RNA sequencing of heart samples of myotonic dystrophic (DM1) patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE67812 | GEO | 2015/04/14
SECONDARY ACCESSION(S): PRJNA280990
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of alternative splicing in heart (left ventricles) samples of 3 adult DM1 patients versus 3 adult controls PolyA RNA from left ventricles (heart) of 3 controls and 3 DM1 patients were analysed by massive parrallel sequencing
2015-04-14 | E-GEOD-67812 | biostudies-arrayexpress
Project description:Analysis of alternative splicing of left ventricles heart samples of 3 DM1 adult versus 3 adult controls PolyA RNA from left ventricles (heart) of 3 controls and 3 DM1 patients were analysed on Exon Array (Affymetrix)
2016-01-21 | E-GEOD-67067 | biostudies-arrayexpress
Project description:Analysis of alternative splicing of left ventricles heart samples of 3 DM1 adult versus 3 adult controls
2016-01-21 | GSE67067 | GEO
Project description:Introduction: Myotonic dystrophy of type 1 (DM1), the most common dystrophy in adults, is an autosomal dominant inherited disease, affecting around 1 in 8000 person. Patients suffering from DM1 develop essentially muscle disorders such as myotonia, muscle weakness, muscle loss and atrophy. The disease is caused by the mutation of the DMPK "Dystrophia Myotonica Protein Kinase" gene. The mutation correspond to an abnormally large expansion of CTG tri-nucleotides repeats located in the 3'-untranslated region of this gene. Expanded CTG repeats are normally transcribed, but accumulates in RNA aggregates that sequester RNA-binding proteins such as the splicing regulator MBNL1. Consequently, due to MBNL1 sequestration, DM1 is characterized by aberrant splicing of a wide number of mRNA, which are themselves responsible for the symptoms observed in the disease. Purpose: To determine as much as possible novel splicing misregulations taking place in DM1 skeletal muscle, we performed a paired-end RNA sequencing (RNA-seq) using muscles samples of normal individuals (CTRL, n=3) versus muscles of DM1 patients (DM1, n=3). The data was analyzed by a bioinformatical software, called MISO, in order to map the alternative splicing changes between normal and DM1 muscle. The aim of this study was to get a broad and precise view of the splicing changes occurring in DM1 muscle.
2017-08-24 | GSE85984 | GEO
Project description:Myotonic dystrophy type 1 (DM1) is a dominantly inherited disease that affects multiple organ systems. Cardiac dysfunction is the second leading cause of death in DM1. We quantified gene expression in heart tissue from a heart-specific DM1 mouse model (EpA960/MCM) which inducibly expresses human DMPK exon 15 containing 960 CUG expanded repeats and that reproduced Celf1 up regulation. To assess if, in addition to splicing and miRNA defects, CUGexp RNA also perturbed the steady state mRNA levels of genes, we carried out a microarray study on wildtype E14, adult, MCM controls and DM1 mouse hearts. As anticipated we noted a large number of genes to be developmentally regulated in wildtype hearts, however, within 72h of induction of CUGexp RNA there appeared to be a coordinate adult-to-embryonic shift in steady state levels of many genes. We identified transcripts over-expressed or under-expressed in hearts of wildtype adult mice, wildtype embryonic day 14 (E14), and DM1 mice induced to express CUGexp RNA for 72h and 1wk, when compared to MCM controls. Multiple group comparison.
2014-01-24 | E-GEOD-48991 | biostudies-arrayexpress
Project description:Myotonic dystrophy type 1 (DM1) is a dominantly inherited disease that affects multiple organ systems. Cardiac dysfunction is the second leading cause of death in DM1. We quantified gene expression in heart tissue from a heart-specific DM1 mouse model (EpA960/MCM) which inducibly expresses human DMPK exon 15 containing 960 CUG expanded repeats and that reproduced Celf1 up regulation. To assess if, in addition to splicing and miRNA defects, CUGexp RNA also perturbed the steady state mRNA levels of genes, we carried out a microarray study on wildtype E14, adult, MCM controls and DM1 mouse hearts. As anticipated we noted a large number of genes to be developmentally regulated in wildtype hearts, however, within 72h of induction of CUGexp RNA there appeared to be a coordinate adult-to-embryonic shift in steady state levels of many genes.
2014-01-24 | GSE48991 | GEO
Project description:Myotonic Dystrophy (DM1), a common neuromuscular disease, has been shown to have detrimental effects on the livers of patients. To study whether DM1 is directly altering liver function or whether these effects are secondary to DM1 induced functional changes in other tissues, we sequenced the transcriptomes of hepatocytes from liver-specific and whole-body murine models of DM1. We found substantial transcriptomic alteration in the liver-specific model, along with distinguishable physiological changes in the livers of both the liver-specific and whole-body models. This data serves as a survey of transcriptomic alterations in occurring in the livers of DM1 patients.
2024-09-26 | GSE252827 | GEO
Project description:Congenital myotonic dystrophy (CDM) is the most severe form of myotonic dystrophy type-1 (DM1). In adult DM1, dysregulation of alternative splicing of many transcripts results in the disease pathology. In CDM, the degree of aberrant splicing is not known, nor is it understood which transcripts are altered. Muscle biopsies were obtained from children with CDM, adults with DM1, healthy adult controls, and pathologically normal pediatric muscle. RNA was isolated and paired-end RNA-Seq was performed. Analysis used MAJIQ to generate percent spliced in (PSI) values. Sample sets were analyzed with Weighted Gene Co-expression Network Analysis (WGCNA) to identify splicing patterns. 11 muscle biopsies from children with CDM (age 2 month-16 years), 9 pediatric controls (age 1 month-13 years), 16 adult DM1 patients (ages 29-57), and 6 adult healthy controls (ages 19-28) were used for analysis. MAJIQ identified 2266 splicing events with adequate read depth and a PSI>0.15. WGCNA identified 4 patterns of splicing. The majority of the splicing events were the same in cases of CDM and DM1, while a subset of splicing changes were unique to CDM, many (e.g., PALLD) specific to development. The relative expression of RNA splicing factors with age may account for differences in the splicing patterns in CDM and DM1. Children with CDM have the RNA splicing events previously identified in adults with DM1, despite a divergent phenotype. There are also a minority of splicing events that are specific to CDM, largely related to transcripts regulating development.
2023-02-03 | GSE126342 | GEO
Project description:In the context of developing an integrative proteogenomics strategy for assessing both differential gene expression and alternative splicing, we generated RNA-seq data (paired-end, 76 bp, 71 million reads per sample on average) from gastrocnemius muscles (right and left hind limb) from five wild-type mice and five HSALR mice (male, 10-12 weeks old) modelling the human disease Myotonic Dystrophy type 1 (DM1).
2023-06-30 | E-MTAB-10842 | biostudies-arrayexpress
Project description:We have developed an inducible, skeletal muscle-specific mouse model of DM1 (CUG960) that expresses 960 CUG repeat-expressing animals (CUG960) in the context of human DMPK exons 11-15. CUG960 RNA-expressing mice induced at postnatal day 1, as well as adult-onset animals, show clear, measurable muscle wasting accompanied by severe histological defects including central myonuclei, reduced fiber cross-sectional area, increased percentage of oxidative myofibers, the presence of nuclear RNA foci that colocalize with Mbnl1 protein, and increased Celf1 protein in severely affected muscles. Importantly, muscle loss, histological abnormalities and RNA foci are reversible, demonstrating recovery upon removal of toxic RNA. RNA-seq and protein array analysis indicate that the balance between anabolic and catabolic pathways that normally regulate muscle mass may be disrupted by deregulation of platelet derived growth factor receptor beta signaling and the PI3K/AKT pathways, along with prolonged activation of AMP-activated protein kinase alpha signaling. Similar changes were detected in DM1 skeletal muscle compared with unaffected controls.
2021-08-19 | GSE181895 | GEO