• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1737-1742
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• 2015

Background: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. Materials and Methods: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. Results: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. Conclusions: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.

• Animal Systematics, Evolution and Diversity
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• v.36 no.4
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• pp.347-353
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• 2020

Although sea slaters Ligia have a significant role in rocky shore habitats, their taxonomic entities have not been clearly understood. In this study, we investigated whether genetic variation inferred from a nuclear genetic marker, namely amplified fragment length polymorphism (AFLP), would conform to that of a mitochondrial DNA marker. Using both the mitochondrial DNA marker and the AFLP marker amplified by the six selective primer sets, we analyzed 95 Ligia individuals from eight locations from East Asia. The direct sequencing of mitochondrial 16S rRNA gene revealed three distinct genetic lineages, with 9.8-11.7 Kimura 2-parameter genetic distance. However, the results of AFLP genotyping analysis with 691 loci did not support those of mitochondrial DNA, and revealed an unexpectedly high proportion of shared polymorphisms among lineages. The inconsistency between the two different genetic markers may be explained by difference in DNA evolutionary history, for example inheritance patterns, effective population size, and mutation rate. The other factor is a possible genomic island of speciation, in that most of the genomic parts are shared among lineages, and only a few genomic regions have diverged.

• Journal of Genetic Medicine
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• v.1 no.1
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• pp.39-43
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• 1997

The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is inherited maternally, in which the MTTL1*MELAS 3243 mutation has been most commonly found as a heteroplasmy of A to G point mutation in the $tRNA^{Leu(UUR)}$ gene. The MTTL1*MELAS 3271 mutation is known to be the second common mutation, though clinical features of both mutations are not remarkably different. Recently, a variety of minor mutations have been reported in patients with MELAS. In this study, major efforts have been made to investigate the allele frequency of major three mutations including MTTL1*MELAS 3243, 3252, 3271 in 10 Korean families with MELAS probands. The PCR and subsequent direct sequencing of the PCR product in the regions spanning these three mutation sites were employed to identify the mutation in each proband. All family members have been screened for the presence of these three mutations by PCR-RFLP assay using Apa I, Acc I and Bfr I restriction enzymes. The MTTL1*MELAS 3243 mutation was most commonly found (7 out of 10 families tested) followed by the MTTL1*MELAS 3271 which was identified in 1 out of 10 families. In the remaining 2 families none of three mutations were found, indicating the presence of either nuclear mutation or yet unidentified mitochondrial DNA mutation in these families.

• BMB Reports
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• v.38 no.6
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• pp.690-694
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• 2005

Transcription termination of the human mitochondrial genome requires specific binding to termination factor mTERF. In this study, mTERF was produced in E. coli and purified by two-step chromatography. mTERF-binding DNA sequences were isolated from a pool of randomized sequences by the repeated selection of bound sequences by gel-mobility shift assay and polymerase chain reaction. Sequencing and comparison of the 23 isolated clones revealed a 16-bp consensus sequence of 5'-GTG$\b{TGGC}$AGANCCNGG-3' in the light-strand (underlined residues were absolutely conserved), which nicely matched the genomic 13-bp terminator sequence 5'-$\b{TGGC}$AGAGCCCGG-3'. Moreover, mTERF binding assays of heteroduplex and single-stranded DNAs showed mTERF recognized the light strand in preference to the heavy strand. The preferential binding of mTERF with the light-strand may explain its distinct orientation-dependent termination activity.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2393-2399
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• 2013

Objective: Mitochondrial DNA (mtDNA) is considered a hotspot of mutations in various tumors. However, the relationship between microsatellite instability (MSI) and mtDNA copy number alterations in lung cancer has yet to be fully clarifieds. In the current study, we investigated the copy number and MSI of mitochondrial genome in lung carcinomas, as well as their significance for cancer development. Methods: The copy number and MSI of mtDNA in 37 matched lung carcinoma/adjacent histological normal lung tissue samples were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) assays for sequence variation, followed by sequence analysis and fluorogenic 5'-nuclease real-time PCR. Student's t test and linear regression analyses were employed to analyze the association between mtDNA copy number alterations and mitochondrial MSI (mtMSI). Results: The mean copy number of mtDNA in lung carcinoma tissue samples was significantly lower than that of the adjacent histologically normal lung tissue samples (p<0.001). mtMSI was detected in 32.4% (12/37) of lung carcinoma samples. The average copy number of mtDNA in lung carcinoma samples containing mtMSI was significantly lower than that in the other lung carcinoma samples (P<0.05). Conclusions: Results suggest that mtMSI may be an early and important event in the progression of lung carcinogenesis, particularly in association with variation in mtDNA copy number.

