Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343448 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4255810_1.fastq.gz | Fastqsanger.gz | |||
| SRR4255810_2.fastq.gz | Fastqsanger.gz | |||
| SRR4255820_1.fastq.gz | Fastqsanger.gz | |||
| SRR4255820_2.fastq.gz | Fastqsanger.gz | |||
| SRR4255860_1.fastq.gz | Fastqsanger.gz |
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Project description:Diet may be modified seasonally or by biogeographic, demographic or cultural shifts. It can differentially influence mitochondrial bioenergetics, retrograde signalling to the nuclear genome, and anterograde signalling to mitochondria. All these interactions have the potential to influence the frequencies of mtDNA types in nature and human health. In a model laboratory system, we fed four diets varying in Protein: Carbohydrate (P:C) ratio (1:2, 1:4, 1:8 and 1:16 P:C) to four Drosophila mitotypes and assayed their frequency in population cages. The nuclear genome was standardised. When fed a high protein 1:2 P:C diet, the frequency of flies harbouring Alstonville mtDNA increased. In contrast, when fed the high carbohydrate 1:16 P:C food the incidence of flies harbouring Dahomey mtDNA increased. This result was repeated when the laboratory diet was replaced by natural fruits having high and low P:C ratios and when the nuclear genome was permuted. Quaternary structural modelling, in vitro assays of electron transport chain protein complexes, and protein gels suggested a V161L mutation in the ND4 subunit of Complex I of Dahomey mtDNA was functionally deleterious and resulted in an increase in larval development time on the 1:2 P:C diet. Conversely, the 1:16 P:C diet resulted in an elegant remodelling of energy metabolism and relative reduction in development time of larvae harbouring Dahomey mtDNA. These data question the use of mtDNA as an assumed neutral maker. We posit that humans with specific mtDNA variations may differentially metabolise carbohydrates, which has implications for a variety of first-world diseases including cardiovascular disease, diabetes, obesity and perhaps Parkinson’s Disease.
2018-11-07 | MTBLS724 | MetaboLights
Project description:Inherited mitochondrial DNA (mtDNA) diseases transmit maternally and cause severe phenotypes. Since no effective treatment or genetic screening is available, nuclear genome transfer between patients’ and healthy eggs to replace mutant mtDNAs holds promises. Since polar body contains very few mitochondria and share same genomic material as oocyte, here we perform polar body transfer to prevent the transmission of inherited mtDNA variants. We compare the value of different germline genome transfer (spindle-chromosome, pronuclear, first and second polar body) in a mouse model. Reconstructed embryos support normal fertilization and produce live offspring. Strikingly, genetic analysis confirms F1 generation after polar body transfer possesses minimal donor mtDNA carry-over compared with spindle-chromosome (low/medium carry-over) and pronuclear (medium/high carry-over) transfer. Moreover, mtDNA genotype remains stable in F2 generation of progeny after polar body transfer. Our preclinical model demonstrates polar body transfer holds great potential in preventing the transmission of inherited mtDNA diseases.
2014-06-19 | GSE56676 | GEO
Project description:Purpose: To develop a pipeline (Splice-Break) for high-resolution quantification of mtDNA deletions, provide a catalogue of human mtDNA deletion breakpoints, and evaluate mtDNA deletions in brains from subjects with psychiatric disorders. Methods: 93 samples from human postmortem brain and blood were obtained from the Southwest Brain Bank (SBB) and University of California, Irvine (UCI) Brain Bank. Total DNA was extracted from frozen homogenate tissue and mtDNA was amplified/enriched using a single long-range PCR. Mitochondrial amplicons were purified by bead purification to retain both wild-type and deleted molecules (i.e., no gel excision was performed). mtDNA-enriched PCR amplicons were prepared for sequencing using standard Illumina protocols for DNA. Samples were sequenced 150-mer paired-end reads, in multiplex (96x per lane), on an unpatterned flowcell (HiSeq 2500). Fastq files were processed using our Splice-Break pipeline for the detection and relative quantification of mtDNA deletions. Results: A catalogue of 4,489 putative mitochondrial DNA (mtDNA) deletions, including their frequency and relative read rate, was produced. Analyses of 93 samples from postmortem brain and blood found 1) the 4,977bp “common deletion” was neither the most frequent deletion nor the most abundant; 2) brain contained significantly more mtDNA deletions than blood; 3) many high frequency deletions were previously reported in MitoBreak, suggesting they are present at low levels in metabolically active tissues and are not exclusive to individuals with diagnosed mitochondrial pathologies; 4) many individual deletions (and cumulative deletion metrics) had significant and positive correlations with age; and 5) the highest deletion burdens were observed in a subset of subjects with major depressive disorder (MDD), and these subjects had mtDNA deletion levels at or above those detected in typical deletion pathologies (e.g., Kearns-Sayre syndrome (KSS) muscle). Conclusions: Collectively, these data suggest the Splice-Break pipeline can detect and quantify mtDNA deletions at a high level of resolution.
