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

doi:10.7554/eLife.04637

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 journal › Article › peer-review

51 Scopus citations

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 language	English (US)
Journal	eLife
Volume	2015
Issue number	4
DOIs	https://doi.org/10.7554/eLife.04637
State	Published - Mar 25 2015
Externally published	Yes

ASJC Scopus subject areas

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

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10.7554/eLife.04637

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Williams, A. L., Williams, A. L., Williams, A. L., Williams, A. L., Genovese, G., Dyer, T., Altemose, N., Truax, K., Jun, G., Patterson, N., Myers, S. R., Curran, J. E., 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, 2015(4). https://doi.org/10.7554/eLife.04637

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

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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",

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AU - Jun, Goo

AU - Patterson, Nick

AU - Myers, Simon R.

AU - Curran, Joanne E.

AU - Duggirala, Ravi

AU - Blangero, John

AU - Reich, David

AU - Przeworski, Molly

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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.

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

Abstract

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