X chromosome inactivation patterns in normal females

Abstract

Since one of the two X chromosomes is randomly inactivated at an early stage of female embryonic development, X-linked markers have been used to study the origin and development of various neoplastic disorders in affected heterozygous women; clonality assays have provided a useful tool to the understanding of the mechanisms underlying the development of neoplasia. Recently, a technique of clonal analysis has been devised that takes advantage of a highly polymorphic short tandem repeat within the X-linked human androgen receptor (AR) gene, resulting in a heterozygosity rate approaching 90%. The rapid expansion of the number of women now suitable for X inactivation analysis has however given rise to new controversies, one of the more troublesome being the possibility of a modification of the pattern of X- chromosome inactivation pattern in blood cells of elderly women. In the present study we analyze with the AR assay a group of 166 healthy females aged between 8 and 94 years, with no history of genetic or neoplastic familial disorders. We failed to find any correlation between age and X- chromosome inactivation pattern (r = 0.17), even subdividing the subjects in different age groups according to the criteria used by other researchers, and therefore reaffirm that, when tested for with well-standardized and accurate criteria, extremely unbalanced inactivation of the X chromosome is a truly uncommon phenomenon in normal women.