Sex-specific recombination predicts parent of origin for recurrent genomic disorders

Mosley, T.; Johnston, H. R.; Cutler, D. J.; Zwick, M. E.; Mulle, J. G.

doi:10.1101/2020.06.01.128553

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bioRxiv · 10.1101/2020.06.01.128553

Sex-specific recombination predicts parent of origin for recurrent genomic disorders

Mosley, T.·Johnston, H. R.·Cutler, D. J.·Zwick, M. E.·Mulle, J. G.

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Abstract

Genomic disorders are caused by structural rearrangements of the genome that generally occur during meiosis1. Often the rearrangements result in large-scale (> 1 kb) copy number variants (CNV; deletions or duplications [≥] 1 kb)2,3. Recurrent pathogenic CNVs harbor similar breakpoints in multiple unrelated individuals and are primarily formed via non-allelic homologous recombination (NAHR)3,4. Several pathogenic NAHR-mediated recurrent CNV loci demonstrate biases for parental origin of de novo CNVs5-9. 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 bring into light the need to consider these differences when seeking to determine the factors underlying risk for structural variation.

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Mosley, T., Johnston, H. R., Cutler, D. J., Zwick, M. E., Mulle, J. G.. 2020-06-02. Sex-specific recombination predicts parent of origin for recurrent genomic disorders. https://doi.org/10.1101/2020.06.01.128553

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