| Abstract No.: | 100 |
| Country: | Canada |
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| Title: | Genomic Approaches to Brain Diseases |
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| Authors/Affiliations: | 1 Guy A. Rouleau*, 1 Julie Gauthier, 1 Amelie Piton, 2 Fadi Hamdan, 1 Yan Yang, 1 Dan Spiegelman, 1 Edouard Henrion, 3 Marie-Pierre Dubé, 4 Pejmun Haghighi, 4 Salvatore Carbonetto, 4 Phil Barker, 5 Christian Néri, 6 Pierre Drapeau;
1 Centre for the Study of Brain Disease, CHUM Research Centre, Notre-Dame Hospital, Montreal, QC; 2 Division of Medical Genetics, Hopital Sainte-Justine, Montreal, QC; 3 Université de Montréal – CRICM, QC; 4 McGill University, Montreal, QC; 5 INSERM
6 Université de Montreal, Department of Pathology and Cellular Biology, Montreal, QC
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| Content: | Genetic factors play an important role in most common brain diseases. However, few disease predisposing genes have been identified, due in part to the complexity of the brain and significant non-allelic genetic heterogeneity. Furthermore, few genomic studies have been designed to study brain diseases, largely for the same reasons as well as the difficulties in obtaining tissue. Recent technological developments have allowed us to explore a novel genomic approach, which we are first applying to Schizophrenia (SCZ) and autism (AUT), which are common, devastating and poorly treated mental disorders. Converging evidence suggests that genetically disrupted synaptogenesis and synaptic plasticity during development may underlie the pathogenesis of such brain disorders. We therefore hypothesize that a significant fraction of SCZ and AUT cases are a result of frequent novel mutations in many different genes involved in synapse formation and function. Our strategy is to identify the underlying synaptic genetic factors predisposing to SCZ and AUT by using a new, two-step strategy: first the direct re-sequencing of 1000 genes coding for proteins which regulate an entire brain-specific “machine”, the synapse, in a large number of patients, and secondly evaluating the functional effects of disease-related variants of these genes in several animal models. This will allow us to identify the most promising mutations for future functional genomics analyses, including transgenic mouse models. In contrast to the all too few mutations discovered to date, we expect to identify a significant number of genes directly causing or increasing the susceptibility to SCZ and AUT. |
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