X Chromosome–Inactivation Patterns of 1,005 Phenotypically Unaffected Females

TLDR: In this article, the significance of skewed patterns of X-chromosome inactivation was evaluated in a population of >1,000 phenotypically unaffected females, and it was shown that only a very small proportion of unaffected females showed significantly skewed inactivation, especially during the neonatal period.

Abstract: X-chromosome inactivation is widely believed to be random in early female development and to result in a mosaic distribution of cells, approximately half with the paternally derived X chromosome inactive and half with the maternally derived X chromosome inactive. Significant departures from such a random pattern are hallmarks of a variety of clinical states, including being carriers for severe X-linked diseases or X-chromosome cytogenetic abnormalities. To evaluate the significance of skewed patterns of X inactivation, we examined patterns of X inactivation in a population of >1,000 phenotypically unaffected females. The data demonstrate that only a very small proportion of unaffected females show significantly skewed inactivation, especially during the neonatal period. By comparison with this data set, the degree of skewed inactivation in a given individual can now be quantified and evaluated for its potential clinical significance.