The role of X inactivation and cellular mosaicism in women's health and sex-specific diseases

JAMA. 2006 Mar 22;295(12):1428-33. doi: 10.1001/jama.295.12.1428.


Sex-specific manifestations of disease are most often attributed to differences in the reproductive apparatus or in life experiences. However, a good deal of sex differences in health issues have their origins in the genes on the sex chromosomes themselves and in X inactivation-the developmental program that equalizes their expression in males and females. Most females are mosaics, having a mixture of cells expressing either their mother's or father's X-linked genes. Often, cell mosaicism is advantageous, ameliorating the deleterious effects of X-linked mutations and contributing to physiological diversity. As a consequence, most X-linked mutations produce male-only diseases. Yet, in some cases the dynamic interactions between cells in mosaic females lead to female-specific disease manifestations.

MeSH terms

  • Autoimmune Diseases / genetics
  • Disease Susceptibility*
  • Female
  • Genes, X-Linked
  • Health Status
  • Humans
  • Mosaicism*
  • Mutation
  • Phenotype
  • Sex Characteristics*
  • X Chromosome Inactivation*