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Presence of epilepsy-associated variants in large exome databases
Journal article   Peer reviewed

Presence of epilepsy-associated variants in large exome databases

Natalya S Cherepanova, Elizabeth Leslie, Polly J Ferguson, Michael J Bamshad and Alexander G Bassuk
Journal of neurogenetics, Vol.27(1-2), pp.1-4
06/2013
DOI: 10.3109/01677063.2013.772176
PMCID: PMC3672316
PMID: 23527921

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Abstract

Mutations in more than twenty genes have been found to cause idiopathic epilepsies, and screening for these variants could facilitate the clinical diagnosis of epilepsy. However, many of the studies that reported putative pathogenic variants for epilepsy tested a relatively small number of control samples making it more likely that a rare non-pathogenic variant could be mistaken as causal. To test the robustness of inferences based on small sample sizes, we investigated whether variants previously reported to cause epilepsy were present in the resequencing data from the large control populations of the 1000 Genomes Project and the NHLBI Exome Sequencing Project. A list of variants associated with epilepsy was compiled using a manual review of the literature for genes associated with epilepsy from a recent International League Against Epilepsy (ILAE) report and two comprehensive genetic studies. We checked for the presence of those variants in the 1000 Genomes Project database and the NHLBI Exome Variant Server (EVS). Of 208 epilepsy-associated variants that we identified from our literature review, only seven were found among 17 thousand chromosomes across 1000 Genomes and the EVS. Consistent with recent published reports, we also found many variants with predicted pathogenicity in epilepsy associated genes in the genomic databases. Our findings suggest that the 1000 Genomes and the EVS datasets may be a valuable resource of control data in research aimed at identifying genes for epilepsy specifically when the model predicts a highly penetrant allele. These databases also elucidate the array of genetic variation in putative epilepsy genes in the general population.

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