title: Skewed X inactivation in healthy individuals and in different diseases.
abstract: In female mammalian cells, one of the two X chromosomes is inactivated in early embryonic life. Females are mosaics for two cell populations, one with the maternal and one with the paternal X as the active chromosome. Skewed X inactivation is arbitrarily defined, often as a pattern where 80% or more of the cells show a preferential inactivation of one X chromosome. Inactivation is presumed to be permanent for all descendants of a cell; however, after about 55 years of age, the frequency of skewed X inactivation in peripheral blood cells increases, probably through selection. Unfavourable skewing of X inactivation, where the X chromosome carrying a mutant allele is the predominantly active X, has been found in affected female carriers of several X-linked disorders; however, for many X-linked disorders, a consistent relationship between the pattern of X inactivation and clinical phenotype has been difficult to demonstrate. One reason for this may be that peripheral blood cells are not a representative or relevant tissue in many disorders. In some severe X-linked disorders, post-inactivation selection takes place against the X chromosome carrying the mutant allele, leading to a completely skewed X-inactivation pattern. Skewed X inactivation has also been reported in young females with breast cancer, and may indicate an effect of X-linked genes on the development of this condition.
  
  
  CONCLUSIONS
  The process of X inactivation and the resultant degree of skewing is clearly important for the expression of genetic diseases. It is also important to consider, however, that under normal conditions the frequency of skewed X inactivation increases with age in peripheral blood cells. Analysis of the expression of a large proportion of the genes on the X chromosome has revealed that X-chromosome inactivation is more heterogeneous than previously thought.
authors.affiliation: Department of Medical Genetics, Rikshospitalet, University Hospital, Oslo, Norway. k.h.orstavik@medisin.uio.no
authors.forename: Karen Helene
authors.initials: KH
authors.lastname: Ørstavik
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics; D000375:Aging / Q000235:genetics; D000818:Animals; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006801:Humans; D012729:Sex Chromosome Aberrations; D014960:X Chromosome; D049951:X Chromosome Inactivation / Q000235:genetics*