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Genome wide identification of aberrant alternative splicing events in myotonic dystrophy type 2
- Source :
- PLoS ONE, Vol 9, Iss 4, p e93983 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Myotonic dystrophy type 2 (DM2) is a genetic, autosomal dominant disease due to expansion of tetraplet (CCTG) repetitions in the first intron of the ZNF9/CNBP gene. DM2 is a multisystemic disorder affecting the skeletal muscle, the heart, the eye and the endocrine system. According to the proposed pathological mechanism, the expanded tetraplets have an RNA toxic effect, disrupting the splicing of many mRNAs. Thus, the identification of aberrantly spliced transcripts is instrumental for our understanding of the molecular mechanisms underpinning the disease. The aim of this study was the identification of new aberrant alternative splicing events in DM2 patients. By genome wide analysis of 10 DM2 patients and 10 controls (CTR), we identified 273 alternative spliced exons in 218 genes. While many aberrant splicing events were already identified in the past, most were new. A subset of these events was validated by qPCR assays in 19 DM2 and 15 CTR subjects. To gain insight into the molecular pathways involving the identified aberrantly spliced genes, we performed a bioinformatics analysis with Ingenuity system. This analysis indicated a deregulation of development, cell survival, metabolism, calcium signaling and contractility. In conclusion, our genome wide analysis provided a database of aberrant splicing events in the skeletal muscle of DM2 patients. The affected genes are involved in numerous pathways and networks important for muscle physio-pathology, suggesting that the identified variants may contribute to DM2 pathogenesis.
- Subjects :
- Fetal Proteins
Male
Epidemiology
Biopsy
lcsh:Medicine
RNA-binding protein
Polymerase Chain Reaction
Muscular Dystrophies
Exon
Medicine and Health Sciences
Myotonic Dystrophy
Clinical Epidemiology
lcsh:Science
Genetics
Multidisciplinary
Autosomal dominant trait
Nuclear Proteins
RNA-Binding Proteins
Exons
Genomics
LIM Domain Proteins
Middle Aged
Neurology
Research Design
Genetic Epidemiology
RNA splicing
Female
Genetic Engineering
Transcriptome Analysis
Research Article
Biotechnology
musculoskeletal diseases
Cell Survival
Clinical Research Design
Formins
tau Proteins
Biology
Research and Analysis Methods
Myotonic dystrophy
medicine
Humans
Calcium Signaling
Muscle, Skeletal
Gene
Adaptor Proteins, Signal Transducing
Population Biology
Genome, Human
Alternative splicing
lcsh:R
Intron
Computational Biology
Biology and Life Sciences
medicine.disease
Genome Analysis
Alternative Splicing
NFI Transcription Factors
Gene Expression Regulation
RNA
lcsh:Q
Genome Expression Analysis
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....d3c6b470157fb1234e2e563997769ebb