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Factors influencing meiotic recombination revealed by whole-genome sequencing of single sperm

Abstract:
Recombination is critical to meiosis and evolution, yet many aspects of the physical exchange of DNA via crossovers remain poorly understood. We report an approach for single-cell whole-genome DNA sequencing by which we sequenced 217 individual hybrid mouse sperm, providing a kilobase-resolution genome-wide map of crossovers. Combining this map with molecular assays measuring stages of recombination, we identified factors that affect crossover probability, including PRDM9 binding on the non-initiating template homolog and telomere proximity. These factors also influence the time for sites of recombination-initiating DNA double-strand breaks to find and engage their homologs, with rapidly engaging sites more likely to form crossovers. We show that chromatin environment on the template homolog affects positioning of crossover breakpoints. Our results also offer insights into recombination in the pseudoautosomal region.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1126/science.aau8861

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Human Genetics Wt Centre
Role:
Author
ORCID:
0000-0002-0836-3418
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Role:
Author
ORCID:
0000-0003-2951-8287
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Role:
Author
ORCID:
0000-0001-6901-6527
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Role:
Author
ORCID:
0000-0001-7977-8496
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Role:
Author
ORCID:
0000-0003-3169-698X


Publisher:
American Association for the Advancement of Science
Journal:
Science More from this journal
Volume:
363
Issue:
6433
Article number:
eaau8861
Publication date:
2019-03-22
Acceptance date:
2019-02-01
DOI:
EISSN:
1095-9203
ISSN:
0036-8075


Language:
English
Keywords:
Pubs id:
pubs:983848
UUID:
uuid:b9e7fcd4-79ad-4c0d-b0aa-7ca91d1fe5a8
Local pid:
pubs:983848
Source identifiers:
983848
Deposit date:
2019-03-22

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