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Wilson病是铜转运障碍的常染色体隐性遗传病,由于铜蓄积引起对肝、脑的毒性。其基因(WD)已定位于染色体13q14.3。在这一区域构建的人工酵母染色体中,我们识别出一段序列,与Menkes病缺陷的ATP酶基因(MNK)编码的铜结合区相似。我们证明该序列构成—P型ATP酶基因的一部分,即Wcl。与原核生物的重金属转运酶非常相似,亦具有6个金属结合区。该基因在肝和肾中表达,位于包含WD基因座在内的约300kb区域内。在两例Wilson病患者中发现Wcl的编码区内的7个碱基的纯合缺失。Wcl被认为就是WD基因。
Wilson’s disease is an autosomal recessive disorder of copper transport disorder that causes liver and brain toxicity due to copper accumulation. Its gene (WD) has been located on chromosome 13q14.3. In the artificial yeast chromosome constructed in this region, we identified a sequence that is similar to the copper binding region encoded by the ATPase gene (MNK) of the Menkes disease defect. We show that this sequence forms part of the P-type ATPase gene, Wcl. Much like the prokaryotic heavy metal transporter, it has six metal binding sites. This gene is expressed in the liver and kidney and is located within the approximately 300 kb region including the WD locus. A seven base homozygous deletion within the coding region of Wcl was found in two Wilson disease patients. Wcl is considered the WD gene.