Worrall, JT;
Tamura, N;
Mazzagatti, A;
Shaikh, N;
van Lingen, T;
Bakker, B;
Spierings, DCJ;
... McClelland, SE; + view all
(2018)
Non-random Mis-segregation of Human Chromosomes.
Cell Reports
, 23
(11)
pp. 3366-3380.
10.1016/j.celrep.2018.05.047.
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Abstract
A common assumption is that human chromosomes carry equal chances of mis-segregation during compromised cell division. Human chromosomes vary in multiple parameters that might generate bias, but technological limitations have precluded a comprehensive analysis of chromosome-specific aneuploidy. Here, by imaging specific centromeres coupled with high-throughput single-cell analysis as well as single-cell sequencing, we show that aneuploidy occurs non-randomly following common treatments to elevate chromosome mis-segregation. Temporary spindle disruption leads to elevated mis-segregation and aneuploidy of a subset of chromosomes, particularly affecting chromosomes 1 and 2. Unexpectedly, we find that a period of mitotic delay weakens centromeric cohesion and promotes chromosome mis-segregation and that chromosomes 1 and 2 are particularly prone to suffer cohesion fatigue. Our findings demonstrate that inherent properties of individual chromosomes can bias chromosome mis-segregation and aneuploidy rates, with implications for studies on aneuploidy in human disease.
| Type: | Article |
|---|---|
| Title: | Non-random Mis-segregation of Human Chromosomes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2018.05.047 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2018.05.047 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | ImageStream; chromosome mis-segregation; cohesion fatigue; aneuploidy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10050365 |
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