Variation in human recombination rates and its genetic determinants.
Despite the fundamental role of crossing-over in the pairing and segregation of chromosomes during human meiosis, the rates and placements of events vary markedly among individuals. Characterizing this variation and identifying its determinants are essential steps in our understanding of the human r...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3117798?pdf=render |
| _version_ | 1818949013151416320 |
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| author | Adi Fledel-Alon Ellen Miranda Leffler Yongtao Guan Matthew Stephens Graham Coop Molly Przeworski |
| author_facet | Adi Fledel-Alon Ellen Miranda Leffler Yongtao Guan Matthew Stephens Graham Coop Molly Przeworski |
| author_sort | Adi Fledel-Alon |
| collection | DOAJ |
| description | Despite the fundamental role of crossing-over in the pairing and segregation of chromosomes during human meiosis, the rates and placements of events vary markedly among individuals. Characterizing this variation and identifying its determinants are essential steps in our understanding of the human recombination process and its evolution.Using three large sets of European-American pedigrees, we examined variation in five recombination phenotypes that capture distinct aspects of crossing-over patterns. We found that the mean recombination rate in males and females and the historical hotspot usage are significantly heritable and are uncorrelated with one another. We then conducted a genome-wide association study in order to identify loci that influence them. We replicated associations of RNF212 with the mean rate in males and in females as well as the association of Inversion 17q21.31 with the female mean rate. We also replicated the association of PRDM9 with historical hotspot usage, finding that it explains most of the genetic variance in this phenotype. In addition, we identified a set of new candidate regions for further validation.These findings suggest that variation at broad and fine scales is largely separable and that, beyond three known loci, there is no evidence for common variation with large effects on recombination phenotypes. |
| first_indexed | 2024-12-20T08:55:56Z |
| format | Article |
| id | doaj.art-98854daad8434a6cbd3625dd94b2744f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T08:55:56Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-98854daad8434a6cbd3625dd94b2744f2022-12-21T19:46:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2032110.1371/journal.pone.0020321Variation in human recombination rates and its genetic determinants.Adi Fledel-AlonEllen Miranda LefflerYongtao GuanMatthew StephensGraham CoopMolly PrzeworskiDespite the fundamental role of crossing-over in the pairing and segregation of chromosomes during human meiosis, the rates and placements of events vary markedly among individuals. Characterizing this variation and identifying its determinants are essential steps in our understanding of the human recombination process and its evolution.Using three large sets of European-American pedigrees, we examined variation in five recombination phenotypes that capture distinct aspects of crossing-over patterns. We found that the mean recombination rate in males and females and the historical hotspot usage are significantly heritable and are uncorrelated with one another. We then conducted a genome-wide association study in order to identify loci that influence them. We replicated associations of RNF212 with the mean rate in males and in females as well as the association of Inversion 17q21.31 with the female mean rate. We also replicated the association of PRDM9 with historical hotspot usage, finding that it explains most of the genetic variance in this phenotype. In addition, we identified a set of new candidate regions for further validation.These findings suggest that variation at broad and fine scales is largely separable and that, beyond three known loci, there is no evidence for common variation with large effects on recombination phenotypes.http://europepmc.org/articles/PMC3117798?pdf=render |
| spellingShingle | Adi Fledel-Alon Ellen Miranda Leffler Yongtao Guan Matthew Stephens Graham Coop Molly Przeworski Variation in human recombination rates and its genetic determinants. PLoS ONE |
| title | Variation in human recombination rates and its genetic determinants. |
| title_full | Variation in human recombination rates and its genetic determinants. |
| title_fullStr | Variation in human recombination rates and its genetic determinants. |
| title_full_unstemmed | Variation in human recombination rates and its genetic determinants. |
| title_short | Variation in human recombination rates and its genetic determinants. |
| title_sort | variation in human recombination rates and its genetic determinants |
| url | http://europepmc.org/articles/PMC3117798?pdf=render |
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