A Wild-Derived Antimutator Drives Germline Mutation Spectrum Differences Among Laboratory Mouse Strains

Kelley Harris, Ph.D.

Assistant Professor of Genome Sciences

University of Washington

Seminar Information

Seminar Date
April 16, 2021 - 2:00 PM


Kelley Harris, Ph.D.


Little is known about the impact of genetic variation on mutation rates within species. We conducted a search for alleles that modulate the germline mutation rate using a panel of recombinant inbred mouse lines descended from the laboratory strains C57BL/6J (B6) and DBA/2J (D2). Mice inheriting D haplotypes at a quantitative trait locus (QTL) on chromosome 4 accumulated C>A germline mutations at a 50% higher rate than strains with B haplotypes. The QTL contains coding variation in Mutyh, a DNA repair gene that underlies C>A-dominated mutational signatures with similar sequence context biases in human cancers. Both Mutyh alleles are present in wild populations of Mus musculus domesticus, and likely represent the first example of segregating variation that affects the germline mutation rate in a mammal.

Speaker Bio

Kelley Harris is an assistant professor of Genome Sciences at the University of Washington. She is a population geneticist who uses patterns of genetic variation to study evolutionary history, particularly the evolution and genetic architecture of DNA replication fidelity.