Parallel Selection Mapping

Gene mapping for complex or quantitative traits remains a challenging task. This is primarily because complex trait variation is caused by numerous quantitative trait loci (QTL), each of relatively small effect size that traditional genetic approaches struggle to isolate. Complex traits are particularly relevant for evolutionary adaptations, since most of them are based on quantitative characters that are likely to involve many genes. Hence, understanding the genetics of complex traits is also a prerogative for understanding the genetics of evolutionary processes.
Bodyweight is an archetypal complex trait in mice. A plethora of resources including mapping crosses, recombinant inbred lines, and long-term selection lines have helped identify many bodyweight QTLs. But despite decades of intensive study, a fine-grained understanding of the genes underlying growth and/or bodyweight remains elusive. Increased bodyweight in house mice has been observed repeatedly and independently, both under long-term artificial selection in the laboratory, and in natural populations in the wild. Since most of these mice are primarily derived from the Western house mouse M. m. domesticus and share recent genetic ancestry, some part of the response to selection is likely to have a shared allelic basis. We applied “parallel selection mapping” to identify this component of shared loci underlying parallel increase in bodyweight across multiple long-term artificial selection experiments in mice.

Status of the project

We have so far published one paper that showed that parallel selection mapping is indeed a viable idea to identify loci of interest at a resolution much better than in QTL experiments (Chan et al. 2012). We have also obtained the genome sequences of the selection lines and are currently analysing them for possible causal variants. In addition, a large QTL panel was produced involving a natural mouse population from an island to assess the overlap between loci detected by artificial selection and natural selection for size.
We are now planning to set up new parallel selection lines for one or two other complex phenotypes. For these we will follow the selection response at a genome-wide scale within the initial generations to detect the dynamics of the response. This will serve as a proof of principle project to show the power of parallel selection for mapping genes involved in generating complex phenotypes.
The parallel selection project was initiated by Frank Chan, who has now moved to a group leader position at the Friedrich-Miescher Laboratory in Tübingen.
Postdoc applications for becoming involved in the new selection line work are welcome.

Publication in the context of this project

  • Chan YF, Jones FC, McConnell E, Bryk J, Bünger L, Tautz, D. (2012). Parallel selection mapping using artificially selected mice reveals bodyweight control loci. Current Biology 22, 794-800.
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