Even when only one causal mutation is involved, additional genetic variants in small (oligogenic) or large numbers (polygenic) contribute to the disease. Innovative bioinformatics tools are required to decipher this genetic architecture in the complete genome sequencing data.
In this project, the IB2 Bioinformatics Institute and the laboratories of experimental neurology and genetics of the ULB joined forces to detect oligo to polygenic inheritance in abnormalities of brain development, including familial focal epilepsy, childhood epileptic encephalopathies and primary microcephaly, three phenotypes for which researchers have extensive collections of sequencing data. Detected gene interactions will be validated in zebrafish as well as in patients’ iPS cells and in mouse ES cells, using, if necessary, genome engineering technologies.
Andrea Gazzo, Tom Lenaerts, Massimo Pandolfo, Catheline Vilain, Marc Abramowicz.
ULB, IB2, Erasme
Gazzo, A. M., Daneels, D., Cilia, E., Bonduelle, M., Abramowicz, M., Van Dooren, S., Smits, G. and Lenaerts, T. (2015). DIDA: A curated and annotated digenic diseases database. Nucleic acids research, 44(D1), D900-D907.
Gazzo, A., Raimondi, D., Daneels, D., Moreau, Y., Smits, G., Van Dooren, S., & Lenaerts, T. (2017). Understanding mutational effects in digenic diseases. Nucleic acids research, 45(15), e140-e140.
Papadimitriou, S., Gazzo, A., Versbraegen, N., Nachtegael, C., Aerts, J., Moreau, Y., Van Dooren, S., Nowé, A., Smits, G. and Lenaerts, T. (2018) Predicting disease-causing variant combinations. (Submitted)
Versbraegen, N., Fouché, A., Nachtegael C., Papadimitriou, S., Gazzo, A., Smits, G. and Lenaerts, T. (2018) Using game theory and decision decomposition to effectively discern and characterise bi-locus diseases. (submitted)
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