X-linked competition — implications for human development and disease
File(s)
Accepted version
Author(s)
Boone, Philip M
Buenaventura, Teresa
King, James WD
Merkenschlager, Matthias
Type
Journal Article
Abstract
During early mammalian female development, X chromosome inactivation leads to random transcriptional silencing of one of the two X chromosomes. This inactivation is maintained through subsequent cell divisions, leading to intra-individual diversity, whereby cells express either the maternal or paternal X chromosome. Differences in X chromosome sequence content can trigger competitive interactions between clones that may alter organismal development and skew the representation of X-linked sequence variants in a cell-type-specific manner — a recently described phenomenon termed X-linked competition in analogy to existing cell competition paradigms. Skewed representation can define the phenotypic impact of X-linked variants, for example, the manifestation of disease in female carriers of X-linked disease alleles. Here, we review what is currently known about X-linked competition, reflect on what remains to be learnt and map out the implications for X-linked human disease.
Date Issued
2025-08-01
Date Acceptance
2025-03-28
Citation
Nature Reviews Genetics, 2025, 26, pp.571-580
ISSN
1471-0056
Publisher
Springer Science and Business Media LLC
Start Page
571
End Page
580
Journal / Book Title
Nature Reviews Genetics
Volume
26
Copyright Statement
Copyright © 2025, Springer Nature Limited. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Publication Status
Published
Date Publish Online
2025-05-12