Grant: Project Grant

Epilepsy affects ~3% of individuals, with half of the cases starting during childhood. Despite the fact that more than 20 anti-epileptic drugs (AEDs) are available, a significant portion of patients with epilepsy will continue to have seizures. This by itself justifies the need to continue to search for the genetic mechanism underlying epilepsies in order to better treat patients. Epilepsy is characterized by great genetic heterogeneity, with the involvement of hundreds of genes. Since the coding variations in genes have been extensively studied in the last few years and cannot explain the genetic cause for a vast majority of epileptic patients, we aim here to study the non-coding portion of the genome of epileptic patients using already available whole-genome sequences and genotyping and genealogical data. Specific aims consist in 1) Prioritization of non-coding genomic regions using genealogies. In this aim we will use the genealogies of patients as well as the identity-by-descent (IBD) genomic segments to identify patients with more or longer shared IBD regions than expected given the genealogical kinship and prioritize within these regions the ones that could be associated to the disease. 2) Investigation of genomic segments prioritized in aim 1 for non-coding causal single nucleotide variants (SNVs), structural variants (SVs) and short tandem repeats (STRs) associated with epilepsy using different bioinformatic tools. With this proposal we expect to increase the number of epileptic patients for whom we can find a genetic cause for their disease. This will allow us to better understand the genetic mechanisms underlying the disease. Moreover, these findings could also give us insights towards better epilepsy management and treatment.