RAPID COMMUNICATION Nonrandom X-Inactivation Patterns in Normal Females: Lyonization Ratios Vary With Age

The utility of X-inactivation based clonality assays for evalu-ation of human neoplasia is well-documented. However, ex-cessive Lyonization is a potential limitation of these assays, because it mimics clonal derivation of cells. The incidence of excessive Lyonization in healthy females is controversial, with reported incidence varying from 4 % to 33%. Several explanations have been offered for the observed variation, including different criteria for excessive Lyonization, diver-sity of X-linked clonality assays, small population sizes and more recently, tissue specificity of X-inactivation patterns. However, it is also possible that stem cell depletion, clonal hematopoiesis, or selection pressures on blood cells results in an increased incidence of excessive skewing. If any of the latter is true, then the incidence of excessive skewing should increase with age in blood cells. To test this hypothesis