Aneuploidy Causes Non-genetic Individuality
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nihms863089.pdf
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Author(s)
Ricci-Tam, Chiara
Hua, Bo
Springer, Michael
Brennan, Christopher M
Moomau, Christine Anne
Hsu, Pei-Hsin
Silberman, Rebecca Estelle
Amon, Angelika B.
Thorburn, Rebecca Ruth
Date Issued
April 2017
Journal
Cell
Publisher
Elsevier BV
Citation
Beach, Rebecca R. et al. “Aneuploidy Causes Non-Genetic Individuality.” Cell 169, 2 (April 2017): 229–242 © 2017 Elsevier Inc
Version
Author's final manuscript
Abstract
Phenotypic variability is a hallmark of diseases involving chromosome gains and losses, such as Down syndrome and cancer. Allelic variances have been thought to be the sole cause of this heterogeneity. Here, we systematically examine the consequences of gaining and losing single or multiple chromosomes to show that the aneuploid state causes non-genetic phenotypic variability. Yeast cell populations harboring the same defined aneuploidy exhibit heterogeneity in cell-cycle progression and response to environmental perturbations. Variability increases with degree of aneuploidy and is partly due to gene copy number imbalances, suggesting that subtle changes in gene expression impact the robustness of biological networks and cause alternate behaviors when they occur across many genes. As inbred trisomic mice also exhibit variable phenotypes, we further propose that non-genetic individuality is a universal characteristic of the aneuploid state that may contribute to variability in presentation and treatment responses of diseases caused by aneuploidy. Keywords:
aneuploidy; non-genetic heterogeneity; cell-to-cell variability; gene dosage effects; biological noise; Down syndrome; cancer
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELL.2017.03.021
