VIB Department of Molecular Genetics, University of Antwerp

The VIB DMG has a longstanding tradition of combining expertise in molecular genetics and clinical neurology to analyze complex neurological diseases of the central and peripheral nervous system. In the next years, the focus will be on increasing our understanding of the molecular aspects of neurodegenerative processes observed in diseases like neurodegenerative dementia and peripheral neuropathies with the ultimate goal to gather sufficient information to open avenues for translational research and potential therapeutic interventions.

The neurodegenerative diseases that VIB DMG is working on are essentially diseases affecting adults. These diseases are generally multifactorial in nature implying that apart from a genetic causation or increased genetic susceptibility also environmental or lifestyle risk factors may play a role in disease onset, penetrance and progression. In the past, we have focused mainly on families in which the disease was inherited as a monogenic trait. This approach has been highly successful with the identification of key genes and proteins such as APP and PSEN1 in Alzheimer disease, GRN and C9orf72 in frontotemporal lobar degeneration and among others PMP22, HSPB1, HSPB8, SPTLC2, YARS and HINT1 in peripheral neuropathies. Several of these genes are being examined in depth with respect to their biological function in neurodegenerative disease processes.

We will continue the gene identification efforts in rare but well documented families that we have ascertained over the years making optimal use of the arsenal of next generation sequencing and –omics technologies. In addition, we will use selected patient cohorts with an apparent high genetic load (e.g. affected relatives) or an extreme phenotype (e.g. very early-onset age). Further, we will invest in the identification and follow-up of risk genes identified in large collaborative genome-wide association studies in which we participate with extended patient/control cohorts of Alzheimer disease, frontotemporal lobar degeneration or Parkinson disease. Novel risk genes will be analyzed in depth for disease association using common polymorphic genetic variants as well as rare or common mutations pointing to disease relevant biological functions e.g. CLU and CR1 in Alzheimer disease. Hereto, we will use the extended patient/control cohorts that are systematically ascertained via the Belgian Neurology (BELNEU) consortium that is coordinated by us or via international consortia in which we participate. To understand the pathogenic role of causal mutations we will continue investing in cellular systems and model organisms such as yeast, mouse and Drosophila or other via strategic collaborations. Comparably, we will invest in the development of rapid assays to identify key pathogenic variants and consequently functional domains associated with risk genes.