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Quantitative trait locus and haplotype mapping in closely related inbred strains identifies a locus for open field behavior

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Abstract

Quantitative trait locus (QTL) mapping in the mouse typically utilizes inbred strains that exhibit significant genetic and phenotypic diversity. The development of dense SNP panels in a large number of inbred strains has eliminated the need to maximize genetic diversity in QTL studies as plenty of SNP markers are now available for almost any combination of strains. We conducted a QTL mapping experiment using both a backcross (N2) and an intercross (F2) between two genetically similar inbred mouse strains: C57BL/6J (B6) and C57L/J (C57). A set of additive QTLs for activity behaviors was identified on Chrs 1, 9, 13, and 15. We also identified additive QTLs for anxiety-related behaviors on Chrs 7, 9, and 16. A QTL on Chr 11 is sex-specific, and we revealed pairwise interactions between QTLs on Chrs 1 and 13 and Chrs 10 and 18. The Chr 9 activity QTL accounts for the largest amount of phenotypic variance and was not present in our recent analysis of a B6 × C58/J (C58) intercross (Bailey et al. in Genes Brain Behav 7:761–769, 2008). To narrow this QTL interval, we used a dense SNP haplotype map with over 7 million real and imputed SNP markers across 74 inbred mouse strains (Szatkiewicz et al. in Mamm Genome 19(3):199–208, 2008). Evaluation of shared and divergent haplotype blocks among B6, C57, and C58 strains narrowed the Chr 9 QTL interval considerably and highlights the utility of QTL mapping in closely related inbred strains.

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Acknowledgments

The authors thank Gary Churchill and Fernando Pardo Manuel de Villena for helpful discussions about the data and for sharing SNP genotype data for IBD mapping in the QTL region. The research described herein was supported by funding from NIH NIDA Grant DA 022392 to LMT and a Novartis Grant SFP-1406 from the Genomics Institute of the Novartis Research Foundation. Genotypes for IBD mapping were generated with support from the National Institute of General Medical Sciences National Centers of Systems Biology program grant GM-076468.

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Authors and Affiliations

  1. Department of Psychiatry, University of North Carolina, Room 1012 Genetic Medicine Bldg, 120 Mason Farm Road, Campus Box 7361, Chapel Hill, NC, 27599, USA

    Amy F. Eisener-Dorman & Lisa M. Tarantino

  2. Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA, 92121, USA

    Laura Grabowski-Boase

  3. Institute of Pharmacogenomics and Individualized Therapy, Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, NC, 27599, USA

    Brian M. Steffy & Tim Wiltshire

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  1. Amy F. Eisener-Dorman
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  2. Laura Grabowski-Boase
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  3. Brian M. Steffy
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  4. Tim Wiltshire
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  5. Lisa M. Tarantino
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Correspondence to Lisa M. Tarantino.

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Eisener-Dorman, A.F., Grabowski-Boase, L., Steffy, B.M. et al. Quantitative trait locus and haplotype mapping in closely related inbred strains identifies a locus for open field behavior. Mamm Genome 21, 231–246 (2010). https://doi.org/10.1007/s00335-010-9260-z

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