We recently published two reviews on mouse genetics which are a great place to start for anyone interesting in learning about the interesting recent developments in the area. While the genetic cross has been the main mouse genetic study design for decades, over the past several years, several novel mouse study designs have been demonstrated to have advantages over the cross.
The first review was written by Jonathan Flint and Eleazar Eskin covers all the major novel strategies (10.1038/nrg3335). The image which is the Nature Reviews Genetics journal cover, ‘Chromatic’ by Patrick Morgan, was inspired by the Review.
The second review covers the Hybrid Mouse Diversity Panel (HMDP) which is a study design developed at UCLA jointly between the Lusis and Eskin groups (10.1007/s00335-012-9411-5).
Flint, J. & Eskin, E., 2012, Genome-wide association studies in mice, Nature reviews. Genetics.
Genome-wide association studies (GWASs) have transformed the field of human genetics and have led to the discovery of hundreds of genes that are implicated in human disease. The technological advances that drove this revolution are now poised to transform genetic studies in model organisms, including mice. However, the design of GWASs in mouse strains is fundamentally different from the design of human GWASs, creating new challenges and opportunities. This Review gives an overview of the novel study designs for mouse GWASs, which dramatically improve both the statistical power and resolution compared to classical gene-mapping approaches.
Ghazalpour, A., Rau, C.D., Farber, C.R., Bennett, B.J., Orozco, L.D., van Nas, A., Pan, C., Allayee, H., Beaven, S.W., Civelek, M., Davis, R.C., Drake, T.A., Friedman, R.A., Furlotte, N., Hui, S.T., Jentsch, J.D., Kostem, E., Kang, H.M., Kang, E.Y., Joo, J.W., Korshunov, V.A., Laughlin, R.E., Martin, L.J., Ohmen, J.D., Parks, B.W., Pellegrini, M., Reue, K., Smith, D.J., Tetradis, S., Wang, J., Wang, Y., Weiss, J.N., Kirchgessner, T., Gargalovic, P.S., Eskin, E., Lusis, A.J. & Leboeuf, R.C., 2012, Hybrid mouse diversity panel: a panel of inbred mouse strains suitable for analysis of complex genetic traits, Mammalian genome : official journal of the International Mammalian Genome Society.
We have developed an association-based approach using classical inbred strains of mice in which we correct for population structure, which is very extensive in mice, using an efficient mixed-model algorithm. Our approach includes inbred parental strains as well as recombinant inbred strains in order to capture loci with effect sizes typical of complex traits in mice (in the range of 5 % of total trait variance). Over the last few years, we have typed the hybrid mouse diversity panel (HMDP) strains for a variety of clinical traits as well as intermediate phenotypes and have shown that the HMDP has sufficient power to map genes for highly complex traits with resolution that is in most cases less than a megabase. In this essay, we review our experience with the HMDP, describe various ongoing projects, and discuss how the HMDP may fit into the larger picture of common diseases and different approaches.