1. Transcriptome alterations in myotonic dystrophy skeletal muscle and heart
- Author
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John W. Day, Sam Sedehizadeh, Thomas A. Cooper, Charles A. Thornton, Christopher B. Burge, Daniel J. Treacy, Thomas T. Wang, David E. Housman, Katy Eichinger, Amanda J. Ward, J. Andrew Berglund, Adam J. Struck, Kirti Bhatt, Joseph Estabrook, Eric T. Wang, David Brook, Hailey Olafson, and Tony Westbrook
- Subjects
Adult ,Male ,RNA Splicing ,Duchenne muscular dystrophy ,Biology ,Myotonic dystrophy ,Genome ,Transcriptome ,03 medical and health sciences ,Exon ,Gene expression ,Genetics ,medicine ,Humans ,Myotonic Dystrophy ,Muscle, Skeletal ,Molecular Biology ,Genetics (clinical) ,Principal Component Analysis ,0303 health sciences ,Base Sequence ,Gene Expression Profiling ,Myocardium ,030305 genetics & heredity ,RNA-Binding Proteins ,Skeletal muscle ,Heart ,General Medicine ,medicine.disease ,Alternative Splicing ,medicine.anatomical_structure ,RNA splicing ,RNA ,Female ,General Article ,Microsatellite Repeats - Abstract
Myotonic dystrophy (dystrophia myotonica, DM) is a multi-systemic disease caused by expanded CTG or CCTG microsatellite repeats. Characterized by symptoms in muscle, heart and central nervous system, among others, it is one of the most variable diseases known. A major pathogenic event in DM is the sequestration of muscleblind-like proteins by CUG or CCUG repeat-containing RNAs transcribed from expanded repeats, and differences in the extent of MBNL sequestration dependent on repeat length and expression level may account for some portion of the variability. However, many other cellular pathways are reported to be perturbed in DM, and the severity of specific disease symptoms varies among individuals. To help understand this variability and facilitate research into DM, we generated 120 RNASeq transcriptomes from skeletal and heart muscle derived from healthy and DM1 biopsies and autopsies. A limited number of DM2 and Duchenne muscular dystrophy samples were also sequenced. We analyzed splicing and gene expression, identified tissue-specific changes in RNA processing and uncovered transcriptome changes strongly correlating with muscle strength. We created a web resource at http://DMseq.org that hosts raw and processed transcriptome data and provides a lightweight, responsive interface that enables browsing of processed data across the genome.
- Published
- 2018
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