Insights into variation in meiosis from 31,228 human sperm genomes
Insights into variation in meiosis from 31,228 human sperm genomes
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DOI：
10.1038/s41586-020-2347-0
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发表时间：
2020-06-03
期刊：
影响因子：
64.8
通讯作者：
McCarroll, Steven A.
中科院分区：
文献类型：
--
作者：
Bell, Avery Davis;Mello, Curtis J.;McCarroll, Steven A.
减数分裂虽然对生殖至关重要，但也是可变的和容易出错的：配子之间、两性之间和同一性别的人类之间的染色体交换率不同，染色体错误分离导致染色体数目异常（非整倍性）（1-8）。为了研究不同的减数分裂结果以及它们如何在染色体、配子和人类之间发生变化，我们开发了Sperm-seq，这是一种同时分析数千个精子基因组的方法。在这里，我们分析了来自20个精子捐献者的31，228个人类配子的基因组，确定了813，122个交叉和787个非整倍体染色体。精子供体的非整倍体率范围从0.01至0.05每配子的非整倍体;交叉部分保护染色体不分离在减数分裂I细胞分裂。一些染色体和供体在减数分裂I期间经历了更频繁的不分离，而另一些则表现出更多的减数分裂II分离失败。精子基因组也表现出许多不能用简单的不分离来解释的基因组异常。不同的重组表型-从交叉率到交叉位置和分离，交叉干扰的测量-在个体和细胞之间存在强烈的共变。我们的研究结果可以与早期的观察纳入一个统一的模型，其中的核心机制，减数分裂染色体的可变物理压实，产生不同的减数分裂表型的个体间和细胞间的变化。
Meiosis, although essential for reproduction, is also variable and error-prone: rates of chromosome crossover vary among gametes, between the sexes, and among humans of the same sex, and chromosome missegregation leads to abnormal chromosome numbers (aneuploidy)(1-8). To study diverse meiotic outcomes and how they covary across chromosomes, gametes and humans, we developed Sperm-seq, a way of simultaneously analysing the genomes of thousands of individual sperm. Here we analyse the genomes of 31,228 human gametes from 20 sperm donors, identifying 813,122 crossovers and 787 aneuploid chromosomes. Sperm donors had aneuploidy rates ranging from 0.01 to 0.05 aneuploidies per gamete; crossovers partially protected chromosomes from nondisjunction at the meiosis I cell division. Some chromosomes and donors underwent more-frequent nondisjunction during meiosis I, and others showed more meiosis II segregation failures. Sperm genomes also manifested manygenomic anomalies that could not be explained by simple nondisjunction. Diverse recombination phenotypes-from crossover rates to crossover location and separation, a measure of crossover interference-covaried strongly across individuals and cells. Our results can be incorporated with earlier observations into a unified model in which a core mechanism, the variable physical compaction of meiotic chromosomes, generates interindividual and cell-to-cell variation in diverse meiotic phenotypes.