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• W2135267901 startingPage "2109" @default.
• W2135267901 abstract "Meiosis is a potentially important source of germline mutations, as sites of meiotic recombination experience recurrent double-strand breaks (DSBs). However, evidence for a local mutagenic effect of recombination from population sequence data has been equivocal, likely because mutation is only one of several forces shaping sequence variation. By sequencing large numbers of single crossover molecules obtained from human sperm for two recombination hotspots, we find direct evidence that recombination is mutagenic: Crossovers carry more de novo mutations than nonrecombinant DNA molecules analyzed for the same donors and hotspots. The observed mutations were primarily CG to TA transitions, with a higher frequency of transitions at CpG than non-CpGs sites. This enrichment of mutations at CpG sites at hotspots could predominate in methylated regions involving frequent single-stranded DNA processing as part of DSB repair. In addition, our data set provides evidence that GC alleles are preferentially transmitted during crossing over, opposing mutation, and shows that GC-biased gene conversion (gBGC) predominates over mutation in the sequence evolution of hotspots. These findings are consistent with the idea that gBGC could be an adaptation to counteract the mutational load of recombination." @default.
• W2135267901 created "2016-06-24" @default.
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• W2135267901 date "2015-02-02" @default.
• W2135267901 modified "2023-10-05" @default.
• W2135267901 title "Crossovers are associated with mutation and biased gene conversion at recombination hotspots" @default.
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• W2135267901 doi "https://doi.org/10.1073/pnas.1416622112" @default.
• W2135267901 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4343121" @default.
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• W2135267901 hasPublicationYear "2015" @default.
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