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

• Published in: eLife 2015-03, Vol.4
• Main Authors: Williams, Amy L, Genovese, Giulio, Dyer, Thomas, Altemose, Nicolas, Truax, Katherine, Jun, Goo, Patterson, Nick, Myers, Simon R, Curran, Joanne E, Duggirala, Ravi, Blangero, John, Reich, David, Przeworski, Molly
• Format: Article
• Language: English
• Subjects: Alleles; Base Composition - genetics; Base Sequence; Bias; Cluster Analysis; complex crossover; Conversion; Crossing Over, Genetic; Deoxyribonucleic acid; DNA; Female; GC-bias; Gene Conversion; Genes and Chromosomes; Genetic recombination; Genomes; Genomics and Evolutionary Biology; haplotype; Haplotypes; Humans; Male; Meiosis; non-crossover; Pedigree; Polymorphism, Single Nucleotide - genetics; Quality control; Recombination; Single-nucleotide polymorphism; Sperm; Typing
• ISSN: 2050-084X; 2050-084X
• 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 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.