Variability in X Chromosome Inactivation Patterns in Multiple Tissues of Elderly Females

Every female somatic cell has 2 X chromosomes, one paternally (Xp) and one maternally derived (Xm). In order to reach an approximately equal dosage effect of genes from each X, one is inactivated in an apparently random manner. Most females show a slight detectable bias towards one X, a small minority showing a marked preference. Significant bias is termed skewing. Acquired age related skewing in peripheral blood has been confirmed by several studies.Secondary selection may occur when a mutation on the either the Xp or Xm confers a survival advantage to a stem cell or its projeny; conversely if the mutation is detrimental, cells bearing that X will be selected against. As well as determining phenotype in X-linked disorders, skewing influences several renal diseases and may be implicated in autoimmune diseases such as scleroderma and systemic lupus. Increased skewing rates have been linked to recurrent pregnancy loss, pre-eclampsia and autism. The role of acquired or chanceskewing as a risk factor for malignancy is currently under investigation.To date most of the studies of X inactivation have been on peripheral blood with a few investigating other relatively accessible tissues such as hair bulb epithelium. We chose to investigate ratios in females >60 years of age in which age related skewing was more likely to occur. Our results show a general concordance between most tissues of the same individual with skewing being evident in the spleen of 2/11 and in the liver of 3/11 females. This study suggests that age related skewing may occur in the liver as well as the haematopoietic system This is the first study looking specifically at skewing ratios in multiple inaccessible tissues of elderly females and the first case reported of skewing in both the liver and spleen of an elderly female. These organs skewed in the same direction supporting the growingevidence that skewing is a selective phenomeno