Next-Generation Sequencing Reveals Regional Differences of the α-Synuclein Methylation State Independent of Lewy Body Disease
Next-Generation Sequencing Reveals Regional Differences of the α-Synuclein Methylation State Independent of Lewy Body Disease
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DOI：
10.1007/s12017-011-8163-9
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发表时间：
2011-12-01
影响因子：
3.5
通讯作者：
Kretzschmar, Hans A.
中科院分区：
文献类型：
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作者：
de Boni, L.;Tierling, S.;Kretzschmar, Hans A.
α-突触核蛋白基因（SNCA）在包括帕金森病（PD）在内的路易体病（LBD）的病因学中起主要作用。引起基因表达升高的点突变和遗传改变与家族性PD有因果关系。表观遗传变化在多大程度上调节α-突触核蛋白的表达，并可能有助于散发性LBD的病因是一个有争议的问题。我们使用454 GS-FLX高分辨率亚硫酸氢盐测序分析了散发性LBD和对照组几个脑区中α-突触核蛋白内含子1的启动子区和CpG富集区的甲基化状态。我们的研究结果表明，不同脑区之间的甲基化水平存在显着差异。α-突触核蛋白的启动子和内含子1的整体甲基化水平在对照组中相当低，与以前报道的结果相比，与LBD没有显著差异。然而，单一CpG分析显示在不同脑区和LBD阶段的不同位置存在显著的高甲基化和低甲基化。检测到与LBD患者年龄相关的甲基化的轻微总体增加。
The alpha-synuclein gene (SNCA) plays a major role in the aetiology of Lewy body disease (LBD) including Parkinson's disease (PD). Point mutations and genetic alterations causing elevated gene expression are causally linked to familial PD. To what extent epigenetic changes play a role in the regulation of alpha-synuclein expression and may contribute to the aetiology of sporadic LBD is a matter of debate. We analysed the methylation state of the promoter region and a CpG-rich region of intron 1 of alpha-synuclein in several brain regions in sporadic LBD and controls using 454 GS-FLX-based high-resolution bisulphite sequencing. Our results indicate that there are significant differences in the level of methylation between different brain areas. The overall methylation levels in the promoter and intron 1 of alpha-synuclein are rather low in controls and-in contrast to previously reported findings-are not significantly different from LBD. However, single CpG analysis revealed significant hyper- and hypomethylation at different positions in various brain regions and LBD stages. A slight overall increase in methylation related to LBD patients' age was detected.