NeuroMolecular Medicine

, Volume 13, Issue 4, pp 310–320 | Cite as

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

  • L. de Boni
  • S. Tierling
  • S. Roeber
  • J. Walter
  • A. Giese
  • Hans A. Kretzschmar
Original Paper

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.

Keywords

Alpha-synuclein Epigenetics Methylation Lewy body disease 

Supplementary material

12017_2011_8163_MOESM1_ESM.doc (2.5 mb)
Supplementary material 1 (DOC 2559 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • L. de Boni
    • 1
  • S. Tierling
    • 2
  • S. Roeber
    • 1
  • J. Walter
    • 2
  • A. Giese
    • 1
  • Hans A. Kretzschmar
    • 1
  1. 1.The Center for Neuropathology and Prion ResearchLudwig-Maximilians-University MunichMunichGermany
  2. 2.The Institute for Genetics and EpigeneticsUniversity of SaarlandSaarbrückenGermany

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