X-chromosome inactivation and human genetic disease

The inactivation of one X-chromosome in females in early development is the process by which the effective dosage of X-linked genes is equalized between XX females and XY males. The mechanism that brings this about is the subject of intense research. The X-linked gene Xist is a key player, which is necessary but not sufficient for the initiation of X-inactivation. It codes for an untranslated RNA that coats the inactive X-chromosome, which takes on properties characteristic of heterochromatin, but how this change in chromatin is brought about remains unknown. Because of X-inactivation, females heterozygous for X-linked genes are mixtures of two types of cells and show a variable phenotype. The proportions of the two types of cells can depart from equality due to cell selection either at the tissue or whole organism level. In rare cases, changes in the Xist gene can cause skewing of X-inactivation. A few genes escape from X-inactivation either wholly or partially.

X-chromosome inactivation is a physiological mechanism that equalizes gene-dosage effects on the sex chromosomes. The occurrence of this normal process affects the phenotype seen in females carrying X-linked mutant genes or chromosome anomalies.