Definition:

X chromosome inactivation is the transcriptional silencing of the majority of genes on one of the two X chromosomes in mammalian females that equalizes the effective dosage of X-linked genes between XX females and XY males. Therefore mammalian females are mosaics for two cell populations with different X chromosomes active. Skewed X inactivation is defined as a pattern where the cells show a preferential inactivation of one X chromosome. The incidence of skewing is shown to be age dependent but in general, skewing does not have any biologic consequence. However, in cases of individuals with nonlethal mutated allele, degree of skewing is predisposing to genetic diseases such as hemophilia A. The key player is the X inactivation-specific transcript (XIST), an X-linked untranslated RNA that coats the inactive X-chromosome.