Chromosome imbalance as a driver of sex disparity in disease.
Chromosome imbalance as a driver of sex disparity in disease.
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DOI：
10.7150/jgen.8123
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Hanover, John A
中科院分区：
文献类型：
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作者：
Abramowitz, Lara K;Olivier-Van Stichelen, Stephanie;Hanover, John A
人们早就认识到，男性和女性患从代谢性疾病到自身免疫性疾病等多种疾病的风险不同。然而，这些差异的根本原因仍然不清楚。对特纳综合征 (45X) 和克兰费尔特综合征 (47XXY) 等染色体异常患者的分析强调了 X 连锁基因剂量作为疾病易感性影响因素的重要性。逃避X失活和X连锁印记可能导致正常男性和女性以及性染色体异常患者之间的转录差异。动物模型支持 X 连锁基因剂量在疾病中的作用，O-连锁 N-乙酰氨基葡萄糖转移酶 (OGT) 成为多效性效应子的主要候选者。 OGT 编码一种高度调控的营养感应表观遗传修饰因子，与免疫、代谢和发育建立了联系。
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.