Age- and tissue-specific variation of X chromosome inactivation ratios in normal women

The incidence of skewed X-inactivation in normal women is controversial, wi th up to 10-fold differences being reported by different authors. In order to clarify this issue, we have conducted a survey of the X-inactivation pat terns in 270 informative females from various age groups, using the androge n receptor gene/polymerase chain reaction assay. Results obtained by using DNA extracted from blood samples show that the incidence of severe skewing (defined here as ratios greater than or equal to 90:10) is relatively commo n and increases with age (P<0.05), occurring in 7% of women under 25 years of age, and 16% of women over 60. In order to study tissue-specific pattern s of X-inactivation, samples of both buccal and urinary epithelia were also obtained from 88 of the females studied. Although there was a significant association of the X-inactivation ratios between each tissue in most indivi duals, wide variations were apparent in some cases, making accurate extrapo lations between tissues impossible. The degree of correlation between each tissue also fell markedly with age. Our data are consistent with the hypoth esis that the major factors in the aetiology of skewed X-inactivation are s econdary selection processes.