Non-random Mis-segregation of Human Chromosomes

Cell Rep. 2018 Jun 12;23(11):3366-3380. doi: 10.1016/j.celrep.2018.05.047.


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.

Keywords: ImageStream; aneuploidy; chromosome mis-segregation; cohesion fatigue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase
  • Aneuploidy
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Chromosome Segregation* / drug effects
  • Chromosomes, Human / genetics
  • Chromosomes, Human / metabolism*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kinetochores / metabolism
  • Nocodazole / pharmacology
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Single-Cell Analysis


  • Carrier Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • WAPL protein, human
  • Nocodazole