斯托尔斯医学研究所Jennifer L. Gerton研究组在研究中取得进展。他们揭示了人类罗伯逊染色体的形成和繁殖。2025年9月24日出版的《自然》发表了这项成果。

这里该研究团队描述了三条人类罗伯逊染色体的完整装配。研究人员在SST1中发现了一个共同的断点，这是一个位于染色体13,14和21上的大卫星DNA，通常发生罗伯逊易位。SST1包含在14号染色体上一个更大的共享同源结构域7中，这使得减数分裂交叉事件成为两条染色体长臂的主题。罗伯逊染色体有两个着丝粒DNA阵列，失去了所有的核糖体DNA。在两种情况下，该课题组研究人员发现两个着丝体阵列中只有一个是有效的。在第三种情况下，两个阵列都可以是活动的，但由于它们的接近，它们通常被单个外部着丝点包围。它们是排列接近和着丝粒表观遗传变化的结合，有利于罗伯逊染色体的稳定繁殖。对黑猩猩和倭黑猩猩基因组组装的研究表明，14号染色体的倒置是人类基因组所特有的。在分子水平上解决人类罗伯逊染色体的结构和表观遗传特征，为更广泛地理解结构变异和染色体进化的分子机制提供了基础。

据了解，罗伯逊染色体是自然界中常见的一种变异染色体。每800人中就有1人携带这些染色体，它们可能导致不育、三体和癌症发病率增高。一个多世纪以来，人们已经从细胞遗传学的角度认识到了它们，但它们的起源仍然未知。

附：英文原文

Title: The formation and propagation of human Robertsonian chromosomes

Author: de Lima, Leonardo Gomes, Guarracino, Andrea, Koren, Sergey, Potapova, Tamara, McKinney, Sean, Rhie, Arang, Solar, Steven J., Seidel, Chris, Fagen, Brandon L., Walenz, Brian P., Bouffard, Gerard G., Brooks, Shelise Y., Peterson, Michael, Hall, Kate, Crawford, Juyun, Young, Alice C., Pickett, Brandon D., Garrison, Erik, Phillippy, Adam M., Gerton, Jennifer L.

Issue&Volume: 2025-09-24

Abstract: Robertsonian chromosomes are a type of variant chromosome that is commonly found in nature. Present in 1 in 800 humans, these chromosomes can underlie infertility, trisomies and increased cancer incidence1,2,3,4,5. They have been recognized cytogenetically for more than a century6, yet their origins have remained unknown. Here we describe complete assemblies of three human Robertsonian chromosomes. We identified a common breakpoint in SST1, a macrosatellite DNA located on chromosomes 13, 14 and 21, which commonly undergo Robertsonian translocation. SST1 is contained within a larger shared homology domain7 that is inverted on chromosome 14, which enables a meiotic crossover event that fuses the long arms of two chromosomes. Robertsonian chromosomes have two centromeric DNA arrays and have lost all ribosomal DNA. In two cases, we find that only one of the two centromeric arrays is active. In the third case, both arrays can be active but owing to their proximity, they are often encompassed by a single outer kinetochore. Thus a combination of array proximity and epigenetic changes in centromeres facilitates the stable propagation of Robertsonian chromosomes. Investigation of the assembled genomes of chimpanzee and bonobo highlights that the inversion on chromosome 14 is unique to the human genome. Resolving the structural and epigenetic features of human Robertsonian chromosomes at a molecular level provides a foundation for a broader understanding of the molecular mechanisms of structural variation and chromosome evolution.

DOI: 10.1038/s41586-025-09540-8

Source: https://www.nature.com/articles/s41586-025-09540-8