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{
  "pmid": "35545679",
  "doi": "10.1038/s41586-022-04701-5",
  "abstract": "Although germline mutation rates and spectra can vary within and between species, common&#xa0;genetic modifiers of the&#xa0;mutation rate have not been identified&#xa0;in nature<sup>1</sup>. Here we searched for loci that influence germline mutagenesis using a uniquely powerful resource: a panel of recombinant inbred mouse lines known as the&#xa0;BXD, descended from the laboratory strains C57BL/6J (B haplotype) and DBA/2J (D haplotype). Each BXD lineage has been maintained by brother-sister mating in the near absence of natural selection, accumulating de novo mutations for up to 50 years on a known genetic background that is a unique linear mosaic of B and D haplotypes<sup>2</sup>. We show that mice inheriting D haplotypes at a quantitative trait locus on chromosome 4 accumulate C&gt;A germline mutations at a 50% higher rate than those inheriting B haplotypes, primarily owing to the activity of a C&gt;A-dominated mutational signature known as SBS18. The B and D quantitative trait locus haplotypes encode different alleles of Mutyh, a DNA repair gene that underlies the heritable cancer predisposition syndrome&#xa0;that causes colorectal tumors with a high SBS18 mutation load<sup>3,4</sup>. Both B and D Mutyh alleles are present in wild populations of Mus musculus domesticus, providing evidence that common genetic variation modulates germline mutagenesis in a model mammalian species.",
  "journal": "Nature",
  "year": 2022,
  "authors": "[\"Sasani TA\", \"Ashbrook DG\", \"Beichman AC\", \"Lu L\", \"Palmer AA\", \"Williams RW\", \"Pritchard JK\", \"Harris K\"]",
  "url": "https://pubmed.ncbi.nlm.nih.gov/35545679/",
  "external_ids": {
    "doi": "10.1038/s41586-022-04701-5",
    "pmid": "35545679"
  },
  "citation_count": 0
}