Open AccessConsequences of aneuploidy in human fibroblasts with trisomy 21
Author(s) -
Sunyoung Hwang,
Paola Cavaliere,
Rui Li,
Lihua Julie Zhu,
Noah Dephoure,
Eduardo M. Torres
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2014723118
Subject(s) - aneuploidy , trisomy , down syndrome , biology , chromosome 21 , gene dosage , genetics , chromosome , gene , gene expression
Significance An abnormal number of chromosomes or aneuploidy accounts for most spontaneous abortions, as missegregation of a single chromosome during development is often lethal. Only individuals with trisomy 21, which causes Down syndrome, can live to adulthood but show cognitive disabilities, increased risk for leukemias, autoimmune disorders, and clinical symptoms associated with premature aging. The mechanisms by which aneuploidy affects cellular function to cause Down syndrome are not understood. Our studies revealed that aneuploidy causes several defects in cells from individuals with Down syndrome. These include increased gene and protein expression, lower viability, and increased dependency on serine to proliferate. Our studies establish a critical role of aneuploidy, independent of triplicated gene identity, in driving cellular defects associated with trisomy 21.