title: 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 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.
authors: Department of Biological Sciences, Columbia University, New York, United States.
authors: Amy L
authors: AL
authors: Williams
authors: Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States.
authors: Giulio
authors: G
authors: Genovese
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States.
authors: Thomas
authors: T
authors: Dyer
authors: Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom.
authors: Nicolas
authors: N
authors: Altemose
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States.
authors: Katherine
authors: K
authors: Truax
authors: Department of Biostatistics, University of Michigan, Ann Arbor, United States.
authors: Goo
authors: G
authors: Jun
authors: Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States.
authors: Nick
authors: N
authors: Patterson
authors: Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom.
authors: Simon R
authors: SR
authors: Myers
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States.
authors: Joanne E
authors: JE
authors: Curran
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States.
authors: Ravi
authors: R
authors: Duggirala
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States.
authors: John
authors: J
authors: Blangero
authors: Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States.
authors: David
authors: D
authors: Reich
authors: Department of Biological Sciences, Columbia University, New York, United States.
authors: Molly
authors: M
authors: Przeworski
mesh_terms: D000483:Alleles; D001482:Base Composition / Q000235:genetics*; D001483:Base Sequence; D016000:Cluster Analysis; D003434:Crossing Over, Genetic; D005260:Female; D005785:Gene Conversion; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
keywords: GC-bias; chromosomes; complex crossover; evolutionary biology; gene conversion; genes; genomics; haplotypes; human; non-crossover; recombination