Next-generation sequencing reveals regional differences of the α-synuclein methylation state independent of Lewy body disease.

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.

journal_name

Neuromolecular Med

journal_title

Neuromolecular medicine

authors

de Boni L,Tierling S,Roeber S,Walter J,Giese A,Kretzschmar HA

doi

10.1007/s12017-011-8163-9

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

310-20

issue

4

eissn

1535-1084

issn

1559-1174

journal_volume

13

pub_type

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