The primary goal of the Epi4K Center Without Walls is to increase understanding of the genetic basis of human epilepsy in order to improve the well-being of patients and family members living with these disorders. This improvement will come in the form of better diagnostics, treatments and cures. To accomplish this goal, Epi4K aims to analyze the genomes of a large number of well-phenotyped epilepsy patients and families collected by investigators from several major research groups. The specific goals of this project (7 of 7 - CNV Detection) are to discover copy number variants (CNVs) from exome and whole genome sequence data;to describe the CNV landscape in epilepsy patients compared to controls;and to evaluate the broader impact of a subset of CNVs in a large case-control comparison study. Dr. Evan Eichler of Genome Sciences and Dr. Heather Mefford of Pediatrics &Genetic Medicine will co-direct this project. The discovery of novel, disease-related CNVs in the Epi4K cohorts will further our understanding of epilepsy genetics and lead to the identification of new epilepsy genes and pathways.
Epilepsy is one of the most common neurological disorders in humans, affecting up to 3% of the population. Although it is clear that there is a strong geneti component for epilepsy, there are still only a few genes known. The Epi4K project will identify new genes and genetic pathways in epilepsy and will directly benefit individuals with epilepsy and their families through improved diagnostic, prognostic and recurrence risk information. Greater understanding of the genes involved in normal development and function of the brain will facilitate improved therapies for this common disorder and benefit society as a whole. Disclaimer: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation, based upon the group's discussion, there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore, the critiques may not fully reflect the final opinions of th individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.
|Gelfman, Sahar; Wang, Quanli; McSweeney, K Melodi et al. (2017) Annotating pathogenic non-coding variants in genic regions. Nat Commun 8:236|
|Roohi, Jasmin; Crowe, Jennifer; Loredan, Denis et al. (2017) New diagnosis of atypical ataxia-telangiectasia in a 17-year-old boy with T-cell acute lymphoblastic leukemia and a novel ATM mutation. J Hum Genet 62:581-584|
|Epi4K Consortium (2016) De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies. Am J Hum Genet 99:287-98|
|Epilepsy Phenome/Genome Project Epi4K Consortium (2015) Copy number variant analysis from exome data in 349 patients with epileptic encephalopathy. Ann Neurol 78:323-8|
|Epi4K Consortium (2012) Epi4K: gene discovery in 4,000 genomes. Epilepsia 53:1457-67|