Epileptogenese von genetischen Epilepsien, TP 2 "Seltene genetische Faktoren in der Epileptogenese"

30.09.2021 bis 29.09.2024

Project P2 will investigate the role of rare genetic factors in GGE and other epilepsies (Task 1), utilizing the largest pool of up to ~50,000 exomes, collected under the umbrella of Epi25 and the ILAE Genomics initiative (led by P2 investigators). P2 will use new state-of-the-art prioritization methods developed during the 1st funding period. We intend to expand on our previous gene and gene-set burden strategies with an additional particular focus on mapping individual risk from rare variants and the convergence of common and rare variants (Task 2). These analyses adopting novel point of views in epilepsy genetics will be performed in close collaboration with P1/P3. Further, we will continue to validate the role of rare variants in functional studies identified within the RU (Task 3). We will investigate a set of highly-interesting variants selected in light of our current findings (e.g. in CACNA1G/1I, KCNA1, GABRA3/B1), based on the prospects of identifying key electrophysiological mechanisms, with continuous updates based on further results. Findings of the RU will be integrated in our analysis methods (e.g. genes and gene sets from sc/snRNA-seq experiments from P4-P7/Z1-INF).