Parent of Origin Effects: Maternal Effects and Genomic Imprinting
We have maintained a long-standing interest in the role that the maternal environment plays in the development of offspring characteristics. An especially interesting aspect of this maternal environment is that while it may be environmental in relation to the developing offspring, genetic variations may occur between mothers that affect the environment they provide for their offspring. These genetic maternal effects can have long-standing effects on progeny phenotype, long after the physical association between mother and offspring is broken. The evolutionary consequences of maternal effects can be severe, leading to such unusual expectations as negative response to positive selection. These maternal effects models can also serve as models for more general kin effects, where a wide variety of relatives may provide genetically-variable environments that impact individual development. This leads to a common model for evolution due to kin and group selection.
We are investigating the genetic basis of both prenatal and postnatal maternal effects, including their direct and epistatic effects and the effects of maternal-offspring genetic interaction on offspring traits.
Also, we are examining the effects of genomic imprinting on growth and obesity. In genomic imprinting, the phenotypic differences between reciprocal heterozygotes (Aa and aA where the first allele is inherited from the father and second from the mother) are significant because the expression of these genes utilizes different combinations of the alleles inherited from the father and mother. Genomic imprinting has been thought to be special and rare. However, we have mapped a number of genomic imprinting effects for growth, obesity, and body composition. We have also developed an approach that can identify the source of parent-of-origin effects as due to maternal effects versus genomic imprinting. We will be following up these mapped effects in later generations of the LG/J by SM/J intercross and hoping to identify the imprinted genes responsible for these effects.
Dr. Jason Wolf, University of Manchester
Dr. Andrea Peripato, Federal University of Sao Carlos
Publications on the Topic
Lawson, H. A., J. M. Cheverud, and J. B. Wolf. 2013. Genomic imprinting and parent-of-origin effects on complex traits. Nature Reviews Genetics, 14: 609-617.
Wolf, J. B. and J. M. Cheverud. 2012. Detecting maternal effect loci by statistical cross fostering. Genetics 191: 261-277.
Chiavegatto, S., Sauce, B., Ambar, G., Cheverud, JM, Peripato, A. 2012. Hypothalamic expression of Peg3 gene is associated with maternal care differences between SM/J and LG/J mouse strains. Brain and Behavior, 2: 365-376.
Hager, R., J. M. Cheverud, and J. B. Wolf. 2012. Genotype-dependent responses to levels of sibling competition over maternal resources in mice. Heredity 108: 515-520.
Wolf, J. B., L. J. Leamy, C. C. Roseman, and J. M. Cheverud. 2011. Genome-wide analysis of prenatal and postnatal maternal genetic effects in mice reveals persistent prenatal effects on offspring growth. Genetics 198: 1069-1082. DOI: 10.1534/genetics.111.130591
Wolf, J. B. and J. M. Cheverud. 2009. A framework for detecting and characterizing genetic background dependent imprinting effects. Mammalian Genome 20: 681-698.
Hager R., J. M. Cheverud and J. B. Wolf. 2009. Change in maternal environment induced by cross-fostering alters genetic and epigenetic effects on complex traits in mice. Proc. Royal Soc., London B. 276:2949-2954.
Cheverud, J. M. and J. B. Wolf. 2009. Genetics and evolutionary consequences of maternal effects. In: Maternal Effects in Mammals, D. Maestripieri and J. M. Mateo (eds.), University of Chicago Press, Chicago, p. 11-37.
Cheverud, J, Hager, R, Roseman, C, Fawcett, G, Wang, B & Wolf, J. (2008) 'Genomic imprinting effects on adult body composition in mice', Proceedings of the National Academy of Sciences, vol. 105, no. 11, pp. 4253-4258. doi:10.1073/pnas.0706562105 [pdf]
Wolf, J, Cheverud, J, Roseman, C & Hager, R. (2008) 'Genome-wide analysis reveals a complex pattern of genomic imprinting in mice', PLoS Genetics, vol. 4, no. 6. doi:10.1371/journal.pgen.1000091 [pdf]
Hager, R, Cheverud, J & Wolf, J. (2008) 'Maternal effects as the cause of parent-of-origin effects that mimic genomic imprinting', Genetics, vol. 178, no. 3, pp. 1755-1762. doi:10.1534/genetics.107.080697 [pdf]
Cui, Y, Cheverud, J & Wu, R. (2007) 'A statistical model for dissecting genomic imprinting through genetic mapping', Genetica, vol. 130, no. 3, pp. 227-239. doi:10.1007/s10709-006-9101-x [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]
Cheverud, J. (2003) 'Evolution in a genetically heritable social environment', Proceedings of the National Academy of Sciences, vol. 100, pp. 4357-4359. doi:10.1073/pnas.0931311100 [pdf]
Peripato, A, de Brito, R, Vaughn, T, Pletscher, L, Matioli, S & Cheverud, J. (2002) 'Quantitative trait loci for maternal performance for offspring survival in mice', Genetics, vol. 162, pp. 1341-1353. pmid:12454078 [pdf]
Wolf, J, Vaughn, T, Pletscher, L & Cheverud, J. (2002) 'Contribution of maternal effect QTL to the genetic architecture of early growth in mice', Heredity, vol. 89, pp. 300-310. doi:10.1038/sj.hdy.6800140 [pdf]
Peripato, A & Cheverud, J. (2002) 'Genetic influences on maternal care', American Naturalist, vol. 160, pp. S173-S185. doi:10.1086/342900 [pdf]
Wolf, J, Brodie III, E, Cheverud, J, Moore, A & Wade, M. (1998) 'Evolutionary consequences of indirect maternal effects', Trends in Ecology and Evolution, vol. 13, pp. 64-70. doi:10.1016/S0169-5347(97)01233-0 [pdf]
Cheverud, J & Moore, A. (1994) 'Quantitative genetics and the role of the environment provided by relatives in behavioral evolution', In: Quantitative genetic studies of behavioral evolution, Boake, C (ed.), University of Chicago Press, Chicago, IL, pp. 67-100.
Cheverud, J. (1984) 'Evolution by kin selection: A quantitative genetic model illustrated by maternal performance in mice', Evolution, vol. 38. pp. 766-777. doi:10.2307/2408388 [pdf]
Bennett, K, Cheverud, J & Booth, S. (1981) 'Deciduous tooth dimensions in fetal rhesus monkeys from mothers with induced diabetes', American Journal of Physical Anthropology, vol. 55, pp. 411-418. doi:10.1002/ajpa.1330550315 [pdf]