scholarly journals Comprehensive next-generation sequence analyses of the entire mitochondrial genome reveal new insights into the molecular diagnosis of mitochondrial DNA disorders

2013 ◽  
Vol 15 (5) ◽  
pp. 388-394 ◽  
Author(s):  
Hong Cui ◽  
Fangyuan Li ◽  
David Chen ◽  
Guoli Wang ◽  
Cavatina K. Truong ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Molecular Diagnosis ◽  
Next Generation ◽  
Sequence Analyses ◽  
Entire Mitochondrial Genome

Mutations in Mitochondrial DNA Is An Adverse Factor for Survival in Patients with Acute Myeloid Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1523-1523
Author(s):  
Trine Silkjaer ◽  
Anni Aggerholm ◽  
Charlotte Guldborg Nyvold ◽  
Peter Hokland ◽  
Jan Maxwell Norgaard
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Myeloid Leukemia ◽  
Base Pairs ◽  
Synonymous Mutations ◽  
Coding Regions ◽  
Entire Mitochondrial Genome ◽  
Acute Myeloid

Abstract BACKGROUND: In acute myeloid leukemia (AML), cytogenetic and molecular genetic abnormalities are known to play an essential role in the pathogenesis and are now accepted to be of paramount prognostic significance. However, mitochondrial dysfunction is also emerging as a major factor of importance in cancer. The mitochondrion has its own double-stranded circular 16.569 base pairs DNA (mtDNA) encoding 13 genes involved in oxidative phosphorylation and the respiratory chain, 2 rRNAs, and 22 tRNAs. As such, they are important in apoptosis and might, thus, be crucial in response to chemotherapy and to disease progression. The purpose of this study was to determine if mtDNA mutations are of importance to outcome of chemotherapy and to long-term survival in AML. METHODS: The whole mitochondrial genome was sequenced using a resequencing system based on 46 PCR amplicons (MitoSEQr, Applied Biosystems, Foster City, CA) performed on a Genetic Analyzer 3130 (Applied Biosystems). Diagnostic bone marrow from 20 patients with AML, treated with curative intent, was analyzed. To avoid problems with misinterpretation of heteroplasmy due to admixture of other non-malignant cells, all patient samples selected had more than 80 percent blasts according to immunophenotyping. Data were analyzed using SeqScape v.2.5, Applied Biosystems and statistically analysis in Stata 10. RESULTS: We sequenced the entire mitochondrial genome in 20 patients with AML with 99.5% base pairs sequenced (in 20 patients 329.734 base pairs were successfully sequenced out of 331.380 possible), and compared our findings with clinical data and survival data. In both coding and non-coding regions, a total number of 432 mutations (substitutions, insertions, and deletions) (range 8–44, median 15.5) were found. Mutations were scattered throughout the entire mitochondrial genome, and observed in all genes as well as in non-coding regions. Though, most were known polymorphisms in the Mitomap database (www.mitomap.org), eleven of the non-synonymous mutations were novel in the Mitomap database. All patients had non-synonymous mutations, resulting in amino acid changes (range 2–10, median 3.5), with a total number of 90 non-synonymous mutations. Two of the known non-synonymous mutations were present in all patients (A8860G, A15326G). While most changes were homoplasmic changes, heteroplasmic ones were observed in 12 of 20 patients (range 1-2). Notably, by dividing the patients by the median of the total number of mutations, patients with less than 16 mutations have a 5 years survival of 50% as compared to 10% for patients with 16 mutations or more. This revealed a significant (p=0.04) impact on overall survival of total number of mutations in both coding and non-coding regions (Fig.). Importantly, regression analysis revealed that the number of mutations was independent of age. The non-synonymous mutations show a trend towards a difference in overall survival (p=0.07). CONCLUSION: This is, to our knowledge, the first demonstration of a prognostic impact on survival in AML patients of mutations in the mitochondrial DNA. Further studies on more patients are, however, clearly warranted to discern by which mechanisms mitochondrial DNA mutations are impacting prognosis in AML. Disclosure: No relevant conflict of interest to declare. Figure Figure

scholarly journals Next-generation sequencing yields complete mitochondrial genome assembly of peaceful betta fish, Betta imbellis (Teleostei: Osphronemidae)

2020 ◽  
Vol 5 (4) ◽  
pp. 3856-3858
Author(s):  
Syed Farhan Ahmad ◽  
Nararat Laopichienpong ◽  
Worapong Singchat ◽  
Aorarat Suntronpong ◽  
Tavun Pongsanarm ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Mitochondrial Genome ◽  
Genome Assembly ◽  
Complete Mitochondrial Genome ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Mitochondrial DNA Methylation and Human Diseases

2021 ◽  
Vol 22 (9) ◽  
pp. 4594
Author(s):  
Andrea Stoccoro ◽  
Fabio Coppedè
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Nuclear Genome ◽  
Epigenetic Modifications ◽  
Human Diseases ◽  
Loop Region ◽  
D Loop

Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

scholarly journals Reduced Variation in Drosophila simulans Mitochondrial DNA

Genetics ◽  
1996 ◽  
Vol 144 (4) ◽  
pp. 1519-1528
Author(s):  
J William O Ballad ◽  
Joy Hatzidakis ◽  
Timothy L Karr ◽  
Martin Kreitman
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Evolutionary Dynamics ◽  
Selective Sweep ◽  
Mitochondrial Gene ◽  
Drosophila Simulans ◽  
Dramatic Reduction ◽  
Nucleotide Variability ◽  
Pooled Samples ◽  
Mitochondrial Gene Mutation

We investigated the evolutionary dynamics of infection of a Drosophila simulans population by a maternally inherited insect bacterial parasite, Wolbachia, by analyzing nucleotide variability in three regions of the mitochondrial genome in four infected and 35 uninfected lines. Mitochondrial variability is significantly reduced compared to a noncoding region of a nuclear-encoded gene in both uninfected and pooled samples of flies, indicating a sweep of genetic variation. The selective sweep of mitochondrial DNA may have been generated by the fixation of an advantageous mitochondrial gene mutation in the mitochondrial genome. Alternatively, the dramatic reduction in mitochondrial diversity may be related to Wolbachia.

scholarly journals A Method for Next-Generation Sequencing of Paired Diagnostic and Remission Samples to Detect Mitochondrial DNA Mutations Associated with Leukemia

2017 ◽  
Vol 19 (5) ◽  
pp. 711-721 ◽  
Author(s):  
Ilaria S. Pagani ◽  
Chung H. Kok ◽  
Verity A. Saunders ◽  
Mark B. Van der Hoek ◽  
Susan L. Heatley ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Mitochondrial Dna Mutations ◽  
Dna Mutations ◽  
Generation Sequencing
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