Even when a single causative gene mutation is involved, a few (oligogenic) to many (polygenic) additional genetic variants contribute to disease outcome. Innovative bioinformatics tools are needed to tackle this complex genetic architecture within whole genome sequencing data.
In this project, the IB2 Bioinformatics Institute, the ULB Experimental Neurology and Genetics labs, will join forces to detect oligo- to polygenic inheritance in brain developmental disorders, including familial focal epilepsy, early infantile epileptic encephalopathies, and primary microcephaly, three phenotypes for which the researchers have large collections of sequencing data. They will validate detected (novel) gene interactions in zebrafish, as well as in iPS cells from patients and in mouse ES cells, using genome-editing technology when necessary.
Principal investigators: Tom Lenaerts – Interuniversity Institute for Bioinformatics in Brussels (IB2) and Machine Learning group -, Massimo Pandolfo – Laboratory of Experimental Neurology, ULB Institute of Neurosciences (UNI) and Department of Neurology, Hôpital Erasme -, Catheline Vilain – Center of Human Genetics at Hôpital St Pierre and Hopital Universitaire des Enfants (HUDERF) -, Marc Abramowicz, Dept of Genetics, Hôpital Erasme and Laboratory of Medical Genetics, IRIBHM.