Meiotic recombination is crucial for human genetic diversity and chromosome segregation accuracy. Understanding its variation across individuals and the processes by which it goes awry are long-standing goals in human genetics. Current approaches for inferring recombination landscapes rely either on population genetic patterns of linkage disequilibrium (LD)—capturing a time-averaged view—or on direct detection of crossovers in gametes or multigeneration pedigrees, which limits data set scale and availability. Here, we introduce an approach for inferring sex-specific recombination landscapes using data from preimplantation genetic testing for aneuploidy (PGT-A). This method relies on low-coverage (<0.05×) whole-genome sequencing of in vitro fertilized (IVF) embryo biopsies. To overcome the data sparsity, our method exploits its inherent relatedness structure, knowledge of haplotypes from external population reference panels, and the frequent occurrence of monosomies in embryos, whereby the remaining chromosome is phased by default. Extensive simulations show our method's high accuracy, even at coverages as low as 0.02×. Applying this method to PGT-A data from 18,967 embryos, we mapped 70,660 recombination events with ∼150 kbp resolution, replicating established sex-specific recombination patterns. We observed a reduced total length of the female genetic map in trisomies compared with disomies, as well as chromosome-specific alterations in crossover distributions. Based on haplotype configurations in pericentromeric regions, our data indicate chromosome-specific propensities for different mechanisms of meiotic error. Our results provide a comprehensive view of the role of aberrant meiotic recombination in the origins of human aneuploidies and offer a versatile tool for mapping crossovers in low-coverage sequencing data from multiple siblings.

中文翻译：

---

母体减数分裂交叉的异常景观导致人类胚胎的非整倍性

减数分裂重组对于人类遗传多样性和染色体分离准确性至关重要。了解它在个体之间的差异以及它出错的过程是人类遗传学的长期目标。目前推断重组景观的方法要么依赖于连锁不平衡（LD）的群体遗传模式（捕获时间平均视图），要么依赖于配子或多代谱系中交叉的直接检测，这限制了数据集的规模和可用性。在这里，我们介绍了一种使用来自非整倍体植入前基因检测（PGT-A）的数据来推断性别特异性重组景观的方法。该方法依赖于体外受精 (IVF) 胚胎活检的低覆盖率 (<0.05×) 全基因组测序。为了克服数据稀疏性，我们的方法利用其固有的相关性结构、来自外部群体参考组的单倍型知识以及胚胎中频繁出现的单体性，从而默认对剩余染色体进行定相。大量的模拟表明我们的方法即使在覆盖率低至 0.02× 的情况下也具有很高的准确性。将此方法应用于来自 18,967 个胚胎的 PGT-A 数据，我们以~150 kbp 的分辨率绘制了 70,660 个重组事件，复制了已建立的性别特异性重组模式。我们观察到，与二体性相比，三体性女性遗传图谱的总长度减少，并且交叉分布中存在染色体特异性改变。基于着丝粒周围区域的单倍型配置，我们的数据表明不同减数分裂错误机制的染色体特异性倾向。我们的结果提供了异常减数分裂重组在人类非整倍体起源中的作用的全面视图，并提供了一种多功能工具，用于绘制来自多个兄弟姐妹的低覆盖率测序数据中的交叉。