J Genomics 2014; 2:77-88. doi:10.7150/jgen.8123 This volume


Chromosome Imbalance as a Driver of Sex Disparity in Disease

Lara K. Abramowitz, Stéphanie Olivier-Van Stichelen, John A. Hanover

Laboratory of Cell and Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892-0851, USA

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Abramowitz LK, Olivier-Van Stichelen S, Hanover JA. Chromosome Imbalance as a Driver of Sex Disparity in Disease. J Genomics 2014; 2:77-88. doi:10.7150/jgen.8123. Available from https://www.jgenomics.com/v02p0077.htm

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It has long been recognized that men and women exhibit different risks for diverse disorders ranging from metabolic to autoimmune diseases. However, the underlying causes of these disparities remain obscure. Analysis of patients with chromosomal abnormalities, including Turner syndrome (45X) and Klinefelter syndrome (47XXY), has highlighted the importance of X-linked gene dosage as a contributing factor for disease susceptibility. Escape from X-inactivation and X-linked imprinting can result in transcriptional differences between normal men and women as well as in patients with sex chromosome abnormalities. Animal models support a role for X-linked gene dosage in disease with O-linked N-acetylglucosamine transferase (OGT) emerging as a prime candidate for a pleiotropic effector. OGT encodes a highly regulated nutrient-sensing epigenetic modifier with established links to immunity, metabolism and development.

Keywords: dosage compensation, Turner syndrome, Klinefelter syndrome, imprinting, O-GlcNAcylation