This core will support data integration and DNA analysis needs of the SRA projects by delivering high density genetic variant profiling of human DNA samples submitted from Project 1 (human forensic SUDEP cases and EMU monitored epilepsy patients with high risk clinical phenotypes). Project 3 will also submit samples of Dravet Syndrome patient-derived IPSCs for analysis of clonal integrity in stem cell-induced neurons and cardiac myocytes. A major benefit of this core is the professional and scientific expertise of the faculty involved. The Director, Dr. John Belmont, has long experience in handling large scale genomic pipeline analysis of pediatric cardiac disease. The bioinformatician and statistician Dr. Chad Shaw has excellent research expertise in variant profiling and curation of personal genomics as well as general statistical knowledge for handling and integration of quantitative physiology and cellular phenotype data. Dr. Amy McGuire, is a pioneer in medical ethics of translational genomic data, and an essential aspect of the genetic information given the life or death import of the genes in this project. These personnel will be assisted in coordinating this project by Dr. Goldman and Noebels.
The Systems Medicine core will provide DNA sequencing and analysis of samples from individuals with epilepsy who have died prematurely, or who have a high clinical risk of sudden unexpected death in epilepsy. This information will help SRA investigators to discover genes that cause SUDEP, as well as develop a clinically useful predictive profile of genetic risk for premature mortality. The core facility will also provide cliical genetic diagnostic services, share data and protocols with the broader research community, and foster collaborations between basic science laboratories and clinical investigators in SUDEP research.
|Goldman, Alica M; Behr, Elijah R; Semsarian, Christopher et al. (2016) Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention. Epilepsia 57 Suppl 1:17-25|
|Goldman, Alica M (2015) Mechanisms of sudden unexplained death in epilepsy. Curr Opin Neurol 28:166-74|
|Lhatoo, Samden; Noebels, Jeffrey; Whittemore, Vicky et al. (2015) Sudden unexpected death in epilepsy: Identifying risk and preventing mortality. Epilepsia 56:1700-6|