التفاصيل البيبلوغرافية
| العنوان: |
Escape from X-inactivation in twins exhibits intra- and inter-individual variability across tissues and is heritable. |
| المؤلفون: |
Zito, Antonino, Roberts, Amy L., Visconti, Alessia, Rossi, Niccolo', Andres-Ejarque, Rosa, Nardone, Stefano, El-Sayed Moustafa, Julia S., Falchi, Mario, Small, Kerrin S. |
| المصدر: |
PLoS Genetics; 2/21/2023, Vol. 18 Issue 2, p1-23, 23p |
| مصطلحات موضوعية: |
X chromosome, LYMPHOBLASTOID cell lines, TWINS, NATURE & nurture, ECOLOGICAL genetics, TISSUES |
| مستخلص: |
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. Author summary: The difference in the number of X-chromosomes between mammalian males and females is compensated by a process known as X-chromosome inactivation (XCI), which turns off one of a female's X chromosomes. XCI is incomplete: some sections of the silenced X chromosome escape inactivation. The 'escape' is complex, and can vary across tissues and potentially across individuals. Because the X chromosome is enriched of genes with immune and neurological functions, this phenomenon has high biomedical relevance. We studied the extent to which escape occurs and varies across tissues and individuals in a large population of twins. We identify novel candidate escape genes, and genes whose escape is specific to a tissue or immune cell type. There is also substantial variability in escape across individuals. Using data from twins, which enable the assessment of the influence of genetics and environment on a trait, we found that both genetic and environmental factors influence escape. Our results allow detailed characterization of escape, and suggest that escape may influence disease risk and phenotype differences between the sexes, and within females. [ABSTRACT FROM AUTHOR] |
|
Copyright of PLoS Genetics is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder