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Thursday, May 15, 2008
Champagne Terrace/Bordeaux (Novotel London West)
11:30 AM
Background: Phenotypic and genetic heterogeneity present major difficulties in research on the genetics of ASD and probably reflect heterogeneity in neurobiological mechanisms. Moreover, ASD traits are present in the general population in a dimensional way, with family members of individuals with ASD being more affected. Different neurocognitive and neurobiological mechanisms may be associated with different modes of (complex) inheritance. As a classical linkage approach has not led to a breakthrough, a comprehensive search for neurobiological mechanisms (intermediate phenotypes) in ASD may yield new cues towards the genetics of ASD. Two independent research groups from the Katholieke Universiteit Leuven have generated convergent results, providing strong arguments for a role of the ‘regulated secretion pathway’ in neurons in the pathogenesis of ASD.
Objectives: 1) Defining patterns of inheritance of (clusters of) symptoms, cognitive traits and biological markers in ASD; 2) Searching for clusters in neurocognitive and neurobiological variables in order to delineate intermediate phenotypes and use these to group families with presumably more homogenous genetic causes; 3) Screening for specific defects in one intermediate phenotype, the ‘regulated secretion pathway’ in a large sample of families; 4) Confirming the intermediate phenotype-hypothesis in subjects with a specific genetic condition and ASD.
Methods: In 100 multiplex families, 300 simplex families and 100 patients with known genetic syndrome associated with ASD, we administer dimensional questionnaires and interviews for the phenotyping, use novel paradigms and existing tasks to measure central coherence, face processing and executive functioning, conduct a clinical genetic examination, carry out molecular genetic testing and test platelet function as a means to functionally test the regulated secretion pathway. In a subgroup we carry out fMRI and DTI.
Results: In this poster we present our research plan and possible candidate genes for ASD.
Conclusions: Multidisciplinary research will lead to new insights in intermediate phenotypes for ASD.
Objectives: 1) Defining patterns of inheritance of (clusters of) symptoms, cognitive traits and biological markers in ASD; 2) Searching for clusters in neurocognitive and neurobiological variables in order to delineate intermediate phenotypes and use these to group families with presumably more homogenous genetic causes; 3) Screening for specific defects in one intermediate phenotype, the ‘regulated secretion pathway’ in a large sample of families; 4) Confirming the intermediate phenotype-hypothesis in subjects with a specific genetic condition and ASD.
Methods: In 100 multiplex families, 300 simplex families and 100 patients with known genetic syndrome associated with ASD, we administer dimensional questionnaires and interviews for the phenotyping, use novel paradigms and existing tasks to measure central coherence, face processing and executive functioning, conduct a clinical genetic examination, carry out molecular genetic testing and test platelet function as a means to functionally test the regulated secretion pathway. In a subgroup we carry out fMRI and DTI.
Results: In this poster we present our research plan and possible candidate genes for ASD.
Conclusions: Multidisciplinary research will lead to new insights in intermediate phenotypes for ASD.