Ontology highlight
ABSTRACT:
PROVIDER: PRJNA543819 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To address the question of whether mtDNA mutations might play a role in familiar ALS (fALS), mtDNA was isolated from whole blood (WB), white blood cells (WBC) and platelets (PLT) from fALS patients and the mitochondrial genome was analyzed using a mtDNA resequencing array (Affymetrix MitoChip v2.0) that allows detection of low-level heteroplasmy in addition to the conventional homoplasmic or heteroplasmic mutations. We distinguished between fALS cases with a prominent maternal (mat) inheritance pattern and fALS cases that do not point to a maternal inheritance pattern (non-mat). As additional controls we compared our results to healthy age and sex matched individuals without any known neurodegenerative background. With this we are aiming to get a deeper insight into a possible role of mtDNA alterations acting as a disease modifier in a subgroup of ALS patients presenting with a maternal transmission of the disease.
2023-07-28 | GSE211250 | GEO
Project description:We generated induced pluripotent stem cells (iPSCs) of two patients with Tetralogy of Fallot (TOF) and three healthy relatives of two unrelated familes. We furhter performed mRNA sequencing of iPSCs (day 0) and derived cardiomyocytes (CMs) at day 15 and 60 of patients and healthy relatives.
2020-06-19 | GSE111230 | GEO
Project description:Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated in the pathogenesis of common late-onset disorders, but it is not clear how they arise and propagate in the humans. Here we show that mtDNA mutations are present in primordial germ cells (PGCs) within healthy female human embryos. Close scrutiny revealed the signature of selection against non-synonymous variants in the protein-coding region, tRNA gene variants, and variants in specific regions of the non-coding D-loop. In isolated single PGCs we saw a profound reduction in the cellular mtDNA content, with discrete mitochondria containing ~5 mtDNA molecules during early germline development. Single cell deep mtDNA sequencing showed rare variants reaching higher heteroplasmy levels in later PGCs, consistent with the observed genetic bottleneck, and predicting >80% levels within isolated organelles. Genome-wide RNA-seq showed a progressive upregulation of genes involving mtDNA replication and transcription, linked to a transition from glycolytic to oxidative metabolism. The metabolic shift exposes deleterious mutations to selection at the organellar level during early germ cell development. In this way, the genetic bottleneck prevents the relentless accumulation of mtDNA mutations in the human population predicted by Muller’s ratchet. Mutations escaping this mechanism will, however, show massive shifts in heteroplasmy levels within one human generation, explaining the extreme phenotypic variation seen in human pedigrees with inherited mtDNA disorders.
2018-02-02 | GSE77882 | GEO
Project description:RIPK1 is known to play an important role in TNF induced immune signaling. We have identified three pedigrees with heterozygos mutations in RIPK1 that disrupts its cleavage. We studied the transcriptional profiles of whole blood from one patient.
2019-03-01 | GSE127572 | GEO
Project description:Purpose: The main objective of this pilot study was to compare blood transcriptional landscape of OI patients with COL1A1 pathogenic variants and their healthy relatives, in order to find out different gene expression and dysregulated molecular pathways in OI. Methods: We performed RNA sequencing analysis of the whole blood in seven individuals affected with different OI severity and their five unaffected relatives from the three families. The data was analyzed using edgeR package of R Bioconductor. Functional profiling and pathway analysis of the identified differently expressed genes was performed with g:GOSt and MinePath web-based tools. Results: We identified 114 differently expressed genes. The expression of 79 genes was up-regulated, while 35 genes were down-regulated. The functional analysis identified a presence of dysregulated interferon signaling pathways (IFI27, IFITM3, RSAD12, GBP7). Additionally, the expressions of the genes related to extracellular matrix organization, Wnt signaling, vitamin D metabolism and MAPK-ERK 1/2 pathways were also altered. Conclusions: The current pilot study successfully captured the differential expression of inflammation and bone metabolism pathways in OI patients.
