Non-crossover gene conversions show strong GC bias and unexpected clustering in humans
- Cornell University, United States
- Broad Institute of Harvard and MIT, United States
- Texas Biomedical Research Institute, United States
- Oxford University, United Kingdom
- University of Michigan, United States
- Columbia University, United States
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 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.
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Ethics
Human subjects: Institutional review board exemption was given for this study from the Broad Institute of Harvard and MIT and the Texas Biomedical Research Institute. The analysis was entirely conducted using anonymous identifiers.
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© 2015, Williams et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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