Consequences of aneuploidy in human fibroblasts with trisomy 21

Abstract

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.