Review ARTICLE

Front. Genet., 13 June 2011 | http://dx.doi.org/10.3389/fgene.2011.00032

Dark matter: are mice the solution to missing heritability?

  • 1 Department of Human Genetics, The University of Chicago, Chicago, IL, USA
  • 2 Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago IL, USA

Genome-wide association studies (GWAS) in humans have identified hundreds of single nucleotide polymorphisms associated with complex traits, yet for most traits studied, the sum total of all these identified variants fail to explain a significant portion of the heritable variation. Reasons for this “missing heritability” are thought to include the existence of rare causative variants not captured by current genotyping arrays, structural variants that go undetected by existing technology, insufficient power to identify multi-gene interactions, small sample sizes, and the influence of environmental and epigenetic effects. As genotyping technologies have evolved it has become inexpensive and relatively straightforward to perform GWAS in mice. Mice offer a powerful tool for elucidating the genetic architecture of behavioral and physiological traits, and are complementary to human studies. Unlike F2 crosses of inbred strains, advanced intercross lines, heterogeneous stocks, outbred, and wild-caught mice have more rapid breakdown of linkage disequilibrium which allow for increasingly high resolution mapping. Because some of these populations are created using a small number of founder chromosomes they are not expected to harbor rare alleles. We discuss the differences between these mouse populations and examine their potential to overcome some of the pitfalls that have plagued human GWAS studies.

Keywords: GWAS, quantitative trait loci, complex traits, forward genetics, advanced intercross lines, heterogeneous stock, outbred mice, wild mice

Citation: Parker CC and Palmer AA (2011) Dark matter: are mice the solution to missing heritability?. Front. Gene. 2:32. doi: 10.3389/fgene.2011.00032

Received: 18 March 2011; Paper pending published: 19 April 2011;
Accepted: 01 June 2011; Published online: 13 June 2011.

Edited by:

Theodore Garland, University of California Riverside, USA

Reviewed by:

Bret Payseur, University of Wisconsin – Madison, USA
Scott A. Kelly, University of North Carolina Chapel Hill, USA

Copyright: © 2011 Parker and Palmer. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Abraham A. Palmer, Department of Human Genetics, University of Chicago, 920 E 58th Street, CLSC-507D, Chicago, IL 60637, USA. e-mail: apalmer@bsd.uchicago.edu