title: Buccal swab as a reliable predictor for X inactivation ratio in inaccessible tissues.
abstract: BACKGROUND
  As a result of the epigenetic phenomenon of X chromosome inactivation (XCI) every woman is a mosaic of cells with either an inactive paternal X chromosome or an inactive maternal X chromosome. The ratio between inactive paternal and maternal X chromosomes is different for every female individual, and can influence an X-encoded trait or disease. A multitude of X linked conditions is known, and for many of them it is recognised that the phenotype in affected female carriers of the causative mutation is modulated by the XCI ratio. To predict disease severity an XCI ratio is usually determined in peripheral blood samples. However, the correlation between XCI ratios in peripheral blood and disease affected tissues, that are often inaccessible, is poorly understood. Here, we tested several tissues obtained from autopsies of 12 female individuals for patch size and XCI ratio.
  
  
  METHODS
  XCI ratios were analysed using methyl-sensitive PCR-based assays for the AR, PCSK1N and SLITRK4 loci. XCI patch size was analysed by testing the XCI ratio of tissue samples with decreasing size.
  
  
  RESULTS
  XCI patch size was analysed for liver, muscle, ovary and brain samples and was found too small to confound testing for XCI ratio in these tissues. XCI ratios were determined in the easily accessible tissues, blood, buccal epithelium and hair follicle, and compared with ratios in several inaccessible tissues.
  
  
  CONCLUSIONS
  Buccal epithelium is preferable over peripheral blood for predicting XCI ratios of inaccessible tissues. Ovary is the only inaccessible tissue showing a poor correlation to blood and buccal epithelium, but has a good correlation to hair follicle instead.
authors.affiliation: Department of Developmental Biology, Erasmus Medical Centre, Rotterdam, Zuid-Holland, The Netherlands Department of Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, Zuid-Holland, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: de Hoon
authors.affiliation: Department of Pathology, The Netherlands Cancer Institute, Amsterdam, Noord-Holland, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Monkhorst
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, Zuid-Holland, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Riegman
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, Zuid-Holland, The Netherlands.
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.affiliation: Department of Developmental Biology, Erasmus Medical Centre, Rotterdam, Zuid-Holland, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Gribnau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D041321:Chromosomes, Human, X; D005260:Female; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism*; D009928:Organ Specificity; D049951:X Chromosome Inactivation
keywords: Genetic screening/counselling; Genetics; Molecular genetics