Laboratory of Neurogenetics

The Laboratory of Neurogenetics is structured around the following research themes:

These three groups contribute to the multidisciplinary neuroscience research of the Institute Born-Bunge.

For further information: visit the website of the Department of Molecular Genetics

Head: Prof. Dr. Christine Van Broeckhoven, PhD, DSc
VIB - Department of Molecular Genetics University of Antwerp Campus Drie Eiken Parking 4, Building V, Room 0.10 Universiteitsplein 1 BE-2610 Antwerpen
Tel: +32 3 265 10 01 Fax: +32 3 265 10 12
mail prof. Christine Van Broeckhoven

Neurodegenerative Brain Diseases

Our research main focus is on the genetics, genomics and neuropathology of neurodegenerative brain diseases, mainly Alzheimer’s disease, frontotemporal dementia and Parkinson’s disease. We aim at identifying causal and risk genes underlying the disease process using positional cloning strategies in the monogenic component of these diseases, and association studies in patient/control samples, triads and nuclear families.
Once a disease gene is known we analyze its biological function in relation to the disease pathology using both cellular and mice models. Also, we analyze in detail the contribution of the respective proteins to the brain pathology using detailed morphological and immunohistochemical studies.
Our research group has contributed to the identification of genes coding for the amyloid precursor protein (APP) and presenilin 1, in which mutation are responsible for early-onset dominant Alzheimer’s disease. For example we have identified key mutations in APP such as the Flemish and Austrian APP mutations. Particularly the Flemish APP mutation has highlighted the relationship between the neuronal and vascular components of Alzheimer pathology. Currently we have broadened our molecular genetics and genomics research to other neurodegenerative brain diseases including frontal temporal dementia and Parkinson’s disease. One of our current major projects here is tau-negative, ubiquitine-positive frontotemporal dementia linked to the tau genomic region at chromosome 17q21. Further, we have developed transgenic mice models for the Flemish and Austrian APP mutations that allow detailed in vivo analysis of the respective pathologies. The cell biology of the mutated proteins is examined in vitro in cultured and primary cell lines. We also provide molecular DNA diagnosis of neurodegenerative brain diseases upon request of medical genetic or neurological centers.
The VIB department of Molecular Genetics also has a Genetic Service Facility that provides high-throughput genetic service including DNA/RNA extraction, generation of lymphoblast cell lines, DNA sequencing and genotyping of genetic variants as well as computational support.

Group leader: Prof. Dr. Christine Van Broeckhoven, PhD, DSc
Tel: +32 3 265 10 01 Fax: +32 3 265 10 12
mail Prof. Christine Van Broeckhoven

Peripheral Neuropathy

Research in our laboratory is focused on inherited disorders of the peripheral nervous system, classified as hereditary motor and/or sensory neuropathies. The most common inherited peripheral neuropathy is Charcot-Marie-Tooth (CMT) disease, and is characterized by progressive weakness and atrophy of foot and hand muscles, with some patients becoming severely handicapped at young age.
Positional cloning has already identified 30 loci and 18 genes for dominant, recessive or X-linked forms. However, an efficient therapy is not yet available for any of the peripheral neuropathies. Our major aim is to identify genes in which mutations result in inherited peripheral neuropathies. The identification of these genes is a first step towards better understanding of fundamental biological processes operating in myelination, axon-Schwann cell interactions, structure of the axonal cytoskeleton and axonal transport.
In 1991, we demonstrated that 1.5 Mb tandem duplication in chromosome 17p11.2 underlies CMT type 1A, the most common form of CMT. This is the first time that a dosage sensitive gene was identified in an autosomal dominant disease. Also, it was the first molecular genetic defect described in CMT. Subsequently, we localised the peripheral myelin protein 22 gene within this duplication.
Our research group has built expertise in identifying chromosomal loci and genes within the human genome using positional cloning techniques. We characterised several large families that represent novel genetic entities, and described a large number of mutations in distinct genes leading to demyelinating and/or axonal forms of CMT. We also performed differential gene expression studies and identified novel candidate genes for motor and/or sensory neuropathies.

Group leader: Vincent Timmerman, PhD
Tel: +32 3 265 10 24 Fax: +32 3 265 10 12
mail prof. Vincent Timmerman

Neurogenetics

Many neuro-degenerative disorders have a genetic etiology or are complex disorders caused by an interaction between environmental and inherited factors. In our research groups we focus on inherited peripheral neuropathies and inherited epilepsy syndromes.
The clinical, electrophysiological and neuropathological characterization of patients affected by these disorders forms the starting point for molecular genetic studies.
Classical linkage studies are performed in extended pedigrees resulting in the mapping of genetic loci and the identification of novel genes. Based on genotype-phenotype studies in homogeneous patient-populations we delineate the range of clinical variables. These observations often provide preliminary insights in the disease mechanisms and help to select specific mutations for additional functional studies. These findings also help to develop algorithms for diagnostic DNA analysis in these disorders.
Our main research topics are the molecular genetics of peripheral neuropathies, idiopathic epilepsy syndromes, progressive external ophthalmoplegia (PEO) and spastic paraplegias. In the epilepsy project we demonstrated that de novo mutations in the sodium channel gene SCN1A are the major cause of severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome), a devastating form of childhood epilepsy. We identified mutations in the mitochondrial DNA polymerase gamma (POLG) gene as the major cause of PEO. In addition we host a molecular diagnostic unit that provides DNA diagnoses and performs research on neurological diseases, and we are curating the Inherited Peripheral Neuropathies Mutation Database (http://www.molgen.ua.ac.be/CMTMutations/) for the European CMT consortium.

Group leader: Prof. Peter De Jonghe, PhD, MD
Tel: +32 3 265 10 50 Fax: +32 3 265 10 12
mail prof. Peter De Jonghe