Non-crossover gene conversions show strong GC bias and unexpected clustering in humans
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/04637 |
| _version_ | 1811236859077984256 |
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| author | 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 Molly Przeworski on behalf of the T2D-GENES Consortium |
| author_facet | 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 Molly Przeworski on behalf of the T2D-GENES Consortium |
| author_sort | Amy L Williams |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:16:24Z |
| format | Article |
| id | doaj.art-16ae6f379cf3443e882d52a9a291051f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:16:24Z |
| publishDate | 2015-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-16ae6f379cf3443e882d52a9a291051f2022-12-22T03:33:25ZengeLife Sciences Publications LtdeLife2050-084X2015-03-01410.7554/eLife.04637Non-crossover gene conversions show strong GC bias and unexpected clustering in humansAmy L Williams0Giulio Genovese1Thomas Dyer2Nicolas Altemose3Katherine Truax4Goo Jun5Nick Patterson6Simon R Myers7Joanne E Curran8Ravi Duggirala9John Blangero10David Reich11Molly Przeworski12on behalf of the T2D-GENES ConsortiumDepartment of Biological Sciences, Columbia University, New York, United States; Department of Systems Biology, Columbia University, New York, United States; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United StatesProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United StatesDepartment of Genetics, Texas Biomedical Research Institute, San Antonio, United StatesWellcome Trust Centre for Human Genetics, Oxford University, Oxford, United KingdomDepartment of Genetics, Texas Biomedical Research Institute, San Antonio, United StatesDepartment of Biostatistics, University of Michigan, Ann Arbor, United StatesProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United StatesWellcome Trust Centre for Human Genetics, Oxford University, Oxford, United KingdomDepartment of Genetics, Texas Biomedical Research Institute, San Antonio, United StatesDepartment of Genetics, Texas Biomedical Research Institute, San Antonio, United StatesDepartment of Genetics, Texas Biomedical Research Institute, San Antonio, United StatesProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States; Department of Genetics, Harvard Medical School, Boston, United States; Howard Hughes Medical Institute, Harvard Medical School, Boston, United StatesDepartment of Biological Sciences, Columbia University, New York, United States; Department of Systems Biology, Columbia University, New York, United StatesAlthough 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.https://elifesciences.org/articles/04637recombinationnon-crossovergene conversionGC-biascomplex crossoverhaplotype |
| spellingShingle | 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 Molly Przeworski on behalf of the T2D-GENES Consortium Non-crossover gene conversions show strong GC bias and unexpected clustering in humans eLife recombination non-crossover gene conversion GC-bias complex crossover haplotype |
| title | Non-crossover gene conversions show strong GC bias and unexpected clustering in humans |
| title_full | Non-crossover gene conversions show strong GC bias and unexpected clustering in humans |
| title_fullStr | Non-crossover gene conversions show strong GC bias and unexpected clustering in humans |
| title_full_unstemmed | Non-crossover gene conversions show strong GC bias and unexpected clustering in humans |
| title_short | Non-crossover gene conversions show strong GC bias and unexpected clustering in humans |
| title_sort | non crossover gene conversions show strong gc bias and unexpected clustering in humans |
| topic | recombination non-crossover gene conversion GC-bias complex crossover haplotype |
| url | https://elifesciences.org/articles/04637 |
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