{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:28:36Z","timestamp":1787851716827,"version":"build-2784847793"},"reference-count":72,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM148071"],"award-info":[{"award-number":["R35GM148071"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-1921341"],"award-info":[{"award-number":["MCB-1921341"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    Mutations are the source of evolutionary novelty but also the cause of genetic diseases and cancer. Mutation rates are known to be heterogeneous along the genome, however the extent to which local mutation rates vary among individuals in a population and are genetically determined is unknown. To test this, we analyzed the chromosomal distribution of somatic mutations in cell lines from 1,662 individuals, controlling for the confounding effects of DNA replication timing on local mutation rates and of\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    -acting modulators on global mutation rates. We describe substantial interindividual variation in mutation rates across the human genome. By comparing mutation-rate variation to individuals\u2019 genotypes, we identified 35 instances in which polymorphic alleles in the population associate with somatic mutation rates in their vicinity. We call these mutation quantitative trait loci (mutQTLs). mutQTLs associated with somatic mutations in lymphoblastoid cell lines and in chronic lymphocytic leukemia, and with germline genetic variants. Two of the four mutQTLs inferred to be associated with germline mutation-rate variation were located within large clusters of zinc-finger genes and transposable elements, where they functioned as\n                    <jats:italic toggle=\"yes\">cis<\/jats:italic>\n                    -mutators conferring an increased rate of mutation in their vicinity. mutQTLs provide a portal into the evolution of mutation rate heterogeneity across the genome and across individuals.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2625619123","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:06:56Z","timestamp":1787850416000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Genetic control of local mutation 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