Research project P5/19 (Research action P5)
The research programme in the network is devoted to the study of inherited human diseases involving the nervous system including diseases of the central and peripheral nervous system, ear and bone. All are diseases that have a major age-related component and because of the ageing population have a major impact on quality of life of the elderly as well as major socio-economical consequences for our Western society.
In 2001 the draft sequence of the human genome became available. The sequence is expected to be complete in 2003, 50 years after the publication of the DNA double helix by Watson and Crick. This will have a major influence on the strategies used by molecular geneticists and cell biologists aiming at dissecting the molecular basis of human diseases. In the post genomic era there will be major shifts from map-based gene discovery to sequence-based gene discovery, from monogenic to multifactorial diseases, from the analysis of one gene to that of multiple genes, from structural genomics to functional genomics, just to name a few. Laboratories will need to adapt to these new strategies efficiently and fast, demanding a huge dynamic from its researchers. It will be necessary for individual academic groups to join large multidisciplinary teams and networks to allow them to remain successful. Networks as the one described here will allow up-scaling and optimising the productivity of genetic-genomic analyses in order to take full advantage of the opportunities offered by the publication of the draft sequence of the human genome. Also, because of the complementary expertise available in the network functional analysis of known and novel genes, and gene defects will be efficient and fast. Further, cell biology studies and animal models of key proteins in specific disease pathways will identify potential candidate genes and will provide insight in the disease pathology.
The major research topics within the network are Alzheimer Dementia, Psychiatric Diseases and Mental Retardation, Hereditary Hearing Impairment, Bone Disorders, Peripheral Neuropathies and Motor Neuron Disease, and Idiopathic Epilepsies and Ion Channel Physiology. Most of these are complex diseases that in the majority of cases involve both genetic and environmental factors. However, in rare cases the disease is inherited as a monogenic trait and in these families disease genes have been identified using the positional cloning strategy allowing for the cloning of the respective gene from its chromosomal position defined by segregation studies. Several of these disease genes have been studied and still are being studied at the cell biology level and in transgenic and knockout mice. Partners in the network have expertise in molecular genetics using both positional cloning and association studies for mapping disease genes, in gene technology, in reversed genetics, in biochemistry, in cell biology using both cultured cell lines and primary cell culture, in electrophysiology, in generating animal models both transgenic and knockout mice and in histological and morphological studies of human and mouse tissues.
The major challenges for this network are to optimise the gene identification strategies by implementing high-throughput genetic analysis and bioinformatics to allow rapid identification of additional disease and susceptibility genes. To optimise complex genetic statistical methods for detecting susceptibility genes in large populations of patients affected with the multifactorial forms of disease. To efficiently implement cell biology and animal models through core facilities for the different diseases and transfer of knowledge of histology and morphology among partners.
