Aneuploidy Causes Non-genetic Individuality

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 chromoso...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2017-04, Vol.169 (2), p.229-242.e21
Main Authors: Beach, Rebecca R., Ricci-Tam, Chiara, Brennan, Christopher M., Moomau, Christine A., Hsu, Pei-hsin, Hua, Bo, Silberman, Rebecca E., Springer, Michael, Amon, Angelika
Format: Article
Language:English
Subjects:
Aneuploidy
Animals
biological noise
cancer
Cell Cycle
Cell Division
cell-to-cell variability
DNA Damage
Down syndrome
gene dosage effects
Gene Expression Regulation
Genetic Heterogeneity
Kinetics
Mice
non-genetic heterogeneity
Phenotype
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. [Display omitted] •Non-genetic individuality is a universal characteristic of the aneuploid state•Chromosome-scale changes in gene dosage decrease robustness of biological networks•Cells with same aneuploid karyotype show cell-cycle and gene expression variability•Inbred trisomic mouse embryos exhibit variability in morphology Aneuploidy leads to phenotypic variability, even in cells that are karyotypically identical.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2017.03.021