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

Elife. 2015 Mar 25;4:e04637. doi: 10.7554/eLife.04637.

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.

Keywords: GC-bias; chromosomes; complex crossover; evolutionary biology; gene conversion; genes; genomics; haplotypes; human; non-crossover; recombination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Composition / genetics*
  • Base Sequence
  • Cluster Analysis
  • Crossing Over, Genetic*
  • Female
  • Gene Conversion*
  • Humans
  • Male
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics