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Hum Mol Genet. 2019 Apr 15;28(8):1312-1321. doi: 10.1093/hmg/ddy432.

Transcriptome alterations in myotonic dystrophy skeletal muscle and heart.

Author information

1
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
2
Koch Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
3
Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL, USA.
4
Center for NeuroGenetics, University of Florida, Gainesville, FL, USA.
5
University of Florida Genetics Institute, University of Florida, Gainesville, FL, USA.
6
Department of Neurology, University of Rochester, Rochester, NY, USA.
7
Department of Biochemistry, University of Oregon, Eugene, OR, USA.
8
School of Life Sciences, Queen's Medical Center, University of Nottingham, Nottingham, UK.
9
Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.
10
Department of Neurology, Stanford University, Palo Alto, CA, USA.
11
Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA.
12
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA.

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.

PMID:
30561649
PMCID:
PMC6452195
[Available on 2020-04-15]
DOI:
10.1093/hmg/ddy432

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