Poster 15
Presenter: Laura Sittig
Wednesday, 3:00 – 5:00pm
Laura J. Sittig, Choongwon Jeong, Emily Tixier, Abraham A. Palmer University of Chicago, Department of Human Genetics, Chicago IL
There are numerous well-documented phenotypic differences among closely related mouse substrains. Since there are relatively few genetic differences between these strains, identification of causal alleles is somewhat analogous to identification of de novo mutations in humans. NextGen sequencing technologies in conjunction with linkage mapping can in principal be used to rapidly identify the casual alleles. We sought to apply this approach to two substrains that have been extensively phenotyped over the years: BALB/cJ and BALB/cByJ. These strains were separated in 1935 when some BALB/cJ stock was moved to NIH and maintained independently, resulting in the BALB/cByJ substrain. Random mutation events are presumed to be the only source of genetic differences between these strains. We reviewed all previously reported genetic differences between these strains and attempted to replicate them in inbred BALB/cJ and BALB/cByJ mice. We also performed whole-genome re-sequencing on both strains. Surprisingly, for most of the traits examined we found either no difference between the strains or that the direction of the difference was opposite to what had been reported previously. Of particular interest, the robust difference in aggression was not confirmed. We performed genotyping for a known CNV to confirm that the strain identities were correct. Our results are similar to those of another group that has observed inconsistent differences in brain morphology between these two substrains. We conclude that the causal genetic differences may not have reached fixation or that there may be environmental or gene by environment interactions that negate the apparent simplicity of this model.