TRANSCRIPTOME 2002: From Functional Genomics to Systems
Gene Expression Profiling in Dysferlin-opathies Using a Dedicated Muscle Microarray
Stefano Campanaro1, Marina Fanin2, Beniamina Pacchioni1, Silvia Trevisan1, Barbara Celegato1, Elena Pegoraro2, Yukiko K. Hayashi3, Giorgio Valle1, Corrado Angelini1 and Gerolamo Lanfranchi1, 1CRIBI Biotechnology Center, University of Padova, ITALY, 2Department of Neurological and Psychiatric Sciences, University of Padova, ITALY, 3Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, JAPAN
We have used gene expression profiling to define transcriptional patterns involved in a muscular dystrophy with known primary biochemical defect (the dysferlin deficiency or limb-girdle dystrophy type 2A) and to correlate them with histopathological changes. We have employed a dedicated muscle-specific microarray composed by 2,700 sequences corresponding to the 400-500 most 3'-terminal region of muscle transcripts. Muscle biopsies from 10 homogeneous patients were used as sources of RNA complex target for array hybridizations. Parallel studies for mutation analysis of the dysferlin gene and immunohistochemical characterization of muscle biopsies were undertaken. We have compared the transcription profiles of patient samples and normal samples for the same type of muscles. The transcription pattern variability among patients was also assessed. We found evidence for incomplete differentiation of myofibers and upregulation of telethonin, FATZ/Myozenin/calsarcin, titin and alpha actin genes. There was also 11-times upregulation of MHC class 1. We also found a metabolic alteration in muscle mitochondria affecting AcylCoA-dehydrogenase and fatty acid binding protein, two genes involved in fatty acid metabolism. Finally, our expression data show that primary dysferlin deficiency induces a corresponding reduction of caveolin 3 and acetylcholinesterase, which are localized in the cell membrane and are involved in intracellular signaling.
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