Sex-specific recombination patterns predict parent of origin for recurrent genomic disorders

• Autores principales: Trenell J. Mosley (Autor), H. Richard Johnston (Autor), David J. Cutler (Autor), Michael E. Zwick (Autor), Jennifer G. Mulle (Autor)
• Formato: Libro
• Publicado: BMC, 2021-06-01T00:00:00Z.
• Materias: article
• Acceso en línea: Connect to this object online.

Sumario

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.

Notas

10.1186/s12920-021-00999-8
1755-8794