Abstract
Abstract
Background
Structural rearrangements of the genome, which generally occur during meiosis and result in large-scale (> 1 kb) copy number variants (CNV; deletions or duplications ≥ 1 kb), underlie genomic disorders. 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.
Methods
We performed a systematic, comprehensive literature search to curate parent of origin data for multiple pathogenic CNV loci. Using a regression framework, we assessed the relationship between parental CNV origin and the male to female recombination rate ratio.
Results
We demonstrate significant association between sex-specific differences in meiotic recombination and parental origin biases at these loci (p = 1.07 × 10–14).
Conclusions
Our results suggest that parental origin of CNVs is largely influenced by sex-specific recombination rates and highlight the need to consider these differences when investigating mechanisms that cause structural variation.
Funder
National Institute of Mental Health
National Institute of General Medical Sciences
National Center for Advancing Translational Sciences
Publisher
Springer Science and Business Media LLC
Subject
Genetics(clinical),Genetics