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Next-Generation Sequencing Reveals Regional Differences of the α-Synuclein Methylation State Independent of Lewy Body Disease

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Abstract

The α-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 α-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 α-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 α-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.

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Acknowledgments

This work was supported by the Friedrich-Baur-Stiftung (Grant Number 13/10) and Brain Net.

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. The Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Feodor-Lynen-Str. 23, 81377, Munich, Germany

    L. de Boni, S. Roeber, A. Giese & Hans A. Kretzschmar

  2. The Institute for Genetics and Epigenetics, University of Saarland, Saarbrücken, Germany

    S. Tierling & J. Walter

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  1. L. de Boni
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  2. S. Tierling
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  3. S. Roeber
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  4. J. Walter
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  6. Hans A. Kretzschmar
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Correspondence to Hans A. Kretzschmar.

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de Boni, L., Tierling, S., Roeber, S. et al. Next-Generation Sequencing Reveals Regional Differences of the α-Synuclein Methylation State Independent of Lewy Body Disease. Neuromol Med 13, 310–320 (2011). https://doi.org/10.1007/s12017-011-8163-9

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