• Korean Journal of Clinical Laboratory Science
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• v.44 no.3
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• pp.128-135
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• 2012

The kidney and cochlea have similar physiological characteristics, specifically the active transport of fluid and electrolytes, similar effects of aminoglycosides and some immunological factors. Several mitochondrial DNA (mtDNA) defects have been identified to be associated with hearing impairment either in syndromic or nonsyndromic forms. Dialysis patients had more oxidative stress than healthy subjects and this elevated oxidative stress leads to alterations of the mtDNA. To generate a more comprehensive analysis of the relationship between mitochondrial variation and hearing loss, two SNPs of 10609, 14668 position showed nominal levels of association with hearing loss. In our result, the mean PTA values in the ESRD patients were $28{\pm}13.9\;(mean{\pm}SD)dB$ and $51.0{\pm}23.2dB$ in low and high frequencies, which were significantly higher than those in the normal controls. 10609T>C and 14668C>T were significantly associated with hearing loss in the ESRD patients. In summary, our results suggest that the polymorphisms of the ND4L subunit gene might be association with ESRD patients and hearing loss.

• Proceedings of the Zoological Society Korea Conference
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• 1998.10b
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• pp.354.1-354
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• 1998

No Abstract, See Full Text

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.20 no.4
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• pp.259-262
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• 2017

Mitochondria play essential role in eukaryotic cells including in the oxidative phosphorylation and generation of adenosine triphosphate via the electron-transport chain. Therefore, defects in mitochondrial DNA (mtDNA) can result in mitochondrial dysfunction which leads to various mitochondrial disorders that may present with various neurologic and non-neurologic manifestations. Mutations in the nuclear gene polymerase gamma (POLG) are associated with mtDNA depletions, and Alpers-Huttenlocher syndrome is one of the most severe manifestations of POLG mutation characterized by the clinical triad of intractable seizures, psychomotor regression, and liver failure. The hepatic manifestation usually occurs late in the disease's course, but in some references, hepatitis was reportedly the first manifestation. Liver transplantation was considered contraindicated in Alpers-Huttenlocher syndrome due to its poor prognosis. We acknowledged a patient with the first manifestation of the disease being hepatic failure who eventually underwent liver transplantation, and whose neurological outcome improved after cocktail therapy.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.24 no.1
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• pp.1-9
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• 2024

Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episode (MELAS) is a rare maternally inherited disorder primarily caused by mutations in mitochondrial DNA, notably the m.3243A>G mutation in the MT-TL1 gene. This mutation impairs mitochondrial function crucial for cellular energy production, particularly in high-energy-demanding organs such as the brain and muscles. MELAS manifests as recurrent stroke-like episodes, seizures, diabetes mellitus, cardiomyopathy, and other multisystemic symptoms that are often present in childhood. The diagnosis combines genetic testing, clinical evaluation, and neuroimaging, with elevated lactate levels and characteristic magnetic resonance imaging (MRI) findings as key indicators. Treatment focuses on symptomatic management and enhancement of mitochondrial function through L-arginine, coenzyme Q10, high-dose vitamins, and taurine supplementation. Studies have identified additional genetic variants linked to MELAS, including mutations in POLG and other mitochondrial genes, further complicating the genetic landscape. Emerging therapies, particularly gene therapy and mitochondria-targeting drugs, offer promising avenues for addressing the underlying genetic defects and improving mitochondrial functioning. Furthermore, ongoing studies continue to enhance our understanding and management of MELAS, with the aim of reducing its burden and improving patient outcomes and quality of life. This review summarizes the current knowledge on the genetics, clinical features, diagnosis, and treatment of MELAS, highlighting the latest advancements and future directions for therapeutic interventions.

• Animal cells and systems
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• v.1 no.4
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• pp.629-635
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• 1997

Previously we reported the migration and rearrangement of a chloroplast gene cluster into mitochondria. The exact genomic locations of the clusters, modes of the gene rearrangement and mechanisms of the interorganellar migration of the clusters have yet to be understood. The detailed analysis needs to include a larger region of DNA surrounding each cluster. To study DNA rearrangement and migration in more detail a cosmid library was constructed using the total rice genomic DNA including nuclear, chloroplast and mitochondrial DNA. From this cosmid library, a sub-library was obtained by selecting the clones hybridized to various regions of chloroplast DNA. According to the hybridization pattern 136 clones from the sub-library were classified into 29 groups. Detailed analysis of these clones revealed that in addition to authentic chloroplast DNA, the clones contain its homologs resulted from rearrangement and mutation. We analyzed two clones in detail, which contain different rp12 homologs resulted from rearrangement and/or migration, respectively.