减数分裂基因的共同变异形成了人类重组和非整倍体，这一成果由约翰霍普金斯大学Rajiv C. McCoy课题组经过不懈努力而取得。相关论文于2026年1月21日发表在《自然》杂志上。

为了解决这一差距，该课题组人员对来自22850对生物父母的139416个体外受精胚胎的植入前基因检测数据进行了回顾性分析。通过追踪单倍型的传播，研究人员鉴定了3809412个交叉，以及92485个非整倍体染色体。非整倍体胚胎的杂交数量低于整倍体胚胎，这与它们在染色体配对和分离中的作用一致。他们的分析进一步揭示了跨越减数分裂内聚蛋白SMC1B的共同单倍型与交叉计数和母体减数分裂非整倍性显著相关，证据支持非编码顺式调节机制。转录组和全表型关联测试也涉及突触复合物组分C14orf39和交叉调节泛素连接酶CCNB1IP1和RNF212在减数分裂非整倍体风险中的变化。更广泛地说，与非整倍体相关的变异通常与重组有次要关联，其中一些变异还表现出与生殖衰老特征有关。他们的发现强调了重组在产生遗传多样性和确保减数分裂保真度方面的双重作用。

研究人员表示，人类妊娠失败的主要原因是非整倍体，通常可以追溯到女性减数分裂期间染色体分离的错误。虽然已知异常交叉重组会带来非整倍性的风险，但有限的数据阻碍了对这些关键分子表型的潜在共享遗传基础的理解。

附：英文原文

Title: Common variation in meiosis genes shapes human recombination and aneuploidy

Author: Carioscia, Sara A., Biddanda, Arjun, Starostik, Margaret R., Tang, Xiaona, Hoffmann, Eva R., Demko, Zachary P., McCoy, Rajiv C.

Issue&Volume: 2026-01-21

Abstract: The leading cause of human pregnancy loss is aneuploidy, often tracing to errors in chromosome segregation during female meiosis1,2. Although abnormal crossover recombination is known to confer risk for aneuploidy3,4, limited data have hindered understanding of the potential shared genetic basis of these key molecular phenotypes. To address this gap, we performed retrospective analysis of pre-implantation genetic testing data from 139,416 in vitro fertilized embryos from 22,850 sets of biological parents. By tracing transmission of haplotypes, we identified 3,809,412 crossovers, as well as 92,485 aneuploid chromosomes. Counts of crossovers were lower in aneuploid versus euploid embryos, consistent with their role in chromosome pairing and segregation. Our analyses further revealed that a common haplotype spanning the meiotic cohesin SMC1B is associated significantly with both crossover count and maternal meiotic aneuploidy, with evidence supporting a non-coding cis-regulatory mechanism. Transcriptome- and phenome-wide association tests also implicated variation in the synaptonemal complex component C14orf39 and crossover-regulating ubiquitin ligases CCNB1IP1 and RNF212 in meiotic aneuploidy risk. More broadly, variants associated with aneuploidy often showed secondary associations with recombination, and several also exhibited associations with reproductive ageing traits. Our findings highlight the dual role of recombination in generating genetic diversity, while ensuring meiotic fidelity.

DOI: 10.1038/s41586-025-09964-2

Source: https://www.nature.com/articles/s41586-025-09964-2