Format

Send to

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

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

Author information

1
Department of Biological Sciences, Columbia University, New York, United States.
2
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States.
3
Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States.
4
Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom.
5
Department of Biostatistics, University of Michigan, Ann Arbor, 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.

KEYWORDS:

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

PMID:
25806687
PMCID:
PMC4404656
DOI:
10.7554/eLife.04637
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center