High-precision genetic mapping of behavioral traits in the diversity outbred mouse population.

Authors

R W Logan
Ray F. Robledo, The Jackson LaboratoryFollow
Jill M. Recla, The Jackson LaboratoryFollow
Vivek M. Philip, The Jackson LaboratoryFollow
Jason A. Bubier, The Jackson LaboratoryFollow
Jeremy Jay, The Jackson LaboratoryFollow
C Harwood
Troy Wilcox, The Jackson LaboratoryFollow
Dan M. Gatti, The Jackson LaboratoryFollow
Carol J. Bult, The Jackson LaboratoryFollow
Gary A. Churchill, The Jackson LaboratoryFollow
Elissa J. Chesler, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

6-2013

JAX Source

Genes Brain Behav 2013 Jun; 12(4):424-47.

Volume

12

Issue

4

First Page

424

Last Page

437

ISSN

1601-183X

PMID

23433259

Abstract

Historically our ability to identify genetic variants underlying complex behavioral traits in mice has been limited by low mapping resolution of conventional mouse crosses. The newly developed Diversity Outbred (DO) population promises to deliver improved resolution that will circumvent costly fine-mapping studies. The DO is derived from the same founder strains as the Collaborative Cross (CC), including three wild-derived strains. Thus the DO provides more allelic diversity and greater potential for discovery compared to crosses involving standard mouse strains. We have characterized 283 male and female DO mice using open-field, light-dark box, tail-suspension and visual-cliff avoidance tests to generate 38 behavioral measures. We identified several quantitative trait loci (QTL) for these traits with support intervals ranging from 1 to 3 Mb in size. These intervals contain relatively few genes (ranging from 5 to 96). For a majority of QTL, using the founder allelic effects together with whole genome sequence data, we could further narrow the positional candidates. Several QTL replicate previously published loci. Novel loci were also identified for anxiety- and activity-related traits. Half of the QTLs are associated with wild-derived alleles, confirming the value to behavioral genetics of added genetic diversity in the DO. In the presence of wild-alleles we sometimes observe behaviors that are qualitatively different from the expected response. Our results demonstrate that high-precision mapping of behavioral traits can be achieved with moderate numbers of DO animals, representing a significant advance in our ability to leverage the mouse as a tool for behavioral genetics. Genes Brain Behav 2013 Jun; 12(4):424-47.

Recommended Citation

Logan R, Robledo RF, Recla JM, Philip VM, Bubier JA, Jay J, Harwood C, Wilcox T, Gatti DM, Bult CJ, Churchill GA, Chesler EJ. High-precision genetic mapping of behavioral traits in the diversity outbred mouse population. Genes Brain Behav 2013 Jun; 12(4):424-47.