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

By 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, T2D-GENES Consortium

Posted 16 Sep 2014
bioRxiv DOI: 10.1101/009175 (published DOI: 10.7554/eLife.04637)

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 the events are likely of meiotic origin. We estimate that a site is involved in a NCO at a rate of 5.7×10-6/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 for which there are also resequencing data, multiple disjoint NCO tracts cluster in close proximity (~20?30 kb), a phenomenon not previously seen in mammals.

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