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

Abstract

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 5.7x10-6/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=5x10-4). 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.