美国华盛顿大学Kelley Harris研究小组发现，一个天然的突变者等位基因塑造小鼠的突变谱变异。2022年5月11日，《自然》杂志在线发表了这项成果。
Author: Sasani, Thomas A., Ashbrook, David G., Beichman, Annabel C., Lu, Lu, Palmer, Abraham A., Williams, Robert W., Pritchard, Jonathan K., Harris, Kelley
Issue&Volume: 2022-05-11
Abstract: Although germline mutation rates and spectra can vary within and between species, common genetic modifiers of the mutation rate have not been identified in nature1. Here we searched for loci that influence germline mutagenesis using a uniquely powerful resource: a panel of recombinant inbred mouse lines known as the 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 haplotypes2. We show that mice inheriting D haplotypes at a quantitative trait locus on chromosome 4 accumulate C>A germline mutations at a 50% higher rate than those inheriting B haplotypes, primarily owing to the activity of a C>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 that causes colorectal tumors with a high SBS18 mutation load3,4. 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.
DOI: 10.1038/s41586-022-04701-5
Source: https://www.nature.com/articles/s41586-022-04701-5
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
