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

Amy L. Williams, Amy L. Williams, Amy L. Williams, 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, David Reich, David Reich, Molly Przeworski, Molly Przeworski

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
JournaleLife
Volume2015
Issue number4
DOIs
StatePublished - Mar 25 2015
Externally publishedYes

Fingerprint

Gene Conversion
Mammals
Single Nucleotide Polymorphism
Cluster Analysis
Genes
Meiosis
Cross-Over Studies
Genetic Recombination
Spermatozoa
Alleles
Genome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Williams, A. L., Williams, A. L., Williams, A. L., Williams, A. L., Genovese, G., Dyer, T., ... Przeworski, M. (2015). Non-crossover gene conversions show strong GC bias and unexpected clustering in humans. eLife, 2015(4). https://doi.org/10.7554/eLife.04637

Non-crossover gene conversions show strong GC bias and unexpected clustering in humans. / Williams, Amy L.; Williams, Amy L.; Williams, Amy L.; 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; Reich, David; Reich, David; Przeworski, Molly; Przeworski, Molly.

In: eLife, Vol. 2015, No. 4, 25.03.2015.

Research output: Contribution to journalArticle

Williams, AL, Williams, AL, Williams, AL, Williams, AL, Genovese, G, Dyer, T, Altemose, N, Truax, K, Jun, G, Patterson, N, Myers, SR, Curran, JE, Duggirala, R, Blangero, J, Reich, D, Reich, D, Reich, D, Przeworski, M & Przeworski, M 2015, 'Non-crossover gene conversions show strong GC bias and unexpected clustering in humans', eLife, vol. 2015, no. 4. https://doi.org/10.7554/eLife.04637
Williams AL, Williams AL, Williams AL, Williams AL, Genovese G, Dyer T et al. Non-crossover gene conversions show strong GC bias and unexpected clustering in humans. eLife. 2015 Mar 25;2015(4). https://doi.org/10.7554/eLife.04637
Williams, Amy L. ; Williams, Amy L. ; Williams, Amy L. ; 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 ; Reich, David ; Reich, David ; Przeworski, Molly ; Przeworski, Molly. / Non-crossover gene conversions show strong GC bias and unexpected clustering in humans. In: eLife. 2015 ; Vol. 2015, No. 4.
@article{414a145419e2409c92042712b00ed755,
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.",
author = "Williams, {Amy L.} and Williams, {Amy L.} and Williams, {Amy L.} and Williams, {Amy L.} and Giulio Genovese and Thomas Dyer and Nicolas Altemose and Katherine Truax and Goo Jun and Nick Patterson and Myers, {Simon R.} and Curran, {Joanne E.} and Ravi Duggirala and John Blangero and David Reich and David Reich and David Reich and Molly Przeworski and Molly Przeworski",
year = "2015",
month = "3",
day = "25",
doi = "10.7554/eLife.04637",
language = "English (US)",
volume = "2015",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "4",

}

TY - JOUR

T1 - Non-crossover gene conversions show strong GC bias and unexpected clustering in humans

AU - Williams, Amy L.

AU - Williams, Amy L.

AU - Williams, Amy L.

AU - Williams, Amy L.

AU - Genovese, Giulio

AU - Dyer, Thomas

AU - Altemose, Nicolas

AU - Truax, Katherine

AU - Jun, Goo

AU - Patterson, Nick

AU - Myers, Simon R.

AU - Curran, Joanne E.

AU - Duggirala, Ravi

AU - Blangero, John

AU - Reich, David

AU - Reich, David

AU - Reich, David

AU - Przeworski, Molly

AU - Przeworski, Molly

PY - 2015/3/25

Y1 - 2015/3/25

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84925881644&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925881644&partnerID=8YFLogxK

U2 - 10.7554/eLife.04637

DO - 10.7554/eLife.04637

M3 - Article

C2 - 25806687

AN - SCOPUS:84984923609

VL - 2015

JO - eLife

JF - eLife

SN - 2050-084X

IS - 4

ER -