Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA339935 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4052651_1.fastq.gz | Fastqsanger.gz | |||
| SRR4052651_2.fastq.gz | Fastqsanger.gz | |||
| SRR4052652_1.fastq.gz | Fastqsanger.gz | |||
| SRR4052652_2.fastq.gz | Fastqsanger.gz | |||
| SRR4052653_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:RNA sequencing of heart samples of myotonic dystrophic (DM1) patients
| PRJNA280990 | ENA
Project description:The prevailing patho-mechanistic paradigm for myotonic dystrophy (DM) is that the aberrant presence of embryonic isoforms is responsible for many, if not most, aspects of the pleiotropic disease phenotype. In order to identify such aberrantly expressed isoforms in skeletal muscle of DM type 1 (DM1) and type 2 (DM2) patients, we utilized the Affymetrix exon array to characterize the largest collection of DM samples analyzed to date, and included non-DM dystrophic muscle samples (NMD) as disease controls. For the exon array profiling on the Human Exon 1.0 ST array (Affymetrix Santa Clara, CA) we used a panel of 28 skeletal muscle biopsies from DM1 (n=8), DM2 (n=10), Becker muscular dystrophy, BMD, (n=3), Duchenne muscular dystrophy, DMD (n=1), Tibial muscular dystrophy, TMD, (n=2) and normal skeletal muscle (n=4). Normal control RNAs were purchased commercially. .CEL files were generated with a pre-commercial version of the Affymetrix processing software, and the headers might be non-standard. In our lab, users of the Partek software could use them, whereas users of GeneSpring had to modify the header information.
2016-01-05 | E-GEOD-48828 | biostudies-arrayexpress
Project description:The prevailing patho-mechanistic paradigm for myotonic dystrophy (DM) is that the aberrant presence of embryonic isoforms is responsible for many, if not most, aspects of the pleiotropic disease phenotype. In order to identify such aberrantly expressed isoforms in skeletal muscle of DM type 1 (DM1) and type 2 (DM2) patients, we utilized the Affymetrix exon array to characterize the largest collection of DM samples analyzed to date, and included non-DM dystrophic muscle samples (NMD) as disease controls.
2016-01-05 | GSE48828 | GEO
Project description:Distinct RNA-mediated impacts on alternative splicing and extracellular matrix gene expression in a mouse model of myotonic dystrophy. Myotonic dystrophy (DM1) is associated with expression of expanded CTG DNA repeats as RNA (CUGexp RNA). To test whether CUGexp RNA creates a global splicing defect, we compared skeletal muscle of two mouse DM1 models, one expressing a CTGexp transgene, and another homozygous for a defective Mbnl1 gene. Strong correlation in splicing changes for ~100 new Mbnl1-regulated exons indicates loss of Mbnl1 explains >80% of the splicing pathology due to CUGexp RNA. In contrast, only about half of mRNA level changes can be attributed to loss of Mbnl1, indicating CUGexp RNA has Mbnl1-independent effects, particularly on mRNAs for extracellular matrix (ECM) proteins. We propose that CUGexp RNA causes two separate effects: loss of Mbnl1 function, disrupting splicing, and loss of another function that disrupts ECM mRNA regulation, possibly mediated by MBNL2. These findings reveal unanticipated similarities between DM1 and other muscular dystrophies. MBNL1 knockout and HSALR mice on FVB background. To test whether CUGexp RNA creates a global splicing defect, we compared skeletal muscle of two mouse DM1 models, one expressing a CTGexp transgene, and another homozygous for a defective Mbnl1 gene. These samples were compared to the skeletal muscle of a wildtype mouse.
2010-01-23 | E-GEOD-17986 | biostudies-arrayexpress
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 the most common form of adult-onset muscular dystrophy and is caused by an repeat expansion [r(CUG)exp] located in the 3' untranslated region of the DMPK gene. Symptoms include skeletal and cardiac muscle dysfunction and fibrosis. In DM1, there is a lack of established biomarkers in routine clinical practice. Thus, we aimed to identify a blood biomarker with relevance for DM1-pathophysiology and clinical presentation.
