Such chiasmata must then be maintained over decades-long meiotic arrest, until meiosis resumes at ovulation. Notably, female meiosis initiates during fetal development, when homologs pair, acquire double-strand breaks, and establish crossovers that form physical linkages (chiasmata) to stabilize the chromosomes. The crossovers that mediate such genetic exchanges during meiosis are also important for ensuring the accuracy of chromosome segregation. Recombination between homologous chromosomes is a key source of human genetic diversity. Together, our results provide a detailed view of the role of aberrant meiotic recombination in the origins of human aneuploidies, as well as a flexible tool for mapping crossovers in low-coverage sequencing data from multiple siblings. Based on haplotype configurations detected in regions surrounding the centromeres, our data additionally indicate that individual chromosomes possess unique propensities for different mechanisms of meiotic error. We observed that the total length of the female genetic map is reduced for trisomies compared to disomies, while the genomic distribution of crossovers is also altered in a chromosome-specific manner. Applying this method to low-coverage PGT-A data from 18,967 embryos, we mapped 70,660 recombination events at an average resolution of ∼150 kbp, replicating key features of sex-specific recombination maps from the literature. Based on extensive simulation, we show that our method retains high accuracy down to coverages as low as 0.02×. To overcome the sparsity of these data, our method exploits its inherent relatedness structure, knowledge of haplotypes from external population reference panels, as well as the frequent occurrence of chromosome loss in embryos, whereby the remaining chromosome is phased by default. Here, we introduce an approach for inferring sex-specific landscapes of recombination from retrospective analysis of data from preimplantation genetic testing for aneuploidy (PGT-A) based on low-coverage (<0.05×) whole-genome sequencing of biopsies from in vitro fertilized (IVF) embryos. Current approaches for inferring the landscape of recombination either rely on population genetic patterns of linkage disequilibrium (LD)-capturing a time-averaged view-or direct detection of crossovers in gametes or multi-generation pedigrees, limiting the scale and availability of relevant datasets. Understanding the landscape of meiotic recombination, its variation across individuals, and the processes by which it goes awry are long-standing goals in human genetics.
Meiotic recombination is a fundamental source of human genetic diversity and is also critical for ensuring the accuracy of chromosome segregation.
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