Genomic imprinting effects on adult body composition in mice

doi:10.1073/pnas.0706562105

Genomic imprinting effects on adult body composition in mice

*Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110;
^†Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom; and
^‡Department of Anthropology, University of Illinois at Urbana–Champaign, Urbana, IL 61801

Edited by James E. Womack, Texas A&M University, College Station, TX, and approved January 17, 2008 (received for review July 12, 2007)

Abstract

Genomic imprinting results in the differential expression of genes, depending on which allele is inherited from the mother and which from the father. The effects of such differential gene expression are reflected in phenotypic differences between the reciprocal heterozygotes (Aa vs. aA). Although many imprinted genes have been identified and play a key role in development, little is known about the contribution of imprinting to quantitative variation in trait expression. Here, we examine this problem by mapping imprinting effects on adult body composition traits in the F₃ generation of an intercross between the Large (LG/J) and Small (SM/J) inbred mouse strains. We identified eight pleiotropic imprinted quantitative trait loci (iQTL) located throughout the genome. Most iQTL are in novel locations that have not previously been associated with imprinting effects, but those on chromosomes 7, 12, and centromeric 18 lie in regions previously identified as containing imprinted genes. Our results show that the effects of genomic imprinting are relatively small, with reciprocal heterozygotes differing by ≈0.25 standard deviation units and the effects at each locus accounting for 1% to 4% of the phenotypic variance. We detected a variety of imprinting patterns, with paternal expression being the most common. These results indicate that genomic imprinting has small, but detectable, effects on the normal variation of complex traits in adults and is likely to be more common than usually thought.

Footnotes

^§To whom correspondence should be addressed at:
Faculty of Life Sciences, University of Manchester, Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom.
E-mail: wolf{at}manchester.ac.uk
Author contributions: J.M.C. and J.B.W. designed research; J.M.C., R.H., G.F., B.W., and J.B.W. performed research; J.M.C., C.R., and J.B.W. contributed new reagents/analytic tools; J.M.C., R.H., and J.B.W. analyzed data; and J.M.C., R.H., and J.B.W. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0706562105/DC1.
↵ ¶ Li J, Jiang T, Proceedings of the Seventh Annual International Conference on Research in Computational Molecular Biology, April 18–21, 2002, Washington, DC.