Aneuploidies involving the X chromosome are distinct from trisomies of autosomes because this chromosome is subject to dosage compensation mediated by a large non-coding RNA Xist (Loda et al. As for monosomies, females with a single X chromosome have Turner’s syndrome (Sybert and McCauley 2004). Females can also survive with three X chromosomes (Triple X syndrome) (Jacobs 1979 Otter et al. An extra copy of the X chromosome in males causes Klinefelter’s syndrome (XXY), the most common aneuploidy after Down syndrome (Jacobs and Strong 1959 Los and Ford 2023). Aneuploidies involving sex chromosomes are also tolerated. The most common aneuploidy in humans that is compatible with life is the trisomy of autosome 21, which causes Down syndrome (cdc.gov). The existence of other genomic alterations, including gene mutations, focal amplifications, chromosomal translocations, and chromosomal rearrangements promoted by chromothripsis, in addition to karyotypic heterogeneity caused by ongoing genomic instability and the complex tumor microenvironments depending on tumor type, can influence the role of aneuploidy in cancer (Burgess 2011, Banerji et al. Recent studies suggest that the role of aneuploidy in tumor biology is complex and context-dependent (Ben-David and Amon 2020). In addition, aneuploidy is a hallmark of cancer cells, and it has long been hypothesized that aneuploidy plays an active role in tumorigenesis (Boveri 2008). Understanding how aneuploidy affects cell physiology is important because the incidence of aneuploidy is associated with human disease and aging (Nagaoka et al. Understanding how aneuploidy affects cell physiology can reveal insights into the selective pressure that aneuploid cancer cells must overcome to support unlimited proliferation.Īneuploidy is defined as the cellular state of having a chromosome number that is not an exact multiple of the haploid number. Despite the adverse effects on cell physiology, aneuploidy is a hallmark of cancer cells. These findings reveal important insights into the possible pathological role of aneuploidy in Down syndrome. Notably, abnormal nuclear morphology of aneuploid cells is associated with increased metabolic demand for de novo synthesis of sphingolipids. Among the conserved aneuploidy-associated phenotypes observed in yeast and human cells are lower viability, increased gene expression, increased protein synthesis and turnover, abnormal nuclear morphology, and altered metabolism. The latter, referred to as aneuploidy-associated phenotypes, are the focus of this review. Several studies support the hypothesis that gaining an extra copy of a chromosome causes gene-specific phenotypes and phenotypes independent of the identity of the genes encoded within that chromosome. In contrast, the cell that gains a chromosome can survive. At the cellular level, mistakes in the segregation of a single chromosome leading to a cell losing a chromosome are lethal. While individuals with trisomy 18 or 13 die soon after birth, people with Down syndrome live to adulthood but have intellectual disabilities and are prone to multiple diseases. Excluding sex chromosomes, viable aneuploidies in humans include trisomies of chromosomes 21, 18, or 13, which cause Down, Edwards, or Patau syndromes, respectively. Mistakes in chromosome segregation leading to aneuploidy are the primary cause of miscarriages in humans.
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