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

  1. Amy L Williams  Is a corresponding author
  2. Giulio Genovese
  3. Thomas Dyer
  4. Nicolas Altemose
  5. Katherine Truax
  6. Goo Jun
  7. Nick Patterson
  8. Simon R Myers
  9. Joanne E Curran
  10. Ravi Duggirala
  11. John Blangero
  12. David Reich
  13. Molly Przeworski
  14. for the T2D-GENES Consortium
  1. Cornell University, United States
  2. Broad Institute of Harvard and MIT, United States
  3. Texas Biomedical Research Institute, United States
  4. Oxford University, United Kingdom
  5. University of Michigan, United States
  6. Columbia University, 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.

Article and author information

Author details

  1. Amy L Williams

    Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, United States
    For correspondence
    awilliams@cornell.edu
    Competing interests
    No competing interests declared.
  2. Giulio Genovese

    Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States
    Competing interests
    No competing interests declared.
  3. Thomas Dyer

    Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
    Competing interests
    No competing interests declared.
  4. Nicolas Altemose

    Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  5. Katherine Truax

    Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
    Competing interests
    No competing interests declared.
  6. Goo Jun

    Department of Biostatistics, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  7. Nick Patterson

    Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States
    Competing interests
    No competing interests declared.
  8. Simon R Myers

    Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  9. Joanne E Curran

    Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
    Competing interests
    No competing interests declared.
  10. Ravi Duggirala

    Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
    Competing interests
    No competing interests declared.
  11. John Blangero

    Department of Genetics, Texas Biomedical Research Institute, San Antonio, United States
    Competing interests
    No competing interests declared.
  12. David Reich

    Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States
    Competing interests
    No competing interests declared.
  13. Molly Przeworski

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    Molly Przeworski, Reviewing editor, eLife.

Ethics

Human subjects: Institutional review board exemption was given for this study from the Broad Institute of Harvard and MIT and the Texas Biomedical Research Institute. The analysis was entirely conducted using anonymous identifiers.

Copyright

© 2015, Williams et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Amy L Williams
  2. Giulio Genovese
  3. Thomas Dyer
  4. Nicolas Altemose
  5. Katherine Truax
  6. Goo Jun
  7. Nick Patterson
  8. Simon R Myers
  9. Joanne E Curran
  10. Ravi Duggirala
  11. John Blangero
  12. David Reich
  13. Molly Przeworski
  14. for the T2D-GENES Consortium
(2015)
Non-crossover gene conversions show strong GC bias and unexpected clustering in humans
eLife 4:e04637.
https://doi.org/10.7554/eLife.04637

Share this article

https://doi.org/10.7554/eLife.04637

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