Skewed X inactivation in X-linked disorders.
X chromosome inactivation is a process by which the dosage of proteins transcribed from genes on the X chromosome is equalized between males (XY) and females (XX) through the silencing of most genes on one of the two X chromosomes in females. Although the choice of which of the two X's is inactivated is entirely random, not all women have a 50:50 ratio of cells with one or the other X chromosomes active. A number of different mechanisms lead to extremely skewed ratios and this can result in expression of the phenotype of X-linked recessive disorders in females. Nonrandom X inactivation patterns are also associated with selective female survival in male-lethal X-linked dominant disorders or with variable severity of the phenotype in women carrying X-linked dominant mutations. These features are important for the study and gene identification of X-linked disorders and for counseling of affected families.
Van den Veyver
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Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
D004200:Diseases in Twins / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D018628:Gene Dosage; D005799:Genes, Dominant / Q000235:genetics; D005804:Genes, Lethal / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008297:Male; D009030:Mosaicism / Q000235:genetics; D009154:Mutation / Q000235:genetics; D012641:Selection, Genetic; D012729:Sex Chromosome Aberrations; D012867:Skin / Q000378:metabolism; D013269:Stochastic Processes; D014960:X Chromosome / Q000235:genetics*