No evidence that skewing of X chromosome inactivation patterns is transmitted to offspring in humans

Skewing of X chromosome inactivation (XCI) can occur in normal females and increases in tissues with age. The mechanisms underlying skewing in normal females, however, remain controversial. To better understand the phenomenon of XCI in nondisease states, we evaluated XCI patterns in epithelial and h...

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Published in:The Journal of clinical investigation 2008-01, Vol.118 (1), p.333-341
Main Authors: Bolduc, Véronique, Chagnon, Pierre, Provost, Sylvie, Dubé, Marie-Pierre, Belisle, Claude, Gingras, Marianne, Mollica, Luigina, Busque, Lambert
Format: Article
Language:English
Subjects:
Adult
Age Factors
Androgens
Biomedical research
Chromosomes, Human, X - physiology
Cohort Studies
Embryos
Epithelial Cells - cytology
Epithelial Cells - physiology
Female
Females
Gene expression
Genes
Genetic transcription
Health aspects
Hematopoietic Stem Cells - physiology
Humans
Incidence
Infant, Newborn
Mothers
Mutation
Quantitative Trait Loci - physiology
X chromosome
X Chromosome Inactivation - physiology
X chromosomes
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Summary:Skewing of X chromosome inactivation (XCI) can occur in normal females and increases in tissues with age. The mechanisms underlying skewing in normal females, however, remain controversial. To better understand the phenomenon of XCI in nondisease states, we evaluated XCI patterns in epithelial and hematopoietic cells of over 500 healthy female mother-neonate pairs. The incidence of skewing observed in mothers was twice that observed in neonates, and in both cohorts, the incidence of XCI was lower in epithelial cells than hematopoietic cells. These results suggest that XCI incidence varies by tissue type and that age-dependent mechanisms can influence skewing in both epithelial and hematopoietic cells. In both cohorts, a correlation was identified in the direction of skewing in epithelial and hematopoietic cells, suggesting common underlying skewing mechanisms across tissues. However, there was no correlation between the XCI patterns of mothers and their respective neonates, and skewed mothers gave birth to skewed neonates at the same frequency as nonskewed mothers. Taken together, our data suggest that in humans, the XCI pattern observed at birth does not reflect a single heritable genetic locus, but rather corresponds to a complex trait determined, at least in part, by selection biases occurring after XCI.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI33166