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Special Communication
March 22/29, 2006

The Role of X Inactivation and Cellular Mosaicism in Women's Health and Sex-Specific Diseases

Author Affiliations

Author Affiliations: The McKusick-Nathans Institute of Genetic Medicine and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Md.

JAMA. 2006;295(12):1428-1433. 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.