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Next-generation sequencing reveals regional differences of the α-synuclein methylation state independent of Lewy body disease.
de Boni, L; Tierling, S; Roeber, S; Walter, J; Giese, A; Kretzschmar, Hans A.
Afiliación
  • de Boni L; The Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Feodor-Lynen-Str. 23, 81377, Munich, Germany. Laura.de_Boni@med.uni.muenchen.de
Neuromolecular Med ; 13(4): 310-20, 2011 Dec.
Article en En | MEDLINE | ID: mdl-22042430
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Análisis de Secuencia de ADN / Metilación de ADN / Enfermedad por Cuerpos de Lewy / Alfa-Sinucleína Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neuromolecular Med Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Análisis de Secuencia de ADN / Metilación de ADN / Enfermedad por Cuerpos de Lewy / Alfa-Sinucleína Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neuromolecular Med Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos