What is skewed X chromosome inactivation?
X chromosome inactivation (XCI) — a process originally hypothesized by Lyon in 1961 (1) and by which one of the two copies of the X chromosome present in females is inactivated — achieves dosage equivalency for X-linked genes between XY males and XX females. A critical tenet of this hypothesis was that the initial choice of which X (maternal or paternal) to inactivate was random but then this choice was stably inherited. An individual cell’s decision to inactivate either the paternal or maternal X is made early in development, at approximately the time of implantation (2). A deviation from equal (50%) inactivation of each parental allele is known as skewing, with common criteria for “skewed” inactivation being arbitrarily defined as the observation of inactivation of the same allele in 75% or 80% of cells (and very skewed inactivation resulting in 90% or 95% of cells with the same allele inactive). A solid understanding of the causes of skewed XCI is needed because skewing is often use
