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大规模测序揭示人精子基因组在减数分裂过程的变异情况
2020-06-05 08:53

美国哈佛医学院Steven A. McCarroll、Avery Davis Bell及其课题组,通过对31,228个人精子基因组进行研究揭示了精子在减数分裂过程中的变异情况。 相关论文在线发表在2020年6月3日的《自然》上。

为了研究减数分裂的各个过程以及它们如何在染色体、配子和人类之间发生变化,研究人员开发了Sperm-seq技术,这是一种能同时分析成千上万个单精子基因组的方法。

研究人员对来自20个精子供体的31,228个人精子基因组进行了分析,确定了813,122个交叉点和787个非整倍染色体。供体精子的非整倍体率为每配子0.01至0.05。交叉部分保护染色体免受减数分裂I期细胞分裂时的非分离作用。

在减数分裂I期,某些染色体和供体进行频繁的非分离,而另一些染色体在减数分裂II期分离失败的次数更多。精子基因组分析还揭示出许多基因组异常,其无法通过简单的非分离来解释。从交叉速率到交叉位置和分离、一种交叉干扰的量度、不同的重组表型在个体和细胞之间变化很大。该研究结果可与早期的研究结果整合为一个统一的模型,即核心机制、减数分裂染色体的可变物理收缩会在不同的减数分裂表型中产生个体以及细胞间的差异。

据悉,虽然减数分裂是繁殖所必需的,但同时该过程也是易变且容易出错的。配子之间、性别之间以及同性人类之间的染色体交换速率各不相同,并且染色体错位导致异常的染色体数(非整倍性)。

附:英文原文

Title: Insights into variation in meiosis from 31,228 human sperm genomes

Author: Avery Davis Bell, Curtis J. Mello, James Nemesh, Sara A. Brumbaugh, Alec Wysoker, Steven A. McCarroll

Issue&Volume: 2020-06-03

Abstract: 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)1,2,3,4,5,6,7,8. 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 many genomic 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.

DOI: 10.1038/s41586-020-2347-0

Source: https://www.nature.com/articles/s41586-020-2347-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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