On the loss of human sex chromosomes in lymphocytes with age: a quantitative treatment

Abstract

Increasing levels of aneuploidy of the sex chromosomes in human lymphocytes with age have been noted for several decades. The percentage of chromosome Y loss can reach up to 1.5% or even more, whereas the levels of X0 cells in females can increase up to 5% with age. Here, I propose simple mathematical models of the dynamics of ‘normal’ sex chromosome loss with age. These exponential models provide more mechanistic insights than linear regressions. They account for the lower incidence of sex chromosome loss in young individuals and its increase with age. Moreover, the exponential models show that aneuploidy of the sex chromosomes provides a selective advantage. As there are no longitudinal data available (for the same individual at different time points), the parameters reported here are average values derived from a population. Hopefully, this study will stimulate further work based on next-generation technologies to obtain better estimates of sex chromosome aneuploidy and of the parameters of the models discussed here.