Nature Genetics36, 1197 - 1202 (2004)
Published online: 17 October 2004; | doi:10.1038/ng1450
Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice
Binnaz Yalcin1, 3, Saffron A G Willis-Owen1, 3, Jan Fullerton1, Anjela Meesaq1, Robert M Deacon2, J Nicholas P Rawlins2, Richard R Copley1, Andrew P Morris1, Jonathan Flint1
& Richard Mott1
1
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford
OX3 7BN, UK.
2
Department of Experimental Psychology, University of Oxford, Oxford, UK.
Here we present a strategy to determine the genetic basis of variance in complex phenotypes that arise from natural, as opposed to induced, genetic variation in mice. We show that a commercially available strain of outbred mice, MF1, can be treated as an ultrafine mosaic of standard inbred strains and accordingly used to dissect a known quantitative trait locus influencing anxiety. We also show that this locus can be subdivided into three regions, one of which contains Rgs2, which encodes a regulator of G protein signaling. We then use quantitative complementation to show that Rgs2 is a quantitative trait gene. This combined genetic and functional approach should be applicable to the analysis of any quantitative trait.
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