2018-11-01 | GSE118615 | GEO
Project description:Inherited mitochondrial DNA (mtDNA) diseases transmit maternally and cause severe phenotypes. Since no effective treatment or genetic screening is available, nuclear genome transfer between patients’ and healthy eggs to replace mutant mtDNAs holds promises. Since polar body contains very few mitochondria and share same genomic material as oocyte, here we perform polar body transfer to prevent the transmission of inherited mtDNA variants. We compare the value of different germline genome transfer (spindle-chromosome, pronuclear, first and second polar body) in a mouse model. Reconstructed embryos support normal fertilization and produce live offspring. Strikingly, genetic analysis confirms F1 generation after polar body transfer possesses minimal donor mtDNA carry-over compared with spindle-chromosome (low/medium carry-over) and pronuclear (medium/high carry-over) transfer. Moreover, mtDNA genotype remains stable in F2 generation of progeny after polar body transfer. Our preclinical model demonstrates polar body transfer holds great potential in preventing the transmission of inherited mtDNA diseases. The objective of the present study was to detect genomic aberrations between PB1 and its counterpart, spindle-chromosome complex in human MII oocyte, PB2 and female pronucleus in human zygote at a single-cell level.
2014-06-19 | E-GEOD-56676 | biostudies-arrayexpress
Project description:The analysis of transcriptional profiles of cybrid cells harbouring two pathogenic mtDNA variants associated with Leigh syndrome i.e., m.9185T>C in the mt-ATP6 gene and m.13513G>A in the mt-ND5 gene, in comparison to cybrid cells harbouring control mtDNA haplogroups or the wt m.13513G variant.
2023-04-01 | E-MTAB-11035 | biostudies-arrayexpress
Project description:Mitochondrial DNA (mtDNA) mutations have been reported in several solid tumors including ovarian cancer (OC), the most lethal gynecologic malignancy, and raised interest as they potentially induce mitochondrial dysfunction and rewiring of cellular metabolism. In this study, we characterized mtDNA mutations in ovarian cancer patient derived xenografts (PDX) and investigated their impact on cancer cells at multiple levels. To correlate the presence of mtDNA mutations and metabolic pathways that were modulated at the transcriptional level, RNA-seq analysis was performed in ascites-derived cells from 19 OC PDX (here named PDOVCA). Results indicated that mtDNA mutated (>50% VAF) PDX were endowed with upregulated glycolysis and other pathways connected with cancer metabolism. Functional analysis demonstrated that mtDNA mutations modulated mitochondria activity, assembly capacity and morphology of mitochondrial complexes in PDX cells. Moreover, PDX cells bearing homoplasmic mtDNA mutations behave as glucose addicted and could barely survive glucose starvation in vitro. These findings led us to investigate whether mtDNA mutations correlated with response to anti-VEGF therapy, which was shown to reduce glucose availability in tumors. Strikingly, PDX bearing homoplasmic pathogenic mtDNA mutations had improved survival upon anti-VEGF treatment in mouse models, compared with PDX lacking mtDNA mutations or bearing them at low frequency. These results hint at mtDNA mutations as new biomarkers of response to antiangiogenic drugs.
2024-12-27 | GSE261674 | GEO
Project description:Type 2 diabetes (T2D), one of the most common metabolic diseases, is the result of insulin resistance or impaired insulin secretion by mitochondrial dysfunctions. Mitochondrial DNA (mtDNA) polymorphisms play an important role in physiological and pathological characteristics of T2D, however, their mechanism is poorly understood. To directly identify candidate mtDNA variants associated with T2D at the genome-wide level, we constructed forty libraries from ten patients with T2D and thirty control individuals for deep sequencing. We characterized their mtDNA atlas, and analyzed their single nucleotide polymorphisms (MtSNPs), insertions and deletions (InDels), and screened potential mtDNA mutation sites associated with T2D. We found ten mtDNA polymorphisms at nucleotides 489T > C, 3105AC > A, 3107N > C, 8701A > G, 9540T > C, 10398A > G, 10400C > T, 10873T > C, 12705C > T and 14783T > C that showed a significant difference between patients and control subjects. Therefore, our results characterize mtDNA atlas of patients with T2D, and further demonstrate that mtDNA variants are participated in the pathophysiology of T2D and other diseases. In addition, mtDNA variants may be candidate molecular biomarkers of T2D, and they may be valuable for early diagnosis of T2D in the future.
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Project description:Low-frequency inherited complement receptor variants are associated with purpura fulminans
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