Non-crossover gene conversions show strong GC bias and unexpected clustering in humans

Although the past decade has seen tremendous progress in our understanding of fine-scale recombination, little is known about non-crossover (NCO) gene conversion. We report the first genome-wide study of NCO events in humans. Using SNP array data from 98 meioses, we identified 103 sites affected by...

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Bibliographic Details
Main Authors: Amy L Williams, Giulio Genovese, Thomas Dyer, Nicolas Altemose, Katherine Truax, Goo Jun, Nick Patterson, Simon R Myers, Joanne E Curran, Ravi Duggirala, John Blangero, David Reich, Molly Przeworski, on behalf of the T2D-GENES Consortium
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2015-03-01
Series:eLife
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Online Access:https://elifesciences.org/articles/04637
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Summary:Although the past decade has seen tremendous progress in our understanding of fine-scale recombination, little is known about non-crossover (NCO) gene conversion. We report the first genome-wide study of NCO events in humans. Using SNP array data from 98 meioses, we identified 103 sites affected by NCO, of which 50/52 were confirmed in sequence data. Overlap with double strand break (DSB) hotspots indicates that most of the events are likely of meiotic origin. We estimate that a site is involved in a NCO at a rate of 5.9 × 10−6/bp/generation, consistent with sperm-typing studies, and infer that tract lengths span at least an order of magnitude. Observed NCO events show strong allelic bias at heterozygous AT/GC SNPs, with 68% (58–78%) transmitting GC alleles (p = 5 × 10−4). Strikingly, in 4 of 15 regions with resequencing data, multiple disjoint NCO tracts cluster in close proximity (∼20–30 kb), a phenomenon not previously seen in mammals.
ISSN:2050-084X