Browsing by Author "Simonic, Ingrid"

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    The search for tourette syndrome genes : a conceptual and experimental approach
    (Stellenbosch : Stellenbosch University, 1999-12) Simonic, Ingrid; Gericke, George S.; Retief, Andries E.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences.
    ENGLISH SUMMARY: Tourette syndrome has been reported in most populations throughout the world. Overall, there appears to be similar clinical phenomenology and psychopathology, which may serve as an indication of the biological nature for the condition. The diagnosis of Tourette syndrome represents a challenge for physicians because of clinical heterogeneity and often-present comorbidity with other known neurobehavioural conditions. Due to these clinical overlaps Tourette syndrome may serve as a model disorder for investigating the relationship between various neurological and behavioral domains of childhood reflecting either the expression of a common biological pathway or a common genetic background. The understanding of the genetic basis of Tourette syndrome is therefore of special importance, because it may provide useful insights for the study of other developmental disorders. However, the lack of objective biological markers of clinical manifestation together with a possible high phenocopy rate, unclear mode of inheritance, incomplete penetrance, and frequent bilinear transmission of predisposing genes represent major obstacles for those attempting to elucidate the genetic basis of Tourette syndrome. The research presented in this document is a result of six years' effort of the author and her collaborators to generate cytogenetic and molecular genetic data contributing to a better understanding of genetic and environmental factors affecting the phenotypic expression of Tourette syndrome. Theoretical and experimental results of this collaborative effort are assembled in seven articles (four published, three currently submitted for a publication) and a general introductory section relating to the problems, methods and methodology described and utilized in data collection for the individual papers. Taken as a whole, while the study of chromosome fragile site expression in Tourette syndrome probands yielded equivocal results leading to a number of rather speculative but interesting interpretations, the results of subsequent molecular genetic studies are far clearer. The three most valuable outcomes of these studies for future genetic investigations in Tourette syndrome gene-mapping efforts in the Afrikaner population, and complex genetic traits in general, are: I. The evidence for association/linkage of at least three genomic regions with Tourette syndrome in the Afrikaner population, with two of the regions (11q23 and 8q22) being suggestively linked to Tourette syndrome by others in different populations and employing different analytical methods. 2. The evidence for extended background linkage disequilibrium in the general Afrikaner population (> 5 cM) which further strengthens existing experimental data demonstrating the suitability of this population for gene-mapping efforts involving complex traits. 3. The proof based on real rather than computer-simulated data that sequential and semiparametric methods of analysis could be sufficiently powerful to generate cumulative evidence for positive linkage with the trait in the regions which repeatedly yielded both highly significant as well as suggestively significant disease-marker associations in the initial set of samples.