Open access
Date
2015Type
- Review Article
ETH Bibliography
yes
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Abstract
X-chromosome inactivation (XCI) is the mechanism by which mammals compensate gene dosage differences between males and females. XCI is required for female development and has implications for human disease. As a result, a single X chromosome is transcriptionally active in both male and female cells. Functional hemizygosity of the X chromosomes greatly predisposes to phenotypic consequences of mutations. In females, X chromosomes are randomly chosen to become inactivated leading to a mosaic pattern of cells expressing genes from either chromosome. This facilitates the masking of phenotypic consequences of heterozygous X-linked mutations. Skewing of XCI in favor of one chromosome can result in increased severity of disease symptoms, if the X chromosome with a gene mutation remains preferentially active. In addition, phenotypic masking of X-linked mutations is not always observed. Rett syndrome represents a paradigm of this statement. Dosage compensation can also mask some aspects of sex chromosome aneuploidies. X-chromosome aneuploidies include Klinefelter, Turner, and X-trisomy syndromes. In all these cases, a single active X chromosome is present. However, in those cases with two or more X chromosomes, some genes from the inactivated X chromosome escape from XCI becoming active. Therefore, dose imbalances of escape genes cause pathologies. Defects in the structure and silencing of the inactive X chromosome are further observed in human pluripotent stem cells and in certain tumors. Taken together, these findings suggest that aspects of XCI are relevant for a large number of human diseases. Here we review basic and clinical research on XCI with the aim of illustrating connections and highlighting opportunities for future investigation. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000102871Publication status
publishedExternal links
Journal / series
Advances in Genomics and GeneticsVolume
Pages / Article No.
Publisher
Dove Medical PressSubject
XCI; X-linked diseases; Sex chromosome aneuploidies; iPSCs; CancerOrganisational unit
03978 - Wutz, Anton / Wutz, Anton
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ETH Bibliography
yes
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