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A genome-wide panel of congenic mice reveals widespread epistasis of behavior quantitative trait loci

Molecular Psychiatry volume 14, pages 631–645 (2009)Cite this article

Abstract

Understanding the genetics of behavioral variation remains a fascinating but difficult problem with considerable theoretical and practical implications. We used the genome-tagged mice (GTM) and an extensive test battery of well-validated behavioral assays to scan the genome for behavioral quantitative trait loci (QTLs). The GTM are a panel of ‘speed congenic’ mice consisting of over 60 strains spanning the entire autosomal genome. Each strain harbors a small (∼23 cM) DBA/2J donor segment on a uniform C57BL/6J background. The panel allows for mapping to regions as small as 5 cM and provides a powerful new tool for increasing mapping power and replicability in the analysis of QTLs. A total of 97 loci were mapped for a variety of complex behavioral traits including hyperactivity, anxiety, prepulse inhibition, avoidance and conditional fear. A larger number of loci were recovered than generally attained from standard mapping crosses. In addition, a surprisingly high proportion of loci, 63%, showed phenotypes unlike either of the parental strains. These data suggest that epistasis decreases sensitivity of locus detection in traditional crosses and demonstrate the utility of the GTM for mapping complex behavioral traits with high sensitivity and precision.

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Acknowledgements

We acknowledge funding from the National Institutes of Health RO1 MH071779.

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Authors and Affiliations

  1. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    G D Gale, R D Yazdi, A H Khan & D J Smith

  2. Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    A J Lusis & R C Davis

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  1. G D Gale
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Correspondence to G D Gale.

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Gale, G., Yazdi, R., Khan, A. et al. A genome-wide panel of congenic mice reveals widespread epistasis of behavior quantitative trait loci. Mol Psychiatry 14, 631–645 (2009). https://doi.org/10.1038/mp.2008.4

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