2020-10-28 | GSE160207 | GEO
Project description:We generated murine fibroblast cybrid cell lines that have identical nuclear genomes and differ only in their mtDNA. We observed increased cellular proliferation and resistance to apoptosis in the mtBALB compared to the mtB6 cybrid cells, phenotypes seen in malignant cells. Based on these observations we investigated whether these phenotypic differences could be caused by a unique spectrum of nuclear gene expression alterations induced by the mtDNA changes. Microarray analysis (Agilent, 44K mouse whole genome chip) was conducted in order to elucidate the expression profile of three independent clones of mtBALB and mtB6 cybrid cells.
2012-06-26 | GSE21855 | GEO
Project description:We performed RNA sequencing on the 3 CMT2A-causing MFN2 mutations patient cell lines and 3 normal control lines, all cultured in galactose, we found striking transcriptional signature for CMT2A was present. And the CMT2A fibroblast transcriptional signature was >90% different from that of primary fibroblasts from a patient with CMT1 with a duplication mutation within the PMP22 gene.
2022-03-30 | GSE158650 | GEO
Project description:Mitochondrial DNA (mtDNA) damage is considered as a possible primary cause of Parkinson’s disease (PD). To explore the issue, mtDNA sequences from whole blood were analyzed in PD patients and controls using a resequencing chip and allelic substitutions were estimated for each nucleotide position (np) along the entire mtDNA sequence. Overall, 58 np showed a different allelic distribution in the two groups; of these, 81% showed an increase of non-reference alleles in PD patients, similar to findings reported in patients with Alzheimer’s disease, albeit in reduced proportion. These results suggest that age-related neurodegenerative diseases could share a mechanism involving mtDNA.
2019-05-21 | GSE113704 | GEO
Project description:We generated murine fibroblast cybrid cell lines that have identical nuclear genomes and differ only in their mtDNA. We observed increased cellular proliferation and resistance to apoptosis in the mtBALB compared to the mtB6 cybrid cells, phenotypes seen in malignant cells. Based on these observations we investigated whether these phenotypic differences could be caused by a unique spectrum of nuclear gene expression alterations induced by the mtDNA changes. Microarray analysis (Agilent, 44K mouse whole genome chip) was conducted in order to elucidate the expression profile of three independent clones of mtBALB and mtB6 cybrid cells. Two-condition experiment, mtB6 vs. mtBALB cells. Biological replicates: 4 control replicates, 4 mutant replicates.
2012-06-25 | E-GEOD-21855 | biostudies-arrayexpress
Project description:Parkinson disease (PD) is a neurodegenerative disease believed to initiate in the brainstem and then spread throughout the brain. The mechanism by which this occurs is not yet fully understood, but here we show that damaged mitochondrial DNA (mtDNA) plays an important role in this process, which can be initiated by dysregulation of the IFNb/IFNAR signalling pathway. We report that lack of neuronal IFNb/IFNAR, which is associated to the development of PD, causes oxidization, mutation, and deletion in mtDNA. Damaged mtDNA is subsequently extruded extracellularly and can induce PD symptoms like motor and cognitive impairments in healthy mouse brains. It even leads to neurodegeneration in brain regions far from the injection site, suggesting that damaged mtDNA triggers the propagation of PD hallmarks through the brain. We further show that the mechanism by which damaged mtDNA causes pathology in healthy neurons is independent of cGAS and IFNb/IFNAR, but it is mediated by activation of dual Toll-like receptor (TLR)4/9 pathways. Through a proteomic analysis of extracellular vesicles containing the damaged mtDNA, we identified the TLR4 activator Ribosomal Protein S3 (Rps3) and established that Rps3 is a key effector protein involved in damaged mtDNA extrusion and recognition. Collectively, these results reveal a new molecular pathway by which damaged mtDNA can initiate and propagate Parkinson's Disease, paving the way for potential new therapies or disease monitoring.
2023-09-18 | PXD038362 | Pride