Non-crossover gene conversions show strong GC bias and unexpected clustering in humans
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
Affiliations
Amy L Williams
Department of Biological Sciences, Columbia University, New York, United States; Department of Systems Biology, Columbia University, New York, United States; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States
Giulio Genovese
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States
Thomas Dyer
Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
Nicolas Altemose
Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom
Katherine Truax
Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
Goo Jun
Department of Biostatistics, University of Michigan, Ann Arbor, United States
Nick Patterson
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States
Simon R Myers
Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom
Joanne E Curran
Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
Ravi Duggirala
Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
John Blangero
Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
David Reich
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States; Department of Genetics, Harvard Medical School, Boston, United States; Howard Hughes Medical Institute, Harvard Medical School, Boston, United States
Molly Przeworski
Department of Biological Sciences, Columbia University, New York, United States; Department of Systems Biology, Columbia University, New York, United States
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.
