Department of Molecular, Cell and Cancer Biology
Cell Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities
An extra copy of chromosome 21 causes Down syndrome, the most common genetic disease in humans. The mechanisms contributing to aneuploidy-related pathologies in this syndrome, independent of the identity of the triplicated genes, are not well defined. To characterize aneuploidy-driven phenotypes in trisomy 21 cells, we performed global transcriptome, proteome, and phenotypic analyses of primary human fibroblasts from individuals with Patau (trisomy 13), Edwards (trisomy 18), or Down syndromes. On average, mRNA and protein levels were increased by 1.5-fold in all trisomies, with a subset of proteins enriched for subunits of macromolecular complexes showing signs of posttranscriptional regulation. These results support the lack of evidence for widespread dosage compensation or dysregulation of chromosomal domains in human autosomes. Furthermore, we show that several aneuploidy-associated phenotypes are present in trisomy 21 cells, including lower viability and increased dependency on serine-driven lipid synthesis. Our studies establish a critical role of aneuploidy, independent of triplicated gene identity, in driving cellular defects associated with trisomy 21.
Down syndrome, aneuploidy, dosage compensation, sphingolipids, trisomy 21
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Copyright © 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
DOI of Published Version
Hwang S, Cavaliere P, Li R, Zhu LJ, Dephoure N, Torres EM. Consequences of aneuploidy in human fibroblasts with trisomy 21. Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2014723118. doi: 10.1073/pnas.2014723118. PMID: 33526671; PMCID: PMC8017964. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Hwang S, Cavaliere P, Li R, Zhu L(, Dephoure N, Torres EM. (2021). Consequences of aneuploidy in human fibroblasts with trisomy 21. Open Access Publications by UMMS Authors. https://doi.org/10.1073/pnas.2014723118. Retrieved from https://escholarship.umassmed.edu/oapubs/4618
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.