Differential isoform expression and selective muscle involvement in muscular dystrophies
| Autor: | Juha Salenius, Sami Huovinen, Joni Keto, Bjarne Udd, Anna Vihola, Sini Penttilä, Sanna Huovinen, Petri Auvinen, Panu Somervuo, Katarina Pelin, Tiina Suominen, Olayinka Raheem, Peter Hackman |
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| Rok vydání: | 2014 |
| Předmět: |
Protein isoform
Gene isoform Male Microarray Gene Expression Real-Time Polymerase Chain Reaction Muscular Dystrophies Pathology and Forensic Medicine 03 medical and health sciences Exon 0302 clinical medicine Gene expression medicine Humans Protein Isoforms Amyotrophic lateral sclerosis Muscle Skeletal Gene 030304 developmental biology Aged Genetics Aged 80 and over 0303 health sciences biology Exons Middle Aged medicine.disease biology.protein Titin Female 030217 neurology & neurosurgery |
| Zdroj: | The American journal of pathology. 185(10) |
| ISSN: | 1525-2191 |
| Popis: | Despite the expression of the mutated gene in all muscles, selective muscles are involved in genetic muscular dystrophies. Different muscular dystrophies show characteristic patterns of fatty degenerative changes by muscle imaging, even to the extent that the patterns have been used for diagnostic purposes. However, the underlying molecular mechanisms explaining the selective involvement of muscles are not known. To test the hypothesis that different muscles may express variable amounts of different isoforms of muscle genes, we applied a custom-designed exon microarray containing probes for 57 muscle-specific genes to assay the transcriptional profiles in sets of human adult lower limb skeletal muscles. Quantitative real-time PCR and whole transcriptome sequencing were used to further analyze the results. Our results demonstrate significant variations in isoform and gene expression levels in anatomically different muscles. Comparison of the known patterns of selective involvement of certain muscles in two autosomal dominant titinopathies and one autosomal dominant myosinopathy, with the isoform and gene expression results, shows a correlation between the specific muscles involved and significant differences in the level of expression of the affected gene and exons in these same muscles compared with some other selected muscles. Our results suggest that differential expression levels of muscle genes and isoforms are one determinant in the selectivity of muscle involvement in muscular dystrophies. |
| Databáze: | OpenAIRE |
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