Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
Naoka Tamura
Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
Alice Mazzagatti
Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
Nadeem Shaikh
Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
Tineke van Lingen
Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
Bjorn Bakker
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, Groningen 9713, the Netherlands
Diana Carolina Johanna Spierings
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, Groningen 9713, the Netherlands
Elina Vladimirou
UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK
Floris Foijer
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, Groningen 9713, the Netherlands
Sarah Elizabeth McClelland
Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK; Corresponding author
Summary: 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. : Worrall et al. show that individual human chromosomes can respond differently to defects in mitosis that lead to chromosome mis-segregation. Following nocodazole washout, chromosomes 1 and 2 are particularly prone to a weakening of centromeric cohesion and elevated rates of chromosome lagging during anaphase. Keywords: ImageStream, chromosome mis-segregation, cohesion fatigue, aneuploidy