2023-05-02 | PXD024107 | Pride
Project description:Myotonic dystrophy type 1 (DM1) is a progressive life-limiting neuromuscular disorder with no available cure. In the current study, we examined the extent to which 12-weeks of cycle ergometry can recuperate clinical and physiological metrics in DM1 patients. Furthermore, we studied the underlying mechanisms through which exercise elicits benefits in skeletal muscle. DM1 was associated with impaired muscle function, fitness, lung capacity, and mitochondrial function. Exercise training induced several clinical, physical, and metabolic advantages in DM1 patients. We highlight that exercise-induced molecular and cellular alterations in patients do not conform with previously published data in murine models and propose an alternative mechanism. Lastly, we briefly outline the involvement of small nucleolar RNAs as a novel component within the DM1 pathophysiology. Taken together, our data supports the efficacy of aerobic training to mitigate the relentless progression of DM1 in individuals affected.
2022-04-01 | GSE184951 | GEO
Project description:Myotonic dystrophy (DM) is the most common autosomal dominant muscular dystrophy and encompasses both skeletal muscle and cardiac complications. Myotonic dystrophy is nucleotide repeat expansion disorder in which type 1 (DM1) is due to a trinucleotide repeat expansion on chromosome 19 and type 2 (DM2) arises from a tetranucleotide repeat expansion on chromosome 3. Developing representative models of myotonic dystrophy in animals has been challenging due to instability of nucleotide repeat expansions, especially for DM2 which is characterized by nucleotide repeat expansions often greater than 5000 copies. To investigate mechanisms of human DM, we generated cellular models of DM1 and DM2. We used regulated MyoD expression to reprogram urine-derived cells into myotubes. In this cell model, we found impaired dystrophin expression, MBNL foci, and aberrant splicing in DM1 but not in DM2 cells. We generated induced pluripotent stem cells (iPSC) from healthy controls, DM1 and DM2 subjects and differentiated these into cardiomyocytes. DM1 and DM2 cells displayed an increase in RNA foci concomitant with cellular differentiation. IPSC-derived cardiomyocytes from DM1 but not DM2 had aberrant splicing and MBNL sequestration. High resolution imaging revealed tight association between MBNL clusters and RNA FISH foci in DM1. Ca2+ transients differed between DM1 and DM2 IPSC-derived cardiomyocytes and from healthy control cells. RNA-sequencing from DM1 and DM2 iPSC-derived cardiomyocytes both altered gene expression as well as distinct splicing patterns as differential between DM1 and DM2. Together these data support that DM1 and DM2, despite some shared clinical and molecular features, have distinct pathological signatures.
2019-02-12 | GSE125638 | GEO
Project description:Myotonic dystrophy type 1 (DM1) is a multisystem genetic disorder involving the muscle, heart, and central nervous system (CNS). The pathogenesis of CNS symptoms prevalent in patients with DM1 remains unelucidated. To elucidate the CNS pathogenesis in DM1, we investigated cell type-specific abnormalities in cortical neurons, white matter glial cells, and spinal motor neurons of patients with DM1 via laser-capture microdissection(LCM).
2022-07-07 | GSE198321 | GEO
Project description:Short tandem repeats (STRs) are prone to expansion mutations that cause multiple hereditary neurological and neuromuscular diseases. To study pathomechanisms using mouse models that recapitulate the tissue specificity and developmental timing of an STR expansion gene, we used rolling circle amplification and CRISPR/Cas9-mediated genome editing to generate Dmpk CTG expansion (CTGexp) knockin models of myotonic dystrophy type 1 (DM1). We demonstrate that skeletal muscle myoblasts and brain choroid plexus epithelial cells are particularly susceptible to Dmpk CTGexp mutations and RNA mis-splicing. Our results implicate dysregulation of muscle regeneration and cerebrospinal fluid homeostasis as early pathogenic events in DM1.
2019-11-15 | GSE137494 | GEO