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Research article
Sex-specific recombination predicts parent of origin for recurrent genomic disorders
Jennifer G Mulle
Emory University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8593-8468
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Genomic disorders are caused by structural rearrangements of the genome that generally occur during meiosis. Often the rearrangements result in large-scale (> 1 kb) copy number variants (CNV; deletions or duplications ≥ 1 kb). Recurrent pathogenic CNVs harbor similar breakpoints in multiple unrelated individuals and are primarily formed via non-allelic homologous recombination (NAHR). Several pathogenic NAHR-mediated recurrent CNV loci demonstrate biases for parental origin of de novo CNVs. However, the mechanism underlying these biases is not well understood. Here we have curated parent of origin data for multiple pathogenic CNV loci and demonstrate a significant association between sex-specific differences in meiotic recombination and parental origin biases at these loci. Our results suggest that parental-origin of CNVs is largely controlled by sex-specific recombination rates, and highlight the need to consider these differences when investigating mechanisms that cause structural variation.
Keywords
Copy number variants, meiotic recombination, parent of origin
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CURRENT STATUS: Under Revision
Version 1
Posted 13 Aug, 2020
No community comments so far
Editorial decision: Major revision
On 11 Nov, 2020
Review #2 received
Received 04 Nov, 2020
Review #1 received
Received 04 Sep, 2020
Reviewer #2 agreed
On 20 Aug, 2020
Reviewers invited
Invitations sent on 13 Aug, 2020
Reviewer #1 agreed
On 13 Aug, 2020
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On 12 Aug, 2020
Editor invited
On 12 Aug, 2020
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On 12 Aug, 2020
First submitted
On 28 Jul, 2020
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Subject Areas
Epigenetics & Genomics
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This preprint is under consideration at BMC Medical Genomics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Sex-specific recombination predicts parent of origin for recurrent genomic disorders
Jennifer G Mulle
Emory University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8593-8468
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 13 Aug, 2020
No community comments so far
Editorial decision: Major revision
On 11 Nov, 2020
Review #2 received
Received 04 Nov, 2020
Review #1 received
Received 04 Sep, 2020
Reviewer #2 agreed
On 20 Aug, 2020
Reviewers invited
Invitations sent on 13 Aug, 2020
Reviewer #1 agreed
On 13 Aug, 2020
Submission checks complete
On 12 Aug, 2020
Editor invited
On 12 Aug, 2020
Editor assigned
On 12 Aug, 2020
First submitted
On 28 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Genomic disorders are caused by structural rearrangements of the genome that generally occur during meiosis. Often the rearrangements result in large-scale (> 1 kb) copy number variants (CNV; deletions or duplications ≥ 1 kb). Recurrent pathogenic CNVs harbor similar breakpoints in multiple unrelated individuals and are primarily formed via non-allelic homologous recombination (NAHR). Several pathogenic NAHR-mediated recurrent CNV loci demonstrate biases for parental origin of de novo CNVs. However, the mechanism underlying these biases is not well understood. Here we have curated parent of origin data for multiple pathogenic CNV loci and demonstrate a significant association between sex-specific differences in meiotic recombination and parental origin biases at these loci. Our results suggest that parental-origin of CNVs is largely controlled by sex-specific recombination rates, and highlight the need to consider these differences when investigating mechanisms that cause structural variation.
Figure 1