Sex-specific recombination predicts parent of origin for recurrent genomic disorders
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
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Posted 13 Aug, 2020
On 11 Nov, 2020
Received 04 Nov, 2020
Received 04 Sep, 2020
On 20 Aug, 2020
Invitations sent on 13 Aug, 2020
On 13 Aug, 2020
On 12 Aug, 2020
On 12 Aug, 2020
On 12 Aug, 2020
On 28 Jul, 2020
Sex-specific recombination predicts parent of origin for recurrent genomic disorders
Posted 13 Aug, 2020
On 11 Nov, 2020
Received 04 Nov, 2020
Received 04 Sep, 2020
On 20 Aug, 2020
Invitations sent on 13 Aug, 2020
On 13 Aug, 2020
On 12 Aug, 2020
On 12 Aug, 2020
On 12 Aug, 2020
On 28 Jul, 2020
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