Moleculor Genetics of Parkinson's Disease

帕金森病的分子遗传学

• 批准号: 09470153
• 负责人: KAWAKAMI Hideshi
• 金额: $ 8.51万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470153/
• 关键词: Parkinson's disease; dopamine transporter; polymorphism; risk factor; Nurrl; Nurr1; 遺伝子

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.

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起着重摄取释放的多巴胺的作用。同时，DAT被认为是多巴胺能细胞摄取环境毒素，促进帕金森病的发生和发展。我们克隆并确定了人DAT基因的结构，该基因长度超过50 kb，由15个外显子组成。我们扩增了帕金森病患者和正常人DNA的所有编码外显子，发现DAT基因的5个多态性。其中两个在外显子内，其他的在外显子外。帕金森病患者外显子中有一个多态性低于对照组。此外，我们还克隆了人类Nurr1基因，该基因全长约8.3kb，由8个外显子和7个内含子组成，并进行了序列测定。Nurr1对中脑DA神经元的发育和分化至关重要。进一步分析人类Nurr1基因的多态性。该基因可能揭示与以DA系统改变为特征的疾病的关联，例如帕金森病和精神分裂症。

项目成果

Morino H,Kamei H,Watanabe C,Katayama S,Kawakami H,Nakamura S.: "Three cases of mitochondrial cytopathy associated with severe neuropathy." Clinical Electroencephalography 1997. 39(3). 193-196

Morino H、Kamei H、Watanabe C、Katayama S、Kawakami H、Nakamura S.：“与严重神经病相关的线粒体细胞病的三例。”

Murata Y: "Characteristic magnetic resonance findings in Machado-Joseph Disease" Archives of Neurology. 55(1). 33-37 (1998)

Murata Y：“马查多-约瑟夫病的特征性磁共振发现”神经病学档案。

Ochi K: "Dentato-rubral tract involvement in adult-onset adrenoleukodystrophy" Am J Neuroradiol. 19(10). 1904 (1998)

Ochi K：“成人发病的肾上腺脑白质营养不良中的齿状红束受累”Am J Neuroradiol。

Tori T,Kawarai T,Nakamura S,Kawakami H.: "Organization of of the human orphan nuclear receptor Nurr1 gene." Gene. (in press).

Tori T、Kawarai T、Nakamura S、Kawakami H.：“人类孤儿核受体 Nurr1 基因的组织。”

Toji H: "No association between apolipoprotein E alleles and olivopontocerebellar atrophy" J Neurological Science. 158(1). 110-112 (1998)

Toji H：“载脂蛋白 E 等位基因与橄榄脑桥小脑萎缩之间没有关联”《神经科学》杂志。