Moleculor Genetics of Parkinson's Disease

我们分析了人类多巴胺转运体(DAT)基因多态性与帕金森病发病风险的关系。DAT起着重新摄取释放的多巴胺的作用。同时，DAT被认为是将环境毒素吸收到多巴胺能细胞中，并在帕金森病的发生和发展过程中发挥作用。我们克隆并测定了人DAT基因的结构，该基因全长50kb，由15个外显子组成。我们从帕金森病患者和正常对照的DNA中扩增了所有编码外显子，发现了DAT基因的5个多态性。其中，2个在外显子上，其余的在外显子外。帕金森病患者外显子中的一个基因多态性低于对照组。此外，我们还克隆了人类Nurr1基因，全长约8.3kb，由8个外显子和7个内含子组成。Nurr1对中脑DA神经元的发育和分化是必不可少的。进一步分析人类Nurr1基因的多态性。基因可能揭示了与以DA系统变化为特征的疾病的关联，如帕金森氏病和精神分裂症。

We analyzed the relationship between the polymorphisms of human dopamine transporter (DAT) and the risk of Parkinson's disease. DAT plays the role of reuptake of released dopamine. In the same time, DAT is believed to uptake the environmental toxins into the dopaminergic cells and to proceed the onset and progress of Parkinson's disease. We cloned and determined the structure of the human DAT gene, which is over 50 kb long, consisting of 15 exons. We amplified all coding exons from the DNAs of Parkinson's disease Patients and normal controls, and then found 5 polymorphisms of the DAT gene. Among them, two are in the exons, the others are out of exons. One of the polymorphism in the exon in Parkinson's disease is less than the control. These results suggest the polymorphism of DAT gene affects the onset of Parkinson's disease.In addition, we cloned and sequenced the human Nurr1 gene, which is approximately 8.3 kb long, consisting of 8 exons and 7 introns. Nurr1 is essential for the development and differentiation of midbrain DA neurons. Further analysis of the polymorphism of the human, Nurr1. gene may reveal the association to diseases characterized by changes of the DA system, such as Parkinson's disease and schizophrenia.