{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zito A"],"funding":["NIHR BioResource","European Research Council","Medical Research Council","Wellcome Trust"],"pagination":["e1010556"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9942974"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(2)"],"pubmed_abstract":["X-chromosome inactivation (XCI) silences one X in female cells to balance sex-differences in X-dosage. A subset of X-linked genes escape XCI, but the extent to which this phenomenon occurs and how it varies across tissues and in a population is as yet unclear. To characterize incidence and variability of escape across individuals and tissues, we conducted a transcriptomic study of escape in adipose, skin, lymphoblastoid cell lines and immune cells in 248 healthy individuals exhibiting skewed XCI. We quantify XCI escape from a linear model of genes' allelic fold-change and XIST-based degree of XCI skewing. We identify 62 genes, including 19 lncRNAs, with previously unknown patterns of escape. We find a range of tissue-specificity, with 11% of genes escaping XCI constitutively across tissues and 23% demonstrating tissue-restricted escape, including cell type-specific escape across immune cells of the same individual. We also detect substantial inter-individual variability in escape. Monozygotic twins share more similar escape than dizygotic twins, indicating that genetic factors may underlie inter-individual differences in escape. However, discordant escape also occurs within monozygotic co-twins, suggesting environmental factors also influence escape. Altogether, these data indicate that XCI escape is an under-appreciated source of transcriptional differences, and an intricate phenotype impacting variable trait expressivity in females."],"journal":["PLoS genetics"],"pubmed_title":["Escape from X-inactivation in twins exhibits intra- and inter-individual variability across tissues and is heritable."],"pmcid":["PMC9942974"],"funding_grant_id":["MR/R023131/1","European Community's Seventh Framework Programme (FP7/2007-2013) to TwinsUK study","Wellcome Trust funds to TwinsUK study","MR/L016311/1","NIHR BioResource to TwinsUK study","MR/L016311/1 to eMedLab Medical Bioinformatics infrastructure"],"pubmed_authors":["Roberts AL","Nardone S","Visconti A","Andres-Ejarque R","Small KS","Zito A","Rossi N","El-Sayed Moustafa JS","Falchi M"],"additional_accession":[]},"is_claimable":false,"name":"Escape from X-inactivation in twins exhibits intra- and inter-individual variability across tissues and is heritable.","description":"X-chromosome inactivation (XCI) silences one X in female cells to balance sex-differences in X-dosage. A subset of X-linked genes escape XCI, but the extent to which this phenomenon occurs and how it varies across tissues and in a population is as yet unclear. To characterize incidence and variability of escape across individuals and tissues, we conducted a transcriptomic study of escape in adipose, skin, lymphoblastoid cell lines and immune cells in 248 healthy individuals exhibiting skewed XCI. We quantify XCI escape from a linear model of genes' allelic fold-change and XIST-based degree of XCI skewing. We identify 62 genes, including 19 lncRNAs, with previously unknown patterns of escape. We find a range of tissue-specificity, with 11% of genes escaping XCI constitutively across tissues and 23% demonstrating tissue-restricted escape, including cell type-specific escape across immune cells of the same individual. We also detect substantial inter-individual variability in escape. Monozygotic twins share more similar escape than dizygotic twins, indicating that genetic factors may underlie inter-individual differences in escape. However, discordant escape also occurs within monozygotic co-twins, suggesting environmental factors also influence escape. Altogether, these data indicate that XCI escape is an under-appreciated source of transcriptional differences, and an intricate phenotype impacting variable trait expressivity in females.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-06-27T03:20:08.793Z","creation":"2025-02-19T02:24:05.716Z"},"accession":"S-EPMC9942974","cross_references":{"pubmed":["36802379"],"doi":["10.1371/journal.pgen.1010556"]}}