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. 2010 Dec 31:11:113.
doi: 10.1186/1471-2156-11-113.

Genomic mapping of social behavior traits in a F2 cross derived from mice selectively bred for high aggression

Derrick L Nehrenberg  1 , Shiliang Wang, Ryan J Buus, James Perkins, Fernando Pardo-Manuel de Villena, Daniel Pomp
Affiliations

Genomic mapping of social behavior traits in a F2 cross derived from mice selectively bred for high aggression

Derrick L Nehrenberg et al. BMC Genet. .

Abstract

Background: Rapid response to selection was previously observed in mice selected for high levels of inter-male aggression based on number of attacks displayed in a novel social interaction test after isolation housing. Attack levels in this high aggression line (NC900) increased significantly within just four generations of selective breeding, suggesting the presence of a locus with large effect. We conducted an experiment using a small (n ≈ 100) F2 cross between the ICR-derived, non-inbred NC900 strain and the low aggression inbred strain C57BL/6J, genotyped for 154 fully informative SNPs, to determine if a locus with large effect controls the high-aggression selection trait. A second goal was to use high density SNP genotyping (n = 549,000) in the parental strains to characterize residual patterns of heterozygosity within NC900, and evaluate regions that are identical by descent (IBD) between NC900 and C57BL/6J, to determine what impacts these may have on accuracy and resolution of quantitative trait locus (QTL) mapping in the F2 cross.

Results: No evidence for a locus with major effect on aggressive behavior in mice was identified. However, several QTL with genomewide significance were mapped for aggression on chromosomes 7 and 19 and other social behavior traits on chromosomes 4, 7, 14, and 19. High density genotyping revealed that 28% of the genome is still segregating among the six NC900 females used to originate the F2 cross, and that segregating regions are present on every chromosome but are of widely different sizes. Regions of IBD between NC900 and C57BL/6J are found on every chromosome but are most prominent on chromosomes 10, 16 and X. No significant differences were found for amounts of heterozygosity or prevalence of IBD in QTL regions relative to global analysis.

Conclusions: While no major gene was identified to explain the rapid selection response in the NC900 line, transgressive variation (i.e. where the allele from the C57BL/6J increased attack levels) and a significant role for dominant gene action were hallmarks of the genetic architecture for aggressive behavior uncovered in this study. The high levels of heterozygosity and the distribution of minor allele frequency observed in the NC900 population suggest that maintenance of heterozygosity may have been under selection in this line.

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Figures

Figure 1
Figure 1
Behavioral legends and distributions of traits measured in the NC900 × C57BL/6J F2 cross. A. Legend of social behavior traits coded as the percent duration of social test time. B. Individual time plots of social behavior percent durations ranked by decreasing percent affiliation levels and increasing percent aggression levels.
Figure 2
Figure 2
Histograms illustrating the social behavior trait distributions. A. Percent bidirectional duration, B. Percent unidirectional duration, C. Percent approach duration, D. Percent affiliative duration, E. Percent passive avoidance duration, F. Percent active avoidance duration, G. Percent freezing duration H. Percent aggression duration, I. Percent aversive duration, J. Attack count, K. Attack latency, L. Percent total social duration
Figure 3
Figure 3
Plots of social behavior QTL genetic effects where A represents the NC900 allele and B represents the C57BL/6J allele. A. Percent total social duration, B. Percent affiliative duration, C. Attack latency, D. Approach count, E. Percent approach duration, F. Affiliative count, G. Percent bidirectional duration, H. Bidirectional count, I. Attack, J. Aggression count, K. Percent aggression duration.
Figure 4
Figure 4
Segregating regions and identity by descent to C57BL/6J in the six NC900 females used for generation of the F2 males for aggression and social interaction testing. Segregating regions are shown as open boxes along the chromosome. Regions of IBD to C57BL/6J are denoted by black lines and regions with haplotypes other than C57BL/6J are shown in red. Regions heterozygous for NC900 are shown as open boxes with two red lines are either heterozygous in NC900 breeders or homozygous with two haplotypes that differ from C57BL/6J. Open boxes with a black and red line are either regions heterozygous in NC900 breeders or homozygous with two haplotypes, one different and the other identical to C57BL/6J
Figure 5
Figure 5
Frequency and distribution of MAF in segregating regions. Black bars represent genome-wide analysis and open bars represent the QTL confidence intervals.
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