X-chromosome inactivation patterns depend on age and tissue but not conception method in humans

Abstract

Female somatic X-chromosome inactivation (XCI) balances the X-linked transcriptional dosages between the sexes, randomly silencing the maternal or paternal X chromosome in each cell of 46,XX females. Skewed XCI toward one parental X has been observed in association with ageing and in some female carriers of X-linked diseases. To address the problem of non-random XCI, we quantified the XCI skew in different biological samples of naturally conceived females of different age groups and girls conceived after in vitro fertilization (IVF). Generally, XCI skew differed between saliva, blood, and buccal swabs, while saliva and blood had the most similar XCI patterns in individual females. XCI skew increased with age in saliva, but not in other tissues. We showed no significant differences in the XCI patterns in tissues of naturally conceived and IVF females. The gene expression profile of the placenta and umbilical cord blood was determined depending on the XCI pattern. The increased XCI skewing in the placental tissue was associated with the differential expression of several genes out of 40 considered herein. Notably, skewed XCI patterns (> 80:20) were identified with significantly increased expression levels of four genes: CD44, KDM6A, PHLDA2, and ZRSR2. The differences in gene expression patterns between samples with random and non-random XCI may shed new light on factors contributing to the XCI pattern outcome and indicate new paths in future research on the phenomenon of XCI skewing.

Measuring X inactivation skew for retinal diseases with adaptive nanopore sequencing

“…With lower coverage, the two groups may not be sufficiently sampled and cluster definition becomes more difficult. It is important to note that skew can vary from tissue to tissue within one individual [4], and certain tissues become more clonal/skewed with age [32, 33]. Therefore there is a risk in extrapolating to a different, inaccessible, disease-relevant tissue.…”

First report on female monozygotic twins discordant for congenital nephrogenic diabetes insipidus

“…This observation strengthened the notion that analysis of XCI patterns in peripheral leukocytes is insufficient. The XCI pattern may differ in different tissues and vary over time (Juchniewicz et al, 2023; Wong et al, 2011). For example, Juchniewicz et al (2023) reported that XCI skew differed between saliva, blood, and buccal swabs in females.…”

“…The XCI pattern may differ in different tissues and vary over time (Juchniewicz et al, 2023; Wong et al, 2011). For example, Juchniewicz et al (2023) reported that XCI skew differed between saliva, blood, and buccal swabs in females. Other mechanisms, such as environmental factors and DNA methylation, may also be involved.…”