Epigenetic signatures – profiling the epilepsies beyond genetics

What is epigenetics? In a single idea: the molecular memory of a cell. The system stores information of previously external (e.g. environmental) or internal (e.g. developmental) stimuli, learns from this experience and responds. A collection of specific tags tells genes whether to be ON or OFF. Hardcore epigeneticists claim that an epigenetic tag should be meiotically and/or mitotically heritable, self-perpetuating, and reversible. DNA methylation is the mechanism coming closest to this ideal. A more liberal definition not focusing on heritability refers to any structural adaptation of the chromatin template that regulates gene expression. This would also include posttranslational histone tail modifications, incorporation of histone variants, chromatin remodeling processes, and action of non-coding RNAs. The large variety, flexibility, interdependence and potential synergistic effects of epigenetic mechanisms could provide the molecular basis for any phenotypic variation in physiological and pathological conditions. In epilepsy research this is especially interesting with regard to the stimulus-driven activity and connectivity of post-mitotic neurons in the adult brain. We set out to study methylation for the most common form of epilepsy in adults. Continue reading

Guilt by association: SCN1A in Temporal Lobe Epilepsy

GWAS. Genome-wide association studies investigate the association of common genetic variants with disease in large patient samples. While this approach has been very successful in many other diseases, the results in epilepsy research have been less convincing. Given the complexity of epilepsy phenotypes, selection of the right epilepsy phenotype has been an ongoing debate. Now, a recent study in Brain finds an intronic variant of the SCN1A gene that is associated with Temporal Lobe Epilepsy (TLE), the most common epilepsy in man. Interestingly, the association with SCN1A seems to be specific for only a particular subtype of focal epilepsies. Continue reading