Identification of a genes for Parkinson's disease

帕金森病基因的鉴定

基本信息

批准号：
14013037
负责人：
TODA Tatsushi
金额：
$ 23.04万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14013037/
关键词：
Parkinson's disease Multifactorial disease SNP susceptibility gene drug effect tailormade therapy microsatellite

项目摘要

Parkinson's disease (PD) is a complex disorder with multiple genetic and environmental factors influencing disease risk. Although several causal genes for Mendelian inherited PD have recently been identified, strong genetic factors that influence idiopathic PD have not yet been identified. To identify susceptibility genes for idiopathic PD, we performed a genome-wide association study using 27,000 microsatellite markers arranged at intervals of 100kb throughout the genome. For the initial screening, we compared the pattern of the PCR products of pooled DNA from 124 patients with PD and 124 controls. We analyzed the 27,000 markers and found associations (p<0.05) in 7.8% of the markers. Then, we have performed systematic and comprehensive 2nd and 3rd screenings on all of these candidate markers using other sets of pooled DNA to exclude false positive associations. and expect that approximately 30 markers will show significant associations throughout all three screenings.Secondly, we have done case-control analysis by using SNPs in multiple candidate genes. We selected candidate genes from the viewpoints of familial PD, dopaminergic neurons, trophic factors, oxidative stress, mitochondria, apoptosis, ubiquitin-proteasome, autophagy, etc. For initial screening, we genotyped 190 patients and 190 controls by Invader method. Of 267 SNPs in 122 candidate genes, 22 SNPs in 16 genes showed p<0.05. We are now confirming these associations by increasing the number of samples to nearly 900 for patients and 900 for controls.SNPs in linkage disequilibrium with these markers may be associated with the pathogenesis of PD.

帕金森氏病（PD）是一种复杂的疾病，具有多种遗传和环境因素影响疾病风险。尽管最近已经鉴定出了Mendelian遗传PD的几种因果基因，但尚未鉴定出影响特发性PD的强遗传因素。为了鉴定特发性PD的易感基因，我们使用了整个基因组中以100KB的间隔排列的27,000个微卫星标记进行了全基因组关联研究。在初始筛选中，我们比较了124例PD患者和124例对照的PCR产物的PCR产物模式。我们分析了27,000个标记，并在7.8％的标记中发现了关联（p <0.05）。然后，我们使用其他合并的DNA对所有这些候选标记进行了系统的，全面的第二和第三次筛选，以排除假阳性关联。并预计大约30个标记将在所有三个筛选中都显示出显着的关联。第二，我们通过在多个候选基因中使用SNP进行了病例对照分析。我们从家族性PD，多巴胺能神经元，营养因子，氧化应激，线粒体，凋亡，凋亡，泛素 - 蛋白酶体，自噬等的角度选择了候选基因，我们通过入侵方法对190例患者进行了基因型，我们进行了190例患者的基因。在122个候选基因中的267个SNP中，16个基因中的22个SNP显示出p <0.05。现在，我们通过将样品数量增加到近900例，对照900来证实这些关联。与这些标记的链接不平衡的SNP可能与PD的发病机理有关。