and Developmental Evolution, vol. 302B, pp. 424-435. doi:10.1002/jez.b.21008 [pdf]

Lewis, M, Cheverud, J & Pikaard, C. (2004) 'Evidence for NORs as the units of regulation in nucleolar dominance in Arabidopsis thaliana inter-ecotype hybrids', Genetics, vol. 167, pp. 931-939. doi:10.1534/genetics.103.026203 [pdf]

Klingenberg, C, Leamy, L & Cheverud, J. (2004) 'Integration and modularity of quantitative trait locus effects on geometric shape in the mouse mandible', Genetics, vol. 166, pp. 1909-1921. doi:10.1534/genetics.166.4.1909 [pdf]

Peripato, A, de Brito, R, Matioli, S, Pletscher, L, Vaughn, T & Cheverud, J. (2004) 'Epistasis among quantitative trait loci affecting litter size in mice', Journal of Evolutionary Biology, vol. 17, pp. 593-602. doi:10.1111/j.1420-9101.2004.00702.x [pdf]

Cheverud, J. (2004) 'Modular pleiotropic effects of quantitative trait loci on morphological traits', In: Modularity in development and evolution, Schlosser, G & Wagner, G (eds.), University of Chicago Press, Chicago, pp. 132-153. [pdf]

Flaherty, L, Abiola, O, Angel, J, Avner, P, Bachmanov, A, Belknap, J, Bennett, B, Blankenhorn, E, Blizard, D, Bolivar, V, Brockmann, G, Buck, K, Bureau, J, Casley, W, Chesler, E, Cheverud, J, Churchill, G, Cook, M, Crabbe, J, Crusio, W, Darvasi, A, de Haan, G, Demant, P, Doerge, R, Elliott, R, Farber, C, Flint, J, Gershenfeld, H, Gibson, J, Gu, W, Himmelbauer, H, Hitzemann, R, Hsu, H, Hunter, K, Iraqi, F, Jansen, R, Johnson, T, Jones, B, Kempermann, G, Lammert, F, Lu, L, Manly, K, Matthews, D, Medrano, J, Mehrabian, M, Mittleman, G, Mock, B, Mogil, J, Montagutelli, X, Morahan, G, Mountz, J, Nagase, H, Nowakowski, R, O'Hara, B, Osadchuk, A, PAigen, B, Palmer, A, Peirce, J, Pomp, D, Rosemann, M, Rosen, G, Schalkwyk, L, Seltzer, Z, Settle, S, Shimomura, K, Shou, S, Sikela, J, Siracusa, L, Spearow, J, Teuscher, C, Threadgill, D, Toth, L, Toye, A, Vadasz, C, Van Zant, G, Wakeland, E, Williams, R, Zhang, H & Zou, F. (2003) 'The nature and identification of quantitatie trait loci: a community's view', Nature Reviews: Genetics, vol. 4, pp. 911-916. doi:10.1038/nrg1206 [pdf]

de Visser, J, Hermisson, J, Wagner, G, Ancel-Meyer, L, Bagheri-Chaichian, H, Blanchard, J, Chao, L, Cheverud, J, Elena, S, Fontana, W, Gibson, G, Hansen, T, Krakauer, D, Lewontin, R, Ofria, C, Rice, S, von Dassow, G, Wagner, A & Whitlock, M. (2003) 'Perspective: Evolution and detection of genetic robustness', Evolution, vol. 57, pp. 1959-1972. doi:10.1111/j.0014-3820.2003.tb00377.x [pdf]

Ehrich, T, Vaughn, T, Koreishi, S, Linsey, R, Pletscher, L & Cheverud, J. (2003) 'Pleiotropic effects on mandibular morphology I. Developmental morphological integration and differential dominance', Journal of Experimental Zoology (Molecular and Developmental Evolution), vol. 296B, pp. 58-79. doi:10.1002/jez.b.00009 [pdf]

Leamy, L, Routman, E & Cheverud, J. (2002) 'An epistatic genetic basis for fluctuating asymmetry of mandible size in mice', Evolution, vol. 56, pp. 642-653. doi:10.1111/j.0014-3820.2002.tb01373.x [pdf]

Cheverud, J. (2001) 'A simple correction for multiple comparisons in interval mapping genome scans', Heredity, vol. 87, pp. 52-58. doi:10.1111/j.1365-2540.2001.00901.pp.x [pdf]

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

Mezey, J, Cheverud, J & Wagner, G. (2000) 'Is the genotype-phenotype map modular? A statistical approach using mouse QTL data', Genetics, vol. 156, pp. 305-311. pmid:10978294 [pdf]

Leamy, L, Pomp, D, Eisen, E & Cheverud, J. (2000) 'Quantitative trait loci for directional but not fluctuating asymmetry of mandible characters in mice', Genetical Research, Cambridge, vol. 76, pp. 27-40. doi:10.1017/S0016672300004559 [pdf]

Routman, E & Cheverud, J. (1998) 'Quantitative trait loci - A new approach to old evolutionary problems', In: Molecular approaches to ecology and evolution, Vol. 2, Schierwater, B, Streit, B, Wagner, G, DaSalle, R (eds.), Birkhauser Verlag, Basel, Switzerland, pp. 211-220.

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