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.
Category
Chromosomal abnormality
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Chromosomal anomalies, excluding gene mutations
Sex chromosome anomalies
LD51 Structural anomalies of chromosome X, excluding Turner syndrome
H00994 Familial skewed X-chromosome inactivation
Comment
Hemophilia A is described in H00219.
XIST [HSA:7503]
Familial skewed X inactivation and X-linked mutations: unbalanced X inactivation is a powerful means to ascertain X-linked genes that affect cell proliferation.
Journal
Am J Hum Genet 62:1555-7; author reply 1557-8 (1998) DOI:10.1086/301858
