Partners and International Organizations
(English)
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Coordinator: Jean Delabar (CNRS 1335, Paris)
Participants: Nicole Creau (CNRS, Paris), Christina Brahe (Univ Cattolica del Sancto Cuore, Roma), Xavier Estivill, Melanie Prichard (Cancer Research Institute, Barcelona), Elizabeth Fisher (St Marys Hospital, London), Anna Kessling (Kennedy Galton Center, Watford Harrow), Marie-Laure Yaspo, Hans Lehrach (Max Plank, Berlin), Dean Nizetic (School of Pharmacy, London), Dania Bricarelli (Galliera Hospital, Genoa), Rafael Oliva (Faculty of Medicine, Barcelona), Michael Petersen (Institute of Child Health, Athens), Marie-Claude Potier (CNRS 2054, Paris), Gerard Roises (INSERM 249, Montpellier), Christine Van Broeckhoven (University of Antwerp), Georges Lutfalla (Institute de Genetique Moleculaire, Montpellier)
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Abstract
(English)
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Chromosome 21 (HC21) is the smallest human chromosome; its long arm is about 37 Mb long and contains between 600-1000 genes. In order to contribute to the completion of the transcription (genic) map and understanding the pathophysiology of HC21 disorders (including Down syndrome) exon trapping was used to clone portions of its genes. More than 800 different unique exons were identified that correspond to approximately 50% of HC21 genes. Subsequently, the cDNAs of 25 novel genes have been cloned, sequenced, mapped on HC21 and their pattern of expression characterized. Experiments to study the contribution of selected genes to the pathophysiology of Down syndrome are in progress. We have made considerable progress in the characterization of two genes related to monogenic disorders.(i) We have identified that the most common cause of progressive myoclonus epilepsy (EPM1) is an expansion of a dodecamer repeat in the 5'flanking region of the cystatin B gene which results in an cell specific reduction of mRNA expression. (ii) We have positionally cloned the gene responsible for autoimmune polyglandular disease (APS1). The gene encodes for a putative transcription factor .In order to better determine the abnormal cellular processes of trisomy 21, we have initiated a comparison of the global gene expression in normal versus trisomy 21 fibroblasts and brains from normal versus trisomy 16 mice. SAGE (serial analysis of gene expression) is used and the results indicate that the expression of genes outside HC21 is modified and may contribute to the pathophysiology of certain phenotypes.
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